Allylmercapturic acid as urinary biomarker of human exposure to allyl chloride

OBJECTIVE: To evaluate the use of urinary mercapturic acids as a biomarker of human exposure to allyl chloride (3-chloropropene) (AC). During three regular shut down periods in a production factory for AC, both types of variables were measured in 136 workers involved in maintenance operations. METHODS: Potential airborne exposure to AC was measured by personal air monitoring in the breathing zone. In total 205 workshifts were evaluated. During 99 workshifts no respiratory protection equipment was used. Mercapturic acid metabolites were measured in urinary extracts by gas chromatography-mass spectrometry (GC-MS). RESULTS: During 86 work shifts when no respiratory protection was used the air concentrations of AC were below the Dutch eight hour time weighted average (8 h-TWA) occupational exposure limit (OEL) of AC (3 mg/m3), whereas in 13 workshifts the potential exposure, as measured by personal air monitoring, exceeded the OEL (3.3 to 17 mg/m3). With the aid of GC-MS, 3-hydroxypropylmercapturic acid (HPMA) was identified as a minor and allylmercapturic acid (ALMA) as a major metabolite of AC in urine samples from the maintenance workers exposed to AC. The concentrations of ALMA excreted were in a range from < 25 micrograms/l (detection limit) to 3550 micrograms/l. The increases in urinary ALMA concentrations during the workshifts correlated well with the 8h-TWA air concentrations of AC (r = 0.816, P = 0.0001, n = 39). Based on this correlation, for AC a biological exposure index (BEI) of 352 micrograms ALMA/g creatinine during an eight hour workshift is proposed. In some urine samples unexpectedly high concentrations of ALMA were found. Some of these could definitely be attributed to dermal exposure to AC. In other cases garlic consumption was identified as a confounding factor. CONCLUSION: The mercapturic acid ALMA was identified in urine of workers occupationally exposed to airborne AC and the increase in ALMA concentrations in urine during a workshift correlated well with the 8 h-TWA exposure to AC. Garlic consumption, but not smoking, is a potential confounding factor for this biomarker of human exposure to AC.     

Chromosomal anomalies in stage D1 prostate adenocarcinoma primary tumors and lymph node metastases detected by fluorescence in situ hybridization

We previously reported a HPLC assay method using fluorimetric detection for the simultaneous determination of urinary N2-(3-aminopropyl)biopterin (oncopterin, a natural pteridine newly found in urine from cancer patients), biopterin and neopterin. We now have observed that an unknown substance, which may be derived from methotrexate, in urine from a patient with stomach cancer interfered with the assay of oncopterin and demonstrated that oncopterin could be completely separated from the unidentified substance by HPLC using a Nucleosil 100-5SA strong cation-exchange column. Furthermore, oncopterin was not detectable by this HPLC-fluorimetric method in urine samples from patients with stomach cancer who were not treated with methotrexate. The content of urinary oncopterin from cancer patients is supposed to be very low, with less than 1 mumol/mol creatinine. The present results indicate that the peak found with elution from the C18 column was a methotrexate-derived compound and co-eluted with the analyte oncopterin.     

'True' fasting serum insulin level, insulin resistance syndrome and coronary artery disease

BACKGROUND: Increased fasting serum insulin level not associated with hypoglycemia is considered to be a practical indicator of the insulin resistance syndrome, a frequent risk factor for atherosclerosis in industrialized countries. However, in most studies, insulin was measured by using antibodies which cross-react with proinsulin and 31/32, 32/33 split products of insulin. We re-examined the correlations between the insulin resistance syndrome and 'true' fasting serum insulin level. METHODS: We studied 242 post-menopausal women (age 63 +/- 8 years), a population in whom insulin resistance syndrome is particularly frequent. Serum insulin was measured by a recent specific microparticle immunoassay. RESULTS: There was a significant correlation between elevated 'true' fasting serum insulin level and various constituents of the insulin resistance syndrome, such as obesity, dyslipidemia (hypertriglyceridemia, increased apolipoprotein B and decreased high-density lipoprotein cholesterol and apolipoprotein A1 concentrations), increased serum glucose, uric acid levels, and plasminogen activator inhibitor type I concentration, as well as increased frequency of diabetes. There was also a correlation between insulin level and various manifestations of coronary artery disease: patients in the highest quartile of 'true' insulin level had significantly more entirely occluded coronary arteries than in the lowest one. Similarly, in the highest insulin quartile more patients had occluded arteries with lumen diameter stenoses greater than 50% (P < 0.05) and more of them had history of previous myocardial infarction approaching the level of significance (P = 0.0587) than in the lowest one. Most of these correlations were also noted in nondiabetic people. CONCLUSIONS: An increase of 'true' fasting serum insulin level is a useful practical index to identify patients with the insulin resistance syndrome exposed to increased risk of coronary artery disease.     

