Healthcare providers' perspectives on discussing HIV status with infected children

The disclosure of HIV status to infected children has received relatively little attention to date in sub-Saharan Africa. We conducted 40 semi-structured interviews with healthcare providers working in a large paediatric HIV clinic in Cape Town, South Africa regarding attitudes and experiences around discussing HIV with infected children. Most providers felt that the optimal age for general discussions about an HIV-infected child's health should happen around age 6, but that specific discussions regarding HIV infection should be delayed to a median of 10 years. Though most providers said that primary caregivers were the most appropriate individuals to lead disclosure discussions, there were strong views that caregivers require support from healthcare providers. These findings indicate the complexities involved in the disclosure of HIV status to infected children, and point to the need for interventions to support caregivers and providers in disclosure discussions.     

Expression of Ki-67, tumor suppressor proteins, growth factor, and growth factor receptor in juvenile respiratory papillomatosis: Ki-67 and p53 as predictors of aggressive disease.

The enhanced proliferation of epithelial cells is a typical feature of respiratory papilloma. The mechanism or mechanisms leading to abnormal epithelial proliferation remain unclear. Overexpression of growth factors and their receptors and inactivation of tumor-suppressor proteins are known to cause cell transformation and proliferation. The objectives of this study were to evaluate the expression of these factors in juvenile respiratory papillomas with correlation to cellular proliferation activity, and to determine whether such expression is associated with the clinical course of the disease. The expression of transforming growth factor-alpha, epidermal growth factor receptor, p53 protein, retinoblastoma proteins and Ki-67 was quantified by immunohistochemistry in paraffin-embedded biopsy specimens taken at the initial surgical excision from children in whom respiratory papillomatosis was diagnosed. Clinical information regarding the number of disease sites, tracheobronchial spread, malignant transformation, and frequency of recurrences was reviewed. Thirty-five specimens were suitable for immunohistochemical evaluation. Ki-67 expression was significantly higher in patients with multiple sites of disease and frequent recurrences. High p53 expression was significantly associated with malignant transformation. We concluded that Ki-67 and p53 expression may be predictive of the clinical course in children with respiratory papillomatosis.     

Single-stage laryngotracheal reconstruction in children: a review of 200 cases.

OBJECTIVE: We reviewed our experience with pediatric single-stage laryngotracheal reconstruction (SSLTR) to identify factors that affect postoperative outcomes, including the need for reintubation and tracheostomy. STUDY DESIGN: Retrospective chart review was done. RESULTS: In total, 190 children underwent 200 SSLTRs; 29% were reintubated, and 15% required postoperative tracheostomy. Currently, 96% are decannulated. The use of anterior and posterior costal cartilage grafting, age less than 4 years, sedation for more than 48 hours, a leak pressure around the endotracheal tube at greater than 20 cm H2O, and moderate/severe tracheomalacia significantly increased the rate of reintubation. The duration of stenting did not affect outcomes. Children with anterior and posterior grafts and those with moderate or severe tracheomalacia were more likely to need a postoperative tracheostomy. CONCLUSION: SSLTR can be effective for the treatment of pediatric laryngotracheal stenosis. Diligent preoperative assessment of the patient and the patient's airway and close postoperative care are important to the success of this operation.     

A longitudinal study of lung function in nonsmoking patients with rheumatoid arthritis

STUDY OBJECTIVE:s: Patients with rheumatoid arthritis (RA) have a high prevalence of pulmonary function test (PFT) abnormality, but the long-term significance of this is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, nonsmoking patients with active RA requiring disease-modifying drugs. We looked for temporal change in lung function and characteristics that would predict subsequent development of PFT abnormality or respiratory symptoms. METHODS: In 1990, 52 patients (44 women; age range, 29 to 78 years; median, 56 years) underwent clinical assessment (drug history, RA severity, immunologic, and inflammatory markers) and PFTs (spirometry, body plethysmography, gas transfer). PFT results were expressed as standardized residuals (SRs). Thirty-eight patients were reassessed in 2000. A self-administered questionnaire was used to identify respiratory symptoms. RESULTS: The prevalence of pulmonary function abnormality was higher than expected compared with a reference population, but there was no significant increase in number over 10 years (8.7% in 1990 and 8.8% in 2000). When assessed by group means and compared with reference values, reduced diffusing capacity of the lung for carbon monoxide (DLCO) and increased ratio of residual volume (RV) to total lung capacity (TLC) [RV/TLC] were the only abnormalities to develop over the study period (mean DLCO in 2000, - 0.47 SR; 95% confidence interval [CI], - 0.91 to - 0.01; RV/TLC, 0.49 SR; 95% CI, 0.13 to 0.84). However, rates of change of pulmonary function variables were not significantly different from zero. Logistic regression did not identify any meaningful relationship between disease characteristics and PFT abnormality. CONCLUSIONS: Asymptomatic patients with RA have a higher prevalence of PFT abnormality than expected, but these do not increase in number over time. We did not identify any patient or disease-specific characteristic that could predict the development of respiratory disease in patients with RA. Analysis using percentage of predicted values, rather than SRs, is misleading as it exaggerates the extent of abnormality present. Abnormal lung function is a common and probably benign finding in nonsmoking, asymptomatic patients with RA.     

Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.

The chemical reactivity of thymine (T), when mismatched with the bases cytosine, guanine, and thymine, and of cytosine (C), when mismatched with thymine, adenine, and cytosine, has been examined. Heteroduplex DNAs containing such mismatched base pairs were first incubated with osmium tetroxide (for T and C mismatches) or hydroxylamine (for C mismatches) and then incubated with piperidine to cleave the DNA at the modified mismatched base. This cleavage was studied with an internally labeled strand containing the mismatched T or C, such that DNA cleavage and thus reactivity could be detected by gel electrophoresis. Cleavage at a total of 13 T and 21 C mismatches isolated (by at least three properly paired bases on both sides) single-base-pair mismatches was identified. All T or C mismatches studied were cleaved. By using end-labeled DNA probes containing T or C single-base-pair mismatches and conditions for limited cleavage, we were able to show that cleavage was at the base predicted by sequence analysis and that mismatches in a length of DNA could be readily detected by such an approach. This procedure may enable detection of all single-base-pair mismatches by use of sense and antisense probes and thus may be used to identify the mutated base and its position in a heteroduplex.     

Amphotericin B vs high-dose ketoconazole for empirical antifungal therapy among febrile, granulocytopenic cancer patients. A prospective, randomized study

We compared high-dose ketoconazole (800 mg/kg per day, orally) with amphotericin B (0.5 mg/kg per day, intravenously) for empirical antifungal therapy in a prospective, randomized study of persistently or recurrently febrile granulocytopenic cancer patients. Among 97 patients eligible for empirical antifungal therapy, 20 (21%) of these patients were ineligible for randomization to ketoconazole treatment because of their inability to tolerate oral medications. Among 72 patients eligible for randomization, 64 were assessable (32 in each arm of the study). Five of six patients with proved fungal infections who were randomized to receive ketoconazole treatment required crossover to amphotericin B treatment because of progressive infection. The conditions of three of these five patients improved after receiving amphotericin B. The frequency of transaminase elevation was higher in those receiving ketoconazole, while the frequency of azotemia was higher in those receiving amphotericin B. Bioavailability of ketoconazole was unpredictable. Amphotericin B remains the drug of choice for empirical antifungal therapy in granulocytopenic patients; whereas, lack of a parenteral formulation, ineffectiveness against proved mycoses, and unreliable bioavailability preclude high-dose ketoconazole from being an appropriate compound for this purpose.