Determinants of organophosphorus pesticide urinary metabolite levels in pregnant women from the CHAMACOS cohort.

Organophosphosphorus pesticides (OPs) are widely used as insecticides in agriculture. Human exposure to OPs has been linked to adverse effects including poorer child neurodevelopment, reduced birth weight, altered serum hormone levels, and reduced semen quality. We measured six OP dialkyl phosphate (DAP) metabolites [three dimethyl alkylphosphates (DMs) and three diethyl alkylphosphates (DEs)] in urine samples collected two times during pregnancy (~13 and ~26 weeks gestation) from 594 women participating in the CHAMACOS birth cohort study and resided in an agricultural community in the United States (U.S.) between 1999 and 2000. Previous studies have shown these women have higher OP exposures compared with the general U.S. population. We examined bivariate associations between prenatal DAP metabolite levels and exposure determinants such as age, season, years living in the US, housing characteristics, fruit and vegetable consumption, occupation and residential proximity to agricultural fields. Final multivariable models indicated that season of urine collection was significantly associated (p < 0.01) with specific gravity-adjusted DM, DE and total DAP metabolites; samples collected in fall and winter had higher concentrations than those collected in spring-summer. Specific gravity-adjusted levels of DM and total DAP metabolites were significantly higher in women who had resided in the U.S. for 5 years or less (p < 0.05). Levels of DM metabolites also increased with daily fruit and vegetable servings (p < 0.01), and levels of DE metabolites were higher in residences with poorer housekeeping quality (p < 0.01) and in mothers that worked in agriculture (p < 0.05). These findings suggest that there are multiple determinants of OP exposure in pregnant women.

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

Influence of age on mitochondrial enzyme levels in Drosophila.

The specific activity and the activity per fly of four mitochondrial enzymes did not change with ageing in male Drosophila melanogaster (Oregon R). The enzymes assayed were rotenone-insensitive NADH-cytochrome c reductase, adenylate kinase, succinate cytochrome c reductase, and malate dehydrogenase, located in the outer membrane, inner membrane space, inner membrane and matrix, respectively. The specific activity of malate dehydrogenase showed no significant change for young and old head, thorax and abdomen. We conclude that there is no specific site for ageing damage in the mitochondrion, when the enzyme activities in this study are used as an indicator. It should be noted, however, that these enzymes represent only a small percentage of the total enzymes present in mitochondria.

Hepatic insulin extraction after major hepatectomy.

BACKGROUND: After major hepatectomy, the remaining liver compensates for its reduced mass and maintains euglycemia through increased hepatic glucose output. The mechanism of this compensation may be a diminished hepatic extraction of portal insulin, which thereby decreases the suppressive effects of insulin on gluconeogenesis. METHODS: Extraction of insulin by the liver was measured using the isolated perfused rat liver model. Fasted Sprague-Dawley rats were studied at 1, 2, 3, 4, 6, and 14 days after 70% hepatectomy. Control rats had no operation, and sham rats were studied 1 day after a sham laparotomy. The difference between portal and caval insulin concentrations was determined and reported as micromoles of insulin extracted per gram liver per minute. RESULTS: Insulin extraction decreased from 191 +/- 22 microU/gm liver/min in control rats to 87 +/- 13.2 microU/gm liver/min at postoperative day 1 (p = 0.0001). Extraction normalized by postoperative day 6. Extraction rates in rats recovering from sham laparotomy were similar to control rats (p = 0.088), suggesting that decreased extraction in hepatectomized rats was not due to postoperative stress. CONCLUSIONS: After 70% hepatectomy, the remaining liver extracts less insulin per gram. This may explain the ability of the reduced liver mass to maintain euglycemia after major hepatectomy.

Cholecystectomy in patients with mild cirrhosis. A more favorable situation.

