Conceptual problems in establishing the critical concentration of cadmium in human kidney cortex

The definition of the "critical concentration" for cadmium is compared with the concepts used to establish this measure in some recent publications. The term has not been clearly defined on a population basis and this has given rise to certain confusion. Different groups of investigators therefore have arrived at different estimates of the "critical concentration" for cadmium in human kidney cortex. A new measure, the "population critical concentration" (PCC) with a clearly defined response rate, is suggested. A reanalysis of the published data indicates that the PCC-10 (10% response rate) for cadmium in kidney cortex is likely to be in the range 180-220 micrograms/g and the PCC-50 is likely to be about 25% higher.     

The applicability of the measurement of urinary thioethers

Summary The excretion of thioethers was measured in the urine of 6 volunteers, who were experimentally exposed to styrene, and 18 styrene workers. In addition, 12 clerks (non-smokers) and 12 sheet-metal workers (smokers) served as control groups. Diet was standardized during the experiments. Thioethers were measured by a spectrophotometric method. The volunteers were exposed to styrene, 210 mg/m³, for 2 h at a 50-W workload. An increase in thioether excretion was observed; the largest was in the urine samples collected between 0.5 and 5 h after the end of the exposure. After 43 h the excretion of thioethers was close to the preexposure level (3.5 mmol/mol creatinine). About 1% of the styrene absorbed was detected as thioethers in urine, which is only about 1/10 of the conversion reported for rats. From excretion rate curves a half-life of about 11 h was calculated for styrene thioethers. The styrene workers were employed at two plants. The average exposure to styrene (time-weighted average 8 h) was estimated to be about 115 mg/m3 (smokers in plant A), 55 mg/m³ (non-smokers in plant A) and 10 mg/m³ (non-smokers in plant B). The excretion of thioethers in exposed workers at plant A was higher by 2–4 mmol/mol creatinine than that in non-exposed controls. In plant B, where exposure was lower, an increase in that amount of thioethers excreted in the urine by exposed workers was less pronounced, and was statistically significant only when post-shift samples were compared with pre-shift samples. The results of the present study indicate that control samples should be collected both from non-exposed groups and from the exposed individuals before work shifts, to improve the likelihood of detecting genotoxic exposure in the work environment.     

Effectiveness of low-dose contrimoxazole prophylaxis against Pneumocystis carinii pneumonia after renal and/or pancreas transplantation

We retrospectively examined the effectiveness of prophylaxis with cotrimoxazole in preventing Pneumocystis carnii pneumonia in recipients of kidney and combined kidney-pancreas transplants between 1985 and 1989. Cotrimoxazole prophylaxis (480 mg daily or 300 mg/m²), when used, was started within 2 months after transplantation and usually continued until 6 months after surgery. Eight (3.7%) of the 214 patients who were not given prophylaxis were infected with Pneumocystis carinii, and there were 4 fatalities (50% mortality). There were no cases among the 161 patients given prophylaxis (P 0.03). No serious adverse effects were noted in the prophylaxis group. It is concluded that prophylaxis against Pneumocystis carinii infection is well tolerated and should be given as soon as possible to all organ transplant recipients for at least 6 months.     

Interobserver reproducibility of percent Gleason grade 4/5 in total prostatectomy specimens

PURPOSE: Recently the percent Gleason grade 4/5 was proposed as a predictor of the outcome of prostate cancer and it has been shown that it adds prognostic information to that given by Gleason score. To our knowledge the interobserver variability of percent Gleason grade 4/5 has not yet been investigated. We assessed the percent Gleason grade 4/5, including the identification of high grade patterns and estimation of the percent tumor area, which is potentially more difficult than conventional Gleason grading. MATERIALS AND METHODS: A consecutive series of 69 total prostatectomy specimens was reviewed. A single slide per specimen was circulated among 4 genitourinary pathologists, who assessed Gleason score and the percent Gleason grade 4/5. Results were compared pairwise and a weighted kappa was calculated for Gleason score and the percent Gleason grade 4/5. RESULTS: The 4 observers had a mean weighted kappa for Gleason score and the percent Gleason grade 4/5 of 0.52 to 0.66 (overall mean 0.56) and 0.58 to 0.72 (overall mean 0.66), respectively. The best agreement for percent Gleason grade 4/5 was in 2 pathologists at the same department (weighted kappa 0.86). Transition zone tumors had a lower weighted kappa for Gleason score but a higher weighted kappa for percent Gleason grade 4/5 than peripheral zone tumors. In cases of the greatest disagreement in the percent Gleason grade 4/5 crush artifact, cribriform cancer and high grade PIN within the tumor were significantly more common. An intraobserver reproducibility of weighted kappa 0.91 was achieved for Gleason score and the percent Gleason grade 4/5. CONCLUSIONS: Interobserver reproducibility of the percent Gleason grade 4/5 is substantial and at least as good as that of the Gleason score. Hence, concern about interobserver variability should not deter pathologists from using the percent Gleason grade 4/5 as a prognostic marker for prostate cancer.     

Phthalates in indoor dust and their association with building characteristics

In a recent study of 198 Swedish children with persistent allergic symptoms and 202 controls without such symptoms, we reported associations between the symptoms and the concentrations of n-butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in dust taken from the childrens' bedrooms. In the present study we examined associations between the concentrations of different phthalate esters in the dust from these bedrooms and various characteristics of the home. The study focused on BBzP and DEHP because these were the phthalates associated with health complaints. Associations have been examined using parametric and nonparametric tests as well as multiple logistic regression. For both BBzP and DEHP, we found associations between their dust concentrations and the amount of polyvinyl chloride (PVC) used as flooring and wall material in the home. Furthermore, high concentrations of BBzP (above median) were associated with self-reported water leakage in the home, and high concentrations of DEHP were associated with buildings constructed before 1960. Other associations, as well as absence of associations, are reported. Both BBzP and DEHP were found in buildings with neither PVC flooring nor wall covering, consistent with the numerous additional plasticized materials that are anticipated to be present in a typical home. The building characteristics examined in this study cannot serve as complete proxies for these quite varied sources. However, the associations reported here can help identify homes where phthalate concentrations are likely to be elevated and can aid in developing mitigation strategies.     

