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Biomedical subjects

M G Korman

Publications and source records attributed to M G Korman.

At least 73 records · Page 4Linked to original sources

Mortality in patients with haematemesis and melaena: a prospective study.

In a prospective study of death in 817 patients with haematemesis and melaena admitted on 894 occasions, the protocol included admission of all patients to a defined unit, early endoscopy and resuscitation, and planned management. Over the three consecutive two-year periods of the study mortality significantly decreased from 9% to 2.4%. Although the operative rate remained the same, the operative mortality fell from 16% to 1.6%. The fall in mortality was greatest in patients with bleeding gastric ulcers. These results suggest that prospective studies with a defined policy can influence the mortality in patients with upper gastrointestinal bleeding.

Adolescent↗

Bleeding duodenal ulcer: reduction in mortality with a planned approach.

In a 6-year prospective study from 1972 to 1978 266 patients were admitted to a haematemesis and melaena unit with bleeding duodenal ulcer. There were 13 deaths, a mortality of 5 per cent. A comparison between the three consecutive 2-year periods of study showed an initial mortality of 6 per cent for the first 4 years falling to 2 per cent for the 93 admissions during the final 2 years of experience. Of the 120 patients treated surgically, 10 died in hospital, giving an operative mortality of 8 per cent. The trend in operative mortality was from 13 per cent for the initial 2-year period to 8 per cent for the second period and to 3 per cent for the final 2 years. The operative rate was consecutively 45, 50 and 34 per cent. There was 1 death in conservatively treated patients during each 2-year period of study. Three types of operation were performed: vagotomy, pyloroplasty and oversewing of the ulcer; Polya gastrectomy; and vagotomy and antrectomy. There was no difference in morbidity and mortality between these operations. At a mean follow-up of 3.1 years, 90 per cent of the patients had a good result from their operation. It is concluded that a prospective system of management with an active policy of early endoscopy, surgery and regular audit reduces the mortality from bleeding duodenal ulcer.

Adult↗

Long-term cimetidine in duodenal ulcer disease.

Forty patients with chronic duodenal ulcer who had healed endoscopically with a 6-week course of cimetidine were randomized double blind to 1 year of either placebo or cimetidine tablets 400 mg bid (20 patients in each group). Patients were seen at monthly intervals, and endoscopy was performed at clinical relapse or on completion of 1 year. One of 20 patients on active cimetidine relapsed clinically and endoscopically at 3 months; 16 of 20 patients on placebo relapsed clinically and endoscopically within 9 months, the majority within 3 months, and 2 were shown to have asymptomatic chronic ulcers at routine 12-month endoscopy. None of the 19 patients on active cimetidine routinely endoscoped at 12 months showed evidence of ulceration. This study confirms a high relapse rate when short-term cimetidine is ceased and indicates that maintenance treatment with cimetidine prevents relapse.

Alcohol Drinking↗

Effects of long-term cimetidine on serum gastrin in duodenal ulcer.

Basal and food-stimulated gastrin were measured in 16 patients with duodenal ulcer before and during long-term maintenance therapy with 400 mg cimetidine twice daily. Basal gastrin (mean +/- SE) rose significantly from 27.5 +/- 3.1 pmol/liter precimetidine to 32.8 +/- 2.1, 37.2 +/- 2.6, and 38.5 +/- 3.3 pmol/liter at 1, 3, and 6 months, respectively. The total integrated gastrin response to a protein meal was 1.67 +/- 0.18 nmol/liter/120 min pre-, and 2.54 +/- 0.35, 3.29 +/- 0.3, and 4.36 +/- 0.4 nmol/liter/120 min at 1, 3, and 6 months, respectively. These increases were significantly higher at each time period. This study has thus demonstrated a progressive increase in both basal and food-stimulated gastrin during cimetidine therapy, and this increase could theoretically lead to an increase in gastric acid secretion following cessation of cimetidine.

Aged↗

The Mallory-Weiss lesion as a cause of upper gastrointestinal bleeding.

A prospective study of patients with upper gastrointestinal bleeding admitted to a haematemesis and melaena unit has revealed an incidence of Mallory-Weiss tears of 8% (59 of 762 patients undergoing endoscopy). Prior vomiting was present in 60% and an associated upper gastrointestinal lesion in 44 percent. The majority of patients had a recent ingestion of alcohol and/or analgesics, whilst 34% had chronic heavy alcohol intake. Approximately 50% of patients required no blood transfusion, while 37% had over three units of blood. No patient in the group required surgical intervention, and one patient died because of general debility. This study suggests that the Mallory-Weiss tear accounts for a significant proportion of patients admitted with upper gastrointestinal bleeding, but that the mortality and morbidity are low.

