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Abstract Background The 516G > T polymorphism in exon 4 of the CYP2B6 gene has been associated with increased plasma Efavirenz (EFV) concentrations. EFV concentrations greater than the recommended therapeutic range have been associated with the increased likelihood of developing adverse CNS effects. The aims of this study were to a) determine the presence of the 516G > T and other CYP2B6 exon 4 polymorphisms in a South African group of HIV-infected individuals b) investigate the relationship between the EFV plasma concentrations, the CYP2B6 516G > T polymorphism and the occurrence of CNS related side effects in this group of patients and c) develop and validate a rapid method for determination of EFV in plasma. Method Data from 80 patients is presented. Genetic polymorphisms in exon 4 of the CYP2B6 gene were identified using PCR amplification of this region followed by sequencing of the amplification products. EFV concentrations were analysed by UPLC-MS/MS. Assessment of the presence of CNS related side effects following EFV initiation were elicited with the use of a questionnaire together with physical examination. Results Plasma EFV concentrations displayed high inter-individual variability amongst subjects with concentrations ranging from 94 μg/l to 23227 μg/l at 2 weeks post initiation of treatment. For the 516G > T polymorphism the following frequencies were observed 23% of patients were TT homozygous, 36% GG and 41% GT. The TT homozygous patients had significantly higher EFV concentrations vs. those with the wild (GG) genotype (p < 0.05). Patients who experienced no side effects had significantly lower EFV plasma concentrations vs. the group of patients which experienced the most severe side effects (p < 0.05). Conclusion The significant association between the 516G > T polymorphism and plasma EFV concentrations has been demonstrated in this study. A rapid and sensitive method for the measurement of plasma EFV concentration was developed and validated.

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed. METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa 200 MZ) or 4 months (4Pa 200 MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa 100 MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed. RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa 200 MZ, 4Pa 200 MZ, 4Pa 100 MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa 200 MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died. CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.

Background: New anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis., Methods: In this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDRplus) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1-14 then 200 mg three times per week (B load PaZ) or oral bedaquiline 200 mg daily (B 200 PaZ). Patients with rifampicin-resistant tuberculosis received 56 days of the B 200 PaZ regimen plus moxifloxacin 400 mg daily (BPaMZ). All treatment groups were open label, and randomisation was not stratified. Patients, trial investigators and staff, pharmacists or dispensers, laboratory staff (with the exception of the mycobacteriology laboratory staff), sponsor staff, and applicable contract research organisations were not masked. The primary efficacy outcome was daily percentage change in time to sputum culture positivity (TTP) in liquid medium over days 0-56 in the drug-susceptible tuberculosis population, based on non-linear mixed-effects regression modelling of log 10 (TTP) over time. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov, NCT02193776, and all patients have completed follow-up., Findings: Between Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to B load PaZ, 60 to B 200 PaZ, and 61 to HRZE) and 60 patients with rifampicin-resistant tuberculosis. 57 patients in the B load PaZ group, 56 in the B 200 PaZ group, and 59 in the HRZE group were included in the primary analysis. B 200 PaZ produced the highest daily percentage change in TTP (5·17% [95% Bayesian credibility interval 4·61-5·77]), followed by B load PaZ (4·87% [4·31-5·47]) and HRZE group (4·04% [3·67-4·42]). The bactericidal activity in B 200 PaZ and B load PaZ groups versus that in the HRZE group was significantly different. Higher proportions of patients in the B load PaZ (six [10%] of 59) and B 200 PaZ (five [8%] of 60) groups discontinued the study drug than in the HRZE group (two [3%] of 61) because of adverse events. Liver enzyme elevations were the most common grade 3 or 4 adverse events and resulted in the withdrawal of ten patients (five [8%] in the B load PaZ group, three [5%] in the B 200 PaZ group, and two [3%] in the HRZE group). Serious treatment-related adverse events affected two (3%) patients in the B load PaZ group and one (2%) patient in the HRZE group. Seven (4%) patients with drug-susceptible tuberculosis died and four (7%) patients with rifampicin-resistant tuberculosis died. None of the deaths were considered to be related to treatment., Interpretation: B 200 PaZ is a promising regimen to treat patients with drug-susceptible tuberculosis. The bactericidal activity of both these regimens suggests that they have the potential to shorten treatment, and the simplified dosing schedule of B 200 PaZ could improve treatment adherence in the field. However, these findings must be investigated further in a phase 3 trial assessing treatment outcomes., Funding: TB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To study the effects of triamcinolone acetonide on health-related quality of life (HRQL) in adult patients with allergic rhinitis., Methods: This study was conducted in South Africa as a placebo-controlled, multicenter, randomized, double-blind study. Following a 7-day baseline run-in, patients were treated for 28 days with either triamcinolone or placebo. Interviewer-assisted quality-of-life assessments were conducted using the Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Total symptom scores, including nasal congestion, were measured using daily diary cards., Results: A total of 337 patients were recruited and 253 patients completed the study per protocol, of which 55 had seasonal allergic rhinitis (SAR) and 198 had persistent allergic rhinitis (PAR). Improvements in the mean scores per area of the RQLQ were significantly better with triamcinolone compared with placebo for the entire study group for activities (P = .04 at visit 4) and sleep, nasal symptoms, emotional problems, and overall score (P = .002, P = .04, P = .03, and P = .04, respectively, at visit 3). When the patients with SAR were separated from the patients with PAR in the analysis, improvement with triamcinolone was better than placebo only in the PAR patients. The overall investigator and patient assessments of relief favored triamcinolone., Conclusions: Triamcinolone given for 4 weeks improves symptom scores and HRQL in patients with allergic rhinitis. The ability of triamcinolone to relieve nasal congestion symptoms in PAR patients was correlated with improvements in HRQL.

