Long-term environmental exposure to perchlorate through drinking water and thyroid function during pregnancy and the neonatal period.

We have conducted a longitudinal epidemiologic study among pregnant women from three cities in northern Chile: Taltal with 114 microg/L, Chañaral with 6 microg/L, and Antofagasta with 0.5 microg/L perchlorate in the public drinking water. We tested the hypothesis that long-term exposure to perchlorate at these levels may cause a situation analogous to iodine deficiency, thus causing increases in thyrotropin (TSH) and thyroglobulin (Tg) levels and decreased levels of free thyroxine (FT4), in either the mother during the early stages of gestation or the neonate at birth, or in the fetus cause growth retardation.

Measurement of trihalomethanes and methyl tert-butyl ether in whole blood using gas chromatography with high-resolution mass spectrometry.

The prevalence of disinfection by-products in drinking water supplies has raised concerns about possible adverse health effects from chronic exposure to these compounds. To support studies exploring the relation between exposure to trihalomethanes (THMs) and adverse health effects, an automated analytical method was developed using capillary gas chromatography (GC) and high-resolution mass spectrometry (MS) with selected ion mass detection and isotope-dilution techniques. This method quantified trace levels of THMs (including chloroform, bromodichloromethane, dibromochloromethane, and bromoform) and methyl tert-butyl ether (MTBE) in human blood.

Identification and elimination of polysiloxane curing agent interference encountered in the quantification of low-picogram per milliliter methyl tert-butyl ether in blood by solid-phase microextraction headspace analysis.

Widespread use of the gasoline additive methyl tert-butyl ether (MTBE) and the subsequent human exposure that follows have led to the need to quantify MTBE in a variety of complex biological matrixes. In this work, we demonstrate our latest MTBE quantification assay for whole blood and uncover previously unidentified contamination sources that prevented routine quantification in the low picogram per milliliter (parts per trillion, ppt) range despite a sensitive and selective analytical approach. The most significant and unexpected sources of contamination were found in reagents and laboratory materials most relevant to sample preparation and quantification.

Analysis of perchlorate in human urine using ion chromatography and electrospray tandem mass spectrometry.

Because of health concerns surrounding widespread exposure to perchlorate, we developed a sensitive and selective method for quantifying perchlorate in human urine using ion chromatography coupled with electrospray ionization tandem mass spectrometry. Perchlorate was quantified using a stable isotope-labeled internal standard ((18)O(4)-perchlorate) with excellent assay precision (coefficient of variation <5% for repetitively analyzed quality control material). Analytical accuracy was established by blind analysis of certified proficiency testing materials prepared in synthetic urine matrix; calculated amounts deviated minimally from true amounts, with percent differences ranging from 2% to 5%.

Measurement of trihalomethanes and methyl tertiary-butyl ether in tap water using solid-phase microextraction GC-MS.

The prevalence of water disinfection byproducts in drinking water supplies has raised concerns about possible health effects from chronic exposure to these compounds. To support studies exploring the relation between exposure to trihalomethanes (THMs) and health effects, we have developed an automated analytical method using headspace solid-phase microextraction coupled with capillary gas chromatography and mass spectrometry. This method quantitates trace levels of THMs (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) and methyl tertiary-butyl ether in tap water.

Epidemic parenteral exposure to volatile sulfur-containing compounds at a hemodialysis center.

Objective: To determine the cause of acute illness on August 30, 2000, among patients at an outpatient dialysis center (center A).

Design: We performed a cohort study of all patients receiving dialysis on August 30, 2000; reviewed dialysis procedures; and analyzed dialysis water samples using microbiologic and chemical assays.

Setting: Dialysis center (center A).

Biomonitoring of chemical exposure among New York City firefighters responding to the World Trade Center fire and collapse.

The collapse of the World Trade Center (WTC) on 11 September 2001 exposed New York City firefighters to smoke and dust of unprecedented magnitude and duration. The chemicals and the concentrations produced from any fire are difficult to predict, but estimates of internal dose exposures can be assessed by the biological monitoring of blood and urine. We analyzed blood and urine specimens obtained from 321 firefighters responding to the WTC fires and collapse for 110 potentially fire-related chemicals.

Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.

Urinary and serum concentrations of seven phytoestrogens in a human reference population subset.

Diets rich in naturally occurring plant estrogens (phytoestrogens) are strongly associated with a decreased risk for cancer and heart disease in humans. Phytoestrogens have estrogenic and, in some cases, antiestrogenic and antiandrogenic properties, and may contribute to the protective effect of some diets. However, little information is available about the levels of these phytoestrogens in the general US population.

5-Chlorouracil, a marker of DNA damage from hypochlorous acid during inflammation. A gas chromatography-mass spectrometry assay.

Hypochlorous acid (HOCl), generated from H2O2 and Cl- by myeloperoxidase in activated neutrophils, causes tissue damage during inflammation. We have developed a simple, sensitive (approximately 0.2 fmol on column) and specific GC-MS assay for the detection of 5-chlorouracil (5-ClUra), a signature product of HOCl-mediated damage to nucleobases.

The development and testing of a dermal exposure system for pharmacokinetic studies of administered and ambient water contaminants.

Introduction: In order to investigate the pharmacokinetics of water-borne chemicals while eliminating exposures by other routes, a dermal exposure system was developed to expose the hand and forearm of human subjects.

Methods: The goal was, primarily, to study the dermal pharmacokinetics of methyl tertiary butyl ether (MTBE), a water contaminant, and, secondarily, the ambient disinfection byproducts (DBPs). MTBE is used as a fuel oxygenate and DBPs result from chlorination of drinking water.

Rosacea: a common, yet commonly overlooked, condition.

