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Biomedical subjects

M Basso

Publications and source records attributed to M Basso.

At least 19 recordsLinked to original sources
PubMed2006

Schedule-dependent activity of 5-fluorouracil and irinotecan combination in the treatment of human colorectal cancer: in vitro evidence and a phase I dose-escalating clinical trial.

Several schedules of 5-fluorouracil (FU) and irinotecan (IRI) have been shown to improve overall survival in advanced colorectal cancer (CRC). Preclinical evidence suggests that the sequential administration of IRI and FU produces synergistic activity, although their clinical use has not been fully optimised. We investigated the interaction between short-term exposure to SN-38, the active metabolite of IRI, and prolonged exposure to FU in human CRC HT-29 cells and observed that the synergism of action between the two agents can be increased by extending the time of cell exposure to FU and reducing the interval between administration of the two agents. Based on these findings, we performed a phase I trial in 25 advanced CRC patients using a modified IRI/FU regimen as first-line therapy and evaluated three dose levels of IRI (150-300 mg/m(2)) and two of continuous infusion of FU (800-1000 mg/m(2)) in a 3-weekly schedule. The most severe grade III-IV toxicities were neutropoenia in four cycles and diarrhoea in three. One patient achieved complete response (4%), 12 a partial response (48%), the overall response rate was 52% (+/-20, 95% CI); seven of 25 patients had stable disease (28%), the overall disease control was 80% (+/-16, 95% CI). This modified IRI/FU schedule is feasible and exhibits potentially interesting clinical activity.

Adult↗
PubMed2006

Pegylated interferon and ribavirin in re-treatment of responder-relapser HCV patients.

BACKGROUND: The re-treatment of patients who relapse after a course of standard interferon and ribavirin with pegylated interferon alfa-2b plus ribavirin is an open issue. AIMS: To evaluate efficacy and safety of treatment with pegylated interferon alfa-2b plus ribavirin and the role of early HCV-RNA assessment as a predictor of sustained response. PATIENTS: Between May 2001 and December 2002, 242 consecutive patients with chronic hepatitis C were enrolled in an open, regional, multicentre study. Seventy-eight of them were responder-relapsers to a previous course of combination therapy. METHODS: Patients were treated with pegylated interferon alfa-2b (1 microg/kg/week) plus ribavirin (800-1200 mg daily). Qualitative HCV-RNA was performed at week 2. Genotypes 1-4 were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. RESULTS: We obtained an overall sustained virological response rate of 41.0% (78.6% for patients with genotypes 2-3). CONCLUSION: This treatment schedule prove to be safe and effective in relapsers with genotype non-1 while genotype 1-4 patients had a low rate of sustained virological response. Qualitative virological assessment after 2 weeks may identify patients who are more likely to reach sustained virological response, but it is not a valid tool for a stopping rule approach.

Adult↗
PubMed2006

A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin.

BACKGROUND: There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. AIM: To evaluate efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in such patients. METHODS: 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months. RESULTS: At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg-interferon were associated with the treatment failure. CONCLUSIONS: The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).

Adult↗
PubMed2006

Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI.

OBJECTIVE: To compare the efficacy of step training with body weight support on a treadmill (BWSTT) with over-ground practice to the efficacy of a defined over-ground mobility therapy (CONT) in patients with incomplete spinal cord injury (SCI) admitted for inpatient rehabilitation. METHODS: A total of 146 subjects from six regional centers within 8 weeks of SCI were entered in a single-blinded, multicenter, randomized clinical trial (MRCT). Subjects were graded on the American Spinal Injury Association Impairment Scale (ASIA) as B, C, or D with levels from C5 to L3 and had a Functional Independence Measure for locomotion (FIM-L) score < 4. They received 12 weeks of equal time of BWSTT or CONT. Primary outcomes were FIM-L for ASIA B and C subjects and walking speed for ASIA C and D subjects 6 months after SCI. RESULTS: No significant differences were found at entry between treatment groups or at 6 months for FIM-L (n = 108) or walking speed and distance (n = 72). In the upper motor neuron (UMN) subjects, 35% of ASIA B, 92% of ASIA C, and all ASIA D subjects walked independently. Velocities for UMN ASIA C and D subjects were not significantly different for BWSTT (1.1 +/- 0.6 m/s, n = 30) and CONT (1.1 +/- 0.7, n = 25) groups. CONCLUSIONS: The physical therapy strategies of body weight support on a treadmill and defined overground mobility therapy did not produce different outcomes. This finding was partly due to the unexpectedly high percentage of American Spinal Injury Association C subjects who achieved functional walking speeds, irrespective of treatment. The results provide new insight into disability after incomplete spinal cord injury and affirm the importance of the multicenter, randomized clinical trial to test rehabilitation strategies.

