Comprehensive assessment of aquatic community responses to a new anionic surfactant, high-solubility alkyl sulfate

High-solubility alkyl sulfate (HSAS) is a new anionic surfactant for use in consumer product applications that provides enhanced water solubility and improved water hardness tolerance. A comprehensive model stream ecosystem investigation was conducted to assess ecological and toxicological effects of HSAS on stream invertebrates. Model streams were dosed with HSAS for a period of 56 days following 56 days of colonization in a single-pass, flow-through system. Exposures were control and 9.1, 24.1, 64.0, 165.8, and 426.5 microg/L based on specific analytical detection methods. Benthic abundance on gravel substrates, drift, and insect emergence were assessed. Several taxonomically unrelated taxa were found sensitive to HSAS and formed the basis of toxicological conclusions. Abundance or biomass of a limpet (Ferrissea), a bivalve (Corbicula), flatworms (Turbellaria), and a mayfly (Stenonema) was reduced at concentrations ranging from 165.8 to 426.5 microg/L. Principal response curve analysis, a constrained form of principal components analysis, demonstrated consistency with univariate analyses and identified similar populations as being sensitive to HSAS. Comparison with historical studies from the same testing site, streams, and experimental design, but with structurally related alkyl sulfate and alkyl ethoxysulfate anionic surfactants, revealed several similar trends in response profiles at the population level for both tolerant and sensitive species. Based on the comprehensive nature of the study, strength of data trends, and demonstrated sensitivity of the aquatic communities contained in the experimental system, the no-observed-effect concentration for HSAS was concluded to be 64.0 microg/L. An application factor of 1 is justified for deriving a predicted no-effect concentration) for HSAS in aquatic systems.     

Bidirectional glenn shunt surgery using lepirudin anticoagulation in an infant with heparin-induced thrombocytopenia with thrombosis

There are few reports of the management of pediatric patients with heparin-induced thrombocytopenia (HIT) requiring cardiac surgery using currently available anticoagulants. We report a case of an infant with HIT requiring a bidirectional Glenn shunt who was successfully managed using lepirudin (r-hirudin, Refludan; Aventis, Bridgewater, NJ). Dosing and monitoring of anticoagulation were difficult, and we suggest caution in the use of lepirudin for cardiac surgery unless reliable monitoring of the degree of anticoagulation becomes available.     

Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on glomerular protein permeability barrier

BACKGROUND: Proteinuria is a significant problem in medicine today, although glomerular events underlying it are unknown. Products of cytochrome P450 (CYP450) pathway of arachidonic acid metabolism are increasingly recognized as playing major roles in renal function. We used in vitro albumin permeability (P(alb)) as a measure of injury and puromycin aminonucleoside (PAN) as an injurious agent to test the hypothesis that 20-hydroxyeicosatetraenoic acid (20-HETE) protects the glomerular filtration barrier from increased P(alb). METHODS: We determined P(alb) in the following experimental groups: (1) isolated rat glomeruli incubated with PAN (5 microg/mL) for 5, 15, 30 or 60 minutes; (2) isolated glomeruli preincubated with 20-HETE (1.0 nmol/L to 100 nmol/L) for 15 minutes followed by additional incubation with PAN (5 microg/mL) for 15 minutes; (3) isolated glomeruli from rats treated with the CYP450 4A inducer clofibrate, and incubated with PAN (5 microg/mL) for 15 minutes; and (4) appropriate controls for each group. CYP450 4A levels were measured in glomeruli isolated from rats treated with clofibrate or vehicle. RESULTS: PAN increased P(alb) of isolated glomeruli as early as 5 minutes (P(alb) 0.33 +/- 0.21, P < 0.05 vs. control). Maximal effect occurred at 30 minutes (P(alb) 0.75 +/- 0.16, P < 0.001 vs. control). Inclusion of 20-HETE (100 nmol/L) blocked the increased P(alb) caused by PAN (P(alb) 0.05 +/- 0.13). Likewise, glomeruli isolated from rats treated with clofibrate were protected from PAN-induced increase in P(alb) (P(alb) 0.19 +/- 0.03). Treatment with clofibrate significantly increased glomerular CYP450 4A expression. CONCLUSION: PAN directly and immediately affects the glomerular permeability barrier. Furthermore, exogenous 20-HETE or clofibrate treatment protects glomeruli from increased P(alb) caused by PAN. Relative lack of 20-HETE may be a general characteristic of proteinuric states. Conversely, measures used to treat and/or prevent proteinuria may act to restore or increase glomerular 20-HETE levels.     

Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds

BACKGROUND: The military presents a unique opportunity to study the incidence of disease in a population with complete knowledge of person-time and occupation. Women in the Army are employed more frequently in non-traditional, industrial jobs such as auto mechanic and motor transport operators than in the general US population, increasing the probability of exposure to industrial chemicals. A cohort to investigate the risk of breast cancer among active duty Army women occupationally exposed to volatile organic chemicals (VOCs) was constructed. METHODS: Age-adjusted incidence rates for breast cancer were calculated for more than 270,000 enlisted women who served between 1980-1996. Twenty-one VOCs, described in previously published literature as having a potential risk of breast cancer, were identified in an Army industrial hygiene survey database. Job title histories were linked to workplace chemical evaluations conducted by Army industrial hygienists, which included a subjective exposure potential rating (high, medium, low, and none) for each VOC. Poisson regression analysis was used to evaluate the association between the exposure rating by job title and breast cancer. RESULTS: The incidence of breast cancer in the cohort was significantly elevated in women younger than 35 years of age, especially among black women, when compared to the age-specific rates in the general population. Women who worked in occupations with a moderate to high exposure potential to at least one VOC had a 48% increased risk (P < 0.05) of breast cancer while on active duty between 1980-1996 when compared to those women with low to no exposure potential. CONCLUSIONS: This study provides preliminary evidence that exposure to one or more of the study VOCs is associated with an increased risk of breast cancer. Further substance-specific, quantitative analyses are warranted.     

Coding patient-centred behaviour in the medical encounter

A patient-centred approach is increasingly advocated and incorporated in medical education. Due to its multi-dimensionality, however, the concept of patient-centredness appears to be hard to measure and, consequently, to evaluate. The objective of this study was to develop an instrument to measure patient-centredness in line with one central dimension, i.e. physicians' explorative communication skills: the tendency to encourage (or discourage) patients to express their perspective on illness and treatment, by displaying facilitating and inhibiting behaviours. The paper describes the development of the patient-centred behaviour coding instrument (PBCI), and first results of validity and reliability of the instrument. The study was conducted in the outpatient division of an academic teaching hospital in The Netherlands, where follow-up encounters were videotaped and coded. Participants were 30 residents and specialists in general internal medicine, rheumatology and gastro-enterology, and 323 patients having a (video-taped) follow-up appointment with one of these physicians. All recorded consultations were coded using the PBCI. Statistical analyses verified the existence of two dimensions of the PBCI: facilitating and inhibiting behaviours. Interestingly, open and closed questions generally appeared to be indicative of both the facilitating and the inhibiting dimension; only open and closed questions with a psycho-social content were unambiguously classified as facilitating behaviours. Reliability of the facilitating behaviours was high, while reliability of the inhibiting behaviours was moderate. Besides infrequent observations of the inhibiting behaviours, low reliability was partly due to individual inter-rater variability. A global rating of patient-centredness appeared to correlate with the two dimensions in the expected direction: positively with the facilitating and negatively with the inhibiting dimension, indicating the convergent validity of the instrument.     

