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Biomedical subjects

S Holt

Publications and source records attributed to S Holt.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of Nissen total and Lind partial transabdominal fundoplication in the treatment of gastro-oesophageal reflux.

Fifty-two patients with gastro-oesophageal reflux disease refractory to medical treatment were randomized to undergo a Nissen total (360 degrees wrap) or Lind partial (300 degrees wrap) transabdominal fundoplication. Each group was comparable in number (26 patients), mean age (47 and 48 years) and sex distribution (eight women). Preoperative and postoperative assessment involved a modified Visick score, 22-h intraoesophageal pH monitoring, endoscopy and manometry. Follow-up was at 6 weeks and between 3 and 33 (mean 13) months. The prevalence of heartburn and regurgitation and the results of pH monitoring improved significantly after both operations (P less than 0.001). At early assessment eight previously asymptomatic patients (31 per cent) from the Nissen group and six (23 per cent) from the Lind group experienced difficulty swallowing. Ten patients (38 per cent) in each group complained of 'gas bloat'. Both complications had improved at late assessment in the majority of patients. No statistically significant advantage could be demonstrated for either operation.

Adult↗
PubMed1992

Computer assessment of life-style in a gastroenterology clinic.

To examine the potential benefit of a computer-assisted interview about life-style in gastroenterology practice, 34 consecutive patients attending a gastroenterology clinic were questioned by a computer using software designed to obtain a comprehensive history of alcohol, caffeine, cigarette, and illicit drug use, together with an assessment of exercise, sexual activity, and nutrition. Comparisons of the information obtained by the computer with clinical records revealed that physicians documented only 3% of the patients as problem drinkers, 3% as caffeine abusers, and 17% as smokers, whereas the computer identified 10% of the patients as problem drinkers, 27% as caffeine abusers, and 43% as smokers. These findings imply that patients may be more apt to tell more about adverse life-style to the computer than to a physician during clinical interview. In a sample patient population from a gastroenterology clinic, a microcomputer provides an acceptable, efficient, and potentially cost-effective way to assess life-style.

Adult↗
PubMed1992

Gastroesophageal physiology after stapled gastroesophagostomy in dogs.

A stapled vertical gastroesophagostomy (VGE) has been proposed for benign esophageal stricture. The VGE involves performing an anastomosis using a linear cutting stapler inserted via a gastrotomy (one limb in the esophagus, the other in the proximal fundus). In phase I of the study, a 50-mm VGE was performed in 13 dogs; 7 received an additional fundoplication. Endoscopy with pinch biopsies, esophageal manometry, and 4-hour ambulatory pH recordings were performed in each dog prior to and 1 month after VGE. The only difference between groups postoperatively was a higher lower esophageal sphincter pressure in the group with the added fundoplication. The incidence of histologic esophagitis was low in both groups. In phase II of the study, a VGE was performed in six dogs using a 75-mm linear cutting stapler, accompanied by fundoplication in each dog. These dogs were then followed for 6 months to more completely assess the long-term risk of developing reflux esophagitis. At necropsy, no gross or histologic evidence of esophagitis was found. The performance of a VGE through the lower esophageal sphincter in normal dogs does not result in significant reflux esophagitis. VGE may be an alternative to resection for esophageal stricture.

Anastomosis, Surgical↗
PubMed1992

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study.

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.

Adult↗
PubMed1992

Relationship of satiety to postprandial glycaemic, insulin and cholecystokinin responses.

The effect of plasma glucose on satiety and the capacity of carbohydrates to stimulate cholecystokinin (CCK) remain unclear. The aim of this study was to test the hypothesis that the magnitude of the postprandial plasma glucose and insulin response is inversely related to the CCK response and to subjective satiety. Seven healthy, male volunteers consumed equal carbohydrate portions (0.5 g/kg body weight) of six test meals (Rice Bubbles, Sustain, Vita-Brits, All-Bran, porridge and white bread) in random order after an overnight fast. An egg and bacon meal was consumed as a non-carbohydrate control providing 0.5 g protein/kg body weight. Serum CCK, plasma glucose and insulin and subjective satiety (measured by a rating scale) were assessed over 3 h and quantified using the glycaemic index (GI), insulin index (II), the peak satiety score and area under the incremental curve (AUC). The observed GIs (mean +/- SE) ranged from 42.5 +/- 2.6 for All-Bran to 116.2 +/- 11.4 for Rice Bubbles, using white bread as the reference food (GI = 100). Peak satiety scores varied eightfold from 0.21 +/- 0.4 for Sustain to 1.64 +/- 0.4 for All-Bran. Significant inverse relationships were observed between the peak satiety score and both the glycaemic and insulin index of the seven meals (r = -0.916, p less than 0.001 and r = -0.926, p less than 0.001). A direct relationship was observed between satiety (AUC) and the CCK response (AUC) (r = 0.73 p less than 0.01). The results suggest that glycaemic and insulin responses to carbohydrate foods are inversely proportional to the CCK response and satiety.

