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Biomedical subjects

J Goldberg

Publications and source records attributed to J Goldberg.

At least 181 records · Page 10Linked to original sources

The impact of cigarette and alcohol consumption on weight and obesity. An analysis of 1911 monozygotic male twin pairs.

BACKGROUND: The objective of this investigation was to examine the relationships among cigarette and alcohol consumption and weight and obesity. Although previous research demonstrated that smoking is associated with reduced weight, data on the relationship between alcohol consumption and weight are conflicting. In addition, the influence of smoking cessation on the risk of obesity at a level that adversely affects health has not been fully examined. METHODS: By means of a cotwin-control research design, cigarette and alcohol consumption and weight measurements derived from 1911 male, monozygotic twins were compared with those of their identical siblings. This approach eliminates confounding from a large number of measurable and unmeasurable environmental experiences and the well-documented influence of inherited factors on weight and cigarette and alcohol consumption. RESULTS: After adjustment for a variety of socioeconomic factors, light (one to 19 cigarettes daily), moderate (20 to 29 cigarettes daily), and heavy (> 29 cigarettes daily) smokers were an average of 3.2, 2.4, and 4.0 kg lighter, respectively, than nonsmokers. Past smokers demonstrated a 33% higher prevalence of clinically significant obesity (body mass index > 27.8 kg/m2) by comparison with their currently smoking siblings (26.5% vs 19.9%, respectively; difference, P < .001) and a 1.8 times increased risk (95% confidence interval, 1.1 to 2.9) of clinically significant obesity by comparison with heavy smokers. By contrast, alcohol consumption had no significant influence on weight or obesity. CONCLUSIONS: Smoking cessation efforts provided by health practitioners to men should consider routinely offering a weight management component to reduce weight gain and further improve the well-documented health benefits of not smoking. It may not be necessary for alcohol treatment programs to adopt a similar policy.

Adult↗

A strategy for assembling samples of adult twin pairs in the United States.

In this paper we develop a methodology for the identification of large numbers of U.S. adult twin pairs. Data for this study derive from the U.S. Department of Defense and the Vietnam Era Twin (VET) Registry. The Department of Defense identified potential male twins (n = 10,002) using a computerized record linkage algorithm based on the same last name, same date of birth, and the same first five digits of the Social Security number. Twinship was confirmed by comparison with the Vietnam Era Twin Registry. We developed a logistic regression model that predicts the probability that a paired record identifies twins based on the absolute difference in the last four digits in the Social Security number, the age of issuance of the Social Security number, and the frequency of occurrence of the last name. We used the estimated coefficients derived from this regression model to assign predicted probabilities of being a twin to each matched record. There is a close correspondence between the observed and expected number of twins when evaluated across deciles of predicted probabilities of being a twin; the value of the Harrell's c index (c = 0.68 +/- 0.0004) indicates the overall predictive accuracy of the regression equation. The results from this study demonstrate the feasibility of identifying adult male-male twin pairs from any large computerized database that contains name, date of birth and Social Security number. However, the selection criteria used in the creation of the computer database must be clearly specified to avoid constructing a biased sample of twins.

Adult↗

A cohort study of stomach cancer risk in men after gastric surgery for benign disease.

BACKGROUND: For the past 40 years, investigators have suggested that there exists an increased risk of stomach cancer following gastric surgery for benign disease. Recent cohort studies have consistently identified an increased risk of stomach cancer beginning 20 years or more following gastric surgery. Validation of this association and elucidation of risk factors related to gastric cancer have been complicated by variability in study designs. PURPOSE: This cohort study was designed to investigate the risk of stomach cancer following gastric surgery and to identify patient and treatment characteristics that may alter this risk. METHODS: Medical admission records of 17077 male military veterans hospitalized during 1970-1971 in U.S. Department of Veterans Affairs (VA) hospitals were examined. From this initial cohort, 1094 patients who died within the 1st year following gastric surgery were excluded. Data analysis was performed on the final cohort consisting of 15,983 patients divided into the following two groups: 1) an exposed group (gastric surgery group) that included 7609 patients receiving gastric surgery for a documented benign disorder and 2) an unexposed group (comparison group) that included 8374 male patients randomly selected from all other hospitalized male patients in the patient database. The comparison group was matched to the gastric surgery group by age (within 10 years), race, hospital, and year of admission. Mortality follow-up utilized the following three sources to identify vital status: 1) the VA Patient Treatment File (1970-1988), 2) the VA Beneficiary Identification Record Linkage System (1970-1989), and 3) the National Death Index (1979-1988). Death certificates were obtained for 99% of the deceased patients. Analyses included estimations of risk using standardized rate ratios (SRRs) and proportional hazards techniques. RESULTS: A statistically significant increase in risk of stomach cancer was demonstrated among males during the 20 years following gastric surgery (SRR = 1.9; 95% confidence interval [CI] = 1.3-2.4; P = .0001). The risk of developing gastric cancer was greatest during the 2nd to 5th postoperative years (SRR = 2.8; 95% CI = 1.6-4.5; P < .01) and during years 11-15 (SRR = 2.5; 95% CI = 1.2-4.8; P < .01). Also, the risk of developing gastric cancer was greatest among those treated by gastrectomy for any type of ulcer (SRR = 2.6; 95% CI = 1.2-4.9; P < .01) and those having any type of gastric surgery when the primary diagnosis was gastric ulcer (SRR = 2.9, 95% CI = 1.4-5.3; P < .01). CONCLUSIONS: This study confirms that men undergoing gastrectomy for benign disease and men receiving any gastric surgery for gastric ulcer are at increased risk for developing gastric cancer. Unlike earlier studies, we find that the increased risk is not delayed for 20 years.

