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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 55 records · Page 3Linked to original sources

Modulation of viscero-somatic H-reflex during bladder filling: a possible tool in the differential diagnosis of neurogenic voiding dysfunctions.

OBJECTIVE: Despite evidence that the activation of visceral afferents modulates spinal motoneurone activity in humans, the circuits responsible for this modulation remain unclear. The aim of the present study was to assess the effect of urinary bladder filling on the excitability of somatic spinal motoneurones in patients affected by overactive bladder secondary to neurogenic and non-neurogenic causes in both patients with bladder underactivity and normal subjects by means of a urodynamic evaluation. METHODS: In order to evaluate the influence of bladder filling on somatic reflexes, we studied the H-reflex evoked by electrical stimuli applied to the tibial nerve at the popliteal fossa and recorded from the soleus muscle. The H-reflex was tested in the following conditions: (1). empty bladder; (2). medium bladder filling; (3). maximum bladder filling; (4). five minutes after bladder emptying. The H-reflex amplitude at empty bladder was considered as the control value. RESULTS: In healthy subjects, we observed a progressive reduction in the H-reflex amplitude during bladder filling. In spinal cord-injured patients affected by a neurogenic overactive bladder, bladder filling failed to inhibit the H-reflex amplitude; a decrease in the H-reflex amplitude similar to that displayed by normal subjects was observed in patients with a non-neurogenic overactive bladder. By contrast, H-reflex behavior was unmodified in neurogenic underactive bladder patients and was similar to normal subjects in psychogenic underactive patients. CONCLUSIONS: As behavior of the H-reflex varies during bladder filling in neurogenic and non-neurogenic overactive bladder patients as well as in neurogenic and non-neurogenic underactive bladder patients, H-reflex modulation may be considered a useful tool in the differential diagnosis of voiding dysfunctions.

Adult↗

Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma.

Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.

Adolescent↗

Prognostic factors in soft tissue sarcomas: a study of 395 patients.

AIMS: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas. METHODS: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997. RESULTS: Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival. CONCLUSIONS: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival.

Adolescent↗

Digital fluorographic video-urodynamics in the long-term morphofunctional evaluation of Alcini's Ileocecourethrostomy and ileal reservoir.

INTRODUCTION: The authors present the functional long-term follow-up by means of digital fluorographic video-urodynamics (DFVUDM) of two different surgical urinary diversions. MATERIALS AND METHODS: 64 of 101 patients submitted to radical cystectomy from 1983 to 1999 for infiltrating bladder cancer, were diverted by means of an Alcini's ileocecourethrostomy (ICUS+T), and the remaining 37 patients by means of an ileal reservoir (IR). All of those orthotopically diverted patients were submitted to an accurate follow-up which included DFVUDM 1, 3, 6, and 9 years after the surgical procedure (mean follow-up 51 +/- 42 months). RESULTS: All the evaluated patients showed a neobladder with good function during both the filling and the voiding phases. In 88.8% of the DFVUDM examinations, it was possible to find a residual peristaltic activity of the neobladder walls. Such a residual peristaltic activity caused urinary leakage during the examination in 11.1% of cases, while vesico-ureteral reflux was detected in 12.5%. The patients voided by relaxing the perineal floor and/or by contracting the abdominal muscles: the emptying of the reservoir was often excellent with average residual urine of 28.5 ml. None of the patients needed clean intermittent catheterization. EMG evaluation of the pelvic floor in some of patients showed a peculiar EMG pattern characterized by an insufficient voluntary control of the perineal musculature with a slight increase of EMG activity during bladder filling. Moreover, an insufficient relaxation of the pelvic floor muscles in the beginning of and during the micturition has been seen. This particular EMG pattern was present in 22.22% of all patients included in this study while it was particularly high (81.81%) in patients with leakage. CONCLUSION: DFVUDM evaluation represents a highly sophisticated tool which allows an accurate long-term morphofunctional evaluation of the urinary diverted patients. In this study, it is shown that the functional results of the two studied surgical procedures, namely Alcini's ICUS+T and IR, are quite similar, demonstrating that the taeniotomies on the cecal tract may have almost the same functional effects of detubularization. Although DFVUDM revealed imperfect functional performances in some patients, the quality of life of diverted patients in our series seems to be satisfactory.

Adult↗

Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alfa-2b and tribavirin.

