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Browse Health
Primary Care Doctor, Family Practitioner
35 years of experience

Credentials

Education ?

Medical School Score Rankings
University of North Texas (1977)
  •  
Top 50%

Affiliations ?

Dr. Thompson is affiliated with 2 hospitals.

Hospital Affiliations

  • Hbo2 America,Llc
  • Hbo2 Works
  • Publications & Research

    Dr. Thompson has contributed to 151 publications.
    Title Nociceptin/orphanin Fq in Inflammation and Sepsis.
    Date January 2011
    Journal British Journal of Anaesthesia
    Excerpt

    Nociceptin/orphanin FQ, N/OFQ, and its receptor NOP represent a non-opioid branch of the opioid superfamily that were first studied for their effects on pain responses. Both N/OFQ and NOP are involved in a wide range of 'non-pain' responses including immunomodulation and cardiovascular control. There is now growing interest in this system in inflammation and sepsis, which is the focus of this review article. The N/OFQ-NOP system is present in immune cells and N/OFQ modifies immunocyte function. On the basis of various in vitro and in vivo studies, N/OFQ increases the inflammatory response in healthy anaesthetized animals and in those with a septic or inflammatory process. It affects tissue perfusion, increases capillary leakage and inflammatory markers, and leads to immune cell chemotaxis. Moreover, NOP activation produces bradycardia and hypotension. Systemic N/OFQ administration also increased mortality in an animal model of sepsis, and there is limited evidence for increased plasma N/OFQ concentrations in patients with sepsis who died compared with those who survived. There is a need for further observational and mechanistic studies in patients with established inflammatory processes or sepsis. These studies may facilitate the design of appropriate clinical studies to evaluate NOP ligands as modifiers of the inflammatory response.

    Title Perceived Barriers to the Sustainability and Progression of Nurse Practitioners.
    Date September 2010
    Journal International Emergency Nursing
    Excerpt

    In 1998 in Victoria, Australia, the Nurse Practitioner (NP) model was considered with projects exploring the potential for NP implementation in emergency departments (EDs).

    Title Assessment of Nociceptin/orphanin Fq and Micro-opioid Receptor Mrna in the Human Right Atrium.
    Date June 2010
    Journal British Journal of Anaesthesia
    Excerpt

    The expression of micro (mu: MOP) and nociceptin/orphanin FQ (NOP) receptors in the human myocardium is controversial. In this polymerase chain reaction (PCR)-based study using human right atrial biopsies, we have (i) probed for mRNA encoding NOP receptor and its endogenous peptide precursor, ppN/OFQ, and mRNA encoding MOP and (ii) attempted to correlate expression with cardiac function.

    Title Paracetamol (acetaminophen) Attenuates in Vitro Mast Cell and Peripheral Blood Mononucleocyte Cell Histamine Release Induced by N-acetylcysteine.
    Date March 2010
    Journal Clinical Toxicology (philadelphia, Pa.)
    Excerpt

    The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro.

    Title Financing of U.s. Biomedical Research and New Drug Approvals Across Therapeutic Areas.
    Date January 2010
    Journal Plos One
    Excerpt

    We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.

    Title Funding of Us Biomedical Research, 2003-2008.
    Date January 2010
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    With the exception of the American Recovery and Reinvestment Act, funding support for biomedical research in the United States has slowed after a decade of doubling. However, the extent and scope of slowing are largely unknown.

    Title Comparison of Different Methods of Ventilation Via Cannula Cricothyroidotomy in a Trachea-lung Model.
    Date December 2009
    Journal British Journal of Anaesthesia
    Excerpt

    Cannula cricothyroidotomy is recommended in recent guidelines as a rescue intervention in the 'cannot-intubate cannot-ventilate' scenario. Several methods of providing ventilation via a cannula cricothyroidotomy have been described, but there are no data comparing these methods and using cannulae of differing diameters.

    Title Selegiline Shortage: Causes and Costs of a Generic Drug Shortage.
    Date August 2009
    Journal Neurology
    Excerpt

    In September 2007, shortages of generic selegiline occurred, forcing patients to either switch to more expensive alternatives or forego treatment. We sought to evaluate prescription trends of generic selegiline and to quantify the economic impact of any resulting drug substitution of more expensive alternatives.

    Title Funding of Parkinson Research from Industry and Us Federal and Foundation Sources.
    Date July 2009
    Journal Movement Disorders : Official Journal of the Movement Disorder Society
    Excerpt

    Funding for biomedical and neuroscience research has increased over the last decade but without a concomitant increase in new therapies. This study's objectives were to determine the level and principal sources of recent funding for Parkinson disease (PD) research and to determine the current state of PD drug development. We determined the level and principal sources of recent funding for PD research from the following sources: US federal agencies, large PD foundations based in the United States, and global industry. We assessed the status of PD drug development through the use of a proprietary drug pipeline database. Funding for PD research from the sources examined was approximately $1.1 billion in 2003 and $1.2 billion in 2005. Industry accounted for 77% of support from 2003 to 2005. The number of drugs in development for PD increased from 67 in 2003 to 97 in 2007. Of the companies with at least one compound in development for PD in 2007, most were small (62% had annual revenue of less than $100 million), and most (53%) were based outside the United States. These companies will likely require partnerships to drive successful development of new PD therapies.

    Title Arterial Pressure Management and Carotid Endarterectomy.
    Date April 2009
    Journal British Journal of Anaesthesia
    Excerpt

    Acute perioperative changes in arterial pressure occur frequently, particularly in patients with cardiovascular disease or those receiving vasoactive medications, or in relation to certain cardiovascular surgical procedures. Both hypo- and hypertension are common in patients undergoing carotid surgery because of unique patho-physiological and surgical factors. Poor arterial pressure control is associated with increased morbidity and mortality after carotid endarterectomy, but good control of arterial pressure is often difficult to achieve in practice. New guidelines have emphasized the benefits of performing carotid surgery urgently in patients with acute neurological symptoms. This strategy may make perioperative arterial pressure control more challenging. However, few specific data are available to guide individual drug therapy. The incidence, implications, and aetiology of haemodynamic instability associated with carotid surgery are reviewed, and some recommendations made for its management. Close monitoring and titration of therapy are probably the most important considerations rather than specific choice of agents.

    Title Urotensin Ii Receptor Expression in Human Right Atrium and Aorta: Effects of Ischaemic Heart Disease.
    Date April 2009
    Journal British Journal of Anaesthesia
    Excerpt

    Urotensin II (UII) and its receptor UT are involved in control of the cardiovascular system and are implicated in heart failure. We measured UT expression by quantitative PCR (Q-PCR) in atrial and aortic tissue, and plasma UII while simultaneously assessing cardiac function in 40 patients undergoing coronary artery bypass surgery.

    Title Quantitative Risk-benefit Analysis of Natalizumab.
    Date August 2008
    Journal Neurology
    Excerpt

    OBJECTIVE: To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS). METHODS: We created a Markov model to evaluate treatment effects on reducing relapses and slowing disease progression using published natural history data and clinical trial results. Health changes, measured in quality-adjusted life-years (QALYs), were based on patient health preferences. Patient cohorts treated with no disease-modifying treatment, natalizumab, subcutaneous interferon beta-1a, and a theoretical "perfect" MS treatment were modeled. Sensitivity analysis was used to explore model uncertainty, including varying risks of developing progressive multifocal leukoencephalopathy (PML). RESULTS: Treatment with natalizumab resulted in 9.50 QALYs over a 20-year time horizon, a gain of 0.80 QALYs over the untreated cohort and 0.38 QALYs over interferon beta-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon beta-1a, the risk had to increase from 1 to 7.6 PML per 1,000 patients treated over 17.9 months. The "perfect" MS treatment accumulated 10.59 QALYs over the 20-year time horizon, 1.89 QALYs above the untreated cohort. Interferon beta-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon beta-1a's relative reduction was increased from 32% to 65%. CONCLUSIONS: A more than sevenfold increase in actual risk of progressive multifocal leukoencephalopathy was required to decrease natalizumab's health gain below that of interferon beta-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.

    Title Comparison of Central Venous and External Jugular Venous Pressures During Repair of Proximal Femoral Fracture.
    Date August 2008
    Journal British Journal of Anaesthesia
    Excerpt

    External jugular venous pressure (EJVP) is a close estimate of central venous pressure (CVP) in patients undergoing mechanical ventilation in the supine position, but the effects of spontaneous respiration and posture on this relationship are not known. In this study, we compared CVP with EJVP measurements in 36 patients undergoing repair of proximal femoral fracture breathing spontaneously in the supine or lateral positions.

    Title Nociceptin and Urotensin-ii Concentrations in Critically Ill Patients with Sepsis.
    Date June 2008
    Journal British Journal of Anaesthesia
    Excerpt

    The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients.

    Title Investigation and Management of the Poisoned Patient.
    Date May 2008
    Journal Clinical Medicine (london, England)
    Title Post-cardiac Arrest Management: More Than Global Cooling?
    Date May 2008
    Journal British Journal of Anaesthesia
    Title Human Peripheral Blood Mononuclear Cells Produce Pre-pro-nociceptin/orphanin Fq Mrna.
    Date March 2008
    Journal Anesthesia and Analgesia
    Excerpt

    Peripheral blood mononuclear cells (PBMC) transcribe mRNA for the nonclassical opioid nociceptin/orphanin FQ (N/OFQ) receptor (NOP). We probed for the N/OFQ precursor, pre-pro-N/OFQ (ppN/OFQ).

    Title Air Entrainment During High-frequency Jet Ventilation in a Model of Upper Tracheal Stenosis.
    Date December 2007
    Journal British Journal of Anaesthesia
    Excerpt

    Previous work has demonstrated that when high-frequency jet ventilation (HFJV) is applied above an airway stenosis, higher distal airway pressures are produced compared with when the same ventilation is delivered below the stenosis (BSV). This study aimed to investigate the mechanisms underlying this finding.

    Title Human Peripheral Blood Mononuclear Cells Express Nociceptin/orphanin Fq, but Not Mu, Delta, or Kappa Opioid Receptors.
    Date October 2007
    Journal Anesthesia and Analgesia
    Excerpt

    Expression of opioid receptors on peripheral blood mononuclear cells (PBMC) is controversial. These receptors are currently classified as classical (MOP/mu/mu, DOP/delta/delta and KOP/kappa/kappa) and nonclassical NOP (nociceptin/orphanin FQ; N/OFQ).

    Title Does Cigarette Smoking Increase Plasma Urotensin Ii Concentrations?
    Date June 2007
    Journal European Journal of Clinical Pharmacology
    Excerpt

    Human urotensin II (UII) acts on the urotensin (UT) receptor and is the most potent mammalian vasoconstrictor identified to date. The role of UII in human cardiovascular regulation remains unclear, and the results of plasma measurements have been conflicting, perhaps because different measurement techniques have been used. The effects of cigarette smoking on plasma UII concentrations are unknown. The primary aim of our study was to demonstrate whether cigarette smoking had any effect on plasma UII concentrations in otherwise healthy volunteers. Our secondary aim was to compare the results obtained from assaying simultaneously using both radioimmunoassay (RIA) and immunoluminometric assay (ILMA).

    Title Quantifying the Risks and Benefits of Natalizumab in Relapsing Multiple Sclerosis.
    Date May 2007
    Journal Neurology
    Excerpt

    Using published data, we quantified the risk and benefits of natalizumab in relapsing multiple sclerosis using quality-adjusted life years (QALYs) as a metric. Over the first 2 years of therapy, the negative health effects from progressive multifocal leukoencephalopathy were small (loss of 0.001 QALYs) relative to the positive effects on relapses and disability resulting in 0.033 QALYs (12 quality-adjusted days) gained. For context, we performed an analogous calculation for interferon beta-1a, which also had a net health benefit of 0.033 QALYs (12 quality-adjusted days).

    Title Cell and Tissue Responses of a Range of Urotensin Ii Analogs at Cloned and Native Urotensin Ii Receptors. Evidence for Coupling Promiscuity.
    Date March 2007
    Journal Naunyn-schmiedeberg's Archives of Pharmacology
    Excerpt

    Urotensin II (U-II) is the peptide ligand for the G-protein-coupled U-II receptor (UT). U-II has been dubbed "the most potent vasoconstrictor identified to date". However, in vivo studies with this system are hampered by the paucity of available ligands. Here, we characterise Chinese hamster ovary (CHO) cells expressing the human UT receptor in the following assays; (1) [(125)I]U-II binding, (2) GTPgamma[(35)S] binding, (3) cAMP formation, and (4) intracellular Ca(2+). We assess activity of 9 U-II analogues using these paradigms and examine their ability to contract isolated rat aorta. CHO(hUT) cells bound [(125)I]U-II with a B (max) and K (d) of 1,110+/-70 fmol/mg protein and 742 pM, respectively. hU-II stimulated GTPgamma[(35)S] binding (pEC(50) 8.38), optimal at low (0.1 muM) GDP concentrations. The hU-II GTPgamma[(35)S] response was partially PTx sensitive and there was a potent (pEC(50) 9.23) low efficacy ( approximately 20% inhibition) coupling to adenylyl cyclase. In CHO(hUT) cells hU-II stimulates calcium release from intracellular stores (pEC(50) 8.80) and calcium influx in a PTx-insensitive manner. In our structure-activity relationship study most ligands acted as full agonists. However, urantide behaved as a partial agonist (pEC(50) 7.67/pK(B) 7.55) in GTPgamma[(35)S] binding, a full agonist (pEC(50) 8.11) for increases in intracellular Ca(2+) and a competitive antagonist in the rat aorta bioassay (pK(B) 8.59). Collectively, these data show promiscuity at high expression and indicate the need for careful multi-assay evaluation of novel U-II analogues. Further modification of urantide, in order to eliminate residual agonist activity and to identify novel ligands for in vivo cardiovascular studies are clearly warranted.

    Title Financial Anatomy of Neuroscience Research.
    Date February 2007
    Journal Annals of Neurology
    Excerpt

    OBJECTIVE: To estimate the level of funding for neuroscience research from federal and industry sources and to examine the therapeutic advances in the neurosciences over the past decade. METHODS: We examined financing for neuroscience research over the past decade from the following principal sponsors of biomedical research: the National Institutes of Health, the pharmaceutical industry, large biotechnology firms, and large medical device firms. We also examined US Food and Drug Administration approvals for new molecular entities and medical devices for indications within the neurosciences. Neuroscience was defined to include funding and approvals for neurological and psychiatric conditions. RESULTS: Total (nominal) industry and government funding for neuroscience research increased from $4.8 billion in 1995 to $14.1 billion in 2005 and doubled after adjusting for inflation. In 2005, the pharmaceutical industry and the largest biotechnology and medical device firms accounted for 58% of total funding. The US Food and Drug Administration approved 40 new molecular entities for indications within the neurosciences from 1995 to 2005, with the annual number of approvals remaining relatively stagnant during this period. From 1995 to 2005, the US Food and Drug Administration also approved 1,679 medical devices in the neurosciences for use. INTERPRETATION: Financing for neuroscience research has increased significantly over the past decade, but new approvals for drugs in the neurosciences have not kept pace with the rapid increase in funding. This lag may represent a natural delay in realizing the return in the investment in scientific research or a decline in the productivity of neuroscience research.

    Title Projected Number of People with Parkinson Disease in the Most Populous Nations, 2005 Through 2030.
    Date February 2007
    Journal Neurology
    Excerpt

    Based on published prevalence studies, we used two different methodologies to project the number of individuals with Parkinson disease (PD) in Western Europe's 5 most and the world's 10 most populous nations. The number of individuals with PD over age 50 in these countries was between 4.1 and 4.6 million in 2005 and will double to between 8.7 and 9.3 million by 2030.

