Nonalcoholic Fatty Liver Disease, Diabetes Mellitus and Cardiovascular Disease: Newer Data

Nonalcoholic fatty liver disease (NAFLD) is the most common, chronic liver disease worldwide. Within this spectrum, steatosis alone is apparently benign, while nonalcoholic steatohepatitis may progress to cirrhosis and hepatocellular carcinoma. NAFLD is strongly associated with obesity, dyslipidemia, type 2 diabetes mellitus, and cardiovascular disease. The pathogenesis of hepatic steatosis is not clearly known, but its main characteristics are considered insulin resistance, mitochondrial dysfunction, increased free fatty acids reflux from adipose tissue to the liver, hepatocyte lipotoxicity, stimulation of chronic necroinflammation, and fibrogenic response. With recent advances in technology, advanced imaging techniques provide important information for diagnosis. There is a significant research effort in developing noninvasive monitoring of disease progression to fibrosis and response to therapy with potential novel biomarkers, in order to facilitate diagnosis for the detection of advanced cirrhosis and to minimize the need of liver biopsy. The identification of NAFLD should be sought as part of the routine assessment of type 2 diabetics, as sought the microvascular complications and cardiovascular disease, because it is essential for the early diagnosis and proper intervention. Diet, exercise training, and weight loss provide significant clinical benefits and must be considered of first line for treating NAFLD

Dietary fat intake as a risk factor for the development of diabetes. Multinational, multicenter study of the Mediterranean Group for the Study of Diabetes (MGDS)

In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes(RDM),42subjectswithundiagnoseddiabetes(UDM)(AmericanDiabetesAssociation criteria—fasting plasma glucose [FPG] 126 mg/dl), and 55 subjects with impaired fasting glucose(IFG)(FPG 110and126mg/dl).Eachgroupwascomparedwithacontrolgroupof nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS— Compared with control subjects, RDM more frequently had a family history of diabetes(49.0vs.14.2%;P0.001),exercisedless(exerciseindex53.5vs.64.4;P0.01),and more frequently had sedentary professions (47.5 vs. 27.4%; P 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P 0.05), whereas total fat (30.2 0.5 vs. 27.8 0.5%; P 0.001) and animal fat (12.2 0.3 vs. 10.8 0.3%; P 0.01) contributed moreandtheplant-to-animalfatratiowaslower(1.50.1vs.1.80.1;P0.01).UDMmore frequentlyhadafamilyhistoryofdiabetes(38.1vs.19.0%;P0.05)andsedentaryprofessions (58.5vs.34.1%;P0.05),carbohydratescontributedlesstotheirenergyintake(47.61.7vs. 52.81.4%;P0.05),totalfat(34.71.5vs.30.41.2%;P0.05)andanimalfat(14.2 0.9 vs. 10.6 0.7%; P 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 0.2 vs. 2.3 0.4; P 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P 0.05). CONCLUSIONS— Our data support the view that increased animal fat intake is associated with the presence of diabetes

Spinal versus General Anaesthesia in Postoperative Pain Management during Transurethral Procedures

We compared the analgesic efficacy of spinal and general anaesthesia following transurethral procedures. 97 and 47 patients underwent transurethral bladder tumour resection (TUR-B) and transurethral prostatectomy (TUR-P), respectively. Postoperative pain was recorded using an 11-point visual analogue scale (VAS). VAS score was greatest at discharge from recovery room for general anaesthesia (P = 0.027). The pattern changed significantly at 8 h and 12 h for general anaesthesia's efficacy (P = 0.017 and P = 0.007, resp.). A higher VAS score was observed in pT2 patients. Patients with resected tumour volume >10 cm3 exhibited a VAS score >3 at 8 h and 24 h (P = 0.050, P = 0.036, resp.). Multifocality of bladder tumours induced more pain overall. It seems that spinal anaesthesia is more effective during the first 2 postoperative hours, while general prevails at later stages and at larger traumatic surfaces. Finally, we incidentally found that tumour stage plays a significant role in postoperative pain, a point that requires further verification

Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy

Women with polycystic ovary syndrome who present with hyperandrogenemia, hyperinsulinemia, and insulin resistance appear to be at high risk of cardiovascular disease. Elevated levels of endothelin-1, a marker of vasculopathy, have been reported in insulin-resistant subjects with endothelial dysfunction. Male gender also seems to be an aggravating factor for cardiovascular disease. In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels. Plasma endothelin-1 levels were measured in 23 obese (mean age, 24.3 +/- 4.6 yr; body mass index, 35 +/- 5.6 kg/m(2)) and 20 nonobese women with polycystic ovary syndrome (24.1 +/- 3.6 yr; body mass index, 21.8 +/- 2.5 kg/m(2)) as well as in 7 obese and 10 nonobese healthy, normal cycling, age-matched women. Additionally, endothelin-1 levels were evaluated in a subgroup of women with polycystic ovary syndrome (10 obese and 10 nonobese) 6 months postmetformin administration (1700 mg daily). Our results showed that obese and nonobese women with polycystic ovary syndrome had higher levels of endothelin-1 compared with the controls [obese, 2.52 +/- 1.87 vs. 0.44 +/- 0.23 pmol/liter (by analysis of covariance, P < 0.02); nonobese, 1.95 +/- 1.6 vs. 0.43 +/- 0.65 pmol/liter (P < 0.009)]. All of the participating women with polycystic ovary syndrome (n = 43) when compared with the total group of controls (n = 17) demonstrated hyperinsulinemia (polycystic ovary syndrome, 24.5 +/- 19.6; controls, 11.2 +/- 3.4 U/liter; P < 0.03), lower glucose utilization (M40) during the hyperinsulinemic euglycemic clamps (3.4 +/- 2.4 vs. 5.6 +/- 1.75 mg/kg.min; P < 0.045, by one-tailed test), and higher levels of endothelin-1 (polycystic ovary syndrome, 2.52 +/- 1.87; controls, 0.44 +/- 0.23 pmol/liter; P < 0.02, analysis of covariance covariate for body mass index). A positive correlation of endothelin-1 with free T levels was also shown (r = 0.4, P = 0.002) as well as a negative correlation of endothelin-1 with glucose utilization (r = -0.3; P = 0.033) in the total studied population. Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P < 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P < 0.01) women with polycystic ovary syndrome, with no change in body mass index. Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 +/- 0.15 ng/ml; fasting insulin, 22.2 +/- 12.1 U/liter; glucose utilization, 2.15 +/- 0.5 mg/kg.min; obese after: total T, 0.5 +/- 0.2 ng/ml; fasting insulin, 11.6 +/- 6 U/liter; glucose utilization, 4.7 +/- 1.4 mg/kg.min 9P < 0.003, P < 0.006, and P < 0.002, respectively); nonobese before: total T, I 0.5 ng/ml; fasting insulin, 15.5 +/- 7.6 U/liter; glucose utilization, 3.4 +/- 0.7 mg/kg.min; nonobese after: total T, 0.8 +/- 0.5 ng/ml; fasting insulin, 9 +/- 3.8 U/liter; glucose utilization, 6 +/- 1.7 mg/kg.min (P < 0.04, P < 0.02, and P < 0.0008, respectively)]. In conclusion, our data clearly demonstrate that women with polycystic ovary syndrome, obese and nonobese, have elevated endothelin-1 levels compared with the age-matched control group. In addition, 6 months of metformin therapy reduces endothelin-1 levels and improves their hormonal and metabolic profile

Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy

Women with polycystic ovary syndrome who present with hyperandrogenemia, hyperinsulinemia, and insulin resistance appear to be at high risk of cardiovascular disease. Elevated levels of endothelin-1, a marker of vasculopathy, have been reported in insulin-resistant subjects with endothelial dysfunction. Male gender also seems to be an aggravating factor for cardiovascular disease. In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels. Plasma endothelin-1 levels were measured in 23 obese (mean age, 24.3 ± 4.6 yr; body mass index, 35 ± 5.6 kg/m2) and 20 nonobese women with polycystic ovary syndrome (24.1 ± 3.6 yr; body mass index, 21.8 ± 2.5 kg/m2) as well as in 7 obese and 10 nonobese healthy, normal cycling, age-matched women. Additionally, endothelin-1 levels were evaluated in a sub-group of women with polycystic ovary syndrome (10 obese and 10 nonobese) 6 months postmetformin administration (1700 mg daily). Our results showed that obese and nonobese women with polycystic ovary syndrome had higher levels of endothelin-1 compared with the controls [obese, 2.52 ± 1.87 vs. 0.44 ± 0.23 pmol/liter (by analysis of covariance, P < 0.02); nonobese, 1.95 ± 1.6 vs. 0.43 ± 0,65 pmol/liter (P < 0.009)]. All of the participating women with polycystic ovary syndrome (n = 43) when compared with the total group of controls (n = 17) demonstrated hyperinsulinemia (polycystic ovary syndrome, 24.5 ± 19.6; controls, 11.2 ± 3.4 U/liter; P < 0.03), lower glucose utilization (M40) during the hyperinsulinemic euglycemic clamps (3.4 ± 2.4 vs. 5.6 ± 1.75 mg/kg·min; P < 0.045, by one-tailed test), and higher levels of endothelin-1 (polycystic ovary syndrome, 2.52 ± 1.87; controls, 0.44 ± 0.23 pmol/liter; P < 0.02, analysis of covariance covariate for body mass index). A positive correlation of endothelin-1 with free T levels was also shown (r = 0.4, P = 0.002) as well as a negative correlation of endothelin-1 with glucose utilization (r = -0.3; P = 0.033) in the total studied population. Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 ± 2.2; endothelin-1 after, 1.1 ± 0.9 pmol/liter; P < 0.003) and nonobese (endothelin-1 before, 2.7 ± 2; endothelin-1 after, 0.7 ± 0.4 pmol/liter; P < 0.01) women with polycystic ovary syndrome, with no change in body mass index. Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 ± 0.15 ng/ml; fasting insulin, 22.2 ± 12.1 U/liter; glucose utilization, 2.15 ± 0.5 mg/kg·min; obese after: total T, 0.5 ± 0.2 ng/ml; fasting insulin, 11.6 ± 6 U/liter; glucose utilization, 4.7 ± 1.4 mg/kg·min 9P < 0.003, P < 0.006, and P < 0.002, respectively); nonobese before: total T, 1 ± 0.5 ng/ml; fasting insulin, 15.5 ± 7.6 U/liter; glucose utilization, 3.4 ± 0.7 mg/kg·min; nonobese after: total T, 0.8 ± 0.5 ng/ml; fasting insulin, 9 ± 3.8 U/liter; glucose utilization, 6 ± 1.7 mg/kg·min (P < 0.04, P < 0.02, and P < 0.0008, respectively)]. In conclusion, our data clearly demonstrate that women with polycystic ovary syndrome, obese and nonobese, have elevated endothelin-1 levels compared with the age-matched control group. In addition, 6 months of metformin therapy reduces endothelin-1 levels and improves their hormonal and metabolic profile

Cutaneous manifestations in relation to immunologic parameters in a cohort of primary myelodysplastic syndrome patients

Background: Cutaneous lesions in myelodysplastic syndrome (MDS) may be specific or not and may reveal bone marrow transformation. Our purpose was to investigate in a cohort of 84 MDS patients the correlation of cutaneous findings with immunologic parameters and prognostic features of MDS in order to clarify their potential clinical significance. Materials and methods: We studied a cohort of 84 newly diagnosed MDS patients in order to assess the cutaneous findings present at the time of diagnosis and during 1 to 3.years of follow-up. We described the clinical variety of cutaneous findings ascertained by histology. We also looked for any association between the group of MDS patients with skin manifestations and MDS subtype, immunologic and prognostic features highlighting transformation to acute leukaemia. Results: Twenty-one patients presented cutaneous manifestations: 1 patient developed leukaemia cutis, 6 patients photosensitivity not associated with autoimmune disease, 3 prurigo nodularis, 2 Sweet's syndrome, 6 leucocytoclastic vasculitis, 2 ecchymoses and purpura associated with preexisting relapsing polychondritis, 1 patient subcutaneous nodules associated with Wegener's granulomatosis and 1 patient with malar rash and oral ulcers associated with preexisting systemic lupus erythematosus. Adjusted for age and gender, the presence of skin findings constitutes a significant predictor of the high-risk MDS subgroup (odds ratio, 3.59; 95% confidence interval, 1.18-10.92). Hypergammaglobulinemia was significantly higher in the MDS subgroup with skin manifestations (P = 0.03). Conclusion: Most MDS patients with cutaneous manifestations belong to the high-risk MDS subgroup and present hypergammaglobulinemia. Early biopsy of skin lesions in myelodysplasia is indicated. © 2007 The Authors Journal compilation © 2007 European Academy of Dermatology and Venereology

Synchronous chromophobe and papillary renal cell carcinoma. First report and review of the pathogenesis theories: Case Report

The coexistence of different subtypes of renal cell carcinoma (RCC) within a single kidney is an extremely unusual entity. Presented herein is the case of a 57-year-old man with two RCC of chromophobe and papillary histology. Very few reports in the literature describe double or triple synchronous renal neoplasms. To our knowledge this is the first report of this RCC subtype combination, which might trigger further investigation on the RCC pathogenesis theories. © 2009 Japanese Society of Pathology