Biomedical subjects

N Warren

Publications and source records attributed to N Warren.

At least 19 recordsLinked to original sources

PubMed2006

Biomonitoring for chromium and arsenic in timber treatment plant workers exposed to CCA wood Preservatives.

This study reports a survey of occupational exposure to copper chrome arsenic (CCA) based wood preservatives during vacuum pressure timber impregnation. The survey involved biological monitoring based on analysis of chromium and arsenic in urine samples collected from UK workers. The aim of the study was to determine the extent of occupational exposure to arsenic and chromium in the UK timber treatment industry. The objectives were to collect and analyse urine samples from as many workers as possible, where CCA wood preservatives might be used, at 6 monthly intervals for 2 years. In addition, to investigate day-to-day variations in urinary excretion of chrome and arsenic by collecting and analysing three samples a week for 3 weeks in subsets of workers and controls (people not occupationally exposed). All urine samples were analysed for chromium and inorganic arsenic. To investigate any residual interference every sample was accompanied by a short questionnaire about recent consumption of seafood and smoking. The analytical methods for arsenic used a hydride generation technique to reduce interference from dietary sources of arsenic and also a technique that would measure total arsenic concentration in urine. The main findings show that workers exposed to CCA wood preservatives have concentrations of inorganic arsenic and chromium in urine that are significantly higher than those from non-occupationally exposed people but below biological monitoring guidance values that would indicate inhalation exposure at UK occupational exposure limits for chromium and arsenic. The effects of consumption of seafood on urinary arsenic were not significant using the hydride generation method for inorganic arsenic but were significant if 'total' arsenic was measured. The 'total' arsenic method could not distinguish CCA workers from controls and is clearly unsuitable for assessment of occupational exposure to arsenic. There was a significant increase in the urinary concentration of chromium in workers over the four sample collection rounds indicating increasing exposure to chromium during the 2 years of the study. This unexpected finding may be worth further investigation. Overall, the study demonstrated the utility of biological monitoring for assessment of occupational exposure to chromium and arsenic.

Arsenic↗

PubMed2006

Nerve conduction and sensorineural function in dental hygienists using high frequency ultrasound handpieces.

BACKGROUND: Oscillatory vibration from industrial power tools poses a well-recognized risk of peripheral nerve injury. There have been reports of elevated vibrotactile perception thresholds (VPT) among dentists, dental technicians, and dental hygienists, using rotary devices and ultrasonics. Elevated VPTs are an indicator of small fiber nerve or mechanoreceptor injury, but the high frequencies associated with dental instruments are presumed by the ISO to exceed physiological response upper thresholds. This study examines nerve conduction and sensorineural deficits in dental hygienists. METHODS: A cross-sectional study of 94 experienced dental hygienists was conducted to assess peripheral nerve function and clinical signs and symptoms. Specialized testing included measurement of VPTs for three different categories of mechanoreceptors, sensory nerve conduction tests with fractionated digit and palmar segments, and measurement of calibrated pinch force with force sensitive resistors (FSRs) during a simulated procedure. RESULTS: Chronic hand paresthesias were described by 44.7% of experienced dental hygienists. Sensory nerve conduction velocity (SNCV) across the wrist-palm segment of the median nerve. VPTs were particularly elevated at the FAII mechanoreceptor among experienced dental hygienists. Compared to participants without carpal tunnel syndrome (CTS), as defined by study criteria, 14 experienced hygienists with diagnosed CTS had almost twice the average weekly use of vibratory instruments -8.3 hr versus 4.5 hr, and had SNCV deficits along the digit -47.11 m/sec (+8.70) versus 42.57 m/sec (+8.25), and across the wrist -44.04 m/sec (+7.15) versus 41.36 m/sec (+9.27). There was a distinct subset of dental hygienists (27%) with a combination of low calibrated pinch force in simulations, subjective loss of strength and elevated VPTs, especially in the FAII mechanoreceptor population -110.82 db (+8.57) versus 104.84 db (+6.80) in the rest of the cohort. This subset also had a higher prevalence of paresthesias (67% vs. 39%) and greater cumulative vibration exposure (OR = 1.206 [CI 1.005-1.448]), than other hygienists. CONCLUSIONS: The high levels of paresthesias observed among dental hygienists appear to be attributable to several pathophysiological mechanisms, including, sensory nerve demyelination at the carpal tunnel and intrinsic to the digits, and dysfunction of fingertip mechanoreceptors. A distinct sub-population appears to exhibit a high level of accumulated abnormality.

