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Biomedical subjects

E A Wilson

Publications and source records attributed to E A Wilson.

At least 19 recordsLinked to original sources

High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients.

Fifty patients with refractory partial seizures took part in a prospective, observational study of adjuvant gabapentin (GBP) in increasing doses. Thirty-three were started on 400 mg GBP daily with further weekly increments of 400 mg until seizures came under control for at least 6 months or to the limit of tolerability. A further 17 patients, not fully controlled on low dose GBP, followed the same regimen. All patients took the drug three times daily. Comparisons were made with seizure numbers during a 3-month baseline during which antiepileptic medication remained unchanged. Overall, 24 of the 50 patients documented a seizure reduction of 50% or more. Fifteen did so at or below 2400 mg GBP daily. Three of these patients became seizure-free. The remaining nine appeared to respond to higher daily doses of GBP (1:2800 mg; 3:3600 mg; 1:4000 mg; 1:4800 mg; 3:6000 mg), with two becoming seizure-free. Side-effects most commonly reported included tiredness, dizziness, headache and diplopia. On GBP doses exceeding 3600 mg daily, three patients developed flatulence and diarrhoea and two more had myoclonic jerks. Mean circulating GBP concentrations (mg/l) at each 1200 mg dose level were as follows: 1200 mg-4.1; 2400 mg-8.6; 3600 mg 13.2; 4800 mg 15.5; 6000 mg-17.2. In six patients, including three taking 6000 mg daily, GBP concentrations continued to rise linearly at each dosage increment. Although limited, our results do not support the suggestion that GBP absorption is saturable. High dose GBP may be effective in controlling seizures in patients with refractory partial epilepsy.

Acetates

Multiple options and unique pathways: a new direction for EMS?

The same forces transforming the health care delivery system also are reshaping EMS. The changing economic and organizational structures of the health services delivery system may predict how EMS systems will redesign themselves. We discuss one template for future EMS systems.

Decision Support Techniques

The Kentucky medical curriculum. A response to the call for educational reform: a GPEP report card.

The resources of an important educational grant provided by the Robert Wood Johnson Foundation, as well as designated local college and medical center funds, provided support for the renewal of the undergraduate medical education program at the University of Kentucky College of Medicine. The fully revised medical curriculum, adapted to changing professional and societal needs and completely in place by the 1994-95 academic year, was influenced by the recommendations of the General Professional Education of the Physician (GPEP) Report, issued by the Association of American Medical Colleges in 1984. This paper details each of the student-centered curricular changes in the context of the GPEP recommendation that it particularly addresses.

Clinical Competence

Does technique or material used affect bladder tissue reactions when injecting teflon or silicone paste?

OBJECTIVES: Submucosal injections of polytetrafluoroethylene (PTFE) and polydimethylsiloxane (PDMS) paste continue to be used for the correction of vesicoureteral reflux and urinary incontinence. Potential distant particle migration and foreign body tissue reactions are thought to be significantly affected by the technique of injection and the paste material used. A study to determine if injection technique, paste material, or pretreatment of the injection site significantly affects local tissue reaction was performed on 44 New Zealand white rabbits. METHODS: Animals were randomly assigned to undergo four distinct injection treatments into the submucosa or bladder muscularis. Prior to injecting 0.1 cc of the PTFE or PDMS paste, some sites were pretreated with 0.1 cc saline to separate tissue planes, epinephrine to cause vasoconstriction, or doxycycline to provide sclerosis. Pretreatment controls were also performed without injecting PTFE or PDMS paste. Animals were killed, and quadrant bladder biopsies were performed at 1 hour (9), 1 day (9), 7 days (10), 1 month (8), and 6 months (8). A single pathologist, blinded to the injection treatments, performed a histologic evaluation to determine bleb location and the degree of inflammation, fibrosis, and epithelial necrosis. RESULTS: Seven of the 12 submucosal PTFE injection treatments were found on biopsy to be primarily within the muscularis, compared to 1 of 9 with PDMS paste. Three of the 24 PTFE injections could not be found at autopsy. Of these, two were injected into the muscularis, and all were discovered at least 1 month following injection. Particles were present in all 22 PDMS injection sites that were retrieved. Pretreatments, especially with doxycycline, resulted in significant epithelial necrosis at 1 and 7 days. At 1 and 6 months there were no differences in inflammation or fibrosis between PTFE and PDMS or any pretreatment combinations with saline or epinephrine. CONCLUSIONS: Correctly injected, silicone (PDMS) paste appears most likely to remain in the submucosal space. Pretreatment injections may cause early epithelial necrosis. PTFE and PDMS elicit similar foreign body reactions over time.