A conservative approach toward elective cholecystectomy in the patient with cirrhosis has been suggested because of the strong likelihood of excessive bleeding, sepsis, and multiple organ failure. We reviewed this problem in two medical centers, studying 27 patients with cirrhosis who had undergone nonemergency biliary tract surgery. Most patients had adequate liver function preoperatively. Most operations were cholecystectomies without duct exploration. Among factors analyzed were liver function tests, coagulation tests, and Child's classification. Prothrombin time was less than 2.5 s above control in 18 patients, more than 2.5 s above control in four patients, and not recorded in five patients. All survived the operation with benign postoperative courses. Only one patient had excessive bleeding; this patient had an elevated prothrombin time preoperatively. We conclude that elective cholecystectomy can be performed safely in patients with cirrhosis who have relatively normal liver function.

Sentinel lymph node biopsy for melanoma in young children.

Lymphoscintigraphy and sentinel lymph node biopsy techniques can be applied successfully to young children with melanoma to detect nodal disease. The authors describe their methods of lymphoscintigraphy and sentinel node biopsy and its application in 2 young children with malignant melanoma of the head and neck.

Thoracoscopic thymectomy for myasthenia gravis in children.

The technique for thoracoscopic in children is described. The average operating time is under 2 hours, and the procedure appears to be safe and effective.

The association of elevated percent bands on admission with failure and complications of interval appendectomy.

BACKGROUND/PURPOSE: The routine use of interval appendectomy for the treatment of perforated appendicitis, with or without abscess, remains controversial. The purpose of this study is to confirm the efficacy of this approach and to identify factors associated with failures and complications. METHODS: All patients (n = 101) with their clinical diagnosis of perforated appendicitis confirmed with imaging were treated prospectively with fluids and intravenous antibiotics (clindamycin, ceftazidime) and were discharged home on oral fluids and analgesics regardless of fever. Intravenous antibiotics were continued at home until the patients were afebrile for 48 hours, and their white blood cell and differential counts were normal. Patients were readmitted at 8 to 12 weeks for an interval appendectomy. Failure to improve by 72 hours of antibiotic therapy mandated an early appendectomy. P values were determined by chi(2) analysis and Student's t test. RESULTS: The 79 patients (78%) successfully treated with interval appendectomy had an overall 6.3% complication rate, and total hospitalization averaged 5.2 days. The treatment in 21 of 22 patients (22%) requiring early appendectomy failed because of a clinical picture suggesting small bowel obstruction. The patients with the failed procedures had a complication rate of 50% and were hospitalized an average of 12.8 days. The overall complication rate for the 101 patients was 15.8%, and the overall total hospitalization was 6.9 days. Patients requiring early appendectomy had a more frequent finding resembling a small bowel obstruction on their initial x-ray (50% v 13%, P = .004) and a higher percent band count on their initial differential blood cell count (22.6% v 7.6%, P<0.0001) than did those successfully treated with interval appendectomy. An initial band count <15% was predictive of an uncomplicated course (84% positive predictive value). CONCLUSIONS: Interval appendectomy without complications is successful in the majority of patients with perforated appendicitis. An elevated initial band count > or =15% is associated with an increased likelihood of failure and complications.

A comparison of the mechanisms of CO2 hydration by native and Co2+-substituted carbonic anhydrase II.

We have measured the pH dependence of kcat and kcat/Km for CO2 hydration catalyzed by both native Zn2+-and metallo-substituted Co2+-bovine carbonic anhydrase II in the absence of inhibitory ions. For the Zn2+-enzyme, the pKa values controlling kcat and kcat/Km profiles are similar, but for the Co2+-enzyme the values are about 0.6 pH units apart. Computer simulations of a metal-hydroxide mechanism of carbonic anhydrase suggest that the data for both native and Co2+-carbonic anhydrase can be accounted for by the same mechanism of action, if we postulate that the substitution of Co2+ for Zn2+ in the active site causes a separation of about 0.6 pH units in the pKa values of His-64 and the metal-bound water molecule. We have also measured the activation parameters for kcat and kcat/Km for Co2+-substituted carbonic anhydrase II-catalyzed CO2 hydration and have compared these values to those obtained previously for the native Zn2+-enzyme. For kcat and kcat/Km we obtain an enthalpy of activation of 4.4 +/- 0.6 and approximately 0 kcal mol-1, respectively. The corresponding entropies of activation are -18 +/- 2 and -27 +/- 2 cal mol-1 K-1.