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Biomedical subjects

M Gottlieb

Publications and source records attributed to M Gottlieb.

At least 37 records · Page 2Linked to original sources
PubMed1997

Breast cancer and pesticides in Hawaii: the need for further study.

Only 30% of all breast cancer can be explained by known risk factors. Increases in breast cancer incidence rates in Hawaii over the past few decades cannot be attributed solely to improvements in screening and detection. Avoidable environmental factors may contribute to a proportion of the unexplained cases. Emerging evidence on endocrine disruption suggests that environmental chemicals may play a role in the development of breast cancer. Agricultural chemicals, including endocrine disruptors, have been used intensively in Hawaii's island ecosystem over the past 40 years leaching into groundwater, and leading to unusually widespread occupational and general population exposures. This paper discusses breast cancer patterns in Hawaii in the context of documented episodes of exposure to two endocrine-disrupting chemicals, chlordane/heptachlor and 1,2-dibromo-3-chloropropane (DBCP), at levels that sometimes exceeded federal standards by several orders of magnitude. In light of this history, detailed geographic-based studies should be undertaken in Hawaii to elucidate the potential role of environmental factors in the development of breast cancer and other diseases.

Adult↗
PubMed1996

Traumatic hypothermia is related to hypotension, not resuscitation.

STUDY OBJECTIVE: To determine whether posttraumatic hypothermia is associated with hemorrhage or with resuscitation. METHODS: We used a sequential hemorrhage-resuscitation rat model. Rats were subjected to hemorrhage (30 mL/kg), then 1 hour of shock, followed by 2:1 crystalloid/blood resuscitation (60 mL/kg) at ambient temperature. A control group underwent neither hemorrhage nor resuscitation. RESULTS: We recorded core temperature and blood pressure every 10 minutes. Temperature drop averaged 3.4 degrees C and was fastest during hypotensive shock. Rate of temperature change correlated with blood pressure (beta = .0102, P < .001), shock phase (beta = .4504, P = .041), and blood pressure during shock phase (beta = .0116, P < .001), but not with resuscitation phase or with duration of shock or resuscitation. Three of 14 rats died during shock, none during resuscitation. An increase in temperature was noted in 1 of 14 rats during shock and in 7 of 11 rats during resuscitation. CONCLUSION: Hemorrhage-associated hypothermia occurs during hypotensive shock, not during fluid resuscitation.

Animals↗
PubMed1996

Ischemic damage in the hippocampus: a silver impregnation and immunocytochemical study in the rat.

Wistar rats were subjected to transient forebrain ischemia for 30 min. After a survival period of two to three days their brains were fixed and sections were processed for Nauta suppressive method (26) to study postischemic degenerative changes and for glial fibrillary acidic protein (GFAP) to study glial reaction. After two days somatodendritic argyrophilia was evident in the CA1a and CA4 areas. The somata and dendrites of CA1 a pyramidal neurons were intensely argyrophilic, and a clear border zone which separated these neurons from undamaged CA1b neurons was detected. In the CA4 area a few degenerating, probably mossy cells were found. Neuronal degeneration then proceeded rapidly during a 72 h survival period, when the somata and dendrites of complete CA1 and CA2 pyramidal cells became intensively argyrophilic. The area of CA4 was full of degenerated neurons, but the CA3 neurons remained intact. Postischemic glial changes were observed after 48h survival. The rostral part of CA1a area contained a higher concentration of astrocytes in the dendritic layer as well as in the pyramidal layer. These astrocytes revealed features of reactive astrocytes. An intense GFAP immunoreactivity with heavily stained astrocytic figures appeared in the CA2, CA3 dendritic layers, stratum molecular of the DG and hilus. The central region of CA4 area contained various vacuoles with clearly stained astrocytes. By 72 h after ischemia the tissue structure changed in all areas since the pyramidal layer contained shrunken neurons and large vacuoles. The GFAP immunoreactivity in the hippocampus was the same or even higher as observed after two days postischemia, but the astrocytes were seen more closely in the relation with the pyramidal cell layer.

Animals↗
PubMed1995

Anemia is prevalent in an urban, African-American adolescent population.