Animals

Fibula free flap.

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Bone Transplantation

New antiepileptic drugs.

No fewer than eight new antiepileptic drugs (AEDs) with diverse mechanisms of action have been introduced into clinical practice in the 1990s. Short monographs on lamotrigine, vigabatrin, gabapentin, oxcarbazepine, felbamate, topiramate and vigabatrin have been prepared for this review. Details are provided of mechanisms of action, clinical pharmacokinetics and adverse drug interactions. Each section concentrates on the efficacy, tolerability and practical use of these drugs. The areas where they have potential for superiority over the established AEDs have been highlighted. Specific indications and dosage schedules have been provided. As many of these AEDs have, as yet, limited licences, an attempt has been made to identify ongoing studies and important omissions. Where possible, the eventual place of the new agent in the pharmacological management of epilepsy has been assessed. A more limited summary has been included of zonisamide which, although licensed in Japan, is still regarded as an investigational drug elsewhere. Short discussions of three of the most promising investigational compounds, namely remacemide, losigamone and levetiracetam, complete the picture.

Acetates

Physicians for the 21st century: implications for medical practice, undergraduate preparation, and medical education.

Changes in medical education and the practice of medicine have resulted from the push for both education and health care reforms. Undergraduates planning application to medical school should broaden their preparation to include communications, computers, economics, and multicultural educational experiences. To prepare graduates for medical practice in the new millennium, the University of Kentucky College of Medicine has implemented a new curriculum focusing on integration of basic and clinical sciences, primary care in ambulatory sites, health promotion and disease prevention, and attention to the ethical, social, psychologic, and financial impact of disease upon the patient, family, and society.

Curriculum

Synaptic organization of serotonin-like immunoreactive amacrine cells in the larval tiger salamander retina.

Immunoelectron microscopy was used to investigate the ultrastructural features and synaptic relationships of serotonin-like immunoreactive amacrine cells in the larval tiger salamander retina. Serotonin-positive somas exhibited an evenly distributed peroxidase reaction product throughout their cytoplasm. Their nuclei were unstained and possessed indented nuclear membranes. Serotonin-immunoreactive processes were generally stained throughout with the exception of their mitochondria, whose morphology was often disrupted by the staining reaction. They were further characterized by an occasional dense-cored vesicle/s in addition to a generally homogeneous population of small, round, clear synaptic vesicles. Serotonin-immunoreactive amacrine cell processes formed conventional synapses that were characterized by symmetrical synaptic membrane densities. A total of 222 synaptic arrangements were observed that involved the immunostained processes of serotonin-amacrine cells. As presynaptic elements, they primarily contacted amacrine cells processes (37.8%). They also provided substantial synaptic input to processes that lacked synaptic vesicles (16.2%) and whose origin was unidentified. Serotonin-processes provided a far fewer number of synaptic contacts onto the processes of bipolar cells (1.4%) and the somas of cells in the amacrine cell layer (0.5%). As postsynaptic elements, they received synaptic inputs from amacrine cells (27.9%) and bipolar cells (16.2%). With the exception of their synapses onto bipolar cells and the somas of cells in the amacrine cell layer, each of the synaptic relationships of serotonin-amacrine cells was observed in each of sublayers 1-5 of the inner plexiform layer.

Ambystoma

Identification and characterization of metalloproteinase inhibitor activity in human ovarian follicular fluid.

