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Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1995

Studies on the pathogenesis of bovine ephemeral fever. IV: A comparison with the inflammatory events in milk fever of cattle.

The study of ephemeral fever in cattle has defined a range of haematological and biochemical changes in blood which are characteristic of an inflammatory response. One of the clinical signs of ephemeral fever, a temporary paralysis reversible by treatment with calcium borogluconate, is similar to that in milk fever (parturient paresis), a disease of multiparous dairy cows. Three separate groups of cows were studied. Four multiparous cows were observed and sampled repeatedly during calving, three similar cows and one cow calving for the first time in a dairy herd were sampled daily before and after calving; and, in other dairy herds, seven cows with milk fever were sampled during illness. One of the cows under repeated observation during calving developed milk fever. The results showed that all the inflammatory indicators in blood were present in the multiparous cows at calving and that these were essentially similar to those established in ephemeral fever. The similarities in the four cows sampled repeatedly during the periparturient period were: a rectal temperature rise of 1 to 1.2 degrees C; rise in circulating neutrophils to peaks between 5700 and 11200 l-6; disappearance of eosinophils for 1 day; hypocalcaemia (plasma Ca < 2.0 mM l-1); fall of plasma zinc to low levels immediately after calving (plasma Zn < 500 micrograms l-1); fall of inorganic phosphate (plasma P < 0.9 mM l-1); rises in copper (plasma Cu > 1000 micrograms l-1) and plasma fibrin to > 8.75 g l-1. Plasma glucose peaked at calving between 5.7 and 8.9 mM l-1 then fell to levels ranging between 3.4 and 3.8 mM l-1. Plasma iron rose in one cow to 1220 micrograms l-1, was unchanged in one cow and fell in the other two to 440 and 860 micrograms l-1 respectively. The three multiparous cows which were sampled daily and calved normally showed similar haematological, macro and micromineral changes and fibrin response as did the seven milk fever cases. In the periparturient period, milk fever cows differed from multiparous cows calving normally, in degree but not in kind, of inflammatory response. It is postulated that an inflammatory event occurs in the periparturient period of multiparous cows which partially accounts for the falls in plasma calcium. This can precipitate a paralysis and other hypocalcaemic signs similar to that seen in acute ephemeral fever.

Animals↗
PubMed1995

Tumor necrosis factor-alpha and basic fibroblast growth factor decrease glial fibrillary acidic protein and its encoding mRNA in astrocyte cultures and glioblastoma cells.

Tumor necrosis factor-alpha is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-alpha. Treatment with tumor necrosis factor-alpha for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-alpha treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-alpha, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-alpha induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-alpha. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-alpha treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.

Animals↗
PubMed1995

Immunohistological comparison of granulated cell proteins in induced immediate urticarial dermographism and delayed pressure urticaria lesions.

Urticarial dermographism and delayed pressure urticaria are two forms of physical urticaria which are well defined clinically and histologically. Previous studies have shown eosinophil granule protein deposition in urticarial reactions, including chronic urticaria, solar urticaria and delayed pressure urticaria. To evaluate and compare the involvement of granulated inflammatory cells in urticarial dermographism and delayed pressure urticaria, we studied sequential biopsies of induced lesions of urticarial dermographism and delayed pressure urticaria by indirect immunofluorescence, to detect eosinophil granule major basic protein (MBP) and neutrophil granule elastase. Biopsies from dermographic lesions at time 0, 5 min, 15 min, 2 h and 24 h, showed few infiltrating eosinophils, with minimal extracellular MBP deposition, and a few infiltrating neutrophils, with minimal neutrophil elastase deposition, throughout the evolution of the lesions. Sequential biopsies of delayed pressure urticaria at time 0, 20 min, 6, 12 and 24 h, showed eosinophil infiltration with extensive MBP deposition beginning at 20 min, and neutrophil infiltration with variable elastase deposition beginning at 20 min. Control tissue specimens from normal volunteers showed neutrophil infiltration and slight degranulation, but no eosinophil infiltration or degranulation. Comparison of urticarial dermographism with delayed pressure urticaria showed marked differences in the patterns of infiltration. Delayed pressure urticaria, with eosinophil and neutrophil degranulation, was strikingly similar to the IgE-mediated late phase reaction. In contrast, eosinophil and neutrophil involvement in urticarial dermographism was minimal. Considering the extent of eosinophil granule protein deposition and the biological activities of the eosinophil granule proteins, the findings in delayed pressure urticaria point to an important pathophysiological role of eosinophils in the disease.

