Histological and biological developmental characterization of the human cerebellar cortex

The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex.     

Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group

Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.     

Kidney Transplant in Black Recipients: Are African Europeans Different from African Americans?

Despite recent improvement, significant racial disparities in outcome still persist after renal transplantation among African American patients in the United States. This study evaluated the association of race and ethnicity with allograft outcomes in a French population of 952 Caucasian (Cauc) patients and 140 African European (AE) patients who underwent renal transplantation in our center between 1987 and 2003. Demographic characteristics were similar for the two cohorts other than cause of end-stage renal failure (more hypertension among AE and more polycystic kidney disease among Cauc) and cold ischemia time (significantly longer for AE). Immunosuppressive treatment was comparable between groups. There were no significant differences between AE and Cauc in the incidence of acute rejection (31% vs. 30%). At 5 years post-transplant, patient survival (93% vs. 92%), graft survival (83% in both groups) and graft function (creatinine clearance 48 mL/min vs. 45 mL/min) were also similar among the AE and Cauc patients. We demonstrate that ethnic origin does not affect outcome after renal transplantation in France. Therefore, differences observed in the United States cannot be only related to immunologic or pharmacologic factors. The results of renal transplantation in patients of African origin could be improved with universal immunosuppressive drug coverage.     

High prevalence of NIDDM and impaired glucose tolerance in Indian, Creole, and Chinese Mauritians. Mauritius Noncommunicable Disease Study Group

Mauritius, a multiethnic island nation in the southwestern Indian Ocean, has one of the world's highest diabetes mortality rates. The prevalence of both impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in 5080 Muslim and Hindu Indian, Creole (mixed African, European, and Indian origin), and Chinese Mauritian adults aged 25-74 yr who were selected by random cluster sampling. Based on a 75-g oral glucose tolerance test and World Health Organization criteria, the age-standardized prevalence of IGT was significantly greater in women (19.7%, 95% confidence interval [CI] 18.1-21.2) than in men (11.7%, CI 10.5-12.8). By contrast, the prevalence of NIDDM was similar in men (12.1%, CI 10.9-13.4) and women (11.7%, CI 10.5-12.8) for all ethnic groups combined. The sex difference in IGT prevalence was seen in all ethnic groups, but for NIDDM, the sex difference was not consistent across ethnic groups. However, age- and sex-standardized prevalence of IGT and NIDDM was remarkably similar across ethnic groups (16.2 and 12.4% in Hindu Indians, 15.3 and 13.3% in Muslim Indians, 17.5 and 10.4% in Creoles, and 16.6 and 11.9% in Chinese, respectively). Three new cases of diabetes were diagnosed for every two known cases. The high prevalence of abnormal glucose tolerance in Indian subjects is consistent with studies of other migrant Indian communities, but the findings in Creole and, in particular, Chinese subjects are unexpected. Potent environmental factors shared between ethnic groups in Mauritius may be responsible for the epidemic of glucose intolerance.     

Regulation of ketogenesis, gluconeogenesis, and glycogen synthesis by insulin and proinsulin in rat hepatocyte monolayer cultures

The metabolic actions of porcine insulin and biosynthetic human proinsulin on fatty acid and glucose metabolism were studied in rat hepatocytes cultured in monolayer for 24 h. Our aim was to establish whether proinsulin action in the liver is similar to insulin action and whether the relative potencies of the two hormones are the same for different metabolic processes. Proinsulin and insulin exerted a similar maximal inhibitory effect on ketone body formation from palmitate and on gluconeogenesis from pyruvate. The half-maximal effective concentration of proinsulin was 11-13 times that of insulin. The antiketogenic effects of insulin and proinsulin were associated with an increased glycerol 3-phosphate content and a decreased affinity of carnitine palmitoyltransferase for its substrate palmitoyl-CoA. When the basal rate of ketogenesis was increased with isobutyl methylxanthine, the half-maximal effective concentrations of both proinsulin and insulin were decreased, but the relative potency of the two hormones was unchanged. Proinsulin and insulin exerted similar maximal stimulatory effects on glycogen synthesis and on the activities of pyruvate kinase, glucose 6-phosphate dehydrogenase, phosphogluconate dehydrogenase, and malic enzyme. The half-maximal effective concentration of proinsulin was 10-30 times that of insulin. These findings are consistent with receptor binding studies on liver membranes that suggest that proinsulin interacts with insulin-specific and not proinsulin-specific receptors. Our findings also suggest that proinsulin action does not differ from insulin action at a postreceptor site.     

