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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 379 records · Page 21Linked to original sources
PubMed1993

Intravesical administration of indium-111-labelled HMFG2 monoclonal antibody in superficial bladder carcinomas.

Tumour-associated HMFG2 monoclonal antibody (MAb) was labelled with indium-111 and administered intravesically to 20 patients with known or suspected superficial bladder carcinoma. The antibody solution was kept in the bladder for 1 hr and was then washed out. Cystoscopy was performed at 2 and 24 hr after instillation. Radioactivity of tumour and normal tissue obtained from the bladder during cystoscopy and cells recovered from urine after the instillation were counted in a gamma-counter. Conventional histology, immunocytochemistry and autoradiography were also performed. Mean uptake at 2 and at 24 hr was higher in tumours than in normal samples. Autoradiography showed selective accumulation of radioactivity in cells which expressed the antigen detected by the HMFG2 MAb. There was no correlation of tumour uptake with the grade of tumour. No radioactivity was found in the blood of patients after the instillation. Based on dosimetric calculations, however, the radiation dose that can be delivered to the tumours is not sufficient to be cytotoxic, possibly due to inadequate penetration and retention by tumour tissue. Nevertheless, the significant difference between antibody uptake by the tumours and that by normal urothelium, observed in our study, allow for the possibility of using this approach therapeutically.

Administration, Intravesical↗
PubMed1993

Emergence of vancomycin-resistant enterococci in New York City.

Enterococci, a common cause of nosocomial infection, are intrinsically resistant to most antimicrobials and readily acquire additional resistance. Vancomycin-resistant enterococci (VRE) have caused clusters of nosocomial infections since 1988. In April, 1991, the New York City Department of Health asked all city laboratories to submit suspected VRE isolates for confirmation. Clinical and epidemiological characteristics of the first 100 patients with VRE were identified, and antimicrobial susceptibility testing, restriction enzyme analysis, and DNA-DNA hybridisation with the vanA gene probe were done. From September, 1989, to October, 1991, 361 patients with VRE were identified at 38 hospitals. The number of hospitals reporting VRE increased from 1 in 1989 to 38 by October, 1991. 98% of 100 VRE infections were nosocomially acquired and 83% patients had received vancomycin and/or a cephalosporin in the 30 days before isolation of VRE. Of 23 isolates from 21 of the first 100 patients, 19 (83%) were resistant to all available antimicrobials. Four vanA probing patterns were noted, and restriction enzyme analysis of the 23 isolates revealed 14 strains. VRE have emerged rapidly in New York City. Molecular analyses suggest that a highly mobile genetic element--eg, a transposon--is responsible for the rapid spread of vancomycin resistance.

Aged↗
PubMed1993

Primary care of patients with human immunodeficiency virus infection. The physician's perspective.

OBJECTIVE: To examine physicians' perceptions, motivations, and influences on their willingness to care for patients with human immunodeficiency virus (HIV). DESIGN: Interviews with 30 physicians. Qualitative content and narrative analyses were performed. SETTINGS: Community-based primary care practices in six moderate-sized cities in the northeastern United States with at least a moderate incidence or prevalence of reported acquired immunodeficiency syndrome cases. PARTICIPANTS: Thirty community-based primary care physicians who had cared for at least two patients with HIV during the previous 2 years. MAIN OUTCOME MEASURE: Qualitative study designed to provide rich descriptive data. RESULTS: Care of patients with HIV was regarded as part of the scope of primary care, and was perceived to be similar to the care of patients with other chronic illnesses. Many physicians were motivated by personal rewards in taking care of patients, intellectual challenge, and desire to serve the underserved. Most believed that practicing physicians have an ethical obligation to care for all patients, regardless of diagnosis. No one "type" of physician could be identified who provides care to patients with HIV. CONCLUSIONS: Primary care physicians can apply their skills in the management of other chronic diseases to the care of patients with HIV. Practicing physicians can find caring for patients with HIV rewarding, stimulating, and enjoyable. Educational programs for physicians need to emphasize psychosocial aspects of HIV care. In addition, physicians need opportunities to recognize and deal effectively with their own emotional responses to the care of patients with HIV.

