Urologists
12 years of experience
Video profile
Accepting new patients
Gould Medical Group
600 Coffee Rd
Modesto, CA 95355
209-524-1211
Locations and availability (4)

Education ?

Medical School
St. George's University (1998)
Surgery

Awards & Distinctions ?

Appointments
Universtiy Of Flordia School Of Medicine- Jacksonville Fl Assistant Professor (2007 - Present)
University Of Florida College Of Medicin
ASSISTANT PROFESSOR
Associations
American Board of Urology
American Urological Association

Affiliations ?

Dr. Patel is affiliated with 1 hospitals.

Hospital Affilations

Score

Rankings

  • Cooper University Hospital
    Urology
    1 Cooper Plz, Camden, NJ 08103
    • Currently 1 of 4 crosses
  • Publications & Research

    Dr. Patel has contributed to 99 publications.
    Title Cleidocranial Dysplasia: a Report of Two Cases.
    Date February 2012
    Journal Journal of the Indian Society of Pedodontics and Preventive Dentistry
    Excerpt

    Cleidocranial dysplasia (CCD) is an autosomal dominant disorder that presents with skeletal dysplasia. It commonly presents with significant dental problems such as retention of multiple deciduous teeth, impaction or delay in eruption of permanent teeth, and often with the presence of supernumerary teeth. We report two cases showing clinical and radiographic features of CCD.

    Title Preliminary Analysis of the Feasibility and Safety of Salvage Robot-assisted Radical Prostatectomy After Radiation Failure: Multi-institutional Perioperative and Short-term Functional Outcomes.
    Date October 2011
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Open radical prostatectomy after radiation treatment failure for prostate cancer is associated with significant morbidity. The purpose of the study is to report multi-institutional experiences while performing salvage robot-assisted radical prostatectomy (sRARP).

    Title Appendicitis, Body Mass Index, and Ct: is Ct More Valuable for Obese Patients Than Thin Patients?
    Date August 2011
    Journal The American Surgeon
    Excerpt

    The purpose of our study is to determine whether body mass index (BMI = weight in kg/height in meters(2)) was related to the rate of negative appendectomy in patients who underwent preoperative CT. A surgical database search performed using the procedure code for appendectomy identified 925 patients at least 18 years of age who underwent urgent appendectomy between January 1998 and September 2007. BMI was computed for the 703 of these 925 patients for whom height and weight information was available. Patients were stratified based on body mass index (BMI 15-18.49 = underweight; 18.5-24.9 = normal weight; 25-29.9 = overweight; 30-39.9 = obese; ≥ 40 = morbidly obese). Negative appendectomy rates were computed. Negative appendectomy rates for patients who did and did not undergo preoperative CT were 27 per cent and 50 per cent for underweight patients, 10 per cent and 15 per cent for normal weight patients, 12 per cent and 17 per cent for overweight patients, 7 per cent and 30 per cent for obese patients, and 10 per cent and 100 per cent for morbidly obese patients. The difference in negative appendectomy rates for overweight patients, obese patients, and morbidly obese patients who underwent preoperative CT as compared with patients in the same BMI category who did not undergo preoperative CT was statistically significant (P ≤ 0.001). The negative appendectomy rates for overweight patients, obese patients, and morbidly obese patients who underwent preoperative CT were significantly lower than for patients in these same BMI categories who did not undergo preoperative CT.

    Title Simultaneous Estimation of Andrographolide and Wedelolactone in Herbal Formulations.
    Date July 2011
    Journal Indian Journal of Pharmaceutical Sciences
    Excerpt

    Andrographolide and wedelolactone are active components of Andrographis paniculata and Eclipta alba, respectively. The extracts of these plants are used in many traditional hepatoprotective formulations. An attempt has been made to develop an accurate, precise and specific HPTLC method to quantify simultaneously both these chemical markers of diversified chemical structures in different dosage forms like tablet and syrup. Precoated silica 60F(254) plates with toluene:acetone:formic acid (9:6:1) as mobile phase and detection wavelength of 254 nm were used. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 400 ng/spot for andrographolide and 100 to 200 ng/spot for wedelolactone. The limit of detection and the limit of quantification for andrographolide were 26.16 and 79.28 ng/spot, respectively and for wedelolactone 5.06 and 15.32 ng/spot, respectively.

    Title Azo Calix[4]arene Based Neodymium(iii)-selective Pvc Membrane Sensor.
    Date May 2011
    Journal Talanta
    Excerpt

    We found that the PVC membrane, containing azo calix[4]arene is a suitable ionophore, exhibited a Nernstian response for neodymium (Nd(3+)) ions (with slope of 19.8±0.2 mV decade(-1) for the triply charged ion) over a wide linear range of 4.0×10(-8) to 1.0×10(-1) mol L(-1) with a detection limit 1.0×10(-8) mol L(-1), a relatively fast response time, in the whole concentration range (<10 s), and a considerable life time at least for four months in the pH range of 4.0-8.0. Furthermore, the electrode revealed high selectivity with respect to all the common alkali, alkaline earth, transition and heavy metal ions, including the members of the lanthanide family other than Nd(3+). Concerning its applications, it was effectively employed for the determination of neodymium ions in industrial waste water as well as in lake water.

    Title Enhancement of Antimicrobial Activity by Synthetic Ion Channel Synergy.
    Date February 2011
    Journal Chemical Communications (cambridge, England)
    Excerpt

    Hydraphile synthetic ion channels were found to enhance the cytotoxicity to E. coli and B. subtilis of erythromycin, kanamycin, rifampicin, and tetracycline when co-administered with the antibiotic at sublethal concentrations of channel.

    Title Gastrostomy-to-gastrojejunostomy Tube Conversion: Impact of the Method of Original Gastrostomy Tube Placement.
    Date November 2010
    Journal Journal of Vascular and Interventional Radiology : Jvir
    Excerpt

    To determine the outcome of gastrostomy tube-to-gastrojejunostomy tube conversion on the basis of the method of original gastrostomy tube placement.

    Title Characteristics of Telemetry Interference with Pacemakers Caused by Digital Media Players.
    Date November 2010
    Journal Pacing and Clinical Electrophysiology : Pace
    Excerpt

    Contemporary implantable heart rhythm devices communicate multiple complex data simultaneously using radiofrequency telemetry. Interference in communication can expose them to the risk of potential corruption, leading to adverse clinical consequences.

    Title Assessment of Thalamic Perfusion in Patients with Mild Traumatic Brain Injury by True Fisp Arterial Spin Labelling Mr Imaging at 3t.
    Date June 2010
    Journal Brain Injury : [bi]
    Excerpt

    To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes.

    Title High Defibrillation Threshold: the Science, Signs and Solutions.
    Date May 2010
    Journal Indian Pacing and Electrophysiology Journal
    Excerpt

    Defibrillation threshold (DFT) testing has traditionally been an integral part of implantable cardioverter defibrillator (ICD) implantation. With the increasing number of patients receiving ICDs, physicians are encountering high DFT more often than before. Tackling the problem of high DFT, warrants an in-depth understanding of the science of defibrillation including the key electrophysiological concepts and the underlying molecular mechanisms. Numerous factors have been implicated in the causation of high DFT. Due consideration to the past medical history, pharmacotherapy, laboratory data and cardiac imaging, help in assessing the pre-procedural risk for occurrence of high DFT. Drugs, procedural changes, type and location of ICD lead system are some of the key players in predicting DFT during implantation. In the event of encountering an unacceptably high DFT, we recommend to follow a step-wise algorithm. Ruling out procedural complications like pneumothorax and tamponade is imperative before embarking on a search for potentially reversible clinical or metabolic derangements. Finally, if these attempts fail, the electrophysiologist must choose from a wide range of options for device adjustment and system modification. Although this review article is meant to be a treatise on the science, signs and solutions for high DFT, it is bound by limitations of space and scope of the article.

    Title Carcinoid Tumors of the Appendix: Are These Tumors Identifiable Prospectively on Preoperative Ct?
    Date April 2010
    Journal The American Surgeon
    Excerpt

    The purpose of this study was to determine if carcinoid tumors of the appendix were identified prospectively on preoperative CT at our institution during the last decade. A surgical database search performed using the Current Procedural Terminology codes for appendectomy and colectomy yielded 2108 patients who underwent appendectomy or colectomy with removal of the appendix from January 1998 through September 2007. Pathology reports were reviewed to identify patients in whom an appendiceal carcinoid tumor was identified. Preoperative CT reports and images were reviewed. Twenty-three carcinoid tumors (1.1%; 15 women [65.2%], eight men [34.8%]; average age 54 years [range, 23 to 86 years]) were identified. Ten patients underwent preoperative CT. No tumors were identified prospectively on CT. Images were available for rereview for eight patients. Studies were acquired with 16- (n = 7) and four- (n = 1) slice CT scanners. Average reported tumor size was 6.1 mm (range, 1.5 to 15 mm; n = 18). A tip or distal location was reported for all tumors for which a location was given (n = 15). Carcinoid tumors occurred in 1.1 per cent of appendix specimens. These tumors were all less than or 1.5 cm in size. Likely as a result of their small size, none of these tumors was identified prospectively on preoperative CT.

    Title Making the Diagnosis of Acute Appendicitis: Do More Preoperative Ct Scans Mean Fewer Negative Appendectomies? A 10-year Study.
    Date February 2010
    Journal Radiology
    Excerpt

    To determine the frequency of preoperative computed tomography (CT) in the evaluation of patients suspected of having appendicitis at one institution during the past 10 years and to determine whether changes in CT utilization were associated with changes in the negative appendectomy rate.

    Title Do Media Players Cause Interference with Pacemakers?
    Date February 2010
    Journal Clinical Cardiology
    Excerpt

    Electrical devices generate electromagnetic fields that may interfere with pacemakers. Media players cause telemetry interference with pacemakers, but it is not known whether they cause direct interference with pacemakers. The purpose of this study was to examine the interaction between pacemakers and 3 different media players.

    Title Extracellular 20s Proteasomes Accumulate in Packed Red Blood Cell Units.
    Date February 2010
    Journal Vox Sanguinis
    Title Vasa Vasorum and Plaque Neovascularization on Contrast-enhanced Carotid Ultrasound Imaging Correlates with Cardiovascular Disease and Past Cardiovascular Events.
    Date January 2010
    Journal Stroke; a Journal of Cerebral Circulation
    Excerpt

    Histological data associate proliferation of adventitial vasa vasorum and intraplaque neovascularization with vulnerable plaques represented by symptomatic vascular disease. In this observational study, the presence of carotid intraplaque neovascularization and adventitial vasa vasorum were correlated with the presence and occurrence of cardiovascular disease (CVD) and events (CVE).

    Title Robotic-assisted Radical Prostatectomy: a Review of Current Outcomes.
    Date December 2009
    Journal Bju International
    Excerpt

    With the widespread diffusion of the screening for prostate cancer, the disease has been diagnosed more commonly in the organ-confined stage, and in younger and healthier men. For these patients, radical prostatectomy (RP) is still the standard treatment. In an effort to decrease the morbidity associated with open RP, minimally invasive approaches have been described, including robotic-assisted RP (RALP). Almost one decade after the introduction of RALP, large and mature series have now been reported. We reviewed the outcomes of the largest series of RALP published recently. We searched Medline for reports published between 2006 and 2009, to identify articles describing intraoperative data, surgical complications, oncological outcomes, continence and potency rates after RALP. Relevant articles were selected and the outcomes evaluated.