Blood Proteins↗
PubMed1995

Effect of acute bile acid pool depletion on total and ionized calcium concentrations in human bile.

Although calcium salts are important components of gallstones, there are few data on the total and ionized calcium content of human bile. Therefore, in 14 fasting T-tube patients studied 7-11 days after cholecystectomy, we measured bile flow, bile acid [BA], total [CaTOT] and free ionized [Ca++] calcium concentrations, in 20-30 min bile collections during acute BA pool depletion induced by 6-8 h of continuous bile drainage. During washout of the BA pool there were parallel falls in bile flow, BA output and total calcium output (correlation coefficients ranging from 0.59 to 0.99; P < 0.02-0.001). In 12 of the 14 patients, [CaTOT] also fell (from 1.84 +/- 0.29 to 1.32 +/- 0.34 mmol L-1) in parallel with [BA] (from 34.0 +/- 14.0 to 8.2 +/- 8.0 mmol L-1; r = 0.75-0.98; P < 0.005). In contrast, biliary [Ca++] remained virtually unchanged. These data suggest that the BAs are linked to the bound, rather than to the free, ionized, fraction of biliary calcium, which is consistent with in vivo calcium binding by BAs. A model is proposed in which BA-induced biliary calcium secretion results from (i) bile acid-induced water flow via solvent drag; and (ii) calcium binding in the bile canaliculus by bile acids, which induces paracellular diffusion of Ca++, thereby maintaining [Ca++] independent of [BA].

Adult↗
PubMed1995

Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.

Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.

Acromegaly↗
PubMed1995

The origin of nocturnal intragastric pH rises in healthy subjects.

BACKGROUND: Duodenogastric reflux (DGR) can produce transient increases in gastric luminal pH. It has been proposed that intragastric pH-metry is a reliable method for the detection of DGR. Our aim was to test the hypothesis that nocturnal increases in antral pH are due solely to DGR. METHODS: Gastric pH was monitored overnight using two glass pH electrodes, one in the antrum adjacent to the tip of a nasogastric tube and one in the corpus. Scheduled antral aspirations were performed hourly to determine base-line concentrations of total bile acids (TBA; a marker of DGR) and thiocyanate (SCN; a marker of swallowed saliva). Additional, triggered aspirations were performed if antral pH exceeded 3.0 for 1 min or more (PHAP; period of high antral pH). TBA and SCN were considered to be increased if they exceeded the 90th percentile of values determined in scheduled aspirates (TBA, 0.88 mM; SCN, 0.67 mM). RESULTS: In 28 of the 62 samples whose aspiration was triggered by a PHAP the pH was less than 3.0, and the sample was not considered to be representative. In the remaining 34 samples the antral luminal pH and the sample pH were concordant; TBA alone was increased in 6 samples, SCN alone was increased in 6 samples, and TBA and SCN were both increased in another 3 samples. Thus, DGR and swallowed saliva alone or in combination accounted for only 15 (45%) of the PHAP in which adequate gastric samples were obtained. CONCLUSION: Samples of gastric antral contents often do not reflect accurately the acidity of gastric fluid in contact with a luminal antral pH electrode. Nocturnal increases in antral pH, detected by a luminal electrode, are frequently due to mechanisms other than duodenogastric reflux or swallowed saliva. Thus, antral pH-metry is not suitable for monitoring the occurrence of duodenogastric reflux.

Adult↗
PubMed1995

Deoxycholic acid influences cholesterol solubilization and microcrystal nucleation time in gallbladder bile.

