Liver tumors in women on contraceptive steroids.

The possible association between oral contraceptives and benign liver tumors has recently been reported. To date the majority of cases have been diagnosed as benign hepatomas (liver cell adenomas). We have had the opportunity to study 13 such cases. Eight have been examples of focal nodular hyperplasia of the liver; however, in addition, there were examples of hepatocellular carcinoma, liver cell adenoma, and possible liver cell hamartoma; all were in women on "the pill." Gynecologists are alerted to the fact that many of the patients present with symptoms of acute abdomen, syncope or shock, and intrahepatic or intraperitoneal bleeding. Prompt diagnosis and treatment may be lifesaving.     

Some psychometric properties of the Test of Basic Auditory Capabilities (TBAC).

This study examined some psychometric properties of the Test of Basic Auditory Capabilities (TBAC). Two experiments are described that evaluate the psychometric functions and the test-retest reliability of the tests comprising the TBAC. The psychometric functions were established for young listeners with normal hearing and the test-retest reliability was evaluated both with young listeners with normal hearing and elderly listeners with hearing impairment. Results indicate that maximum scores on the TBAC are reached at presentation levels of at least 65-75 dB SPL. In addition, the reliability analyses indicate that the TBAC is a reliable measure for both young listeners with normal hearing and elderly listeners with hearing impairment when at least one practice test is given.     

Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells

CXC ligand 12 (CXCL12; also known as stromal cell-derived factor 1alpha/SDF-1alpha) chemoattracts hematopoietic stem and progenitor cells (HSCs/HPCs) and is thought to play a crucial role in the mobilization of HSCs/HPCs from the bone marrow. CD26 (dipeptidylpeptidase IV [DPPIV]) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N-terminus of polypeptide chains. CD26 has the ability to cleave CXCL12 at its position-2 proline. We found by flow cytometry that CD26 is expressed on a subpopulation of normal Sca-1+c-kit+lin- hematopoietic cells isolated from mouse bone marrow, as well as Sca-1+c-kit-lin- cells, and that these cells possess CD26 peptidase activity. To test the functional role of CD26 in CXCL12-mediated normal HSC/HPC migration, chemotaxis assays were performed. The CD26 truncated CXCL12(3-68) showed an inability to induce the migration of sorted Sca-1+c-kit+lin- or Sca-1+c-kit-lin- mouse marrow cells compared with the normal CXCL12. In addition, CXCL12(3-68) acts as an antagonist, resulting in the reduction of migratory response to normal CXCL12. Treatment of Sca-1+c-kit+lin- mouse marrow cells, and myeloid progenitors within this population, or Sca-1+c-kit-lin- cells with a specific CD26 inhibitor, enhanced the migratory response of these cells to CXCL12. Finally, to test for potential in vivo relevance of these in vitro observations, mice were treated with CD26 inhibitors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization. This treatment resulted in a reduction in the number of progenitor cells in the periphery as compared with the G-CSF regimen alone. This suggests that a mechanism of action of G-CSF mobilization involves CD26.     

Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects

OBJECTIVES: To determine the levels of residual HIV DNA and RNA in blood and gut reservoirs in aviremic patients, assess correlations among compartmental measurements of HIV burden, and evaluate association with clinical parameters. DESIGN: Cross-sectional analysis of baseline data only, on 40 patients enrolled in phase II study evaluating efficacy of autologous gene-modified CD4+ and CD8+ T cells. All patients were on stable antiretroviral regimen with undetectable plasma HIV RNA (< 50 copies/ml). METHODS: Measurements repeatedly performed over 8-12 weeks pre-intervention: blood HIV DNA, analysis of rectal mucosa-associated lymphoid tissue for both HIV RNA and HIV DNA, and quantitative co-culture of HIV from CD8-depleted peripheral blood mononuclear cells (PBMC). RESULTS: Quantifiable levels of HIV detected in compartments despite undetectable levels of plasma HIV RNA: HIV co-culture of PBMC (88%), blood HIV DNA (95%), rectal biopsy HIV DNA (95%), rectal biopsy HIV RNA (65%). A significant correlation existed among various measures of HIV burden (HIV co-culture, blood HIV DNA, rectal biopsy HIV RNA and DNA) but not between assays and clinical parameters [duration of highly active antiretroviral therapy (HAART), type of HAART]. All assays had comparable or less variability than in plasma viral load assays; HIV co-culture had the highest coefficient of variability whereas the blood HIV DNA assay had the lowest and was considered the most reliable assay. CONCLUSIONS: The data support safety, feasibility and high compliance of quantifying reservoirs of residual HIV in treated subjects with undetectable plasma HIV RNA. Lack of correlation between levels of HIV in residual reservoirs and duration of HAART suggests treatment-mediated viral suppression alone does not lead to reproducible decay in HIV reservoirs.     