    Title In Vitro and in Vivo Pharmacological Characterization of the Novel Ut Receptor Ligand [pen5,dtrp7,dab8]urotensin Ii(4-11) (ufp-803).
    Date December 2006
    Journal British Journal of Pharmacology
    Excerpt

    The novel urotensin-II (U-II) receptor (UT) ligand, [Pen(5),DTrp(7),Dab(8)]U-II(4-11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to the right, revealing a competitive type of antagonism and a pA(2) value of 7.46. In the FLIPR [Ca(2+)](i) assay, performed at room temperature in HEK293(hUT) and HEK293(rUT) cells, U-II increased [Ca(2+)](i) with pEC(50) values of 8.11 and 8.48. Urantide and UFP-803 were inactive as agonists, but antagonized the actions of U-II by reducing, in a concentration-dependent manner, the agonist maximal effects with apparent pK(B) values in the range of 8.45-9.05. In a separate series of experiments performed at 37 degrees C using a cuvette-based [Ca(2+)](i) assay and CHO(hUT) cells, urantide mimicked the [Ca(2+)](i) stimulatory effect of U-II with an intrinsic activity (alpha) of 0.80, while UFP-803 displayed a small (alpha=0.21) but consistent residual agonist activity. When the same experiments were repeated at 22 degrees C (a temperature similar to that in FLIPR experiments), urantide displayed a very small intrinsic activity (alpha=0.11) and UFP-803 was completely inactive as an agonist. In vivo in mice, UFP-803 (10 nmol kg(-1)) antagonized U-II (1 nmol kg(-1))-induced increase in plasma extravasation in various vascular beds, while being inactive alone. In conclusion, UFP-803 is a potent UT receptor ligand which displays competitive/noncompetitive antagonist behavior depending on the assay. While UFP-803 is less potent than urantide, it displayed reduced residual agonist activity and as such may be a useful pharmacological tool.

    Title Monitoring the Monitors--beyond Risk Management.
    Date July 2006
    Journal British Journal of Anaesthesia
    Title Relationship Between Perioperative Troponin Elevation and Other Indicators of Myocardial Injury in Vascular Surgery Patients.
    Date March 2006
    Journal British Journal of Anaesthesia
    Excerpt

    In 2000 the European Society of Cardiology and the American College of Cardiology published a consensus document revising the definition of myocardial infarction. The usefulness of this revised definition has been challenged. It has been suggested that, rather than any release of cardiac troponin being potentially diagnostic of myocardial infarction, a diagnostic threshold consistent with significant myocardial injury should be defined.

    Title Limits on Spin-independent Interactions of Weakly Interacting Massive Particles with Nucleons from the Two-tower Run of the Cryogenic Dark Matter Search.
    Date March 2006
    Journal Physical Review Letters
    Excerpt

    We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.

    Title Impairment of Sustained Attention After Major Gynaecological Surgery.
    Date January 2006
    Journal European Journal of Anaesthesiology
    Excerpt

    The sustained attention to response task (SART) test is a sensitive indicator of deficits in sustained attention and is simple to perform. Sustained attention is impaired for a short period after minor surgery under general anaesthesia but the magnitude and duration of this effect after major surgery is unknown. We used the SART test to investigate deficits in sustained attention in patients undergoing major surgery under general anaesthesia.

    Title Effects of Helium on High Frequency Jet Ventilation in Model of Airway Stenosis.
    Date November 2005
    Journal British Journal of Anaesthesia
    Excerpt

    The addition of helium to the inspired gas may facilitate ventilation in the presence of clinically evident upper airway obstruction. However, there are no data on the effects of using a helium-oxygen mixture during high frequency jet ventilation (HFJV) in upper airway obstruction.

    Title Effects of Pre-eclampsia on Maternal Plasma, Cerebrospinal Fluid, and Umbilical Cord Urotensin Ii Concentrations: a Pilot Study.
    Date November 2005
    Journal British Journal of Anaesthesia
    Excerpt

    Urotensin II (UII) is the most potent endogenous vasoconstrictor identified to date. Pre-eclampsia is associated with arteriolar vasospasm but the precise underlying mechanism is uncertain and we hypothesized that UII concentrations might also be elevated. In this study we measured UII concentrations in maternal plasma and cerebrospinal fluid (CSF), and umbilical vein plasma from pre-eclamptic (PET) and normotensive patients undergoing elective Caesarean section under spinal or combined spinal-epidural anaesthesia.

    Title Cough and Glottic-stop Reflex Sensitivity in Health and Disease.
    Date March 2005
    Journal Chest
    Excerpt

    Little is known about the normal ranges and repeatability of cough reflex sensitivity measurements, or the relationship of cough reflex sensitivity to other upper airway reflexes in subjects with chronic dry cough. We set out to define the normal range of cough reflex sensitivity and its repeatability in health and disease, and to assess its relationship to the glottic-stop reflex.

    Title Urantide Mimics Urotensin-ii Induced Calcium Release in Cells Expressing Recombinant Ut Receptors.
    Date February 2005
    Journal European Journal of Pharmacology
    Excerpt

    Urotensin-II is the natural ligand of the UT receptor. This novel system is involved in the regulation of cardiovascular functions. Recently, a urotensin-II analog ([Pen5,DTrp7,Orn8]urotensin-II(4-11)) named urantide, has been proposed as a selective and potent UT receptor antagonist. In order to pharmacologically characterize this new compound, urantide was tested on the native UT receptors of the rat aorta and on the human recombinant receptors expressed in CHO cells (CHO(hUT)). Indeed, urantide behaves as a competitive, potent (pA2 8.24), and pure antagonist in the rat aorta bioassay, while as an agonist (pEC50 8.11) in a calcium mobilization assay performed in CHO(hUT) cells. Urantide should be considered a low efficacy partial agonist.

    Title First Results from the Cryogenic Dark Matter Search in the Soudan Underground Laboratory.
    Date January 2005
    Journal Physical Review Letters
    Excerpt

    We report the first results from a search for weakly interacting massive particles (WIMPs) in the Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory. Four Ge and two Si detectors were operated for 52.6 live days, providing 19.4 kg d of Ge net exposure after cuts for recoil energies between 10 and 100 keV. A blind analysis was performed using only calibration data to define the energy threshold and selection criteria for nuclear-recoil candidates. Using the standard dark-matter halo and nuclear-physics WIMP model, these data set the world's lowest exclusion limits on the coherent WIMP-nucleon scalar cross section for all WIMP masses above 15 GeV/c2, ruling out a significant range of neutralino supersymmetric models. The minimum of this limit curve at the 90% C.L. is 4 x 10(-43) cm2 at a WIMP mass of 60 GeV/c2.

    Title The Metabolism of Cyclamate to Cyclohexylamine in Humans During Long-term Administration.
    Date May 2004
    Journal Toxicology and Applied Pharmacology
    Excerpt

    A group of 14 subjects, who had been identified from 261 volunteers in a 1-week screen as being able to metabolize the sweetener cyclamate to cyclohexylamine (>0.2% of a daily dose), and 31 nonconverters (<0.2% metabolism) were given calcium cyclamate tablets (equivalent to 250 mg cyclamic acid, 3 times daily) for a period of 13 weeks. The metabolism of cyclamate to cyclohexylamine was determined using twice-weekly timed (3 h) urine collections during week 1-3 and 7-13. Urine specimens were collected on all other study days to investigate day-to-day fluctuations in cyclohexylamine excretion. Analyses of the twice weekly timed urine collections showed that subjects recruited as nonconverters essentially remained nonconverters. Of the converters, three showed consistently low metabolism, five showed erratic metabolism, five showed low metabolism initially, which increased during the latter part of the study, and one subject showed consistently high metabolism throughout the study. Analysis of the day-to-day urine specimens showed marked intrasubject variability. The plasma concentrations of cyclohexylamine measured on weeks 1-3 and 7-13 reflected the urine profiles. The highest individual long-term average steady-state excretion values based on the 3-h urine collections and daily samples were 21%, 23%, 25%, 29%, 34%, and 38%. The maximum % metabolism detected in the high converters occasionally reached the value of 60% reported in previous short-term studies, but this high activity was not maintained, and was followed by periods of lower metabolism. The results of this metabolism study support an acceptable daily intake (ADI) of 0-11 mg/kg body weight per day.

    Title Ideal Peri-operative Management of Patients with Cardiovascular Disease: the Quest Continues.
    Date May 2004
    Journal Anaesthesia
    Title A Comparison of Cerebrospinal Fluid and Plasma Urotensin Ii Concentrations in Normotensive and Hypertensive Patients Undergoing Urological Surgery During Spinal Anesthesia: a Pilot Study.
    Date November 2003
    Journal Anesthesia and Analgesia
    Excerpt

    Urotensin II is a novel endogenous vasoconstrictor. There are no data describing cerebrospinal fluid (CSF) concentrations in humans. Therefore, in this study, we aimed to quantify and compare plasma and CSF urotensin II concentrations in patients with essential hypertension and matched controls. Twenty male patients (10 receiving >6 mo of treatment for essential hypertension and 10 normotensive controls scheduled to undergo urological surgery under spinal anesthesia) were recruited into this single-blinded cohort study. Plasma and CSF urotensin II concentrations were measured by radioimmunoassay, along with mean arterial blood pressure (MAP), before admission, on the day of admission, and immediately before anesthesia. CSF and plasma urotensin II concentrations were low. Median (range) values in CSF for all 20 patients were significantly lower than plasma by approximately 15% (19.0 pg/mL [10.6-24.9 pg/mL] compared with 22.3 pg/mL [17.7-28.4 pg/mL]; P = 0.004). There were no significant differences between normotensive and hypertensive patients in either CSF or plasma concentrations. However, there was a significant positive correlation between average MAP and CSF urotensin II concentrations (r(2) = 0.44; P = 0.036) in the hypertensive group. IMPLICATIONS: Urotensin II is the most potent known endogenous human vasoconstrictor. In this pilot study, we report for the first time that cerebrospinal fluid levels are smaller than plasma levels and that there may be some association with increased blood pressure.

    Title Extravasation and Tissue Necrosis Secondary to Central Line Infusions.
    Date September 2003
    Journal Anaesthesia
    Title Acute Effects of Drugs of Abuse.
    Date August 2003
    Journal Clinical Medicine (london, England)
    Title Using the Sustained Attention to Response Test to Detect Cognitive Dysfunction After Day Case Surgery.
    Date February 2003
    Journal European Journal of Anaesthesiology
    Excerpt

    Cognitive dysfunction has been reported after general anaesthesia, but its assessment is time consuming and difficult to evaluate. This pilot study assessed the feasibility of using the Sustained Attention to Response Test to assess 35 ASA I-II adults (mean age 31.6 yr) undergoing day case surgery under general anaesthesia, and 25 ASA I-II adults (mean age 47.8 yr) undergoing day case surgery under local anaesthesia.

    Title Complete Airway Obstruction in a Ventilated Patient After Oesophageal Dilatation.
    Date November 2002
    Journal British Journal of Anaesthesia
    Excerpt

    A case of instrumental perforation of the oesophagus is presented. This caused systemic sepsis, requiring tracheal intubation and positive pressure ventilation. Sudden unexpected life-threatening airway obstruction was caused by distal tracheal compression by a peritracheal abscess. The aetiology and management of distal tracheal obstruction is discussed.

    Title Comparing Methods of Administering High-frequency Jet Ventilation in a Model of Laryngotracheal Stenosis.
    Date September 2002
    Journal Anesthesia and Analgesia
    Excerpt

    We administered high-frequency jet ventilation (HFJV) to a tracheal-lung model with connectors of internal diameter 2.5-8.5 mm to simulate ventilation through varying degrees of laryngotracheal stenosis. With reductions in diameter, end-expiratory pressure (EEP) and peak inspiratory pressure (PIP) increased. During supraglottic, translaryngeal, and transtracheal HFJV, respectively, EEP was > or =10 mm Hg at diameters narrower than 5.5, 4.0, and 3.5 cm, and PIP was >20 mm Hg at diameters narrower than 5.5, 3.5, and 3.0 cm. EEP and PIP were greater during supraglottic HFJV than during translaryngeal and transtracheal HFJV (P < 0.01). At diameters of <3.5 and 4.0 cm, respectively, PIP and EEP increased and were significantly greater (P < 0.01) during translaryngeal HFJV than during transtracheal HFJV. In a second experiment, the degree of ventilation and air entrainment was assessed by administering nitrous oxide 4 L/min to the model. Nitrous oxide concentrations were significantly (P < 0.01) smaller and nitrogen concentrations were significantly (P < 0.01) larger during supraglottic HFJV than either translaryngeal or transtracheal HFJV. The larger EEP and PIP associated with supraglottic HFJV may be attributable to increased ventilation and air entrainment compared with translaryngeal and transtracheal HFJV. IMPLICATIONS: Ventilatory driving pressure during supraglottic high-frequency jet ventilation may be reduced to minimize high airway pressures and hence the potential for pulmonary barotrauma in patients with laryngotracheal stenosis.

    Title Pharmacokinetics of Transdermal Fentanyl.
    Date September 2002
    Journal Anesthesia and Analgesia
    Title Comparison of External Jugular and Central Venous Pressures in Mechanically Ventilated Patient.
    Date July 2002
    Journal Anaesthesia
    Excerpt

    We compared central venous pressures, measured via a 150 mm triple lumen catheter in the internal jugular vein with simultaneous external jugular venous pressures, measured with a 5 mm cannula in the external jugular vein, in 24 patients undergoing major surgery. Patients were mechanically ventilated in the supine position. Six sets of paired measurements of mean central venous pressure and mean external jugular venous pressure were taken by a blinded observer, in random order and at end-expiration at 30-min intervals during surgery. Four patients were not studied because of a failure to cannulate the external jugular vein. The remaining 20 patients yielded 111 sets of paired measurements. The mean difference between external jugular venous pressure and central venous pressure was 0.3 mmHg over a range of central venous pressure of 0-22 mmHg. Limits of agreement were 3.6 to +3.0 mmHg (95% CI 4.1 to +3.5 mmHg). We conclude that external jugular venous pressure is an accurate estimate of central venous pressure in surgical patients undergoing mechanical ventilation.

    Title Effects of Remifentanil and Alfentanil on the Cardiovascular Responses to Induction of Anaesthesia and Tracheal Intubation in the Elderly.
    Date May 2002
    Journal British Journal of Anaesthesia
    Excerpt

    BACKGROUND: We compared the effects of remifentanil and alfentanil on arterial pressure and heart rate at induction of anaesthesia and tracheal intubation in 40 ASA I-III patients aged greater than 65 yr, in a randomized double-blind study. METHODS: Patients received either remifentanil 0.5 microg kg(-1) over 30 s, followed by an infusion of 0.1 microg kg min(-1) (group R) or alfentanil 10 microg kg(-1) over 30 s, followed by an infusion of saline (group A). Anaesthesia was then induced with propofol, rocuronium, and 1% isoflurane with 66% nitrous oxide in oxygen. RESULTS: Systolic arterial pressure (SAP) and mean arterial pressure (MAP) decreased after the induction of anaesthesia (P<0.05) and increased for 3 min after intubation in both groups (P<0.05), but remained below baseline values throughout. Heart rate remained stable after induction of anaesthesia but increased significantly from baseline after intubation for 1 and 4 min in groups R and A, respectively (P<0.05). There were no significant between-group differences in SAP, MAP, and heart rate. Diastolic pressure was significantly higher in group A than group R at 4 and 5 min after intubation (P<0.05). Hypotension (SAP < 100 mm Hg) occurred in four patients in group R and three patients in group A. CONCLUSIONS: Remifentanil and alfentanil similarly attenuate the pressor response to laryngoscopy and intubation, but the incidence of hypotension confirms that both drugs should be used with caution in elderly patients.