Adolescent↗

The protective effect of cimetidine on stress-induced acute gastric ulceration in the rat.

The effect of intraperitoneal cimetidine, an H2 receptorantagonist, has been assessed on the development of cold-restraint induced acute gastric ulcers in rats. Cimetidine in doses ranging from 20-100 mg per kg body weight significantly reduced the incidence of acute gastric ulceration compared with saline controls in this model. The protective effect of cimetidine suggests a prophylactic role for this agent in stress-induced gastric or duodenal ulceration in man.

Animals↗

The effect of cimetidine on gastrin release in ulcer disease.

The effect of a single dose of 400 mg of the H2-receptor antagonist cimetidine on protein meal stimulated immunoreactive gastrin was assessed in ten patients with gastric ulcer and ten patients with duodenal ulcer. In gastric ulcer patients, serum gastrin (mean +/- SE) rose from 34 +/- 2.2 pmol.l-1 to a peak of 80 +/- 5.0 pmol.l-1 at 45 minutes without and from 36 +/- 2.2 to 107 +/- 8.0 pmol.l-1 at 60 minutes with cimetidine; in duodenal ulcer it rose from 26 +/- 3.0 to 47 +/- 5.1 pmol.l-1 at 45 minutes without and 26 +/- 3.2 to 52 +/- 5.1 pmol.l-1 at 60 minutes with cimetidine. Integrated gastrin responses in gastric ulcer were 4900 +/- 800 pmol.l-1 120 minutes without and 7000 +/- 900 pmol.l-1 120 minutes with cimetidine and 1560 +/- 300 pmol.l-1 120 minutes without and 2620 +/- 400 pmol.l-1 120 minutes with cimetidine in duodenal ulcer patients. These gastrin increases after cimetidine are comparable to those achieved with continuous intragastric neutralisation with alkali.

Adult↗

Serum gastrin after 12 months' continuous cimetidine therapy for duodenal ulcer.

Serum immunoreactive gastrin was measured in 14 patients with duodenal ulcer before and during a 12-month course of cimetidine 400 mg bd. All patients were symptomatically well during the cimetidine therapy and both basal gastrin and that in response to a protein rich meal were assessed before, at six months and at 12 months during therapy. The basal and post-prandial gastrin were significantly higher at six and 12 months on cimetidine than before cimetidine but the six and 12 month levels were similar. This study thus shows that the progressive increase in serum gastrin during six months of continuous cimetidine therapy does not occur beyond this time period.

Adult↗

Long-term cimetidine does not alter serum prolactin.

The effect of repeated cimetidine ingestion on serum prolactin values was studied prospectively in 17 men with proven duodenal ulcers. These patients received 400 mg of cimetidine twice daily for 12 weeks but showed no alteration in their mean serum prolactin levels. Cimetidine-induced hyperprolactinaemia is not the explanation for the development of gynaecomastia in men exposed to this drug.

Administration, Oral↗

Determinants of fasting and postprandial serum bile acid levels in healthy man.

The relationship between serum levels of conjugates of cholic acid measured by radioimmunoassay, bile acid absorption, and hepatic clearance was studied in order to define the determinants of fasting and postprandial serum bile acids in healthy man. Acute or chronic interruption of the enterohepatic circulation caused a significant decrease in basal serum levels of cholyl conjugates, while liquid or solid meals caused a marked and reproducible increase in serum cholyl conjugates. A temporal correlation was demonstrated postprandially or after intravenous cholecystokinin between intestinal transit of bile acids and simultaneous changes in levels of serum cholyl conjugates. Finally, the plasma disappearance of intravenously injected cholylglycine was shown to be unaffected by serum levels of endogenous cholyl conjugates. These data are consistent with the interpretation that, in the presence of normal hepatic function, the major determinant of serum bile acids is their rate of intestinal absorption.

Adult↗

Diurnal serum levels of primary conjugated bile acids. Assessment by specific radioimmunoassays for conjugates of cholic and chenodeoxycholic acid.

