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Biomedical subjects

C S Williams

Publications and source records attributed to C S Williams.

At least 91 records · Page 5Linked to original sources
PubMed1996

Blunted renal vascular response to angiotensin II is associated with a common variant of the angiotensinogen gene and obesity.

OBJECTIVE: Recently, we reported evidence for genetic linkage between human essential hypertension and the angiotensinogen gene (AGT) and an association with a common molecular variant of this gene (methionine 235 --> threonine or T235). Other studies had led us to hypothesize that blunted renal plasma flow responses to infused angiotensin II (Ang II) when in high salt balance may reflect increased intrarenal formation of Ang II, a condition that might promote hypertension. Here we examine the relationship between AGT genotype and renal vascular response to infused Ang II. METHODS: Hypertensive (n = 34, all off medication) and normotensive (n = 57) members of families with a history of hypertension (age 18-60 years) as well as 29 normotensive volunteers without a family history of hypertension were studied after controlled diets with 200 mequiv./day sodium. Ang II was infused at a mildly pressor dose (3 ng/kg/min) and renal plasma flow was determined by steady-state plasma para-aminohippurate concentration. RESULTS: After correction for covariates in multivariate analyses, participants homozygous for the T235 variant had significantly diminished renal plasma flow responses to the Ang II infusion (P = 0.005). Changes in renal arterial resistance were also blunted in the T235 homozygotes. Similar results were found when analysis was restricted to normotensive participants or subdivided based on family history of hypertension. No confounding factors associated with AGT genotype that could explain these differences were found. Furthermore, obesity, which also suppressed renovascular response to Ang II, was found to interact significantly (P = 0.017) with genotype such that, among T235 homozygotes, obesity had a greater blunting effect on renal vascular response. CONCLUSIONS: Expected renovascular response to infused Ang II was blunted in persons with the AGT TT genotype. This is the first report of an association between a specific gene variant and altered renal physiology in humans with particular relevance to essential hypertension.

Adolescent↗
PubMed1996

Tuberculin testing in two Liverpool social clubs: the effects of a tuberculosis outbreak on background positivity.

BACKGROUND: Tuberculin testing remains the standard method for assessing infection due to tuberculosis in the UK. However, there are no data on the incidence of tuberculin positivity among the general adult population in the UK and consequently interpretation of Heaf test results is often difficult. METHODS: During the investigation of an outbreak of tuberculosis in a Liverpool social club 198 members were interviewed and Heaf tested and 171 members of a second social club in Liverpool were similarly screened as a control group. Comparisons between the results from the two populations provided both an estimate of baseline Heaf test positivity in indigenous white adults from a British inner city population, and a measure of the effect on this baseline of recent exposure to tuberculosis. RESULTS: In both club populations the proportion of positive Heaf tests increased with age. Independent of age, the tuberculosis exposed population had a higher proportion of positive Heaf grade results (40.9%) than those in the control group (26.9%). Multivariate analysis confirmed both the differences in Heaf results between clubs and between age groups but identified no other behavioural or medical factors which affected Heaf test results. CONCLUSIONS: Heaf test positivity increases with age at least up to 54 years, and recent exposure to tuberculosis increases the proportion of positive Heaf tests in each age group. Interpretation of positive Heaf tests when assessing the effects of a tuberculosis outbreak should take account of background levels of Heaf positivity.

Adolescent↗
PubMed1996

Prostaglandin endoperoxide synthase: why two isoforms?

Prostaglandin endoperoxide synthase-1 [prostaglandin G/H synthase-1 (PGHS-1)] and PGHS-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. We refer to these isoforms as cyclooxygenase-1 (COX-1) and COX-2 in this review. This brief review focuses on recent developments in the study of these enzymes. Alterations in the expression levels of COX-2 result in distinct phenotypic changes in intestinal epithelial cells. Overexpression of COX-2 in intestinal epithelial cells results in increased adhesion to extracellular matrix proteins and inhibition of apoptosis. Disruption of the COX-2 gene in mice results in renal dysplasia, cardiac fibrosis, and defects in the ovary. Interestingly, disruption of the COX-1 gene results in distinct phenotypic changes different from those observed for COX-2. COX-1 null mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice. These two closely related enzymes must have distinct functions in the organisms, since lack of their expression causes distinct phenotypic changes for each respective isoform.

Amino Acid Sequence↗
PubMed1996

Lack of linkage between the endothelial nitric oxide synthase gene and hypertension.

