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Biomedical subjects

B Williams

Publications and source records attributed to B Williams.

At least 199 records · Page 11Linked to original sources
PubMed1998

Comparison of irbesartan vs felodipine in the regression after 1 year of left ventricular hypertrophy in hypertensive patients (the SILVER trial). Study of Irbesartan in Left VEntricular hypertrophy Regression.

The SILVER (Study of Irbesartan in Left VEntricular hypertrophy Regression) trial is designed to test the hypothesis that the newly developed angiontensin-II receptor antagonist, irbesartan, will produce a greater reduction in left ventricular (LV) mass than felodipine ER, in a population of hypertensive patients defined by seated diastolic blood pressure (SeDBP) in the range 95-115 mmHg or seated systolic blood pressure (SeSBP) in the range 160-200 mm Hg. A population of 360 men and women of non-childbearing potential, >18 years of age, with hypertension, newly diagnosed or after a 3-week washout from previous anti-hypertensive or vasodilator therapies, will be randomised at approximately 80-90 European sites. Add-on therapy with hydrochlorothiazide and atenolol will be allowed for blood pressure control. Patients will be studied by two-dimensional and M-mode echocardiography at baseline (central validation of LV hypertrophy), on randomisation day, and after 6 and 12 months randomised therapy. Blinded analysis of echocardiograms will be performed at a central laboratory, which will provide measurements of the LV mass index (LVMI), determined by M-mode readings according to Devereux formula and using the Penn convention. The primary end-point of the study will be the change in LVMI from baseline to 12 months. The study power is 90% to detect differences between groups from baseline of approximately 8 g/m2.

Adolescent↗
PubMed1998

The role of the gastroenterologist in the provision of artificial nutrition support.

BACKGROUND: Nutrition support is required for the prevention or treatment of malnutrition in patients with intestinal failure and those who are unable to eat. AIMS: To determine the demands upon gastroenterologists for nutrition support, the available resources, and compliance with the British Society of Gastroenterology (BSG) guidelines. METHOD: A questionnaire was circulated to all 483 consultant physician members of the BSG. RESULTS: There were 336 (70%) replies. Fifty-three per cent of respondents reported malnutrition in 20% or more of their patients. Seventy-nine per cent of consultants supervised patients on enteral feeding, and 64% supervised parenteral feeding. Feeding jejunostomy was used by 61% of Teaching Hospital (TH) consultants but only 38% of District General Hospital (DGH) consultants (P < 0.001). Twenty-seven per cent of respondents headed, or were members of, a nutrition support team (NST). Forty-five and 38% of respondents did not follow written protocols for peripheral and central parenteral nutrition, respectively. Fifty-five per cent monitored catheter complications, of whom 44% reported catheter infections in 5% or more of their patients. Weights of inpatients were obtained by 76% of DGH consultants and 91% of TH consultants (P < 0.001). Fifty-eight per cent of respondents did not arrange for nutritional screening. Ninety-six per cent of consultants could access a dietitian, 55% had access to an NST and 36% had a nutrition nurse specialist (NNS). An NNS was available to 57% of TH consultants but only 23% of DGH consultants (P < 0.001). CONCLUSIONS: Gastroenterologists have a major role in nutrition support. Facilities are suboptimal. Observing guidelines may improve nutritional care. These findings have implications for resources and training.

Data Collection↗
PubMed1998

Evaluation of a training package in the assessment and management of depression in primary care.

This study aimed to evaluate the impact on the behaviour and attitudes of experienced general practitioners of a 10-hour training package in the assessment and management of depression. Twenty general practitioners participated. Both subjective and objective assessments were carried out which suggested significant improvements in both assessment and management skills. However, subjectively reported changes were not always supported by the objective data obtained from rating role-played interviews. The role-played patients rated the doctors as better communicators after training. All participants felt attending the course was beneficial. They all felt more confident in their abilities to deal with depression and said the skills they had learnt on the course would be useful to them in their future work. An outcome study is now underway in order to assess whether the training package, which has been demonstrated to have an impact on the behaviour, skills and attitudes of doctors, has an impact on the health of patients.