    Title Predictors of Hemodynamic Compromise with Propofol During Defibrillator Implantation: a Single Center Experience.
    Date September 2009
    Journal Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing
    Excerpt

    Intra-operative hypotension has been reported in cardiac resynchronization therapy defibrillator (CRT-D) clinical trials but this phenomenon is not well characterized. The purpose of this study was to understand the frequency and determinants of intra-operative hypotension in patients undergoing defibrillator implantations.

    Title Relation of Porphyria to Atrial Fibrillation.
    Date August 2009
    Journal The American Journal of Cardiology
    Excerpt

    Porphyrias are a group of inherited disorders affecting enzymes in the heme biosynthesis pathway, leading to overproduction and/or accumulation of porphyrin or its precursors. Porphyrias have been associated with autonomic dysfunction, which in turn can develop atrial fibrillation (AF). The purpose of this study was to characterize the prevalence of AF and atrial flutter (AFl) in patients with porphyrias. A single-center retrospective cohort study was designed using data from chart reviews of patients who were admitted to the hospital from January 2000 to June 2008. Fifty-six distinct cases were found with a discharge diagnosis of porphyria including all its subtypes. From the same database, age- and gender-matched controls were identified using computer-generated random numbers. We selected 1 age- and gender-matched control for each case. Electrocardiograms and echocardiograms were reviewed by 2 independent reviewers. Only patients with available 12-lead electrocardiograms that showed AF/AFl were labeled with that diagnosis. All patients with a diagnosis of porphyria were included in the study irrespective of their age. Seven of 56 patients with porphyria met inclusion criteria, yielding a prevalence of AF/AFl of 12.5%. This association was significant (p = 0.028, relative risk 7.45, 95% confidence interval 1.01 to 66.14) compared with the age- and gender-matched control group (2%). In conclusion, our observations suggest that porphyria may be significantly associated with AF/AFl.

    Title Thrombosis of the Brachial Artery After Closed Dislocation of the Elbow.
    Date August 2009
    Journal The Journal of Bone and Joint Surgery. British Volume
    Excerpt

    The brachial artery is rarely injured after closed dislocation of the elbow. We describe an unusual variation of this injury, namely, a delayed thrombosis of the brachial artery after a closed dislocation sustained during a low-energy fall. This has not previously been described in the English literature, but may be more common than this suggests. We stress the importance of a thorough neurovascular examination and vigilance in regard to this potentially disastrous complication.

    Title Proteasome Peptidase Activities Parallel Histomorphological and Functional Consequences of Ischemia-reperfusion Injury in the Lung.
    Date July 2009
    Journal Experimental Lung Research
    Excerpt

    Several lines of evidence suggest that the proteasome contributes to ischemia-reperfusion injury (I-RI) of organs. Although I-RI contributes to multiple disease processes in the lung, the regulation of proteasome activities during pulmonary I-RI is unknown. Thus, the authors performed a pilot study to define time-related changes of lung proteasome peptidase activities and to evaluate if possible alterations correspond to morphological and functional consequences of I-RI using a rat model. Animals underwent 120 minutes of unilateral lung ischemia. Ischemic and contralateral lungs were harvested at multiple time points for up to 168 hours of reperfusion (I-R30 min-168 h). Chymotryptic-like (CT-L) and tryptic-like (T-L) proteasome peptidase activities were measured in lung extracts. An early I-R-associated inactivation of proteasome activities paralleled impairment of oxygenation, edema formation, and degree of histopathology, and resolved with restoration of function within 24 to 72 hours. Although functional and histomorphological baseline conditions were still not fully achieved at I-R168h, proteasome activities increased continuously 1.4-fold (CT-L) and 5.7-fold (T-L) until I-R168h. Apparent K(M) values for the CT-L/T-L substrates were not influenced by I-R. This pilot study establishes an initial link between proteasome activities and physiological relevant consequences of lung I-RI, and further points towards a possible role of the proteasome during the postischemic tissue repair process.

    Title A Media Player Causes Clinically Significant Telemetry Interference with Implantable Loop Recorders.
    Date June 2009
    Journal Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing
    Excerpt

    The implantable loop recorder is a useful diagnostic tool for intermittent cardiovascular symptoms because it can automatically record arrhythmias as well as a patient-triggered ECG. Media players have been shown to cause telemetry interference with pacemakers. Telemetry interference may be important in patients with implantable loop recorders because capturing a patient-triggered ECG requires a telemetry link between a hand-held activator and the implanted device. The purpose of this study was to determine if a media player causes interference with implantable loop recorders.

    Title A Dosimetric Comparison of Mammosite and Clearpath High-dose-rate Breast Brachytherapy Devices.
    Date May 2009
    Journal Brachytherapy
    Excerpt

    A new form of partial breast irradiation (PBI), ClearPath (CP) breast brachytherapy, has been introduced. We present our results of a dosimetric comparison of MammoSite (MS) and CP PBI.

    Title Cardiac Steatosis and Myocardial Dysfunction.
    Date March 2009
    Journal Journal of the American College of Cardiology
    Title New Drugs for Type 2 Diabetes Mellitus: What is Their Place in Therapy?
    Date January 2009
    Journal Drugs
    Excerpt

    Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulfonylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women.Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on beta cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety.In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.

    Title Cocaine and Alcohol: a Potential Lethal Duo.
    Date January 2009
    Journal The American Journal of Medicine
    Title Heart Rate Variability in a Man with Anorexia.
    Date December 2008
    Journal The American Journal of Medicine
    Title A Brief Report: the Use of High-frequency Oscillatory Ventilation for Severe Pulmonary Contusion.
    Date September 2008
    Journal The Journal of Trauma
    Excerpt

    BACKGROUND: Severe pulmonary contusions are a common cause of acute respiratory distress syndrome (ARDS) and are associated with significant morbidity. High frequency oscillatory ventilation (HFOV) is a ventilatory mode that employs a lung protective strategy consistent with the ARDSNet low tidal volume ventilation strategy and may result in reduced morbidity. The objective of this report is to examine the impact of HFOV on blunt trauma patients with severe pulmonary contusions who failed or were at a high risk of failing conventional mechanical ventilation. METHODS: We undertook a retrospective chart review of all patients at our institution who received HFOV for severe pulmonary contusions. Patients were placed on HFOV when their mean airway pressure (mP(aw)) surpassed 30 cm H2O and their FIO2 was greater than 0.6. Baseline demographic data including injury severity score (ISS), length of time requiring HFOV, total ventilator days, and inhospital mortality were collected. Serial determinations of oxygenation index (OI) and the PaO2/FIO2 ratio (P/F) were made up to 72 hours after initiation of HFOV. A linear mixed model was used to analyze the slope (beta) of the regression line of P/F versus time and that of OI versus time. RESULTS: Seventeen patients were identified who underwent HFOV for ARDS due primarily to pulmonary contusions. Mean ISS was 36.6, mean APACHE II score was 21.7, and the mean time before initiation of HFOV was 2.0 days. P/F increased significantly after HFOV was initiated (beta = 12.1; 95% confidence interval 7.9 to 16.4, p < 0.001). OI significantly decreased after HFOV implementation (beta = -1.8; 95% confidence interval -2.3 to -1.3, p < 0.001). Mortality rate was 17.6%. CONCLUSIONS: The early use of HFOV appears to be safe and efficacious in blunt trauma patients sustaining pulmonary contusions, and results in a rapid improvement in OI and the P/F ratio.

    Title Comparison of Open and Laparoscopic Nephrectomy in Obese and Nonobese Patients: Outcomes Stratified by Body Mass Index.
    Date August 2008
    Journal The Journal of Urology
    Excerpt

    Laparoscopic radical nephrectomy has been accepted as the preferred management for low stage renal masses not amenable to partial nephrectomy. Early in the mid 1990s several studies suggested that obesity should be a relative contraindication to laparoscopy. We present our surgical outcomes and complications in patients undergoing open and laparoscopic nephrectomy, stratified by body mass index.

    Title Retrograde Endoscopic-assisted Percutaneous Renal Access: a Novel "lasso" Technique to Achieve Rapid Secure Access to the Collecting System.
    Date June 2008
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Image-guided percutaneous renal access for placement of an access sheath for percutaneous nephrolithotomy can be a challenging procedure, especially in patients with nondilated collecting systems, obstructed infundibula (stones or stricture), or extreme body habitus. We describe our experience using ureteroscopy along with a zero-tip stone basket to facilitate a through-and-through (percutaneous-urethra) access to the collecting system.

    Title Electromagnetic Interference with Pacemakers Caused by Portable Media Players.
    Date June 2008
    Journal Heart Rhythm : the Official Journal of the Heart Rhythm Society
    Excerpt

    BACKGROUND: Electromagnetic fields generated by electrical devices may cause interference with permanent pacemakers. Media players are becoming a common mode of portable entertainment. The most common media players used worldwide are iPods. These devices are often carried in a shirt chest pocket, which may place the devices close to an implanted pacemaker. OBJECTIVE: The purpose of this study was to determine if iPods cause interference with pacemakers. METHOD: In this prospective, single-blinded study, 100 patients who had cardiac pacemakers were tested with four types of iPods to assess for interference. Patients were monitored by a single-channel ECG monitor as well as the respective pacemaker programmer via the telemetry wand. iPods were tested by placing them 2 inches anterior to the pacemaker and wand for up to 10 seconds. To simulate actual use, standard-issue headphones were plugged into the iPods. To maintain consistency, the volume was turned up maximally, and the equalizer was turned off. A subset of 25 patients underwent testing on 2 separate days to assess for reproducibility of interference. Pacemaker interference was categorized as type I or type II telemetry interference. Type I interference was associated with atrial and/or ventricular high rates on rate histograms. Type II interference did not affect pacemaker rate counters. Electromagnetic emissions from the four iPods also were evaluated in a Faraday cage to determine the mechanism of the observed interference. RESULTS: One hundred patients (63 men and 37 women; mean age 77.1 +/- 7.6 years) with 11 single-chamber pacemakers and 89 dual-chamber pacemakers underwent 800 tests. The incidence of any type of interference was 51% of patients and 20% of tests. Type I interference was seen in 19% of patients and type II in 32% of patients. Reproducibility testing confirmed that interference occurred regardless of pacing configuration (unipolar or bipolar), pacing mode (AAI, VVI, or DDD), and from one day to the next. Electromagnetic emissions testing from the iPods demonstrated maximum emissions in the pacemaker carrier frequency range when the iPod was turned "on" with the headphones attached. CONCLUSION: iPods placed within 2 inches of implanted pacemakers monitored via the telemetry wand can cause interference with pacemakers.

    Title Systemic Ubiquitin Release After Blunt Trauma and Burns: Association with Injury Severity, Posttraumatic Complications, and Survival.
    Date April 2008
    Journal The Journal of Trauma
    Excerpt

    Recent data suggest that ubiquitin (Ub) is systemically released after trauma, has pleiotropic effects on host defense mechanisms, and that Ub administration reduces fluid shifts into tissues during inflammation. Ub release after burns (B) has not been studied and its association with injury severity and outcome after blunt trauma (T) is unknown. Thus, we evaluated Ubs association with injury severity and outcomes after B and T.

