Interferon-alpha (IFN alpha) daily dose versus IFN alpha plus ribavirin for treatment-naive chronic hepatitis c patients infected by genotype 1b

INTRODUCTION: Infection with hepatitis C virus genotype 1b (HCV1b) is known to be a predictive factor of poor response to both interferon-alpha (IFN alpha) alone and IFN alpha plus ribavirin combination therapy.STUDY DESIGN, PATIENTS AND METHODS: This randomised study evaluated the efficacy and safety of daily IFN alpha administration versus the combination of IFN alpha plus ribavirin in treatment-naive patients infected with chronic HCV1b. Sixty-two patients were randomised to receive either human leucocyte IFN alpha 6MU three times weekly for 12 months plus ribavirin 15 mg/kg/day for the first 6 months (group A: 29 patients), or human leucocyte IFN alpha 3MU daily for 12 months (group B: 33 patients). Response was evaluated by monitoring serum alanine aminotransferase (ALT) and HCV-RNA levels during treatment and follow-up (12 months). RESULT AND CONCLUSION: Both treatment schedules were relatively well tolerated. Normal ALT levels and negative serum HCV-RNA were observed in 16 of 29 patients (55%) of group A and in 18 of 33 patients (54.5%) of group B at the end of treatment, as well as in 10 of 29 patients (34.5%) of group A and in 12 of 33 patients (36%) of group B at the end of the follow-up. There was no significant difference between the response rates obtained with the two regimens. In naive patients with chronic HCV1b infection, the efficacy of daily administration with IFN alpha is similar to that of IFN alpha plus ribavirin administered three times a week.     

Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates

We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members.     

The long pentraxin PTX3 up-regulates tissue factor in activated monocytes: another link between inflammation and clotting activation

Pentraxin-3 (PTX3), an acute-phase protein that belongs to the family of the PTXs, is found elevated in septic shock and increased in patients with acute myocardial infarction. As tissue factor (TF) plays a key role in thrombosis and inflammation associated with atherosclerosis and as we have recently reported that PTX3 increases TF synthesis in endothelial cells, we tested whether PTX3 could modulate TF expression in monocytes. Monocytes from peripheral blood of healthy donors were incubated with highly purified PTX3 with or without lipopolysaccharide (LPS). Cells were then disrupted, and procoagulant activity was assessed by a one-stage clotting time. PTX3 enhanced TF activity and antigen from LPS-stimulated monocytes in a dose-dependent way. The effect was specific, as other PTXs, such as C-reactive protein and serum amyloid P component, were ineffective. Moreover, the increase in activity was specific for LPS, as in the presence of other TF-inducing agents such as interleukin-1beta and tumor necrosis factor alpha, PTX3 was not effective. The increase in TF activity requires mRNA synthesis, as assessed by polymerase chain reaction. The mechanism by which PTX3 modulates TF synthesis resides in an enhanced IkappaB, alpha phosphorylation and degradation and increased migration of the transacting factor c-Rel/p65 into the nucleus, as determined by Western blot and electro-mobility shift assay. These results show that PTX3 is an enhancer of the expression of TF by mononuclear cells. In the area of vascular injury, during the inflammatory response, cell-mediated fibrin deposition takes place. PTX3 increases TF expression, thus potentially playing a role in thrombogenesis and wound healing.     

Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective,randomized, single-blind,placebo-controlled clinical trial

BACKGROUND: Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms. METHODS: After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method. RESULTS: After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period. CONCLUSIONS: In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes.     