Adult↗

PubMed2005

Selection of GM2, fucosyl GM1, globo H and polysialic acid as targets on small cell lung cancers for antibody mediated immunotherapy.

Glycolipids GM2, GD2, GD3, fucosyl GM1, sialyl Lewis a (sLe(a)) and globo H, and polysialic acid on embryonal NCAM, are cell-surface antigens expressed on small cell lung cancer (SCLC) biopsy specimens. They are all candidates for inclusion in a polyvalent, antibody-inducing vaccine or for adoptive therapy with monoclonal antibodies (mAbs) against SCLC. To identify the minimum optimal combination of target antigens on SCLC and to confirm that antibodies against this combination might be able to mediate complement activation and lysis in the majority of cases, we tested ten SCLC cell lines with fluorescence activated cell sorter (FACS) and complement dependent cytotoxicity (CDC) assays using mAbs against these seven target antigens individually or pooled in different combinations. We find that (1) none of these mAbs demonstrated strong FACS reactivity with more than 6 of the 10 cell lines, (2) no mAb had strong CDC reactivity with more than 4 of the cell lines, (3) when the mAbs were pooled, nine cell lines were strongly positive by FACS and nine cell lines were strongly positive by CDC, and (4) mAbs against GM2, FucGM1, globo H and polysialic acid was the minimum optimal combination for inducing FACS reactivity. The addition of mAbs against sLe(a), GD2 and GD3 had no additional impact by FACS and only minimal additional impact in CDC assays. H345, the only cell line that had less than 30% CDC with the four mAb pool was strongly positive by FACS. To understand the lack of correlation between FACS and CDC in the case of H345, the ten cell lines were screened for expression of complement resistance factors CD55 and CD59. Three cell lines were strongly positive for CD55 and eight were strongly positive for CD59. Overall, no correlation was seen between expression of either of these factors on the ten cell lines and sensitivity to CDC. In the case of H345 however, complement resistance of H345 is demonstrated to be mediated primarily by CD59, and in the presence of mAb against CD59, the four mAb MEM-43 pool induced strong (94%) CDC. CD59 inhibits membrane attack complex formation but not activation of earlier complement components. Consequently, all ten cell lines are good targets for complement activation by the four antibody pool and for elimination by effector mechanisms including complement mediated inflammation and opsonization. These findings support our plan to develop a tetravalent vaccine against SCLC targeting GM2, fucosyl GM1, globo H and polysialic acid.

Antibodies, Monoclonal↗

PubMed2005

Trends in work-related musculoskeletal disorder reports by year, type, and industrial sector: a capture-recapture analysis.

BACKGROUND: Musculoskeletal disorders (MSD) are thought to be declining based on Bureau of Labor Statistics survey data, but there is also evidence of MSD under-reporting, raising the possibility of contrary trends. The magnitude of MSD under-reporting over time, and its industry distribution have not been adequately described. METHODS: Capture-recapture analysis of 7 years of Connecticut MSD (1995-2001), utilizing Workers' Compensation and physician reporting data was performed. RESULTS: Only 5.5%-7.9% of MSD cases appear to be reported to Workers Compensation annually. The capture-recapture estimated average annual rate for upper-extremity MSD was 133.1 per 10,000 employed persons, far above BLS rates. By industry, Manufacturing, State Government, and the Finance/Insurance/Real Estate sectors all had significantly higher MSD rates than Wholesale/Retail Trade. CONCLUSIONS: Upper-extremity MSD appears to be significantly under-reported, and rates are not decreasing over time. Capture-recapture methods provide an improved surveillance method for monitoring temporal trends in injury rates.