    Title Dynamics of Tissue Ubiquitin Pools and Ubiquitin-proteasome Pathway Component Activities During the Systemic Response to Traumatic Shock.
    Date February 2008
    Journal Physiological Research / Academia Scientiarum Bohemoslovaca
    Excerpt

    Based on the biological significance of the ubiquitin-proteasome pathway (UPP) and its potential role during sepsis, burns and ischemia-reperfusion injury, we hypothesized that the systemic response to traumatic shock (TS) is accompanied by tissue-specific UPP alterations. Therefore, we studied tissue ubiquitin pools, chymotryptic- and tryptic-like proteasome peptidase activities and ubiquitin-protein ligation (UbPL) rates in skeletal muscle, heart, lung, liver, spleen and kidney using a clinically relevant porcine model (bilateral femur fracture/hemorrhage followed by fluid resuscitation). TS induced a systemic reduction of tissue-specific high molecular mass ubiquitin-protein conjugates (>50 kDa). Free ubiquitin was unaffected. The dynamic organ patterns of ubiquitin pools paralleled the typical physiological response to TS and resuscitation. Reduction of ubiquitin-protein conjugates was most pronounced in heart and lung (p<0.05 vs. control) and accompanied by significant increases in proteasome peptidase and UbPL activities in these organs. Unlike all other tissues, spleen proteasome peptidase and UbPL activities were significantly reduced 10 h after TS. These findings support the concept that the UPP could play an important role in regulation of cell functions during the early whole-body response to TS. The UPP might be a therapeutic target to improve the metabolic care after TS, particularly in the heart, lung, and spleen.

    Title Images in Clinical Medicine. Paget's Disease of the Mandible.
    Date February 2008
    Journal The New England Journal of Medicine
    Title Subtype-specific Conformational Differences Within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins.
    Date January 2008
    Journal Journal of Virology
    Excerpt

    The V3 region of the human immunodeficiency virus type 1 gp120 Env protein is a key domain in Env due to its role in interacting with the coreceptors CCR5 and CXCR4. We examined potential subtype-specific V3 region differences by comparing patterns of amino acid variability and probing for subtype-specific structures using 11 anti-V3 monoclonal antibodies (V3 MAbs). Differences between the subtypes in patterns of variability were most evident in the stem and turn regions of V3 (positions 9 to 24), with the two subtypes being very similar in the base region. The characteristics of the binding of V3 MAbs to Env proteins of the subtype B virus JR-FL and the subtype C virus BR025 suggested three patterns, as each group of MAbs recognized a specific conformation- or sequence-based epitope. Viruses pseudotyped with Env from JR-FL and BR025 were resistant to neutralization by the V3 MAbs, although the replacement of the Env V3 region of the SF162 virus with the JR-FL V3 created a pseudotyped virus that was hypersensitive to neutralization. A single mutation in V3 (H13R) made this chimeric Env selectively resistant to one group of V3 MAbs, consistent with the mAb binding properties. We hypothesize that there are intrinsic differences in V3 conformation between subtype B and subtype C that are localized to the stem and turn regions and that these differences have two important biological consequences: first, subtype B and subtype C V3 regions can have subtype-specific epitopes that will inherently limit antibody cross-reactivity, and second, V3 conformational differences may potentiate the frequent evolution of R5- into X4-tropic variants of subtype B but limit subtype C virus from using the same mechanism to evolve X4-tropic variants as efficiently.

    Title Cardiac Proteasome Dysfunction During Cold Ischemic Storage and Reperfusion in a Murine Heart Transplantation Model.
    Date January 2008
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Recent observations suggest that the ubiquitin-proteasome system (UPS) contributes to the pathophysiology of myocardial ischemia-reperfusion injury. Since its regulation during cold ischemia-reperfusion is unknown, we evaluated the cardiac UPS in a model of heart transplantation in mice. Cardiac ubiquitylation rates and ubiquitin-protein conjugates increased after 3h of cold ischemia (CI) and normalized post-transplant. 20S proteasome content and proteasome peptidase activities were unchanged after CI. 4h/24h post-transplant 20S proteasome concentrations decreased and chymotryptic-like but not tryptic-like proteasome peptidase activity was inactivated. Epoxomicin sensitivity of the proteasome increased 5.7-fold during CI and normalized 4h/24h post-transplant. This was accompanied by the disappearance of a 13.5 kDa-ubiquitin-conjugate during CI that could be attenuated by addition of epoxomicin to the preservation fluid. We conclude that substrate specificity of the proteasome changes during cold ischemia and that proteasome inhibition preserves the physiological ubiquitin-protein conjugate pool during organ preservation. Reduced proteasome activity during reperfusion is caused by a decrease in proteasome content and enzyme inhibition.

    Title Distribution and Interrelationship of Ubiquitin Proteasome Pathway Component Activities and Ubiquitin Pools in Various Porcine Tissues.
    Date November 2007
    Journal Physiological Research / Academia Scientiarum Bohemoslovaca
    Excerpt

    The ubiquitin-proteasome pathway fulfills major biological functions, but its physiologic tissue distribution and the interrelationship between pathway component activities and ubiquitin pools are unknown. Therefore, we analyzed free and conjugated ubiquitin, ubiquitin-protein ligation rates (UbPL) and chymotryptic- and tryptic-like proteasome peptidase activities in porcine skeletal muscle, heart, lung, liver, spleen and kidney (n=5 each). There were considerable differences between tissues (p<0.05 for all parameters). Lung and spleen showed high levels of free and conjugated ubiquitin and high UbPL. Proteasome activities were highest in kidney and heart. There were linear relationships between tryptic-like and chymotryptic-like proteasome peptidase activities (r(2) = 0.624, p<0.001) and between free and conjugated ubiquitin tissue levels (r(2) = 0.623, p<0.001). Tissue levels of free and conjugated ubiquitin correlated linear with UbPL (p<0.005), but they were not correlated with proteasome peptidase activities. The results suggest that tissue ubiquitin pools are tightly regulated and indicate a constant proportion of conjugated ubiquitin. They further support the hypothesis that ubiquitin-protein ligase systems, and probably deubiquitylating enzymes, are key regulators of ubiquitin homeostasis. The detected differences are suggestive of tissue-specific roles of ubiquitin-proteasome pathway components. Besides the known importance of the ubiquitin proteasome pathway in heart, kidney and the immune system, the results suggest the lung as another organ in which ubiquitin proteasome pathway components may also significantly contribute to disease processes.

    Title Pacemaker Interference with an Ipod.
    Date September 2007
    Journal Heart Rhythm : the Official Journal of the Heart Rhythm Society
    Title Case Report: Intrarenal Arteriovenous Fistula After Ureteroscopic Stone Extraction with Holmium Laser Lithotripsy.
    Date August 2007
    Journal Journal of Endourology / Endourological Society
    Excerpt

    A 79-year-old woman presented with gross hematuria 10 days after flexible ureteroscopic stone extraction with holmium laser lithotripsy. Work-up revealed a bleeding intrarenal arteriovenous fistula that was embolized. To our knowledge, this is the first report of this complication causing delayed hematuria after ureterorenoscopy.

    Title Regulation of the Ubiquitin Proteasome System in Mechanically Injured Human Skeletal Muscle.
    Date July 2007
    Journal Physiological Research / Academia Scientiarum Bohemoslovaca
    Excerpt

    Metabolic consequences of direct muscle trauma are insufficiently defined. Their effects on the ubiquitin-proteasome pathway (UPP) of protein degradation in human skeletal muscles are as yet unknown. Thus, we investigated whether the UPP is involved in the metabolic response evoked in directly traumatized human skeletal muscles. Biopsies were obtained from contused muscles after fractures and from normal muscles during elective implant removal (control). As estimated by western blot analyses, concentrations of free ubiquitin and ubiquitin protein conjugates were similar in extracts from injured and uninjured muscles. Ubiquitin protein ligation rates were reduced after injury (1.5+/-0.2 vs. 1.0+/-0.15 fkat/microg; p=0.04). Chymotryptic-, tryptic- and caspase-like proteasome peptidase activities (total activity minus activity in the presence of proteasome inhibitors) increased significantly after trauma (p=0.04 - 0.001). Significant increases in total chymotryptic- and caspase-like activities were attributable to proteasome activation. Our results extend the possible role of the UPP in muscle wasting to direct muscle trauma. They further suggest that the effects of direct mechanical trauma are not limited to the proteasome and imply that ubiquitin protein ligase systems are also involved. Based on the potential role of the UPP in systemic diseases, it might also be a therapeutic target to influence muscle loss in critically ill blunt trauma patients, in which large proportions of muscle are exposed to direct trauma.

    Title Post Glenn Shunt: How to Pace?
    Date July 2007
    Journal Pacing and Clinical Electrophysiology : Pace
    Title Prolongation of Skin Graft Survival by Exogenous Ubiquitin.
    Date March 2007
    Journal Transplantation
    Excerpt

    Recently, it was shown that exogenous ubiquitin has anti-inflammatory actions in vivo and that the ubiquitin-decapeptide 50-59 has immunosuppressive effects similar to cyclosporine. Immunosuppressive effects of the native ubiquitin molecule and its therapeutic potential in transplantation are unknown. We tested the hypothesis that ubiquitin inhibits alloreactivity and increases allograft survival in a murine model of skin transplantation in fully mismatched strain combinations (C3H/HEJ-DBA2). Ubiquitin dose-dependently inhibited mixed leukocyte reaction in C3H/HEJ splenocytes in vitro. Intraperitoneal ubiquitin administration (25 microg/h for 14 days) was well-tolerated, dose-dependently increased ubiquitin serum concentrations and median allograft survival from 10 days (with albumin; control) to 17 days in DBA2 mice (survival ratio: 1.7, 95% confidence interval: 1.266-2.134; P=0.0005). The in vivo effects in this study combined with our previous work strongly indicate that ubiquitin is a potent immune modulator with broad therapeutic potential. Ubiquitin treatment could be a novel strategy to improve immunosuppressive regimens in transplantation.

    Title Nonoperative Management of Asymptomatic Traumatic Pulmonary Hernia in a Young Child.
    Date February 2007
    Journal The Journal of Trauma
    Title Extracellular Ubiquitin Increases in Packed Red Blood Cell Units During Storage.
    Date December 2006
    Journal The Journal of Surgical Research
    Excerpt

    Ubiquitin (Ub) is involved in intracellular protein metabolism, but may also have extracellular roles in host defense and immunomodulation. Erythrocytes contain high amounts of Ub and hemolysis is one potential source of extracellular Ub in vivo. Since hemolysis also occurs with storage of packed RBC units (pRBCs) in vitro, we hypothesized that Ub is released during storage and that it correlates with immunological properties of pRBCs.