CD26 is essential for normal G-CSF-induced progenitor cell mobilization as determined by CD26-/- mice

OBJECTIVE: In spite of the wide usage of mobilized peripheral blood hematopoietic stem and progenitor cells (HSC/HPC) for transplantation, the mechanism of granulocyte colony-stimulating factor (G-CSF)-induced HSC/HPC mobilization has yet to be fully determined. Our previous studies suggested that that G-CSF-induced mobilization may involve the extracellular peptidase CD26 (DPPIV/dipeptidylpeptidase IV). We set out to establish whether CD26 was an essential component of normal G-CSF-induced mobilization of HSC/HPC. MATERIALS AND METHODS: Normal wild-type (WT) control C57BL/6 mice and CD26 knockout (CD26(-/-)) mice, also on a C57BL/6 background, were treated with or without G-CSF and peripheral blood cells, bone marrow cells, and spleen cells were assessed for CFU-GM, BFU-E, and CFU-GEMM content. RESULTS: No statistical difference in the number of CFU-GM, BFU-E, or CFU-GEMM in the peripheral blood, bone marrow, or spleen of untreated WT vs untreated CD26(-/-) mice was observed. G-CSF treatment of WT mice resulted in the mobilization of HPC into the peripheral blood. The number of HPC detected in G-CSF-treated CD26(-/-) mouse peripheral blood was significantly less than the corresponding number of HPC detected in G-CSF-treated WT mouse peripheral blood after either a 2- or 4-day G-CSF regimen. CONCLUSIONS: CD26 plays a critical role in G-CSF-induced mobilization of HPC.     

Suicide in Northern Ireland: a comparison of two quinquennia (1982–1986 and 1987–1991)

This study compares government records of death by suicide, in Northern Ireland, during two quinquennia in the decade 1982–1991. Specifically these quinquennia are 1982–1986 l 1987–1991. During the latter quinquennium there was an increse m rate for males in most age groups, except the 45–54 and the over 65 years age groups. However, females had an increased rate in the 15–24 and 35–54 years age groups, but have a decreased rate in the other age groups. There has been a decrease in the rate of suicides by poisoning with solids and liquids for both sexes. However, male suicide rates by more violent methods have increased substantially during the latter quinquennium. Three cohorts of males, those in the 15–24, 25–34, and 55–64 age groups, have shown substantial increases during the latter quinquennium. Suggestions for psychiatric intervention strategies are made.     

Aplastic anemia and paroxysmal nocturnal hemoglobinuria: search for a pathogenetic link

