Meso-2,3-dimercaptosuccinic acid induces calcium transients in cultured rhesus monkey kidney cells

The maintenance of intracellular Ca2+ homeostasis is critical to many cellular functions that rely on the calcium ion as a messenger. While attempting to characterize the effects of lead on intracellular calcium levels ([Ca2+]i) in LLC-MK2 Rhesus Monkey kidney cells, we observed that treatment with the metal chelating drug, meso-2,3-dimer-captosuccinic acid (DMSA) evoked transient increases in [Ca2+]i. Changes in [Ca2+]i were monitored using the Ca2+ indicator dye Fura-2 and a dual wavelength fluorescence imaging system. In the presence of 2 mM extracellular Ca2+, DMSA treatment caused a concentration-dependent (15-500 microM) transient increase in [Ca2+]i returning to baseline levels within 30-60 s. Pharmacologic concentrations of DMSA (30 microM) stimulated a three-fold increase in [Ca2+]i, which was spatiotemporally comparable to Ca2+ transients induced by other calcium agonists. Depletion of inositol trisphosphate (IP3)-sensitive [Ca2+]i stores with the smooth endoplasmic reticulum calcium-ATPase (SERCA) inhibitor thapsigargin did not prevent DMSA-elicited increases in [Ca2+]i, suggesting that Ca2+ mobilized by DMSA was either extracellular or from an non-IP3 releasable Ca2+ pool. Treatment with glutathione, cysteine, or 2-mercaptoethanol caused similar but not identical calcium transients. Adenosine-5'-trisphosphate (ATP) also elicited transient increases in [Ca2+]i similar to those of DMSA. No transient increases in [Ca2+]i were elicited by DMSA or ATP in the absence of extracellular calcium. These data indicate that DMSA and other sulfhydryl compounds trigger an influx of extracellular calcium, suggesting a previously unobserved and unanticipated interaction between DMSA and the Ca2+ messenger system.     

Investigation of an acute chemical incident: exposure to fluorinated hydrocarbons

OBJECTIVES—To assess whether attendance at the site after an incident in a sewer was associated with symptoms in emergency personnel and whether the prevalence of symptoms was associated with estimated levels of exposure to any chemical hazard.
METHODS—Symptoms experienced by people attending an incident involving two dead sewer workers suggested the presence of a chemical hazard, before environmental sampling confirmed any toxic agent. Self reported symptoms, estimated exposures, and biomarkers of exposure for likely agents from all 254 people who attended the incident and a referent occupational group matching the 83 emergency personnel who went to the Accident and Emergency department (A and E) in the first 48 hours were recorded. The prevalence of symptoms and concentrations of creatine phosphokinase in serum of the 83 early patients at A and E were compared with their referent occupational group. In all workers who attended the incident, the trends in symptom prevalences and concentrations of creatine phosphokinase in serum were examined by distance from the site and predefined exposure category.
RESULTS—Among all workers who attended the incident, symptoms of shortness of breath and sore throat were significantly associated with indirect estimates of exposure but not associated with concentrations of creatine phosphokinase. Freon was detected in two blood samples. The early patients at A and E reported more symptoms than their matched reference group and their median concentrations of creatine phosphokinase were higher.
CONCLUSIONS—The association between symptoms and concentrations of creatine phosphokinase with attendance at the site indicated the presence of a continuing hazard at the site and led to extra precautions being taken. Comparison values from the referent occupational group prevented unnecessary medical follow up.


Keywords: pollution; chemical; population     

Autoimmune inner ear disease: therapy

Sixty-six patients with this disease have been treated to date with cyclophosphamide and prednisolone resulting in significant improvement in hearing. In some patients the vestibular compartment may be involved as well, but the clinical pattern is significantly different enough from Meniere's disease to distinguish it by the careful historian. The cornerstone of treatment is cyclophosphamide, abetted by prednisolone. A test of treatment is to date the best method of determining who to treat for cure.     

Infantile glycerol kinase deficiency— a condition requiring prompt identification

Infantile glycerol kinase deficiency (GKD) is an X-linked genetic disease characterized clinically by adrenal insufficiency and muscular dystrophy. The enzyme defect leads to increased levels of glycerol in blood and urine, which can be used for diagnosis. Without recognition of this condition, the chances for life-saving steroid treatment and for genetic counselling are missed. We report clinical, endocrinological, biochemical, and morphological findings in two non-related boys. One of them died in early infancy. The other is thriving at the age of 2 years although he is suffering from a myopathy not distinguishable from Duchenne muscular dystrophy. We discuss when to suspect and how to confirm the diagnosis of infantile GKD, and under what precautions the condition is detectable by commonly used screening procedures for inborn errors of metabolism.     

