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C O Record

Publications and source records attributed to C O Record.

At least 37 records · Page 2Linked to original sources
PubMed1996

Incidence and causes of rectal bleeding in general practice as detected by colonoscopy.

BACKGROUND: Rectal bleeding is common, but it is still unclear which patients require investigation to exclude serious pathology, although it is known that colectoral cancer is very rare under the age of 40 years. Few studies have examined all patients presenting to their primary health physician rather than screening whole populations. AIM: The aim of this study was to investigate the view that all patients over the age of 40 who present to their general practitioner with rectal bleeding should undergo investigation by colonoscopy to rule out serious pathology, regardless of symptomatology. METHOD: A prospective study was carried out of 99 consecutive patients over 40 years presenting with rectal bleeding to 17 general practices in Newcastle upon Tyne. RESULTS: Serious pathology was detected by colonoscopy in 44.4% of patients. The diagnoses were: colorectal carcinoma, eight cases (two Dukes' grade A, two Dukes' grade B, four Dukes' grade C); one or more polyps, 25 cases (in 17 cases at least one polyp was 5 mm or greater in diameter); inflammatory bowel disease, 11 cases. In the remaining 55 patients, bleeding was associated with diverticular disease (16 cases) and haemorrhoids (28 cases). No cause was found in 11 patients. This high rate of pathology may be partly caused by selection of cases for referral by the general practitioner, despite efforts to minimize this. Three symptoms as elicited by the colonoscopist were found to be significantly associated with serious disease: blood mixed with stool (P < 0.001); change in bowel habit (P < 0.005); and the presence of abdominal pain (P < 0.025). However, symptoms elicited on primary presentation were less helpful and symptoms changed significantly between consultation with the general practitioner and colonoscopy. CONCLUSION: All patients over the age of 40 years presenting with rectal bleeding should be referred for flexible sigmoidoscopy or colonoscopy. Symptoms are unhelpful in deciding who requires investigation.

Adult↗
PubMed1995

An HPLC assay for sn-1,2-diacylglycerol.

A method for the analysis of 1,2-diacylglycerols in biological samples is presented. After tissue extraction and derivatisation with 3,5-dinitrobenzoyl chloride, samples are analysed by normal phase HPLC, using a 3.9 x 300 mm microPorasil column, and ultraviolet detection at 254 nm. The method gives quantitative recovery of 1,2-diacylglycerol, and is of sufficient sensitivity to allow quantitation of 1,2-diacylglycerol in human muscle needle biopsy specimens, from as little as 10 mg muscle. Human skeletal muscle from fasted control subjects was found to have a 1,2-diacylglycerol content of 455 +/- 78 nmol/g wet weight. The method is robust, giving intra- and inter-assay coefficients of variation of 2.9% and 5.9%, respectively, and should prove useful for the analysis of 1,2-diacylglycerol levels in human disease states, such as diabetes, in which no measurements of 1,2-diacylglycerol have yet been undertaken.

Animals↗
PubMed1995

The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy.

BACKGROUND/AIMS: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy. METHODS: Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [18O]quinolinic acid. RESULTS: Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and III in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma. CONCLUSIONS: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures.

Acute Disease↗
PubMed1995

Synaptosomal glutamate transport in thioacetamide-induced hepatic encephalopathy in the rat.

Dysfunction of excitatory glutamatergic neurotransmission has been implicated in the cause of hepatic encephalopathy. Brain microdialysis studies in various animal models of portal systemic encephalopathy (PSE) and encephalopathy associated with acute liver failure, have established that an increase in extracellular glutamate occurs but the mechanisms of this are unclear. We have measured oxygen consumption, citrate synthase activity (as indices of energy state and mitochondrial content, respectively), calcium-dependent glutamate release, and high-affinity, sodium-dependent glutamate uptake by synaptosomes prepared from rats with thioacetamide-induced encephalopathy. (2 doses of thioacetamide 200 mg/kg with a 24-hour interval). Synaptosomes were prepared either by a modified P2 method (glutamate release study) or by discontinuous sucrose density gradient centrifugation (all other studies). There was no significant difference in synaptosomal oxygen consumption, citrate synthase activity, glutamate release, total synaptosomal glutamate content, or the Kd for glutamate uptake between the encephalopathy group and the controls. However, there was a marked decrease in the maximal velocity of transport (Vmax) for glutamate uptake in synaptosomes from encephalopathic rats, 2.64 versus 4.40 nmol/min/mg (P < .05). The results of this study provide evidence of impaired glutamate uptake in the rat thioacetamide model of hepatic encephalopathy, which could account for the elevated extracellular glutamate seen in the condition.