The risk of pneumonectomy over the age of 70. A case-control study.

OBJECTIVE: A higher mortality has been reported after pneumonectomy over the age of 70. The aim of the study was to quantify the additional risk due to age after standard pneumonectomy for lung cancer by a case-control study. METHODS: Our clinical database was reviewed to search for patients aged 70 years or more who underwent standard pneumonectomy for lung cancer between 1998 and 2005. A control group of patients younger than 70 (one case/two controls) was matched for sex, cardiovascular disease, American Association of Anaesthetists score, respiratory function, side of pneumonectomy, induction chemotherapy and stage. Overall mortality and morbidity were compared. Long-term survival data were also analysed. RESULTS: During the considered period, 35 patients aged 70 years or more underwent pneumonectomy (30 males, median age 73 years, 15 right-sided procedures). The control group was composed of 70 patients. The two groups were homogeneous in the variables used for matching. Overall mortality and morbidity were 11.4 and 54.2% in the elderly group as compared to 4.3 and 41.6% in controls (p-value not significant). Elderly patients experienced a higher rate of respiratory complications (25.7%) as compared to controls (8.3%, p=0.01). At univariate analysis, the only risk factor for death was the occurrence of respiratory complications (OR 6.5, CI 1.8-18.2). At multivariate analysis, age >or=70 years (OR 5.36, CI 1.48-19.3) and preoperative chemotherapy (OR 7.65, CI 2.04-28.6) were confirmed as predictors of respiratory complications. Five-year survival was 17.5% in the elderly group and 53.6% in the control group (p=0.003). Elderly patients with a better respiratory function (FEV1>70%) had a 5-year survival of 45.4%. CONCLUSIONS: In the elderly patients, the risk of respiratory complications after pneumonectomy is increased as compared to younger patients with equivalent respiratory function. Age and preoperative chemotherapy are independent risk factors for respiratory complications. A lower mortality and a better long-term survival are obtained in elderly patients with a better respiratory function (FEV1>or=70%).     

Cytologic diagnosis of non-oxyphil follicular neoplasias of the thyroid. Multivariate classification procedure based on quantitative nucleolar features.

The study was done on cytologic material of 58 non-oxyphil follicular neoplasias of the thyroid, 32 of which were adenomas and 26 carcinomas. Three groups of nucleolar features were quantified using a routine microscope with an ocular micrometer: frequency-, size-, and margination-related features. Since value overlap was present between two categories for all the variables, stepwise discriminant analysis was applied. The following three features were selected by the computer for calculation of one canonical discriminant function: percentage of marginated nucleoli, percentage of nuclei with one nucleolus, mean major nucleolar diameter. The percentage of agreement between morphologic and computer classifications was 95%. Two follicular adenomas were allocated to the carcinoma category, whereas one follicular carcinoma was allocated to the adenoma category. Out of 58, 52 were diagnosed by the computer into one of the two diagnostic categories with a very high probability, i.e. P greater than 0.75, the remaining 6 being considered intermediate.     

A model to predict long-term sustained response to interferon therapy in chronic hepatitis C

Interferon therapy is used widely for chronic hepatitis C but only a minority of treated patients achieve a long-lasting sustained response. We have developed, by logistic regression, a mathematical model to estimate the probability of sustained response in an individual patient with chronic hepatitis C when treated with interferon-α (IFN-α). The model, which includes age, sex, disease duration, pretreatment serum γ-glutamyl-transpeptidase, alanine aminotransferase and virus genotype, was developed from a database of 307 patients and validated in a new set of 200 patients. It performed well as goodness-of-fit ( P = 0.71 and P = 0.15 in the development and test sample, respectively) and discrimination (area under receiver operating curve = 0.79 in the development and 0.78 in the test sample, respectively). This model may provide decision support in the treatment of chronic hepatitis C with IFN-α.