    Title Simulation Training for a Mass Casualty Incident: Two-year Experience at the Army Trauma Training Center.
    Date November 2006
    Journal The Journal of Trauma
    Excerpt

    BACKGROUND: Civilian and military mass casualty incidents (MCI) are an unfortunate reality in the 21st century, but there are few situational training exercises (STX) to prepare for them. To fill this gap, we developed a MCI STX for U.S. Army Forward Surgical Teams (FST) in conjunction with the U.S. Army Trauma Training Center. METHODS: After a standardized briefing, each FST has 60 minutes to unpack, setup, and organize a standard equipment cache into an emergency room, operating room, and intensive care unit. In an adjacent room, five anesthetized swine are prepared with standardized, combat-relevant injuries. The number and acuity of the total casualties are unknown to the FST and arrive in waves and without warning. A realistic combat environment is simulated by creating resource limitations, power outages, security breaches, and other stressors. The STX concludes when all casualties have died or are successfully treated. FSTs complete a teamwork self-assessment card, while staff and FST surgeons evaluate organization, resource allocation, communication, treatment, and overall performance. Feedback from each FST can be incorporated into an updated design for the next STX. RESULTS: From 2003-2005, 16 FSTs have completed the STX. All FSTs have had collapses in situational triage, primary/ secondary surveys, and/or ATLS principles (basic ABCs), resulting in approximately 20% preventable deaths. CONCLUSIONS: We concluded (1) a MCI can overwhelm even combat- experienced FSTs; (2) adherence to basic principles of emergency trauma care by all FST members is essential to effectively and efficiently respond to this MCI; (3) by prospectively identifying deficiencies, future military or civilian performance during an actual MCI may be improved; and (4) this MCI STX could provide a template for similar programs to develop, train, and evaluate civilian surgical disaster response teams.

    Title Prehospital Hboc-201 After Traumatic Brain Injury and Hemorrhagic Shock in Swine.
    Date August 2006
    Journal The Journal of Trauma
    Excerpt

    BACKGROUND: Data are limited on the actions of hemoglobin based oxygen carriers (HBOCs) after traumatic brain injury (TBI). This study evaluates neurotoxicity, vasoactivity, cardiac toxicity, and inflammatory activity of HBOC-201 (Biopure, Cambridge, Mass.) resuscitation in a TBI model. METHODS: Swine received TBI and hemorrhage. After 30 minutes, resuscitation was initiated with 10 mL/kg normal saline (NS), followed by either HBOC-201 (6 mL/kg, n = 10) or NS control (n = 10). Supplemental NS was administered to both groups to maintain mean arterial pressure (MAP) >60 mm Hg until 60 minutes, and to maintain cerebral perfusion pressure (CPP) >70 mm Hg from 60 to 300 minutes. The control group received mannitol (1 g/kg) and blood (10 mL/kg) at 90 minutes and half (n = 5) received CPP directed phenylephrine (PE) therapy after 120 minutes. Serum cytokines were measured with ELISA and coagulation was evaluated with thromboelastography. Brains were harvested for neuropathology. RESULTS: With HBOC administration, MAP, CPP, and brain tissue PO2 were restored within 30 minutes and maintained until 300 minutes. Clot strength and fibrin formation were maintained and 9/10 successfully extubated. In contrast, with control, MAP and brain tissue PO2 did not correct until 120 minutes, after mannitol, transfusion and 40% more crystalloid. Furthermore, without PE, CPP did not reach target and 0/5 could be extubated. Lactate, heart rate, cardiac output, mixed venous oxygenation, muscle oxygenation, serum cytokines, and histology did not differ between groups. CONCLUSIONS: After TBI, a single HBOC-201 bolus with minimal supplements provided rapid resuscitation, while maintaining CPP and improving brain oxygenation, without causing cardiac dysfunction, coagulopathy, cytokine release, or brain structural changes.

    Title Investigating the Role of the Growth Hormone-insulin-like Growth Factor (gh-igf) Axis As a Determinant of Male Bone Mineral Density (bmd).
    Date March 2006
    Journal Bone
    Excerpt

    The GH-IGF axis has profound effects on bone metabolism and may be important in the etiology of idiopathic osteoporosis. Serum IGF-I is often low in men with osteoporosis, which may be attributable to GH hypo-secretion or hepatic GH insensitivity. We studied the GH-IGF axis in depth to look for evidence to support these hypotheses.

    Title Cytosolic Ubiquitin and Ubiquitylation Rates in Human Peripheral Blood Mononuclear Cells During Sepsis.
    Date January 2006
    Journal Shock (augusta, Ga.)
    Excerpt

    The ubiquitin system plays a crucial role in the immune system, and ubiquitylation is regarded as one of the most common posttranslational modifications of proteins. However, its regulation in human peripheral blood mononuclear cells during sepsis is unknown. Thus, we investigated cytosolic levels of free and conjugated ubiquitin and the total ubiquitylation rate in cell free extracts from healthy donors (n = 10) and patients (n = 10) with sepsis. During sepsis, the total ubiquitin concentration was significantly reduced (P < 0.001), which was caused by a significant decrease in conjugated ubiquitin (7.4 +/- 1.9 ng vs. 11.75 +/- 1.4 ng conjugated ubiquitin/mug protein, P < 0.001), whereas free ubiquitin was unchanged. The proportion between free and conjugated ubiquitin showed a linear relationship in physiologic conditions (r, 0.76, P = 0.001) but not in sepsis (r, 0.27, P = 0.12). These changes were accompanied by a decreased total ubiquitin protein ligase activity (1.7 +/- 1.1 pkat/mg vs. 5.7 +/- 2.9 pkat/mg, P = 0.002). The tight regulation of the cytosolic ubiquitin pool appears to be significantly altered during sepsis. In addition to alterations in ubiquitin turnover, these findings suggest that reduced ubiquitylation rates also contribute to the decrease in endogenous conjugated ubiquitin. This indicates that a major pathway of posttranslational protein modification in all eukaryotes is profoundly altered in peripheral blood mononuclear cells from critically ill sepsis patients. This may contribute to the well-known impairment of host defense mechanisms in sepsis.

    Title Ubiquitin Reduces Fluid Shifts After Traumatic Brain Injury.
    Date November 2005
    Journal Surgery
    Excerpt

    Ubiquitin has well-described intracellular properties. Recent data also suggest pleiotropic effects of extracellular ubiquitin, including induction of apoptosis, regulation of immune functions, and therapeutic potential during fluid resuscitation from severe trauma. However, the actions of exogenous ubiquitin after traumatic brain injury (TBI) are unknown.

    Title Resuscitation with Pressors After Traumatic Brain Injury.
    Date November 2005
    Journal Journal of the American College of Surgeons
    Excerpt

    BACKGROUND: The purpose of the study was to compare initial resuscitation with arginine vasopressin (AVP), phenylephrine (PE), or isotonic crystalloid fluid alone after traumatic brain injury and vasodilatory shock. STUDY DESIGN: Anesthetized, ventilated swine (n = 39, 30 +/- 2 kg) underwent fluid percussion traumatic brain injury followed by hemorrhage (30 +/- 2mL/kg) to a mean arterial pressure < 30mmHg, then were randomized to 1 of 5 groups to maintain mean arterial pressure > 60mmHg for 30 to 60minutes, then cerebral perfusion pressure > 60mmHg for 60 to 300minutes, either unlimited crystalloid fluid only (n = 9), arginine vasopressin + fluid (n = 9), phenylephrine + fluid (n = 9), arginine vasopressin only (n = 5), or phenylephrine only (n = 5). Heterologous transfusions were administered if hematocrit was < 13, and mannitol was administered if intracranial pressure was > 20 mmHg. Cerebrovascular reactivity was evaluated with serial CO(2) challenges. RESULTS: In all groups, physiologic variables were similar at baseline and at the end of shock. On resuscitation, all achieved mean arterial pressure and cerebral perfusion pressure goals. Brain tissue PO(2)s were similar. With fluid only, more blood and mannitol were required, intracranial pressure and peak inspiratory pressure were higher, and cerebrovascular reactivity was decreased (all p < 0.05 versus pressor + fluid). With either pressor + fluid, cardiac output, heart rate, lactate, and mixed venous O(2) saturation were similar to fluid only, but total fluid requirements and urine output were both reduced (p < 0.05). With either pressor only, intracranial pressure remained low, but mixed venous O(2) saturation, cardiac output, and urine output were decreased (all p < 0.05 versus other groups). CONCLUSIONS: To correct vasodilatory shock after traumatic brain injury, a resuscitation strategy that combined either phenylephrine or arginine vasopressin plus crystalloid was superior to either fluid alone or pressor alone.

    Title Inhibition of Cyclooxygenase with Indomethacin Phenethylamide Reduces Atherosclerosis in Apoe-null Mice.
    Date August 2005
    Journal Biochemical Pharmacology
    Excerpt

    Non-selective inhibition of cyclooxygenase (COX) has been reported to reduce atherosclerosis in both rabbit and murine models. In contrast, selective inhibition of COX-2 has been shown to suppress early atherosclerosis in LDL-receptor null mice but not more advanced lesions in apoE deficient (apoE(-/-)) mice. We investigated the efficacy of the novel COX inhibitor indomethacin phenethylamide (INDO-PA) on the development of different stages of atherosclerotic lesion formation in female apoE(-/-) mice. INDO-PA, which is highly selective for COX-2 in vitro, reduced platelet thromboxane production by 61% in vivo, indicating partial inhibition of COX-1 in vivo. Treatment of female apoE(-/-) mice with 5mg/kg INDO-PA significantly reduced early to intermediate aortic atherosclerotic lesion formation (44 and 53%, respectively) in both the aortic sinus and aorta en face compared to controls. Interestingly, there was no difference in the extent of atherosclerosis in the proximal aorta in apoE(-/-) mice treated from 11 to 21 weeks of age with INDO-PA, yet there was a striking (76%) reduction in lesion size by en face analysis in these mice. These studies demonstrate the ability of non-selective COX inhibition with INDO-PA to reduce early to intermediate atherosclerotic lesion formation in apoE(-/-) mice, supporting a role for anti-inflammatory approaches in the prevention of atherosclerosis.

    Title Cutaneous Larva Migrans: the Creeping Eruption.
    Date January 2004
    Journal Cutis; Cutaneous Medicine for the Practitioner
    Excerpt

    Cutaneous larva migrans (CLM) is the most common tropically acquired dermatosis. It is caused by hookworm larvae, which are in the feces of infected dogs and cats. The condition occurs mainly in the Caribbean and New World, and anyone walking barefoot or sitting on a contaminated beach is at risk. Ancylostoma braziliense and Ancylostoma caninum are the most common hookworms responsible for CLM. The lesions, called creeping eruptions, are characteristically erythematous, raised and vesicular, linear or serpentine, and intensely pruritic. The conditions respond to oral and/or topical application of thiabendazole. Humans become an accidental dead-end host because the traveling parasite perishes, and its cutaneous manifestations usually resolve uneventfully within months.

