Biomedical subjects
Publications and source records attributed to S Rogers.
An evaluation of program failures in the treatment of combat-related posttraumatic stress disorder has led some reviewers to conclude that the focus of treatment should be shifted away from combat trauma and directed toward other problems. A more detailed examination of these programs reveals that they rarely involve the systematic use of the most soundly-validated PTSD treatment, trauma-focused therapy.
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The identification of an association between variants in the human melanocortin 1 receptor (MC1R) gene and red hair and fair skin, as well as the relation between variants of this gene and coat color in animals, suggests that the MC1R is an integral control point in the normal pigmentation phenotype. In order to further define the contribution of MC1R variants to pigmentation in a normal population, we have looked for alterations in this gene in series of individuals from a general Irish population, in whom there is a preponderance of individuals with fair skin type. Seventy-five per cent contained a variant in the MC1R gene, with 30% containing two variants. The Arg151Cys, Arg160Trp, and Asp294His variants were significantly associated with red hair (p = 0.0015, p < 0.001, and p < 0.005, respectively). Importantly, no individuals harboring two of these three variants did not have red hair, although some red-haired individuals only showed one alteration. The same three variants were also over-represented in individuals with light skin type as assessed using a modified Fitzpatrick scale. Despite these associations many subjects with dark hair/darker skin type harbored MC1R variants, but there was no evidence of any particular association of variants with the darker phenotype. The Asp294His variant was similarly associated with red hair in a Dutch population, but was infrequent in red-headed subjects from Sweden. The Asp294His variant was also significantly associated with nonmelanoma skin cancer in a U.K. population. The results show that the Arg151Cys, Arg160Trp, and Asp294His variants are of key significance in determining the pigmentary phenotype and response to ultraviolet radiation, and suggest that in many cases the red-haired component and in some cases fair skin type are inherited as a Mendelian recessive.
This in-vitro study was designed to investigate the effects of commonly prescribed antibiotics on sperm movement characteristics, viability and the ability of spermatozoa to undergo the acrosome reaction. Spermatozoa were obtained by swim-up from normozoospermic semen and cultured for 24 h with increasing concentrations of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine. Tetracycline at concentrations as low as 2.5 microg/ml led to a significant dose-dependent inhibition in percent rapid-moving spermatozoa, mean path velocity (VAP), straight-line velocity (VSL) and curvilinear velocity (VCL), but at 50 microg/ml tetracycline all spermatozoa were static. Erythromycin had significant effects on rapid movement, VAP, VSL and VCL only at concentrations >100 microg/ml. In contrast, percent rapid-moving spermatozoa was significantly enhanced at low concentrations of chloroquine (5 microg/ml), but significantly inhibited by higher concentrations. Co-trimoxazole did not adversely affect percent rapid-moving spermatozoa below 500 microg/ml, at which concentration movement was decreased by 34%. The mean lateral head displacement (ALH) was significantly enhanced by 5 microg/ml co-trimoxazole and reduced at 1 mg/ml erythromycin. The effects of these drugs were mostly irreversible. Amoxycillin had no effect on sperm movement characteristics over the dose range used, though it inhibited viability at high doses. Viability was significantly reduced at concentrations of all drugs which affect rapid sperm movement; these concentrations of drugs did not appear to affect the ability of spermatozoa to undergo the acrosome reaction. The results from this study, when combined with known effects on spermatogenesis, should facilitate the choice of drugs for the treatment of both genitourinary and unrelated infections in men who are attempting to conceive.
OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.
1. Although employers in the public mental health arena may be expected to hire consumers of mental health services, it has been much more difficult for people with mental disabilities to find work in the private sector, or to return to such jobs after an acute episode of mental illness. 2. Many consumer-and survivor-run services around the country offer those with mental illness not only volunteer and employment opportunities, job training, and placement services, but also good role models and hope for the future. 3. How to address gaps in résumés is still controversial. However, since it is illegal for employers to ask questions designed to elicit information about illness, many experts advise consumers to get the job first; they can disclose their illness and ask for reasonable accommodations later.
