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Biomedical subjects

S Holt

Publications and source records attributed to S Holt.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

A somatostatin analogue is protective against retrograde bile salt-induced pancreatitis in the rat.

Despite the proposal that somatostatin or its stable analogue, octreotide (SMS-201,995), may exert an ameliorating effect on acute pancreatitis, data concerning its beneficial effect in this situation are conflicting. This study examines the effects of octreotide on acute pancreatitis, resulting from the retrograde injection of a bile salt (taurocholate) plus saturating trypsin into the common bile-pancreatic duct of the rat. Octreotide given before the induction of pancreatitis significantly reduced the levels of serum amylase and lipase, ascites amylase concentration, degree of leukocyte infiltration, and focal areas of pancreatic tissue necrosis. In contrast, administration of octreotide as soon as 5 min following induction had no demonstrable ameliorating effects on the pancreatitis. These results indicate that octreotide may have application to prophylaxis of acute pancreatitis in cases where bile salts may play a role in pathogenesis, but may not be beneficial in established acute pancreatitis.

Acute Disease↗

Proton-pump inhibition for acid-related disease.

Omeprazole and lansoprazole are the forerunners of a group of substituted benzimidazole compounds that block the gastric proton pump. These drugs exert a potent antisecretory effect by blocking the final common pathway of acid secretion. Prolonged, potent reduction of acid secretion using omeprazole has resulted in significant therapeutic advantage over existing antisecretory medication, such as H2 receptor antagonists (H2RAs). Research experience with lansoprazole indicates that it has treatment properties for acid-related disease that are similar to those of omeprazole. Omeprazole has been used successfully in the treatment of reflux esophagitis and the Zollinger-Ellison syndrome in the United States over the past year and has received approval recently as first-line therapy for duodenal ulcer disease. Research involving more than 20,000 individuals, postmarketing surveillance studies, and thorough safety studies in man and animals have shown omeprazole to be well tolerated, with an incidence and spectrum of adverse events in clinical trials similar to those observed with H2RAs.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Famotidine (20 mg) b.d. relieves gastrooesophageal reflux symptoms in patients without erosive oesophagitis. Famotidine/GERD Investigation Group.

Previous clinical trials have evaluated a large number of symptomatic individuals with heartburn. Most studies have documented the need for multiple daily dosing with H2-antagonists to achieve clinical and statistical efficacy for symptom relief. The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens, 40 mg nocte and 20 mg b.d. with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis. Famotidine (20 mg) b.d. reduced and eventually completely relieved gastro-oesophageal reflux disease symptoms in most patients during the 6-week trial. Global assessment of improvement at 2 and 6 weeks indicated significantly greater improvement with a b.d. treatment regimen than with either a 40 mg nocte or placebo treatment. No statistically significant differences between famotidine and placebo in the number of patients who experienced clinical adverse experiences were noted and no serious adverse events attributable to famotidine occurred. Based upon these findings, patients with gastro-oesophageal reflux symptoms experience good relief of their complaints with twice daily famotidine in standard doses.

Administration, Oral↗

Antireflux surgery.

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Gastroesophageal Reflux↗

Scintigraphic measurement of oropharyngeal transit in man.

Scintigraphic studies of the oropharyngeal transit of a liquid bolus were performed in 15 healthy controls, 12 patients with symptoms of oral-pharyngeal dysphagia, and 13 patients with neuromuscular disease, who did not have dysphagia. Gamma camera imaging of the head, neck, and upper thorax was undertaken, in the lateral projection, during the swallowing of the radiolabeled bolus of water. Inspection of summed images permitted the selection of regions of interest (ROI) to represent the mouth, pharynx, and upper esophagus. Transit times between each ROI were calculated and compared. Significant prolongation of bolus transit time between the mouth and esophagus was present in both patients with and without dysphagia (0.59 +/- 0.38 sec and 0.33 +/- 0.7 sec; mean +/- SD, respectively) compared with controls (0.26 +/- 0.04 sec P less than 0.001, P less than 0.01, respectively, Mann-Whitney U test). Repeat studies in 25 individuals indicated that the transit measurements were more reproducible between swallows in normal subjects than in patients with symptoms. Deglutitive scintigraphy provides a noninvasive technique for the quantitative study of swallowing and its disorders.

Adult↗

Measurement of gastric emptying rate in humans. Simplified scanning method.

Simultaneous measurements of the gastric emptying rate of the solid and liquid phase of a dual-isotope-labeled test meal were made using a gamma camera and a simple scintillation detector, similar to that used in a hand-held probe. A simple scanning apparatus, similar to that used in a hand-held scintillation probe, was compared with simultaneous measurements made by a gamma camera in 16 healthy males. A dual-labeled test meal was utilized to measure liquid and solid emptying simultaneously. Anterior and posterior scans were taken at intervals up to 120 min using both a gamma camera and the scintillation probe. Good relative agreement between the methods was obtained both for solid-phase (correlation range 0.92-0.99, mean 0.97) and for liquid-phase data (correlation range 0.93-0.99, mean 0.97). For solid emptying data regression line slopes varied from 0.75 to 1.03 (mean 0.84). Liquid emptying data indicated that slopes ranged from 0.71 to 1.06 (mean 0.87). These results suggested that an estimate of the gamma measurement could be obtained by multiplying the scintillation measurement by a factor of 0.84 for the solid phase and 0.87 for the liquid phase. Correlation between repeat studies was 0.97 and 0.96 for solids and liquids, respectively. The application of a hand-held probe technique provides a noninvasive and inexpensive method for accurately assessing solid- and liquid-phase gastric emptying from the human stomach that correlates well with the use of a gamma camera, within the range of gastric emptying rate in the normal individuals in this study.

Adult↗