Focal segmental glomerulosclerosis and partial deletion of chromosome 6p: a case report.

We treated a patient with 6p partial deletion syndrome diagnosed after proteinuria was detected during developmental examination 3 years after birth. External anomalies included ocular hypertelorism, saddle nose, elongated philtrum, tent-like lips, and low-set auricles. Mental retardation was evident. The karyotype was 46,XX,del(6) (p.22.1-p22.3) with an interstitial deletion. The kidneys showed no abnormality on imaging such as hydronephrosis, atrophy, or malformation. Examination of a renal biopsy specimen disclosed focal segmental glomerulosclerosis. No cardiac anomaly or Rieger anomaly, which often are present in this syndrome, were noted.

Sepsis in previously healthy neonates discharged home after delivery in Soweto, South Africa.

BACKGROUND: There is a paucity of data on the aetiology of neonatal sepsis in sub-Saharan Africa. OBJECTIVES: To investigate the incidence, aetiology and outcomes of physician-diagnosed sepsis in hospitalised neonates who had previously been discharged home after delivery in Soweto, South Africa. METHODS: A retrospective review using data abstracted from clinical and laboratory databases identified physician-diagnosed sepsis cases in neonates admitted to the general paediatric wards at Chris Hani Baragwanath Academic Hospital from January 2015 to September 2016. Neonates with physician-diagnosed sepsis were categorised into two groups based on putative pathogens recovered from blood and/or cerebrospinal fluid specimens: (i) culture-confirmed sepsis; and (ii) culture-negative sepsis. RESULTS: Of 1 826 neonatal admissions, 1 025 (56.2%) had physician-diagnosed sepsis: 166 (16.2%) with culture-confirmed sepsis and 859 (83.8%) with culture-negative neonatal sepsis. The commonest pathogens causing culture-confirmed neonatal sepsis were Streptococcus viridans (n=53; 26.5%), S. agalactiae (n=38; 19.0%), and Staphylococcus aureus (n=25; 12.5%). The case fatality rates for culture-confirmed sepsis and culture-negative sepsis were 10.8% (18/166) and 2.6% (22/859), respectively. The odds of death occurring during hospitalisation was 10-fold (95% confidence interval 3.7 - 26.9) higher in neonates with culture-confirmed sepsis compared with culture-negative sepsis. CONCLUSIONS: In our setting, physician-diagnosed sepsis represents a huge disease burden in previously healthy neonates hospitalised from home. Most sepsis cases were attributed to S. viridans, S. agalactiae and S. aureus.

Phylogeny of Litsea and related genera (Laureae-Lauraceae) based on analysis of rpb2 gene sequences.

The relationship between Litsea and related genera is currently unclear. Previous molecular studies on these taxa using cpDNA and nrITS were unable to produce well-resolved phylogenetic trees. In this study, we explored the potential of the rpb2 gene as a source of molecular information to better resolve the phylogenetic analysis. Although rpb2 was believed to be a single-copy gene, our cloning results showed that most species examined possessed several copies of these sequences. However, the genetic distance among copies from any one species was low, and these copies always formed monophyletic groups in our molecular trees. Our phylogenetic analyses of rpb2 data resulted in better resolved tree topologies compared to those based on cpDNA or nrITS data. Our results show that monophyly of the genus Litsea is supported only for section Litsea. As a genus, Litsea was shown to be polyphyletic. The genera Actinodaphne and Neolitsea were resolved as monophyletic groups in all analyses. They were also shown to be sisters and closer to the genus Lindera than to the genus Litsea. Our results also revealed that the genus Lindera is not a monophyletic group.

Maternal and neonatal vitamin D status at birth in black South Africans.

