Development of a synthetic PCB mixture resembling the average polychlorinated biphenyl profile in Chicago air.

Studies of environmental and toxic effects of polychlorinated biphenyls (PCBs) are ideally performed with PCB mixtures reflecting the composition of environmental PCB profiles to mimic actual effects and to account for complex interactions among individual PCB congeners. Unfortunately, only a few laboratory studies employing synthetic PCB mixtures have been reported, in part because of the challenges associated with the preparation of complex PCB mixtures containing many individual PCB congeners. The objective of this study was to develop a PCB mixture that resembles the average PCB profile recorded from 1996 to 2002 at a satellite station of the Integrated Atmospheric Deposition Network located at the Illinois Institute of Technology (IIT) in Chicago, Illinois, using commercial PCB mixtures. Initial simulations, using published Aroclor profiles, showed that a mixture containing 65% Aroclor 1242 and 35% Aroclor 1254 was a good approximation of the target profile. A synthetic Chicago air mixture (CAM) was prepared by mixing the respective Aroclors in this ratio, followed by GC/MS/MS analysis. Comparison of the PCB profile of the synthetic mixture with the target profile suggests that the synthetic PCB mixture is a good approximation of the average IIT Chicago air profiles (similarity coefficient cos θ = 0.82; average relative percent difference = 84%). The synthetic CAM was also a reasonable approximation of the average of 184 PCB profiles analyzed in 2007 at 37 sites throughout Chicago as part of the University of Iowa Superfund Basic Research Program (isbrp), with a cos θ of 0.70 and an average relative percent difference of 118%. While the CAM and the two Chicago air profiles contained primarily di- to pentachlorobiphenyls, higher chlorinated congeners, including congeners with seven or eight chlorine atoms, were underrepresented in the synthetic CAM. The calculated TCDD toxic equivalency quotients of the synthetic CAM (2.7 ng/mg PCB) and the IIT Chicago air profile (1.6 ng/mg PCB) were comparable, but lower by two orders of magnitude than the isbrp Chicago air profile (865 ng/mg PCB) due to surprisingly high PCB 126 levels in Chicago air. In contrast, the calculated neurotoxic equivalency quotients of the CAM (0.33 mg/mg PCB) and the two Chicago air profiles (0.44 and 0.30 mg/mg PCB, respectively) were similar. This study demonstrates the challenges and methods of creating and characterizing synthetic, environmental mixtures of PCBs.

Influence of dietary fat on the enantioselective disposition of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in female mice.

Although ingestion is the major route of exposure to polychlorinated biphenyls (PCBs), dietary factors altering their absorption and excretion are only poorly understood. In the present study, (+/-)-PCB 136 was administered orally to female C57BL/6 mice fed an unrefined (URD, 10% fat) or high fat (HFD, 40% fat) diet to investigate the effect of the dietary fat content on the disposition of PCBs. Three days after administration, PCB levels in the adipose tissue were significantly lower in HFD animals than URD animals, partly due to a higher excretion rate of PCB 136 in the HFD group. (+)-PCB 136 was enriched in all organs and in feces. In both groups, enantiomeric fractions in feces increased each day after administration. We hypothesize that low EF (enantiomeric fraction) values in feces excreted within 24h of exposure are due to the presence of undigested, racemic PCB. Higher EF values in feces excreted after two and three days are due to excretion of previously absorbed PCBs. Overall, our study suggests that the EF value may be a good tool to investigate the absorption and excretion of PCBs in vivo.

Toxicity of synthetic musks to early life stages of the freshwater mussel Lampsilis cardium.

Polycyclic musk fragrances are common additives to many consumer products. As a result of their widespread use and slow degradation rates, they are widely found in aquatic environments. This study reports on the lethal and sublethal toxicity of the polycyclic musks AHTN (Tonalide) and HHCB (Galaxolide) to glochidial (larval) and juvenile life stages of the freshwater mussel Lampsilis cardium (Rafinesque, 1820). In glochidia, 24-h median lethal concentrations (LC50s) ranged from 454 to 850 microg AHTN/L and from 1000 to >1750 microg HHCB/L (water solubility). Results for 48-h tests were similar to the 24-h tests. In 96-h tests with juveniles, we did not observe a dose-response relation between mortality and either musk. However, the growth rate was reduced by musk exposure. The median effective concentrations (EC50s, based on growth) were highly variable and ranged from 108 to 1034 microg AHTN/L and 153 to 831 microg HHCB/L. While all adverse effects occurred at concentrations that are much greater than those reported in natural waters (low microg/L to ng/L), these results indicate the potential for adverse effects on these long-lived organisms from exposure to synthetic musk fragrances.

