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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 469 records · Page 26Linked to original sources
PubMed1991

Biochemical adaptations to training: implications for resisting muscle fatigue.

Skeletal muscle activity is invariably associated with a decline in force-generating capacity (fatigue). The build-up of metabolic by-products such as intracellular H+ and inorganic phosphate (Pi) has been shown to be one of the potential mechanisms of muscle fatigue. The use of phosphorus magnetic resonance spectroscopy is a repeatable and useful tool to study the effect of pH and Pi on force development. When maximal exercise is preceded by submaximal exercise to reduce the starting muscle pH and increase Pi, the degree of muscle fatigue correlates more strongly with H2PO4- than pH or Pi alone. However, other studies in humans have found that H2PO4- does not always correlate well with fatigue. The use of ramp exercise protocols allow repeatable and sensitive measurement of changes in muscle metabolism in response to endurance training. Chronic electrical stimulation in dogs and endurance training in humans results in reduced pH and Pi changes at the same exercise intensities. This means that the effect of pH and Pi in depressing force development is reduced, which could partially explain the increased fatigue resistance seen following endurance training.

Exercise↗
PubMed1991

Allergic inflammation and its pharmacological modulation in asthma.

While most asthma occurs in association with atopy, the relationship of this to clinical expression of the disease is not clearly understood. Allergen provocation causes an immediate bronchoconstriction (early asthmatic reaction) due to the release of mast-cell-derived histamine, prostaglandin D2 and leukotriene C4. The late reaction and attendent increase in bronchial responsiveness are associated with eosinophil influx, activation and mediator secretion, resulting in mucosal swelling in addition to smooth muscle contraction. Endobronchial biopsy and broncho-alveolar lavage have provided compelling evidence that both mast cells and eosinophils contribute to disordered airway function in 'clinical' asthma and that these cells are under the control of T lymphocytes. Topical corticosteroids which produce beneficial clinical effects probably do so by inhibiting those factors that maintain mast cell and eosinophil populations and their enhanced activation. The most likely contenders for these regulatory functions are the cytokines, particularly interleukin-3, -4 and -5.

Adrenal Cortex Hormones↗
PubMed1991

Airway inflammation and atopic asthma: a comparative bronchoscopic investigation.

Flexible fibre-optic bronchoscopy under local anaesthesia has been used to investigate the cellular airway events in atopic asthma. The findings have been compared to those from atopic individuals without asthma and non-atopic healthy controls, in an attempt to discern those changes relevant to clinical disease expression. Immunohistochemical and electron-microscopic analyses of airway biopsies identified that an atopic diathesis is associated with tissue eosinophil infiltration and mast cell degranulation. The eosinophilia was greatest in those atopic individuals with asthma. Flow-cytometric analysis of airway lavage revealed significantly enhanced T lymphocyte activation in clinical asthma. These findings are consistent with the hypothesis that T lymphocyte activation, through cytokine release, amplifies the tissue eosinophilia in asthma and that this combination is associated with clinical disease expression.

Asthma↗
PubMed1991

Effect of daily etidronate on the osteolysis of multiple myeloma.

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Aged↗
PubMed1991

Value of urologic investigation in a targeted group of women with recurrent urinary tract infections.

According to the conclusions of clinical studies, excretory urography and cystoscopy are of no value in managing the majority of women who have a history of recurrent urinary tract infection (UTI). Of 475 women with recurrent UTIs, 186 were prospectively targeted for evaluation by cystoscopy and ultrasonography or excretory urography from selection criteria based on the degree of complicating factors, to determine the value of urologic investigation. Thirty-nine patients had significant detectable abnormalities, and 20 of them required surgical intervention. Definite indications for urologic evaluation include hematuria (gross hematuria and persistent microscopic hematuria between infections), pyelonephritis and a presentation that is not typical for simple uncomplicated UTIs (obstructive symptoms, infection with urea-splitting bacteria, clinical impression of persistent infection or urinary calculi). Diabetes itself does not warrant urologic evaluation. The findings from this study suggest that cystoscopy and upper urinary tract evaluation do play a role in the management of a selected group of women with UTIs.

Adult↗
PubMed1991

Haloalkylamine-induced renal papillary necrosis: a histopathological study of structure-activity relationships.