Adult↗
PubMed1998

Influence of ethnic origin on nuchal translucency screening for Down's syndrome.

OBJECTIVE: To determine the influence of ethnic origin on access to and equity of nuchal translucency screening for Down's syndrome in a multiethnic population. DESIGN: An observational study in a district general hospital with a large multiethnic population. SUBJECTS: 1944 women attending at a hospital antenatal clinic. MAIN OUTCOME MEASURES: First-trimester fetal nuchal translucency measurements at 10-14 weeks in women from different ethnic groups. RESULTS: The racial origin of the screened population was not significantly different from that of the population attending for initial antenatal examination. Multiple regression analysis showed a small but significant difference in nuchal translucency measurement between fetuses of different ethnic origin. CONCLUSION: Nuchal translucency screening can be effectively and equitably delivered to a multiethnic population. Although there are significant differences in nuchal translucency measurement between ethnic groups, these differences are too small to require correction when nuchal translucency is used to screen for Down's syndrome.

Asian People↗
PubMed1998

Extending the pipeline for minority physicians: a comprehensive program for minority faculty development.

Medical schools must become more successful in training minority faculty. Minority faculty development programs at schools of medicine must involve trainees from the undergraduate years (if not before) through junior faculty and must involve MD and combine-degree (MD-PhD) students. The authors describe the comprehensive minority faculty development program at the University of Pennsylvania School of Medicine, which involves minority undergraduates, medical students, residents, fellows, and faculty. This program provides the administrative staff and research methodologists to assist trainees at all levels across all departments in the school of medicine. The principal student recruitment program is the undergraduate premedicine enrichment program. The medical student component provides general counseling, research development, and activities to enhance performance in the clinical courses. The components for advanced trainees (residents, fellows, and postdoctoral trainees) and faculty consist of training in research methods, mentoring, teaching skills, and scientific writing skills. Through this program, the University of Pennsylvania School of Medicine has increased the number of under-represented minority faculty by 32% since 1993-94 and created an environment conducive to the professional growth and development of minority faculty.

Black or African American↗
PubMed1998

Mechanical influences on vascular smooth muscle cell function.

The increase in vascular wall stress imposed by hypertension has been strongly implicated in the pathogenesis of cardiovascular disease. Much of this chronic cyclical mechanical strain is experienced by the vascular smooth (VSM) cells of the vascular media. The cellular mechanisms whereby VSM cells sense and respond to changing mechanical forces are poorly understood. This review focuses on an emerging field of cardiovascular research in which the direct effects of mechanical strain on VSM cells and isolated blood vessels in organ culture have been characterized, in vitro. Cyclical mechanical strain profoundly influences cultured VSM cell orientation, growth and phenotype. Mechanical strain also increases the secretory function of VSM cells leading to increased extracellular matrix protein production. Vasoactive mediators such as angiotensin II potentiate these effects. Mechanical strain increases VSM cell release of platelet derived growth factor, transforming growth factor beta1, fibroblast growth factor and vascular endothelial growth factor, which act in autocrine or paracrine loops to influence VSM and endothelial cell growth and function. Mechanical strain may also activate local tissue renin-angiotensin systems and regulate expression of angiotensin II receptors within the cardiovascular system. The mechanism whereby VSM cells transduce mechanical stimuli into an intracellular signal and biological response, i.e. 'mechanotransduction', is strongly dependent on integrins. Moreover, specific matrix protein:integrin engagements lead to differential VSM cells responses via the selective activation of numerous intracellular signalling pathways including; mitogen-activated protein kinase, focal adhesion kinase and c-Src. The study of vascular mechanotransduction has begun to delineate the complex cellular basis of cardiovascular structural and functional modification in hypertension.

Animals↗
PubMed1998

The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel.