OBJECTIVE: To determine the prevalence of anemia in urban indigent African-American adolescents. DESIGN: Cross-sectional sample of hemoglobin values. SETTING: School-based clinic and health fair in an inner-city, predominantly African-American public high school. SUBJECTS: Ninety-nine adolescents presenting for preparticipation athletic physical examinations between August and December 1990 and 76 adolescents participating in screening activities at a high school health fair on March 12, 1991. METHODS: Finger-stick and venipuncture hemoglobin samples were obtained from presumably healthy adolescents. The percentage of anemic students was determined by means of a hemoglobin cutoff of less than 120 g/L, and with the exclusion of samples from pregnant students or those positive for sickle cell trait or disease. MAIN OUTCOME MEASURES: Hemoglobin values in 169 students. RESULTS: The mean +/- SD hemoglobin level for girls was 115 +/- 15 g/L; 50% of the girls had hemoglobin levels less than 120 g/L. The mean hemoglobin level for boys was 129 +/- 13 g/L; 16.5% of boys had hemoglobin levels less than 120 g/L. CONCLUSION: Anemia may be a common condition in inner-city African-American adolescents.

Adolescent↗
PubMed1995

Crithidia luciliae: effect of purine starvation on S-adenosyl-L-methionine uptake and protein methylation.

The utilization of S-adenosyl-L-[methyl-3H]methionine ([3H-methyl]AdoMet) by Crithidia luciliae was assessed under nutrient-replete and purine-starvation conditions. Uptake experiments with intact cells demonstrated that the radiolabel from this molecule was accumulated by purine-starved organisms at a rate approximately 10-fold greater than that observed in those cultivated in nutrient-replete medium. Purine-starved cells also incorporated the radiolabel into trichloroacetic acid insoluble material at an approximately 10-fold faster rate than nutrient-replete cells. No differences, however, were observed in the intracellular levels of AdoMet and its metabolites between organisms cultivated under the two conditions. Results of comparative labeling studies with [3H-methyl]AdoMet, S-adenosyl-L-[carboxyl-14C]methionine, L-[methyl-3H]methionine and L-[35S]methionine in the presence and absence of cycloheximide demonstrated that the incorporation of label from [3H-methyl]AdoMet was due to transmethylation and was independent of protein synthesis. Further, approximately 15 methylated protein bands were identified by SDS-PAGE analysis. Lysates from both purine-starved and nutrient-replete organisms demonstrated similar levels of activity of three protein methyltransferases (PMI, II, III). The differences observed in [3H-methyl]AdoMet utilization between purine-starved and nutrient-replete C. luciliae may reflect the enhanced purine transport capacity which results from purine starvation.

Adenosine↗
PubMed1995

Isolation and characterization of the gene encoding the surface membrane 3'-nucleotidase/nuclease of Leishmania donovani.

Leishmania donovani and related trypanosomatid protozoa possess an externally oriented surface membrane enzyme capable of hydrolyzing both 3'-nucleotides and nucleic acids. By virtue of these activities, this 3'-nucleotidase/nuclease (3'-NT/Nu), previously shown to be analogous to fungal and plant class-I single-strand-specific nucleases, is thought to play a critical role in the salvage of purines, essential for the survival of these organisms. The 43-kDa 3'-NT/Nu was purified from L. donovani promastigotes and trypsin treated. Four of the released tryptic peptide fragments yielded amino-acid sequence information (Pept-1 to Pept-4) which provided the basis for the preparation of oligonucleotide primers used for PCR amplification of an approx. 300-bp DNA fragment. This fragment was cloned, sequenced and used to probe a genomic L. donovani cosmid library. Nucleotide sequence analysis of a 4.5-kb SmaI fragment, isolated from a cosmid clone, revealed an open reading frame (ORF) of 1434 nt encoding a 477-amino-acid protein. Pept-1 to Pept-4 were mapped onto the ORF-deduced protein sequence. Peptides corresponding to Pept-1 to Pept-4 were synthesized and used to immunize rabbits. The resulting anti-peptide antibodies recognized the 43-kDa protein on Western blots and immunoprecipitated the native 3'-nucleotidase activity from L. donovani membrane extracts. Further, the ORF-deduced protein shared significant sequence identity with the S1 and P1 fungal nucleases of Aspergillus oryzae and Penicillium citrinum, respectively. Cumulatively, these results demonstrated that the ORF corresponded to a gene for the L. donovani 3'-nucleotidase/nuclease. In Northern blots a nucleotide probe specific for the 3'-NT/Nu gene hybridized to a single 2.5-kb messenger RNA. Results of Southern blot analyses were consistent with the 3'-NT/Nu being encoded by a single copy gene. These data constitute the first report of the gene for this unique trypanosomatid surface membrane enzyme.

Amino Acid Sequence↗
PubMed1994

Willingness to perform euthanasia. A survey of physician attitudes.