Nitric oxide is an important vasodilator formed in many tissues, including the vascular endothelium. Because of the relationship between nitric oxide and basal vascular tone, genes regulating nitric oxide have been suggested as candidate genes involved with the development of hypertension. At least three isoforms of nitric oxide synthase have been identified. Two of the isoforms, endothelial and inducible nitric oxide synthase, may have particular importance in hypertension. The gene coding for endothelial nitric oxide synthase on chromosome 7 has been cloned. Polymorphic dinucleotide repeats within this nitric oxide synthase gene were used to test for linkage to hypertension in 259 hypertensive siblings from 112 Utah hypertensive sibships. The resulting 194 sibpairs shared 108 alleles identical by state compared to the expected 108.1 alleles shared as estimated from CEPH allele frequencies. After weighting for different sibship sizes, there was only a 3.9% excess allele sharing (P = 0.21). Allele sharing in more severe hypertensive sibpairs (either two antihypertensive medications or an unmedicated diastolic blood pressure (BP) of 100 mm Hg or higher) showed a 6% excess over expected sharing of alleles (P = 0.28). There was no difference between male and female sibpair sharing of alleles (5.2% vs 7.8%, respectively, both not significant). Therefore, there was no evidence that the gene for endothelial nitric oxide synthase was linked to hypertension in these sibpairs.

Adult↗
PubMed1996

The pathophysiology of carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is the most frequently encountered peripheral compressive neuropathy. Although the clinical diagnosis and treatment of CTS have been well defined, the pathophysiologic basis still is not understood completely. This article summarizes current thought and research pertinent to the pathophysiology of CTS.

Carpal Tunnel Syndrome↗
PubMed1995

Ultrasonographic imaging of the hand and wrist in rheumatoid arthritis.

OBJECTIVE: To assess ultrasound findings in patients with rheumatoid arthritis affecting the hand and wrist compared to normal volunteers. DESIGN: Metacarpophalangeal and carpal articulations were imaged ultrasonically. Two readers reviewed static images for synovial, cartilaginous, and bony abnormalities using severity and probability scales. Ultrasound findings were correlated with disease activity. PATIENTS: Ten normal volunteers and 29 patients with known rheumatoid arthritis. RESULTS: Synovial abnormalities and erosions were most commonly identified in the rheumatoid hand and wrist (p < 0.01). Criteria used for normal and abnormal cartilage did not predict normal and disease states. Significant differences in synovial abnormalities and erosions were observed between the inactive and mildly active disease groups as well as the active and mildly active disease groups (p < 0.01). CONCLUSION: Ultrasound can detect abnormalities of the hand and wrist in patients with rheumatoid arthritis compared to normal volunteers. Normal articular anatomy is well demonstrated ultrasonically.

Adult↗
PubMed1995

Pronephric carcinoma: chromosomes of cells rescued from apoptosis by an oncogenic herpesvirus detected with a polymerase chain reaction.

The amphibian pronephros is fated to die during early development. Pronephric cells undergo apoptosis and their function is replaced by the mesonephros, which becomes the functional kidney of the adult frog. Tadpoles of the northern leopard frog, Rana pipiens, were inoculated with a Lucké tumour herpesvirus (LTV) preparation. Most of the animals developed typical Lucké renal carcinomas at metamorphosis. Fewer developed carcinomas of the pronephric cell type. A pronephric carcinoma, rescued from apoptosis by the herpesvirus, was harvested from a post-metamorphic frog. The tumour was judged to be pronephric by its anatomical location (in the anterior part of the body) and because both mesonephric kidneys were intact and tumour-free upon removal of the tumour mass. A tumour fragment was fixed for histological examination, which confirmed that the tissue was a renal carcinoma. A further fragment was subjected to short-term culture in order to produce metaphase cells for cytogenetical analysis. Based upon silverstained nucleolar organizing region numbers, 14 of 15 metaphase cells were estimated to have the diploid number (2N = 26) of chromosomes and a karyotype was constructed which did not appear to differ from that of normal cells. A single cell was estimated to be tetraploid (4N = 52). This is the first report of chromosomes of a pronephric Lucké carcinoma. LTV replicates only in tumour tissue maintained in the cold. Because the frog in this study had been maintained in the laboratory at 22 degrees C for about 10 months, no viruses would have been detectable with electron microscopy. However, the presence of Lucké herpesvirus DNA was detected in tumour homogenates by polymerase chain reaction amplification of a 1.2 kbp Hind III restriction fragment of the LTV DNA. The presence of LTV DNA provided assurance that the rescued pronephric tumour was indeed a Lucké carcinoma.

Animals↗
PubMed1995

The flexor digitorum longus: an anatomic and microscopic study for use as a tendon graft.

