Growth, morbidity, and mortality in a cohort of institutionalized HIV-1-infected African children

OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors.     

Genome scanning using endogenous LTR-like elements for rapid DNA-fingerprinting of breast-cancer and transformed human breast epithelial-cells

In the present work genomic DNAs from nine primary breast cancers and transformed human breast epithelial cell lines obtained by treatment of MCF 10F, a spontaneously immortalized human breast epithelial cell line, with benzo(a)pyrene (BP) or 7,12 dimethyl benz(a)anthracene (DMBA), were used for genomic scanning. The treatment of MCF 10F with BP gave rise to different clones designated BP1 and BP1E, the latter being a tumorigenic cell line. Treatment with DMBA gave rise to D3 and D3-1 clones. The clones D3-1 and BP1 have been transfected with the plasmid pH06T1 containing the mutated c-Ha-ras oncogene resulting in the D3-1Tras and BP1T-ras cell lines, that are highly tumorigenic in SCID mice. Genomic DNA are separately hybridized to two different probes representing different families of human endogenous retrovirus like sequences (RTLV-H and HERV-K LTR). The technique of genomic scanning allows the mapping of each tumor or cell line and comparison with its counterpart obtained from the adjacent normal tissue of the same patient or with the untreated MCF 10F cells. DNA changes such as deletions, amplifications and/or rearrangements were detected in 5 of the tumor pairs studied. We have identified genomic alterations that involved amplification of a 10 kb band in the transformed cell lines. The cell lines D3-1Tras and BP1T-ras show, in addition, the presence of a second band of 4.5 kb in size. A third band of 500 bp size was found in clones D3-1 and BP1E that have a more aggressive behavior in vitro than their precursors D3 and BP1 cells respectively. In conclusion the present report indicates that genomic scanning detects DNA aberrations in primary primary tumors and in human breast epithelial cells transformed with chemical carcinogens and/or oncogene transfection that are not present in their normal counterpart. These results further indicate that detection of endogenous retrovirus elements may help in genome mapping and can be a useful tool for detecting genomic changes in the preliminary screening of DNA extracted from primary breast cancer and transformed cells.     

Cell cycle analysis can differentiate thin melanomas from dysplastic nevi and reveals accelerated replication in thick melanomas

Cell replication integrates aberrations of cell cycle regulation and diverse upstream pathways which all can contribute to melanoma development and progression. In this study, cell cycle regulatory proteins were detected in situ in benign and malignant melanocytic tumors to allow correlation of major cell cycle fractions (G1, S-G2, and G2-M) with melanoma evolution. Dysplastic nevi expressed early cell cycle markers (cyclin D1 and cyclin-dependent kinase 2; Cdk2) significantly more (p?<?0.05) than common nevi. Post-G1 phase markers such as cyclin A, geminin, topoisomerase IIα (peaking at S-G2) and aurora kinase B (peaking at G2-M) were expressed in thin (≤1 mm) melanomas but not in dysplastic nevi, suggesting that dysplastic melanocytes engaged in the cell cycle do not complete replication and remain arrested in G1 phase. In malignant melanomas, the expression of general and post-G1 phase markers correlated well with each other implying negligible cell cycle arrest. Post-G1 phase markers and Ki67 but none of the early markers cyclin D1, Cdk2 or minichromosome maintenance protein 6 (Mcm6) were expressed significantly more often in thick (>1 mm) than in thin melanomas. Marker expression did not differ between metastatic melanomas and thick melanomas, with the exception of aurora kinase A of which the expression was higher in metastatic melanomas. Combined detection of cyclin A (post-G1 phase) with Mcm6 (replication licensing) and Ki67 correctly classified thin melanomas and dysplastic nevi in 95.9 % of the original samples and in 93.2 % of cross-validated grouped cases at 89.5 % sensitivity and 92.6 % specificity. Therefore, cell cycle phase marker detection can indicate malignancy in early melanocytic lesions and accelerated cell cycle progression during vertical melanoma growth.     

