Histamine-2 receptor antagonists and gastric cancer.

We conducted a case-control study at Group Health Cooperative of Puget Sound to evaluate the relation between longterm histamine-2 (H2) receptor antagonist use and gastric cancer. We identified 113 cases and 452 controls and estimated a relative risk (RR) of 2.0 [95% confidence interval (C1) = 1.0-3.9]. When we evaluated the effect of time-since-first-use, the RR estimates were 6.5, 1.2, and 1.0 for 2-4 years of use, 5-9 years, and > or = 10 years, respectively. The data provide substantial evidence that long-term H2 antagonist use is not associated with gastric cancer.

DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis.

The objective of the present study was to determine whether abnormal epithelial DNA content (aneuploidy) in colonic biopsy specimens from ulcerative colitis (UC) patients correlated with and predicted histological progression to dysplasia. Aneuploidy was absent in 20 low-cancer risk patients. In 81 high-cancer risk patients aneuploidy correlated significantly with the severity of histological abnormality (negative, indefinite, dysplasia, or cancer). Statistically our data suggest that many more biopsy specimens than are usually taken are needed to detect focal dysplastic lesions. Prospective study of 25 high risk patients without dysplasia revealed 5 with aneuploidy, all of whom progressed to dysplasia in 1-2.5 years, whereas 19 patients without aneuploidy did not progress to either aneuploidy or dysplasia within 2-9 years. Our data indicate that aneuploidy in mucosal biopsy specimens correlates with histological grade and identifies a subset of patients without dysplasia who are more likely to develop it. It was concluded that more frequent and extensive colonoscopic surveillance of this minority subset of high risk patients and less frequent surveillance in the remaining majority may reduce cost and detect more curable lesions.

Coffee and alcohol use and the risk of ulcerative colitis.

We performed a population-based, case-control study of the risk of ulcerative colitis associated with coffee and alcohol use among the 304,000 members of a prepaid health plan. We compared coffee and alcohol use histories before ulcerative colitis onset in 209 cases and an equal number of age- and sex-matched controls selected from the enrollment file of the prepaid health plan. Neither coffee use, amount of coffee consumed daily, or cumulative coffee consumption before disease onset altered the risk of developing ulcerative colitis. A decreased risk of ulcerative colitis was associated with alcohol consumption before disease onset among never-smokers only. This risk declined as daily alcohol consumption increased. These results suggest that alcohol consumption may lower ulcerative colitis incidence.

Effects of cigarette smoking on the clinical course of ulcerative colitis.

We assessed the effect of smoking on the clinical course of ulcerative colitis in 209 subjects by comparing disease severity in smokers and non-smokers as measured by yearly number of hospitalizations for ulcerative colitis treatment and the need for a colectomy. Hospitalization for ulcerative colitis treatment occurred less frequently in persons who smoked after disease onset, but the colectomy rate in persons who smoked after disease onset and non-smokers was similar. Both hospitalization and colectomy for treatment of ulcerative colitis occurred more frequently among smokers who quit before disease onset. Furthermore, hospitalization and colectomy occurred most frequently in the heaviest smokers who quit before disease onset. We found no strong evidence of a therapeutic effect of smoking after ulcerative colitis onset on this illness's clinical course, but smoking before disease onset may affect the clinical severity of this illness.

Choice of non-steroidal anti-inflammatory drug in persons treated for dyspepsia.

Prior use of analgesics among 1327 new users of cimetidine over the age of 65 at Group Health Cooperative of Puget Sound was much more common than among 5308 members of similar age and sex who had never taken cimetidine. The excess included not only most non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, but also extended to paracetamol. New users of cimetidine who had not received analgesics in the preceding 2 years were preferentially given recently introduced NSAIDs if an NSAID was subsequently prescribed. Review of prior studies of analgesic use and ulcer diseases reveals a regular association between ulcer and preceding use of paracetamol, a drug for which no causal association to ulcer is thought to exist. General increases in use of analgesics by elderly dyspeptic patients may have given rise to artefact in reported associations between manifestations of ulcer disease and NSAIDs.

Drug-induced parenchymal renal disease in outpatients.

