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Credentials

Education ?

Medical School
Ross University (1998)

Publications & Research

Dr. Palmer has contributed to 223 publications.
Title A Clinical Index to Stratify Hospitalized Older Adults According to Risk for New-onset Disability.
Date September 2011
Journal Journal of the American Geriatrics Society
Excerpt

Many older adults who are independent prior to hospitalization develop a new disability by hospital discharge. Early risk stratification for new-onset disability may improve care. Thus, this study's objective was to develop and validate a clinical index to determine, at admission, risk for new-onset disability among older, hospitalized adults at discharge.

Title The Influence of Tobacco Smoking on Adhesion Molecule Profiles.
Date July 2011
Journal Tobacco Induced Diseases
Excerpt

Sequential interactions between several adhesion molecules and their ligands regulate lymphocyte circulation and leukocyte recruitment to inflammatory foci. Adhesion molecules are, therefore, central and critical components of the immune and inflammatory system. We review the evidence that tobacco smoking dysregulates specific components of the adhesion cascade, which may be a common factor in several smoking-induced diseases. Smoking causes inappropriate leukocyte activation, leukocyte-endothelial adhesion, and neutrophil entrapment in the microvasculature, which may help initiate local tissue destruction. Appropriate inflammatory reactions may thus be compromised. In addition to smoke-induced alterations to membrane bound endothelial and leukocyte adhesion molecule expression, which may help explain the above phenomena, smoking has a profound influence on circulating adhesion molecule profiles, most notably sICAM-1 and specific sCD44 variants. Elevated concentrations of soluble adhesion molecules may simply reflect ongoing inflammatory processes. However, increasing evidence suggests that specific soluble adhesion molecules are immunomodulatory, and that alterations to soluble adhesion molecule profiles may represent a significant risk factor for several diverse diseases. This evidence is discussed herein.

Title Analysis of Circulating Insulin-like Growth Factor-1 (igf-1) and Igf Binding Protein-3 (igfbp-3) in Tobacco Smokers and Non-smokers.
Date July 2011
Journal Tobacco Induced Diseases
Excerpt

IGF-1 and the major serum IGF-1 binding protein, IGFBP-3, are under extensive investigation as potential prognostic markers of specific malignancies and vascular diseases. However, there is conflicting evidence that tobacco smoking may influence systemic concentrations of IGF-1 and IGFBP-3.

Title Diagnostic Value and Clinical Utility of Contrast Enhanced Ultrasound in Intestinal Diseases.
Date January 2011
Journal Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
Excerpt

Contrast enhanced ultrasound (CEUS) has recently gained increasing attention as it clearly improves the visualisation of perfusion in various tissues. The development of second generation contrast enhancing agents used in low-mechanical-index harmonic ultrasound has enabled real-time assessment of the microvascular circulation and quantification of bowel wall vascularity. For this review Medline was searched for clinical studies using CEUS to investigate the gastrointestinal tract. Many studies demonstrate that acute or chronic inflammation of the intestinal wall is accompanied by increased perfusion of the mesentery, which can be displayed semi-quantitatively using contrast enhanced ultrasound analyzing time intensity curves. In contrast, ischemia is characterized by hypoperfusion of the mesenteric arteries and the bowel wall. The most promising sonographic approach in assessing splanchnic arteries and the bowel wall is combining the analysis of superior and inferior mesenteric inflow by pulsed Doppler scanning (systolic and diastolic velocities, resistance index) with the end-organ vascularity by CEUS. CEUS at a preliminary stage has been described as clinically important in a variety of gastrointestinal disorders, particularly in patients with Crohn's disease. CEUS facilitates the detection of disease extent and activity, and its luminal and extraluminal complications.

Title Perioperative Care of the Elderly Patient: an Update.
Date January 2011
Journal Cleveland Clinic Journal of Medicine
Excerpt

Elderly patients pose unique challenges perioperatively. They are more likely than younger surgical patients to be mentally and physically compromised at baseline, which increases the risk of delirium and postoperative cognitive dysfunction. Postoperative cognitive risk can be predicted, however, and effective strategies exist to reduce this risk. Elderly patients are also at increased risk of a precipitous postoperative decline in physiologic reserve, which can lead to organ failure. General recommendations for the perioperative care of elderly patients include avoiding drugs that raise the risk of delirium, ensuring adequate caloric and fluid intake, getting the patient out of bed and into physical therapy as soon as possible, and early planning for discharge. An elderly patient's postoperative cognitive risk and its impact on quality of life should be factored into the decision whether to undergo surgery. Family conferences are recommended to address the many questions and challenges that surgery in an elderly person can pose.

Title Risk of Implant Failure and Marginal Bone Loss in Subjects with a History of Periodontitis: a Systematic Review and Meta-analysis.
Date November 2010
Journal Clinical Implant Dentistry and Related Research
Excerpt

A number of studies have suggested that implant failure and associated bone loss is greater in subjects with a history of periodontitis.

Title Accuracy of Measuring the Cortical Bone Thickness Adjacent to Dental Implants Using Cone Beam Computed Tomography.
Date October 2010
Journal Clinical Oral Implants Research
Excerpt

To assess the accuracy of measuring the cortical bone thickness adjacent to dental implants using two cone beam computed tomography (CBCT) systems.

Title Strategies for Culture of 'unculturable' Bacteria.
Date October 2010
Journal Fems Microbiology Letters
Excerpt

Molecular ecology methods are now well established for the culture-independent characterization of complex bacterial communities associated with various environmental and animal habitats and are revealing the extent of their diversity. By comparison, it has become clear that only a small minority of microorganisms are readily cultivated in vitro, with the majority of all bacteria remaining 'unculturable' using standard methods. Yet, it is only through the isolation of bacterial species in pure culture that they may be fully characterized, both for their physiological and pathological properties. Hence, the endeavour to devise novel cultivation methods for microorganisms that appear to be inherently resistant to artificial culture is a most important one. This minireview discusses the possible reasons for 'unculturability' and evaluates advances in the cultivation of previously unculturable bacteria from complex bacterial communities. Methods include the use of dilute nutrient media particularly suited for the growth of bacteria adapted to oligotrophic conditions, and the provision of simulated natural environmental conditions for bacterial culture. This has led to the recovery of 'unculturables' from soil and aquatic environments, likely to be due to the inclusion of essential nutrients and/or signalling molecules from the native environment.

Title Quality of Care in Hospital and Postdischarge Mortality.
Date October 2010
Journal Journal of the American Geriatrics Society
Title An Internet-based Communication Network for Information Transfer During Patient Transitions from Skilled Nursing Facility to the Emergency Department.
Date October 2010
Journal Journal of the American Geriatrics Society
Excerpt

To determine whether the implementation of an Internet-based communication system improves the amount of essential information conveyed between a skilled nursing facility (SNF) and the emergency department (ED) during patient care transitions.

Title Cultivation of a Synergistetes Strain Representing a Previously Uncultivated Lineage.
Date July 2010
Journal Environmental Microbiology
Excerpt

Subgingival plaque samples obtained from human subjects with periodontitis, shown to include previously uncultivable members of the phylum Synergistetes, were used to inoculate Cooked Meat Medium (CMM). The presence of Cluster A (uncultivable) Synergistetes was monitored by fluorescent in situ hybridization (FISH) and quantitative PCR (Q-PCR). Cluster A Synergistetes were found to grow in CMM in co-culture with other plaque bacteria and growth was stimulated by the addition of mucin and serum. Plaque samples were also used to inoculate Blood Agar (BA) plates and growth of Cluster A Synergistetes was revealed after anaerobic incubation, by colony hybridization with specific probes. Surface growth on the plates in regions identified by colony hybridization was harvested and used to inoculate fresh plates, thus enriching for Cluster A Synergistetes. Cross-streaks of other plaque bacteria were also used to stimulate Synergistetes growth. In the early passages, no discrete Synergistetes colonies were seen, but after eight passages and the use of cross-streaks of other bacteria present in the enriched community, colonies arose, which consisted solely of Cluster A Synergistetes cells, as determined by 16S rRNA gene PCR and cloning. This is the first report of the successful culture of a member of the uncultivable branch of this phylum.

Title The Decision to Extract or Retain Compromised Teeth is Not Helped by the Application of a Scoring System.
Date June 2010
Journal The Journal of Evidence-based Dental Practice
Excerpt

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: A Novel Decision-Making Process for Tooth Retention or Extraction J Periodontol 2009;80:476-491. Avila G, Galindo-Moreno P, Soehren S, Misch CE, Morelli T, Wang H-L. REVIEWER: Richard M. Palmer, PhD, BDS, FDS RCS PURPOSE/QUESTION: Is it possible to devise a system to help in the decision-making process of tooth extraction/retention based on a critical evaluation of the literature? SOURCE OF FUNDING: University of Michigan Periodontal Graduate Student Research Fund TYPE OF STUDY/DESIGN: Comprehensive literature review LEVEL OF EVIDENCE: Level 3: Other evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable.

Title Modification of Thiol Functionalized Aptamers by Conjugation of Synthetic Polymers.
Date May 2010
Journal Bioconjugate Chemistry
Excerpt

Aptamers are known for their short in vivo circulating half-life and rapid renal clearance. Their conjugation to poly(ethylene glycol) (PEG) is a way to improve their residence in the body. Two aptamers (AptD and AptF), having a disulfide protected thiol modification on the 3' end, have been conjugated to maleimide activated PEGs of various molecular weights and structures (linear PEG20; branched PEG20 and 40; PolyPEG17, 40, and 60 kDa). The high yield coupling (70-80% in most of the cases) could be achieved using immobilized tris[2-carboxyethyl]phosphine hydrochloride (TCEP) as reducing agent at pH 4. The affinity of PEGylated AptD for its target was reduced by conjugation to linear PEG20 and branched PEG40, but not to branched PEG20 and PolyPEGs. This work demonstrates an alternative approach to PEGylation of aptamers, and that the effect of PEG on the affinity for the target varies according to the structure and conformation of the synthetic polymer.

Title Cdx Genes, Inflammation and the Pathogenesis of Barrett's Metaplasia.
Date September 2009
Journal Trends in Molecular Medicine
Excerpt

Metaplasia is the conversion of one cell or tissue type to another and can predispose patients to neoplasia. Perhaps one of the best-known examples of metaplasia is Barrett's metaplasia (BM), a pathological condition in which the distal oesophageal epithelium switches from stratified squamous to intestinal-type columnar epithelium. BM predisposes to oesophageal adenocarcinoma and is the consequence of long-term acid bile reflux. The incidence of BM and oesophageal adenocarcinoma has risen dramatically in recent years. A key event in the pathogenesis of BM is the induction of oesophageal CDX2 expression. Importantly, recent data reveal the molecular mechanisms that link inflammation in the development of Barrett's metaplasia, CDX2 and the progression to cancer. This review highlights the relationship between inflammation, metaplasia and carcinogenesis.

Title Potentially Inappropriate Medication Prescribing in Outpatient Practices: Prevalence and Patient Characteristics Based on Electronic Health Records.
Date July 2009
Journal The American Journal of Geriatric Pharmacotherapy
Excerpt

Some older adults receive potentially inappropriate medications (PIMs), increasing their risk for adverse events. A literature search did not find any US multicenter studies that measured the prevalence of PIMs in outpatient practices based on data from electronic health records (EHRs), using both the Beers and Zhan criteria.

Title Diversity and Morphology of Members of the Phylum "synergistetes" in Periodontal Health and Disease.
Date June 2009
Journal Applied and Environmental Microbiology
Excerpt

Members of the phylum "Synergistetes" have frequently been detected in the human oral cavity at sites of dental disease, but they have rarely been detected in studies of oral health. Only two oral "Synergistetes" taxa are cultivable. The aims of this study were to investigate the diversity of "Synergistetes" in the oral cavity, to establish whether "Synergistetes" taxa are more strongly associated with periodontitis than with oral health, and to visualize unculturable "Synergistetes" in situ. Sixty samples (saliva, dental plaque, and mucosal swabs) were collected from five subjects with periodontitis and five periodontally healthy controls. Using phylum-specific 16S rRNA gene primers, "Synergistetes" were identified by PCR, cloning, and sequencing of 48 clones per PCR-positive sample. Subgingival plaque samples were labeled with probes targeting rRNA of unculturable oral "Synergistetes" using fluorescent in situ hybridization (FISH). Analysis of 1,664 clones revealed 12 "Synergistetes" operational taxonomic units (OTUs) at the 99% sequence identity level, 5 of which were novel. "Synergistetes" OTU 4.2 was found in significantly more subjects with periodontitis than controls (P = 0.048) and was more abundant in subgingival plaque at diseased sites than at healthy sites in subjects with periodontitis (P = 0.019) or controls (P = 0.019). FISH analysis revealed that unculturable oral "Synergistetes" cells were large curved bacilli. The human oral cavity harbors a diverse population of "Synergistetes." "Synergistetes" OTU 4.2 is associated with periodontitis and may have a pathogenic role.

Title Smoking Behaviour and Attitudes to Periodontal Health and Quit Smoking in Patients with Periodontal Disease.
Date February 2009
Journal Journal of Clinical Periodontology
Excerpt

The aim of this study was to assess oral health-related beliefs and attitudes, health behaviour of smokers in relation to the Transtheoretical Model (TTM) of behaviour change, willingness to have smoking cessation provided together with periodontal treatment.

Title Recovery of Activities of Daily Living in Older Adults After Hospitalization for Acute Medical Illness.
Date January 2009
Journal Journal of the American Geriatrics Society
Excerpt

To compare functional outcomes in the year after discharge for older adults discharged from the hospital after an acute medical illness with a new or additional disability in their basic self-care activities of daily living (ADL) (compared with preadmission baseline 2 weeks before admission) with those of older adults discharged with baseline ADL function and identify predictors of failure to recover to baseline function 1 year after discharge.

Title Periodontal Tissue Engineering and Regeneration: Consensus Report of the Sixth European Workshop on Periodontology.
Date January 2009
Journal Journal of Clinical Periodontology
Excerpt

To review the scientific preclinical background and clinical studies of current methods of periodontal regeneration in the treatment of infrabony defects and soft tissue deficiencies.

Title Immediate and Early Replacement Implants and Restorations.
Date August 2008
Journal Sadj : Journal of the South African Dental Association = Tydskrif Van Die Suid-afrikaanse Tandheelkundige Vereniging
Excerpt

There have been rapid developments in dental implant treatment protocols to reduce the time between implant placement and restoration. Implants may be placed immediately following tooth extraction or following a period of healing to allow resolution of residual infection or sufficient bone and soft tissue healing. Early restoration and loading of implants has to be carefully controlled to avoid increased failure and complications. Advantages and disadvantages of the various techniques are described.

Title The Management of Developmentally Absent Maxillary Lateral Incisors--a Survey of Orthodontists in the Uk.
Date March 2008
Journal British Dental Journal
Excerpt

To investigate the orthodontic management of patients with developmentally absent maxillary lateral incisors.

Title Demonstration of in Vivo Transfer of Doxycycline Resistance Mediated by a Novel Transposon.
Date January 2008
Journal The Journal of Antimicrobial Chemotherapy
Excerpt

The aim of this study was to investigate the transfer of bacterial doxycycline resistance between oral bacteria in subjects receiving systemic doxycycline for the treatment of periodontitis.

Title The Division "synergistes".
Date December 2007
Journal Anaerobe
Excerpt

The "Synergistes" group of organisms are a phylogenetic cluster of Gram-negative anaerobes related to Synergistes jonesii, sufficiently distinct from all other phyla to be considered a distinct phylum or Division. They are widely distributed in nature although normally only a minor constituent of the bacterial community in each habitat. They have evolved to adapt to each habitat, and therefore exhibit a wide range of physiological and biochemical characteristics, although all cultivable taxa so far studied have the ability to degrade amino acids. They are found in the human mouth where they appear to be more numerous in tooth and gum disease than health. They have also been found in the human gut and soft tissue infections. Their role in human disease has yet to be established but improved knowledge of the characteristics that enable their identification should increase the likelihood of their recognition when present at diseased sites.

Title A Brief Risk Stratification Tool to Predict Functional Decline in Older Adults Discharged from Emergency Departments.
Date October 2007
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: To determine the effectiveness of the six-item Triage Risk Screening Tool (TRST) to assess baseline functional status and predict subsequent functional decline in older community-dwelling adults discharged home from the emergency department (ED). DESIGN: Secondary data analysis of a randomized, controlled trial. SETTING: EDs of two urban academic hospitals. PARTICIPANTS: Six hundred fifty community-dwelling adults aged 65 and older presenting to the ED and discharged home. Patients were categorized a priori as "high risk" if they had cognitive impairment or two or more risk factors on the TRST. MEASUREMENTS: Functional status: summed activity of daily living (ADL) and instrumental activity of daily living (IADL) scores at baseline, 30 days, and 120 days. Self-perceived physical health: standardized physical health component of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Functional decline: loss of one or more ADLs and one or more IADLs from ED baseline at 30 and 120 days. Decline in self-perceived physical health: follow-up SF-36 standardized physical health component scores four or more points lower than baseline. RESULTS: TRST scores correlated with baseline ADL impairments, IADL impairments, and self-perceived physical health at all endpoints (P<.001). A TRST score of two or more was moderately predictive of decline in ADLs or IADLs (30-day ADL area under the receiver operating characteristic curve (AUC)=0.64; 95% confidence interval (CI)=0.56-0.72; 120-day ADL AUC=0.66; 95% CI=0.58-0.74) but not perceived physical health. CONCLUSION: The TRST identifies baseline functional impairment in older ED patients and is moderately predictive of subsequent functional decline after an initial ED visit. The TRST provides a valid proxy measure for assessing functional status in the ED and may be useful in identifying high-risk patients who would benefit from referrals for further evaluation or surveillance upon ED discharge.

Title A Comparison of Bone Mineral Density in the Spine, Hip and Jaws of Edentulous Subjects.
Date September 2007
Journal Clinical Oral Implants Research
Excerpt

The aim was to investigate the relationship between bone mineral density (BMD) of the jaws (mandible and maxilla) and other skeletal sites. In addition, the influence of gender, smoking and the number of years without natural teeth were examined.

Title Astra Tech Single-tooth Implants: an Audit of Patient Satisfaction and Soft Tissue Form.
Date September 2007
Journal Journal of Clinical Periodontology
Excerpt

To investigate patient centred outcomes, soft tissue morphology, and bone levels.

Title Breakaway Forces of Flat and Domed Surfaced Magfit Implant Magnet Attachments.
Date August 2007
Journal The European Journal of Prosthodontics and Restorative Dentistry
Excerpt

The aim of this in vitro study was to compare the resistance to separation (breakaway force) of flat (Magfit-IP-BF) and domed (Magfit-IP-BD) implant magnet attachments subjected to non-axial forces. The separating forces were applied by an Instron Universal Testing Instrument to single magnet attachments at angles of 0 degrees, 2 degrees, 5 degrees 10 degrees, and 20 degrees from the axial line of the components (angle of pull) and at crosshead speeds of 0.5 mn/min and 5 degrees mm/min. The breakaway forces were significantly (p < 0.0001) inversely related to the angle of pull for both flat magnets and for domed magnets. At the slow crosshead speed, the breakaway forces recorded for the domed magnets were significantly greater than those recorded for the flat magnets for angles of pull greater than 5 degrees. At the faster crosshead speed, the breakaway forces recorded for the domed magnets were significantly greater than those recorded for the flat magnets for angles of pull greater than 2 degrees. This apparent superiority of domed magnets under non-axially directed separating forces could influence the choice of magnet attachment for implant overdentures as intraoral displacing forces are multidirectional. Domed magnets may also be advantageous where implants are not parallel.

Title Management of Smoking Patients by Specialist Periodontists and Hygienists in the United Kingdom.
Date June 2007
Journal Journal of Clinical Periodontology
Excerpt

To assess the management of patients who are current smokers in dental practice.

Title The Relationship of Indwelling Urinary Catheters to Death, Length of Hospital Stay, Functional Decline, and Nursing Home Admission in Hospitalized Older Medical Patients.
Date March 2007
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: To determine the association between indwelling urinary catheterization without a specific medical indication and adverse outcomes. DESIGN: Prospective cohort. SETTING: General medical inpatient services at a teaching hospital. PARTICIPANTS: Five hundred thirty-five patients aged 70 and older admitted without a specific medical indication for urinary catheterization. INTERVENTION: Indwelling urinary catheterization within 48 hours of admission. MEASUREMENTS: Death, length of hospital stay, decline in ability to perform activities of daily living (ADLs), and new admission to a nursing home. RESULTS: Indwelling urinary catheters were placed in 76 of the 535 (14%) patients without a specific medical indication. Catheterized patients were more likely to die in the hospital (6.6% vs 1.5% of those not catheterized, P=.006) and within 90 days of hospital discharge (25% vs 10.5%, P<.001); the greater risk of death with catheterization persisted in a propensity-matched analysis (hazard ratio (HR)=2.42, 95% confidence interval (CI)=1.04-5.65). Catheterized patients also had longer lengths of hospital stay (median, 6 days vs 4 days; P=.001); this association persisted in a propensity-matched analysis (HR=1.46, 95% CI=1.03-2.08). Catheterization was not associated (P>.05) with decline in ADL function or with admission to a nursing home. CONCLUSION: In this cohort of older patients, urinary catheterization without a specific medical indication was associated with greater risk of death and longer hospital stay.

Title Is Surgical Thrombectomy to Salvage Failed Autogenous Arteriovenous Fistulae Worthwhile?
Date January 2007
Journal The American Surgeon
Excerpt

The Dialysis Outcomes Quality Initiatives guidelines emphasize placement of autogenous arteriovenous (AV) fistulae for patients on hemodialysis. This recommendation is based on studies that demonstrate enhanced patency for AV fistulae compared with grafts. However, closer review of the data demonstrates that although primary patency of AV fistulae is superior to grafts, the secondary patency rates are equivalent. This suggests that secondary procedures to maintain fistula patency are inferior to those performed on arteriovenous grafts. Surgical thrombectomy of AV fistulae can be challenging. It is often difficult to completely remove thrombus adjacent to the anastomosis of the fistula, and pseudoaneurysms within the fistula can prevent passage of the thrombectomy catheter and complete removal of thrombus from the fistula. Consequently, some surgeons simply abandon thrombosed AV fistulae and place a new access. We have developed a method for completely clearing thrombus from failed AV fistulae by locating the fistulotomy close to the arterial anastomosis and using a technique to manually extract thrombus from the fistula before passing a thrombectomy catheter. The purpose of this study was to review our results with this procedure. Between 2001 and 2004, 10 patients with a previously functioning AV fistula presented with thrombosis. There were seven brachiocephalic fistulae and three radiocephalic fistulae. All patients underwent surgical thrombectomy and fistulography. Five patients underwent balloon angioplasty of a venous stenosis and one patient underwent surgical revision of an arterial stenosis. Technical success, defined as being able to completely clear thrombus from the fistula and treat the cause for fistula failure, was achieved in 70 per cent (7/10) of cases. Technical failure was caused by vein rupture during the balloon angioplasty in two cases and a central venous occlusion that could not be treated in one case. The 6-month primary and secondary patency for cases that were technically successful was 51 and 69 per cent, respectively. Our conclusion was that surgical thrombectomy can significantly extend fistula functionality in patients who present with thrombosis.

Title Is Minimally Invasive Parathyroidectomy Reasonable in the Nonuniversity Setting?
Date December 2006
Journal American Journal of Surgery
Excerpt

BACKGROUND: Minimally invasive parathyroidectomy (MIPX) hinges on accurate preoperative localization and the intraoperative parathyroid hormone (IOPTH) assay to confirm adequate resection. Our goal was to evaluate the results of this technique when applied in a nonuniversity setting. METHODS: All patients undergoing parathyroidectomy at our institution from August 2000 until June 2005 were retrospectively reviewed. Patients were divided into 2 groups: bilateral cervical exploration versus MIPX based on adequate preoperative localization. RESULTS: There were 271 patients who underwent parathyroidectomy during the study period. Of these cases, 204 patients with primary hyperparathyroidism composed our study group. We observed that 136 patients (67%) had unilaterally positive localization studies (group 1), and MIPX was successfully completed in 52% of cases. CONCLUSIONS: Although nearly all patients with single-gland disease should be candidates for MIPX, we found that adequate preoperative imaging and concurrent thyroid disease limited successful completion of the minimally invasive procedure.

Title Atypical Anxiolytic-like Response to Naloxone in Benzodiazepine-resistant 129s2/svhsd Mice: Role of Opioid Receptor Subtypes.
Date December 2006
Journal Psychopharmacology
Excerpt

Mice of many 129 substrains respond to environmental novelty with behavioural suppression and high levels of anxiety-like behaviour. Although resistant to conventional anxiolytics, this behavioural phenotype may involve stress-induced release of endogenous opioids.

Title Implant Failure is Higher in Grafted Edentulous Maxillae.
Date December 2006
Journal The Journal of Evidence-based Dental Practice
Title Pilot Study of the Efficacy of Renzapride on Gastrointestinal Motility and Symptoms in Patients with Constipation-predominant Irritable Bowel Syndrome.
Date September 2006
Journal Alimentary Pharmacology & Therapeutics
Excerpt

To investigate the efficacy and safety of renzapride, a potent 5-hydroxytryptamine type-4 receptor full agonist and 5-hydroxytryptamine type-3 receptor antagonist in patients with constipation-predominant irritable bowel syndrome.

Title Investigation of Periodontal Destruction Patterns in Smokers and Non-smokers.
Date August 2006
Journal Journal of Clinical Periodontology
Excerpt

Previous work has suggested that tobacco smoking has a local as well as a systemic effect on the severity of periodontal disease. Objective: To test the hypothesis that smokers have more disease in the upper anterior region.

