Reporting of adverse drug reactions by hospital pharmacists: pilot scheme.
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Adverse Drug Reaction Reporting Systems↗
Biomedical subjects
J M Smith
Publications and source records attributed to J M Smith.
Receptor-associated constitutive protein tyrosine phosphatase activity controls the kinase function of JAK1.
Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an increase in the phosphotyrosine content of many cellular proteins. However, the level at which the primary signaling event is affected is still unclear. We show that Jaks are activated by tyrosine phosphorylation in cells that are briefly exposed to the PTP inhibitor pervanadate (PV), resulting in tyrosine phosphorylation and functional activation of Stat6 (in addition to other Stats). Mutant cell lines that lack Jak1 activity fail to support PV-mediated [or interleukin 4 (IL-4)-dependent] activation of Stat6 but can be rescued by complementation with functional Jak1. The docking sites for both Jak1 and Stat6 reside in the cytoplasmic domain of the IL-4 receptor alpha-chain (IL-4Ralpha). The glioblastoma-derived cell lines T98G, GRE, and M007, which do not express the IL-4Ralpha chain, fail to support Stat6 activation in response to either IL-4 or PV. Complementation of T98G cells with the IL-4Ralpha restores both PV-mediated and IL-4-dependent Stat6 activation. Murine L929 cells, which do not express the gamma common chain of the IL-4 receptor, support PV-mediated but not IL-4-dependent Stat6 activation. Thus, Stat6 activation by PV is an IL-4Ralpha-mediated, Jak1-dependent event that is independent of receptor dimerization. We propose that receptor-associated constitutive PTP activity functions to down-regulate persistent, receptor-linked kinase activity. Inhibition or deletion of PTP activity results in constitutive activation of cytokine signaling pathways.
Amino Acid Sequence↗
Evolution of genetic redundancy.
Genetic redundancy means that two or more genes are performing the same function and that inactivation of one of these genes has little or no effect on the biological phenotype. Redundancy seems to be widespread in genomes of higher organisms. Examples of apparently redundant genes come from numerous studies of developmental biology, immunology, neurobiology and the cell cycle. Yet there is a problem: genes encoding functional proteins must be under selection pressure. If a gene was truly redundant then it would not be protected against the accumulation of deleterious mutations. A widespread view is therefore that such redundancy cannot be evolutionarily stable. Here we develop a simple genetic model to analyse selection pressures acting on redundant genes. We present four cases that can explain why genetic redundancy is common. In three cases, redundancy is even evolutionarily stable. Our theory provides a framework for exploring the evolution of genetic organization.
Animals↗
Crystallization of cytochrome b562 from Erwinia chrysanthemi.
Cytochrome b(562) from Erwinia chrysanthemi has been crystallized using the hanging-drop vapour-diffusion method with ammonium sulfate as the precipitant. X-ray precession photographs show that the crystals formed belong to either of the enantiomorphic space groups P4(1)2(1)2 or P4(3)2(1)2 with the cell parameters a = b = 98.6 and c = 62.7 A. Estimation of the crystal density and consideration of the possible values for V(m) indicate that there is either a dimer or trimer in the asymmetric unit. Experiments using the synchrotron radiation source at the CCLRC Daresbury Laboratory have shown that the crystals diffract to at least 2.7 A resolution. An analysis of the N-terminal sequence indicates that this cytochrome shows limited homology to the cytochrome b(562) from E. coli. Determination of the structure will therefore allow analysis of the relationship between these two proteins.
Journal Article↗
Upper limb work-related musculoskeletal disorders among newspaper employees: cross-sectional survey results.
At a metropolitan newspaper office in Canada with extensive video display terminal (VDT) use, researchers carried out a survey (n = 1,007, 84% response) to establish baseline prevalence of work-related musculoskeletal disorders (WMSDs) and to identify demographic, postural, task, and psychosocial factors associated with WMSD symptoms. One-fifth of the respondents reported moderate or worse upper limb pain recurring at least monthly or lasting more than a week over the previous year. Logistic regression showed that employees who faced frequent deadlines and high psychological demands (fast work pace and conflicting demands), had low skill discretion and social support, spent more time keyboarding, or who had their screen in a non-optimal position were more likely to report moderate to severe symptoms. Women reported significantly higher levels of symptoms than men.
Adult↗
Environmental causes of enamel defects.