A comparison of esomeprazole and lansoprazole for control of intragastric pH in patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Intragastric acid suppression is the most direct measure of the pharmacodynamic efficacy of proton pump inhibitors, which are the most effective drugs for acid-related diseases. AIM: To compare the effectiveness of once and twice daily dosing of lansoprazole and esomeprazole in controlling intragastric acidity (target gastric pH > 4.0) over a 24-hour period. METHODS: In an open-label, two-way crossover study, 45 Helicobacter pylori-negative patients with gastro-oesophageal reflux disease were randomized to receive one of two regimens: 30 mg lansoprazole or esomeprazole 40 mg once daily. Intragastric pH was assessed by 24-hour pH monitoring on day 5 of each regimen. Dosing was increased to twice daily and pH was reassessed on day 10. Following a 14-day washout, patients were crossed over to the other medication and the dosage regimens and pH assessments were repeated. RESULTS: Data were analysed from 35 patients who completed all scheduled assessments and had 24-hour monitoring for each end-point. Mean time pH > 4.0 and mean 24-hour pH were highest for esomeprazole 40 mg twice daily, followed by lansoprazole 30 mg twice daily, esomeprazole 40 mg once daily and lansoprazole 30 mg once daily. Esomeprazole 40 mg twice daily provided superior control of intragastric pH compared with either once or twice daily dosing of lansoprazole and once daily dosing of esomeprazole (P < 0.01). Esomeprazole 40 mg once daily was comparable with lansoprazole 30 mg twice daily and both were superior to lansoprazole 30 mg once daily (P < 0.01). CONCLUSIONS: Response to acid suppression treatment depends on the treatment selected. Esomeprazole 40 mg twice daily provided better control of intragastric pH than all other regimens evaluated. Esomeprazole 40 mg daily, however, was comparable with lansoprazole 30 mg twice daily and superior to lansoprazole 30 mg once daily.

Influenza vaccine effectiveness among elderly nursing home residents: a cohort study.

Outbreaks of influenza in nursing homes still occur, even when a large portion of residents have been inoculated with inactivated vaccine. Data were collected in 1991--1992 from 83 eligible skilled nursing homes located in southern Lower Michigan to determine the effectiveness of inactivated influenza vaccine in preventing influenza-like illness and influenza-associated pneumonia. Surveillance was conducted to identify the occurrence of influenza in the homes and, at the end of the season, specific data were gathered on all residents of homes with influenza activity. Age- and sex-adjusted estimates of vaccine effectiveness were calculated using Cox proportional hazards models for each nursing home. Estimates were pooled using precision-based weights calculated from data for each home. Vaccine was found to be 33% effective in preventing total respiratory illness (influenza-like illness and clinically diagnosed pneumonia). In prevention of pneumonia alone, vaccine was 43% effective. The estimate for prevention of pneumonia rose to 55% if the period under consideration was limited to the time of peak influenza activity. Given the number of eligible homes and the cohort methodology used, the results support continuation of current policy, encouraging use of vaccine in all nursing home residents.

Results from the Lake Michigan Mass Balance study: concentrations and fluxes of atmospheric polychlorinated biphenyls and trans-nonachlor.

In this paper, we summarize the data and methods used to estimate atmospheric exchange of polychlorinated biphenyls (PCBs) and trans-nonachlor with Lake Michigan. This work was conducted as part of the Lake Michigan Mass Balance (LMMB) study. For the atmospheric component of the LMMB, more than 400 gas- and particulate-phase samples were collected at eight sites on the shore around the lake (shoreline) and at 14 sites on the lake (over-water). We review the quality of the data set; describe the concentrations in atmospheric gas and particulate phases; report local, instantaneous, net gas fluxes; and estimate annual deposition of the particle-associated compounds. The quality of the data set is high except for a subset of over-water samples where PCB contamination is suspected. Gas-phase trans-nonachlor concentrations (although not the resulting gas fluxes) are inversely correlated with latitude and positively correlated with temperature. Gas-phase sigmaPCBs (sum of 98 congener groups) are highest in concentration at the Chicago site and lowest at the Sleeping Bear Dunes site. The resulting sigmaPCB gas fluxes exhibit a seasonality that reflects elevated summertime gas-phase concentrations not compensated by temperature-corrected Henry's law coefficients. Particulate-phase deposition is much smaller in magnitude than gas fluxes, for either compound. Gas and particulate fluxes are comparable only at the Chicago site and only when large (> 10 microm) particulates are considered.