BACKGROUND: In the United States, few studies have examined important variables in physician attitudes toward the practice of euthanasia, such as the patient's underlying disease, mental capacity, and age, and the physician's specialty and religion. We administered a case-based survey to analyze the impact of such specific variables on physician attitudes toward the practice. METHODS: A four-section survey solicited (1) physician responses to three hypothetical cases in which patients requested euthanasia; (2) physicians' general opinions about euthanasia and how its legalization might affect them personally and professionally; and (3) demographic information. Analysis focused on physicians' characteristics as they related to their responses to the various aspects of euthanasia elicited in the survey. Univariate and multivariate analyses, using logistic regression, were performed. RESULTS: Completed and analyzable surveys were returned by 740 physicians. We found that physicians felt more comfortable with euthanasia requests from nondecisional, nonterminal patients who had left advance directives than they did with requests from decisional patients suffering from grave illnesses or injuries, or from decisional patients who had early signs of a progressive but nonlethal neurologic disease. We also found that physicians' specialties and religions correlated with their responses to the hypothetical cases and with their generalized attitudes toward euthanasia. CONCLUSIONS: Given the disparity in responding physicians' attitudes toward euthanasia, along with the fact that values based on religious affiliation or profession may underlie many physicians' opposition to the practice, we conclude that if euthanasia is to be legalized, safeguards protective of patients and physicians must be incorporated.

Adult↗
PubMed1993

Effect of postischaemic recirculation on DNA synthesis in vulnerable rat brain regions.

Incorporation of labelled thymidine into DNA of different rat brain regions was studied after 30 min of forebrain ischaemia and recirculation periods up to 24 hours. The amount of label incorporated into DNA showed a different pattern in the brain. After 1 hour of recirculation, the incorporation was reduced in the cortex and in the striatum, without any significant change in the hippocampus. After 3 to 9 hours the incorporation remained depressed in the cortex, diminished in the hippocampus, and increased by 2-2.5 fold in the striatum. Later, after 24 hours, the DNA labelling returned to control values in the striatum and in the cortex, but was increased in the hippocampus.

Animals↗
PubMed1993

Effect of postischaemic recirculation on DNA synthesis in vulnerable rat brain regions.

Incorporation of labelled thymidine into DNA of different rat brain regions was studied after 30 min of forebrain ischaemia and recirculation periods up to 24 hours. The amount of label incorporated into DNA showed a different pattern in the brain. After 1 hour of recirculation, the incorporation was reduced in the cortex and in the striatum, without any significant change in the hippocampus. After 3 to 9 hours the incorporation remained depressed in the cortex, diminished in the hippocampus, and increased by 2-2.5 fold in the striatum. Later, after 24 hours, the DNA labelling returned to control values in the striatum and in the cortex, but was increased in the hippocampus.

Animals↗
PubMed1992

Blood transfusion and postoperative infection in orthopedic patients.

Adverse effects of the transfusion of homologous blood on tumor recurrence and resistance to bacterial infection have been reported previously, but the findings are inconclusive. A retrospective review of patients undergoing orthopedic surgery was conducted, and the rate of the postoperative infectious complications was compared among those receiving homologous blood, autologous blood, both types, or no transfusion support. An overall postoperative infection rate of 6.1 percent was observed: 6.9 percent among persons receiving homologous blood, 5.0 percent among those receiving autologous blood, 11.9 percent among those receiving both homologous and autologous blood, and 4.9 percent among those not receiving transfusions (p = 0.37). Among patients receiving homologous blood, a subset of 15 patients received homologous whole blood and had an infection rate of 20 percent. Significant predictors of postoperative infection included increasing age, spinal surgery, high admission hematocrit, and greater time in surgery. Of factors relating to transfusion, only the use of homologous whole blood was a significant predictor of postoperative infection, which suggests a detrimental effect of homologous plasma. It can be concluded that, in this group of patients undergoing relatively nontraumatic surgery, several variables that are not related to transfusion, as well as the use of homologous whole blood, were significant predictors of postoperative infection.

Bacterial Infections↗
PubMed1992

Basic epidemiologic and statistical methods in clinical research.

Various study designs and approaches to statistical analysis in clinical research have their own underlying rationales and limitations for interpretation. This information is presented in an intuitive and accessible manner, relying minimally on basic algebra. Epidemiologic concepts of study design and interpretation, bias and confounding, hypothesis testing, and sample size and power are explained. Statistical tests and their appropriate applications are discussed for mean comparisons (t tests and ANOVA), percentages (chi-square), survival analysis, and correlation and regression. Applicable nonparametric tests are also introduced.