A large number of causes of enamel defects, both environmental and genetic, have been described. However, many of these are derived from case histories and studies of individual conditions. What is needed now is a systematic investigation of the problem. The first requirement in exploring the aetiology further is the standardization of both the clinical diagnosis and the descriptive terminology. This has been provided by the Fédération Dentaire Internationale Developmental Defects of Enamel Index. Comparing studies using standardized methods, including this index, has highlighted areas for closer investigation. The total prevalence of enamel defects in a population needs to be established as a baseline for studies on aetiology. Sixty-eight per cent of 1518 school children in London have enamel defects in the permanent dentition, with 10.5% having 10 or more teeth affected and 14.6% having hypoplasia, i.e. missing enamel. These findings are in contrast to the 37% with hypoplasia found in a group of third to fifth century Romano-Britons from Dorset, England, suggesting further consideration of possible environmental and genetic differences between the two populations. An overall long-term study of dental development in low birth weight children has shown significantly more (P < 0.001) enamel defects related to major health problems during the neonatal period. By using standardized, reproducible criteria in prevalence studies to gain an overview of the problem and then studying specific groups or conditions, it is possible to identify general and specific factors in the aetiology of enamel defects and investigate further the varying role of genetic and environmental effects.
Adolescent↗
Inhibition of nitric oxide synthase by L-NAME improves ventricular performance in streptozotocin-diabetic rats.
The overall goal of this study was to determine if activation of the nitric oxide synthetic pathway suppressed basal ventricular performance and the responsiveness to beta-adrenergic stimulation characteristic of cardiac function in the 8-week streptozotocin (60 mg/kg, i.v.) diabetic (STZ-Db) rat. Left ventricular performance was measured in isolated working hearts, before and at the peak response to 0.8 microM dobutamine, in the absence or presence of NG-nitro-L-arginine methyl ester (L-NAME, 1 mM), a non-selective inhibitor of nitric oxide synthase (NOS). Ventricular performance was suppressed in the STZ-Db heart under basal (decreased heart rate, cardiac output, aortic flow -dP/dt) and dobutamine-stimulated (diminished rise in +dP/dt and maximum systolic pressure) conditions. L-NAME had minimal effects on basal or dobutamine-stimulated ventricular performance in control hearts. In contrast, L-NAME infusion in hearts from STZ-Db returned the depressed heart rate to control values, which was correlated with an increase in aortic flow. In addition, the dobutamine-stimulated rise in maximum systolic pressure and +dP/dt were similar in the control and STZ-Db rats in the presence of l-NAME. Western blot analysis detected the presence of inducible nitric oxide synthase (NOS) and a significant (P<0.001) increase in the constitutive NOS in ventricular myocytes from STZ-Db rats. These data suggest that an increased production of nitric oxide by NOS in ventricular myocytes from STZ-Db animals suppressed basal ventricular performance and the responsiveness to beta-adrenergic stimulation in diabetic hearts.
Adrenergic beta-Agonists↗
Blink reflex to supraorbital nerve stimulation in the cat.
Neurophysiological studies of the blink reflex to supraorbital nerve stimulation were conducted in eight alert, adult male cats. The cat, like other mammals, shows both short-latency (R1) and long-latency (R2) orbicularis oculi electromyographic (OOemg) components. Measures of OOemg latency, duration, integrated area, and maximum amplitude (MA) were obtained at a stimulus magnitude of 1.5xR2 threshold. The mean (+/-SE) minimal latencies for R1 and R2 were 8.26+/-0.85 and 22.97+/-1.53 ms, respectively. On average, R1 MA was larger than R2 MA. R1 and R2 area measures were similar. Three stimulus paradigms were tested. In a paired-stimulus paradigm, the interstimulus interval (ISI) was randomly varied from 100 to 1200 ms. Ratios were constructed for the OOemg area and MA by dividing the test response by the conditioning response. In this paradigm, although a significant linear relationship was observed only between ISI and R2 MA, conditioning effects were noted on both R1 and R2 area and MA test responses at several ISIs. In a habituation paradigm, both R2 and R1 showed habituation at stimulus frequencies from 0.5 to 2 Hz. In a stimulus-response paradigm, stimulus magnitude was randomly varied between threshold and 2xthreshold. In this paradigm, OOemg area and MA of both R1 and R2 were linearly related to stimulus magnitude. Neither the systemically administered centrally acting alpha2-adrenergic antagonist yohimbine nor agonist clonidine had significant effects on blink reflex parameters, habituation, or the paired-stimulus paradigm. Overall, these results suggest that there are important similarities in the control and modulation of the R1 and R2 components of the blink reflex to supraorbital nerve stimulation in cats.
Adrenergic alpha-Agonists↗
Pulmonary embolism and normal oxygenation: application of PIOPED-derived likelihood ratios.
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Aged↗
Na+/K(+)-ATPase activity in vascular smooth muscle from streptozotocin diabetic rat.
