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Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the differentiation and proliferation of erythroid cells. To determine the cellular mechanism of action of these growth factors, we measured changes in intracellular free calcium concentration (jCaJ) in single human erythroid precursors in response to recombinant erythropoietin and GM-CSF. [CaJ in immature erythroblasts derived from cultured human cord blood erythroid progenitors was measured with fluorescence microscopy digital video imaging.When stimulated with erythropoietin, [CaJ in the majority of erythroblasts increased within 3 min, peaked at 5 min, and returned toward baseline at 10 min. The percentage of cells that responded to erythropoietin stimulation increased in a dose-dependent manner. Additional stimulation with GM-CSF in cells previously exposed to erythropoietin resulted in a second [Ca¢J increase. Immature erythroblasts treated with GM-CSF followed by erythropoietin responded similarly to each factor with a rise in [Ck]. The source of transient calcium is intracellular since erythroblasts were incubated in medium devoid of extracellular calcium. Our observations suggest that changes in [CaJ may be an intracellular signal that mediates the proliferative/differentiating effect of hematopoietic growth factors.

Gastric dysrhythmias have been recorded from patients with a variety of nausea syndromes. The aim of this study was to measure gastric myoelectric activity in women with and without nausea during the first trimester of pregnancy. In 32 pregnant women gastric myoeletric activity was recorded for 30-45 min with cutaneous electrodes that yielded electrogastrograms (EGGs). Frequencies of the EGG waves were analyzed visually and by computer. Subjects rated their nausea at the time of EGG recording on a visual analog scale with 0 representing no nausea and 300 mm severe nausea. Gastric dysrhythmias were found in 26 pregnant subject: Seventeen had tachygastrias (EGG frequencies of 4-9 cpm), five had 1- to 2-cpm EGG waves, and four had flat-line patterns Mean nausea scores of the subjects with tachygastrias, 1- to 2-cpm, and flat-line patterns were 64.8 +/- 13, 93.4 +/- 23, and 77.2 +/- 36, respectively. Six pregnant subjects had normal 3-cpm EGG patterns, and their nausea scores averaged 2.8 +/- 1.1 (P less than 0.05 compared with nausea scores in subjects with tachygastrias, 1- to 2-cpm, and flat-line rhythms). Six subjects with gastric dysrhythmias during pregnancy were restudied after delivery; each of these subjects had normal 3-cpm EGG patterns and none had nausea. Thus, gastric dysrhythmias are objective pathophysiologic events associated with symptoms of nausea reported during the first trimester of pregnancy.

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A low-sulfated chondroitin sulfate proteoglycan (CSPG) has been shown to be the receptor for the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) in human placenta. Recently, hyaluronic acid (HA) has been suggested as an additional receptor even though IRBC binding to HA and the presence of HA at locations where IRBCs adhere in the placenta have not been established. In this study, we investigated whether HA is also a receptor for IRBC binding. IRBCs from infected placentas as well as those from different laboratory strains could bind to CSPG but not to HA. In a cell depletion assay, IRBCs from infected placentas could bind quantitatively to CSPG. Although CSPG is present both in the intervillous space and on the syncytiotrophoblast surface, HA is absent in these locations. These data conclusively demonstrate that CSPG, but not HA, is a receptor for IRBC adherence in the placenta. Our data also show, for the first time, that the IRBC-binding CSPG in the placenta is of fetal origin and that, in P. falciparum-infected placentas, the CSPG level is significantly increased, which could exacerbate IRBC adherence and placental pathogenesis. These results have important implications for the development of Of the estimated 2 to 3 million annual fatalities attributable to malaria, Ͼ90% of death is caused by Plasmodium falciparum, the most virulent among the four protozoan parasites that cause malaria in humans.1-3 Although several factors are likely to contribute to the virulence of P. falciparum, it is widely thought that sequestration of parasite-infected red blood cells (IRBCs) in the microvascular capillaries of vital organs plays a central role.3-12 The IRBC sequestration has been reported to be mediated by endothelial cell adhesion molecules, such as thrombospondin, CD36, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, P-selectin, and platelet endothelial cell adhesion molecule/ CD31. [3][4][5][6][7][8][9][10][11][12] The array of different adhesive mechanisms used by the parasite seems to confer a selective advantage for its efficient survival in the host by switching from one adherent type to another as the host develops adhesion inhibitory antibodies and other phenotype-specific immunity. Thus, in malaria endemic areas, almost all individuals by adulthood develop immunity that effectively controls infection and avoid pathogenesis. However, in the case of women during pregnancy, placenta expresses a new receptor that was previously unavailable for IRBC adherence.

