Thrombocytopoietic properties of oncostatin M

Oncostatin M (OM) is a 28-kD glycoprotein that exhibits a panoply of biologic effects. Based on histologic observations of increased splenic megakaryocytes in nude mice implanted with an OM-secreting cell line, the thrombocytopoietic properties of OM in mice were investigated in culture and in vivo. Alone, OM did not induce megakaryocytic colony formation, but in combination with murine interleukin-3 (IL-3), OM markedly enhanced colony formation. The effects of OM on colony formation were similar to those of IL-6. OM alone augmented acetylcholinesterase in short-term marrow cultures. In normal mice, the administration of OM augmented platelet counts without increasing other circulating blood cell counts. The increment in counts exceeded that observed with IL-6. The kinetics of the OM response suggested that maximal increases in platelets occurred 3 days after the cessation of OM administration, irrespective of the duration of administration. In irradiated mice, OM administration accelerated platelet recovery and prevented the decrease in red blood cells observed in irradiated control animals. The data show that OM behaves as a megakaryocytic maturation factor in vitro and augments platelet production in vivo. Based on these animal data, OM may have potential clinical utility as a thrombocytopoietic agent.     

Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis

The plasminogen activation system is one of the enzyme systems held responsible for bone and cartilage degradation in rheumatoid arthritis (RA). In this study, we evaluated the effect of tranexamic acid (TEA), an inhibitor of plasminogen activation, on urinary collagen cross-link excretion and radiological joint damage in rat adjuvant arthritis (AA) and on urinary collagen cross-link excretion in patients with RA. In the animal study, adjuvant arthritis was induced in male Lewis rats. From day 7 onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo was administered orally. Study groups consisted of TEA-treated normal rats (C + TEA), placebo-treated normal rats (C + plac), AA rats treated with TEA (AA + TEA) or with placebo (AA + plac). To monitor joint destruction, urinary collagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) was measured by high-performance liquid chromatography at days 14 and 21. Radiological evaluation of joints was performed at day 21. In the patient study, TEA was administered to nine patients with RA as adjuvant medication (approximately 20 mg/kg body weight, three times daily) for 12 weeks. Urinary HP and LP excretion levels were measured before and during TEA treatment, and 4 weeks after the cessation of TEA treatment. In AA + TEA rats, a significant reduction of HP and a tendency towards a reduction of LP excretion were found compared with AA + plac rats (P < 0.05), at day 14, whereas the HP/LP ratio did not change. No difference was observed in HP, LP excretion, HP/LP ratio and radiological damage score between the TEA- and placebo-treated AA rats at day 21. In RA patients, a significant reduction of HP and LP excretion was found during the TEA treatment period (P < 0.05). After the cessation of TEA treatment, HP and LP excretion increased towards baseline levels. No effect on disease activity was observed. The plasmin antagonist TEA reduced the excretion of collagen pyridinoline cross-links in both experimental and rheumatoid arthritis. As such, this study not only supports the involvement of the plasminogen activation system in the destructive phase of arthritis, but also suggests a beneficial effect of therapeutic strategies directed against inhibition of matrix proteolysis.      

Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.     

长爪沙鼠发情周期规律与判定方法

目的 研究长爪沙鼠发情周期,揭示发情规律,优化判定方法。方法 连续18 d采集50只长爪沙鼠阴道上皮脱落细胞涂片,采用角化细胞计数法研究长爪沙鼠发情周期规律。比较瑞氏染色、HE染色和直接镜检判定发情周期4个时相的优缺点。结果 长爪沙鼠的发情周期有稳定型、不稳定型、假孕三种类型。其中稳定型占68.6%,发情周期为（106.3±35.0）h,可分为4个时相。4个时相角化细胞的比例分别为发情前期（13.5±7.8）%、发情期（86.7±9.9）%、发情后期（27.9±12.8）% 和发情间期（3.3±2.8）%。结论 角化细胞计数能准确地判定长爪沙鼠的发情周期及各个时相。直接镜检法能快速反映阴道脱落细胞的形态。     

Utilization of supplemental iron by premature infants fed fortified human milk

We measured red blood cell iron incorporation (RBC-inc) in 13 human milk-fed premature infants (birthweight 1037 +/- 289 g, gestational age 27 +/- 2 wk, weight at start of study 1571 +/- 426 g) who were receiving full tube-feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC-inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24-h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC-inc was similar between the two methods of supplemental iron administration (4.7 +/- 2.5% vs 4.6 +/- 1.5%, respectively). Although these values are lower than RBC-inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC-inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants.     

Three children with congenital toxoplasmosis: early report from a Swedish prospective screening study

The aim of this prospective study was to define the incidence of congenital toxoplasmosis in Sweden. Blood eluates collected on filter papers, Guthrie cards, from 40978 newborn babies were analysed for specific immunoglobulin M (IgM) and IgG antitoxoplasma antibodies. This is a preliminary report of three children with congenital toxoplasmosis, defined by the occurrence of antitoxoplasma-specific IgM antibodies. Two children were asymptomatic at birth. They were both normally developed at the age of 12 and 15 months, respectively. The third child had unidentified but uncomplicated symptoms of infection in the neonatal period. As a result of the screening congenital toxoplasmosis was confirmed and treatment instituted. Microphthalmus and peripheral chorioretinitis were detected in one eye. In spite of the chemotherapeutic treatment he developed hydrocephalus needing neurosurgical intervention at the age of 3 months. His development at 14 months was normal. The incidence in Sweden of congenital toxoplasmosis detected by specific IgM antitoxoplasma antibodies in blood from filter papers is less than 1:10000.     

舌黏膜尿道成形治疗尿道狭窄的初步报告

目的:探讨舌黏膜补片法尿道成形治疗尿道狭窄的疗效。方法:采用舌黏膜尿道成形治疗尿道狭窄14例。尿道狭窄段3.5~14cm,平均6.2cm;术前耻骨上膀胱造瘘8例,余6例排尿均较为困难,最大尿流率2.5~5.5ml/s,平均3.8ml/s。结果:术后随访2~8个月,1例因伤口感染致尿道皮肤瘘,余患者均排尿通畅,最大尿流率增至22~51ml/s,平均29.6ml/s。结论:舌黏膜具有取材方便、对患者创伤小、抗感染力强等特点,是一种较好的尿道替代物,尤其适合尿道狭窄段<6cm的患者。