Objective: To evaluate the effect of fexofenadine on driver behavior, decision-making, and reaction time in a blinded, randomized, parallel, placebo-controlled study., Methods: A total of 259 male and female adult volunteers participated in a standardized BMW advanced driving test (the skid-pan test; Pretoria, South Africa) and a decision and reaction test of the Vienna Psychomotor Test System. The psychomotor test focused on mean decision times, mean reaction time, decision errors and reaction errors. After a baseline pretest run, the test was repeated 2.6 hours after ingesting either fexofenadine hydrochloride (180 mg) or placebo (the posttest; 1:1)., Results: Two hundred fifty-five volunteers were included in the final efficacy analysis (195 males and 60 females). There was a reduction in the road test time going from the pretest to the posttest, signifying a learning effect, and an increase in the decision time. Although there was a consistent increase in the number of errors committed in the road test, decision time, and reaction time, there were no significant differences between the placebo and the fexofenadine groups. Although significant differences were observed between men and women for the road test time (P < 0.001), decision time (P < 0.001), and reaction time (P = 0.003), there were no differences between the fexofenadine and placebo groups in these subgroups., Conclusions: No differences were found between the fexofenadine and placebo groups on reaction times, decision-making, driver behavior, or adverse effects.

Sixty-four Thoroughbred and Anglo-Arab mares aged 6-12 years were used, of which 40 were non-lactating and 24 lactating. Foals from these 24 mares were weaned at the age of 6 months. Non-lactating and lactating mares were divided into 4 dietary groups each. The total daily protein intake and the protein quality (essential amino-acid content) differed in the 4 groups of non-lactating and 4 groups of lactating mares. The mares were covered and the effect of the quantity and quality of dietary protein on serum progestagen concentrations during pregnancy was studied. A sharp decline in serum progestagen concentrations was recorded in all dietary groups from Days 18 to 40 of pregnancy, with some individual mares reaching values of less than 4 ng/ml. Serum progestagen concentrations recorded in some of the non-lactating mares on the low-quality protein diet increased to higher values (p < 0.05) than those of mares in the other 3 dietary groups at 35-140 days of pregnancy. A similar trend was observed for the lactating mares on a low-quality protein diet at 30-84 days of pregnancy. No such trends were observed in any of the other dietary groups. High-quality protein supplementation increased serum progestagen concentrations during the 1st 30 days of pregnancy. Lactation depressed serum progestagen concentrations until after the foals were weaned.

