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Biomedical subjects

A H Williams

Publications and source records attributed to A H Williams.

At least 19 recordsLinked to original sources
PubMed2005

Fine mapping chromosome 16q12 in a collection of 231 systemic lupus erythematosus sibpair and multiplex families.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder influenced by multiple genetic and environmental factors. Linkage of SLE to chromosome 16q12-13 (LOD score=3.85) was first identified in pedigrees collected at the University of Minnesota, and has been replicated in several independent SLE collections. We performed fine mapping using microsatellites to further refine the susceptibility region(s), and the best evidence for linkage was identified at marker D16S3396 (LOD=2.28, P=0.0006). Evidence of association was suggested in the analysis of all families (D16S3094, P=0.0516) and improved to the level of significance (P=0.0106) when only the Caucasian families were analyzed. Subsets of pedigrees were then selected on the basis of clinical manifestations, and these subsets showed evidence for association with several markers: GATA143D05 (renal, P=0.0064), D16S3035 (renal, P=0.0418), D16S3117 (renal, P=0.0366), D16S3071 (malar rash, P=0.03638; neuropsychiatric, P=0.0349; oral ulcers, P=0.0459), D16S3094 (hematologic, P=0.0226), and D16S3089 (arthritis, P=0.0141). Together, these data provide further evidence that an important susceptibility gene(s) for SLE is located at 16q12.

Chromosomes, Human, Pair 16↗
PubMed2005

Loci contributing to adult height and body mass index in African American families ascertained for type 2 diabetes.

Height and body mass index (BMI) have high heritability in most studies. High BMI and reduced height are well-recognized as important risk factors for a number of cardiovascular diseases. We investigated these phenotypes in African American families originally ascertained for studies of linkage with type 2 diabetes using self-reported height and weight. We conducted a genome wide scan in 221 families containing 580 individuals and 672 relative pairs of African American descent. Estimates of heritability and support for linkage were assessed by genetic variance component analyses using SOLAR software. The estimated heritabilities for height and BMI were 0.43 and 0.64, respectively. We have identified major loci contributing to variation in height on chromosomes 15 (LOD = 2.61 at 35 cM, p = 0.0004), 3 (LOD = 1.82 at 84 cM, p = 0.0029), 8 (LOD = 1.92 at 135 cM, p = 0.0024) and 17 (LOD = 1.70 at 110 cM, p = 0.0044). A broad region on chromosome 4 supported evidence of linkage to variation in BMI, with the highest LOD = 2.66 at 168 cM (p = 0.0005). Two height loci and two BMI loci appear to confirm the existence of quantitative trait loci previously identified by other studies, providing important replicative data to allow further resolution of linkage regions suitable for positional cloning of these cardiovascular disease risk loci.

Black People↗
PubMed2001

Serum cystatin C in patients with myeloma.

BACKGROUND: Cystatin C is a low molecular weight protein thought to be synthesised by all nucleated cells and freely filtered by the kidney. It has been proposed as a marker for GFR; however, it has been suggested that there may be limitations to its use, because it may be over-expressed in some tumour cells and the abnormal tissue growth may also lead to an increased circulating level. METHODS: We investigated the serum cystatin C levels in 60 patients with myeloma, comparing results with those for serum creatinine, beta(2)-microglobulin and the paraprotein concentration. RESULTS: We found no correlation between cystatin C and the paraprotein concentration in these patients. CONCLUSION: These results suggest that disease burden does not correlate to the circulating level of cystatin C in patients with myeloma.

Adult↗
PubMed1999

Private enterprise and public good: ethical issues in the funding of clinical research.

Health-care centres, universities, and the researchers and clinicians working in them are encouraged to procure research funding through the development of commercial relationships. There are positive, practical, and morally relevant arguments in support of this initiative, but the move also raises ethical issues concerning potential conflicts of interest. These include conflicts between an institution's or researcher's responsibilities to each other, to research subjects, and to the public, and competing financial interests. This article examines developments in research funding and ethical difficulties that may arise in the present administrative context. It provides suggestions for the development of guidelines by institutions that are supportive of investigators in their endeavors to enhance clinical care through crucial external funding and the implementation of research.

Biomedical Research↗
PubMed1995

Myeloma during a decade: clinical experience in a single centre.