Carcinoma, Transitional Cell↗
PubMed1991

Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study.

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m2 orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4+ cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to Pneumocystis carinii pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Low-dose amphotericin B prophylaxis against invasive Aspergillus infections in allogeneic marrow transplantation.

PURPOSE: Invasive Aspergillus infections cause significant morbidity and mortality in marrow transplant patients. In this study, we examined whether administration of intravenous low-dose prophylactic amphotericin B could reduce the incidence and mortality associate with invasive aspergillosis in patients undergoing allogenic marrow transplantation. PATIENTS AND METHODS: The subjects of this analysis were 186 consecutive patients undergoing allogeneic marrow transplantation in an adult bone marrow transplant unit between July 1, 1985, and September 30, 1990, utilizing consistent disease-specific chemoirradiation and graft-versus-host disease protocols. The incidence, morbidity, and case fatality of invasive aspergillosis in the study group receiving amphotericin chemoprophylaxis were compared with that in two historic cohorts managed without prophylactic amphotericin B. Univariate and multivariate statistical analyses were performed to examine whether an apparent protective effect could be attributed to differences in patient and treatment variables among the cohorts and to determine potential toxicities of the chemoprophylaxis regimen. RESULTS: There was a significant reduction in both the incidence (p = 0.003) and mortality (p = 0.03) of invasive aspergillosis in patients receiving amphotericin B chemoprophylaxis as compared with those not receiving chemoprophylaxis. The prophylactic amphotericin B schedule, as employed here, was not associated with increased renal or hepatic toxicity as compared with that in historically managed patients. CONCLUSION: These data suggest that the risks of invasive aspergillosis in allogeneic marrow transplant recipients can be reduced by administration of prophylactic amphotericin B during the pretransplant and peritransplant periods.

Adolescent↗
PubMed1991

Purification and characterization of the 3'-nucleotidase/nuclease from promastigotes of Leishmania donovani.

The surface membrane-associated 3'-nucleotidase/nuclease (3'-N'ase) of Leishmania donovani has been purified from detergent extracted promastigotes by anion and cation exchange, lectin affinity and gel filtration chromatography. SDS-PAGE analysis of the purified enzyme preparation revealed a 43-kDa polypeptide as well as faster migrating bands. These bands co-migrated, following both one- and two-dimensional electrophoretic analyses, with enzyme activity as determined by an in situ 3'-nucleotidase gel activity assay. It is suggested that the lower molecular weight species arise during purification as a result of proteolytic cleavage of the intact 43-kDa enzyme. The 3'-N'ase exhibited a pI of 5.4, as revealed by 2-dimensional gel electrophoresis. The glycoprotein nature of the 3'-N'ase was suggested by its binding to concanavalin A and by its electrophoretic shift following incubation with N-glycanaseR. In nucleotidase and nuclease assays, the 3'-N'ase was most active with 3'-AMP and poly(A), respectively. Both nucleotidase and nuclease activities exhibited broad pH optima with peaks at 8.5 and 7.5, respectively. At pH 8.5 nucleotidase activity was inhibited by EDTA, Zn2+ and thiols, but was insensitive to tartrate, molybdate and fluoride ions, commonly used inhibitors of phosphatases. The properties of the leishmanial 3'-N'ase was similar to the 3'-N'ase purified from purine-starved Crithidia luciliae, a related trypanosomatid protozoan, and to group of nucleases from fungi and germinating plant seedlings.

5'-Nucleotidase↗
PubMed1991

Chronic effects of focused electrohydraulic shock waves on renal function and hypertension.

The chronic effects of focused electrohydraulic shock waves were studied in a minipig model. Fifteen animals underwent a unilateral nephrectomy and compensatory renal hypertrophy was allowed to take place over a minimum of six months. Baseline studies were then carried out consisting of 1) serum creatinine, blood urea nitrogen, and plasma renin levels 2) intra-arterial blood pressure measurement and 3) 3H-inulin clearance. Ten of the animals then underwent 8 shockwave treatments (2500 shocks per treatment), alternately to the upper and lower pole of the kidney, at two weeks intervals. A total of 20,000 shock waves were administered to each minipig over the four month period. The five control pigs underwent sham procedures. The renal function and blood pressure evaluations were then repeated. No significant decrease in renal function was noted in the experimental animals when compared to the controls. In addition, renin mediated hypertension was not observed despite the excessive number of total shock waves delivered to the kidney.

Animals↗