Gulf War illnesses: causation and treatment.

Soldiers returning from the Gulf War in 1991 described a range of symptoms, including some consistent with the chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Well-defined adverse health events attributable to service in the Gulf occurred. However, controlled epidemiological studies in Gulf War veterans and controls describe significant excesses of symptoms that were not clearly associated with pathologic disease. At least 12% of veterans currently receive some form of disability from the Department of Veterans Affairs. A number of reports outline theories proposed to explain the excess, but few are scientifically supported. Management guidelines for this spectrum of disorders resembles that of many of "emerging overlap syndromes," including multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia. They include the establishment of a trusting doctor-patient relationship, negotiations around a common ground of scientific and etiologic beliefs, non-labeling of the disorder, and work toward recovery in the absence of clear etiologic answers.     

Medical care expenditures for diabetes, its chronic complications, and its comorbidities.

BACKGROUND: Medical expenditures for diabetes are estimated, including expenditures for chronic complications of diabetes, unrelated conditions for which diabetics are at higher risk, and various comorbidities that raise the cost of medical care. METHODS: A variety of national data sources are used to disaggregate the Health Care Financing Administration's national health expenditures in 1995 by sex, age, and diagnosis. Expenditures for chronic complications and other unrelated conditions for which diabetics have higher rates of utilization are determined by analysis of attributable risks. Additional expenditures generated by extra hospital inpatient days and higher charges for nursing home and home health care for comorbidities are estimated by regression analyses. Sensitivity analysis is used to calculate a range of estimated expenditures. RESULTS: Total expenditures attributed to diabetes are $47.9 billion in 1995, including $18.8 billion for first listed diabetes, $18.7 billion for chronic complications, $8.5 billion for unrelated conditions, and $1.9 billion for comorbidities. The range of total expenditures is $34.3 to $63.7 billion. CONCLUSIONS: Comprehensive accounting of expenditures more accurately assesses the economic burden of diabetes and potential savings from prevention, especially of chronic complications. This analysis is illustrative for other chronic illnesses.     

Differential response of fast hindlimb extensor and flexor muscles to exercise in adult spinalized cats

Adult cats were spinal transected (T12-13) and maintained for approximately 6 months. Spinal cats were either not trained (N-T) or trained for 30 min/day to either step on a treadmill (Stp-T) or stand (Std-T). Spinalization resulted in a decrease in the mass and maximum tension potential of the medial gastrocnemius (MG), a fast ankle extensor. These adaptations were ameliorated in Std-T but not Stp-T cats. The maximum rate of shortening was elevated by 18 (ns), 34, and 19 (ns)% in the N-T, Std-T, and Stp-T cats, respectively, a finding consistent with a shift in the percentage of fast fibers, a decrease in the percentage of fibers expressing only type I myosin heavy chain, and an increase in myofibrillar adenosine triphosphatase activity. The shift toward a faster fiber type profile in the tibialis anterior (TA), a fast ankle flexor, was of a lesser magnitude than in the MG. There were no significant effects on the contractile properties of the TA in any group of spinal cats. The greater preservation of muscle mass, shift toward faster physiological and biochemical properties, and fatigability in the MG of Std-T than Stp-T cats suggest that factors other than the level of activation and force generation must play a role in muscle homeostasis. From a clinical perspective, the results indicate that muscles innervated by motor neurons below the level of a complete spinal cord lesion are affected differentially by specific neuromuscular activity patterns.     

Spontaneous abortion in the British semiconductor industry: An HSE investigation. Health and Safety Executive.