Adult↗

PubMed2004

Segmental nerve conduction velocity in vibration-exposed shipyard workers.

OBJECTIVES: Segmental sensory nerve conduction velocity (SNCV) was measured from the wrists to the hands and digits of a population of vibration-exposed shipyard workers. This study was designed to investigate whether SNCV was selectively slowed in the fingers and whether a laboratory approach could be adapted for robust field use. METHODS: Wrist-palm, palm-proximal digit, and digital segments were determined from stimulation at the wrist with recording electrodes placed distally and adjusted to individual anatomy. The cohort was selected on the basis of current use of vibratory tools. RESULTS: Wrist-palm and digital segments were slower than palm-proximal digit segments for dominant and non-dominant hands and for both ulnar and median nerves. In the dominant-hand median nerve of participants with current exposure, the SNCV was 41.4 m/s (SD 8.0) for the wrist-palm segment, 50.8 (SD 9.5) for the palm segment, and 42.1 m/s (SD 9.3) for the digital segment. Temperature had an important effect on nerve conduction velocity but not equally across segments. Other explanatory variables had modest effect on SNCV. CONCLUSIONS: Reduced SNCV in the digits may be a consequence of industrial exposure to vibration. Each sensory nerve segment appeared to have a different characteristic velocity and different pattern of association with skin temperature. There are differences between median and ulnar nerve segments, with potentially important consequences when standard distances are used to assess wrist-digit velocity.

Carpal Tunnel Syndrome↗

PubMed2003

Classification of dermal exposure modifiers and assignment of values for a risk assessment toolkit.

This paper describes how default dermal exposure values can be adjusted with modifier values for specific work situations. The work presented here is supplementary to a toolkit developed for the EU RISKOFDERM project. This toolkit is intended for the assessment and management of dermal risks in small and medium sized enterprises. Potential dermal exposure (on the outer envelope of the body) is estimated with an algorithm whereby modifier values are applied multiplicatively to dermal default exposure values. These exposure modifiers with their assigned factors are intended to increase or decrease the potential (default) dermal exposure accordingly. Default estimates are modified to obtain two modified defaults: potential exposure rate to the hands and to the body. Quantitative exposure data is at present inadequate and insufficient to derive meaningful information that can be used for the selection of independent modifiers and the assignment of appropriate values. Instead, available information from the literature was considered and, in combination with expert judgement, 15 potential dermal modifiers were selected. Modifiers were classified and grouped into non-overlapping groups in order to avoid double scoring. Values were assigned to modifiers in three different exposure routes, i.e. direct contact, surface contact and deposition. Depending on the significance of a modifier, the values assigned to modifiers were weighted in equal steps on a log-scale. The values assigned to modifiers as presented in this paper are open to validation and revision once new data become available.

Evidence-Based Medicine↗

PubMed2003

Deriving default dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises.

This paper describes the derivation of default task-based dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises (SMEs). A set of separately determined dermal exposure modifiers have been applied to published studies of dermal exposure to obtain 'normalized' dermal exposure data sets. These data sets are grouped according to task and then further subdivided by making a distinction between processes involving solid and liquid products. For each of the resulting 12 groups, two default exposure rates are required: potential exposure rate to the hands and potential exposure rate to the body. Default values for risk assessment are then derived by taking a weighted average of the 75th percentiles of these normalized exposure distributions. In addition, a measure of peak surface concentration is required to take into account the risk of local skin effects. The higher of the (modified) hand and body exposure rates after applying the relevant penetration factors for clothing and gloves is used. Usually this will be the hand exposure rate. These default values serve as robust initial exposure estimates in a risk assessment toolkit for SMEs.

Humans↗

PubMed2003

Determinants of dermal exposure relevant for exposure modelling in regulatory risk assessment.

Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European research programme, an analysis of potential dermal exposure determinants was made based on the available studies and models and on the expert judgement of the authors of this publication. Only a few potential determinants appear to have been studied in depth. Several studies have included clusters of determinants into vaguely defined parameters, such as 'task' or 'cleaning and maintenance of clothing'. Other studies include several highly correlated parameters, such as 'amount of product handled', 'duration of task' and 'area treated', and separation of these parameters to study their individual influence is not possible. However, based on the available information, a number of determinants could clearly be defined as proven or highly plausible determinants of dermal exposure in one or more exposure situation. This information was combined with expert judgement on the scientific plausibility of the influence of parameters that have not been extensively studied and on the possibilities to gather relevant information during a risk assessment process. The result of this effort is a list of determinants relevant for dermal exposure models in the scope of regulatory risk assessment. The determinants have been divided into the major categories 'substance and product characteristics', 'task done by the worker', 'process technique and equipment', 'exposure control measures', 'worker characteristics and habits' and 'area and situation'. To account for the complex nature of the dermal exposure processes, a further subdivision was made into the three major processes 'direct contact', 'surface contact' and 'deposition'.

Humans↗

PubMed2002

Reduced stress-induced hyperthermia in mGluR5 knockout mice.

It hs been suggested that metabotropic glutamate receptor subtype 5 (mGluR5) play a role in the expression of anxiety, based on anxiolytic-like effects of the selective mGluR5 antagonist MPEP (2-methyl-6-(phenylethynyl)pyridine) in rodent models of anxiety, including stress-induced hyperthermia (SIH). To examine the suggested role of mGlu5 receptors in the expression of anxiety, we examined the stress response in mice lacking mGluR5 in several variations of the SIH procedure. In this paradigm, stress causes a mild increase in body temperature that can be blocked by known anxiolytic agents. Three procedures were employed: classical SIH using rectal-probe measurement of body temperature, and radiotelemetric measurement of body temperature in response to either saline injection or to the introduction of an intruder into the home cage. In all three procedures the mGluR5-knockout mice displayed a significant attenuation of the hyperthermic response to stress compared to littermate wild-type control mice. To confirm that our observations were likely to be due to the absence of mGluR5 in the knockout mice we also tested the effect of the recently described selective mGluR5 antagonist MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine) in both the wild-type and mGluR5 knockout mice. Administration of MTEP in the wild-type mice, but not the mGluR5 knockout mice, attenuated SIH. That the mGluR5 knockout mice displayed an anxiolytic-like phenotype and that the mGluR5 antagonist, MTEP, showed a anxiolytic-like effect only in mice possessing mGluR5 further supports the suggestion that mGluR5 antagonists may be useful in the treatment of anxiety.

Animals↗

PubMed2001

Capture-recapture estimation of unreported work-related musculoskeletal disorders in Connecticut.

BACKGROUND: Estimates of the extent of musculoskeletal disorders (MSD) are usually based upon workers' compensation reports, although recent reports indicate that there may be widespread under-reporting of MSD. METHODS: An estimate of the incidence of arm and hand work-related MSD was made using capture-recapture analysis of the overlap between state workers' compensation reports and physician reports in Connecticut for 1995. The resulting estimate was compared to a population-based survey of MSD. RESULTS: There was very small overlap between the two state injury reporting systems: 6.7% of 793 reported workers' compensation cases, or 8% of 661 physician's reports. The estimate for MSD not captured by either system was 13,285, resulting in 14,686 (95% CI: 9,733-18,453) total reported and non-reported cases. This compares to an estimate of 13,775 cases (95% CI: 8,800-18,800) based on a phone survey. CONCLUSIONS: This analysis points to substantial under-reporting of MSD in Connecticut: estimates of unreported cases exceed those officially reported by a factor of 11:1. The findings have an important bearing on injury prevention programs and policy making.

Connecticut↗

PubMed2001

Impact of a joint labor-management ergonomics program on upper extremity musculoskeletal symptoms among garment workers.