Biological derivation of a range of cephalometric norms for children of African American descent (after Steiner).

The purpose of this study was to report a normal range of anteroposterior apical base differences and concomitant interincisor inclinations and locations derived from a sample of American children (12 to 16 years) of African descent with normal occlusion (statistically defined). Standard cephalometric radiographs of 40 boys and 40 girls were traced and the Steiner Analysis performed. In addition to the ANB angle, 6 supplemental anteroposterior apical base separation estimators were measured, mean values established, and correlation (r) associations performed. The range of anteroposterior apical base difference was -0.5 degrees to 9.5 degrees estimated by the ANB angle or a linear distance of +/-6.5 mm using the Wits Appraisal. The angular and linear distance of the upper incisor to NA line (compensations) ranged from a low of 12 degrees and 3 mm to a high of 39 degrees and 14 mm. The angular and linear distance of the lower incisor to the NB line ranged from a low of 17 degrees and 3 mm to a high of 47.5 degrees and 17.5 mm. Biologically, the results suggested a wide range of equally acceptable sagittal apical base relationships and associated compensations in upper and lower incisor inclinations; normal occlusion was viewed as the reference point. Considering the usage of such descriptive terms as "ideal," "acceptable compromises," and "individualized treatment goals," to describe the angulation and inclination of the incisor teeth, the need for a distinction between biologically derived reference norms and esthetic preference reference norms is apparent when analyzing normal occlusion.

The diagnosis and work-up of the patient with gastroparesis.

Gastroparesis-or delayed gastric emptying--is associated with upper gastrointestinal symptoms that include early satiety, nausea, vomiting, regurgitation, fullness, and bloating. Gastroparesis should be considered in the diagnosis of a patient with these symptoms after mechanical and structural lesions have been ruled out. This review briefly summarizes gastric motor physiology and discusses the etiology and diagnostic approach to the treatment of a patient with possible gastroparesis. We highlight the methods available to measure gastric motility and describe their relative advantages and disadvantages.

Determination and validation of a predictive model for Clostridium difficile diarrhea in hospitalized oncology patients.

BACKGROUND: Clostridium difficile colitis in the cancer patient receiving chemotherapy is a frequent cause of morbidity which may prolong hospitalization. Techniques for identifying infection often delay the initiation of therapy. PATIENTS AND METHODS: In this retrospective case-control analysis, we identified predictors for C. difficile-associated diarrhea in 29 patients hospitalized from 1988 to 1993 on a hematologic malignancy/bone marrow transplant unit (hospital A). We then validated our model with 58 C. difficile cases and 74 controls admitted to an oncology unit from a different institution (hospital B). RESULTS: We found that low intensity of chemotherapy (P < 0.001), lack of parenteral vancomycin use (P = 0.03) and hospitalization within the past two months (P = 0.05) were independently predictive of C. difficile colitis by multivariate analysis. These variables were weighted for predictive capability using a receiver operator characteristic score; low intensity chemotherapy was assigned two points, lack of parenteral vancomycin received one point and prior hospitalization one point (P < 0.001 by chi 2 for trend). The receiver operating characteristic (ROC) curve areas were 0.78 for patients at hospital A and 0.70 at hospital B indicating moderate drop off in discrimination. Compared to hospital A patients, hospital B patients hospitalized between 1989 and 1994 were more often women (P = 0.04), received less systemic vancomycin (P = 0.01), were less frequently neutropenic (P < 0.05), and received less intense chemotherapy regimens (P < 0.05). Despite these differences in demographics in patients between these institutions, our predictive model was validated in hospital B patients (P = 0.02 by chi 2 for trend). CONCLUSIONS: The results of this study may help clinicians predict the risk of C. difficile disease in the hospitalized immunocompromised oncology patient and may help guide empiric therapy while awaiting results of stool toxin assays.