Hospitalizations for patients with newly diagnosed renal disease were reviewed for the period 1972 to 1983 at Group Health Cooperative of Puget Sound to identify those instances where the renal disease might have been caused by a drug(s). After careful review of 496 admissions, only nine instances were found in which a drug etiology of the renal disease could not be safely ruled out on a case history basis. From this study, it is estimated that the frequency of newly diagnosed, outpatient drug-induced renal disease requiring hospitalization is rare, on the order of one per 300,000 persons per year.

Neurologic events following diphtheria-tetanus-pertussis immunization.

The frequency of serious neurologic events following the administration of 106,000 doses of diphtheria-tetanus-pertussis vaccine at Group Health Cooperative of Puget Sound was determined using a population-based case-control study with disease ascertainment through pharmacy and hospitalization records. There were no cases of acute unexplained encephalopathies in close temporal relation to vaccination. There was the new onset of one serious seizure disorder in the three days following immunization, with 1.13 expected on the basis of chance alone.

Nonsteroidal anti-inflammatory drugs and hospitalization for gastroesophageal bleeding in the elderly.

Hospitalization because of bleeding from the stomach or esophagus occurred 4.8 times per million person-days among persons over 64 years of age who filled a prescription for nonsteroidal anti-inflammatory drugs (NSAIDs) within 90 days of hospitalization, and 3.4 times per million person-days among nonusers of NSAIDs over 64 years of age at the Group Health Cooperative of Puget Sound, Seattle. The NSAID users included those who had used these drugs on a long-term basis as well as those who were recent users only. The observed difference in rates (1.3 hospitalizations per million person-days; 95% confidence interval, -0.2 to 3.4 hospitalizations per million person-days) is incompatible with any major increase in the frequency of hospitalization for gastroesophageal bleeding in the elderly. No single NSAID appeared to carry an exceptional risk. Both chance and uncontrollable selection factors could provide plausible explanations for the small rate differences observed between users and nonusers.

Diphtheria-tetanus-pertussis immunization and sudden infant death syndrome.

We compared the recency of diphtheria-tetanus-pertussis (DTP) immunization in healthy children with birthweights greater than 2500 gms who died of sudden infant death syndrome (SIDS) to that of age-matched reference children, using a modified case-control analysis. Focusing on very narrow time intervals following immunization, we found the SIDS mortality rate in the period zero to three days following DTP to be 7.3 times that in the period beginning 30 days after immunization (95 per cent confidence interval, 1.7 to 31). The mortality rate of non-immunized infants was 6.5 times that of immunized infants of the same age (95 per cent CI, 2.2 to 19). The latter result and to some extent the former appear to be ascribable to known risk factors for SIDS. Although the mortality ratios for SIDS following DTP, as estimated from this study, are high the period of apparently elevated risk was very short, so that only a small proportion of SIDS cases in infants with birthweights greater than 2500 gms could be associated with DTP.

[A model system for the study of repair of DNA double-strand breaks in Saccharomyces cerevisiae]. / Model'naia sistema dlia izucheniia reparatsii dvunitevykh razryvov DNK u drozhzhei Saccharomyces cerevisiae.

The efficiency of "LiCl transformation" in Saccharomyces cerevisiae haploid cells by an autonomously replicating pLL12 plasmid carrying yeast LEU2 and LYS2 genes is increased (by an order or more) when the plasmid is linearized by the restriction endonuclease XhoI cleavage of a unique site in LYS2 gene. Transformants were selected on the medium lacking leucine. This phenomenon has been shown to be a result of recombinational repair of double-strand breaks (DSB) of plasmid DNA stimulated by a restriction endonuclease. The kinetic data have shown the process of plasmid DNA DSB repair to consist of two phases. The completion of the first phase occurs during an hour and the second phase occurs in 14-18 hours. DNA double-strand gaps (the deleted sequences of plasmid LYS2 gene in DSB region) with maximal length of 2-2.5 kb are repaired with the same efficiency as DSB. The genetic control of the recombinational repair of plasmid DNA DSB has been studied.

Non-steroidal anti-inflammatory drugs and hospital admission for perforated peptic ulcer.

The frequency of hospital admission for perforated ulcer was not measurably affected by concurrent use of non-steroidal anti-inflammatory drugs (NSAID) during nearly 30 million person-days of NSAID use at Group Health Cooperative of Puget Sound. Whether patients had ever used cimetidine or antacids, drugs which indicate the presence of ulcer disease or symptoms, was strongly predictive of perforation in the same population (rate ratio 5.1; 95% CI 2.6-10.0). Perforation rates increased sharply with age but were similar for men and women.