The haloalkylamine 2-bromoethanamine (BEA) causes necrosis of renal papillae of rats within 24 h of a single intraperitoneal dose greater than or equal to 100 mg/kg. Nine structural analogues of BEA, differing by halide substitution, alkyl chain elongation or amine substitution, were tested for their ability to induce renal papillary lesions in rats. Three compounds (2-chloroethanamine, 3-bromopropanamine and 2-chloro-N,N-dimethylethanamine) induced lesions which were morphologically indistinguishable from those of BEA. All the molecular structural variations investigated reduced papillotoxicity compared with BEA, the parent compound. A variety of non-renal lesions including hepatic, adrenal, testicular and lymphoid necroses were also encountered. The most toxic compound was 2-fluorethanamine, a 5 mg/kg dose of which was lethal and induced renal corticomedullary mineralization and centrilobular hepatic necrosis. One analogue, 3-bromo-2-hydroxypropanamine, caused rapid and extensive necrosis of the adrenal pars fasciculata and reticularis, simulating human Waterhouse Friderichsen syndrome. The three newly identified renal papillotoxins are all theoretically capable of generating direct-acting alkylating species in solution and their activity as direct-acting mutagens in the Ames bacterial mutagenicity test with TA100 (indicating base pair substitution) closely correlated with their potency as papillotoxins. We therefore hypothesize that non-enzymically formed direct-acting alkylating species mediate these papillary lesions, and that the target selectivity of haloalkylamine toxicity most probably results from the accumulation of these alkylating species in papillary tissue.

Animals↗
PubMed1991

Antitussive effects of diphenhydramine on the citric acid aerosol-induced cough response in humans.

This controlled crossover study in twenty healthy volunteer subjects utilized the citric acid aerosol-induced cough response as a means to demonstrate the effectiveness of 25 mg of diphenhydramine as an antitussive. Entry was limited to only those subjects who manifested a consistent, quantitatively definable response to a 5% citric acid challenge. Subjects were initially dosed with either a placebo vehicle or 25 mg diphenhydramine in a 10 ml formulation. Following drug ingestion, subjects were challenged at 15, 30, 45, 60, 120, and 240 minutes. Three days later, subjects were administered the alternate treatment and rechallenged at the same time points. Diphenhydramine was effective at the earliest time point assessed, 15 minutes, and continued to be as effective over the entire 4-hour duration of the test period. For the placebo vehicle, the mean cough counts did not change significantly from baseline. Neither the putative soothing effect of a liquid formulation nor accommodation to the citric acid spray can account for all the early and consistently significant activity of diphenhydramine in suppressing the cough response. The early onset of activity of diphenhydramine may be due to its local anesthetic properties or may indicate that the dose of diphenhydramine required for effective antitussive activity is lower than that required for effective antihistaminic activity. These results require further corroboration in direct comparisons of various doses of diphenhydramine with positive controls in both this model and clinical cough counting models employing pathologic cough indices. A 25 mg dose of diphenhydramine appears to be effective as an antitussive agent.

Administration, Inhalation↗
PubMed1991

The need for a pathological classification of asthma.

Historically, asthma has been described in functional terms as reversible airways obstruction and bronchial hyperresponsiveness. Whilst there is no agreed definition of asthma, studies involving bronchoalveolar lavage and endobronchial biopsy are highlighting inflammatory processes as an essential component of the disorder. With the success already achieved in quantifying mast cells, neutrophils, eosinophils, T-cells, monocytes and fibroblasts in the bronchial mucosa it should be possible to investigate the cellular basis of asthma, both in relation to clinical patterns of disease and their response to treatment. With such information it may well be possible that a definition of asthma could be arrived at based on pathology rather than function alone.

Asthma↗
PubMed1990

Oxidants, ATP depletion, and endothelial permeability to macromolecules.

