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Biomedical subjects

S Holt

Publications and source records attributed to S Holt.

At least 109 records · Page 6Linked to original sources

Cholecystostomy: a safe alternative?

We have studied retrospectively 27 patients undergoing cholecystostomy for acute cholecystitis over the past decade. The mean age of the patients was 60 years, and 17 were female. 'Difficult dissection' was the reason given for cholecystostomy in 18 cases and in the remainder the patients were deemed unfit for cholecystectomy. An operative cholangiogram was performed in only two cases, and none of the patients had a primary common bile duct exploration. Post-operative cholangiograms in 14 patients revealed common bile duct stones in three (21%). Three elderly patients (mean age 79) died in hospital. At a mean follow-up of one year, 26% of patients had come to elective cholecystectomy, and there had been a further three unrelated deaths. We conclude that under difficult circumstances, cholecystostomy may be a safe alternative to cholecystectomy. These patients have a high incidence of choledocholithiasis, and thus we would recommend operative cholangiograms in all patients. However, early ERCP and sphincterotomy may be a safe alternative if this service becomes more widely available.

Acute Disease↗

A prospective, multi-center clinical trial of the Taylor intragastric balloon for the treatment of morbid obesity.

This report describes the result of a prospective, multicenter clinical trial of the Taylor intragastric balloon for the treatment of morbid obesity. Sixty patients, who had failed sustained weight loss on prior dietary restriction and behavior modification programs, were enrolled in four clinical centers. The Taylor intragastric balloon, a 550-ml, pear-shaped, liquid-filled, silicone device, was inserted in all patients for a period of 16 wk, and patients were maintained on a dietary restriction and behavior modification program. During the study period, patients experienced a 11.6% decrease in mean weight and an 11.4% decrease in body mass index. Seven balloons deflated spontaneously. Examination of these balloons revealed a manufacturing defect that was subsequently corrected. No further deflations occurred. Effects of the balloons on gastric mucosa were minimal with no gastric erosions or ulcerations noted.

Adult↗

Digitalislike immunoreactive substances and extracellular fluid volume status in chronic hemodialysis patients.

Circulating digitalislike immunoreactive substances (DLIS) may represent a class of volume-sensitive natriuretic factors. Chronic renal failure patients are known to have elevated levels of circulating natriuretic activity and also to have detectable DLIS. Using digoxin radioimmunoassay, DLIS levels were measured in desalted, deproteinized plasma from 15 stable hemodialysis patients. Predialysis DLIS was 109.3 +/- 6.3 pg/mL (digoxin equivalents) and decreased to 97.5 +/- 5.9 pg/mL following dialysis (P less than 0.001). Predialysis DLIS correlated with weight gain from the prior dialysis (P less than 0.01). The degree of extracellular fluid volume expansion predialysis also correlated with predialysis DLIS (P less than 0.01). Postdialysis DLIS also correlated with postdialysis extracellular fluid volume status (P less than 0.01). DLIS levels in dialysis patients were higher than in 50 normal subjects (30.0 +/- 1.2 pg/mL; P less than 0.001). Also, the changes in DLIS with dialysis were paralleled by similar changes in simultaneously measured human alpha-atrial natriuretic peptide (ANP) levels. These results demonstrate that (1) DLIS levels are higher in hemodialysis patients than in normal individuals; (2) with dialysis, DLIS levels increase and decrease in association with extracellular fluid volume expansion and removal, respectively; (3) DLIS levels correlate with the degree of extracellular fluid volume expansion in dialysis patients; and (4) DLIS levels change in parallel with levels of another class of natriuretic factor ANP. These characteristics are consistent with the hypothesis that DLIS represents a volume-sensitive factor.

Adult↗

Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus.

The 37-amino acid peptide called amylin is a major component of the islet amyloid deposited in the pancreases of persons with type 2 diabetes mellitus. We report the isolation of a partial cDNA clone and a phage lambda genomic clone of the coding region of the amylin gene. The DNA sequence encodes a protein sequence identical to that of amylin isolated from the amyloid found in the diabetic pancreas and shows that amylin is likely to be synthesized as a precursor peptide, now named proamylin. We have demonstrated that the amylin gene is present on chromosome 12 and that it is probably transcribed in the islets of Langerhans. The sequences of the genes for amylin and the calcitonin gene-related peptides (CGRPs) show strong similarity, especially over their 5' coding regions, where both peptides have a conserved intramolecular disulfide bridge, and also over their 3' coding regions, where the presence of a glycine codon strongly suggests that the carboxyl-terminal residue of amylin, like that of CGRP, is amidated. To examine the functional relevance of these posttranslational modifications, the biological activity of amylin synthesized with or without the disulfide bridge and/or amidation was measured. It was found that both features are necessary for full biological activity, thereby confirming the functional importance of those regions of the molecule whose sequences are conserved at both protein and genetic levels.

Amino Acid Sequence↗

Increased plasma PGE2, 6-keto-PGF1 alpha, and 12-HETE levels following experimental concussive brain injury.