Adult↗
PubMed1993

Imaging of pulmonary vascular disease by intravascular ultrasound.

To assess the ability of intravascular ultrasound (IVUS) to image changes in the pulmonary arterial wall associated with pulmonary hypertension (PHT), 10 subjects requiring diagnostic right and left heart catheterization were studied. In addition to measurements of pulmonary artery pressure and pulmonary vascular resistance and pulmonary angiography, when indicated, all underwent simultaneous IVUS imaging in the pulmonary arterial system using a 20 MHz ultrasound transducer mounted on a 2 mm diameter catheter. Four patients had normal pulmonary artery pressures and 6 had varying degrees of PHT. Satisfactory ultrasound images were obtained in 9 out of the 10 patients. In those with normal pulmonary artery pressures ultrasound showed a thin vessel wall with no distinction between separate layers. In patients with systemic PHT, a three-layered vessel wall was apparent and areas compatible with intimal proliferation were seen. In a patient with pulmonary embolic disease areas consistent with mural thrombus were detected at sites of luminal narrowing on the pulmonary angiogram. IVUS is capable of imaging some of the morphological changes in the wall of the pulmonary artery known to occur in longstanding PHT and may therefore become a useful adjunct to haemodynamic measurements and pulmonary angiography for the in vivo assessment of pulmonary vascular disease.

Adolescent↗
PubMed1993

Detection of ampicillin resistance in Enterococcus spp. by disk diffusion and two commercial automated systems.

A total of 154 Enterococcus faecium and 48 Enterococcus faecalis isolates, 55% of which were ampicillin-resistant, were used to evaluate two commonly used automated systems, Vitek's GPS-TA card (bioMérieux, USA) and MicroScan's POS MIC Type 6 panel (Baxter Health-care, USA), and the NCCLS disk diffusion method for the detection of ampicillin resistance. MicroScan panels were read by the Walk/Away system and by visual inspection. The results were as follows: disk diffusion, 100% sensitive and specific; Vitek, 100% sensitive and 95% specific; and MicroScan, when read by the Walk/Away, 85% sensitive and 98% specific. When MicroScan was interpreted by visual inspection, however, sensitivity increased to 96%.

Ampicillin Resistance↗
PubMed1993

Acute hyperinsulinemia increases neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats.

Neuropeptide Y, a major hypothalamic peptide, stimulates feeding, insulin secretion and weight gain when injected intrahypothalamically. Hypothalamic NPY may be regulated by insulin availability at hypothalamic level, as its activity is apparently inhibited by intrahypothalamic insulin administration and is stimulated under insulin-deficient conditions. To determine the effects of acute physiological hyperinsulinemia, we measured regional hypothalamic NPY levels in rats during a hyperinsulinemic, euglycemic clamp. Seven male Wistar rats with implanted jugular cannulae, fasted for 24 h, were infused with insulin at 100 mU/h together with variable-rate glucose to maintain euglycemia (3.9 +/- 0.1 mmol/l), for 150 min. Controls were infused for the same period with polygeline vehicle alone (n = 8), and had blood glucose concentrations of 4.0 +/- 0.5 mmol/l. Insulin levels were 80.2 +/- 3.9 mU/l in insulin-infused rats and 15.2 +/- 1.4 mU/l in polygeline-treated controls (p < 0.001). NPY levels, measured by radioimmunoassay, were significantly higher in the arcuate nucleus/median eminence (ARC/ME) of hyperinsulinemic rats than in controls (4.8 +/- 1.2 vs 2.5 +/- 0.6 fmol/micrograms protein; p < 0.001), but were comparable with controls in 7 other hypothalamic regions. Acute physiological hyperinsulinemia therefore increases NPY levels selectively in the ARC/ME. Insulin could cause NPY accumulation in the ARC by blocking its transport to NPY-sensitive areas. This would be consistent with the suggestions that insulin inhibits hypothalamic NPY activity and also acts as a central satiety factor.