Recent experimental studies have shown that intrasynovial donor tendons have the capacity to heal with minimal alteration in the gliding surface when grafted to an intrasynovial location. In order to evaluate the flexor digitorum longus of the foot as a potential matched donor tendon for use in flexor tendon grafting, we dissected 15 feet (75 toes) and 10 hands (50 fingers) to determine the intrasynovial lengths of the flexor digitorum longus and flexor digitorum profundus and to determine a method of tendon graft harvest. Specimens were taken from the intrasynovial portion of each tendon for evaluation by light and electron microscopy. The intrasynovial tendons of the hand and foot were similar in vascularity, cellularity, gliding surface, and ultrastructure. The flexor digitorum longus tendon of the foot was a mean length of 12 cm to the area of tendon confluence in the midfoot, which will usually provide enough tendon length for grafting from the distal phalanx to the palm of the hand. Because of the difference in length of the synovial sheaths of the fingers and toes, some extrasynovial tendon will be transferred to the synovial space when a flexor digitorum longus tendon is used.

Cadaver↗
PubMed1995

Assessing risk for the onset of functional dependence among older adults: the role of physical performance.

BACKGROUND: Approximately 10% of nondisabled, community-dwelling adults aged 75 years and older lose independence in basic activities of daily living (ADLs) each year. The purpose of this study was to evaluate whether simple tests of physical performance could identify older adults, independent in their basic ADLs, who were at increased risk for the onset of functional dependence. METHODS: Among a representative cohort of 1103 community-dwelling adults aged 72 years and older, we evaluated the 664 subjects who were cognitively intact and independent in their basic ADLs at the baseline interview. All cohort members had undergone a comprehensive assessment, including a battery of qualitative and timed performance tests. The main outcome event was the onset of functional dependence, defined as a new disability in one or more of the seven basic ADLs at the 1-year follow-up. RESULTS: Functional dependence developed in 53 (9%) of the 563 subjects who had complete data at the 1-year follow-up. Eight of the 12 qualitative tests and all six of the timed tests were significantly associated (P < .05) with the onset of functional dependence. Both qualitative and timed performance tests demarcated subjects into groups at low and high risk for functional dependence. Four timed tests--chair stands, rapid gait, 360 degrees turn, and bending over--showed a threshold phenomenon, where the rate of new dependence increased slowly with worsening performance until a critical point (or threshold) was reached, and the rate of dependence increased substantially. For timed chair stands, for example, the rates of functional dependence within quarters of worsening performance were 5.3%, 6.3%, 6.7%, and 16%. The risk of functional dependence was markedly elevated (30%-50%) for subjects who were unable to perform the timed tests. CONCLUSIONS: Several simple tests of physical performance were strongly associated with the onset of functional dependence. These results support the potential use of physical performance tests to develop a risk assessment strategy that could identify subgroups of older persons, independent in all ADLs, who are at increased risk for functional dependence.

Activities of Daily Living↗
PubMed1995

Functional disability among elderly blacks and whites in two diverse areas: the New Haven and North Carolina EPESE. Established Populations for the Epidemiologic Studies of the Elderly.

This study examines the prevalence of functional disability (limitation in at least one basic activity of daily living) among elderly Black and White community residents in the New Haven (n = 2812) and North Carolina (n = 4162) sites of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). In New Haven, elderly Blacks, particularly women below age 75, had a higher prevalence of disability compared with Whites, which was partially attributable to a higher prevalence of chronic conditions. In North Carolina, Blacks had only a slightly higher risk of being disabled than Whites, and this was fully accounted for by differences in socioeconomic status. Black-White differences in the prevalence of functional disability reveal geographic variation.

Activities of Daily Living↗
PubMed1994

Diabetes mellitus, advances and their implications for aerospace medicine.

The authors describe a case of Type 1 diabetes mellitus (insulin dependent) in a 34-year-old fighter pilot, which included a 15-month remission ("honeymoon period"). The pathogenesis, characteristics, diagnosis, evaluation, and the aeromedical implications of Type 1 diabetes are discussed. The use of C-peptide values in accessing beta cell function is also discussed. The risk of poorly controlled diabetes, diabetic ketoacidosis, and visual acuity fluctuations were major reasons to disqualify this individual when in remission. The importance of determining the type of diabetes for prognosis and aeromedical disposition is stressed.

Adult↗
PubMed1994

A study of calcium and vitamin D metabolism in Chinese patients with pulmonary tuberculosis.

