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Biomedical subjects

A Venter

Publications and source records attributed to A Venter.

At least 37 records · Page 2Linked to original sources

Early bactericidal activity of amoxicillin in combination with clavulanic acid in patients with sputum smear-positive pulmonary tuberculosis.

The early bactericidal activity (EBA) of an antituberculosis agent is the rate of decrease in viable colony-forming units (CFU) per milliliter of sputum during the first 2 d of treatment of patients with previously untreated smear-positive pulmonary tuberculosis. The objective of this open randomized study was to evaluate the EBA of the combination of amoxicillin 3 g and clavulanic acid 750 mg. Ten patients with a mean age of 34 y and a mean weight of 56 kg received amoxicillin/clavulanic acid and 5 patients with a mean age of 34 y and a mean weight of 57 kg received no drug. In the patients receiving 1 dose of amoxicillin/clavulanic acid daily for 2 d the mean log10CFU/ml of sputum before treatment was 6.7402 (SD 0.539) and after 2 d of treatment 6.7046 (SD 0.609); the corresponding values in patients receiving no drug were 6.7823 (SD 0.563) and 6.7502 (SD 0.673), respectively. The EBA of 0.018 (SD 0.130) in patients receiving amoxicillin/clavulanic acid did not differ significantly from that of 0.016 (SD 0.069) in patients receiving no drug. It is unlikely that the combination of amoxicillin/clavulanic acid has an important place in the treatment of tuberculosis with the exception of those patients with multidrug-resistant tuberculosis who are otherwise therapeutically destitute.

Adult↗

Sources of variation in studies of the early bactericidal activity of antituberculosis drugs.

The early bactericidal activity (EBA) of antituberculosis drugs can be measured as the daily fall in cfu counts of Mycobacterium tuberculosis in sputum, usually during the first 2 days of treatment. In studies of low potency drugs, it is necessary to compare the treated group of patients with a group who receives no chemotherapy (Nil group). Over the past 10 years, five Nil groups of between five and 13 patients have been studied in Cape Town and two Nil groups in Hong Kong. There was a suggestion of an increase in variation within the Cape Town groups, as shown by a regression of variance size against study date (P = 0.06), which could not be attributed to technical causes. It might indicate increasing host resistance in the Western Cape epidemic of tuberculosis. Since the weighted mean of all Nil groups at Cape Town was 0.00036, very close to zero, it would seem safe to test means of treated groups against zero thus increasing precision and avoiding ethical problems in delaying treatment. In contrast to Nil groups, the variation found in five groups who received 300 mg isoniazid daily (INH 300) was uniform and homoscedastic, possibly because the additional variation was caused mainly by individual differences in plasma isoniazid concentrations and patient body weights. The mean EBA in the INH 300 series was 0.575 with 95% confidence limits of 0.515 and 0.636.

Anti-Infective Agents↗

The early bactericidal activity of a low-clearance liposomal amikacin in pulmonary tuberculosis.

The early bactericidal activity (EBA) of a liposomal preparation of amikacin (MiKasome) with a long plasma half-life of 120-200 h was examined in seven patients with newly diagnosed, smear-positive pulmonary tuberculosis. Liposomal amikacin was given in slow iv infusions of 30 mg total amikacin/kg body weight on three successive days. Cfu counts were set up on 16 h sputum collections preceding the first dose and following each dose and were used for calculating the EBA. Despite the high concentrations of total amikacin, >1000 mg/L, obtainable in plasma, no evidence of EBA was obtained. In view of the considerable activity of liposomal amikacin in experimental murine tuberculosis, this finding indicates that liberation of amikacin from the long-life liposomes occurs only in macrophages that are not usually present in the vicinity of the large extracellular clumps of bacilli in the cavity caseum.

Adult↗

AIDS in China.

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Adult↗

The early bactericidal activity of amikacin in pulmonary tuberculosis.