Lipomatous myofibroblastoma: a potential diagnostic pitfall in the spectrum of the spindle cell lesions of the breast

We report on two cases of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately three quarters of the entire tumour area. Both tumours consisted of a well-circumscribed lipomatous tumour mass containing dispersed nodular or irregularly shaped spindled cellular areas. The fatty component was represented exclusively by mature adipocytes, uniform in size and shape, lacking nuclear pleomorphism. The cellular areas contained spindly to oval cells with morphological and immunophenotypical features typical of MFB. The two components were so intimately admixed that a finger-like infiltrating growth pattern was apparent. The cases reported here as "lipomatous MFB" aim to clarify further the morphological spectrum of MFB of the breast. Lipomatous MFB may potentially mimic other benign or aggressive tumour-like lesions or even bland-looking malignant spindle cell tumours such as fibromatosis, nodular fasciitis, spindle cell lipoma, spindle cell liposarcoma, spindle cell variant of metaplastic carcinoma, spindle cell malignant myoepithelioma, and low-grade fibrosarcoma/malignant fibrous histiocytoma. The histogenesis of the present bimorphic mesenchymal tumours could be explained as the result of a dual, myofibroblastic and lipomatous, differentiation from a common pluripotential mesenchymal precursor cell, probably represented by the vimentin+/CD34+ fibroblast of the mammary stroma.     

Psychopathological dimensions of depression: a factor study of the 17-item Hamilton depression rating scale in unipolar depressed outpatients

BACKGROUND: Agreement on the factor structure of the Hamilton Depression Rating Scale (HDRS) has not been consistent among studies, and some investigators argued that the scale's factor structure is not reliable. This study aimed at shedding more light on this debated issue. METHODS: We studied 186 adults with unipolar depression (Major Depressive Disorder, n=80; Dysthymic Disorder, n=71; Depressive Disorder Not Otherwise Specified, n=25; Adjustment Disorder, n=10). They had no comorbid DSM-IV axis I or axis II disorders, and had received no treatment with antidepressant drugs in the previous 2 months. The factor structure of the scale was studied using the principal factor method, followed by oblique rotation. Factor scores were computed for each subject using the regression method. RESULTS: Using the scree-test criterion for factor extraction, we obtained a four-factor solution, explaining 43.8% of total variance. The four factors extracted were identified as (1) somatic anxiety/somatization factor; (2) a psychic anxiety dimension; (3) a pure depressive dimension; and (4) anorexia factor. Patients with Major Depressive Disorder scored significantly higher than patients with other diagnoses on the pure depressive dimension. LIMITATIONS: These results need to be replicated in different cultures, using analogous factoring techniques. CONCLUSIONS: Though not exhibiting factorial invariance in the stricter sense of the term, the 17-item HDRS did exhibit a relatively reliable factor structure. Our analysis provides further evidence that the scale is multidimensional. However, as long as the multidimensional character of the scale is taken into account the scale should be able to play a useful role in clinical research.     

Epidemiology of tuberculosis in immigrant patients hospitalised in Infectious Diseases Units in Italy: multicentric study

In order to retrospectively evaluate the prevalence of immigrant patients affected by active tuberculosis, we analysed the clinical data of 2255 immigrant patients hospitalised during 2002 in ordinary admission or in Day Hospital in 48 Clinics of Infectious Diseases. In all, 303 patients were affected by active tuberculosis (13.4% of the total immigrant hospitalised patients); 30 patients (9.9%) were also HIV-positive. There was a considerable male gender bias (62.5%); the mean age was 29.7 years; 144 patients were from Africa (47.5%), 72 (23.7%) from Asia, 47 (15.5%) from eastern Europe and 40 (13.2%) from South America. The clinical variants were: pulmonary (57.7%), lymph node (15.8%), meningitis (13.8%), intestinal (4.2%), bone (3.3%), pleurical (2.3%), peritoneal (2.3%) and renal (0.6%). We conclude that tuberculosis is a very frequent disease among immigrants, especially of African origin. The high percentage is due to several factors, such as no vaccine prophylaxis and poor, overcrowded living conditions. It is fundamental to focus on the need to provide better health support for all subjects by setting up screening plans to estimate the real incidence of this pathology and ensure medical treatment to prevent the spread of this infection among immigrants and the local host population.