Sixty-four Thoroughbred and Anglo-Arab mares aged 6-12 years were randomly allocated to 4 dietary groups and fed diets that differed in the total protein content and quality (essential amino-acids). Forty mares were non-lactating and 24 lactating. Eight mares were withdrawn from the investigation owing to injuries or gynaecological pathology. An overall conception rate of 94.6% and a foaling rate of 80% was achieved. Five of 14 (35.7%) mares (Group 1) fed a low-quality protein diet suffered from early embryonic loss before 90 days of pregnancy compared to 3 of 41 (7.3%) mares in the remaining groups that received the higher-quality protein in their diets. Serum progestagen concentrations of mares in Group 1 that suffered foetal loss were indicative of luteal function insufficiency during the 1st 40 days post-ovulation. Non-lactating mares in all 4 groups gained on average approximately 30 kg in mass during the 90 days before the breeding period. Lactating mares in Group 1 (low-quality protein) lost on average 25 kg in mass during lactation, with no weight loss observed among the lactating mares in the other 3 groups. No difference in the diameter of the embryonic vesicle was found between dietary groups until Day 35 of pregnancy.

Pregnant Anglo-Arab and Thoroughbred mares (n = 24) were divided randomly according to age and breed into 4 groups of 6 mares each from approximately 6 weeks before their expected foaling date. Diets received by the 4 groups varied in essential amino-acid and total protein contents. Serum progestagen, FSH and LH concentrations were determined from the day of parturition until foal heat and during the 1st oestrous cycle following foal heat. Serum progestagen, FSH and LH concentrations did not differ between the treatment groups. Progestagen concentrations were high (mean = 7.0: 5.2-16.4 ng/ml) at parturition but decreased rapidly within 48 h. As progestagen concentrations decreased LH concentrations increased from Days 3-6 post partum to reach maximum values at, or the day after ovulation. FSH concentrations declined 3-4 d after parturition and increased 2-3 d before ovulation at foal heat. The duration of elevated progestagen concentrations during the luteal phase of the subsequent oestrous cycle affected the interovulatory period. A 12-14 d FSH cyclical releasing pattern occurred. Season/photoperiod affected the resumption of normal oestrous cyclicity during the post partum period. The duration of the 1st oestrous cycle after foal heat in mares fed a low-quality protein diet showed a greater range (13-30 d) compared to mares fed a high-quality protein diet (18-26 d).

The effect of total protein intake and protein quality on the serum concentrations of certain reproductive hormones during the anovulatory, transitional and ovulatory periods were studied in 36 Anglo-Arab mares. High-quality protein stimulated FSH and LH production during the late transitional period. Serum progestagen and melatonin concentrations were unaffected by the quality of protein nutrition during the anovulatory period. Mares receiving high-quality protein exhibited a 10-14-day cyclical pattern of FSH release approximately 4-6 weeks earlier than the mares fed the lower-quality protein diet, and also ovulated 3-4 weeks earlier than the mares on the lower-quality protein diet. Progesterone concentrations during the 1st oestrous cycle after the anovulatory period were unaffected by protein quality in the diet.

The effect of 4 different diets, in terms of protein quantity and quality, on total serum protein (TSP), albumin and globulin was investigated. Non-pregnant mares that were not lactating (n = 36), pregnant mares that had foaled (n = 24) and their foals (n = 24) were used in this study. Daily total protein intake had no effect on blood protein concentrations in the mares. Total protein intake and quality (available essential amino-acids) did affect the body mass of mares during lactation. When mares were fed the minimum recommended (National Research Council 1989) total daily protein, foal mass decreased by approximately 25% at weaning compared to the foals whose dams were on a higher level of protein intake. The TSP concentrations of foals at birth were on average 10 g/l lower than those of the mares. Albumin concentrations of foals during the first 60 days of life were on average 2-3 g/l lower than those of the mares. Globulin concentrations of foals were approximately 5 g/l lower than those of mares at weaning.

In the main experiment the total daily protein intake and quality (essential amino-acids) was varied in 4 groups of mares. The incidence of oestrus in mares during the transitional period was unaffected by protein nutrition. Ovarian activity, as evaluated by follicular development and size of the ovaries, was affected. Mares that received low-quality protein (Groups 1 and 2) had a higher number of smaller follicles (< 10 mm) that developed during the transitional period compared to mares on a high-quality protein intake (Groups 3 and 4). The mares that received the high quality protein ovulated 2-3 weeks earlier in the breeding season in a synchronised period of 4-5 weeks compared to a period of 6-8 weeks in Groups 1 and 2. The duration of the subsequent oestrous cycles was not affected. There was no difference in the diameter of the largest follicle of mares between groups on the day before ovulation. In a separate experiment, 5 maiden Anglo-Arab mares, 4-5 years of age, were slaughtered at different stages during the anovulatory, transitional and ovulatory periods of the breeding cycle. The morphology of the ovaries and uteri of these mares was described and photographed for use as guidelines when comparing ovarian changes and follicular activity of mares.