Title Immediate and Early Replacement Implants and Restorations.
Date August 2006
Journal Dental Update
Excerpt

There have been rapid developments in dental implant treatment protocols to reduce the time between implant placement and restoration. Implants may be placed immediately following tooth extraction or following a period of healing to allow resolution of residual infection or sufficient bone and soft tissue healing. Early restoration and loading of implants has to be carefully controlled to avoid increased failure and complications. Advantages and disadvantages of the various techniques are described. CLINICAL RELEVANCE: The clinician should adopt a treatment protocol that ensures a high success rate and a long-term functional and aesthetic implant restoration. Rapid treatment protocols can be considered when they do not compromise these goals, and the clinician is sufficiently experienced in their application.

Title Maintenance of Osseointegrated Implant Prostheses.
Date May 2006
Journal Dental Update
Excerpt

Implant-retained prostheses need to be re-evaluated on a regular basis. This should include review of the effectiveness of oral hygiene procedures to maintain soft tissue health, evaluation of the integrity and function of the prosthetic superstructure and comparison of radiographic bone levels at appropriate intervals. Clinical Relevance: All dental care professionals need to be aware of the maintenance care requirements of patients treated with dental implants. With the increase in numbers of patients treated there will be greater demands to provide this care in general practices.

Title Perioperative Care of the Elderly Patient.
Date April 2006
Journal Cleveland Clinic Journal of Medicine
Excerpt

Perioperative management is typically more complicated in older patients than in younger patients and requires more assessment and evaluation before surgery as well as precautionary steps after surgery to manage these high-risk patients.

Title Novel Subgingival Bacterial Phylotypes Detected Using Multiple Universal Polymerase Chain Reaction Primer Sets.
Date March 2006
Journal Oral Microbiology and Immunology
Excerpt

Molecular ecological analysis based on 16S rRNA gene sequence analysis is well established for the characterisation of complex bacterial communities. However, 'universal' PCR primers can introduce biases into the analysis of the species composition of clone libraries because of mismatches between the primer and target organism sequences. In this study, three universal primer sets were compared for the analysis of the microflora in subgingival plaque.

Title Unexpected Findings During Thyroid Surgery in a Regional Community Hospital: a 5-year Experience of 738 Consecutive Cases.
Date January 2006
Journal The American Surgeon
Excerpt

Unexpected findings during thyroid surgery in a nonuniversity setting have rarely been reported in large series. Our goal was to describe the unexpected findings during thyroid surgery in a busy regional community hospital. All thyroid operations conducted by the teaching staff at Greenville Memorial Hospital, a 735-bed nonuniversity regional hospital, from December 1998 through December 2003 were reviewed. Pre- and post-operative diagnoses, surgical procedure, and specimen histopathology were examined. Unexpected findings were defined as either thyroid pathology not anticipated based on preoperative diagnosis or as unsuspected nonthyroidal disease found during cervicotomy. During the 5-year study period, 738 patients presented with thyroid disease requiring surgery. Incidental thyroid cancer was discovered in 28 cases (3.8%), the predominance being papillary microcarcinoma. Synchronous benign thyroid disease, separate from the indication from surgery, was observed in 56 patients (7.6%). Forty patients had unexpected nodular goiter and 16 had lymphocytic thyroiditis. Primary hyperparathyroidism was observed in 33 patients (4.5%). Both solitary adenomas (22 cases) and multigland parathyroid disease (11 cases) were seen. Unexpected nonendocrine findings were less common, including solitary cases of large cell carcinoma, metastatic endometrial carcinoma, and tracheal duplication (bronchogenic cyst). In conclusion, unexpected findings during thyroid surgery at a busy community hospital are fairly common. Indeed, an unanticipated finding is encountered in one out of seven operations on the thyroid gland. Although most are of unclear clinical significance, there is a surprisingly high incidence of hyperparathyroidism. This underscores the need for preoperative screening, as the "thyroid patient" may also be the "parathyroid patient."

Title Mechanisms of Action of Environmental Factors--tobacco Smoking.
Date October 2005
Journal Journal of Clinical Periodontology
Excerpt

To review the potential biological mechanisms underlying the effects of tobacco smoking on periodontitis.

Title A Prospective 3-year Study of Fixed Bridges Linking Astra Tech St Implants to Natural Teeth.
Date September 2005
Journal Clinical Oral Implants Research
Excerpt

Connecting teeth and osseointegrated implants in fixed reconstructions is not generally recommended because of differences in their response to loading.

Title A Retrospective Study of Periodontal Disease Severity in Smokers and Non-smokers.
Date September 2005
Journal British Dental Journal
Excerpt

Smoking has been associated with increased risk of periodontitis. The aim of the present study was to compare the periodontal disease severity of adult heavy smokers and never-smokers referred for assessment and treatment of chronic periodontitis.

Title Should Quit Smoking Interventions Be the First Part of Initial Periodontal Therapy?
Date August 2005
Journal Journal of Clinical Periodontology
Title The Influence of Vitamin C on Systemic Markers of Endothelial and Inflammatory Cell Activation in Smokers and Non-smokers.
Date July 2005
Journal Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Excerpt

To determine the influence of vitamin C supplementation (500 mg, bd, 14 days) on the circulating concentrations of soluble ICAM-1 (a marker of endothelial activation), neopterin (a marker of monocyte activation), and neutrophil elastase (a marker of neutrophil activation) in smokers and non-smokers in a randomised, double-blind, placebo-controlled trial in a hospital setting.

Title Evaluation of a New Periodontal Probe Tip Design. A Clinical and in Vitro Study.
Date November 2004
Journal Journal of Clinical Periodontology
Excerpt

In the search for an accurate periodontal probe which does not frequently penetrate the pocket base, a new tip has been designed which is flattened, and of 1 mm width and 0.45 mm thickness. This study aimed to evaluate the physico-mechanical and clinical properties of this probe (test) in comparison to a conventional 0.5 mm circular probe (control).

Title The Longitudinal Accuracy of Fit of Titanium Implant Superstructures Superplastically Formed on Investment Models.
Date July 2004
Journal Dental Materials : Official Publication of the Academy of Dental Materials
Excerpt

To measure the effect of three special liquid proportions and five forming temperatures on the length of superplastically formed titanium dental implant superstructures made using Rematitan dental casting investment.

Title Diagnosis-related Group-adjusted Hospital Costs Are Higher in Older Medical Patients with Lower Functional Status.
Date January 2004
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: To determine whether hospital costs are higher in patients with lower functional status at admission, defined as dependence in one or more activities of daily living (ADLs), after adjustment for Medicare Diagnosis-Related Group (DRG) payments. DESIGN: Prospective study. SETTING: General medical service at a teaching hospital. PARTICIPANTS: One thousand six hundred twelve patients aged 70 and older. MEASUREMENTS: The hospital cost of care for each patient was determined using a cost management information system, which allocates all hospital costs to individual patients. RESULTS: Hospital costs were higher in patients dependent in ADLs on admission than in patients independent in ADLs on admission ($5,300 vs $4,060, P<.01). Mean hospital costs remained higher in ADL-dependent patients than in ADL-independent patients in an analysis that adjusted for DRG weight ($5,240 vs $4,140, P<.01), and in multivariate analyses adjusting for age, race, sex, Charlson comorbidity score, acute physiology and chronic health evaluation score, and admission from a nursing home as well as for DRG weight ($5,200 vs $4,220, P<.01). This difference represents a 23% (95% confidence interval=15-32%) higher cost to take care of older dependent patients. CONCLUSION: Hospital cost is higher in patients with worse ADL function, even after adjusting for DRG payments. If this finding is true in other hospitals, DRG-based payments provide hospitals a financial incentive to avoid patients dependent in ADLs and disadvantage hospitals with more patients dependent in ADLs.

Title Dealing with Esthetic Demands in the Anterior Maxilla.
Date December 2003
Journal Periodontology 2000
Title Fecal Incontinence in Elderly Patients: Common, Treatable, Yet Often Undiagnosed.
Date October 2003
Journal Cleveland Clinic Journal of Medicine
Excerpt

It is important for primary care physicians to take fecal incontinence seriously and not dismiss it as a normal part of aging. Elderly patients may be reluctant to admit fecal incontinence, so clinicians need to ask about it. Two of the most common causes are fecal impaction (especially in nursing home patients) and rectosphincter dysfunction in people with diabetes.

Title Gingival Bleeding on Probing Increases After Quitting Smoking.
Date September 2003
Journal Journal of Clinical Periodontology
Excerpt

Gingival inflammation associated with plaque accumulation is delayed or impaired in smokers. Anecdotal evidence suggests that smokers who quit experience an increase in gingival bleeding.

Title A Brief Risk-stratification Tool to Predict Repeat Emergency Department Visits and Hospitalizations in Older Patients Discharged from the Emergency Department.
Date June 2003
Journal Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
Excerpt

OBJECTIVES: To evaluate the predictive ability of a simple six-item triage risk screening tool (TRST) to identify elder emergency department (ED) patients at risk for ED revisits, hospitalization, or nursing home (NH) placement within 30 and 120 days following ED discharge. METHODS: Prospective cohort study of 650 community-dwelling elders (age 65 years or older) presenting to two urban academic EDs. Subjects were prospectively evaluated with a simple six-item ED nursing TRST. Participants were interviewed 30 and 120 days post-ED index visit and the utilization of EDs, hospitals, or NHs was recorded. Main outcome measurement was the ability of the TRST to predict the composite endpoint of subsequent ED use, hospital admission, or NH admission at 30 and 120 days. Individual outcomes of ED use, hospitalization, and NH admissions were also examined. RESULTS: Increasing cumulative TRST scores were associated with significant trends for ED use, hospital admission, and composite outcome at both 30 and 120 days (p < 0.0001 for all, except 30-day ED use, p = 0.002). A simple, unweighted five-item TRST ("lives alone" item removed after logistic regression modeling) with a cut-off score of 2 was the most parsimonious model for predicting composite outcome (AUC = 0.64) and hospitalization at 30 days (AUC = 0.72). Patients defined as high-risk by the TRST (score > or = 2) were significantly more likely to require subsequent ED use (RR = 1.7; 95% CI = 1.2 to 2.3), hospital admission (RR = 3.3; 95% CI = 2.2 to 5.1), or the composite outcome (RR = 1.9; 95% CI 1.7 to 2.9) at both 30 days and 120 days than the low-risk cohort. CONCLUSIONS: Older ED patients with two or more risk factors on a simple triage screening tool were found to be at significantly increased risk for subsequent ED use, hospitalization, and nursing home admission.

Title Unsteadiness Reported by Older Hospitalized Patients Predicts Functional Decline.
Date June 2003
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: To determine whether a simple question about steadiness at admission predicts in-hospital functional decline and whether unsteadiness at admission predicts failure of in-hospital functional recovery of patients who have declined immediately before hospitalization. DESIGN: Prospective cohort study. SETTING: One university hospital and one community teaching hospital. PARTICIPANTS: One thousand five hundred fifty-seven hospitalized medical patients aged 70 and older. MEASUREMENTS: On admission, patients reported their steadiness with walking and whether they could perform independently each of five basic activities of daily living (ADLs) at admission and 2 weeks before admission (baseline). For the primary analysis, the outcome was decline in ADL function between admission and discharge. For the secondary analysis, the outcome was in-hospital recovery to baseline ADL function in patients who experienced ADL decline in the 2 weeks before admission. RESULTS: In the primary cohort (n = 1,557), 25% of patients were very unsteady at admission; 22% of very unsteady patients declined during hospitalization, compared with 17%, 18%, and 10% for slightly unsteady, slightly steady, and very steady patients, respectively (P for trend =.001). After adjusting for age; medical comorbidities; Acute Physiology, Age, and Chronic Health Evaluation II score; and admission ADL, unsteadiness remained significantly associated with ADL decline (odds for decline for very unsteady compared with very steady = 2.6, 95% confidence interval = 1.5-4.5). In the secondary analysis, predicting ADL recovery in patients who declined before hospitalization (n = 563), 46% of patients were very unsteady at admission. In this cohort, 44% of very unsteady patients failed to recover, compared with 35%, 36%, and 33% for each successively higher level of steadiness, respectively (P for trend = 0.06). After multivariate adjustment, greater unsteadiness independently predicted failure of recovery (P for trend = 0.02). CONCLUSION: A simple question about steadiness identified patients at increased risk for in-hospital ADL decline and, in patients who lost ADL function immediately before admission, failure to recover.

Title Loss of Independence in Activities of Daily Living in Older Adults Hospitalized with Medical Illnesses: Increased Vulnerability with Age.
Date May 2003
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: To describe the changes in activities of daily living (ADL) function occurring before and after hospital admission in older people hospitalized with medical illness and to assess the effect of age on loss of ADL function. DESIGN: Prospective observational study. SETTING: The general medical service of two hospitals. PARTICIPANTS: Two thousand two hundred ninety-three patients aged 70 and older (mean age 80, 64% women, 24% nonwhite). MEASUREMENTS: At the time of hospital admission, patients or their surrogates were interviewed about their independence in five ADLs (bathing, dressing, eating, transferring, and toileting) 2 weeks before admission (baseline) and at admission. Subjects were interviewed about ADL function at discharge. Outcome measures included functional decline between baseline and discharge and functional changes between baseline and admission and between admission and discharge. RESULTS: Thirty-five percent of patients declined in ADL function between baseline and discharge. This included the 23% of patients who declined between baseline and admission and failed to recover to baseline function between admission and discharge and the 12% of patients who did not decline between baseline and admission but declined between hospital admission and discharge. Twenty percent of patients declined between baseline and admission but recovered to baseline function between admission and discharge. The frequency of ADL decline between baseline and discharge varied markedly with age (23%, 28%, 38%, 50%, and 63% in patients aged 70-74, 75-79, 80-84, 85-89, and > or =90, respectively, P <.001). After adjustment for potential confounders, age was not associated with ADL decline before hospitalization (odds ratio (OR) for patients aged > or =90 compared with patients aged 70-74 = 1.26, 95% confidence interval (CI) = 0.88-1.82). In contrast, age was associated with the failure to recover ADL function during hospitalization in patients who declined before admission (OR for patients aged > or =90 compared with patients aged 70-74 = 2.09, 95% CI = 1.20-3.65) and with new losses of ADL function during hospitalization in patients who did not decline before admission (OR for patients aged > or =90 compared with patients aged 70-74 = 3.43, 95% CI = 1.92-6.12). CONCLUSION: Many hospitalized older people are discharged with ADL function that is worse than their baseline function. The oldest patients are at particularly high risk of poor functional outcomes because they are less likely to recover ADL function lost before admission and more likely to develop new functional deficits during hospitalization

Title Effect of Nicotine Replacement and Quitting Smoking on Circulating Adhesion Molecule Profiles (sicam-1, Scd44v5, Scd44v6).
Date April 2003
Journal European Journal of Clinical Investigation
Excerpt

Soluble ICAM-1 (sICAM-1; sCD54), sCD44v5 and sCD44v6 are circulating adhesion molecules, with immunomodulatory potential, that have been frequently attributed diagnostic, prognostic and aetiological significance in a number of inflammatory and malignant diseases. We have previously shown that systemic concentrations of these molecules are increased significantly in tobacco smokers, but reduce to within normal levels at 12 months following successful quitting.

Title Cytokine Release by Osteoblast-like Cells Cultured on Implant Discs of Varying Alloy Compositions.
Date April 2003
Journal Clinical Oral Implants Research
Excerpt

The aims of this study were (i). to assess the morphological features of osteo-blast-like, osteosarcoma cells (cell line SaOS-2) cultured on implant surfaces of varying alloys and (ii). to evaluate the biological activity of these cells, following their adhesion onto these surfaces.

Title Analysis of Two Common Alpha 1-antitrypsin Deficiency Alleles (pi*z and Pi*s) in Subjects with Periodontitis.
Date April 2003
Journal Journal of Clinical Periodontology
Excerpt

pi alpha 1-Antitrypsin deficiency is a genetically determined condition resulting in predisposition to certain inflammatory diseases due to a protease: antiprotease imbalance that is exacerbated by tobacco smoking. Limited evidence suggests that there may be a significant enrichment of mild alpha 1-antitrypsin deficiency phenotypes in subjects with chronic inflammatory periodontal disease.

Title Case Finding and Referral Model for Emergency Department Elders: a Randomized Clinical Trial.
Date January 2003
Journal Annals of Emergency Medicine
Excerpt

STUDY OBJECTIVE: Elderly emergency department patients have complex medical needs and limited social support. A transitional model of care adapted from hospitals was tested for its effectiveness in the ED in reducing subsequent service use. METHODS: A randomized clinical trial was conducted at 2 urban, academically affiliated hospitals. Participants were 650 community-residing individuals 65 years or older who were discharged home after an ED visit. Main outcomes were service use rates, defined as repeat ED visits, hospitalizations, or nursing home admissions, and health care costs at 30 and 120 days. Intervention consisted of comprehensive geriatric assessment in the ED by an advanced practice nurse and subsequent referral to a community or social agency, primary care provider, and/or geriatric clinic for unmet health, social, and medical needs. Control group participants received usual and customary ED care. RESULTS: The intervention had no effect on overall service use rates at 30 or 120 days. However, the intervention was effective in lowering nursing home admissions at 30 days (0.7% versus 3%; odds ratio 0.21; 95% confidence interval [CI] 0.05 to 0.99) and in increasing patient satisfaction with ED discharge care (3.41 versus 3.03; mean difference 0.37; 95% CI 0.13 to 0.62). The intervention was more effective for high-risk than low-risk elders. CONCLUSION: An ED-based transitional model of care reduced subsequent nursing home admissions but did not decrease overall service use for older ED patients. Further studies are needed to determine the best models of care for this setting and for at-risk patients.

Title Nutritional Requirements with Aging. Prevention of Disease.
Date January 2003
Journal Clinics in Geriatric Medicine
Excerpt

Early recognition of and intervention for nutritional disorders may help prevent functional disability and mortality in elderly patients. Prevention of nutritional disorders in older adults is often multidimensional and may require multidisciplinary collaboration. Proactive education of the older adult, early recognition of nutritional deficiencies, and rectification of the nutritional disorders are the keys to achieving ideal nutritional status in elders and enabling them to achieve successful aging.

Title Heterogeneity in Older People: Examining Physiologic Failure, Age, and Comorbidity.
Date January 2003
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: To derive a clinically relevant age-independent physiologic failure scoring system and to use this system to examine aspects of the association of physiologic failure, age, and comorbidity with inpatient mortality. DESIGN: Retrospective, secondary analysis of a derivation and validation cohort selected from the Cleveland Health Quality Choice Coalition data set. SETTING: Thirty hospitals in greater Cleveland. PARTICIPANTS: Thirty-one thousand nine hundred seventy-six inpatients aged 50 and older discharged in 1993 with a diagnosis of congestive heart failure, pneumonia, or stroke. MEASUREMENTS: The Inpatient Physiologic Failure Score (IPFS) was developed and used to calculate physiologic failure. Forty-four candidate variables were examined for their association with inpatient mortality, and 12 were selected. A point value (2, 3, 4, or 6) based on adjusted odds ratio was assigned for an abnormal result for each of the 12 common physiologic variables. Each patient's abnormal physiology points were summed to produce a physiologic failure score (range 0-39). Comorbidity was quantified using the Patient Management Category Severity Scale. The association between mortality and increasing physiologic failure, increasing age and comorbidity, and distribution of physiologic failure with increasing age and comorbidity were examined. A threshold age was sought. Models for predicting inpatient mortality were developed. RESULTS: Twelve physiologic variables constitute the IPFS. Increasing physiologic failure, age, and comorbidity were associated with increasing mortality. Increasing physiologic failure was not associated with increasing age or comorbidity. We did not find a threshold age. The area under the receiver operating characteristic (ROC) curve for predicting inpatient mortality for IPFS was 0.730, and for comorbidity was 0.741 (not significant). The area under the ROC curve for a mortality prediction model based on age was significantly less (0.603). Accounting for patient age did not significantly improve the predictive ability of the IPFS model (area = 0.752, P <.05). The complete model best predicted mortality (0.829). CONCLUSIONS: The IPFS represents a clinically relevant method for scoring physiologic failure. Physiologic failure, age, and comorbidity are independently and differently associated with inpatient mortality. Physiology fails independent of age and comorbidity.

Title A Prospective Study of Single Stage Surgery for Implant Supported Overdentures.
Date December 2002
Journal Clinical Oral Implants Research
Excerpt

To investigate the clinical and psychological outcomes with ball attachment supported mandibular overdentures on Branemark implants placed in a single stage surgical approach. MATERIAL AND METHODS Sixteen edentulous patients aged 32-74, with atrophic (flat) mandibular residual alveolar ridges, and a history of having difficulty coping with technically adequate mandibular dentures made within the last 2 years were recruited. Mark II Branemark implants were placed using a single stage surgical technique with healing abutments placed at time of surgery. Mandibular complete dentures were modified by relieving the areas over the abutments and a resilient liner was placed. After a period of 3 months, healing abutments were replaced with ball abutments and new complete dentures were made and the patients followed for a period of 2 years. Patients completed the General Health Questionnaire (GHQ) and answered further questions relating to the functional and psychological impact of complete denture wearing before treatment and 3 months after the dentures were provided. Patients additionally completed the GHQ 2 years after overdenture insertion.

Title Expression of Icam-1 and E-selectin in Gingival Tissues of Smokers and Non-smokers with Periodontitis.
Date June 2002
Journal Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
Excerpt

Tobacco smoking affects systemic concentrations of soluble intercellular adhesion molecule (ICAM)-1, but its effect on local expression of adhesion molecules in gingival tissue has not been studied previously.

Title Serum Albumin Concentration and Clinical Assessments of Nutritional Status in Hospitalized Older People: Different Sides of Different Coins?
Date May 2002
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: Malnutrition is common in hospitalized older people, and some have advocated routine nutritional screening. Serum albumin and clinically based measures such as the Subjective Global Assessment (SGA) are two potential methods of assessing nutritional status in hospitalized older people. Although both measures are strongly associated with prognosis, it is not clear whether they measure similar or different clinical constructs. Our goal was to assess the degree of clinical concordance between these measures. DESIGN: Cross-sectional study. SETTING: The inpatient medical service of a university teaching hospital. PARTICIPANTS: Three hundred eleven older (aged > or =70) patients. MEASUREMENTS: We independently measured serum albumin and performed the SGA on 311 older medical patients (aged > or =70) shortly after hospital admission. The SGA classified patients as well nourished, moderately malnourished (generally 5% weight loss with mild examination findings), or severely malnourished (generally >10% weight loss with marked findings) based on findings from a directed history and examination. We compared the distribution of clinical rating in patients with differing albumin levels and examined diagnostic test characteristics of albumin as a predictor of malnutrition as diagnosed on clinical examination. RESULTS: The mean age of subjects was 79.9; 64% were women, 42% were African American. Discordance between albumin and the SGA was common. For example, 38% of patients with albumin levels of 4.0 g/dL or higher were at least moderately malnourished on the SGA, whereas 28% of patients with albumin levels lower than 3.0 g/dL were rated as well nourished. No choice of albumin level was associated with simultaneously acceptable sensitivity and specificity as a predictor of SGA ratings. The area under the receiver operating characteristic curve for albumin level as a predictor of SGA rating was 0.58, suggesting that the ability of either measure to predict the other measure is only marginally better than chance. CONCLUSIONS: Albumin levels and clinical assessments, two possible measures of nutritional status in hospitalized older people, are often discordant. To some extent, this reflects limitations in both measures as markers of nutritional status. However, it also demonstrates that, in this population, albumin and clinical assessments of nutritional status reflect fundamentally different clinical processes.

Title Establishing a Case-finding and Referral System for At-risk Older Individuals in the Emergency Department Setting: the Signet Model.
Date April 2002
Journal Journal of the American Geriatrics Society
Excerpt

Older emergency department (ED) patients have complex medical, social, and physical problems. We established a program at four ED sites to improve case finding of at-risk older adults and provide comprehensive assessment in the ED setting with formal linkage to community agencies. The objectives of the program are to (1) improve case finding of at-risk older ED patients, (2) improve care planning and referral for those returning home, and (3) create a coordinated network of existing medical and community services. The four sites are a 1,000-bed teaching center, a 700-bed county teaching hospital, a 400-bed community hospital, and a health maintenance organization (HMO) ED site. Ten community agencies also participated in the study: four agencies associated with the hospital/HMO sites, two nonprofit private agencies, and four public agencies. Case finding is done using a simple screening assessment completed by the primary or triage nurse. A geriatric clinical nurse specialist (GCNS) further assesses those considered at risk. Patients with unmet medical, social, or health needs are referred to their primary physicians or to outpatient geriatric evaluation and management centers and to community agencies. After 18 months, the program has been successfully implemented at all four sites. Primary nurses screened over 70% (n = 28,437) of all older ED patients, GCNSs conducted 3,757 comprehensive assessments, participating agency referrals increased sixfold, and few patients refused the GCNS assessment or subsequent referral services. Thus, case finding and community linkage programs for at-risk older adults are feasible in the ED setting.

Title Outcomes Following Physical Restraint Reduction Programs in Two Acute Care Hospitals.
Date February 2002
Journal The Joint Commission Journal on Quality Improvement
Excerpt

Physical restraint rates can be reduced safely in long term care settings, but the strategies used to prevent wandering, falls, and patient aggression have not been tested for their effectiveness in preventing therapy disruption. A restraint reduction program (RRP) consisting of four core components (administrative, educational, consultative, and feedback) was implemented in 1998-1999 in 14 units at two acute care hospitals in geographically distant cities.

Title Tobacco Smoking with Periodontal Disease.
Date December 2001
Journal Journal of Clinical Periodontology
Title Elevated Systemic Concentrations of Soluble Icam-1 (sicam) Are Not Reflected in the Gingival Crevicular Fluid of Smokers with Periodontitis.
Date October 2001
Journal Journal of Dental Research
Excerpt

Raised serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in smokers could have immunomodulatory effects in periodontitis. The aim of this study was to compare serum and gingival crevicular fluid (GCF) concentrations of sICAM-1 in smokers and non-smokers with periodontal disease. sICAM-1 in serum and GCF collected from age- and gender-matched smokers (n = 14) and non-smokers (n = 14) with periodontitis were measured by ELISA. Mean serum sICAM-1 concentrations were significantly elevated in smokers (331 ng mL(-1)), compared with non-smokers (238 ng mL(-1), p = 0.008). However, the concentration of sICAM-1 in the GCF was significantly lower in the smokers (83 ng mL(-1)), compared with non-smokers (212 ng mL(-1), p = 0.013). The difference between concentrations of sICAM-1 in GCF and serum was significant only in smokers (p < 0.001). Since GCF is a serum-derived tissue exudate, these results suggest that, in smokers, circulating sICAM-1 molecules are affected either in their passage from the periodontal microvasculature or within the periodontal tissues.

