Non-cystic fibrosis bronchiectasis: A single-centre retrospective study in Johannesburg, South Africa.

Background: Bronchiectasis, once rarely encountered, appears to be increasing in prevalence in South Africa (SA) and globally. There is a lack of published data on non-cystic fibrosis (CF) bronchiectasis, specifically in low- to middle-income countries, despite the high rates of risk factors such as HIV, pulmonary tuberculosis, and other infections. Objectives: Given this lack of data, to review the characteristics of adult patients with non-CF bronchiectasis at a tertiary academic hospital in Johannesburg, SA. Methods: This was a single-centre, retrospective record review, including all cases of non-CF bronchiectasis that were in the records of the adult pulmonology clinic at Charlotte Maxeke Johannesburg Academic Hospital as of April 2017. Results: There were 197 patients, with a slight predominance of males, and the patients were generally young. The HIV rate was higher than the national average (34.8% v. 13.7%), and the HIV-positive patients had a high TB prevalence (86.9%). Pseudomonas spp. were cultured from sputum in 15.3% of cases. Fewer than half of the cohort had the diagnosis of bronchiectasis confirmed by high-resolution chest tomography. Airway obstruction (forced expiratory volume in 1 second/forced vital capacity ratio <70%) was observed in 47.0% of patients. Treatment with a short-acting beta-2-agonist was prescribed in 62.9%, a long-acting beta-2-agonist in 43.6% and inhaled corticosteroids in 51.3%. Antibiotic therapy during exacerbations was used in 44.2%, mainly amoxycillin-clavulanate (66.7%). Conclusion: While single centre and retrospective, this study adds to the data on non-CF bronchiectasis in sub-Saharan Africa and should encourage further research to increase our understanding of adult non-CF bronchiectasis in SA. Study synopsis: What the study adds. This study adds to published data detailing the clinical characteristics of adult non-cystic fibrosis (CF) bronchiectasis in low- and middle-income countries (LMICs).Implications of the findings. As a retrospective descriptive study, the findings summarise the characteristics of adults with non-CF bronchiectasis in a cohort from Johannesburg, South Africa. The findings suggest that the characteristics of bronchiectasis in this region appear to be similar in several ways to those in other LMICs, but quite different from those in the developed world.

Characterization of the ABCA4 gene in Stargardt's Disease in Trinidad and Tobago

Objectives: Stargardt's disease is an autosomal recessive macular dystrophy caused by mutations in the photoreceptor cell-specific ATP-binding cassette sub-family A member 4, transporter (ABCA4) gene. We studied (i) the predicted effects of mutations on the function of the ABCA4 transporter and (ii) the existence of four common mutations in local Stargardt patients. Design and Methodology: (i) The freeware PROVEAN (Protein VariationEffect Analyzer; J. Craig Venter Institute, CA,USA) was used to predict the deleterious effect257 mutations in the ABCA4 gene. PROVEANscores below -2.5 were considered deleterious.One-way ANOVAs were used to detect anysignificant differences in mean (±SE) PROVEANscores among mutation types or protein domains I,II, III or IV. (ii) Using saliva, DNA was isolated from three Stargardt patients. Chromosomal regions were amplified by PCR, sequenced (Macrogen Inc., Seoul, Korea) and sequence alignment (NCBI, MD, USA) used to detect the presence of four mutations; c.768G>T (p.Val256=), c.4469G>A (p.Cys1490Tyr), c.6079C>T (p.Leu2027Phe) and c.1804C>T (p.Arg602Trp). Results: (i) Sixty-three percent of mutations predicted deleterious effects. There were no significant (p<0.05) differences between mean PROVEAN scores among mutation types (substitutions, - 4.49±0.20; deletions/insertions, -6.35±0.67) or protein domains (domain I, -4.79 ± 0.39; domain II, -4.65 ± 0.36; domain III, -5.48 ± 0.51; domain IV, -4.39 ± 0.34). (ii) These mutations were not detected in Stargardt's patients. Conclusion: (i) Functionality of the ABCA4 protein is affected by multiple mutations. (ii) Novel mutations are present in local patients. Currently, we seek to profile novel mutations in six families using molecular inversion probes.

Cofactors for the acquisition of HIV-1 among heterosexual men: prospective cohort study of trucking company workers in Kenya.