The serum levels of conjugates of chenodeoxycholic acid (chenyl conjugates) and of cholic acid (cholyl conjugates) were determined by specific radioimmunoassays during a 24-hour period, which included three liquid meals and an overnight fast, in five healthy volunteers, five patients with previous cholecystectomy, five patients with documented bile acid malabsorption because of ileal resection, and four pregnant women. In healthy subjects, fasting-state levels of chenyl conjugates, when compared with those of cholyl conjugates, were higher; postprandially, levels of chenyl conjugates rose to a peak sooner (30 minutes vs 60 minutes) and to higher levels (5.2 +/- 1.3 muM vs 2.0 +/- 0.5 muM, M +/- SE). In cholecystectomised patients, the integrated areas under the curve for both bile acids were similar to those of the healthy controls, but postprandial peaks were less marked. In patients with bile acid malabsorption, postprandial rises of chenyl conjugates were lower but remained relatively constant throughout the day, whereas cholyl conjugate levels diminished progressively with each successive meal, consistant with depletion of the cholyl, but not the chenyl, pool. In three of four pregnant women, the postprandial rise of chenyl conjugates was disproportionately less compared with that of healthy controls. These results confirm the dynamic complexity of serum bile acid levels in man and indicate that the major circulating primary bile acids are chenyl conjugates. They support previous proposals that jejunal absorption of chenyl conjugates is important in the normal enterohepatic circulation of bile acids; and they suggest an abnormality in the enterohepatic circulation in pregnancy.

Chenodeoxycholic Acid↗

Cimetidine treatment of duodenal ulceration: short term clinical trial and maintenance study.

Eighty-five patients with endospcopically confirmed duodenal or pyloric canal ulcers entered a double blind trial with 1200 mg of cimetidine per day or placebo for 6 weeks. Eighty-four per cent of patients treated with cimetidine and 38 percent of those receiving placebo healed their ulcers (P less than 0.001). Measurement of basal acid output and maximal acid output before and after treatment showed no significant change but patients who failed to heal their ulcers had a higher basal acid output and maximal acid output than those who healed. Patients who smoked or drank alcohol had the same healing rate as abstainers. Sity-seven patients with duodenal ulceration healed by a 6-week course of cimetidine were randomly allocated to 400 mg of cimetidine twice daily or placebo in the maintenance trial. Actuarial analysis of the number of relapses in each group demonstrates that cimetidine is highly effective in preventing relapse.

Adult↗

Duodenal ulcer.

Duodenal ulcer is a common disease which places heavy demands on health care costs. The aetiology is unknown, but its pathogenesis is related to acid secretion. The characteristic symptom is chronic epigastric pain which precedes meals, occurs one to three hours after food, and one to two hours after retiring. The pain is relieved by food or antacids. Barium meal remains the prime investigation, but flexible endoscopy allows accurate visualization of the ulcer particularly in a scarred deformed duodenum. Complications include haemorrhage, perforation and obstruction. Time-honoured therapy including diet, antacids and anticholinergics simply relieves pain, whilst newer drugs (Tagamet, De-Nol, and Duogastrone) are effective in healing the ulcer. Surgery is indicated for complications or inadequately relieved pain.

Adult↗

Severe chronic active liver disease. Prognostic significance of initial morphologic patterns.

To determine the usefulness of recognizing the different morphologic patterns of chronic active liver disease (CALD), we compared clinical and biochemical features as well as responses to treatment in 32 patients with chronic active hepatitis (CAH); 36 with subacute hepatitis and bridging necrosis (SHB); 30 with subacute hepatitis and multilobular necrosis (SHMN); and 30 with cirrhosis and active hepatitis (Cirrh). The morphological lesions did not correlate with clinical or etiologic features. Patients with CAH had less severe biochemical abnormalities, entered remission more often, and failed to respond to treatment less frequently than those with SHMN or Cirrh. SHB and SHMN resembled each other in many regards and showed greater functional changes than CAH. Cirrhosis developed more often after SHMN than CAH and was associated with a poorer prognosis than CAH. Serial liver biopsies revealed all possible histologic transitions, with reduction of inflammation usually occurring in patients treated with steroids and extension of inflammation being more frequent in those not receiving these drugs. CAH, SHB, SHMN, and Cirrh, therefore, reflect the degree and extent of disease activity at any given time in CALD, rather than representing different conditions. Identification of the initial morphologic lesion is helpful because of differences in prognosis.

