Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.     

Prognostic value of 24-hour blood pressure in pregnancy.

CONTEXT: Elevated blood pressure (BP) measured at the physician's office may reflect true hypertension or white coat hypertension (WCH). The prognostic value of WCH among pregnant women is unknown. OBJECTIVE: To assess the prognostic value of WCH in pregnancy. DESIGN: Prospective cohort study conducted between September 1994 and October 1997. SETTING: Community hospital. PATIENTS: Women without preexisting hypertension and not treated with antihypertensive drugs aid with high (n = 148) or normal (n = 106) office BP (high office BP was defined as > or =140 mm Hg systolic and/or > or =90 mm Hg diastolic) matched for gestational age during their third trimester of pregnancy. All women underwent 24-hour noninvasive BP monitoring, and women without hypertension on 24-hour monitoring (125/74 mm Hg or less for average 24-hour BP) with office hypertension were classified as having WCH. Women were followed up through the end of pregnancy. MAIN OUTCOME MEASURES: Duration of pregnancy, gestational hypertension, preeclampsia or eclampsia, cesarean delivery, placental and neonatal weight, and length of maternal and neonatal hospital stays for those with and without elevated office BP. RESULTS: After application of exclusion criteria, data for 7 women were removed from the analysis. For the remaining subjects, in the group with elevated BP, prevalence of WCH was 29.2% (42/144). Duration of pregnancy was similar in the normotensive and WCH groups (39.6 vs 39.8 weeks; P = .50), but shorter (38.3 weeks; P<.001) in the true hypertension group. Incidence of preeclampsia was similar in the normotensive and WCH groups (5.8% vs 7.1 %; P = .86) but higher in the true hypertension group (61.7%; P<.001). Frequency of cesarean delivery was lower in the normotensive (12.4%) than in the WCH (45.2%; P = .008) and true hypertension (41.1 %; P = .009) groups. Neonatal weight was lower (P<.001) in the true hypertension (mean, 2911 g) than in the normotensive (3336 g) and WCH groups (3435 g), which did not differ (P = .68). The duration of neonatal hospital stay did not differ between the normotensive and the WCH group (5.3 vs 6.9 days; P = .13) but was longer in the true hypertension group (12.3 days; P<.001). CONCLUSIONS: In women with elevated BP during their third trimester of pregnancy, 24-hour BP was superior to office BP (distinguishing true hypertension from WCH) for prediction of the outcome of pregnancy. Outcomes in the normotensive and WCH group were comparable, but the increased incidence of cesarean delivery in the WCH group may reflect decision-making processes influenced by office BP.     

The final destiny of acantholytic cells in pemphigus is Fas mediated

Background  Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective  This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods  Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results  All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4⁺CD69⁺ cells. Additionally, CD19⁺ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion  This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

Conflicts of interest

None declared.     

Accessing rural populations: role of the community pharmacist in a breast and cervical cancer screening programme

RATIONALE: Community pharmacists are one of the most frequently visited health care providers in the USA. The article describes a demonstration project which used community pharmacists to educate and enrol low to moderate income and medically under-served women into a statewide breast and cervical cancer screening programme. METHODS: The Nebraska Department of Health programme entitled, 'Every Woman Matters', funded through the Centers of Disease Control and Prevention, provided no cost or low cost mammography and pap smears to eligible women. Patient enrolment packets were distributed to 91 pharmacies expressing an initial interest in participating. These were reduced to 28 pharmacies based on their commitment level during the initial 3 months of the study. RESULTS: One hundred and fourteen patient referrals were generated from the 28 network pharmacies; two from pharmacies in urban areas, and 112 referrals from rural sites. All referrals were from the 22 independently owned pharmacies in the study. CONCLUSIONS: Results suggest that the use of independent community pharmacies in the rural setting can be an effective method of recruiting women into public health programmes.     

Nuclear RNA sequences coding for alpha and beta globins in erythroid cells: evidence for multiple intermediate molecules

The poly (A)-containing nuclear RNA from dimethylsulfoxide-induced Friend leukemia cells was fractionated by acrylamide gel electrophoresis in denaturing conditions and analyzed for alpha and beta globin RNA sequences. The results indicate that nuclear RNA contains one species of large-size RNA (0.6 X 10(6) daltons), which is the putative precursor for beta globin mRNA only. In addition, it was shown by electrophoretic analysis that the complex of RNA molecules not resolved by sucrose gradient centrifugation (11S) comprises sequences of decreasing size (0.34, 0.28, and 0.26 X 10(6) daltons), which might be the precursors of alpha and beta globin mRNA.     

The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal- cell-independent expansion and differentiation of human fetal pro-B cells in vitro

The effects of a novel cytokine FLK2/FLT3 ligand (FL) on human fetal bone marrow-derived CD34+CD19+ pro-B cells were analyzed in a stromal- cell-independent, serum-deprived culture system. FL, like interleukin-3 (IL-3), synergized with IL-7 in promoting pro-B cell growth, and differentiation of these cells into CD34-CD19+clgM+slgM- pre-B cells, whereas a small proportion of these cells even differentiate into more mature slgM+ B cells. In contrast, KIT ligand (KL) and granulocyte- macrophage colony-stimulating factor (GM-CSF) were ineffective in promoting IL-7-dependent pro-B cell growth and differentiation. Maximal levels of pro-B cell expansion, generally resulting in 15- to 30-fold increases in cellularity, were obtained in cultures supplemented with optimal doses of FL + IL-7 + IL-3. The addition of mouse bone marrow stromal cells further enhanced the proliferation and differentiation of pro-B cells obtained in the presence of these three cytokines. Under these conditions, cultures could be maintained for more than 4 weeks, and in general 40- to 50-fold increases in cell numbers were observed by 3 weeks of culture. The percentages of clgM+ and slgM+ B cells increased 1.5- to 3-fold and 2-fold, respectively, suggesting that stromal cells may provide additional costimulatory signals for human B- cell growth and differentiation that are different from IL-7, IL-3, and FL. Collectively, our results indicate that FL, in contrast to KL, strongly promotes long-term expansion and differentiation of human pro- B cells in the presence of IL-7 or in combination of IL-7 and IL-3, which is a novel property of this hematopoietic growth factor.