Title Validation of Smoking Status in Clinical Research into Inflammatory Periodontal Disease.
Date October 2001
Journal Journal of Clinical Periodontology
Excerpt

Tobacco smoking is an accepted risk factor for periodontal disease. Most studies in the periodontal literature rely on reported smoking habits which can be unreliable. This review specifically addresses this problem.

Title Comparison of the Validity of Periodontal Probing Measurements in Smokers and Non-smokers.
Date October 2001
Journal Journal of Clinical Periodontology
Excerpt

AIM: To determine whether the reduced inflammation and bleeding and increased fibrosis reported in tobacco smokers affect the validity of clinical probing measurements by altering probe tip penetration. METHOD: A constant force probe was used to measure probing depths and sound bone levels at six sites on 64 molar teeth (384 sites) in 20 smoking and 20 non-smoking patients from grooves made with a bur at the gingival margin prior to extraction. Connective tissue attachment levels were measured from the grooves with a dissecting microscope following extraction. Data were analysed using robust regression with sites clustered within subjects. RESULTS: Sites in smokers showed more calculus but less bleeding than sites in non-smokers (p<0.05). The mean clinical probing depth was not significantly different (smokers: 5.54 mm, confidence intervals=4.81 to 6.28; non-smokers: 6.05 mm, ci=5.38 to 6.72). The corresponding post-extraction pocket depth measurements (smokers: 4.95 mm, ci=4.30 to 5.61; non-smokers: 5.23 mm, ci=4.49 to 5.96) were less than clinical probing depth in sites from both smokers and non-smokers (p<0.01). However, the proportional difference was less in smokers (p<0.05), particularly in deeper pockets, indicating that clinical probe tip penetration of tissue was greater in non-smokers. Regression analysis indicated that the presence of calculus and bleeding also influenced the difference in clinical probe penetration (p<0.05). CONCLUSION: Clinical probing depth at molar sites exaggerates pocket depth, but the probe tip may be closer to the actual attachment level in smokers due to less penetration of tissue. This may be partly explained by the reduced inflammation and width of supra-bony connective tissue in smokers. These findings have clinical relevance to the successful management of periodontal patients who smoke.

Title Dose-years As an Improved Index of Cumulative Tobacco Smoke Exposure.
Date August 2001
Journal Medical Hypotheses
Excerpt

In assessing the link between tobacco smoking and disease, it is important to determine longterm, cumulative exposure to tobacco smoke as accurately as possible. Conventional methods of assessing exposure to tobacco smoke each have intrinsic limitations. Self-reporting of tobacco use, and the conversion of this data to pack-years, can be prone to error due to individuals wishing to conceal smoking habits, inaccurate reporting of daily cigarette consumptions or years of smoking, and failure to take into account the variation that exists in inter-individual smoking experiences. Measurement of cotinine, a major metabolite of nicotine in humans, is a reliable method of monitoring recent doses of tobacco smoke exposure. Cotinine concentrations, however, may remain stable in smokers over the longer term. Therefore, dose-years, and more specifically cotinine-years, may represent an improved index of cumulative tobacco smoke exposure.

Title Production of Volatile Sulphur Compounds in Diseased Periodontal Pockets is Significantly Increased in Smokers.
Date July 2001
Journal Oral Diseases
Excerpt

This study was undertaken in order to test the hypothesis that the consequences of tobacco smoking may include increased synthesis of toxic volatile sulphur compounds in diseased periodontal pockets.

Title Development and Validation of a Prognostic Index for 1-year Mortality in Older Adults After Hospitalization.
Date July 2001
Journal Jama : the Journal of the American Medical Association
Excerpt

CONTEXT: For many elderly patients, an acute medical illness requiring hospitalization is followed by a progressive decline, resulting in high rates of mortality in this population during the year following discharge. However, few prognostic indices have focused on predicting posthospital mortality in older adults. OBJECTIVE: To develop and validate a prognostic index for 1 year mortality of older adults after hospital discharge using information readily available at discharge. DESIGN: Data analyses derived from 2 prospective studies with 1-year of follow-up, conducted in 1993 through 1997. SETTING AND PATIENTS: We developed the prognostic index in 1495 patients aged at least 70 years who were discharged from a general medical service at a tertiary care hospital (mean age, 81 years; 67% female) and validated it in 1427 patients discharged from a separate community teaching hospital (mean age, 79 years; 61% female). MAIN OUTCOME MEASURE: Prediction of 1-year mortality using risk factors such as demographic characteristics, activities of daily living (ADL) dependency, comorbid conditions, length of hospital stay, and laboratory measurements. RESULTS: In the derivation cohort, 6 independent risk factors for mortality were identified and weighted using logistic regression: male sex (1 point); number of dependent ADLs at discharge (1-4 ADLs, 2 points; all 5 ADLs, 5 points); congestive heart failure (2 points); cancer (solitary, 3 points; metastatic, 8 points); creatinine level higher than 3.0 mg/dL (265 micromol/L) (2 points); and low albumin level (3.0-3.4 g/dL, 1 point; <3.0 g/dL, 2 points). Several variables associated with 1-year mortality in bivariable analyses, such as age and dementia, were not independently associated with mortality after adjustment for functional status. We calculated risk scores for patients by adding the points of each independent risk factor present. In the derivation cohort, 1-year mortality was 13% in the lowest-risk group (0-1 point), 20% in the group with 2 or 3 points, 37% in the group with 4 to 6 points, and 68% in the highest-risk group (>6 points). In the validation cohort, 1-year mortality was 4% in the lowest-risk group, 19% in the group with 2 or 3 points, 34% in the group with 4 to 6 points, and 64% in the highest-risk group. The area under the receiver operating characteristic curve for the point system was 0.75 in the derivation cohort and 0.79 in the validation cohort. CONCLUSIONS: Our prognostic index, which used 6 risk factors known at discharge and a simple additive point system to stratify medical patients 70 years or older according to 1-year mortality after hospitalization, had good discrimination and calibration and generalized well in an independent sample of patients at a different site. These characteristics suggest that our index may be useful for clinical care and risk adjustment.

Title A Clinical, Radiographic, and Microbiologic Comparison of Astra Tech and Brånemark Single Tooth Implants.
Date June 2001
Journal Clinical Implant Dentistry and Related Research
Excerpt

The soft tissues around single tooth implants differ fundamentally from the gingiva around natural teeth. There are very limited data comparing soft tissues around different implant systems.

Title The Relationship of Sedation to Deliberate Self-extubation.
Date May 2001
Journal Journal of Clinical Anesthesia
Excerpt

STUDY OBJECTIVES: To evaluate the relationship between sedative therapy and self-extubation in a large medical-surgical intensive care unit (ICU). DESIGN: Retrospective, case-controlled study. SETTING: Large teaching hospital. PATIENTS: All adult patients who underwent unplanned self-extubation during a 12-month period (n = 50). Each patient was matched to two control patients who did not self-extubate based on age, gender, dates in hospital and diagnosis. INTERVENTIONS: none. MEASUREMENTS: Data collected included time to self extubation, dosages and types of benzodiazepines, opioid analgesics, antipsychotics, and hypnotics. Data on the degree of agitation as assessed by nursing staff also were obtained. MAIN RESULTS: When compared to controls, patients in the self-extubation group were more likely to have received benzodiazepines (59% vs. 35%; p < 0.05), but equally likely to have received opioids and/or paralytic drugs. Patients who self-extubated were twice as likely as controls to be agitated (54% vs. 22%; p < 0.05). Use of benzodiazepines was more common in agitated patients than in nonagitated patients (62% vs. 35%; p < 0.02). Among nonagitated patients who self-extubated, increased use of benzodiazepines (57% vs. 29%; p < 0.05) was noted when compared to nonagitated controls. CONCLUSIONS: In intubated ICU patients, benzodiazepines may not consistently treat agitation effectively or prevent self-extubation. Such an effect may be due to paradoxical excitation, disorientation during long-term administration, or differences in drug administration between ICU and operating room (OR) environments.

Title A 5-year Prospective Study of Astra Single Tooth Implants.
Date April 2001
Journal Clinical Oral Implants Research
Excerpt

To evaluate the AstraTech Implant ST (Molndal, Sweden) for single tooth replacement clinically and radiographically after 5 years in function.

Title Long Term Periodontal Problems--the Chemotherapeutic Aspect.
Date April 2001
Journal British Dental Journal
Title Plasma Concentrations of Reputed Tumor-associated Soluble Cd44 Isoforms (v5 and V6) in Smokers Are Dose Related and Decline on Smoking Cessation.
Date February 2001
Journal Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Excerpt

There is some evidence to suggest that smoking may affect circulating levels of CD44 (sCD44) molecules. Therefore, we investigated the effect of smoking on the circulating level of sCD44 by comparing the change in total sCD44, sCD44v5, and sCD44v6 concentrations over 1 year in a group of people who quit smoking (n = 30) and a control group of people who continued to smoke (n = 30). Smoking status and compliance were monitored by analysis of plasma cotinine and expired CO levels and also by self-reported tobacco use. We show a dose-dependent relationship between smoke intake and baseline plasma concentrations of reputed tumor-associated CD44 variant isoforms (sCD44v5 and sCD44v6) in smokers (n = 60). There was a significant decline in the level of both sCD44v5 and sCD44v6 in quitters as compared with continuing smokers [-13.2 (95% confidence interval, -7.6 to -18.8; P < 0.001) and -62.2 ng/ml (95% confidence interval, -33.9 to -90.6; P < 0.001), respectively], but not in the total sCD44 concentration. These results show that the increased concentrations of sCD44v5 and sCD44v6 in smokers are dose related and reversible and suggest that the attributed diagnostic specificity and prognostic value of sCD44 molecules in malignant and inflammatory disease may be affected by smoking status.

Title Effects of a Multicomponent Intervention on Functional Outcomes and Process of Care in Hospitalized Older Patients: a Randomized Controlled Trial of Acute Care for Elders (ace) in a Community Hospital.
Date January 2001
Journal Journal of the American Geriatrics Society
Excerpt

BACKGROUND: Older persons frequently experience a decline in function following an acute medical illness and hospitalization. OBJECTIVE: To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients. DESIGN: Randomized controlled trial. SETTING: Community teaching hospital. PATIENTS: A total of 1,531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997. INTERVENTION: ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness. MEASUREMENTS: The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction. RESULTS: Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P = .027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; P = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P < .05). CONCLUSIONS: ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes.

Title Circulating Concentrations of C-reactive Protein and Total Sialic Acid in Tobacco Smokers Remain Unchanged Following One Year of Validated Smoking Cessation.
Date December 2000
Journal European Journal of Clinical Investigation
Excerpt

Elevated plasma concentrations of C-reactive protein (CRP) and total sialic acid (TSA) have been associated with increased cardiovascular risk. Additionally, levels of both CRP and TSA have been reported to be significantly elevated in smokers. However, it is not clear if the raised TSA and CRP levels noted in smokers are directly attributable to the smoking experience, or if they may be elevated due to a secondary mechanism(s), such as smoking-induced tissue inflammation.

Title Dramatic Decline in Circulating Intercellular Adhesion Molecule-1 Concentration on Quitting Tobacco Smoking.
Date October 2000
Journal Blood Cells, Molecules & Diseases
Excerpt

The concentration of soluble ICAM-1 (sICAM-1) is significantly elevated in smokers, but it is unclear if smoking is the direct cause of elevated sICAM-1 levels, if the relationship between smoking and sICAM-1 level is dose-dependent, and if smoking cessation may lead to a decline in sICAM-1. We sought to clarify the relationship between smoking and sICAM-1 in a group of smokers who quit smoking for 1 year (n = 30) and a control group who continued to smoke (n = 30). A dose-dependent relationship between plasma sICAM-1 concentration and daily cigarette consumption (P = 0.02), plasma cotinine level (P = 0.02), and expired CO level (P = 0.007) was observed at baseline (n = 60). The mean change in sICAM-1 concentration after 52 weeks was greater for quitters than for continuing smokers (mean difference = -71.1 ng/ml, P < 0.001). The influence of smoking on sICAM-1 needs to be carefully considered in clinical trials. Soluble ICAM-1 remains bioactive and may contribute to pathogenic processes; therefore, reduction in the concentration of circulating ICAM-1 molecules may directly contribute to the health benefits associated with smoking cessation.

Title Maternal Protein Deficiency Causes Hypermethylation of Dna in the Livers of Rat Fetuses.
Date July 2000
Journal The Journal of Nutrition
Excerpt

Maternal protein deficiency during pregnancy is associated with changes in glucose tolerance and hypertension in the offspring of rats. In this study the growth of rat fetuses was examined when the dams were fed diets containing 18% casein, 9% casein or 8% casein supplemented with threonine. The extra threonine was added to reverse the decrease in circulating threonine concentrations that occurs when pregnant rats are fed protein-deficient diets. The fetuses of the group fed the low protein diet supplemented with threonine were significantly smaller than those of the control group and not significantly different from those fed low protein. Homogenates prepared from the livers of dams fed the diet containing 9% casein oxidized threonine at approximately twice the rate of homogenates prepared from dams fed the diet containing 18% casein. We conclude that circulating levels of threonine fall as a consequence of an increase in the activity of the pathway that metabolizes homocysteine produced by the transulfuration of methionine. Serum homocysteine was unaffected in the dams fed low protein diets compared with controls, but was significantly greater in dams fed the low protein diet supplemented with threonine. Elevated levels of homocysteine are associated with changes in the methylation of DNA. The endogenous methylation of DNA was greater than that of controls in the livers of fetuses from dams fed the 9% protein diets and increased further when the diet was supplemented with threonine. Our results suggest that changes in methionine metabolism increase homocysteine production, which leads to changes in DNA methylation in the fetus. An increase in maternal homocysteine may compromise fetal development, leading to the onset of glucose intolerance and hypertension in adult life.

Title Rna Turnover and Protein Synthesis in Fish Cells.
Date July 2000
Journal Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Excerpt

Protein synthesis in fish has been previously correlated with RNA content. The present study investigates whether protein and RNA synthesis rates are similarly related. Protein and RNA synthesis rates were determined from 3H-phenylalanine and 3H-uridine incorporation, respectively, and expressed as % x day(-1) and half-lives, respectively. Three fibroblast cell lines were used: BF-2, RTP, CHSE 214, which are derived from the bluegill, rainbow trout and Chinook salmon, respectively. These cells contained similar RNA concentrations (approximately 175 microg RNA x mg(-1) cell protein). Therefore differences in protein synthesis rates, BF-2 (31.3 +/- 1.8)>RTP (25.1 +/- 1.7)>CHSE 214 (17.6 +/-1.1), were attributable to RNA translational efficiency. The most translationally efficient RNA (BF-2 cells), 1.8 mg protein synthesised x microg(-1) RNA x day(-1), corresponded to the lowest RNA half-life, 75.4 +/- 6.4 h. Translationally efficient RNA was also energetically efficient with BF-2 cells exploiting the least costly route of nucleotide supply (i.e. exogenous salvage) 3.5-6.0 times more than the least translationally efficient RNA (CHSE 214 cells). These data suggest that differential nucleotide supply, between intracellular synthesis and exogenous salvage, constitutes the area of pre-translational flexibility exploited to maintain RNA synthesis as a fixed energetic cost component of protein synthesis.

Title Laser Doppler Flowmeter Measurement of Relative Gingival and Forehead Skin Blood Flow in Light and Heavy Smokers During and After Smoking.
Date June 2000
Journal Journal of Clinical Periodontology
Excerpt

To determine the effect of the smoking experience on relative blood flow in gingiva and to compare this to skin.

Title Relationship Between Nutritionally-mediated Placental Growth Restriction and Fetal Growth, Body Composition and Endocrine Status During Late Gestation in Adolescent Sheep.
Date April 2000
Journal Placenta
Excerpt

The aim was to investigate the consequences of nutritionally-mediated placental growth restriction on fetal organ growth, conformation, body composition and endocrine status during late gestation. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. Post-transfer, adolescent dams were offered a high (H) or moderate (M) level of a complete diet to promote rapid or moderate maternal growth rates, respectively (n=7 per group). After day 100 of gestation the feed intake of the M dams was adjusted weekly to maintain body condition score. Liveweight gain during the first 100 days of gestation was 301+/-24 and 90+/-4.6 g/day for the H and M groups, respectively. Maternal plasma concentrations of insulin, IGF-I and urea were significantly higher and non-esterified fatty acid concentrations significantly lower in H compared with M dams prior to slaughter on day 128 of gestation. At this stage of gestation, total placentome weight was 50 per cent lower in H compared with M groups (P< 0.001) and was associated with a 37 per cent reduction in fetal weight (P< 0.01). All variables of fetal conformation and absolute fetal organ weights, with the exception of the adrenal glands, were lower (P< 0. 05) in the fetuses from H intake dams. However, relative fetal organ weights expressed as g/kg fetal body weight, with the exception of the gut, were not influenced by maternal dietary intake. Furthermore, fetal weight but not maternal nutritional group were predictive of individual organ weight for all organs dissected. Together these results imply that growth restriction in the fetuses derived from H intake dams was largely symmetrical. Fetal plasma concentrations of insulin, IGF-I and glucose were attenuated (P< 0.05) in fetuses from H compared with M groups. The lower fetal body weight in the former group was associated with a reduction in absolute but not relative crude protein (P< 0.01) and fat content (P< 0.05). Total fetal liver glycogen content but not concentration was (P< 0.05) reduced in H versus M groups. The lower mass of both the placenta and fetal liver was due to a reduction in cell number rather than an alteration in cell size. Thus, over-nourishing adolescent sheep is associated with a major restriction in placental growth which mediates a gradual slowing of fetal growth during the final third of pregnancy.

Title Potential Mechanisms of Susceptibility to Periodontitis in Tobacco Smokers.
Date March 2000
Journal Journal of Periodontal Research
Excerpt

Tobacco smoking is probably the most important, controllable environmental risk factor in periodontitis. It results in changes in the vascular, inflammatory, immune and healing responses. The degree of exposure to tobacco smoking can be measured in pack years or by measuring serum cotinine and nicotine levels. In a previous paper we reported elevated levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) in smokers, regardless of periodontal status. Elevated sICAM-1 has been found to be a risk marker for cardiovascular disease. In the present paper we report the short-term effects of an episode of smoking on blood flow and levels of sICAM-1. Human volunteers included non-smokers, light smokers and heavy smokers. Relative blood flow was monitored in the gingivae and forehead skin using a laser Doppler flowmeter and serum levels of sICAM-1, cotinine and nicotine measured before during and up to 60 min following an episode of smoking. We could not provide evidence to support the theory that there is localized vasoconstriction within the gingival tissues. In contrast, there was a significant increase in blood flow in the forehead skin of light smokers which was not observed in non-smoking controls or in heavy smokers, suggesting a long-term tolerance in this latter group. The level of sICAM-1 remained unchanged during this episode, further suggesting a long-term effect. In a parallel group of subjects, we were able to demonstrate a direct significant correlation between sICAM and serum cotinine levels. These observations may be relevant to aetiological mechanisms in periodontitis and other smoking-associated diseases.

Title Functional Status Before Hospitalization in Acutely Ill Older Adults: Validity and Clinical Importance of Retrospective Reports.
Date March 2000
Journal Journal of the American Geriatrics Society
Excerpt

OBJECTIVES: Retrospective reports of patients' functional status before hospital admission are often used in longitudinal studies and by clinicians caring for hospitalized patients. However, the validity of these reports has not been established. Our aim was to examine the validity of retrospective reports by testing hypotheses about the relationships these measures would have with other clinical measures if they were valid. DESIGN: A prospective cohort study. PARTICIPANTS AND SETTING: A total of 2877 older patients (mean age 81, 36% women) hospitalized on the general medical service at two hospitals. For 1953 of the subjects, the patient was the primary respondent, whereas for 924 subjects, a surrogate was the primary respondent. MEASUREMENTS: Shortly after hospital admission, patients or surrogates reported whether the patient was independent in each of five activities of daily living (ADLs) on admission and at baseline 2 weeks before admission. Outcome measures included reported independence in each ADL 3 months after the hospitalization and survival to 1 year. RESULTS: Patients' retrospective reports of their ADL function 2 weeks before admission had a clinically plausible relationship with ADL function at the time of admission, in that patients independent in an ADL on admission rarely reported they were dependent in that ADL 2 weeks before admission (range 2-6%). Surrogates were somewhat more likely than patients to report that patients independent on admission were dependent 2 weeks before admission (range 5-14%). Retrospective reports of prehospitalization ADL function demonstrated strong evidence of predictive validity for both patients' and surrogates' reports. For example, among patients dependent in bathing on admission, patients who were reported as independent 2 weeks before admission were much more likely than those reported as dependent 2 weeks before admission to be independent 3 months after hospitalization (68% vs 20%, P < .001 for patient respondents; 30% vs 5%, P < .001 for surrogate respondents). Similarly, among patients dependent in bathing on hospital admission, survival 1 year after hospitalization was much higher in patients who were independent in bathing 2 weeks before admission than patients who were dependent 2 weeks before admission (76% vs 59%, P < .001 for patient respondents; 60% vs 45%, P < .001 for surrogate respondents). Results were similar for each of the other four ADLs. In a logistic regression model controlling for the number of ADLs reported as dependent on admission, the number of ADLs reported as dependent 2 weeks before admission was significantly associated with 1-year mortality among both patient (odds ratio (OR) = 1.39 per dependent ADL, 95% confidence interval (CI) - 1.26-1.54) and surrogate (OR = 1.14, 95% CI = 1.06-1.24) respondents. CONCLUSIONS: Hospitalized patients' assessments of their ability to perform ADLs before their hospitalization have evidence of face and predictive validity. These measures are strong predictors of important health outcomes such as functioning and survival. In particular, among patients dependent in ADL function on hospital admission, these results highlight the prognostic importance of inquiring about the patient's functional status before the onset of the acute illness.

Title Dementia Ddx. Office Diagnosis of the Four Major Types of Dementia.
Date February 2000
Journal Geriatrics
Excerpt

The prevalence of dementia increases with age from 1% at age 60 to about 40% at age 85. Four types of dementia--Alzheimer's disease, diffuse Lewy body dementia, frontotemporal dementia, and vascular dementia--account for 90% of all cases. The office-based physician can recognize these dementing illnesses in older patients by using existing consensus criteria. Differential diagnosis has an important bearing on patient management and prognosis, due to the potential value of treatment with some medications, possible drug toxicities in certain circumstances, and the complex care needs of patients and their families.

Title Geriatric Assessment.
Date December 1999
Journal The Medical Clinics of North America
Excerpt

A comprehensive geriatric assessment involves the evaluation of the physical, psychosocial, and environmental factors affecting the health of an elderly person. In the office setting a geriatric assessment is best accomplished by the use of screening questions, which are incorporated into the patient's medical questionnaire; the use of validated, brief screening tests that measure the patient's performance of daily living activities, cognition, nutritional status, and risk of falls; and a review of the patient's personal values and social support network. The screening assessment can be completed in an average of ten minutes by using self-administered questionnaires and brief performance-based measures of physical functioning. The comprehensive assessment performed on the initial visit with an elderly patient will help to (1) improve diagnostic accuracy, (2) guide the selection of interventions to restore or preserve health, (3) recommend an optimal environment for care, (4) predict health outcomes, and (5) monitor clinical change over time. The effectiveness of geriatric assessment has been demonstrated in clinical trials and is likely to be most effective when conducted by the patient's primary care physician.

Title Effects of Functional Status Changes Before and During Hospitalization on Nursing Home Admission of Older Adults.
Date December 1999
Journal The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Excerpt

BACKGROUND: Functional status changes before and during hospitalization may have important effects on outcomes in older adults, but these effects are not well understood. We determined the influence of functional status changes on the risk of nursing home (NH) admission after hospitalization. METHODS: Subjects were 551 general medical patients > or = 70 years old (66% female; mean age = 80 years) admitted from home to a large Midwestern teaching hospital. Functional status change measures were based on patients' need for assistance in five personal activities of daily living (ADL) 2 weeks prior to hospital admission, the day of admission, and the day of discharge. Sociodemographic and clinical characteristics were included in multivariate models predicting NH admission. RESULTS: Functional status change categories were: stable in function before and during hospitalization (45% of study patients); decline in function before and improvement during hospitalization (26%); stable before and decline during hospitalization (15%); decline before and no improvement during hospitalization (13%). In multivariate analyses, patients in the decline-no improvement group (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.46-6.96) and patients in the stable-decline group (OR = 2.77; 95% CI = 1.29-5.96) were at greater risk for NH admission than patients in the stable-stable group. In a multivariate model that controlled for ADL function at hospital discharge, functional status change was no longer statistically significantly associated with NH admission. CONCLUSIONS: Discharge function is a key risk factor for NH admission among hospitalized older adults. Because functional status changes before and during hospitalization are key determinants of discharge function, they provide important clues about the potential to modify that risk. Functional recovery during a hospital stay after prior functional decline, and prevention of in-hospital functional decline after prior functional stability, are important targets for clinical intervention to minimize the risk of NH admission.