SETTING: Stellenbosch University, a tertiary care hospital in Cape Town, South Africa. OBJECTIVE: To determine the early bactericidal activity (EBA) of amikacin in dosages of 5 mg/kg, 10 mg/kg and 15 mg/kg body weight in comparison to that of isoniazid 6 mg/kg body weight or no drug. DESIGN: An open, randomised trial. PATIENTS: Patients with previously untreated, sputum smear-positive pulmonary tuberculosis. INTERVENTION: Patients received amikacin 5 mg/kg (12 patients), 10 mg/kg (13 patients) or 15 mg/kg (15 patients), isoniazid 6 mg/kg (9 patients) or no drug (10 patients). RESULTS: The rate of decrease in log viable colony forming units of Mycobacterium tuberculosis per ml of sputum per day during the first 2 days of treatment with amikacin 5 mg/kg, 10 mg/kg and 15 mg/kg was 0.041 (SD 0.100), 0.045 (SD 0.144) and 0.052 (SD 0.096), respectively, 0.515 (SD 0.173) in the patients receiving isoniazid 6 mg/kg, and 0.041 (SD 0.113) in those receiving no drug. The EBA found in patients receiving amikacin did not differ significantly from that of the no drug group. However, as the EBA in the no drug group was the highest ever encountered at Stellenbosch University, the mean in patients receiving drug was tested against 0 and found to differ significantly (P = 0.03), suggesting minimal activity. Mean amikacin serum concentrations 1 hour after intramuscular drug administration were 13.5 microg/ml, 26.7 microg/ml and 39.2 microg/ml in the patients receiving 5 mg, 10 mg and 15 mg per kg body weight, respectively. CONCLUSION: Despite serum concentrations well in excess of the minimal inhibitory concentration of 2-4 microg/ml, the EBA of amikacin in patients with smear-positive pulmonary tuberculosis was only just detectable.

Adolescent↗

Early bactericidal activity of paromomycin (aminosidine) in patients with smear-positive pulmonary tuberculosis.

The early bactericidal activity of the aminoglycoside paromomycin (aminosidine) in doses of 7.5 and 15 mg/kg of body weight was measured in 22 patients with previously untreated smear-positive pulmonary tuberculosis. The fall in log(10) CFU per milliliter of sputum per day during the first 2 days of treatment for 7 patients receiving a paromomycin dosage of 7.5 mg/kg/day was 0.066, with a standard deviation (SD) of 0.216 and confidence limits from -0.134 to 0.266, and that for 15 patients receiving 15 mg/kg/day was 0.0924, with an SD of 0.140 and confidence limits from 0.015 to 0.170. The difference between the mean and zero was not significant for the 7. 5-mg/kg dose group but was significant for the 15-mg/kg dose group (t = 2.55, P = 0.023). Since paromomycin has no cross-resistance with streptomycin and has no greater toxicity than other aminoglycosides, these results suggest that it has the potential to substitute for streptomycin in antituberculosis regimens and may be a particularly valuable addition to the drug armamentarium for the management of multidrug-resistant tuberculosis.

Adolescent↗

Epilepsy in rural South African children--prevalence, associated disability and management.

OBJECTIVE: To determine the prevalence of epilepsy and its associated disabilities in rural South African children aged 2-9 years. SETTING: Eight villages in the district of Bushbuckridge, Northern Province, South Africa. DESIGN: A two-phase design was used. The first phase involved screening children on a house-to-house basis by interviewing mothers or caregivers using an internationally validated questionnaire for detecting childhood disability in developing countries. The second phase consisted of a paediatric/neurodevelopmental assessment of the children who screened positive. RESULTS: A total of 6,692 children were screened; 722 (10.8%) had a paediatric evaluation and 49 (0.73%) had epilepsy. The lifetime and active prevalences of epilepsy in these children were 7.3/1,000 and 6.7/1,000 respectively. Associated developmental disability was recorded in 35 affected children (71.4%), including 8 (16.3%) in whom this was moderate to severe. More than a half of the children with epilepsy (57.1%) did not receive anticonvulsant medication. CONCLUSION: The prevalence of epilepsy in the rural childhood population investigated is higher than that recorded in most similar studies from sub-Saharan Africa, and the poor utilisation of appropriate anticonvulsant treatment is cause for concern. This study highlights the paucity of relevant information on the epidemiology of epilepsy in South Africa and that the system available for its management, especially in rural areas, appears to have functional deficiencies. Appropriate research is needed to identify the problems in service delivery and to enable the planning and implementation of an appropriate primary health care-based system for the diagnosis and management of epilepsy in children.