The association of paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) raises the yet unresolved questions as to whether these two disorders are different forms of the same disease. We compared two groups of patients with respect to cytogenetic features, glycosylphosphatidylinositol (GPI)-linked protein expression, protein C/protein S/thrombomodulin/antithrombin III activity, and PIG-A gene expression. The first group consisted of eight patients with PNH (defined as positive Ham and sucrose tests at diagnosis), and the second, 37 patients with AA. Twelve patients with AA later developed a PNH clone. Monoclonal antibodies used to study GPI-linked protein expression (CD14 [on monocytes], CD16 [on neutrophils], CD48 [on lymphocytes and monocytes], CD67 [on neutrophils and eosinophils], and, more recently, CD55, CD58, and CD59 [on erythrocytes]) were also tested on a cohort of 20 normal subjects and five patients with constitutional AA. Ham and sucrose tests were performed on the same day as flow- cytometric analysis. Six of 12 patients with AA, who secondarily developed a PNH clone, had clinical symptoms, while all eight patients with PNH had pancytopenia and/or thrombosis and/or hemolytic anemia. Cytogenetic features were normal in all but two patients. Proteins C and S, thrombomodulin, and antithrombin III levels were within the normal range in patients with PNH and in those with AA (with or without a PNH clone). In patients with PNH, CD16 and CD67 expression were deficient in 78% to 98% of the cells and CD14 in 76% to 100%. By comparison, a GPI-linked defect was detected in 13 patients with AA, affecting a mean of 32% and 33% of CD16/CD67 and CD14 cell populations, respectively. Two of three tested patients with PNH and 1 of 12 patients with AA had a defect in the CD48 lymphocyte population. In a follow-up study of our patient cohort, we used the GPI-linked molecules on granulocytes and monocytes investigated earlier and added the study of CD55, CD58, and CD59 on erythrocytes. Two patients with PNH and 14 with AA were studied for 6 to 13 months after the initial study. Among patients with AA, four in whom no GPI-anchoring defect was detected in the first study had no defect in follow-up studies of all blood-cell subsets (including erythrocytes). Analysis of granulocytes, monocytes, and erythrocytes was performed in 7 of 13 AA patients in whom affected monocytes and granulocytes were previously detected. A GPI-anchoring defect was detected on erythrocytes in five of six.(ABSTRACT TRUNCATED AT 400 WORDS)     

Students' expectations of postregistration degree programmes

The needs of postregistration students pursuing degree-linked clinical courses have received little attention and there are few insights concerning their aspirations when they enrol on such courses. Thus the aim of this study was to explore postregistration students' perceptions of the specific needs of their patient/client group and to examine how they envisaged the course on which they had just enrolled might help them to meet these needs in addition to their own requirements for professional and personal development. Data were collected by group interview from 62 students enrolling on eight different postregistration courses, all employed in an acute hospital trust. The results were analysed inductively. They indicated that students had internalized the state of the healthcare market and were keenly aware of the need to fulfil the expectations of employers and the public, while fulfilling their own needs for education and pursuing their own professional and career trajectories. They appeared ambitious and yet appeared to demonstrate empathy for patients and their families and felt a tremendous desire to provide care of a high quality through the optimal development of technical expertise. Students' emphasis on the importance of keeping abreast of technological developments should not be lightly dismissed considering its prominent position within the acute areas where they were employed, especially as it did not replace their desire to promote the caring aspects of their work.     

Liver-derived fetal hematopoietic stem cells selectively and preferentially home to the fetal bone marrow

In the course of ontogeny, the homing site for the hematopoietic stem cells (HSC) moves with certain predictability from the yolk sac to the liver/spleen and then to the marrow. The pattern of this migration has thus far been established mostly on a morphologic basis. To delineate further the course of this migration and to gain insight into its possible mechanism, we used in utero transplantation of allogeneic or xenogeneic HSC in preimmune sheep fetuses. Sex chromosome, type of hemoglobin, and species-specific surface markers were used to follow the path of transplanted cells in the fetus. Before the development of the bone marrow, transplanted HSC (liver- or marrow-derived) homed exclusively to the liver/spleen. With the development of marrow, around day 60 of gestation (term, 145 days), homing occurred also in the nascent marrow and by day 80 transplanted cells homed exclusively to the marrow. This suggests that there may be a hierarchy in homing sites, with those of the marrow having higher affinity than those of liver/spleen. Interestingly, despite a change in homing that was followed by the expansion of the marrow compartment of HSC (ie, HSC proliferation), these cells did not participate actively in blood cell formation during most of the prenatal period. Liver remained the major hematopoietic organ throughout the gestation. It was only during the perinatal period that this organ assumed the function of hematopoiesis from the liver. This lack of expression of HSC in fetal marrow can possibly be attributable to the immaturity of marrow stroma required for differentiation and maturation of progenitors and the orderly egress of mature cells into the blood stream. The availability of this model allows us to begin studies in the molecular mechanism of stem cell homing in vivo during ontogeny.