BACKGROUND: The role combination therapy with interferon alfa-2b and tribavirin (US: ribavirin) plays in producing sustained virological responses in patients with HIV and chronic hepatitis C (HCV) infection is still unknown. OBJECTIVES: To determine the feasibility and sustained response of interferon alfa-2b and tribavirin combination therapy. DESIGN: Phase II study. METHODS: Seventeen patients were enrolled at the National Cancer Institute, Aviano, Italy and received combination therapy with interferon alfa-2b 3 MIU subcutaneously three times a week plus tribavirin 1000-1200 mg/day for 24 weeks. Antiretroviral therapy was concomitantly given in all but one patient. RESULTS: At the end of treatment, five (31%) patients achieved clearance of HCV RNA and 11 (69%) showed normalized liver function enzyme levels. In three patients, serum HCV RNA concentration was still undetectable 24 weeks after treatment, with an overall sustained virological response rate of 19% The serum liver enzymes were still normal in 10 patients 24 weeks after treatment, the overall sustained biochemical response rate being 62% All patients with HCV RNA clearance at the end of treatment and 24 weeks after treatment had a concomitant biochemical response. Overall the combination treatment was well tolerated. CONCLUSIONS: Our data confirm that the combination of interferon alfa-2b and tribavirin is well tolerated and feasible in patients with HIV-HCV co-infection and it can be associated safely with highly active antiretroviral therapy. The sustained response achieved with the drug combination does not seem to be any better than that achieved with 12 months of monotherapy with interferon alfa-2b.

Adult↗

Discordant HHV8 detection in a young HIV-negative patient with Kaposi's sarcoma and sarcoidosis.

Human herpesvirus 8 (HHV8), which has been suggested as the causal agent of Kaposi's sarcoma (KS), has also been implicated in the pathogenesis of sarcoidosis. We describe a patient affected concomitantly by sarcoidosis and KS. HHV8 sequences were detected with PCR only on KS lesions, whereas sarcoid tissues did not harbor HHV8 DNA. Immune dysfunction related to sarcoidosis may have facilitated the oncogenic role of HHV8 and the development of KS.

Adult↗

Dermoscopic criteria for melanoma in situ are similar to those for early invasive melanoma.

BACKGROUND: Dermoscopy is a noninvasive technique that increases the diagnostic accuracy of pigmented skin lesions, particularly improving the diagnosis of patients with cutaneous melanoma in situ (CMIS) and early invasive melanoma. To establish reliable and reproducible dermoscopic criteria for the diagnosis of CMIS, the authors conducted a retrospective clinical study of 37 patients with CMIS and 53 patients with invasive cutaneous melanomas (ICM). METHODS: The 37 patients with CMIS were divided into three groups: those with CMIS lesions measuring < or = 5 mm in greatest dimension (8 patients), those with CMIS lesions measuring from > 5 mm to < or = 10 mm in greatest dimension (20 patients), and those with CMIS lesions measuring > 10 mm in greatest dimension (9 patients). The 53 patients with ICM were divided into two groups according to Breslow index: those with ICM lesions measuring < or = 0.75 mm in tumor thickness (19 patients) and those with ICM lesions measuring > 0.75 mm in tumor thickness (34 patients). Lesions were examined with a dermatoscope and were photographed at a magnification of x10. Dermoscopic criteria were evaluated from examination of the photomicrographs. RESULTS: Blue-whitish veil, gray-blue areas, black dots, and irregular extensions and branched streaks were the most relevant dermoscopic criteria for CMIS and were present in 78%, 76%, 73%, and 62% of lesions, respectively. Brown globules, irregular pigment network, pseudopods, and depigmentation were present in 57%, 54%, 54%, and 51% of CMIS lesions, respectively. White scar-like areas and linear and/or dotted vascular patterns, two criteria that are associated frequently with ICM, were not found in our patients with CMIS. No clinically significant differences were observed between the three groups of CMIS patients. CONCLUSIONS: Dermoscopic criteria for CMIS were similar to those for ICM, although white scar-like areas and linear and/or dotted vascular patterns were observed only in patients with ICM. Dermoscopic criteria appeared to be independent of CMIS lesions size.

Adolescent↗

Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential.

Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.

Antibodies, Monoclonal↗

Physical activity and risk of ovarian cancer: an Italian case-control study.

