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Biomedical subjects

J Zimmerman

Publications and source records attributed to J Zimmerman.

At least 73 records · Page 4Linked to original sources

Does dietary calcium supplementation reduce the risk of colon cancer?

Several recent studies have examined the hypothesis that calcium supplementation (1.2-2.0 g/day) protects against colon cancer in persons at high risk. The effect of supplementation was assessed by comparing the labeling index of rectal biopsy specimens before and after supplementation. Although in most studies the labeling index tended to decrease during supplementation, the results were inconsistent. It is also unclear whether the decrease in the index correlates with a decrease in occurrence or recurrence of colonic tumors. Use of calcium prophylaxis for persons at risk for colon cancer should be reserved for controlled clinical trials.

Calcium↗

Gastro-duodenal injury associated with intake of 100-325 mg aspirin daily.

During the year 1991, 43 patients with upper gastrointestinal bleeding and one with severe epigastric pain associated with intake of non-steroidal anti-inflammatory drugs were admitted for emergency endoscopy to our unit. Fourteen patients (33%) had been treated with 100-325 mg aspirin daily, 11 of them for at least one year. The mean age of this group was 71. Only two patients had a previous history of peptic ulcer. Five patients used anticoagulants or antiplatelet drugs concomitantly with aspirin. The endoscopic diagnosis of the sources of bleeding was erosive gastritis in eight patients, gastric ulcer in four, duodenal ulcer in five and oesophageal ulcer in one. Our results support findings by other groups, showing that doses of aspirin as low as 75 mg daily should be used in the management of elderly patients with thrombo-embolic disease.

Acute Disease↗

Influence of dose and route on transmission of encephalomyocarditis virus to swine.

The susceptibility of swine to infection with encephalomyocarditis virus (EMCV) was assessed. Transmission of EMCV in a single exposure by gavage or intranasal routes was highly dose dependent. In a direct comparison, animals were exposed to EMCV by gavage, intranasal, intramuscular, intratracheal, or transdermal routes. A higher proportion of animals exposed by transdermal (5/5), intratracheal (5/5), or intramuscular (5/5) routes than those exposed by intranasal (2/5) or gavage (3/5) routes became infected. The large quantity of virus required to infect animals intranasally or orally suggests that transmission by these routes may not occur routinely in the field. Transmission of EMCV by wound contamination (transdermally) has not been reported previously. Although EMCV was recovered from rectal, external genitalia, and pharyngeal swabs, there was no evidence of pig-to-pig transmission of EMCV from experimentally infected animals to comingled sentinels.

Animals↗

Evaluation of serological pseudorabies tests for the detection of antibodies during early infection.

Six enzyme-linked immunosorbent assays, a latex agglutination test, and the standard microtitration serum virus neutralization test were compared for their ability to detect antibodies against pseudorabies virus (PRV) during the early stages of infection. Thirty-five pigs were infected intranasally with 10(5)-10(7) TCID50 of either the Iowa 4892 pneumotropic or the Becker strain of PRV. Blood samples were drawn from experimentally inoculated animals on days 4-10, 14, and 21 postchallenge. Test sensitivity estimates and comparisons among tests were made for each sampling day over the 21-day monitoring period. Results of this study demonstrated differences among tests in 1) the time from inoculation to initial antibody detection, 2) the time to detect > or = 95% of the infected pigs, and 3) the time from initial antibody detection to determination of > or = 95% as positive. By day 10 postchallenge, no statistically significant difference in diagnostic sensitivity was observed among the 8 tests compared in the study.

Animals↗

Acute upper gastrointestinal bleeding in Jerusalem 1988-91: causes, characteristics and relation to nonsteroidal anti-inflammatory drugs.