    Title Effects of Local Blood Flow on the Percutaneous Absorption of the Organophosphorus Compound Malathion: a Microdialysis Study in Man.
    Date April 2002
    Journal Archives of Toxicology
    Excerpt

    Malathion [O,O-dimethyl-S-(1,2-dicarbethoxyethyl)phosphorodithioate] is an organophosphorus insecticide widely used in veterinary medicine and in humans for the treatment of lice. In this study, the rate of the percutaneous absorption of malathion has been measured in human skin, in vivo, using microdialysis. Malathion was detected in tissue dialysate within 30 min of its topical application to the skin of the volar surface of the forearm of healthy volunteers. The concentration of malathion in dialysate increased with lengthening duration of exposure to reach a steady state concentration at 2 h. Prolonged exposure to malathion caused a marked and long-lasting erythema localized to the area of contact. There was no evidence of local tissue oedema or of a neurogenically mediated flare or itch response following topical application. Reducing skin blood flow by the addition of the vasoconstrictor noradrenaline to the dialysis probe perfusate caused an eight-fold increase in the recovery of malathion in the dialysate, which failed to reach a steady state within 5 h. Together, these data confirm that malathion can be absorbed percutaneously and that its distribution within the cutaneous tissue space is influenced by local skin blood flow. They suggest that the increase in skin blood flow caused by malathion may itself play a significant role in enhancing its systemic uptake.

    Title Molecular Targeting of Malignant Gliomas with Novel Multiply-mutated Interleukin 13-based Cytotoxins.
    Date December 2001
    Journal Critical Reviews in Oncology/hematology
    Excerpt

    A vast majority of high-grade gliomas over-express a receptor for interleukin 13 (IL13). This glioma-associated receptor for IL13 is interleukin 4 (IL4)-independent. This is in contrast to the physiological and IL4-shared receptor for the IL13, IL13/4 receptor, which is found on many normal organs. IL13-based Pseudomonas exotoxin (PE)-containing cytotoxic fusion proteins have been shown to be very potent anti-glioma agents. However, native IL13-based cytotoxins interact with both forms of the IL13 receptor. Therefore, mutations in IL13 were made in order to diminish/eliminate IL13's interaction with the shared IL13/4 receptor of normal tissue. These mutations encompassed amino acids located on alpha-helix A and C of IL13. We have engineered double or triple mutants of IL13 linked to various forms of PE. We found that these mutations could be successfully incorporated into IL13 without the loss of the protein's ability to selectively deliver the toxin to glioma cells while reducing their toxicity.

    Title Analgesia for Circumcision in a Paediatric Population: Comparison of Caudal Bupivacaine Alone with Bupivacaine Plus Two Doses of Clonidine.
    Date December 2001
    Journal Paediatric Anaesthesia
    Excerpt

    Clonidine is often used to improve the duration and quality of analgesia produced by caudal epidural blockade, although the optimum dose of clonidine with bupivacaine remains uncertain.

    Title Comparison of Effects of Remifentanil and Alfentanil on Cardiovascular Response to Tracheal Intubation in Hypertensive Patients.
    Date December 2001
    Journal British Journal of Anaesthesia
    Excerpt

    In a randomized double-blind study, we compared the effect of remifentanil and alfentanil on the cardiovascular response to laryngoscopy and tracheal intubation in patients on long-term treatment for hypertension. Forty ASA II-III patients were allocated to receive (i) remifentanil 0.5 microg kg(-1) followed by an infusion of 0.1 microg kg min(-1) or (ii) alfentanil 10 microg kg(-1) followed by an infusion of saline; all patients received glycopyrrolate 200 microg before the study drug. Anaesthesia was induced with propofol and rocuronium and maintained with 1% isoflurane and 66% nitrous oxide in oxygen. Laryngoscopy and tracheal intubation were performed after establishment of neuromuscular block. Arterial pressure and heart rate (HR) were measured non-invasively at 1 min intervals from 3 min before induction until 5 min after intubation. Systolic (SAP), diastolic and mean arterial pressure decreased significantly after induction in both groups (P<0.05). Maximum increases in mean SAP after laryngoscopy and intubation were 35 and 41 mm Hg in the remifentanil and alfentanil groups, respectively. After intubation, arterial pressure did not increase above baseline values in either group. HR remained stable after induction of anaesthesia, but increased above baseline values after intubation. Mean maximum HR was 87 beats min(-1) for the remifentanil group (12 beats min(-1) above baseline; P=0.065) and 89 beats min(-1) for the alfentanil group (15 beats min(-1) above baseline; P<0.05). There were no significant differences between groups in HR or arterial pressure at any time. There were no incidences of bradycardia. Seven patients in the remifentanil group and four in the alfentanil group received ephedrine for hypotension (i.e. SAP<100 mm Hg).

    Title Comparison of the Effects of Intravenous Alfentanil and Esmolol on the Cardiovascular Response to Double-lumen Endobronchial Intubation.
    Date May 2001
    Journal Anaesthesia
    Excerpt

    We compared the effect of alfentanil 10 microg.kg-1 and esmolol 1.5 mg.kg-1 on the cardiovascular responses to laryngoscopy and double-lumen endobronchial intubation in two groups of 20 ASA 2-3 patients undergoing pulmonary surgery, in a randomised double-blind study. Arterial pressure and heart rate decreased after induction of anaesthesia and increased after intubation in both groups (p < 0.05) but remained at or below baseline values, and changes were comparable in both groups. Plasma catecholamine concentrations decreased after induction of anaesthesia in both groups (p < 0.05). Epinephrine concentrations increased in the esmolol group after intubation (p < 0.05) but remained below baseline in the alfentanil group (p < 0.05). Norepinephrine concentrations increased significantly in both groups after intubation but were higher in the esmolol group (p < 0.05). Although both esmolol 1.5 mg.kg-1 and alfentanil 10 microg.kg-1 similarly attenuated the arterial pressure and heart rate response to endobronchial intubation, plasma catecholamine concentrations increased in the esmolol group to values greater than previously reported after tracheal intubation.

    Title Endovascular Aaa Repair Attenuates the Inflammatory and Renal Responses Associated with Conventional Surgery.
    Date February 2001
    Journal Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists
    Excerpt

    To quantify the inflammatory and renal parameters in comparative cohorts of patients undergoing surgical or endovascular repair of abdominal aortic aneurysms (AAAs).

    Title Comparison of Ketamine and Morphine for Analgesia After Tonsillectomy in Children.
    Date July 2000
    Journal British Journal of Anaesthesia
    Excerpt

    In a double blind study we compared the effects of i.m. ketamine with morphine on postoperative analgesia in children undergoing tonsillectomy. Eighty children (aged 6-15 yr) were randomized to receive either i.m. morphine 0.1-0.15 mg kg-1 or ketamine 0.5-0.6 mg kg-1, after induction of a standard general anaesthetic. Pain scores 30 min after extubation were higher (P < 0.05) in the ketamine group, but were similar thereafter to the morphine group. Mean (SD) times to recovery from anaesthesia were 20.1 (SD 6.5) min in the ketamine group compared to 14.2 (5.6) min in the morphine group (P < 0.01). There were no differences in supplemental analgesia requirements, or the incidence of vomiting or dreaming between the groups. We conclude that ketamine 0.5 mg kg-1 i.m. may be an alternative analgesic for children undergoing tonsillectomy.

    Title Anaesthesia for Manipulation of Forearm Fractures in Children: a Survey of Current Practice.
    Date July 2000
    Journal Paediatric Anaesthesia
    Excerpt

    Despite recent recommendations that all children presenting for urgent or emergency surgery should be treated as though they have a full stomach, a local audit had shown a wide variation in technique used for anaesthesia in children after trauma. Therefore, a postal questionnaire was sent to 500 anaesthetists regarding their preferred anaesthetic technique for a 6-year-old child requiring manipulation of a forearm fracture. Four clinical situations were presented differing in the timing of surgery in relation to the injury, starvation times before injury and the administration of opioid analgesia. Rapid sequence induction and tracheal intubation was preferred by 83% of all anaesthetists for surgery on the day of injury if the child had eaten 2 h prior to injury and had received opioid analgesia, but the percentage was significantly lower in experienced anaesthetists (P < 0.05) compared with trainees, and was 34.5% overall if surgery was delayed until the following day. Only 19.3% would perform a rapid sequence induction for surgery on the day of injury if the child had not eaten for 6 h before the injury. We conclude that not all anaesthetists believe that rapid sequence induction is necessary for anaesthesia after forearm fractures, despite recent recommendations.

    Title Upper Airway Reflex Sensitivity Following General Anaesthesia for Day-case Surgery.
    Date May 2000
    Journal Anaesthesia
    Excerpt

    We have studied changes in upper airway reflex sensitivity following general anaesthesia using dilute ammonia vapour as a chemical stimulant in 16 patients undergoing elective laparoscopic gynaecological surgery. We measured the threshold concentration of ammonia vapour required to elicit a transient reduction of inspiratory flow caused by glottic closure, defined as a glottic stop. Measurements of upper airway reflex sensitivity and auditory reaction time were obtained before surgery, and at 60 and 120 min after recovery. Auditory reaction time was depressed significantly at 60 min but was similar to baseline values 120 min after recovery. Upper airway reflex sensitivity remained significantly reduced at 60 and 120 min despite the return of auditory reaction time to normal. The lack of correlation between upper airway reflex sensitivity and auditory reaction time suggests that central nervous system depression alone does not explain the delayed recovery in airway reactivity.

    Title Effect of Meloxicam on Postoperative Pain After Abdominal Hysterectomy.
    Date April 2000
    Journal British Journal of Anaesthesia
    Excerpt

    We studied 36 patients, allocated randomly to receive meloxicam 15 mg rectally (n = 18) or placebo suppository (n = 18) before total abdominal hysterectomy in a double-blind study. Visual analogue scores for pain at rest (P < 0.005), on movement (P < 0.05) and on coughing (P < 0.05) were significantly decreased in the meloxicam group during the first 24 h after surgery. Mean 24-h PCA morphine requirements were 33.2 (SD 16.9) mg and 38.2 (20.8) mg in the meloxicam and placebo groups, respectively (ns). There was no difference in the incidence of nausea, vomiting or sedation between groups.

    Title Infiltration of the Abdominal Wall with Local Anaesthetic After Total Abdominal Hysterectomy Has No Opioid-sparing Effect.
    Date April 2000
    Journal British Journal of Anaesthesia
    Excerpt

    We have measured the effect of infiltration of the deep and superficial layers of the abdominal wound on morphine consumption and pain for 48 h after operation, in 40 patients undergoing total abdominal hysterectomy, in a double-blind randomized study. Patients received wound infiltration with 0.9% normal saline 40 ml or 40 ml of 0.25% bupivacaine with epinephrine 1:200,000. There were no significant differences between groups in morphine consumption, linear analogue scores for pain at rest or on movement, nausea or sedation during the first 48 h after operation. We conclude that infiltration of the deep and superficial layers of the wound of a Pfannenstiel incision with local anaesthetic solution did not confer additional analgesia in patients undergoing major gynaecological surgery.

    Title Comparison of Different Doses of Remifentanil on the Cardiovascular Response to Laryngoscopy and Tracheal Intubation.
    Date April 2000
    Journal British Journal of Anaesthesia
    Excerpt

    We have compared three bolus and infusion regimens of remifentanil on the cardiovascular response to laryngoscopy and orotracheal intubation in three groups of 20 ASA I-II female patients, in a randomized, double-blind study. Patients in group 1 received glycopyrolate 200 micrograms i.v. followed by a bolus dose of remifentanil 1 microgram kg-1 over 30 s and an infusion of remifentanil at a rate of 0.5 microgram kg-1 min-1. The other patients received remifentanil 0.5 microgram kg-1 over 30 s and an infusion of 0.25 microgram kg-1 min-1 with (group 2) or without (group 3) pretreatment with glycopyrrolate 200 micrograms. All patients then received a sleep dose of propofol, rocuronium 0.6 mg kg-1 and 1% isoflurane with 67% nitrous oxide in oxygen. Laryngoscopy and tracheal intubation were performed 3 min later. Heart rate and arterial pressure were recorded at 1-min intervals from before induction of anaesthesia until 5 min after intubation. Baseline heart rate was similar in all groups, but decreased in group 3 (no glycopyrrolate) after induction and remained significantly lower after intubation compared with the other groups (P < 0.05). Heart rate and arterial pressure increased slightly after intubation in each group but there were no significant differences in mean arterial pressure between groups at any time. The incidence of bradycardia (one patient in group 2) and hypotension (two patients in groups 1 and 2 and three patients in group 3) was low.

    Title Effect of a Remifentanil Bolus Dose on the Cardiovascular Response to Emergence from Anaesthesia and Tracheal Extubation.
    Date March 2000
    Journal British Journal of Anaesthesia
    Excerpt

    We have examined the effect of remifentanil on the haemodynamic response to emergence from anaesthesia and tracheal extubation in 40 ASA I-II female patients undergoing diagnostic laparoscopy, in a randomized, double-blind study. All patients received a standard general anaesthetic comprising propofol, vecuronium and 1% isoflurane with 66% nitrous oxide in oxygen. At the end of surgery, a bolus dose of remifentanil 1 microgram kg-1 (n = 20) or saline placebo (n = 20) was given and tracheal extubation was performed when standard criteria were achieved. Arterial pressure and heart rate were recorded non-invasively at 1-min intervals from the end of surgery. Remifentanil attenuated the increase in both mean arterial pressure (P < 0.001) and heart rate (P < 0.05) at extubation. Mean time to extubation was 7.2 (SEM 0.6) min and 4.0 (0.5) min in the remifentanil and saline groups, respectively (P < 0.001). There was no difference in the incidence of coughing at extubation, time to recovery from anaesthesia or time to fitness for discharge from the recovery room.

    Title Retargeting Interleukin 13 for Radioimmunodetection and Radioimmunotherapy of Human High-grade Gliomas.
    Date November 1999
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    A vast majority of patients with glioblastoma multiforme (GBM), a high-grade glioma, overexpress abundant amounts of a receptor for interleukin (IL)-13 in situ. This receptor is more restrictive because it is IL-4-independent and therefore differs from the IL-13/4 signaling receptor of normal tissue that is shared with IL-4. We previously identified one of the sites on the human IL (hIL)-13 molecule that is important for its interaction with the IL-13/4 receptor, a residue of glutamic acid at position 13. In this study, we mutated the cytokine and produced hIL-13.E13Y, in which the glutamic acid was substituted by tyrosine. This additional tyrosine residue was therefore strategically located within the region of IL-13 interaction with the signaling physiological receptor. hIL-13.E13Y did not transduce signals through the IL-13/4 receptor, whereas its interaction with the more restrictive, GBM-associated receptor remained intact. The mutated hIL-13 could be readily radiolabeled. Radiolabeled hIL-13.E13Y produced specific autoradiographic images of human GBM specimens. We demonstrate an effective way to redirect hIL-13 to its more restrictive receptor found in high-grade gliomas by mutagenizing the cytokine, and, concomitantly, we equipped hIL-13 with an additional tyrosine residue for higher specific activity radiolabeling.

