Fine particulate air pollution and mortality in 20 U.S. cities.
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Air Pollutants↗
Biomedical subjects
J Schwartz
Publications and source records attributed to J Schwartz.
Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3.
Growth hormone (GH) regulates transcription factors associated with c-fos, including C/EBPbeta. Two forms of C/EBPbeta, liver-activating protein (LAP) and liver inhibitory protein (LIP), are dephosphorylated in GH-treated 3T3-F442A fibroblasts. GH-induced dephosphorylation of LAP and LIP is reduced when cells are preincubated with phosphatidylinositol 3'-kinase (PI3K) inhibitors. GH activates Akt and inhibits glycogen synthase kinase-3 (GSK-3). Lithium, a GSK-3 inhibitor, increases GH-dependent dephosphorylation of LAP and LIP. Both are in vitro substrates of GSK-3, suggesting that GSK-3 inactivation contributes to GH-promoted dephosphorylation of C/EBPbeta. Alkaline phosphatase increases binding of LAP homodimers and decreases binding of LIP homodimers to c-fos, suggesting that dephosphorylation of C/EBPbeta modifies their ability to bind DNA. Both alkaline phosphatase- and GH-mediated dephosphorylation comparably increase binding of endogenous LAP in 3T3-F442A cells. In cells overexpressing LAP and GSK-3, LAP binding decreases, suggesting that GSK-3-mediated phosphorylation interferes with LAP binding. Expression of constitutively active GSK-3 reduced GH-stimulated c-fos promoter activity. These studies indicate that PI3K/Akt/GSK-3 mediates signaling between GH receptor and the nucleus, promoting dephosphorylation of C/EBPbeta. Dephosphorylation increases binding of LAP complexes to the c-fos promoter and may contribute to the participation of C/EBPbeta in GH-stimulated c-fos expression.
3T3 Cells↗
Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the Normative Aging Study.
Between 1991 and 1997, the authors studied 833 participants of the Normative Aging Study in a substudy of bone lead levels (measured by K-shell x-ray fluorescence), blood lead levels, and hypertension. Among these subjects, 337 were classified as normotensive, and 182 and 314 were classified as having borderline and definite hypertension, respectively, at baseline. These bone and blood lead levels were typical of those of community-exposed men. Among the 519 subjects with no history of definite hypertension at baseline, cross-sectional analyses revealed positive associations between systolic blood pressure and bone lead levels. Of the 474 subjects who were free from definite hypertension at baseline and had follow-up data, 74 new cases of definite hypertension were reported. Baseline bone lead levels were positively associated with incidence of hypertension. In proportional hazards models that controlled for age, age squared, body mass index, and family history of hypertension, an increase in patella (trabecular) lead from the midpoint of the lowest quintile to that of the highest quintile was associated with a rate ratio of definite hypertension of 1.71 (95% confidence interval: 1.08, 2.70). No association was found with blood lead level. These results support the hypothesis that cumulative exposure to lead, even at low levels sustained by the general population, may increase the risk of hypertension.
Adult↗
Laparoscopic splenectomy in patients with refractory or relapsing thrombotic thrombocytopenic purpura.
HYPOTHESIS: Thrombotic thrombocytopenic purpura (TTP) is a rare and serious hematological disease. First-line therapy is plasma exchange, often used in combination with corticosteroids, vincristine, aspirin, and dipyridamole. The role of splenectomy for patients resistant to or dependent on plasma therapy and for the prevention of TTP relapses is not yet determined. Laparoscopic splenectomy (LS) is effective and safe for the treatment of the chronic relapsing form of TTP. INTERVENTION: We performed LS in 8 patients with refractory or relapsing TTP. The operative as well as the early and late postoperative course and complications were recorded. RESULTS: The mean duration of LS was 70 minutes (range, 35-180 minutes). There were no serious bleeding complications during or after surgery. Convalescence was rapid, and the mean hospital stay was 2.5 days (range, 1-9 days). Patients were followed up for a mean of 32 months (range, 19-54 months). Seven patients are in remission with no relapse of TTP. One patient with familial TTP had multiple relapses before and after surgery. CONCLUSIONS: Laparoscopic splenectomy for refractory or relapsing TTP is safe and associated with low morbidity and fast recovery. It is effective in the long-term prevention of TTP relapses in most patients, and it should probably be considered early in the course of chronic, relapsing TTP.
