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Biomedical subjects

R G Long

Publications and source records attributed to R G Long.

At least 19 recordsLinked to original sources
PubMed1992

Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

OBJECTIVE: To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN: Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING: The medical wards of University and City Hospitals, Nottingham. SUBJECTS: 1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES: Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS: Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS: Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena.

Age Factors↗
PubMed1992

Calmodulin content and activity in normal and coeliac duodenum.

Calmodulin is an important modulator of intracellular calcium processes and may be implicated in the calcium malabsorption of coeliac disease. The calmodulin content in extracts of duodenal biopsy specimens from 48 normal control subjects and 28 patients with coeliac disease was determined. Radioimmunoassay was used to measure immunoreactive calmodulin while a cyclic adenosine 3',5'-monophosphate phosphodiesterase activity assay was used to measure biologically active calmodulin. Calmodulin values measured by both assays were similar for control and disease groups. Mean (SEM) immunoreactive calmodulin values were 1.68 (0.09) micrograms/mg protein for controls and 1.67 (0.15) and 1.45 (0.15) micrograms/mg protein for partial and total villous atrophy respectively. These values were not significantly different. Biologically active calmodulin values were 2.77 (0.21), 1.82 (0.34), and 3.24 (0.33) micrograms/mg protein for control, partial, and total villous atrophy subjects respectively. The biologically active calmodulin values in the partial villous atrophy group were significantly lower than in controls and total villous atrophy subjects. In the phosphodiesterase assay, the calmodulin antagonist trifluoperazine inhibited the activity stimulated by purified calmodulin and by the extracts to the same extent. These results show that calmodulin values are normal in coeliac disease and provide no evidence that changes in calmodulin account for the abnormal calcium absorption in these patients.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Fatal fulminant hepatic failure in a 'solvent abuser'.

The case of a 17 year old abuser of butane aerosols who developed fulminant hepatic failure after taking a proprietary engine or carburetor cleaner is described. Fatalities as a result of liver failure due to volatile hydrocarbons or solvents have not previously been reported. The likely toxins included isopropyl alcohol, methyl amyl alcohol, butylated hydroxytoluene as well as petroleum products, and evidence for their toxicity is reviewed. The possibility of increased susceptibility to hepatotoxins after enzyme induction by abuse of volatile agents is discussed. Hepatic dysfunction should be sought in patients who abuse solvents or volatile hydrocarbons and supportive measures instituted promptly when required.

Adolescent↗
PubMed1991

A comparison of roxatidine and ranitidine for the acute treatment of duodenal ulcer.

Roxatidine acetate is a new histamine H2-antagonist of about twice the potency of ranitidine on a weight-for-weight basis. Two hundred and thirty-two patients participated in a double-blind randomized trial of duodenal ulcer healing comparing 300 mg ranitidine nocte with 150 mg roxatidine nocte. Endoscopy was repeated fortnightly to 4 weeks in each of four participating centres. Usual exclusion criteria applied but NSAID users were allowed. There were no important demographic differences between treatment recipients. Three analyses were used: protocol (dropouts and violators not included), intention-to-treat I (dropouts considered failures), and intention-to-treat II (dropouts considered failures, but violators outcome included). Healing rates differed markedly (but not significantly) with each analysis. After 2 weeks of treatment ulcers had healed in 51% versus 45% using the intention to treat I analysis with roxatidine and ranitidine, respectively; by the protocol analysis the healing proportions were 60% and 55%. These differences between treatments were not significant. After 4 weeks of treatment healing rates ranged from 71% to 83% on roxatidine and between 69% and 84% on ranitidine depending on the analysis. Differential healing proportions of smokers and non-smokers were non-significant (83% vs. 79%). Both drugs were well tolerated and adverse events were similar with each agent. Roxatidine should prove as effective as ranitidine for acute duodenal ulcer treatment.

Adult↗
PubMed1991

Calmodulin independence of human duodenal adenylate cyclase.

The calmodulin and calcium dependence of human adenylate cyclase from the second part of the duodenum was assessed in washed particulate preparations of biopsy specimens by investigating (a) the concentration dependent effects of free [Ca2+] on enzyme activity, (b) the effects of exogenous calmodulin on enzyme activity in ethylene glycol bis (b-aminoethyl ether)N,N'-tetra-acetic acid (EGTA) washed particulate preparations, and (c) the effects of calmodulin antagonists on enzyme activity. Both basal (IC50 = 193.75 (57.5) nmol/l (mean (SEM)) and NaF stimulated (IC50 = 188.0 (44.0) nmol/l) adenylate cyclase activity was strongly inhibited by free [Ca2+] greater than 90 nmol/l. Free [Ca2+] less than 90 nmol/l had no effect on adenylate cyclase activity. NaF stimulated adenylate cyclase activity was inhibited by 50% at 2.5 mmol/l EGTA. This inhibition could not be reversed by free Ca2+. The addition of exogenous calmodulin to EGTA (5 mmol/l) washed particulate preparations failed to stimulate adenylate cyclase activity. Trifluoperazine and N-(8-aminohexyl)-5-IODO-1-naphthalene-sulphonamide (IODO 8) did not significantly inhibit basal and NaF stimulated adenylate cyclase activity when measured at concentrations of up to 100 mumol/l. These results suggest that human duodenal adenylate cyclase activity is calmodulin independent but is affected by changes in free [Ca2+].

Adenylyl Cyclases↗
PubMed1991

The practice of rectal examination.