The relationship between physical activity and the risk of ovarian cancer was analyzed using data from a case-control study conducted between 1992 and 1999 in Italy. Cases were 1,031 women with incident, histologically confirmed, invasive epithelial ovarian cancer and controls were 2,411 women admitted to hospital for acute non-neoplastic, non-hormonal conditions. Compared to women with the lowest level of occupational physical activity, the ORs of ovarian cancer obtained adjusting for center, year of interview and age for women with the highest level of physical activity were 0.70, 0.52 and 0.64 (all statistically significant) respectively, at ages 15-19, 30-39 and 50-59 years, with significant trends in risk for the 2 youngest age groups. The corresponding ORs became 0.89, 0.67 and 0.76 after further allowance for several co-variates of ovarian cancer, including education, which was positively associated with cancer risk. No significant association was found with leisure-time physical activity though the risk was below unity in women with the highest level of activity. The multivariate OR was 0.44 for women with the highest level of combined occupational plus leisure-time physical activity. The inverse relationship between occupational physical activity and ovarian cancer risk was not heterogeneous across strata of selected co-variates.

Adolescent↗

Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas.

This study was aimed at defining the histogenesis of the pathologic spectrum of lymphoma arising in the context of human immunodeficiency virus (HIV) infection. Toward this aim, 87 AIDS-related non-Hodgkin lymphomas (AIDS-NHL) and 16 Hodgkin lymphomas arising in HIV+ patients (HIV-HL) were comparatively analyzed for the expression pattern of several B-cell histogenetic markers, including BCL-6 (expressed by centroblasts and centrocytes), MUM1/IRF4 (expressed by late centrocytes and post-germinal center [GC] B cells), and CD138/syn-1 (expressed by post-GC B cells). Expression of MUM1, BCL-6, and syn-1 segregated 3 major phenotypic patterns among AIDS-NHL and HIV-HL: (1) the BCL-6+/MUM1-/syn-1- pattern, selectively clustering with a large fraction of AIDS-Burkitt lymphoma (17 of 19) and of systemic AIDS-diffuse large cell lymphoma (12 of 16); (2) the BCL-6-/MUM1+/syn-1- pattern, associated with a fraction of AIDS-immunoblastic lymphoma (8 of 24); and (3) the BCL-6-/MUM1+/syn-1+ pattern, associated with systemic and primary central nervous system immunoblastic lymphoma (14 of 24) and with primary effusion lymphoma (10 of 10), plasmablastic lymphoma of the oral cavity (7 of 7), and HIV-HL (15 of 16). Analysis of nonneoplastic lymph nodes showed that the 3 phenotypic patterns detected in AIDS-NHL and HIV-HL correspond to distinct stages of physiologic B-cell development-centroblasts (BCL-6+/MUM1-/syn-1-), late GC/early post-GC B cells (BCL-6-/MUM1+/syn-1-), and post-GC B cells (BCL-6-/MUM1+/syn-1+). Expression of the Epstein-Barr virus-encoded latent membrane protein-1 clustered with the BCL-6-/MUM1+/syn-1+ profile throughout the clinicopathologic spectrum of AIDS-NHL and HIV-HL. Overall, these results define novel histogenetic subsets of AIDS-NHL and HIV-HL and may provide novel tools for refining the diagnosis of these disorders.

B-Lymphocytes↗

Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study.

BACKGROUND: The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival. METHODS: Patients aged 15-65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). All statistical tests are two-sided. RESULTS: From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low-intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results. CONCLUSIONS: Standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.

Adolescent↗

Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease.

Multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) are two B-cell lymphoproliferative diseases associated with Kaposi's sarcoma-associated herpes virus/human herpesvirus-8 (KSHV/HHV-8). Although MCD is considered a prelymphoma state, it is not known whether a pathogenetic link exists between MCD and PEL. This paper reports the clinico-pathological features of four cases of PEL (two pericardial, one pleural, and one peritoneal) developing in the context of HIV-associated MCD. Effusions, lymph nodes, spleen, and additional tissues from three autopsies were examined for morphology/immunophenotype, search for HHV-8 DNA, and assessment of immunoglobulin heavy chain gene (IgH) configuration using polymerase chain reaction (PCR)-based techniques. MCD and PEL samples contained HHV-8 DNA. Clonal IgH rearrangements were detected only in PEL, whereas MCD tissues were polyclonal. Light-chain immunostaining confirmed B-cell clonality in PEL (two lambda, one kappa, one not tested) and polyclonality in MCD. The autopsies revealed different morphological variants of visceral KS and multi-organ atypical infiltrates exhibiting immunoblastic/plasmablastic features reminiscent of PEL morphology, with a restriction of lambda-positive cells. In two cases, using microdissection and IgH PCR analysis, multiple/discrete bands were found in the infiltrates, compatible with polyclonality/oligoclonality. The case showing an oligoclonal IgH ladder contained a rearrangement of identical junctional size to the PEL clone; however, further analysis with PEL-derived clonotypic primers and sequencing of PCR products showed no amplification and nucleotide diversity, respectively, indicating that the two B-cell populations examined were clonally unrelated. These data show that MCD and PEL may co-exist in HIV-infected patients, suggesting a relevant association between these two HHV-8-related disorders. Although a definite clonal relationship between MCD and PEL was not demonstrated, it is hypothesized that in some MCD cases, within expanded polyclonal B-cell populations secondary to HHV-8 infection, clonal expansions may occur that localize into a body cavity, i.e. PEL.

Adult↗

Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma.

OBJECTIVE: The aim of this prospective study was to evaluate the influence of secondary cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer. METHODS: Between June 1993 and June 1999, 149 patients after primary treatment underwent secondary cytoreductive surgery: 69 (46.3%) had recurrence-free interval (RFI) 7-12 months, 59 (39.6%) RFI 13-24 months, and 21 (14.1%) RFI >24 months. Exclusion criteria included secondary cytoreduction during second-look laparotomy, interval cytoreduction, and palliative surgery in patients with intestinal obstruction or progressive disease. RESULTS: The median follow-up was 27 months. According to multivariate analysis, RFI groups, prior chemotherapy combination, and residual tumor after secondary surgery were associated independently with overall survival. Residual tumor after secondary surgery was by far the most strongly predictive factor for patient's survival (hazard ratio (HR) 2.65; 95% confidence interval (CI) 1.43-4.92). The 2-year survival rates were 22.3, 62.9, and 22.7%, respectively, for patients with RFI 7-12, 13-24, and >24 months. The 5-year survival was 29% for patients with RFI 13-24 months. No patients with RFI 7-12 and >24 months outlived the 4-year estimate. Unexpectedly, RFI >24 months was not correlated significantly with overall survival. However, 17 patients (81%) with RFI >24 months were heavily treated with chemotherapy before secondary surgery. CONCLUSIONS: Patients who have documented gross disease preoperatively should be selected for a secondary debulking operation; the entity of surgical effort would be modulated in relation to previous treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Primary effusion lymphoma: a liquid phase lymphoma of fluid-filled body cavities.

Primary effusion lymphoma (PEL) is a B-cell neoplasm characterized by infection of the tumor clone by human herpesvirus type-8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV) and by liquid growth in fluid-filled body spaces. During its entire clinical course, the lymphoma tends to remain localized to the serous body cavities with no formation of solid tumor masses. The epidemiology of PEL points to a close link with underlying immunodeficiency of the host, as most cases develop in individuals severely immunocompromised because of preexisting acquired immunodeficiency syndrome. The histogenesis and pathogenesis of PEL have been clarified to a sizeable extent by intensive investigations performed since the disease recognition in 1995. PEL is composed of postgerminal center B cells, which bridge immunoblastic and anaplastic features and typically display a non-B, non-T phenotype consistent with late stages of B-cell differentiation. HHV-8/KSHV is thought to play a major role in PEL pathogenesis via expression of several viral latent genes, which have the potential to affect B-cell growth. Other factors involved in PEL pathogenesis include deregulation of cytokine and growth factor autocrine loops, molecular alterations of the tumor DNA, cell cycle abnormalities, stimulation and selection by antigen, and infection by Epstein-Barr virus, which occurs in 70% of PEL cases. In the years since the disease discovery, the distinctiveness of the biological and clinicopathological features of PEL has prompted its recognition as an independent lymphoma category by the World Health Organization classification system of hematologic neoplasms.

Diagnosis, Differential↗

Amebic abscess of urachal remnants.

We report a rare case of amebic abscess of the urachus, mimicking an urachal neoplasm: no previous reports of amebic infection of the urachus were found in the literature. The challenges of the differential diagnosis between urachal abscess and carcinomas based both on clinical and radiological data are discussed.

Abdomen↗