Metalloproteinase inhibitors regulate collagenase activity in the extracellular matrix. To assess the role of metalloproteinase inhibitors in the ovulatory process, inhibitor activity was examined in human follicular fluid collected 2-4 h before ovulation. The relationship between inhibitor activity and steroid content was determined, and the inhibitors were partially purified and characterized. Inhibitory activity in follicular fluid (n = 25) correlated with both follicular estradiol (P less than 0.001) and progesterone (P less than 0.02) concentrations per follicle. Chromatographic separation of the follicular fluid on Sepharose 6B isolated two peaks of inhibitory activity. The inhibitor from the small mol wt (Mr) peak shared many of the properties of tissue inhibitors of metalloproteinase. It was stable in response to heat (60 C) and methylamine (200 mM), and was destroyed by reduction and alkylation, a procedure reported to destroy previously characterized inhibitors. Partial purification by affinity and ion exchange chromatography demonstrated the inhibitor to be a glycoprotein with an approximate Mr of 28-29K. The large Mr inhibitor had an approximate size of 700K and exhibited many of the characteristics of alpha 2-macroglobulin, a serum-derived metalloproteinase inhibitor. It was sensitive to heat, methylamine, and reduction and alkylation. Thus, follicular fluid contains metalloproteinase inhibitor activity that is steroid related and may be hormonally regulated. Ovarian metalloproteinase inhibitors may act to regulate connective tissue remodeling during follicular rupture.

Chorionic Gonadotropin

Expression of plasminogen activator (PA) and a PA inhibitor in human granulosa cells from preovulatory follicles.

Studies with rat ovarian cells indicate that proteolytic enzymes, such as plasminogen activator (PA), play a role in the tissue remodeling that occurs before ovulation. In the rat, gonadotropins appear to increase granulosa cell tissue-type plasminogen activator (t-PA) content by increasing the cellular concentration of t-PA mRNA as well as by modulating the activity of a specific PA inhibitor (PAI). We obtained granulosa cells from preovulatory follicles of women undergoing either in vitro fertilization or gamete intra-fallopian tube transfer in order to evaluate the roles of PA and PAI in human ovulation. Samples of granulosa cell total RNA were hybridized with probes for t-PA, urokinase-type PA, PAI type 1 (PAI-1), or inhibin A-chain (as a control). Northern analyses revealed that the RNA of granulosa cells from preovulatory follicles contained little or no detectable PA mRNA. In contrast, two species of PAI mRNA were detected in relative abundance. The signal intensity produced by the PAI-1 probe varied by about 8-fold among patient samples, suggesting that PAI-1 may be useful as a marker of follicular maturation and differentiation. These results demonstrate that human granulosa cells collected immediately before ovulation contain PA inhibitor mRNA, yet have little or no PA mRNA.

Cells, Cultured

Dietary history and nutritional state in treated coeliac patients.

The gluten content and nutritional adequacy of the diet of a group of adult coeliac patients supposedly following a gluten-free diet for at least one year were assessed. Results were considered in relation to the nutritional state of these patients, determined by anthropometric measurement, and the histological appearance of jejunal biopsies taken at the time of nutritional assessment. Imperfect gluten avoidance, mild malnutrition and mild histological abnormalities on jejunal biopsy were frequent findings. A careful dietary and nutritional assessment when considered in light of histological findings at jejunal biopsy helps to identify the causes of persisting symptoms or malnutrition in treated coeliac patients. A normal jejunal biopsy in a malnourished patient whose dietary compliance is good should prompt a search for an alternative diagnosis.

Adolescent

Natural history of diabetes presenting age 40-69 years: a prospective study of the influence of intensive dietary therapy.

Two hundred and twenty-three newly-diagnosed symptomatic diabetic patients with onset age 40-69 years enrolled in a prospective study of intensive dietary management of diabetes were observed for a period of six years and the data obtained is analysed. The variables studied were weight and fasting levels of plasma glucose and insulin, and of serum total cholesterol and triglyceride. These tests were monitored throughout the study and in addition the oral glucose tolerance test was analysed at entry to the study, after six months intensive dietary management and again after 72 months. Blood pressure, electrocardiogram and the presence of posterior tibial artery pulsation were recorded at entry to the study and at 36 months and 72 months. Approximately 80 per cent of the patients were managed solely by dietary restriction for the entire six years, but 25 patients received oral hypoglycaemic drugs and 26 required insulin treatment. Weight, and fasting glucose and triglyceride values fell in the first few months of intensive dietary management. Analysis of possible risk factors in survivors and patients dead at six years showed no significant differences, apart from a higher mean age at diagnosis in those who died. During the six years of intensive dietary management the mortality from all causes in these diabetic patients was no greater than that for the general population of Northern Ireland.

Adult