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Biomedical subjects

J Zimmerman

Publications and source records attributed to J Zimmerman.

At least 91 records · Page 5Linked to original sources
PubMed1991

The beginning development of a model for joint research between a hospital social work department and a school of social work.

Efforts of agencies and schools of social work to encourage goals of research and professional writing among their staff and faculty have brought uneven results. A medical center and a graduate school of social work are in the process of implementing a joint research model which encourages practice based research and publication. This paper describes the beginning structures of the model and the questions addressed in the formative process.

Humans↗
PubMed1991

Crohn's colitis complicated by superimposed invasive amebic colitis.

The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD.

Adult↗
PubMed1991

Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency.

The diuretic drug triamterene has previously been shown to be a competitive inhibitor of folate absorption in the rat intestine (J Lab Clin Med 1986;108:272-6). We therefore investigated whether human subjects who are taking the drug on a long-term basis are at increased risk of folate deficiency. In each of two free-living populations, a study was performed to compare the folate status of triamterene users with those not taking the drug. The first population consisted of 272 elderly individuals not living in institutions who were participants in a nutrition status survey and who were taking a variety of antihypertensive medications; 32 of these individuals were daily users of triamterene. The hemoglobin concentration, red blood cell (RBC) count, and mean corpuscular volume (MCV) values were not significantly different between the triamterene users and nonusers. The female triamterene users had a slightly higher serum folate level than the female nonusers (p less than 0.04); a similar pattern was observed among the men, although the difference was not statistically significant. The second population consisted of 27 individuals attending a hypertension clinic; 18 subjects were taking 50 to 150 mg of triamterene per day and nine were taking antihypertensive drugs other than triamterene. The hemoglobin concentration, RBC count, MCV, serum folate values, and RBC folate values were found to not differ significantly between the triamterene users and the hypertensive controls (p greater than 0.05). These data suggest that chronic triamterene administration in individuals not living in institutions, at the doses examined in this study, is not associated with indications of folate deficiency.

Aged↗
PubMed1990

Folic acid transport in organ-cultured mucosa of human intestine. Evidence for distinct carriers.

The transport of folic acid was investigated in organ-cultured endoscopic biopsy specimens of intestinal mucosa from normal subjects. In the proximal small intestine at pH 5.5 and 6.5, [3H]folic acid accumulated to concentrations 2.64- and 2.17-fold higher than those of the medium, respectively, but at pH 7.5 the concentration was same as that of the medium. Saturability of initial rates of uptake was demonstrable with respect to luminal concentrations of [H+] and folic acid. Two proton-dependent transport mechanisms were evident: (a) a carrier with a low affinity for H+ and a low capacity for folic acid, and (b) a high-affinity, high-capacity carrier (Km, 635 and 54.6 nmol/L [H+]; Vmax, 0.066 and 2.583 pmol folic acid/microL intracellular water per 10 minutes, respectively). Kinetic studies of folic acid uptake at pH 5.5 and 7.5 revealed a difference in Km for folic acid (15.76 and 34.38 mumol/L, respectively) with no change in Vmax. In the colon, folic acid did not accumulate against a concentration gradient, and the initial rate of uptake was not affected by luminal pH. The accumulation of folic acid in colonic mucosa was significantly higher at pH 5.5 than at 7.5 and showed significant regional variation, with optimal uptake in the sigmoid colon. Methotrexate inhibited folic acid uptake competitively both in the proximal small intestine and in the cecum (inhibition constant 6.9 and 54 mumol/L, respectively, at pH 5.5). These data indicate the presence of a proton-dependent, active transport of folic acid in the proximal small intestine at pH 5.0-6.5. At pH 7.5 and in the mucosa of the colon, uptake of folic acid proceeds by facilitated diffusion through a low-affinity carrier.

Biological Transport, Active↗
PubMed1990

The effects of testicular trauma on fertility in the Lewis rat and comparisons to isoimmunized recipients of syngeneic sperm.

