Biomedical subjects
Publications and source records attributed to J Schwartz.
Patients undergoing photopheresis are required to ingest the drug 8-MOP as part of their treatment. This drug causes nausea as a side effect. Ginger taken prior to 8-MOP may substantially reduce this side effect. This study compared patients' nausea when taking 8-MOP with and without ginger.
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Varicella, usually a benign infection of childhood, is known to be associated with more serious complications, especially in adults and immunocompromised patients. Of these, varicella pneumonitis is the most common. Primary varicella hepatitis has been described, though rarely, in immunocompromised patients. We present a case of a previously healthy human immunodeficiency virus-negative 26-year-old immigrant from El Salvador in whom primary varicella developed that rapidly progressed to fulminant hepatic failure, disseminated intravascular coagulation, and death. Autopsy revealed evidence of varicella in the liver, adrenal glands, and myometrium. To our knowledge, this is the first report of a fatal case of varicella hepatitis in a previously healthy, immunocompetent patient.
Earlier studies of a site-specific mutant of protein kinase C beta 1 (PKC beta 1) altered at Thr635 and Thr642 indicated that these phosphorylation sites are critical for enzymatic function (Zhang, J., Wang, L., Petrin, J., Bishop, W. R., and Bond, R. W. (1993) Proc. Natl. Acad. Sci. U.S.A. 90,6130-6134). To determine the contribution of the individual threonines, we report here on two site-specific mutants in which either Thr635 or Thr642 was changed to alanine. When transiently overexpressed in Cos cells wild-type PKC beta 1 exists in two forms: a Triton-insoluble form with high electrophoretic mobility and a slower migrating Triton-soluble form. Mutation at Thr642 (but not Thr635) results in production of only the fast-migrating form. [35S]Methionine pulse-chase labeling indicates that wild-type PKC beta 1 is synthesized as the fast-migrating form and is subsequently converted to the slow-migrating form. 32P labeling shows that only the slow-migrating form is a phosphoprotein. Mutation of Thr642 abolishes this phosphorylation. Finally, the Thr642 mutant PKC beta 1 lacks enzymatic activity and, when expressed in NIH 3T3 cells, reduces phorbol ester-induced c-fos promoter activity. These results indicate that Thr642 phosphorylation is an early event in the processing of newly synthesized PKC beta 1 and is required for enzymatic function. These results support a role for a PKC kinase in PKC processing and activation.
Several studies have reported associations between airborne particles and/or ozone and hospital admissions for respiratory disease. This study examined whether such an association could be seen in Birmingham, Alabama, one of the few cities in the United States with daily monitoring of inhalable particles. Daily counts of hospital admissions were computed by date of admission from Medicare records for pneumonia and chronic obstructive pulmonary disease for the years 1986-1989. Classification was by discharge diagnosis. The daily average of ozone and particulate matter with an aerodiameter of < or = 10 microns (PM10) from all monitoring stations in Birmingham was computed. Approximately six admissions for pneumonia and two for chronic obstructive pulmonary disease were observed each day. In Poisson regression analysis controlling for time trends, seasonal fluctuations, and weather, inhalable particles were a risk factor for admission for pneumonia (for an increase of 100 micrograms/m3 in daily concentration, relative risk (RR) = 1.19, 95% confidence interval (CI) 1.07-1.32) and chronic obstructive pulmonary disease (RR = 1.27, 95% CI 1.08-1.50). The results were not sensitive to alternative methods for controlling for seasonal patterns and weather, nor to the exclusion of very hot or cold days. Ozone was more weakly associated with admissions for pneumonia, with a 2-day lag (RR = 1.14, 95% CI 0.94-1.38), and for chronic obstructive pulmonary disease, with a 1-day lag (RR = 1.17, 95% CI 0.86-1.60). The risks are for an increase in ozone exposure of 50 parts per billion. Tests for nonlinearity in the relation between inhalable particles and admissions were not significant, and nonparametric smoothing found no evidence of a threshold in the relation.