BACKGROUND: Vitamin D deficiency (VDD) in pregnant women has been associated with adverse pregnancy and neonatal outcomes. 25-hydroxyvitamin D (25(OH)D) levels are affected by numerous factors, including vitamin D intake, skin pigmentation, latitude and season of the year; they therefore vary by race and country. Vitamin D status in pregnant women and their offspring in South Africa (SA) is not well established. OBJECTIVES: To assess vitamin D status by measuring serum 25(OH)D in pregnant black SA women and their offspring in Johannesburg (latitude 26°S) and to assess whether vitamin D status is affected by maternal HIV infection. METHODS: We prospectively enrolled pregnant women and their healthy neonates, and measured 25(OH)D in maternal and cord blood at delivery. Pregnant women were stratified by their HIV status. Predictors of maternal and neonatal VDD (levels <30 nmol/L) were assessed using multiple logistic regression analysis. RESULTS: A total of 291 pregnant women and their healthy neonates were enrolled over a 21-month period. Mean (standard deviation) maternal and cord blood 25(OH)D levels were 57.0 (29.7) and 41.9 (21.0) nmol/L and the prevalence of VDD was 15.9% and 32.8%, respectively. On average, concentrations of 25(OH)D in cord blood were ~80% of those in the mother. There was no association between cord 25(OH)D and gestational age, but levels were associated with birth weight (p<0.001). There were no differences in maternal or cord blood 25(OH)D levels between those HIV-infected or uninfected. The predictor of VDD in mothers was giving birth in winter (odds ratio (OR) 2.87, 95% confidence interval (CI) 1.47 - 5.61), and in neonates the predictors were maternal age (OR 16.5, 95% CI 1.82 - 149), being born in winter (OR 3.68, 95% CI 2.05 - 6.61), being born by caesarean section (OR 4.92, 95% CI 1.56 - 15.57) and being of low birth weight (OR 1.99, 95% CI 1.13 - 3.50). CONCLUSIONS: Among black SA women delivering in Johannesburg, about one in six mothers and one in three neonates have 25(OH)D levels indicative of VDD. Maternal HIV status appears not to affect levels of 25(OH)D in either the mother or her neonate. Research on the effects of VDD on the outcomes of pregnancy and the best methods to combat the high prevalence of VDD in women of childbearing age in the SA context is required.

Empyema in children hospitalised at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective study.

BACKGROUND: There is a paucity of information on empyema in children from low- and middle-income countries since the introduction of the pneumococcal conjugate vaccine. OBJECTIVES: To describe the aetiology and management of empyema in a setting of high HIV and tuberculosis (TB) prevalence. METHODS: A retrospective descriptive study was undertaken between January 2012 and December 2016 in children aged <14 years at a large secondary-tertiary referral hospital in Soweto, South Africa. Cases of empyema were identified through administrative databases. Clinical, laboratory and radiological data were extracted from patient records. RESULTS: We identified 65 cases of protocol-defined empyema, including 22 (33.8%) referred from surrounding hospitals. The median age at presentation was 53.2 months (interquartile range (IQR) 19.5 - 103.6). Thirteen patients (20.0%) were HIV-infected and 6 (9.2%) were HIV-exposed but uninfected. A bacterial pathogen was identified in 36 cases (55.3%). The commonest causative organisms were Staphylococcus aureus (14/65, 21.5%) and Streptococcus pneumoniae (5/65, 7.7%). Treatment for TB, initiated in 28 children (43.1%), was more frequent in HIV-infected children (10/13, 76.9%) (p=0.011); however, microbiological evidence of TB was present in only 5 cases (7.7%). Forty-three children (66.2%) had an intercostal drain (ICD) inserted and 16 (24.6%) a pigtail percutaneous catheter, while a fibrinolytic was only used in 6 (10.2%). Eight children (12.3%) had a thoracotomy and 7 (10.7%) had video-assisted thorascopic drainage, all of whom had a prior ICD inserted, a median of 20 days (IQR 10 - 33) before surgery. Overall, 7 children (10.8%) were mechanically ventilated and 1 (1.5%) died. CONCLUSIONS: Our study showed a dominance of S. aureus as a cause of empyema. A high proportion of HIV-infected children with empyema were initiated on TB treatment, highlighting challenges in managing TB-HIV co-infection. Although fibrinolytics or early surgery are recommended, neither practice was common in this setting.

Incidence of tuberculosis meningitis in a high HIV prevalence setting: time-series analysis from 2006 to 2011.

SETTING: This study was undertaken at a tertiary hospital in Soweto, a peri-urban low-middle income setting. Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis. OBJECTIVE: To describe the incidence, mortality and clinical features of TBM in human immunodeficiency virus (HIV) infected and non-infected children in South Africa from 2006 to 2011. DESIGN: A retrospective, cross-sectional descriptive study. METHODS: Electronic databases and individual patient records of all children with a discharge diagnosis of TBM were reviewed to yield incidence rate ratios (IRR) in HIV-infected and non-infected children. Clinical, laboratory and radiological characteristics were compared between HIV-infected and non-infected children with TBM. RESULTS: Overall TBM incidence per 100 000 population in 2006 was 6.9 (95%CI 4.4-10.3) and 9.8 (95%CI 6.9-13.6) in 2009, but had subsequently declined to 3.1 (95%CI 1.6-5.5) by 2011. There was a significant reduction in the IRR of TBM among HIV-infected children (IRR 0.916, P = 0.036). The overall case fatality ratio was 6.7%. Clinical features, cerebrospinal fluid and computed tomography brain findings were similar in HIV-infected and non-infected children. CONCLUSION: TBM incidence decreased over the study period from 2006 to 2011, and was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels.