REHABILITATING SEVERELY HEAD-INJURED ADOLESCENTS: THREE CASE REPORTS

The case reports of 3 severely head-injured adolescents, who developed psychiatric sequelae after the trauma, are presented. All 3 cases displayed various socially disinhibited behaviours. Individually tailored treatment programmes helped these young people manage their maturational tasks of adolescence. Several issues, central to this rehabilitative work, are discussed, including the personal significance of the adolescent's injury, identity issues and defence mechanisms; a family perspective on coping with the injured adolescent and the components of a therapeutic package.     

Choice of NSAID and management strategy in rheumatoid arthritis and osteoarthritis. The impact on costs and outcomes in the UK

OBJECTIVE: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective therapy for rheumatoid arthritis, they are associated with significant adverse effects, the management of which imposes additional costs on the healthcare system. Prescribing NSAIDs which have a lower risk of major adverse effects as the first-line NSAID for patients with rheumatoid arthritis and osteoarthritis may be expected to lead to an improvement in clinical outcomes and reduce overall treatment costs. This analysis examines data from a published randomised controlled trial of 5 NSAIDs to explore these hypotheses. DESIGN AND SETTING: Data from a clinical trial comparing 5 NSAIDs were combined with published cost data to construct 2 clinical decision models, reflecting alternative approaches to the management of major and minor adverse effects in the UK. INTERVENTIONS: The 5 NSAIDs evaluated in the analysis were nabumetone, diclofenac, ibuprofen, piroxicam and naproxen, although only the results for ibuprofen and nabumetone are reported. MAIN OUTCOME MEASURES AND RESULTS: The total cost of care per patient receiving nabumetone was estimated to be between 25 pounds sterling (Pound) and 41 Pounds more expensive than ibuprofen. In a hypothetical cohort of 100,000 patients, there were between 690 and 821 more major adverse effects using ibuprofen than nabumetone. The cost per life-year gained (LYG) from using nabumetone rather than ibuprofen ranged between 1880 Pounds and 2517 Pounds (1995 values), depending upon the management of adverse effects. CONCLUSIONS: These results indicate that: (i) prescribing the newer, currently more expensive, NSAIDs will not necessarily lead to cost savings; (ii) the management of adverse effects can have a significant impact on costs; and (iii) the additional cost may be justifiable in terms of the mortality and morbidity gains associated with the new lower-risk NSAIDs.     

The safety and efficacy of intraoperative heparin in total hip arthroplasty

A single dose of unfractionated heparin (15 U/kg), administered intravenously before surgery on the femur suppresses thrombogenesis during total hip replacement. Nine hundred eighty-nine patients (1021 hips) who received one dose of intraoperative heparin with hypotensive epidural anesthesia were followed up prospectively for 3 months. Asymptomatic deep vein thrombosis assessed by ultrasound in the first 198 consecutive patients showed an incidence of 7.1% (14 of 198). The incidence of clinical deep vein thrombosis in the subsequent 791 patients was 0.88% (seven of 791). Symptomatic pulmonary embolism occurred in 0.5% (five of 989). No patients died and there was one major bleeding episode. Based on this favorable experience, intraoperative heparin appears safe and efficacious as thromboembolic prophylaxis.     

Molecular typing of ampicillin-resistant, non-beta-lactamase-producing Enterococcus faecium isolates from diverse geographic areas.

Molecular typing methods were compared by using 66 ampicillin-resistant, non-beta-lactamase-producing Enterococcus faecium clinical isolates from diverse geographic areas. Whole-plasmid analysis, restriction enzyme analysis of plasmid DNA with EcoRI and HindIII, and contour-clamped homogeneous electric field electrophoresis with digestion by SmaI and ApaI were performed on all isolates. Whole-plasmid analysis identified 47 different groups. Restriction enzyme analysis of plasmid DNA identified 50 groups when EcoRI was used and 51 groups when HindIII was used. Results with EcoRI and HindIII differed in 9 of 66 isolates. Grouping results with whole-plasmid analysis differed from results of restriction enzyme analysis of plasmid DNA (combining EcoRI and HindIII) in 20 of 66 isolates. Contour-clamped homogeneous electric field electrophoresis identified 46 groups when SmaI was used and 44 groups when ApaI was used. Results with SmaI and ApaI differed in 3 of 66 isolates. Grouping results with contour-clamped homogeneous electric field electrophoresis (combining SmaI and ApaI) differed from results of restriction enzyme analysis of plasmid DNA (combining EcoRI and HindIII) in 17 of 66 isolates. The combined use of whole-plasmid analysis, restriction enzyme analysis of plasmid DNA with two enzymes, and contour-clamped homogeneous electric field electrophoresis with two restriction enzymes should be considered when E. faecium is typed for epidemiologic investigation.