Animals↗
PubMed1994

Monosaccharide composition of haptoglobin in liver diseases and alcohol abuse: large changes in glycosylation associated with alcoholic liver disease.

Liver damage through prolonged intake of high amounts of alcohol is a serious problem that affects many members of the population. The aim of this study was to investigate changes in the glycosylation of haptoglobin (Hp) resulting from alcoholic liver diseases. The monosaccharide composition was measured in Hp isolated from 48 healthy individuals, 15 alcohol abusers (AA); 25 patients with alcoholic liver disease, including those with alcoholic cirrhosis (ALD/AC), and 17 other patients with either chronic active hepatitis (AH) or primary biliary cirrhosis (BC). Fucose was elevated per mol of Hp in 70%, 44%, and 33% of the individuals in the ALD/AC, BC and AA groups, respectively. Fucose was not elevated in the AH group. N-acetylglucosamine was also elevated in the ALD/AC group. Expressing results per 3 mol of mannose suggested the presence of higher branching with increased fucose content in Hp from all the abnormal groups except the AH group. More structural information is required to develop the diagnostic potential of carbohydrate measurements of Hp in alcoholic liver diseases.

Acetylglucosamine↗
PubMed1994

Growth hormone, insulin-like growth factor-1 and insulin resistance in cirrhosis.

Cirrhosis is characterized by paradoxical growth hormone secretion in response to glucose and insulin infusion. To ascertain whether this abnormality contributes to insulin resistance, euglycemic hyperinsulinemic glucose clamps were performed on six patients with cirrhosis and six normal control subjects. Each patient with cirrhosis underwent two clamps in random order, a clamp with somatostatin (250 micrograms/hr) together with insulin and glucagon replacement, and a control clamp without somatostatin. The normal subjects underwent the control clamp only. During the control clamp, growth hormone levels were considerably higher in the patients with cirrhosis (6.1 +/- 0.4 vs. 0.5 +/- 0.4 mU/L, p < 0.02), and glucose uptake was considerably lower (3.29 +/- 0.56 vs. 9.52 +/- 1.14 mg/kg/min, p < 0.001). Indirect calorimetry indicated that the defect was accounted for by lower nonoxidative glucose disposal (1.23 +/- 0.45 vs. 6.00 +/- 0.73, p < 0.001). Peripheral glucose uptake, exemplified by forearm glucose uptake (0.27 +/- 0.04 vs. 1.22 +/- 0.42 mg/100 ml/min, p < 0.02), and calculated insulin sensitivity (24 +/- 8 vs. 114 +/- 20 microliters/kg/min per mU/L) were particularly diminished. In the patients with cirrhosis somatostatin suppressed growth hormone levels (6.1 +/- 1.2 to 1.2 +/- 0.4 mU/L, p < 0.05). However, no significant changes occurred in whole-body glucose uptake (3.29 +/- 0.56 vs 3.01 +/- 0.54 mg/kg/min), forearm glucose uptake (0.27 +/- 0.04 vs 0.30 +/- 0.01 mg/100 ml/min) or insulin sensitivity (24 +/- 8 vs, 35 +/- 10 microliters/kg/min/mU/L, p = 0.42).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Octreotide treatment does not improve impaired glucose uptake in cirrhosis.