Rectal (both digital and rigid sigmoidoscopic) examination is an important part of the clinical examination. The aim of this study was to find out the opinions of the patients to this routine examination at the time of referral by their general practitioner and during their first hospital interview. Assessment of the value for the rectal examination was also examined. We questioned 103 patients attending their second out-patient interview through a simple questionnaire. We discovered that patients considered awareness and explanation important: patients preferred to be told of the possibility of rectal examination prior to hospital consultation. Explanation of the method and reason was expected from hospital doctors. Formal consent was expected; informed verbal consent should be sufficient. Where logistically possible, a chaperone should always be present. Rectal examination would have facilitated the diagnosis in 47% of the patients examined. Thus, rectal examination should be performed on all patients where symptoms are referable to the lower gastrointestinal tract and where a possible diagnosis may be made or facilitated.

Adolescent↗
PubMed1990

Effect of vasoactive intestinal peptide on cyclic adenosine monophosphate production in enterocytes isolated from human duodenal biopsy specimens.

A modification of a cell isolation technique used in animal studies was developed to remove enterocytes from duodenal biopsy specimens. Citrate-ethylenediaminetetra-acetic acid treatment removed enterocytes from any underlying lamina propria and produced single cells and strips of cells. A mean (SEM) of 4.39 (2.06) x 10(6) cells was obtained from nine duodenal biopsy specimens. Enterocyte recovery was estimated enzymatically using alkaline phosphatase activity and was found to be 61%. Cytological assessment of the cells with CAM 5.2 showed that 98% of the cells isolated were enterocytes with an intact brush border. The cells responded well to vasoactive intestinal peptide stimulation in the absence of an exogenously added adenosine triphosphate regenerating system. The addition of vasoactive intestinal peptide to duodenal enterocytes produced a biphasic dose dependent increase in cyclic adenosine monophosphate production. Stimulation of these cells with 10(-13)M vasoactive intestinal peptide resulted in a 50% stimulation over basal value while 10(-6)M vasoactive intestinal peptide led to a fivefold increase in cyclic adenosine monophosphate production. We conclude that duodenal biopsy specimens are a good source of human intestinal cells for the study of enterocyte physiology. The cells were viable and highly responsive to vasoactive intestinal peptide.

Adult↗
PubMed1989

Small bowel biopsy for disaccharidase levels: evidence that endoscopic forceps biopsy can replace the Crosby capsule.

Lactase, sucrase and maltase activities in endoscopic biopsies from the second part of the duodenum were compared to those in Crosby capsule biopsies from the proximal jejunum. In patients with villous atrophy disaccharidase activities were reduced compared with histologically normal mucosa in the duodenum and jejunum. Disaccharidase activities were significantly lower in the duodenum than in the proximal jejunum of patients with histologically normal mucosa and in those with partial villous atrophy but not significantly different for total villous atrophy patients. Primary and secondary disaccharidase deficiencies can be identified in biopsies from the duodenum. Duodenal biopsy is a valid alternative to jejunal biopsy for the diagnosis of disaccharidase deficiency.

Atrophy↗
PubMed1987

Twenty-four-hour intragastric acidity and clinical trial of bedtime enprostil 70 micrograms compared with ranitidine 300 mg in duodenal ulcer.

The effects of bedtime 70 micrograms and twice daily 35 micrograms doses of enprostil on 24-hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 micrograms twice daily, and by 48% with 70 micrograms at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 micrograms. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p = 0.0065 and 94% vs 68%, respectively at 8 weeks, P = 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.

Adult↗
PubMed1987

Review: long-acting somatostatin analogues.

This article reviews the chemistry, actions and chemical applications of somatostatin and its analogues. At present, their gastroenterological use should be considered in patients with the carcinoid syndrome and functioning pancreatic endocrine tumours; in endocrinology there is interest in their use for the management of patients with resistant acromegaly. With these possible exceptions, somatostatin analogues should at present be used only in the context of clinical trials.

Acromegaly↗
PubMed1987

Carcinoma of the colon presenting with dyspepsia.

Three patients with upper abdominal symptoms responding to anti-ulcer medication are reported who had negative upper gastrointestinal endoscopies. Subsequent barium enemas showed that each of the patients had either a carcinoma of the transverse colon or caecum. Investigation of the colon should be considered in all such cases.

Adult↗
PubMed1986

Stimulation by 1,25-dihydroxyvitamin D3 of adenylate cyclase along the villus of chick duodenum.

Administration of 650 pmol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] to vitamin D-deficient chicks increased adenylate cyclase activity in the basolateral membrane of duodenal epithelial cells within 24 h. This increase in enzymatic activity was accompanied by an increase in calmodulin content of the basolateral membrane. Although neither exogenously added calmodulin (up to 10 micrograms/ml) nor calcium (from 10(-7)-10(-5) M) stimulated enzyme activity, calmodulin antagonists trifluoperazine, W7, and W13 inhibited it. When calmodulin content, adenylate cyclase activity, and alkaline phosphatase activity were measured in cells sequentially eluted from the tip to the base of the villus, cells from the midregion and base had the highest calmodulin content and adenylate cyclase activity, whereas alkaline phosphatase activity (a brush border membrane enzyme) was highest in cells eluted from the tip. Adenylate cyclase activity was increased by 1,25-(OH)2D3, particularly in cells from the midvillus. Our results indicate that the response of adenylate cyclase activity to 1,25-(OH)2D3 varies along the villus and suggest that calmodulin may be involved.

Adenylyl Cyclases↗