Little is known about the effects of biliary deoxycholic acid on the partitioning of biliary cholesterol between vesicles and micelles and on the rate of nucleation of cholesterol microcrystals, key steps in gallstone formation. Therefore, 43 samples of fresh gallbladder bile were obtained from a heterogeneous group of patients with and without stones. Univariate and multivariate analyses were then applied to determine the inter-relationships between biliary cholesterol saturation, total lipid concentration, and bile acid species and (1) the distribution of biliary cholesterol between vesicles and micelles and (2) the cholesterol microcrystal nucleation time. The percentage of deoxycholic acid in bile was shown to be linearly related to the cholesterol saturation index (r = .54; P < .001), the vesicular cholesterol:phospholipid molar ratio (r = .53; P < .001), and the molar concentration of cholesterol in the vesicles (r = .59; P < .001). The mean proportion of biliary deoxycholic acid conjugates was also greater in patients with rapid nucleation times (23.4 +/- SEM 1.1%) than in those with slow nucleation times (17.3 +/- 1.9%; P < .05). As total bile lipid concentration increased, the proportion of total biliary cholesterol in vesicles decreased (r = .53; P < .001), whereas the molar concentration of vesicular cholesterol increased (r = .42, P < .01). The cholesterol saturation indices, total bile lipid concentration, and proportion of biliary deoxycholate were independent determinants of the molar concentration of cholesterol in vesicles. We conclude that relative increases in the percentage of deoxycholic acid and in bile lipid concentration, favor the partitioning of cholesterol into vesicles. In turn, this leads to an increase in the vesicular cholesterol:phospholipid molar ratio and thus to a decrease in the cholesterol microcrystal nucleation time.

Adult↗
PubMed1994

Volumetric MRI assessment of temporal lobe structures in schizophrenia.

This magnetic resonance imaging (MRI) study was designed to investigate whether patients with schizophrenia have focal or lateralized deficits in the volumes of temporal lobe structures. Estimated volumes of the temporal lobes, hippocampi, superior temporal gyri, lateral ventricles, third ventricle, temporal horns of the lateral ventricles, and a frontal-parietal reference area (FPRA) were quantified for each hemisphere. The schizophrenic group had less gray matter (GM) in the temporal lobes and the FPRA relative to controls. Ventricular volumes were significantly larger in the schizophrenic group, as was cerebrospinal fluid (CSF) volume for temporal lobe sulci. No significant differences in hippocampal volumes emerged between groups. The magnitude of GM deficit was not greater in the temporal lobes relative to the FPRA. These results confirm the presence of bilateral GM volume deficits of the temporal lobes in schizophrenia but do not support the hypothesis that structural changes preferentially affect the temporal lobes or the left cerebral hemisphere.

Adult↗
PubMed1994

Gastric mucosal toxicity of duodenal juice constituents in the rat. Acute studies using ex vivo rat gastric chamber model.

To determine the acute gastrotoxicity of refluxed duodenal contents, an ex vivo rat gastric chamber was used to study mucosal damage produced by conjugated and unconjugated human bile acids and lysolecithin at neutral and acidic pH; the effects of trypsin, human duodenal aspirate, and combinations of chenodeoxycholic acid, lecithin, and lysolecithin were also studied. At neutral pH, all bile acids except tauroursodeoxycholic acid, caused dose-dependent falls in mucosal potential difference and losses of mucosal nucleic acid into the chamber fluid, indicating mucosal damage. The di-alpha-hydroxy bile acids, deoxycholic and chenodeoxycholic acids, were more gastrotoxic than cholic and ursodeoxycholic acids, and all unconjugated bile acids were more toxic than their conjugated species, none of which produced damage at concentrations below 2.0 mM. For all but the taurine conjugates, bile acid-induced changes in potential difference were lower at acidic then at neutral pH. Lysolecithin gastrotoxicity, comparable at neutral pH to that of chenodeoxycholic acid, was also reduced at acidic pH. Lecithin decreased the gastrotoxicity of chenodeoxycholic acid and lysolecithin. Trypsin produced no damage, and the gastrotoxicity of human duodenal aspirate was unaffected by prior heat inactivation of pancreatic enzymes.

