1141174724Complement activation induces dysregulation of angiogenic factors and causes fetal loss

Complement is an important effector in pregnancy loss in the antiphospholipid syndrome. We now test the hypothesis that complement activation is a necessary intermediary event in the pathogenesis of recurrent spontaneous miscarriage in DBA/2-mated female CBA/J mice (CBAxDBA), a well-studied model of autoantibody-independent pregnancy failure. Blockade of C3 activation with Crry-Ig completely rescued pregnancies in CBAxDBA mice (Crry-Ig vs untreated 8.5 ± 6.3% fetal resorptions vs 28.0 ± 7.2%, P <  0.01). Inhibition of C5 cleavage with anti-C5 mAb and blockade of C5a receptors with a peptide antagonist also prevented pregnancy loss (8.6 ± 4.4% and 8.0 ± 5.9% resorptions, respectively, P <  0.01 versus control). Inhibition of the alternative pathway resulted in pregnancy outcomes similar to controls (8.4 ± 6.6% versus 9.2 ± 3.2% resorptions). In CBAxDBA matings, we observed elevated plasma levels of soluble VEGF receptor-1 (sVEGFR-1; a potent anti-angiogenic molecule), increased placental inflammatory infiltrates and defective development of placenta. Our complement inhibitory strategies blocked the increase in sVEGFR-1, prevented functional deficiency of VEGF and rescued pregnancies. We confirmed the importance of complement as a proximal effector in in vitro studies; monocytes stimulated with C5a released sVEGFR-1 which sequesters VEGF required for normal placental development. Our data indicate that complement activation leads to recruitment of inflammatory cells and production of inhibitors of angiogenesis (sVEGFR-1) which cause placental dysfunction and fetal injury. These studies identify key innate immune effectors that mediate poor pregnancy outcomes and provide novel and important targets for prevention of recurrent pregnancy loss in patients.     

Effect on platelet properties of exposure to temperatures below 20 degrees C for short periods during storage at 20 to 24 degrees C

Background : When platelet concentrates (PCs) are shipped over long distances, it is not always possible to ensure that their temperature is maintained at 20 to 24°C. In addition, PCs are not agitated as during routine storage. Study Design and Methods : Studies have been conducted to evaluate how exposure to temperatures below 20°C in the absence of agitation influences properties of platelets. In initial studies, exposure to 4°C for 3 or 5 hours or to 12°C for 5 or 17 hours on Day 2 of a 5- to 6-day storage period was associated with a loss of discoid shape. This was reflected by slightly lower but statistically different morphology scores after storage compared to those observed with control platelets that were stored only at 20 to 24°C. In addition, a qualitative difference in morphology was noted in controls and PCs held at 16°C for 17 hours. In more detailed studies, both the in vivo viability and in vitro properties of platelets exposed between Day 1 and Day 2 to either 12°C or 16°C for 17 hours were evaluated. The protocol involved a paired study design (n = 4 for each exposure temperature) with the simultaneous storage of two identical PCs, one exposed to 12 or 16°C and the other one maintained at 20 to 24°C throughout the 5-day storage. Results : Exposure to 12°C significantly reduced (p < 0.05 by paired t test) the in vivo recovery to 37.6 ± 13.8 percent (mean ± 1 SD) from 47.8 ± 11.5 percent and the survival time to 2.0 ± 0.3 days from 6.5 ± 1.4 days. On exposure to 16°C, the differences in viability from those of control units were much less but still significant. The in vivo recovery was 42.7 ± 3.8 percent compared to 49.2 ± 3.0 percent and the survival time was 3.5 ± 1.2 days compared to 6.6 ± 0.3 days. The loss of in vivo viability of the test platelets was associated with a loss of discoid shape, as reflected by morphology scores, extent of shape change, and mean platelet volume. In addition, platelet metabolism also appeared to be affected, as suggested by increased lactate production. All of the in vitro properties except for total ATP and residual glucose that were statistically different from those of controls on exposure to 12°C were also significantly different on exposure to 16°C. Conclusion : These findings demonstrate that platelets undergo substantial changes in in vivo viability and in vitro properties when they are exposed to temperatures below 20°C for short periods.     

A blinded clinical comparison of MR imaging and CT in neuroradiology

The sensitivity and specificity of magnetic resonance (MR) imaging and computed tomography (CT) were compared in blinded readings of images of a consecutive series of patients with subsequently proved diagnoses. Overall, MR imaging was less sensitive than CT because of its lower sensitivity in detecting benign tumors. With a similar experimental protocol, the effects of technical refinements or contrast media on the sensitivity of MR imaging can be determined.     

Percutaneous transluminal dilatation of the iliac artery: long-term results

One hundred fifty-four patients with stenosis of the iliac artery underwent percutaneous transluminal angioplasty (PTA). These patients were followed for 1-7 years. The long-term results of the PTAs were analyzed by computer, and life tables were generated for dilatations of the iliac arteries with unimpaired flow and for those with an obstruction in the outflow tract. The accumulative 7-year patency rate was 90%, which agrees with other reports. This study demonstrates that the long-term results of PTA of iliac arterial stenoses are competitive with reconstructive vascular surgery. PTA should be the treatment of choice in patients with iliac arterial stenoses.     