    Title Mutants of Interleukin 13 with Altered Reactivity Toward Interleukin 13 Receptors.
    Date November 1999
    Journal The Journal of Biological Chemistry
    Excerpt

    Interleukin 13 (IL13) belongs to a family of cytokines whose members exhibit structural homology, despite amino acid sequence dissimilarity. For example, while of limited sequence homology, IL13 and IL4 share a signaling receptor, IL13/4 receptor, on a variety of human normal cells. However, a subclass of IL4-independent IL13 receptors is overexpressed on certain transformed cells, including human malignant gliomas. We introduced mutations into human (h) IL13 to determine the site(s) involved in interaction with the shared receptor and/or the glioma-associated receptor. This analysis identified at least three protein regions that are needed for signaling through the shared receptor. These regions were localized to alpha-helices A, C, and D and were mainly separate from the region(s) needed to interact with the glioma-associated receptor. Glutamic acids at positions 13 and 16 in hIL13 alpha-helix A, arginine and serine at positions 66 and 69 in helix C, and arginine at position 109 in helix D were found to be important in inducing biological signaling since their specific mutation resulted in loss and/or gain of function phenomena. We demonstrate that the molecular requirements of hIL13 to interact with its respective receptors are generally distinct and can be controlled by mutagenesis of the cytokine.

    Title Nocturnal Hypoxaemia and Respiratory Function After Endovascular and Conventional Abdominal Aortic Aneurysm Repair.
    Date May 1999
    Journal British Journal of Anaesthesia
    Excerpt

    Respiratory function, assessed by pre- and postoperative spirometry, and overnight pulse oximetry recordings, was compared prospectively in patients undergoing infrarenal abdominal aortic aneurysm repair by endovascular or conventional surgery. Episodic hypoxaemia was common in both groups before operation and up to the fifth night after operation. The frequency and severity of hypoxaemia were greater in the conventional group (P < 0.05). FEV1 and FVC decreased significantly on the third and fifth days after operation in both groups (P < 0.05); decreases in FVC were greater in patients undergoing conventional surgery. On the fifth day after operation, FVC had recovered to 86% and 64% of preoperative values in the endovascular and conventional groups, respectively (P < 0.05). Duration of surgery was greater (P < 0.05) and duration of postoperative artificial ventilation significantly less (P < 0.05) after endovascular repair. Postoperative PCA morphine consumption and duration of use were significantly greater (P < 0.05) in patients undergoing conventional abdominal aortic aneurysm surgery.

    Title Cardiovascular and Catecholamine Responses During Endovascular and Conventional Abdominal Aortic Aneurysm Repair.
    Date April 1999
    Journal European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery
    Excerpt

    To compare changes in plasma catecholamines, acid-base status and cardiovascular dynamics in patients undergoing endovascular or conventional infrarenal abdominal aortic aneurysm (AAA) repair under standard general anaesthesia.

    Title Perioperative Pharmacokinetics of Transdermal Fentanyl in Elderly and Young Adult Patients.
    Date November 1998
    Journal British Journal of Anaesthesia
    Excerpt

    The perioperative pharmacokinetics of transdermally-delivered fentanyl were compared in 10 young adult (mean [range] age 32.7, [25-38] yr) and eight elderly (mean [range] age 73.7 [64-82] yr) patients following abdominal surgery. Transdermal fentanyl patches designed to release 50 micrograms h-1 were applied 2 h preoperatively and left in place for 72 h. Plasma fentanyl concentrations were measured by radioimmunoassay during patch application and for 30 h after patch removal. The mean half-time (time for plasma concentrations to double after patch application) was 4.2 h in the younger group and 11.1 h in the elderly group (P < 0.005). Mean maximum plasma concentrations were 1.9 ng ml-1 and 1.5 ng ml-1 in the younger and elderly groups respectively (ns). There were no differences in the time at which maximum plasma concentrations occurred (tmax), elimination half-life after patch removal, or AUC(0-infinity).

    Title Inhibition of the Adherence of Cholera Toxin and the Heat-labile Enterotoxin of Escherichia Coli to Cell-surface Gm1 by Oligosaccharide-derivatized Dendrimers.
    Date November 1998
    Journal Biochemical Pharmacology
    Excerpt

    The adherence of either cholera toxin or the heat-labile enterotoxin of Escherichia coli to monosialoganglioside gal(beta1-3)galNAc(beta1-4)[sialic acid (alpha2-3)]gal(beta1-4)glc(beta)1-ceramide (GM1) present on the surface of epithelial cells lining the intestine is the first step of a series that results in the induction of a watery diarrhea. While cholera is more severe, both can lead to death as a result of dehydration. To determine the potential of defined multivalent oligosaccharides, synthesized by the covalent attachment of multiple phenylisothiocyanate (PITC) derivatives of gal(beta1-3)galNAc(beta1-4)[sialic acid(alpha2-3)]gal(beta1-4)glc (oligo-GM1) to the arms of a poly(propylene imine) dendrimer, as therapeutic agents for these diseases, their ability to inhibit adherence of the toxins to cell surface-associated GM1 was determined. They not only inhibited choleragenoid (binding subunit of cholera toxin) binding to GM1-treated NCTC-2071 cells (chemically transformed murine fibroblasts) at 5 degrees, but also inhibited adherence of the choleragenoid, cholera toxin, and heat-labile enterotoxin of E. coli to GM1-treated NCTC-2071 cells at 37 degrees. Inhibition was observed whether the toxin was preincubated with the oligo-GM1-PITC-derivatized dendrimer prior to addition to cells or given just after the addition of the derivatized dendrimer to cells. The derivatized dendrimer had no effect on cell viability, as monitored by trypan blue exclusion. Blue-shifts in tryptophan fluorescence emission spectra maxima induced by adherence of either choleragenoid, cholera holotoxin, or the heat-labile enterotoxin of E. coli to oligo-GM1-PITC-derivatized dendrimers were similar to those induced by adherence to GM1 or oligo-GM1. Comparable shifts were not observed when the toxins were incubated with gangliosides that fail to function as receptors.

    Title Endovascular Abdominal Aortic Aneurysm Repair in the 'hostile Abdomen'.
    Date October 1998
    Journal Journal of the Royal College of Surgeons of Edinburgh
    Title Correlations Between Ultrasonographic Findings and Specific Hepatic Diseases in Cats: 72 Cases (1985-1997).
    Date July 1998
    Journal Journal of the American Veterinary Medical Association
    Excerpt

    To identify correlations between ultrasonographic findings and specific hepatic diseases in cats.

    Title Effect of Remifentanil on the Haemodynamic Response to Orotracheal Intubation.
    Date July 1998
    Journal British Journal of Anaesthesia
    Excerpt

    We have examined the effect of remifentanil on the haemodynamic response to orotracheal intubation in a randomized, double-blind study. We studied 40 patients allocated to one of four groups of 10 each, to receive the following immediately before induction of anaesthesia: remifentanil 1 microgram kg-1 bolus over 30 s, followed by an infusion of 0.5 microgram kg-1 min-1; saline placebo only; glycopyrrolate 200 micrograms and remifentanil 1 microgram kg-1 bolus over 30 s, followed by an infusion of 0.5 microgram kg-1 min-1; or glycopyrrolate 200 micrograms only. Anaesthesia was induced with propofol, vecuronium and 1% isoflurane with 66% nitrous oxide in oxygen. The trachea was intubated under direct laryngoscopy 3 min after induction of anaesthesia. Arterial pressure and heart rate were measured non-invasively, immediately before induction of anaesthesia and then at 1-min intervals. Remifentanil was found to effectively attenuate the pressor response to intubation (P < 0.05 for the increase in mean arterial pressure; P < 0.01 for the increase in heart rate). In the absence of a concurrent vagolytic agent, remifentanil was associated with bradycardia or hypotension, or both, in five of 10 patients, compared with one patient who received remifentanil and glycopyrrolate.

    Title Oligosaccharide-derivatized Dendrimers: Defined Multivalent Inhibitors of the Adherence of the Cholera Toxin B Subunit and the Heat Labile Enterotoxin of E. Coli to Gm1.
    Date April 1998
    Journal Glycoconjugate Journal
    Excerpt

    Poly(propylene imine) dendrimers having four or eight primary amino groups and a Starburst (PAMAM) dendrimer having eight primary amino groups were used as core molecules, to which phenylisothiocyanate derivatized (PITC) galbeta1-3galNAcbeta1-4[sialic acid alpha2-3]-galbeta1-4glc (oligo-GM1) residues were covalently attached to yield multivalent oligosaccharides. The synthesis of the oligo-GM1-PITC derivatized dendrimers was monitored using high performance thin layer chromatography, infrared spectroscopy, sialic acid content, and mass spectroscopy. The ability of multivalent oligo-GM1-PITC dendrimers to inhibit the binding of 125I-labeled cholera toxin B subunit and the heat labile enterotoxin of E. coli to GM1-coated microtiter wells was determined. IC50s obtained for the oligo-GM1-PITC dendrimers, GM1, and the oligosaccharide moiety of GM1 indicated that the derivatized dendrimers inhibited binding of the choleragenoid and the heat labile enterotoxin to GM1-coated wells at a molar concentration five- to 15-fold lower than native GM1 and more than 1,000-fold lower than that of the free oligosaccharide.

    Title Half-life of Intracameral Gentamicin After Phacoemulsification.
    Date October 1997
    Journal Journal of Cataract and Refractive Surgery
    Excerpt

    PURPOSE: To determine the half-life of intracameral gentamicin administered during phacoemulsification. SETTING: Southampton Eye Unit, Southampton General Hospital, England. METHODS: Thirty-one patients having scleral tunnel phacoemulsification were given intracameral gentamicin in the irrigation fluid. Samples of fluid were taken from the anterior chamber at the end of the operation and at various times postoperatively. The concentration of gentamicin in the samples was determined by fluorescence polarization immunoassay and the half-life calculated for a single compartment model using a peeling algorithm. RESULTS: The concentration of gentamicin in the anterior chamber after phacoemulsification decreased by half every 51 minutes (95% confidence interval, 42 to 66 minutes). CONCLUSION: Intracameral gentamicin was cleared from the anterior chamber after phacoemulsification at a rate that prevents the maintainance of the bactericidal levels required for reliable antibiotic prophylaxis.

    Title The Cardiovascular Responses to Double Lumen Endobronchial Intubation and the Effect of Esmolol.
    Date September 1997
    Journal Anaesthesia
    Excerpt

    The cardiovascular responses to double lumen endobronchial intubation and the effect of esmolol were examined in two groups of 10 ASA 2 & 3 patients undergoing pulmonary surgery in a double blind, placebo-controlled study. Endobronchial intubation was associated with a significant increase in arterial pressure and heart rate (p = 0.004), and a significant increase in plasma noradrenaline concentrations (p < 0.01) in the control group. The haemodynamic changes were smaller (p < 0.001) in the patients who received esmolol compared with the changes in the the control group. The increase in plasma noradrenaline concentrations was significantly greater (p < 0.05) in the esmolol group. The pressor response to endobronchial intubation in this study was of a similar magnitude to that known to occur in response to tracheal intubation.

    Title Attenuation of B5r Mutants of Rabbitpox Virus in Vivo is Related to Impaired Growth and Not an Enhanced Host Inflammatory Response.
    Date July 1997
    Journal Virology
    Excerpt

    The rabbitpox virus (RPV) B5R protein, synthesized late in infection, is found as a 45-kDa membrane-associated protein of the envelope of infectious extracellular enveloped virus (EEV) and as a 38-kDa protein secreted from the cell by a process independent of morphogenesis. The protein is not found associated with intracellular mature virus (IMV). Deletion of the gene attenuates the virus (RPV delta B5R) in animals (mice and rabbits), has relatively little effect on formation of IMV, prevents EEV formation in some but not all cells, and leads to a reduced host range. Analysis of the sequence of the protein suggests relatedness to factor H of the complement cascade. Collectively, these observations suggest that attenuation of the virus in vivo could be linked to an inhibition of the inflammatory response, a deficiency in growth, or both. In this report we have analyzed the behavior of RPV delta B5R in infected mice and rabbits and conclude that attenuation of the mutant virus likely results from simple failure to grow within the infected animal and that the inflammatory response probably contributes little to the observed attenuation.

    Title Improved Respiratory Function and Analgesia Control After Endovascular Aaa Repair.
    Date April 1997
    Journal Journal of Endovascular Surgery : the Official Journal of the International Society for Endovascular Surgery
    Excerpt

    Endovascular abdominal aortic aneurysm (AAA) repair has been proposed as a minimally invasive alternative to conventional surgery and may offer significant advantages in respiratory function and analgesic requirements due to the absence of an abdominal incision.

    Title Postal Survey on the Long-term Use of Neuromuscular Block in the Intensive Care.
    Date February 1997
    Journal Intensive Care Medicine
    Excerpt

    To assess the long-term use of neuromuscular blocking (NMB) agents in intensive care, especially with reference to the potential problems of the long-term use of NMB drugs in the intensive care unit (ICU).

    Title Development of Monoclonal Antibodies for Measurement of Immunoglobulin G Antibody Responses in Blue and Gold Macaws (ara Ararauna).
    Date December 1996
    Journal American Journal of Veterinary Research
    Excerpt

    To produce monoclonal antibodies (MAB) with specificity for the heavy chain of macaw IgG; to incorporate these MAB into an ELISA to measure IgG responses of macaws inoculated with bovine serum albumin (BSA); and to evaluate the antigenicity of BSA in Blue and Gold Macaws.

    Title Maternal Immunoglobulin G Antibody Transfer and Development of Immunoglobulin G Antibody Responses in Blue and Gold Macaw (ara Ararauna) Chicks.
    Date December 1996
    Journal American Journal of Veterinary Research
    Excerpt

    To document the maternal transfer of IgG antibodies from Blue and Gold Macaw hens to chicks via the egg; to measure serum IgG half-life in macaw chicks; and to measure the ability of 2- to 10-week-old macaw chicks to generate primary and secondary IgG responses.

    Title Remifentanil--an Opioid for the 21st Century.
    Date September 1996
    Journal British Journal of Anaesthesia
    Title Forcep Deliveries.
    Date August 1996
    Journal Clinics in Perinatology
    Excerpt

    A historical review of the development of forceps and the refinements made that lend them to different clinical situations are presented. The proper settings for their use and the choice of instruments and methods of application for traction and rotation are discussed. The risks to mother and infant are considered. Following these general precepts should allow for continued safe usage in modern day obstetrics.

