The association between oil spill cleanup-related total hydrocarbon exposure and diabetes.

BACKGROUND: Although evidence suggests relationships between some crude oil components and glycemic dysregulation, no studies have examined oil spill-related chemical exposures in relation to type 2 diabetes mellitus (DM) risk. This study examined the relationship between total hydrocarbon (THC) exposure among workers involved in the 2010 Deepwater Horizon (DWH) oil spill and risk of DM up to 6 years afterward. METHODS: Participants comprised 2660 oil-spill cleanup or response workers in the prospective GuLF Study who completed a clinical exam and had no self-reported DM diagnosis prior to the spill. Maximum THC exposure was estimated with a job-exposure matrix based on interview data and personal measurements taken during cleanup operations. We defined incident DM by self-reported physician diagnosis of DM, antidiabetic medication use, or a measured hemoglobin A1c value ≥ 6.5%. We used log binomial regression to estimate risk ratios (RRs) for DM across ordinal categories of THC exposure. The fully adjusted model controlled for age, sex, race/ethnicity, education, employment status, and health insurance status. We also stratified on clinical body mass index categories. RESULTS: We observed an exposure-response relationship between maximum daily ordinal THC exposure level and incident DM, especially among overweight participants. RRs among overweight participants were 0.99 (95% CI: 0.37, 2.69), 1.46 (95% CI: 0.54, 3.92), and 2.11 (95% CI: 0.78, 5.74) for exposure categories 0.30-0.99 ppm, 1.00-2.99 ppm, and ≥3.00 ppm, respectively (ptrend = 0.03). CONCLUSION: We observed suggestively increasing DM risk with increasing THC exposure level among overweight participants, but not among normal weight or obese participants.

The effect of preload on electromyographic train-of-four ratio at the first dorsal interosseous muscle during spontaneous recovery from neuromuscular blockade.

Accurate and reliable quantitative neuromuscular function monitoring is desirable for the optimal management of neuromuscular blockade, selection of the most appropriate reversal agent and dosage, and assessing the completeness of reversal to exclude residual neuromuscular blockade. Applying preload to the thumb may affect the precision of electromyography. This study compared the precision and agreement of electromyography with and without preload during recovery from non-depolarising neuromuscular blockade. After induction of anaesthesia and before neuromuscular blockade, the supramaximal current required at the first dorsal interosseous muscle with and without preload was determined. During recovery, train-of-four ratios were recorded using electromyography every 20 seconds. Alternating pairs of measurements (with and without preload) were obtained until spontaneous recovery was achieved. The preload device applied a resting tension of 75-150 g to the thumb. Bland-Altman analysis for repeated measurements was used to assess precision and agreement of electromyography responses with and without muscle preload. Two hundred and seventy-five sets of repeated measurements were collected from 35 participants. The repeatability coefficient for train-of-four ratios recorded by electromyography with a preload was 0.030 (95% confidence intervals, CI, 0.028 to 0.031) versus 0.068 (95% CI 0.064 to 0.072) without. Train-of-four ratios with preload demonstrated a bias of +0.038 (95% CI 0.037 to 0.042) compared to electromyography without, with 95% limits of agreement of 0.035-0.111. Preload significantly improved the precision of electromyographic train-of-four ratios, with 95% of consecutive measurements differing by less than 3%. Furthermore, electromyography with preload demonstrated a positive bias of 0.04 compared with electromyography alone, the clinical significance of which requires further research.

Therapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double-blind, placebo-controlled, randomised volunteer study.

