Application of metabolomics to understanding biofilms in water distribution systems: a pilot study.

Biofilms formed in pipes are known to contribute to waterborne diseases, accelerate corrosion and cause aesthetic taste and odour issues within the potable water supply network. This paper describes a pilot study, undertaken to assess the potential of using metabolomics to monitor bacterial activity in biofilms of an urban water network. Using samples from a water mains flushing programme, it was found that a profile of intracellular and extracellular metabolites associated with microbial activity could be obtained by analysing samples using gas chromatography mass spectrometry. Chemometric analysis of the chromatograms in conjunction with data from the mass spectrometer showed that it is possible to differentiate between biofilms from different pipe materials and planktonic bacteria. This research demonstrates that metabolomics has the potential for investigating biofilms and other microbial activity within water networks, and could provide a means for enhancing monitoring programmes, understanding the source of water quality complaints, and optimising water network management strategies.

A pathway to a more sustainable water sector: sustainability-based asset management.

The water sectors of many countries are faced with the need to address simultaneously two overarching challenges; the need to undertake effective asset management coupled with the broader need to evolve business processes so as to embrace sustainability principles. Research has thus been undertaken into the role sustainability principles play in asset management. As part of this research, a series of 25 in-depth interviews were undertaken with water sector professionals from around Australia. Drawing on the results of these interviews, this paper outlines the conceptual relationship between asset management and sustainability along with a synthesis of the relevant opinions voiced in the interviews. The interviews indicated that the participating water authorities have made a strong commitment to sustainability, but there is a need to facilitate change processes to embed sustainability principles into business as usual practices. Interviewees also noted that asset management and sustainability are interlinked from a number of perspectives, especially in the way decision making is undertaken with respect to assets and service provision. The interviews also provided insights into the research needed to develop a holistic sustainability-based asset management framework.

Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway.

Previously, dietary supplementation with dried plums, a rich source of polyphenolic compounds with antioxidant and anti-inflammatory properties, has been shown to improve bone density, microstructure and biomechanics in female animal models of osteopenia. We designed this study to determine the extent to which dried plum prevents skeletal deterioration in gonadal hormone deficient male animals and to begin to understand its mechanism of action. Sixty 6-month-old male Sprague-Dawley rats were either sham-operated (Sham = 1 group) or orchidectomized (ORX = 4 groups) and randomly assigned to dietary treatments: standard semi-purified diet (Control) with either LD = 5%, MD = 15%, or HD = 25% (w/w) dried plum for 90 days. At the end of the treatment period, both the MD and HD dried plum completely prevented the ORX-induced decrease in whole body, femur, and lumbar vertebra bone mineral density (BMD). Biomechanical testing indicated that the MD and HD of dried plum prevented the ORX-induced decrease in ultimate load of the cortical bone as well as the compressive force and stiffness of trabecular bone within the vertebrae. Analyses of trabecular microarchitecture of the distal femur metaphysis and vertebral body revealed that HD dried plum protected against the decrease in trabecular bone volume (BV/TV) induced by ORX. In the distal femur, all doses of dried plum improved trabecular number (TbN) and separation (TbSp) compared to the ORX-control group, while MD and HD dried plum prevented the ORX-induced changes in vertebral TbN and TbSp. At the end of the 90-day treatment, no remarkable changes in serum osteocalcin or alkaline phosphatase in any of the treatment groups were observed, while serum insulin-like growth factor (IGF)-I was increased by dried plum. The ORX-induced increase in urinary deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried plum coinciding with down-regulation of gene expression for receptor activator of NFkappa-B ligand (RANKL) and osteoprotegerin (OPG) in the bone. We conclude that dried plum prevents osteopenia in androgen deficient male rats, and these beneficial effects may be attributed in part to a decrease in osteoclastogenesis via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.

