Early bactericidal activity of antituberculosis agents

The assessment of the early bactericidal activity (EBA) of antituberculosis agents by measurement of viable colony-forming units (CFU) of Mycobacterium tuberculosis in sputum of patients with smear-positive pulmonary tuberculosis is now an established methodology for the early clinical evaluation of a new antituberculosis agent. EBA establishes the daily rate at which a specific dose of a new agent reduces the number of viable bacilli present in sputum during the first 14 days of treatment. Simultaneous study of pharmacokinetics offers the opportunity to evaluate the relationship between dosage, serum concentration, efficacy and specific host or mycobacterial factors relevant to the agent under investigation. Recently the clinical efficacy of several new classes of antituberculosis agents has been confirmed by EBA studies, and these have shown these agents to have a relatively slow onset of detectable activity; by contrast, the newer fluoroquinolones have an EBA over days 0-2 comparable to that of isoniazid and may prove valuable in the prevention of resistance amongst companion drugs. Recent experience has shown that time to detection of metabolic activity in liquid media reflects drug activity in a manner comparable to that of CFU counting and needs further exploration. Copyright © 2011 S. Karger AG, Basel.Revie

Pyrazinamide pharmacokinetics and efficacy in adults and children

Pyrazinamide (PZA) is an essential sterilizing drug and with rifampicin enables six-month short-course antituberculosis chemotherapy. Despite routine use for nearly forty years uncertainty remains regarding the most appropriate PZA dosage for children. In view of this uncertainty literature relating to the efficacy and pharmacokinetics of PZA in children treated for tuberculosis and in adult volunteers and patients was reviewed. Making use of the PZA maximum concentration (Cmax) following various PZA dosages in different groups straight line regression of concentration on dosage was fitted through the origin by least squares and weighted for the numbers of subjects. The fitted line offers an approximation of the likely PZA Cmax that would result from a particular dosage. The slopes of Cmax/dosage of the fitted lines are 1.32 (SE 0.099) for paediatric patients, 1.36 (SE 0.051) for adult volunteers and 1.35 (SE 0.037) for adult patients; there is little difference between the Cmax concentrations achieved in children and adults, whether patients or healthy volunteers, following various mg/kg body weight dosages, suggesting that children and adults receiving the same mg/kg body weight PZA dosage will reach a similar Cmax. Children can receive the same mg/kg body weight PZA dosage as adults. © 2011 Elsevier Ltd. All rights reserved.Article in Pres

The pharmacokinetics and pharmacodynamics of rifampicin in adults and children in relation to the dosage recommended for children

The dosages of antituberculosis agents recommended for treatment of childhood tuberculosis often reflect those for adult patients with similar mg/kg body weight dosages and ranges advised. Literature relating to the pharmacokinetics and pharmacodynamics of rifampicin (RMP) is reviewed and the serum concentrations reached by adults, both patients and healthy volunteers and children, established or not established on RMP, compared. Straight line regression of maximum RMP serum concentrations (Cmax) on dosage, weighted for the number of individuals, found slopes (SE) of 1.025 (0.067) and 0.881 (0.046) respectively for adult volunteers not established and established on RMP (P = 0.076), and similarly 0.748 (0.057) and 0.684 (0.038) respectively for adult patients (P < 0.001) and 0.622 (0.050) and 0.368 (0.041) respectively for children (P < 0.001). These results indicate that for equivalent RMP dosages adult patients reach a lower Cmax than adult volunteers and that adults, both volunteers and patients established on RMP reach higher Cmax values than children; children established on RMP require approximately twice the mg/kg body weight dosage of RMP to reach serum concentrations equivalent to those of adults. It is noteworthy that many adult patients receiving currently recommended RMP dosages also do not reach the often recommended RMP 2 h serum concentration of 8 μg/mL. © 2011 Elsevier Ltd. All rights reserved.Article in Pres

Effect of tramadol on depth of anaesthesia

We have studied 51 patients who were anaesthetized with propofol and suxamethonium followed by 0.7% isoflurane and 66% nitrous oxide in oxygen to see if tramadol caused lightening of anaesthesia. A two-channel EEG was recorded and music was played via headphones. Two groups received tramadol 200 and 100 mg i.v. and the third group received saline. Tramadol caused significant, dose-dependent activation of the EEG, evidenced by increased frequencies and decreased amplitudes, but these changes were small and probably unimportant. Derived EEG variables did not approach values known to be associated with near-awakening during isoflurane anaesthesia. No patient moved on skin incision and there were no incidences of free recall.Articl

Ethambutol dosage for the treatment of children: Literature review and recommendations

