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Biomedical subjects

J S Maritz

Publications and source records attributed to J S Maritz.

At least 19 recordsLinked to original sources

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.

Adult↗

Monitoring the ingestion of anti-tuberculosis drugs by simple non-invasive methods.

This investigation retrospectively assessed inexpensive non-invasive qualitative methods to monitor the ingestion of anti-tuberculosis drugs isoniazid, rifampicin and rifapentine. Results showed that commercial test strips detected the isoniazid metabolites isonicotinic acid and isonicotinylglycine as efficiently as the isonicotinic acid method in 150 urine samples. The presence of rifamycins in urine samples (n=1085) was detected by microbiological assay techniques and the sensitivity compared to the n-butanol extraction colour test in 91 of these specimens. The proportions detected by the two methods were significantly different and the sensitivity of the n-butanol procedure was only 63.8% (95% CL 51.2-76.4%) as compared to that of the superior microbiological method. Final validation (n=691) showed that qualitative assays measure isoniazid and rifamycin ingestion with an efficiency similar to high-performance liquid chromatography. The qualitative procedures may therefore be valuable in clinical trials and in tuberculosis clinics to confirm drug ingestion.

Antitubercular Agents↗

Isoniazid pharmacokinetics in children treated for respiratory tuberculosis.

AIMS: To define the pharmacokinetics of isoniazid (INH) in children with tuberculosis in relation to the N-acetyltransferase 2 (NAT2) genotype. METHODS: The first order elimination rate constant (k) and area under the concentration curve (AUC) were calculated in 64 children <13 years of age (median 3.8) with respiratory tuberculosis from INH concentrations determined 2-5 hours after a 10 mg/kg INH dose. The NAT2 genotype was determined; 25 children were classified as homozygous slow (SS), 24 as heterozygous fast (FS), and 15 as homozygous fast (FF) acetylators. RESULTS: The mean (SD) k values of the genotypes differed significantly from one another: SS 0.254 (0.046), FS 0.513 (0.074), FF 0.653 (0.117). Within each genotype a median regression of k on age showed a significant decrease in k with age. The mean (SD) INH concentrations (mg/l) two hours after INH administration were SS 8.599 (1.974), FS 5.131 (1.864), and FF 3.938 (1.754). A within genotype regression of 2-hour INH concentrations on age showed a significant increase with age. A within genotype regression of 3-hour, 4-hour, and 5-hour concentrations on age also showed a significant increase with age in each instance. In ethnically similar adults, mean (SD) 2-hour INH concentrations (mg/l) for each genotype were significantly higher than the children's: SS 10.942 (1.740), FS 8.702 (1.841), and FF 6.031 (1.431). CONCLUSIONS: Younger children eliminate INH faster than older children and, as a group, faster than adults, and require a higher mg/kg body weight INH dose to achieve serum concentrations comparable to adults.

Adolescent↗

The influence of human N-acetyltransferase genotype on the early bactericidal activity of isoniazid.

The elimination of isoniazid is subject to the influence of the N-acetyltransferase 2 (NAT2) genotype, and individuals may be homozygotic slow, heterozygotic fast, or homozygotic fast acetylators of isoniazid. The early bactericidal activity (EBA) of an antituberculosis agent can be determined by quantitative culture of Mycobacterium tuberculosis in sputum samples obtained from patients with pulmonary tuberculosis during the first days of treatment. In these studies, the EBA of isoniazid during the first 2 days of treatment was determined for 97 patients with sputum smear-positive pulmonary tuberculosis following isoniazid doses of < or =37.5 mg, 75 mg, 150 mg, 300 mg, and 600 mg. The NAT2 genotype was determined in 70 patients, and the association between EBA and genotype was examined in this subgroup. Similarly, the relationship between EBA and isoniazid serum concentration was evaluated in 87 patients. The mean EBA of isoniazid increased with dose, but it levelled off between doses of 150 mg (mean EBA, 0.572) and 300 mg (mean EBA, 0.553). Significant differences were found in the mean EBA of isoniazid between the homozygous slow acetylator group and the heterozygous fast acetylator group and between the homozygous slow acetylator group and the homozygous fast acetylator group, but not between the heterozygous fast acetylator group and the homozygous fast acetylator group. The EBA appeared to reach a maximum at a 2-h isoniazid concentration of 2-3 microg/mL. These data confirm a significant effect of NAT2 genotype on the EBA of isoniazid over a range of doses.