    Title Pesticide Incidents Reported to the Health and Safety Executive 1989/90- 1991/92.
    Date December 1995
    Journal Human & Experimental Toxicology
    Excerpt

    1. Data concerning pesticide incidents investigated by the Field Operations Division (FOD) of the Health and Safety Executive (HSE) in Great Britain have been collated for the three year period April 1989 to March 1992. Over this period the HSE investigated 613 incidents concerning pesticides: 338 related to general or environmental complaints not involving human poisoning and 275 were suspected poisoning incidents. 2. The two hundred and seventy-five suspected poisoning incidents were assessed by the Pesticide Incidents Appraisal Panel (PIAP) as 'confirmed', 'likely', 'unlikely', 'not confirmed', or that there were 'insufficient data' to make an assessment. Assessed data are unavailable for eight incidents reported in 1989. 3. Four hundred and eighteen members of the public were involved in 202 assessed incidents and 79 workers were exposed in 65 assessed incidents. Overall, 129 (48%) incidents were assessed as 'confirmed' or 'likely', 121 (45%) as 'unlikely' or 'not confirmed' and in 17 (6%) there were 'insufficient data' to form a judgement. Incidents occurring in an occupational setting were assessed as 'confirmed' or 'likely' more frequently (62%) than those involving members of the public (44%). 5. Thirty-six per cent of those involved in a 'confirmed' poisoning incident were working with a pesticide or were in close proximity to the operator; 41% were on private property adjacent to a field being sprayed and a further 23% involved those walking, cycling or jogging past a sprayed field.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Some Selected Psychological and Social Characteristics of Veteran Psychiatric Inpatients Without Stable Housing.
    Date October 1995
    Journal Psychological Reports
    Excerpt

    In this study were compared scores on selected MMPI subscales and demographic variables from 58 veterans with stable housing and 54 veterans without stable housing. Both groups were selected from the same inpatient psychiatric treatment program at the Houston VA Medical Center. The MMPI was administered and a number of demographic variables were collected from patients' archival computerized records. Comparison of MMPI scores indicated that patients without housing had marginally significantly higher scores on the clinical research subscale PD4A (Social Alienation). They were also significantly less likely to be married or employed. Logistic regression analysis indicated that, when multiple predictors were considered, marital status was the only significant risk factor for absence of stable housing. Results underscore the relevance of social services to treatment, discharge, and rehabilitation planning when working with veterans without stable housing.

    Title Some Outcome Predictors for Use in Vocational Rehabilitation Planning.
    Date October 1995
    Journal Psychological Reports
    Excerpt

    This study examined some predictor variables for positive outcome with a state vocational rehabilitation agency. Referrals to the agency from VA Counseling Psychology were analyzed to develop guidelines for identifying clients with good probability for positive outcome in their vocational rehabilitation planning. All subjects had a history of substance-abuse treatment at the Houston VA Medical Center. Analyses suggested a number of factors are relevant when assessing potential for successful vocational rehabilitation. Provision of drug-free housing, recent work history, and discharge status from a substance-abuse program were identified as relevant factors.

    Title Deaths from Pesticide Poisoning in England and Wales 1990-1991.
    Date August 1995
    Journal Human & Experimental Toxicology
    Excerpt

    1. Data on deaths from pesticide poisoning occurring in England and Wales in 1990 and 1991 have been collated. Pesticides were responsible for 44 of 3978 deaths from poisoning (excluding carbon monoxide and other gases) over this period. 2. At least 66% of all pesticide fatalities were due to suicide and overall there was a predominance of males (male:female ratio 2.4:1). Eighty per cent of deaths occurred in those more than 44 years old and no child under 10 years old died, although almost 50% of suspected pesticide poisoning incidents involve this age group. 3. Herbicides were responsible for 35 of the 44 deaths; seven were caused by insecticides, one by a molluscicide and one by an unspecified agent. The herbicide, paraquat, was responsible for 33 of 44 deaths (75%) and, although fewer fatalities have occurred from this cause in recent years, paraquat remains the most common cause of fatal pesticide poisoning in England and Wales.

    Title Disseminated Subcutaneous Mycobacterium Fortuitum Infection in a Dog.
    Date June 1995
    Journal Journal of the American Veterinary Medical Association
    Excerpt

    A 15-month-old 27.7-kg sexually intact male Doberman Pinscher was examined because of multiple subcutaneous abscesses on the neck, trunk, and limbs that developed 2 months after a dog bite and were refractory to antibiotic treatment. Incubation of a biopsy specimen at 37 C on a Lowenstein-Jensen agar slant for 8 days yielded growth of a Runyon's Group IV mycobacterium, and disseminated subcutaneous Mycobacterium sp infection was diagnosed. The organism was identified as M fortuitum, and was susceptible to amikacin, doxycycline, cefoxitin, minocycline, trimethoprim/sulfadiazine, and sulfisoxazole. Lesions resolved after 8 months of treatment with doxycycline (5 mg/kg of body weight, PO, q 12 h). The cause of dissemination was unknown; however, delay in debridement of the bite wound and corticosteroid use in initial wound management may have potentiated dissemination.

    Title Mapping and Investigation of the Role in Pathogenesis of the Major Unique Secreted 35-kda Protein of Rabbitpox Virus.
    Date February 1995
    Journal Virology
    Excerpt

    Following infection, many secreted poxvirus proteins are able to modulate the host immune response through interactions with cytokines or components of the complement pathway. A comparison of the secreted protein profiles from cells infected with vaccinia Western Reserve (VV-WR), cowpox virus Brighton strain, or rabbitpox virus (RPV) showed an abundant 35-kDa protein present only in the supernatants from RPV-infected cells. The gene encoding this protein was identified and mapped by N-terminal sequencing of the protein. Examination of the predicted amino acid sequence showed it to be identical to the 35-kDa secreted protein of the Lister strain of vaccinia virus described by Patel et al. (1990, J. Gen. Virol. 71, 2013-2021). The counterpart of this gene in the commonly studied VV-WR strain is truncated and encodes a 7.5-kDa protein under control of the well-characterized p7.5 promoter. While nonessential for replication in cell culture, conservation of this gene in at least two orthopoxvirus strains suggested that this protein might play an important role in vivo. Following intranasal inoculation of Balb/c mice at several doses (10(3), 10(4), or 10(5) PFU), a mutant of RPV lacking a functional 35-kDa gene (RPV delta 35) appeared to induce an earlier onset and more severe illness at low, sublethal doses (10(3) PFU) than was observed with wild-type (wt) RPV. At higher doses (10(4) or 10(5) PFU), the behavior of wt RPV and RPV delta 35 became indistinguishable and the overall LD50 values were similar. Intradermal infection of rabbits simultaneously, at separate sites, with RPV and RPV delta 35 showed no gross or microscopic differences between either primary skin lesions or viremic extension of each virus into the lungs. Therefore, this abundant secreted protein does not appear to play a major role in the virulence of the virus.

    Title Suspected Paediatric Pesticide Poisoning in the Uk. I--home Accident Surveillance System 1982-1988.
    Date December 1994
    Journal Human & Experimental Toxicology
    Excerpt

    1. Between 1982 and 1988, 239,350 children under 10 years old attended 20 A & E Departments in England and Wales (22 departments throughout the UK in 1988) as a result of a home accident. 15,144 of 239,350 were suspected cases of poisoning and 514 attendances involved pesticides. 2. 501 of 514 children who attended hospital were under 6 years old and 41% were thought to have ingested a rodenticide, 37% an insecticide or other animal poison, 13% an herbicide or fungicide and 9% other pesticides. 3. Overall 189 of 514 children were admitted to hospital and of these 189 cases 35% were discharged home in less than one day; 94% left hospital within 2 days. 4. Using these data we estimate that over the period of study approximately 1,850 children annually attended an Accident and Emergency Department in the UK with suspected pesticide poisoning and that some 450 were admitted to hospital. However, the morbidity from this cause is low and no deaths from pesticide poisoning have been reported in children in England and Wales for more than two decades.

    Title Suspected Paediatric Pesticide Poisoning in the Uk. Ii--home Accident Surveillance System 1989-1991.
    Date December 1994
    Journal Human & Experimental Toxicology
    Excerpt

    1. Between 1989 and 1991, 121,708 children less than 10 years old attended 22 Accident and Emergency (A & E) Departments in the UK as a result of an accident at home; 6,478 of these were cases of suspected poisoning. 2. Two hundred and fifty (124 boys and 126 girls) of 6,478 cases involved pesticides. Forty two per cent of these children were thought to have been poisoned by rodenticides, 33% by a different animal poison, 13% by an herbicide or fungicide, 7% by creosote and 5% by mothballs; a pattern similar to that observed in previous years. 3. Fifty-seven of 250 children (23%) were admitted to hospital. The proportion of children admitted to hospital between 1989 and 1991 is smaller than that observed between 1982-1988 (37%). Forty-six per cent of children were discharged home within one day and 95% within 2 days, whereas between 1982 and 1988 only 35% of children were discharged within one day. No child died during the study confirming the low morbidity. 4. Using these data we estimate that between 1989 and 1991 approximately 1,500 children annually attended an A & E Department in the UK with a diagnosis of suspected pesticide poisoning and that some 350 children were admitted each year.

    Title Establishing a Personal Financial Plan.
    Date May 1994
    Journal Nursing Management
    Title Cardiac Output Measurement and Continuous Venovenous Haemofiltration.
    Date February 1994
    Journal Anaesthesia
    Title The Effects of Serpin Gene Mutations on the Distinctive Pathobiology of Cowpox and Rabbitpox Virus Following Intranasal Inoculation of Balb/c Mice.
    Date November 1993
    Journal Virology
    Excerpt

    Intranasal infection of Balb/c mice with 106 plaque forming units (PFU) of wild-type cowpox virus (CPV) and rabbitpox virus (RPV) induced strikingly different pulmonary pathology despite nearly identical clinical signs of illness and LD50. Intranasal infection with CPV induced severe peribronchial, peribronchiolar, and perivascular hemorrhage with a mixed inflammatory cell infiltrate, bronchial and bronchiolar epithelial cell hyperplasia with intracytoplasmic acidophilic inclusion bodies, and alveolar hemorrhage and edema. In contrast, infection with RPV induced a mixed peribronchial and peribronchiolar inflammatory cell infiltrate, multifocal areas of bronchiolar epithelial cell coagulation necrosis, alveolar edema, and a conspicuous absence of pulmonary hemorrhage. Viremia was not detected following CPV infection and only 1 of 11 mice had brain-associated virus at death. Mice infected with RPV exhibited a viremia 2-3 days after infection and all mice had virus associated with the brain at death. Mice infected with viruses containing certain serine protease inhibitor (SPI) gene mutations (CPV delta SPI-1, CPV delta SPI-3, and RPV SPI-1-) exhibited no difference in clinical disease manifestation when compared with those infected with wild-type viruses. However, inactivation of the SPI-2 genes in either CPV or RPV resulted in disease attenuation and alteration of pulmonary pathology. Mice infected with the CPV delta SPI-2 mutant showed decreased pulmonary hemorrhage, reduced inflammation, and an absence of alveolar edema, while mice infected with the RPV delta SPI-2 mutant had a marked increase in intrapulmonary inflammatory cells and only a transient viremia.

    Title An Ap-1-like Motif in the First Intron of Human Pro Alpha 1(i) Collagen Gene is a Critical Determinant of Its Transcriptional Activity.
    Date April 1993
    Journal Molecular and Cellular Biochemistry
    Excerpt

    The first intron of the human Pro alpha 1(I) collagen gene contains an orientation-dependent enhancer composed of both positive and negative cis-acting elements involved in the transcriptional regulation of this gene. Deletion of a 360 bp Sau 3A intronic fragment spanning nucleotide +494 to +854 (S360) resulted in dramatic down-regulation of pCOL-KT (Thompson et al., J Biol Chem 266: 2549-2556, 1991). Using a DNaseI protection assay, we demonstrate a single footprint located at +590 to +615 in the S360 fragment; nuclear extracts prepared from mesenchymal and nonmesenchymal cells exhibited similar binding characteristics. A double stranded oligonucleotide representing a consensus Ap-1 binding sequence competed with S360 for binding. In contrast to what occurred in response to S360 deletion which was always accompanied by reduced expression, the deletion of the Ap-1 binding site (+598 to +off) caused either increased or decreased expression of the reporter gene depending on the target cell. Site-directed mutations in the Ap-1-like cis-element of Pro alpha 1(I) were also tested in transient expression assays. Consistent with the paradoxical results of Ap-1 deletion, we observed that the functional consequences of mutations in the Ap-1 site also varied in different cells. In A204 cells, one point mutation, which resulted in the loss of protein binding to S360, led to increased CAT activity while another point mutant, which retained binding of the Ap-1 like trans-acting factor(s), showed decreased CAT expression. The effects of these two mutations in the HFL-1 cells were exactly opposite of what was seen for A204 cells. Based on these observations, we postulate that the Ap-1 site plays a critical role in the transcriptional activity of the human Pro alpha 1(I) gene. The implications of an apparently dual mode of regulation through a single cis-regulatory element are discussed.

    Title Paraneoplastic Leukocytosis Associated with a Rectal Adenomatous Polyp in a Dog.
    Date October 1992
    Journal Journal of the American Veterinary Medical Association
    Excerpt

    A dog with a rectal adenomatous polyp had extreme neutrophilic leukocytosis, monocytosis, and eosinophilia consistent with a paraneoplastic syndrome. Resolution of the leukogram abnormalities after tumor excision supported this belief. Except for a lack of circulating myeloblasts, the dog had leukogram findings consistent with a neutrophilic leukemoid reaction.

    Title The Transcriptional Tissue Specificity of the Human Pro Alpha 1 (i) Collagen Gene is Determined by a Negative Cis-regulatory Element in the Promoter.
    Date October 1992
    Journal The Biochemical Journal
    Excerpt

    The transcriptional activity of plasmid pCOL-KT, in which human pro alpha 1 (I) collagen gene upstream sequences up to -804 and most of the first intron (+474 to +1440) drive expression of the chloramphenicol acetyltransferase (CAT) gene [Thompson, Simkevich, Holness, Kang & Raghow (1991) J. Biol. Chem. 266, 2549-2556], was tested in a number of mesenchymal and non-mesenchymal cells. We observed that pCOL-KT was readily expressed in fibroblasts of human (IMR-90 and HFL-1), murine (NIH 3T3) and avian (SL-29) origin and in a human rhabdomyosarcoma cell line (A204), but failed to be expressed in human erythroleukaemia (K562) and rat pheochromocytoma (PC12) cells, indicating that the regulatory elements required for appropriate tissue-specific expression of the human pro alpha 1 (I) collagen gene were present in pCOL-KT. To delineate the nature of cis-acting sequences which determine the tissue specificity of pro alpha 1 (I) collagen gene expression, functional consequences of deletions in the promoter and first intron of pCOL-KT were tested in various cell types by transient expression assays. Cis elements in the promoter-proximal and intronic sequences displayed either a positive or a negative influence depending on the cell type. Thus deletion of fragments using EcoRV (nt -625 to -442 deleted), XbaI (-804 to -331) or SstII (+670 to +1440) resulted in 2-10-fold decreased expression in A204 and HFL-1 cells. The negative influences of deletions in the promoter-proximal sequences was apparently considerably relieved by deleting sequences in the first intron, and the constructs containing the EcoRV/SstII or XbaI/SstII double deletions were expressed to a much greater extent than either of the single deletion constructs. In contrast, the XbaI* deletion (nt -804 to -609), either alone or in combination with the intronic deletion, resulted in very high expression in all cells regardless of their collagen phenotype; the XbaI*/(-SstII) construct, which contained the intronic SstII fragment (+670 to +1440) in the reverse orientation, was not expressed in either mesenchymal or nonmesenchymal cells. Based on these results, we conclude that orientation-dependent interactions between negatively acting 5'-upstream sequences and the first intron determine the mesenchymal cell specificity of human pro alpha 1 (I) collagen gene transcription.