AIM: To evaluate the use of azathioprine in the treatment of severe adult atopic eczema and review the relevant literature. BACKGROUND: Effective treatment of severe adult atopic eczema may necessitate the use of agents such as systemic steroids, PUVA or cyclosporin, which are associated with significant morbidity. Azathioprine is an effective alternative which can induce disease remission and may be less toxic. METHODS: Ten patients treated with azathioprine 0.7-2.5 mg/kg per day for a minimum period of 12 months were evaluated in a retrospective follow-up study. RESULTS: Clearance or marked improvement was noted in eight patients; three of these later became refractory to the drug. Side-effects were few and were well-tolerated. One patient was found to have lymphoma 8 months after stopping treatment. CONCLUSION: Azathioprine is an effective and cheaper alternative to cyclosporin in the treatment of severe adult atopic eczema. Its long-term toxicity remains unclear.
The recombinant human p38 MAP kinase has been expressed and purified from both Escherichia coli and SF9 cells, and has been crystallized in two forms by the hanging drop vapor diffusion method using PEG as precipitant. Both crystal forms belong to space group P2(1)2(1)2(1). The cell parameters for crystal form 1 are a = 65.2 A, b = 74.6 A and c = 78.1 A. Those for crystal form 2 are a = 58.3 A, b = 68.3 A and c = 87.9 A. Diffraction data to 2.0 A resolution have been collected on both forms.
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Fatigue is one of the most common and least understood symptoms of many chronic and disabling conditions. This qualitative study used a convenience sample (N = 13) of individuals with multiple sclerosis (MS). A semistructured interview guide was used to elicit a description of the experience of fatigue. Its perceived antecedents, and the self-care strategies used to manage it. Data were gathered during two 90 minute interviews. Five themes were identified that describe the experience of fatigue for persons with MS. Categories of self-care strategies included energy conservation, recharge efforts, enhancing resistance to fatigue, and temperature control. Further research is needed to explore the effects of specific interventions in the management of fatigue.
OBJECTIVES: To assess the effect on renal blood flow and renal function of placing a Wallstent (Schneider (Europe) AG) across the renal artery origins in an animal model. DESIGN: Laboratory animal study. MATERIALS AND METHODS: Six Large White pigs had Wallstents placed across the origins of one or both renal arteries. Preoperative jugular venous blood samples were submitted for blood count and urea and electrolyte estimation. The pigs were recovered for 6 weeks. At sacrifice the renal arteries and their origins were examined by aortography and direct pressure measurements were recorded from the renal arteries and both the stented and unstented portions of the aorta. Renal venous blood samples were submitted for blood count, urea and electrolyte and renin estimation while renal arterial blood samples were submitted to examination for red blood cell fragmentation. The aorta with contained stent, renal arteries and kidneys were submitted for histological examination. RESULTS: At sacrifice no renal arteries had occluded and the stent-covered origins appeared normal with no evidence of stenosis. This was confirmed histologically. There was no statistically significant difference between the arterial pressures measured in the stented and unstented portions of aorta and the renal arteries whether or not their origins had been covered by the stent. There was no statistically significant difference between the urea and electrolyte and renin levels of renal venous blood samples irrespective of whether or not the relevant kidney had a stent across its renal artery origin. Renal arterial blood samples showed no evidence of red blood cell fragmentation and histological examination of the kidneys showed no evidence of infarction or micro-emboli. Examination of the specimens by light and scanning electron microscopy demonstrated partial endothelialisation of the stents but the renal artery origins remained widely patent despite being crossed by at least one wire in all cases. CONCLUSIONS: It may be necessary to place stents across renal artery origins during endovascular repair of abdominal aortic aneurysms. It would appear that covering renal artery origins with a Wallstent has no effect on renal perfusion pressure or function in this short-term animal model.