Platelet transfusion containing ABO-incompatible plasma and hepatic veno-occlusive disease after hematopoietic transplantation in young children

BACKGROUND: Hepatic veno-occlusive disease is a major limiting factor of high-dose chemotherapy in children. The cells lining the hepatic vascular endothelium express blood group A and/or B antigens according to the patient's blood group. We designed a study evaluating the impact of platelet concentrates containing ABO-incompatible plasma transfused to young children with a high risk of hepatic veno-occlusive disease. METHODS: In all, 186 consecutive children (median age: 4 years, range: 0.75-17 years), treated with high-dose chemotherapy containing busulfan followed by hematopoietic stem cell transplantation for neuroblastoma (n=112) or brain tumor (n=74) between 1988 and 1998, were investigated. The main endpoint was the occurrence of hepatic veno-occlusive disease. Multivariate analysis was performed using a Cox's regression model with transfusion of platelet concentrates containing ABO-incompatible plasma as a time-dependent covariate. RESULTS: We found that 73 out of 186 (39%) children developed hepatic veno-occlusive disease after transplantation. Multivariate analysis demonstrated that two factors significantly increased the risk of hepatic veno-occlusive disease occurrence: transfusion of platelet concentrates containing ABO-incompatible plasma (P=0.003) and use of melphalan in the conditioning regimen (P=0.006). Conversely, the number of platelet concentrates transfusions per week, child's age, weight, sex, and use of cyclophosphamide in the conditioning regimen had no effect. CONCLUSIONS: Transfusion of platelet concentrates containing ABO-incompatible plasma increases the risk of hepatic veno-occlusive disease in young children treated with a busulfan-containing regimen. Binding of A and/or B antigens expressed on the surface of hepatic endothelial cells may promote this complication. Transfusion of platelet concentrates containing ABO-incompatible plasma should be avoided in these children.     

Impact of smoking on fracture healing and risk of complications in limb-threatening open tibia fractures

OBJECTIVES: Current data show smoking is associated with a number of complications of the fracture healing process. A concern, however, is the potential confounding effect of covariates associated with smoking. The present study is the first to prospectively examine time to union, as well as major complications of the fracture healing process, while adjusting for potential confounders. SETTING: Eight Level I trauma centers. PATIENTS: Patients with unilateral open tibia fractures were divided into 3 baseline smoking categories: never smoked (n = 81), previous smoker (n = 82), and current smoker (n = 105). OUTCOME MEASURE: Time to fracture healing, diagnosis of infection, and osteomyelitis. METHODS: Survival and logistic analyses were used to study differences in time to fracture healing and the likelihood of developing complications, respectively. Multivariate models were used to adjust for injury severity, treatment variations, and patient characteristics. RESULTS: After adjusting for covariates, current and previous smokers were 37% (P = 0.01) and 32% (P = 0.04) less likely to achieve union than nonsmokers, respectively. Current smokers were more than twice as likely to develop an infection (P = 0.05) and 3.7 times as likely to develop osteomyelitis (P = 0.01). Previous smokers were 2.8 times as likely to develop osteomyelitis (P = 0.07), but were at no greater risk for other types of infection. CONCLUSION: Smoking places the patient at risk for increased time to union and complications. Previous smoking history also appears to increase the risk of osteomyelitis and increased time to union. The results highlight the need for orthopaedic surgeons to encourage their patients to enter a smoking cessation programs.     

Immunolocalization of estrogen receptor alpha and beta in human fetal prostate

PURPOSE: We examined the immunolocalization of estrogen receptor (ER)alpha and ERbeta in the human fetal prostate. MATERIALS AND METHODS: Tissue sections from human fetal prostates at 7 to 22 weeks of gestation were stained with antibodies to ERalpha, ERbeta, and cytokeratin 10 and 14. RESULTS: ERalpha expression was not detected until 15 weeks of gestation with sparse staining in the utricle. By 19 weeks increased ERalpha expression was seen in the luminal cells of the ventral urogenital epithelium (UGE), basal cells of the dorsal UGE, utricle, distal periurethral ducts, peripheral stroma and posterior prostatic duct. K14 was detected in basal cells of the UGE and in several posterior acini. At 22 weeks ERalpha expression was more intense in all of these areas. ERbeta was expressed throughout the UGE, ejaculatory ducts, müllerian ducts and entire stroma at 7 weeks. Intense ERbeta staining was observed in these areas and in the prostatic buds by 8 weeks with persistent intense staining through 22 weeks. CONCLUSIONS: To our knowledge we report the first immunolocalization of ERalpha in the human fetal prostate and the earliest demonstration of ERbeta expression in the prostate at 7 weeks of gestation. ERbeta expression is intense during ductal morphogenesis, suggesting a role in normal glandular growth and proliferation. The induction of squamous metaplasia in the UGE, distal periurethral ducts and utricle is associated with ERalpha expression in these areas, while the induction of squamous metaplasia in peripheral prostatic acini is associated with peripheral stromal ERalpha expression. This study suggests estrogen signaling pathways in the human fetal prostate via ERalpha that involve epithelial-epithelial and epithelial-stromal interactions.     