    Title Opioid Agonists Differentially Regulate Mu-opioid Receptors and Trafficking Proteins in Vivo.
    Date December 2002
    Journal Molecular Pharmacology
    Excerpt

    Chronic opioid agonist treatment produces tolerance and in some cases opioid receptor internalization and down-regulation. Both morphine and etorphine induce tolerance; however, only etorphine produces mu-opioid receptor (muOR) down-regulation. In vitro studies implicate dynamin-2 (DYN-2) and G-protein receptor kinase-2 (GRK-2) in these processes. Therefore, we examined etorphine and morphine effects on regulation of GRK-2 and DYN-2 in mouse spinal cord. Mice were treated for 7 days with etorphine (200 microg/kg/day infusion) or morphine (40 mg/kg/day infusion + one 25-mg implant pellet). Controls were implanted with a placebo pellet. On the 7th day after implantation mice were tested for i.t. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) analgesia. In other mice, spinal cord was removed for [(3)H]DAMGO binding studies or GRK-2 and DYN-2 protein and mRNA abundance were determined. Both etorphine and morphine produced significant tolerance (ED(50) shift = 7.6- and 7.3-fold for morphine and etorphine, respectively). Etorphine decreased spinal muOR density by approximately 30%, whereas morphine did not change muOR density. Etorphine increased ( approximately 70%) DYN-2 protein abundance and decreased its mRNA (31%), whereas it had no effect on GRK-2 protein and mRNA abundance. Morphine had no effect on either DYN-2 or GRK-2 protein or mRNA abundance. These data raise the possibility that unequal receptor regulation by etorphine and morphine might be due to differential regulation of trafficking proteins. Overall, receptor down-regulation associated with chronic etorphine treatment may accelerate dynamin-related activity. Finally, the decrease in DYN-2 mRNA may be related to stabilization of DYN-2 protein abundance, which might inhibit transcription.

    Title Determination and Use of a Transition State for the Enzyme Estrone Sulfatase (es) from a Proposed Reaction Mechanism.
    Date March 2002
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    Using the postulated mechanism for the enzyme estrone sulfatase (ES), we have determined a possible transition state for the reaction catalysed by ES as a representation of the active site. Using the derived structure, we have undertaken the molecular modelling of several steroidal and non-steroidal inhibitors in an attempt to rationalise the inhibitory activity of a number of potent inhibitors.

    Title Conditioned Blood Reperfusion During Angioplasty (cobra) Treatment of Acute Myocardial Infarction.
    Date January 2002
    Journal Perfusion
    Excerpt

    Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device. The present study characterizes the properties of a blood-conditioning filter and describes its clinical effect when used in conjunction with active hemoperfusion for acute MI. The filter reduces leukocytes by 99.9998 +/- 0.0002% (p<0.0001) and platelets by 99.9934 +/- 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that was 'conditioned' by filtration, was studied using the Langendorff isolated rabbit heart preparation. The deposition of membrane attack complex and the resultant functional myocardial impairments [reflected in hemodynamic and biochemical measurements, including developed pressure, coronary blood flow, lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by blood conditioning. Integration of the blood-conditioning filter into an active hemoperfusion system during primary percutaneous transluminal coronary angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any complications. Reperfusion of occluded coronary arteries with 300 cm3 of conditioned blood led to significant improvement in echocardiographic global wall motion scores (in standard deviations) following treatment (-1.64 +/- 0.18 to -1.45 +/- 0.15, p=0.02). Initial reperfusion of totally occluded coronary arteries with conditioned blood leads to acutely improved ventricular function. Collectively, these data provide a strong indication for continued investigation of conditioned blood reperfusion in angioplasty following acute MI for the long-term effect upon recovery of salvagable myocardium.

    Title Macrophage Lipoprotein Lipase Promotes Foam Cell Formation and Atherosclerosis in Low Density Lipoprotein Receptor-deficient Mice.
    Date September 2000
    Journal The Journal of Biological Chemistry
    Excerpt

    The role of macrophage lipoprotein lipase (LPL) expression in atherosclerotic lesion formation was examined in low density lipoprotein receptor (LDLR(-/-)) mice using dietary conditions designed to induce either fatty streak lesions or complex atherosclerotic lesions. First, LDLR(-/-) mice chimeric for macrophage LPL expression were created by transplantation of lethally irradiated female LDLR(-/-) mice with LPL(-/-) (n = 12) or LPL(+/+) (n = 14) fetal liver cells as a source of hematopoietic cells. To induce fatty streak lesions, these mice were fed a Western diet for 8 weeks, resulting in severe hypercholesterolemia. There were no differences in plasma post-heparin LPL activity, serum lipid levels, or lipoprotein distribution between these two groups. The mean lesion area in the proximal aorta in LPL(-/-) --> LDLR(-/-) mice was significantly reduced by 33% compared with LPL(+/+) --> LDLR(-/-) mice, and a similar reduction (38%) in lesion area was found by en face analysis of the aortae. To induce complex atherosclerotic lesions, female LDLR(-/-) mice were lethally irradiated, transplanted with LPL(-/-) (n = 14), LPL(+/-) (n = 13), or LPL(+/+) (n = 14) fetal liver cells, and fed the Western diet for 19 weeks. Serum cholesterol and triglyceride levels did not differ between the three groups. After 19 weeks of diet, the lesions in the proximal aorta were complex with relatively few macrophages expressing LPL protein and mRNA in LPL(+/+) --> LDLR(-/-) mice. Analysis of cross-sections of the proximal aorta demonstrated no differences in the extent of lesion area between the groups, whereas en face analysis of the aortae revealed a dose-dependent effect of macrophage LPL on mean aortic lesion area in LPL(-/-) --> LDLR(-/-), LPL(-/+) --> LDLR(-/-), and LPL(+/+) --> LDLR(-/-) mice (1.8 +/- 0. 2%, 3.5 +/- 0.5% and 5.9 +/- 0.8%, respectively). Taken together, these data indicate that macrophage LPL expression in the artery wall promotes atherogenesis during foam cell lesion formation, but this impact may be limited to macrophage-rich lesions.

    Title Human Cytomegalovirus Ul37 Immediate-early Regulatory Proteins Traffic Through the Secretory Apparatus and to Mitochondria.
    Date July 2000
    Journal The Journal of General Virology
    Excerpt

    The human cytomegalovirus (HCMV) UL36-38 immediate-early (IE) locus encodes the UL37 exon 1 (pUL37x1) and UL37 (gpUL37) regulatory proteins, which have anti-apoptotic activities. pUL37x1 shares its entire sequence, including a hydrophobic leader and an acidic domain, with the exception of one residue, with the amino terminus of gpUL37. gpUL37 has, in addition, unique N-linked glycosylation, transmembrane and cytosolic domains. A rabbit polyvalent antiserum was generated against residues 27-40 in the shared amino-terminal domain and a mouse polyvalent antiserum was generated against the full-length protein to study trafficking of individual UL37 proteins in human cells that transiently expressed gpUL37 or pUL37x1. Co-localization studies by confocal laser scanning microscopy detected trafficking of gpUL37 and pUL37x1 from the endoplasmic reticulum to the Golgi apparatus in permissive U373 cells and in human diploid fibroblasts (HFF). Trafficking of gpUL37 to the cellular plasma membrane was detected in unfixed HFF cells. FLAG-tagged gpUL37 trafficked similarly through the secretory apparatus to the plasma membrane. By using confocal microscopy and immunoblotting of fractionated cells, gpUL37 and pUL37x1 were found to co-localize with mitochondria in human cells. This unconventional dual trafficking pattern through the secretory apparatus and to mitochondria is novel for herpesvirus IE regulatory proteins.

    Title Sustained Improvement in Flow-mediated Vasodilation After Short-term Administration of Dobutamine in Patients with Severe Congestive Heart Failure.
    Date February 1999
    Journal Circulation
    Excerpt

    BACKGROUND: In patients with severe congestive heart failure (CHF), short-term administration of dobutamine exerts sustained clinical benefits that are partially mediated by a training-like effect on skeletal muscle. Recently, physical training has been shown to enhance endothelial function in the skeletal muscle vasculature by improving endothelial function. Whether the dobutamine-induced training effect is also associated with an improvement in endothelial function in the skeletal muscle vasculature is currently unknown. METHODS AND RESULTS: Flow-mediated vasodilation in response to peak reactive hyperemia was evaluated in the forearms of 9 patients with severe CHF who were treated with dobutamine for 72 hours. Resting and peak hyperemic brachial artery blood flow and diameter (BABF [mL/min] and BAD [mm], respectively) were measured by 2-dimensional and Doppler ultrasonography at baseline, at 3 and 72 hours during dobutamine infusion, and at 2 and 4 weeks after discontinuation of dobutamine therapy. In addition, the brachial artery response to sublingual (SL) administration of nitroglycerin (NTG) was evaluated at baseline and at 2 and 4 weeks after discontinuation of dobutamine therapy. Ten patients with severe CHF who did not receive dobutamine served as control subjects. Resting BABF was significantly increased at 3 and 72 hours (391.2+/-31.8 and 366.8+/-31.0 mL/min, respectively, compared with 289.8+/-18.6 mL/min at baseline; P<0.05). Peak hyperemic BABF was not altered by dobutamine infusion compared with baseline values. The increase in BAD during peak hyperemic response was greater after infusion of dobutamine for 72 hours (15.2+/-2.7% versus 9.1+/-1.8%, P<0.05) and remained significantly greater for >/=2 weeks after discontinuation of dobutamine (12.3+/-2.2% versus 9.1+/-1.8%, P<0.05). In contrast to the peak hyperemic response, the increase in BAD (%) induced by SL NTG was unchanged by administration of dobutamine for 72 hours. Two and 4 weeks after discontinuation of dobutamine, NTG-induced increases in BAD were similar to the BAD noted at baseline. CONCLUSIONS: In patients with severe CHF, short-term administration of dobutamine for 72 hours selectively improves vascular endothelial function for >/=2 weeks.

    Title Gross, Histological, and Microvascular Anatomy and Biomechanical Testing of the Spring Ligament Complex.
    Date March 1997
    Journal Foot & Ankle International / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society
    Excerpt

    In recent years there has been an increased interest in the treatment of acquired pes planus. The breakdown of the medial longitudinal arch is most often seen at the talonaviculocalcaneal articulation. This suggests a relationship between the ligamentous complex at this articulation and acquired pes planus. This study was undertaken to gain a better understanding of the gross, histologic, and microvascular anatomy, as well as the biomechanics of the ligamentous structures surrounding the talonaviculocalcaneal articulation. Cadaver dissections of 38 fresh-frozen feet were performed. Detailed descriptions of the gross anatomy of the superomedial calcaneonavicular ligament, inferior calcaneonavicular ligament, and the superficial deltoid ligament were recorded. Their relationships to the posterior tibialis tendon and to the bones of the talonaviculocalcaneal articulation are described. The histology and microvascularity of these structures were also studied. Preliminary biomechanical testing was performed. It was found there are two definitive anatomic structures that are commonly called the spring ligament: the superomedial calcaneonavicular ligament (SMCN) and the inferior calcaneonavicular ligament (ICN). The SMCN ligament was found to have histologic properties that suggest significant load bearing. The histology of the ICN ligament suggests a pure tensile load function. The deltoid ligament and the posterior tibialis tendon had direct attachments to the SMCN ligament in all specimens. An articular facet composed of fibrocartilage was found in each SMCN ligament specimen. The microvascular structures showed an avascular articular facet present in the ligament. The biomechanical testing showed that the SMCN ligament and ICN ligament had strength similar to ankle ligaments. This study suggests this "spring ligament complex" has more of a "sling" function for the talar head. It is hoped that the better understanding of this region will add to our understanding of the etiology of pes planus and possible treatment alternatives.