    Title 192iridium Brachytherapy, Using an Intracavitary Afterload Device, for Treatment of Intranasal Neoplasms in Dogs.
    Date June 1992
    Journal American Journal of Veterinary Research
    Excerpt

    After surgical removal of a primary intranasal neoplasm, an implant device, designed to deliver 192iridium (192Ir) brachytherapy, was positioned in the nasal cavity of 8 dogs. Ribbons containing 192Ir seeds were placed in the device, using an afterloading technique. Dosimetry, to a dose of 7,000 to 10,000 centiGray (cGy), was calculated to encompass the site previously occupied by the tumor and a 1-cm margin of surrounding normal tissue. The quantity of 192Ir implanted varied between 16.69 and 100.80 mg of radium equivalent. The duration of implantation ranged from 90 to 168 hours. All dogs tolerated the implant well, but had a mucoid nasal discharge after radiotherapy. The implant device allowed rapid application and removal of the radioactive ribbons. Mean (+/- SD) radiation exposure to each radiotherapist during seed loading and unloading was 14.4 (+/- 5.3) and 4.5 (+/- 0.9) mrem, respectively. A uniform dose distribution around the intranasal implant device was achieved; however, dogs that received doses in excess of 9,400 cGy at the dorsolateral surface of the nose and/or hard palate had bone and soft tissue necrosis between 70 and 120 days after treatment. One dog was euthanatized 50 days after treatment because of metastatic disease, and 2 dogs were euthanatized because of local tumor recurrence at 125 and 212 days. Death, considered unrelated to treatment, occurred in 1 dog that was euthanatized 27 days after treatment and in 3 dogs that died 30, 93, and 456 days after treatment. Necropsy was performed on 3 of these dogs and evidence of intranasal neoplasia was not observed. One dog remained disease-free at 587 days after treatment.

    Title Evaluation of Survival Times After Limb Amputation, with and Without Subsequent Administration of Cisplatin, for Treatment of Appendicular Osteosarcoma in Dogs: 30 Cases (1979-1990).
    Date May 1992
    Journal Journal of the American Veterinary Medical Association
    Excerpt

    Appendicular osteosarcoma was diagnosed in 30 dogs. Fifteen dogs were treated by limb amputation alone, and 15 dogs were treated by limb amputation followed by 2 doses of cisplatin given IV approximately 2 and 7 weeks after limb removal. Mean survival time after limb amputation alone +/- SD was 190 +/- 138 days (median, 168 days); 7 dogs survived longer than 6 months, and 3 dogs survived more than 1 year. Fourteen of 15 dogs treated by amputation and administration of cisplatin survived a mean of 315 +/- 158 days (median, 290 days) after amputation, and 1 dog was still alive at 1,095 days; 13 dogs survived longer than 6 months and 5 dogs survived more than 1 year. Survival time was significantly (P less than 0.05) greater in dogs given cisplatin.

    Title Basic Immunologic Principles of Allergic Diseases.
    Date March 1992
    Journal Seminars in Veterinary Medicine and Surgery (small Animal)
    Title In Vivo Fungal Presence and Growth on Two Resilient Denture Liners.
    Date August 1991
    Journal The Journal of Prosthetic Dentistry
    Excerpt

    To determine whether two intraoral-setting resilient denture liners supported the in vivo presence or growth of oral commensal fungi, the liners were randomly placed in the mandibular complete dentures of 14 patients. Cytologic smears were made from the liner surfaces at 1 hour and 1, 2, 7, 14 and 30 days after intraoral placement. Yeast forms were observed in six patient trials of material A and in two trials of material B. Hyphae were observed in only one patient trial of material A and in two trials of material B. When yeast forms and hyphae findings were combined and were considered as indicative of fungal presence or growth, the prevalence up to 30 days was seven for material A and four for material B. Statistical analysis revealed no significant difference in the prevalence of fungal presence or growth between the two resilient denture liners tested.

    Title Stimulation of Mature Canine Intervertebral Disc by Growth Factors.
    Date June 1991
    Journal Spine
    Excerpt

    Although the role of growth factors in the regulation of phenotype, maintenance, and repair of cartilaginous tissues has been extensively evaluated, the response of intervertebral disc to growth factors has not been investigated. A tissue culture system for annular, transitional, and nuclear regions of mature canine intervertebral disc was devised to assess the proliferative response, as determined by 3H-thymidine incorporation, and the biosynthetic response, assayed by 35S-sulfate incorporation into proteoglycan, of these tissues to growth factors. The culture system achieved steady-state conditions in serum-free mediums at 4 days and was perturbed by plasma-derived equine serum, fetal calf serum, insulin-like growth factor-1, epidermal growth factor, fibroblast growth factor, and transforming growth factor-beta. Incorporation rates by the tissue regions of up to five times the control rate were recorded; the nucleus and transition zone responded more than anulus. Transforming growth factor-beta and epidermal growth factor elicited greater responses than fibroblast growth factor; insulin-like growth factor-1 produced a marginally significant response in the nucleus and no response in the anulus and transition. The intervertebral disc appeared to respond to the growth factors differently than cartilage, and this may represent inherent differences in cell biology. The biologic significance and basis of these responses require further evaluation. However, the responses observed, particularly in the nucleus and transition zone suggest the possibility that disc repair can be modulated by growth factors. A therapeutic approach to degenerative disc disease involving enhanced tissue repair by exogenous growth factors would be of great clinical significance.

    Title Magnetic Resonance Imaging Reflects the Chemical Changes of Aging Degeneration in the Human Intervertebral Disk.
    Date June 1991
    Journal The Journal of Rheumatology. Supplement
    Excerpt

    T2 weighed spin echo magnetic resonance images (MRI) of the intervertebral disks of 4 lumbar spines were graded and the nuclei pulposi were analyzed for water, collagen and proteoglycan. The brightness of the nuclear image correlated directly with the proteoglycan concentration, but not with the water or collagen. The dark midnuclear cleft had a collagen concentration slightly higher and a water concentration slightly lower than the adjacent zones; no corresponding differences in proteoglycan were seen, although the relationship with MRI grade was confirmed.

    Title Genomic Organization of the Human Procollagen Alpha 1(ii) Collagen Gene.
    Date April 1991
    Journal European Journal of Biochemistry / Febs
    Excerpt

    The nucleotide sequence of the human procollagen alpha 1(II) collagen gene extending from within the first intron through exon 15, and part of the 15th intron has been determined. This sequence analysis (7056 bases) identifies the intron/exon organization of the region of this gene encoding the N-propeptide and part of the triple-helical domain. Structural comparison of this with the genes of other human fibrillar collagens shows considerable diversity in terms of size and number of introns and exons that encodes the N-propeptide domain. Although the genomic structure of the human procollagen alpha 1(II) gene is quite different from the rat procollagen alpha 1(II) gene, the nucleotide coding sequences are 89% identical.

    Title In Vitro Methylation of the Promoter and Enhancer of Pro Alpha 1(i) Collagen Gene Leads to Its Transcriptional Inactivation.
    Date March 1991
    Journal The Journal of Biological Chemistry
    Excerpt

    We created pCOL-KT, a plasmid construct in which the promoter/enhancer of human Pro alpha 1(I) gene is linked to the chloramphenicol acetyl transferase reporter gene. The Pro alpha 1(I) promoter/enhancer in pCOL-KT was methylated in vitro and tested for transcriptional activity by transient expression analysis. Methylation of the construct with bacterial methylases reduced transcriptional activity about 25-fold. Site-specific methylation of eight potential canonical sites of eukaryotic methylation within the promoter greatly reduced transcriptional activity. Chromatin conformation of the transfected pCOL-KT DNA was analyzed by nuclease sensitivity. Although both methylated and unmethylated transfected DNA had increased susceptibility to DNase I compared with the endogenous gene, the methylated transfected DNA showed increased resistance to nuclease when compared with unmethylated transfected DNA, indicating that the methylation of the DNA alters the chromatin conformation. We also tested the ability of a human rhabdomyosarcoma cell line that does not express type I collagen to support transcription from an exogenously added Pro alpha 1(I) promoter/enhancer. The transformed cell line is able to support transcription from the Pro alpha 1(I) promoter/enhancer. Treatment of the transformed cell line with 5-azacytidine, a potent inhibitor of DNA methylation, resulted in transcriptional activation of the Pro alpha 1(I) gene. These findings, along with the extreme methylation sensitivity of the Pro alpha 1(I) promoter and enhancer, suggest that DNA methylation may be an important mechanism of transcriptional inactivation of interstitial collagen genes.

    Title Decompensation After Cotrel-dubousset Instrumentation of Idiopathic Scoliosis.
    Date January 1991
    Journal Spine
    Excerpt

    Spinal decompensation after corrective surgery for scoliosis appears to be a significant problem after Cotrel-Dubousset instrumentation (CDI). CDI produces torsional changes in the instrumented and uninstrumented spine that could result in spinal imbalance. Preoperative and postoperative three-dimensional analysis including computed tomography (CT) scans to measure vertebral rotation and segmental rotation were performed to evaluate the importance of torsional changes. Moe/King Type II deformities had a substantially greater risk of imbalance. Deformities instrumented over fewer spinal segments were less likely to decompensate. Specifically, instrumentation excluding the mobile transition segment, determined by maximum segmental rotation and segmental Cobb angle, was likely to decompensate. Derotation and deformity correction excessive in relation to preoperative side bending flexibility and segmental rotation frequently resulted in imbalance. Spinal imbalance after CDI can be reduced by avoiding overcorrection and inclusion of mobile transition segments.

    Title The Iridovirus Frog Virus 3: a Model for Trans-acting Proteins.
    Date December 1990
    Journal Microbiological Sciences
    Excerpt

    The amphibian Iridovirus, frog virus 3 (FV3), produces at least two trans-activating proteins that stimulate the expression of viral genes. One of these proteins induces transcription from the promoter of an immediate-early FV3 gene, whereas the other induces transcription from exogenously methylated DNA. These proteins may serve as a model for both viral and cellular trans-acting factors.

    Title Human Hla-dr Beta Gene Hypervariable Region Homology in the Biobreeding Bb Rat: Selection of the Diabetic-resistant Subline As a Rheumatoid Arthritis Research Tool to Characterize the Immunopathologic Response to Human Type Ii Collagen.
    Date December 1990
    Journal The Journal of Experimental Medicine
    Excerpt

    Collagen arthritis (CA), an autoimmune model of rheumatoid arthritis (RA), has been studied in various animals. However, it has not been studied in an animal with a genetic background relevant to RA. We selected rats from a diabetic-resistant (DR) subline of the diabetic BB rat because they have an autoimmune disease-prone background, but not the immunodeficiencies of the diabetic BB rat, and the third hypervariable region (HVRIII) of the BB RT1.D beta gene appeared to encode a nucleotide sequence of the human HLA DR beta gene, which has been reported to be associated with susceptibility to RA. We synthesized oligonucleotide primers flanking the RT1.D beta HVRIII, cloned polymerase chain reaction-amplified DNA into M13mp18, and confirmed the presence of the susceptibility sequence (SS) (RRRAA) by the dideoxy sequencing method in a colony of DR BB/Wor-UTM rats. When immunized with human type II collagen (CII) in incomplete Freunds adjuvant (IFA), arthritis developed rapidly by day 10 with 100% incidence. Light and electron microscopy revealed an unusually severe and aggressive, bidirectional pattern of cartilage resorption by synovial and subchondral mononuclear and multinucleated inflammatory cells. These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype. This study provides further support to the role of CA as a relevant RA model, the specific roles of the CB11 fragment as a major site of arthritogenic epitopes, and of antibody mechanisms in the pathogenesis of CA. Furthermore, the identification of an RA SS in an immune response gene of the DR BB rat presents a novel opportunity to determine with an animal model the role of other antigens as well as this SS in RA.

    Title Semitendinosus Repair Augmentation of Acute Anterior Cruciate Ligament Rupture.
    Date September 1990
    Journal Canadian Journal of Sport Sciences = Journal Canadien Des Sciences Du Sport
    Excerpt

    The semitendinosus tendon has been used since 1980 by the senior author (J.P.M) to augment anterior cruciate ligament repair surgery in cases of acute rupture. There are two major criticisms of this technique: first, the semitendinosus tendon lacks adequate tensile strength functionally to replace the normal anterior cruciate ligament; and second, the semitendinosus is an important hamstring muscle, the loss of which has the potential to weaken the dynamic control of the knee. Objective measurement of success or failure of this procedure is provided by KT1000 arthrometer laxity testing for static recovery of stability, and by Cybex isokinetic dynamometer testing of peak torque and fatigue index to evaluate muscular rehabilitation. Thirty-seven patients were examined using these techniques in a standardized protocol at least two years after surgery. Results show excellent return of static stability and near-normal recovery of strength and endurance of quadriceps and hamstring muscles.

    Title Human Neutrophil Collagenase. A Distinct Gene Product with Homology to Other Matrix Metalloproteinases.
    Date August 1990
    Journal The Journal of Biological Chemistry
    Excerpt

    We have identified and sequenced a cDNA encoding human neutrophil collagenase from a lambda gt11 cDNA library constructed from mRNA extracted from the peripheral leukocytes of a patient with chronic granulocytic leukemia. The library was screened with an oligonucleotide probe constructed from the putative zinc-binding region of fibroblast collagenase. Eleven positive clones were identified, of which the one bearing the largest insert (2.2 kilobases (kb)) was sequenced. From the nucleotide sequence of the 2.2-kb cDNA clone we have deduced a 467-amino acid sequence representing the entire coding sequence of the enzyme. The deduced protein was confirmed as neutrophil collagenase by conformity with the amino-terminal sequence analyses of three tryptic peptides of purified neutrophil collagenase. The cDNA clone hybridizes to a 3.3-kb mRNA present in RNA extracted from human bone marrow but did not hybridize with RNA isolated from U937 cells induced to differentiate with phorbol myristate acetate. Neutrophil collagenase was found to possess 57% identity with the deduced protein sequence for fibroblast collagenase with 72% chemical similarity. Certain regions of the molecule, including the putative zinc-binding region, are highly conserved. When compared with the published sequence for fibroblast collagenase, neutrophil collagenase contains four additional sites for glycosylation. Medium from COS-7 cells transfected with a pcDNA1 eucaryotic expression vector containing cDNA for neutrophil collagenase degraded type I collagen into the three-quarter, one-quarter fragments characteristic of mammalian interstitial collagenase activity. Thus, definitive evidence based on the cDNA sequence confirms the neutrophil collagenase is a distinct gene product and a member of the family of matrix metalloproteinases.

    Title Preliminary Evaluation of a Scheme for Grading the Gross Morphology of the Human Intervertebral Disc.
    Date August 1990
    Journal Spine
    Excerpt

    A five-category grading scheme for assessing the gross morphology of midsagittal sections of the human lumbar intervetebral disc was developed. The ability of three observers to categorize a series of 68 discs with a wide spectrum of morphologies established the comprehensiveness of the classification. Three independent observers tested the reproducibility of the procedure by assignment of grades blindly to duplicate images of 68 discs taken from 15 spines. The intraobserver agreement ranged from 87 to 91%. The interobserver agreement was 61, 64, and 88% for the three pairs, the two low values being attributable to the bias of one observer. The agreement between the assigned and average grades was 85, 92, 68, 90, and 76% for Grades I through V, respectively. Except for Grade III, the disagreements were attributable mainly to the bias of one observer. Both the increase in the grade with age and the finding that all the discs within 14 of 15 spines had a narrow range of grades demonstrated the biologic credibility of the scheme.

    Title Does Increasing Haemoglobin Concentration and Haematocrit Have a Pressor Effect in Dialysis Patients?
    Date April 1990
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    The haemodynamic consequences of differing rates of rise of haemoglobin and haematocrit in haemodialysis and CAPD patients were examined. Pre-dialysis mean arterial pressure, weight and haematological indices were recorded in 100 established haemodialysis patients prior to a 2-unit blood transfusion and repeated, pre-dialysis, within 1 week. Haemoglobin rose from 6.7 +/- 0.2 to 9.3 +/- 0.1 g/dl, weight was unchanged, and there was a small fall in mean arterial pressure. Similar indices were recorded, including the mid-arm circumference (MAC) in 100 CAPD patients 1 month after starting CAPD and at the time of maximum haemoglobin within the first year. Haemoglobin rose from 8.5 +/- 0.1 to 10.7 +/- 0.1 g/dl, weight increased slightly, but there was no change in MAC: weight ratio and there was a small fall in mean arterial pressure. In neither group was there a change in antihypertensive medication. In conclusion, increasing the haemoglobin concentration and haematocrit of dialysis patients within the range described in this study did not promote elevated blood pressure.