Safety and efficacy of long-term use of rimantadine for prophylaxis of type A influenza in nursing homes.

The safety and efficacy of rimantadine for long-term prophylaxis of influenza A (H3N2) infection were evaluated among elderly residents in 10 nursing homes. Within each nursing home, participating residents were randomly assigned to receive placebo or rimantadine at 100 or 200 mg/day. Residents were evaluated daily for symptoms and significant health events as possible side effects, as well as for influenza-like illness. The study medications were administered to 328 residents for up to 8 weeks, with no statistically significant differences in the frequencies of gastrointestinal or central nervous system symptoms between the groups. However, residents in the active medication groups were more likely to withdraw from the study and to experience various health events including death; some but not all of these differences were statistically significant. Efficacy evaluations were carried out on the 68 vaccinated residents in the two nursing homes with demonstrated influenza virus activity. Rimantadine appeared to provide an additional protective effect beyond vaccination in reducing the risk of clinical and laboratory-confirmed influenza-like illness; however, the efficacy estimates were never statistically significant. The efficacies of the 100- and 200-mg/day dosages were generally similar. When data for the 100- and 200-mg/day dosage groups were combined and compared with data for the group receiving placebo, the efficacy of rimantadine in reducing the risk of clinical influenza-like illness was estimated to be 58 percent (P = 0.079). The results suggest the relative safety and clinical efficacy of using rimantadine for influenza prophylaxis among vaccinated elderly individuals and support the recommendation for a dosage reduction to 100 mg/day in this population.

The joint effects of race and age on the risk of end-stage renal disease attributed to hypertension.

To describe the joint effects of race and age on the risk of end-stage renal disease (ESRD) attributed to hypertension (ESRD-HT), we analyzed data for white and black adults, 20 to 84 years of age, reported by the United States Renal Data System during the period 1987 to 1990. The risk of ESRD-HT increased substantially with age for both blacks and whites; however, at each age, the risk was greater for blacks. A more in-depth description of the combination of effects involving race and age on ESRD-HT incidence was provided by two models of joint effects, one additive and the other multiplicative. Both models used the 20- to 24-year age group as the referent. Under the additive model the risk of ESRD-HT in blacks attributable to the joint effects between race and age increased continuously from younger to older groups. This indicates that although ESRD-HT risk increases with age for both blacks and whites, the increase for blacks is greater than expected if the effects of race were independent of the effects of age. However, the multiplicative model indicated that the proportional increase with age in ESRD-HT risk among blacks, as compared with whites, was more striking for younger ages (< or = 50 years among women and < or = 40 years among men), and especially so for men. This suggests a more accelerated course of hypertension toward ESRD for blacks (especially younger men) than for whites. A conceptual model to explain these patterns of race-age joint effects is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of countercurrent multiplication in renal ammonium handling: regulation of medullary ammonium accumulation.

Ammonium (NH3 plus NH4+), produced predominantly in the proximal tubule, is transferred to the final urine by a process involving countercurrent multiplication of ammonium which generates an ammonium concentration gradient in the renal medulla. It was hypothesized that if urinary ammonium excretion rates are controlled in part by the medullary ammonium gradient, changes in hydration and acid-base state should cause changes in the medullary ammonium gradient consistent with expected changes in urinary ammonium concentrations. To test that hypothesis, rats were subjected to water diuresis, water deprivation, water deprivation plus furosemide, and dietary acid and base loads and corticomedullary ammonium gradients in their kidneys were then measured. Sections were cut along the corticomedullary axis to yield slices of cortex, outer stripe of outer medulla, inner stripe of outer medulla, and three levels of the inner medulla. The total ammonia content of homogenized slices was measured by either a membrane ammonia electrode or an enzymatic technique. Kidneys from water-deprived animals showed a distinct ammonium gradient along the corticomedullary axis, with the highest contents found at the tip of the papilla. The gradient was attenuated by water diuresis and abolished by furosemide. Acid loading enhanced the gradient, and base loading abolished it. These results indicate that the corticomedullary ammonium gradient is regulated in response to changes in hydration and acid-base state.