Brief report: Youth pathways out of homelessness – Preliminary findings

While there exists an extensive body of knowledge regarding the risks associated with youth homelessness, very little work has addressed the process of exiting street contexts. This paper reports baseline findings from an ongoing longitudinal study assessing factors associated with a successful transition out of homelessness. Fifty-one formerly homeless youth who obtained stable housing in the past 2 months to 2 years participated in this study which took place in two Canadian urban centres. Findings include poorer functioning across all domains for youth residing in housing contexts without supports, a lack of relationship between psychological and behavioural aspects of community integration, and the central role of self-concept in mental health and quality of life. These findings suggest the need for ongoing support for youth exiting street spaces and social contexts, with attention to the importance of self-concept and psychological aspects of community integration.     

Nitric oxide deficiency contributes to large cerebral infarct size

The purpose of this study was to examine the role played by a deficit in nitric oxide (NO) in contributing to the large cerebral infarcts seen in hypertension. Cerebral infarction was produced in rats by occlusion of the middle cerebral artery (MCA). Studies were performed in Sprague-Dawley (SD) rats subjected to NO synthase blockade (N(G)-nitro-L-arginine [L-NNA], 20 mg x kg(-1) x d(-1) in drinking water) and in spontaneously hypertensive stroke-prone rats (SHRSP). NO released in the brain in response to MCA occlusion was monitored with a porphyrinic microsensor in Wistar-Kyoto rats. The increment in NO released with MCA occlusion was 1.31+/-0.05 micromol/L in L-NNA-treated rats, 1.25+/-0.04 micromol/L in SHRSP, 2. 24+/-0.07 micromol/L in control SD rats, and 2.25+/-0.06 micromol/L in Wistar-Kyoto rats (P<0.0001 for control versus the other groups). Infarct sizes in the L-NNA-treated and control SD rats were 8.50+/-0. 8% and 5.22+/-0.7% of the brain weights, respectively (P<0.05). The basilar arterial wall was significantly thicker in L-NNA-treated rats compared with their controls. We conclude that both the deficit in NO and the greater wall thickness contribute to the larger infarct size resulting from MCA occlusion in SHRSP and in L-NNA-treated rats compared with their respective controls.     

Borrelia burgdorferi and the causative agent of human granulocytic ehrlichiosis in deer ticks, Delaware

During the 1998 hunting season in Delaware, 1,480 ticks were collected from 252 white- tailed deer; 98% were Ixodes scapularis, a significant increase from the 85% reported in 1988. Ticks were tested for Borrelia burgdorferi and the causative agent of human granulocytic ehrlichiosis. Infection rates remained stable in New Castle and Kent counties, but increased from <1% to 8% in sussex county.     

PPD-induced monocyte chemotactic factor production by human milk cells

The functional capability of antigen-stimulated breast milk cells to produce an immunologic mediator was examined. Colostrum and comparison peripheral blood samples were obtained from ten women, two to four days postpartum, and supernatants from PPD-stimulated mononuclear cell cultures were assayed for the lymphokine, monocyte chemotactic factor. Five of the ten women studied had a history of a positive tuberculin skin test and one had received BCG immunization. Peripheral blood lymphocyte cultures and colostrum cell cultures from four of these six women produced monocyte chemotactic factor. These results demonstrated the functional capability of antigen-stimulated colostral cells to produce immunologic mediators.     

Spinal cord stimulation electrode design: prospective,randomized, controlled trial comparing percutaneous and laminectomy electrodes-part I: technical outcomes