One hundred and fifty-six patients with multiple myeloma were treated over a period of 12 years at St. Bartholomew's Hospital. The progress of the disease was affected in 96/156 patients (61%). Response was defined as achieving a plateau of M component. A partial or complete response was seen in 68/120 patients treated conventionally (56.5%), and in 28/36 patients treated with high-dose therapy (77.7%). The median survival of the group as a whole was 20 months, with a 2-year survival of just over 40%. In the 36 patients treated with high-dose therapy, median survival was 6 years, and in a small group who have had maintenance Interferon therapy, the median has not yet been reached. In a univariate analysis, age, intensity of therapy, haemoglobin and creatinine levels were significant, but multivariate analysis showed that only age and intensity of therapy were independent predictors for survival. The outlook for relapsed patients who showed progression of disease remains poor, but palliation was best achieved by steroid and Interferon in combination. Patients who achieve complete responses and are maintained on Interferon appear to be doing better both in terms of freedom from symptoms and in survival, and methods to enable an elderly population to tolerate this form of therapy need to be explored.

Adult↗
PubMed1993

Treatment of young rams with an agonist of GnRH delays reproductive development.

The objective of this study was to determine if the continuous treatment of young rams with an agonist of gonadotropin-releasing hormone (GnRH) in the period immediately prior to puberty would delay the onset of adult sexual behavior and retard testicular development. In the first experiment the GnRH agonist was shown to be effective in suppressing the plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult wethers (neonatally castrated rams) when administered by either a biocompatible slow release implant (implant) or a mini osmotic pump (minipump) that released the agonist for 4 weeks. The minipumps were more effective than the implants in suppressing the secretion of LH and FSH. In a second experiment, administration of the GnRH agonist by implant or minipump to prepubertal rams for 16 weeks immediately prior to puberty inhibited the development of sexual behavior, reduced the plasma concentrations of testosterone, retarded testicular and epididymal development, and inhibited growth rates. The effects on sexual behavior were clearly reversible but testicular and epididymal weights were still reduced in treated rams 8 weeks after the end of treatment. These results indicate that the reproductive function of rams is sensitive to gonadotropins and testicular hormones immediately prior to puberty. The agonist of GnRH was successfully delivered to the rams in a biocompatible implant which may offer a practical means of manipulating reproductive function in young rams.

Animals↗
PubMed1992

Teicoplanin in open fractures: a preliminary report.

The occurrence of infection following open fractures varies with the severity of the fracture and associated soft tissue damage. In order to study the effect of antibiotics given prophylactically, teicoplanin has been used in a prospective study. On admission, fractures were graded according to the severity of the tissue damage: Type I--soft tissue injury less than 1 cm Type II--soft tissue injury more than 1 cm. Type III fractures characterized by extensive soft tissue and bone damage were not included in the study. Type I patients were given a single dose of teicoplanin, 400 mg i.v.; Type II patients were given a single dose of teicoplanin, 400 mg i.v., followed by two further intravenous injections at 12 and 24 hours. Patients were assessed for the presence of wound and bone infections and follow up was for 1 year. Preliminary results, predominantly from Type II fractures involving long bones, show that teicoplanin is effective in lowering the incidence of infection following open fractures.

Adolescent↗
PubMed1991

Infections due to gram-positive organisms in children: possible role for teicoplanin.

The disruptive effect on, and potentially hazardous exposure to nosocomial infection, together with the relative cost of hospitalization, of children favours the need for ambulatory care. An increasing proportion of infections in children are due to beta-lactam resistant Gram-positive organisms. Teicoplanin is proposed as a suitable candidate for treating paediatric patients with serious Gram-positive infections in hospital or ambulatory care. The experience acquired in children is still limited. However, over 200 paediatric patients have been treated with once or twice daily im or iv teicoplanin in daily doses of 3-10 mg/kg. The main clinical diagnoses were skin and soft tissue infections, skeletal infections and septicaemia. The drug was safe and clinical efficacy was greater than 90%. Comparative studies with defined uniform protocols are now required to assess the potential of this drug.

Anti-Bacterial Agents↗
PubMed1991

Teicoplanin monotherapy of serious infections caused by gram-positive bacteria: a re-evaluation of patients with endocarditis or Staphylococcus aureus bacteraemia from a European open trial.

We have examined case records for patients who received teicoplanin alone for endocarditis or Staphylococcus aureus bacteraemia. All patients with streptococcal endocarditis were cured (viridans group 14/14; Group D 4/4). Cure rates for other organisms were: Enterococcus faecalis 3/5; S. aureus 5/10 and coagulase negative staphylococci 2/3. Doses for six patients who failed because of poor response were 3.3-4.2 mg/kg. Teicoplanin treatment cured 41/48 patients with S. aureus bacteraemia; treatment failed in two patients because of adverse events. Doses in the remaining treatment failures were 2.1-5.0 mg/kg. In comparison, 48 patients in Dundee hospitals received ten different drugs in 20 combinations for S. aureus bacteraemia; 29 patients received cloxacillin or flucloxacillin but initial doses varied from 0.25-2.0 g. We conclude that the European database does provide evidence that teicoplanin monotherapy is effective for serious infection with Gram-positive bacteria. Doses for staphylococcal infection should probably be at least 6 mg/kg. The upper limit of the teicoplanin dosage range remains to be determined but there is evidently considerable confusion about appropriate regimens for 'standard' therapy.