Adolescent↗
Health effects of air pollution exposure on children and adolescents in São Paulo, Brazil.
Children and adolescents have been considered more susceptible to the effects of air pollution than adults. In order to investigate the responses of children of different ages to air pollution exposure, daily records of hospital admissions for children in five age groups (equal or less than 2 years of age, 3-5, 6-13, 14-19, and all ages together, i.e., from 0-19 years of age) were obtained from January 1993 to November 1997 in São Paulo, Brazil, and were compared to daily records of PM10, O3, SO2, CO and NO2 concentrations in ambient air. For each age group a generalized additive Poisson regression was fitted controlling for smooth functions of time, temperature, humidity, and days of the week, with an additional indicator for holidays. Polynomial distributed lag models were used to estimate the 7-day cumulative effect of each pollutant. Children 2 years or less were the most susceptible to the effects of all five pollutants with an increase of 9.4% (95% CI: 7.9,10.9) in respiratory admissions associated with each interquartile range increase in PM10. The oldest group was the second most susceptible to air pollutants, with each interquartile range increase in PM10 associated with a 5.1% (95% CI: 0.3,9.8) increase in respiratory admissions. An interquartile range increase in CO was associated with an 11.3% (95% CI: 5.9,16.8) increase in respiratory hospitalizations. When a multipollutant model was used, the effect of PM10 on respiratory admissions for all ages together was unchanged, while the SO2 and the other pollutants effect was substantially reduced. This study showed that daily respiratory hospital admissions for children and adolescents in São Paulo increased with air pollution, and that the largest effects were found for the youngest (2 years or less) and oldest (14-19 years) age groups.
Adolescent↗
Liver failure in a patient treated with long-term rosiglitazone therapy.
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Aged↗
Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I safety and colposcopy study.
Vaginally applied gels offer a promising approach for preventing unwanted pregnancies and sexually transmitted infections. Cellulose sulfate (CS) is a non-cytotoxic antifertility agent that also exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV. This was a randomized, double-blinded, Phase I study of 2.5 mL and 5.0 mL doses of 6% CS gel. A single vaginal application of the gel followed by five consecutive daily doses was assessed for genital irritation, safety, vaginal leakage, and product acceptability compared to two controls, Conceptrol, which is a marketed contraceptive gel containing nonoxynol-9, and K-Y jelly. The results suggest that the safety of 6% CS was comparable to that of Conceptrol and K-Y jelly, and it may be associated with less genital irritation. The 2.5 mL dose of CS may be preferable according to the participants' reports of leakage. All the products had similar acceptability profiles.
Administration, Intravaginal↗
Maryland's ethics committee legislation--a leading edge model or a step into the abyss?
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Decision Making, Organizational↗
Intrapituitary interactions: another level of endocrine regulation.
1. Factors, produced within the anterior pituitary, act locally to influence many acute and developmental changes in neighbouring cells. 2. Broad spectra of factors and activities characterize these paracrine interactions. 3. Cleavage products of pro-opiomelanocortin, other than those that act as systemic hormones, are produced by neonatal gonadotrophs and these peptides stimulate mitosis and differentiation of lactotrophs. 4. Activins and follistatins exert opposing effects on gonadotrophs. The stimulatory activity of activins is modulated extracellularly through protein-protein interactions with follistatin. Within gonadotrophs, the stimulatory activity of activins is self-limiting through receptor-mediated stimulatory and inhibitory signal transduction pathways. 5. During the oestrous cycle, the interactions between gonadotroph cells and epidermal growth factor (EGF), acting as a local signal, occur on multiple levels. Levels of expression of EGF receptors on cells vary as a function of the cycle, as do EGF-induced changes in gene expression and proliferation of cells.