Analysis of Variance↗
PubMed1994

The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones.

BACKGROUND/AIMS: Treatment of acromegaly with octreotide inhibits cholecystokinin release and gallbladder contraction and induces gallbladder stones. However, little is known about the effects of octreotide on bile composition. METHODS: Fresh gallbladder bile was obtained from three groups: (1) 11 nonacromegalic patients with cholesterol gallstones, (2) 6 acromegalic patients with octreotide-associated stones (treatment, 300-600 micrograms/day for 3-66 months), and (3) 8 acromogalic patients with no stones before octreotide treatment, 5 of whom were reexamined after 3-24 months of therapy. RESULTS: Compared with stone-free acromegalic patients untreated with octreotide, bile from patients with cholesterol stones and from acromegalic patients with octreotide-associated stones had greater saturation indices (mean +/- SEM) (1.52 +/- 0.17 and 1.32 +/- 0.14 vs. 0.90 +/- 0.05, respectively; P < 0.01); more cholesterol in vesicles (61.2% +/- 4.5% and 67.7% +/- 7.2% vs. 37.7% +/- 3.5%; P < 0.009); more unstable vesicles (cholesterol/phospholipid ratios, 0.97 +/- 0.12 and 0.81 +/- 0.16 vs. 0.52 +/- 0.05; P < 0.02); more rapid nucleation (< 5 and < 5 days vs. > 18 days; P < 0.003); and more deoxycholic acid (22.8% +/- 2.4% and 23.6% +/- 4.8% vs. 13.9% +/- 1.4%; P < 0.05). In the paired studies, the saturation indices increased from 0.89 +/- 0.07 before octreotide treatment to 1.12 +/- 0.03 during octreotide treatment (P < 0.02), as did the percentage of deoxycholic acid from 13.3% +/- 2.1% to 24.9% +/- 2.7% (P < 0.03). CONCLUSIONS: Acromegalic patients with octreotide-associated gallstones and stone-free acromegalic patients treated with octreotide have similar changes in bile composition to those in patients with "conventional" cholesterol gallstone disease.

Acromegaly↗
PubMed1994

Changes in serum calcium levels influence biliary calcium levels in humans.

BACKGROUND/AIMS: There are few data on the influence of serum calcium on biliary total and ionized calcium levels in humans. The aims of the study were to increase serum calcium levels short-term by intravenous calcium infusion and study the resultant changes in total and ionized calcium concentrations ([CaTOT] and [Ca2+]) in T-tube bile. METHODS: Serum and biliary total and ionized calcium concentrations were measured over an 8-hour period in 7 postcholecystectomy patients with T tubes before, during, and after a 4-hour intravenous infusion of 10% calcium gluconate. RESULTS: During the infusion, serum [CaTOT] increased from 2.08 +/- 0.14 mmol/L (mean +/- SD) to 3.18 +/- 0.33 mmol/L, and serum [Ca2+] increased from 1.13 +/- 0.13 mmol/L to 1.68 +/- 0.13 mmol/L. After a 20-40-minute time lag, there were corresponding increases in biliary [CaTOT] from 1.90 +/- 0.45 mmol/L to 2.80 +/- 0.52 mmol/L and in biliary [Ca2+] from 0.70 +/- 0.11 mmol/L to 1.19 +/- 0.16 mmol/L. When the data were pooled, serum [Ca2+] showed significant correlations with both biliary [CaTOT] (n = 128; r = 0.56; P < 0.001) and biliary [Ca2+] (n = 128; r = 0.64; P < 0.001). CONCLUSIONS: These results support the hypothesis that the biliary tree is freely permeable to calcium ions and that serum calcium level is one determinant of biliary calcium concentration. Our data may also explain the observation that patients with hypercalcemia are reported to have a greater than normal prevalence of calcified gallstones.

Aged↗