Hypertension is a common multifactorial disorder associated with considerable morbidity and mortality. The kidney plays a major role in the long term regulation of blood pressure. Liddle syndrome (pseudo-hyperaldosteronism) is one of a number of monogenic disorders of salt and water transport. In a kindred with at least four affected members suffering from Liddle syndrome, we confirmed by direct DNA sequencing the identity of a novel heterozygous mutation in h betaENaC, the gene encoding the beta subunit of the amiloride sensitive epithelial sodium channel which is expressed in the distal nephron. Single stranded conformational polymorphism analysis showed cosegregation of the mutant allele within the kindred with the Liddle phenotype. An insertion of an additional cytosine into a string of six located between codons 593 and 595 results in a sequence frameshift and is predicted to produce a protein truncated by 34 amino acids. The availability of a molecular diagnostic tool has implications for the management of hypertension and genetic counselling in families with Liddle syndrome.

Aldosterone↗
PubMed1998

A potential role for angiotensin II-induced vascular endothelial growth factor expression in the pathogenesis of diabetic nephropathy?

Diabetic nephropathy often co-exists with other manifestations of microangiopathy, in particular retinopathy. Recent clinical evidence suggests that inhibition of the renin-angiotensin system in humans can delay the development and/or progression of diabetic nephropathy and perhaps also retinopathy. The benefits of this therapeutic strategy may in part be explained by inhibition of the nonhaemodynamic actions of angiotensin II (Ang II). The recognized nonhaemodynamic actions of Ang II include the augmented release of many growth factors. Ang II can stimulate the release of vascular endothelial growth factor (VEGF) from human vascular tissues. VEGF is a family of potent cytokines which act to induce angiogenesis and markedly increase microvascular permeability. VEGF is abundantly expressed in the renal glomerulus, specifically within the podocyte, where its function is unknown. VEGF is also expressed in the retina and increased retinal VEGF expression occurs in diabetes and has been implicated in the pathogenesis of diabetic retinopathy. This review considers the potential clinical significance of Ang II-induced VEGF expression, if any, in the pathogenesis of diabetic nephropathy and retinopathy.

Angiotensin II↗
PubMed1998

Spontaneous cleft palate in a newborn gorilla (Gorilla gorilla gorilla).

OBJECTIVE: We report the first case of cleft palate in a newborn male gorilla (Gorilla gorilla gorilla). CASE HISTORY AND RESULTS: The full-term infant was born to clinically healthy, wild-caught parents and survived 5 days. Autopsy disclosed a unilateral cleft palate, moderate scalp hemorrhage (birth versus postnatal trauma), cerebral edema, and a sterile fibrin vegetation in the heart. The palate was also shorter and narrower than expected, and the biorbital breadth was reduced; otherwise, growth and development appeared normal. Standard cranial and intraoral radiographs and three-dimensional reconstructions of computerized tomographic (CT) scans provided thorough and noninvasive methods of studying the craniofacial complex and extracranial skeleton. By this technique, major findings were: intact premaxilla, interpremaxillary, and premaxillary/maxillary sutures; intramaxillary cleft with ipsilateral choanal atresia; mildly asymmetric inferior turbinates; and normal nasal septum and vomer. CONCLUSIONS: Except for choanal atresia, cleft palate was not associated with other major craniofacial or extracranial anomalies in this case. Choanal atresia has been observed at times with cleft palate, but to our knowledge, the association has not been reported in nonhuman primates. Cleft palate, with or without cleft lip, has been recognized in a variety of nonhuman primates, including the lemur, marmoset, tamarin, squirrel monkey, and macaque. Some occurrences are spontaneous, while others are syndromic and/or arise from genetic or teratogenic influences. Each mode of presentation is poorly understood in nonhuman primates, but in this case, the absence of relevant environmental or parental history suggests that the occurrence was spontaneous. Anatomic studies of nonhuman primates are particularly valuable when they involve endangered species and will hopefully increase our understanding of the pathogenesis and etiology of congenital disorders, as well as other relationships between nonhuman primates and humans.

