Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy.

Thrombopoietin (TPO), the ligand for the receptor protooncogene c-mpl, has been cloned and shown to be the critical regulator of platelet production. Several features of c-Mpl expression, including its presence on erythroid cell lines, and the panmyeloid transformation characteristic of myeloproliferative leukemia (MPL) viral disease led us to investigate whether this receptor-ligand system may play a role in erythropoiesis. We report that although TPO alone did not support the growth of either early or late erythroid progenitors, it acted in synergy with erythropoietin to expand these populations. Moreover, while the effects on erythropoiesis in normal animals were modest, TPO greatly expanded the number of erythroid progenitors and blood reticulocytes and was associated with accelerated red cell recovery in myelosuppressed mice. Together, these data strongly suggest that erythroid progenitors respond to TOP and that this newly cloned cytokine, critical for platelet production, can augment erythropoiesis in states of marrow failure.     

Design and validity of a questionnaire to assess sexuality in pregnant women

Background

A review of validated methods for assessing female sexual dysfunction and a review of male and female sexual dysfunction did not refer to any specific questionnaire for evaluating sexuality during pregnancy. A study was performed at the Obstetrics and Gynecology Department of Botucatu Medical School, São Paulo State University, Brazil to design and validate a pregnancy sexuality questionnaire, the Pregnancy Sexual Response Inventory (PSRI).

Methods

Women with a singleton pregnancy between 10 and 35 weeks of gestation were randomly recruited. There were five phases in the development of the PSRI: (1) item selection; (2) item development; (3) determination of internal consistency, reliability and convergence; (4) content validity; and (5) determination of inter-interviewer reliability. Internal consistency and reliability were evaluated using Cronbach's alpha. Inter-interviewer reliability was assessed by evaluating the responses of 18 academics at various institutions, using Kappa Index and Student t test.

Results

Good internal consistency and reliability were obtained (Cronbach's alpha coefficient = 0.79). Among the 18 academics, 13 totally agreed (K = 1.0), three partially agreed (K = 0.67) and two disagreed (K = 0.33) with the proposed questions. Comparisons of the mean PSRI domain scores made between the primary investigators and the other interviewers showed no significant differences in all domains (p > 0.05).

Conclusion

PSRI is a new validated instrument for evaluating sexuality and sexual activity and related health concerns during pregnancy.     

Priorities in emergency obstetric care in Bolivia––maternal mortality and near-miss morbidity in metropolitan La Paz

Objective  To document the frequency and causes of maternal mortality and severe (near-miss) morbidity in metropolitan La Paz, Bolivia.
Design  Facility-based cross-sectional study.
Setting  Four maternity hospitals in La Paz and El Alto, Bolivia, where free maternal health care is provided through a government-subsidised programme.
Population  All maternal deaths and women with near-miss morbidity.
Methods  Inclusion of near-miss using clinical and management-based criteria.
Main outcome measures  Maternal mortality ratio (MMR), severe morbidity ratio (SMR), mortality indices and proportion of near-miss cases at hospital admission.
Results  MMR was 187/100 000 live births and SMR was 50/1000 live births, with a relatively low mortality index of 3.6%. Severe haemorrhage and severe hypertensive disorders were the main causes of near-miss, with 26% of severe haemorrhages occurring in early pregnancy. Sepsis was the most common cause of death. The majority of near-miss cases (74%) were in critical condition at hospital admission and differed from those fulfilling the criteria after admission as to diagnostic categories and socio-demographic variables.
Conclusions  Pre-hospital barriers remain to be of great importance in a setting of this type, where there is wide availability of free maternal health care. Such barriers, together with haemorrhage in early pregnancy, pre-eclampsia detection and referral patterns, should be priority areas for future research and interventions to improve maternal health. Near-miss upon arrival and near-miss after arrival at hospital should be analysed separately as that provides additional information about factors that contribute to maternal ill-health.     

A possible role of ID-Migraine™ in the emergency department: study of an emergency department out-patient population

Headache symptoms account for 1–3% of admissions to an emergency department (ED). Most patients affected by a primary headache (PH) have migraine, although they are often misdiagnosed as 'headache not otherwise specified'. We investigated the possibility of using ID-Migraine (ID-M) to improve migraine recognition in the ED setting. We planned a pilot study involving ED out-patients with a diagnosis of PH. Diagnoses of a blinded headache expert were subsequently matched with the ID-M results. We tested ID-M on 230 patients (199 PH, 31 secondary headaches). Considering only PH, ID-M exhibited a sensitivity of 0.94 and specificity of 0.83 with a positive predictive value (PPV) of 0.99. The ID-M is a simple migraine screener with high sensitivity, high specificity and high PPV, even in an ED-derived population. Methodical use of this tool in an ED setting may, once a secondary headache has been excluded, lead to rapid diagnosis of migraine.     

