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.     

The pelvic epithelium of the rat kidney: A scanning and transmission electron microscopic study

The renal pelvis of the rat is characterized by extensions called specialized fornices that penetrate into the outer zone of the outer medulla (a type II as classified by Pfeiffer, 1968, 1970). The renal pelvic epithelium, therefore, covers areas of the kidney from the inner medulla, the inner and outer stripe of the outer medulla, and the cortex. The renal pelves of seven rats were studied by transmission and scanning electron microscopy. The transitional epithelium on the nonparenchymal surface of the pelvis was three to four cell layers thick (zone 0–1). This epithelium became thinner where it covered the renal cortex (zone 1–2) or the outer medulla. Although the apical cells of the epithelium retained the asymmetric luminal unit-membrane plaques, the number of cytoplasmic fusiform vesicles decreased as one studied the epithelium progressing over the zones from cortex toward papilla. Scanning electron microscopy demonstrated a small number of surface cells of a different morphology that were characterized by apical microvilli. The number of these microvillous lining cells increased as the epithelium covering the outer (zone 2–3) and inner (zone 3–4) stripe regions of the outer medulla was viewed, until the inner medulla was entirely covered by this cell type. In a reciprocal manner, the cells with the asymmetric apical plaques decreased in numbers and in their morphologic specialization in each successive region. The epithelium surrounding the inner medulla (zone 6–7) was completely devoid of this transitional cell type. Judging from the morphologic characteristics of the epithelia, one could surmise that little exchange of urea, water, and salts would occur with the extrarenal connective tissue or the cortical parenchyma. Recycling of urea might become more important physiologically with the outer stripe parenchyma, and even more so with the increased surfaces of the inner stripe parenchyma that lined the secondary pyramid, as well as with the epithelium lining the inner medulla.     

Mechanical properties of dilated human ascending aorta

Dilation of the ascending aorta, associated with Marfan Syndrome, bicuspid aortic valve, or advanced age, may lead to aortic dissection and rupture. Mathematical models can be used to assess the relative importance of increased wall stresses and decreased strength in these mechanical failures. To obtain needed inputs for such models, mechanical properties of dilated human ascending aorta were measured in vitro. Specimens for opening angle, biaxial elastic, and uniaxial circumferential strength tests were cut from excised tissue obtained from 54 patients (age 18–81 years) undergoing elective aortic graft replacement surgery. Opening angle was significantly greater in patients older than 50 years (262°±76°, n=21) compared to younger patients (202°±70°, n=13 All biaxial elastic specimens n=40 exhibited nonlinear stress-strain behavior. Rapid increases in circumferential and axial stresses occurred at lower strains in the older patient group than in the younger. Mean strength was significantly lower in older patients (1.35±0.37 MPa, n=14) than younger (2.04 ± 0.46 MPa, n=11, age <50 years). These changes in mechanical properties suggest that age may influence the risk of aortic dissection or rupture of dilated ascending aorta. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8719Hh     

Neutrophils Injure Bronchial Epithelium after Ozone Exposure

Neutrophil (PMN) influx is an early, prominent finding in the airways of humans after experimental inhalation of ozone (O3), however the potential for PMN to contribute to epithelial injury in this setting is unknown. Bronchial epithelial cells of the human BEAS 2B R1.4 cell line or primary human bronchial epithelial cells underwent DNA labeling by incubation with BrdU. Monolayers were exposed to O3 (0.05 to 1 ppm) or filtered air for 60 min., and subsequently incubated with PMN for 2 h. Epithelial cell cytolysis was significant only in BEAS exposed to O3 and co-cultured with PMN. Apoptosis was maximal in BEAS exposed to O3 + PMN. Primary bronchial epithelial cells were resistant to injury; no cytolysis was detected, and apoptosis was detected only after treatment with 10 mM H₂O₂. Neutrophils may increase damage to the respiratory epithelium after O3 exposure, but primary bronchial epithelial cells are resistant to PMN and ozone induced injury.     

From segment to somite: segmentation to epithelialization analyzed within quantitative frameworks.

One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization.     

Summary of complementation groups of UV-sensitive CHO cell mutants isolated by large-scale screening

A summary is given for the lineage and complementation groupassignments of 153 UV-sensitive mutants of the CHO AA8 cellline. The distribution of mutants among six complementationgroups was highly non-random, with the great majority of theisolates belonging to groups 1 and 2. This asymmetry is consistentwith the known hemizygosity of these two linked loci in CHOcells. The relative numbers of mutants induced in group 2 wasfound to depend greatly on the type of mutagen used. Mutagenesiswith UV radiation, ethyl methanesulfonate (EMS), N-methyl-N'-nitro-N-nitroso-guanidine and 7-bromomethylbenz[a]anthraceneproduced high frequencies of group 2 mutants. In contrast, ICR170and ICR191, which are thought to produce mostly frameshift mutations,yielded very few mutants in group 2. These results are of particularimportance in light of the recent finding that the human ERCC2gene, which corrects group 2 mutants, has very strong homologywith the yeast gene RAD3. RAD3 is an essential gene for viabilityin yeast, and the low recovery of group 2 mutants using theframeshift agents strongly suggests that frameshift mutationstend to be lethal in the hamster ERCC2 locus. Several mutagen-sensitivedouble mutants were isolated in two-step selections from EMS-,mitomycin C- or UV-sensitive parental cells, including the lineUVU1, the first mammalian line with two mutations that affectUV sensitivity. The first mutation inactivated excision repair,and the second mutation appears to have affected some otherrecovery process. UVU1 should be useful for studying recoveryprocesses that are separate from nucleotide excision repair. ¹To whom correspondence should be addressed     

Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family

A 7-month-old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which documented a deletion corresponding to cDNA probe 1-2a in the dystrophin gene, in the propositus and in an affected male cousin of his mother. “Idiopathic” hyperCKemia was found in the propositus, his father, and 5 of his relatives. We suggest that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of the maternal DMD gene and of a paternal gene, causing hyperCKemia. © 1995 Wiley-Liss, Inc.     

Genetic linkage analysis identifies new proximal and distal flanking markers for the X-linked agammaglobulinemia gene locus, refining its localization in Xq22

Genetic linkage analysis has been instrumental in mapping thegene for X-linked agammaglobulinemia (XLA) to the proximal longarm of the human X chromosome, to Xq22. Due to the relativerarity of this disease the localization of the gene within Xq22has remained imprecise. We have investigated twenty-nine familiesaffected by XLA and have found no recombinants with the DXS178locus in over 30 informative meioses. DXS178 is now the mostreliable and informative locus for use in pre-natal diagnosisand carrier detection of XLA. In addition, we have identifiednew closely linked proximal and distal flanking markers forXLA, DXS442 and DXS101, respectively. These loci are separatedby 2cM, considerably reducing the extent of DNA within whichthe XLA locus can be contained. This will open up the way formore directed positional cloning efforts for the isolation ofthe XLA gene.