Four rations that differed in their crude protein and essential amino-acid content were compiled. Digestibility of the crude protein and essential amino-acid contents were determined biologically in a feeding trial using 4 Anglo-Arab stallions. Their respective daily diets were: Diet 1:2 kg cubes, 5 kg tef hay (Eragrostis tef); Diet 2:2 kg cubes, 5 kg lucerne hay (Medicago sativa); Diet 3:2 kg cubes, 5 kg tef hay, 200 g fishmeal; Diet 4:2 kg cubes, 5 kg lucerne hay, 200 g fishmeal. The concentrations of the amino-acids threonine, iso-leucine, leucine and arginine were increased in the total ration when lucerne hay replaced the tef hay while fishmeal supplementation increased the methionine and lysine contents, which provided a wide-range of concentrations of digestible amino-acids in each of the 4 rations.

The microscopic uterine involutionary changes were studied in Boer goats (n = 16) from 2 h to 34 d post partum. The endometrial epithelium showed a linear decrease in thickness with time post partum. A highly significant negative correlation (r = -0.94; P less than 0.01) was found between the endometrial epithelium layer thickness and time post partum. The lamina propria layer showed a rapid decrease during the first 20 d post partum and then tended to level out. According to the statistical model (y = AeBt + Ct2) fitted by 25.2 d post partum, the thickness of the lamina propria layer was static. The myometrium decreased significantly (P less than 0.01) in thickness from Day 24 to Day 34 post partum. The thickness of the serosa followed a linear-type decrease during the observation period, while in the glandular epithelium the decrease was rapid during the first 12 d following parturition. The uterine glands reached normal size 22.1 d after parturition. The involution process of the uterus was microscopically complete by Day 28 post partum, the main indicator being the degree of recovery of the endometrial epithelium over the caruncular areas.

A prospective study was undertaken of 298 asthmatic children attending a paediatric allergy clinic in Bloemfontein. A detailed history was obtained, and skin tests were performed. Male predominance and an early age of onset were confirmed. Symptomatic allergic rhinitis was an extremely common finding. A family history of allergy was obtained in over 90% of cases. Respiratory tract infections, changes in the weather and exercise were found to be the most common asthma-inducing factors. Common allergens were grass pollen (63%) and animal danders. House-dust mite (25%) and dietary allergens (less than 20%) were relatively uncommon. The failure to recognise the symptoms of asthma in children, particularly young children, was identified as an ongoing problem.

Comprehensive blood typing (17 factors) and electrophoretic protein markers (haemoglobins, transferrins and albumins) were determined on S.A. Mutton Merino sheep (n = 275). The frequencies of these genetic markers were compared between ram lambs with normal and ram lambs with bent-legs and in a second trial between non-affected ewes and their lambs and ewes and lambs which were considered to be carriers of genetic factors resulting in the bent-leg syndrome. The presence of blood factors 2, 3 and 13 and the absence of factors 8, 10 and 17 is possibly linked to the bent-leg syndrome. Although the frequencies of TFA and TFD alleles were higher in the suspected carrier animals than non-affected animals, no definite linkage to the bent-leg syndrome was found. Haemoglobin and albumin type showed no correlation with the bent-let syndrome.

The effect of age of the ewe and pregnancy on concentrations of plasma calcium, phosphorus and magnesium and its relationship to the bent-leg syndrome in lambs, were investigated. This study included Merino ewes (n = 74), Dohne Merino ewes (n = 127), S A Mutton Merino ewes (n = 123) and S A Mutton Merino lambs (n = 145). Over a period of 8 years, 52 S A Mutton Merino ram lambs out of a total of 602 ram lambs weaned (8,6%), developed the bent-leg syndrome compared to the 2 ewe lambs out of 591 ewe lambs (0,3%) weaned. It was found that both the age of the ewe and pregnancy had no contributing effect in the development of this syndrome. The ewes of which the offspring developed the bent-leg syndrome, had an inverse plasma Ca:P ratio. Approximately 15% of the S A Mutton Merino ewes which gave birth to offspring which developed the bent-leg syndrome, had more than one lamb which developed this condition over the past 8 years. It is suggested that these ewes are carriers of certain genetic factors which can cause excessive phosphorus absorption. No differences in the concentration of plasma calcium, phosphorus and magnesium were found between ewe and ram lambs.