Animals↗
PubMed1993

Socioeconomic disadvantage and child morbidity: an Australian longitudinal study.

While an extensive body of literature has demonstrated an association between socioeconomic status and child mortality, there have been relatively few papers which discuss the impact of socioeconomic inequality on child morbidity. This absence of data is partly attributable to methodological problems (need for large samples, the difficulty of assessing morbidity) and partly to the absence of relevant official health statistics. This paper reports results from the Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes. The sample comprises 8556 consecutive pregnancies, of which over 90% were followed up to birth. Of those mothers giving birth, approx. 70% of children were successfully given a health assessment five years after the birth (mothers report of the child's health using a set of standard indicators). The results indicate a consistent pattern with the children of the most socioeconomically disadvantaged mothers manifesting the worst health. Thus children living in socioeconomic disadvantage have a higher rate of health service utilisation, more chronic health problems and poorer dental health. The paper discusses some social policies for redressing these inequalities.

Adolescent↗
PubMed1993

Widespread increases in regional hypothalamic neuropeptide Y levels in acute cold-exposed rats.

Neuropeptide Y injected into the hypothalamus or third ventricle stimulates feeding and inhibits the sympathetic activation of brown adipose tissue. To clarify the involvement of hypothalamic neuropeptide Y in cold-induced thermogenesis, groups of rats exposed to 4 degrees for 2.5 or 18 h were compared with warm-adapted rats (22 degrees C). Neuropeptide Y was measured in eight selected hypothalamic regions, including those known to be involved in the regulation of energy expenditure. Activation of brown adipose tissue was confirmed by significant six- to nine-fold increases in brown adipose tissue uncoupling protein messenger RNA. Compared with warm-adapted controls, neuropeptide Y levels were significantly raised by 80-170% in several hypothalamic regions of rats exposed to cold for 2.5 h, namely the medial preoptic area, paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus and lateral hypothalamic area. Neuropeptide Y levels in 18-h cold-exposed rats were similarly elevated in these regions and were also significantly increased in the anterior hypothalamic area (75%). By contrast, neuropeptide Y levels in the arcuate nucleus, the main hypothalamic site of synthesis, were not increased by cold exposure, being significantly reduced by 21% after 2.5 h exposure and comparable with controls after 18 h. As neuropeptide Y injection inhibits brown adipose tissue activation, we suggest that the rapid and dramatic increases in neuropeptide Y levels in specific hypothalamic regions occur because cold exposure might inhibit the release of neuropeptide Y and so cause accumulation of neuropeptide Y in these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1993

Pharmacokinetics and antiviral activity of recombinant human interferon-beta ser17 in African green monkeys.

The pharmacokinetics and antiviral activity of recombinant human interferon-beta ser17 (Betaseron) were evaluated in African green monkeys. In one study, animals infected with simian varicella virus were administered Betaseron intravenously (i.v.), intramuscularly (i.m.), or subcutaneously (s.c.) at doses of 1 x 10(6) or 1 x 10(7) IU/kg twice daily for 10 days. In another study, infected animals received Betaseron s.c. at doses of 1 x 10(6) IU/kg twice daily, 2 x 10(6) IU/kg once daily, 4 x 10(6) IU/kg every other day, or 6 x 10(6) IU/kg every 3 days for 10 days. Following i.v. administration, mean clearance, steady-state volume of distribution, and terminal half-life values for Betaseron were 0.36 +/- 0.08 liters/hr.kg, 0.65 +/- 0.09 liters/kg, and 1.9 +/- 0.43 h, respectively. Although bioavailability following i.m. and s.c. administration was only 30-50%, antiviral activity, as measured by reduction in viremia and appearance of skin rash, was comparable for i.v., i.m., and s.c. administration of 1 x 10(6) IU/kg of Betaseron twice daily. With increasing dose (1 x 10(6) IU/kg to 1 x 10(7) IU/kg), both the area under the serum concentration-time curve (AUC) and antiviral activity of Betaseron tended to increase. When comparing various s.c. dosing regimens, there was significant accumulation of Betaseron in serum with repeated twice-daily dosing. However, no accumulation of Betaseron in serum was observed if the dosing interval was less frequent than once daily. Antiviral activity was greatest with twice-daily or once-daily s.c. administrations of Betaseron.