Forearm glucose uptake during a hyperglycaemic (10 mmol/l) glucose clamp was diminished to 33% of the normal value (p = 0.012) in six cirrhotic patients compared with matched control subjects. Fasting insulin concentrations were significantly elevated in the cirrhotic patients confirming insulin resistance which may have been induced by chronic hyperinsulinaemia. The cirrhotic patients received one week of treatment with 50 micrograms octreotide subcutaneously three times daily which reduced pre-dose fasting insulin levels from 26.2 +/- 7.9 to 18.1 +/- 6.2 mU/l p < 0.005, and post dose levels to 7.0 +/- 3.5 mU/l p < 0.005. However when the glucose clamp was repeated 20 hours after the last dose of octreotide no change was detected in clamp glucose requirements, forearm glucose uptake, or stimulated insulin secretion. It was concluded that one week of lowering insulin levels does not reverse the insulin resistance of cirrhosis.

Adult↗
PubMed1993

Diacylglycerol/protein kinase C signalling: a mechanism for insulin resistance?

It is proposed that an intracellular cycle exists to limit or terminate the insulin signal. The cycle involves increased synthesis of sn-1,2-diacylglycerol (DAG) in response to insulin. The DAG activates protein kinase C (PKC) which phosphorylates glycogen synthase either directly or through other protein kinases to render it inactive. Protein kinase C may also inhibit the insulin receptor by phosphorylation of receptor serine residues. Insulin resistance could then arise as a consequence of a persistent increase in DAG levels. Such an increase could occur in three different ways. Chronic hyperinsulinaemia could increase DAG levels by de-novo synthesis from phosphatidic acid, by hydrolysis of phosphatidylcholine, or by hydrolysis of glycosyl-phosphatidylinositol; DAG is also formed by hydrolysis of phosphatidylinositol 4,5-biphosphate (PIP2). This reaction, known as the 'PI response,' may be the connection between hypertension and insulin resistance. A third mechanism for an increase in DAG involves neural abnormalities. Thus, muscle denervation in the rat is characterized both by a profound insulin resistance and a large increase in DAG. It is possible that a similar increase occurs in humans and may explain the association between denervation, inactivity, and insulin resistance.

Animals↗
PubMed1993

Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis.

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.

Adolescent↗
PubMed1993

Culture negative cytotoxin positive stools in community acquired diarrhoea.

In a significant proportion of cases of community acquired diarrhoea no recognised pathogen is detected. Verocytotoxin producing Escherichia coli (VTEC) are associated with haemorrhagic colitis and the haemolytic uraemic syndrome but their role in community acquired diarrhoea is not fully understood. Using a method of toxin enhancement in mixed faecal culture, 175 stools negative on culture for recognised pathogens were tested for the presence of cytotoxin and 28% were found to be positive. Nine were neutralised by anti-VT1, 29 by anti-VT2, and eight by neither. No control stool samples yielded any cytotoxin. VTEC should be considered as a causative agent in sporadic community acquired diarrhoea.

Adolescent↗
PubMed1993

Brain indoles in human hepatic encephalopathy.

The neurotransmitter serotonin has a profound effect on the control of sleep; thus excess serotonin activity in the brain could be responsible for impaired consciousness in hepatic encephalopathy. Furthermore, an increased brain level of 5-hydroxy-indoleacetic acid has been a consistent finding in various animal models of the condition. In this study, using high-performance liquid chromatography with fluorometric detection, we examined levels of brain serotonin (5-hydroxytryptamine) and its precursors and metabolites in 16 patients dying with hepatic encephalopathy complicating acute and chronic liver disease and 9 control subjects matched for age, sex, postmortem delay in brain retrieval and length of frozen tissue storage. In patients with chronic liver disease, serotonin level was significantly increased in thalamus (p < 0.02); levels of its metabolite 5-hydroxyindoleacetic acid were increased in frontal cortex (p < 0.05), globus pallidus (p < 0.05) and putamen (p < 0.01). Levels of the precursor amino acid tryptophan were increased in thalamus (p < 0.01) and globus pallidus (p < 0.01); in both patient groups levels of 5-hydroxytryptophan and the tryptamine metabolite indoleacetic acid were increased in all brain areas studied. 5-Hydroxytryptamine levels were also increased in thalamus, frontal cortex and globus pallidus in the three patients with fulminant liver failure. Our findings are consistent with disordered neurotransmission, especially in the thalamus, an area of particular importance in the regulation of consciousness, alertness and attention in human beings.

5-Hydroxytryptophan↗