MR correlates of cerebral atrophy in patients with multiple sclerosis

Objective To investigate the in-vivo correlates of brain atrophy in patients with multiple sclerosis (MS) by assessing the relationship between normalized measures of brain volume (NBV) and other magnetic resonance (MR) measures of tissue damage. Background Brain atrophy diffusely occurs and progressively increases in patients with MS. Nevertheless, the mechanisms leading to brain atrophy in this disease are not fully understood. Methods MR examinations were performed in 20 patients with relapsing-remitting MS. Conventional MRI was used to assess NBV and total brain T2-hyperintense and T1-hypointense lesion volumes. Proton MR spectroscopic imaging and diffusion tensor MR imaging were also performed for large portions of brain containing mainly normal-appearing tissue to provide indices of tissue damage, including N-acetylaspartate to creatine ratio (NAA/Cr) and mean diffusivity (). Results Values of NBV correlated significantly with those of average brain (r = -0.58, p = 0.007) and NAA/Cr (r = 0.67, p < 0.001). The relationship of these markers of tissue damage to NBV was also found when NAA/Cr and were computed together in a composite MR score (r = 0.70, p < 0.001). In contrast, NBV values did not correlate with measurements of average lesion , T₂ and T₁ weighted total brain MRI lesion volumes. Conclusions This study suggests that brain atrophy in MS is not simply due to axonal loss, but rather reflects a more generalized process that involves various brain tissue components. Damage to the normal-appearing tissue rather than the extent and intrinsic pathology of macroscopic lesions seems to be important in the destructive process leading to MS-related irreversible cerebral atrophy. Received: 13 September 2001 Received in revised form: 18 January 2002 Accepted: 4 March 2002     

BDNF binding to truncated trkB.T1 does not affect gene expression

Truncated trkB.T1 is a splice variant of the neurotrophin receptor trkB. In spite of its abundance, and ability to bind and internalize BDNF, it is not clear whether it can transmit BDNF signaling. We tested this hypothesis by searching for proteins binding the evolutionarily conserved cyto-domain of trkB.T1, and by studying BDNF-induced changes of gene expression through DNA microarrays. Cells bearing trkB.T1 receptors presented morphological changes. However, no cytoplasmic interactors of trkB.T1 were found. In addition, BDNF-dependent modulation of gene expression was detected in cells bearing trkB.TK but not trkB.T1 receptors. These results suggest that the main function of trkB.T1 is to regulate local availability of neurotrophins and that it is unable to sense changes in BDNF availability.     

Postsplenectomy immunodepression and its implications: an underestimated problem

The most important sequelae of splenectomy is immunity depression. This study, conducted in three phases, was aimed at confirming this clinical condition. Data from our phase 1 study clearly show that patients undergoing splenectomy for trauma are in a critical condition because of a latent immunodeficiency shown by skin tests (ST) and in vitro evaluation of the aspecific immune activity. Because the in vitro study of the unspecific immunity that we used seems to be more expensive and complicated than ST, the aim of the phase 2 study was to compare the efficacy and the limits of the two assays (ST versus in vitro study) in detecting the immunodeficiency status of the splenectomized patient. The aim of the phase 3 study was to ascertain whether postsplenectomy immunodeficiency could be a consequence of an altered equilibrium between the lymphocyte subpopulations T helper (Th)1/Th2, evaluated by serum dosage of interferon-gamma and interleukin-4.     

Depression in primary care. A nationwide epidemiological survey

BACKGROUND: Most epidemiological studies on depression in primary care are conducted at single sites, and variations in reported prevalence may depend on characteristics of health care services and other local factors. OBJECTIVES: Our aim was to investigate the prevalence of depression in primary care in Italy and its association with physical illness, disability and health care utilization. METHODS: This nationwide epidemiological study involved 191 primary care physicians (PCPs) who assessed during one index week 1896 patients aged 14 and over attending their clinics. Screening was conducted by using the General Health Questionnaire-12. Probable cases were assessed by PCPs with the WHO ICD-10 Checklist for Depression and rated for severity of physical illness. RESULTS: The prevalence of current depression ranged between 7.8 and 9.0% in the three main Italian areas, with no significant variations. A linear increase from North to South was observed for psychological distress, disability and frequency of medical consultation. Depression was associated with severe, but not with mild or moderate physical illness. Depression was also associated with disability and accounted for an increased rate of consultation. CONCLUSION: Because of the disability associated with depression and of its impact on health care utilization, guidelines and intervention strategies are needed.     

Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application

A novel class of cationic block copolymers constituted by a neutral hydrophilic poly(ethylene glycol) (PEG) block and a positively charged poly(dimethylamino)ethyl methacrylate block was prepared for delivery of DNA. These block copolymers spontaneously assemble with DNA to give in aqueous medium micellar-like structures. Five of these novel block copolymers (K1-5), differing in the length of both the PEG chain and the linear charge density of the poly(dimethylamino)ethyl methacrylate block, were prepared and analyzed for gene delivery, gene expression and safety. All five block copolymers protected DNA from DNAse I digestion and delivered the DNA into the cell. However, only three of them (K1, K2 and K5) released the DNA at level allowing efficient gene expression into cells. No toxic effects of both the copolymers alone or their DNA complexes were observed in vitro or in mice. In addition, copolymers were scarcely immunogenic. These results indicate that this novel class of cationic block copolymers is safe and possesses the biological characteristics required for DNA delivery, thus, representing promising vehicles for DNA vaccination.     

Addressing inequity in health and health care in Mexico

Despite the fact that life expectancy at birth in Mexico has improved from forty-two years in 1940 to seventy-three in 2000, major inequalities persist in health and access to health care. The Mexican health care system has evolved into a series of disjointed subsystems that are incapable of delivering universal health insurance. Without greatly restructuring the way health care is financed, performance with respect to equity will remain poor. This paper presents the inequities of the system and describes how the current system contributes to the status quo rather than redressing the situation. After tracing the origins of the present system, we discuss policy initiatives for moving toward universal health insurance.     

Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients

90K, also known as Mac-2 binding protein, is a secreted glycoprotein that binds galectins, beta1-integrins, collagens, and fibronectin, and has some relevance in cell-cell and cell-extracellular matrix adhesion. Previous studies have shown that serum levels of 90K have prognostic value in several neoplasms. In the present study, the role of the expression of 90K as an adverse prognostic indicator in 72 pathological stage I non-small cell lung cancer patients was investigated immunohistochemically. All of the patients underwent complete surgical removal of the tumor. The median length of follow-up care was 54 months. High level of 90K expression (90K staining of > or =50% of the neoplastic cells) was observed in 20 of the 72 (28%) tumors. Expression of 90K was confirmed by ELISA. The results showed that a high expression of 90K correlates with adverse prognosis. Among patients with high 90K expression, the disease-free and overall survival rates were significantly lower than the same rates of those with low expression (P = 0. 0001 and P = 0. 0003, respectively). The incidence of distant metastases in the patients with high 90K expression (60%; 12 of 20 patients) was significantly higher than that of in the patients with low expression (21%; 11 of 53 patients; P = 0.0038). The results of multivariate analysis confirmed that a high 90K expression was a significant factor to predict poor prognosis. We suggest that 90K expression could be a useful prognostic factor in patients with stage I non-small cell lung cancer, likely as an indicator of the metastatic propensity of the tumor.     

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting

PURPOSE: To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. MATERIAL: A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. METHOD: TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. RESULTS: Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. CONCLUSIONS: The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.