    Title Transcription of Methylated Viral Dna by Eukaryotic Rna Polymerase Ii.
    Date October 1989
    Journal Cell Biophysics
    Excerpt

    The genome of the large icosahedral DNA virus, frog virus 3 (FV3), is heavily methylated at the cytosine residues of dCdG dinucleotide pairs, with more than 22% of the total cytosine residues in the form of 5-methylcytosine (5mC). This methylation is carried out postreplicatively in the cytoplasm of infected cells by a virus-encoded DNA methyltransferase. DNA methyltransferase activity was shown to copurify with a 26 kD virus-induced, DNA-binding protein that had an altered mobility in extracts from cells infected with a DNA-methyl-transferase deficient mutant of FV3. Immediately after infection, the highly methylated parental DNA is transcribed in the nucleus by the host cell RNA polymerase II. As FV3 induces the synthesis of a protein that can override the inhibitory effect of methylation on the transcription of exogenous promoters methylation in vitro, we suggest that this protein is a factor evolved by this virus to allow transcription from methylated promoters by eukaryotic RNA polymerase II.

    Title Lymphatic Filariasis. Brugia Malayi Infection in the Ferret (mustela Putorius Furo).
    Date September 1989
    Journal The American Journal of Pathology
    Title Molecular Mechanisms of Collagen Gene Expression.
    Date August 1989
    Journal Molecular and Cellular Biochemistry
    Excerpt

    Collagens are a structurally and functionally heterogenous group of proteins encoded by a family of genes that share evolutionary history. Collagen gene expression is regulated both in developmental, tissue-specific manners as well as in response to a variety of biologic and pharmacologic inducers. In the present review we have attempted to synthesize a conceptual overview of the available information from studies aimed at deciphering the molecular mechanisms of collagen gene expression. We have chosen to focus our discussion mainly, although not exclusively, to observations relating to type I collagen gene for a number of practical reasons. The underlying theme that emerges from this survey of the literature is that the regulation of collagen gene expression is complex, utilizing transcriptional, posttranscriptional and translational mechanisms. Although the transcriptional control mechanisms that involve activation and modulation of collagen gene transcription by RNA polymerase II appear to predominate, preferential stabilization of collagen mRNAs and modulation of translational discrimination appear to play significant roles in the regulation of collagen biosynthesis under some physiological situations. Molecular organization of the regulatory regions of collagen genes reveal a mosaic of subdomains with overlapping sequence motifs, involved in positive and negative transcriptional regulation. The precise identity of the cis-acting subdomains of the promoter/enhancer-proximal DNA of collagen gene and how they interact with the trans-acting nuclear protein(s) have yet to be elucidated and will remain the focus of future studies.

    Title Methylation of the Promoter for an Immediate-early Frog Virus 3 Gene Does Not Inhibit Transcription.
    Date December 1988
    Journal Journal of Virology
    Excerpt

    Methylation of critical sites within the promoter region of eucaryotic genes has been shown to inhibit transcription by RNA polymerase II. However, although the large DNA virus frog virus 3 (FV3) has a highly methylated genome, it uses host RNA polymerase II for at least the immediate-early stage of transcription. We have previously shown that an FV3-induced trans-acting protein allows transcription from adenovirus promoters inactivated by methylation. Since FV3 immediate-early genes are transcribed in the absence of de novo protein synthesis, it appears that the virus-induced trans-acting protein that allows transcription from methylated templates is not required for transcription of the immediate-early FV3 genes, possibly because they are not methylated in critical regulatory sequences. In this study, we used site-directed mutagenesis to alter the three CpG dinucleotide sequences in the promoter region of an immediate-early FV3 gene and thereby created sites recognized by bacterial methylases. Transient-expression assays demonstrated that neither the mutations nor methylation of the mutated sites inhibited transcription from the FV3 promoter in FV3-infected cells. These findings support the hypothesis that the immediate-early genes of FV3 do not contain methylatable sites in regions critical for transcription. The function of the virus-induced trans-acting protein that can override the inhibitory effect of methylation may therefore be to facilitate the transcription of methylated delayed-early or late FV3 genes.

    Title The Individual Cost of Treating Aids.
    Date October 1988
    Journal The Internist
    Title Enhanced Inflammation to Brugia Malayi Microfilariae in Ferrets Infected with Trichinella Spiralis.
    Date April 1988
    Journal The Journal of Parasitology
    Title A Randomized Trial Comparing Vindesine and Cisplatinum to Vindesine and Methotrexate in Advanced Non Small Cell Lung Carcinoma.
    Date March 1988
    Journal European Journal of Cancer & Clinical Oncology
    Excerpt

    Combination chemotherapy using vindesine and cisplatinum has been reported to be active in non-small cell lung carcinoma (NSCLC). In an attempt to reduce the potential neurotoxicity of this combination, and to assess the role of cisplatinum, a randomized trial has compared vindesine and cisplatinum to vindesine and methotrexate in 48 patients with advanced symptomatic NSCLC. Patient characteristics were similar in the two treatment arms. Objective tumour response and survival were similar for both treatments. No complete response occurred. Four patients receiving vindesine/cisplatinum (16%) and three patients receiving vindesine/methotrexate (13%) had a partial response. All responses occurred in patients with a performance status of 70% or more and no response was seen in patients with squamous cell carcinoma. Median survival for both regimens was 16 weeks. Toxicity was considerable and only six patients (12.5%) felt better on treatment. Nausea and vomiting were more frequent in the vindesine/cisplatinum arm, but mild neurotoxicity was more common in the vindesine/methotrexate arm. The low response rates, short survival and significant toxicity suggest that the role of combination chemotherapy in NSCLC remains to be established.

    Title Infection with Frog Virus 3 Allows Transcription of Dna Methylated at Cytosine but Not Adenine Residues.
    Date October 1987
    Journal Virology
    Excerpt

    The genome of the iridovirus, frog virus 3, is highly methylated at cytosine residues by a virus-encoded DNA methyltransferase. We have shown previously that an FV3-induced trans-acting protein alters either host RNA polymerase II or methylated template to allow transcription from promoters inactivated by methylation. We now present evidence that the ability of FV3-infected cells to transcribe methylated DNA is specific for DNA methylated at cytosine residues. Eukaryotic promoters were inactivated by methylation of either adenine or cytosine residues, and tested for transcriptional activity. Only promoters inactivated by cytosine methylation were transcribed in FV3-infected cells. We also show that the dinucleotide sequence in which the methylcytosine is found appears to have no effect on the ability of FV3 to trans-activate the methylated promoters.

    Title Neurotoxicosis Associated with the Use of Hexachlorophene in a Cat.
    Date July 1987
    Journal Journal of the American Veterinary Medical Association
    Excerpt

    Two weeks after daily topical application of hexachlorophene, a 4-week-old female kitten developed cardiovascular collapse, corneal ulcers, trembling, lethargy, and weakness. The kitten was euthanatized. At necropsy, the tissues appeared macroscopically normal; however, microscopic examination of tissue specimens indicated status spongiosis, astrocytosis, and microgliosis of the cerebral and cerebellar white matter and corticospinal tracts. Neuronal cell bodies forming the affected white matter were intact, indicating that demyelination may have been the cause of the lesions. The neurologic lesions were considered compatible with those of hexachlorophene-induced toxicosis.

    Title Parental Influences on Substance Use: Gender Differences and Stage Theory.
    Date July 1987
    Journal Journal of Drug Education
    Title Parental, Personality, and Peer Correlates of Psychoactive Mushroom Use.
    Date December 1986
    Journal Journal of Drug Education
    Title Trans-activation of a Methylated Adenovirus Promoter by a Frog Virus 3 Protein.
    Date November 1986
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    The high degree of methylation of the frog virus 3 (FV3) genome suggests that FV3-infected cells are capable of transcribing highly methylated DNA. We tested this hypothesis by assaying the transcriptional activity of adenovirus promoters known to be inhibited by methylation. Plasmid constructs containing the E1a and E2aE promoters of adenovirus type 12 linked to the gene for chloramphenicol acetyltransferase [(CAT) EC 2.3.1.28], when methylated and introduced into eukaryotic cells, promoted CAT synthesis only when the cells were subsequently infected with FV3. Mapping of transcriptional initiation sites revealed that the same sites in the E1a promoter were used for the initiation of transcription in uninfected and infected cells. Moreover, Southern blots showed that transfected plasmid DNA from FV3-infected cells was not demethylated. The absence of CAT-specific RNA in transfected cells infected with FV3 in the presence of protein synthesis inhibitors demonstrated that a virus-induced protein was responsible for the trans-activation. Inhibition of transcription from the methylated template by alpha-amanitin indicated that a functional host RNA polymerase II is required for transcription of methylated DNA in FV3-infected cells. The virus-induced trans-acting protein presumably alters either host RNA polymerase II or the methylated DNA template to allow transcription from the methylated adenovirus promoters.

    Title Antibody and Cellular Immune Responses to Microfilarial Antigens in Ferrets Experimentally Infected with Brugia Malayi.
    Date September 1986
    Journal Zeitschrift Für Parasitenkunde (berlin, Germany)
    Excerpt

    Eleven of 15 ferrets experimentally infected with Brugia malayi became amicrofilaremic after a brief patency; only four ferrets remained patent after 6 months of infection and two of these ferrets developed a high, persistent microfilaremia. Blastogenic responses of peripheral blood lymphocytes to antigens of microfilariae (mf), assayed in vitro, demonstrated an antigen sensitivity at prepatent, patent and postpatent periods of infection. Lymphocytes from ferrets with high microfilaremia had elevated background responses in culture which were directly correlated with the number of circulating mf. This background response was attributed to antigenic stimulation by mf present in the lymphocyte cultures; addition of mf to cultures of lymphocytes from postpatent ferrets induced responses equivalent to those observed in microfilaremic ferrets. Lymphocyte responses to the mitogen, concanavalin A, did not differ significantly among microfilaremic, amicrofilaremic and uninfected ferrets. Antibody in IgG to antigens of mf measured by ELISA and by immunoblots from SDS-PAGE showed similar patterns of response in ferrets which became amicrofilaremic and in the few ferrets which remained microfilaremic. prausnitz-Kustner tests demonstrated no consistent differences in titers to microfilarial antigens between patent and amicrofilaremic ferrets. The results suggest a high level of immune responsiveness to antigens of mf in infected ferrets with no evidence of immunosuppression associated with prolonged microfilaremia or of major changes in immune responses with development of amicrofilaremic infections.

    Title Elucidation of the B-genome Donor to Triticum Turgidum by Unique- and Repeated-sequence Dna Hybridizations.
    Date May 1986
    Journal Biochemical Genetics
    Excerpt

    In vitro DNA:DNA hybridizations and hydroxyapatite thermal-elution chromatography were employed to identify the diploid Triticum species ancestral to the B genome of T. turgidum. Unique and repeated sequences from the various Triticum species were separated by hybridization and thermal elution on hydroxyapatite. Unique- and repeated-sequence fractions of labeled T. turgidum var. durum DNA were hybridized to the corresponding fractions of unlabeled DNAs of T. searsii, T. speltoides, T. longissimum, T. sharonensis, and T. bicorne. Thermal stability profiles were constructed to evaluate base-sequence complementarity between T. turgidum var. durum and the diploid Triticum species. The heteroduplex thermal stabilities indicated that, of the five species examined, T. searsii was the most closely related to the B genome of T. turgidum var. durum. The thermal stability profiles further indicated that the repeated DNA fractions from the Triticum species are more similar than the unique-sequence fractions. This indicates that all of the Triticum species are very closely related and, in all probability, have diverged from a single progenitor species.

    Title Brugia Malayi: Intravenous Injection of Microfilariae in Ferrets As an Experimental Method for Occult Filariasis.
    Date October 1985
    Journal Experimental Parasitology
    Excerpt

    Microfilaremia, immune responses, and pathology were compared in ferrets infected with 100 third-stage larvae of Brugia malayi (subperiodic strain) or injected intravenously with 10(6) microfilariae. Ferrets (Mustela putorius furo) inoculated with third-stage larvae typically became patent during the third month after infection, with a mean patency of 123 +/- 25 (SE) days. Ferrets injected intravenously with microfilariae exhibited a relatively constant microfilaremia for 3-4 weeks and usually cleared microfilariae before the fourth month. Ferrets that cleared microfilariae after intravenous injection of microfilariae or after infection with third-stage larvae failed to become patent or became amicrofilaremic within 3 weeks after a challenge intravenous injection of 10(6) microfilariae. Clearance of circulating microfilariae was associated with eosinophilia and serum antibody specific for the microfilarial sheath in ferrets injected with microfilariae and in most ferrets infected with third-stage larvae. Ferrets infected with third-stage larvae and necropsied after clearance of microfilariae had tissue inflammatory reactions to microfilariae characteristic of occult filariasis (tropical eosinophilia) in man; these ferrets exhibited immediate cutaneous hypersensitivity and circulating reaginic antibody to antigens of microfilariae. In ferrets necropsied following two intravenous injections of microfilariae, the majority of ferrets examined within 10 days after clearance of microfilariae had visible liver lesions to microfilariae identical to those of the ferrets infected with third-stage larvae; immediate cutaneous hypersensitivity and reaginic antibody were not consistently detected in ferrets injected with microfilariae. Sera from ferrets that had cleared circulating microfilariae were transferred passively into ferrets made microfilaremic by intravenous injection of microfilariae. Sera with microfilarial sheath-reactive IgG antibody titers (greater than or equal to 1:200) and microfilarial agglutination titers (greater than or equal to 1:40) rapidly cleared injected microfilariae (less than 24 hr); this serum also cleared or greatly reduced circulating microfilariae established by an infection with third-stage larvae; only the IgG-containing fraction of the sera was active in immune clearance. Sera that cleared microfilariae of B. malayi did not clear circulating microfilariae of Dirofilaria immitis or prevent recurrence of circulating microfilariae of B. malayi in ferrets infected with adult filariae.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Mushroom Use by College Students.
    Date September 1985
    Journal Journal of Drug Education
    Title Identification of the G-genome Donor to Triticum Timopheevii by Dna:dna Hybridizations.
    Date June 1985
    Journal Biochemical Genetics
    Excerpt

    In vitro DNA:DNA hybridizations and hydroxyapatite thermal-elution chromatography were employed to identify the diploid Triticum species ancestral to the G genome of Triticum timopheevii. Total genomic, unique-sequence, and repeated-sequence fractions of 3H-T. timopheevii DNA were hybridized to the corresponding fractions of unlabeled DNAs of T. searsii, T. speltoides, T. sharonensis, T. longissimum, and T. bicorne. The heteroduplex thermal stabilities indicated that, of the five species examined, T. speltoides was the most closely related to the G genome of T. timopheevii. Thus, T. speltoides appears to be the G-genome donor to T. timopheevii. The thermal stability profiles further indicated that the repeated DNA fractions from the five diploid species and the tetraploid T. timopheevii are more similar than the unique DNA fractions. This indicates that all of these species are closely related and that the sequences which comprise the current repeated fractions in the various species have not undergone any significant change since the formation of various species.