We studied four treatment regimens of oral alendronate in 60 patients with active Paget's disease. Two groups received an oral daily dose of either 40 or 80 mg of alendronate for 3 months, followed by placebo for a further 3 months: the other two groups received treatment with 40 or 80 mg per day for 6 months. Activity of alkaline phosphatase and urinary hydroxyproline excretion were measured before, during, and after treatment, at intervals for a total follow-up of 1 year. A transiliac bone biopsy was performed in 24 patients before and after the treatment. An additional 16 patients had a third biopsy more than a year after stopping treatment. Alendronate induced a marked suppression in the urinary excretion of hydroxyproline within 2 weeks (p < 0.01) followed by a fall in serum activity of alkaline phosphatase at 1 month (p < 0.01) in all treatment groups. Nine months after the start of treatment patients treated with 80 mg for 6 months had a significantly lower mean alkaline phosphatase activity compared to the other treatment groups (p < 0.02), which persisted at 1 year (p < 0.05). Alkaline phosphatase decreased to within the laboratory reference range in all patients given 80 mg for 6 months. In contrast, alkaline phosphatase decreased to within the laboratory reference range in 73-83% of patients given 80 mg for 3 months and the 40 mg dose. Histomorphometric assessment showed a decrease in indices of bone turnover in the pagetic biopsies. None of the biopsies taken after treatment showed evidence of impaired mineralization of bone. Gastrointestinal side effects occurred in 25% of patients of whom two withdrew from treatment. We conclude that oral alendronate is an effective agent for the treatment of Paget's disease of bone.
The crystal structure of human p38 mitogen-activated protein (MAP) kinase in complex with a potent and highly specific pyridinyl-imidazole inhibitor has been determined at 2.0 A resolution. The structure of the kinase, which is in its unphosphorylated state, is similar to that of the closely-related ERK2. The inhibitor molecule is bound in the ATP pocket. A hydrogen bond is made between the pyridyl nitrogen of the inhibitor and the main chain amido nitrogen of residue 109, analogous to the interaction from the N1 atom of ATP. The crystal structure provides possible explanations for the specificity of this class of inhibitors. Other protein kinase inhibitors may achieve their specificity through a similar mechanism. The structure also reveals a possible second binding site for this inhibitor, with currently unknown function.
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This qualitative study was undertaken to clarify an emerging explanatory model of health-promoting behaviors, and quality of life in individuals with chronic disabling conditions. Twenty individuals with multiple sclerosis shared their stories regarding health promotion, domains of quality of life, and factors that affected these domains. Health-promoting behaviors were viewed as essential to the process of rehabilitation and maintaining an acceptable quality of life. Important quality-of-life issues were related to domains other than function. Implications are that health promotion efforts need to be encouraged and supported in individuals with chronic disabling conditions.
Fever is a host defense response that provides a sign of an ongoing process related to infection, inflammation, drug reactions, neoplasms, autoimmune diseases, and vascular disorders. The most frequent causes of fever in acutely ill patients are infection and inflammation, but fever may be caused by one or more of a long list of pathophysiologic processes.
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Computational fluid dynamics (CFD) has become an indispensable part of aerospace research and design. The solution procedure for incompressible Navier-Stokes equations can be used for biofluid mechanics research. The computational approach provides detailed knowledge of the flowfield complementary to that obtained by experimental measurements. This paper illustrates the extension of CFD techniques to artificial heart flow simulation. Unsteady incompressible Navier-Stokes equations written in three-dimensional generalized curvilinear coordinates are solved iteratively at each physical time step until the incompressibility condition is satisfied. The solution method is based on the pseudocompressibility approach. It uses an implicit upwind-differencing scheme together with the Gauss-Seidel line-relaxation method. The efficiency and robustness of the time-accurate formulation of the numerical algorithm are tested by computing the flow through model geometries. A channel flow with a moving indentation is computed and validated by experimental measurements and other numerical solutions. In order to handle the geometric complexity and the moving boundary problems, a zonal method and an overlapped grid embedding scheme are employed, respectively. Steady-state solutions for the flow through a tilting-disk heart valve are compared with experimental measurements. Good agreement is obtained. Aided by experimental data, the flow through an entire Penn State artificial heart model is computed.