Risk of ulcerative colitis among former and current cigarette smokers.

We performed a case-control study of the effect of tobacco smoking on the risk of acquiring ulcerative colitis among the 304,000 members of a health maintenance organization. Smoking histories before the date of the onset of ulcerative colitis were compared in 212 cases and an equal number of controls matched for age and sex who were selected from the enrollment file of the health maintenance organization. The relative risk of ulcerative colitis among current cigarette smokers as compared with nonsmokers was 0.6 (95 percent confidence interval, 0.4 to 1.0); however, among former cigarette smokers it was 2.0 (95 percent confidence interval, 1.1 to 3.7). These values remained after adjustment for socioeconomic factors and for coffee and alcohol consumption. The higher risk among former smokers could not be explained by postulating that smokers gave up tobacco near the time of disease onset because of early symptoms of ulcerative colitis. The relative risk of ulcerative colitis among former smokers increased in proportion to the cumulative number of cigarettes smoked before the onset of disease, suggesting a causal relationship between this exposure and disease occurrence. No difference in risk was observed among current smokers according to cumulative amount smoked. We conclude that former and current tobacco use may have opposite effects on the risk of acquiring ulcerative colitis.

Outpatient drug-induced parenchymal liver disease requiring hospitalization.

A case-history study of drug-induced liver disorders requiring hospitalization was carried out at the Group Health Cooperative of Puget Sound, a health maintenance organization with about 280,000 members, for the five-year period from January 1, 1977 to December 31, 1981. During this time, there were 12 instances of hospitalization for liver disorders judged to be probably (nine cases) or possibly (three cases) attributable to outpatient drug ingestion (other than antitumor agents). The rate was on the order of one per 100,000 person-years at risk. Drugs implicated as probable causes were ampicillin (two cases), carbamazepine (one case), erythromycin (one case), methyldopa (one case), sulfasalazine (one case), quinidine (one case), trimethoprim/sulfamethoxazole (one case), and multiple drugs (one case).

Certain nonsteroidal antiinflammatory drugs and hospitalization for upper gastrointestinal bleeding.

In this follow-up study we attempted to estimate the risk of hospitalization for upper gastrointestinal bleeding (exclusive of bleeding from duodenal ulcer) caused by taking certain nonsteroidal antiinflammatory drugs (NSAIDs) in people below the age of 65 years. The final figures represent our best estimate, taking into account all of the available information, and suggest that NSAIDs (excluding aspirin) rarely cause gastrointestinal bleeding from the stomach that requires hospitalization in this age group. A formal analysis of the data according to classic techniques was not feasible since numerous important confounding factors could not be controlled. Indeed, the results indicated that such formal analysis is unnecessary. The data as they stand are of considerable value in providing a reasonable estimate of attributable risk for the drugs studied.

Long-term follow-up study of cimetidine.

In a 5-year follow-up study of 8553 recipients of cimetidine at Group Health Cooperative of Puget Sound, we examined the frequency of uncommon serious illness requiring hospitalization that may have been drug induced. With the possible exception of one patient with probable drug-induced liver disease, we did not find any instances of serious illness requiring hospitalization that could be attributed with reasonable certainty to cimetidine. This large study provides reassurance that cimetidine is a relatively safe medication.

Pyloric stenosis and maternal Bendectin exposure.

As part of a long-term follow-up of structural disorders present at birth or shortly thereafter in infants born at Group Health Cooperative of Puget Sound, all infants with a diagnosis of pyloric stenosis born between July 1, 1977 and June 30, 1982, were identified. Automated pharmacy profiles were examined to determine whether an association between maternal Bendectin use in the first trimester and infantile hypertrophic pyloric stenosis existed. Among the 3,835 women exposed to Bendectin while pregnant, in this group of 13,346 births, 13 had infants who developed pyloric stenosis, and among the 9,511 women not exposed, 13 had infants who developed pyloric stenosis, resulting in a risk ratio estimate of 2.5 (95% confidence interval (CI) 1.2-5.2). When mothers were divided according to the number of prescriptions for Bendectin filled, the relative risk estimate increased from 1.2 (95% CI 0.4-4.4) in women who filled only one prescription to 7.6 (95% CI 4.9-11.6) in women who filled five or more prescriptions for Bendectin during their pregnancy.