PURPOSE: Recombinant gamma interferon (rIFN-gamma) inhibits IgE synthesis in vitro by human peripheral blood mononuclear cells (PBMC). These data suggest a role for rIFN-gamma in the treatment of patients with severe atopic dermatitis (AD) and elevated IgE levels. The purpose of this study was to determine the effect of rIFN-gamma treatment on IgE production in patients with AD. PATIENTS AND METHODS: Twenty-two patients with chronic severe AD were treated with rIFN-gamma. In part I of the study, 14 patients were treated with daily subcutaneous injections at three successive dose levels (0.01 mg/m2, 0.05 mg/m2, and 0.1 mg/m2) for 5 days with 2 days off between each dose level. In part II, eight patients received rIFN-gamma at 0.05 mg/m2, daily for 6 weeks. One patient from part I and eight patients from part II of the study received three times per week maintenance thereby for up to 14 months. Prior to and at selected times during and after treatment, the clinical and immunologic status of the patients was assessed. RESULTS: In part I, spontaneous de novo IgE synthesis by PBMC was inhibited in 10 patients receiving rIFN-gamma at 0.01 mg/m2 (p = 0.038) and in nine at 0.1 mg/m2 (p = 0.066). There was no reduction of serum IgE levels at any of the three dose levels. Total clinical severity showed improvement at each dose level (p less than 0.04) with worsening 3 days after discontinuation of treatment. In part II, there was no significant inhibition of spontaneous IgE synthesis by PBMC nor was there any reduction of serum IgE. Nevertheless, there was a progressive and significant reduction (p less than 0.01) in total clinical severity over the 6 weeks of daily rIFN-gamma with a sustained improvement during maintenance therapy. CONCLUSION: The results of this pilot study suggest that rIFN-gamma may be efficacious in the treatment of AD and that further clinical trials are warranted.

Flunisolide aerosol for treatment of severe, chronic asthma in steroid-independent children.

The efficacy and safety of flunisolide aerosol were studied in 46 steroid-independent children with asthma inadequately controlled by nonsteroid drugs. This was a double-blind, placebo-controlled, parallel study lasting eight weeks. Patients were randomly assigned either flunisolide by inhalation, 0.5 mg twice a day, or placebo. Effectiveness was evaluated daily by symptom scores, by Wright peak flow measurements twice daily, and weekly by spirometry and physical examination. Adrenal function and throat cultures for Candida were evaluated before and after the test-drug treatment period. Flunisolide was administered to 25 patients and 21 received placebo. Most symptom scores were statistically significantly better in flunisolide-treated than in placebo-treated patients; these included severity of wheezing (P = .01), chest tightness (P = .01) and shortness of breath (P = .02), and frequency (P = .001) and severity of asthma attacks (P = .03). In addition, placebo-treated patients used significantly more bronchodilators than flunisolide-treated patients. In the final therapeutic effectiveness evaluation, 72% of flunisolide-treated patients received very good or good ratings, whereas only 29% of placebo-treated patients received these ratings (P = .005). No patient developed thrush, evidence of adrenal suppression, or other severe adverse reaction. Flunisolide aerosol was shown to be effective and safe in controlling asthma in children who were candidates for oral steroid therapy.

Short-term double-blind evaluation of flunisolide aerosol for steroid-dependent asthmatic children and adolescents.

The purpose of this study was to compare the effectiveness of flunisolide aerosol prescribed as .5 mg (two inhalations) twice daily and placebo in terms of oral steroid sparing ability in a population of 32 known steroid-dependent children and adolescents. Patients were stabilized on the lowest tolerated dose of daily AM or alternate AM oral corticosteroid for at least one month before entering the study. They were randomly assigned to either flunisolide or placebo treatment for the 12-week, double-blind trial. Patients were seen every two weeks for symptom assessment, physical examination, and pulmonary function testing. Tests of adrenal function were done initially and at the study's conclusion. The flunisolide group had improved asthma control compared with the placebo group. The daily oral steroid requirement decreased in 100 percent of the flunisolide group compared with 53 percent of the placebo group (P less than .01). Pulmonary function and endocrine function remained stable for both groups. There were no adverse effects. Flunisolide aerosol in doses of .5 mg twice daily appears to be topically active and to have oral steroid potential without apparent adverse effects.

Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers.

OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY DESIGN: This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except for a higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product.

Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities.

Sixty-four women with primary dysmenorrhea participated in a double-blind, parallel trial of maproxen sodium versus placebo during three menstrual cycles. Comparative measures employed to assess the efficacy of the medications included changes in pain intensity during each dysmenorrheic episode, the degree of pain relief afforded, the necessity of using a supplementary analgesic, and the extent to which medication enabled the patients to continue their daily activities unimpeded. By these measures, naproxen sodium was significantly superior as compared to the placebo. Particularly striking was the fact that of 22 naproxen sodium treated women who historically had to stay at home from work and/or in bed, only 5 remained incapacitated compared with 21 of 26 patients of the placebo group. Only 1 patient experienced side effects (nausea and hypomenorrhea) from naproxen sodium.

A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients.

Many aspects of the normal immune response are depressed after severe injury. Reduced monocyte human leukocyte antigen-DR (HLA-DR) levels have closely correlated with the development of major infection. After a pilot study with recombinant interferon-gamma (rIFN-gamma) showed restoration of depressed HLA-DR levels after major injury, a multicenter, prospective, randomized, double-blind trial was conducted. Two hundred thirteen trauma patients who were at high risk of infection received either placebo or rIFN-gamma (100 micrograms) subcutaneously each day for 10 days after admission. One hundred ninety-three patients were evaluable with respect to primary end points. Patients treated with rIFN-gamma were older (p = 0.10) and had more severe modes of injury (p = 0.02). By the third day, both monocyte HLA-DR antigen expression and outcome predictive score were significantly better in the rIFN-gamma-treated group than in the placebo group (p = 0.0001 and p = 0.0006, respectively). Nine deaths occurred in patients treated with rIFN-gamma compared with 12 deaths in the placebo group (p = 0.46). Major infections requiring surgical drainage or debridement occurred in 17 patients treated with rIFN-gamma compared with 22 treated with placebo. No difference between treatment arms was noted in overall major or minor infection rates, but there were fewer severe infections that required reoperation or computer tomographic-guided drainage in patients receiving IFN-gamma. While these results suggest that rIFN-gamma may be useful in some aspects of infection in the patient with severe trauma, a larger trial with longer treatment will be needed to prove the comprehensive value of rIFN-gamma.

Effectiveness of sodium hypochlorite in preventing inoculation of periapical tissues with contaminated patency files.

The aim of this study was to analyze the effectiveness of 5.25% sodium hypochlorite (NaOCI) in preventing inoculation of periapical tissues with contaminated patency files. Twenty-eight extracted human permanent teeth with single canals were used in the study. Group I teeth were filled with NaOCl, and #15 stainless steel files contaminated with Streptococcus sanguis (ATCC #10556) were allowed to pass through the NaOCI into the culture medium. The teeth in group II were also filled with NaOCl, but the contaminated files used in group II canals were immersed in NaOCl for 10 s prior to being placed into the canals and cultured. The negative control group used sterile files (0% growth), the first positive control group used contaminated patency files in teeth with empty canals (100% growth), and the second positive control group placed contaminated files into broth next to teeth filled with NaOCl (to evaluate potential chlorine leakage; 100% growth). The experimental results showed no positive growth of S. sanguis for groups I and II, indicating that the NaOCl present in the canal after irrigation was sufficient to kill the test organism.

Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium.

Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles. The women were divided into two groups: 15 women were given naproxen sodium (the sodium salt of d-2-(6-methoxy-2-naphthyl) propionic acid) and 17 women received placebo tablets. The women were prescribed two tablets (550 mg) at the first sign of menstrual pain and one tablet (275 mg) thereafter every six hours, as required. There were no significant differences between the two groups in physical characteristics, obstetric and gynecologic histories, including the character of dysmenorrhea and pretreatment pain intensity scores (p = 0.7). Following intake of the drug or placebo, the participants rated the relief provided by the medication with a six-point scoring system. When the scores for pain relief were tallied for the three treatment cycles, the naproxen sodium group averaged 13.7 +/- 0.65 standard error, while the placebo group averaged 8.8 +/- 0.95 standard error out of a possible maximum relief score of 18. The difference between the two groups was statistically significant at p = 0.0004. Few patients reported side effects.