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Effect of temperature on permeability of mucosa to water.

In previous studies it has been demonstrated that frozen human vaginal mucosa can be used as a model of buccal mucosa for in vitro permeability studies on a variety of chemical compounds, including drugs. However, most of the latter studies have, for the sake of convenience, been conducted at room temperature (+/- 20 degrees C). The objective of the present study was to determine the effects of increased temperature on steady state flux rates of water through vaginal mucosa. Specimens of clinically healthy human vaginal mucosa were obtained from excess tissue removed during a vaginal hysterectomy from a single patient, snap-frozen in liquid nitrogen at -85 degrees C and banked for 8 months. After thawing in PBS buffer, seven sections from the vaginal mucosa were mounted in flow-through diffusion cells (exposed area 0.039 cm2) and their permeability to tritiated water determined using a continuous flow-through perfusion system at temperatures of 25 degrees, 30 degrees and 37 degrees C. Permeability experiments were performed in triplicate at each temperature setting. Specimens were examined histologically before and after permeability experiments. Mean water flux rates at steady state (16-24 h) were found to be 1760 +/- 22 SEM, 2623 +/- 63 SEM and 4155 +/- 70 SEM cpm. cm-2.min-1, at temperatures of 25 degrees, 30 degrees and 37 degrees C, respectively. A linear regression analysis and plot (r2 = 0.99) displayed a slope of 200 +/- 13 SEM cpm. cm-2.min-1/degree C. The results of this study clearly demonstrated the temperature-dependency of flux rates of water across vaginal mucosa, and this should be taken into account whenever the in vitro vaginal/buccal model is used at room temperature for predicting in vivo buccal drug absorption kinetics.

Analysis of Variance↗

Genome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis.

Mycobacterium tuberculosis strains resistant to two or more of the first line antituberculosis drugs (MDR) are a serious threat to successful tuberculosis control programmes. For this retrospective study, 85 follow-up drug resistant isolates from 23 patients residing in a community with a high incidence of tuberculosis were collected and the level of in-vitro resistance to antibiotics determined quantitatively. PCR-SSCP and sequencing techniques were used to screen for gene mutations associated with resistance in 31 follow-up samples from a smaller group of eight patients. DNA fingerprint analysis was done on sequential isolates to confirm identity. Although treatment had a profound effect on changes in drug resistance patterns, the MIC for a particular agent remained constant in follow-up isolates. DNA fingerprinting and mutational analysis (14 different loci) showed that the genome of MDR strains of M. tuberculosis is relatively stable during the course of therapy. The rpoB gene was the most frequently mutated structural gene involved in drug resistance and a novel C to T mutation upstream of open reading frame (ORF)1 of the inhA operon was detected. No evidence was found of the presence of strain W (New York) in this group of MDR strains. The results stress the importance of confirming individuality of strains for the accurate calculation of frequencies of particular mutations associated with drug resistance, particularly in a high incidence area. Approximately one-half (47.8%) of the patients had isolates resistant to concentrations just above the critical concentration for isoniazid (MICs of 0.2-5 mg/L). Therefore, these patients and their contacts who develop primary drug-resistant tuberculosis may respond to higher dosages of treatment which could have a considerable impact on the cost and the ease of management of resistant tuberculosis.

Antitubercular Agents↗

Caregivers' expectations of services at Baragwanath Hospital, Soweto and their understanding of the child's disability.

Sixty-one caregivers were interviewed before and after their first visit with the child in their care to specialist neurodevelopmental outpatient clinics at Baragwanath Hospital, Soweto. The interview focused on their understanding of the child's disability and their expectations of the service offered at the clinics. Before consultation the majority of caregivers had a fair understanding of the child's functional problems and the short-term complications, but after the consultation levels of understanding decreased significantly. Caregivers left the consultation with a significantly improved understanding of the aetiology of the problem. Understanding of long-term complications did not differ significantly before and after the consultation. These findings may reflect the consultative process, as professionals may be more comfortable discussing aetiology than long-term complications. Caregivers in a state of shock may be unable to absorb all the information given, and translation during consultation may also be a confounding factor. Even though more than half the caregivers had no idea what services the clinics offered prior to the consultation, the majority (81%) indicated they were satisfied with the service after the consultation.

Adult↗