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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 433 records · Page 24Linked to original sources

Intravenous "pulse" cyclophosphamide therapy of crescentic glomerulonephritis.

Pulse steroids and monthly intravenous cyclophosphamide with a rapid steroid taper were used to treat seven patients with crescentic glomerulonephritis. Despite major impairment of renal function, all patients had a marked improvement in GFR by six months and improvement in proteinuria occurred in six of the seven patients. Two patients were able to discontinue dialysis. The doses of steroids and cyclophosphamide used were less than in comparable studies and side-effects of therapy were minimal. Repeat renal biopsies at over one year demonstrated marked glomerulosclerosis despite relatively stable renal function. Histologic analysis of total glomerular involvement indices on serial biopsies suggested no recruitment of new glomeruli into the crescenteric process once treatment had been initiated. Thus, intravenous pulse cyclophosphamide with pulse steroid therapy appears to be a safe and effective initial therapy for some patients with RPGN. Significant glomerulosclerosis on repeat biopsies suggests that glomerulosclerosis may be predetermined by the initial degree of irreversible glomerular damage and that the long-term course of the disease remains guarded.

Adult↗

'Brittle' diabetes.

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Diabetes Mellitus, Type 1↗

Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes.

Some insulin-dependent diabetic patients who have clear symptoms of hypoglycaemia during animal insulin treatment have reported loss of these symptoms when human insulin preparations are introduced. A survey of Mersey Region, UK, identified eleven patients whose awareness of hypoglycaemia was lost after introduction of human insulin but returned with animal insulin treatment; seven took part in the study. Acute hypoglycaemia was induced in these patients on two occasions by intravenous infusion of porcine or human soluble insulin (2.5 mU.kg-1, min-1) in random order. There was no significant difference between porcine and soluble insulin in the plasma glucose profile; mean (SEM) plasma glucose fell from 7.1 (0.4) mmol/l to a nadir of 1.5 (0.1) mmol/l with porcine insulin and from 7.1 (0.5) mmol/l to 1.6 (0.2) mmol/l with human insulin. An acute autonomic reaction occurred in all seven patients, at a similar plasma glucose concentration (1.9 [0.1] mmol/l with porcine insulin; 2.0 [0.2] mmol/l with human insulin). There were no significant differences in the frequency of symptoms or signs of hypoglycaemia between the two insulin species, nor any consistent differences in plasma glucagon, cortisol, growth hormone, adrenaline, or noradrenaline responses to hypoglycaemia. Symptomatic and hormonal responses to acute hypoglycaemia induced by porcine and human soluble insulins therefore seem to be almost indistinguishable, even in patients carefully selected for their apparent loss of hypoglycaemia awareness with human insulin.

Acute Disease↗

Brittle diabetes.

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Diabetes Mellitus, Type 1↗

A survey of the visual acuity of Brisbane drivers.

OBJECTIVE: To conduct a survey of the visual acuity of a group of Brisbane Drivers. SETTING: The outpatient department of the Princess Alexandra Hospital, Brisbane. PARTICIPANTS: Five hundred and three subjects drawn from patients, visitors and staff attending the outpatient department on 10 working days from December 5 to December 16, 1988. MAIN OUTCOME MEASURES: Subjects' age, driver's licence details and driving history were gathered by questionnaire. Visual acuity was assessed with the aid of a Snellen chart. RESULTS: Nearly 6% of the survey group had visual acuity worse than 6/12; 15% had never had their eyes tested other than for licensing purposes; 21% stated that their last ophthalmic or optometric examination was more than five years previously; and 8% failed to meet the Queensland visual acuity requirements for their class of licence. CONCLUSIONS: The monocular driver is not detected by current licence testing procedures in Queensland. Many licence holders do not meet the present visual acuity criteria of the Queensland Department of Transport.

Accidents, Traffic↗

Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast.

The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.

Adolescent↗

Intravesical administration of radiolabeled antitumor monoclonal antibody in bladder carcinoma.