Oxidants can reversibly increase the permeability of endothelium to ions and macromolecules. Oxidants also deplete ATP in cultured endothelial cells. We asked if oxidant-mediated ATP depletion, alone, accounted for the effects of oxidants on endothelial permeability to macromolecules. When porcine pulmonary artery endothelial cells were exposed to 2.5 mmol/LH2O2, ATP was depleted to 31.7% +/- 1.8% of control within 15 minutes and was reduced to 23.1% +/- 2.0% of control after 30 minutes. To determine if this magnitude of ATP depletion could account for the oxidant-induced increase in endothelial permeability to macromolecules, we measured ATP in endothelial cells exposed to metabolic inhibitors of ATP production. We then measured the effects of these metabolic inhibitors on endothelial monolayer permeability to macromolecules. ATP levels were reduced to 44% +/- 4% of control by 12 mmol/L deoxyglucose (DOG) in the absence of glucose and to 2% +/- 1.3% of control by DOG with 25 nmol/L antimycin A in the absence of glucose. Reduction of endothelial cell ATP to these levels with the metabolic inhibitors did not alter the flux of albumin or dextran across the endothelial monolayers. Thus ATP depletion, by itself, does not explain oxidant-induced changes in endothelial permeability to macromolecules.

Adenosine Triphosphate↗
PubMed1990

Probing the transglutaminase-mediated, posttranslational modification of proteins during development.

Sphaerechinus granularis eggs were fertilized in seawater in the presence of 0.2 mM dansylcadaverine, and development was allowed to take place with this compound in the medium. gamma-Glutamyldansylcadaverine, indicative of the utilization of the amine tracer by intrinsic transglutaminase, was isolated from the embryonic proteins, and identity of the product with the chemically synthesized gamma-glutamyl derivative of dansylcadaverine was confirmed. Covalent labeling of proteins occurring during development was examined by means of electrophoresis in NaDodSO4, followed by immunoblotting with an antibody that specifically recognized the dansyl hapten. There was an increase in the total uptake of the tracer at an essentially constant rate with each cell division, from 2- to 8- and 64-cell stages. Moreover, multiple protein labeling was evident in all specimens. The described concept of studying posttranslational modifications in vivo by transglutaminase through detection of the haptenic or specific ligand recognizable group of an incorporated small amine substrate will undoubtedly be of general utility for probing the functions of this family of enzymes in other cell types as well.

Animals↗
PubMed1990

Transfer of technology. Cancer education.

Advances in research are transmitted to practicing physicians through a variety of continuing medical education approaches. Physicians are sophisticated managers of their learning and use group and self-instruction methods. Local hospitals and professional societies along with reading are major sources of continuing education. Cancer education to transmit the latest advances draws on all methods of continuing medical education. A study of practicing physicians' interests and preferences in cancer education provides guidance about tailoring continuing medical education to physician needs. The use of personal computers may be important in bringing information directly to the physician in the practice setting. The challenge is to provide educational opportunities in a variety of ways to meet the diverse needs of the practicing medical community.

American Cancer Society↗
PubMed1990

Comparison of biomaterials for facial bone augmentation.

We compared the gross behavior of and microscopic response to implant materials currently in clinical use for facial bone augmentation at different sites in dogs. Materials evaluated include porous polytetrafluoroethylene carbon (Proplast), large-pore high-density polyethylene (Medpor), solid medical-grade silicone rubber (Silastic), polyamide mesh (Supramid), and autogenous rib bone. The subjects were 12 mixed-breed dogs and the materials were implanted directly on bone with periosteum removed at one of three sites in the dog's face (malar eminence, nasal dorsum, and chin). Animals were killed 3 months after surgery and stability of the implants was graded by manual manipulation. Blocks of tissue, including the study materials and underlying bone, were examined microscopically after sectioning. Stability results are tabulated and histologic appearance is described by site for each material evaluated. These data demonstrate marked variability of stability and cellular response depending on the site of implantation. From these data one may conclude that the site of implantation and implant movement are essential factors in determining the nature of the tissue response and fate of an implant. Solid and porous alloplastic materials show an acceptable tissue response, but neither demonstrates the ability to consistently provide an implant that is stable on underlying bone.

Animals↗
PubMed1990

Clozapine for psychosis in Parkinson's disease.

The clinical efficacy of clozapine, an atypical antipsychotic, in treating levodopa-induced hallucinations was investigated in five patients with Parkinson's disease under open label conditions. Two patients could not tolerate clozapine, even in doses as low as 12.5-25 mg daily, because of extreme sedation. Three patients could tolerate clozapine and experienced improvement or elimination of their hallucinations at doses below 100 mg daily. Despite a significant risk of adverse effects, cautious use of clozapine in low doses may be beneficial for patients with levodopa-induced psychosis who do not respond to more conservative measures.

Aged↗