The currently recommended daily dose of ethambutol (EMB) for the treatment of tuberculosis (TB) in children varies from a maximum daily dose of 15 mg/kg body weight daily (without a range) to 15-20 mg/kg and 20 mg/kg (range 15-25 mg/kg). Published evidence relating to the dosage, toxicity and pharmacokinetics of EMB in children and adults is reviewed and a dose of EMB for use in childhood is recommended. Using key words 'ethambutol', 'childhood', 'TB', 'pharmacokinetics', 'bioavailability' and 'toxicity', Medline searches were conducted; cross-references were sought from original papers, books and conference proceedings dating from 1961. When English summaries were available, data were extracted from papers in languages other than English. EMB has a dose-related efficacy best seen when given to adults alone or with a single other drug. Together with isoniazid (INH), a dose of 15 mg/kg EMB gave better results than 6 mg/kg, and 25 mg/kg better than 15 mg/kg. The occurrence of ocular toxicity was also dose-related; >40% of adults developed toxicity at doses of >50 mg/kg, and 0-3% at a dose of 15 mg/kg/daily. Peak serum EMB concentrations increase in relation to dose, but are significantly lower in children receiving the same dosage. In only 2 of 3811 children (0.05%) receiving EMB doses of 15-30 mg/kg was EMB stopped due to possible ocular toxicity; children of all ages can be given EMB in daily doses of 20 mg/kg (range 15-25 mg/kg) and three times weekly intermittent doses of 30 mg/kg body weight without undue concern. © 2006 The Union.Revie

Facial profile changes with various orthodontic premolar extraction sequences during growth.

http://www.scopus.com/inward/record.url?eid=2-s2.0-4043052406&partnerID=40&md5=e9ac4d1678f763e2ac0bd50d7158fdb

Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol

Background: Previous studies suggest that the risk of tardive dyskinesia is increased with higher doses of conventional antipsychotics. This study evaluates the 12-month incidence of tardive dyskinesia in subjects with first-episode psychosis who were treated with very low doses of haloperidol. Method: Fifty-seven subjects with first-episode psychosis and a DSM-IV diagnosis of schizophreniform disorder, schizophrenia, or schizoaffective disorder were treated according to a fixed protocol with a mean dose of haloperidol of 1.68 mg/day and prospectively studied for 12 months. Subjects were assessed for extrapyramidal symptoms and psychiatric symptoms at 3-month intervals. Data were gathered from 1999 to 2001. Results: Twelve-month incidence of probable or persistent tardive dyskinesia according to Schooler and Kane criteria was 12.3% (N = 7). Subjects with tardive dyskinesia did not differ from the rest of the sample regarding gender, race, duration of untreated psychosis, or baseline clinical characteristics. Subjects with tardive dyskinesia were older compared with subjects without tardive dyskinesia (37.14 ± 9.23 vs. 27.30 ± 8.09 years, respectively; t = -2.77, df = 30, p = .01) and received higher mean doses of haloperidol at 12 months (2.80 ± 1.64 vs. 1.39 ± 0.69 mg/day, respectively; t = -3.13, df = 25, p = .004). Cox regression analysis revealed that age at inclusion (p = .031), percentage change in negative symptoms (p = .028), and dose of haloperidol at 12 months (p = .016) were significant predictors of risk for tardive dyskinesia. Conclusion: Incidence of tardive dyskinesia was at least as high as in other samples treated with standard doses of conventional antipsychotics. Subjects at risk for tardive dyskinesia could not be identified on the basis of initial clinical features or acute treatment response. Risk of tardive dyskinesia was related to age, antipsychotic dose, and worsening of negative, depressive, and parkinsonian symptoms.Articl

Validation of psychometric scales for malingering in a student sample

Objective. To determine South African cut scores for established tests of malingering. Design. A prospective study with an experimental group of subjects that was instructed to feign illness and a control group instructed to perform optimally on a set of psychometric tests. Setting. The study was conducted at the Medical School and main campus of the University of Stellenbosch. Subjects. Seventy-six under- and postgraduate university students. Outcome measures. Each subject completed the Dot-Counting Test (DCT), the Rey 15-item Test (Rey 15-item), the 21-item verbal memory Forced Choice Test (FCT), and the Structured Inventory of Malingered Symptomatology (SIMS). Results. The DCT correctly identified 94% of the feigners by the combined (grouped and ungrouped dots) time score, using a cut-off time of ≤ 63.5 seconds. The Rey 15-item was less specific than the other tests and only the number-of-rows-correct score produced significant results with a correct classification of 88%. A cut score of ≤ 15 for the FCT correctly classified 94% of the malingerers and 100% of the subjects who were asked to perform optimally. The SIMS correctly classified 97% of subjects when a cut score of ≤ 20 was used. Conclusions. The most effective discriminators were the total time to complete the DCT, recognition memory on the 21-item FCT, and the SIMS total score. The results of this study should assist clinicians in South Africa in improving the diagnosis of malingering.Articl