Rosacea is a common, but often overlooked, skin condition of uncertain etiology that can lead to significant facial disfigurement, ocular complications, and severe emotional distress. The progression of rosacea is variable; however, typical stages include: (1) facial flushing, (2) erythema and/or edema and ocular symptoms, (3) papules and pustules, and (4) rhinophyma. A history of exacerbation by sun exposure, stress, cold weather, hot beverages, alcohol consumption, or certain foods helps determine the diagnosis; the first line of treatment is avoidance of these triggering or exacerbating factors.

Determination of aniline derivatives in oils related to the toxic oil syndrome by atmospheric pressure ionization-tandem mass spectrometry.

In 1981, an unknown disease appeared in Spain, the Spanish Toxic Oil Syndrome. Nowadays and despite all efforts, the etiological agent is still unknown. Early studies showed a link between this illness and the consumption of denatured rapeseed oil fraudulently processed and marketed as edible oil.

Storage time and deodorization temperature influence the formation of aniline-derived compounds in denatured rapeseed oils.

In 1981 an epidemic, named Toxic Oil Syndrome, occurred in Spain as a result of ingestion of rapeseed oil denatured with 2% aniline, which had been imported for industrial use but was fraudulently diverted and processed for human consumption. Two groups of chemical compounds have been identified in the ingested toxic oil: fatty acid anilides and amino-propanediol derivatives. The objective of this work was to assess the effect of several refining process variables on the formation of 3-(N-phenylamino)-1,2-propanediol (PAP) esters.

HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine.

The elevated exposure of children to hormonally active dietary phytoestrogens has led to the need for rapid, sensitive, and precise assays for phytoestrogen metabolites in physiological matrices. Here we report the development of a high-performance liquid chromatography (HPLC) MS/MS method for the quantitative detection of seven phytoestrogens in human serum and urine. The method uses enzymatic deconjugation of the phytoestrogen metabolites followed by solid phase extraction (SPE) and reverse-phase HPLC.

Levels of seven urinary phthalate metabolites in a human reference population.

Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate.

Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS.

Because of the ubiquity of phthalates and their potential role in increasing risk for cancer and reproductive dysfunction, the need for human exposure assessment studies is urgent. In response to this need, we developed a high-throughput, robust, sensitive, accurate, and precise assay for simultaneous measurement of trace levels of eight phthalate metabolites in human urine by HPLC-MS/MS. Human urine samples were processed using enzymatic deconjugation of the glucuronides followed by solid-phase extraction.

Tuberculous cerebellar abscess.

Background: Tuberculosis is an important illness with an increasing occurrence. Although considered primarily a pulmonary disease, tuberculosis can affect any organ system. Central nervous system involvement is potentially devastating and occurs with escalating frequency in both immunocompetent and immunologically incompetent populations.

Family practice house officer perceptions of faculty teaching behaviors.

In 1985, Wolverton and Bosworth published an often referenced study of family practice teaching behaviors. Their research identified 20 "most helpful" and 10 "least helpful" behaviors. In 1994 all United States Army family practice house officers were asked by survey to rate each of the original 38 Wolverton and Bosworth teaching behaviors as "not at all helpful," "somewhat helpful," "moderately helpful," "very helpful," or "most helpful" in aiding their learning.

Army family practice: does our training meet our needs?

Objectives: (1) To determine the perceived adequacy of residency training for current practice by Army family physicians; (2) to ascertain if differences exist by residency setting: medical center, medical activity, or civilian.

Methods: Surveys were mailed to the 334 family physicians in the Army in 1993. Training in various subject areas was rated as inadequate, adequate, or overly prepared.

Peroxynitrite-mediated nitration of peptides: characterization of the products by electrospray and combined gas chromatography-mass spectrometry.

Peroxynitrite (ONOO-) can react with a wide range of biomolecules resulting in peroxidation, oxidation, and/or nitration and as a consequence cause their inactivation. In this study mass spectrometry (MS) combined with both liquid (LC) and gas chromatography (GC) has been employed to identify the products formed following ONOO- treatment of three peptides at physiological pH: leucine-enkephalin (YGGFL), V3 loop (GPGRAF), and LVV-hemorphin7 (LVVYPWTQRF). LC-MS analysis of leucine-enkephalin following ONOO treatment indicated the formation of products corresponding in mass to mono- and dinitrated forms of the starting material.

Apoptosis of late-stage erythroblasts in megaloblastic anemia: association with DNA damage and macrocyte production.

An in vitro model of folate-deficient erythropoiesis has been developed using proerythroblasts isolated from the spleens of Friend virus-infected mice fed an amino acid-based, folate-free diet. Control proerythroblasts were obtained from Friend virus-infected mice fed the same diet plus 2 mg folic acid/kg diet. Our previous studies showed that, after 20 to 32 hours of culture in folate-deficient medium with 4 U/mL of erythropoietin, the folate-deficient proerythroblasts underwent apoptosis, whereas control erythroblasts survived and differentiated into reticulocytes over a period of 48 hours.

Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage.

Folate deficiency causes massive incorporation of uracil into human DNA (4 million per cell) and chromosome breaks. The likely mechanism is the deficient methylation of dUMP to dTMP and subsequent incorporation of uracil into DNA by DNA polymerase. During repair of uracil in DNA, transient nicks are formed; two opposing nicks could lead to chromosome breaks.

Inflammation and NO(X)-induced nitration: assay for 3-nitrotyrosine by HPLC with electrochemical detection.

The identification of 15N-labeled 3-nitrotyrosine (NTyr) by gas chromatography/mass spectroscopy in protein hydrolyzates from activated RAW 264.7 macrophages incubated with 15N-L-arginine confirms that nitric oxide synthase (NOS) is involved in the nitration of protein-bound tyrosine (Tyr). An assay is presented for NTyr that employs HPLC with tandem electrochemical and UV detection.