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.     

Sensitization to turnip rape and oilseed rape in children with atopic dermatitis: a case-control study

Turnip rape and oilseed rape 2S albumins are new allergens in children with atopic dermatitis suspected for food allergy. We recently found that 11% (206/1887) of these children had a positive skin prick test to seeds of oilseed rape ( Brassica napus ) and/or turnip rape ( Brassica rapa ). In the present case-control study we examined how the children with atopic dermatitis sensitized to turnip rape and oilseed rape had been breast-fed and whether they had some common sensitization pattern to certain foods or pollens. A total of 64 children with atopic dermatitis and a positive skin prick test to turnip rape and/or oilseed rape (≥5 mm) were examined. Sixty-four age- and sex-matched children with atopic dermatitis but negative skin prick tests to turnip rape and oilseed rape served as case controls. The turnip rape and/or oilseed rape sensitized children with atopic dermatitis had significantly more often positive skin prick tests reactions and IgE antibodies to various foods (cow's milk, egg, wheat, mustard; p < 0.01) and pollens (birch, timothy, mugwort; p < 0.01) than the control children. They had been exclusively breast-fed for a longer period (median 4 months; p < 0.05) and had more often associated asthma (36%) and allergic rhinitis (44%). Children with atopic dermatitis sensitized to oilseed rape and turnip rape had high frequency of associated sensitizations to all foods and pollens tested showing that oilseed plant sensitization affects especially atopic children who have been sensitized to multiple allergens.     

Renal impairment and hypertension in brain tumor patients treated in childhood are mainly associated with cisplatin treatment

BACKGROUND: This study was designed to evaluate the renal consequences of the treatment of brain tumor patients diagnosed in childhood. PROCEDURE: One hundred four primary brain tumor patients diagnosed before 17 years of age from 1983 to 1997 had been treated in Tampere University Hospital, Finland. Of the 80 survivors 52 (65.0%) were examined at a median age of 14.4 years (range 3.8-28.7) and median 6.0 years (range 1.2-14.8) after the last treatment. The main outcome measures were blood pressure (BP), renal function, and calcium metabolism. RESULTS: Eight patients (15.4%) were hypertensive. Elevated BP was observed especially after exposure both to cisplatin and cranial irradiation. Spinal radiation did not increase the risk of elevated BP. Other adverse effects were observed only in patients treated with cisplatin. Five out of 14 patients treated with cisplatin evinced renal glomerular dysfunction (GFR < 87 mL/min/1.73 m2) immediately after treatment. They had a high cumulative dose of cisplatin (490-880 mg/m2). Recovery from renal glomerular dysfunction was observed in one patient. Nine of 14 patients were hypomagnesemic at the close of cisplatin treatment. Thereafter the magnesium level decreased in 10/14 cases (P = 0.006). During the study 10/14 were hypomagnesemic (P < 0.001); one evinced severe symptomatic hypomagnesemia. Low plasma phosphate (P = 0.016) and potassium levels (P = 0.026), tubular proteinuria (P = 0.055), metabolic alkalosis (P = 0.071), and hyperuricemia (P = 0.114) were also more common in patients on cisplatin treatment. CONCLUSIONS: Elevated BP is common among brain tumor patients treated in childhood. After cisplatin treatment renal glomerular dysfunction appears mostly to be permanent. Persistent and even progressive changes in renal tubular function are seen.     

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.