Animals↗
Feasibility of photopheresis to reduce the occurrence of restenosis after percutaneous transluminal coronary angioplasty: a clinical pilot study.
BACKGROUND: Photopheresis was evaluated as a means of preventing restenosis on the basis of immune modulation. METHODS: This was a prospective, randomized, controlled clinical trial analyzing clinical restenosis at 6 months after percutaneous transluminal coronary angioplasty (PTCA). Seventy-eight patients with single-vessel angioplasty were randomly assigned to a control group of 41 patients and a treatment group of 37 patients. At 6 months, there were 72 evaluable patients: 39 control patients and 33 treated. Twenty-nine control patients received balloon PTCA only and 10 patients received stents. Twenty treated patients received PTCA only and 13 patients received stents. Baseline clinical characteristics of both groups were similar. The treatment group received photopheresis for a total of 5 treatments. Primary end points were death from any cause, myocardial infarction, ischemia, and repeat revascularization procedures. RESULTS: By intention-to-treat analysis, clinical restenosis occurred in 27% of control patients versus 8% of treated patients (P =.040, relative risk = 0.30). CONCLUSIONS: Photopheresis therapy in patients undergoing balloon PTCA with and without stent deployment has been shown to be effective in reducing restenosis. The use of photopheresis in such patients merits further investigation.
Adolescent↗
Respiratory health and air pollution: additive mixed model analyses.
We conduct a reanalysis of data from the Utah Valley respiratory health/air pollution study of Pope and co-workers (Pope et al., 1991) using additive mixed models. A relatively recent statistical development (e.g. Wang, 1998; Verbyla et al., 1999; Lin and Zhang, 1999), the methods allow for smooth functional relationships, subject-specific effects and time series error structure. All three of these are apparent in the Utah Valley data.
Journal Article↗
Is there harvesting in the association of airborne particles with daily deaths and hospital admissions?
Although many studies have shown that airborne particles are associated with increased daily death and hospitalization rates, some have questioned whether these events are occurring in persons who would die or enter the hospital within a few days in any case. This hypothesis is usually called the harvesting effect. Harvesting is postulated to occur because the size of the pool of susceptibles decreases as a result of air pollution. I have developed a framework for examining this hypothesis. I used a smoothing technique that allowed me to examine the association between daily deaths and daily hospital admissions net of any such rebound that occurred within a fixed time scale. By varying that time scale I could look at effects net of rebounds on successively larger time scales, ranging from 15 to 60 days. I examined daily deaths and hospital admissions in Chicago for the years 1988-1993. In baseline analyses, particulate matter less than 10 microm in aerodynamic diameter (PM10) was associated with increased daily deaths and hospital admissions for heart disease, pneumonia, and chronic obstructive pulmonary disease. A 10 microg/m3 increase in PM10 was associated with a 0.89% increase in daily deaths (95% confidence interval = 0.61-1.16%), for example. Using smoothing to look at effects net of short-term rebounds, the effect-size estimates for daily deaths and for chronic obstructive pulmonary disease admissions more than doubled. They did not change for pneumonia and heart disease admissions. The increased effect size for daily deaths occurred only for deaths outside of the hospital. These results are consistent with air pollution increasing the size of the risk pool and for most of the deaths being advanced by months to years.
Air Pollution↗
Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 project.
We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities' pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 microg/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.
Aged↗
Is air pollution a risk factor for low birth weight in Seoul?
Environmental factors contributing to reduced birth weight are of great concern because of the well-known relation of birth weight to infant mortality and adverse effects in later life. We examined the associations between air pollution exposures during pregnancy and low birth weight among all full-term births (gestational age 37-44 weeks) for a 2-year period (January 1996 through December 1997) in Seoul, South Korea. We evaluated these associations with a generalized additive logistic regression adjusting for gestational age, maternal age, parental educational level, parity, and infant sex. We used smoothing plots with generalized additive models to analyze the exposure-response relation for each air pollutant. The adjusted relative risk of low birth weight was 1.08 [95% confidence interval (CI) = 1.04-1.12] for each interquartile increase for carbon monoxide concentrations during the first trimester of pregnancy. The relative risks were 1.07 (95% CI = 1.03-1.11) for nitrogen dioxide, 1.06 (95% CI = 1.02-1.10) for sulfur dioxide, and 1.04 (95% CI = 1.00-1.08) for total suspended particles also for interquartile increase in exposure. Carbon monoxide, nitrogen dioxide, sulfur dioxide, and total suspended particle concentrations in the first trimester of pregnancy period are risk factors for low birth weight.