Identification of the receptor for erythropoietin on human and murine erythroleukemia cells and modulation by phorbol ester and dimethyl sulfoxide

Erythropoietin, a glycoprotein that regulates erythropoiesis, initiates its biological effects by binding to a cell-surface receptor. Little is known about the structure of the erythropoietin receptor and the events that follow binding of erythropoietin to its receptor, in part because of the difficulty of obtaining sufficient quantities of cells that express the erythropoietin receptor. We used both iodinated and metabolically labeled erythropoietin to characterize the receptor on a variety of erythroleukemia cell lines not previously tested, and we have identified both human and murine cell lines that display large numbers of erythropoietin receptors. Both erythropoietin-responsive and -nonresponsive cell lines exhibit a single class of binding sites. The human erythroleukemia cell line OCIM1 exhibits approximately 3000 erythropoietin receptors per cell with a Kd of 280 pM. The erythropoietin-responsive Rauscher red 5-1.5 murine erythroleukemia cell line displays approximately 1700 receptors per cell with a Kd of 440 pM. The GM979 murine erythroleukemia cell line has approximately 1600 receptors per cell with a Kd of 660 pM. Induction of the erythroid phenotype by dimethyl sulfoxide or its suppression by phorbol 12-myristate 13-acetate was accompanied by an increase or decrease, respectively, in erythropoietin receptor number. Affinity crosslinking of labeled erythropoietin to the receptor identified two proteins corresponding to estimated molecular masses of 95 and 105 kDa. The OCIM1, Rauscher, and GM979 erythroleukemia cell lines provide a useful model for the study of postreceptor signaling events, as well as a convenient source for purification of the erythropoietin receptor.     

PREVALENCE OF ANTIBODIES TO HEPATITIS C VIRUS IN HOSPITALIZED POPULATION SUBSETS

Prevalence of antibodies to hepatitis C virus (anti-HCV antibody) was ascertained in different subsets of hospitalized patients. Anti-HCV antibody testing was done using a third generation test The anti-HCV positivity in the sera of 308 tuberculosis patients, who had been given streptomycin, was 12.3 per cent It was 7.1 percent among 84 cardiac patients undergoing invasive cardiac procedures, 15.6 per cent in 77 patients on haemodialysis and 41.2 per cent patients with surgical jaundice. It is surmised that hospitalization, particularly parenteral therapy and invasive procedures during hospitalization, puts patients at higher risk of contracting HCV infecticn.KEY WORDS: Hepatitis C Virus, Hospitalization, Hospital infection, Prevalence     

Symposium: reproduction in baboons. Some reproductive studies in the baboon

A captive colony of baboons has been used for three decadesfor various reproductive studies where application of findingsto human therapeutics was desired. The characteristics of themenstrual cycle in baboons are very similar to those of women,except that of the baboon is slightly longer and there is alower luteal phase concentration of oestradiol. The durationof pregnancy in baboons is about two-thirds that of humans butpatterns of oestrogen and progesterone secretion are virtuallyidentical. The principal oestrogen produced by the pregnantbaboon is oestrone, while oestriol is the most abundant in humanpregnancies. Chorionic gonadotrophin (CG) is elevated significantlyonly in the first trimester of a baboon pregnancy, while humanpregnancy concentrations of this hormone are about one-thirdof the first trimester level in the second and third trimesters.Breeding success of baboons in captivity depends on care beingtaken to cull infertile animals from the colony prior to commencingmatings. Under optimal conditions, fertility rates can reachnearly 80%. Female baboons have been successfully used to gaininsights into antifertility effects of contraceptive vaccinesdirected against CG, spermatozoa and ovum antigens. Extensiveuse of the colony for developing a human chorionic gonadotrophin(HCG) antifertility vaccine has been invaluable for progressin this field. Other pharmaceuticals and devices have been successfullytested in baboons, but costs and mandated regulations for themanagement of these non human primates have made their currentuse in meaningful studies extremely difficult.