Signaling mechanisms leading to regulation of gene transcription by growth hormone (GH) and other molecules that signal via the cytokine receptor family have been elusive. Based upon recent findings that GH and interferons activate JAK family tyrosine kinases, we have identified a novel signaling pathway leading from the GH receptor to the nucleus. We report that in 3T3-F442A fibroblasts, GH stimulates tyrosyl phosphorylation of a protein recognized by antibody to p91, a component of DNA-binding complexes that are activated by tyrosyl phosphorylation in response to interferons alpha and gamma. In addition, a GH-inducible DNA binding factor (GHIF) is identified that binds to the c-sis-inducible element of the c-fos promoter. GHIF contains a protein antigenically related to p91 and is tyrosyl-phosphorylated. These findings indicate that in signaling between their receptors and the nucleus, GH and interferons utilize related or identical components, including JAK family tyrosine kinases and proteins in the p91 family. When combined with recent findings that many members of the cytokine receptor family activate JAK kinases, including some cytokines that activate p91-related proteins, these findings suggest that signaling pathways involving JAK kinases and p91 family members may be broadly distributed.
The air pollution disasters in London in 1952, the Meuse valley in 1930, and in Donoroa, Pennsylvania, in 1948 made it clear that extremely high levels of particulate-based smog could produce large increases in the daily mortality rate. Recent studies of fluctuations in daily air pollution and daily mortality have reported associations at much lower concentrations in London during the 1960s and in Philadelphia, Steubenville, Santa Clara, St. Louis, Utah valley, Detroit, and eastern Tennessee in the 1970s and 1980s. Whether these associations are causal or not is a matter of considerable public health concern. If the detailed pattern of the deaths at these lower concentrations appeared similar to the pattern in London, this would strengthen the argument for causality. To examine this issue, the death certificates from Philadelphia were examined on the 5% of the days with the highest particulate air pollution and the 5% of the days with the lowest particulate air pollution during the years 1973-1980. There was little difference in weather between the high and low pollution days, but total suspended particulate matter concentrations averaged 141 micrograms/m3 on the high pollution days versus 47 micrograms/m3 on the low pollution days. The relative risk of dying on the high pollution days was 1.08 P < 0.0001. The relative increase was higher for COPD (1.25) and pneumonia (1.13). Deaths were also elevated for heart disease and stroke; however, there was a substantial increase in the reports of respiratory factors as contributing causes for those underlying causes of death. Dead-on-arrival deaths and deaths outside of hospitals and clinics were also disproportionately increased. This paralleled the pattern seen in London in 1952. The age pattern of the relative risk of death was also similar. This adds to the evidence that the association is causal.
The air pollution disaster in London in 1952 established that very high levels of particulate-based smog can cause dramatic increases in daily mortality. Recently, more than a dozen studies at much lower particle concentrations have reported evidence that exposure to lower levels of airborne particles results in smaller, but nonzero increases in daily mortality. These studies were examined in a meta-analysis. A primary focus of the meta-analysis was to examine effect size estimates across large differences in both the levels of potential confounding factors and in their correlation with airborne particle concentration. In the primary meta-analysis, airborne particle concentration was a significant risk factor for elevated mortality (RR = 1.06, 95% CI = 1.05-1.07). The relative risk is for a 100 micrograms/m3 increase in TSP concentration. While mortality peaked in the cold months in all locations, in the majority of the studies airborne particle concentrations were highest in the warm months, indicating that seasonal patterns were not responsible for the observed associations. The relative risk was 1.06 (95% CI = 1.05-1.07) when the analysis was restricted to cities with summer peaking pollution. The relative risk was identical in cities with above average annual temperatures and cities with colder climates. It was also identical in drier and more humid climates, and similar across a wide range of correlations between temperature and airborne particle concentrations. These results suggest that inadequate weather control was not responsible for the association. A detailed examination of data from Philadelphia showed that control for season and weather was adequate for removing all long-term seasonal and subseasonal patterns from the mortality data, and that using a very flexible nonlinear fit to the weather factors did not disturb the association with TSP. The most reasonable interpretation of this pattern of results is that the association is causal. This is supported by other studies which have reported that particulate air pollution was associated with lung function deficits, increased symptoms, and increased hospitalization.