Animals↗
PubMed1993

Renal transplantation following immunoadsorption in highly sensitized recipients.

Five highly sensitized patients, with panel reactivity greater than 80% for 1.75-5 years, were treated by extracorporeal staphylococcal protein-A immunoadsorption, prednisolone, and cyclophosphamide. The five patients underwent treatment of 18-40 (mean 31) liters of plasma, respectively in 4-7 (mean 5.6) sessions. This reduced the titer of cytotoxic antibodies to sensitizing antigens to < 1/8 in all cases and abolished reactivity to crossreacting antigens. Two patients required retreatment following resynthesis of cytotoxic antibodies. All five patients have been transplanted, and four of these now have stable serum creatinines of 168 mumol/L at 34 months, 208 mumol/L at 29 months, 96 mumol/L at 5 months, and 125 mumol/L at 3 months posttransplantation. One patient had primary graft dysfunction due to acute tubular necrosis; the kidney was removed after eight weeks and showed cortical necrosis without evidence of acute rejection.

Adult↗
PubMed1993

Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating levels may not reflect tumour activity.

Parathyroid hormone-related protein is responsible for the hypercalcaemia caused by many tumours. Measurement of parathyroid hormone-related protein is becoming more accessible with the introduction of commercial assays. We report a case of hypercalcaemia of malignancy secondary to parathyroid hormone-related protein in a woman with renal carcinoma. The parathyroid hormone-related protein was assayed using a new immunoradiometric assay. We demonstrated an initial fall in parathyroid hormone-related protein and calcium levels after surgery and a rise in both before clinical relapse. However, the clinical relapse was itself associated with a fall in serum parathyroid hormone-related protein, nephrogenous cAMP and calcium, suggesting that the tumour had stopped producing parathyroid hormone-related protein or perhaps that post-translational processing had occurred as the tumour advanced. The tumour was investigated for parathyroid hormone-related protein mRNA content using reverse transcriptase polymerase chain reaction, both at diagnosis in surgically removed material, and using post-mortem specimens. The level of parathyroid hormone-related protein mRNA, while present, was much reduced in the recurrent tumour suggesting that active parathyroid hormone-related protein production fell substantially as the tumour advanced. This case suggests that, although demonstration of parathyroid hormone-related protein in hypercalcaemia is useful for diagnosis, tumoral secretion of this product may alter.

Adenocarcinoma, Clear Cell↗
PubMed1993

Prediction of outcome of preterm infants with severe bronchopulmonary dysplasia.