    Title Patient Misunderstanding of Dosing Instructions.
    Date November 1996
    Journal Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine
    Excerpt

    OBJECTIVE: To compare outpatients' understanding of medication dosing instructions written in terms of daily frequency with patients' understanding of instructions specifying hourly intervals. DESIGN: Prospective cohort study involving patient interviews. SETTING: A university hospital outpatient pharmacy. PATIENTS: Five hundred patients presenting new and refill prescriptions to the hospital outpatient pharmacy. INTERVENTION: Patients were interviewed using a standardised questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 71 patients with prescriptions specifying dosing instructions in hourly intervals (e.g., q6h), 55 (77%) misinterpreted the recommended frequency of dosage compared with only 4 (0.99%) of the 429 patients with dosing instructions specifying daily frequency (e.g., qid) (relative risk 83; 95% confidence interval 31-200). This difference remained when patient subgroups were evaluated by education level, new versus refill prescriptions, and analgesic versus nonanalgesic medications. CONCLUSIONS: This study indicates that the intended dosing regimen is frequently misunderstood when the physician writes outpatient prescriptions in hourly intervals. To promote optimal patient compliance, the outpatient prescription label should state the number of times a day a medication is to be taken.

    Title The Superior Peroneal Retinaculum: an Anatomic Study.
    Date December 1994
    Journal Foot & Ankle International / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society
    Excerpt

    The superior peroneal retinaculum is thought to be the primary restraint to subluxation and/or dislocation of the peroneal tendons as they pass posterior to the distal fibula. The descriptions in anatomy texts vary widely. This anatomical study describes the different patterns of insertions for the superior peroneal retinaculum and its relationship to the peroneal tendons and the ligaments of the lateral ankle.

    Title Desquamative Interstitial Pneumonia: a Case Presentation.
    Date April 1994
    Journal Maryland Medical Journal (baltimore, Md. : 1985)
    Excerpt

    A 25-year-old African-American woman presented in the emergency room of a community hospital complaining of shortness of breath. The patient was admitted with a diagnosis of atypical pneumonia. Her respiration worsened despite intravenous erythromycin, nebulized albuterol, 40% oxygen via ventimask, and guaifenesin. An open lung biopsy revealed pulmonary tissue showing interstitial fibrosis with lymphocytes and histiocytes scattered within the fibrous tissue. Numerous alveoli contained mononuclear cells as seen in desquamative interstitial pneumonia. The patient did not respond to methylprednisolone and died on the eighteenth hospital day.

    Title Atrial Septal Dissection After Mitral Valve Replacement Demonstrated by Transesophageal Echocardiography.
    Date February 1994
    Journal American Heart Journal
    Title Altered Pressure-volume Relation of Right Atrium and Venoatrial Junction in Diabetic Rats.
    Date November 1992
    Journal The American Journal of Physiology
    Excerpt

    Previous studies have indicated a blunted volume reflex in diabetic rats. This alteration of the volume reflex may be due to differences in distensibility of the right atrium and venoatrial junction, which contain a large number of volume receptors. This study was designed to determine whether the distensibility of the right atrium and venoatrial junction is altered in the diabetic rat. The distensibility was assessed by measuring the stiffness constants [slope of pressure-volume (P-V) curve] of the right atrium and venoatrial junction in 2-wk streptozotocin-induced diabetic rats. The P-V data of the right atrium and venoatrial junction were measured in control and diabetic rats over a range of 0-10 mmHg by infusion of isotonic saline in KCl-arrested, in situ hearts. Similar P-V data also were determined in an additional group of diabetic rats under daily insulin treatment, which normalized plasma glucose. The mean slope of the P-V curve of the right atrium and venoatrial junction in the diabetic rats was significantly greater than the mean slope of the control and insulin-treated diabetic rats. The results indicate that diabetic rats have stiffer right atria and venoatrial junctions, which may reduce stimulation of the volume receptors to acute volume loading. In addition, the increased stiffness in the diabetic rats was prevented by chronic insulin treatment. An altered afferent limb of the volume reflex in diabetic rats contributing to blunted diuretic and natriuretic responses to volume loading may be due to these documented changes in the distensibility of the right atrium and venoatrial junction.

    Title Atrial Compliance Determines the Nature of Passive Atrial Stretch and Plasma Atrial Natriuretic Factor in the Conscious Dog.
    Date April 1992
    Journal Cardiovascular Research
    Excerpt

    STUDY OBJECTIVE--The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. DESIGN--Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. EXPERIMENTAL MATERIAL--Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters. MEASUREMENTS AND MAIN RESULTS--During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1. CONCLUSIONS--Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.

    Title Chronic Elevation of Norepinephrine in Conscious Dogs Produces Hypertrophy with No Loss of Lv Reserve.
    Date March 1992
    Journal The American Journal of Physiology
    Excerpt

    Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To determine whether the left ventricle from dogs with chronic norepinephrine infusion can sustain additional functional loads, we altered ventricular preload or afterload and determined both global and left ventricular (LV) wall function. Dogs were instrumented to measure LV wall function, LV internal base diameter, and LV pressures and were allowed to fully recover. Preload was altered by volume loading and afterload by injection of phenylephrine. Osmotic infusion pumps were implanted to continuously release norepinephrine at 0.5 micrograms.kg-1.min-1 for 28 days, and the volume loading and phenylephrine were repeated on days 14 and 28. Heart rate decreased, whereas there were no differences in mean arterial pressure, maximum first derivative of LV pressure (dP/dt), LV dP/dt/developed pressure of 40 mmHg, LV dP/dt/end-diastolic circumference, slope of the pressure-diameter relation, peak systolic wall stress, LV/end-diastolic diameter, or LV/end-systolic diameter during norepinephrine infusion. Diastolic and systolic wall thickness and chamber weights were increased (P less than 0.05). Indexes of diastolic function, including end-diastolic pressure, end-diastolic pressure-end-diastolic diameter relationship, maximum negative dP/dt, and the time constant (tau) were unchanged after chronic norepinephrine infusion, although maximum end-diastolic pressure during volume loading was increased from 17.7 +/- 2.0 to 21.7 +/- 1.0 mmHg. Chronic norepinephrine infusion did not alter tau, and tau increased equivalently with phenylephrine injection in both normal (36 +/- 1 to 62 +/- 5 ms) dogs and in those chronically infused with norepinephrine (36 +/- 1 to 56 +/- 5 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Renal Responses to Acute Volume Expansion and Atrial Natriuretic Factor in Streptozotocin-induced Diabetic Rats.
    Date January 1992
    Journal Diabetes Research and Clinical Practice
    Excerpt

    The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to volume expansion (VE) and atrial natriuretic factor (ANF) in 4-week diabetic rats. Diabetes was induced in two groups of male Sprague Dawley rats using streptozotocin (STZ), while a control group of rats was treated with vehicle alone, four weeks prior to the experiment. One group of diabetic rats was treated daily with insulin for the four weeks prior to the experiment. Before, during and after VE (1.2 ml/min for 15 min), urine flow and sodium excretion were measured from innervated and denervated kidneys in the three groups of anesthetized rats. Then the renal response to infusion of ANF (0.25 microgram/kg/min for 15 min) were observed in these rats. During VE, urine flow and sodium excretion from innervated kidneys, but not from denervated kidneys, were significantly lower in diabetic rats than those in control rats. Urine flow and sodium excretion from innervated as well as denervated kidneys of the diabetic rats failed to increase compared to the control rats in response to ANF. Correcting the diabetic condition with insulin (third group) rectified the blood glucose levels and the blunted responses to either VE or ANF. At the initial level, glomerular filtration rate (GFR) was not significantly different among the three groups. During VE and ANF infusion, changes in GFR was not parallel to changes in excretory parameters, therefore the hemodynamic change may not be the main reason for the blunted renal responses in diabetic rats. This study demonstrates that: (1) the volume reflex is blunted in the 4-week diabetic rats, which is in part due to the presence of tonic renal nerve activity, (2) renal responses to ANF are blunted in the 4-week diabetic rats, and (3) insulin treatment in diabetic rats normalizes the altered renal responses to either acute volume expansion or ANF.

    Title Altered Function and Structure of the Heart in Dogs with Chronic Elevation in Plasma Norepinephrine.
    Date November 1991
    Journal Circulation
    Excerpt

    We have previously shown that chronic elevation of plasma norepinephrine leads to a functional independent increase in left ventricular weight. The goals of the present study were to determine quantitatively the component of the myocardium that accounted for the observed structural changes and to determine the function of the hypertrophied myocardium.

    Title Carotid Baroreceptor Function in Dogs with Chronic Norepinephrine Infusion.
    Date July 1991
    Journal Hypertension
    Excerpt

    Carotid baroreceptor function, the compliance of the carotid sinus wall, and the structure of the carotid artery were examined in dogs with elevated plasma norepinephrine (2,000-4,000 pg/ml) for 28 days. The dogs with high norepinephrine were normotensive (100 +/- 4.0 versus 98 +/- 4.0 mm Hg; p greater than 0.05) with bradycardia (65 +/- 4.0 versus 87 +/- 16 beats/min; p less than 0.05) compared with normal dogs in the conscious state. However, after pentobarbital anesthesia blood pressure was significantly higher in dogs with chronic norepinephrine infusion (165 +/- 6 mm Hg) compared with normal dogs (132 +/- 6 mm Hg). To assess baroreceptor sensitivity, multiunit carotid baroreceptor activity was recorded from the right carotid sinus nerve, and the carotid sinus wall compliance (sonomicrometers) was measured during nitroglycerin and phenylephrine injections. The threshold and saturation pressures increased from 96 +/- 3.9 to 117 +/- 4.2 mm Hg and from 145 +/- 4.3 to 171 +/- 5.7 mm Hg, respectively, in the normal dogs compared with the high norepinephrine dogs. The most striking differences were the marked increases in sensitivity of carotid baroreceptors (0.47 +/- 0.05 versus 1.99 +/- 0.45 spikes.sec-1.mm Hg-1; p less than 0.01) and maximum firing frequency of the baroreceptors (24 +/- 3.1 versus 48 +/- 4.4 spikes/sec; p less than 0.01), whereas the carotid sinus wall compliance was unchanged (0.014 +/- 0.003 versus 0.012 +/- 0.002 mm/mm Hg; p greater than 0.05). Similar alterations were observed using single fiber recordings, that is, an increase in threshold and saturation pressures and slope of baroreceptor units in dogs with elevated norepinephrine. The wall thickness and area of the carotid artery were determined. Both increased significantly (0.77 +/- 0.06 versus 1.30 +/- 0.12 mm and 9.0 +/- 0.8 versus 11.9 +/- 0.9 mm2; p less than 0.05) in dogs chronically infused with norepinephrine while the dry weight-to-wet weight ratio of left carotid artery tissue also increased from 26.0 +/- 0.73% to 29.0 +/- 0.57%. These studies indicate that 1) one of the possible mechanisms responsible for bradycardia in the conscious dogs with high norepinephrine is enhanced sensitivity of carotid baroreceptors; 2) the enhanced sensitivity of carotid baroreceptors is not due to a change in compliance of the carotid sinus wall; and 3) chronic elevation of norepinephrine causes hypertrophy or hyperplasia of the wall of the common carotid artery.

