Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women.

Tamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or post-menopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity.     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

The contribution of twins to perinatal mortality in Jamaica

Summary. The Jamaican Perinatal Mortality Survey collected data that have been used in this paper to estimate: (1) the rate of multiple deliveries on the island; (2) the way in which this varies with demographic features; and (3) the causes of perinatal mortality among twins on the island.
The survey consisted of two phases: a study of all births in the months of September and October 1986 (the cohort months) and a study of all perinatal deaths in the 12 months from 1 September 1986 to 31 August 1987.
Among the 10408 pregnancies in the cohort months, 99(1.0%) were multiple pregnancies. The twinning rate showed statistically significant trends with maternal age and parity but no association with social factors.
Among the 2020 perinatal deaths occurring in the 12-month period, 173 (8.6%) were twins, with particularly high contribution to the Wigglesworth group 'deaths from immaturity'. Mortality rate of twins was significantly lower if mothers resided in areas where there were good obstetric and paediatric facilities.     

Assessment of risk of perinatal death in Jamaica

Summary. Data from the Jamaican Perinatal Mortality Survey had been used to create a statistical model using logistic regression.¹ From this a simple additive scoring system to predict perinatal death was devised and tested on the 2 cohort months of the study.
The score had a theoretical range of 0–28 points, with the higher the score, the greater the likelihood of a perinatal death. For a cut-point of 7, sensitivity was 43% and specificity 84%. A cut-point of 8 resulted in 27% sensitivity and 94% specificity. Higher cut-points resulted in much reduced sensitivity but enhanced specificity (e.g. cut-point 10: 11% sensitivity, 99% specificity).
However, it is likely that these estimates are optimistically high, and to achieve unbiased estimates of sensitivity and specificity the score needs to be tested on a sample of the population from which it was not derived before implementation takes place. Meanwhile, the cut-off level for implementation will depend on appropriate resources available.     

Antenatal and perinatal care in Jamaica: do they reduce perinatal death rates?

Summary. Information concerning 9919 singleton pregnancies delivered in Jamaica in the 2-month period of September and October 1986 and surviving the early neonatal period were compared with 1847 singleton perinatal deaths occurring in the 12-month period from 1 September 1986 to 31 August 1987, classified according to the Wigglesworth schema.
Logistic regression was used to assess features of antenatal and intrapartum care that were associated with the different groups of perinatal death after taking account of environmental, maternal and medical factors.
In Jamaica, 67% of all mothers took iron during pregnancy. These mothers appeared to have a lower risk of perinatal death. This does not appear to be an artefact related to the gestation at which the mother delivers, and was particularly associated with antepartum fetal deaths.
Commencement of antenatal care in the first trimester appeared to reduce the risk of all perinatal deaths, and for intrapartum asphyxia in particular. It is speculated that the mechanism may involve early detection and treatment of anaemia and syphilis.
Quality of perinatal care available in the area of residence, as measured by the presence of consultant obstetricians and a paediatric consultant unit, is shown to be significantly related to a reduction in deaths from intrapartum asphyxia, but it appeared not to be related to antepartum fetal deaths.     

Online cancer services: types of services offered and associated health outcomes

There are advantages and disadvantages associated with utilization of online health services among individuals living with cancer. Accessing accurate, reliable health-related information online gives patients the power to enhance their understanding of information they obtain from their health care providers. However, online health information can often be confusing for patients to interpret, and it can sometimes be conflicting or incorrect. Based on a framework by Eysenbach, the following paper discusses various types of cancer services that are available online, and it addresses both positive and negative health outcomes that have been linked to utilizing such services.     

Detection of cytomegalovirus infection during a vaccine clinical trial in healthy young women: seroconversion and viral shedding.

BACKGROUND: An antibody method based on absorption of serum with cytomegalovirus (CMV) glycoprotein B (gB) was developed for detection of infection during clinical trials of CMV gB vaccine. Previous study showed that this method detected the antibody response to infection and was negative with vaccine induced immunity. OBJECTIVES: In an ongoing efficacy trial of CMV gB vaccine the ability of the gB-absorbed CMV IgG assay to detect CMV infection was assessed and compared with viral culture results. STUDY DESIGN: Two hundred and ninety two healthy, seronegative young women in a phase II, double-blind, placebo-controlled, clinical trial of recombinant CMV gB vaccine (sanofi pasteur) with MF59 adjuvant (Chiron) were randomized to receive CMV gB vaccine or placebo (1:1) on a 0, 1 and 6 month schedule. Participants were screened every 3 months for CMV infection using the gB-absorbed CMV IgG assay, and a subgroup was also screened for infection with viral cultures. Viral culture (urine, vaginal swab and saliva) was used to confirm CMV infection in all subjects with a positive gB-absorbed CMV IgG result. RESULTS: Evidence of CMV infection (gB-absorbed CMV IgG levels>or=5.0 AU/ml) was found in 23/292 (7.88%) study participants. The gB-absorbed CMV IgG levels of their first positive serum ranged from 15.7 to 251.0 AU/ml with a mean of 77.0 AU/ml and a median of 44.9 AU/ml. Cytomegalovirus was isolated from all 23 of them from culture specimens collected after their first positive gB-absorbed CMV IgG. The time to first CMV positive culture from first positive gB-absorbed CMV IgG ranged from 0 to 12 weeks with a median of 2 weeks. CONCLUSIONS: The gB-absorbed CMV IgG assay detects CMV infection in CMV gB vaccine clinical trials earlier and more rapidly than virus culture and does not reveal whether subjects received CMV gB vaccine or placebo.     

Mechanical characteristics of skinned and intact muscle fibres from the giant barnacle,Balanus nubilus

Intact muscle fibres fromBalanus nubilus develop tensions of up to 600 kN sd m⁻² during electrical stimulation. The rise of tension occurs with a half-time (177 ms at 12° C) about fivefold longer than that of tetanised frog muscle at the same temperature. The response of myofibrillar bundles to a rapid stretch resembles that of frog muscle but has a y_o value (i.e. the size of an instantaneous release necessary to just discharge tension) which is ca. 2.5 times smaller, and phase 2 of the tension transient (the “quick phase”) occurs at a rate comparable to that of frog muscle. In contrast, the ATPase activity (0.018 mmoles · kg wet weight⁻¹ · s⁻¹) of this preparation and its maximum shortening velocity (0.15–0.16 muscle lengths · s⁻¹) are both at least fivefold slower than frog muscle. These findings can be accounted for by a cross-bridge cycle in barnacle muscle in which events prior and subsequent to the tension generating step(s) occur at a rate at least fivefold slower than comparable steps in frog muscle, but the step(s) associated with tension development occur at similar rates in the two preparations. Since the rate of mechanical relaxation in barnacle muscle is modified in the presence of intracellular calcium buffers and by depolarisation-induced elevation of the free calcium during the relaxation phase, it is proposed that the time course of relaxation is not determined exclusively by the kinetics of the cross-bridge cycle, but is also dependent on the free calcium concentration during relaxation.