Adolescent↗

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

The Visual Treatment Objective (VTO) is an extremely valuable tool in the process of working out the treatment plan for the individual. This is especially true for the inexperienced operator. Often it becomes clear that extractions are indicated, but there remains uncertainty as to which teeth should be chosen for extractions to give the best results. As it is necessary to express the expected change in profile due to growth of the nose and also of the chin, VTO construction is helpful in determining the extraction decision. Clinical experience and research projects have indicated that the use of mean values has definite limitations when constructing a VTO for an individual. The primary objective of this investigation was to provide formulae by means of which anteroposterior changes in the facial profile of growing individuals for whom four premolar extraction treatment is proposed can be predicted with a greater measure of certainty. The records of 248 growing Caucasian orthodontic patients (120 males and 128 females) were selected and divided into Group 44 (four first premolar extractions), Group 45 (upper first premolar and lower second premolar extractions) and Group 55 (four second premolar extractions). Formulae are presented for the prediction of the amount of incisor retraction, anteroposterior nose growth and for chin growth. The formulae were derived by regression of incisor retraction, anteroposterior nose growth and chin growth on various predictors, and could be used in the construction of VTO's for selected cases.

Adolescent↗

Early bactericidal activity of antituberculosis agents.

The early bactericidal activity (EBA) of an antituberculosis agent is arbitrarily defined as the fall in log(10) colony forming units (cfu) of Mycobacterium tuberculosis per ml sputum per day during the first 2 days of treatment. Determining the EBA is an important preliminary step in the clinical evaluation of an antituberculosis agent. We review the results of eight published studies of the EBA of different antituberculosis agents, the impact of these results on our understanding of the actions of the respective agents, the clinical characteristics and sputum findings of patients included in these studies, and explore sources of variation in the EBA results. Patients in these studies had a mean age of 31-36 years, a mean weight of 50-57 kg, 67% were male and 56% had lung involvement covering an area of more than one lung, and 90% had multicavitary disease. None of these findings were related to EBA in any study. The mean log(10) cfu per ml sputum in the first specimen was 6.474. This was related to radiological extent of disease and cavity size in one study (p < 0.001) and, in the case of isoniazid to EBA with a rise in EBA of 0.094 (95% CL 0.029-0.158) for each tenfold rise in cfu counts/ml sputum. The overall variation in EBA in these studies was 0.0303, that due to laboratory processing of specimens was 0.0011, and due to patient characteristics and sputum sampling 0.0212. The EBA is a reproducible investigation that has contributed significantly to our knowledge of the actions and characteristics of both established and new antituberculosis agents. The greatest source of variation in EBA results appears to be that due to interpatient variation in disease characteristics and sputum sampling.

Antitubercular Agents↗

Primipaternity and duration of exposure to sperm antigens as risk factors for pre-eclampsia.

OBJECTIVE: To establish whether primipaternity and duration of unprotected sexual cohabitation is associated with an increased risk of pre-eclampsia. METHOD: At a tertiary referral center, the study had a case and control group of 60 multigravid women each, as well as a case and control group of 50 primigravid women each. Information was compiled by means of a confidential questionnaire. RESULT: After multiple logistic regression analysis using age, smoking, hypertension in previous pregnancies, change of paternity and duration of unprotected sexual cohabitation as predictors, the regression coefficients for change of paternity and sexual cohabitation of longer than 6 months in multigravid women were -0.4 (P = 0.15) and -1.4 (P = 0.03), respectively. CONCLUSION: Multigravid women with a period of unprotected sexual cohabitation of longer than 6 months had a decreased risk of pre-eclampsia. Primipaternity was not a significant risk factor for pre-eclampsia.