We analyzed 321 consecutive episodes of community-based acute upper gastrointestinal bleeding admitted to the Hadassah University Hospital in Jerusalem during 1988-91. Of these 71% were in males aged 56.2 +/- 1.2 years (mean +/- SE) and 29% were in females (67.9 +/- 1.7 years, P < 0.001). The main diagnoses were duodenal ulcer (39.5%), gastric ulcer (16.9%), esophageal varices (10.0%), erosive gastritis (8.2%) and esophagitis (7.5%). The distribution of these diagnoses differed significantly between the genders (P = 0.0003). In males the prevalence of duodenal ulcer and of esophageal varices was higher, and that of gastric ulcer and esophagitis lower, than in females. Gastric ulcer patients were oldest, were the least likely to have received anti-ulcer medications prior to admission, and had the highest levels of urea and the lowest levels of hemoglobin on admission. Use of nonsteroidal anti-inflammatory drugs increased significantly with age and was reported in 35% of the cases (aspirin in doses < 1.0 g/day in 21%, nonsalicylate anti-inflammatory agents in 11%, aspirin plus other anti-inflammatory drugs in 3%). Use of systemic corticosteroids was reported in 4%. The most distinctive features of the population with acute upper gastrointestinal bleeding in the present study compared to other series were the significantly higher proportion of duodenal ulcers and the lower proportion of Mallory-Weiss tears.

Acute Disease↗

Neutrophil mediators, Pseudomonas, and pulmonary dysfunction in cystic fibrosis.

Proteolytic enzymes derived from inflammatory cells or Pseudomonas aeruginosa may destroy lung matrix in cystic fibrosis (CF). Antielastases appear to be overwhelmed by large amounts of free neutrophil elastase (NE) activity in lower respiratory tract secretions, and proteolytic or oxidant stress is thought to account for such deficiency. The purpose of this study was to measure NE and myeloperoxidase activity in bronchoalveolar lavage fluid (BAL) from patients with CF and to correlate levels of these mediators with the degree of airflow obstruction and density of P. aeruginosa in BAL. We measured NE activity in BAL fluid from 14 patients with respiratory exacerbations of CF. NE complexed with alpha 1-antiprotease in peripheral blood was measured in 13 of the 14 patients subjected to BAL and in 21 additional patients who did not undergo BAL. Because oxidants generated by myeloperoxidase may contribute to increased elastase activity via inactivation of alpha 1-antiprotease, myeloperoxidase activity in BAL was also measured. We found that elastase activity in BAL correlated significantly with the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC ratio) (r = -0.80, p < 0.001) and FEV1 percent predicted (r = -0.62, p = 0.02). Myeloperoxidase activity also significantly correlated with airflow obstruction (FEV1/FVC ratio, r = -0.70, p = 0.005; FEV1 percent predicted, r = -0.52, p = 0.05). However, the degree of airflow obstruction, NE activity, myeloperoxidase activity, or total neutrophils in BAL did not correlate with the density of P. aeruginosa (CFU/ml) or total pathogen burden in BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Drug interactions in intestinal transport of folic acid and methotrexate. Further evidence for the heterogeneity of folate transport in the human small intestine.

The effect of sulfasalazine and olsalazine on the transport of [3H]folic acid and of [3H]methotrexate (MTX) was investigated in organ-cultured endoscopic biopsy specimens of small intestinal mucosa from normal subjects. Biopsy specimens obtained from patients undergoing routine diagnostic upper gastrointestinal endoscopy were organ-cultured at pH 5.5 and the effect of these two drugs on the initial rate of uptake of the two folates was determined. Both drugs inhibited the transport of [3H]folic acid with similar Ki values (1.38 and 1.32 mM for sulfasalazine and olsalazine, respectively). However, the uptake of [3H]MTX was only partially inhibited by sulfasalazine and was unaffected by olsalazine. Sulfasalazine inhibited 26.2% of the total flux of MTX, in close agreement with the fraction of MTX flux that has been shown previously to be inhibited by folic acid. These data corroborate previous findings of heterogeneity of transport of MTX in the mucosa of the human small intestine.

Aminosalicylic Acids↗

Methotrexate transport in the human intestine. Evidence for heterogeneity.

