Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction

Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of integral of approximately-150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/microliters (2,000 to 61,000/microliters) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/microliters (92,000 to 175,000/microliters) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/microliters (1,000 to 51,000 /microliters) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure.     

Hemolytic uremic syndrome in children in northern India

We observed 73 patients with the hemolytic uremic syndrome (HUS) in 9 years (1980–1988), comprising 34% of patients with acute renal failure treated over the same period. There were 53 boys and 20 girls; 59% were below the age of 2 years and 33% between 2 and 5 years. Acute, usually severe dysentery, responding poorly to various antibiotics, was the prodromal illness in 80%, whereas 12% had watery diarrhea. Most patients had severe renal involvement with anuria in 56% and oliguria in 30%. A polymorphonuclear leukocytosis was present in 85% of cases, but had no correlation with the highest levels of blood urea. Coagulation abnormalities suggesting consumption coagulopathy were found in 24 of 30 cases. The results of stool culture showedShigella species in 7 cases and nontyphoidalSalmonella in 9.Escherichia coli were isolated in 11 cases, but were not further characterized. Renal biopsy showed total or patchy cortical necrosis in 20 of 50 cases. The patients were managed with supportive care, including transfusion of fresh blood or plasma and dialysis as required. The mortality was 60%, being chiefly related to the duration of renal failure and presence of renal cortical necrosis, whereas persistent dysentery and infections were complicating factors. The presence of convulsions and coagulation defects had no relation to the outcome. Our observations indicate that HUS in children in northern India is mostly related to dysentery, likely to be shigellosis, and is usually associated with severe renal damage and a high death rate.     

A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque

We investigated the spatiotemporal activation pattern, produced by one visual stimulus, across cerebral cortical regions in awake monkeys. Laminar profiles of postsynaptic potentials and action potentials were indexed with current source density (CSD) and multiunit activity profiles respectively. Locally, we found contrasting activation profiles in dorsal and ventral stream areas. The former, like V1 and V2, exhibit a 'feedforward' profile, with excitation beginning at the depth of Lamina 4, followed by activation of the extragranular laminae. The latter often displayed a multilaminar/columnar profile, with initial responses distributed across the laminae and reflecting modulation rather than excitation; CSD components were accompanied by either no changes or by suppression of action potentials. System-wide, response latencies indicated a large dorsal/ventral stream latency advantage, which generalizes across a wide range of methods. This predicts a specific temporal ordering of dorsal and ventral stream components of visual analysis, as well as specific patterns of dorsal- ventral stream interaction. Our findings support a hierarchical model of cortical organization that combines serial and parallel elements. Critical in such a model is the recognition that processing within a location typically entails multiple temporal components or 'waves' of activity, driven by input conveyed over heterogeneous pathways from the retina.      

Brain phantom: high-resolution imaging with SPECT and I-123

Inverse Monte Carlo (IMOC) is a unified reconstruction algorithm for single photon emission computed tomography (SPECT) that provides simultaneous compensation for attenuation and collimator divergence. IMOC was applied to the reconstruction of SPECT images of a brain phantom with iodine-123 and high-resolution collimation. Projection sets containing 80,000, 540,000, and 5.2 million counts were reconstructed. Comparison with filtered back-projection reconstructions showed that the IMOC reconstructions provided superior noise and resolution characteristics at all three photon densities. Results of this study indicate that IMOC may allow the use of high-resolution, low-sensitivity collimation for SPECT studies, which have traditionally provided photon yields too low for useful imaging.     

Out of hospital needlestick injuries

Retrospective analysis showed that 67 children had presented in Edinburgh with needlestick injuries on 70 occasions over five years. Worryingly, 10 children sustained injuries pretending to be intravenous drug abusers. Despite risks of hepatitis B and HIV infection, protection and follow up were inadequate. Publicity about discarded needles and a treatment plan for use in accident and emergency departments are recommended.     

Radiation sensitivity of resting and activated nonspecific cytotoxic cells of T lineage and NK lineage

Natural killer (NK) cell-mediated killing of tumor cells is a radiation- sensitive function that in most subjects is completely abrogated by treatment of the effector cells with 3,000 cGy. The radiation sensitivity of LAK (lymphokine-activated killer) cells and their precursors, the bulk of which are NK cells, is undetermined. In this study, functional cytotoxicity assays and electron microscopy were used to determine the effect of radiation on the cytotoxic function of NK cells, LAK cells (generated by three-day culture of peripheral blood lymphocytes with IL-2), and LAK cell precursors (lymphocytes irradiated prior to culture with IL-2). For comparison, we analyzed the radiation sensitivity of lectin-dependent cell-mediated cytotoxicity (LDCC), which is primarily a function of CD3+ CD8+ granular lymphocytes. We also analyzed the radiation sensitivity of nonspecific cytotoxicity mediated by mitogen-activated T cells (AK activity). Following 3,000 cGy irradiation, NK cells retained their ability to bind to tumor cell targets but, as shown by both morphologic and functional analyses, they did not undergo activation after conjugate formation, and were unable to release the content of their granules. In order to evaluate LDCC, lymphocytes were depleted of CD16+ cells and tested in a cytotoxicity assay in the presence of Con A. The radiation sensitivity curve was comparable to that of NK cell-mediated cytotoxicity. IL-2-treated lymphocytes (LAK cells) were relatively radioresistant as compared with untreated NK cells, and their cytotoxic function was not abrogated until treatment with greater than 10,000 cGy. Cells receiving such radiation doses displayed cytoplasmic blebbing and damage of their cytoskeletal structures, with disruption of centrioles and microtubules, and disarray of the intermediate filaments. As was shown with NK cells, irradiated LAK cells formed conjugates with tumor targets but failed to degranulate. The radiation sensitivity of nonspecific cytotoxicity mediated by mitogen-activated T cells was identical to that of LAK effector cells. Doses up to 2,000 cGy did not prevent generation of LAK cells from blood lymphocytes, but 3,000 cGy did so. Blast transformation similar to that observed in IL-2- stimulated controls occurred when lymphocytes irradiated with 3,000 cGy were cultured with IL-2. These transformed cells were not cytotoxic and displayed a normal cytoskeletal apparatus but did not bear electron- dense granules.(ABSTRACT TRUNCATED AT 400 WORDS)