HLA-DPB1 E69 genotype and exposure in beryllium sensitisation and disease.

OBJECTIVES: Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case-control study assessed the contribution of genetics and exposure in the development of BeS and CBD. METHODS: Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Lifetime-average beryllium exposure estimates were based on workers' job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity. RESULTS: Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS. CONCLUSIONS: Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.

Intramuscular cobinamide as an antidote to methyl mercaptan poisoning.

BACKGROUND: Methyl mercaptan occurs naturally in the environment and is found in a variety of occupational settings, including the oil, paper, plastics, and pesticides industries. It is a toxic gas and deaths from methyl mercaptan exposure have occurred. The Department of Homeland Security considers it a high threat chemical agent that could be used by terrorists. Unfortunately, no specific treatment exists for methyl mercaptan poisoning. METHODS: We conducted a randomized trial in 12 swine comparing no treatment to intramuscular injection of the vitamin B12 analog cobinamide (2.0 mL, 12.5 mg/kg) following acute inhalation of methyl mercaptan gas. Physiological and laboratory parameters were similar in the control and cobinamide-treated groups at baseline and at the time of treatment. RESULTS: All six cobinamide-treated animals survived, whereas only one of six control animals lived (17% survival) (p = 0.0043). The cobinamide-treated animals returned to a normal breathing pattern by 3.8 ± 1.1 min after treatment (mean ± SD), while all but one animal in the control group had intermittent gasping, never regaining a normal breathing pattern. Blood pressure and arterial oxygen saturation returned to baseline values within 15 minutes of cobinamide-treatment. Plasma lactate concentration increased progressively until death (10.93 ± 6.02 mmol [mean ± SD]) in control animals, and decreased toward baseline (3.79 ± 2.93 mmol [mean ± SD]) by the end of the experiment in cobinamide-treated animals. CONCLUSION: We conclude that intramuscular administration of cobinamide improves survival and clinical outcomes in a large animal model of acute, high dose methyl mercaptan poisoning.

Isocyanate induced allergic contact dermatitis in a university undergraduate student: An occupational dermatitis case report, review of laboratory safety regulations, and implications for campus research.

A 19-year-old female college undergraduate developed an intensely swollen, erythematous and pruritic rash on the face and hands while working in an optical fabrication lab producing photosensitive polymers. She had no respiratory symptoms. The rash was consistent with contact dermatitis and there was no clinical evidence of respiratory involvement with normal spirometry. A review of the safety data sheets of chemicals used in the laboratory revealed several known sensitizers, including 6-hexamethylene diisocyanate (HDI), dibutyl phthalate, and 2,4,6-tribromophenyl acrylate. Patch testing confirmed the patient's sensitization to HDI. A subsequent worksite visit identified several hazardous chemicals that were used without appropriate hazard communication, training, standard operating procedures, or personal protective equipment. Simple exposure controls were recommended and instituted, and the patient was able to return to work in the laboratory without the recurrence of symptoms. This case demonstrates the importance of hazard identification, communication, and safety training in academic laboratories, for students and workers. A medical evaluation can identify hazards as well as lead to improvements in exposure controls and safe return to research.

Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model.

Hydrogen sulfide (H2 S), a high-threat chemical agent, occurs naturally in a variety of settings. Despite multiple incidents of exposures and deaths, no FDA-approved antidote exists. A rapid-acting, easy to administer antidote is needed. We conducted a randomized control trial in swine comparing intramuscular administration of aminotetrazole cobinamide (2.9 mL, 18 mg/kg) to no treatment following inhalation of H2 S gas. We found that aminotetrazole cobinamide administered 2 min after the onset of respiratory depression-defined as a tidal volume of less than 3 mL/kg for 2 consecutive minutes-yielded 100% survival, while all control animals died. Respiratory depression resolved in the treatment group within 3.6 ± 1.5 min (mean ± SD) of cobinamide administration, whereas control animals had intermittent gasping until death. Blood pressure and arterial oxygen saturation (SO2 ) returned to baseline values within 5 and 10 min, respectively, of cobinamide treatment, and plasma lactate concentration decreased to less than 50% of the highest value by the end of the experiment. In control animals, plasma lactate rose continuously until death. We conclude that intramuscular aminotetrazole cobinamide is effective in a large animal, inhalational model of acute, severe H2 S poisoning.