Title Stimulation of Myofibrillar Protein Degradation and Expression of Mrna Encoding the Ubiquitin-proteasome System in C(2)c(12) Myotubes by Dexamethasone: Effect of the Proteasome Inhibitor Mg-132.
Date November 1999
Journal Journal of Cellular Physiology
Excerpt

Addition of the synthetic glucocorticoid, dexamethasone (Dex) to serum-deprived C(2)C(12) myotubes elicited time- and concentration-dependent changes in N(tau)-methylhistidine (3-MH), a marker of myofibrillar protein degradation. Within 24 h, 100 nM Dex significantly decreased the cell content of 3-MH and increased release into the medium. Both of these responses had increased in magnitude by 48 h and then declined toward basal values by 72 h. The increase in the release of 3-MH closely paralleled its loss from the cell protein. Furthermore, Dex also decreased the 3-MH:total cell protein ratio, suggesting that myofibrillar proteins were being preferentially degraded. Incubation of myotubes with the peptide aldehyde, MG-132, an inhibitor of proteolysis by the (ATP)-ubiquitin (Ub)-dependent proteasome, prevented both the basal release of 3-MH (>95%) and the increased release of 3-MH into the medium in response to Dex (>95%). Northern hybridization studies demonstrated that Dex also elicited similar time- and concentration-dependent increases in the expression of mRNA encoding two components (14 kDa E(2) Ub-conjugating enzyme and Ub) of the ATP-Ub-dependent pathway. The data demonstrate that Dex stimulates preferential hydrolysis of myofibrillar proteins in C(2)C(12) myotubes and suggests that the ATP-Ub-dependent pathway is involved in this response.

Title Potential Intracellular Targets for Anabolic/anti-catabolic Therapies.
Date September 1999
Journal Current Opinion in Clinical Nutrition and Metabolic Care
Excerpt

The intracellular signalling pathways controlling muscle protein synthesis and proteolysis are potential targets for anabolic/anti-catabolic therapy. In this review, we consider both the potentiation of the effect of anabolic hormones and suppression of the catabolic action of cytokines. Potential candidates, in particular isoforms of the protein kinase C family, and their role in the control of ribosomal action and the ubiquitin-proteasome proteolytic system are discussed.

Title Translocation of Protein Kinase C Isoforms in Rat Muscle in Response to Fasting and Refeeding.
Date August 1999
Journal The British Journal of Nutrition
Excerpt

Weanling rats were offered food ad libitum, or fasted for 18 h, or fasted and refed for times ranging from 5 to 30 min. Five protein kinase C (PKC) isoforms (alpha, epsilon, zeta, theta and mu) were detected in the hindlimb muscles by Western immunoblotting. PKC forms epsilon and theta were abundant in plantaris, but not in soleus muscle, and no difference in localization was detected between fed rats and those fasted for 18 h. PKC forms alpha and mu were affected by fasting and refeeding. PKC-mu was found only in the cytosolic fraction of the plantaris muscle of the fasted animal, but in the fully-fed animals it was also associated with the membrane fraction. The pattern of localization observed in the fully-fed state was restored in the fasted rats by 20 min refeeding. In contrast, PKC-alpha was not detected in the cytosolic fraction of the plantaris in fasted animals but rapidly reappeared there on refeeding, being restored to 20% and 80% of the fed value within 5 and 30 min of refeeding respectively. The timing of these changes was correlated with the increase in serum insulin concentration, which was significantly elevated above the fasted value by 5 min and at subsequent times. These data suggest a possible role for PKC isoforms alpha and mu in the metabolic changes that occur in skeletal muscle on transition between the fasted and the fed state.

Title The Effects of Maternal Protein Restriction on the Growth of the Rat Fetus and Its Amino Acid Supply.
Date August 1999
Journal The British Journal of Nutrition
Excerpt

Maternal protein deficiency causes fetal growth retardation which has been associated with the programming of adult disease. The growth of the rat fetus was examined when the mothers were fed on diets containing 180, 90 and 60 g protein/kg. The numbers of fetuses were similar in animals fed on the 180 and 90 g protein/kg diets but the number was significantly reduced in the animals fed on the 60 g protein/kg diet. The fetuses carried by the mothers fed on the 90 g protein/kg diet were 7.5% heavier than those of mothers fed on 180 g protein/kg diet on day 19 of gestation, but by day 21 the situation was reversed and the fetuses in the protein-deficient mothers were 14% smaller. Analysis of the free amino acids in the maternal serum showed that on day 19 the diets containing 90 and 60 g protein/kg led to threonine concentrations that were reduced to 46 and 20% of those found in animals fed on the control (180 g/kg) diet. The other essential amino acids were unchanged, except for a small decrease in the branched-chain amino acids in animals fed on the 60 g protein/kg diet. Both low-protein diets significantly increased the concentrations of glutamic acid+glutamine and glycine in the maternal serum. On day 21 the maternal serum threonine levels were still reduced by about one third in the group fed on the 90 g protein/kg diet. Dietary protein content had no effect on serum threonine concentrations in nonpregnant animals. Analysis of the total free amino acids in the fetuses on day 19 showed that feeding the mother on a low-protein diet did not change amino acid concentrations apart from a decrease in threonine concentrations to 45 and 26% of the control values at 90 and 60 g protein/ kg respectively. The results suggest that threonine is of particular importance to the protein-deficient mother and her fetuses. Possible mechanisms for the decrease in free threonine in both mother and fetuses and the consequences of the change in amino acid metabolism are discussed.

Title Clinical Intervention Trials: the Ace Unit.
Date June 1999
Journal Clinics in Geriatric Medicine
Excerpt

The loss of independent self-care by older patients during hospitalization for an acute illness can be modified by specific interventions. Acute care geriatric units appear to be the most effective intervention, but geriatric consultation on specific units, comprehensive discharge planning, and nutritional support also appear to have beneficial effects on clinical outcomes of hospitalization. These studies highlight the potential of geriatricians, in the setting of interdisciplinary care, to improve the process of patient care and to serve as directors of medical units that focus on management of acutely ill older patients.

Title Non-surgical Periodontal Treatment with and Without Adjunctive Metronidazole in Smokers and Non-smokers.
Date May 1999
Journal Journal of Clinical Periodontology
Excerpt

To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers.

Title Depressive Symptoms and 3-year Mortality in Older Hospitalized Medical Patients.
Date March 1999
Journal Annals of Internal Medicine
Excerpt

BACKGROUND: Depressive symptoms are common in hospitalized older persons. However, their relation to long-term mortality is unclear because few studies have rigorously considered potential confounders of the relation between depression and mortality, such as comorbid illness, functional impairment, and cognitive impairment. OBJECTIVE: To measure the association between depressive symptoms and long-term mortality in hospitalized older persons. DESIGN: Prospective cohort study. SETTING: General medical service of a teaching hospital. PATIENTS: 573 patients 70 years of age or older. MEASUREMENTS: Depressive symptoms (Geriatric Depression Scale score), severity of acute illness (Acute Physiology and Chronic Health Evaluation II score), burden of comorbid illness (Charlson comorbidity index score), physical function (a nurse assessed dependence in six activities of daily living), and cognitive function (modified Mini-Mental State Examination) were measured at hospital admission. Mortality over the 3 years after admission was determined from the National Death Index. Mortality rates among patients with six or more depressive symptoms were compared with those among patients with five or fewer symptoms. RESULTS: The mean age of the patients was 80 years; 68% of patients were women. Patients with six or more depressive symptoms had greater comorbid illness, functional impairment, and cognitive impairment at admission than patients with fewer depressive symptoms. Three-year mortality was higher in patients with six or more depressive symptoms (56% compared with 40%; hazard ratio, 1.56 [95% CI, 1.22 to 2.00]; P < 0.001). After adjustment for age, acute illness severity, comorbid illness, functional impairment, and cognitive impairment at the time of admission, patients with six or more depressive symptoms continued to have a higher mortality rate during the 3 years after admission (hazard ratio, 1.34 [CI, 1.03 to 1.73]). Although depressive symptoms contributed less to the mortality rate than did the total burden of comorbid medical illnesses, the excess mortality rate associated with depressive symptoms was greater than that conferred by one additional comorbid medical condition. CONCLUSIONS: Depressive symptoms are associated with long-term mortality in older patients hospitalized with medical illnesses. This association is not fully explained by greater levels of comorbid illness, functional impairment, and cognitive impairment in patients with more depressive symptoms.

Title Prevalence and Patterns of Physical Restraint Use in the Acute Care Setting.
Date December 1998
Journal The Journal of Nursing Administration
Excerpt

Nurse executives usually have the principal responsibility to respond to the national movement to reduce physical restraint use in hospitals. The results of this three-site, interdisciplinary, prospective incidence study (based on more than 49,000 observations collected on 18 randomly selected days) reveal new patterns in the rationale and types of restraints used. The authors discuss how the results can be used in measuring success and allocating resources for restraint reduction programs.

Title Effect of Loading on Bone Regenerated at Implant Dehiscence Sites in Humans.
Date December 1998
Journal Clinical Oral Implants Research
Excerpt

Few investigations have studied the long-term fate of bone formed following the technique of guided tissue regeneration. The aim of the present study was to evaluate bone fill around implant fixtures with dehiscence defects and to study its response to loading. Ten patients were treated with overdentures supported by 2 fixtures ad modum Brånemark. A third 7 mm x 3.75 mm diameter fixture was placed for the purposes of the study in the most anterior part of the mandible with a dehiscence defect of 4 to 5 mm on the buccal aspect (and 3 to 4 threads exposed) which was covered with a Gore-Tex membrane and buried beneath the mucosa. Fixtures were exposed after 5 months (stage 2), ball abutments connected and loaded through an overdenture for 1 year. Nine fixtures were functioning well after 1 year of loading, 6 of which were retrieved with a trephine for histological examination and compared with 6 unloaded fixtures retrieved in our previously reported study. The bone area filling the thread profiles (BA%) and the bone to metal contact (BMC%) were measured in the 3 most apical and 3 most coronal thread profiles on the buccal and lingual surfaces. Statistically significant higher BMC% (P < 0.01) were observed in loaded fixtures in the apical regions (buccal: loaded 51%, unloaded 25%; lingual: loaded 49%, unloaded 24%). Differences approached significance for the regeneration site (loaded 22%, unloaded 6%) but were no different for the coronal lingual region (loaded 28%, unloaded 20%). There were no differences for BA%. This study confirms that there is an increase in bone to metal contact with time and following fixture loading and that this may also occur with bone regenerated under Gore-Tex membranes.

Title Development and Cell Fate in Interspecific (mus Musculus/mus Caroli) Orthotopic Transplants of Mouse Molar Tooth Germs Detected by in Situ Hybridization.
Date September 1998
Journal Archives of Oral Biology
Excerpt

Interpretation of results from previous tooth germ transplantation studies is limited by the inability to distinguish between donor and host cells unequivocally. Furthermore, ectopic transplantation sites have generally been used and the relevance of this to tooth development in situ is uncertain. The aim here was to determine cell fate in orthotopic tooth germ transplants using an interspecific mouse marker system. Mandibular first molar tooth germs were dissected from Mus musculus (CD1) and Mus caroli mice (age range 15-19 day embryo) and transplanted interspecifically into the alveolar crypt of extirpated first mandibular molars in neonatal M. musculus (CD1) and M. caroli hosts. Grafts were recovered at intervals up to 4 weeks postoperatively. Paraffin wax-embedded sections were examined using routine histological techniques and in situ hybridization with a biotinylated DNA probe (pmSat5) specific for M. musculus, to distinguish between donor and host cells. Development of M. musculus tooth germs in M. caroli mandibles and vice versa was similar and transplants progressed to incipient root formation. Vascularization of transplants was chimaeric, being donor-derived in the pulp and host-derived more peripherally. The investing soft tissues comprised a mixture of donor and host cells, predominantly donor. Donor cells were also found in the soft tissue of intertrabecular spaces in the surrounding bone, but alveolar osteocytes were almost entirely host-derived. Long-term survival of grafts was limited and few donor cells were present after 2 weeks. This study provides an unequivocal demonstration of the origin of all cells present in transplanted tooth germs.

Title Adjunctive Systemic and Locally Delivered Metronidazole in the Treatment of Periodontitis: a Controlled Clinical Study.
Date August 1998
Journal British Dental Journal
Excerpt

To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole.

Title Tools for Assessing the Frail Elderly. Geriatric Evaluation Focuses on Improving Quality of Life.
Date July 1998
Journal Postgraduate Medicine
Excerpt

Questionnaires and screening scales can help physicians identify physical, functional, social, and psychological problems often seen in frail elderly patients and also assess caregiver strain. Physicians should review with patients and caregivers the main findings and discuss plans for further evaluation and management, including laboratory tests, vaccinations, and advance directives.

Title Growth and Metabolism of Fetal and Maternal Muscles of Adolescent Sheep on Adequate or High Feed Intake: Possible Role of Protein Kinase C-alpha in Fetal Muscle Growth.
Date June 1998
Journal The British Journal of Nutrition
Excerpt

From days 4-104 of pregnancy, adolescent sheep, weighing 43.7 (SE 0.87) kg were offered a complete diet at two different intakes (approximately 5 or 15 kg/week) designed to meet slightly, or well above, maternal maintenance requirements. The fetal and maternal muscles were taken on day 104 of pregnancy and analysed for total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal weight gain, weighed more (76.5 (SE 4.5) v 50.0 (SE 1.7) kg) and had muscles with a greater fresh weight, whilst their fetuses had smaller muscles, than those fed at a lower intake. Plantaris muscle of the ewes fed at the high intake contained more RNA and protein; again the opposite situation was found in the fetal muscle. On the higher maternal intakes, the DNA, RNA and protein contents of the fetal plantaris muscle were less than in fetuses of ewes fed at the lower intake. To investigate the possible mechanisms involved in this decrease in fetal muscle mass, cytosolic and membrane-associated muscle proteins were subjected to Western immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a family of enzymes known to play an important role in cell growth. Five PKC isoforms (alpha, epsilon, theta, mu, zeta) were identified in fetal muscle. One of these, PKC-alpha was located predominantly in the cytosolic compartment in the smaller fetuses of the ewes fed at a high plane of nutrition, but was present to a greater extent in the membranes of the more rapidly growing fetuses of the ewes fed at the lower intake. This was the only isoform to demonstrate nutritionally related changes in it subcellular compartmentation suggesting that it may mediate some aspects of the change in fetal growth rate.

Title The Relation Between Health Status Changes and Patient Satisfaction in Older Hospitalized Medical Patients.
Date June 1998
Journal Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine
Excerpt

OBJECTIVE: To examine the relation between two patient outcome measures that can be used to assess the quality of hospital care: changes in health status between admission and discharge, and patient satisfaction. DESIGN: Prospective cohort study. SETTING AND PATIENTS: Subjects were 445 older medical patients (aged > or =70 years) hospitalized on the medical service of a teaching hospital. MEASUREMENTS AND MAIN RESULTS: We interviewed patients at admission and discharge to obtain two measures of health status: global health and independence in five activities of daily living (ADLs). At discharge, we also administered a 5-item patient satisfaction questionnaire. We assessed the relation between changes in health status and patient satisfaction in two sets of analyses, that controlled for either admission or discharge health status. When controlling for admission health status, changes in health status between admission and discharge were positively associated with patient satisfaction (p values ranging from .01 to .08). However, when controlling for discharge health status, changes in health status were no longer associated with patient satisfaction. For example, among patients independent in ADLs at discharge, mean satisfaction scores were similar regardless of whether patients were dependent at admission (i.e., had improved) or independent at admission (i.e., remained stable) (79.6 vs 81.2, p = .46). Among patients dependent in ADLs at discharge, mean satisfaction scores were similar regardless of whether they were dependent at admission (i.e., remained stable) or independent at admission (i.e., had worsened) (74.0 vs 75.7, p = .63). These findings were similar using the measure of global health and in multivariate analyses. CONCLUSIONS: Patients with similar discharge health status have similar satisfaction regardless of whether that discharge health status represents stable health, improvement, or a decline in health status. The previously described positive association between patient satisfaction and health status more likely represents a tendency of healthier patients to report greater satisfaction with health care, rather than a tendency of patients who improve following an interaction with the health system to report greater satisfaction. This suggests that changes in health status and patient satisfaction are measuring different domains of hospital outcomes and quality. Comprehensive efforts to measure the outcomes and quality of hospital care will need to consider both patient satisfaction and changes in health status during hospitalization.

Title Does Delirium Contribute to Poor Hospital Outcomes? A Three-site Epidemiologic Study.
Date June 1998
Journal Journal of General Internal Medicine
Excerpt

To determine the independent contribution of admission delirium to hospital outcomes including mortality, institutionalization, and functional decline.

Title Improving Functional Outcomes in Older Patients: Lessons from an Acute Care for Elders Unit.
Date May 1998
Journal The Joint Commission Journal on Quality Improvement
Excerpt

BACKGROUND: Hospitalization often marks the beginning, and may be partially responsible for, a downward trajectory characterized by declining function, worsening quality of life, placement in a long term care facility, and death. At the University Hospitals of Cleveland, an Acute Care for Elders (ACE) unit that reengineered the process of caring for older patients (> or = 70 years of age) to improve functional outcomes was established in September 1990. DESCRIPTION OF INTERVENTION: The general principles of ACE included an approach to care guided by the biopsychosocial model and recognition of the importance of fitting the hospital environment to the patient's needs. The design of the intervention was consistent with principles of comprehensive geriatric assessment and continuous quality improvement. Care, which focused on maintaining function, was directed by an interdisciplinary team that considered the patient's needs both at home and in the hospital. The major components of the ACE Unit intervention included patient-centered nursing care (daily assessment of functional needs by nursing, nursing-based protocols to improve outcomes, daily rounds by a multidisciplinary team), a prepared environment, planning for discharge, and medical care review. RESULTS: In a randomized trial comparing ACE with usual care, patients receiving ACE had improved functional outcomes at discharge. The costs to the hospital for ACE unit care were less than for usual care. The functional status of ACE and usual care patients was similar 90 days after discharge. FUTURE DIRECTIONS: The ACE unit intervention is being expanded to preserve the improvements observed during the hospitalization in the outpatient setting. In addition, needs other than function which are critical to patients' long-term quality of life are being considered.

Title A Prospective Study of Astra Single Tooth Implants.
Date May 1998
Journal Clinical Oral Implants Research
Excerpt

A new design of single tooth implant (AstraTech, Molndal Sweden) featuring a microthreaded conical neck and TiO blast surface was evaluated clinically and radiographically after 2 years in function. Fifteen patients (age range 16 to 48) with missing maxillary anterior teeth (6 central incisors, 8 laterals, 1 bicuspid) had 4, 13 mm and 11, 15 mm implants placed under local anaesthesia and left for a period of 6 months before exposure and abutment connection/crown fabrication. All patients were seen at 4 to 6 monthly intervals for hygienist maintenance. Radiographs using Rinn holders and a long cone technique were taken at the crown insertion and after 1 year (14 subjects) and 2 years (12 subjects). All implants were successfully integrated at stage 2, and no implants have been lost. The internal conical seal design of the abutment/implant interface facilitated connection and there were no cases of abutment screw loosening. No soft tissue problems were observed, and the gingival morphology/health was well maintained. One crown was recemented after 18 months in function, and 1 crown was replaced because of a fracture to the porcelain incisal edge. At crown insertion, the mean bone level was 0.46 to 0.48 mm apical to the top of the implant and there were no statistically significant changes in the bone level over the 2 years of the study. In conclusion, the single tooth Astra implants were highly successful and bone changes within the first 2 years of function were comparable with other systems reporting high long-term success rates.

Title Signalling Pathways Regulating Protein Turnover in Skeletal Muscle.
Date April 1998
Journal Cellular Signalling
Excerpt

The protein content of skeletal muscle is determined by the relative rates of synthesis and degradation which must be regulated coordinately to maintain equilibrium. However, in conditions such as fasting where amino acids are required for gluconeogenesis, or in cancer cachexia, this equilibrium is disrupted and a net loss of protein ensues. This review, utilising studies performed in several situations, summarizes the current state of knowledge on the possible signalling pathways regulating protein turnover in skeletal muscle and highlights areas for future work.

Title Implant Placement: Surgical Techniques and Considerations.
Date March 1998
Journal Dental Update
Excerpt

Successful implant surgery largely depends on good planning and meticulous technique. The former requires an appreciation of the restorative requirements and visualization of the desired end result. This may be easier for the clinician who is delivering both aspects of treatment, but in other circumstances requires close collaboration between prosthodontist and surgeon. This paper focuses on the surgical techniques involved in implant surgery, because successful osseointegration is achievable only with careful surgical preparation.

Title Periodontal Treatment: Non-surgical or Surgical?
Date March 1998
Journal Dental Update
Excerpt

Successful treatment of periodontal disease depends upon the extent of disease, susceptibility of the individual to disease, and the motivation and expectations of the patient. The dental surgeon must balance these factors with the practical and financial constraints of treatment. Many dental practitioners find it extremely difficult to decide on a particular course of treatment: this article will help those in doubt to choose the treatment appropriate to their individual patients.

Title Cytokeratin Phenotypes at the Dento-gingival Junction in Relative Health and Inflammation, in Smokers and Nonsmokers.
Date February 1998
Journal Oral Diseases
Excerpt

OBJECTIVES: The cells of the junctional epithelium (JE) provide and maintain the epithelial attachment, and remain morphologically and phenotypically distinct from oral sulcular (OSE) and external oral epithelia (EOE), from which they may be regenerated de novo. Expression of cytokeratins (CK) in human epithelia has been shown to be highly site-specific, implying a functional role. The aims of this study were to differentiate between the cytokeratin profiles of JE, OSE, EOE and pocket epithelia (PE) in health and disease, in smokers and non-smokers. MATERIALS AND METHODS: The cytokeratin profiles of 40 samples of healthy and clinically inflamed human gingival tissue taken from 15 smokers and 25 non-smokers were studied by immunocytochemistry. Cryostat sections of fresh frozen gingival tissues were stained with a panel of monoclonal antibodies (mAb) and visualised by a biotin-Streptavidin-peroxidase complex technique. RESULTS: JE and PE expressed an identical range of cytokeratins irrespective of the inflammatory or smoking status, with the exception of CK4 expression, which tended to be increased in smokers. The OSE and EOE expressed non-cornifying and cornifying differentiation cytokeratins respectively, but in the presence of inflammation, both these epithelia showed increased expression of CK19 at a basal level in association with expression of one or more of the simple cytokeratins. JE/PE expressed CK17 in external layers only, approximating the tooth surface. All epithelia expressed CK6, 16 the markers of high cell turnover. CONCLUSIONS: CK 19 was a consistent differentiation marker for JE and PE. Expression of CK8, 18 was enhanced by inflammation. CK4 expression increased in association with smoking. Markers of differentiation were not always co-expressed equally within a pair. Pairs were not always completely mutually exclusive with frequent co-localisation.

Title Bioassay of Prostacyclin and Endothelium-derived Relaxing Factor (edrf) from Porcine Aortic Endothelial Cells. 1985.
Date December 1997
Journal British Journal of Pharmacology
Title Characteristics and Outcomes of Patients Who Self-extubate from Ventilatory Support: a Case-control Study.
Date November 1997
Journal Chest
Excerpt

To identify factors associated with the occurrence of deliberate self-extubation and to describe associated patient outcomes.

Title When Your Patient is Hospitalized: Tips for Primary Care Physicians.
Date October 1997
Journal Geriatrics
Excerpt

Outcomes of hospitalization of elderly patients can be improved through a systematic and comprehensive approach that physicians can incorporate into their practices. The first step is to recognize the patients who are at risk for functional decline in hospital, despite appropriate treatment of their acute illness. Many of these patients will present with one or more of the common geriatric syndromes, functional dependency, cognitive dysfunction (delirium), mood disorders (depression), and malnutrition. The next step is to avoid iatrogenic illness from diagnostic tests or medications and deconditioning due to immobility. Finally, discharge planning can help to ensure that patients receive needed services when they leave the hospital.

Title A Randomized Controlled Trial of a 2% Minocycline Gel As an Adjunct to Non-surgical Periodontal Treatment, Using a Design with Multiple Matching Criteria.
Date July 1997
Journal Journal of Clinical Periodontology
Excerpt

Topical locally delivered minocycline is an adjunctive to non-surgical periodontal treatment, but there are few reported trials. Previous trials have reported differences between changes in probing depth in treatment and control groups, but no differences in probing attachment level. In the present study, 30 subjects were paired according to gender, age, ethnic group, smoking habits, and probing depths. Both groups received intensive oral hygiene education and root planing with local anaesthesia. Active or placebo gel was placed subgingivally at planed sites in each subject according to a double-blind protocol, immediately after instrumentation, and 2 and 4 weeks later. A periodontal examination was made with a constant force probe before instrumentation, and 6 and 12 weeks later, 2 subjects failed to complete the study, and their pairs were therefore not included in the analysis. Results were tested with analysis of covariance. Differences between groups in mean probing depth did not reach statistical significance at any visit (baseline: test (T) = 5.93 mm, control (C) = 5.74 mm; 6 weeks: T = 3.53 mm, C = 3.63 mm; 12 weeks: T = 3.29 mm, C = 3.44 mm), but mean probing attachment levels were different (p < 0.05) at both reassessments (baseline: T = 6.86 mm, C = 6.83 mm; 6 weeks: T = 4.93 mm, C = 5.30 mm; 12 weeks T = 4.91 mm, C = 5.27 mm). There was also a difference in the number of sites with bleeding on deep probing at 12 weeks (p < 0.05). This trial showed that adjunctive minocycline gel provided a more advantageous outcome for nonsurgical periodontal treatment in terms of probing attachment level and bleeding on deep probing. This trial was a good example of experimental, as opposed to community, design, and used limited resources to show a clear result.

