Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,2,4-trisubstituted-5-imidazolones.

Nine 1-(3,4-dimethoxyphenylethyl)-2-methyl-4-(substituted benzylidene)-5-imidazolones were synthesized, characterized by their sharp melting points, elemental analyses and infrared spectra and evaluated for anticonvulsant activity. All 1,2,4-trisubstituted-5-imidazolones at a dose of 100 mg/kg i.p. possessed anticonvulsant activity and the degree of protection observed against pentylenetetrazol-induced convulsions in mice ranged from 20 to 60%. These 1,2,4-trisubstituted-5-imidazolones selectively inhibited in vitro oxidation of the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate and NADH by rat brain homogenates while the NAD-independent oxidation of succinate remained unaltered. The anti-convulsant activity possessed by 1,2,4-trisubstituted-5-imidazolones was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates.     

Prostaglandin D2-induced potentiation of hexobarbitone hypnosis in rats: role of 5-hydroxytryptamine

Prostaglandin D2 (PGD2) produced a dose-related increase in the duration and incidence of induction of sleep induced by hexobarbitone, in rats. Pretreatment with pharmacological agents known to reduce selectively brain 5-hydroxytryptaminergic activity, significantly inhibited PGD2-induced potentiation of hexobarbitone, indicating that this potentiation is mediated by 5-hydroxytryptamine.     

Submucous lipoma of the ileocaecal valve presenting as caecal volvulus

Caecal volvulus is a well described but unusual condition. We report here, a case of caecal volvulus in a 53-year-old Caucasian woman associated with intussuscepted submucous lipoma of the ileocaecal region. The imaging and pathology are presented. Submucous lipoma of the ileocaecal region is uncommon but well described. It can be mistaken as carcinoma of the ascending colon on barium enema and on computed tomography scan. The combination with caecal volvulus is a rare occurrence.     

MR imaging features of pigmented villonodular synovitis of the cervical spine

Pigmented villonodular synovitis (PVNS) is a benign proliferative disorder primarily occurring in the large joints of the appendicular skeleton such as the knee and hip joints. We present an unusual case of PVNS involving the cervical spine in an adult. MR imaging showed an enhancing mass lesion arising from the posterior elements of the cervical spine and hyperintensity on the T2-weighted images, without evidence of T2 susceptibility effects. Gross total excision of the tumor was performed, and the diagnosis was established by histopathology.     

Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.     

Environmental exposure and leptospirosis, Peru

Human infection by leptospires has highly variable clinical manifestations, which range from subclinical infection to fulminant disease. We conducted a population-based, cross-sectional seroepidemiologic study in Peru to determine potential relationships of environmental context to human exposure to Leptospira and disease associated with seroconversion. Three areas were studied: a flooded, urban slum in the Peruvian Amazon city of Iquitos; rural, peri-Iquitos villages; and a desert shantytown near Lima. Seroprevalence in Belen was 28% (182/650); in rural areas, 17% (52/316); and in a desert shantytown, 0.7% (1/150). Leptospira-infected peridomestic rats were found in all locales. In Belen, 20 (12.4%) of 161 patients seroconverted between dry and wet seasons (an incidence rate of 288/1,000). Seroconversion was associated with history of febrile illness; severe leptospirosis was not seen. Human exposure to Leptospira in the Iquitos region is high, likely related both to the ubiquity of leptospires in the environment and human behavior conducive to transmission from infected zoonotic sources.     

Effects of NMDA glutamate receptor antagonist drugs on the volitional consumption of ethanol by a genetic drinking rat

The ability of drugs that reduce NMDA receptor activity on the volitional consumption of ethanol in the genetic drinking rat, mHEP line, was investigated. After the consumption of ethanol solutions and water by each male or female mHEP rat had stabilized on its preferred concentration, different doses of LY 274614, a competitive NMDA antagonist, MK 801, a non-competitive NMDA antagonist, (+)-HA-966 or ACPC (1-aminocyclopropane-1-carboxylic acid), antagonists of the glycine site were administered daily for three days. The dose of 3.0 mg/kg i.p. LY 274614 reduced the consumption of ethanol by 64% compared to the pre-treatment baseline, while 0.3 mg/kg of MK 801 reduced consumption by 44%, 20 mg/kg (+)-HA-966 reduced consumption by 47% and 300 mg/kg of ACPC reduced consumption by 30%. These doses of LY 274614 and MK 801 reduced the ability of Sprague-Dawley rats to walk on a rotorod. Effects of these drugs on food intake were small except for the 20 mg/kg dose of (+)-HA-966. Therefore, the drugs did not have an anti-caloric effect and manipulations of the glutamatergic system through NMDA receptors may modify the consumption of ethanol. This interaction should be explored further for its therapeutic potential and to better understand the control by central neuronal systems of the consumption of ethanol.