Adult male Lewis (LEW) rats were used to investigate the effects of unilateral testicular trauma on fertility. Comparisons were made between normal and experimental rats immunized with syngeneic sperm in Complete Freund's Adjuvant (CFA). Matings within the three groups yielded offspring to all normal males, no offspring to the immunized rats, and 27% (3/11) fertility in the trauma group (p less than 0.001). The contralateral testis demonstrated decreased volumes, various degrees of aspermatogenesis and smaller seminiferous tubular diameters, in both the trauma and immunized groups compared to the controls. Similar histopathologic findings of chronic granulomatous inflammation within contralateral testes in both the trauma and immunized groups suggested a common immune etiology for infertility via possible disruption of the blood-testis barrier.

Animals↗
PubMed1990

Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome.

HA-1A, a human monoclonal immunoglobulin M antibody that binds specifically to the lipid A domain of endotoxin, was administered to septic patients to evaluate the safety, pharmacokinetics, and immunogenicity of the antibody. Thirty-four patients received a single infusion of either 25 mg, 100 mg, or 250 mg, and were followed clinically for 14 to 21 days after treatment. HA-1A serum levels were measured before infusion and frequently after infusion with a radiometric assay. A one-compartment pharmacokinetic model was fit to the measured serum levels, and accurately described the changes in HA-1A level over time in each dose group (r2 = .99). The mean +/- SEM apparent volume of distribution of HA-1A was 48.5 +/- 4.5 ml/kg, and the mean serum clearance was 2.8 +/- 0.4 ml/kg.h. The mean serum half-life of HA-1A was 15.9 +/- 1.5 h. The mean serum level one hour after a 100-mg dose was 33.2 +/- 2.4 micrograms/ml, and the mean concentration 24 h later was 9.1 +/- 1.6 micrograms/ml. The dose administered and presence of Gram-negative bacterial infection did not significantly influence the volume of distribution or serum clearance. No adverse reactions to HA-1A were observed, and no antibodies against HA-1A were detected in any patient. These data indicate that the pharmacokinetics of HA-1A are well described by a one-compartment pharmacokinetic model, and that HA-1A is safe and nonimmunogenic in patients with sepsis.

Adult↗
PubMed1990

Rectal administration of nonsteroidal antiinflammatory drugs. Effect on rat gastric ulcerogenicity and prostaglandin E2 synthesis.

Oral administration of nonsteroidal antiinflammatory drugs induces gastroduodenal mucosal damage in experimental animals as well as in humans. The aim of the present study was to evaluate the effect of rectally administered nonsteroidal antiinflammatory drugs on gastric mucosal damage, as well as on mucosal prostaglandin E2 synthesis. Fasting male rats were treated intrarectally with 0.5 ml 1% NaHCO3 solution containing several concentrations of either indomethacin, aspirin, ibuprofen, diclofenac, ketoprofen, or sulindac and concomitantly received 1 ml of 150 mM HCL intragastrically. Control rats received intrarectally the vehicle only. After 4 h, lesions in the secretory part of the stomach were scored and mucosal prostaglandin E2 synthesis was determined by the ex vivo prostaglandin generation technique. Dose-dependent mucosal damage was observed in indomethacin- and diclofenac-treated rats. Ketoprofen damage did not show dose dependency. In sulindac- and aspirin-treated rats, as well as in controls, no damage was detected. All drugs induced a significant and comparable degree of inhibition of prostaglandin E2 synthesis. There was no correlation between the severity of the mucosal damage and the inhibition of prostaglandin E2 synthesis. The ulcerogenicity of rectally administered nonsteroidal antiinflammatory drugs is therefore not directly related to the degree of inhibition of prostaglandin E2 synthesis and is probably related to the specific chemical and pharmacokinetic properties of each individual drug.

Administration, Rectal↗
PubMed1989

Absolute bioavailability and noncompartmental analysis of intravenous and intramuscular Cefotan (cefotetan) in normal volunteers.