Title Measuring Prognosis and Case Mix in Hospitalized Elders. The Importance of Functional Status.
Date June 1997
Journal Journal of General Internal Medicine
Excerpt

OBJECTIVE: Although physical function is believed to be an important predictor of outcomes in older people, it has seldom been used to adjust for prognosis or case mix in evaluating mortality rates or resource use. The goal of this study was to determine whether patients' activity of daily living (ADL) function on admission provided information useful in adjusting for prognosis and case mix after accounting for routine physiologic measures and comorbid diagnoses. SETTING: The general medical service of a teaching hospital. PARTICIPANTS: Medical inpatients (n = 823) over age 70 (mean age 80.7, 68% women). MEASUREMENTS: Independence in ADL function on admission was assessed by interviewing each patient's primary nurse. We determined the APACHE II Acute Physiology Score (APS) and the Charlson comorbidity score from chart review. Outcome measures were hospital and 1-year mortality, nursing home use in the 90 days following discharge, and cost of hospitalization. Patients were divided into four quartiles according to the number of ADLs in which they were dependent. MAIN RESULTS: ADL category stratified patients into groups that were at markedly different risks of mortality and higher resource use. For example, hospital mortality varied from 0.9% in patients dependent in no ADL on admission, to 17.4% in patients dependent in all ADLs. One-year mortality ranged from 17.5% to 54.9%, nursing home use from 3% to 33%, and hospital costs varied by 53%. In multivariate analyses controlling for APS. Charlson scores, and demographic characteristics, compared with patients dependent in no ADL, patients dependent in all ADLs were at greater risk of hospital mortality (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.1-58.8), 1-year mortality (OR 4.4; 2.7-7.4), and 90-day nursing home use (OR 14.9; 6.0-37.0). The DRG-adjusted hospital cost was 50% higher for patients dependent in all ADLs. ADL function also improved the discrimination of hospital and 1-year mortality models that considered APS, or Charlson scores, or both. CONCLUSIONS: ADL function contains important information about prognosis and case mix beyond that provided by routine physiologic data and comorbidities in hospitalized elders. Prognostic and case-mix adjustment methods may be improved if they include measures of function, as well as routine physiologic measures and comorbidity.

Title Paraneoplastic Cerebellar Degeneration. Case Report and Literature Review.
Date June 1997
Journal Archives of Internal Medicine
Excerpt

Paraneoplastic cerebellar degeneration (PCD) presents with acute or subacute onset of ataxia, dysarthria, and intention tremor. In patients older than 50 years, acute or subacute cerebellar degeneration is paraneoplastic in origin in 50% of cases. Paraneoplastic cerebellar degeneration most often precedes a potentially curable remote malignancy. Less often, PCD occurs in a patient with a known malignancy or heralds the onset of a recurrence. The presence of specific antibodies in serum samples helps to guide identification of the occult underlying malignancy. Physicians should entertain the diagnosis of PCD when older patients present with signs of cerebellar degeneration without an obvious cause. A systematic evaluation, including the selection of appropriate imaging and laboratory studies, will often enable physicians to identify the responsible cancer. However, because PCD can precede a cancer by months to years, periodic reevaluation is needed when the cancer remains occult.

Title The Role of the Dental Team in the Promotion of Smoking Cessation.
Date June 1997
Journal British Dental Journal
Excerpt

Dentists and their support staff are in an ideal position to help patients cut down or stop smoking. In this paper Professor Palmer and Dr Newton review the literature on the promotion of smoking cessation in dental settings so that members of the dental team will feel more confident about helping and assisting patients to reduce their smoking habits.

Title Development and Cell Fate in Interspecific (mus Musculus/mus Caroli) Intraocular Transplants of Mouse Molar Tooth-germ Tissues Detected by in Situ Hybridization.
Date May 1997
Journal Archives of Oral Biology
Excerpt

Mandibular first molar tooth germs were dissected from Mus musculus (CDI) and Mus caroli (age range: 14-day embryo to 1-day postnatal). Most of the tooth germs were separated enzymically into epithelial and mesenchymal components. Interspecific tissue recombinations and intact M. caroli tooth germs were grown in the anterior chamber of the eye of adult CDI mice for 24 weeks. Recombinations of M. caroli enamel-organ epithelium with M. musculus, dental papilla and follicle mesenchyme developed into normal teeth with advanced root, periodontal ligament and bone formation, thereby confirming extensive epithelial-mesenchymal interactions across the species barrier. Labelling sections by in situ hybridization with a M. musculus-specific DNA probe (pMSat5) showed that almost all cells in the pulp, periodontal ligament and bone were M. musculus, including cementoblasts. Reduced enamel epithelium and epithelial cell rests derived from donor M. caroli enamel organ were unlabelled. This indicates that any cementogenic role of Hertwig's epithelial root sheath must be short-lived. The immunological privilege of the intraocular transplantation site in M. musculus CDI mice did not extend to grafts including xenogeneic M. caroli dental mesenchyme. Thus, intact M. caroli tooth germs and recombinations of M. musculus enamel organ with M. caroli dental papilla and follicle showed limited development, with no root formation, and were populated almost exclusively with labelled host M. musculus lymphocytes.

Title Regulation of Phospholipase D in L6 Skeletal Muscle Myoblasts. Role of Protein Kinase C and Relationship to Protein Synthesis.
Date May 1997
Journal The Journal of Biological Chemistry
Excerpt

The addition of vasopressin or 12-O-tetradecanoylphorbol-13-acetate (TPA) to prelabeled L6 myoblasts elicited increases in [14C]ethanolamine release, suggesting the activation of phospholipase D activity or activities. While the effects of both agonists on intracellular release were rapid and transient, when extracellular release of [14C]ethanolamine was measured, the effect of vasopressin was again rapid and transient, whereas that of TPA was delayed but sustained. Effects of both agonists on intra- and extracellular release were inhibited by the protein kinase C (PKC) inhibitor, Ro-31-8220, and PKC down-regulation by preincubation with TPA. The formation of phosphatidylbutanol elicited by vasopressin and TPA mirrored their effects on extracellular [14C]ethanolamine release in that the former was transient, whereas the latter was sustained. Responses to both agonists were abolished by PKC down-regulation. When protein synthesis was examined, the stimulation of translation by TPA and transcription by vasopressin were inhibited by Ro-31-8220. In contrast, down-regulation of PKC inhibited the synthesis response to TPA but not vasopressin. Furthermore, following down-regulation, the effect of vasopressin was still blocked by the PKC inhibitors, Ro-31-8220 and bisindolylmaleimide. Analysis of PKC isoforms in L6 cells showed the presence of alpha, epsilon, delta, mu, iota, and zeta. Down-regulation removed both cytosolic (alpha) and membrane-bound (epsilon and delta) isoforms. Thus, the elevation of phospholipase D activity or activities induced by both TPA and vasopressin and the stimulation of translation by TPA involves PKC-alpha, -epsilon, and/or -delta. In contrast, the increase in transcription elicited by vasopressin involves mu, iota, and/or zeta. Hence, although phospholipase D may be linked to increases in translation elicited by TPA, it is not involved in the stimulation of transcription by vasopressin.

Title Relation Between Symptoms of Depression and Health Status Outcomes in Acutely Ill Hospitalized Older Persons.
Date March 1997
Journal Annals of Internal Medicine
Excerpt

BACKGROUND: Older patients often have poor health status outcomes after hospitalization. Symptoms of depression are common in hospitalized older persons and may be a risk factor for these poor outcomes. OBJECTIVE: To determine whether symptoms of depression predict worse health status outcomes in acutely ill, older medical patients, independent of health status and severity of illness at hospital admission. DESIGN: Prospective cohort study. SETTING: Medical service of a teaching hospital. PATIENTS: 572 hospitalized medical patients older than 70 years of age. MEASUREMENTS: 15 symptoms of depression, health status, and severity of illness were measured at admission. The main outcome was dependence in basic activities of daily living at discharge and 30 and 90 days after discharge. Other outcome measures were dependence in instrumental activities of daily living, fair or poor global health status, and poor global satisfaction with life. RESULTS: The median number of symptoms of depression on admission was 4. Patients with 6 or more symptoms on admission (n = 196) were more likely than patients with 0 to 2 symptoms (n = 181) to be dependent in basic activities of daily living (odds ratio, 2.47 [95% CI, 1.58 to 3.86]) after controlling for demographic characteristics and severity of illness. At each subsequent time point, patients with more symptoms of depression on admission were more likely to be dependent in basic activities of daily living. This association persisted after adjustment for dependence in basic activities of daily living, severity of illness, and demographic characteristics on admission. The odds ratios comparing patients who had 6 or more symptoms with those who had 0 to 2 symptoms were 3.23 (CI, 1.76 to 5.95) at discharge, 3.45 (CI, 1.81 to 6.60) 30 days after discharge, and 2.15 (CI, 1.15 to 4.03) 90 days after discharge. At each time point, patients with 6 or more symptoms of depression were more likely to have more dependence in instrumental activities of daily living, worse global health status, and less satisfaction with life. CONCLUSIONS: Symptoms of depression identified a vulnerable group of hospitalized older persons. The health status of patients with more symptoms of depression was more likely to deteriorate and less likely to improve during and after hospitalization. This association was not attributable to health status or severity of illness on admission. The temporal sequence and magnitude of this association, its consistency over time with different measures, and its independence from the severity of the somatic illness strongly support a relation between symptoms of depression on admission and subsequent health status outcomes.

Title Insulin and Insulin-like Growth Factor-i Responsiveness and Signalling Mechanisms in C2c12 Satellite Cells: Effect of Differentiation and Fusion.
Date March 1997
Journal Biochimica Et Biophysica Acta
Excerpt

In proliferating C2C12 myoblasts, serum and physiological concentrations of insulin and IGF-I stimulated protein synthesis and RNA accretion. After fusion, the multinucleated myotubes remained responsive to serum but not to insulin or IGF-I, even though both insulin and type-I IGF receptor mRNAs increased in abundance. Protein synthetic responses to insulin and IGF-I in myoblasts were not inhibited by dexamethasone, ibuprofen or Ro-31-8220, thus phospholipase A2, cyclo-oxygenase and protein kinase C did not appear to be involved in the signalling mechanisms. Neither apparently were polyphosphoinositide-specific phospholipase C or phospholipase D since neither hormone increased inositol phosphate, phosphatidic acid, choline or phosphatidylbutanol production. Only the phosphatidylinositol-3-kinase inhibitor, wortmannin, and the 70 kDa S6-kinase inhibitor, rapamycin, wholly or partially blocked the effects of insulin and IGF-I on protein synthesis. 2-deoxyglucose uptake remained responsive to insulin and IGF-I after fusion and was also inhibited by wortmannin. The results suggest that the loss of responsiveness after fusion is not due to loss of receptors, but to the uncoupling of a post-receptor pathway, occurring after the divergence of the glucose transport and protein synthesis signalling systems, and that, if wortmannin acts at a single site, this is prior to that point of divergence.

Title Soluble Adhesion Molecules in Serum of Smokers and Non-smokers, with and Without Periodontitis.
Date March 1997
Journal Journal of Periodontal Research
Title Repartitioning of Maternal Muscle Protein Towards the Foetus Induced by a Polyclonal Antiserum to Rat Gh.
Date January 1997
Journal The Journal of Endocrinology
Excerpt

Growth and protein accretion were studied in maternal muscle and liver and in foetuses of rats on day 20 of pregnancy. In young rats, weighing 120 g at mating, muscle mass and protein content of three hind-limb muscles, soleus, plantaris and gastrocnemius, increased on average by 7% compared with non-pregnant controls although the rate of muscle protein synthesis was decreased. In mature rats, rates of muscle protein synthesis were also reduced on day 20 of pregnancy but no change in muscle mass was observed. Rates of liver protein synthesis and accretion were increased in the pregnant animals; the effect was larger in the young pregnant rat. Administration of an antibody to rat GH (anti-rGH) for 10 days to young pregnant rats reversed the effect on the same three maternal muscles and resulted in a 9-11% lower muscle mass and protein content, compared with control pregnant animals. In both young and mature dams serum IGF-I concentrations were halved on day 20 of pregnancy, a further small reduction was observed in response to anti-rGH. No significant change in serum insulin or corticosterone levels was observed. Anti-rGH treatment also reduced food intake but foetal weight at 20 days was significantly increased (14%). The effects on maternal muscle were not the result of loss of appetite associated with anti-GH administration as, in rats pair-fed to the intake of the anti-rGH group, maternal muscle and foetal weights were the same as in animals with food available ad libitum. The data suggest that the GH/IGF axis is involved in the partitioning of nutrients between the dam and the foetus.

Title A Double-blind Trial of Tetracycline in the Management of Early Onset Periodontitis.
Date November 1996
Journal Journal of Clinical Periodontology
Excerpt

The aim of the study was to evaluate the adjunctive effect of systemic tetracycline (250 mg qds for 14 days) in sequential root planing and surgical phases of treatment in a randomised, double-blind controlled trial. 38 patients who were under 26 years of age, in good general health and with localised (15 test/15 control) or generalised (4 test/4 control) early onset periodontitis completed the non-surgical phase. Data were analysed by ANOVA using baseline covariates and transformations where appropriate. Improvements in probing depth, probing attachment level and bleeding on probing were significantly better in the group treated with adjunctive tetracycline, at 3 months post-treatment. 26 patients (13 test/13 control) subsequently completed the surgical phase (modified Widman flap surgery with adjunctive tetracycline or placebo as before) and were re-examined at 6 months and 12 months. In the test group, 58% of the originally affected teeth required surgery compared to 75% in the control group. Surgery produced further reductions in mean probing depths but no further gains in probing attachment. There were no further statistically significant differences between test and control groups for any of the clinical measures, although the tetracycline group appeared to maintain an advantage. In conclusion, systemically administered tetracycline is a useful adjunct in the management of early onset periodontitis, particularly in non-surgical treatment.

Title N Tau-methylhistidine Turnover in Skeletal Muscle Cells Measured by Gc-ms.
Date September 1996
Journal The American Journal of Physiology
Excerpt

A method that employs gas chromatography-mass spectrometry has been developed to measure N tau-methylhistidine (3-methylhistidine; 3-MH) synthesis and release from skeletal muscle myotubes in vitro. It shows excellent linearity (0.9999) over the range studied (0-4 nmol), high recovery (92.6%), and low coefficient of variation (1.6%). 3-MH release from myotubes was essentially linear over a 96-h incubation, whereas the loss of 3-MH from cell protein accelerated with increasing time, an effect due, at lest in part, to decreasing rates of total protein synthesis. When incubated in either glutamine-free or methionine-free medium for 48 h, 3-MH in cell protein and appearing in the medium were greatly reduced compared with the 48-h controls, suggesting that hypertrophy was greatly reduced. Similar but lesser trends were observed with adenosine 3',5' -cyclic monophosphate. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) appeared to both stimulate 3-MII synthesis and inhibit its release during a 48-h incubation. The development of this method facilitates detailed investigation into the mechanisms through which agents such as TPA regulate myofibrillar protein degradation.

Title Elastase in Gingival Crevicular Fluid from Smokers and Non-smokers with Chronic Inflammatory Periodontal Disease.
Date September 1996
Journal Oral Diseases
Excerpt

To compare elastase concentrations in gingival crevicular fluid (GCF) from individual sites of smokers and non-smokers.

Title The Soft Connective Tissues of the Gingiva and Periodontal Ligament: Are They Unique?
Date September 1996
Journal Oral Diseases
Excerpt

The connective tissues of the gingiva and periodontal ligament share a common embryonic development from cells of the cranial neural crest. This review paper describes the relationship of these tissues in tooth germ initiation, development and eruption.

Title Cyclic Amp Stimulates Protein Synthesis in L6 Myoblasts and Its Effects Are Additive to Those of Insulin, Vasopressin and 12-0-tetradecanoylphorbol-13-acetate. Possible Involvement of Mitogen Activated Protein Kinase.
Date May 1996
Journal Biochimica Et Biophysica Acta
Excerpt

The role of cyclic AMP as a second messenger in the stimulation of protein synthesis and the potential involvement of mitogen activated protein (MAP) kinase in this response was studied in L6 myoblasts. Dibutyryl-cAMP (dbt-cAMP) increased protein synthesis at 90 min and 6 h in a concentration-dependent manner. The responses at 90 min were probably mediated by increased translation as they were not blocked by actinomycin D; effects at 6 h were accompanied by increases in RNA content implying a transcriptional component. 100 nM 12-0-tetradecanoylphorbol-13-acetate (TPA), 1 nM Insulin (90 min incubations) and 100 nM vasopressin (6 h incubation) also increased protein synthesis and these responses were additive with those of 500 micron dbt-cAMP. Responses to forskolin were similar to dbt-cAMP whilst 1,9-dideoxyforskolin had no effect. Cell extracts immunoblotted with MAP kinase antibody showed bands corresponding to approx. 42, 44, 54 and 83 kDa. 500 micron dbt-cAMP elicited an increase in activity of both the 42 and 44 kDa bands when assayed by the 'in gel' method and a similar response was also observed with forskolin. TPA and vasopressin also stimulated the activity of these two isoforms, but had no significant additive or inhibitory effects when added in combination with 500 micron dbt-cAMP. In contrast, although 1 nM insulin alone had no effect, a synergistic response in terms of MAP kinase activation was observed in the presence of dbt-cAMP. The data demonstrate that cAMP stimulates protein synthesis in L6 cells and suggest a role for MAP kinase in this event.

Title Measurement of Protein Degradation by Release of Labelled 3-methylhistidine from Skeletal Muscle and Non-muscle Cells.
Date May 1996
Journal Journal of Cellular Physiology
Excerpt

The rates of [3H]N(tau)-methylhistidine (3-MH) accumulation in the medium, following pulse labelling of cells for 48 h with [3H]methionine, were used to measure myofibrillar protein degradation. In fused C2C12 myotubes, incubation for 24 or 48 h after the labelling period gave rates of myofibrillar degradation of 38 and 42%/day. In a leucine free medium, these rates were similar; 40 and 47%/day, respectively. Using identical conditions +/- leucine, but in the absence of [3H]-methionine, rates of protein accretion and synthesis over 24-48 h were measured. From these data, rates of total protein degradation were calculated by difference and were similar to myofibrillar degradation rates. We have used the same pulse labelling protocol to assess whether the method is applicable to non-muscle cell lines based on the knowledge that 3T3 fibroblasts contain actin in the cytoskeleton. 3-MH was detected both in protein and upon its release into the medium. Actin degradation measured over a 48 h period gave a value half that obtained for total degradation, but the results suggest that the release of 3-MH by fibroblasts in vivo could be appreciable. The development of this methodology should provide a useful tool to investigate signalling mechanisms regulating actin degradation in a variety of cell types.

Title Evaluation of Guided Tissue Regeneration in the Treatment of Paired Periodontal Defects.
Date January 1996
Journal British Dental Journal
Excerpt

The aim of the present study was to compare guided tissue regeneration with conventional surgery in matched periodontal defects within the same subject. Twenty pairs of sites in nine subjects were treated. Surgery was performed at both test and control sites on the same visit. Random allocation was not performed until all preparation and root instrumentation had been completed. Test defects were covered with e-PTFE membranes (Gore-Tex) and secured with sutures. Membranes were removed after 5-6 weeks with a second surgical procedure, whereas the control sites were not re-operated. At 12 months probing depth reductions were significantly greater at the Gore-Tex treated sites (P<0.05) but no difference in probing attachment level gains were found when compared with conventional flap surgery.

Title Stimulation of Protein and Dna Synthesis in Mouse C2c12 Satellite Cells: Evidence for Phospholipase D-dependent and -independent Pathways.
Date December 1995
Journal Journal of Cellular Physiology
Excerpt

In C2C12 myoblasts, 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated a phospholipase D (PLD) to degrade phosphatidylcholine (PC) as measured by the release of choline and an increase in the formation of phosphatidic acid (PA) (or phosphatidylbutanol [PtdBuOH] in the presence of 0.5% butanol). Exogenous PLD also stimulated choline release, PA and PtdBuOH formation. The protein kinase C (PKC) inhibitor, Ro-31-8220, and PKC downregulation significantly inhibited the effects of TPA but Ro-31-8220 had no effect on PLD action. Neither basic Fibroblast Growth Factor (bFGF) or Epidermal Growth Factor (EGF) increased PLD activity. All agonists stimulated protein synthesis during both a 90 min and a 6 hr incubation and increased RNA accretion after 6 hr. The response at 90 min was not inhibited by the transcription inhibitor, actinomycin D. Ro-31-8220 and PKC downregulation significantly inhibited all the effects of TPA. In contrast, Ro-31-8220 significantly inhibited the increase in RNA accretion elicited by PLD but had no effect on the ability of agonists other than TPA to enhance protein synthesis. All agonists also stimulated thymidine incorporation into DNA. The effects of EGF, bFGF, and PLD were rapid and transient whereas that of TPA was delayed and sustained. Ro-31-8220 and PKC downregulation significantly inhibited the response due to TPA. Furthermore, Ro-31-8220 also significantly inhibited the effects elicited by EGF and PLD but not that induced by bFGF. In differentiated myotubes, TPA and PLD, but not bFGF or EGF, again stimulated choline release and PtdBuOH formation. However, all agents failed to stimulate protein synthesis and RNA accretion. The data demonstrate the presence in C2C12 myoblasts, but not differentiated myotubes, of both a PLD-dependent and PLD-independent pathway(s) leading to the stimulation of protein synthesis, RNA accretion, and DNA synthesis.

Title Tear Film, Pharmacology of Eye Drops, and Toxicity.
Date October 1995
Journal Current Opinion in Ophthalmology
Excerpt

Various new topical ophthalmic drug delivery systems show promise for increasing bioavailability, reducing epithelial toxicity, and improving patient compliance. Microparticulates are drug-containing polymeric particles that are placed in the fornix and release ocular medication by diffusion, chemical reaction, polymer degradation, or ion exchange and can be used to deliver many topical ophthalmic medications, including antibiotics and antimetabolites. Soft drugs are activated enzymatically at the site of application and are rapidly converted to inactive metabolites when exposed to the ocular environment, improving bioavailability at the target site, and reducing the potential for ocular and systemic side effects. Applications include soft beta-blockers, soft corticosteroids, and soft anticholinergics. Collasomes are made up of collagen pieces suspended in a viscous vehicle; this formulation is similar to that of corneal collagen shields, but is more useful for chronic therapy because the collasomes can be instilled by the patient and cause less blurring of vision. Potential uses include delivery of hydrophobic antimetabolites such as cyclosporine to prevent graft rejection and delivery of lipids for the therapy of dry eyes. Ideal replacements for dysfunctional tear layers, especially the lipid layer, have not yet been developed. The toxic effects of preservatives in topical ocular medications, particularly in artificial tears, often outweigh the benefits and preservative-free tear preparations are almost always preferable.

Title Evidence That Protein Kinase C and Mitogen Activated Protein Kinase Are Not Involved in the Mechanism by Which Insulin Stimulates Translation in L6 Myoblasts.
Date September 1995
Journal Bioscience Reports
Excerpt

Insulin stimulated a concentration-dependent increase in protein synthesis in L6 myoblasts which was significant at 1 nM. This response was not prevented by the transcription inhibitor, actinomycin D. The protein kinase C (PKC) inhibitor, Ro-31-8220, and downregulation of PKC by prolonged incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), had no effect on the ability of insulin to stimulate protein synthesis whilst completely blocking the response to TPA. In contrast, insulin failed to enhance protein synthesis significantly in the presence of either ibuprofen, a selective cyclooxygenase inhibitor or rapamycin, an inhibitor of the 70 kDa S6 kinase. When cell extracts were prepared and assayed for total myelin basic protein kinase activity, a stimulatory effect of insulin was not observed until the concentration approached 100-fold (i.e. 100 nM) that required to elicit increases in protein synthesis. Upon fractionation on a Mono-Q column, 100 nM insulin increased the activity of 3 peaks which phosphorylated myelin basic protein. Two of these peaks were identified as the 42 and 44 kDa forms of Mitogen Activated Protein (MAP) kinase by immunoblotting. In contrast, 1 nM insulin had no effect on the activity of these peaks. The data suggest that physiologically relevant concentrations of insulin do not stimulate translation in L6 cells through either PKC or the 42/44 kDa isoforms of MAP kinase and that this response is, at least in part, mediated through the activation of the 70 kDa S6 kinase by cyclooxygenase metabolites.

Title Periodontology: a Clinical Approach. 7. Integrated Treatment Planning.
Date August 1995
Journal British Dental Journal
Title A Corneal Lens/shield System to Promote Postoperative Corneal Epithelial Healing.
Date July 1995
Journal Journal of Cataract and Refractive Surgery
Excerpt

We used a disposable bandage soft contact lens piggybacked onto a medicated, 12-hour corneal collagen shield to promote postoperative corneal epithelial healing and to provide sustained delivery of high levels of medications after corneal surgery in patients known to have poor corneal epithelial wound healing characteristics. Our experience with three patients indicates that the collagen shield dissolves completely by the first postoperative day and that the bandage lens remains in place with good mobility until it is removed when epithelialization is complete. This system eliminates the need for painful manipulation and placement of a bandage soft contact lens in an edematous, inflamed eye during the immediate postoperative period.

Title Periodontology: a Clinical Approach. 6. Reconstructive Periodontal Treatment.
Date July 1995
Journal British Dental Journal
Title Periodontology: a Clinical Approach. 5. Treatment of Multi-rooted Teeth.
Date July 1995
Journal British Dental Journal
Title Periodontology: a Clinical Approach. 4. Periodontal Surgery.
Date June 1995
Journal British Dental Journal
Excerpt

Results from comparative surgical studies have shown small differences between methods when evaluated over a few years post-surgically. Early interim results suggest that apical repositioning is more effective at reducing probing depth, replaced flaps (such as the modified Widman technique) offer slight advantages in terms of gain in clinical attachment, and procedures which involve extensive bone removal or exposure result in more bone loss and loss of attachment. The replaced flaps should in theory produce better aesthetics than the apical repositioned flap. In the long term however, the former tend to recede slightly whilst there is some coronal rebound in the latter, thereby producing relatively little difference between them when good plaque control is maintained. In all procedures there is loss in height of the interdental tissues, even if the labial tissue is maintained, and this can be aesthetically displeasing to some individuals. However it should also be remembered that effective non-surgical treatment can result in similar changes in tissue height and contour, and there is no guarantee of preservation of pre-existing dentogingival aesthetics. All routine periodontal treatment results in gingival shrinkage to some degree. In many cases periodontal surgery will, in reality, involve a combination of replacement, apical repositioning and resection due to the uneven pattern of disease and different anatomical constraints of the palate, tuberosities and retromolar regions. This is shown in figure 12. In summary the surgical procedures should: 1. Produce well contoured flaps of even thickness which are tailored to the shape of the tooth surfaces and permit good coverage of the alveolar bone and any bone defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Acute Hospital Care of the Elderly: Minimizing the Risk of Functional Decline.
Date June 1995
Journal Cleveland Clinic Journal of Medicine
Excerpt

Between 25% and 60% of older patients in the hospital undergoing care for an acute illness risk some loss of independent physical function. This loss may lead to prolonged hospital stay, nursing-home placement, or death. The risk of functional decline is related to the hospital environment, as well as to the physical frailty of the patient, disease severity, and cognitive impairment. An interdisciplinary approach may prevent functional decline. The aim is to modify the physical environment, prevent iatrogenic illness, detect and treat functional impairments, promote mobility, assess and treat nutritional problems, and address the patient's personal needs and values.