Tumor associated AUA1 monoclonal antibody and 11.4.1. nonspecific monoclonal antibody, which does not react with human tissues, were radiolabeled with 111In and administered intravesically to 23 patients undergoing cystoscopy for bladder carcinoma. The antibody solution remained in the bladder for 1 h and then was washed out prior to cystoscopy. Tumor and nontumor samples were obtained during cystoscopy and were counted in a gamma counter. Conventional and immunoperoxidase staining with both antibodies were also performed. AUA1 reacted with all bladder carcinomas while 11.4.1. was negative in all cases. The mean uptake of AUA1 at 2, 24, and 48 h after the instillation (expressed as 10(3) x percentage of injected dose/g of tissue) was: 6.12 +/- 5.50 (SD), 1.70 +/- 2.57, 0.30 +/- 0.17 in the tumors and 0.32 +/- 0.50, 0.22 +/- 0.30, 0 in the nontumor areas, and for 11.4.1. it was: 0.075 +/- 0.075, 0.025 +/- 0.025 in the tumors and 0.30 +/- 0.42, 0.15 +/- 0.26 in the nontumor areas. The uptake of AUA1 by the tumors correlated with the tumor grade. There was no radioactivity in the blood at 2 h, and at 1, 2, and 3 days after the instillation. Our results indicate that intravesical administration of radiolabeled monoclonal antibody AUA1 targets selectively to tumor tissue without any significant normal tissue uptake. This finding might allow the development of a nontoxic and specific therapeutic approach for superficial bladder carcinoma.

Administration, Intravesical↗

Suppurative keratitis in rural Bangladesh: the value of gram stain in planning management.

External eye disease which result in corneal scarring are an important cause of blindness in Bangladesh and at the Chittagong Eye Infirmary and Training Complex (EITC) over 200 cases of suppurative keratitis are managed each year. We reviewed the records of 127 cases of microbial keratitis to determine the relative contributions of Gram stain and culture to diagnosis of the causative organism. There were 107 culture-proven cases of microbial keratitis amongst the 127 patients in this study. Gram stain was positive in 89 cases which represents 70% of the total and 83% of all culture-proven cases. Streptococcus pneumoniae and Pseudomonas sp were the commonest bacteria isolated and Aspergillus sp and Fusarium sp the commonest fungi. In 20 cases (16%) no organism was isolated on Gram stain or culture. Our results support the use of both Gram stain and culture in isolation of the causative organism in cases of suppurative keratitis in Bangladesh. However the low cost of Gram stain and its useful recovery rates for both bacteria and fungi support its use as an initial investigation for microbial keratitis at the secondary level of eye care in rural Bangladesh.

Anti-Bacterial Agents↗

Hypothalamic neuropeptide Y receptor characteristics and NPY-induced feeding responses in lean and obese Zucker rats.

Increased hypothalamic neuropeptide Y levels have previously been demonstrated in several hypothalamic nuclei of the (fa/fa) Zucker rat. This study set out to characterise hypothalamic NPY receptors in both genotypres and to study the effect of exogenous NPY on feeding behavior in these rats. Spontaneous daytime food intake was raised in the obese rat (p less than 0.05). Total hypothalamic receptor density (Bmax) was reduced in the obese rat compared with the lean rat (by 56%, p less than 0.005), but affinity remained unaltered. The lowest dose of NPY tested (23.5 pmol) stimulated daytime feeding in lean rats after 1, 2 and 3 hours but was inaffective in the obese rat (p less than 0.05). At two higher doses (235 pmol and 2.35 nmol), NPY was equipotent in both genotypes over 1 and 2 hours but NPY-induced feeding was attenuated over 3 hours in the obese rat. These results suggest an overactive endogenous NPYergic system in the obese (fa/fa) rat which might contribute to hyperphagia and obesity in this strain.

Animals↗

Increased neuropeptide Y concentrations in the lateral hypothalamic area of the rat after the onset of darkness: possible relevance to the circadian periodicity of feeding behavior.

Neuropeptide Y (NPY) is a major hypothalamic peptide which powerfully stimulates feeding when injected into the hypothalamus and is implicated in circadian rhythmicity. To investigate whether NPY is involved in the increased feeding that follows the onset of darkness in rats, NPY levels were measured in discrete hypothalamic areas before and after darkness. Four groups of eight adult female Wistar rats were habituated to a 12:12 hour light:dark cycle, with food presented at the onset of darkness (19.00 hours). One group was sacrificed during the 3 hours before darkness and another in the first 2.5 hours after darkness, with food provided as usual. To distinguish any effects of feeding itself, the study was repeated with two further groups, but food was not provided after darkness. Seven hypothalamic regions were microdissected from slices of fresh brain and acid-extracted for radioimmunoassay of NPY. NPY levels (fmol/microgram protein) were significantly higher (p less than 0.01) in the lateral hypothalamic area (LHA) of the dark-phase group in both studies. In the other six regions, NPY levels did not differ between light and dark phases. The LHA regulates the circadian rhythmicity of feeding and NPY injection here stimulates feeding. Alterations in NPY in the LHA around the onset of darkness may be related to the initiation of dark-phase feeding.

Animals↗

Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity.

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.