Adult↗

Discussion of preferences for life-sustaining care by persons with AIDS. Predictors of failure in patient-physician communication.

OBJECTIVES: To assess the determinants of communication about resuscitation between persons with acquired immunodeficiency syndrome (AIDS) and their physician. DESIGN AND SETTING: Structured patient interview at a staff-model health maintenance organization (HMO), an internal medicine group practice at a private teaching hospital, and an AIDS clinic at a public hospital. PATIENTS: 289 persons with AIDS. MAIN RESULTS: Only 38% of patients had discussed their preferences for resuscitation with their physician. Using logistic regression, we found that patients were less likely to have discussed resuscitation with their physician if they were nonwhite (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.24 to 0.99), had never been hospitalized (OR, 0.52; 95% CI, 0.27 to 0.99), or were cared for in the HMO (OR, 0.44 relative to the private teaching hospital; 95% CI, 0.23 to 0.82). Patients were more likely to have discussed their preferences if they were not currently taking zidovudine (OR, 1.76; 95% CI, 1.02 to 3.03) and if they had decided to defer life-sustaining therapy (OR, 2.30; 95% CI, 1.35 to 3.91). Among nonwhites, those with a nonwhite physician were more likely to have discussed resuscitation (OR, 4.38; 95% CI, 1.13 to 16.93). Of patients who had not discussed their preferences for life-sustaining care, 72% wanted to do so. Patient desire for discussion of this issue did not vary by race, severity of illness, hospitalization status, use of zidovudine, or site of care. CONCLUSIONS: A majority of persons with AIDS in this study had not discussed their preferences for life-sustaining care with their physician, despite the desire to do so. Interventions to improve patient-physician communication about resuscitation for nonwhites and other groups at risk of inadequate discussion might lead to clinical decisions that are more consistent with patient preferences.

Acquired Immunodeficiency Syndrome↗

Do genes influence exposure to trauma? A twin study of combat.

Data from 4,029 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975) were used to examine genetic and non-genetic factors that influence wartime exposure to traumatic events. Specific events examined were volunteering for service in Vietnam, actual service in Southeast Asia, a composite index of 18 combat experiences, and information from military records about being awarded combat decorations. Correlations within monozygotic (MZ) and dizygotic (DZ) twin pairs for volunteering for service in Vietnam were 0.40 and 0.22, respectively. For actually serving in Southeast Asia, the MZ correlation was 0.41 and the DZ correlation was 0.24. Analysis of twin pairs in which both siblings served in Southeast Asia (n = 820) demonstrated a correlation for self-reported combat experiences within MZ and DZ pairs of 0.53 and 0.30, respectively. Heritability estimates ranged from 35 to 47%. The family environment did not have a significant effect on any of the variables. Analyses of data from military records regarding being awarded a combat decoration provided very similar results to those found for self-reported combat experiences.

Adult↗

Arthrobacter D-xylose isomerase: protein-engineered subunit interfaces.