Adult↗

The factor structure for positive and negative symptoms in South African Xhosa patients with schizophrenia.

Most studies investigating the symptom dimensions of schizophrenia utilising the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) favour a three factor model. This study sought to investigate the factor structure of both the global and individual items of the SANS and SAPS in a large sample of South African Xhosa patients with schizophrenia. A total of 422 subjects participated. Both principal components and factor analytical procedures were applied. For the global items, a two-factor solution representing positive and negative symptoms accounted for 59.9% of the variance. Alternatively, the three-dimensional model of negative, psychotic and disorganisation factors was supported by a five-factor solution if the more heterogeneous items of attention and alogia were ignored. Analysis of the individual items yielded a five-factor solution with the negative symptoms splitting into diminished expression and disordered relating, and the positive symptoms separating into factors for psychosis, thought disorder and bizarre behaviour. Our findings are very similar to those from other parts of the world, providing evidence that the factor structure for the symptoms of schizophrenia is relatively resistant to cultural influences. This is particularly true for negative symptoms.

Adult↗

Cultured pulp fibroblasts: are they suitable for in vitro cytotoxicity testing?

The use of cell cultures to test the biocompatibility of dental materials is gaining in importance. Any cytotoxic effects that restorative materials may have will be on the dental pulp and for that reason cultured pulp cells should be the model of choice for biocompatibility testing. The aim of this investigation was to study the growth and morphologic characteristics and toxic response of human pulp lines and to compare these parameters to those of human buccal mucosa fibroblasts. Twenty-one specimens of pulp tissue and six from buccal mucosa were cultured using standard techniques. Six pulp cell lines were cultured successfully as were all six from the buccal mucosa specimens. From these specimens, 12 growth curves were computed. To study the morphology of the cultured cells, they were observed microscopically and classified into three morphological types: slender elongated cells (type I), epithelioid shaped cells (type II) and large stellate cells (type III). Their numbers and proportions were determined for each cell line and compared statistically. To gauge sensitivity to toxic materials, cells were exposed to concentrations of arecoline. An analysis of the growth curves showed no statistical difference between pulp cells and buccal mucosa cells; the slopes of the curves, however, differed significantly between individual cell lines, and these individual differences were greater among pulp cell lines. The morphology of the pulp and mucosa fibroblasts was similar microscopically. There was no significant difference between the number and proportion of the cell types in the two groups, but there were significant differences between the individual cell lines. Pulp cells showed a greater inhibition of growth when exposed to arecoline. Because pulp fibroblasts are difficult to culture, their reported survival rate is poor; due to the differences that exist between individual cell lines, we conclude that pulp cells when used as single cell lines or even pooled may not be ideal for testing biocompatibility, especially if reproducibility is a prerequisite. Any evaluation will require tests on not one, but several cell lines in order to minimize the effect of inter-cell-line differences. Their greater sensitivity to toxic substances, on the other hand, may show that pulp cells could be more sensitive indicators of cytotoxicity.

Adult↗

Infants of women with severe early pre-eclampsia: the effect of absent end-diastolic umbilical artery doppler flow velocities on neurodevelopmental outcome.

Umbilical artery Doppler flow velocity waveform studies were performed over a period of 4 y on 242 women with severe pre-eclampsia before 34 wk gestation. Sixty-eight (28%) had absent end-diastolic umbilical artery Doppler flow velocities. One hundred and ninety-three infants survived to hospital discharge and were followed at 6-monthly intervals until 48 mo of age. The mean corrected developmental quotient was 94 +/- 8 at 24 mo of age and 87 +/- 9 at 48 mo. Ninety-two percent of the infants had a developmental quotient of >80 at 24 mo and 72% at 48 mo of age. This decline is thought to be due to the impact of social circumstances. There were no differences between the developmental quotients of the infants with normal and those with absent end-diastolic umbilical artery Doppler flow velocities at either 24 or 48 mo of age. At 24 mo of age, infants with absent end-diastolic umbilical artery Doppler flow velocities scored lower in the Performance subscale test (p = 0.03). The developmental quotients of infants from poorer socioeconomic backgrounds were significantly lower than those living in more privileged circumstances. At 48 mo, 153 (97%) of the children presented with normal gross motor development. Four infants had cerebral palsy. No differences were noted in the motor outcomes between the infants of women with normal umbilical artery waveforms and those with absent end-diastolic umbilical artery Doppler flow velocities.

