Acquired and inherited thrombophilia in women with unexplained fetal losses

OBJECTIVE: The purpose of this study was to investigate the possible role of inherited and acquired thrombophilia in women with unexplained abortions and intrauterine fetal death. STUDY DESIGN: We included 75 women with >/=1 unexplained fetal loss, and 75 control subjects with at least 1 healthy term infant and without gestational complications. All of these women were tested for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; deficiencies of antithrombin-III, protein C, and protein S; and the presence of antiphospholipid antibodies and fasting homocysteine concentration. A placental histologic study was also carried out. RESULTS: Thirty-five percent of the 75 patients had thrombophilia (control subjects, 16%; P =.008; odds ratio, 2.78). This prevalence was more prominent in second and third trimesters (P =.0002; odds ratio, 6.3), and the presence of combined genetic defects was associated with intrauterine fetal death (P =.04; odds ratio, 12; 95% CI, 1.44-102). When we analyzed the overall gestations of the patients, we observed an increase of intrauterine fetal death in patients with thrombophilia (P =.01) and early pregnancy loss in patients without thrombophilia (P =.02). The analysis of the correlation between extensive placental infarctions and thrombophilic defects rendered values in the boundaries of significance (P =.05). CONCLUSION: The significant high prevalence of biologic causes in patients with late fetal loss suggests that a study of thrombophilia should be carried out, together with an assessment of a preventive treatment.     

Hemodynamic state and the role of angiotensin II in ovarian hyperstimulation syndrome in the rabbit

Objective: To investigate the hemodynamic state in the ovarian hyperstimulation syndrome (OHSS) in the rabbit model and to determine the role of angiotensin II in the pathophysiology of this syndrome.

Design: Experimental study.

Setting: Physiology laboratory.

Animal(s): Female New Zealand rabbits were studied; 16 rabbits were stimulated with gonadotropins, and 6 were controls. Six of the stimulated rabbits received additional treatment with captopril.

Main Outcome Measure(s): Cardiac index, blood pressure, and heart rate were recorded.

Result(s): Gonadotropin-stimulated rabbits had significant enlargement of ovaries that was not modified by captopril. Ascites was present in 80% of animals in the OHSS group; captopril significantly decreased the incidence and volume of ascites. The three groups did not differ in blood pressure, heart rate, cardiac index, and total peripheral resistance.

Conclusion(s): In rabbits with OHSS, ascites are a primary event. Such animals are normotensive and have normal vascular resistance and cardiac index. Angiotensin-converting enzyme inhibition decreases the incidence of OHSS in the rabbit model by 30%, suggesting that angiotensin II may play a role in the formation of ascites.     

The association of benign and malignant ovarian adenofibromas with breast cancer and thyroid disorders

An unexpected association with breast cancer and thyroid disorders was found during a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papillary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibromas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thyroid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast cancer and 16% of each one of these groups had thyroid disorders. This unexpected association found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits.     

Spontaneous pneumothorax during pregnancy

Spontaneous pneumothorax complicating pregnancy is rare. Only 41 cases have been previously published. We describe a case of spontaneous pneumothorax successfully treated with tube thoracostomy during the 38th week of pregnancy. Under epidural anesthesia, the patient had vaginal delivery of a healthy male infant 36 hours after tube thoracostomy.     

The potential role of the HIV-1 immunogen (Remune) as a therapeutic vaccine in the treatment of HIV infection

Immune-based therapies, such as therapeutic vaccination, that might preserve, restore, enhance and induce new HIV-specific immunologic responses are currently being explored. HIV-specific immunotherapy with Remune (The Immune Response Corp.) offers the opportunity to boost immune responses against HIV-1. The clinical trial program in a wide range of subjects has established the efficacy of Remune in stimulating an appropriate immune response in HIV-positive individuals. Furthermore, a recent unblinded study conducted in Europe has documented a significant effect of Remune on viral load. Evidence regarding clinical end points is more difficult to collect. The same studies have revealed no serious safety issues in a total of more than 2000 Remune-treated patients. It is therefore reasonable to suggest that the risk-benefit ratio of Remune could be positive.     

Mechanism of induction of complement susceptibility of erythrocytes by spider and bacterial sphingomyelinases

We have recently shown that the sphingomyelinase toxins P1 and P2 from the venom of the spider Loxosceles intermedia induce complement (C)-dependent lysis of autologous erythrocytes by induction of the cleavage of cell surface glycophorins through activation of an endogenous metalloproteinase facilitating the activation of the alternative pathway of C. Phospholipase D (PLD) from Corynebacterium pseudotuberculosis shows some degree of homology with the spider sphingomyelinases and can induce similar clinical symptoms to those observed after spider envenomation. The aim of this study was to investigate if the bacterial PLD-induced haemolysis of human erythrocytes was C dependent and if cleavage of glycophorins occurred. We show here that haemolysis of both PLD- and P1-treated human erythrocytes was C dependent, but while PLD-mediated haemolysis was dependent on activation of the classical pathway of C, P1 induced lysis via both the classical and alternative pathways. P1, but not PLD, induced cleavage of glycophorins and no change in expression of complement regulators was induced by either of the toxins. In both cases, annexin V binding sites were exposed, suggesting that the membrane asymmetry had been disturbed causing exposure of phosphatidylserine to the cell surface. Our results suggest that C susceptibility induced by L. intermedia and C. pseudotuberculosis PLD is a result of exposure of phosphatidylserine, and the higher potency of P1 toxin can be explained by its additional effect of cleavage of glycophorins.