Analysis of Variance↗

Altered sensitivity of digital blood flow to acute vibration in patients with vasospastic disease.

Fifteen patients with primary Raynaud's, 18 patients with vibration induced white finger (VWF) and 15 controls were exposed to sine wave vibration, with an amplitude of 0.15 mm and frequencies of 40, 80 and 120 Hz. Baseline digital blood flow was measured using venous occlusion strain gauge plethysmography. A digit was vibrated for 1 min and subsequent blood flow measurements were taken from both vibrated and non-vibrated digits. Vibration at 40 Hz causes a significant decrease in flow in the vibrated digits of the control group only (P less than 0.05, Wilcoxon test). Vibration at 80 Hz shows a significant decrease in blood flow in the vibrated digits of both the control and the VWF groups (P less than 0.005) and also in the non-vibrated digits of the VWF group (P less than 0.05). Vibration at 120 Hz significantly decreases blood flow in the vibrated digits of normal control, VWF and Raynauds group (P less than 0.001). The Raynaud's non-vibrated digits also had decreased flow (P less than 0.005). These results imply that patients with established vasospastic disease are less sensitive to the direct effects of acute vibration than controls. The results also imply that vibration at 40, 80 and 120Hz affect digital blood flow in controls through local mechanism. Vibration at certain frequencies, appears to modulate blood flow in patients with vasospastic disease by acting through central mechanisms.

Adult↗

Reliability of questionnaire responses as compared with interview in the elderly: views of the outcome of transurethral resection of the prostate.

Three hundred and eighty-eight men undergoing transurethral resection of the prostate for benign prostatic hypertrophy completed a presurgical questionnaire and three follow-up questionnaires 3, 6 and 12 months after surgery. The questionnaires covered details of prostatic symptoms, general health, and expectations and results of surgery. At each follow-up point 40 randomly selected patients were interviewed by two female research assistants. The response rate to the questionnaires was over 90% at each follow-up point while that for the interviews was lower at around 80%. We examine the reliability of the postal questionnaires in assessing health status by comparing questionnaire and interview responses, with a view to the wider employment of such a method in the follow-up of surgical patients. In general, and as reported elsewhere, responses to questions on easily defined topics are highly comparable between questionnaire and interview. Responses to more subjective questions are moderately reliable, but with a tendency for postal questionnaires to underestimate a patient's health problems. It is difficult to assess the reliability of the questionnaires with regard to questions of an intimate nature since such questions caused embarrassment during interview with consequent incomplete responses.

Adult↗

The mental health of women 6 months after they give birth to an unwanted baby: a longitudinal study.

This study reports a longitudinal prospective study of the impact of an unwanted pregnancy on the mental health of the mother. Data are derived from a Brisbane, Australian sample of 8556 mothers who were enrolled at their first clinic visit (mean gestation 18 weeks) and then interviewed again some 3-5 days after the birth and when the baby was 6 months of age. Standard scales of mental health were administered on each of these occasions and mothers whose babies were unwanted were compared with the rest of the sample. The results indicate that mothers of unwanted children have somewhat higher rates of anxiety and depression than the comparison group, but that the magnitude of the mental health differences between the two groups: (a) diminishes over the period of the follow-up, (b) may be partly attributable to the prior poor mental health of women giving birth to an unplanned and unwanted baby, (c) is such that relatively few women who give birth to an unwanted baby experience mental health problems. The paper considers the implications of these results for health planners, notes the absence of contrary data and the need to acknowledge that these results may reflect situational factors which are characteristic of but not necessarily limited to Brisbane.

Adolescent↗

The effect of dietary change on in vitro erythrocyte haemolysis, skin lesions and alopecia in common marmosets (Callithrix jacchus).

1. The effect of dietary change on common marmosets (Callithrix jacchus) exhibiting high in vitro erythrocyte haemolysis, skin lesions and alopecia was investigated. 2. The experimental diet was low in lipid, high in vitamin E and was devoid of n-3 long chain polyunsaturated fatty acids. 3. There were significant increases in the concentrations of plasma alpha-tocopherol (vitamin E) (P less than 0.05), all-trans retinol (vitamin A) (P less than 0.001) and total lipid (P less than 0.025), and a reduction in fibrinogen (P less than 0.02) concentration and neutrophil count (P less than 0.02). 4. Moreover, the mean in vitro erythrocyte haemolysis declined from an initial value of 64% to less than 2%, and there was a regression of skin lesions and alopecia with complete fur regrowth. 5. The amelioration of the conditions appear to be due to high circulating vitamin E which provided protection against oxidative stress, and the correction of membrane n-6:n-3 balance.

Alopecia↗