Validity of the 'Ten Questions' for screening serious childhood disability: results from urban Bangladesh

A survey of 2576 children aged two to nine years was carried out in Dhaka, Bangladesh, as part of a collaborative study to test the validity of a questionnaire (the Ten Questions) for screening severe childhood disabilities in community settings. Approximately 7% of the children were positive on the screen and this rate was slightly higher in boys than girls. The sensitivity, specificity and negative predictive value of the Ten Questions were perfect or nearly perfect for severe and moderate (serious) disabilities. The positive predictive value was only 22% for serious disabilities, but 70% of children classified as false positives were found to have mild disabilities or other conditions (such as ear infections) for which early detection and treatment could be beneficial. No major age or gender differences in the validity of the questionnaire were apparent, but this finding needs additional study and confirmation with studies based on larger samples. In general, the results indicate that the Ten Questions is a valid tool for screening serious disabilities in children and can potentially improve the efficiency of health services by reducing the number of children requiring attention from professionals. Future studies using the Ten Questions should foster greater attention to the dimensions of childhood disability as a public health problem in the less developed world.     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

The impact of the Safe Kids/Healthy Neighborhoods Injury Prevention Program in Harlem, 1988 through 1991.

OBJECTIVES. This study evaluated the effectiveness of a community coalition to prevent severe injuries to children in Central Harlem, New York, NY. It was hypothesized that injury incidence rates would decline during the intervention (1989 through 1991) relative to preintervention years (1983 through 1988); that the decline would be greatest for the targeted age group (5 through 16 years) and targeted injury causes (traffic accidents, assaults, firearms, outdoor falls); and that the decline would occur in the intervention community rather than a control community. METHODS. Surveillance of injuries that result in hospitalization and/or death among children in the two communities has been under way since 1983. Data from this surveillance were used to test whether the incidence of severe injury declined during the intervention; other temporal variations were controlled by Poisson regression. RESULTS. The incidence of injury among school-aged children in central Harlem declined during the intervention. The decline was specific to the targeted age group and targeted causes. A nonspecific decline also occurred in the control community. CONCLUSIONS. The declining incidence rate in Central Harlem is consistent with a favorable program effect, but additional investigation of possible secular trend or spillover effects is needed.     

Optometry in nursing homes.

Studies predict a 50 percent increase in residential long-term care need by the year 2000. Statistics show that the age group served by these facilities is at a much higher risk for sight threatening eye conditions. A review of the current literature as well as original data collected in Ohio indicates that residents in long-term care facilities are underserved with regard to eye care. This paper discusses the need for increased optometric participation in the primary eye care services for residents of long-term care facilities.     

Early and late dilatation for acquired subglottic stenosis

There has been widespread use of periodic dilatations in the management of subglottic stenosis. However, some authorities have questioned the value in the overall rehabilitation of patients affected by this disorder. The first phase of this study included fourteen large dogs in which acute subglottic lesions were created by use of a high-speed electric drill and electrocautery. Twelve animals served as the experimental group and two animals were controls. Obstructing lesions developed in all the animals within 7 to 21 days. When at least a 50% obstruction developed in an animal, a treatment plan was instituted that included at least weekly dilatation, removal of granulations, and administration of intralesional steroids and/or systemic steroids and antibiotics. The two control animals became totally obstructed and were killed. Varying degrees of subglottic stenosis developed in all twelve experimental animals after 8 weeks of dilatation, but none required a tracheotomy. These twelve animals were then subjected to 8 additional weeks of dilatation and antibiotics, and supplemental steroids were used in some animals from this study. It can be concluded that early periodic dilatation and granulation removal in the acutely injured subglottis is effective in prevention of severe stenosis, late periodic dilatations in chronic subglottic stenosis are not helpful in further alleviation of obstruction, the concomitant use of antibiotics and systemic steroids did not appreciably prevent or alter the development of subglottic stenosis, and the concomitant use of intralesional steroids appeared to be of benefit in the management of chronic acquired subglottic stenosis.     