Neostigmine reverses non-depolarising neuromuscular blockade, but may cause muscle weakness when administered after full recovery of neuromuscular function. We hypothesised that neostigmine in therapeutic doses impairs muscle strength and respiratory function in awake healthy volunteers. Twenty-one volunteers were randomised to receive two doses of either intravenous (i.v.) neostigmine 2.5 mg with glycopyrrolate 450 µg (neostigmine group, n = 14) or normal saline 0.9% (placebo group, n = 7). The first dose was administered immediately after obtaining baseline measurements, and the second dose was administered 15 min later. All 14 volunteers in the neostigmine group received the first dose, mean (SD) 35 (5.8) µg.kg-1 , but only nine of these volunteers agreed to receive the second dose, 34 (3.5) ?g.kg-1 . The primary outcome was hand grip strength. Secondary outcomes were train-of-four ratio, single twitch height, forced expiratory volume in 1 s, forced vital capacity, forced expiratory volume in 1 s/forced vital capacity ratio, oxygen saturation, heart rate and mean arterial pressure. The first dose of intravenous neostigmine with glycopyrrolate resulted in reduced grip strength compared with placebo, -20 (20) % vs. +4.3 (9.9) %, p = 0.0016; depolarising neuromuscular blockade with decreased single twitch height, -14 (11) % vs. -3.8 (5.6) %, p = 0.0077; a restrictive spirometry pattern with decreased predicted forced expiratory volume in 1 s, -15 (12) % vs. -0.47 (3.4) %, p = 0.0011; and predicted forced vital capacity, -20 (12) % vs. -0.59 (3.2) %, p < 0.0001 at 5 min after administration. The second dose of neostigmine with glycopyrrolate further decreased grip strength mean (SD) -41 (23) % vs. +1.0 (15) %, p = 0.0004; single twitch height -25 (15) % vs. -2.5 (6.6) %, p = 0.0030; predicted forced expiratory volume in 1 s -23 (24) % vs. -0.7 (4.4) %, p = 0.0063; and predicted forced vital capacity, -27.1 (22.0) % vs. -0.66 (3.9) %, p = 0.0010. Train-of-four ratio remained unchanged (p = 0.22). In healthy volunteers, therapeutic doses of neostigmine induced significant and dose-dependent muscle weakness, demonstrated by a decrease in maximum voluntary hand grip strength and a restrictive spirometry pattern secondary to depolarising neuromuscular blockade.

Comparison of kinemyography and electromyography during spontaneous recovery from non-depolarising neuromuscular blockade.

This study compared two commercially available quantitative neuromuscular function monitoring techniques, kinemyography (KMG) and electromyography (EMG), to assess whether KMG could be used interchangeably with EMG to exclude residual neuromuscular blockade (RNMB). Train-of-four (TOF) ratios were recorded every 20 seconds using KMG at the adductor pollicis and EMG at the first dorsal interosseous of the same hand during spontaneous recovery from shallow neuromuscular blockade. TOF ratios were compared using Bland-Altman analysis for repeated measurements. The precision of each device was assessed by the repeatability coefficient. Agreement between devices was assessed by the bias and limits of agreement. Clinically acceptable agreement was defined as a bias <0.025 within limits of agreement ±0.05. We recorded 629 sets of TOF ratios from 23 patients. The repeatability coefficient for KMG was 0.05 (95% confidence interval [CI] 0.05 to 0.06) and for EMG 0.10 (95% CI 0.10 to 0.11). Overall, the bias of KMG TOF ratios against EMG TOF ratios was 0.11 (95% CI 0.10 to 0.12), with limits of agreement -0.11 to 0.32. In the 0.80 to 0.99 TOF range, the bias was 0.08 (95% CI 0.06 to 0.09) and the limits of agreement were -0.12 to 0.27. Overall, TOF ratios measured by KMG were on average 0.11 higher than EMG. In the 0.80 to 0.99 TOF range, KMG TOF ratios were 0.08 higher. EMG and KMG are not interchangeable because the bias is large and the limits of agreement are wide. Thus a maximum TOF ratio of 1.0 on KMG may not exclude RNMB.

High-risk residual gastric content in fasted patients undergoing gastrointestinal endoscopy: a prospective cohort study of prevalence and predictors.