Cefotetan (1 g) was administered to 12 normal volunteers as a 30 minute intravenous infusion and as an intramuscular injection. The pharmacokinetic parameters were estimated using noncompartmental analysis. The mean +/- SD maximum plasma concentration, terminal half-life, and systemic clearance after intravenous infusion were 158 +/- 21 micrograms/mL, 4.54 +/- 1.05 hours, and 29.1 +/- 3.8 mL/min/1.73 m2, respectively. Renal clearance and nonrenal clearance accounted for 63.1% and 36.9% of the systemic clearance, respectively. The mean +/- SD maximum plasma concentration, time to maximum concentration, terminal half-life, and absolute bioavailability after intramuscular injection were 75.5 +/- 8.7 micrograms/mL, 1.33 +/- 0.48 hours, 4.32 +/- 0.77 hours, and 0.931 +/- 0.193, respectively. Moment analysis gave average +/- SD mean residence times (MRT) of 4.98 +/- 0.75 and 5.86 +/- 0.77 hours after intravenous and intramuscular administration, respectively. The average +/- SD mean absorption time (MAT) after intramuscular injection was 1.11 +/- 0.57 hours. The mean +/- SD steady-state volume of distribution after intravenous infusion was 0.129 +/- 0.024 L/kg. The mean +/- SD cumulative percentage of the dose excreted in the urine in 24 hours were 61.1 +/- 11.4% and 50.4 +/- 13.5% after intravenous and intramuscular dosing, respectively. The maximum urinary cefotetan concentrations occurred during the first 2 hours after dosing by both routes of administration. Cefotetan tautomer was detected in the plasma and urine of all subjects after both routes of administration, but the mean concentrations were only minimal compared to those for cefotetan. In conclusion, intramuscular cefotetan (1 g) is rapidly and almost completely absorbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

H2-antagonist inhibition of human neutrophil superoxide anion synthesis.

In the mmol/L concentration range, cimetidine and ranitidine suppress superoxide anion generation by isolated intact human neutrophils. However, at normal pharmacologic concentrations in the mumol/L range, even prolonged exposure of neutrophils to these agents has no demonstrable effect on toxic oxygen species synthesis. In vitro inhibition does not involve neutrophil activation-densensitization or neutrophil cytotoxicity and is reversible to a great extent by drug washout. In the examination of possible free-radical scavenging action of these drugs, it was demonstrated that both drugs inhibit superoxide anion production by xanthine oxidase but not by chelated iron. This raises the possibility that these agents may bear structural similarities to oxypyrazolopyrimidines such as allopurinol.

Cimetidine↗
PubMed1989

Atypical auricular pyoderma gangrenosum simulating fungal infection.

We describe a patient with a highly unusual appearance of pyoderma gangrenosum. The pyoderma was located on the auricular region and preceded other manifestations of inflammatory bowel disease by 11 years. There was no correlation between the course of the pyoderma and the clinical activity of the associated bowel disease. Mycotic superinfections masked and delayed the diagnosis in our patient for several years. Only when typical pyoderma gangrenosum lesions developed on the legs at the site of trauma and responded dramatically to systemic corticosteroids was the correct diagnosis established. Pyoderma gangrenosum with secondary fungal infection was thus distinguished from deep ulcerated skin fungal infection simulating pyoderma.

Adult↗
PubMed1989

Kinetic analysis of the effect of luminal pH on transport of folic acid in the small intestine.

Transport of folic acid in the small intestine is markedly affected by luminal pH and is optimal at pH 5.5-6.5. To clarify the nature of this pH sensitivity, we measured transport of [3H] folic acid into rat jejunum at pH 5.5 and 7.4, at folic acid concentrations of 1 to 30 microM, using the influx chamber method. At this range of concentrations, uptake of folic acid exhibited Michaelis-Menten kinetics. In order to determine the kinetic parameter which is pH sensitive, we have fitted a modified Michaelis-Menten equation to the pooled data at the two pH conditions such as they share a common Vmax but distinct Km values. This model fitted closely the experimental data (F = 0.693), yielding Km values (+/- SE) of 24.22 (+/- 5.96) and 36.32 (+/- 8.73) microM for pH 5.5 and 7.4 respectively. The difference in the Km at the two pH conditions was statistically significant (p less than 0.01). The change in affinity for folic acid transport at the two pH conditions may reflect different membrane carriers, or may be due to protonation of a membrane carrier and/or the folic acid molecule, favored at low pH.

Acid-Base Equilibrium↗