Previous investigations have shown that brain prostaglandin levels are transiently elevated following experimental fluid percussion brain injury. Associated with these increased prostaglandin levels there is free radical production and abnormalities in cerebral arteriolar function. The purpose of this study was to determine whether experimental fluid percussion brain injury in cats is associated with increased systemic levels of prostaglandins and the lipoxygenase product, 12-HETE. Blood samples were collected before and at various periods of time after 2.7 atm of fluid percussion brain injury was produced in adult cats. Prostaglandin and 12-HETE analysis was performed by radioimmunoassay after extraction of the plasma samples. The control levels for 6-keto-PGF1 alpha, PGE2, and 12-HETE were 477 +/- 42, 2,372 +/- 431, and 13,328 +/- 1,769 pg/ml, respectively. Following injury all three eicosanoids reached peak plasma levels by 1-5 min after injury. The percentile increases for all eicosanoids were similar and increased from 70 to 110%. The increases were sustained at up to 30 min postinjury and by 1 h after injury were at control levels. As in previous studies, hypertension following injury was maximal by 1 min postinjury and blood pressure had returned to near normal levels by 5 min postinjury. These studies demonstrate prolonged systemic increases in eicosanoids following injury. Since free radical production and vascular damage occur concomitantly with eicosanoid production, the prolonged increases in these products suggest that there is an attainable therapeutic window following injury during which administration of free radical scavengers may decrease radical damage and reduce the consequences of injury.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Identification and intervention for alcohol abuse.

Early diagnosis of alcohol abuse with brief intervention, in appropriate clinical settings, offers great promise for the reduction of the prevalence of alcohol related morbidity and mortality. Secondary prevention of alcohol abuse offers promise for a reduction in alcohol related mortality and morbidity that cannot be readily achieved in an acceptable manner with primary preventive or conventional rehabilitative measures. A concerted medical effort, using simple diagnostic methodology to find cases and offer advice about drinking, will undoubtedly result in a positive impact on alcohol problems.

Alcohol Deterrents↗

Endometriosis and the gut.

Six patients with endometriosis involving the intestine are described and illustrate the variety of symptoms which may occur in this condition, many of which are frequently associated with the more common gastrointestinal illnesses. A correct preoperative diagnosis based on history, clinical examination, radiology, and endoscopy may be difficult to make, and when first discovered at laparotomy endometriosis can easily be mistaken for other inflammatory, or neoplastic processes. A histological diagnosis should always be made before definitive treatment.

Adult↗

Effect of hypophysectomy on energy balance and brown fat activity in obese Zucker rats.

Hypophysectomy (HYPX) in genetically obese (fa/fa) Zucker rats significantly reduced body weight and energy gains and stimulated energy expenditure (by 34%), the thermic response to food (by 144%), and brown adipose tissue (BAT) mitochondrial GDP-binding capacity (by 190%) compared with pair-fed, sham-operated obese rats. These changes in energy balance in obese HYPX rats were reversed by corticosterone replacement (1 mg/day), but the increased BAT activity was only partly restored to normal. HYPX had only small effects on energy balance in lean Zucker rats compared with pair-fed, sham-operated lean controls but increased the acute thermic response to food and BAT mitochondrial GDP-binding capacity; these effects were inhibited by replacement of HYPX rats with corticosterone. The results suggest that alterations in the hypothalamic-pituitary-adrenal axis play a fundamental role in the development and maintenance of genetic obesity.

Adipose Tissue, Brown↗

Mapping of 12 translocation breakpoints in the Xp21 region with respect to the locus for Duchenne muscular dystrophy.

Over 20 females have been reported to carry reciprocal X; autosome translocations with breakpoints in Xp21 and to suffer from Duchenne muscular dystrophy (DMD). We have positioned nine of these breakpoints with respect to the Duchenne gene by mapping probes from the DMD region against a panel of somatic cell hybrids, each containing one of the translocation chromosomes from a different female patient; further information has also been obtained by in situ hybridization, including the breakpoint location in a tenth DMD patient. We have also characterized two translocation breakpoints that lie in the same chromosomal region but which are not associated with the expression of DMD. All the DMD-associated translocation breakpoints examined lie at several sites within the DMD locus and between the two non-DMD breakpoints.

Cell Line↗

A randomised controlled trial of adjuvant hormono-chemotherapy in Stage II breast cancer.

From 1979 to 1984 women with histologically proven Stage II breast cancer were entered into a randomised controlled trial of adjuvant hormono-chemotherapy following mastectomy. Adjuvant therapy was started within 2 weeks of surgery and was given for 6 months as continuous 'Tamoxifen' and 6-monthly cycles of vincristine, adriamycin and cyclophosphamide (VAC). Of the 157 women randomised 82 were assigned to the control group and 75 to the adjuvant group. Comparing the two groups by life table analysis the rate of recurrence was found to be significantly greater in the control group (n = 46) than in the adjuvant group (n = 25) (Peto log rank test chi 2 = 7.46 P less than 0.01). Although there were more deaths amongst the control patients (n = 31) than in those randomised to receive adjuvant therapy (n = 18), this difference did not achieve statistical significance (chi 2 = 2.80 P less than 0.1). This analysis has shown that although adjuvant hormono-chemotherapy may significantly delay recurrence the trial has failed to demonstrate any significant improvement in the survival of women with Stage II breast cancer following mastectomy.

Adult↗