Mutants of Arthrobacter D-xylose isomerase were constructed in which one or two disulphide bridges or additional salt bridges were introduced at the A-A* subunit interfaces. These showed no change in enzyme activity or stability compared with the wild-type enzyme. However, a Tyr253 mutant in which a disulphide bridge was introduced at the A-B* subunit interface showed reduced thermostability that was identical in both oxidized and reduced forms, and also reduced stability in urea. X-ray-crystallographic analysis of the Mn(2+)-xylitol form of oxidized Y253C (the Tyr253-->Cys mutant) showed a changed conformation of Glu185 and also alternative conformations for Asp254, which is a ligand to the Site-[2] metal ion. With fructose, Mg(2+)-Y253C has a similar Km to that of the wild-type, and its Vmax. is also similar below pH 6.4, but declined thereafter. In the presence of Co2+, Y253C has lower activity than wild-type at all pH values, but its activity also declines at alkaline pH. These results suggest that electrostatic repulsion from the new position of Glu185 causes Asp254 to move when His219 is unprotonated, thereby preventing M2+ binding at Site [2]. These results also suggest that subunit dissociation does not lie on the pathway of thermal inactivation of D-xylose isomerase, but that movements of active-site groups are a trigger for conformational changes that initiate the unfolding process.

Aldose-Ketose Isomerases↗

A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms.

We studied 4042 Vietnam era veteran monozygotic and dizygotic male twin pairs to determine the effects of heredity, shared environment, and unique environment on the liability for 15 self-reported posttraumatic stress disorder symptoms included in the symptom categories of reexperiencing the trauma, avoidance of stimuli related to the trauma, and increased arousal. Quantitative genetic analysis reveals that inheritance has a substantial influence on liability for all symptoms. Symptoms in the reexperiencing cluster and one symptom in the avoidance and numbing cluster are strongly associated with combat exposure, and monozygotic pairs are more highly concordant for combat exposure than dizygotic pairs. By fitting a bivariate genetic model, we show that there are significant genetic influences on symptom liability, even after adjusting for differences in combat exposure; genetic factors account for 13% to 30% of the variance in liability for symptoms in the reexperiencing cluster, 30% to 34% for symptoms in the avoidance cluster, and 28% to 32% for symptoms in the arousal cluster. There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms.

Asia, Southeastern↗

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia.

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1 beta genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1 beta gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy.

Aged↗

Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study.

In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine. Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate.

Adult↗

Pre-admission clinic.

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Anesthesia Department, Hospital↗

Audit of intensive care unit admissions from the operating room.

An audit of 265 intensive care unit (ICU) admissions from the operating room was performed for the year 1991. In a quality assurance exercise we identified 34 unanticipated ICU admissions (UIAs) by a retrospective peer review of the medical charts. Of these UIAs, 16 were deemed predictable and seven preventable. Five of the seven potentially preventable UIAs were judged to have had inappropriate intravenous fluid management. This has prompted changes in our education programme. In an assessment of our resource management, we evaluated prospectively collected data on the Apache II scores on the day of admission, the incidence of ICU-specific interventions, length of stay in ICU, and outcomes. ICU-specific interventions were not initially required in 36% of admissions and these patients had a low risk (1.1%) of eventually requiring ICU-specific interventions. In comparison with patients requiring ICU-specific interventions, they had lower Apache II scores (10.2 vs 13.1), shorter ICU stays (medians of one vs two days), lower ICU mortality (0 vs 8.2%), P < 0.05, but hospital mortality was not different (7.4 vs 15.3%). This audit has prompted reorganisation of our intensive care services, so that patients not requiring ICU-specific interventions will be managed in an intermediate care area with nurse:patient ratios of 1:3 or 4, in comparison with 1:1 or 2 ratios in the intensive care area.

Ambulatory Surgical Procedures↗

The serial study of c-myc expression in bone marrow biopsy specimens during treatment for acute myelogenous leukaemia.

The AMEX method of fixation permitted the serial study of c-myc expression in bone-marrow (BM) biopsies obtained from 6 patients with acute myelogenous leukaemia (AML) and one with myelodysplastic syndrome (MDS) during therapy with various cytotoxic and bioactive agents. BM cytotoxic therapy and therapy with bioactive agents was capable of altering c-myc expression in vivo. While cytotoxic therapy was generally associated with a fall in myc expression, it did not produce a dramatic effect on myc expression. Recombinant human granulocyte-macrophage colony-stimulating factor (RhGM-CSF) can increase and retinoic acid/alpha-interferon can decrease c-myc expression in myeloid cells in vivo.

Adult↗

Undernutrition as a risk factor for cervical intraepithelial neoplasia: a case-control analysis.