Intravenous amiodarone for life-threatening tachyarrhythmias in children and young adults.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of intravenous amiodarone in young patients. BACKGROUND: Oral amiodarone therapy has proved useful for problematic arrhythmias in children, but its pharmacokinetics with the oral route preclude its use in several acute settings. METHODS: Intravenous amiodarone was administered in 1-mg/kg body weight aliquots followed by continuous infusion to patients with potentially life-threatening tachyarrhythmias that had not been abolished by standard therapies. RESULTS: Ten patients (mean age 6.8 years) received intravenous amiodarone: for ventricular tachycardia in seven patients and for atrial tachycardia, junctional tachycardia and multiple arrhythmias in one patient each. Surgery for congenital heart defects had been performed previously in six patients. Two patients had a hamartoma causing ventricular tachycardia. Six of 10 patients had complete resolution of arrhythmia with intravenous amiodarone: 4 of 7 with ventricular tachycardia, 1 of 1 with atrial tachycardia and 1 of 1 with postoperative junctional ectopic tachycardia. Intravenous amiodarone was not successful in the two patients with a hamartoma but slowed ventricular tachycardia in one, allowing successful surgical cure. Average drug load at the time of effect was 4.8 mg/kg body weight. Four patients had transient hypotension during loading, corrected with volume or low dose calcium. Intravenous infusion of amiodarone, 10 mg/kg per day, continued an average of 3 days. Four of 10 patients died, all of nonarrhythmic causes not attributable to intravenous amiodarone. CONCLUSIONS: Intravenous amiodarone was well tolerated in this small series of patients. Postoperative ventricular tachycardia was responsive to intravenous amiodarone in 80% (8 of 10) of the patients (95% confidence interval 40% to 99%). Use of this drug in acute, postoperative tachyarrhythmias may be lifesaving in some patients when standard intravenous therapies fail.

Decreased brain pathology in organophosphate-exposed rhesus monkeys following benzodiazepine therapy.

Two benzodiazepine compounds, midazolam and diazepam, were administered as adjunctive treatment to soman-exposed rhesus monkeys to evaluate their effects on acute soman intoxication. Monkeys were pretreated orally with pyridostigmine, exposed to soman, and treated i.m. with atropine, pralidoxime chloride (2-PAM), and with midazolam, diazepam or sterile water (control). All monkeys that received the benzodiazepines recovered sooner and exhibited no convulsions. Neuronal degenerative and necrotic lesions were decreased or eliminated in the entorhinal cortex, caudate nucleus, and hippocampus of those animals that received benzodiazepine therapy. These findings support the continued evaluation of drugs with anticonvulsant activity as standard adjunct therapy for soman intoxication.

Pharmacokinetics of physostigmine intramuscularly administered to guinea pigs.

Physostigmine pharmacokinetics was determined in guinea pigs following im administration of 5-146 micrograms/kg. Eighteen male guinea pigs were divided into three equal groups and given dosages of 5, 27, and 146 micrograms/kg, respectively. Physostigmine was given in the right hind limb and blood samples were collected at various times up to 300 min postinjection via an indwelling carotid catheter. Unbound physostigmine plasma concentrations were analyzed by HPLC. The concentration-time profile for each animal was fitted to standard pharmacokinetic models. A one-compartment open model with first-order absorption and elimination provided the best fit. For all dosage groups, physostigmine concentrations peaked in approximately 30 min. Apparent volumes of distribution (assuming 100% bioavailability) ranged from 1.9 to 2.2 L/kg. Systemic clearances and elimination half-lives were 30-36 mL/min/kg and 40-50 min, respectively. The area under the concentration-time curve and the Cmax were linearly related to the dose, indicating pharmacokinetic linearity. In conclusion, physostigmine, intramuscularly administered to the guinea pig, is absorbed, distributed, and eliminated rapidly, and the pharmacokinetics behave linearly within the 5-146-micrograms/kg dosage range.

Retrospective assessment of exposure through modeling in a study on cancer risks among workers exposed to phenoxy herbicides, chlorophenols and dioxins.

OBJECTIVES: The study aimed at developing a model for the retrospective assessment of exposures in epidemiologic studies when little or no data on past exposures are available. METHODS: A deterministic model was developed for the level of exposure by industrial hygienists involved in an international study on cancer risks among phenoxy herbicide or chlorophenol manufacturing workers and pesticide sprayers. The general source-receptor model was used as the conceptual framework for the model. RESULTS: The model included variables related to job, the emission of chemicals, contact with chemicals, personal protection, and other relevant determinants of exposure. Cumulative dose indices were calculated from the duration of exposure (from the work histories) and the level of exposure (from the model). CONCLUSIONS: Deterministic modeling in complex exposure situations may provide more valid and reliable results than its conventional alternative, subjective assessment by an expert.

Transformational leadership.

