Congenital Becker''s nevus with a familial association

Coprecipitates were prepared using different ratios of flutamide with polyvinyl pyrrolidine (PVP), polyethylene glycol (PEG) 4000 and 6000. Drug solubility in carrier solutions, thin layer chromatography (TLC), differential scanning calorimetry (DSC), infra-red spectroscopy (IR), uniformity of drug content, drug dissolution from its respective systems and effect of aging on the physico-chemical parameters of stored flutamide-polymer system were studied. PEG 6000 was found to be the most efficient polymer in increasing both the solubility and the release rate of flutamide. Interaction was found to be complete in certain ratios of drug/polymer systems. The dissolution pattern of flutamide from all the prepared systems appeared to fit a first order mechanism. Physico-chemical parameters of flutamide/carrier systems were not influenced by storage.     

Rat parvovirus type 1: the prototype for a new rodent parvovirus serogroup

A newly recognized parvovirus of laboratory rats, designated rat parvovirus type 1a (RPV-1a), was found to be antigenically distinct. It was cloned, sequenced, and compared with the University of Massachusetts strain of rat virus (RV-UMass) and other autonomous parvoviruses. RPV-1a VP1 identity with these viruses never exceeded 69%, thus explaining its antigenic divergence. In addition, RPV-1a had reduced amino acid identity in NS coding regions (82%), reflecting phylogenetic divergence from other rodent parvoviruses. RPV-1a infection in rats had a predilection for endothelium and lymphoid tissues as previously reported for RV. Infectious RPV-1a was isolated 3 weeks after inoculation of infant rats, suggesting that it, like RV, may result in persistent infection. In contrast to RV, RPV-1a was enterotropic, a characteristic previously associated with parvovirus infections of mice rather than rats. RPV-1a also differed from RV in that infection was nonpathogenic for infant rats under conditions where RV infection causes high morbidity and mortality. Thus, RPV-1a is the prototype virus of an antigenically, genetically, and biologically distinct rodent parvovirus serogroup.     

Assessment of the dysexecutive syndrome in schizophrenia

BACKGROUND: Cognitive neuropsychological theories hypothesize a role for frontal lobe executive deficits in the aetiology of schizophrenic symptoms. The study examined the performance of a schizophrenic group on the Behavioural Assessment of the Dysexecutive Syndrome (BADS; Wilson et al. 1996), a test battery which assesses the 'everyday' difficulties associated with the dysexecutive syndrome. Performance of the schizophrenics was contrasted with that of brain injured and healthy volunteer groups. METHODS: Matched groups of 31 schizophrenic patients, 35 patients with brain injuries and 26 healthy volunteers were administered the BADS. Patients were also given tests of general intelligence and memory. Patients and their relatives/carers also completed a questionnaire rating day-to-day failures of executive functioning. RESULTS: Schizophrenic and brain-injured patients showed impairment on the BADS, compared to healthy controls. There were no significant differences between the two patient groups. Significant impairment was found in a subgroup of 16 schizophrenics who showed otherwise intact general intellectual functioning, suggesting the existence of a specific executive deficit. Among the schizophrenic patient group there was evidence of a dissociation between executive and memory impairments. A significant correlation existed between performance on the BADS and relatives ratings of executive problems for the brain injured group, but not for the schizophrenic group. CONCLUSIONS: The BADS is a useful tool for identifying executive deficits in people with a diagnosis of schizophrenia, especially those who are otherwise generally intellectually intact. This is particularly important in the context of rehabilitation and community transition programmes.     

Comparison of methods to assess coronary heart disease prevalence in South Asians

BACKGROUND: Migrants from the Indian subcontinent (South Asian migrants) in the United Kingdom have high mortality from coronary heart disease (CHD) in comparison to the indigenous population. Few studies have assessed the prevalence of CHD in South Asians, and the applicability of conventional survey methods in this population is not known. In this pilot random population survey of South Asian men and women living in West London, the prevalence of CHD as judged by the Rose questionnaire, past cardiac history, cardiologist and resting electrocardiogram were compared. METHODS: Subjects aged 30-64 years from randomly selected households were invited for a cardiological assessment. A lay person administered the Rose questionnaire and recorded the past cardiac history. A cardiologist also made an independent assessment and a 12-lead electrocardiogram was recorded and analysed according to the Minnesota code. RESULTS: Three hundred and seventy-six individuals (192 men and 184 women) were assessed. The prevalence of angina in men and women, respectively, was 3.1% and 4.9% by the Rose questionnaire; 2.6% and 2.2% by past cardiac history; and 4.2% and 0.5% according to the cardiologist. The prevalence of myocardial infarction in men and women, respectively, was 5.2% and 2.2% by the Rose questionnaire, 3.6% and zero by past cardiac history and 3.6% and 0.5% by the cardiologist. Q/QS codes were present in 1.6% men and 0.5% women and ischaemic codes in 13% men and 14% women. Ischaemic changes were not associated with any cardiac history in 72% of men and 92% of women. For a diagnosis of CHD in men, there was poor agreement between the Rose questionnaire and either the past cardiac history or the cardiologist's assessment, but moderate agreement between the past cardiac history and the cardiologist. Agreement was poor between all three methods for a positive diagnosis of CHD in women. CONCLUSION: Current accepted epidemiological methods for assessing CHD prevalence may be inaccurate in South Asians, especially women. Electrocardiogram abnormalities suggestive of ischaemia are common in South Asians and are usually not associated with evidence of CHD. Thus, their value as indicators of CHD is questionable.     

Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients

BACKGROUND: A sustained-release formulation of bupropion (bupropion SR), developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form, has not been evaluated in active comparator trials. This randomized, double-blind, parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline. METHOD: Outpatients with moderate to severe major depressive disorder (DSM-IV) received bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Clinical Global Impressions scale for Severity of Illness (CGI-S), and for Improvement (CGI-I) were completed, and adverse events were assessed in the clinic periodically throughout treatment. Patients' orgasm function was also assessed. RESULTS: Mean HAM-D, HAM-A, CGI-I, and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group; no between-group differences were observed on any of the scales. Orgasm dysfunction was significantly (p < .001) more common in sertraline-treated patients compared with bupropion SR-treated patients. The adverse events of nausea, diarrhea, somnolence, and sweating were also experienced more frequently (p < .05) in sertraline-treated patients. No differences were noted between the two treatments for vital signs and weight. CONCLUSION: This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression. Both compounds were relatively well tolerated, and orgasm dysfunction, nausea, diarrhea, somnolence, and sweating were reported more frequently in sertraline-treated patients.     

Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain

Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant agents that selectively interact with the alpha2delta subunit of voltage-dependent calcium channels. This report describes the activities of these two compounds in a rat model of postoperative pain. An incision of the plantaris muscle of a hind paw induced thermal hyperalgesia and tactile allodynia lasting at least 3 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia and von Frey hairs for tactile allodynia. A single s.c. dose of gabapentin, 1 h before surgery, dose-dependently (3-30 mg/kg) blocked the development of allodynia and hyperalgesia with a minimum effective dose (MED) of 10 and 30 mg/kg, respectively. The highest dose of gabapentin prevented development of hyperalgesia and allodynia for 24 and 49 h, respectively. Similar administration of S-(+)-3-isobutylgaba also dose-dependently (3-30 mg/kg, s.c.) prevented development of hyperalgesia and allodynia with MED of 3 and 10 mg/kg, respectively. The highest dose of S-(+)-3-isobutylgaba completely blocked development of both nociceptive responses for 3 days. The administration of S-(+)-3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery also completely blocked the maintenance of hyperalgesia and allodynia, but its duration of action was much shorter (3 h). The administration of morphine (1-6 mg/kg s.c.) 0.5 h before surgery prevented the development of thermal hyperalgesia with a MED of 1 mg/kg. However, unlike gabapentin and S-(+)-3-isobutylgaba, it had little effect on the development of tactile allodynia. It is suggested that gabapentin and S-(+)-3-isobutylgaba may be effective in the treatment of postoperative pain.     

Biochemistry and pharmacokinetics of potent non-steroidal cytochrome P450(17alpha) inhibitors

Two potent non-steroidal inhibitors (CB7645 and CB7661) of human cytochrome P450(17alpha) were tested for in vivo activity in WHT mice. There were no signs of toxicity, but there was no effect on the androgen-dependent organs. The pharmacokinetics and biochemistry of the compounds in mice were investigated. Following i.p. administration of 0.5 mmol/kg of CB7645 and CB7661, peak plasma levels of 13.4 and 3.4 microM, respectively, occurred after 2-4 h, both compounds were cleared rapidly (terminal half-lives 2.7 and 3.3 h, respectively) and neither was detectable at 24 h. CB7645 produced some decrease in plasma testosterone at 4 h, but this was not sustained. When tested in vitro against the WHT testicular enzyme, the CB7645 and CB7661 were competitive inhibitors with K(i) values of 10 and 13 nM, respectively. However, the K(m) for the substrate progesterone was lower at 4.3 nM. These data indicate that, for effective and continuous inhibition of the murine cytochrome P450(17alpha) enzyme, higher peak levels of the compounds would be required, and these levels would need to be maintained throughout the treatment period.     

Unilateral asymptomatic carotid disease does not require surgery

If a stimulus (e.g. tone or light) is repeatedly pre-exposed without consequences, it subsequently shows retarded conditioning when paired with a reinforcer (e.g. footshock) compared with a non-pre-exposed stimulus. This is latent inhibition (LI). Haloperidol-treated animals show potentiated LI, and it has been suggested that this is due to retarded switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that the slowed control of behaviour by the stimulus-reinforcement contingency is due to a haloperidol-induced decrease in the impact, or salience, of the reinforcer, and thus should be antagonized by increasing the impact of reinforcement. Two experiments tested this prediction. In both, LI was assessed using an off-baseline conditioned emotional response procedure in rats licking for water. In Experiment 1, rats were given 10 light pre-exposures and conditioned with two footshocks of either a low (0.5 mA) or a high (1 mA) intensity. In Experiment 2, rats were given 30 pre-exposures and conditioned with either two or five footshocks of 1 mA. In Experiment 1, no-drug controls did not show LI at both shock intensities. Haloperidol (0.1 mg/kg) was ineffective in potentiating LI at low-intensity shock, but produced LI when shock level was increased. In Experiment 2, no-drug controls showed LI with two but not five conditioning trials. Haloperidol was ineffective in potentiating LI with two conditioning trials, but produced LI with five conditioning trials. Although the effect of haloperidol on LI could thus be modified by manipulating shock intensity or the number of conditioning trials, the direction of such modification indicates that the potentiating effect of haloperidol on LI is not in general antagonized by increasing the impact of reinforcement.