Forty-four preterm infants of less than 30 weeks gestation and birthweight < or = 1250 g, with severe bronchopulmonary dysplasia requiring mechanical ventilation for at least 28 days, were reviewed. Twenty-seven infants (61%) survived; 17 died. There were no significant differences between survivors and non-survivors with respect to birthweight, gestational age, sex, Apgar score at 5 min or pulmonary diagnosis. Non-survivors displayed more severe changes on chest X-ray than the survivors. Peak inspiratory pressure (PIP), ventilator rate (VR), ventilator index and mean airways pressure were significantly higher in the non-surviving infants on days 2, 3, 4, 7, 14, 21 and 28, with non-survivors also having significantly higher alveolar-arterial oxygen gradients and lower arterial-alveolar oxygen ratios than the survivors. Discriminant analysis with cross-validation by pairing PIP and VR on day 28 produced a positive predictive value for non-survival of 88% and a negative predictive value of 89%. This result was better than was obtained for any other pair of ventilator parameter or oxygenation index. Discriminant analysis by combining X-ray appearances with ventilator settings did not improve the prediction. Having established a statistical model based on the PIP and VR of ventilator-dependent preterm infants on day 28, the outcome can be predicted with a high degree of confidence. This has the immediate potential application of indicating to staff in the neonatal unit a realistic approach to take when counselling parents of these infants.

Bronchopulmonary Dysplasia↗
PubMed1993

The prostatron transurethral microwave device in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia.

There is currently considerable interest in the development of non-surgical means of managing bladder outflow obstruction due to benign prostatic hyperplasia (BPH). We report the results of a 1-year follow-up of 140 men (mean age 67.2 years) presenting with symptoms of bladder outflow obstruction treated for 1 h in a single session by the Prostatron transurethral thermotherapy system. Symptom scores, using a system modified from Boyarsky, fell from baseline values of 23.7 to 11.6. Maximum urinary flow values increased from a mean of 10.1 to 12.4 ml/s. Although residual urine volumes decreased slightly, this was not statistically significant. A self-administered postal questionnaire returned by 114 patients 1 year after Prostatron treatment, and by 87 patients of similar age who had undergone transurethral resection of the prostate (TURP) in the same institution, revealed that patient satisfaction regarding the outcome of each procedure was higher for TURP than thermotherapy. However, more patients suffered sexual dysfunction after TURP than after microwave treatment. It was concluded that although treatment with the Prostatron device produces subjective and objective improvement in a proportion of patients with BPH, more work needs to be done to improve the overall results and to pre-identify patients who experience little or no benefit from this therapy.

Aged↗
PubMed1993

The urolume, a permanently implanted prostatic stent for patients at high risk for surgery. Results from 5 collaborative centres.

Ninety-six men considered unfit for prostatic surgery underwent the insertion of a permanently implanted super alloy mesh stent (Urolume) at 5 European centres. Ninety were able to void immediately, 2 required a second stent to enable them to void and 4 voided after a period of suprapubic catheter drainage. Seven patients required the subsequent insertion of a further stent to cover the prostatic urethra completely and in 8 cases the stent was removed. Objective and symptomatic evidence of relief of bladder outflow obstruction was shown throughout the period of study. Severe irritative symptoms were seen in the majority of patients for periods of up to 3 months and resulted in removal of the stent in 3. At 12 months, 15 of 27 patients who underwent cystoscopy had complete epithelialisation of the stent and in 11 cases there was more than 70% epithelialisation. Fourteen patients developed encrustation on exposed parts of the stent during follow-up. This was associated with the development of a urinary infection in 9. The positioning of the stent in subsequent studies has been altered to overcome this problem.

Aged↗
PubMed1993

Evaluation of Ki-67 monoclonal antibody as prognostic indicator for prostatic carcinoma.

Prostate tissue containing either primary adenocarcinoma (45 patients) or benign hyperplasia (15 patients) was immunostained with the monoclonal antibody Ki-67, which recognises a human nuclear antigen expressed by human cycling cells. The percentage of cells staining positive was considered a measure of proliferation. This derived Ki-67 index was higher for carcinomas than for hyperplastic glands. Within the group of carcinomas, Ki-67 indices in patients with metastatic disease were significantly higher than in those without and there was a trend towards increasing Ki-67 indices with increasing Gleason grade. When patients with prostate cancer were prospectively followed up, the Ki-67 index did not predict either disease progression or hormone responsiveness. Ki-67 immunostaining may define a group of patients with prostate cancer of poor prognosis.

Adenocarcinoma↗