In these uncertain times in the healthcare industry, administrators are asked to do more with less time and resources. Because of the extended roles they are playing in today's organizations, radiology administrators are looked upon as agents of change. What leadership skills do they need in this turbulent and uncertain healthcare environment? What are the trait's of tomorrow's leaders? The transformational leader is the one who will guide us through this changing healthcare environment. Several behavioral patterns emerge as important traits for tomorrow's leaders to have-individual consideration, intellectual stimulation and charisma. Tomorrow's leader must view each person as an individual, showing genuine concern and belief in each person's ability to perform. Transformational leaders stimulate others by encouraging them to be curious and try new ideas. The final characteristic, charisma, is the ability to inspire others. Luckily, leaders are made, not born: today's leaders can learn to be responsive, to draw out new ideas from employees, and to communicate self-esteem, energy and enthusiasm.

Comparison of dried plum supplementation and intermittent PTH in restoring bone in osteopenic orchidectomized rats.

UNLABELLED: Bone loss was confirmed after 90 days in 50 6-month-old male Sprague Dawley rats that were sham-operated or orchidectomized (ORX). In this study, we have shown that dried plum (DP) has potent effects on bone in terms of bone mass, microarchitecture, and strength in osteopenic male rats. Although these changes may be mediated through the suppression of bone resorption, the fact that the restoration in some of the bone structural and biomechanical parameter shares some similarities with parathyroid hormone (PTH) should not be overlooked. Further investigation is needed on a mechanistic level to clarify the influence of DP on bone metabolism. INTRODUCTION: This study was designed to investigate the extent to which DP reverses bone loss in osteopenic ORX rats and to compare its effects to PTH. MATERIALS AND METHODS: Fifty, 6-month-old male Sprague Dawley rats were sham-operated or ORX, and bone loss was confirmed after 90 days. The ORX groups were assigned to control (AIN-93M) diet, 25% DP diet, or PTH (80 microg/kg) for 90 days. RESULTS: DP induced an 11% increase in vertebral and femoral BMD compared to ORX-controls. BMD in the PTH-treated group was increased by 20.7% (vertebra) and 17.9% (femur). Vertebral trabecular bone volume (BV/TV) and number were increased by DP and trabecular separation was decreased compared to controls, which were similar to PTH. Alterations in trabecular bone of the femur were similar to those in the vertebra, but DP did not restore BV/TV to the same extent. Cortical thickness was improved by DP and further enhanced by PTH. DP tended to decrease urinary deoxypyridinoline and calcium, but did not alter alkaline phosphatase or osteocalcin. CONCLUSION: We conclude that though the degree of improvement was not equivalent to PTH with regard to all parameters, DP reverses bone loss due to ORX and the mechanisms should be further investigated.

Hexachlorobenzene exposure in the production of chlorophenols.

Workers involved in the production of pentachlorophenol (PCP) may be exposed to one of its contaminants, hexachlorobenzene (HCB). PCP is produced commercially in the USA by direct chlorination of phenol with chlorine gas in the presence of a catalyst at gradually rising temperatures up to 200 degrees C. Other contaminants formed in PCP production are isomers of hexa-, hepta- and octachlorodibenzo-para-dioxin and isomers of tetra-, penta-, hexa-, hepta- and octachlorodibenzofuran. This paper presents the analytical results of personal breathing-zone, area-air and surface-wipe samples collected at a typical PCP manufacturing plant. The personal breathing-zone samples showed that workers were exposed to HCB concentrations ranging from less than 0.0001 to 0.12 mg/m3. Area-air samples taken throughout the manufacturing plant showed that HCB concentrations ranged from less than 0.0001 to 0.63 mg/m3. Surface-wipe samples showed contamination ranging from less than 0.1 to 3.7 micrograms/wipe.

The influence of cryopreservation on murine oocyte water permeability and osmotically inactive volume.

Osmotic experiments were performed on unfrozen (N = 18) and cryopreserved (N = 21) ICR murine oocytes in order to determine whether a standard cryopreservation process alters membrane water permeability (hydraulic conductivity, Lp) and/or osmotically inactive volume (Vb). Oocytes, initially in an isotonic (288 mOsm) NaCl solution, were exposed to 900 mOsm NaCl in a microdiffusion chamber. Cell size changes were videotaped and analyzed using a parameter estimation program. Best estimates for a two-parameter model (Lp and Vb) which includes the osmotically inactive volume as a fitting parameter are presented for the first time. The cryopreservation process produced no significant difference between the mean Lp or the mean Vb values for the unfrozen control population (Lp = 0.64 +/- 0.15 micron/min/atm, Vb = 24.7 +/- 2.9%) and the cryopreserved population (Lp = 0.63 +/- 0.12 micron/min/atm, Vb = 28.0 +/- 10.8%). While the cryopreservation process did not cause significant changes in the mean values of Lp, Vb, or the variability of Lp, it did produce more variability of Vb. The cause of the increased variability of Vb produced by cryopreservation is unknown. These results suggest that the osmotic properties of unfrozen control oocytes can be used as a reasonable approximation for frozen-thawed oocytes. They also suggest that multiple parameter models and parameter estimation methods may be useful in developing a more comprehensive understanding of the more subtle alterations in osmotic properties that were detected here. Statistical tests were also used for the first time to confirm the assumption that all of the experimental populations were derived from normal distributions.