    Title Regulation of Plasma Anf After Increases in Afterload in Conscious Dogs.
    Date January 1991
    Journal The American Journal of Physiology
    Excerpt

    Although atrial stretch is the primary stimulus for atrial natriuretic factor (ANF) secretion, hormones may directly affect ANF secretion or may indirectly influence ANF by changing left ventricular afterload, thereby altering atrial stretch. To determine whether direct effects are important for the release of ANF in vivo, we measured changes in plasma ANF and in atrial wall function in the conscious dog after the administration of vasopressin, angiotensin II, and phenylephrine and by mechanically increasing left ventricular afterload by partial aortic occlusion. Injections of phenylephrine, angiotensin II, and arginine vasopressin (AVP) that were chosen to cause similar changes in systemic arterial pressure resulted in similar changes in atrial pressure and diameter. Maximum V wave atrial wall stress increased to 283 +/- 12, 311 +/- 41, 327 +/- 24, and 277 +/- 22 g/cm2 for AVP, angiotensin, phenylephrine, and occlusion, respectively, and plasma ANF increased to 242 +/- 81, 248 +/- 62, 299 +/- 95, and 190 +/- 53 pg/ml. There were significant linear correlations between left ventricular afterload and left atrial pressure, and each method for increasing left ventricular afterload shifted the position to the left on an atrial pressure-diameter, compliance curve, by a similar degree. Thus changes in left ventricular afterload result in changes in atrial wall function and similar changes in plasma ANF. No hormonal-specific increase in plasma ANF was found in conscious dogs after increases in afterload.

    Title Global Myocardial Hypertrophy in Conscious Dogs with Chronic Elevation of Plasma Norepinephrine Levels.
    Date April 1990
    Journal Journal of Molecular and Cellular Cardiology
    Excerpt

    Chronically elevated plasma norepinephrine is associated with many disease states in which myocardial hypertrophy is also found, yet whether the hypertrophy results from the hemodynamic actions of catecholamines or a trophic effect is still unknown. The goal of our study was to determine the extent of hypertrophy following 28 days of norepinephrine infusion and the role of altered hemodynamics as the stimulus for the hypertrophy in conscious dogs. In a retrospective study gross cardiac weights were examined in 25 control instrumented dogs (controls) and in 41 instrumented dogs with elevated norepinephrine (NE). In the NE dogs LV (94 +/- 2.8 g), septum (33 +/- 1.5 g) and total heart weights (172 +/- 4.5 g) were greater than in controls (85 +/- 5.0, 31 +/- 1.9, and 158 +/- 9.0 g, respectively). The LV (3.95 +/- 0.10 g/kg), RV (1.91 +/- 0.06), septum (1.38 +/- 0.06) and total weight (7.23 +/- 0.15) to body weight ratios were also significantly greater (3.32 +/- 0.12, 1.73 +/- 0.08, 1.24 +/- 0.06, and 6.28 +/- 0.23 g/kg). The dry/wet weight ratios were not different in the two groups. After cutting the hearts into 1 cm rings, the planimetered area of each ring showed that the wall thickness increased at all levels, e.g. at the base by 25 +/- 3.2%. The chamber internal diameter was significantly increased only near the apex in the NE dogs making the heart more cylindrical in shape. There was no obvious sign of fibrosis in any layer of the myocardium. In physiologic studies, no index of contractility was altered including: LV dP/dt, LV dD/dt, shortening, LV dWT/dt and there was also no change in preload. Heart rate was significantly reduced throughout the 28 days of study. Cardiac output was reduced and there were no significant changes in cardiac work. Thus in these dogs NE caused a 19% and 10% increase in LV and RV to body weight ratios, respectively, without any obvious hemodynamic stimulus.

    Title Atriopeptin 24 Regulates Myocardial Function Via Frank-starling Mechanism in Conscious Dogs.
    Date March 1990
    Journal The American Journal of Physiology
    Excerpt

    Recent studies have shown that the infusion of atriopeptins decreases blood volume because of the diuresis and also because of changes in vascular volume. In dogs chronically instrumented for the measurement of left ventricular pressure and internal left ventricular diameter, infusion of atriopeptin 24 (500 ng.kg-1.min-1 for 1 h), steady-state plasma levels of 6,000 pg/ml resulted in 5.9 +/- 1.7% decrease in left ventricular (LV) end-diastolic diameter (EDD) from 34.7 +/- 2.3 mm (P less than 0.05) and no significant change in LV first derivative of pressure with time (dP/dt), LV first derivative of dimension with time, LV dP/dt divided by internal diastolic circumference or percent shortening. Hematocrit increased from 42 to 46% (P less than 0.05). During pacing, infusion of atriopeptin 24 still reduced LV EDD by 7.5 +/- 1.8% from 32 +/- 2.8 mm (P less than 0.05), although there were no changes in the indexes of inotropic state. These results were unaffected by combined autonomic receptor blockade or by ganglionic blockade. Inflation of a hydraulic occluder around the aorta during the infusion of atriopeptin 24 to return LV EDD to preinfusion levels did not cause any index of myocardial contractility to increase significantly. At lower infusion rates that resulted in plasma atriopeptin levels of 2,000 pg/ml, atriopeptin 24 still reduced LV EDD without effect on inotropic state. Thus in the conscious dog, atriopeptins reduce preload independent of neuronal influences and without affecting inotropic state.

    Title Atrial Wall Function and Plasma Atriopeptin During Volume Expansion in Conscious Dogs.
    Date April 1989
    Journal The American Journal of Physiology
    Excerpt

    Mean left atrial pressure is believed to be an accurate estimate of atrial stretch in vivo and is used to assess the stimulus for atriopeptin release in both animals and humans. However, for a number of years it has been known that atrial stretch receptor discharge occurs during specific phases of the atrial cycle and that B-receptor discharge correlates with the passive filling of the atrium, which occurs during the V wave. The purpose of this study was to develop the concept that phase-specific changes in atrial wall stress are responsible for atriopeptin secretion. In chronically instrumented conscious dogs, volume expansion (1,000 ml of saline in 5 min) increased left atrial pressure and dimensions and caused a 663 +/- 189% increase in plasma immunoreactive atriopeptin from 44 pg/ml. At this time, mean left atrial pressure increased only 202 +/- 36% (mean +/- SE), whereas A wave pressure increased 146 +/- 19% and V wave pressure increased 290 +/- 67%. A and V wave dimensions increased only a few percent. After developing atrial wall thickness constants for diastole (KCl fixation) and systole (BaCl2 fixation), calculated atrial A wave wall stress increased 163 +/- 25%, and V wave wall stress increased 346 +/- 85%. Minute wall stress (wall stress times heart rate) gave an even better correlation with changes in plasma atriopeptin. V wave minute wall stress increased 690 +/- 168%, whereas A wave wall stress increased 366 +/- 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title The Effect of Autoclaving and Enzyme Supplementation of Guar Meal on the Performance of Chicks and Laying Hens.
    Date August 1985
    Journal Poultry Science
    Excerpt

    Four experiments with broilers and one with laying hens were conducted to study the effects of processing and hemicellulase supplementation of guar meal (37.0% protein) on growth, feed efficiency, and egg production. Guar meal at 0, 10, and 15%, either in raw form or autoclaved at 100, 102, or 132 C for 3, 15, or 30 min, was fed alone or in the presence of 0 to 250 ppm hemicellulase. In an experiment utilizing full-term broilers, 10 and 15% autoclaved guar meal was fed in the presence of lincomycin (3.3 ppm) or in combination with lincomycin and hemicellulase (25 ppm). The laying hen experiment was conducted with 36-week-old hens for 8 weeks. They were fed the raw or autoclaved meal (102 C, 15 min) alone and in combination with 30 ppm hemicellulase. The raw guar meal depressed growth and the depression was dose-related. Autoclaving at 102 C for 15 min increased growth and feed efficiency. A higher temperature or a longer time of autoclaving failed to give any further increase in growth or feed efficiency. The lowest (16.5 ppm) hemicellulase was as effective as the highest (250 ppm) in increasing growth and feed efficiency of chicks when added to guar meal diets. Penicillin had no effect on growth or feed efficiency when added to the diet containing autoclaved guar meal in the presence of hemicellulase. Dry heating at 150 C for 6 hr or water treatment of guar meal was not effective in stimulating growth or feed efficiency. Guar meal also increased stickiness of droppings; autoclaving enhanced the effect, whereas hemicellulase prevented the sticky droppings.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Effect of Dietary Cereal Grain, Citrus Pectin, and Guar Gum on Liver Fat in Laying Hens and Young Chicks.
    Date January 1982
    Journal Poultry Science
    Excerpt

    One laying hen and three chick experiments were conducted to study the effect of cereal grains, citrus pectin, and guar gum on liver fat of chicks and hens and on serum cholesterol of chicks. Feeding of wheat, rye, or 2% pectin in place of corn reduced liver fat content. The decrease in liver fat of hens fed wheat or rye was larger than that of those fed 2% pectin (P less than .05). The smallest amount of liver fat was found in livers of hens fed the rye diet. Wheat or pectin did not affect egg production of egg weight, but rye caused a significant decline in egg production in comparison with other treatments. Addition of 4% pectin or 2% guar gum to the corn control diet lowered liver fat, serum cholesterol (P less than .05), and body weight in chicks (P less than .05). Penicillin added to the diets containing 2% guar gum gave an increase in body weight (P less than .05) but had no effect on body weight of chicks fed diets containing 4% pectin. In contrast, pectinase prevented growth depression by pectin and guar gum. Pectinase also increased liver fat and serum cholesterol of birds fed the diet containing pectin or guar gum. When the corn control diet was pair-fed to the pectin diet, growth of the pair-fed chicks was better than that of the pectin-fed birds but was lower than that of birds fed the control diet ad libitium. Pectin-fed birds again had lower liver fat the serum cholesterol than the control birds. The reduced feed intake of chicks pair-fed the corn control diet had no effect on liver fat content.

    Title The Effect of Vitamin B12 on the Tolerance of Chicks for High Levels of Dietary Fat and Carbohydrate.
    Date April 1981
    Journal Poultry Science
    Excerpt

    Three experiments were conducted with White Leghorn chicks hatched from hens fed diets varying in levels of protein, fat, and vitamin B12. Adding animal fat at a level of 10% in the chick diet caused growth depression of vitamin B12 deficient chicks, regardless of protein or energy level of hen or chick diet. Increasing the level of fat to 20% in the chick diet caused further growth depression and increased mortality. Feed efficiency of vitamin B12 deficient chicks was severely depressed by each additional increment in the fat level. Increasing protein content from 20 to 30% in the chick diet resulted in severe growth depression and poor feed efficiency. Although the added fat in the 30% protein chick diet depressed growth of chicks hatched from hens fed the 16 and 32% protein with added fat, it improved growth of those hatched from hens fed the similar diets with no added fat. Added fat in the 30% protein chick diet also improved feed efficiency of all chicks regardless of breeder diet treatments. Chicks hatched with an adequate carry-over of vitamin B12 from hens or chicks fed a diet with 10 micrograms of added vitamin B12/kg of feed did not show the growth depression caused by the high level of fat in the 20 and 30% protein chick diets. Feed efficiency was greatly improved by the addition of vitamin B12 to all chick diets. In a 22% protein vitamin B12 deficient diet, isocaloric substitution of glucose for fat depressed chick growth significantly and this growth depression was counteracted by supplementing the diet with 10 or 100 micrograms of vitamin B12/kg of feed. The vitamin B12 requirement was not increased by such substitution in the 22% protein diet. In contrast, isocaloric substitution of fat for glucose in the 32% protein chick diet increased the vitamin B12 need for optimum growth.