Low-cost, Small-scale Decontamination of Laboratory Equipment by Using Chlorine Dioxide Gas.

A significant concern in laboratory animal medicine is contamination due to pathogen outbreaks and how to adequately decontaminate small equipment. Many factors play a role in the selection of the decontamination method including cost, efficacy, personnel time and safety. Chlorine dioxide (ClO2) gas is an effective method, but decontamination often requires a ClO2 gas generator with a specialized air-tight exposure chamber. Although this method works well for large-scale decon- tamination, the use of a gas generator may be impractical and too costly for smaller-scale decontamination. The goal of this study was to create and validate an effective, small-scale decontamination method that uses ClO2 gas and which is an affordable, efficient, safe, and reproducible. First, we identified a product that generates ClO2 gas after the combination of 2 dry reagents. To find an affordable exposure chamber, we evaluated the ability of 4 household totes with gasket-seal lid systems to retain ClO2 gas and relative humidity (RH). The efficacy of decontamination was validated by concurrently using 2 different biologic indicators (BI), Bacillus atrophaeus (B.a.) and Geobacillus stearothermophilus (G.s.). All household totes evaluated held sufficient gas and RH for a 15-h cycle, providing adequate contact time to inactivate both BI evaluated. Our results suggest that a total exposure dose of 71 ± 42 ppm-h of ClO2 gas over 15 h at 90% or greater RH is adequate to inactivate both B.a. and G.s. There was no statistical significance between the 2 BI as indicators for decontamination; 65 of 230 (28.3%) B.a. and 75 of 230 (32.6%) G.s spore strips were positive for growth (P = 0.36). In conclusion, we successfully combined a variety of low-cost materials to establish an effective, small-scale method to decontaminate laboratory equipment. Depending on the size of the tote and whether BI are used, the cost of our method is roughly 1% that of large-scale ClO2 gas generators used with specialized air-tight exposure chambers.

UrgoClean: a new dressing for desloughing exuding wounds.

Wound debridement plays a key role in wound bed preparation and the healing of chronic wounds. A variety of techniques can be used to achieve debridement and autolytic debridement is frequently the clinician's first choice. This is aided by dressings including hydrogels and hydrocolloids, which provide the moist environment required for white blood cells to function. This product focus uses 12 case studies to examine the effectiveness of UrgoClean in wound debridement.

The management of a patient with chronic oedema: a case study.

Chronic oedema is a complex long-term condition that can have profound effects on the patient. Therefore, it is vital that the district nurse has the knowledge and skills to manage an individual to ensure a therapeutic concordant relationship. This feature seeks to consider best-practice management of a patient with chronic oedema.

Parental influence on children with attention-deficit/hyperactivity disorder: II. Results of a pilot intervention training parents as friendship coaches for children.

We report findings from a pilot intervention that trained parents to be "friendship coaches" for their children with Attention-Deficit/Hyperactivity Disorder (ADHD). Parents of 62 children with ADHD (ages 6-10; 68% male) were randomly assigned to receive the parental friendship coaching (PFC) intervention, or to be in a no-treatment control group. Families of 62 children without ADHD were included as normative comparisons. PFC was administered in eight, 90-minute sessions to parents; there was no child treatment component. Parents were taught to arrange a social context in which their children were optimally likely to develop good peer relationships. Receipt of PFC predicted improvements in children's social skills and friendship quality on playdates as reported by parents, and peer acceptance and rejection as reported by teachers unaware of treatment status. PFC also predicted increases in observed parental facilitation and corrective feedback, and reductions in criticism during the child's peer interaction, which mediated the improvements in children's peer relationships. However, no effects for PFC were found on the number of playdates hosted or on teacher report of child social skills. Findings lend initial support to a treatment model that targets parental behaviors to address children's peer problems.