Weight reduction improves markers of hepatic function and insulin resistance in type-2 diabetic patients with non-alcoholic fatty liver.

OBJECTIVE: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing dramatically affecting up to 30% of the population worldwide. At present, treatment options are limited and pharmacological management of NAFLD has had disappointing results. Some of the best available evidence to improve NAFLD concerns lifestyle modification. OBJECTIVE: To detect the degree of weight reduction needed to improve the markers of hepatic function and insulin resistance in type-2 diabetics with NAFLD. METHODS: One hundred type-2 diabetic male patients with NAFLD were included into this study and divided into two equal groups. Group (A) received aerobic exercise training in addition to diet regimen. Group (B) received no treatment intervention. RESULTS: There was a 26.99%, 40.8%, 33.81%, 32.73%, 37.8% and 15 % reduction in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT) and Homeostasis Model Assessment-Insulin Resistance-index (HOMA-IR) and BMI respectively in group (A) at the end of the study. While there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. CONCLUSION: About 15 % reduction in BMI is effective to improve the liver condition and insulin resistance in type-2 diabetics with NAFLD.

High efficacy and low toxicity of APL induction with concurrent idarubicin/ATRA followed by a novel and simplified outpatient post-remission therapy using single doses of idarubicin and intermittent ATRA.

Acute promyelocytic leukemia (APL) is one of the most curable myeloid malignancies because of its great sensitivity to all-trans retinoic acid (ATRA) and response to anthracycline therapy. In an attempt to simplify post-remission therapy, deliver adequate dose of anthracycline and reduce treatment related toxicity, we entered 26 consecutively newly diagnosed, previously untreated APL patients in a pilot treatment program consisting of concurrent induction using idarubicin/ATRA followed by an exclusive outpatient post-remission therapy using single dose of idarubicin and intermittent ATRA, every 4 weeks. Of 25 evaluable patients, two (8%) died early during induction due to hemorrhagic complications, and 23 (92%) achieved complete remission. Overall survival at 4.2 years was 90% (CI 76.4-100), and 3.6 years disease-free survival was 78% (CI 60.6-95.4). The treatment outcome of this program is encouraging; however, the result of this study needs to be validated in larger cohort of patients and optimally in a randomized comparison with other current post-remission approaches.

Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone.

Hepatic veno-occlusive disease (VOD) is one of the most common and important regimen-related toxicities observed after hematopoietic stem cell transplantation (HSCT). There are no universally accepted preventative or therapeutic approaches for VOD. We prospectively evaluated the safety and efficacy of a short course of methylprednisolone (MP) in 48 patients undergoing allogeneic HSCT who were diagnosed with hepatic VOD. MP was administered at a dose of 0.5 mg/kg i.v. every 12 h for a total of 14 doses, and then discontinued without taper. Thirty (63%) patients responded with a reduction in total serum bilirubin of 50% or more after 10 days of treatment. In univariate analysis, non-responders had a higher total bilirubin at the start of MP therapy, more weight gain, evidence of fungal infection and platelet refractoriness. High SGPT and early engraftment were significant factors among responders. Twenty-five of the 30 responders survived up to day +100, whereas all but three non-responders died within 100 days post-HSCT, for a probability of survival of 58% among responders and 10% for non-responders. Prospective comparative studies are needed to confirm the observed encouraging outcome of MP therapy for VOD.

Second allogeneic bone marrow transplantation after myeloablative conditioning analysis of 43 cases from single institution.

Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT1), median age was 11.5 years (range, 0.16-45 years). BMT1 was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, beta-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT1 was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT2) was 14 years (range, 0.41-46.7 years). Indications for BMT2 were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT1 to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT1 to BMT2 interval was 13 months (range, 1-107 months). For BMT2, the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT1 and chemotherapy conditioning +/- ATG for those who received radiation containing conditioning at BMT1. Bone marrow was the stem cell source for all patients at BMT2 and all except three autologous peripheral stem cell transplantation patient at BMT1. Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT2. At a median follow up of 36 months after BMT2, 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD +/- 9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT1-BMT2 interval of > or = 6 months (P=0.0007) and age at BMT2 < or = 10 years (P=0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant (P=0.23). There was no statistically significant difference in survival outcome of BMT2 using same donor vs. alternate related donor (P=0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age < or = 10 years and with an interval of > or = 6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor.

Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study.

OBJECTIVE: To examine whether polymorphism in the RANTES gene is associated with HIV disease outcome. DESIGN: RANTES, a ligand of the major HIV co-receptor, CCR5, is known to block HIV-CCR5 interactions. Recently, two single nucleotide polymorphisms in the RANTES gene promoter region, designated -403G/A and -28C/G, have been described. Both polymorphisms can affect in-vitro promoter activity, and the RANTES -403A, -28G haplotype has been associated with a slower CD4 cell count decline rate in a Japanese cohort. METHODS: We compared RANTES compound genotype frequencies between HIV-positive and exposed-uninfected participants of the Multicenter AIDS Cohort Study (MACS) and rates of progression to AIDS for MACS seroconverters. RESULTS: We found that the two most common RANTES promoter compound genotypes, G1 (-403G/G, -28C/C) found in 67% of Caucasians, and G4 (-403G/A, -28C/C) found in 23% of Caucasians, were associated with altered risk of HIV transmission and progression, particularly in individuals who lacked the protective CCR5 mutation, CCR5delta32. In this study, individuals with a G4 compound genotype were more likely to acquire HIV than individuals with a G1 compound genotype (OR 1.72, P = 0.016) and the risk increased when individuals possessing CCR5delta32 were omitted from consideration (OR 2.13, P = 0.005). Among seroconverters lacking CCR5delta32, those who had the G4 compound genotype progressed significantly slower to AIDS-1993 than those with the G1 compound genotype (median time to AIDS 7.6 versus 5.4 years; RH 0.65; P = 0.007). CONCLUSIONS: These data implicate the RANTES-403A allele as a risk factor for HIV transmission and as a protective factor for HIV progression.

RANTES gene polymorphism in polymyalgia rheumatica, giant cell arteritis and rheumatoid arthritis.

OBJECTIVE: To investigate whether a biallelic polymorphism (A or G) occurring within the promoter region of the RANTES gene (position-403) is associated with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and rheumatoid arthritis (RA). METHODS: A PCR-RFLP method was used to genotype cases and controls for this polymorphism. 3 groups of patients were examined; these comprised GCA patients who did not exhibit features of PMR (n = 30), PMR patients who did not exhibit features of GCA (n = 53) and RA patients (n = 99). All patients and controls (n = 65) originated from the area surrounding Lugo, Galicia, NW Spain. RESULTS: A significant increase in the frequency of allele A was found in PMR patients compared with normal controls. A marginal increase of this allele frequency was observed in RA but not in GCA patients. CONCLUSION: This is the first report of an association of a RANTES gene polymorphisms with PMR and RA. Our data suggest a possible role for of RANTES in the development of both PMR and RA.