To assess the strength of the association between blood lead and children's IQ, a meta-analysis of the studies examining the relationship in school age children was performed. Emphasis was given to the size of the effect, since that allows comparisons that are informative about potential confounding and effect modifiers. Sensitivity analyses were also performed. A highly significant association was found between lead exposure and children's IQ (P < 0.001). An increase in blood lead from 10 to 20 micrograms/dl was associated with a decrease of 2.6 IQ points in the meta-analysis. This result was robust to inclusion or exclusion of the strongest individual studies and to relaxing the age requirements (school age children) of the meta-analysis. Adding eight studies with effect estimates of 0 would still leave a significant association with blood lead (P < 0.01). There was no evidence that the effect was limited to disadvantaged children and there was a suggestion of the opposite. The studies with mean blood lead levels of 15 micrograms/dl or lower in their sample had higher estimated blood lead slopes, suggesting that a threshold at 10 micrograms/dl is implausible. The study with the lowest mean blood lead level was examined using nonparametric smoothing. It showed no evidence of a threshold down to blood lead concentrations of 1 microgram/dl. Lead interferes with GABAergic and dopaminergic neurotransmission. It has been shown to bind to the NMDA receptor and inhibit long-term potentiation in the hippocampal region of the brain. Moreover, experimental studies have demonstrated that blood levels of 10 micrograms/dl interfere with a broad range of cognitive function in primates. Given this support, these associations in humans should be considered causal.
While sophistication in public health research has been increasing substantially in the past few decades, sophistication in decision making about public health and environmental issues has not been increasing in parallel. Measures that are inexpensive tend to be implemented and measures that are expensive tend not to be implemented by makers of public policy. That is often independent of the degree of public health protection afforded by the measures. Understanding and addressing this pattern is crucial to the control of lead exposure of critical populations. People are still exposed to lead in our society not because anyone believes that exposure is good, but because reducing exposure costs money. Maintaining exposure also has its costs, however. It is more difficult to measure them, and they are often ignored in decision making--but they are not small, and attempts to measure them have been made. The high cost of reducing lead exposure of critical populations is the reason that progress in reducing lead-paint exposure has been minimal in the 18 years since the passage of the Lead-Based Paint Poisoning Prevention Act and that it took from the time of the initial proposal in 1973 until 1986 before lead was substantially eliminated from gasoline. In its 1986 rule making, the EPA estimated that the elimination of lead from gasoline would cost more than $500 million per year. Removing leaded paint is estimated to cost billions of dollars. The difference is that the EPA promulgated its rule of removing lead from gasoline, whereas HUD has had little success in removing leaded paint from housing. One reason that the EPA was successful in implementing such an expensive regulation was that it provided detailed estimates of the health and welfare benefits that would accrue and the monetary value of some of the benefits. The EPA cost-benefit analysis demonstrated that the monetary benefits of its regulation far exceeded the costs. That neutralized the cost issue and focused the debate over the regulation on questions of timing. A detailed benefit analysis of reducing lead in drinking water has caused the EPA to consider tighter water lead standards than initially envisioned. Despite years of concern about the consequences of leaded paint poisoning, children continue to be poisoned by leaded paint because it will cost billions of dollars to abate the hazard, and demand for these dollars has lost out to competing needs.(ABSTRACT TRUNCATED AT 400 WORDS)
Viscera slide is the normal, longitudinal movement of the intraabdominal viscera caused by respiratory excursions of the diaphragm. By detecting areas of restricted viscera slide, ultrasonic imaging was used to identify anterior abdominal wall adhesions prior to laparotomy or laparoscopy. Transcutaneous ultrasound examination was performed on 110 patients. A prediction of adhesions was made for each patient and then compared to the findings during subsequent laparotomy or laparoscopy. Only patients with previous abdominal surgery or history of peritonitis demonstrated adhesions. Sensitivity and specificity of viscera slide ultrasound in predicting adhesions were 90% and 92%. Nine out of 10 false results involved misinterpretation of ultrasound images of the lower one-third of the abdomen. Ultrasonic imaging of viscera slide is highly accurate in detecting abdominal wall adhesions. This technique is most useful in guiding the insertion of trocar in laparoscopic surgery, and as a noninvasive method in studying the formation of adhesions.
