Structural findings in the basal ganglia in genetically determined and idiopathic Parkinson's disease

A bilateral compensatory increase of basal ganglia (BG) gray matter value (GMV) was recently demonstrated in asymptomatic Parkin mutation carriers, who likely have an increased risk to develop Parkinson's disease (PD). We hypothesized BG morphological changes in symptomatic Parkin mutation carriers (sPARKIN-MC) and idiopathic PD patients (iPD) after the occurrence of PD symptoms, reflecting the breakdown of compensatory mechanisms. Nine sPARKIN-MC, 14 iPD, and 24 controls were studied clinically and with voxel-based morphometry. Analysis of variance revealed mainly BG decrease of GMV in sPARKIN-MC and to a lesser extent in iPD. However, a slight increase in GMV was also found in the right globus pallidus externus in sPARKIN-MC and in the right putamen in iPD. This may reflect a structural correlate of functional compensation that can only partially be maintained when nigrostriatal neurodegeneration becomes manifest. Simple regression analyses with the UPDRS-III and disease duration score revealed a distinct more bilateral linear decrease of BG GMV in sPARKIN-MC than in iPD that may correspond to previous findings showing a symmetric reduction in putaminal (18)F-DOPA-uptake and bilateral manifestation of symptoms in sPARKIN-MC. In symptomatic PD, BG are subject to a progressive atrophy, which gradually increases with disease severity and duration.     

Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic effect has not yet been defined. The aim of the present study was to investigate the effect of MTX treatment (7.5- 15 mg/week) on synovial tissue in RA. For this purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks after initiation of MTX therapy. Immunohistochemistry was performed using monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)- 1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for disease activity improved during the period of treatment. Immunohistochemical analysis revealed a statistically significant decrease in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial scores for inflammatory cells, monokines and adhesion molecules suggests that the anti- inflammatory effect of MTX is, in part, dependent on a reduction in monokine-inducible vascular adhesion molecules and subsequent reduction of cell traffic into joints.      

Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells

Fusion proteins present in leukemic cells frequently contain a new amino acid at the fusion point. We tested whether a peptide (BCR1/25) encompassing the fusion region of the hybrid molecule pml/RAR alpha, which is selectively expressed by acute promyelocytic leukemia (APL) cells, can be recognized by human T lymphocytes in vitro. CD4+ lymphocytes, at both polyclonal and clonal level, recognized peptide BCR1/25 in an HLA-DR--restricted fashion on presentation by autologous antigen-presenting cell (APC) or by APC expressing the HLA-DR11 restricting molecule. Control peptides corresponding to the normal pml and RAR alpha proteins were not recognized. One clone (DEG5) also exerted a high and specific cytotoxicity against autologous cells pulsed with BCR1/25. The autologous DE LCL containing a transduced pml/RAR alpha fusion gene and expressing a bcr1 type of the pml/RAR alpha hybrid protein induced the proliferation of DE anti-BCR1/25 T cell clones. It is concluded that the bcr1 type-pml/RAR alpha fusion protein of APL contains an antigenic site, absent from the normal parent molecules and recognized by human CD4+ lymphocytes.     

Prospective randomized controlled trial comparing partially absorbable lightweight mesh and multifilament polyester anatomical mesh in laparoscopic inguinal hernia repair

Introduction

Tension‐free mesh repair is currently the gold standard treatment for inguinal hernia. Recent evidence has shown that both open and laparoscopic approaches to inguinal hernia repair can achieve good results. Lots of meshes with different properties are available on the market, but direct comparisons between them are scare. We conducted a prospective randomized controlled trial comparing a partially absorbable lightweight mesh (ULTRAPRO?) and a multifilament polyester anatomical mesh (Parietex?) in laparoscopic total extraperitoneal inguinal hernia repair.