To evaluate the relationship between cervical intraepithelial neoplasia (CIN) and undernutrition, a pair-matched case-control study was conducted in a low-income urban population. As a broad measure of nutritional status, serum albumin, serum ferritin, hematocrit, percent desirable weight, and percent calories consumed as protein were examined. Cases (n = 102) had biopsy-confirmed CIN I, II, or III, and clinic controls (n = 102), matched on age, race, and clinic, had normal Pap smears. Survey-collected data and frozen serum were utilized to study the hypothesized association. Crude and adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regressions. Results suggest a protective role for serum ferritin for those in the highest quartile relative to those in the lowest quartile. Controlling for smoking and monthly personal income, an adjusted odds ratio of 0.2 with a corresponding 95% confidence interval of 0.1-0.7 was observed. Similar findings were noted when all other available CIN risk factors were controlled. In addition, a dose gradient was present for dietary iron intake (p = 0.01). No associations were observed between each of the other undernutrition indexes and CIN. Although only high levels of serum ferritin were associated with a protective effect against CIN, when coupled with the results from other studies that suggest carotenoids, folates, and vitamin C to be protective, the overall hypothesis that poor nutriture is associated with CIN remains viable. Lack of an association with the other nutritional indexes may reflect the relatively sufficient nutritional status of low-income individuals residing in the United States, as opposed to the undernourished population of the Third World.

Adolescent↗

The toxicity of daily inhaled amphotericin B.

Inhaled amphotericin was administered to 29 patients with prolonged neutropenia and toxicity was analyzed. Treatment consisted of 30 mg of amphotericin B administered by nebulizer once daily via either a hand-held nebulizer or face mask. The mean duration of treatment was 16 days. Toxicity was minimal and patient had significant toxic reaction to the inhaled medication. This study documents that nebulized amphotericin B has less than 10% incidence of severe toxicity with 95% confidence level. Guidelines for future trials and use are suggested.

Administration, Inhalation↗

Long-term outcome of patients with acute myelogenous leukemia: the role of maintenance therapy, consolidation therapy and the predictive value of two in vitro assays.

Three successive strategies used to treat acute myelogenous leukemia (AML) patients who entered complete remission are compared with respect to their long term efficacy (> 5 years). Additionally, the ability of two in vitro assays to identify patients who would be long term remitters was assessed. With respect to the proportion of patients in long term remission, 5 years of maintenance therapy, intensive consolidation therapy plus 3 years of additional therapy, and 4 courses of consolidation therapy produced equivalent results with 18 to 22% of patients in remission at 7 years. Patients whose leukemia cells retained high levels of cytosine arabinoside triphosphate (araCTP) and who received maintenance therapy were less likely to experience early relapse than comparably treated patients whose leukemia cells failed to retain araCTP. The failure of leukemia cells to clone in vitro was also associated with a lower early relapse rate for patients who received maintenance therapy. Neither the ability of leukemia cells to retain araCTP nor their ability to clone in vitro were of prognostic significance for patients treated with 4 courses of intensive consolidation therapy.

Arabinofuranosylcytosine Triphosphate↗

Frequency of fetal anomalies in sonographically detected polyhydramnios.

One hundred and five patients who met the criterion of having an amniotic fluid pocket depth greater than 8.0 cm were categorized as polyhydramniotic. Of these cases, 82% were singleton pregnancies and 18% were twin pregnancies. The degree of polyhydramnios correlated directly with the probability that an anomaly would be detected. For the lowest rank group (pocket depth of 8 to 9.5 cm), 50% of fetuses manifested an anomaly, whereas the highest rank (16.0 cm or greater pocket depth) carried an 88% risk for an anomaly. Overall, 63% of pregnancies with polyhydramnios revealed anomalies. Sonography found all to be anomalous. There were three false diagnoses of potential anomalies. Monochorionic anomalies of twinning (twin transfusion syndrome and acardiac twin) and gastrointestinal anomalies among singletons were the most commonly seen abnormalities. However, a broad spectrum of anomalies was represented in the study group. Only five diabetic mothers were seen in our study cohort, and in each of them the pregnancy was further complicated by an associated fetal anomaly.

Brain↗

Pentostatin increases the acute toxicity of high dose cyclophosphamide.

One dose of pentostatin was added to a standard cyclophosphamide (CY) based transplant regimen in two patients in an attempt to decrease the rate of non-engraftment in haploidentical allogeneic BMT. Despite a normal cardiac history and evaluation prior to transplant, both patients suffered fatal cardiac toxicity within 48 h of receiving the chemotherapy. This phenomenon was further investigated in an animal model. Laboratory rats were treated with progressive doses of CY in a range that produces acute cardiac toxicity. Successive groups of rats were treated with either pentostatin or fludarabine and CY at 400 mg/kg. Neither pentostatin nor fludarabine alone produced early mortality. However, a marked increase in early mortality was noted in those animals treated with pentostatin and high-dose CY. The addition of fludarabine did not increase the early toxicity of CY. Autopsy revealed no gross or microscopic abnormalities in the animals. The implications of adding agents that interfere with adenosine metabolism to CY based transplant regimens is discussed.

Adult↗