In this prospective cohort study, we examined the residual gastric contents of 255 fasted patients undergoing gastrointestinal endoscopy. The volume and pH of residual gastric contents collected by suction under direct visualisation during gastroscopy were accurately quantified. All patients completed the minimum two-hour fast for clear fluids and 97.2% of patients completed the minimum six-hour fast for solids. High-risk residual gastric content, defined as volume >25 ml and pH <2.5, was present in 12.2% (95% CI 8.7% to 16.7%) of patients. We used multiple logistic regression analysis to identify demographic and clinical factors associated with high-risk residual gastric content. The odds of having high-risk residual gastric content were reduced with increase in age (adjusted odds ratio 0.77, 95% CI 0.61 to 0.96, P=0.0230), and use of a proton pump inhibitor or histamine type 2 receptor antagonist (adjusted odds ratio 0.24, 95% CI 0.10 to 0.55, P=0.0013), and were increased in male patients (adjusted odds ratio 2.36, 95% CI 1.06 to 5.28, P=0.0348). Notably, residual gastric content was classified as high-risk in 20.4% of patients who did not take a proton pump inhibitor or histamine type 2 receptor antagonist versus only 5.6% of those who did. Our findings suggest that, despite currently recommended fasting, males presenting for endoscopy are more likely to have high-risk gastric content than females, and that the incidence appears to be reduced with increasing age, and by the use of proton pump inhibitors or histamine type 2 receptor antagonists, we were unable to confirm or exclude an effect of body mass index, peptic pathology, diabetes or other clinical or demographic factors in our study population.

Comparison of electromyography and kinemyography during recovery from non-depolarising neuromuscular blockade.

In this study, two commercially available quantitative neuromuscular function monitoring techniques, electromyography (EMG) and kinemyography (KMG), were compared with respect to repeatability and accuracy during late recovery from neuromuscular blockade. Train-of-four (TOF) ratios were recorded in 30 patients using KMG and EMG at the adductor pollicis muscle. Measurements were taken on the same hand using the Datex-Ohmeda NeuroMuscular Transmission monitor (GE Healthcare, Helsinki, Finland). Instrumental precision was evaluated using the coefficient of repeatability, while accuracy was assessed using the bias and limits of agreement. The coefficients of repeatability were similar for both techniques (0.035 for KMG and 0.043 for EMG), indicating a similar level of precision. KMG overestimated the TOF ratios measured with EMG with a bias of 0.11 (95% limits of agreement: -0.13 to 0.35). At a TOF ratio of 0.90 the bias was 0.08 (95% limits of agreement: -0.08 to 0.25). This means that at a TOF ratio of 0.90 measured with KMG will be approximately equivalent to a TOF ratio of 0.80 measured with EMG at the adductor pollicis muscle, but it may indeed be as low as 0.65 or as high as 1.00. Therefore, TOF ratios measured by KMG and EMG cannot be used interchangeably.

A survey of the management of neuromuscular blockade monitoring in Australia and New Zealand.

This survey of anaesthetists in Australia and New Zealand aimed to investigate their attitudes and practice relating to the management of neuromuscular blockade monitoring. All medical practitioner members (3188) of the Australian and New Zealand Societies of Anaesthetists were invited to complete an anonymous survey, which was available online for two months. A total of 678 survey questionnaires were completed (response rate 21%). Most respondents (71.4%) underestimated the incidence of residual neuromuscular blockade and 63.2% believed this to be a significant clinical problem. Objective monitoring of neuromuscular function was used routinely only by 17% of respondents, although 70% believed routine monitoring would reduce the incidence of residual neuromuscular blockade. Only 25% of respondents correctly indicated that quantitative train-of-four counts of greater than 90% were the accepted criteria for safe extubation, with 52% using clinical judgement only. Only 29% of respondents believed neuromuscular function monitors should be part of minimum monitoring standards; quantitative neuromuscular function monitors were not available in 42% of the hospitals in which the respondents practiced. Despite the low response rate, the large sample size and heterogeneity of respondents make the findings of this survey concerning. There is a need for more education, availability of appropriate monitoring equipment and evidence-based guidelines for management of neuromuscular blockade in Australia and New Zealand.

Sugammadex antagoniza el bloqueo neuromuscular provocado por rocuronio en dos tipos de trastornos neuromusculares: distrofia miotónica y atrofia muscular espinal / Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy

Las enfermedades neuromusculares como la distrofia miotónica (o enfermedad de Steinert) y la atrofia muscular espinal se asocian con las complicaciones perioperatorias relacionadas con la debilidad muscular. Estos pacientes presentan una hipersensibilidad a los bloqueantes neuromusculares no despolarizantes que podría derivar en curarización residual postoperatoria con complicaciones respiratorias. Para evitarlo conviene antagonizar satisfactoriamente el bloqueo neuromuscular (BNM). Sugammadex es el primer relajante selectivo y antagoniza los bloqueos neuromusculares por rocuronio y vecuronio. Se notifican dos casos donde los pacientes recibieron sugammadex para antagonizar un bloqueo neuromuscular provocado por rocuronio. El antagonismo de los BNM por rocuronio en ambos casos fue rápido, eficaz y sin recurarización, no se observaron preocupaciones de seguridad(AU)