Methods

This study was a single‐center, prospective randomized controlled trial to compare the surgical handling and clinical outcomes between two different types of meshes. All operations were performed using a standardized operative protocol. This study was approved by the Institutional Review Board of the Hong Kong East Cluster Health Service in 2009 (reference number: 2009‐087). The study was registered in the Australian New Zealand Clinical Trial Registry (ACTRN12610000031066).

Results

From October 2009 to August 2011, 85 laparoscopic total extraperitoneal inguinal hernia repairs were performed. The mean mesh handling time was 152 s for the ULTRAPRO group and 206 s for the Parietex group (P = 0.001). There were three cases of seroma formation in the ULTRAPRO group and nine in the Parietex group (P = 0.02). The overall recurrence rate was 2.5%.

Conclusion

It took less time to manipulate the flat mesh (ULTRAPRO) than the anatomical mesh (Parietex) in laparoscopic total extraperitoneal inguinal hernia repair, but the time difference was small. Lightweight mesh and heavyweight mesh offered similar clinical outcomes in terms of discomfort sensation and foreign body sensation during long‐term follow‐up.

     

Frequency of impalpable prostate adenocarcinoma and precancerous conditions in Greek male population: an autopsy study

A series of 212 prostate specimens of men dead between August 2002-August 2004, have been sectioned in consecutive autopsies and subjected to whole mount analysis in purpose to determine the epidemiology of impalpable prostate cancer in Greece. Impalpable prostate carcinomas were found in 40 cases (18.8%) most in the peripheral region. In all, 29 of 40 impalpable cancers (70.7%) had volume less than 1 cm3. Most of impalpable carcinomas were of favorable (Gleason score 2-4) or intermediate (Gleason score 5 and 6) histological type (55 and 27.7%, respectively) while only five (12.5%) were undifferentiated (Gleason score 7 and 8). In all, 24 (60%) of the 40 impalpable carcinomas were multifocal and consisted of two or more foci, most of small size (<0.5 cm3). Most of the impalpable cancers found in this autopsy study were potentially insignificant tumors (relatively low volume, favorable or intermediate histological pattern and absence of invasiveness). Prostate intraepithelial neoplasia (PIN) coexisted with impalpable carcinomas, in almost half of the cancer-positive specimens. There was a positive correlation between PIN foci and coexistent cancer foci in most of the cases. Frequency rate and pathological features of both entities show significant variations in medical literature. Since the incidence of clinical prostate cancer in Greece is relatively low, and according to our autopsy findings, it is plausible that the frequency of clinical prostate cancer in a certain population could be related to the prevalent model of impalpable cancer as well as to the frequency and extend of the precancerous lesions.     

Long-term treatment with intracavernosal injections in diabetic men with erectile dysfunction

Aim： To assess the behavior of patients with diabetes mellitus （DM） and erectile dysfunction （ED） during 10 consecutive years of treatment with self-injection of vasoactive drugs. Methods： Thirty-eight diabetic men, including 12 with type Ⅰ and 26 with type Ⅱ diabetes, were followed up regularly for 10 years after they began self-injecting for severe ED. Real time rigidity assessment was used for the objective determination of the initial dosage and then doses were regulated in order to introduce an erection suitable for penetration and maintenance of erection for approximately 30 min. Patients were followed up every two months, and doses were increased only when the treatment response was not satisfactory. Results： The number of injections used per year by the patients was reduced each year （mean numbers： 50 in the first year and 22.5 in the 10th） and treatment shifted towards stronger therapeutic modalities （mixtures of vasoactive drugs instead of prostaglandin E1 alone）. Type Ⅰ diabetic men were standardized to a level of treatment as early as 5 years after the initiation of treatment. That level was finally reached by type Ⅱ patients after another 4-5 years. Conclusion： Treatment with self-injections of vasoactive drugs in diabetic men with severe El） is a safe and effective alternative in the long term. Diabetic men of both types show the same preferences in quality and quantity of treatment after 10 years. The key point for maintenance in treatment is the adjustment of the therapeutic method and dosage to optimal levels for satisfactory erections. （Asian J Androl 2006 Mar; 8： 219-224）