Metabolism of polycyclic aromatic hydrocarbons in the rat ovary. Comparison with metabolism in adrenal and liver tissues

The activities of polycyclic aromatic hydrocarbon metabolizing enzymes and their regulation in the rat ovary were investigated and compared to those in the rat adrenal and liver. 7,12-Dimethylbenz[a]anthracene and benz[a]pyrene, both potent carcinogens, were converted by ovarian microsomes to hydrophilic products by the same cytochrome P-450 dependent monooxygenase with an apparent K_m of about 0.05–0.1 μM. These data indicate that the ovarian AHH has a 20- and 200-fold higher affinity for polycyclic aromatic hydrocarbons than the adrenal and liver, respectively. 3-Methylcholanthrene (MC) and 7,12-dimethylbenz[a]anthracene apparently induce ovarian AHH but in an irreproducible manner, suggesting a possible regulation by endogenous factors. Among various inhibitors tested, ellipticine, SU-9055 and α-napthoflavone were the most efficient; steroids, e.g. cholesterol and estradiol, were less efficient inhibitors. A comparison of the adrenal and liver with respect to metabolite patterns for DMBA and BP reveals that there are striking qualitative as well as quantitative similarities between the adrenal and ovarian systems, whereas the liver appears to be different. Also, glutathione-S-transferase activity is inducible by MC in the liver but not in the adrenal or ovary. DT-diaphorase is induced by MC in all three organs but only by DMBA in the liver and ovary. In contrast, epoxide hydrolase is not induced by MC or DMBA in either of these organs. These results suggest that the ovarian and adrenal systems involved in bioactivation and detoxification of xenobiotics are closely related whereas those of the liver are different.     

Ultrasonographic screening for abdominal aortic aneurysm: Analysis of surgical decisions for cost-effectiveness

A mathematic model is created to determine the economic cost per year of anticipated prolongation of life that would result from a program of abdominal ultrasonographic (US) screening for abdominal aortic aneurysm. The protocol involves US screening at age 60,67, and 74 years with additional annual follow-up US and examination if an aneurysm of less than 40 mm is detected. Larger aneurysms are assumed to be sent for early elective resection. The benefits and risks for a subset of men with symptoms of intermittent claudication (IC) as an additional risk factor of atherosclerosis is calculated for comparison. Many of the factors on which these calculated costs and benefits are based are approximations and inferences. These include operative mortality for elective and emergent cases, charges for each such condition, cost of US, and anticipated survival following successful aneurysmectomy both with and without concomitant IC. Sensitivity analysis is performed to show how variations in the major parameters alter the outcome of the calculated cost per year of anticipated extension of life.

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Resumen Se ha creado un modelo matemático para determinar los costos económicos anuales de la prolongación de la vida que puede esperarse de un programa de tamizaje por ultrasonografía (US) abdominal para la detección de aneurismas asintomáticos de la aorta abdominal. El protocolo implica el tamizaje por US a las edades de 60, 67, y 74 años, con seguimiento anual por US y examen si se detecta un aneurisma de menos de 40 mm. Se asume que aneurismas de un tamaño mayor son remitidos para resección electiva. Para efectos de comparación se han calculado los riesgos y beneficios para un subgrupo de hombres con síntomas de claudicación intermitente (CI) como un factor de riesgo adicional de aterosclerosis.Muchos de los factores sobre los cuales se han calculado los costos y beneficios se fundamentan en aproximaciones y en inferencias. Estos incluyen mortalidad operatoria para casos electivos y de emergencia, cargos para tales condiciones, costos de la US, y predicción de la supervivencia después de un aneurismectomía electiva en patientes con y sin CI concomitante. Se realizó un análisis de sensibilidad para demostrar como las variaciones en los parámetros mayores alteran el cálculo de los costos anuales de la predecible extensión de la vida.

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Résumé On a mis au point un modèle mathématique pour déterminer les coûts annuels engendrés par la prolongation de vie anticipée par la pratique de l'échographie abdominale de routine pour détecter les anévrysmes de l'aorte abdominale. Le protocole comporte des examens à l'âge de 60, 67, et 74 ans et, par la suite, chaque année si un anévrysme inférieur à 40 mm est détecté. Les anévrysmes plus volumineux sont sensés être adressés en chirurgie vasculaire pour une cure à froid. A titre de comparaison, on a calculé les avantages et les inconvénients d'un sousgroupe de patients présentant des symptômes de claudication intermittente comme un facteur de risque supplémentaire.Bien des facteurs avec lesquels on a calculé le coût et les bénéfices ne sont que des approximations: mortalite opératoire des interventions urgentes et électives, coût de ces opérations, coût de l'échographie, survie anticipée après excision d'anévrysme avec ou sans claudication intermittente concomitante. L'analyse des sensibilités montre comment les variations des paramètres essentiels modifient l'évolution du coût par an de la prolongation de la vie.