BACKGROUND: The UK Health and Safety Executive (HSE) conducted a study to examine the risk of spontaneous abortion (SAB) in British female semiconductor industry workers, following reports from the USA which suggested an association between risk of SAB and work in fabrication rooms and/or exposure to ethylene glycol ethers. METHODS: A nested case-control study based on 2,207 women who had worked at eight manufacturing sites during a 5-year retrospective time frame was established; 36 cases were matched with 80 controls. RESULTS: The overall SAB rate in the industry was 10.0%. (65 SABs/651 pregnancies) The crude odds ratio (OR) for fabrication work was 0.65 (95% CI 0.30-1.40). This was essentially unchanged after adjustment for a range of potential confounding factors in the first 3 months of pregnancy and was reduced to 0.58 (95% CI 0.26-1.30) after adjustment for smoking in the previous 12 months. There were no statistically significantly elevated ORs for any work group or any specific chemical or physical exposure in the industry. CONCLUSIONS: There is no evidence of an increased risk of SAB in the British semiconductor industry. Am. J. Ind. Med. 36:557-572, 1999. Published 1999 Wiley-Liss, Inc.     

Induction and inhibition of pesticide-metabolizing enzymes: roles in synergism of pesticides and pesticide action

Synergism of the toxic action of pesticides is discussed with particular emphasis on the methylenedioxyphenyl (benzodioxole) (MDP) synergists and on how studies of these compounds may relate to the general significance of pesticide synergism. MDP compounds function as both inhibitors and inducers of cytochrome P450 isoforms, the two processes proceeding, in vivo, at different rates. Inhibition is mediated through the formation of metabolite inhibitory complexes, and induction involves both aryl hydrocarbon (Ah)-dependent and Ah-independent mechanisms. The significance of this biphasic effect on multienzyme xenobiotic metabolizing systems is illustrated by considerations of the insecticide phorate.     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

Preferential methylation of target organ DNA by the oesophageal carcinogen N-nitrosomethylbenzylamine

Male Wistar rats received a single i.v. injection of the oesophageal carcinogen N-nitroso[methyl-14C]-methylbenzylnitrosamine (2.5 mg/kg body weight). Rapid distribution of the carcinogen occurred, with highest initial concentrations in liver and kidney. Within 10 min after the injection, 14C-labelled metabolites accounted for 50% of the total radioactivity present in the oesophagus, for approximately 25% in liver and forestomach, and for less than 20% in all other organs investigated. Decay of the carcinogen in rat serum followed first-order kinetics with a half-life of 35 min. Of the total radioactivity administered, 49% was exhaled as 14CO2 within 10 h and an additional 5-10% was excreted via urine and faeces. Four hours after a single i.v. injection of N-nitroso-[methyl-14C]benzylnitrosamine methylation of purine bases in DNA was most extensive in the oesophagus, followed by liver, lung and forestomach DNA. In the remaining tissues, DNA methylation was either considerably less (kidney, glandular stomach, spleen) or not at all detectable (ileum, colon, brain). At this time the concentration of the promutagenic base O6-methylguanine in oesophageal DNA was six times higher than in lung and nine times higher than in hepatic DNA. These data suggest that in the rat the selective induction of oesophageal tumours by N-nitrosomethylbenzylamine and related asymmetrical nitrosamines is mediated by a preferential bioactivation of the carcinogen in the target organ.     

Studies in menorrhagia: (a) mefenamic acid, (b) endometrial prostaglandin concentrations

Twenty-two women with unexplained heavy menstrual blood loss (average loss for two cycles of >80 ml) were treated with the prostaglandin synthetase inhibitor menfenamic acid during two consecutive menstruations. There was a significant reduction in menstrual blood loss on mefenamic acid therapy, the median loss being 137 ml before treatment and 76 ml while on treatment. Reduction in menstrual loss was achieved in 20 of the 22 patients but varied from a 2% to 78% reduction. The greater the menstrual loss before treatment, the more it was reduced on mefenamic acid therapy. Endometrial concentrations of prostaglandins E2 and F2 alpha in the follicular phase of the cycle were similar whether or not patients had menorrhagia. In the luteal phase, however, 6 of 14 patients with menorrhagia had higher endometrial prostaglandin E2 and F2 alpha concentrations than all 13 controls.