Title Periodontology: a Clinical Approach. 3. Non-surgical Treatment and Maintenance.
Date June 1995
Journal British Dental Journal
Title Periodontology: a Clinical Approach. 2. Periodontal Diagnosis and Prognosis.
Date May 1995
Journal British Dental Journal
Title A Randomized Trial of Care in a Hospital Medical Unit Especially Designed to Improve the Functional Outcomes of Acutely Ill Older Patients.
Date May 1995
Journal The New England Journal of Medicine
Excerpt

Older persons who re hospitalized for acute illnesses often lose their independence and are discharged to institutions for long-term care.

Title Periodontology: a Clinical Approach. 1. Periodontal Examination and Screening.
Date May 1995
Journal British Dental Journal
Excerpt

Periodontology has witnessed some of the most intensive and extensive research in dentistry over the last 30 years. This has led to a much clearer understanding of the aetiology of periodontal diseases and clinical studies have done much to compare and improve treatment modalities. The wealth of literature can certainly lead to confusion but for the most part should ultimately result in a more rational application of diagnostic and treatment methods. This new series is based upon the authors' wide experience in clinical practice and interpretation of the scientific literature.

Title Applications for a Corneal Mattress Suture in Anterior Limbal Wound Repairs.
Date April 1995
Journal Ophthalmic Surgery
Excerpt

We describe the use of a corneal mattress suture to manage two complications of trabeculectomy: first, to repair an anterior conjunctival tear/disinsertion in a limbus-based conjunctival flap; and, second, to restore wound integrity by reinforcing a focal section of scleromalacia or to close a perforation remaining from a previous cataract wound encountered during complicated trabeculectomy. In each setting, a single, double-armed 10-0 nylon corneal mattress suture is used as an anchor to establish a watertight limbal-wound closure. Additionally, for repairing an area of a scleromalacia/perforation, the corneal mattress suture can be used to incorporate a graft of Tenon's fascia into the wound.

Title Effect of Dietary Protein Quality, Feed Restriction and Short-term Fasting on Protein Synthesis and Turnover in Tissues of the Growing Chicken.
Date January 1995
Journal The British Journal of Nutrition
Excerpt

The effect of dietary protein quality and quantity on fractional rates of protein synthesis (ks) and degradation (kd) in the skeletal muscle, liver, jejunum and skin of young growing chickens was studied. Chickens were either fasted overnight or were fed at frequent intervals, using continuous feeders, with equal amounts of a diet containing soya-bean meal as the sole protein source, unsupplemented, or supplemented with either lysine or methionine. Each of the three diets was provided at 2 or 0.9 x maintenance. On the higher intake, birds on the unsupplemented diet gained weight, lysine supplementation decreased and methionine supplementation increased body-weight gain (by -23% and +22% respectively). Birds fed at 0.9 x maintenance lost weight; supplementation with methionine or lysine did not influence this weight loss. None of the dietary regimens had significant effects on protein synthesis rates in any of the tissues, thus the mechanism whereby muscle mass increased in response to methionine supplementation appeared to be a decrease in the calculated rate of protein degradation. Similarly, on the 0.9 x maintenance diet the failure of the animals to grow appeared to be due to an increase in the rate of protein degradation rather than an effect on synthesis. Conversely, muscle ks was decreased in fasted chickens previously fed on the unsupplemented diet at 2 x maintenance, and in birds which had received the 0.9 x maintenance diet fasting resulted in a similar reduction in protein synthesis in muscle; ks in the liver and jejunum was also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Stimulation of Protein Synthesis and Phospholipase D Activity by Vasopressin and Phorbol Ester in L6 Myoblasts.
Date January 1995
Journal Biochimica Et Biophysica Acta
Excerpt

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and vasopressin on protein synthesis and phospholipase D (PLD) activity were investigated in L6 myoblasts. TPA stimulated a concentration-dependent increase in protein synthesis (EC50 approx. 10 nM) during a 90 min incubation, but had no effect after 6 h. The maximum increase was about 15% and was mediated through changes in translation, as TPA had no effect on RNA accretion and the response was not prevented by actinomycin D. TPA also stimulated PLD activity as measured by an 8-fold increase in the formation of phosphatidylbutanol (PtdBuOH) and the release of choline (EC50 5-10 nM). In contrast to TPA, vasopressin stimulated protein synthesis (maximum increase 30%, EC50 approx. 10 nM) and RNA accretion after 6 h, but had no effect after 90 min. Vasopressin also increased PtdBuOH production 4-5-fold (EC50 approx. 0.5 nM) and choline release (EC50 approx. 1 nM). The addition of a highly purified preparation of PLD (2-10 units/ml) from Streptomyces sp. to L6 cells stimulated a concentration-dependent increase in choline release and protein synthesis after both 90 min (maximum stimulation 13%) and 6 h (maximum stimulation 12%). PLD also stimulated RNA accretion after 6 h but not 90 min. The data support a role for PLD in the regulation of protein synthesis in L6 cells.

Title Effects of a Polyclonal Antiserum to Rat Growth Hormone on Circulating Insulin-like Growth Factor (igf)-i and Igf-binding Protein Concentrations and the Growth of Muscle and Bone.
Date December 1994
Journal The Journal of Endocrinology
Excerpt

A polyclonal antiserum to rat GH (anti-rGH) injected into rats for 3 or 8 weeks markedly reduced the weight, total protein and RNA content of muscles of the hind limb. These effects were prevented when bovine GH (bGH) was administered simultaneously. In a second experiment, the effects of 8 weeks of treatment with anti-rGH on the growth of the whole body, muscle and bone were investigated. Body weights of rats were decreased by 58% by treatment with anti-rGH; muscle weights were reduced by slightly more than the decrease in body weight (by 64%, 65% and 61% respectively for plantaris, soleus and gastrocnemius). The weight of the tibia was decreased by 54%, its length was decreased by 23%, cortical width and overall width were reduced by 26% and 18% respectively, suggesting a possible role for GH in osteoclastic activity. Serum total insulin-like growth factor-I (IGF-I) concentrations were decreased by 80-90% in both experiments by anti-rGH; these changes were prevented in the first experiment by concurrent treatment with anti-rGH and bGH. The serum IGF-binding protein-3 (IGFBP-3) concentration was also decreased by anti-rGH in experiment 1 (by 86%); the response of the 28-32 kDa IGFBPs was smaller (-35%), and was restored to control values by simultaneous injection of bGH. Western immunoblotting using an antiserum to IGFBP-2 showed that there was a marked decrease from neonatal to adult stages which was independent of anti-rGH treatment. This clearly demonstrated a dissociation of the reciprocal relationship supposed to exist between IGFBPs-2 and -3. The 24 kDa IGFBP-4 was unaffected by anti-rGH but replacement therapy with bGH doubled its concentration. Although the effects on body and muscle weight were prevented when rats were given anti-rGH and bGH simultaneously, the possibility of mediation by other hormones cannot be precluded.

Title Healing of Implant Dehiscence Defects with and Without Expanded Polytetrafluoroethylene Membranes: a Controlled Clinical and Histological Study.
Date November 1994
Journal Clinical Oral Implants Research
Excerpt

Bone augmentation around implant fixtures using the technique of guided tissue regeneration has been described in a number of reports. The aim of this study was to evaluate bone fill around dehiscence defects at matched defects randomly allocated to test (expanded polytetrafluoroethylene; Gore-Tex) or control treatments within the same patient. Six edentulous subjects were treated with overdentures supported by 2 fixtures ad modum Bränemark. In addition, 2 experimental 7-mm fixtures with nearly identical dehiscence defects on the labial aspect were placed in the anterior part of the mandible. Baseline defect heights ranged from 2.5 to 4.0 mm with 2 to 4 threads exposed. The test fixture dehiscence was covered with a Gore-Tex membrane secured with a cover screw. The experimental fixtures were exposed after 5 months at stage 2 surgery and measurements and photographs repeated. The fixtures were then removed with a trephine and processed for histological evaluation. Regeneration of a hard tissue resembling bone was observed in 4 of 6 cases treated with Gore-Tex, amounting to between 95 and 100% elimination of the dehiscence and total coverage of the threads. However, in one of these cases, histological evaluation showed that it was soft tissue and not bone, and in a further case soft tissue regeneration was apparent both clinically and histologically. In another case there was no significant regeneration at either test or control defects. Although there was a trend for the Gore-Tex-treated dehiscences to respond more favourably, the differences in clinical and histological measurements between test and control failed to reach statistical significance.

Title The L-arginine: Nitric Oxide Pathway.
Date November 1994
Journal Current Opinion in Nephrology and Hypertension
Excerpt

The L-arginine: nitric oxide pathway is widely recognized as an important regulator of cell function and communication in a variety of physiological and pathophysiological situations. Recent advances in the biochemistry and molecular biology of nitric oxide synthases have contributed significantly to our understanding of the regulation of nitric oxide synthesis in health and disease. This pathway has been implicated in the pathogenesis of septic shock, hypertension, and atherosclerosis as well as in the antihypertensive action of converting enzyme inhibitors. Progress in this field, which spans the cardiovascular, immune, and nervous systems, has been rapid, and its full potential is yet to be realized.

Title Nitric Oxide Generation. A Predictive Parameter of Acute Allograft Rejection.
Date October 1994
Journal Transplantation
Excerpt

The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an important mediator in host defense mechanisms and may therefore play a role in the acute allograft response. We have studied NO generation in liver allograft rejection and determined its value in immunological monitoring. Stable end products of this pathway have been determined serially in 50 primary liver recipients and compared with 2 known mediators and markers of acute allograft rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma concentrations of acid-labile nitrosocompounds (NOx), which increased during acute allograft rejection (P < 0.0001), correlated with rejection severity and were reduced after administration of supplemental high dose glucocorticoids. Concentrations were significantly lower in nonrejection graft complications but were elevated during episodes of sepsis. Correlations between plasma NOx levels and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic analysis of these variables, plasma NOx was the most predictive parameter of an episode of acute cellular rejection. Nitric oxide generation in FK506-treated patients was lower compared with patients receiving a CsA-based immunosuppression regimen and was associated with a reduced frequency of acute rejection in the FK506 group. These data are consistent with a role for NO in the cellular alloantigen immune response and indicate that monitoring of plasma levels of NOx may be useful in the detection of acute allograft rejection.

Title Arachidonate Activation of Protein Kinase C May Be Involved in the Stimulation of Protein Synthesis by Insulin in L6 Myoblasts.
Date July 1994
Journal Bioscience Reports
Excerpt

Insulin stimulated protein synthesis in L6 myoblasts but did not increase the labelling of DAG or the release of phosphocholine from phosphatidylcholine. The DAG lipase inhibitor, RHC 80267, more than doubled the amount of label appearing in DAG but did not stimulate protein synthesis. Even in the presence of the DAG lipase inhibitor insulin failed to have any effect on DAG labelling, and conversely RHC 80267 did not modify the insulin-induced increase in protein synthesis. These results suggest that endogenous DAG production is not involved in the stimulation of protein synthesis by insulin. However, exogenous diacylglycerols (1-oleoyl-2-acetyl glycerol and 1-stearoyl-2-arachidonoyl glycerol) both stimulated protein synthesis in L6 myoblasts. The efficacy of the former (arachidonate-free) DAG suggested that their action was by activation of protein kinase C rather than by arachidonate release and prostaglandin formation. Ibuprofen, an inhibitor of cyclo-oxygenase failed to block the effects of insulin whereas a second cyclo-oxygenase inhibitor, indomethacin had only a partial inhibitory effect. The protein kinase C (PKC) inhibitor, RO-31-8220, totally blocked the effect of insulin. Since indomethacin is also recognised to inhibit phospholipase A2, the data suggests that insulin acts on protein synthesis in myoblasts by arachidonate activation of PKC.

Title A Medical Unit for the Acute Care of the Elderly.
Date June 1994
Journal Journal of the American Geriatrics Society
Excerpt

Older patients often experience a loss of independent physical functioning during the course of an acute illness requiring hospitalization. This functional decline is associated with serious sequelae including prolonged hospital stay, nursing home placement, and mortality. Elements of hospitalization may contribute to the progression or persistence of functional decline. The Unit for Acute Care of the Elderly (ACE Unit) at University Hospitals of Cleveland is an acute care general medical service that is designed to foster the independent functioning of patients. The Prehab Program of Patient Centered Care on the ACE Unit is a multifaceted intervention that integrates geriatric assessment into the optimal medical and nursing care of patients in an interdisciplinary environment. The Prehab Program has several key elements tailored to each individual patient's needs: a prepared environment, patient-centered care, multidimensional assessment and nonpharmacologic prescriptions, medical care review, and home planning. Standards of care serve to reduce the risk of iatrogenic illness resulting from polypharmacy, use of physical restraints, and diagnostic procedures. Nurse-initiated guidelines contribute to prevention of functional decline and to restoration of independent patient functioning. The effectiveness of the ACE Unit is being evaluated in a randomized clinical trial.

Title Immunohistochemical Analysis of Tissues Regenerated from Within Periodontal Defects Treated with Expanded Polytetrafluoroethylene Membranes.
Date May 1994
Journal Journal of Periodontology
Excerpt

Immunocytochemical analysis was carried out on samples of 5-, 6-, and 9-week old regenerated soft tissue taken from healing periodontal defects treated by guided tissue regeneration using expanded polytetrafluorethylene (ePTFE) membranes. A panel of monoclonal and polyconal antibodies to cytokeratins, vimentin, and collagen was used to label cells and collagen types I, III, and IV. Epithelium was identified in 7 of the 9 samples examined, in addition to mesenchymal cells staining positively for vimentin and co-distribution of collagen types I, III, and IV in all samples. Clinical observations indicated that exposure of the ePTFE membranes during healing was a frequent occurrence, and the presence and quantity of epithelium found within the healing defect beneath the membrane may be related to the extent to which this occurs.

Title Vasopressin Stimulates Phospholipase D, Protein Synthesis and Rna Accretion in L6 Myoblasts.
Date April 1994
Journal Biochemical Society Transactions
Title Effects of Growth Hormone and an Antiserum to Rat Growth Hormone on Serum Igf-i and Muscle Protein Synthesis and Accretion in the Rat.
Date April 1994
Journal The Journal of Endocrinology
Excerpt

Rats were injected twice daily for up to 10 days with GH or with a polyclonal antiserum to rat GH, commencing at 21-22 days of age. Administration of bovine or human GH (1mg/day) improved whole body growth rates by 22% and 29% respectively. Plantaris muscle mass was also increased, by 7 and 14% respectively. Anti-GH injected twice daily resulted in a 7% decrease in body weight at 4 days and a 10% reduction by 10 days. Similar decreases were observed in the total protein content of plantaris and soleus muscles. The decrease in the fractional rate of protein synthesis was proportionately greater than the decline in protein content in plantaris muscle whereas in the soleus no change in the rate of protein synthesis was observed, suggesting that the effect on this muscle was due to an increase in the rate of protein degradation. Serum total IGF-I was unchanged by treatment with either GH or anti-GH while the amount of hepatic IGF-I mRNA was also unaffected by anti-GH injection. These data are consistent with a direct effect of GH or an effect mediated by an autocrine/paracrine mechanism of action on muscle but do not support a role for serum total IGF-I as an endocrine mediator of GH action.

Title Regional and Cardiac Haemodynamic Effects of Ng, Ng,dimethyl-l-arginine and Their Reversibility by Vasodilators in Conscious Rats.
Date March 1994
Journal British Journal of Pharmacology
Excerpt

1. A series of experiments was carried out on 3 separate groups of male Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide donors, S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso-glutathione (SNOG), sodium nitroprusside (SNP), and the vasodilator, hydralazine. 2. As previously reported for L-NMMA, ADMA (1-100 mg kg-1) caused dose-dependent pressor and bradycardic effects, accompanied by renal, mesenteric and hindquarters vasoconstrictions. The magnitude and duration of these effects were similar for ADMA and L-NMMA, consistent with their being equipotent inhibitors of nitric oxide synthase. 3. Infusion of SNAP or SNOG (300 micrograms kg-1 h-1) after injection of ADMA or L-NMMA (100 mg kg-1) reversed the pressor but did not abolish the vasoconstrictor, effects of ADMA or L-NMMA. However, a higher dose of SNAP (3 mg kg-1 h-1) caused complete reversal of the pressor and mesenteric haemodynamic effects of ADMA (100 mg kg-1), although its renal and hindquarters vasoconstrictor effects were not abolished. 4. Infusion of SNP (300 micrograms kg-1 h-1) after administration of L-NMMA (100 mg kg-1), caused complete reversal of its pressor and mesenteric and hindquarters haemodynamic effects, and reduced substantially its renal vasoconstrictor action; hydralazine (7.5 mg kg-1 h-1) was almost as effective as SNP in reversing all these variables. 5. In animals chronically instrumented for the measurement of cardiac haemodynamics, ADMA(100 mg kg-1) caused a pressor effect accompanied by a rise in central venous pressure, and reductions in heart rate, cardiac index, stroke index, peak aortic flow, maximum rate of rise of aortic flow and total peripheral conductance. The reversal of the pressor effect of ADMA by SNAP (300 microg kg-1 h-1) was accompanied by a reduction of central venous pressure below resting levels and a further diminution of stroke index; all other variables showed an increase, but they still remained below resting levels (with the exception of heart rate).6. Thus, following inhibition of NO synthesis, pharmacological intervention with NO donors, or other vasodilators, may cause normalisation of the mean arterial pressure without necessarily returning all associated cardiovascular variables to normal.

Title Cloning, Characterization, and Expression of a Cdna Encoding an Inducible Nitric Oxide Synthase from the Human Chondrocyte.
Date January 1994
Journal Proceedings of the National Academy of Sciences of the United States of America
Excerpt

Incubation of human articular chondrocytes with interleukin 1 beta results in the time-dependent expression of nitric oxide (NO) synthase. We report here the isolation of a cDNA clone which encodes a protein of 1153 amino acids with a molecular mass of 131,213 Da and a calculated isoelectric point of 7.9. CHO cells transfected with a plasmid harboring this cDNA clone expressed NO synthase activity that was inhibited by some L-arginine analogues. The deduced amino acid sequence of the human chondrocyte inducible NO synthase shows 51% identity and 68% similarity with the endothelial NO synthase and 54% identity and 70% similarity with the neuronal NO synthase. The similarity (88%) between the human chondrocyte NO synthase cDNA sequence and that reported for the murine macrophage suggests that the inducible class of enzyme is conserved between different cell types and across species.

Title Vascular Smooth Muscle Contains a Depletable Store of a Vasodilator Which is Light-activated and Restored by Donors of Nitric Oxide.
Date October 1993
Journal The Journal of Pharmacology and Experimental Therapeutics
Excerpt

Endothelium-denuded strips of rabbit thoracic aorta relax on exposure to light. This response is similar to endothelium-dependent relaxation as it is inhibited by hemoglobin and methylene blue, and is mediated by an increase in cyclic GMP. We now demonstrate that photorelaxation decreases on repeated exposure to light. The response can be restored by treating the depleted smooth muscle strips with acidified nitrite, but not nitrite alone, and with the nitric oxide donors, S-nitrosopenicillamine and glyceryl trinitrate, but not with hydralazine. These data indicate that photorelaxation is mediated in part by a "pool" of light-activated vasodilator(s) and suggest that this may act as a store of nitric oxide which could play a role in the regulation of vascular tone.

Title Induction of Nitric Oxide Synthase in Human Chondrocytes.
Date June 1993
Journal Biochemical and Biophysical Research Communications
Excerpt

Incubation of human chondrocytes with interleukin-1 beta, tumour necrosis factor or endotoxin induced the expression of NO synthase. The synthesis of NO induced by IL-1 beta was concentration- and time- dependent, occurred after a lag period of approximately 6h and was inhibited by NG-monomethyl-L-arginine, cycloheximide, dexamethasone and hydrocortisone, but not by indomethacin. The activity of NO synthase from activated chondrocytes was not affected by EGTA or by the calmodulin inhibitor W-13. Northern blot analysis, with a rabbit chondrocyte inos probe, showed a 4.4kb positively hybridising band from activated human chondrocytes. Thus, human articular chondrocytes express an inducible NO synthase from the same family as the rabbit chondrocyte and rodent macrophage enzymes. This family appears to vary in terms of in vitro Ca(2+)-dependence and sensitivity to glucocorticoids.

Title The Discovery of Nitric Oxide in the Vessel Wall. A Unifying Concept in the Pathogenesis of Sepsis.
Date April 1993
Journal Archives of Surgery (chicago, Ill. : 1960)
Title Guided Tissue Regeneration--why, when and How?
Date March 1993
Journal Dental Update
Excerpt

Chronic periodontitis results in the destruction of the collagen fibre attachment to cementum, apical migration of the epithelial attachment, contamination of the exposed root surface by plaque and loss of alveolar bone. Regeneration can be defined as the restitution of lost tissues to a state which existed before destruction. As such, it is an ultimate and ideal goal and in most circumstances is currently beyond our capabilities. However, research in periodontology over the last 10 years or so has made considerable advances and is perhaps unique in proposing a new and fundamental treatment modality--guided tissue regeneration.

Title The Role of Nitric Oxide in Endotoxic Shock: Effects of Ng-monomethyl-l-arginine.
Date February 1993
Journal Journal of Cardiovascular Pharmacology
Excerpt

The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5-h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied by an increase in plasma NOx and ALT. Forty percent of these rats died during the experiment. There was no change in blood pressure in rats treated with dexamethasone (1 mg/kg) 1 h before and 2 h after LPS and the increase in NOx and ALT was significantly inhibited. None of the rats in this group died. Administration of 10 mg/kg of NG-monomethyl-L-arginine (L-NMMA) prevented the fall in blood pressure and partially prevented the increase in NOx and ALT. None of the animals in this group died. In contrast, 300 mg/kg of L-NMMA caused an initial increase in blood pressure followed by a rapid fall and enhanced the increase in ALT while abolishing the elevation of NOx. All of these animals died before the end of the experiment. However, when rats treated with high doses of L-NMMA were given a continuous infusion of S-nitroso-N-acetylpenicillamine (SNAP, 300 micrograms/kg/h), the blood pressure was maintained at control levels and no mortality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Immunohistochemical Analysis of Cells Attached to Teflon Membranes Following Guided Tissue Regeneration.
Date January 1993
Journal Journal of Periodontology
Excerpt

A wide panel of monoclonal antibodies to various keratins together with an anti-vimentin antibody to label mesenchymal cells were used to label cells attached to expanded polytetrafluorethylene (ePTFE) membranes removed 6 weeks postoperatively from 7 patients. All membranes demonstrated variable amounts of adherent tissue, within which vimentin-positive cells were detected. In 8 of the 18 samples, no epithelial cells were detected. Seven of the 18 samples demonstrated small groups of epithelial cells on both sides of the membranes, staining predominantly as basal cells. The remaining 3 samples were more densely populated by epithelium which expressed a diverse keratin profile. Thus, the membranes were successful in establishing mesenchymal cell proliferation, as evidenced by vimentin positivity, but did not totally exclude epithelium.

Title Increased Concentrations of Nitrite in Synovial Fluid and Serum Samples Suggest Increased Nitric Oxide Synthesis in Rheumatic Diseases.
Date January 1993
Journal Annals of the Rheumatic Diseases
Excerpt

Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) together with serum samples from healthy volunteers matched for age and sex. Serum nitrite concentrations in patients with RA and OA were significantly higher than in controls. In both disease groups synovial fluid nitrite was significantly higher than serum nitrite, implying nitric oxide synthesis by the synovium. Serum and synovial fluid nitrite concentrations in RA were also significantly higher than those in OA. These data show increased nitric oxide production in RA and OA and suggest a role for nitric oxide as an inflammatory mediator in rheumatic diseases.

Title Commentary on Viewpoint Article by A H Henderson, M J Lewis, A M Shah, and J A Smith (april, Pages 305-8)
Date January 1993
Journal Cardiovascular Research
Title Role of Nitric Oxide Synthesis in the Regulation of Coronary Vascular Tone in the Isolated Perfused Rabbit Heart.
Date December 1992
Journal Cardiovascular Research
Excerpt

The aim was to study the effects on coronary vascular tone of three inhibitors of nitric oxide (NO) synthesis.

Title Stimulation of Actin and Myosin Synthesis in Rat Gastrocnemius Muscle by Clenbuterol; Evidence for Translational Control.
Date December 1992
Journal Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology
Excerpt

1. A transient rise in fractional rates of protein and actomyosin synthesis was observed in gastrocnemius muscles of rats fed clenbuterol for 1-2 days but the muscle RNA:protein ratio was unchanged, therefore protein synthesis per unit RNA (kRNA) also increased. 2. Myosin heavy and light chains and actin showed increased incorporation of [3H]phenylalanine at 2 days; these changes were proportional to increases in total protein synthesis. 3. The ratios actin mRNA:18S RNA and fast myosin heavy chain mRNA:18S RNA were unaffected by clenbuterol. 4. The data suggest that the clenbuterol-induced increase in muscle protein synthesis involves both translational control and increased tissue RNA.