Incidence and predictors of radial nerve palsy with the anterolateral brachialis splitting approach to the humeral shaft

Purpose: Fractures of the humeral shaft are common and account for 3%e5% of all orthopedic injuries. This study aims to estimate the incidence of radial nerve palsy and its outcome when the anterior approach is employed and to analyze the predictive factors. Methods: The study was performed in the department of orthopaedics unit of a tertiary care trauma referral center. Patients who underwent surgery for acute fractures and nonunions of humerus shaft through an anterior approach from January 2007 to December 2012 were included. We retrospectively analyzed medical records, including radiographs and discharge summaries, demographic data, surgical procedures prior to our index surgery, AO fracture type and level of fracture or nonunion, experience of the operating surgeon, time of the day when surgery was performed, and radial nerve palsy with its recovery condition. The level of humerus shaft fracture or nonunion was divided into upper third, middle third and lower third. Irrespective of prior surgeries done elsewhere, the first surgery done in our institute through an anterior approach was considered as the index surgery and subsequent surgical exposures were considered as secondary procedures. Results: Of 85 patients included, 19 had preoperative radial nerve palsy. Eleven (16%) patients developed radial nerve palsy after our index procedure. Surgeons who have two or less than two years of surgical experience were 9.2 times more likely to induce radial nerve palsy (p=0.002). Patients who had surgery between 8 p.m. and 8 a.m. were about 8 times more likely to have palsy (p=0.004). The rest risk factor is AO type A fractures, whose incidence of radial nerve palsy was 1.3 times as compared with type B fractures (p=0.338). For all the 11 patients, one was lost to follow-up and the others recovered within 6 months. Conclusion: Contrary to our expectations, secondary procedures and prior multiple surgeries with failed implants and poor soft tissue were not predictive factors of postoperative deficit. From our study, we also conclude that radial nerve recovery can be reasonably expected in all patients with a postoperative palsy following the anterolateral approach.     

Household Food Insecurity,Maternal Nutritional Status,and Infant Feeding Practices Among HIV-infected Ugandan Women Receiving Combination Antiretroviral Therapy

Household food insecurity (HHFI) may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore described the prevalence of HHFI and explored if it was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. We assessed these outcomes using bivariate and multivariate analyses among 178 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. HHFI was common; the prevalence of severe, moderate, and little to no household hunger was 7.3, 39.9, and 52.8 %, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower body mass index (BMIs) at enrollment (21.3 vs. 22.5, p < 0.01) and prior to delivery (22.6 vs. 23.8, p < 0.01). BMI across time during pregnancy, but not gestational weight gain, was significantly lower for MSHH [adjusted beta (95 % CI) ?0.79 (?1.56, ?0.02), p = 0.04; ?2.06 (?4.31, 0.19), p = 0.07], respectively. The prevalence (95 % CI) of EBF at 6 months was 67.2 % (59.7–73.5 %), and the proportion of women BF at 12 months was 80.4 % (73.3–85.7 %). MSHH was not associated with prevalence of EBF at 6 months or BF at 12 months. However, among those women still EBF at 4 months (81.4 % of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR 2.38, 95 % CI 1.02–5.58). The prevalence of HHFI, maternal malnutrition, and suboptimal infant feeding practices are high and the causal relationships among these phenomena must be further explored.     

Muscle structural,energetic and functional benefits of endurance exercise training in sickle cell disease

Sickle cell disease (SCD) patients display skeletal muscle hypotrophy, altered oxidative capacity, exercise intolerance and poor quality of life. We previously demonstrated that moderate-intensity endurance training is beneficial for improving muscle function and quality of life of patients. The present study evaluated the effects of this moderate-intensity endurance training program on skeletal muscle structural and metabolic properties. Of the 40 randomized SCD patients, complete data sets were obtained from 33. The training group (n = 15) followed a personalized moderate-intensity endurance training program, while the non-training (n = 18) group maintained a normal lifestyle. Biopsies of the vastus lateralis muscle and submaximal incremental cycling tests were performed before and after the training program. Endurance training increased type I muscle fiber surface area (P = .038), oxidative enzyme activity [citrate synthase, P < .001; β-hydroxyacyl-CoA dehydrogenase, P = .009; type-I fiber cytochrome c oxidase, P = .042; respiratory chain complex IV, P = .017] and contents of respiratory chain complexes I (P = .049), III (P = .005), IV (P = .003) and V (P = .002). Respiratory frequency, respiratory exchange ratio, blood lactate concentration and rating of perceived exertion were all lower at a given submaximal power output after training vs non-training group (all P < .05). The muscle content of proteins involved in glucose transport and pH regulation were unchanged in the training group relative to the non-training group. The moderate-intensity endurance exercise program improved exercise capacity and muscle structural and oxidative properties. This trial was registered at www.clinicaltrials.gov as #NCT02571088.