Hernia survey of the Section on Surgery of the American Academy of Pediatrics

The members of the Section on Surgery of the American Academy of Pediatrics were surveyed to determine the practice of North American pediatric surgeons in infants with inguinal hernia (IH). Case-scenario multiple-choice-design questionnaires regarding hernias and hydroceles were sent to all members of the Surgical Section, and responses were received from 292 (50%). In healthy full-term infant boys with asymptomatic reducible IH, 82% of responders perform repair electively, no matter what the age or weight. In full-term girls with a reducible ovary, 59% perform surgery at the next available time; if the ovary is nonreducible but asymptomatic, 44% operate emergently or urgently and 42% at the next elective slot. In former preemies, the pattern of repair is as follows. (1) For those recently discharged after 2 months in the neonatal intensive care unit (NICU) with reducible IH, 65% perform the repair when convenient. (2) A general anesthetic is used in 70%; 15% use spinal anesthesia, and 11% use caudal block with sedation. (3) If the repair is done in the hospital outpatient (same-day) unit, 36% wait until 50 weeks postconception (PC) and 33% wait until 60 weeks PC. (4) if the baby's weight is at least 1,000 g. 71% perform the repair before discharge. The pain control choice after childhood IH repair is Tylenol for 30%, local infiltration biquivacaine for 30%, caudal block for 22%, regional block for 11%, and Tylenol/codeine combined for 7%. In 6-week-old full-term infants with communicating hydroceles without definite "hernia," two thirds treat as an IH with elective repair as soon as possible. With respect to contralateral exploration in infants with unilateral IH, 65% perform it in males if they are < or = 2 years of age and 84% use it in females of up to 4 years of age. This approach is not influenced by presenting side, presence of hydrocele, or history of prematurity. Laparoscopic evaluation of the contralateral IH is performed by only 6% of responders, 40% of whom use the open ipsilateral sac for laparoscope introduction.     

Fat and female fecundity: prospective study of effect of body fat distribution on conception rates

OBJECTIVES: To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN: Prospective cohort study of all women who had entered a donor insemination programme. SETTING: One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS: Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES: Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS: A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS: Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.     

Dynamic kinetic asymmetric cycloadditions of isocyanates to vinylaziridines

The first examples of the use of racemic vinylaziridines in a Pd-catalyzed dynamic kinetic asymmetric transformation have been examined. Optimization studies of the Pd-catalyzed addition of vinylaziridines to isocyanates revealed that the chiral ligand between trans-1,2-diaminocyclohexane and 2-diphenylphosphino-1-naphthoic acid is superior to that involving 2-diphenylphosphino benzoic acid. Surprisingly, high ee's required the use of an acid whose pKa was about 4.7 +/- 0.1 as a cocatalyst. Both acetic acid and hydroxybenzotriazole meet this requirement. Less electrophilic isocyanates (e.g., benzyl, p-methoxyphenyl) gave higher ee's than more electrophilic ones (phenyl or benzoyl). Both N-benzyl and N-arylaziridines react well to give good yields and ee's, whereas N-tosylaziridines gave lower ee's. A 1,1-disubstituted aziridine led to the formation of a tertiary C-N bond with ee's comparable to the formation of the secondary C-N bond. The products were easily reduced almost quantitatively to the sensitive imidazolidines which can be readily hydrolyzed to the vicinal diamines. The reactivity pattern is consistent with a Curtin-Hammett situation wherein the enantiodiscriminating event is the cyclization of a rapidly equilibrating dynamic pi-allyl palladium intermediate.     

The necessary role of the autopsy in cardiovascular epidemiology

The autopsy rate in the United States today is remarkably low, with proportionally fewer autopsies for natural causes of death. Consequently, most cardiovascular epidemiology studies do not use autopsy data and rely on death certificates, medical records, questionnaires, and family interviews as sources of mortality information. These practices introduce a high degree of variability and uncertainty regarding cause of death. This review illustrates the necessity for increased use of autopsies in cardiovascular epidemiology by critically evaluating other measures of cardiovascular disease (CVD) incidence. We evaluated the literature regarding CVD as cause of death and conducted discussions with cardiologists, pathologists, and epidemiologists. No attempt was made for meta-analysis. This review shows the limited reliability of death certificates, medical records, and interviews as sources of mortality statistics. In addition, the autopsy's role in clearly indicating the presence of CVD is illustrated. The autopsy used in conjunction with medical records is the only reliable means for establishing cause of death from CVD. There is an urgent need to reassess the current dependence of statistical mortality data on death certificates and other inadequate sources of CVD incidence. Death certificates, in general, are inadequately monitored for quality control and appropriate administrative oversight. With an increase in the number of hospitals performing no autopsies to investigate cause of death, a uniform national autopsy database is needed.