OBJECTIVES: Insulin-deficient diabetes impairs carbohydrate metabolism in a variety of tissues. Vascular smooth muscle may be susceptible to the diabetes-induced disturbance in glycolysis since Na+/K(+)-ATPase in this tissue preferentially utilizes ATP generated by glycolysis. The purpose of this study was to determine if chronic exposure to the metabolic alterations associated with insulin-deficient diabetes directly inhibited Na+/K(+)-ATPase activity, or its regulation, in vascular smooth muscle. METHODS: Diabetes was induced by intravenous administration of streptozotocin (60 mg/kg). After 12 weeks, Na+/K(+)-ATPase activity in aorta and superior mesenteric artery was evaluated under a variety of conditions. Na+/K(+)-ATPase was estimated by measuring the influx of rubidium-86 (86Rb) in the presence or absence of the Na+/K(+)-ATPase inhibitor, ouabain. The metabolism of [3H]glucose and [14C]glucose was used to estimate glycolysis or glucose oxidation, respectively. RESULTS: Glycolysis and glucose oxidation were decreased in aortic smooth muscle (27 and 34%, respectively). An intact endothelium was associated with a marked decrease in ouabain-sensitive (pump-mediated) 86Rb uptake in diabetic aorta. However, ouabain-sensitive 86Rb uptake was similar in de-endothelialized aorta and superior mesenteric artery from diabetic and non-diabetic rats under both unstimulated conditions and during maximal stimulation. Removal of glucose or oxygen reduced ouabain-sensitive 86Rb uptake to a similar extent in both groups. In contrast, the receptor-mediated stimulation of ouabain-sensitive 86Rb uptake by insulin was decreased. CONCLUSIONS: These results suggest that intrinsic Na+/K(+)-ATPase activity is not diminished in diabetic vascular smooth muscle under physiological conditions and that the impairment of cellular metabolism in diabetic blood vessels does not limit stimulation of Na+/K(+)-ATPase activity. However, modulation of Na+/K(+)-ATPase activity by endothelial factors or insulin appears to be altered in aorta from diabetic rats.
Animals↗
Schistosome resistance to praziquantel: Fact or fiction?
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Comment↗
Congenital absence of the scaphoid without other congenital abnormality: a case report.
Congenital absence of the scaphoid without associated thumb or radial hypoplasia is a rare condition. This report is the third case presented in the literature of this condition. The case presented is of a patient who presented initially with wrist pain. Radiographs revealed a congenitally absent scaphoid and examination revealed no evidence of thumb hypoplasia. A brief review of the literature on congenital absence of the scaphoid is discussed.
Activities of Daily Living↗
High-intensity focused ultrasound in the treatment of benign prostatic hyperplasia.
OBJECTIVE: To assess the role of high-intensity focused ultrasound (HIFU) in the treatment of symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Thirteen patients (mean age 65 years, range 58-74) were treated with HIFU as part of a phase-2 clinical trial and evaluated prospectively using the International Prostate Symptom Score, uroflowmetry, and transrectal and transabdominal ultrasonography to determine prostate size and post-void residual urine volume, respectively. The results and the patients' satisfaction were assessed at regular intervals for 2 years. RESULTS: The new procedure was learned quickly and was easy to perform. Symptom scores decreased from a mean of 23 before treatment to 5 after 12 months and 7 after 2 years. There was an initial improvement in flow rates but they then declined. The size of the prostate and the post-void residual volume were both decreased after treatment. CONCLUSIONS: The treatment is safe, easy to implement and was effective in substantially reducing symptom scores in these few patients. However, we would not encourage its use as an alternative to other well established treatment modalities until it has been assessed fully in a randomized trial.
Aged↗
Anatomic study of the superficial perineal neurovascular pedicle: implications in vulvoperineal flap design.
Thirty superficial perineal neurovascular pedicles from 15 formaldehyde-fixed female cadavers were dissected and analyzed with the purpose of establishing the anatomic basis for the design and elevation of vulvoperineal fasciocutaneous flaps based on their anatomic elements. The average internal diameter of the superficial perineal artery was 0.53 +/- 0.2 mm, determined by means of an image analysis system. Three distinct anatomic patterns of cutaneous arterial vascularization were seen bilaterally, and two types of vulvoperineal fasciocutaneous flaps are described.
Arteries↗
Characteristics of youth-onset noninsulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus at diagnosis.