Adult↗

Radioimmunoassay of unsulfated lithocholates.

A simple, rapid, precise radioimmunoassay for total unsulfate species of lithocholate (lithocholyglycine, lithocholyltaurine, and lithocholate) in serum is described. Antiserum was raised in rabbits by injection of lithocholylglycine coupled to bovine serum albumin (prepared by a carbodiimide method) and emulsified in complete Freund's adjuvant; antisera capable of measuring 40-120 pmol at 1:400 dilution were obtained. The tracer was [11, 12-3[H]lithocholyglycine. The radioimmunoassay featured a 2-hr binding step at 42 decrease C and a 1-hr separation step using polyethylene glycol. The antibody had the following relative specificities: lithocholyglycine and lithocholytaurine, 1; lithocholate, 1.5; chenodeoxycholyglycine, 20; and deoxycholylglycine, 55. There was no binding of various other free or conjugated sulfated and unsulfated bile acids. The mean fasting-state level in 50 healthy subjects was 0.3 mu mol/l (0.14 microgram/ml), but 11 of the 50 subjects had level too low to measure by this technique.

Antibody Specificity↗

Radioimmunoassay of sulfated lithocholates.

A sensitive, rapid radioimmunoassay for sulfated species of lithocholic acid (sulfolithocholyglycine, sulfolithocholyltaurine, and sulfolithocholic acid) was developed and used to measure the total concentration of sulfated lithocholates in serum from healthy human subjects. Sulfolithocholylglycine was conjugated to bovine serum albumin by a carbodiimide procedure, and the reaction product, emulsified in Freund's adjuvant, was injected into rabbits. The antiserum obtained was capable to binding 40% of [3H]sulfolithocholylglycine at 1:1000 dilution. The assay featured a 2-hr binding step at 42 degrees C followed by precipitation of bound tracer with polyethylene glycol at 4 degrees C. The assay can be used with 0.1 ml of serum and was reproducible. The antibody had little affinity for the 3-sulfate of cholic or chenodeoxycholic acid, a number of steroid sulfates, or unsulfated bile acids. In 50 healthy subjects, mean (+/-SE) fasting-state serum levels of immunoreactive sulfated lithocholyl conjugates (+sulfated lithocholate) was 1.6 +/- 0.1 micrometer; based on results with a separate radioimmunoassay for unsulfated lithocholyl conjugates, most of the lithocholate in serum in healthy man is present in sulfated form.

Antibody Specificity↗

Development of an intravenous bile acid tolerance test. Plasma disappearance of cholylglycine in health.

To develop an intravenous bile acid tolerance test that might be useful for detecting impaired liver function or liver injury, the plasma disappearance of intravenously injected cholyglycine was characterized in healthy man by a radiommunoassay, specific for conjugates of cholic acid, on serial samples of venous blood. Cholylglycine disappearance was rapid (mean half-life plus or minus S.E. equals 2.6 plus or minus 0.1 minutes) and of first-order kinetics; the rate of disappearance was independent of dose between 2 and 15 mumoles per kilogram of body weight. A dose of 5 mumoles per kilogram was selected as an optimal dose, and its clearance was defined in 45 healthy subjects. After intravenous injection of this dose, conjugates of cholic acid increased 10-fold, but in all subjects the concentration of these bile acids had returned to 1 muM (the upper limit of normal, fasting state) by 10 minutes. No side effects were observed.

Adult↗

Validity and sensitivity of an intravenous bile acid tolerance test in patients with liver disease.

A bile acid tolerance test, which measures the plasma disappearance rate of injected cholyglycine by radioimmunoassay, was studied in 36 patients with biopsy-proved chronic liver disease and compared to fasting-state levels of conjugated cholic acid and other conventional liver tests. In 25 patients in whom one or more of the conventional tests for liver disease showed abnormal results, fasting-state levels of conjugated cholic acid were increased in 20, but plasma disappearance of cholyglycine was delayed in all. Of the 11 other patients in whom conventional tests were within normal limits, fasting-state levels of conjugated cholic acid were increased in three of 10, but cholyglycine disappearance was dealyed in nine of 11. The bile acid tolerance test indicated liver disease more sensitively than the fasting-state level of conjugated cholic acid, which, in turn, was more sensitive than other conventional liver tests.

Cholic Acids↗