Blood Flow Velocity↗

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↗

The fibroblast population in oral submucous fibrosis.

The purpose of the investigation was to compare the morphology of fibroblasts cultured from healthy oral mucosa and mucosa of patients with oral submucous fibrosis (OSF) and to collate the occurrence of cell types of similar morphology. Cells cultured from biopsy specimens from the buccal mucosa of six subjects who did not chew the areca nut and six patients with OSF who chewed areca nut were grown according to standard techniques. Ninety cells per cell line were recorded daily for 8 days, classified into types F1, F2 and F3 according to their morphology, and the results statistically analyzed. We found that there was a relative increase of F3 cells in relation to F1 cells in OSF, resulting in the ratio of F3 to F1 cells being significantly larger in OSF than the ratio in the controls. As it has been reported that F3 cells in rat connective tissues produce significantly more collagen types I and III than F1 cells, we concluded that a change of fibroblast population has occurred in OSF and that this relative increase of F3 cells in humans, which could be committed to the production of large quantities of collagen, can be an explanation for the excessive collagen formation in OSF.

Adult↗

The early bactericidal activity of isoniazid related to its dose size in pulmonary tuberculosis.

Collections of sputum from 105 patients with newly diagnosed pulmonary tuberculosis were made before and at 1 and 2 d after the start of chemotherapy with isoniazid (INH) alone given to groups of patients in doses of 600 mg, 300 mg, 150 mg, 75 mg, 37.5 mg, 18.75 mg, and 9 mg daily, as well as from an untreated group. Counts of colony forming units (cfu) of Mycobacterium tuberculosis in the collections were set up on plates of selective 7H10 medium. The early bactericidal activity (EBA) of INH was defined as the decrease in log10 cfu/ml sputum/day during the first 2 d of treatment. A smooth curve relating EBA to log dose was obtained, with 600 mg INH yielding the highest mean EBA of 0.539, and 18.75 mg INH yielding the lowest EBA (0.111) that could be distinguished from the bactericidal activity of the untreated group. The ratio of the usual dose of 300 mg INH to the lowest dose, of 18.75 mg, that produced a detectable EBA, termed the therapeutic margin, was therefore 16, in contrast to the lower therapeutic margin of 4 for rifampin. The EBA was related to the INH acetylator genotype of patients treated with 600 mg or 9 mg INH.

Acetylation↗

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.

Adolescent↗

Lecithin:cholesterol acyltransferase activity and high-density lipoprotein subfraction composition in type 1 diabetic patients with improving metabolic control.

On initial diagnosis or when metabolic control is poor, subjects with type 1 (insulin-dependent) diabetes mellitus often exhibit decreased high density lipoprotein (HDL) cholesterol levels, which have been associated in numerous studies in non-diabetic subjects with atherosclerosis and coronary artery disease. We measured the activities of plasma lecithin:cholesterol acyltransferase (LCAT), post-heparin lipoprotein lipase, and the composition of the HDL subfractions HDL2 and HDL3, in ten poorly controlled type 1 diabetic patients admitted to a metabolic ward (six women and four men, aged 18-37 years). The measurements were repeated after metabolic control had been optimised and again a week after discharge. The results were compared with those of ten healthy normolipidaemic subjects matched for age, sex and body mass. LCAT activity increased significantly (P < 0.05) with improved metabolic control in the diabetic patients, and showed positive within-person correlation with HDL2 cholesterol ester (r = 0.67; P < 0.01), HDL2 free cholesterol (r = 0.67; P < 0.01), phosphatidylcholine (r = 0.49; P < 0.05), total phospholipids (r = 0.50; P < 0.01) and apolipoprotein A-I (apo A-I: r = 0.72; P < 0.01). With improving metabolic control HDL2 lipid levels increased more than twofold and the compositional changes in HDL2 were reflected by an increased apo A-I:apo A-II ratio (P < 0.05) and a decreased triglyceride:apo A-I ratio (P < 0.05). Changes in HDL3 levels and composition were minor. The results of this study indicate that an increase in LCAT activity increases the concentration and changes the composition of HDL2 in type 1 diabetic patients with improved metabolic control.