A retrospective job exposure matrix for estimating exposure to 2,3,7, 8-tetrachlorodibenzo-p-dioxin.

BACKGROUND: A job exposure matrix was developed to estimate the 2,3, 7,8-tetrachlorodibenzo-p-dioxin exposure of 3,538 workers who produced 2,4,5-trichlorophenol and its derivatives. METHODS: Daily TCDD exposure scores that were plant, process, and period specific were estimated for each job title as the product of 1) the concentration of TCDD (microg/g); 2) a qualitative factor to account for the extent of worker contact and 3) time exposed to TCDD contamination. Daily scores were summed to compute individual cumulative TCDD exposure scores. RESULTS: Daily TCDD exposure scores ranged from 0.001 to 1,250. Cumulative TCDD scores ranged from 0.002 to 1,559,430. The 393 workers with records of chloracne in the TCDD exposure cohort (11%) had markedly higher cumulative scores than those with no record of chloracne (a median score of 11,546 vs. 77). CONCLUSIONS: The cumulative TCDD exposure scores incorporate both duration and level of exposure, and permit the relative ranking of worker exposures for the evaluation of exposure-response relationships between TCDD exposure and mortality in an updated cohort study analysis.

Field method for the determination of hexavalent chromium by ultrasonication and strong anion-exchange solid-phase extraction.

A simple, fast, sensitive, and economical field method was developed and evaluated for the determination of hexavalent chromium (CrVI) in environmental and workplace air samples. By means of ultrasonic extraction in combination with a strong anion-exchange solid-phase extraction (SAE-SPE) technique, the filtration, isolation, and determination of CrVI in the presence of trivalent chromium (CrIII) and potential interferents was achieved. The method entails (1) ultrasonication in basic ammonium buffer solution to extract CrVI from environmental matrixes; (2) SAE-SPE to separate CrVI from CrIII and interferences; (3) elution/acidification of the eluate; (4) complexation of chromium with 1,5-diphenylcarbazide; and (5) spectrophotometric determination of the colored chromium-diphenylcarbazone complex. Several critical parameters were optimized in order to effect the extraction of both soluble (K2CrO4) and insoluble (PbCrO4) forms of CrVI without inducing CrIII oxidation or CrVI reduction. The method allowed for the dissolution and purification of CrVI from environmental and workplace air sample matrixes for up to 24 samples simultaneously in less than 90 min (including ultrasonication). The results demonstrated that the method was simple, fast, quantitative, and sufficiently sensitive for the determination of occupational exposures of CrVI. The method is applicable for on-site monitoring of CrVI in environmental and industrial hygiene samples.

Acceleration of atrial ectopic tachycardia as a guide to successful radiofrequency ablation.

Three children with atrial ectopic tachycardia (AET), ages 7-10 years, underwent radiofrequency ablation (RFA). Two had AET localized to the inferolateral orifice of the right atrial appendage, one had AET at the posteroinferior orifice of the left atrial appendage. Each patient received RFA at 15-16 watts for 30 seconds per application. Acceleration of AET rate was observed only during successful RFA application in each patient, occurring within 5 seconds and lasting 2-4 seconds. All unsuccessful applications failed to show this phenomenon. Observation of acceleration of AET rate during RFA was a useful predictor of successful procedure, possibly indicating destruction of abnormally automatic substrates.

Application of a new radiometric high-performance liquid chromatographic assay to define physostigmine pharmacokinetics in guinea pigs.

