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Biomedical subjects

F E Murray

Publications and source records attributed to F E Murray.

At least 19 recordsLinked to original sources

Elemental analysis of neurofibrillary tangles in Alzheimer's disease using proton-induced X-ray analysis.

We have investigated the elemental content of hippocampal slices from normal human brain and from brains of Alzheimer's disease patients by X-ray fluorescence using both electron and proton beam microprobes. The sections have been stained with a dye--toluidine blue--which contains sulphur so that the X-ray fluorescence map can be correlated with known intracellular sites as seen under the light microscope. The results show that associated with neurofibrillary tangles and Hirano bodies (the distinctive internal visual features of cells from Alzheimer's disease patients) there is increased calcium. We cannot confirm that there are peculiarities in the distribution of aluminium in cells.

Alzheimer Disease

Effect of indomethacin and misoprostol on fasted gallbladder volume and meal-induced gallbladder contractility in humans.

Impaired gallbladder contractility is a prerequisite for gallstone formation in animal models. Prostaglandins are important mediators of gallstone formation and may affect gallbladder contractility in animals. The aim of this study was to evaluate the effect of indomethacin, an inhibitor of prostaglandin synthesis, and misoprostol, a synthetic prostaglandin, on gallbladder contractility in man. Seven male volunteers (18-33 years old, mean age 23 years) were studied under blinded conditions after an overnight fast, during control periods and following ingestion of indomethacin 125 mg (75 mg at 10 PM, 50 mg at 6:30 AM) or misoprostol 800 micrograms (400 micrograms at 10 PM, 400 micrograms at 6:30 AM) orally. Gallbladder residual volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal stimulus. Fasting gallbladder volume (milliliters) was similar in all three periods [control 20.8 (1.6); indomethacin 20.8 (2.9); misoprostol 18.3 (1.6)]. The fatty meal stimulus caused prompt contraction, resulting in minimum residual volume of 7.5 (1.4) ml in the control period. Pretreatment with misoprostol or indomethacin did not affect the minimum volume obtained compared with control period [misoprostol: 5.8 (1.4) ml; indomethacin 5.9 (1.3) ml)]. Thus administration of indomethacin and misoprostol had no effect on fasting gallbladder volume or gallbladder contractility in humans as assessed by ultrasonography.

Adolescent

Impaired fatty-meal-stimulated gallbladder contractility in patients with Crohn's disease.

1. The incidence of gallstones in patients with Crohn's disease is increased compared with that in healthy control subjects. This is in part due to reduced terminal ileal bile salt absorption and consequent increased cholesterol saturation in bile. The aim of this study was to evaluate gallbladder contractility, a second important factor in the pathogenesis of gallstones, in Crohn's disease. 2. Thirty patients with Crohn's disease and no known biliary tract disease and nine healthy control subjects were studied. After an overnight fast, gallbladder volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal. 3. Compared with healthy control subjects, patients with Crohn's disease had similar fasting gallbladder volumes (control, 18.7 +/- 2.3 ml; Crohn's disease, 18.2 +/- 2.3 ml). Percentage emptying was significantly impaired at 30, 40 and 50 min in patients with Crohn's disease compared with control subjects. Patients with Crohn's disease limited to the small bowel had gallbladder contractility that was comparable with that of control subjects, whereas in those with large-bowel disease, minimum residual gallbladder volume was significantly smaller than in control subjects. Patients with both large- and small-bowel Crohn's disease demonstrated the most marked abnormalities, with gallbladder volumes significantly larger than those of control subjects at 30, 40 and 50 min. Likewise, patients with Crohn's disease who had undergone previous bowel resection had impaired emptying at 30, 40 and 50 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Development of biliary sludge in patients on intensive care unit: results of a prospective ultrasonographic study.

Biliary sludge may be a precursor of gall stones in man. The aim of this study was to determine the incidence of biliary sludge in a prospective study of 36 patients admitted to the intensive care unit for longer than two days. The presence of biliary sludge was determined by ultrasonography. Biliary sludge developed in 17 patients (47%), after a mean of 5.5 days in the intensive care unit. Patients who developed biliary sludge spent longer in the intensive care unit (14.2 d (1.3)), compared with patients who did not (8.3 d (1.4)); (p = 0.003). Ten of the patients with biliary sludge had a recognised risk factor: total parenteral nutrition (five), abdominal surgery (two), or both (three). All neurosurgical patients (four) who required total parenteral nutrition developed biliary sludge. Seven patients with biliary sludge had no previously recognised risk factor, five of whom had severe head trauma or neurosurgery. In conclusion, biliary sludge develops frequently and rapidly in patients admitted to an intensive care unit. Neurosurgical procedures are associated with biliary sludge formation. (Sludge is commonly associated with the development of cholestatic liver biochemistry.)

Adolescent

Management of reflux oesophagitis: role of weight loss and cimetidine.

A double blind clinical trial was performed to evaluate the effect of weight loss and cimetidine in the treatment of reflux oesophagitis. Thirty-two patients were evaluated by endoscopy, L.O.S.P. determination, oesophageal scintigraphy and ambulatory 24 hour oesophageal pH monitoring. Patients were randomly allocated into treatment using a regimen of placebo/weight loss or cimetidine/weight loss. Assessments were repeated after 8-12 weeks. A similar weight loss and improvement in symptoms and endoscopy appearances was seen in both groups. In contrast there was no significant change in frequency or duration of reflux on 24-hour pH monitoring or oesophageal scintigraphy or L.O.S.P. We conclude that weight loss may have an important role in the treatment of reflux oesophagitis and should be recommended to patients as an early therapeutic intervention. Cimetidine did not confer any additional benefit to that obtained from weight loss alone.