Adolescent↗

The clinical and biochemical effects of two combination oral contraceptive agents.

A comparison of the effects of two low-dose oral contraceptives on lipid metabolism was undertaken in an open-group comparative design study at the Family Planning Clinic, Groote Schuur Hospital, Cape Town. Sixty healthy women aged 18-35 years requesting oral contraception were allocated alternately to use a monophasic oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel (Marvelon, group A), or a triphasic oral contraceptive containing 30-40 micrograms ethinyloestradiol and 50-125 micrograms levonorgestrel (Triphasil, group B). The changes in the lipoprotein profile elicited by the two preparations differed significantly. Group A subjects had a much greater triglyceridaemic response (42.4%) than group B (14.6%) and had a significant increase in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (Apo-A1). In group B, HDL-C decreased and Apo-A1 showed little change. Non-HDL-C (NHDL-C) and Apo-B levels hardly changed in either group. The atherogenic ratios, NHDL-C/HDL-C and Apo-B/Apo-A1 were higher in group B. This study confirmed a significant difference in the response of plasma lipoproteins to the two oral contraceptive preparations. The evidence suggests that the desogestrel-containing oral contraceptive elicits a less atherogenic lipoprotein profile than does the levonorgestrel-containing preparation. Although unsupported by direct clinical evidence that changes in the lipoprotein pattern induced by oral contraceptives cause atherosclerosis, these effects should be considered when prescribing oral contraceptives for women who have risk factors for cardiovascular disease.

Adolescent↗

Female alcoholics. IV. Admission problems and patterns.

In an age-matched sample of male and female inpatient alcoholics (n = 518) of the same ethnic background, subjects under 35 years of age described significantly more problem areas than older age groups. Elderly subjects over 55 were the least articulate group. The first-ever addiction treatment subjects reported the lowest mean number of years of problem drinking, the lowest mean Michigan Alcoholic Screening Test scores and the lowest mean daily alcohol intakes. They also displayed greater current social stability than the 2 readmission treatment categories. The general determinants of admission to this addiction unit centered around the experience of crises, social instability and psychological complaints. The most important specific determinants for the individual subject were the propensity to fight when drunk, followed by a positive parental history of excess alcohol intake. Criminal and occupational factors were infrequently encountered in female subjects, but widowhood was common in the older ones.

Adult↗

Female alcoholics. III. Some clinical associations of the Michigan Alcoholism Screening Test and diagnostic implications.

In an age-matched sample of male and female inpatient alcoholics of the same ethnic background, the mean Michigan Alcoholism Screening Test (MAST) score declined significantly with age group and was lowest in elderly people. Females and first-admission subjects recorded lower mean MAST scores. A correlation was noted in both sexes between reported alcohol consumption and MAST scores. Although screening tests such as MAST have been found of value in detecting alcoholism in high-risk populations, this study of some of the MAST parameters in a clinical population suggests that some of the "invisible" and older alcoholics might not be grossly disturbed persons and that other more subtle behavioural clues to diagnosis should be determined. Despite the limitations inherent in any diagnostic technique, the ultimate detection of invisible alcoholics lies at the interface of clinical judgement, the use of screening tests, community awareness and the development of personal responsibility.

Adult↗