    Title Effect of Gamma Irradiation, Penicillin, And/or Pectic Enzyme on Chick Growth Depression and Fecal Stickiness Caused by Rye, Citrus Pectin, and Guar Gum.
    Date January 1981
    Journal Poultry Science
    Excerpt

    The effects of gamma irradiation of rye, corn, pectin, and guar gum and supplementation of procaine penicillin and/or pectic enzyme (Irgazyme-100) were studied. Addition of 62.5% rye, 4% pectin, or 2% guar gum in place of corn significantly reduced chick growth (P < .05). Exposure to gamma irradiation, procaine penicillin, or pectic enzyme supplementation improved the growth of chicks fed rye. Growth response on the rye diet to one or more combinations of gamma irradiation, procaine penicillin, and pectic enzyme was greater than that of gamma irradiation, procaine penicillin, or pectic enzyme alone. Gamma irradiation or pectic enzyme supplementatin of pectin or guar gum improved chick growth and almost eliminated their growth depressing properties. A combination of gamma irradiation and pectic enzyme failed to give a further significant increase in growth over that of either alone. Addition of procaine penicillin to diets containing rye, irradiated pectin, or guar gum elicited a significant growth response, but the response was greatly reduced when diets contained irradiated guar gum or irradiated pectin. Feces of chicks fed diets containing rye, pectin, or guar gum adhered to screen floors in much greater amounts than for corn-fed chicks. Gamma irradiation, procaine penicillin, or pectic enzyme had no significant effect on fecal condition of birds fed diets containing rye or guar gum. In contrast, fecal condition of birds fed guar gum was significantly improved by a combination of gamma irradiation and pectic enzyme supplement. Gamma irradiation almost eliminated and pectic enzyme supplementation completely eliminated properties of pectin causing sticky feces. Results indicate that the component of rye that causes sticky feces was not changed by gamma irradiation and/or pectic enzyme, and, therefore, is different from the growth depressing factor and from citrus pectin.

    Title Effect of Drug Additives and Type of Diet on Methionine Requirement for Growth, Feed Efficiency, and Feathering of Broilers Reared in Floor Pens.
    Date January 1981
    Journal Poultry Science
    Title The Effect of Levels of Protein and Vitamin B12 in Hen Diets on Egg Production and Hatchability of Eggs and on Livability and Growth of Chicks.
    Date April 1978
    Journal Poultry Science
    Title Effects of Protein and Fat in the Diets on Hatchability of Eggs and Chick Growth.
    Date April 1978
    Journal Poultry Science
    Title Effects of Different Cereal Grains in Diets for Laying Hens on Production Parameters and Liver Fat Content.
    Date September 1976
    Journal Poultry Science
    Excerpt

    Two experiments were conducted with White Leghorn laying hens to study the effects of different cereal grains on production criteria and liver fat content. The results of Experiment 1, in which pullets 21 weeks of age were used for a period of 22 weeks indicated that Gaines wheat or triticale (Trailblazer) were equal to corn in supporting egg production, egg weight and body weight, with comparable feed consumption. Henry wheat(a hard red winter class) was slightly, yet significantly (P less than 0.05) inferior to corn for the above criteria. No significant differences were observed among four treatments in wet liver weight and liver fat content. Hens fed the corn diet had significantly (P less than 0.05) lower carcass fat followed by the hens fed triticale in comparison with those fed Gaines or Henyry wheat. Mortality was very low and not related to dietary treatments. Neither dietary fat nor energy content was related to fat content of liver and carcass of the hens. Body weight and liver fat content were not closely related to each other. Wet liver weight was the only significantly (P less than 0.05) related factor to liver fat content. In the second experiment, in which hens 33 weeks of age were used for an experimental period of 20 weeks, opaque-2 corn was slightly superior to normal corn and triticale was comparable to normal corn in supporting egg production and egg weight. Supplementation of the diets containing the two corns and triticale with lysine failed to improve egg production and egg weight. Hens fed the diets containing either normal corn or opaque-2 corn as the only grain in the diet had significantly (P less than 0.05) higher liver fat content in comparison with hens fed the diet containing triticale as the only grain. Mortality, however, was much higher among hens fed triticale-containing diets in comparison with groups fed corn-containing diets in spite of the fact that they had significantly lower liver fat content. Regardless of dietary treatments or grains used, the hens that died were diagnosed to have fatty liver hemorrhagic syndrome. Dietary fat content was postively and significantly (P less than 0.05) related to liver fat content. Dietary energy or body weight was not closely related to liver content. Liver fat content and mortality were negatively related to each other. The higher for content did not adversely affect laying performance.

    Title Isolation of (+) Usnic Acid from Sudanese Drug Usnea Molliuscula.
    Date June 1975
    Journal Planta Medica
    Title Craniovertebral Anomalies. A Clinical and Radiological Study of 32 Cases.
    Date June 1972
    Journal Indian Journal of Medical Sciences
    Title Spastic Paraplegia--an Aetiological and Clinical Study.
    Date August 1971
    Journal Journal of the Indian Medical Association
    Title [alkaloids of Some African Tabernaemontana].
    Date May 1969
    Journal Annales Pharmaceutiques Françaises
    Title The Seed Alkaloids of Hunteria Umbellata.
    Date January 1968
    Journal Tetrahedron
    Title Investigations of Certain Nigerian Medicinal Plants. Vii. The Anatomy of the Leaf of Hedranthera Barteri (hook. F.) Pichon.
    Date July 1966
    Journal Planta Medica
    Title [voacanga Alkaloids: Structure of Epivoacangarine and Epivoacorine, Alkaloids from the Bark of the Trunk of Voacanga Bracteata Stapf].
    Date April 1966
    Journal Bulletin De La Société Chimique De France
    Title Vincamajine, the Major Alkaloid of Leaves of Rauwolfia Mannii Stapf.
    Date December 1965
    Journal The Journal of Pharmacy and Pharmacology
    Title The Seed Alkaloids of Hunteria Umbellata: the X-ray Crystal Structure of Corymine Hydrobromide Monohydrate.
    Date November 1965
    Journal Chemistry & Industry
    Title Investigations of Certain Nigerian Medicinal Plants. Vi. The Anatomy of the Root and Rhizome of Hedranthera Barteri (hook. F.) Pichon.
    Date November 1965
    Journal Planta Medica
    Title Age Associated Alterations in Structure and Function of the Cardiovascular System.
    Date
    Journal The American Journal of Geriatric Cardiology
    Excerpt

    The process of aging leads to significant changes in the structure and function of the cardiovascular system. Some of these changes result directly in pathological effects, while others serve to exacerbate the effects of cardiovascular diseases. The changes in the walls of the peripheral arteries lead to increased systolic and pulse pressures. In the myocardium, there is an age associated loss of myocytes. The remaining cells have reduced inotropic capacity. The aging heart also shows increased stiffness in both animal and human studies. Cardiac function is shown to be normal at rest in the aging population, however, during exercise, the aging heart shows a significantly smaller reserve. The increased mortality rates in setting of myocardial infarction and/or congestive heart failure in the elderly may be related to reduced muscle mass and loss of cardiac myocytes. Conversely, the aging population may receive greater benefit from the protective effects of beta-adrenergic antagonists and angiotensin converting enzyme inhibitors.

    Title Reel Syndrome-not a Twiddler Variant.
    Date
    Journal Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing
    Excerpt

    We report three cases of an unusual form of "reel syndrome" characterized by isolated, reeling dislodgement of a single lead in patients with dual-chamber or biventricular devices. One of these patients presented with worsening heart failure due to loss of left ventricular pacing and the others were detected incidentally during scheduled device checks. We suspect that a ratchet mechanism was probably responsible for this and that this type of dislodgement is not a twiddler variant. We propose a simple solution for prevention.

    Title Electromagnetic Interference in an Implantable Loop Recorder Caused by a Portable Digital Media Player.
    Date
    Journal Pacing and Clinical Electrophysiology : Pace
    Excerpt

    The implantable loop recorder has been shown to be a cost-effective tool for diagnosis of intermittent cardiovascular symptoms such as syncope and palpitations. Electromagnetic interference in these recorders may be caused by commonly encountered electronic devices such as antitheft electronic surveillance systems and magnetic resonance imaging cameras. In this report, we describe interference in two patients with implantable loop recorders from a portable digital media player.

    Title Guillain-barré Syndrome with Asystole Requiring Permanent Pacemaker: a Case Report.
    Date
    Journal Journal of Medical Case Reports
    Excerpt

    ABSTRACT:

    Title A Treatment Protocol for Restoring Occlusal Vertical Dimension Using an Overlay Removable Partial Denture As an Alternative to Extensive Fixed Restorations: a Clinical Report.
    Date
    Journal The Open Dentistry Journal
    Excerpt

    Treatment options for patients with severe attrition resulting in reduced occlusal vertical dimension are often limited to fixed prosthesis to reestablish proper occlusal vertical dimension and functional occlusion. In some cases such as when there are limited finances, minimal esthetic concerns, and medical considerations fixed prosthesis may not be the ideal treatment option. Overlay removable partial dentures (ORPDs) can be used as a provisional or interim prosthesis as well as permanent prosthesis in these cases. While ORPDs can provide a reversible and relatively inexpensive treatment for patients with a significantly compromised dental status, there is not much scientific evidence in the literature on ORPDs. Most studies published on ORPDs to date are primarily reviews and clinical reports. In this article, literatures on ORPDs are summarized and a patient treated with interim and permanent ORPDs is presented. This article reviews previously published literatures on the use of ORPDs. Indications, advantages and disadvantages are discussed. Treatment protocol with an example of the prosthodontic treatment of a patient with severely worn dentition with an interim ORPD and later a permanent ORPD are discussed in details.

    Title Liver X Receptor: a Novel Therapeutic Target.
    Date
    Journal Indian Journal of Pharmaceutical Sciences
    Excerpt

    The liver X receptors alpha and beta are orphan nuclear receptors that are key regulators in maintaining cholesterol homeostasis. Originally they were found to play an important role in reverse cholesterol transport, a pathway for the removal of excess cellular cholesterol. However several groups have now shown that the liver X receptors also functions in lipid and carbohydrate metabolism, cellular differentiation, apoptosis and many immune responses. Tissue distribution of the two paralogues differs with liver X receptor beta ubiquitously expressed, while liver X receptor alpha is confined to the liver, kidney, intestine, spleen, adipose tissue, macrophages and skeletal muscle. The endogenous ligands for the liver X receptors are certain oxidized derivatives of cholesterol, the oxysterols. Upon activation by oxysterols, the receptors form obligate heterodimers with retinoid X receptors alpha, beta and gamma; and become competent to activate the transcription of target genes.

    Title Effects of Ethanol Extract of Ficus Bengalensis (bark) on Inflammatory Bowel Disease.
    Date
    Journal Indian Journal of Pharmacology
    Excerpt

    The present study was designed to evaluate the effects of ethanol extract of Ficus bengalensis Linn. bark (AEFB) on inflammatory bowel disease (IBD).

    Title Retropubic, Laparoscopic, and Robot-assisted Radical Prostatectomy: a Critical Review of Outcomes Reported by High-volume Centers.
    Date
    Journal Journal of Endourology / Endourological Society
    Excerpt

    To critically review perioperative outcomes, positive surgical margin (PSM) rates, and functional outcomes of several large series of retropubic radical prostatectomy (RRP), laparoscopic RP (LRP), and robot-assisted radical prostatectomy (RARP) currently available in the literature.


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