A sensitive high-performance liquid chromatographic method was developed to determine pharmacokinetic parameters of [3H]physostigmine from serial plasma samples from guinea pigs. Physostigmine was totally resolved from its metabolite, eseroline. The limit of sensitivity was 0.05 ng/ml from 0.2 ml plasma. Extraction efficiency was 99.6%. Within-run and among-run coefficients of variation (n = 6) for 0.2, 0.75, 1.5 and 2.5 ng/ml [3H]physostigmine ranged from 0.7 to 20% and 16 to 32%, respectively. Physostigmine (5 micrograms/kg) intramuscularly administered to the guinea pig (n = 6) reached maximum serum concentration (1.5 ng/ml) in 26 min. The apparent volume of distribution and systemic clearance were 1.4 l/kg and 26 ml/min/kg, respectively. This method was successful in defining physostigmine pharmacokinetic parameters in guinea pigs and can be employed for other small animal pharmacokinetic studies.

Quantitative determination of trucking industry workers' exposures to diesel exhaust particles.

As part of a case-control mortality study of trucking industry workers, exposures to diesel aerosol were measured among the four major presumably exposed job groups (road drivers, local drivers, dock workers, and mechanics) in the industry. Eight industrial hygiene surveys were conducted during both warm and cold weather at eight U.S. terminals and truck repair shops. A single-stage personal impactor was used to sample submicrometer-sized diesel particles on quartz fiber filters. Laboratory and field studies demonstrated that the elemental carbon content of the particles is a useful and practical marker of exposure to vehicular diesel exhaust. A thermal-optical analysis technique was used to determine the concentration of elemental carbon in the filter samples. Overall geometric mean exposures to submicrometer-sized elemental carbon ranged from 3.8 micrograms/m3 in road (long distance) drivers (N = 72) to 13.8 micrograms/m3 in dock workers (N = 75). Geometric mean background area concentrations, measured in the same cities where workers were sampled, were 2.5 micrograms/m3 on major highways (N = 21) and 1.1 micrograms/m3 in residential areas (N = 23). A factorial analysis of variance indicated that exposures in two job groups, dock workers (particularly those exposed primarily via diesel forklift trucks, introduced relatively recently) and mechanics (working in poorly ventilated shops during cold weather), were significantly higher than background concentrations and were significantly higher than the exposures in the local and road drivers. The exposures of the truck drivers could not be distinguished from background highway concentrations but were significantly higher than background concentrations in residential areas.

Chloracne associated with employment in the production of pentachlorophenol.

To evaluate the association between exposure to pentachlorophenol (PCP) and the occurrence of chloracne, we studied the medical and personnel records for individuals employed in the manufacturing of PCP. Forty-seven cases of chloracne were identified among 648 workers (7.0%) assigned to PCP production at a single plant between 1953 and 1978. The annual incidence rate varied considerably, ranging from 0 (in 1953) to 1.46 (in 1978). No linear trend in the risk of chloracne was observed with the duration of employment in the pentachlorophenol department. Workers with a documented episode of direct skin contact with PCP had a significantly increased risk of chloracne compared with workers who did not have a documented episode of direct skin contact (cumulative incidence ratio = 4.6; 95% confidence interval 2.6-8.1). Our results confirm that chloracne is associated with exposure to PCP contaminated with hexachlorinated, heptachlorinated, and octachlorinated dibenzo-p-dioxins and dibenzofurans.

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Review of employment and chemical production records at a Missouri chemical plant and of questionnaires with self-reported occupational exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2,3,7,8-TCDD) for 16 Missouri workers has explained the wide diversity of 2,3,7,8-TCDD levels previously reported in the workers' adipose tissue (3.5-750 ppt on whole-weight basis). We show that the highest exposures reported to date in the United States occurred in a group of nine production workers who made products contaminated with 2,3,7,8-TCDD. The nine workers had adipose tissue levels with a mean of 246 ppt and a range of 42 to 750 ppt. Seven persons who worked at the same chemical company, but not in the 2,3,7,8-TCDD-contaminated process, had a mean of 8.7 ppt and a range of 3.5 to 25.8 ppt. We also report serum levels of 2,3,7,8-TCDD in these individuals. The adipose tissue from a subset of four production workers with elevated levels of 2,3,7,8-TCDD and seven Missouri residents with normal 2,3,7,8-TCDD levels was also analyzed for other isomers of the PCDDs and PCDFs. The mean adipose tissue level of 2,3,7,8-TCDD in the subset of production workers was 45 times higher than the mean level in the unexposed Missouri residents, but similar levels of the other PCDDs and PCDFs were found in both groups.