K.G. Wormsley

INHIBITION OF PENTAGASTRIN-STIMULATED AND NOCTURNAL GASTRIC SECRETION BY RANITIDINE: A New H2-receptor Antagonist

Ranitidine hydrochloride (an H2-receptor-blocking drug which does not contain the imidazole nucleus of histamine) powerfully inhibited nocturnal and pentagastrin-stimulated gastric secretion in fifteen patients with duodenal ulceration. The drug is satisfactorily absorbed and therefore warrants clinical trial.

VERY LONG-TERM TREATMENT OF PEPTIC ULCER WITH CIMETIDINE

In an open trial, 96 patients with endoscopically proven peptic ulcers were randomly allocated to treatment with cimetidine (1 g/day) for periods of 3, 6, 9, or 12 months. After their courses of treatment, the patients were followed up for at least 6 months. In 92% the ulcers had healed after treatment for 1 month, and in a further 5% the ulcers healed during the next 2 months. Ulcers recurred during treatment in 24% of patients and within 6 months of withdrawal of treatment in a further 43%. In nearly a third of patients the recurrences were asymptomatic and were discovered only through routine endoscopic studies. Continuous treatment with full doses of cimetidine for a year seems to prevent relapse of the majority of ulcers which have healed during treatment; but it does not cure the ulcer disease, since relapse generally occurs quite rapidly when treatment is discontinued.

Chronic and Acute Studies Indicating Absence of Exocrine Pancreatic Feedback Inhibition in Dogs

Chronic administration of raw soybean flour containing active trypsin inhibitor to dogs reduced the pancreatic output of trypsin and chymotrypsin in response to cholecystokinin. Dogs stimulated by a meat meal showed no consistent alteration in the output of trypsin and chymotrypsin when given additional duodenal infusions of trypsin and chymotrypsin, or canine pancreatic juice, or ovalbumin trypsin inhibitor. Two dogs, whose pancreas was stimulated by intraduodenal infusion of amino acids, showed no consistent change when trypsin, or trypsin together with trypsin inhibitors, or trypsin together with canine pancreatic juice was infused concurrently into the duodenum. These results indicate that feedback control of pancreatic enzyme secretion, of the type proposed on the basis of studies similar to the present in rats, does not exist in dogs.

DOES MAINTENANCE THERAPY KEEP DUODENAL ULCERS HEALED

34 patients were endoscopically reexamined once a month while receiving ranitidine 150 mg at night to sustain remission of a duodenal ulcer. The cumulative recurrence rate after 1 year of maintenance treatment was 48%. 71% of recurrences were painless when first detected. The monthly percentage probabilities for asymptomatic ulcers rehealing, remaining unchanged, and causing pain were 33%, 63%, and 4%, respectively. Because painless ulcers may reheal, the number of ulcer recurrences detected during maintenance trials depends on the frequency of endoscopic reexamination of symptomless patients. Endoscopic examination of symptomless patients every 6 months would have failed to detect nearly half of all recurrences in this study. Thus an accurate assessment of the true incidence of asymptomatic (and, therefore, total) recurrences requires frequent endoscopic re-examination of symptomless patients. The clinical value of maintenance treatment should be judged by prevention of symptoms and complications, since it is not possible--either practically or mathematically--to determine the true incidence of ulcer recurrence, and because asymptomatic recurrences are irrelevant, provided maintenance treatment is continued.

Maintenance Therapy of Duodenal and Gastric Ulcer with H2-Receptor Antagonists

Maintenance therapy with either ranitidine or cimetidine has been administered for up to 5 years to several hundred patients suffering from duodenal or gastric ulcer disease. Maintenance treatment prevented symptomatic ulcer relapse in approximately three-quarters of patients over this period of time. About half of symptomatic ulcer relapses occurred during the 1st year of maintenance therapy, and thereafter the symptomatic recurrence rate was extremely low. Potentially the most important effect of maintenance therapy was to reduce the incidence of ulcer complications, particularly haemorrhage (from 6.2% to 0.4% during the 1st year of duodenal ulcer maintenance). Maintenance therapy is therefore likely to reduce ulcer morbidity and to be cost-beneficial in patients who have previously experienced an ulcer complication and are at an increased risk of the same complication in the future. Maintenance therapy with 300 mg ranitidine daily was more effective than 150 mg ranitidine at night in smokers and may be a useful therapeutic option for smokers who relapse during maintenance therapy with 150 mg ranitidine at night or for smokers in whom it is mandatory to prevent ulcer recurrence because of a previous complication. Asymptomatic ulcers occurring during maintenance therapy are clinically benign, and rehealing such ulcers does not alter the subsequent clinical course. Point prevalences of asymptomatic reulceration should not be used when assessing the clinical value of maintenance therapy.

Adaptive Mutagenesis-Cause of Alimentary Cancer?

The tissues of the alimentary tract react to abnormal functional demands or to injury from environmental chemicals by reactions which involve change in morphology, functional characteristics and cellular proliferation. The work hyperplasia, wound repair or response to xenobiotics may become distorted by inherent, or induced, genomic abnormalities of the affected cells. It seems that some of the reactions are programmed or planned and depend on predetermined changes in gene expression. Although the reactions permit survival in the face of environmental hazards, the necessary alterations in gene expression may predispose to malignant change in the affected cells.

Session 6: Is Hypergastrinaemia Dangerous for Man?

Wormsley KG. Is hypergastrinaemia dangerous for man? Scand J Gastroenterol 1991, 26(suppl 180), 174–178Several gastric mucosal diseases and the response to powerful gastric secretory inhibitors are accompanied by hypergastrinaemia. When the gastric mucosa is functioning normally, hypergastrinaemia may be dangerous as a consequence of gastric hypersecretion. When the gastric mucosa is functionally abnormal, hypergastrinaemia produces no apparent adverse effects on health. However, the diseases giving rise to hypergastrinaemia are very dangerous because they are often the precursors of gastric cancer. In view of the probable mechanisms of gastric carcinogenesis. it is argued that therapeutic achlorhydria is also potentially dangerous irrespective of the absence or presence of ‘hypergastrinaemia’.

CIMETIDINE MAINTENANCE: HOW LONG?

a total peak lod score > 6 (odds of 106 :1) at -L 2 000. Two additional conclusions may be drawn from these data. First there is no evidence that the genes for the salt-losing and compensated forms of adrenogenital syndrome have a different linkage distance to HLA-B. Second, Dupont et al. observed that adrenogenital syndrome is on the HLA-B side of HLA-A, basing the suggestion on a single family with an HLA-B: HLA-A recombinant. Child 2 in our family A is either a paternal Bf:HLA-A recombinant or a maternal HLA-B:HLA-A recombinant. In the former case the adrenogenital syndrome gene segregates with Bf, and in the latter the gene segregates with HLA-B, confirming, in either event, that the gene for the adrenogenital syndrome is on the HLA-B side of HLA-A. There is no evidence for association of the gene(s) for adrenogenital syndrome with a specific HLA-B allele in the nine reported families; thus, the HLA-B and adrenogenitalsyndrome loci are apparently far enough apart for linkage disequilibrium not to be prominent. The adrenogenital syndrome locus (loci) may lie as much as a few centimorgans from HLA-B. More precise mapping will be possible when red-cellglyoxalase : HLA recombinants are found in families with the