ABSTRACT
Abnormally high myocardial performance index (MPI) is a Doppler-derived marker of combined systolic and diastolic left ventricular (LV) dysfunction. To identify early stage allograft dysfunction by MPI, we studied 154 long-term heart transplantation (HT) recipients (131 male, aged 51 +/- 13 years at HT, mean follow up 8.4 +/- 3.5 years), with normal left ventricular ejection fraction (LVEF) and free from acute rejection (AR), and 25 normals (13 male, aged 39 +/- 16 years). Rejection score (RS) on endomyocardial biopsy was calculated in the first year. MPI was prolonged (0.45 +/- 0.18 vs. 0.28 +/- 0.10, P = 0.0001) in patients and directly related with mean time from HT (P = 0.001), higher cumulative dosages of cyclosporine at 3 months (P = 0.01), 6 months (P = 0.03), 1 year (P = 0.02), 3 years (P = 0.04) and with cumulative dosage of methylprednisolone at 1 year (P = 0.002). The index was inversely related with mean age at HT (P = 0.002) and tended to be directly related with RS at 1 year (P = 0.05). Thus, MPI is abnormal in long-term HT recipients with normal LVEF. Its direct relation with time from HT as well as immunosuppressive load suggests an early stage of graft dysfunction because of chronic rejection. Extended prospective studies are warranted to clarify its potential role as a negative prognostic marker in HT.
Subject(s)
Graft Rejection/physiopathology , Heart Transplantation , Stroke Volume , Ventricular Dysfunction, Left/diagnosis , Adult , Aged , Biomarkers , Blood Pressure , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: The aim of this study was to describe the clinical characteristics of hepatitis C virus (HCV)-infected patients with primary biliary cirrhosis (PBC) by comparison to patients with both antimitochondrial (AMA) positive and AMA negative PBC. METHODS: All patients consecutively diagnosed as having PBC between 1973 and 1999 who had a regular follow-up of at least 2 yr were prospectively included in the study. The mean follow-up was 8.3 +/- 5.7 yr. Survival was calculated according to Kaplan-Meier curves. RESULTS: A total of 170 patients with PBC were considered. The syndrome with PBC and HCV infection (HCV-infected PBC patients) was recorded in 14 patients (13 women and one man), whereas 135 patients had AMA positive PBC and 18 had AMA negative PBC. Only three patients fulfilled the criteria for overlap syndrome involving PBC and autoimmune hepatitis. At presentation, the HCV-infected PBC group had significantly lower levels of ALP, gamma-glutamyl transpeptidase, and IgM than the AMA positive or AMA negative PBC patients (p < 0.01). With regard to the autoantibody profile, there was a significant association with LKM and HCV-infected PBC patients (21.4%), whereas ANA was significantly higher in AMA negative PBC patients than in the other two groups (83% vs 21.4% in the HCV-infected PBC patients and 38.5% in the AMA positive PBC group). No differences were found regarding the association with autoimmune conditions. During follow-up, hepatocellular carcinoma (HCC) developed more frequently in the PBC/HCV overlap group (i.e., three of 14 vs four of 135 patients with AMA positive PBC, p < 0.05). Survival curves were similar in HCV-infected PBC patients and AMA positive PBC, whereas the AMA negative group had a significantly slower decline (relative risk (RR) = 2.44, p < 0.05). CONCLUSION: HCV-infected PBC patients are characterized by a biochemical profile with a modest rise in cholestatic enzymes but a high risk of developing HCC during follow-up.
Subject(s)
Hepatitis C/complications , Liver Cirrhosis, Biliary/complications , Chi-Square Distribution , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique, Indirect , Follow-Up Studies , Genotype , Hepatitis C/pathology , Humans , Liver Cirrhosis, Biliary/genetics , Liver Cirrhosis, Biliary/pathology , Liver Function Tests , Male , Middle Aged , Mitochondria, Liver , Prospective Studies , Risk FactorsABSTRACT
Lipocalin type prostaglandin-D-synthase (L-PGDS), also called beta-trace, is an extracellular protein very abundant in compartments beyond blood-tissue barriers, such as the cerebrospinal fluid, the aqueous humor, the amniotic fluid and the seminal fluid. In the latter fluid the major function of L-PGDS does not seem to be the synthesis of prostaglandin D(2) (PGD(2)) from its precursor PGH(2), which is very unstable in aqueous solution. Instead, seminal L-PGDS, an important carrier of bile pigments, retinoids, thyroid hormones and essential fatty acids, would contribute to providing, beyond the blood-testis barrier, thyroid hormones and retinoids to the developing germ cells in the seminiferous tubules and the maturing spermatozoa in the epididymis.