Adult

Non-mucin proteins in the matrix of human cholesterol gallstones.

Human cholesterol gallstones contain a pigmented organic matrix that may originate from biliary sludge. The cholesterol gallstone matrix contains mucin, bile pigments, and calcium salts. The goal of this study was to examine whether non-mucin proteins are present in the matrix of cholesterol gallstones. Matrix was prepared from cholesterol gallstones from 18 patients. Proteins were identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and by molecular sieve high-performance liquid chromatography (HPLC). Two proteins were present in each gallstone and migrated with or just adjacent to standards of bovine serum albumin on SDS-PAGE. Several additional lower molecular weight proteins were identified, but not in every gallstone. Protein fractions contained visible pigment after chloroform extraction, and pigment co-eluted with proteins on HPLC, suggesting binding of pigments to proteins in the matrix. We conclude that low molecular weight proteins are present in the cholesterol gallstone matrix. The major protein appears to be serum albumin, although definitive identification has not been established. The origin of these matrix proteins and their possible significance in the pathogenesis of cholesterol cholelithiasis is unknown.

Bilirubin

Geriatric constipation: brief update on a common problem.

Constipation occurs frequently in the elderly and is often multifactorial in origin. A search for an underlying cause is necessary, and can often be found by taking an adequate history and performing a thorough physical examination. A minority of patients require further investigation, guided by the clinical setting. Management should be directed at correcting the underlying cause and providing dietary advice and, less commonly, medication to allow restoration of a normal bowel habit.

Aged

Bile salts stimulate glycoprotein release by guinea pig gallbladder in vitro.

Alterations in the composition of bile during cholesterol gallstone formation appear to be responsible for increased release of gallbladder mucin, a potent cholesterol nucleating agent. We investigated the effects of bile salts on release of radiolabeled glycoproteins by explants of guinea pig gallbladder in organ culture. Bile salts, in concentrations of 1 to 5 mmol/L, caused a dose-dependent release of [3H]-glycoproteins with a range of potencies in this order: chenodeoxycholate greater than deoxycholate much greater than cholate greater than ursodeoxycholate = control. Chenodeoxycholate and deoxycholate were significantly more potent than cholate (p less than 0.0001). Unconjugated and taurine-conjugated bile salts were of similar potency. Bile salts also caused increased release of glycoproteins from explants of guinea pig gastric antrum and colon. The bile salts released after bile salt exposure included mucin and lower molecular weight glycoproteins from the gallbladder. Release of glycoproteins in response to bile salts was not inhibited by indomethacin, atropine or propranolol, nor was it dependent on extracellular calcium or microtubules. Glycoprotein release in response to bile salts was associated with membrane damage as indicated by a dose-dependent leakage of the cytoplasmic enzyme lactate dehydrogenase, although light microscopy did not reveal structural damage to epithelial cells. We conclude that hydrophobic bile salts stimulate gallbladder glycoprotein release in vitro by a detergent effect on the plasma membrane rather than by a receptor-mediated secretory pathway.

Animals

Granulomatous hepatitis in secondary syphilis.

An unusual case of a well-documented granulomatous hepatitis in secondary syphilis in a 47-year-old male is presented. This hepatic pathology in secondary syphilis is summarised, and a review of the literature regarding syphilitic granulomatous hepatitis presented.

Granuloma

Isolation and characterization of peptides from the protein core of bovine gallbladder mucin.

Gallbladder mucin may promote cholesterol gallstone formation by accelerating cholesterol monohydrate crystal nucleation in supersaturated bile. In this study, peptides were isolated from the mucin protein core by protease digestion and molecular-sieve high-performance liquid chromatography. Tryptic peptides were purified by anion exchange or reverse-phase high-performance liquid chromatography, and amino acid compositions were determined. Tryptic peptides were (a) nonglycosylated, (b) selectively enriched in serine, glutamic acid plus glutamine, and glycine, and (c) depleted in threonine and proline compared with native gallbladder mucin. Bilirubin derivatized with Woodward's reagent K covalently bound to purified mucin. Tryptic digestion of the mucin-bilirubin complex yielded low-molecular-weight nonglycosylated peptides with covalently bound bilirubin. These data indicate that the mucin protein core contains at least two distinct domains. One domain is rich in threonine and proline and contains the majority of covalently bound carbohydrate. A second domain, possibly internally located, is nonglycosylated, enriched in serine, glutamic acid plus glutamine, and glycine, and binds hydrophobic ligands such as bilirubin and 1-anilino-8-naphthalene sulfonate. Hydrophobic domains on the mucin protein core may contribute to the pathogenesis of cholesterol cholelithiasis.

Amino Acids

Response to Simko.

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Esophageal Neoplasms

Mesenteric vein thrombosis associated with Klinefelters syndrome--a case report.

A case of mesenteric vein thrombosis presenting as gastrointestinal hemorrhage in a patient with Klinefelter's syndrome is reported, an association not previously described. The diagnosis was made preoperatively and was confirmed by angiography. The patient underwent a small bowel resection and made an uneventful recovery. A possible association between Klinefelter's syndrome and a hypercoagulable state, previously suggested elsewhere, is emphasized.

Adult