Chloramphenicol was found to cross the blood-brain barrier into the cerebrospinal fluid of children with pyogenic meningitis effectively both at days 2 and 10 of therapy. It is recommended as the drug of choice in the treatment of children with Haemophilus influenzae meningitis.

The morphological changes in the post partum corpus luteum was investigated by light microscopy on 16 ewes during the normal breeding season (March/April). The increase in luteal tissue results from hypertrophy and not from hyperplasia of the granulosa and thecal cells. Two types of lutein cells were found in the corpus luteum: a large light-staining cell and a small dark-staining cell. These might reflect the 2 extremes of a spectrum of cells in different functional states, or they might represent cell lines derived from the follicular granulosa and the thecal interna, respectively.

Attention is drawn to the beneficial effect of improved nutrition during winter and early spring on the ovarian activity of mares. Furthermore, the necessity of an adequate plane of nutrition during early pregnancy to prevent embryonic resorption is stressed.

Two thoroughbred mares bearing twins as diagnosed by rectal palpation, were subjected to nutritional stress by drastically reducing the daily ration. This resulted in a marked reduction in plasma progestagen levels and the death of either one or both of the twin embryos.

Cortisol and growth hormone concentrations in the plasma were determined in 26 children with kwashiorkor, 13 with marasmus, and 21 controls. Cortisol levels were high in babies with kwashiorkor and marasmus, but higher in the former, in relation to a constant body mass. The concentration of plasma cortisol correlated positively with the body mass deficit in kwashiorkor (r = 0,66) and in children with low mass for age (r = 0,75). Growth hormone levels were elevated in both kwashiorkor and marasmus. The proposed role of these hormones in metabolic adaptation to malnutrition is discussed.

Plasma calcium, phosphorus and magnesium concentrations were determined in ewes and their single and twin lambs from birth for 120 days in Merino, Dohne Merino and South African Mutton Merino sheep. Mineral concentrations as well as the plasma calcium: phosphorus ratio were compared between breeds. Throughout the experimental period, plasma calcium and phosphorus concentrations were higher in both single and twin lambs than in the ewes of all 3 breeds. No breed differences in plasma calcium concentrations were found. Animals of the S.A. Mutton Merino breed had significantly higher (P less than 0.05) plasma phosphorus concentrations than the other 2 breeds. The plasma Ca:P ratio in the Merino and Dohne Merino ram lambs was approximately 1.1:1 and in the S.A. Mutton Merino 0.9:1. This converse plasma Ca:P ratio found in both the S.A. Mutton Merino ewes and lambs is believed to result in an induced plasma ionised calcium deficiency which leads to improper calcification of bone. This is believed to be a contributing factor in the bent-leg syndrome. No difference was recorded in body mass between ram lambs suffering from the bent-leg syndrome and unaffected ram lambs. Plasma magnesium concentrations were not affected by breed or age of the animals.

Appropriate exercise will provoke an attack of bronchospasm in virtually all asthmatic children. Exercise-induced asthma can effectively be prevented by pre-exercise treatment with sympathomimetic drugs or sodium cromoglycate, and there is no reason why an asthmatic should not participate in sporting activities. Running at a steady pace for 6 - 8 minutes (submaximal effort) is the most asthmagenic exercise, whereas swimming is the least athmagenic.

Plasma renin activity was found to be correlated positively with muscle water content and the presence of oedema in rats with protein energy malnutrition, whereas the muscle potassium content showed a negative correlation with muscle water content. Malnourished rats also showed an inability to dispose of a water load. Nevertheless, the ability of malnourished rats to excrete injected hormones and to clear the plasma of bromosulphthalein proved to be normal. It is therefore concluded that, although the inability to balance consumption and excretion of water may in part be the result of increased effective plasma renin activity, the increased plasma concentration results from increased secretion rather than from decreased inactivation.

Plasma renin activity was measured by bio-assay in 52 children with kwashiorkor, in 28 with marasmus and in 21 healthy children. Plasma renin activity was significantly increased in children with kwashiorkor and marasmus, compared with healthy children, and in children who died, compared with survivors. No strict causal relationship could be found between plasma renin activity and the degree of oedema in kwashiorkor. Increased renin activity probably results from a terminal change in cardiovascular function.