Adult↗
PubMed1992

Long-term prognostic significance of thymidine labelling index in primary breast cancer.

Tumour growth rates, as measured by incorporation of tritiated thymidine, have been reported as being of prognostic importance in breast cancer. We have measured the thymidine labelling index (TLI) of 185 early breast cancers, followed-up for a minimum of 8 years. Above median TLI was associated with higher tumour grade, but not with other prognostic factors. TLI was not predictive of survival in either univariate or multivariate analysis. The inter- and intra-observer reproducibilities of TLI measurements were poor, which may be a factor limiting its usefulness as a prognostic indicator in breast cancer.

Breast Neoplasms↗
PubMed1992

Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer.

DNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model. 64% of tumours were DNA aneuploid. The median SPF was 4.5% for DNA diploid, and 10.9% for DNA aneuploid tumours. There were small reductions in survival at 10 years for DNA aneuploid tumours, and for tumours with above median SPF, but these were not statistically significant. The relative hazard for DNA aneuploid tumours was 1.20 (95% CI 0.81-1.76), and for high SPF was 1.31 (95% CI 0.87-1.98). Neither factor was statistically correlated with survival in multivariate analysis. Technical and theoretical factors limit the accuracy and reproducibility of flow cytometric data, and may explain the lack of prognostic information given.

Breast Neoplasms↗
PubMed1992

Barrett's esophagus: observations on diagnosis and management.

Barrett's esophagus is a premalignant condition that may often pass unrecognized in clinical practice. In adults, this condition is generally believed to be caused by chronic gastroesophageal reflux resulting in a metaplastic change in the epithelium of the esophagus. Diagnosis of Barrett's esophagus is established by careful biopsy of the involved esophageal mucosa. Periodic surveillance is recommended because of the risk of carcinoma. Antireflux surgery has not been shown to result consistently in the regression of the metaplastic epithelium, but potent acid suppression offers a new therapeutic approach that leads to healing of esophagitis and the potential regression of Barrett's epithelium.

Barrett Esophagus↗
PubMed1991

Intragastric device for weight loss. Effect on energy intake in dogs.

It remains unclear whether or not intragastric devices promote weight loss. To elucidate if an intragastric balloon reduces energy intake by a placebo effect of inducing satiety, five free-feeding dogs had balloons inserted via a gastric cannula. Meal intake was assessed with the balloons inflated to 200 and 500 ml with saline and compared with intake during a control period when the animals maintained stable weight. Average energy intake during the control period was 0.3 MJ/kg/day. Inflation to 200 ml had no significant effect on intake (0.31 MJ/kg/day), whereas inflation to 500 ml significantly reduced energy intake to 0.14 MJ/kg/day (P less than 0.0001). An intragastric balloon does create aversion to feeding, presumably by producing satiety, but the effect is volume dependent.

Animals↗
PubMed1991

Omeprazole. Overview and opinion.

Omeprazole, a substituted benzimidazole, is a specific inhibitor of the enzyme H+/K(+)-ATPase, which is found on the secretory surface of the parietal cell. This enzyme, the "proton pump," catalyzes the final step in acid secretion. Omeprazole is a powerful inhibitor of gastric acid secretion. At the time of writing, omeprazole has been licensed in the United States for the treatment of severe grades of gastroesophageal reflux disease (GERD) as well as GERD unresponsive to treatment with currently available agents, and for the treatment of Zollinger-Ellison syndrome and other gastric hypersecretory states. Most recently, it has been recommended by the FDA advisory committee for approval as first-line therapy in duodenal ulcer disease.

Duodenal Ulcer↗
PubMed1991

Observations on a proposed measure of genotoxicity in rat gastric mucosa.

