Corticotrophin-releasing factor immunostaining is present in placenta and fetal membranes from the first trimester onwards and is not affected by labour or administration of mifepristone

BACKGROUND AND OBJECTIVES Corticotrophin releasing factor (CRF) is present in the human placenta and fetal membranes. Placental CRF content and plasma CRF concentrations rise throughout gestation and fail rapidly after delivery. The regulation of CRF production from the placenta is poorly understood. The objective of this study was to use the antiprogestin, mifepristone, to determine whether progesterone has a regulatory effect on CRF production in the first trimester of pregnancy. PATIENTS Women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE, analogue, gemeprost (16,16-dimethyl-trans- Δ²-PGE₁ methyl ester) vaginally 2-4 hours prior to the procedure; or with 600 mg mifepristone 48 hours prior to receiving 1 mg gemeprost vaginally), second trimester therapeutic abortion (600 mg mifepristone, 1 mg gemeprost), In association with pre-term delivery (gestation 25-34 weeks) and at term (gestation 35-42 weeks) by spontaneous delivery, induced labour or elective Caesarean section. MEASUREMENTS immunohistochemical localization Of CRF and quantification of CRF content by radioimmunoassay of tissue extracts, in human placenta and fetal membranes. RESULTS CRF was Immunolocalized to the syncytlo-trophoblast cells of the placenta at ail stages of gestation from 5 to 42 weeks. In the fetal membranes CRF immunoreactlvity was localized in the epithelial and subepithelial cells of the amnion, some cells of the reticular and cellular layers of the chorion, and in decidual stroma. This pattern was seen in all tissues studied. Pretreatment with prostaglandins, mifepristone or both during the first trimester did not alter the distribution or the intensity of the CRF Immunostaining. Placental CRF content rose throughout gestation but, consistent with the Lmmunostaining results, was unaffected by the administration of mifepristone or by labour. CONCLUSIONS CRF is localized in the syncitlotropho-blast cells of the placenta and is clearly present early in the first trimester of pregnancy. The lack of an effect of mifepristone or mode of delivery suggests that syncytlo-trophoblast produces CRF constitutively throughout pregnancy.     

Anticoagulant effects of sulphonated polyurethanes.

Sulphonated polyurethanes have been shown to have excellent blood contacting properties. In this paper, similar polyurethanes which are water soluble have been investigated to determine their influence on thrombus formation. These polymers were shown to delay clotting times in the following ways: by direct complex formation between the polymer and thrombin; by interference with fibrin polymerization; and by complex interactions between polymer, thrombin, plasma antiproteases and fibrinogen in plasma.     

Therapeutic challenges in hepatitis C-infected injection drug using patients

Hepatitis C Viral (HCV) infection in the injection drug user (IDU) population is a major medical concern. Concurrent substance abuse, co-morbid mental health conditions, poor socioeconomic status and a complex treatment protocol that is often incompatible with the life styles of IDUs combine to account for poor uptake and completion of HCV treatment. This article discusses HCV antiviral treatment issues relevant to IDUs chronically infected with this virus. The effect of non-injected substances of abuse on treatment outcome is considered. Priority issues requiring research are discussed.     

Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100mg/m², IV_Y day 8), Adriamycin (30mg/m², IV_Y days 1,2), teniposide (75 mg/rn², IV, day 1), cyclophophamide (300 mg/m², po, days one to five), Oncovin (1.4 mg/m², IV: maximum 2 mg, days 8,15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m², IV, day 1), Adriamycin (50 mg/m², IV, day 1), Oncovin (1.4 mg/m² IV: maximum 2 mg, day 1) and prednisolone (100 mg, PO, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p 0.0001), mucositis (p= 0.002) and infections (p= 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification. (Aust NZ J Med 1992; 22: 123–128.)     

Complex I,Iron, and ferritin in Parkinson's disease substantia nigra

Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron-ferritin ratio and complex I activity in the substantia nigra samples.     

Transplantation for myocarditis: a controversy revisited.

Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy (IDC). Worldwide, approximately 45% of all heart transplants are performed for IDC and up to 8% for myocarditis. Early reports suggested that survival after transplantation for myocarditis was poor and patients had an increased risk of rejection. More recently, larger case series suggest that overall survival after transplantation for myocarditis is similar to survival after transplantation for other causes. However, certain disorders, including cardiac sarcoidosis and giant cell myocarditis (GCM), require heightened surveillance for post-transplantation disease recurrence. We present the case of a 42-year-old man with recurrence of GCM 8 years after transplantation and review the literature on the role of cardiac transplantation for patients with myocarditis.