OBJECTIVE: To determine the prevalence, incidence, and correlates of HIV-1 infection in a cohort of east African trucking company employees. METHODS: HIV-1-seronegative trucking company employees were enrolled in a prospective cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually transmitted diseases, and sexual behavior. RESULTS: The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8%. Among 752 HIV-1-seronegative men who were followed, the HIV-1 annual seroincidence was 3.1%. In univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10 years or less of sexual activity, occupation as a driver/driver's assistant, occupational travel for more than 14 days per month, religion other than Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a girlfriend/casual partner, extramarital sex, and enrollment seropositivity to Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P values < or = 0.05). Using multivariate analysis, HIV-1 acquisition was independently associated with 10 years or less of sexual activity (hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a driver/driver's assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3, 95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up. Risk factors for HIV-1 seroconversion included years of sexual activity, occupation, religion, uncircumcised status, and unprotected sex with a prostitute. This population is an appropriate target for HIV-1 prevention trials and behavioral interventions.

Cardiovascular risk factors in school children from low middle income families in Karachi, Pakistan.

Serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were determined on 239 school children aged 5-19 years belonging to lower middle class families. The mean TC, LDL-C, HDL-C and TG ranged from 3.70-4.37 mmol/L, 2.17-2.70 mmol/L, 0.94-1.14 mmol/L, 1.07-1.26 mmol/L respectively. In general, girls had higher TC, LDL-C and HDL-C levels. There was no significant difference in the TG levels between boys and girls. Thirty-three percent of the girls and 22% of the boys had TC level > or = 4.4 mmol/L, the level at which dietary intervention is recommended for children. Fifty-three percent of the girls and 37% of the boys had TG levels > or = than the 90th percentile of the levels for children of similar age and sex in North America. The HDL-C levels were low with 37% of the girls and 44% of boys having values < or = the 10th percentile of levels for North American children. The mean daily intake of cholesterol ranged from 241 mg to 364 mg/day. Except for the 5-9 year olds, boys had a higher cholesterol intake than girls (P < 0.005). Twenty-two percent of the boys and 32% of the girls were overweight but weight status was significantly associated with elevated TC levels only in the boys (P < 0.05). Activity level was not significantly related to TC levels but girls who were active had significantly higher HDL-C levels than girls who were sedentary (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of 3,5,3'-triiodothyronine on phosphoenolpyruvate carboxykinase, fatty acid synthetase and malic enzyme activity of liver and brown fat of fetal and neonatal rats.

Pregnant rats were injected with triiodothyronine (T3) on the 19th and 20th days of pregnancy. This elevated fetal T3 plasma values and caused a large rise in fetal liver phosphoenolpyruvate carboxykinase (PEPcK) activity. At the same time PEPcK activity in fetal brown fat was inhibited. Essentially the same effect of T3 was also noted when injected into postnatal rats. T3 injections also elevated fatty acid synthetase activity in brown fat of weanling rats but, in contrast to corticosteroids, had no effect earlier in life. No effect was noted in the liver, except a slight decrease in the fetus. T3 injections to suckling rats elevated plasma levels of insulin and glucagon within 24 h.

The response of cyclic nucleotide content in liver and brown fat of rats weaned to different diets.

Rats were weaned on the 18th or 30th postnatal day to a high-fat, high-carbohydrate or atherogenic diet. Twenty-four hours later, hepatic levels of cyclic guanosine 3',5'-monophosphate (cyclic GMP) and adenosine, 3',5'-cyclic monophosphate (cyclic AMP) were found to be higher in male animals aged 31 days fed the high-fat than those fed the high-carbohydrate diet. Prematurely weaned rats (day 18) reacted in the same way. However, feeding either diet resulted in higher hepatic cyclic nucleotide levels than found in rats kept with the dam. The atherogenic diet was least effective in raising these levels. After a 24-hour fast, cyclic nucleotide levels in liver and brown fat were elevated and hepatic levels could not be lowered by 6 hours of feeding the high-fat or atherogenic diet. In male 40-day-old rats, however, feeding for 2 hours was sufficient to lower these levels, more so with a high-carbohydrate than a high-fat diet. Since blood levels of glucagon are high, and those of insulin are low in 18-day-old rats that are not weaned and since their hepatic cyclic nucleotide levels are low, it is suggested that other factors, in addition to blood hormone levels, play a role in regulating cyclic nucleotide levels.