Neuromuscular disorders like myotonic dystrophy (dystrophia myotonica or Steinert's disease) and spinal muscular atrophy are associated with perioperative complications related to muscle weakness. These patients have an increased sensitivity to non-depolarising neuromuscular blocking agents, which can lead to postoperative residual curarization (PORC) and its associated respiratory complications. Adequate reversal of neuromuscular blockade is essential to prevent this. Sugammadex is the first selective relaxant binding agent and it reverses rocuronium- and vecuronium-induced neuromuscular block. Two cases are reported in which the patients received sugammadex to reverse a rocuronium-induced neuromuscular block. Reversal of the rocuronium-induced neuromuscular block (NMB) in both cases was fast, effective and without recurarization, and no safety concerns were observed(AU)

Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy.

Neuromuscular disorders like myotonic dystrophy (dystrophia myotonica or Steinert's disease) and spinal muscular atrophy are associated with perioperative complications related to muscle weakness. These patients have an increased sensitivity to non-depolarising neuromuscular blocking agents, which can lead to postoperative residual curarization (PORC) and its associated respiratory complications. Adequate reversal of neuromuscular blockade is essential to prevent this. Sugammadex is the first selective relaxant binding agent and it reverses rocuronium- and vecuronium-induced neuromuscular block. Two cases are reported in which the patients received sugammadex to reverse a rocuronium-induced neuromuscular block. Reversal of the rocuronium-induced neuromuscular block (NMB) in both cases was fast, effective and without recurarization, and no safety concerns were observed.

Comparison of evoked electromyography in three muscles of the hand during recovery from non-depolarising neuromuscular blockade.

The evoked electromyographic responses to supramaximal train of four stimulation of three muscles, all innervated by the ulnar nerve, were compared during recovery from non-depolarising neuromuscular blockade. The abductor digiti minimi was the most resistant to neuromuscular blockade (P <0.001) and the most repeatable (repeatability coefficient 4.4%) when compared with the adductor pollicis (5.9%) and the first dorsal interosseous (5.8%). The abductor digiti minimi had a bias of 0.1 compared to the adductor pollicis and first dorsal interosseous and its limits of agreement were more acceptable (-0.10 to 0.30) at a train of four ratio of 0.9. The electromyography train of four of the adductor pollicis and first dorsal interosseous at 0.8 is equivalent to an electromyography train of four of 0.9 at abductor digiti minimi.

Blood pressure estimation in the human fetal descending aorta.

OBJECTIVES: The objectives of this study were to estimate fetal blood pressure non-invasively from two-dimensional color Doppler-derived aortic blood flow and diameter waveforms, and to compare the results with invasively derived human fetal blood pressures available from the literature. METHODS: Aortic pressures were calculated from digitally recorded color Doppler cineloops of the fetal descending aorta by applying the Womersley model in combination with the two-element Windkessel model, assuming constant pulse wave velocity during the second half of pregnancy. The results were compared with invasively derived human fetal blood pressures obtained from the literature. RESULTS: In 21 normal pregnancies the estimated mean aortic pressure regression line increased linearly from 28 mmHg at 20 weeks of gestation to 45 mmHg at 40 weeks of gestation. The pulse pressure based on the regression line increased linearly from 21 mmHg at 20 weeks of gestation to 29 mmHg at 40 weeks of gestation. The aortic compliance exhibited a log linear relationship with the gestational age and a statistically significant eightfold increase was observed between 20 and 40 weeks. The aortic downstream peripheral resistance exhibited an exponentially decaying relationship across the same gestational age range. Non-invasively derived aortic systolic and diastolic aortic pressures were comparable with previously reported invasively derived systolic and diastolic umbilical arterial pressures; however, the mean pressures differed significantly from those reported in the umbilical artery in a separate study. The aortic systolic pressures calculated in this study were significantly higher than invasively derived left ventricular systolic pressures that have been previously reported in the literature. CONCLUSIONS: This study demonstrates the feasibility of estimating arterial blood pressure in the human fetus. The method described is of potential use in assessing fetal blood pressure non-invasively, particularly for studying relative changes with time.