Anti-Bacterial Agents↗
PubMed1991

A review of the safety profile of teicoplanin.

Safety of teicoplanin has been assessed in 3377 patients treated in Europe up to the end of June 1990. One or more adverse events were experienced by 10% of patients. Age and teicoplanin dose had no significant effect on the incidence or type of adverse event. In comparative trials the incidence and profile of adverse events to teicoplanin have been similar to those seen with beta-lactam therapy. Impaired renal function occurred consistently more frequently with vancomycin therapy than with teicoplanin therapy, particularly when these drugs were co-administered with aminoglycosides. Severe skin reactions have not been reported with teicoplanin, which, unlike vancomycin, does not cause infusion rate-related release of histamine. These data provide further evidence that teicoplanin is safer than vancomycin and does not have dose-related adverse effects in the dose range 3-10 mg/kg.

Animals↗
PubMed1991

Do patients presenting to accident and emergency departments have low serum anticonvulsant concentrations?

It is often felt that poorly controlled epileptic patients, who are taking anticonvulsant medication, are over represented in A&E departments compared to the general population. This A&E based study set out to determine whether such patients do have inadequate serum anticonvulsant levels, when they present following a seizure, to A&E departments. All epileptic patients, taking medication, who presented to the A&E departments of St. Bartholomew's and Hackney Hospitals, London, over a 4-month period were studied. Serum anticonvulsant concentrations were measured on their arrival in the departments. Forty-six patients were studied. Only 21% of anticonvulsant drug concentrations were within 'therapeutic' ranges. A total of 66% were below 'therapeutic' ranges and 13% were potentially toxic. The implication of these findings is discussed.

Adolescent↗
PubMed1990

Modulation of expression of MHC antigens in the kidneys of mice by murine interferon-alpha/beta.

We have analyzed the effects of interferon-alpha/beta on MHC expression in the murine kidney, and compared these results with the MHC modulating effects of interferon-gamma. Natural murine interferon-alpha/beta was administered to B10.BR mice (H-2k), i.p., twice daily for 3 days. Expression of MHC antigens was assessed on day 4 by immunoperoxidase staining with biotinylated monoclonal antibodies to class I (KkDk) and class II (I-Ak) antigens. Interferon-alpha/beta significantly decreased the number of class II-positive renal cortical dendritic cells from 62.0/mm2 to 12.6/mm2 (P less than 0.001). A similar but less dramatic decrease was seen in cardiac dendritic cells. Little or no change in class II expression was observed in proximal tubules or glomeruli. Interferon-alpha/beta induced marked class I staining in the glomerulus, arterial endothelium, and Bowman's capsule. Proximal tubule cells also showed increased class I expression, but were less responsive than glomeruli. Thus, the effects of interferon-alpha/beta contrast with those of interferon-gamma, which increases class II expression on proximal tubules, induces relatively more class I expression in proximal tubules than glomeruli, and increases class II-positive dendritic cells. Furthermore, these results suggest that treatment with interferon-alpha/beta may have a complex effect on the immune response to a renal allograft due to its differential effects on class I and class II cell surface expression.

Animals↗
PubMed1989

Hospital CEO turnover: implications for trustees.

Many turnovers are positive for both CEOs and organizations, but there is still cause for concern. Three hospital management experts analyze the results of a recent survey of CEO turnover and examine the concerns of hospital executives, employees, medical staff members, and trustees.

Governing Board↗
PubMed1988

Direct single-reagent fluorescence polarisation immunoassay for valproic acid in serum.

A fluorescence polarisation immunoassay for quantitating serum concentrations of valproic acid was developed and validated. Its low molecular weight and lack of structural features caused difficulties in producing suitable antibodies. However, success was achieved using 2-propyl-6-aminohexanoic acid to make the fluorescein-labelled drug and two immunogens, the first using glutaraldehyde to link the drug derivative to keyhole limpet haemocyanin, and the second by carbodiimide activation of cellulose hydroxyl groups and coupling them to the drug derivative and killed Mycobacteria. It was found that both immunogens produced a good antibody response in sheep. The antibodies were highly specific and the assay results correlated well with an in-house gas-liquid chromatographic method.

Chromatography, Gas↗