The influence of governmental policy on community health partnerships and community care networks: an analysis of three cases

This is a comparative analysis of hospitals' efforts in three communities to pursue collaborative ventures to advance community health. The events occurred over a two-year period characterized by increasing market competition and national debate about comprehensive health care financing reform. The study objectives are to better understand factors that contributed to the initiation of the collaborative efforts, and factors that sustained, hindered, or thwarted these efforts. The study explores how the collaborative ventures in these three communities fared in the face of multiple and conflicting policies and the simultaneous creation of larger, competing health systems. A number of concluding generalizations address the impact of interorganizational dynamics and public policy initiatives on community health partnerships.     

Increase of the background human exposure to mercury through fish consumption due to gold mining at the Tapajós River region, Pará State, Amazon

Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant status were investigated in hypertensive, 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Total plasma calcium and magnesium concentrations were similar between both rat strains; however, systolic blood pressure in SHR was greater than in WKY at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg; p < or = 0.05), confirming hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations were lower (p < or = 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio compared with WKY counterparts. No significant differences in the relative proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY. Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were similar in SHR and WKY counterparts. A possible compensatory effect to the oxidative status of SHR was suggested by the significant (p < 0.05) increase in both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities. Despite these results, in vitro oxidative challenge studies with H2O2 demonstrated a greater susceptibility of liver to GSH depletion in the SHR, although no parallel change in thiobarbituric acid reactive substances (TBARS) production was observed. The comparatively lower plasma cholesterol observed in hypertensive SHR paralleled specific differences in liver catalase and glutathione redox antioxidant enzyme activities.     

Mature human hematopoietic cells in donor bone marrow complicate interpretation of stem/progenitor cell assays in xenogeneic hematopoietic chimeras

Xenogeneic hematopoietic chimeras have been used to assay the growth and differentiation of human stem/progenitor cells. The presence of human hematopoietic cells in immunodeficient mice transplanted with human marrow cells may be caused by proliferation and differentiation of early stem/progenitor cells and/or proliferation of mature cells. Unpurified human marrow mononuclear cells, T cell-depleted, or stem/progenitor cell-enriched (CD34+ or CD34+CD38-) populations were injected into sublethally irradiated NOD/LtSz scid/scid (NOD/SCID) mice. High levels of human cells were detected in mice (hu/mu chimeras) transplanted with each of the above human marrow populations. Large numbers of mature human T lymphocytes were found in marrow, spleens, and thymuses from hu/mu chimeras that had been transplanted with unpurified human mononuclear marrow cells. Human immunoglobulin was detected in sera from these chimeras, and some exhibited a clinical syndrome suggestive of graft-versus-host disease. In contrast, in hu/mu chimeras that had received T cell-depleted or stem/progenitor cell-enriched populations, multilineage hematopoiesis (myeloid, B lymphoid, and progenitor cells by immunophenotype) was detected but T lymphocytes and human immunoglobulin were not; in addition, no human cells were detected in the thymuses. Thus, injection of adult human marrow cells into immunodeficient mice can result in hematopoietic chimerism for at least 3 months after transplant. However, the types of cells present in hu/mu chimeras differ depending on the human cell population transplanted. This should be taken into account when hematopoietic chimeras are used to assess human stem/progenitor cell function.     

Results of a genome-wide genetic screen for panic disorder

There is some controversy over whether or not a discrete site that integrates vomiting activities in somatic and autonomic nerves is present in the medulla oblongata. On the basis of our previous studies, we hypothesized that the temporal patterns of muscle contractions in vomiting are generated by a central pattern generator in the retrofacial area of the rostral medulla. To investigate this hypothesis further, the effects of electrical and chemical lesions of the medullary area were observed in decerebrate paralyzed dogs. Efferent activities of the phrenic and abdominal muscle nerves were recorded to recognize fictive vomiting. The right half of the medulla oblongata was transversely severed about 3 mm rostral to the obex. Fictive vomiting responses to vagal stimulation still appeared after hemisection in all 11 dogs. In addition, stimulation of the contralateral reticular area dorsomedial to the retrofacial nucleus produced fictive vomiting even after hemisection. An electrical lesion or injection of kainic acid (0.5-1.0 microl) was applied at the point where reticular stimulation induced fictive vomiting. After this destruction, no activities that corresponded to fictive vomiting could be induced by stimulation of vagal afferents or the reticular site. Salivation was decreased by hemisection, and decreased further, but was not completely abolished, with destruction of the reticular area. Kainic acid is known to selectively destroy neural cell bodies. Therefore, we concluded that neuronal somata in the reticular formation dorsomedial to the retrofacial nucleus play an essential role in the central patterning of vomiting activities in peripheral motor nerves.     