    Title Pathology of Experimental Infection with Brugia Malayi in Ferrets: Comparison with Occult Filariasis in Man.
    Date April 1985
    Journal Acta Tropica
    Excerpt

    Ferrets experimentally infected with Brugia malayi (subperiodic strain) developed eosinophilia at patency and usually became amicrofilaremic. Ferrets necropsied within 3 months after becoming amicrofilaremic had granulomas and focal reactions to degenerating microfilariae in their livers, lungs and lymph nodes essentially identical to those of tropical eosinophilia. Four of 7 ferrets that received multiple inoculations of larvae, developed edema of the inoculated paw and leg after becoming amicrofilaremic and 6 of these 7 ferrets had granulomatous lymphangitis and lymphadenitis of inoculated limbs but not the lesions of lung and liver characteristic of occult infection.

    Title Osteochondral Lesions of the Talus in a Sports Medicine Clinic. A New Radiographic Technique and Surgical Approach.
    Date January 1985
    Journal The American Journal of Sports Medicine
    Excerpt

    A retrospective review of 11 patients seen at the University of British Columbia Sports Medicine Clinic with osteochondral lesions of the talus was undertaken. From our data, a number of points became apparent. There was a predominance of posteromedial talar dome lesions. A flexion-inversion ankle injury could be documented in the majority of cases. There was frequently a long delay in diagnosing these ankle sprain mimics. Historical details which should raise one's index of suspicion include: (1) history of flexion-inversion injury; (2) exercise-related ankle pain; (3) sensations of "clicking and catching"; and (4) persistent swelling. Surgery produced consistently good early results in these active patients without osteotomizing the medial malleolus. Experimental analysis and clinical experience suggest that the optimal radiographic technique for identifying the posteromedial osteochondral lesion consists of an anteroposterior view of the ankle in maximum plantar flexion with the kilovoltage set at 70.

    Title The Histology and Ultrastructure of the Meyers-kouwenaar Body in Ferrets Infected with Brugia Malayi.
    Date January 1985
    Journal The American Journal of Tropical Medicine and Hygiene
    Excerpt

    A study was made of the Meyers-Kouwenaar (MK) body in the livers of experimentally infected ferrets. Meyers-Kouwenaar bodies, the carcasses of microfilariae (mff) covered by deposits of Splendore-Hoeppli (SH) material, were found in small abscesses of eosinophils and in granulomas. The SH deposits varied from an eosinophilic, hyaline fringe around intact mff to multilayered deposits surrounding an unrecognizable granular remnant. In abscesses, peroxidase activity was intense in SH deposits and the surrounding eosinophils. The presence and localization of IgG were variable in MK bodies, as detected by an enzyme-linked immunohistologic assay; and antigens of mff were not detected in the SH deposits. Electron microscopy of the MK body demonstrated a layered, radial deposition of amorphous and granular material on the mff and a structural heterogeneity which apparently included leukocyte granules and other cell organelles. Leukocytes surrounding MK bodies in abscesses were often degranulated and degenerate; incorporation of lysosomes of eosinophils and cellular debris into the SH deposits at the periphery of the MK bodies was indicated.

    Title Additional Evidence Implicating Triticum Searsii As the B-genome Donor to Wheat.
    Date May 1984
    Journal Biochemical Genetics
    Excerpt

    In vitro DNA:DNA hybridizations and hydroxyapatite thermal-elution chromatography were employed to identify the diploid wheat species ancestral to the B genome of Triticum turgidum. 3H-T. turgidum DNA was hybridized to the unlabeled DNAs of T. urartu, T. speltoides, T. sharonensis, T. bicorne, T. longissimum, and T. searsii. 3H-Labeled DNAs of T. monococcum and a synthetic tetraploid AADD were hybridized with unlabeled DNAs of T. urartu and T. searsii to determine the relationship of the A genome of polyploid wheat and T. urartu. The heteroduplex thermal stabilities indicated that T. searsii was most closely related to the B genome of T. turgidum (AB) and that the genome of T. urartu and the A genome have a great deal of base-sequence homology. Thus, it appears that T. searsii is the B-genome donor to polyploid wheat or a major chromosome donor if the B genome is polyphyletic in origin.

    Title Maternal Deaths in New Jersey--1979.
    Date February 1983
    Journal The Journal of the Medical Society of New Jersey
    Title Microfilaremia and Antibody Responses in Cba/h and Cba/n Mice Following Injection of Microfilariae of Brugia Malayi.
    Date January 1982
    Journal The Journal of Parasitology
    Title Glycohemoglobin Determinations in Normal Pregnancy and in Insulin-dependent Diabetics.
    Date December 1980
    Journal Obstetrics and Gynecology
    Excerpt

    Minor components of adult hemoglobin (A1a,b, and c) are known to increase in the presence of sustained elevations of maternal blood glucose. This study demonstrates the correlation between glycosylated hemoglobin components and the usual shorter term indices of diabetic control. In addition, a correlation was noted between glycosylated hemoglobin values and birth weight and placental weight. Glycohemoglobin values serve as an accurate index of long-term control of blood sugar and are helpful in assessing the efficacy of the treatment plan.

    Title Update of Developments in Obstetrics and Gynecology.
    Date September 1980
    Journal The Journal of the Medical Society of New Jersey
    Title Clearance of Microfilariae of Dipetalonema Viteae in Cba/n and Cba/h Mice.
    Date June 1980
    Journal The Journal of Parasitology
    Title Maternal Deaths in New Jersey--1977.
    Date January 1980
    Journal The Journal of the Medical Society of New Jersey
    Title Specific Inhibition of the Incorporation of Tritiated Thymidine in Regenerating Rat Liver by a Rat Hepatocytes Supernatant.
    Date January 1978
    Journal Revue Canadienne De Biologie / éditée Par L'université De Montréal
    Excerpt

    Studies on endogenous inhibitors obtained from supernatant fluids of rat hepatocytes indicated that the supernatant arrests the normal cell cycle at two points, namely, before the beginning of the S phase and at the onset of metaphase when assayed in regenerating liver cells in situ. The specificity of this (these) inhibitory substance(s) was evidenced by the finding that no inhibition of cell division was observed in situ in tongue, intestine, or kidneys of animals injected with concentrations of the hepatocyte supernatant that inhibited cell division in regenerating liver. When higher concentrations of the inhibitor-containing supernatant were used, only the tongue epithelial cells were affected in addition to the regenerating liver cells.

    Title Carcinoma of the Colon.
    Date August 1975
    Journal Nursing Times
    Title Monitoring of the High Risk Pregnancy: Part Iii, Postpartum.
    Date May 1975
    Journal The Journal of the Medical Society of New Jersey
    Title [necrosis and Hyperbasophilia in the Rat Hepatic Parenchyma].
    Date August 1974
    Journal Revue Canadienne De Biologie / éditée Par L'université De Montréal
    Title Monitoring of the High Risk Pregnancy. I. Antepartum.
    Date May 1974
    Journal The Journal of the Medical Society of New Jersey
    Title Monitoring of the High Risk Pregnancy. Ii. Intrapartum.
    Date May 1974
    Journal The Journal of the Medical Society of New Jersey
    Title Effect of Acth and Metyrapone on Estriol, 17-hydroxycorticosteroid, 17-ketosteroid, Pregnanediol and Pregnanetriol Excretion Late in Pregnancy.
    Date June 1969
    Journal The Journal of Clinical Endocrinology and Metabolism
    Title Ovarian and Parovarian Tumors in Infants and Children.
    Date May 1967
    Journal American Journal of Obstetrics and Gynecology
    Title Granulosa-cell Carcinoma Arising in a Cystic Teratoma of the Ovary. Report of a Case.
    Date February 1967
    Journal Obstetrics and Gynecology
    Title Reproductive Ability After Metroplasty.
    Date December 1966
    Journal Obstetrics and Gynecology
    Title The Oculo-dento-digital Dysplasia Syndrome.
    Date September 1966
    Journal American Journal of Ophthalmology
    Title Survival and Management of the Second-born Twin.
    Date August 1966
    Journal Obstetrics and Gynecology
    Title Bacterial Enhancement of Self-limiting Outgrowth Formation on Datura.
    Date May 1966
    Journal Phytopathology
    Title Public Reporting of Quality Data for Stroke: is It Measuring Quality?
    Date
    Journal Stroke; a Journal of Cerebral Circulation
    Excerpt

    BACKGROUND AND PURPOSE: Public reporting of quality data is becoming more common and increasingly used to improve choices of patients, providers, and payers. We reviewed the scope and content of stroke data being reported to the public and how well it captures the quality of stroke care. METHODS: We performed a cross-sectional survey of all report cards within the Agency for Healthcare Research and Quality Report Card Compendium. Stroke quality data were categorized into one of 5 groups: structure, process, outcomes, utilization, and finances. We also determined the congruence of mortality ratings of New York hospitals provided by 2 different report cards. RESULTS: Of 221 available report cards, 19 (9%) reported quality information regarding stroke and 17 specifically addressed the quality of hospital-based stroke care. The most frequent data reported were utilization measures (n=15 report cards) and outcome measures (n=14 report cards). Data regarding finances (n=4), structure of care (n=2), and process of care (n=1) were reported infrequently. Ratings were incongruent in 61 of the 157 hospitals (39%) with the same hospital being rated below average on one report care and average on another in 44 hospitals. CONCLUSIONS: Publicly reported quality data pertaining to patients with stroke are incomplete, confusing, and inaccurate. Without further improvements and a better understanding of the needs and limitations of the many stakeholders, targeted transparency policies for stroke care may lead to worse quality and large economic losses.

    Title Clinical Characteristics of Mephedrone Toxicity Reported to the Uk National Poisons Information Service.
    Date
    Journal Emergency Medicine Journal : Emj
    Excerpt

    Objective To describe the patterns and clinical features of toxicity related to recreational use of mephedrone and other cathinones in the UK using data collected by the National Poisons Information Service (NPIS). Methods The number of accesses to TOXBASE, the NPIS online poisons information database, details of consecutive cases uploaded onto TOXBASE and the number and details of telephone enquiries made to the NPIS by health professionals in the UK were collected for the period March 2009 to February 2010. Results Over the year of study there were 2901 TOXBASE accesses and 188 telephone enquiries relating to cathinones, the majority relating to mephedrone (TOXBASE 1664, telephone 157), with a month-on-month increase in numbers. In 131 telephone enquiries concerning mephedrone, alone or in combination with alcohol, common clinical features reported included agitation or aggression (n=32, 24%, 95% CI 18% to 33%), tachycardia (n=29, 22%, 95% CI 16% to 30%), confusion or psychosis (n=18, 14%, 95% CI 9% to 21%), chest pain (n=17, 13%, 95% CI 8% to 20%), nausea (n=15, 11%, 95% CI 7% to 18%), palpitations (n=14, 11%, 95% CI 6% to 18%), peripheral vasoconstriction (n=10, 8%, 95% CI 4% to 14%) and headache (n=7, 5%, 95% CI 2% to 11%). Convulsions were reported in four cases (3%, 95% CI 1% to 8%). One exposed person died following cardiac arrest (1%, 95% CI 0% to 4%), although subsequent investigation suggested that mephedrone was not responsible. Conclusions Toxicity associated with recreational mephedrone use is increasingly common in the UK. Sympathomimetic adverse effects are common and severe effects are also reported. Structured data collected by the NPIS may be of use in identifying trends in poisoning and in establishing toxidromes for new drugs of abuse.

    Title Intravenous Paracetamol Overdose: Two Case Reports and a Change to National Treatment Guidelines.
    Date
    Journal Archives of Disease in Childhood
    Excerpt

    Two cases of 10-fold accidental overdose with intravenous paracetamol are presented. Case 1: A 5-month-old child with intussusception received 90 mg/kg intravenous paracetamol over an 8 h period. She was not initially treated with an antidote and developed hepatic impairment. Case 2: A 6-month-old child received a single dose of 75 mg/kg intravenous paracetamol. The child was treated with N-acetylcysteine and remained well without hepatic impairment. Therapeutic errors such as 10-fold overdosing are relatively common in children. Case 1 demonstrates that intravenous paracetamol is a potentially dangerous drug. This should be taken into consideration when prescribing the intravenous formulation. The concentration-time nomogram used following oral paracetamol overdose should be used with caution following intravenous overdose. Significant overdose should be discussed with the National Poisons Information Service whose guidance suggests intervention with antidote following an overdose above 60 mg/kg.

    Title Stakeholders' Perspective on Issues and Challenges Associated with Care and Treatment of Aging-related Cognitive Impairment Disorders in Singapore.
    Date
    Journal International Psychogeriatrics / Ipa
    Excerpt

    ABSTRACTBackground: An expanding elderly population poses challenges for the provision of care and treatment for age-related physical and mental disorders. Cognitive impairment (CI)/dementia is one such mental disorder that is on the rise in Singapore and has concomitant implications for social and health systems. The objective of this study is to understand the perspectives of prominent stakeholders about current and future issues and challenges associated with CI/dementia among the elderly in Singapore.Methods: Using indepth interviews, this qualitative study obtained the views of multiple stakeholders on issues and challenges associated with CI/dementia in Singapore. The 30 individuals interviewed as part of the study included clinicians, policy-makers, researchers, community workers, administrators, and caregivers. Using a framework approach, interview texts were indexed into domains and issues by utilizing NVivo 9.0 software.Results: The stakeholders expressed concerns related to multiple domains of the CI/dementia care system: attitude and awareness, economics, education, family caregiving, inputs to care system, living arrangements, prevention, screening and diagnosis, and treatment and management of care. Within each domain, multiple issues and challenges were identified by respondents.Conclusions: The study identifies a complex set of inter-related issues and challenges that are associated with the care and treatment of people with CI/dementia. The results suggest that CI and dementia profoundly affect patients, families, and communities and that the issues related to the two disorders are truly system-wide. These findings lay the foundation for utilization of a systems approach to studying CI/dementia and provide an analytic framework for future research on complex health care issues.

    Title Flumazenil Use in Benzodiazepine Overdose in the Uk: a Retrospective Survey of Npis Data.
    Date
    Journal Emergency Medicine Journal : Emj
    Excerpt

    Objective Benzodiazepine (BZD) overdose (OD) continues to cause significant morbidity and mortality in the UK. Flumazenil is an effective antidote but there is a risk of seizures, particularly in those who have co-ingested tricyclic antidepressants. A study was undertaken to examine the frequency of use, safety and efficacy of flumazenil in the management of BZD OD in the UK. Methods A 2-year retrospective cohort study was performed of all enquiries to the UK National Poisons Information Service involving BZD OD. Results Flumazenil was administered to 80 patients in 4504 BZD-related enquiries, 68 of whom did not have ventilatory failure or had recognised contraindications to flumazenil. Factors associated with flumazenil use were increased age, severe poisoning and ventilatory failure. Co-ingestion of tricyclic antidepressants and chronic obstructive pulmonary disease did not influence flumazenil administration. Seizure frequency in patients not treated with flumazenil was 0.3%. The frequency of prior seizure in flumazenil-treated patients was 30 times higher (8.8%). Seven patients who had seizures prior to flumazenil therapy had no recurrence of their seizures. Ventilation or consciousness improved in 70% of flumazenil-treated patients. Flumazenil administration was followed by one instance each of agitation and brief seizure. Conclusions Flumazenil is used infrequently in the management of BZD OD in the UK. It was effective and associated with a low incidence of seizure. These results compare favourably with the results of published randomised controlled trials and cohort studies, although previous studies have not reported the use of flumazenil in such a high-risk population. This study should inform the continuing review of national guidance on flumazenil therapy.

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