OBJECTIVE: To describe the characteristics of youth-onset noninsulin-dependent diabetes mellitus (NIDDM) at diagnosis and compare them with youths with insulin-dependent diabetes mellitus (IDDM) when matched for age, sex, and geographic region of residence. STUDY DESIGN: Medical records of youths referred for evaluation of diabetes to a pediatric tertiary care center from 1988 to 1995 were reviewed to identify youths diagnosed with NIDDM. Patients selected for study met National Diabetes Data Group criteria for type of diabetes. RESULTS: Fifty patients with NIDDM were reviewed and compared with similar IDDM patients. The NIDDM female:male ratio was 1.6:1 and 74% were African-American. Only 18% of the IDDM patients were African-American. The mean body mass index +/- standard error at diagnosis of NIDDM patients was 35 +/- 1.1 kg/m in contrast to IDDM, 20 +/- .8 kg/m. Ninety-six percent of NIDDM and 24% of IDDM youths had a body mass index >/=85th percentile. More then 30% of NIDDM youths presented with hypertension. Diabetic ketoacidosis was present in >25% of NIDDM patients. Acanthosis nigricans was documented in 86% of NIDDM and 0% of IDDM patients. CONCLUSIONS: In Arkansas, youths with NIDDM are characterized by significant obesity in contrast to youths with IDDM. Physical characteristics such as obesity, acanthosis nigricans, and hypertension on examination of any youth with new-onset diabetes should raise suspicion of NIDDM.
Acanthosis Nigricans↗
Plasma von Willebrand factor in thoroughbreds in response to high-intensity treadmill exercise.
OBJECTIVE: To determine whether plasma von Willebrand factor (vWf) concentration changes in horses during and after treadmill exercise. ANIMALS: 5 mature, fit Thoroughbreds. PROCEDURE: A blood sampling catheter was placed in the right jugular vein. A warm-up period was followed by a 3-minute rest period. Horses were galloped at racing pace until fatigued (about 2 minutes). Blood samples were collected prior to warm-up, during the postwarm-up rest period, 1 minute into the run, at cessation of the run, and 5 to 120 minutes after cessation of the run. vWf activity was measured by ELISA and corrected for plasma volume changes (measured by changes in plasma albumin concentration). Platelet-poor plasma from 10 clinically normal, resting horses was pooled, assigned a value of 100 U/dl, and served as a control for all assays. RESULTS: vWf activity began increasing 1 minute after horses reached full speed. At 5 minutes after cessation of exercise, vWf values had increased by mean of 92% (P < 0.05) from baseline. vWf activity returned baseline by 15 minutes after exercise, and remained there until 90 minutes after exercise, when it began to increase. CONCLUSION AND CLINICAL RELEVANCE: The spontaneous decrease in vWf values after completion of exercise was unexpected because vWf has a long half-life in circulation. This unexpected finding is compatible with increased vWf consumption and suggests that microvascular trauma may occur in horses during strenuous exercise.
Animals↗
Minimally invasive coronary artery bypass grafting: initial Connecticut experience.
We report the initial Connecticut experience with minimally invasive coronary artery bypass grafting. This procedure allows bypass grafting to the left anterior descending coronary artery utilizing the internal mammary artery as the conduit. The procedure is minimally invasive because it is performed through a mini-thoracotomy incision in the fourth anterior intercostal space and it is conducted without the use of cardiopulmonary bypass. The procedure has been applied to 13 patients operated between February and October 1996. All but one patient selected were poor candidates for conventional coronary artery bypass surgery because of advanced age (6), chronic renal failure/dialysis/kidney transplant (4), redo status with vulnerable grafts (1), severe peripheral vascular disease (6), severe chronic obstructive pulmonary disease (4). All patients survived operation and were discharged in good condition. Mean postoperative intubation time was seven hours and mean hospital stay was 4.5 days despite the very high pre-existing comorbidity of these patients. All patients are alive at the current follow-up time. Two patients required a conventional bypass procedure for occlusion of the minimally invasive graft, the first because of diffuse disease in the target artery and the second attributable to the technical limitations of minimally invasive coronary artery bypass grafting; both tolerated the subsequent procedure well. All patients are now angina-free. All four grafts studied by routine postoperative angiography were widely patent. Routine post-operative exercise nuclear imaging was normal in an additional patient. This procedure of minimally invasive coronary artery bypass grafting offers significant advantages compared to the conventional bypass procedure (short hospital stay, quick recovery, and, especially, avoidance of cerebrovascular accidents caused by the heart-lung machine). This minimally invasive procedure is expected to apply to a growing percentage of patients. The procedure, especially vis-à-vis angioplasty, may well offer the superior long-term patency of the mammary conduit achieved with a modest initial "investment" in hospital stay, costs of medical care, and discomfort and disability. A prospective, randomized trial comparing angioplasty and minimally invasive coronary artery bypass grafting is warranted.
Aged↗