Butoconazole vaginal cream in the treatment of vulvovaginal candidiasis. Comparison with miconazole nitrate and placebo.

A double-blind, parallel study was conducted comparing a new imidazole derivative, butoconazole nitrate, with placebo and miconazole nitrate for the treatment of vulvovaginal candidiasis. Patients were randomly assigned to six treatment regimens. Butoconazole was found to be an effective antifungal agent in both the six- and three-day treatment schedules. The incidence of local side effects from both tested imidazoles was low.

Episodic asthma as a bronchial provocation test.

This study, originally designed to investigate the efficacy of a new inhaled steroid, flunisolide, in New Orleans, demonstrated that episodic asthma (known as "New Orleans Asthma") still occurs in that city. Although its outbreaks are less frequent and severe than reported in previous years, they are still intense enough to affect asthmatics who are on maximal drug therapy. We found in this study that patients who were taking a sympathomimetic, methyl xanthine, and steroids both by inhalation (flunisolide) and by mouth (prednisone) required more prednisone during outbreaks. During such outbreaks the use of flunisolide not only delayed the need for more prednisone but also reduced the dosage needed. Furthermore, flunisolide had over-all prednisone-sparing benefits during the course of the whole 18-week study. Finally, throughout the study, asthma was less frequent in patients on flunisolide therapy, their over-all therapeutic response being significantly better than that of a control group. The authors conclude that New Orleans Asthma provides a natural provocation for extrinsic asthmatics in their normal milieu and thus provides an ideal situation for testing new anti-asthmatic treatments, especially in individuals with severe asthma in whom deliberate challenge may be unethical.

Naproxen sodium in uterine pain following intrauterine contraceptive device insertion.

In a double-blind parallel trial, repeated doses of naproxen sodium (550 mg initially, followed by 275 mg every 6 hours as needed) and placebo were administered to a group of intrauterine contraceptive device (IUD) users in whom dysmenorrhea and premenstrual uterine pain developed or increased following the insertion of the IUD. Seventeen subjects were treated with naproxen sodium and 16 received placebo. The study covered three episodes of uterine pain and/or cramping. Efficacy of pain relief was judged by: (1) the overall relief which the patients experienced during the treatment and (2) the changes in the pain intensity (measured on a 6 point scale). By both these criteria, naproxen sodium was statistically significantly superior to placebo (p = 0.02); consequently, naproxen sodium appears to offer a new treatment modality for pain associated with IUD usage.

Anaprox in dysmenorrhea: reduction of pain and intrauterine pressure.

In a double-blind parallel trial, 24 dysmenorrheic women received a single dose of Anaprox (1,100 mg) or placebo. Over the next 2 hours, pain intensity was scored and intrauterine pressure was measured using an immobilized microballoon. At the end of 2 hours, all 11 patients given Anaprox (but only three of the 13 given placebo) experienced complete pain relief (p = 0.0004). The resting intrauterine pressure (IUP) decreased from a mean of 51.4 to 26.8 mm Hg in the Anaprox-treated group, while in the placebo group the mean resting IUP values remained essentially unchanged ( drop from 55.4 to 51.9 mm Hg was observed). This difference between the two treatment groups was statistically significant in favor of Anaprox (p = 0.03). Several patients from each group were given 0.2 mg of ergonovine by intramuscular injection following the 2 hour trial. In both groups, the resting IUP increased within 30 minutes; the corresponding increase in pain intensity was more pronounced, however, in the placebo group. These results support the premise that a decrease in resting IUP is directly linked to the pain-relieving effects of Anaprox.

PIP: 24 women with regular menstrual cycles but suffering from dysmenorrhea were studied in a double-blind parallel trial to determine the effects of anaprox on pain reduction. 11 patients received anaprox (1100 mg) and 13 received placebos while a microballoon-tipped catheter was inserted into the uterine cavity to measure intrauterine pressure. After 2 hours, all patients experienced complete pain relief and their IUP (intrauterine pressure) decreased from a mean 51.4 to 26.8 mm Hg, while only 3 of the 13 patients experienced relief having a mean IUP decrease from 55.4 to 51.9 mm Hg. Patients who showed the greatest reduction in IUP also showed the most pain relief. 6 of the 11 women were given ergonovine by injection and although their IUP increased their dysmenorrhea was minimal; whereas, in 7 of the 13 women given ergonovine injection, 4 had an increase in dysmenorrhea within 30 minutes.