Development of autologous, oligoclonal, poorly functioning T lymphocytes in a patient with autosomal recessive severe combined immunodeficiency caused by defects of the Jak3 tyrosine kinase

Defects of the common gamma chain subunit of the cytokine receptors (gamma c) or of Jak3, a tyrosine kinase required for gamma c signal transduction, result in T-B+ severe combined immunodeficiency (SCID). However, atypical cases, characterized by progressive development of T lymphocytes, have been also reported. We describe a child with SCID caused by Jak3 gene defects, which strongly but not completely affect Jak3 protein expression and function, who developed a substantial number (> 3,000/microL) of autologous CD3+CD4+ T cells. These cells showed a primed/activated phenotype (CD45R0+ Fas+ HLA-DR+ CD62L(lo)), defective secretion of T-helper 1 and T-helper 2 cytokines, reduced proliferation to mitogens, and a high in vitro susceptibility to spontaneous (caused by downregulation of bcl-2 expression) as well as activation-induced cell death. A restricted T-cell receptor repertoire was observed, with oligoclonal expansion within each of the dominant segments. These features resemble those observed in gamma c-/y and in Jak3-/- mice, in which a population of activated, anergic T cells (predominantly CD4+) also develops with age. These results suggest that residual Jak3 expression and function or other Jak3-independent signals may also permit the generation of CD4+ T cells that undergo in vivo clonal expansion in humans; however, these mechanisms do not allow development of CD8+ T cells, nor do they fully restore the functional properties of CD4+ T lymphocytes.     

Preparation and kinetic characterization of a series of betaW37 variants of human hemoglobin A: evidence for high-affinity T quaternary structures

Four variants of human beta globin in which the Trp at position 37 has been replaced with a Tyr, Ala, Gly, or Glu have been expressed in Escherichia coli. These globins have been combined with normal human alpha chains and heme to form tetrameric hemoglobin molecules. A technique for the preparation of alpha chain dimers, which are cross-linked between their alpha99 lysine residues, has been developed, and these alpha dimers were combined with two of the beta globins, betaW37G and betaW37E, to form the corresponding cross-linked variants. The kinetics of CO binding to the deoxygenated derivatives following rapid mixing and of CO rebinding following flash photolysis have been examined as functions of pH in the presence and absence of the organic phosphate inositol hexaphosphate, IHP. The kinetic measurements indicate that replacement of the tryptophan with other residues destabilizes the hemoglobin tetramer, resulting in considerable dissociation of even the deoxygenated hemoglobins into alphabeta dimers at micromolar protein concentrations. Substitutions at beta37 also alter the properties of the deoxygenated hemoglobin tetramer. The alteration of the functional properties of the T states of these variants as well as the tendency of the deoxygenated derivatives to dissociate into alphabeta dimers increases in the order HbA < betaW37Y < betaW37A < betaW37G < betaW37E. Stabilizing the betaW37G or betaW37E tetramers by addition of IHP or by cross-linking does not restore the normal functional properties of the T state. Measurements of the geminate rebinding of CO establish a kinetic difference between the normal R state tetramer and the alphabeta dimer consistent with quaternary enhancement, the greater affinity of oxygen for the R state tetramer than for the alphabeta dimer. Kinetics of geminate rebinding also suggest that quaternary enhancement may be altered by substitutions at the beta37 position.     

The velocity potential and the interacting force for two spheres moving perpendicularly to the line joining their centers

The velocity potential around two spheres moving perpendicularly to the line joining their centers is given by a series of spherical harmonics. The appropriateness of the truncation is evaluated by determining the residual normal surface velocity on the spheres. In evaluating the residual normal velocity, a recursive procedure is constructed to evaluate the spherical harmonics to reduce computational effort and truncation error as compared to direct transformation or numerical integration. We estimate the lift force coefficient for touching spheres to be 0.577771, compared to the most accurate earlier estimate of 0.51435 by Miloh (1977).