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The metabolic disposition and elimination process of the anhydride co-polymer poly[1,3-bis(p-carboxy-phenoxypropane):sebacic acid] 20:80 [P(CPP:Sa)20:80] implanted in the rat brain was studied. Two polymers were prepared, one with [14C]SA and unlabelled CPP, and the other co-polymer with [14C]CPP and unlabelled SA. With these two polymers we were able to study the metabolic disposition of each monomer after polymer degradation. Polymer wafers loaded with N,N-bis(2-chloroethyl)-N-nitrosourea or without the drug were implanted in the rat brain. For the rats implanted with the [14C]SA-labelled polymer, approximately 40% of the radioactivity was found in the expired CO2, 10% in the urine, about 2% in the faeces and about 10% remained in the device 7 d after implantation. On the other hand, only 4% of the [14C]CPP monomer was eliminated by urine and faeces during this period. The drug-loaded polymer degraded faster than the blank polymer. This study supports the theory that the polymer is a biodegradable material that can be used for the direct and specific delivery of drugs into a targeted organ and can provide continued release of drugs over a period of time.
Cigarette smoking increases the total peripheral blood leukocyte count but its effect on the differential cell count in peripheral blood is largely unexplored. We studied 6138 subjects between the ages of 30 and 74 years who were seen as part of the First National Health and Nutrition Examination Survey in 1971 to 1974 to assess the relationship of current smoking status, number of cigarettes smoked per day, pack-years of smoking, and years since quitting, to the absolute and percent count of neutrophils, eosinophils, lymphocytes, and monocytes in peripheral blood. The relationship of cigarette smoking to the differential cell counts was adjusted for age, race, sex, and obesity by multiple regression. Pack-years smoked, years since quitting, and current number of cigarettes smoked per day were all independent predictors of the absolute neutrophil count and of the absolute lymphocyte count. Number of cigarettes smoked per day was the only smoking variable predictive of the absolute monocyte count and the absolute eosinophil count. When differential cell counts were considered as a percent of total leukocytes, the results were somewhat different. Neutrophils were disproportionately increased by current number of cigarettes smoked per day. Increased cigarette smoking decreased the proportion of white blood cells that were lymphocytes or eosinophils. Other smoking variables had no influence on percent counts for the specific white cell types in peripheral blood. These data suggest that the effect of cigarette smoking on differential cell counts is not uniform and is primarily influenced by current smoking behavior, although long-lasting effects of past smoking are also evident.
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We assessed the relationship between dietary vitamin C intake and the level of pulmonary function (forced expiratory volume in 1 s, FEV1) in 2526 adults seen as part of the first National Health and Nutrition Examination Survey (NHANES I) between 1971 and 1974. Multiple-linear-regression analysis was performed with in FEV1 as the dependent variable. After age, height, body mass index, race, sex, cigarette smoking, and employment status were controlled for, dietary vitamin C intake was positively and significantly associated with the level of FEV1 (beta = 0.00132, P = 0.01). Interaction terms for vitamin C intake and smoking and vitamin C intake and respiratory disease were not significant. These data are consistent with the hypothesis that vitamin C intake has a protective effect on pulmonary function.
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