Animals↗
PubMed1998

Cell biology and possible therapeutic applications of anti-CD3-activated killer-T cells (review).

Polyclonal T lymphocyte populations can be stimulated with anti-CD3 antibody to proliferate, secrete cytokines, and mediate MHC-unrestricted cytotoxic activity against a wide range of tumor target cells. Because anti-CD3-activated killer-T (AK-T) cells may be useful in the immunotherapy of human cancers, it is important to understand the signaling pathways and cell-surface structures involved in the induction and tumoricidal effector function of AK-T cells. Studies in the mouse model system have characterized the cytokines, signal transduction pathways, and costimulatory molecules involved in AK-T cell development. The recognition/adhesion and subsequent signaling events which lead to tumoricidal activity by mouse AK-T cells have also been defined. These findings, providing they translate accurately to the human system, may allow for the design of effective strategies to use AK-T cells for the treatment of human cancers. However, to date, the encouraging results obtained with anti-CD3 antibody/AK-T cell-based immunotherapies in mouse models of cancer have not been duplicated in clinical trials. The most likely explanation for this dis-appointing result is that tumor-reactive T lymphocytes in long term tumor-bearers fail to function correctly in the tumor microenvironment due to tumor-induced immune suppression and defects in key signal transduction molecules. It is clear that a detailed understanding of the inhibitory effect of established tumors on host T cells and the means to overcome tumor-induced immunosuppression are needed before anti-CD3 antibody/AK-T cell-based immunotherapies can be expected to succeed in the clinical setting.

Animals↗
PubMed1998

Understanding the epidemic of HIV in South Africa. Analysis of the antenatal clinic survey data.

OBJECTIVES: To investigate the magnitude and the time course of the HIV epidemic in the provinces of South Africa from the antenatal clinic HIV surveys. DESIGN: We analysed the data on the provincial prevalences of HIV infection from 1990 to 1996 using maximum likelihood methods to determine the intrinsic growth rate and probable asymptotic prevalence of HIV among women attending antenatal clinics. SUBJECTS: Women attending antenatal clinics and included in the national HIV prevalence surveys conducted by the Department of Health. RESULTS: 1. In KwaZulu-Natal the epidemic is likely to peak at a prevalence of about 23% (95% confidence interval (CI) 19-36%). 2. The intrinsic doubling time does not differ significantly among the provinces. 3. The average length of the intrinsic doubling time is 12.0 months (95% CI 11.3-12.8 months). 4. The force of infection is approximately 1.00/year at age 16 years and declines at a rate of about 5% per year of age above 16 years. CONCLUSIONS: South Africa is likely to experience one of the worst HIV epidemics in Africa. The lack of statistically significant differences between the growth rates of the epidemic in the various provinces constrains the possible explanations that can be advanced to explain the time course of the epidemic and may in part be a consequence of migrancy. The intrinsic growth rate is higher than previous estimates and it is possible that in those provinces where the prevalence is still low it will eventually reach the same levels as in KwaZulu-Natal.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Cost effectiveness of day and inpatient psychiatric treatment: results of a randomised controlled trial.