Tension-free vaginal tape and laparoscopic mesh colposuspension for stress urinary incontinence

OBJECTIVE: To compare objective and subjective outcomes after the tension-free vaginal tape procedure (TVT) with laparoscopic mesh colposuspension as a primary treatment for female stress urinary incontinence. Objective outcome measures were stress test and 48-hour pad test. METHODS: In 6 departments of gynecology in Finland, including 4 university teaching hospitals and 2 central hospitals, 128 women with urodynamic stress incontinence were randomly allocated to 2 treatment groups. Seventy were treated with TVT and 51 by means of laparoscopic mesh colposuspension. There were 7 dropouts. Inclusion criteria were history of stress incontinence, positive stress test, and urodynamic conformation of stress incontinence. Exclusion criteria were age older than 70 years, previous incontinence surgery, more than 3 episodes of urinary tract infection within the last 2 years, coincident other gynecological surgery, body mass index more than 32 kg/m(2), urethral closure pressure less than 20 cm H(2)O, and residual volume more than 100 mL in preoperative urodynamic evaluation. Assessment took place before treatment and at 12 months postoperatively with the cough stress test, Urge Score, 48-hour pad test, King's College Health Questionnaire, Visual Analog Scale, and Urinary Incontinence Severity Score. RESULTS: When negative stress test was used as criteria for cure, 85.7% of women in the TVT group and 56.9% in the laparoscopic mesh colposuspension group were objectively cured. Subject satisfaction was significantly better after the TVT procedure than after laparoscopic mesh colposuspension. CONCLUSION: Treatment with TVT results in higher objective and subjective cure rates at 1 year than treatment by means of laparoscopic mesh colposuspension.     

Absence of association between organic solvent exposure and risk of chronic renal failure: a nationwide population-based case-control study

Exposure to organic solvents has been suggested to cause or exacerbate renal disease, but methodologic concerns regarding previous studies preclude firm conclusions. We examined the role of organic solvents in a population-based case-control study of early-stage chronic renal failure (CRF). All native Swedish residents aged 18 to 74 yr, living in Sweden between May 1996 and May 1998, formed the source population. Incident cases of CRF in a pre-uremic stage (n = 926) and control subjects (n = 998), randomly selected from the study base, underwent personal interviews that included a detailed occupational history. Expert rating by a certified occupational hygienist was used to assess organic solvent exposure intensity and duration. Relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for potentially important covariates. The overall risk for CRF among subjects ever exposed to organic solvents was virtually identical to that among never-exposed (OR, 1.01; 95% confidence interval [CI], 0.81 to 1.25). No dose-response relationships were observed for lifetime cumulative solvent exposure, average dose, or exposure frequency or duration. The absence of association pertained to all subgroups of CRF: glomerulonephritis (OR, 0.96; 95% CI, 0.68 to 1.34), diabetic nephropathy (OR, 1.02; 95% CI, 0.74 to 1.41), renal vascular disease (OR, 1.16; 95% CI, 0.76 to 1.75), and other renal CRF (OR, 0.92; 95% CI, 0.66 to 1.27). The results from a nationwide, population-based study do not support the hypothesis of an adverse effect of organic solvents on CRF development, in general. Detrimental effects from subclasses of solvents or on specific renal diseases cannot be ruled out.     

Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6–8 years of age

Potential contributions of environmental chemicals and conditions to the etiology of Autism Spectrum Disorders are the subject of considerable current research and speculation. The present paper describes the results of a study undertaken as part of a larger project devoted to the connection between properties of the indoor environment and asthma and allergy in young Swedish children. The larger project, The Dampness in Buildings and Health (DBH) Study, began in the year 2000 with a questionnaire distributed to parents of all children 1–6 years of age in one Swedish county (DBH-I). A second, follow-up questionnaire (DBH-III) was distributed in 2005. The original survey collected information about the child, the family situation, practices such as smoking, allergic symptoms, type of residence, moisture-related problems, and type of flooring material, which included polyvinyl chloride (PVC). The 2005 survey, based on the same children, now 6–8 years of age, also asked if, during the intervening period, the child had been diagnosed with Autism, Asperger's syndrome, or Tourette's syndrome. From a total of 4779 eligible children, 72 (60 boys, 12 girls) were identified with parentally reported autism spectrum disorder. A random sample of 10 such families confirmed that the diagnoses had been made by medical professionals, in accordance with the Swedish system for monitoring children's health. An analysis of the associations between indoor environmental variables in 2000 as well as other background factors and the ASD diagnosis indicated five statistically significant variables: (1) maternal smoking; (2) male sex; (3) economic problems in the family; (4) condensation on windows, a proxy for low ventilation rate in the home; (5) PVC flooring, especially in the parents’ bedroom. In addition, airway symptoms of wheezing and physician-diagnosed asthma in the baseline investigation (2000) were associated with ASD 5 years later. Results from the second phase of the DBH-study (DBH-II) indicate PVC flooring to be one important source of airborne phthalates indoors, and that asthma and allergy prevalence are associated with phthalate concentrations in settled dust in the children's bedroom. Because these associations are among the few linking ASD with environmental variables, they warrant further and more extensive exploration.