Current methods for the study of the toxicological effects of antisecretory medications on the gastric mucosa possess disadvantages or limitations. A novel assay has been proposed to assess gastric mucosal genotoxicity in which the proton-pump inhibitor omeprazole has been reported to induce direct damage to cellular DNA, raising questions about the safety of this drug. To define the applicability of this proposed measure of genotoxicity and to examine the effects of omeprazole in this assay, control agents, known carcinogens, and omeprazole in various doses and formulations were administered to rats by gavage, followed by [3H]thymidine labeling of DNA in vivo approximately 14 hours later. The incorporation of the [3H]thymidine label into DNA of gastric mucosal cells liberated by limited pronase digestion was in close agreement with published results for negative and positive controls. Omeprazole, administered in doses ranging from 10 mg/kg to 300 mg/kg, did not increase [3H]thymidine incorporation into cellular DNA in this assay. The gastric carcinogen 1-methyl-2-nitro-1-nitrosoguanidine at 20 and 50 mg/kg increased [3H]thymidine incorporation. Pretreatment in vivo with hydroxyurea before [3H]thymidine labeling to inhibit replicative DNA synthesis suppressed [3H]thymidine incorporation more than 97% in negative controls and MNNG and more than 93% in omeprazole treatments. This indicates that replicative DNA synthesis was almost totally responsible for the [3H]thymidine incorporation and the contribution of unscheduled DNA synthesis to the total [3H]thymidine incorporation is minor. Flow cytometric analysis of the cell cycle of the gastric mucosal cells liberated by the limited pronase digestion indicated significant contamination of the preparation with dividing cells (4% in negative controls and 14% in MNNG-treated positive controls). These findings indicate that the proposed screening assay for genotoxicity in rat gastric mucosa is not a reliable measure of unscheduled DNA synthesis in its present form, and conclusions about genotoxic effects of any drug using this assay as initially proposed appear questionable.

Animals↗
PubMed1991

The long term prognostic significance of c-erbB-2 in primary breast cancer.

The expression of the c-erbB-2 oncogene has been evaluated using an immunohistochemical technique with the 21N polyclonal antibody in paraffin embedded tissue from 465 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and four (22%) patients exhibited positive staining. This was not associated with any other variables. Expression of the oncogene was associated with significantly poorer survival which was independent of other tumour variables.

Breast Neoplasms↗
PubMed1991

The long term prognostic significance of oestrogen receptor analysis in early carcinoma of the breast.

The long term prognostic significance of oestrogen receptors was assessed in a prospective study of 767 patients presenting between the years 1975 and 1981 with stage 1 and 2 breast cancer treated by mastectomy with either full axillary dissection or nodal sampling. Oestrogen receptor binding was determined by a dextran coated charcoal method and median follow up was 11 years. Oestrogen receptors were present in 396 (54%) of tumours. Absence of oestrogen receptors was associated with tumours of high histological grade, but there was no relationship between nodal status or tumour size. Oestrogen receptor status did not predict survival for the group as a whole or when stratified by nodal status. In multivariate analysis both nodal status and tumour size were powerful independent prognostic factors, but oestrogen receptors failed to achieve statistical significance.

Analysis of Variance↗
PubMed1991

Relative effectiveness of milks with reduced amounts of lactose in alleviating milk intolerance.

The relative effectiveness of five milk products with various levels of lactose reduction [0%, 50%, 80% (#1), 80% (#2), and 95%] was evaluated in six subjects with lactose malabsorption. Breath hydrogen was measured for 4 h after consumption of 300 mL of each product in a single-blind, randomized design. The mean +/- SEM maximum breath-hydrogen rise (ppm) after the 0%, 50%, 80% (#1), 80% (#2), and 95% lactose-reduced (LR) milks was 31 +/- 6, 7 +/- 3, 5 +/- 3, 5 +/- 2, and 8 +/- 3, respectively. The difference between whole milk and the LR milks was statistically significant (P less than 0.05) but there was no difference between any of the LR milks. Whole milk provoked symptoms in most subjects whereas 95% LR milk produced none. Only one of six subjects reacted to the 50% and 80% LR milks. The results suggest that a 50% level of lactose reduction in milk may be adequate to relieve the signs and symptoms of milk intolerance in the majority of healthy adults with lactose malabsorption.

Adult↗
PubMed1991

Sex differences in gallstone pancreatitis.

From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p less than 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p less than 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p less than 0.0001). In the nonpancreatic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p less than 0.0001), and in men (p less than 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis.

Acute Disease↗