A role for changes in platelet production in the cause of acute coronary syndromes.

Platelets are heterogeneous with respect to their size, density, and reactivity. Large platelets are more active hemostatically, and platelet volume has been found to be increased both in patients with unstable angina and with myocardial infarction. Furthermore, platelet volume is a predictor of a further ischemic event and death when measured after myocardial infarction.

Cytochemical detection of a senescence-associated beta-galactosidase in endothelial and smooth muscle cells from human and rabbit blood vessels.

A beta-galactosidase activity has recently been used as a histochemical marker of replicative senescence in human fibroblasts and keratinocytes. To establish whether this marker could be used to detect senescence of vascular cells, we have investigated its presence in cultures of serially passaged human umbilical vein endothelial cells and rabbit aortic smooth muscle cells. beta-Galactosidase activity was detected by light microscopy using the chromogenic substrate 5-bromo-4-chloro-3-indolyl beta-d-galactopyranoside.

The impact of blood culture reporting and clinical liaison on the empiric treatment of bacteraemia.

Aims: To assess the impact of blood culture results and early clinical liaison on the treatment of patients with bacteraemia.

Methods: 123 patients with significant positive blood cultures were followed over a nine month period in a 620 bed teaching hospital. The impact of early blood culture reporting and clinical liaison on the cost and appropriateness of treatment was assessed.

Protein kinase C mediates the mitogenic action of thrombopoietin in c-Mpl-expressing UT-7 cells.

Protein kinase C (PKC) has been implicated in signal transduction events elicited by several hematopoietic growth factors. Thrombopoietin (TPO) is the major regulator of megakaryocytic lineage development, and its receptor, c-Mpl, transduces signals for the proliferation and differentiation of hematopoietic progenitors. In this study we have examined the effect of TPO on the subcellular distribution of PKC (a measure of enzyme activation) in a growth factor-dependent pluripotent hematopoietic cell line that was engineered to express the c-Mpl receptor (UT-7/mpl).

The adventitia, endothelium and atherosclerosis.

Despite many theories, the initiating circumstances for the development of atherosclerosis remain obscure. The development of animal models of atherosclerosis was based upon the different theories of the origins of atherosclerosis which suggested that it originates at the intimal surface of the vessel. A more recent model of atherosclerosis involves perivascular manipulation of the vessel by positioning of a hollow silastic collar around the artery.

Megakaryocytes and platelets in vascular disease.

Platelets are anucleate cells with no DNA. They are derived from their precursor, the megakaryocyte (MK), whose differentiation is characterized by nuclear polyploidization through a process called endomitosis. Changes in the MK-platelet-haemostasis axis may precede acute thrombotic events.

Antimicrotubule agents induce polyploidization of human leukaemic cell lines with megakaryocytic features.

In most eukaryotic cells the regular alternation of chromosome reduplication and cell division is controlled by interdependent relationships which prevent progression to the next cell-cycle phase unless the preceding phase has been completed. Megakaryocytes become polyploid by allowing many rounds of DNA replication without completion of intervening mitoses. To assess the role of cell-cycle dependencies in megakaryocytopoiesis we examined human cell lines which express megakaryocytic features for their ability to continue DNA synthesis and undergo polyploidization in the presence of mitotic poisons.

Absence of human immunodeficiency virus (HIV) proviral sequences in seronegative hemophilic men and sexual partners of HIV-seropositive hemophiliacs.

To detect latent infection with human immunodeficiency virus (HIV), specimens of peripheral blood leukocytes from HIV-seronegative hemophiliacs and from sexual partners of HIV-seropositive hemophiliacs were examined by polymerase chain reaction (PCR). The primer pair SK 38/39 derived from the gag region and/or the primer pair SK 68/69 corresponding to a conserved region of the env gene were used. Whereas HIV proviral DNA was detected by PCR in samples from 86 (97%) of 89 HIV-seropositive hemophiliacs, no HIV-DNA was found in blood samples of 198 HIV-seronegative hemophiliacs at risk.

Chronic delta hepatitis in haemophiliacs.

The seroepidemiological profile of HBV and HDV was investigated in 640 male haemophiliacs. Twenty-seven of forty-four HBsAg carriers were anti-HDV-IgG positive, 22 were also anti-HDV-IgM positive. A markedly lower prevalence of HDV infection was found in patients with anti-HBc in the absence of HBsAg and anti-HBs (6/41).

Clinical safety of recombinant factor VIII. The rFactor VIII Clinical Trial Group.

The safety of rFVIII has been studied in patients with severe or moderate hemophilia A in a noncontrolled observation study. A total of 40 patients participated in the study. Thirteen patients were included in stage I and 40 patients in stage II.

Heterosexual transmission of HIV in hemophiliacs.

Of 686 hemophiliacs who are being treated at our institution, 402 (59%) are HIV-sero-positive. One hundred seventy-eight heterosexual partners of HIV-infected hemophiliacs have been serologically examined; 19 (11%) are HIV-positive. So far none of the seropositive partners suffers from ARC or AIDS.

Natural history of HIV-infection in hemophiliacs: clinical, immunological, and virological findings.

At our institution 686 hemophiliacs are being treated. Of them 402 (59%) are anti-HIV-seropositive. The general use of heat-treated clotting factor products was begun in July 1983, and from May 1984 all patients exclusively used heat-treated clotting factors.