Sensitivity to house-dust and the mites Dermatophagoides pteronyssinus and D. farinae was the commonest cause of asthma in children living in the Cape Peninsula. Of 103 asthmatic children examined, 65,5% had positive skin tests to these allergens. Only a small number of the children were sensitive to pollens, feathers, moulds or food. The median serum IgE level was 496 U/ml, with a range of 18-15972 U/ml, and the median blood eosinophil count was 691/microliter (range 93-8 159) in 102 of the children.

The depressing effect on plasma progestagen levels of pregnant mares subjected to specific stressful conditions such as severe pain, infectious diseases, emotional disturbances and exogenous corticosteroids are described. It is concluded that the detrimental effect of stress, evident from its negative influence on plasma progestagen concentrations, could play a major role in the occurrence of pregnancy failure in the Thoroughbred mare.

Paraffin pneumonia is a common form of poisoning but pneumatocoeles are an uncommon complication. This is a report of the computerized tomography (CT) of seven patients who developed pneumatocoeles after the ingestion of paraffin. The finding on the CT are presented and the situation and characteristics of the pneumatocoeles are indicated.

Vascularised transplantation of the Fallopian tube is a technically feasible operation, but its functional result remains questionable. This article documents a pregnancy after vascularised contralateral autotransplantation of the oviduct in a ewe.

The cord blood levels of IgG, IgA and IgM in newborn white, coloured and black infants in the Western Cape were measured using a nephelometric technique. A statistically significant difference was found between the IgG values in the different population groups, but no significant difference was found in IgA and IgM values.

A combination of amoxycillin and clavulanic acid 4:1 was administered to 35 children (aged 2 to 10 years) with infections. The combination was administered orally as a suspension, every 8 h for 5 to 7 days. Sixteen children (aged 2 to 5 years), received 125 mg amoxycillin and 31.25 mg clavulanic acid, and 19 (6 to 10 years) received 250 mg amoxycillin and 62.5 mg clavulanic acid per dose. Following the first dose serum concentrations of amoxycillin and clavulanic acid were determined by microbiological assay. In the younger group receiving the lower dosage (mean: amoxycillin 9.11 mg/kg and clavulanic acid 2.34 mg/kg), the mean peak concentration of amoxycillin was 3.5 mg/l and of clavulanic acid 1.2 mg/l, occurring 1.32 h and 1.39 h, respectively, after administration. In the older group receiving the higher dosage (mean: amoxycillin 12.35 mg/kg and clavulanic acid 3.14 mg/kg) the mean peak serum level of amoxycillin was 4.0 mg/l and of clavulanic acid 1.3 mg/l, occurring 1.43 h and 1.23 h, respectively, after administration. The higher dose per kilogram body weight resulted in a higher peak serum concentration both of amoxycillin and clavulanic acid. The formulation was well tolerated by all the children and no serious side-effects were recorded. Treatment was considered clinically effective in all cases.

A case of agenesis of the right lung associated with hypoplasia of the fourth right rib is described. Diagnosis was confirmed by bronchographic and angiographic demonstration of absence of any lung tissue on the right. The possible aetiology, differential diagnosis and prognosis of this anomaly are discussed.

The effects of injecting histamine phosphate, in serial 10-fold dilutions ranging from 0.0001 to 0.1 mg/ml histamine base, intradermally into three groups of nonatopic healthy volunteers with varying degrees of skin pigmentation were studied. The wheal sizes in the 30 Negroid subjects with darkly pigmented skins were consistently greater than those in both the 30 Caucasian subjects with light skin pigmentation and the 15 mixed Caucasian/Negroid subjects with light brown skins. The overall wheal response was the smallest in the Caucasian subjects. The differences in wheal sizes were greatest between the Negroid and Caucasian subjects for all dilutions, and these differences were statistically significant (p less than 0.005). From this study it appears that skin pigmentation has a profound effect on the wheal response to intradermally injected histamine. It is speculated that this difference in response may be related to the melanin pigment in the skin.

Paraffin pneumonia is a common form of poisoning, but pneumatoceles are an uncommon complication. This is a report of 6 patients who developed pneumatoceles after the ingestion of paraffin. These children's ages varied from under 18 months to 4 years; they were clinically more ill and were hospitalised longer than those who did not develop pneumatoceles. The pneumatoceles were discovered at the earliest on day 6 and, although extensive and in 2 cases bilateral, caused no clinical impairment of respiratory function. The pneumatoceles appear to resolve spontaneously but this may take more than 200 days.