Mortality trends and setbacks: global convergence or divergence?

Health trends over much of the past century have been generally, and notably, positive throughout the world. In several regions, however, life expectancy has declined over the past 1-2 decades. This trend suggests that the expectation that emerged in the 1960s and 1970s of worldwide gains and convergence in population health status is not guaranteed by a general deterministic process. National populations can now be clearly grouped into those that have achieved rapid gains in life expectancy; those whose gains are slower or are perhaps plateauing; and those in which the trends have reversed. Over the past two centuries, outside times of war and famine, such reversals have been rare. Exploration of these varied population health trends elucidates better the close relation between population health and the processes of economic, social, and technological change. Such analysis has shown that the health status of human populations should be a guiding criterion in the debate on sustainable development.     

The evolving pattern of avoidable mortality in Russia

BACKGROUND: Life expectancy at birth in Russia is over 12 years less than in western Europe. This study explores the possible role of medical care in explaining this gap by examining the evolving pattern of mortality amenable to timely and effective medical care in Russia compared with Estonia, Latvia, and Lithuania, and the UK. METHODS: Analysis of standardized death rates from causes amenable to health care (treatable) or inter-sectoral health policies (preventable) in all regions and decomposition of differences in life expectancy between Russia and the UK by age, sex, and cause of death for the period 1965-1999/2000. RESULTS: Death rates from treatable causes remained stable between the mid-1960s and mid-1980s in Russia and the Baltic republics while steadily falling in the UK to less than half the rate in Russia. In the 1990s, rates increased in the former Soviet republics, reaching a peak in 1994 but reversing again in Russia in 1998. Deaths from causes amenable to inter-sectoral health interventions were higher in the UK in 1965 than in the Soviet Union but subsequently fell steadily while they increased in the East. Between 1965 and 1999, the male life expectancy gap between Russia and the UK rose from 3.6 to 15.1 years (women: 1.6 and 7.4 years). Treatable causes became an increasingly important contributor to this gap, accounting for almost 3 years by the end of the 1990s in men and 2 years in women. In Russia, elimination of treatable causes of death would have increased life expectancy by 2.9 years in men in 1995/99 compared with 1.2 years in the UK (women: 3.3 and 1.8 years), suggesting that, were the outcomes of health care achieved in the UK to be obtained in Russia, life expectancy for men might improve by about 1.7 years and for women by about 1.5 years. CONCLUSIONS: Our findings suggest that the Soviet health care system has failed to match the achievements of the West over the past three decades, highlighting the need to establish a system that provides effective and equitable care for the Russian population.     

Health expectancy in the Russian Federation: a new perspective on the health divide in Europe

OBJECTIVES: To compare life expectancy and healthy life expectancy in the Russian Federation and in countries of Eastern and Western Europe. METHODS: WHO mortality data and data on self-reported health from the World Values Survey and the Russian Longitudinal Monitoring Survey were used to compare the above three regions. Life expectancy was calculated using Sullivan''s method, with years of life lived divided into healthy and unhealthy. The gap in healthy life expectancy between the Russian Federation and Western Europe was examined by decomposing the difference by gender and age. FINDINGS: The probability of remaining alive and healthy declines faster in the Russian Federation than in Western Europe, with the gap between Eastern Europe and the Russian Federation widening at older ages. In the Russian Federation, this rapid decline is due mainly to the high probability of death or of poor health for men and women, respectively. CONCLUSIONS: There is a large toll of premature male mortality in the Russian Federation but there also appears to be a substantial burden of ill-health among women. As in other countries, the responses of men and women to adversity differ, leading to premature death in men but survival in a poor state of health in women. Epidemiological studies including objective measures of health would help policy-makers to estimate more precisely the scale and nature of this problem. Policy-makers must recognize that health expectancy in the Russian Federation is reduced in both men and women.     

Multiple sclerosis: specificity of MR for diagnosis

The specificity of magnetic resonance (MR) imaging in the diagnosis of multiple sclerosis (MS) has not been measured systematically. Conventional MR head images with sagittal localizer and axial multiple-echo sequences with long repetition times were obtained in 92 patients with clinically verified MS (Schumacher criteria), 100 healthy volunteers, 60 subjects with hypertension, and eight patients with dementia. Two readers, without the aid of any clinical or demographic information, classified each of the 260 studies as MS or not MS. The readers classified the studies again after being supplied with the subjects' ages and sex. True-negative and true-positive diagnoses of MS were tabulated. The specificity of the MR diagnosis of MS (true-negative results in proportion to all non-MS studies) was 95%-99% with all the control groups included. There is a small risk of misinterpreting incidental periventricular white matter foci as plaques of MS in MR studies.