OBJECTIVE: To compare direct and indirect costs of day and inpatient treatment of acute psychiatric illness. DESIGN: Randomised controlled trial with outcome and costs assessed over 12 months after the date of admission. SETTING: Teaching hospital in an inner city area. SUBJECTS: 179 patients with acute psychiatric illness referred for admission who were suitable for random allocation to day hospital or inpatient treatment. 77 (43%) patients had schizophrenia. INTERVENTIONS: Routine inpatient or day hospital treatment. MAIN OUTCOME MEASURES: Direct and indirect costs over 12 months, clinical symptoms, social functioning, and burden on relatives over the follow up period. RESULTS: Clinical and social outcomes were similar at 12 months, except that inpatients improved significantly faster than day patients and burden on relatives was significantly less in the day hospital group at one year. Median direct costs to the hospital were 1923 pounds (95% confidence interval 750 pounds to 3174 pounds) per patient less for day hospital treatment than inpatient treatment. Indirect costs were greater for day patients; when these were included, overall day hospital treatment was 2165 pounds cheaper than inpatient treatment (95% confidence interval of median difference 737 pounds to 3593 pounds). Including costs to informants when appropriate meant that day hospital treatment was 1994 pounds per patient cheaper (95% confidence interval 600 pounds to 3543 pounds). CONCLUSIONS: Day patient treatment is cheaper for the 30-40% of potential admissions that can be treated in this way. Carers of day hospital patients may bear additional costs. Carers of all patients with acute psychiatric illness are often themselves severely distressed at the time of admission, but day hospital treatment leads to less burden on carers in the long term.

Adolescent↗
PubMed1997

Regulation of large calcium-activated potassium channels by protein phosphatase 2A.

Vasodilating agents induce relaxation of mesangial cells, in part through cGMP-mediated activation of large calcium-activated potassium channels (BKCa). Normally quiescent in cell-attached patches, the response of BKCa to nitric oxide, atrial natriuretic peptide, and dibutyryl cGMP (Bt2cGMP) is characterized by a biphasic increase and then decrease ("rundown") in open probability. Using the patch-clamp method in conjunction with phosphatase inhibitors, we investigated whether the run-down phase was the result of dephosphorylation by an endogenous protein phosphatase. In cell-attached patches, cantharidic acid (500 nM), okadaic acid (100 nM), and calyculin A (100 nM), nondiscriminant inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A) at these concentrations, caused a significantly greater and sustained response of BKCa to Bt2cGMP. Within 2 min, the response of BKCa to the combination of cantharidic acid and Bt2cGMP was greater than the response to these agents added separately. Incubation of mesangial cells with okadaic acid for 20 min at a concentration (5 nM) specific for PP2A increased the basal open probability of BKCa and completely inhibited rundown after activation by Bt2cGMP. Incubation with calyculin A (10 nM), a more potent inhibitor of PP1, did not affect BKCa activity. In inside-out patches, Bt2cGMP plus MgATP caused a sustained activation of BKCa that was inhibited by exogenous PP2A but not PP1. It is concluded that either BKCa or a tightly associated regulator of BKCa is a common substrate for endogenous cGMP-activated protein kinase, which activates BKCa, and PP2A, which inactivates BKCa, in human mesangial cells.

Cell Adhesion↗
PubMed1997

Idiopathic syringomyelia and the importance of occult arachnoid webs, pouches and cysts.

Syringomyelia is the condition in which longitudinal cavities are found within the spinal cord. The use of drainage procedures has been widely practised with good short term results. However, the long-term results in some large series have been less favourable. There are many associated conditions and in most forms a blockage to the normal flow of CSF, either at the foramen magnum or in the spinal canal, can be identified. Most surgeons would now direct their efforts to the establishment of normal CSF flow rather than a shunting procedure. In a certain group of patients, even with the advent of sophisticated MRI, no associated abnormality or CSF block is easily identified. This type of syringomyelia is often termed idiopathic. We report 10 patients with symptomatic syringomyelia without readily recognized predisposing factors. In eight patients preoperative myelography revealed a block to the flow of contrast compatible with subarachnoid obstruction. Eight patients underwent laminectomy and division of the obstructing arachnoid webs. Five experienced good improvement and three only moderate improvement. Two of the patients underwent syrinx shunting procedures only, which resulted in a worsening of their symptoms. At operation one patient was found to have an arachnoid cyst. We believe that patients with idiopathic symptomatic syringomyelia may need myelography to identify such arachnoid abnormalities. Subsequent surgery should be directed at the establishment of normal CSF flow by laminectomy and excision of the offending lesion.

Adult↗