Design characteristics that affect speed of information access and clarity of presentation in an electronic neuroanatomy atlas.

Functional Neuroanatomy, an interactive electronic neuroanatomical atlas, was designed for first year medical students. Medical students have much to learn in a limited time; therefore a major goal in the atlas design was that it facilitate rapid, accurate information retrieval. To assess this feature, we designed a testing scenario in which students who had never taken a neuroanatomy course were asked to complete two equivalent tests, one using the electronic atlas and one using a comparable hard copy atlas, in a limited period of time. The tests were too long to be completed in the time allotted, so test scores were measures of how quickly correct information could be retrieved from each source. Statistical analysis of the data showed that the tests were of equal difficulty and that accurate information retrieval was significantly faster using the electronic atlas when compared with the hard copy atlas (P < 0.0001). Post-test focus groups (n = 4) allowed us to infer that the following design features contributed to rapid information access: the number of structures in the database was limited to those that are relevant to a practicing physician; all of the program modules were presented in both text and image form on the index screen, which doubled as a site map; pages were layered electronically such that information was hidden until requested, structures available on each page were listed alphabetically and could be accessed by clicking on their name; and an illustrated glossary was provided and equipped with a search engine.

Comparison between color Doppler cineloop- and conventional spectral Doppler-derived maximum velocity and flow in the umbilical vein.

OBJECTIVE: To compare the umbilical venous flow velocity derived from color Doppler cineloop recordings with that derived from conventional spectral Doppler in normal pregnancies. METHOD: In 18 uncomplicated pregnancies between 19 and 39 weeks' gestation, color Doppler was used to find the maximum velocity in the cross-sectional vessel area of a free-floating loop of the umbilical vein. The maximum velocity was determined using the software tool HDI_Lab (Philips Medical Systems) after tracing the vessel area of interest. Conventional spectral Doppler was then used to determine the maximum velocity with the High-Q machine option. The cross-sectional area of the umbilical vein was determined using B-mode imaging and was subsequently used to determine the umbilical volume flow from both Doppler methods. Assuming a parabolic flow profile in the umbilical vein, the mean velocity is equal to half the maximum velocity. The fetal weight was estimated from fetal biometry using the four-parameter Hadlock formula. RESULTS: Maximum velocity was significantly (P = 0.003) higher with color Doppler cineloop (14.3 +/- 2.5 cm/s) compared with spectral Doppler (12.7 +/- 3.2 cm/s). Therefore, using the same cross-sectional area for both methods, the umbilical blood flow was significantly higher (P = 0.001) with color Doppler cineloop (127.9 +/- 59.0 mL/min) than it was with spectral Doppler (112.8 +/- 54.1 mL/min). The umbilical blood flow expressed as volume flow per kg fetal weight was significantly (P = 0.01) higher with color Doppler cineloop (126.0 +/- 57.0 mL/min/kg) than it was with spectral Doppler (115.0 +/- 53.0 mL/min/kg). CONCLUSIONS: Umbilical venous flow velocity derived from color Doppler cineloops is approximately 10% higher than that derived from spectral Doppler-derived velocity. The reduced angle dependence of the color Doppler cineloop technique and the large sampling area of the cross-sectional vessel should allow better determination of the correct maximum velocity in the umbilical vein.

Wall shear stress and related hemodynamic parameters in the fetal descending aorta derived from color Doppler velocity profiles.

This paper presents a methodology for estimating the wall shear stress in the fetal descending aorta from color Doppler velocity profiles obtained during the second half of pregnancy. The Womersley model was applied to determine the wall shear stress and related hemodynamic parameters. Our analysis indicates that the aortic diameter can be modeled as a function of the gestational age in weeks as: Diameter (mm) = 0.17.ga + 0.15 (R2 = 0.64, p < 0.001). The aortic volume flow showed a log linear gestational age-related increase that fit the model: F (mL/min) = e(0.08.ga + 3.49) (R2 = 0.61, p < 0.001). The Womersley number increased linearly with gestational age from 3.3 to 6.2 (p < 0.001) and the pressure gradient decreased linearly from 2.68 to 1.16 mPa/mm (p = 0.003) during the second half of pregnancy; the mean wall shear stress for the study group was 2.2 Pa (SD = 0.59) and was independent of gestational age. This study suggests that the size of the fetal aorta adapts to flow demands and maintains constant mean wall shear stress.

