The role of epsilon phenotype in brain glucose consumption in Alzheimer’s disease

The aim of our study was to investigate the impact of the epsilon phenotype in brain glucose consumption in a population with Alzheimer’s disease. Statistical Parametric Mapping (SPM8) was used to investigate differences in brain glucose consumption (as detectable by means of 18F FDG-PET/CT) in the population examined. A total of 129 patients (72 females and 57 males) with a diagnosis of probable AD according to the NINCDS-ADRDA criteria underwent the PET/CT examination. The mean (SD) age of the patients was 70 (± 7) years; the mean Mini-Mental State Examination was 19(± 5.6). 59 expressed epsilon 4 phenotype (E4) and 70 expressed the epsilon 3 phenotype (E3). Cerebral spinal fluid amyloid, tau, and t-tau have been measured resulting equal to 367.4 (± 149.1), 584.7 (± 312.1), and 79.2(± 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered as high risk of AD, were classified as IAD. Age, sex, MMSE, scholarship, and CSF parameters were used as a covariate in the SPM analyses. We did not find significant differences in age, gender, and MMSE and CSF parameters among groups. In the analysis of the AD group as compared to AD-E3, AD-E4 subjects show a significant reduction of brain glucose consumption in inferior frontal gyrus bilaterally (BA 45, BA 47). In the analysis of the IAD group as compared to IAD-E3, IAD-E4 subjects show a significant reduction of brain glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and between IAD-E4 and AD-E4 (and vice versa analysis) resulted not significant. APO-e4 is related to a major involvement of the frontal cortex confirming its role of risk factor in AD, while APO-3 seems not related to a specific pattern, supporting the hypothesis of neutral/protective role in AD.     

A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit

We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production.     

Can dedicated ambulances improve the efficiency of the neonatal emergency transport service?

OBJECTIVE: To assess whether dedicated ambulances would improve the efficiency of the neonatal emergency transport service (NETS). METHODS: The efficiency of NETS was investigated in the Lazio region, Italy, by comparing data collected during the first 6 months of 1997 (from 1 January to 30 June), with those collected during the same months of 2000, using NETS availability and time investment as indicators. The data yielded by the study were reported as number and percentage, and were analyzed by SPSS 10.1 software; chi2 analysis with Pearson's correction was used to assess the statistical significance of the differences between the two groups; p < 0.05 was considered statistically significant. RESULTS: Our investigation showed a reduced availability of the service in 2000, compared to 1997 (90.4% vs. 95%; p < 0.03). We also noted that in 2000 all dedicated ambulances remained off duty for 26 days, owing to engine failure. The response time and the total transfer time where much longer in 2000 than in 1997 (response time > 30 min in 8% vs. 3%, p < 0.008; total transfer time > 120 min in 37% vs. 30%, p < 0.04). CONCLUSIONS: The reduced efficiency in 2000 was mainly due to the lack of ambulances used to replace the dedicated ambulances. However, the type of ambulance that may provide the best replacement for NETS remains an unsolved question.     

Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations.

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA(Ile) gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject.     

Single dose therapy of vaginal candidiasis: a comparative trial of fenticonazole vaginal ovules versus clotrimazole vaginal tablets

An open, randomized comparative clinical trial was performed in 153 patients suffering from symptomatic vaginal candidiasis confirmed by mycological tests. Patients were allocated at random into two groups: the first group (consisting of 75 subjects) was treated with a single vaginal ovule of fenticonazole (600 mg) and the second group (consisting of 78 subjects) was treated with a single vaginal tablet of clotrimazole (500 mg). Therapeutic efficacy was assessed by microbiological and clinical criteria 7 days and 1 month (when possible) after the single dose treatment. At the first follow-up visit, complete disappearance of the signs and symptoms or a highly significant reduction of their intensity was observed in both treatment groups. No significant difference was evident between the two drugs. At 7 days, the mycological tests gave negative results in 92% of the patients in the fenticonazole group and in 88.5% of the patients in the clotrimazole group. The difference between the two treatment groups was again not statistically significant. The second follow-up visit was performed in 55 (73.3%) patients of the fenticonazole group and in 52 (66.7%) patients of the clotrimazole group. The results indicate that 83.6% of patients in the fenticonazole group and 69.2% of patients in the clotrimazole group were still disease free at the time of this visit. Both drugs were well tolerated. Mild, local and short lasting side-effects were reported in only 5 cases of the group treated with fenticonazole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer.

Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation. INTRODUCTION: Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation. MATERIALS AND METHODS: Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study. RESULTS: After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study. CONCLUSIONS: Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.     

Antagonist muscle inhibition before rapid voluntary movements of the human wrist.

When a fast voluntary movement is performed from a background condition of sustained antagonist muscle activation, there is often a decrease in antagonist muscle activity before the onset of the first agonist muscle burst (AG1) that continues until the onset of the antagonist muscle burst (ANT). We studied how controlling the peak velocity, movement size, and the magnitude of antagonist muscle loading affected antagonist muscle inhibition (AntI). AntI was more pronounced during movements with lower velocity and greater size, and when performed in the direction of heavier background loads, but its variation could not be related to any single kinematic or kinetic variable in all circumstances. When AntI was larger, ANT was smaller, suggesting that AntI does not play a role similar to the premotor silence of the agonist seen before AG1 when the movement is made from a background of sustained agonist contraction. When AntI was larger, the size of AG1 was also smaller, showing that, according to the motor task, different levels of reciprocal inhibition and coactivation occur at the onset of the movement. Both AG1 and AntI produce force in the direction of the desired movement, and the central nervous system selects an appropriate balance between the two, using AntI when possible.     

emm Gene distribution among erythromycin-resistant and -susceptible Italian isolates of Streptococcus pyogenes

The phenotypes and genetic determinants for macrolide resistance were determined for 167 erythromycin-resistant Streptococcus pyogenes strains. A cMLS phenotype was shown in 18% of the erythromycin-resistant strains, while inducible resistance was apparent in 31% and the M phenotype was apparent in 50%. The emm gene type of this set of resistant isolates and that of 48 erythromycin-sensitive isolates were determined. emm2 and emm48 were recorded only in the resistant strains of the M phenotype, while approximately all of the strains harboring the emm22 gene had the cMLS phenotype. More than 80% of the emm89-positive strains had the iMLS phenotype, and the same portion of emm4 strains presented the M phenotype. emm3 is recorded only among sensitive strains. The distribution of frequencies of the genetic determinant for the virulence factor M protein was significantly different both among organisms of different types of resistance and between resistant and sensitive populations of S. pyogenes under study.