Electrostimulation for the prevention of deep venous thrombosis in patients with major trauma: a prospective randomized study

BACKGROUND: Current methods of posttraumatic thromboprophylaxis (heparins and sequential compression devices) are inadequate. New methods should be tested. Muscle electrostimulation (MEST) has been used over the years with mixed-but predominantly encouraging-results for a variety of conditions, including prevention of deep venous thrombosis (DVT). It has not been tested in multiple trauma patients. METHODS: Trauma patients with Injury Severity Score higher than 9 who were admitted to the intensive care unit and had a contraindication for prophylactic heparinization were randomized to groups MEST and control. MEST patients received 30-minute MEST sessions twice daily for 7 to 14 days. Venous flow velocity and venous diameter were measured by duplex venous scan. Venography-or, if not available, duplex-was used to evaluate the presence of proximal and peripheral DVT between days 7 and 15. RESULTS: After exclusions, 26 MEST and 21 control patients completed the study and received outcome evaluation by venography (25) or duplex (22). Three patients in each group developed proximal DVT (11.5% vs 14%, P = .79), and an additional 4 (15%) MEST group and 3 (14%) control group patients developed peripheral DVT ( P = .96). There was no difference in venous flow velocity or venous diameter between the groups. CONCLUSIONS: MEST was not effective in decreasing DVT rates in major trauma patients.     

A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery

OBJECTIVE: This study was undertaken to evaluate the effect of triiodothyronine replacement on the early postoperative course of neonates undergoing aortic arch reconstruction. METHODS: We performed a randomized, double-blind, placebo-controlled trial of triiodothyronine supplementation in neonates undergoing either a Norwood procedure or two-ventricle repair of interrupted aortic arch and ventricular septal defect. Patients were assigned to receive a continuous infusion of triiodothyronine (0.05 micro/kg/h) or placebo for 72 hours after cardiopulmonary bypass. Primary end points were a composite clinical outcome score and cardiac index at 48 postoperative hours. RESULTS: We enrolled 42 patients (triiodothyronine n = 22, placebo n = 20). Baseline characteristics were similar in the treatment groups. Study drug was discontinued prematurely because of hypertension (n = 1) and ectopic atrial tachycardia (n = 1), both cases in the triiodothyronine group. Free and total triiodothyronine levels were higher in the triiodothyronine group than in the placebo group at 24, 48, and 72 postoperative hours (P < .001). The median clinical outcome scores were 2.0 (range 0-4) with triiodothyronine and 2.0 (range 0-7) with placebo (P = .046). Compared with those in the placebo group, neonates assigned to triiodothyronine had shorter median time to negative fluid balance (2.0 vs 2.5 days, P = .027). Cardiac index values were 2.11 +/- 0.64 L/min x m2 with triiodothyronine and 2.05 +/- 0.72 L/min x m2 with placebo (P = .81). Heart rate and diastolic blood pressure were not influenced by triiodothyronine supplementation, but systolic blood pressure was higher in the triiodothyronine group (P < .001). No serious adverse events were attributed to triiodothyronine administration. CONCLUSION: Triiodothyronine supplementation was safe and resulted in more rapid achievement of negative fluid balance after aortic arch reconstruction. Cardiac index at 48 hours was not significantly improved.