Adult↗
Selection bias and confounding in case-crossover analyses of environmental time-series data.
The case-crossover study design is a popular analytic tool for estimating the effects of triggers of acute outcomes by environmental exposures. Although this approach controls for time-invariant confounders by design, it may allow for selection bias and confounding by time-varying factors. We conducted a simulation study of the sensitivity of the symmetric bidirectional case-crossover design to time-varying patterns in exposure and outcome. We identified the effects of selection bias and confounding on symmetric bidirectional case-crossover results and offer strategies to eliminate or reduce these biases. Selection bias results when exposure in the reference periods is not identically representative of exposure in the hazard periods, even when the distribution of exposure is stationary. This bias can be estimated and removed. Selection bias also occurs when the distribution of exposure is nonstationary, but the adjusted symmetric bidirectional case-crossover methodology substantially controls for this. Confounding results from a common temporal pattern in the exposure and the outcome time series, but can also be the result of patterns in exposure and outcome that, although asymptotically uncorrelated, are correlated at finite series lengths. All three biases are reduced by choosing shorter referent-spacing lengths. This effect is illustrated using data on air pollution and daily deaths in Chicago.
Air Pollution↗
The time course of weather-related deaths.
We carried out time-series analysis in 12 U.S. cities to estimate both the acute effects and the lagged influence of weather on total daily deaths. We fit generalized additive Poisson regressions for each city using nonparametric smooth functions to control for long time trend and barometric pressure. We also controlled for day of the week. We estimated the effect and the lag structure of both temperature and humidity on the basis of a distributed lag model. In cold cities, both high and low temperatures were associated with increased deaths. In general, the effect of cold temperatures persisted for days, whereas the effect of high temperatures was restricted to the day of the death or the immediately preceding day and was twice as large as the cold effect. The hot temperature effect appears to be primarily harvesting. In hot cities, neither hot nor cold temperatures had much effect on deaths. The magnitude of the effect of hot temperature varied with central air conditioning use and the variance of summertime temperatures. We saw no clear pattern for humidity effect. These dissimilarities indicate that analysis of the impact of any climatic change should take into account regional weather differences and harvesting.
Age Factors↗
The lag structure between particulate air pollution and respiratory and cardiovascular deaths in 10 US cities.
To assess differences in the lag structure pattern between particulate matter < 10 microns/100 microns in diameter (PM10) and cause-specific mortality, we performed a time-series analysis in 10 US cities using generalized additive Poisson regressions in each city; nonparametric smooth functions were used to control for long time trend, weather, and day of the week. The PM10 effect was estimated based on its daily mean, 2-day moving average, and the cumulative 7-day effect by means of an unconstrained distributed lag model. A 10-microgram/m3 increase in the 7-day mean of PM10 was associated with increases in deaths due to pneumonia (2.7%, 95% confidence interval [CI]: 1.5, 3.9), chronic obstructive pulmonary disease (1.7%, 95% CI: 0.1, 3.3), and all cardiovascular diseases (1.0%, 95% CI: 0.6, 1.4). A 10-microgram/m3 increase in the 2-day mean of PM10 was associated with a 0.7% (95% CI: 0.3, 1.1) increase in deaths from myocardial infarction. When the distributed lag was assessed, two different patterns could be observed: respiratory deaths were more affected by air pollution levels on the previous days, whereas cardiovascular deaths were more affected by same-day pollution. These results contribute to the overall efforts so far in understanding how exposure to air pollution promotes adverse health effects.
Air Pollutants↗
Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III.
BACKGROUND: An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. METHODS: Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. RESULTS: The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. CONCLUSIONS: The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.
Adolescent↗