The transport of methotrexate (MTX) was investigated in organ-cultured endoscopic biopsy specimens of intestinal mucosa from normal subjects. In biopsy specimens from the proximal small intestine incubated with [3H]MTX (0.1 microM) for 2 hr at pH 5.5, [3H]MTX accumulated in the intracellular fluid to a concentration 3.5-fold higher than that of the medium, but at pH 6.5 and 7.5, the concentration was the same as that of the medium. In biopsy specimens from the cecum incubated under similar conditions, no accumulation against a concentration gradient was found. However, the accumulation of MTX was significantly higher at pH 5.5 than at 7.5. At [MTX] = 0.1 microM, the initial rate of MTX transport in the small intestine was significantly affected by medium pH and was optimal at pH 5.5. The relationship between the initial rate of uptake and medium [H+] was hyperbolic, suggestive of saturability with respect to [H+] with a Km of 132.2 nm [H+], corresponding to a medium pH of 6.88. At medium [MTX] = 10 microM, this effect was abolished. At pH 5.5, the relationship between the initial rate of uptake and medium [MTX] was sigmoidal, suggestive of a positive cooperativity, with napp of 1.8. [MTX] at 0.5 Vmax was 20.37 microM. Folic acid inhibited 37% of MTX flux. At pH 7.5, the relationship between the initial rate of uptake of MTX and medium [MTX] was linear. These data indicate the presence of a proton-dependent active transport of MTX in the human proximal small intestine, which is partially shared with folic acid.

Biological Transport↗

Decreased levels of soluble amyloid beta-protein precursor in cerebrospinal fluid of live Alzheimer disease patients.

The amyloid beta-protein is deposited in senile plaques and the cerebrovasculature in Alzheimer disease (AD). Since it is derived from proteolytic processing of its parent protein, the amyloid beta-protein precursor (APP), we investigated whether levels of the secreted forms of APP are altered in cerebrospinal fluid (CSF) of AD patients. Quantitative immunoblotting studies with the anti-APP monoclonal antibody P2-1 revealed that probable AD patients had markedly lower CSF APP levels than did demented non-Alzheimer-type patients and healthy control subjects. Using antibody P2-1 in an enzyme-linked immunosorbent assay, we measured CSF levels of APP in a larger population consisting of 13 patients diagnosed with probable AD, 18 patients diagnosed with dementia (non-Alzheimer type), and 16 nondemented, healthy controls. Mean CSF levels of APP were approximately 3.5-fold lower in the live patients diagnosed with probable AD compared to the demented non-Alzheimer-type controls or the nondemented, healthy individuals. These findings suggest that abnormal metabolism of APP is reflected in the extracellular fluids of the central nervous system and that CSF levels of soluble APP provide a useful biochemical marker to assist in the clinical diagnosis of AD.

Alzheimer Disease↗

Families with adolescents: escaping problem lifestyles.

Using the concepts of "restraints" and reciprocal patterns, a specific approach for understanding and working with families of adolescents is offered. The organizing idea is the "restraint" that revolves around a difficulty both parents and youngsters have in making a distinction between what parents want for their youngsters and what the young person might want. This difficulty may come from the parents' ideas and beliefs about parenting and from their own growing-up experience, from the adolescent's "not completely storied" lives, and/or from societal discourse about adolescence. Restraint of ideas can be constructed as reciprocal patterns and located in dominant narratives that families may have about themselves. A restorying process allows families to separate from the problem pattern and focus on the youngsters' willingness to have ideas for themselves.

Adolescent↗

Seasonal fluctuations in acute upper gastrointestinal bleeding: lack of effect of nonsteroidal anti-inflammatory drugs.

The seasonal pattern of community-based acute bleeding from the upper gastrointestinal (UGI) tract was studied prospectively in 1988-1991. Out of 3343 emergency admissions to the Departments of General Surgery, 321 (9.6%) were due to acute UGI bleeding. There was a significant monthly variation in the total number of admissions, as well as in the number of admissions due to acute UGI bleeding (p < 0.0001). However, there was no correlation between the two. Significant seasonal fluctuations were noted both in the absolute number of admissions due to acute UGI bleeding and in the percentage of UGI bleeding admissions of the total number of admissions to the Departments of General Surgery (p = 0.0002). During summer (July through September), the incidence declined significantly to a nadir of 5.5% of total number of admissions in July. The seasonal fluctuation correlated closely with the incidence of duodenal ulcer, but not with that of gastric ulcer. The seasonal pattern was consistent both in patients who had used aspirin or other nonsteroidal anti-inflammatory drugs as well as in those who had not.

Anti-Inflammatory Agents, Non-Steroidal↗

Sigmoid volvulus presenting as chronic secretory diarrhea responsive to octreotide.