OBJECTIVE: The clinical use of spinal cord stimulation for treatment of chronic intractable pain has been increasingly successful because of recent technical improvements, particularly the development of multiple-contact electrodes supported by programmable implanted pulse generators. Contemporary electrodes can be placed percutaneously in some cases and require a limited laminectomy in other cases. METHODS: We performed a prospective, randomized, controlled trial comparing two prototypical electrode designs, using a computerized system that allows direct patient interaction and quantitative measurements. A series of 24 patients with chronic lumbosacral pain syndromes first underwent testing with percutaneous four-contact electrodes and then underwent implantation, at the same spinal level, of one of two different electrode configurations; 12 patients received a new percutaneous four-contact electrode of the same design and 12 received an insulated four-contact array, which was implanted via laminectomy. RESULTS: The insulated array performed significantly (P = 0.0005-0.0047) better than the temporary percutaneous electrode for the same patients, according to all three measures tested (ratings of paresthesia coverage of pain, coverage calculated from patient drawings, and amplitudes), at the "usage" amplitude for the three standard bipoles examined. The insulated array also performed significantly (P = 0.0000-0.026) better than the permanent percutaneous electrode in terms of coverage ratings and amplitude requirements. Low back coverage ratings were significantly better for the insulated array than for the temporary percutaneous electrode, and scaled amplitudes necessary for low back coverage were significantly better for the permanent percutaneous electrode than for the temporary electrode. In comparison with the percutaneous temporary electrode, at subjectively identical stimulation intensities, the permanent insulated array required significantly lower amplitude. CONCLUSION: We can immediately infer from these technical data that the use of an insulated array, in comparison with a percutaneous electrode, would double battery life. Extended follow-up monitoring will be required to assess the extent to which the technical advantages we observed for the insulated array might be associated with improved clinical outcomes.     

De novo deletion within the telomeric region flanking the human alpha globin locus as a cause of alpha thalassaemia

We have identified and characterized a Scottish individual with alpha thalassaemia, resulting from a de novo 48 kilobase (kb) deletion from the telomeric flanking region of the alpha globin cluster which occurred as a result of recombination between two misaligned repetitive elements that normally lie approximately 83 kb and 131 kb from the 16p telomere. The deletion removes two previously described putative regulatory elements (HS-40 and HS-33) but leaves two other elements (HS-10 and HS-8) intact. Analysis of this deletion, together with eight other published deletions of the telomeric region, showed that they all severely downregulated alpha globin expression. Together they defined a 20.4-kb region of the human alpha cluster, which contains all of the positive cis-acting elements required to regulate alpha globin expression. Comparative analysis of this region with the corresponding segment of the mouse alpha globin cluster demonstrated conserved non-coding sequences corresponding to the putative regulatory elements HS-40 and HS-33. Although the role of HS-40 as an enhancer of alpha globin expression is fully established, these observations suggest that the role of HS-33 and other sequences in this region should be more fully investigated in the context of the natural human and mouse alpha globin loci.     

Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN

Important roles have been suggested for caspase-8, caspase-9 and Apaf-1 in controlling tumor development and their sensitivity to chemotherapeutic agents. Methylation and deletion of Apaf-1 and CASP8 results in the loss of their expression in melanoma and neuroblastoma, respectively, while CASP9 localization to 1p36.1 suggests it is a good candidate tumor suppressor. The status of CASP9 and Apaf-1 expression in numerous neuroblastoma cell lines with/without amplified MYCN and chromosome 1p36 loss-of-heterozygosity (LOH) was therefore examined to test the hypothesis that one or both of these genes are tumor suppressors in neuroblastoma. Although CASP9 is included in the region encompassing 1p36 LOH in all neuroblastoma cell lines examined, the remaining CASP9 allele(s) express a functional caspase-9 enzyme. Apaf-1 is also expressed in all neuroblastoma tumor cell lines examined. Thus, the CASP9 or Apaf-1 genes do not appear to function as tumor suppressors in MYCN amplified neuroblastomas. However, approximately 20% of the neuroblastoma cell lines with methylated CASP8 alleles are also highly resistant to staurosporine (STS)- and radiation-induced cell death, presumably because cytochrome c is not released from mitochondria. This suggests that a second, smaller sub-group of MYCN amplified neuroblastoma tumors exists with defect(s) in apoptotic signaling components upstream of caspase-9 and Apaf-1. Since no consistent differences in Bcl-2, Bcl-x(L) or Bax expression were seen in the STS- and radiation-resistant neuroblastomas, it suggests that a unique mitochondrial signaling factor(s) is responsible for the defect in cytochrome c release in this sub-group of tumors.