Clinical course and management of acute and chronic viral hepatitis during pregnancy.

Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.

Impaired mammary function and parathyroid hormone-related protein during lactation in growth-restricted spontaneously hypertensive rats.

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) during lactation, including stimulation of mammary and pup growth. As spontaneously hypertensive rat (SHR) pups are growth restricted compared with the control Wistar Kyoto (WKY), we examined the relative roles of pup suckling and maternal lactational environment on pup growth, mammary PTHrP, and milk PTHrP and calcium concentrations. SHR pups were lighter compared with the control from 6 days. SHR mammary PTHrP content and milk PTHrP were lower but maternal plasma PTHrP was raised compared with WKY. SHR mammary morphological development was also impaired compared with control. Cross fostering growth-restricted pups onto WKY mothers increased pup weight in association with normal mammary function and higher milk PTHrP and calcium. Control pups suckling on an SHR mother had reduced body weight. Both cross fostering groups were associated with increased maternal and milk PTHrP concentrations, indicating the importance of suckling, together with a functional mammary gland. The results suggested that impaired SHR mammary function and milk PTHrP are associated with a reduced SHR postnatal growth. Our data also indicated that milk and mammary PTHrP are regulated by different mechanisms but that they are influenced by the maternal lactational environment and the suckling pup.

Reduced fetal, placental, and amniotic fluid PTHrP in the growth-restricted spontaneously hypertensive rat.

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) in stimulating cell growth and differentiation, placental calcium transport, and placental vasodilatation. As spontaneously hypertensive rat (SHR) fetuses are growth restricted compared with those of its normotensive control, the Wistar Kyoto (WKY) rat, we examined intrauterine PTHrP and total and ionic calcium concentrations in these rats. Fetal plasma PTHrP concentrations, but not total calcium concentrations, were lower in the SHR compared with WKY (P < 0.05). SHR placental concentrations of PTHrP were lower than in WKY (P < 0.03) and failed to show the increase observed in WKY near term (P < 0.05). PTHrP concentrations in amniotic fluid from SHR were not raised near term and were lower compared with WKY (P < 0.0005). The increased ionic calcium concentrations in amniotic fluid in the WKY near term (P < 0.05) were not detected in the SHR. Thus SHR fetal plasma, placental, and amniotic fluid PTHrP concentrations were reduced and associated with fetal growth restriction. We suggest that PTHrP may play a role in the etiology of both growth restriction during pregnancy and hypertension later in life.

Lipoprotein abnormalities in chronic renal failure and dialysis patients.

Lipoprotein abnormalities are common in patients with chronic renal failure (CRF) on either dialysis or conservative therapy. In order to investigate the changes in lipid and apolipoprotein pattern from early CRF to dialysis treatment, plasma lipids with apoproteins AI, B, E, CII, CIII, CII/CIII ratio, E/CIII ratio, parathyroid hormone (PTH) and insulin levels were examined in 72 patients with different degrees of CRF and 31 patients on hemodialysis (HD), and compared the values of 28 controls. A significant decrease in the Apo CII/CIII ratio was the earliest lipoprotein abnormality to occur in CRF. Hypertriglyceridemia (HTG) with reduced high-density lipoprotein cholesterol levels, increased Apo CIII and decreased Apo E/Apo CIII ratio only occurred in more advanced renal failure (creatinine clearance < 31 ml/min). HD patients showed a general worsening of the lipoprotein profile with elevated Apo E levels and indirect evidence of remnant accumulation. While PTH did not have any significant influence on lipoprotein pattern, increased insulin levels during HD might partly account for the HTG of these patients. Our results point to elevated Apo CIII, reduced Apo CII/Apo CIII and Apo E/ Apo CIII ratios as typical features of uremic hyperlipidemia and show that a defective triglyceride removal is the major pathogenetic mechanism of uremic HTG. HD treatment seems generally to worsen the lipid and apolipoprotein pattern observed in the predialytic stage of CRF.

Lipids and apolipoproteins change during the progression of chronic renal failure.

Uremic hyperlipidemia was recently suggested to contribute to progression of chronic renal failure (CRF). To investigate the relationship between lipoprotein abnormalities and decline of renal function, plasma lipids with apoproteins A1, B, E, CII, CIII, CII/CIII and E/CIII ratios, parathyroid hormone (PTH), insulin and glucose levels were examined in 72 patients with different degrees of CRF and compared to 28 patients of a reference group. A significant decrease of CII/CIII ratio was already evident below a Ccr of 60 ml/min, while increased apo-CIII and triglycerides (TG) with reduced HDL-cholesterol (HDL-C) levels occurred below a Ccr of 30 ml/min. Both TG and apo-CIII showed a positive correlation with creatinine levels. On the contrary, apo-CII/apo-CIII and HDL-C inversely correlated with the progression of renal failure. PTH and insulin showed a positive correlation with TG, the former being also inversely related to apo-CII/apo-CIII ratio. Our results point to early apolipoprotein changes in the course of CRF. Elevated apo-CIII and reduced apo-CII/apo-CIII ratio may be considered the most typical features of uremic hyperlipidemia and likely account for the impaired TG removal and the hypertriglyceridemia (HTG). Secondary hyperparathyroidism may contribute to reduce peripheral lipolytic activity and cause HTG. A contributory role of hyperlipidemia in the progression of renal disease is also supported.

Surgical pathological staging of endometrial carcinoma and results of treatment.

114 women with endometrial carcinoma at clinical stage 1 to 3 were treated with surgery as first line of treatment. Patients were classified as being low or high risk on the basis of the surgical pathological patterns of the tumor. Disease limited to the uterine body, G1-G2 tumors and myometrial invasion of less than 1/3, identified low risk patients which received no adjuvant therapy. All the others were considered high risk and treated with radiation therapy. Patients were retrospectively restaged according to 1988 FIGO guidelines and survival was analyzed. Cox's proportional hazards method was employed to identify independent prognostic factors. Disease free survival (DFS) was 90% for stage 1, 83% for stage 2, and 43% for stage 3 patients. Lymphatic spread was associated to the poorer prognosis. Proportional hazards model showed that tumor grading, myometrial invasion and lymphatic spread were significantly related to the time of relapsing. Low risk patients showed better outcomes despite not having received adjuvant treatment, thus post-operative therapy is not indicated in this subset of patients. Radiation adjuvant therapy for high risk patients did not give satisfactory results. Failures were observed both locally and distantly calling for new adjuvant strategies. Surgical pathological staging of endometrial cancer is currently mandatory. Retroperitoneal lymph node sampling is indicated in patients with high risk pre- (advanced clinical disease, undifferentiated tumors) or intra-operative (deep myometrial invasion, enlarged pelvic nodes) prognostic factors. All prognostic indicators must be obtained from surgery and pathology in order to assess the risk of relapse.