Secretory diarrhea can be seen in a variety of pathologic states; however, intermittent colonic obstruction usually is not considered as a possible cause. We report a 68-yr-old patient with chronic secretory diarrhea and hypokalemia due to intermittent sigmoid volvulus. Because the volvulus was not originally diagnosed, the patient was treated with the long-acting somatostatin analogue octreotide for 1 yr, with marked clinical improvement. Surgical resection of the redundant sigmoid responsible for the volvulus resulted in prompt and complete resolution of all signs and symptoms. Detailed macroscopic and microscopic examination of the resected specimen was normal. The patient continues to be asymptomatic 12 months after surgery. Increased colonic fluid and electrolyte secretion was caused by intermittent sigmoid volvulus and resulted in chronic secretory diarrhea.

Aged↗

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder.

Measurements of the lithium concentration in the occipital pole of the head and calf muscle of nine patients with bipolar disorder in remission were performed using in vivo lithium-7 nuclear magnetic resonance spectroscopy (7Li NMR). 7Li NMR measurements were performed on a 1-m-bore, 1.85-T, superconducting magnet supplemented with a multinuclear spectrometer, using 11.5-cm-diameter surface coils. The average lithium concentration in the occipital pole was 0.36 +/- 0.10 mEq/L, whereas in the muscle it was 0.50 +/- 0.17 mEq/L, both lower than the average serum lithium concentration (0.79 +/- 0.23 mEq/L). The average brain/serum lithium concentration ratio was 0.47 +/- 0.12 whereas the average muscle/serum lithium concentration ratio was 0.66 +/- 0.20. There was a positive correlation between the brain versus serum and brain versus muscle lithium concentrations. The hypothesis is advanced that the minimal effective concentration of brain lithium concentration for maintenance treatment of bipolar disorder is around 0.2-0.3 mEq/L.

Adult↗

Prevalence of inflammatory bowel disease in family members of Jewish Crohn's disease patients in Israel.

A familial study of 189 Jewish Crohn's disease patients was conducted in order to evaluate the risk for inflammatory bowel disease (IBD) in relatives of the patients and to try to understand better the genetic component in the etiology of the disease among Jews. One hundred fifty-seven patients filled out questionnaires that were verified by personal interviews. In 10 families (6.6%), a first-degree relative of the propositus was found to have IBD, seven Crohn's disease and three ulcerative colitis. Among first-degree relatives, siblings were more frequently affected: of 400, five had Crohn's disease and one ulcerative colitis. Among 304 parents, two had Crohn's disease and two ulcerative colitis, while none of the propositi's children had IBD. The prevalence of first-degree relatives with Crohn's disease was similar in the 98 and 45 families of Ashkenazi and non-Ashkenazi origin: 5.1% and 4.4%, respectively. The risk for siblings of the probands to be affected were also similar in the two groups: 1.5% and 1.8%; while parents of the probands were affected only in the group of Ashkenazi Jews.

Adolescent↗

Comparison of the rates of adverse drug reactions. Ionic contrast agents, ionic agents combined with steroids, and nonionic agents.

The influence of ionic agents alone, of diatrizoate plus two oral doses of methylprednisolone premedication, and of a nonionic agent (iohexol) upon the frequency and severity of adverse drug reactions (ADRs) was compared in ten hospitals during three separate time periods from 1985 to 1989. Nonionic agents were found to reduce significantly total ADRs; 52 of 8857 patients receiving nonionic agents experienced reactions, versus 263 of 6006 patients for ionics (P less than .0001). The frequency of reactions classed as mild (2.9% for ionic agents versus 0.476 for nonionic agents: P less than .001), moderate (1.2% versus 0.1%; P less than .001), or severe (0.37% versus 0.01%; P less than .001), also favored nonionic agents. Steroid premedication provided some protection, but iohexol was significantly better with respect to mild reactions (2.9% versus 0.4%, P less than .001), moderate reactions (0.9% versus 0.1%, P less than .01), and severe reactions (0.25% versus 0.01%, P less than .01). The contrast medium was the greatest risk factor for adverse reaction (odds ratio 7.3), while prior contrast reaction (odds ratio 6.25), and hay fever (odds ratio 2.3) were found to be significant independent risks. We conclude that nonionic agents are safer for intravenous use than ionic agents given alone or with corticosteroid premedication.

Diatrizoate Meglumine↗