This study evaluated the effect of an ergonomics intervention program on the prevalence and intensity of symptoms of upper extremity work-related musculoskeletal disorders among 36 garment workers performing an operation called spooling. Adjustable chairs were introduced and workers were trained in their use. Symptom surveys were administered prior to and 6 months after introduction of adjustable chairs. Quantitative pre- and post-intervention measurement of joint position was performed utilizing videotapes among a subgroup of nineteen. Eighty nine percent of the cohort reported pain in either the neck or at least one upper extremity anatomic site prior to the adjustable chair intervention. Among subjects reporting pain at baseline, there were significantly decreased pain levels in 10 of 11 anatomic sites after the intervention. Among all subjects, the proportion reporting pain decreased for each anatomic site following the intervention, with statistically significant decreases in 3 sites. However, there were only modest declines in awkward posture among the videotaped subgroup. This study suggests that introduction of an ergonomics program focused on education and introduction of an adjustable chair may diminish musculoskeletal symptomatology in apparel manufacturing workers.

Adult↗

PubMed2001

The creation of ergonomic data sheets for hazard communication of work-related musculoskeletal disorders.

Information on human health hazards caused by chemical exposure has traditionally been supplied through Material Safety Data Sheets (MSDS). This report describes development of an analogous Ergonomic Data Sheet (EDS) to address hazards of work-related musculo-skeletal disorders (WRMSD) from use of hand tools. The EDS includes sections on risk factors for WRMSD, design aspects of the tool that decrease risks, precautionary measures, and objective testing of the tool compared to other comparable tools. The EDS can be used within an Ergonomic Communication Program similar to a Hazard Communication Program.

Communication↗

PubMed2000

Biomechanical, psychosocial, and organizational risk factors for WRMSD: population-based estimates from the Connecticut upper-extremity surveillance project (CUSP).

In a case-control study of a population-based telephone survey of 3,798 working adults, symptoms of work-related musculoskeletal disorder (WRMSD) were associated with biomechanical, psychosocial, and organizational factors. In several models, biomechanical exposures with strong associations were static postures (odds ratios [ORs] = 2.00-5.45); repeated pushing, pulling, lifting (ORs = 1.86-12.75); and repeated neck bending (ORs = 1.07-12.8). Psychosocial and organizational factors consistently retained in these models were demands (ORs = 1.26-1.59) and organizational support (ORs = 0.53-0.79). Decision latitude entered less frequently (ORs = 0.30-0.49). This research may have implications for intervention strategies. First, reducing both biomechanical and psychosocial risk may be more effective than focusing solely on engineering controls. Second, organizational culture and policy may have strong implications for WRMSD prevalence and control.

Adult↗

PubMed2000

H RAS mutations in haematologically normal individuals.

INTRODUCTION: Point mutations in N, K and H RAS have been found in adverse haematological malignancies. The background frequency of RAS mutations in the normal population has yet to be determined. Here we report the results of a screen for RAS mutations from normal individuals. MATERIALS AND METHODS: DNA from peripheral blood or bone marrow from 115 haematologically normal individuals was screened for point mutations in N, K and H RAS, at amino acid positions 12, 13 and 61. The screening was done using polymerase chain reaction and oligonucleotide hybridisation and candidate mutations were subsequently confirmed by cloning and sequencing. RESULTS AND CONCLUSION: Point mutations were identified in DNA from two of the 115 individuals. Both mutations resulted in an amino acid substitution at position 12 in H RAS. Both individuals with detectable H RAS mutations remain haematologically normal.

Adult↗

PubMed2000

A role for Pax6 in the normal development of dorsal thalamus and its cortical connections.

