HCV infection and extrahepatic manifestations

Hepatitis C virus infection is associated with various extrahepatic manifestations such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis and porphyria cutanea tarda. The link between mixed cryoglobulinemia and hepatitis C virus infection is actually well known. Interferon alpha therapy decreases hepatitis C viremia and improves the clinical signs and biochemical abnormalities of cryoglobulinemia. The rare combination of hepatitis C and panarteritis nodosa has still not been confirmed. The sicca syndrome also seems to be associated with hepatitis C virus, but this is not the typical Sjogren's syndrome. It is not yet well established if hepatitis C virus plays a pathogenic role in the development of thyroid dysfunction and autoimmune thyroiditis. Probably interferon therapy may be implicated in the development in this and other extrahepatic manifestations of hepatitis C virus infection. Although an epidemiological association of hepatitis C with lichen planus, neuropathies and other diseases has been observed, the etiological role and the pathogenic involvement of the hepatitis C infection remains unclear. Extrahepatic clinical manifestations are frequently observed in hepatitis C virus patients and involve primarily the joints, muscles, and skin. The most frequent immunological abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies.     

Expression profiles of a human pancreatic cancer cell line upon induction of apoptosis search for modulators in cancer therapy

We analyzed the differential gene expression in the pancreatic cancer cell line NP-18 upon induction of apoptosis caused by cyclin-dependent kinase inhibition triggered by either overexpression of the tumor suppressor gene p16(INK4A)using an adenoviral construction or incubation with the chemical inhibitors, roscovitine or olomoucine. Screening was performed using cDNA arrays from Clontech that allowed the determination of the expression of 1,176 genes specifically related with cancer. The analysis was carried out using the Atlas Image 2.01 (Clontech) and GeneSpring 4.2 (Silicon Genetics) softwares. Among the differentially expressed genes, we chose for further validation histone deacetylase 1 (HDAC1), von Hippel Lindau and decorin as upregulated genes, and Sp1, hypoxia-inducible factor-1 alpha and DNA primase as downregulated genes. The changes in the expression of these genes to mRNA were validated by quantitative RT-PCR and the final translation into protein by Western blot analysis. Inhibition of HDAC activity, Sp1 binding and DNA primase expression led to an increase in the level of apoptosis, both in parental cells and in doxorubicin-resistant cells. Therefore, these proteins could constitute possible targets to develop modulators in cancer chemotherapy that would increase or restore apoptosis.     

Surgical lung cancer. Risk operative analysis

STUDY OBJECTIVE: To identify those variables that are associated with operative morbidity or mortality in cases of thoracotomy in lung cancer. SETTING: Third level university hospital. PATIENTS: Consecutive patients with thoracotomy due to lung cancer operated on between 1994 and 1997 (n = 115). METHODS: Pre- and postoperative variables potentially associated with operative morbidity or mortality were retrieved prospectively as follows: demographic and clinical characteristics of the patients, cardiopulmonary function characteristics, tumour characteristics, and treatment characteristics. A bivariate analysis of all variables under evaluation was carried out in order to identify those variables associated with operative morbidity and mortality. A multivariable analysis of the selected variables was then conducted using a logistic model. RESULTS: The predicted postoperative product (predicted FEV1 x predicting diffusing capacity of carbon monoxide), the carbon monoxide diffusion coefficient (Kco) and the contralateral pulmonary perfusion are variables that relate to the overall morbidity or mortality (number of events 63, 55%) (-2 log likelihood chi2 = 22.9; R2 = 0.27). For variables associated with postoperative morbidity, the best associative model combines functional variables (diffusion, predicted FEV1), endoscopic variables (obstructed segments to be resected), clinical variables (comorbidity) and an important postoperative variable, the pathological tumoural staging (pN) (number of events 49, 43%) (-2 log likelihood chi2 = 32.9; R2 = 0.36). CONCLUSION: The numerous variables under analysis are poorly associated with morbidity or mortality after thoracotomy in lung cancer. With regard to postoperative morbidity, the best associative models combine information that is known pre- and postoperatively and which is provided by both the patient and the tumour.     

Central-peripheral sensory axonopathy in a juvenile case of Alpers-Huttenlocher disease

Peripheral ataxia is reported in a juvenile case of Alpers-Huttenlocher disease (AHD). Neurophysiological and neuropathological investigations revealed a central-peripheral axonopathy, affecting the deep sensation carried by the peripheral nerve fibres and the posterior tracts of the cord, due to neuronal loss of the sensory ganglia. Involvement of the sensory pathways is regarded as a major feature of juvenile AHD. Received: 28 October 2002, Received in revised form: 2 January 2003, Accepted: 15 January 2003 Present address: A. Polo, MD, Neurology Unit, Hospital of Piove di Sacco (PD), Italy Correspondence to: A. Simonati, MD     

Histologic evolution of high-intensity focused ultrasound in rabbit muscle

RATIONALE AND OBJECTIVES: The purpose of this study was to examine the histologic evolution over time of rabbit skeletal muscle thermally ablated with high-intensity focused ultrasound. The objectives included determining the extent and focality of damage created by this noninvasive, transcutaneous ablative technology. METHODS: Transcutaneous, thermal ablation with an external focused ultrasound transducer was applied to the paraspinous muscles of 19 rabbits. At varying times, up to 100 days after therapy, single sonications were examined histologically. RESULTS: Initially, only subtle staining changes were identified within lesions. In the chronic phase (day 51-100), the muscle was replaced or infiltrated by variable amounts of scar and fat similar to degenerative muscle disorders. Histologic changes were limited to the tissue within the intensity focus of the transducer and were not seen in intervening tissues. DISCUSSION: The current study took a systematic approach to study the long term, in vivo histologic effects of single HIFU lesions in a nonregenerative tissue. This experience in muscle tissue will provide a basis for understanding ultrasound effects for clinical applications such as treatment of uterine fibroids, cardiac tissue, and sarcomas.     

Gender differences in alcoholic cardiomyopathy

The incidence, presentation, clinical features, and evolution of several cardiomyopathies have clear gender-related differences. In general, women show a different response to noxious cardiac agents than men, and they differ in myocardial adaptation to a variety of cardiac insults. Specifically in alcohol-induced heart disease, women have shown different alcohol metabolism features and distinct pathophysiologic mechanisms leading to a higher sensitivity to alcohol-induced heart damage. In preclinical alcohol-induced ventricular dysfunction, women were more sensitive to the toxic effects of ethanol than men. In overt alcoholic cardiomyopathy, women showed about the same prevalence of cardiomyopathy as men, despite having consumed far less ethanol. This supports a greater female propensity to alcohol-induced cardiac damage.