Title Glucocorticoids Do Not Affect the Induction of a Novel Calcium-dependent Nitric Oxide Synthase in Rabbit Chondrocytes.
Date November 1992
Journal Biochemical and Biophysical Research Communications
Excerpt

Incubation of rabbit articular chondrocytes with interleukin-1 beta caused time-dependent expression of NO synthase, determined as nitrite, after a lag period of 6h. The synthesis of nitrite was concentration-dependent and was inhibited by cycloheximide and NG-monomethyl-L-arginine, but not by dexamethasone or hydrocortisone. The synthesis of NO in the 100,000g supernatant of activated chondrocytes was inhibited by EGTA, but not by the calmodulin inhibitors W-13 or trifluoperazine. The synthesis of NO was half-maximal at approximately 20nM free Ca2+. Endotoxin also induced the expression of this NO synthase. Thus, rabbit articular chondrocytes express a novel inducible NO synthase which is Ca(2+)-dependent, and whose induction is not prevented by glucocorticoids.

Title Effect of the Beta-adrenoceptor Agonist Clenbuterol and Phytohaemagglutinin on Growth, Protein Synthesis and Polyamine Metabolism of Tissues of the Rat.
Date November 1992
Journal British Journal of Pharmacology
Excerpt

1. The kidney bean lectin, phytohaemagglutinin (PHA), induced a marked atrophy of skeletal muscle which was evident from the changes in tissue composition (protein, RNA, DNA and polyamine content) and from the reduction in weight and protein synthesis of hind leg muscles of rats fed on kidney bean-diets for four days. The beta-adrenoceptor agonist, clenbuterol, induced skeletal muscle hypertrophy by transiently stimulating protein synthesis. As a consequence, the muscle loss caused by a short exposure to PHA was, in part, ameliorated by clenbuterol treatment. 2. Cardiac muscle was affected to a lesser extent than skeletal muscle by both clenbuterol and the lectin. However, there was evidence that protein synthesis in heart was reduced by PHA. 3. PHA had opposite effects on the gut, the lectin-induced hyperplasia of the jejunum was accompanied by a large increase in protein synthesis. Clenbuterol alone had no effect on the jejunum whereas a combination of PHA and clenbuterol appeared to exacerbate the effect of the lectin on gut. 4. Both the lectin-induced gut growth and the hypertrophy of skeletal muscle caused by clenbuterol were preceded by the accumulation of polyamines in the respective tissues. Of particular note was the observation that a significant increase in the proportion of the intraperitoneally injected 14C-labelled spermidine or putrescine taken up by the growing tissues could be detected by the second day. Therefore, the measurement of uptake of labelled polyamines may be used as a sensitive indicator of early alterations in tissue metabolism.

Title The Role of Induction of Nitric Oxide Synthesis in the Altered Responses of Jugular Veins from Endotoxaemic Rabbits.
Date November 1992
Journal British Journal of Pharmacology
Excerpt

1. Endotoxaemia is characterized by hypotension, peripheral vasodilatation and a reduced response to vasoconstrictors. Clinical studies have indicated that venodilatation contributes to the haemodynamic changes, although there is no direct evidence for abnormal venous reactivity. In the present study, the role of nitric oxide (NO) in modifying the responses of rabbit isolated jugular veins was examined in vitro, 4 h after intravenous injection of endotoxin. 2. Treatment with endotoxin reduced the contractile response to the thromboxane-mimetic, 9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U-46619). This affect was endothelium-independent. The response was partially restored by the NO synthase inhibitor. NG-monomethyl-L-arginine (L-NMMA 300 microM). 3. Jugular veins from control animals did not contract to L-NMMA whereas those from endotoxin-treated animals showed concentration-dependent contractions to L-NMMA. The contractions produced by L-NMMA were reversed by L-arginine but not by D-arginine. Treatment of the animals with dexamethasone (4 mg kg-1) 1 h prior to administration of endotoxin significantly attenuated the response to L-NMMA. 4. The response to sodium nitroprusside did not differ significantly between veins from control and endotoxin-treated animals. Endothelial denudation did not alter the sensitivity of the veins to sodium nitroprusside. Acetylcholine produced endothelium-dependent relaxations which were similar in veins from control and endotoxin-treated animals. 5. The results of this study demonstrate that intravenous administration of endotoxin induces hyporesponsiveness to U-46619 in jugular veins. This effect is mediated, at least in part, by the induction of NO synthesis in smooth muscle. The induction is prevented by prior treatment with dexamethasone.

Title Interleukin-8 Inhibits the Induction of Nitric Oxide Synthase in Rat Peritoneal Neutrophils.
Date September 1992
Journal Biochemical and Biophysical Research Communications
Excerpt

The effect of interleukin(IL)-8 and leukotriene B4 (LTB4) on the induction of nitric oxide (NO) synthase in rat peritoneal neutrophils (PMN) ex vivo was studied. IL-8, but not LTB4, caused concentration-dependent inhibition of the induction of a Ca(2+)-independent NO synthase ex vivo. The effect of IL-8 was not attributable to the synthesis of an inhibitor of this enzyme. These findings suggest complex regulatory control of the induction of NO synthase by cytokines.

Title Nitric Oxide Synthase Inhibitors Cause Sustained, but Reversible, Hypertension and Hindquarters Vasoconstriction in Brattleboro Rats.
Date August 1992
Journal European Journal of Pharmacology
Excerpt

Homozygous male Brattleboro rats were given a solution of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) to drink for a period of 7 days. There was a persistent elevation of mean arterial blood pressure, accompanied by a significant hindquarters vasoconstriction. Within 9 h of withdrawal of L-NMMA all variables were not different from pre-L-NMMA values. Brattleboro rats (n = 3) which had been drinking NG-nitro-L-arginine methyl ester (L-NAME) solution (0.05 mg ml-1) for 5-6 months showed an increased blood pressure which reversed to normal within 48 h after withdrawing the L-NAME. Thus, inhibition of nitric oxide synthesis leads to long-lasting, but reversible, hypertension.

Title The Role of Nitric Oxide in Endothelial Cell Damage and Its Inhibition by Glucocorticoids.
Date July 1992
Journal British Journal of Pharmacology
Excerpt

Incubation of vascular endothelial cells with S.typhosa endotoxin and interferon-gamma caused a time- and concentration-dependent reduction in the viability of the cells. The cytotoxic effect was inhibited in a concentration-dependent manner by NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, and by the glucocorticoids dexamethasone and hydrocortisone, two inhibitors of the induction of NO synthase. These findings indicate that in these cells the cytotoxic effect of endotoxin is mediated by the NO synthesized by an inducible NO synthase. This induction of NO synthase in vascular endothelial cells may represent a mechanism of local endothelial damage during endotoxin shock and other immunologically based conditions.

Title Ridge Recontouring and Crown Lengthening Prior to Bridge Placement.
Date July 1992
Journal Restorative Dentistry
Excerpt

This report describes crown lengthening and ridge recontouring to facilitate the provision of an aesthetic bridge pontic. A short clinical crown on one of the abutment teeth and a prominent edentulous ridge were probably related to a traumatic episode which caused the avulsion of the missing incisor in childhood.

Title Nitric Oxide Functions As an Inhibitor of Platelet Adhesion Under Flow Conditions.
Date June 1992
Journal Circulation
Excerpt

Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation. An inhibitory role on platelet adhesion has been suggested from experiments with washed platelets under static conditions. We have determined whether endothelium-derived and exogenous NO also regulates platelet adhesion in whole blood under flow conditions.

Title Thermospray Tandem Mass Spectrometric Analysis of Oxygen Incorporation into Citrulline by Nitric Oxide Synthase.
Date June 1992
Journal Biological Mass Spectrometry
Excerpt

Citrulline is formed as a co-product in the biosynthesis of nitric oxide from L-arginine by the action of either constitutive or inducible nitric oxide synthase which is present in a variety of cells. We have previously shown that the oxygen atom incorporated into both nitric oxide and citrulline derives from molecular oxygen and not water. This paper describes the tandem mass spectrometric analysis of citrulline synthesized by the macrophage cell line J774 in the presence of native or guanidino-labelled arginine and air or isotopically enriched oxygen. The results confirm that oxygen is incorporated into the ureido position of citrulline.

Title Periodontal and Restorative Treatment in a Patient with Familial Gingival Fibromatosis: a Case Report.
Date June 1992
Journal Quintessence International (berlin, Germany : 1985)
Excerpt

A case is described in which excision of excess gingival tissue by conventional gingivectomy and simple restorative treatment with porcelain veneers produced a dramatic improvement in the patient's appearance with minimal sacrifice of sound tooth tissue.

Title Catalase Inhibits Nitric Oxide Synthesis and the Killing of Intracellular Leishmania Major in Murine Macrophages.
Date March 1992
Journal European Journal of Immunology
Excerpt

Mouse peritoneal macrophages activated with interferon-gamma (IFN-gamma) and lipopolysaccharide produce substantial amounts of nitric oxide (NO), which correlates with the elimination of the intracellular protozoan parasite Leishmania major. Both the production of NO and the leishmanicidal function of the activated macrophages can be significantly inhibited by catalase in a dose- and time-dependent manner. These results could not be interpreted by the reduction of H2O2 by catalase since the removal of H2O2 by the addition of glutathione peroxidase had no effect on the NO synthesis or the leishmanicidal function of activated macrophages. Furthermore, catalase did not affect the induction of NO synthase in IFN-gamma-activated macrophages. In contrast, the inhibition of NO synthesis and leishmanicidal activity by catalase was reversed in a dose-dependent manner by the addition of tetrahydrobiopterin, a cofactor of NO synthase. Taken together, these results not only further support the central role of NO as the cytotoxic moiety, but also suggest that hydrogen peroxide may interfere with NO production by affecting the levels of cofactor needed for its synthesis.

Title Coronary Vasodilatation Induced by Endotoxin in the Rabbit Isolated Perfused Heart is Nitric Oxide-dependent and Inhibited by Dexamethasone.
Date March 1992
Journal British Journal of Pharmacology
Excerpt

The coronary vasoconstriction induced by the thromboxane mimetic U46619 (9, 11 dideoxy methanoepoxy 9 alpha, 11 alpha prostaglandin F2 alpha, 3-30 nM) was significantly attenuated in hearts obtained from rabbits treated with endotoxin (lipopolysaccharide, LPS, 200 micrograms kg-1, i.v.) 4 h before isolation of the heart. Under these conditions the vasoconstriction induced by two inhibitors of nitric oxide (NO) synthase, NG-monomethyl-L-arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO) (1-100 microM for each) was significantly enhanced when compared to that induced in hearts from control animals. Both the decreased response to U46619 and the increased response to inhibitors of NO synthase were significantly attenuated by administration of dexamethasone (4 mg kg-1, i.v.) 90 min before treatment with LPS. These data are consistent with the induction, by LPS, of an NO synthase, and the inhibition of this induction by dexamethasone. The enhanced NO synthesis contributes to the haemodynamic changes known to occur in endotoxin shock.

Title Constitutive and Inducible Nitric Oxide Synthases Incorporate Molecular Oxygen into Both Nitric Oxide and Citrulline.
Date January 1992
Journal The Journal of Biological Chemistry
Excerpt

Nitric oxide (NO) is synthesized by a number of cells from a guanidino nitrogen atom of L-arginine by the action of either constitutive or inducible NO synthases, both of which form citrulline as a co-product. We have determined the source of the oxygen in both NO and in citrulline formed by the constitutive NO synthase from the vascular endothelium and brain and by the inducible NO synthase from the murine macrophage cell line J774. All these enzymes incorporate molecular oxygen both into NO and into citrulline. Furthermore, activated J774 cells form NO from omega-hydroxyl-L-arginine, confirming the proposal that this compound is an intermediate in the biosynthesis of NO.

Title Inhibition of Nitric Oxide Synthesis in Septic Shock: How Much is Beneficial?
Date January 1992
Journal Lancet
Excerpt

Hypotension in septic shock is often resistant to treatment with vasoconstrictors and appears to be mediated by production of nitric oxide (NO). Reversal of endotoxin-induced hypotension in rats was achieved by intravenous injection of 30 mg/kg NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endogenous NO synthesis. A lower dose of 3 mg/kg L-NMMA was ineffective, but 300 mg/kg L-NMMA accelerated and enhanced the fall in blood pressure. NO synthase inhibitors may be helpful in the treatment of hypotension associated with sepsis or therapeutic use of cytokines, but complete inhibition of endogenous NO synthesis may be counterproductive.

Title A New Technique of Local Anesthesia for Panretinal Photocoagulation.
Date January 1992
Journal Ophthalmic Surgery
Excerpt

We report a technique of local anesthetic administration used in 26 consecutive patients undergoing panretinal photocoagulation. A blunt-tipped irrigating cannula delivered 3 cc of anesthetic into the posterior sub-Tenon's space through a small opening in conjunctiva and Tenon's capsule. Immediate anesthesia, with no serious complications, was obtained in 38 of 40 eyes, facilitating administration of rapid, high-intensity laser burns. Although our experience with it is limited, we believe that this technique allows avoidance of many of the potential complications associated with the passage of a needle into the retrobulbar space.

Title Synthesis of Nitric Oxide in the Bovine Retina.
Date December 1991
Journal Biochemical and Biophysical Research Communications
Excerpt

In the absence of light, high concentrations of cGMP open ion channels in the plasma membranes of rod outer segments. The source of stimulation of retinal guanylate cyclase is not known. Nitric oxide is a potent stimulator of guanylate cyclase in other cell systems. The present data demonstrate that nitric oxide synthase, an enzyme responsible for the production of nitric oxide, is present in retina, and specifically in the rod outer segments. This enzyme uses L-arginine as a substrate and is NADPH- and calcium- dependent. L-arginine-derived nitric oxide may be a source of activation of guanylate cyclase in the retina.

Title Induction of Nitric Oxide Synthase in Rat Peritoneal Neutrophils and Its Inhibition by Dexamethasone.
Date November 1991
Journal European Journal of Immunology
Excerpt

Rat peritoneal polymorphonuclear leukocytes (PMN) elicited with oyster glycogen contain a Ca(2+)-independent nitric oxide (NO) synthase which is induced in vivo in a time-dependent manner. When washed PMN containing low levels of enzyme activity were cultured ex vivo further expression of NO synthase was observed. This was inhibited by cycloheximide indicating that de novo synthesis of the enzyme occurred during the ex vivo incubation. Enzyme activity was enhanced by interferon (IFN)-gamma, but not by tumor necrosis factor (TNF)-alpha when added ex vivo. However, IFN-gamma and TNF-alpha synergized to increase further the expression of NO synthase. Treatment of rats with dexamethasone inhibited the induction of NO synthase in elicited PMN. This treatment reduced the accumulation of PMN by approximately 30%, without affecting cell viability. Dexamethasone also inhibited the induction of the NO synthase ex vivo in a concentration-dependent manner. Furthermore, the enhanced enzyme activity following treatment of PMN with cytokines was also inhibited by dexamethasone. Once induced, dexamethasone did not affect enzyme activity. These data indicate that PMN elicited in the rat peritoneum with oyster glycogen express an NO synthase in vivo and ex vivo. The induction of the enzyme can be further stimulated ex vivo with IFN-gamma and TNF-alpha and inhibited by dexamethasone. The inhibition of the induction of NO synthase in the PMN by dexamethasone may contribute to the anti-inflammatory activity of this and other glucocorticoids.

Title Nitric Oxide: Physiology, Pathophysiology, and Pharmacology.
Date August 1991
Journal Pharmacological Reviews
Title Biosynthesis and Actions of Nitric Oxide.
Date August 1991
Journal Seminars in Perinatology
Title Inhibition of the Induction of Nitric Oxide Synthase by Glucocorticoids: Yet Another Explanation for Their Anti-inflammatory Effects?
Date August 1991
Journal Trends in Pharmacological Sciences
Title Modulation of Platelet Aggregation by an L-arginine-nitric Oxide Pathway.
Date July 1991
Journal Trends in Pharmacological Sciences
Title Dexamethasone-induced Catabolism and Insulin Resistance in L6 Myoblasts Are Reversed by the Removal of Serum.
Date July 1991
Journal Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology
Excerpt

1. One hundred nanomolar dexamethasone reduced protein synthesis by 16% and also decreased the accretion of protein and RNA in L6 myoblasts when foetal calf serum was present; these effects were reversed when serum was omitted from the medium. 2. Insulin (100 microU/ml) increased protein synthesis, protein accretion and RNA accretion both in the presence and the absence of serum. 3. Dexamethasone inhibited the effects of 100 microU insulin/ml in the presence of serum and induced insulin resistance; in the presence of 25 or 100 nM dexamethasone insulin was ineffective at concentrations below 250 microU and 1 mU/ml respectively.

Title Identification of N-iminoethyl-l-ornithine As an Irreversible Inhibitor of Nitric Oxide Synthase in Phagocytic Cells.
Date July 1991
Journal British Journal of Pharmacology
Excerpt

1. The synthesis of nitric oxide (NO) from L-arginine by rat peritoneal neutrophils (PMN) and the murine macrophage cell-line J774 and the inhibition of this synthesis by N-iminoethyl-L-ornithine (L-NIO), NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine (L-NNA) and its methyl ester (L-NAME) were investigated. 2. L-NIO was the most potent inhibitor in both types of cells while L-NMMA was less active. L-NNA and L-NAME had no significant effect in PMN and L-NNA produced only approximately 40% inhibition of the generation of NO in the J774 cells at the highest concentration tested (300 microM). 3. The inhibitory effect of L-NIO was rapid in onset, requiring 10 min pre-incubation to achieve its full inhibitory activity, while the other compounds required 20-60 min pre-incubation to achieve their full effect. 4. The inhibitory effect of L-NIO (10 microM) on intact cells could not be reversed by L-arginine (300 microM) but could be prevented by concomitant incubation with this compound (300 microM), while the effect of the other inhibitors could be reversed by a 3-5 fold molar excess of L-arginine. 5. The NO synthase from both PMN and J774 cells was cytosolic and NADPH- but not Ca2(+)-dependent, with Km values for L-arginine of 3.3 +/- 0.8 and 4.2 +/- 1.1 microM respectively. 6. L-NIO was the most potent inhibitor of the neutrophil and J774 enzymes with IC50 values of 0.8 +/- 0.1 and 3 +/- 0.5 microM respectively. Furthermore, the effect of L-NIO was irreversible. The other three compounds were less potent, reversible inhibitors. 7. The inhibitory effects of all these compounds were enantiomerically specific. 8. These data indicate that L-NIO is a novel, potent, rapid in onset and irreversible inhibitor of NO synthase in phagocytic cells. The rapid uptake of L-NIO compared with the other compounds indicates that phagocytic cells have different uptake mechanisms for L-arginine analogues.

Title Effects of Inhibition of Nitric Oxide Formation on Basal Vasomotion and Endothelium-dependent Responses of the Coronary Arteries in Awake Dogs.
Date July 1991
Journal The Journal of Clinical Investigation
Excerpt

The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses greater than or equal to 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular end-diastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest does of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholine-stimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions.

Title Effects of the Cyclo-oxygenase Inhibitor, Fenbufen, on Clenbuterol-induced Hypertrophy of Cardiac and Skeletal Muscle of Rats.
Date May 1991
Journal British Journal of Pharmacology
Excerpt

1. When rats were fed with clenbuterol for 7 days skeletal muscle mass increased by 21% in the tonic soleus and phasic plantaris muscles and a 16% hypertrophy of the heart was also induced. Fenbufen, fed to rats for the same period, blocked the hypertrophy of the heart but not that of the skeletal muscles. 2. When feeding of fenbufen commenced 3 days before the administration of clenbuterol, plasma prosta-glandin F2 alpha (PGF2 alpha) was reduced by 79%; there was again no effect of fenbufen on clenbuterol-induced increases in the RNA or protein content of plantaris, nor in the increased area of fast or slow twitch fibres in the soleus. In the heart the clenbuterol-induced increases in the RNA (+21%) and protein content (+20%) were totally inhibited. 3. The effects of clenbuterol on heart muscle appear to be mediated by a cyclo-oxygenase metabolite of arachidonic acid whilst the effects on skeletal muscle are not.

Title Development and Mechanism of a Specific Supersensitivity to Nitrovasodilators After Inhibition of Vascular Nitric Oxide Synthesis in Vivo.
Date April 1991
Journal Proceedings of the National Academy of Sciences of the United States of America
Excerpt

The mechanism of the increased sensitivity to nitrovasodilators after removal of endothelial nitric oxide (NO) was investigated in vitro and in vivo. The vasoconstrictor potency of phenylephrine and the force of contraction of rat isolated aortic rings were significantly enhanced after endothelium removal or treatment with inhibitors of endothelial NO synthase. Furthermore, these procedures led to a significant decrease in the basal levels of cGMP in the vascular rings. Moreover, the potency of glyceryl trinitrate (n3Gro) and sodium nitroprusside (SNP) as relaxing agents and the ability of SNP to induce increases in cGMP in aortic rings were significantly enhanced in those rings denuded of endothelium or treated with the inhibitors. These procedures did not affect the vasodilator actions of isoprenaline or 8-bromo-cGMP. In the anesthetized rat, treatment with the inhibitors enhanced significantly the hypotensive responses to n3Gro without affecting those to isoprenaline. These data indicate that the removal of the basal NO-mediated vasodilator tone in the cardiovascular system leads, at the level of the soluble guanylate cyclase, to a specific supersensitivity to nitrovasodilators in vivo. The existence of such a phenomenon has important implications for understanding the local physiological control of blood flow, its pathological disturbances, and the mechanism of action of nitrovasodilators.

Title Characterization of Three Inhibitors of Endothelial Nitric Oxide Synthase in Vitro and in Vivo.
Date April 1991
Journal British Journal of Pharmacology
Excerpt

1. Three analogues of L-arginine were characterized as inhibitors of endothelial nitric oxide (NO) synthase by measuring their effect on the endothelial NO synthase from porcine aortae, on the vascular tone of rings of rat aorta and on the blood pressure of the anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO) and NG-nitro-L-arginine methyl ester (L-NAME; all at 0.1-100 microM) caused concentration-dependent inhibition of the Ca2(+)-dependent endothelial NO synthase from porcine aortae. 3. L-NMMA, L-NIO and L-NAME caused an endothelium-dependent contraction and an inhibition of the endothelium-dependent relaxation induced by acetylcholine (ACh) in aortic rings. 4. L-NMMA, L-NIO and L-NAME (0.03-300 mg kg-1, i.v.) induced a dose-dependent increase in mean systemic arterial blood pressure accompanied by bradycardia. 5. L-NMMA, L-NIO and L-NAME (100 mg kg-1, i.v.) inhibited significantly the hypotensive responses to ACh and bradykinin. 6. The increase in blood pressure and bradycardia produced by these compounds were reversed by L-arginine (30-100 mg kg-1, i.v.) in a dose-dependent manner. 7. All of these effects were enantiomer specific. 8. These results indicate that L-NMMA, L-NIO and L-NAME are inhibitors of NO synthase in the vascular endothelium and confirm the important role of NO synthesis in the maintenance of vascular tone and blood pressure.

Title Nitric Oxide and Prostacyclin. Divergence of Inhibitory Effects on Monocyte Chemotaxis and Adhesion to Endothelium in Vitro.
Date April 1991
Journal Arteriosclerosis and Thrombosis : a Journal of Vascular Biology / American Heart Association
Excerpt

Monocyte-endothelial interactions are of fundamental importance in determining the movement of monocytes from the blood stream into the vessel wall. This study reports that two endothelium-derived factors, nitric oxide and prostacyclin, alter in vitro monocyte behavior. Nitric oxide (greater than 10(-5) M) inhibited monocyte adhesion to porcine aortic endothelial cell monolayers, whereas prostacyclin (10(-9) to 10(-5) M) had no effect. Both nitric oxide and prostacyclin inhibited monocyte chemotaxis stimulated by N-formyl-methionyl-leucyl-phenylalanine and induced dose-dependent increases in intracellular cyclic guanosine monophosphate and cyclic adenosine monophosphate concentrations, respectively. The cell surface expression of the CD11b/CD18 adhesion receptor, a glycoprotein complex known to mediate monocyte intracellular adhesion, was not altered by either nitric oxide or by prostacyclin. Thus, endothelium-derived nitric oxide and prostacyclin may have a physiological role in modulating monocyte-vascular wall interactions. Alterations in this system may contribute to the increased monocyte emigration from the blood stream into the vessel wall observed in atherogenesis.

Title The Role of Nitric Oxide in Mediating Endothelium Dependent Relaxations in the Human Epicardial Coronary Artery.
Date March 1991
Journal International Journal of Cardiology
Excerpt

We have examined the ability of the endothelium of human epicardial coronary arteries to secrete vasorelaxant substances in response to pharmacological stimulation and under basal conditions. In addition, we have attempted to characterise the chemical identity and biochemical pathway for the synthesis of endothelial derived relaxing factor. Human epicardial coronary arteries were removed from patients who were undergoing heart transplantation for reasons other than ischaemic heart disease. Arteries were cut into segments and suspended in 5 ml organ baths containing a modified Tyrodes solution at 37 degrees C, and gassed with a mixture of 95% oxygen and 5% carbon dioxide. Substance P (10(-10) - 10(-7) M) elicited a dose-dependent relaxation of the coronary segments but this action of substance P was dependent upon an intact endothelium. The maximum response of substance P was equivalent to 89 +/- 8.5% of the maximum effect induced by 1 microgram/ml glyceryl trinitrate. This vasorelaxant effect of substance P was unaffected by the presence of 10(-6) M indomethacin. L-NG-monomethyl-arginine (10(-4) M), a specific inhibitor of formation of nitric oxide from L-arginine, antagonised the relaxations induced by substance P, decreasing the maximum response of substance P to 34 +/- 10.5% of the response to glyceryl trinitrate. Upon application, L-NG-monomethyl-arginine caused a further 23.1 +/- 3.0 increase in tension on preconstricted vessels. This increase in tension was reversed with the addition of L-arginine, but was unaffected by D-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Regional Haemodynamic Changes During Oral Ingestion of Ng-monomethyl-l-arginine or Ng-nitro-l-arginine Methyl Ester in Conscious Brattleboro Rats.
Date March 1991
Journal British Journal of Pharmacology
Excerpt

Homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler probes and intravascular catheters to permit continuous monitoring of regional haemodynamics. Over a 9 h period, rats drinking water showed no systematic changes in heart rate or mean arterial blood pressure although renal, mesenteric and hindquarters vascular conductances fell. These changes showed diurnal rhythms, probably related to the nocturnal habits of rats. In separate groups of animals spontaneous oral ingestion of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) or NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg ml-1) caused marked hypertension but no significant bradycardia. Compared to control animals, rats drinking L-NMMA for 9 h showed significantly greater mesenteric and hindquarters vasoconstrictions, and rats drinking L-NAME showed greater vasoconstrictions in all 3 vascular beds.