Purpose To investigate the long-term (6- and 12-month) effects of the Strong Healthy Women intervention on health-related behaviors, weight and body mass index (BMI), and weight gain during pregnancy. Strong Healthy Women is a small-group behavioral intervention for pre- and interconceptional women designed to modify key risk factors for adverse pregnancy outcomes; pretest–posttest findings from a randomized, controlled trial have been previously reported. The following questions are addressed: 1) were significant pretest–posttest changes in health-related behaviors (previously reported) maintained over the 12-month follow-up period; 2) did the intervention impact weight and BMI over the 12-month follow-up period; and 3) did the intervention impact pregnancy weight gain for those who gave birth during the follow-up period? Methods Data are from 6- and 12-month follow-up telephone interviews of women in the original trial of the Strong Healthy Women intervention (n = 362) and from birth records for singleton births (n = 45) during the 12-month follow-up period. Repeated measures regression was used to evaluate intervention effects. Main Findings At the 12-month follow-up, participants in the Strong Healthy Women intervention were significantly more likely than controls to use a daily multivitamin with folic acid and to have lower weight and BMI. The intervention’s effect on reading food labels for nutritional values dropped off between the 6- and 12-month follow-up. Among those who gave birth to singletons during the follow-up period, women who participated in the intervention had lower average pregnancy weight gain compared with controls. Although the intervention effect was no longer significant when controlling for pre-pregnancy obesity, the adjusted means show a trend toward lower weight gain in the intervention group. Conclusion These findings provide important evidence that the Strong Healthy Women behavior change intervention is effective in modifying important risk factors for adverse pregnancy outcomes and may improve an important pregnancy outcome, weight gain during pregnancy. Because the intervention seems to help women manage their weight in the months after the intervention and during pregnancy, it may be an effective obesity prevention strategy for women before, during, and after the transition to motherhood.

Direct thrombin inhibitors are commonly used anticoagulants in patients with known or suspected heparin-induced thrombocytopenia (HIT). All three direct thrombin inhibitors available in the United States-argatroban, bivalirudin, and lepirudin-are pregnancy category B drugs based on animal studies, but little data are available on the safety of these agents during human pregnancy. Whereas several case reports support the safe use of lepirudin, only one case report has been published with argatroban and none with bivalirudin. We describe a 26-year-old pregnant woman with portal vein thrombosis and thrombocytopenia treated with argatroban for possible HIT during her last trimester. An argatroban infusion was started at 2 microg/kg/minute during her 33rd week of pregnancy, with the dosage titrated based on the activated partial thromboplastin time; infusion rates ranged from 2-8 microg/kg/minute. Treatment continued until her 39th week of pregnancy, when labor was induced. Argatroban therapy was discontinued 7 hours before epidural anesthesia. The patient successfully delivered a healthy male newborn, devoid of any known adverse effects from argatroban. The infant was found to have a small ventricular septal defect and patent foramen ovale at birth, but it is unlikely that these were caused by argatroban since organogenesis occurs in the first trimester. Even though the cause of this patient's thrombocytopenia was later determined to be idiopathic thrombocytopenic purpura, this is an important case that adds to the literature on use of argatroban during pregnancy.

Hypertrophic cardiomyopathy and abnormal ventricular diastolic filling in the infant of the diabetic mother is related to poor maternal glycemic control. Evaluation of fetuses of well controlled diabetic mothers has not been examined. Eleven fetuses of nondiabetic mothers (normals) and 9 fetuses of well controlled insulin-dependent diabetic mothers (FODMs) underwent serial evaluation of cardiac growth and ventricular diastolic filling using M-mode and Doppler echocardiography at 20-26 weeks' (period 1), 27-33 weeks' (period 2), 34-40 weeks' (period 3),m and 48-72 hours after birth (period 4). Indices of right and left ventricular diastolic filling included time velocity integral ratios (E/A and %E/E+A). Cardiac growth and birth weight in the two groups were similar consistent with "good" glycemic control. This conclusion was supported by similar maternal glycosylated hemoglobin (%A1C) prenatally and newborn %A1C and C-peptide values postnatally. Heart rate before and after birth and placental resistance prenatally were similar. Both normals and FODMs demonstrated an increase in left ventricular E/A and %E/E+A ratios from period 1 to 4 (p < 0.0001). This shift occurred earlier (by period 2) in normals (p < 0.01). Right ventricular filling ratios increased by period 4 in normals only (p < 0.01). No differences were noted between the groups during any period. Good glycemic control in FODMs results in normal cardiac growth and ventricular diastolic filling. Progression of diastolic filling is abnormally delayed, however, and is presumably more exaggerated in poorly controlled diabetics.