Hypercalcaemia can occur in patients with tuberculosis. To further characterize the calcium and vitamin D metabolism in this disorder, serum calcium, 25(OH)D, 1,25(OH)2D and parathyroid hormone and the interrelationships between serum calcium, 25(OH)D and 1,25(OH)2D were compared in 24 untreated Chinese patients with culture-positive pulmonary tuberculosis and 24 age and sex-matched controls in Hong Kong. Albumin adjusted serum calcium was significantly higher in patients (2.33 +/- 0.07 compared with 2.20 +/- 0.09 mmol l-1, P < 0.001), despite a lower calcium intake (426 +/- 208 compared with 564 +/- 335 mg day-1). No significant group difference was found in serum 25(OH)D or 1,25(OH)2D concentrations. There was a positive correlation between serum 25(OH)D and 1,25(OH)2D concentrations in the patient group (r = 0.50, P < 0.02), but a negative one in the control group (r = -0.48, P < 0.05). Serum parathyroid hormone was significantly lower in patients (20.9 +/- 8.5 compared with 38.2 +/- 14.5 pmol l-1, P < 0.001). In the patient group, no correlation between the radiographic extent of disease and serum calcium or 1,25(OH)2D concentrations was seen. Our findings confirmed that serum calcium is raised in tuberculosis but the effect may be reduced by a low calcium intake and a low parathyroid hormone level. Although the calcium and vitamin D metabolism appeared to be altered in tuberculosis, no direct relationship between serum calcium and 1,25(OH)2D, was found.

Adult↗
PubMed1993

Tuberculosis and poverty.

OBJECTIVE: To examine whether the historical link between tuberculosis and poverty still exists. DESIGN: Retrospective study examining the notifications of all forms of tuberculosis by council ward over a six year period and correlating this with four indices of poverty; council housing, free school meals, the Townsend overall deprivation index, and the Jarman index. SETTING: The 33 electoral wards of the city of Liverpool. SUBJECTS: 344 residents of Liverpool with tuberculosis. RESULTS: The rate of tuberculosis was correlated with all measures of poverty, the strongest correlation being with the Jarman index (r = 0.73, p < 0.0001). This link was independent of the high rates of tuberculosis seen in ethnic minorities. CONCLUSION: Tuberculosis remains strongly associated with poverty.

Adolescent↗
PubMed1993

Tuberculin testing in residential homes for the elderly.

BACKGROUND: Evidence from the United States has shown that tuberculin sensitivity increases with length of stay among residents in homes for the elderly, implying an increasing risk of infection. There is no evidence as to whether or not residents in homes in the United Kingdom have a similar risk. METHODS: A study was undertaken to determine whether residence in a home for the elderly increases the risk of tuberculosis infection. Over a six month period all residents in homes for the elderly in Liverpool received a tuberculin test. A health questionnaire was completed by the field team for each resident. A total of 2665 residents in homes for the elderly were surveyed. RESULTS: Heaf test grade positivity declined with age, the odds ratio being 0.71 for each 10 year period. Adjusting for age, there was no change in Heaf test grade with length of stay in the home. Heaf test positivity was stronger in smokers (odds ratio 1.59) than ex-smokers (odds ratio 1.20) and non-smokers. Heaf test grade positivity was directly related to pack years. Allowing for age and smoking, the odds ratio for men compared with women for a positive test was 1.62 (95% confidence interval 1.32 to 1.99). CONCLUSIONS: Heaf test positivity declines with age. Residence in a home for the elderly is not associated with increased rate of tuberculosis sensitivity. Smoking and male gender is associated with increased Heaf test positivity.

Adult↗
PubMed1993

Cytogenetic analysis of triploid renal carcinoma in Rana pipiens.

To provide a cytogenetic marker for nuclear transplantation experiments, triploid Rana pipiens embryos were produced. These embryos were injected with Lucké tumor herpesvirus. The chromosome profile of a renal carcinoma that developed in one of these triploid embryos was compared to the chromosomal profiles of a naturally occurring diploid renal carcinoma and a diploid renal tumor maintained as serial anterior eye chamber allografts for over 7 yr. Examination of Ag-NOR-stained chromosome spreads from the putative triploid and naturally occurring putative diploid tumor revealed the expected results. The vast majority of the chromosome spreads, 54/57 (95%) and 6/7 (86%), respectively, displayed euploid chromosome and Ag-NOR profiles: 3N = 39 with three Ag-NORs at the secondary constrictions in the long arm of chromosome 10 (10q) and 2N = 26 with two Ag-NORs in 10q. Chromosome profiles from the long-term allografted tumor were highly aneuploid (82%) and, based on their Ag-NOR content, displayed variations in their 2N, 3N, and 4N numbers. These data indicate that the majority of recently transformed triploid Lucké tumor cells can provide donor nuclei suitable for the characterization of developmental potential.

Animals↗
PubMed1993

The research challenge for the Professions Allied to Medicine.

The transfer of health care schools into Higher Education, coupled with the universal development of degree programmes has resulted in the need to develop research strategies for the Professions Allied to Medicine (PAMs). While considerable reliance has to be placed on the University sector to lead and encourage research activity, it is essential to recognise the need to maintain and develop links with clinical colleagues and to promote the growth of interdisciplinary research. A variety of areas which could allow early fruition of collaborative work between the professions are proposed.

Allied Health Occupations↗