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Aim: Little is known about pyridoxine nutriture of children treated with isoniazid (INH) regimens. This study documents plasma pyridoxal 5′-phosphate (PLP) concentrations in children, HIV-infected and HIV-uninfected, receiving INH regimens. Methods: Children from the Western Cape of South Africa hospitalized for tuberculosis (TB) management were studied. Plasma PLP concentrations were determined on enrolment, 1-month after commencing TB treatment, and again after 4-month’s treatment. The children received a supplement meeting pyridoxine requirements. Results: Nineteen HIV-infected and 33 HIV-uninfected children received INH (dosage range 4–20 mg/kg) daily. Mean PLP plasma concentrations on enrolment were 8.32 (SD 6.75) ng/mL and 11.28 (SD 3.02) ng/mL in HIV-infected and HIV-uninfected children, respectively (p = 0.11) and after 4-month’s treatment 6.75 (SD 2.71) ng/mL and 14.76 (SD 7.96) ng/mL (p

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.

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.

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

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.

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.

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.

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.

A model is proposed for the fitting of species-area curves to data from the Stellenbosch region, South Africa. Basic assumptions of the model are finiteness of the number of species in a finite area, and random distribution of plant species over the region. The model involves a distribution of densities of different species, and the parameters of this distri- bution are useful for describing and classifying communities. The data of the Stellenbosch region suggest that the assump- tions of the model break down in areas greater than 500 m2.

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 (P0.05) with improved metabolic control in the diabetic patients, and showed positive within-person correlation with HDL2 cholesterol ester (r = 0.67; P0.01), HDL2 free cholesterol (r = 0.67; P0.01), phosphatidylcholine (r = 0.49; P0.05), total phospholipids (r = 0.50; P0.01) and apolipoprotein A-I (apo A-I: r = 0.72; P0.01). 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 (P0.05) and a decreased triglyceride:apo A-I ratio (P0.05). 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.

In today’s subscription-based industries of which telecommunication businesses, Internet services, medical aid, and the insurance industry are examples, management activities should be customer-centred and performance should be measured based on the firm’s customer value. In this study we investigate customer survival time in the Internet service providers industry. From the database of an Internet service provider, a random sample of 30 000 customers was selected. Factors potentially associated with churn in the ISP industry are investigated in this study. There are mainly two groups: demographic variables (gender, age, language and number of children) and usage related variables (the IT background of the customer and customer segment). Factors are examined individually. Nonparametric survival analysis techniques are used to analyse the data. Demographics and usage related factors have shown potential in determining the survival time of the customer and the event of churn. In particular, age and number of children and the customer usage segment appeared to be extremely important. The customers with age less than 26 years have higher risk of churn, while customers who use Internet for business purposes appeared to be more loyal. A special retention strategy should be formulated for these groups.

We studied the early bactericidal activity of twice the standard dose of rifampin in subjects with pulmonary tuberculosis evidenced by positive smears. The observed mean 2-day activity was almost double that reported at the standard dose. Further studies are warranted to establish whether higher rifampin doses might assist in shortening tuberculosis treatment.

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.

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.

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.

Empirical Bayes Methods. By J. Maritz and T. Lwin. ISBN 0 412 27760 3. Chapman and Hall, London, 1989. xii + 284 pp. £27.50.

Data derived from regular serial dental examinations were used to calculate d.m.f. indices for the canine and molar teeth. The annual increments of these indices were analysed in those children who attended for every annual examination between the ages of 2 years and 8 years (Group A) and for those who attended at least two successive annual examinations during this same period (Group B). In both groups, there was a negative binomial distribution of the annual increments of d.m.f. indices, for each age interval in both sexes. After a suitable transformation, tests showed that there were no real sex differences in the mean annual increments of the d.m.f. indices during the age range that was studied. There were low correlations between successive annual d.m.f. increments. The possible models from which such a finding could result have been discussed. It is considered likely that real changes occurred, with time, in the “risk” levels of the individual children that were examined.

Six volunteers raised their rectal temperatures to 104℉ by 40–50 minutes' work at 93℉ wet-bulb temperature. The rates of fall in rectal temperatures were studied during cooling by six different methods. The most rapid method of cooling occurred when subjects sat at rest in an air condition of 90℉ dry bulb and 87℉ wet bulb and evaporative cooling was accelerated by wetting the body surface continuously for 1 hour; no significant difference in cooling was observed between airflows of 120 ft/min. and a jet of compressed air held 1–3 ft from subjects. Merely seating individuals in air conditions of 70℉ with 20% relative humidity in still air was almost as effective. Immersion in cold water and sitting in air conditions of 90℉ (D.B.) and 87℉ (W.B.) without aiding evaporative cooling are significantly less effective than the foregoing methods. Resting subjects at 97℉ (D.B.), 93℉ (W.B.) and 120 ft/min. air velocity results in very slow cooling. ‘Afterdrop’ in rectal temperature after ice-cold water cooling may be associated with severe circulatory shock. Oral temperatures are a less reliable index of core temperature than rectal. Submitted on February 16, 1959

At least five separate determinations were made of oxygen intake and heart rates at various levels of work on a bicycle ergometer, up to and above the maximum level of O2 intake of four highly trained men. From these measurements it has been possible to fit appropriate curves to the experimental data and test for their goodness of fit. At low rates of work a straight line fits both O2 intake and heart rate plots against work rate, but at high work rates the curves tend toward an asymptote. The O2 intake curve reaches its asymptote more slowly than does the heart rate; hence, if heart rate is plotted against O2 intake and a straight line fitted and extrapolated to the maximum value of heart rate, the O2 intake at this value is an underestimate of the actual measured maximum O2 intake. Because of the characteristic slope of the best-fit curve of oxygen intake against work rate, the criteria proposed by some earlier investigators for the level of O2 intake at which the maximum is unequivocally attained, is open to criticism. An alternative is proposed. The maximum levels of O2 intake and maximum heart rate of trained men studied over 4 months is remarkably constant, having average coefficients of variation of 4.3% and 3.5%, respectively. Submitted on December 2, 1958

The basis of statistical tests of significance of association between fluoride level in drinking water and cancer death rates is discussed. Reference is made to two reported studies in each of which cancer death rates of a number of [U.S.] cities were used. It is argued that between city variation should be taken into account when performing tests of significance. In one of the two studies this was done informally; in the other between city variation was ignored. (EXCERPT)