Title Glucocorticoids Inhibit the Expression of an Inducible, but Not the Constitutive, Nitric Oxide Synthase in Vascular Endothelial Cells.
Date February 1991
Journal Proceedings of the National Academy of Sciences of the United States of America
Excerpt

Vascular endothelial cells contain a constitutive nitric oxide (NO) synthase that is Ca2(+)-dependent. In addition, we have found that these cells express, after activation with interferon-gamma and lipopolysaccharide, an inducible Ca2(+)-independent NO synthase that is distinct from the constitutive enzyme. The generation of NO by this enzyme was detectable after a lag period of 2 hr, reached a maximum between 6 and 12 hr, and was maintained for the duration of the experiment (48 hr). The expression of the inducible NO synthase was inhibited by the protein synthesis inhibitor cycloheximide, a compound that had no direct effect on the activity of either of the two enzymes. Furthermore, hydrocortisone and dexamethasone, but not progesterone, inhibited the expression of the inducible enzyme, without directly affecting the activity of either enzyme, without directly affecting the activity of either enzyme. The effect of these steroids was inhibited in a concentration-dependent manner by cortexolone, a partial agonist of glucocorticoid receptors. Thus, the inhibition of the induction of an NO synthase by glucocorticoids is a receptor-mediated event involving the inhibition of the synthesis of mRNA for de novo synthesis of this enzyme. The induction of this NO synthase may contribute to the pathophysiology of immunologically based conditions. Furthermore, the inhibition of this induction by anti-inflammatory steroids may explain some of the therapeutic and adverse effects of these compounds.

Title Acute Effects of Corticosterone on Tissue Protein Synthesis and Insulin-sensitivity in Rats in Vivo.
Date February 1991
Journal The Biochemical Journal
Excerpt

The effect of corticosterone treatment on the sensitivity of muscle protein synthesis to insulin infusion was assessed in post-absorptive young rats. To select the optimal time period for corticosterone treatment, protein synthesis was measured by injection of L-[2,6-3H]phenylalanine (1.5 mmol/kg body weight) 1, 4, 12 or 24 h after injection of corticosterone (5 mg/kg body wt.). Muscle protein synthesis was significantly decreased at 4 h and the effect was maximal by 12 h; liver protein synthesis was elevated at 12 h and 24 h. The dose-response of muscle protein synthesis to a 30 min infusion with 0-150 munits of insulin/h was then compared in rats pretreated with corticosterone (10 mg/100 g body wt.) or vehicle alone. When no insulin was infused, corticosterone inhibited protein synthesis in gastrocnemius muscle. High doses of insulin stimulated protein synthesis, but the inhibition by corticosterone was similar to that in the absence of insulin. At intermediate doses of insulin there was an increased requirement for insulin to elicit an equivalent response in muscle protein synthesis. Plantaris muscle responded in a manner similar to that of gastrocnemius, but neither soleus muscle nor liver responded significantly to insulin. These data suggest that corticosterone has two modes of action; one which is independent from and opposite to that of insulin, and a second which causes insulin-resistance through a decrease in sensitivity rather than a change in responsiveness.

Title The Crucial Role of Physiological Ca2+ Concentrations in the Production of Endothelial Nitric Oxide and the Control of Vascular Tone.
Date January 1991
Journal British Journal of Pharmacology
Excerpt

1. The effect of varying the extracellular Ca2+ concentration on the basal and acetylcholine (ACh)-induced release of nitric oxide (NO) from the rabbit aorta was investigated by use of a superfusion bioassay system. 2. Changes between 0.5 and 2.0 mM in the concentration of Ca2+ superfusing the detector bioassay tissues or perfusing endothelium-denuded donor aortae had no effect on the tone of these tissues. 3. Increasing the concentration of Ca2+ perfusing endothelium-containing donor aortae from zero to 1.25 mM caused a transient (24 +/- 9 min), concentration-dependent basal release of NO, which was attenuated at higher concentrations of Ca2+ (1.5-2.0 mM). 4. The duration of the effect of Ca2+ on the basal release of NO was increased by a concomitant infusion of L-arginine (100 microM) through the donor aorta. 5. Changes in the concentration of Ca2+ between 0.5 and 2.0 mM had a similar biphasic effect on the release of NO induced by ACh, which was also maximal at 1.25 mM Ca2+. 6. When Ca2+ was removed from the Krebs buffer perfusing the donor aorta, the basal release of NO declined within 2 min. In contrast, the release of NO induced by ACh declined progressively over 60 min. 7. Thus changes in the concentration of Ca2+ around the physiological range modulate the synthesis of NO by the vascular endothelium and consequently, vascular tone. This may account for the effects of dietary Ca2+ supplements on the control of some hypertensive states.

Title Dexamethasone Prevents the Induction by Endotoxin of a Nitric Oxide Synthase and the Associated Effects on Vascular Tone: an Insight into Endotoxin Shock.
Date January 1991
Journal Biochemical and Biophysical Research Communications
Excerpt

The relationship between vascular tone and the induction by endotoxin of a nitric oxide (NO) synthase was studied in vitro in rings of rat thoracic aorta. In rings with and without endothelium there was a time-dependent induction of NO synthase accompanied by both spontaneous and L-arginine-induced relaxation and by reduced contractility to phenylephrine. These effects, which were attributable to the presence of endotoxin in the Krebs' buffer, were attenuated by cycloheximide, polymyxin B and inhibitors of NO synthase. Furthermore, dexamethasone inhibited the induction of NO synthase and the consequent effects on vascular tone. These findings indicate that prevention of the induction of NO synthase by glucocorticoids may be an important component of their therapeutic action.

Title Control of Regional Blood Flow by Endothelium-derived Nitric Oxide.
Date May 1990
Journal Hypertension
Excerpt

The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation with NG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3-300 mg/kg) caused a dose-dependent, long-lasting (5-90 minutes), and enantiomerically specific increase in mean blood pressure and also caused bradycardia. The increase in blood pressure was accompanied by a dose-dependent and long-lasting vasoconstriction in the internal carotid, mesenteric, renal, and hindquarters vascular beds that could be attenuated, in a concentration-dependent manner, by L-arginine but not by D-arginine. In contrast, L-arginine did not affect the pressor or vasoconstrictor effects of vasopressin. These results indicate that nitric oxide production by vascular endothelial cells contributes to the maintenance of blood pressure and to the control of the resting tone of different vascular beds in the conscious rat.

Title Role of Endothelium-derived Relaxing Factor in Regulation of Renal Hemodynamic Responses.
Date April 1990
Journal The American Journal of Physiology
Excerpt

An endothelium-derived relaxing factor (EDRF) has recently been identified as nitric oxide (NO), originating from endothelial cell metabolism of L-arginine. In vitro studies suggest that EDRF/NO stimulates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels in vascular smooth muscle cells, resulting in the vasorelaxant effects of endothelium-dependent vasodilators such as acetylcholine (ACh). The importance of EDRF/NO in normal physiology or disease states remains uncertain. We therefore investigated the relationship between ACh-induced hemodynamic responses, synthesis of EDRF/NO, and changes in the rate of urinary cGMP excretion in the anesthetized rat in vivo. Intravenous infusion of ACh resulted in hypotension, maintenance of glomerular filtration rate, and renal vasodilatation. ACh induced a dose-dependent increase in urinary cGMP excretion, an effect that was not observed with equihypotensive doses of the endothelium-independent vasodilator, prostacyclin. Rates of cGMP excretion were significantly correlated with the fall in systemic blood pressure induced by ACh. Treatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of enzymatic synthesis of nitric oxide from L-arginine, prevented the ACh-induced increase in urinary cGMP excretion as well as the systemic and renal hemodynamic effects of ACh. Plasma levels of atrial natriuretic peptide were unchanged by ACh infusion. Intravenous infusion of L-NMMA was associated with increased blood pressure and decreased basal rates of urinary cGMP excretion. This hypertensive effect was reversed by administration of L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Ng-monomethyl-l-arginine Does Not Inhibit the Hindquarters Vasodilator Action of Endothelin-1 in Conscious Rats.
Date March 1990
Journal European Journal of Pharmacology
Excerpt

Regional haemodynamic responses to endothelin-1 were assessed in conscious, unrestrained Long Evans rats, chronically instrumented with pulsed Doppler flow probes. Bolus injection of endothelin-1 (0.04 nmol) caused an early transient hypotension and increase in hindquarters vascular conductance. In the presence of NG-monomethyl-L-arginine (L-NMMA), which inhibits endothelial cell nitric oxide production, the hindquarters vasodilator response to endothelin-1 was unchanged and similar to that seen in the presence of vasopressin when the latter was infused to simulate the pressor effects of L-NMMA. These results indicate that the hindquarters vasodilatation in response to endothelin-1 is not dependent upon release of nitric oxide from endothelial cells.

Title The Cyclo-oxygenase Inhibitors Indomethacin and Ibuprofen Inhibit the Insulin-induced Stimulation of Ribosomal Rna Synthesis in L6 Myoblasts.
Date January 1990
Journal The Biochemical Journal
Excerpt

Insulin stimulated total RNA accretion and the incorporation of [3H]uridine into RNA in L6 skeletal-muscle myoblasts. Incorporation of uridine into the rRNA was measured after either separation of 18 S and 28 S rRNA species by agarose-gel electrophoresis or separation of dissociated 40 S and 60 S ribosomal subunits on sucrose density gradients. Both methods showed a stimulation by insulin of uridine incorporation into the RNA of the two subunits. Two non-steroidal anti-inflammatory drugs, indomethacin and ibuprofen, which inhibit the metabolism of arachidonic acid by the cyclo-oxygenase pathway, inhibited the insulin-induced accretion of total cellular RNA and the incorporation of uridine into the RNA of both ribosomal subunits. The effect of insulin was observed both by using a tracer dose of [3H]uridine (5 microM) and in the presence of a high concentration (1 mM) of uridine to minimize possible changes in intracellular precursor pools. Neither insulin nor indomethacin was found to affect the incorporation of uridine into the total intracellular nucleotide pool, or the conversion of uridine into UTP. The ability of inhibitors of arachidonic acid metabolism to prevent insulin-induced increases in RNA metabolism suggests that a prostaglandin or other eicosanoid is involved in the signal mechanism whereby insulin stimulates RNA synthesis.

Title The Impact of the Prospective Payment System on the Treatment of Hip Fractures in the Elderly.
Date November 1989
Journal Archives of Internal Medicine
Excerpt

A review of 386 Medicare patients with hip fractures admitted to a private, suburban, teaching hospital from 1981 through 1987 revealed that since the implementation of the prospective payment system in 1984, average hospital stays declined from 17.0 days to 12.9 days (24.1%). Although the mean number of physical therapy sessions declined from 11.1 to 9.8 (11.7%), the average number of treatments per day during the physical therapy phase actually increased from 1.2 before to 1.4 after the prospective payment system. The proportion of patients discharged to nursing homes remained the same (52.9% vs 53.6%); the proportion of patients remaining in a nursing home 6 months after hospital discharge did not differ significantly (22.6% vs 19.9%). Furthermore, there were no differences in the 6-month ambulation status. Total adjusted average hospital charges for the pre- and post-prospective payment system groups did not increase significantly ($7295 vs $7565). These findings do not support the contention that the quality of care provided Medicare patients with hip fractures has deteriorated in this hospital environment.

Title Indomethacin Inhibits the Insulin-induced Increases in Rna and Protein Synthesis in L6 Skeletal Muscle Myoblasts.
Date July 1989
Journal Prostaglandins
Excerpt

Rates of accretion of RNA and protein and rates of protein synthesis were measured in sub-confluent cultures of L6 myoblasts. Insulin (100 microU/ml) stimulated protein synthesis by 15% within 30 min and by 40% at two and six hours. By six hours insulin also increased the accretion of RNA (+15%). The cyclo-oxygenase inhibitor indomethacin did not reduce the basal rate of RNA or protein accretion in L6 cells but reduced the rate of protein synthesis by 16%. When added together with insulin, indomethacin inhibited the hormonally-stimulated rate of protein synthesis and also significantly reduced the accretion of RNA. Indomethacin still reduced the effects of insulin on protein synthesis when added to the cells two hours after the hormone. Synthesis of RNA measured by the incorporation of [3H]-uridine was also stimulated by insulin but was inhibited by indomethacin only when the drug was present throughout the incubation. Inhibition of protein synthesis by cyclo-oxygenase inhibitors may be the result of both a direct action on translational efficiency and an effect on RNA synthesis.

Title Effect of Timing and Number of Baseline Blood Pressure Determinations on Postural Blood Pressure Response.
Date May 1989
Journal Journal of the American Geriatrics Society
Excerpt

We hypothesized that the blood pressure response to standing may depend on the method of establishing baseline blood pressure. Three hundred elderly subjects previously completed a postural blood pressure protocol with three supine baseline blood pressure readings obtained two minutes apart prior to standing. Comparison of the readings showed a significant drop between the first and the second (P less than .001) but not between the second and third supine systolic blood pressures. The difference between the first supine systolic blood pressure and the one minute standing blood pressure was significantly greater than that between the third supine systolic blood pressure and the one minute standing blood pressure (P less than .001). A second group was prospectively studied to determine whether the change in blood pressure after standing was greater if only a single baseline reading was taken rather than multiple readings, and whether the decline in blood pressure over three readings was related to duration supine or to the number of blood pressures taken. This group also demonstrated a decline in systolic blood pressure with three serial readings. We conclude that supine blood pressure declines significantly between the first and second readings taken two minutes apart and is secondary to the repetition of readings and not the duration supine. However, this change in supine blood pressure does not significantly alter the blood pressure response to standing. Thus, it appears that a single baseline supine blood pressure measurement is adequate for determining the postural blood pressure response, and that pooling of multiple baseline readings may not be appropriate.

Title Steatosis and Cirrhosis in an Obese Diabetic. Resolution of Fatty Liver by Fasting.
Date May 1987
Journal Digestive Diseases and Sciences
Excerpt

A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.

Title The Effect of Insulin and Intermittent Mechanical Stretching on Rates of Protein Synthesis and Degradation in Isolated Rabbit Muscle.
Date November 1985
Journal The Biochemical Journal
Excerpt

Tyrosine balance and protein synthesis were studied during the same incubation in isolated rabbit forelimb muscles. From these measurements, protein degradation was calculated. Isolated muscles were usually in a state of negative amino acid balance, principally as a result of the 75% decrease in protein synthesis. Muscles from rabbits starved for 18 h had lower rates of both protein synthesis and degradation compared with muscles from normally fed rabbits. Intermittent mechanical stretching and the addition of insulin at 100 microunits/ml increased rates of both protein synthesis and degradation. Increases in the rate of protein synthesis were proportionately greater in the muscles from starved animals. In muscles from both fed and starved donors, increases in protein-synthesis rates owing to intermittent stretching and insulin were proportionately greater than the increases in degradation rates. For example, insulin increased the rate of protein synthesis in the muscles from starved donors by 111% and the rate of degradation by 31%. Insulin also increased the rate of protein synthesis when added at a higher concentration (100 munits/ml); at this concentration, however, the rate of protein degradation was not increased. The suppressive effect of insulin on high rates of protein degradation in other skeletal-muscle preparations may reflect a non-physiological action of the hormone.

Title The Influence of Changes in Tension on Protein Synthesis and Prostaglandin Release in Isolated Rabbit Muscles.
Date November 1983
Journal The Biochemical Journal
Excerpt

Intermittent stretching of isolated rabbit muscles increased the rate of protein synthesis by 70% and prostaglandin-F2 alpha release by 105%. Both effects of intermittent stretching were blocked by indomethacin and meclofenamate; the absence of Ca2+ together with added EGTA also inhibited both processes. The residual influence of intermittent stretching on protein synthesis was closely correlated with prostaglandin-F2 alpha release, which may be the link between mechanical activity and protein synthesis in skeletal muscle.

Title Protein Synthesis in Isolated Rabbit Forelimb Muscles. The Possible Role of Metabolites of Arachidonic Acid in the Response to Intermittent Stretching.
Date October 1983
Journal The Biochemical Journal
Excerpt

Protein synthesis was measured in isolated intact rabbit muscles by the incorporation of [3H]phenylalanine added at a high concentration (2.5 mM) to the incubation medium. Intermittent mechanical stretching substantially increased the rate of protein synthesis relative to that in control muscles incubated under a constant tension. Indomethacin and meclofenamic acid, inhibitors of the enzyme cyclo-oxygenase, which converts free arachidonic acid into the prostaglandins, prostacyclins and thromboxanes, decreased the rate of protein synthesis in intermittently stretched muscles, but had no effect on synthesis rates in the unstimulated controls. Arachidonic acid at concentrations of 0.2 and 1.0 microM gave a highly significant increase in the rate of protein synthesis in muscles incubated under a constant tension. The ability of arachidonic acid to increase protein-synthesis rates was abolished by the addition of indomethacin. Activation of protein synthesis by intermittent stretching persisted for 10-20 min after the stretch stimulation had ceased. Indomethacin, added either during the initial incubation with intermittent stretching or during the subsequent period when protein synthesis was measured after stimulation had ceased, decreased protein-synthesis rates. This decrease was similar whether indomethacin was present during the initial, final or entire incubation period. In experiments analogous with those in (4) above, when Ca2+ was withheld and EGTA added for the entire incubation, rates of protein synthesis were again decreased. The rates of protein synthesis observed when Ca2+ was present during either an initial stimulation phase or a final, unstimulated, measurement phase were similar, and were intermediate between control rates and those in muscles incubated without Ca2+ for the whole experiment. Two prostaglandins, F2 alpha (2.8 microM) and A1 (28 microM), increased rates of protein synthesis in unstimulated muscles, but prostaglandins E2 and D2 and the leukotrienes C4 and D4 failed to do so. It is concluded that the stretch-stimulated increase in protein synthesis may be caused by activation of membrane phospholipases, release of arachidonic acid and a consequent increase in prostaglandin synthesis.

Title The Effect of Intermittent Changes in Tension on Protein and Collagen Synthesis in Isolated Rabbit Muscles.
Date March 1982
Journal The Biochemical Journal
Excerpt

Isolated intact rabbit muscles were incubated in a medium containing radioactive proline. The rates of synthesis of collagen and total muscle protein after incubation with a constant tension or intermittent mechanical stretching were compared with the rates in vivo. Muscles incubated under a constant tension synthesized protein at 22% of the rate observed in vivo; intermittent mechanical stretching resulted in an increase of 73% in the rate of protein synthesis, to 38% of that found in vivo. Collagen synthesis was affected in the same way as total protein synthesis by both types of incubation, therefore the relative rates of collagen and total protein synthesis were unchanged. ATP concentration in the isolate muscles and the uptake of glucose from the medium were increased by intermittent mechanical stretching. Incubating the muscles with a gas phase containing 5% O2 decreased the rate of protein synthesis, abolished the effect of intermittent mechanical stretching, lowered the concentration of ATP and increased the lactate concentration. The rate of protein synthesis in muscles maintained with a constant or intermittently applied tension was not affected by a previous period of incubation with the other type of stimulus.

Title Protein and Collagen Synthesis in Isolated Rabbit Muscles: Effects of Changes of Tension in Vitro [proceedings].
Date July 1980
Journal Biochemical Society Transactions
Title Protein and Collagen Synthesis in Rat Diaphragm Muscle Incubated in Vitro: the Effect of Alterations in Tension Produced by Electrical or Mechanical Means.
Date April 1980
Journal The International Journal of Biochemistry
Title The Influence of Nicotine on Granulocytic Differentiation - Inhibition of the Oxidative Burst and Bacterial Killing and Increased Matrix Metalloproteinase-9 Release.
Date
Journal Bmc Cell Biology
Excerpt

BACKGROUND: Neutrophils leave the bone marrow as terminally differentiated cells, yet little is known of the influence of nicotine or other tobacco smoke components on neutrophil differentiation. Therefore, promyelocytic HL-60 cells were differentiated into neutrophils using dimethylsulfoxide in the presence and absence of nicotine (3-(1-methyl-2-pyrrolidinyl) pyridine). Differentiation was evaluated over 5 days by monitoring terminal differentiation markers (CD11b expression and formazan deposition); cell viability, growth phase, kinetics, and apoptosis; assessing cellular morphology and ultrastructure; and conformational changes to major cellular components. Key neutrophil effector functions (oxidative burst, bacterial killing, matrix metalloproteinase release) were also examined. RESULTS: Nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone (p < 0.05), but did not affect any other marker of neutrophil differentiation examined. However, nicotine exposure during differentiation suppressed the oxidative burst in HL-60 cells (p < 0.001); inhibited bacterial killing (p < 0.01); and increased the LPS-induced release of MMP-9, but not MMP-2 (p < 0.05). These phenomena may be alpha-7-acetylcholine nicotinic receptor-dependent. Furthermore, smokers exhibited an increased MMP-9 burden compared to non-smokers in vivo (p < 0.05). CONCLUSION: These findings may partially explain the known increase in susceptibility to bacterial infection and neutrophil-associated destructive inflammatory diseases in individuals chronically exposed to nicotine.

Title Factors Affecting Survival and Usefulness of Implants Placed in Vascularized Free Composite Grafts Used in Post-head and Neck Cancer Reconstruction.
Date
Journal Clinical Implant Dentistry and Related Research
Excerpt

ABSTRACT Background: Bone-containing vascularized grafts have been used successfully to reconstruct post-cancer surgical defects. Dental implants can be placed in these bone-containing grafts to allow implant-supported prosthodontic reconstruction of these patients. Purpose: The aim of this study was to evaluate the survival of dental implants used in the rehabilitation of subjects treated with bone-containing vascularized grafts to compare usability of implants placed at the time of reconstruction and after healing. Materials and Methods: A cross-sectional study was undertaken to examine survival rates of implants placed in vascularized bone-containing grafts either immediately at the time of surgical reconstruction or after 3 months healing. Other factors such as graft type, whether radiation therapy was given, and implant type were recorded. Results: A total of 41 patients had 145 implants placed in 47 vascularized bone-containing flaps. Increased failure rate of implants was seen in immediately placed implants. There was also a significant increase in the number of osseointegrated implants that were prosthodontically unusable or sub-optimally placed in the immediate placement group. Radiation therapy was associated with a significant increase in failure rate. Modern implant surfaces appeared to perform better than machined/turned surfaces. Graft donor site did not influence implant survival. Conclusion: This study demonstrated the difficulties encountered with immediate placement of dental implants at the time of post-cancer reconstructive surgery.

Title The Acute Influence of Tobacco Smoking on Adhesion Molecule Expression on Monocytes and Neutrophils and on Circulating Adhesion Molecule Levels in Vivo.
Date
Journal Addiction Biology
Excerpt

Abstract Soluble adhesion molecules have been reported as risk markers of a wide range of human diseases and specific adhesion molecules may play a direct role in pathological processes. Serum soluble intercellular adhesion molecule-1 (sICAM-1) is known to be significantly elevated in smokers compared to non-smokers. We examined the acute effects of smoking a standard 2R1 research cigarette on the serum concentration of sICAM-1 and other circulating adhesion molecules (sP-selectin, sE-selectin, sL-selectin, sVCAM-1 and sPECAM-1) in heavy smokers (serum cotinine >/= 100 ng/ml), light smokers (serum cotinine </= 60 ng/ml) and non-smokers (serum cotinine </= 10 ng/ml) by ELISA. Adhesion molecule expression on the cell surface of monocytes and neutrophils in peripheral blood was examined by flow cytometry. The sICAM-1 concentration directly correlated to serum cotinine concentration (p= 0.047) and nicotine load (p= 0.033) in smokers and was significantly elevated compared to non-smokers (p= 0.037). Other than a decrease in the concentration of sP-selectin over 1 hour regardless of smoking, no significant temporal alterations of any adhesion molecule were observed following the smoking experience or in the non-smoking control group. No significant difference in surface expression of ICAM-1, CD18, PECAM-1 or L-selectin on peripheral monocytes or neutrophils was observed over a 1-hour period following smoking. These data suggest that the elevated concentration of sICAM-1 in smokers is not due to an immediate effect of smoking.

Title Risk Management in Clinical Practice. Part 9. Dental Implants.
Date
Journal British Dental Journal
Excerpt

Patients have high expectations of dental implants in terms of appearance, function and longevity. It is essential that these expectations are realistically managed and that treatment of the highest standard is provided. This involves very careful evaluation, including clinical and radiographic, and presentation of the pros and cons of treatment alternatives. Provision of a successful implant restoration requires many skills including a surgical procedure to place the implant in the best possible position and prosthodontic techniques to provide an aesthetic restoration in occlusal harmony with the rest of the dentition. Recognition of risk factors and long-term maintenance requirements are equally important. Clinicians involved in these treatments must obtain adequate training and develop skills through treatment of straightforward cases using well established protocols before embarking on more demanding cases.

Title Implementing an Internet-based Communication Network for Use During Skilled Nursing Facility to Emergency Department Care Transitions: Challenges and Opportunities for Improvement.
Date
Journal Journal of the American Medical Directors Association
Excerpt

To explore the feasibility of implementing an Internet-based communication network for communication of health care information during skilled nursing facility (SNF)-to-ED care transitions, and to identify potential barriers to system implementation.

Title The Effect of Smoking on Periodontal Bone Regeneration: a Systematic Review and Meta-analysis.
Date
Journal Journal of Periodontology
Excerpt

The effect of smoking on soft tissues after periodontal treatment has been extensively studied. However, little focus has been placed on the impact of smoking on bone regeneration after treatment. The aim of this review is to systematically assess the effect of smoking on bone regeneration after periodontal treatment.

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