     

Potential antipsychotic agents 5. Synthesis and antidopaminergic properties of substituted 5,6-dimethoxysalicylamides and related compounds

A series of 3-substituted 5,6-dimethoxysalicylamides III (9-13 and 15) has been synthesized from the corresponding 2,5,6-trimethoxybenzoic acids. Relaxation times T1 and carbon chemical shifts of the methoxy groups in III showed that the 6-methoxy group adopts a nearly perpendicular orientation and the 5-methoxy group takes on a more coplanar orientation with respect to the ring plane in solution. The salicylamides III display a very high and stereoselective affinity for the [3H]spiperone and [3H]raclopride binding sites in vitro. Regioisomeric salicylamides IV also exhibit pronounced, but lower than III, affinity for the [3H]spiperone binding site. The structural requirements were further assessed by studies of the related amino analogues 23 and 24 and hydroxy analogue 27. The 3-bromo compound 11 (FLB 463) was studied in various in vivo models and compared with the dopamine-D2 antagonists sulpiride, raclopride, eticlopride, and haloperidol. The high potency of 11 to selectively block dopamine-D2 receptors in vitro and in vivo combined with indications on a low potential for motor side effects makes it a very interesting new member of the class of substituted salicylamides.     

Quantitative EMG and muscle tension in painful muscles in fibromyalgia

Examinations were performed in 22 female fibromyalgic patients and in 9 healthy controls. The biceps brachii, trapezius, and tibial anterior muscles were examined electromyographically. The changes found were minor and non-specific. This implies that there is no important loss of motor units and no conspicuous muscle fiber degeneration in fibromyalgia. Our investigation also failed to demonstrate any electrically detectable muscle activity in muscles where the patients during the examination reported pain (paraspinal, trapezius and tibial anterior muscles). This means that muscle tension cannot be a prominent pathogenetic factor in fibromyalgia and that factors other than muscle tension are responsible for maintaining the pain in fibromyalgia.     

Total Hip Replacement in Avascular Necrosis of Femoral Head

Background

A study was conducted to evaluate the role of total hip replacement in cases of advanced avascular necrosis of the head of femur in patients admitted to two tertiary care military hospitals. 20 patients reporting with avascular necrosis of femoral head were taken for study.

Methods

Out of 20 patients, 16 were males and 4 were females. In 7 cases there was history of chronic alcohol intake and among them one patient was on steroids for long time for the treatment of bronchial asthma. 2 patients developed avascular necrosis of the femoral head following pregnancy and in two cases, it was post-traumatic. In the remaining nine cases, no cause was found and were so considered idiopathic. They were evaluated pre-operatively and total hip replacement was done in all twenty cases.

Results

Patients were evaluated using Harris hip score. There was improvement of the score in all cases.

Conclusion

Total hip replacement is a boon for patients of advanced avascular necrosis of femoral head.Key Words: Avascular necrosis, Total hip arthroplasty, Harris hip score     

Outbreak of Viral Hepatitis E in a Regimental Training Centre

Background

An outbreak of viral hepatitis occurred in a regimental centre with 265 cases occurring during a 3 months period.

Methods

190 serum samples were tested for IgM antibodies against viral hepatitis E by Enzyme Immuno Assay (EIA) and for antibodies against Hepatitis A and Hepatitis B viruses. Epidemiological investigation comprised review of surveillance data, filling up epidemiological case sheet, sanitary survey, inspection of water supplies and bacteriological examination of water for coliforms.

Result

97.4% of the serum samples were positive for IgM antibodies against Hepatitis E virus. Two leaks were detected in water pipelines, which were passing through contaminated areas around improperly functioning septic tanks and soak pits. The attack rate among recruits being supplied water through leaking pipelines was 11.1% whereas it was 2.89% in those not directly exposed. This difference was statistically significant (p<0.001). Bacteriological examination of water showed a high coliform count.

Conclusion

The outbreak of viral hepatitis E occurred due to sewage contamination of water pipelines.Key Words: Hepatitis E, Outbreak