Occupation and the risk of adult glioma in the United States.

OBJECTIVE: Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. METHODS: Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. RESULTS: Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. CONCLUSIONS: This is our first analysis of occupation and will guide future exposure-specific assessments.

Two-dimensional and M-mode echocardiography of the fetal coronary sinus.

OBJECTIVE: To document fetal coronary sinus dimensions in normal pregnancy. METHODS: Two hundred and sixty-five normal fetuses in which congenital cardiac defects had been excluded were examined cross-sectionally between 21 and 38 weeks of gestation. From the apical or basal four-chamber view the transducer was tilted towards the inferior cardiac surface in order to visualize the coronary sinus by real-time ultrasound. Maximum systolic and diastolic diameters were measured using M-mode. Reference ranges were constructed and the ratio of systolic and diastolic diameters calculated. Data from two fetuses, one with supraventricular tachycardia and a second one with hydrops secondary to anemia, were also compared. RESULTS: Visualization and measurement of the coronary sinus were successful in 258 (97.4%) patients. The coronary sinus systolic and diastolic diameters increased significantly with gestational age (maximum systolic diameter, 1.6 mm at 21 weeks to 4 mm at 38 weeks; maximum diastolic diameter, 0.9 mm at 20 weeks to 2.2 mm at 38 weeks). The ratio of systolic to diastolic diameters remained relatively constant (range, 1.7-2.1) and therefore was unrelated to gestational age. In the fetuses with supraventricular tachycardia and hydrops, both diameters of the coronary sinus were increased and diminished fluctuation in size during the cardiac cycle was observed. CONCLUSIONS: The described sonographic approach provides an effective method for measurement of coronary sinus dimensions. The normative data may facilitate the detection of coronary sinus dilation as an indirect marker for abnormalities in venous return to the heart.

A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9.

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH.

Determining the probability of pesticide exposures among migrant farmworkers: results from a feasibility study.

BACKGROUND: Migrant and seasonal farmworkers are exposed to pesticides through their work with crops and livestock. Because workers are usually unaware of the pesticides applied, specific pesticide exposures cannot be determined by interviews. We conducted a study to determine the feasibility of identifying probable pesticide exposures based on work histories. METHODS: The study included 162 farm workers in seven states. Interviewers obtained a lifetime work history including the crops, tasks, months, and locations worked. We investigated the availability of survey data on pesticide use for crops and livestock in the seven pilot states. Probabilities of use for pesticide types (herbicides, insecticides, fungicides, etc.) and specific chemicals were calculated from the available data for two farm workers. The work histories were chosen to illustrate how the quality of the pesticide use information varied across crops, states, and years. RESULTS: For most vegetable and fruit crops there were regional pesticide use data in the late 1970s, no data in the 1980s, and state-specific data every other year in the 1990s. Annual use surveys for cotton and potatoes began in the late 1980s. For a few crops, including asparagus, broccoli, lettuce, strawberries, plums, and Christmas trees, there were no federal data or data from the seven states before the 1990s. CONCLUSIONS: We conclude that identifying probable pesticide exposures is feasible in some locations. However, the lack of pesticide use data before the 1990s for many crops will limit the quality of historic exposure assessment for most workers.

A method for assessing occupational pesticide exposures of farmworkers.

BACKGROUND: The health of farmworkers as related to pesticide exposure is of concern but assessing exposures for epidemiologic studies requires different techniques than approaches used for studies of industrial workers. METHODS: A review of the literature identified possible factors that affect exposure intensity. A model was developed to estimate an exposure score. Exposures in the literature were estimated using the model and compared to the measurements in the literature. RESULTS: Three studies were found with information appropriate for evaluation of the model. There was a statistical difference between the means of the scores corresponding to above and below the median of the measurements. The correlation coefficient between the scores and the measurements from the literature was 0.77. CONCLUSIONS: Although the evaluation was limited, the model appeared to work well, but more testing is needed. More research is also needed to increase understanding of what affects the exposures of these workers.