Development of miotic cross-tolerance between pyridostigmine and sarin vapor.

The organophosphorous nerve agent sarin (GB) and the carbamate pyridostigmine bromide (PB) both inhibit acetylcholinesterase (AChE), leading to overstimulation of muscarinic receptors. Both GB and PB produce miosis through stimulation of ocular muscarinic receptors. This study investigated 2 hypotheses: (1) that the miotic response to PB would decrease following repeated injections; and (2) that repeated administration of PB would result in tolerance to the miotic effect of GB vapor. Rats were injected intramuscularly with saline, 0.04 mg/kg, 0.5 mg/kg, or 1.4 mg/kg of PB twice daily for 8 consecutive days. After day 3, animals injected with 1.4 mg/kg PB developed miotic tolerance. Twenty-four (24) h following the final PB injection, the rats were exposed to GB vapor (4.0 mg/m(3)). A similar magnitude of miosis was observed in all groups after GB exposure. However, the rate of recovery of pupil size in animals pretreated with 0.5 and 1.4 mg/kg PB was significantly increased. Twenty (20) h following exposure to GB vapor, the pupils of animals pretreated with 1.4 mg/kg PB had recovered to 77% +/- 4% of their pre-exposure baseline, whereas the saline-injected controls had recovered to only 52% +/- 2% of their pre-exposure baseline. The increased rate of recovery does not appear to be a result of protection of pupillary muscarinic receptors by the higher doses of PB, as there was no longer PB present in the animal at the time of GB exposure. These results demonstrate the development of tolerance to the miotic effect of PB following repeated exposures, and also suggest that cross-tolerance between PB and GB occurs. However, because the magnitude of the response was not reduced, the PB pretreatment and its associated miotic cross-tolerance does not appear to diminish the effectiveness of miosis as a biomarker of acute exposure to nerve agent vapor.     

Use of a geographic information system to track smelter-related lead exposures in children: North Lake Macquarie, Australia, 1991–2002

Background  

To determine patterns of childhood lead exposure in a community living near a lead and zinc smelter in North Lake Macquarie, Australia between 1991 and 2002.     

Systematic review of methods to diagnose infection in foot ulcers in diabetes.

AIM: To undertake a systematic review of the diagnostic performance of clinical examination, sample acquisition and sample analysis in infected foot ulcers in diabetes. METHODS: Nineteen electronic databases plus other sources were searched. To be included, studies had to fulfil the following criteria: (i) compare a method of clinical assessment, sample collection or sample analysis with a reference standard; (ii) recruit diabetic individuals with foot ulcers; (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12-item checklist. RESULTS: Three eligible studies were identified, one each on clinical examination, sample collection and sample analysis. For all three, study groups were heterogeneous with respect to wound type and a small proportion of participants had foot ulcers due to diabetes. No studies identified an optimum reference standard. Other methodological problems included non-blind interpretation of tests and the time lag between index and reference tests. Individual signs or symptoms of infection did not prove to be useful tests when assessed against punch biopsy as the reference standard. The wound swab did not perform well when assessed against tissue biopsy. Semiquantitative analysis of wound swab might be a useful alternative to quantitative analysis. The limitations of these findings and their impact on recommendations from relevant clinical guidelines are discussed. CONCLUSION: Given the importance of this topic, it is surprising that only three eligible studies were identified. It was not possible to describe the optimal methods of diagnosing infection in diabetic patients with foot ulceration from the evidence identified in this systematic review.     

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.     

Impact of a Pharmacist-Based Consult Service on Nutritional Rehabilitation of Nonambulatory Patients with Severe Developmental Disabilities

A pharmacist consult service was developed to evaluate the appropriateness of enteral feeding through a permanent ostomy in 24 nonambulatory patients with severe developmental disabilities. Several problems with enteral nutrition were identified. Policies to improve them were instituted, and several educational presentations were made. Pharmacists' actions were implemented, including assessment of energy needs by indirect calorimetry and rearrangement of enteral feeding schedules to achieve optimal nutrition support and pharmacotherapy administration. By the fourth month of the consult service, body weight in these patients increased from 101 ± 6% of baseline to 109 ± 7% (p<0.05). Weight continued to increase through the seventh month of the consult service to 116 ± 12% of baseline (p<0.0001). Measured resting energy expenditure for the group was 889 ± 170 kcal/day compared with the predicted 1055 ± 163 kcal/day.     

Performance measures for evaluating services for people with a first episode of psychosis

Aim: The purpose of this project was to operationalize and apply a previously identified set of performance measures designed to evaluate services for those experiencing a first episode of a schizophrenia spectrum disorder. Methods: Operational definitions were developed for previously identified measures through an iterative process of discussions between clinical experts and health‐care evaluators. Data were collected from existing sources including corporate databases, clinical databases and chart review. Results: Definitions were developed for 44 measures covering seven of eight domains recommended for service level evaluation by the Canadian Institute for Health Information domains. Forty measures could be calculated. Conclusions: The measures represent a comprehensive set of performance measures suitable for the evaluation of services for people with a first‐episode psychosis. The measures could be used by other services in order to establish standards and norms for routine clinical practice.