The transcription factor Pax6 is widely expressed throughout the developing nervous system, including most alar regions of the newly formed murine diencephalon. Later in embryogenesis its diencephalic expression becomes more restricted. It persists in the developing anterior thalamus (conventionally termed "ventral" thalamus) and pretectum but is downregulated in the body of the posterior (dorsal) thalamus. At the time of this downregulation, the dorsal thalamus forms its major axonal efferent pathway via the ventral telencephalon to the cerebral cortex. This pathway is absent in mice lacking functional Pax6 (small eye homozygotes: Sey/Sey). We tested whether the mechanism underlying this defect includes abnormalities of the dorsal thalamus itself. We exploited a new transgenic mouse ubiquitously expressing green fluorescent protein tagged with tau, in which axonal tracts are clearly visible, and co-cultured dorsal thalamic explants from Pax6(+/+ )or Pax6(Sey/Sey )embryos carrying the transgene with wild-type tissues from other regions of the forebrain. Whereas Pax6(+/+ )thalamic explants produced strong innervation of wild-type ventral telencephalic explants in a pattern that mimicked the thalamocortical tract in vivo, Pax6(Sey)(/Sey) explants did not, indicating a defect in the ability of mutant dorsal thalamic cells to respond to signals normally present in ventral telencephalon. Pax6(Sey)(/Sey) embryos also showed early alterations in the expression of regulatory genes in the region destined to become dorsal thalamus. Whereas in normal mice Nkx2.2 and Lim1/Lhx1 are expressed ventral to this region, in the mutants their expression domains are throughout it, suggesting that a primary action of Pax6 is to generate correct dorsoventral patterning in the diencephalon. Our results suggest that normal thalamocortical development requires the actions of Pax6 within the dorsal thalamus itself.

Alternative Splicing↗

PubMed2000

Reporting of work-related musculoskeletal disorder (MSD) to workers compensation.

In contrast to theories of moral hazard, it appears that workers under-report cases to Workers' Compensation. In a population-based phone survey of work-related MSDs, it was found that cases were more likely to be reported if they were called work-related by a doctor, had surgery, or took time off from work. Higher rates of filing were found for lower education, having a union at the workplace, working in manufacturing, and for blue-collar occupations. Fear of the consequences of filing was significantly related to filing, but was not a strong association. A lack of perceived management support and lower decision latitude was associated with a higher rate of filing. Perceived knowledge of the Workers' Compensation system was not associated with filing. In general, a broader perspective of looking not just at reported claims but also unreported work-related illnesses is important for understanding both the magnitude of the problem as well as the impact of changes in Workers' Compensation laws.

Journal Article↗

PubMed1999

The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex.

The cerebral cortex develops from the dorsal telencephalon, at the anterior end of the neural tube. Neurons are generated by cell division at the inner surface of the telencephalic wall (in the ventricular zone) and migrate towards its outer surface, where they complete their differentiation. Recent studies have suggested that the transcription factor Pax6 is important for regulation of cell proliferation, migration and differentiation at various sites in the CNS. This gene is widely expressed from neural plate stage in the developing CNS, including the embryonic cerebral cortex, where it is required for radial glial cell development and neuronal migration. We report new findings indicating that, in the absence of Pax6, proliferative rates in the early embryonic cortex are increased and the differentiation of many cortical cells is defective. A major question concerns the degree to which cortical defects in the absence of Pax6 are a direct consequence of losing the gene function from defective cells themselves, rather than being secondary to abnormalities in other cells. Cortical defects in the absence of Pax6 become much more pronounced later in cortical development, and we propose that many result from a compounding of abnormalities in proliferation and differentiation that first appear at the onset of corticogenesis.

Animals↗

PubMed1998

Laparoscopic cholecystectomy in multiple laparotomy Crohn's disease.

Patients with complicated Crohn's disease often require several surgical procedures resulting in multiple adhesions. They also have an increased incidence of gallstones. Laparoscopic cholecystectomy is associated with several advantages but is problematic for the inexperienced surgeon in the presence of multiple adhesions. Laparoscopic cholecystectomy was performed successfully in three patients with Crohn's disease who had previous extensive abdominal surgery. The average operative time was 75 min, with an average hospital stay of 2 days and minimal blood loss. There were no postoperative complications. Provided specific precautions are taken during establishment of the pneumoperitoneum, an adequate adhesiolysis can be performed, rendering laparoscopic cholecystectomy feasible and safe in such patients.

Cholecystectomy, Laparoscopic↗