Characterization of the mitogenic signal from an oncogene ras protein

Wild-type or cellular RAS proteins function at the end of the G1 phase of the cell cycle, but they cannot signal quiescent cells to start cycling. By contrast, the oncogenic or "activated" RAS proteins produced by certain mutant ras genes can start quiescent cells cycling and appear to be involved in a large fraction of human cancers. One of these "activated" RAS proteins is the temperature-sensitive viral K-RAS protein produced by tsKSV-NRK rat kidney fibroblasts. Reactivating this viral K-RAS protein in serum-starved quiescent cells by lowering the temperature from a non-permissive 41 degrees C to a permissive 36 degrees C is a powerful mitogenic signal which starts the progression of cells through the various stages of the cell cycle even in the absence of serum growth factors. This first signal is associated with transient surges of cytosolic Ca2+ and membrane-associated protein kinase C activity, but is not mediated by signals from the protein-tyrosine kinase receptors of known K-RAS-induced autocrine mitogens such as TGF alpha and PDGF. While the importance of the Ca2+ transient is uncertain, the transient surge of membrane-associated protein kinase C activity appears to be involved in the process by which the viral RAS protein triggers the G0 to G1 transition. The need for the viral K-RAS protein does not end with this first signal. The protein also operates briefly at the end of the G1 phase and then, after chromosome replication, it also stimulates events necessary for the initiation of mitosis.     

New rat model of Pneumocystis carinii infection.

Rats free of latent Pneumocystis carinii organisms were immunosuppressed with adrenal corticosteroids and transtracheally injected with P. carinii. These animals subsequently developed P. carinii pneumonia. Infection was accomplished by using organisms from infected rat lung or from culture. Diffuse infection was produced with no significant differences in the numbers of organisms found in various lobes of the lungs. Infections progressed over time so that by 6 weeks postinoculation all animals were heavily infected. Infection by transtracheal injection has three advantages over current models. First, transtracheal injection provides a reliable model which is not dependent on naturally occurring latent Pneumocystis infection. Second, transtracheal injection allows the perpetuation of specific Pneumocystis strains. Third, transtracheal injection is a more rapid and economical means of producing severe Pneumocystis pneumonia.     

The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability

Fanconi anemia (FA) is a rare multi-genic, autosomal and X-linked recessive disorder characterized by hematological abnormalities, developmental defects and increased cancer susceptibility. Patient-derived FA cells display heightened sensitivity to DNA cross-linking agents such as mitomycin C (MMC). In response to DNA damaging agents, and during S-phase of the cell cycle, the FA pathway is activated via the mono-ubiquitination of FANCD2 (FANCD2-Ub), signaling its translocation to discrete nuclear foci, where it co-localizes with the central DNA repair proteins BRCA1 and RAD51. However, the exact function of activated FANCD2-Ub remains unclear. Here, we have characterized the role of the FA pathway in response to DNA replicative stress by aphidicolin (APH) and hydroxyurea (HU). The FA pathway is strongly activated in response to both agents. In addition, using patient-derived FA cell lines and siRNA targeting FANCD2, we demonstrate a functional requirement for the FA pathway in response to low doses of APH: a replicative stress treatment known to result in chromosome breakage at common fragile sites. Both the total number of chromosome gaps and breaks and breaks at the specific common fragile sites FRA3B and FRA16D were significantly elevated in the absence of an intact FA pathway. Furthermore, we demonstrate that APH activates the mono-ubiquitination of both FANCD2 and PCNA and the phosphorylation of RPA2, signaling processive DNA replication arrest. Following APH treatment, FANCD2-Ub co-localizes with PCNA (early) and RPA2 (late) in discrete nuclear foci. Our results demonstrate an integral role for the FA pathway in the DNA replication stress response.     

Protein kinase C in IL- 2 signal transduction

Interleukin-2 (IL-2), secreted principally by activated helper T-cells, plays a pivotal role in the generation and regulation of the immune response. The various biologic functions of IL-2 have been the focus of intensive study over the years and have been well worked out. By contrast, an understanding of the intracellular signals coupled to the IL-2 receptor and responsible for mediating IL-2 effects in T-cells is far less developed, and the role that protein kinase C (PKC) may play in the various cellular responses to IL-2 receptor activation is unclear. In this article we will discuss IL-2, its receptors, and IL-2 signal transduction in relation to the physiological roles PKC activation may play in IL-2-mediated activation of T-cells and other hematopoietic cells.