Adolescent↗
PubMed2006

A distinctive erythematous macular exanthem of the adult: a new entity?

BACKGROUND: Delineating a new exanthem is difficult. Atypical or modified types of already known conditions can easily be mistaken for new entities. OBJECTIVES: To report 29 cases of an acute, self-limiting exanthem never described before. METHODS: Clinical description, serology, polymerase chain reaction (PCR) and other laboratory investigations. RESULTS: The eruption starts with bright pink-red slightly oedematous macules symmetrically arranged on the trunk. The lesions tend to coalesce, and spread to the limbs on which they may acquire a marginated annular appearance. The lesions invariably spare the face (including oral mucous membranes), palms and soles. The eruption is pruritic and lasts 20-30 days, clearing spontaneously. The disease has a predilection for men aged 17-56 years and occurs mostly between spring and summer. Serological tests, PCR assays and investigations for bacteria, parasites or viruses were consistently negative. CONCLUSIONS: The clinical picture does not recall any of the classical exanthems or their atypical forms.

Acute Disease↗
PubMed2005

Cutaneous presentation of recurrence of lymphoepithelioid T-cell lymphoma (Lennert's lymphoma).

Lennert's lymphoma (LL) is a T-cell lymphoma characterized by the presence of atypical T lymphocytes, admixed with histiocytes and epithelioid granulomas. Patients present with superficial lymph node involvement, mainly in the cervical areas; thoracic adenopathies and involvement of deep abdominal lymph nodes are rare. Cutaneous involvement is infrequent, reported to occur in only 4-11% of patients, and even rarer is the onset of cutaneous lesions as first sign of a recurrence. We report a female patient who presented with papules and nodules on the trunk and upper limbs as the first manifestation of recurrent LL.

Fatal Outcome↗
PubMed2005

Non-antigen-specific CD8(+) T suppressor lymphocytes in diseases characterized by chronic immune responses and inflammation.

Recent studies on regulatory lymphocytes demonstrate that CD8(+) T suppressor (Ts) cells may have great relevance in controlling immune system homeostasis and avoiding development of chronic inflammatory diseases. Among the three subpopulations of CD8(+) Ts cells so far recognized in humans, the type 2 (non-antigen-specific) cell is characterized by the capacity to inhibit both T cell proliferation and cytotoxic T lymphocyte activity through secretion of soluble factors. Previous work has shown the impairment of in vitro generation of type 2 CD8(+) Ts cells from the peripheral blood of relapsed patients with multiple sclerosis, systemic lupus erythematosus, or systemic sclerosis. Here, similar findings are demonstrated for patients with human immunodeficiency virus or chronic hepatitis C virus infection. Furthermore, the presence of type 2 CD8(+) Ts cells infiltrating diseased tissues in patients with autoimmune thyroiditis or cancer is shown. Collectively, these findings suggest that type 2 CD8(+) Ts cells may be involved in the control of pathologic chronic immune responses, contributing in some cases to the pathogenesis of the disease.

Antibodies, Monoclonal↗
PubMed2004

Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.

BACKGROUND: Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenetic role. Recently, we graded scleroderma microangiopathy by nailfold videocapillaroscopy (NVC) into three NVC patterns (early, active and late). The aim of the present study was to confirm, in a larger number of SSc patients, the presence of three patterns of microvascular damage, and to detect any possible relationship between these patterns and both specific serum autoantibodies and the subsets of cutaneous involvement. METHODS: Two hundred and forty-one consecutive patients (227 women and 14 men) affected by SSc were recruited. One hundred and forty-eight patients were affected by limited cutaneous SSc (lSSc) and 93 patients by diffuse cutaneous SSc (dSSc). The ages at onset of Raynaud's phenomenon (RP) and SSc, the durations of RP and SSc, ANA and antitopoisomerase I (anti-Scl70) and anticentromere (ACA) antibodies were investigated in all patients. The SSc patients were subdivided on the basis of the NVC pattern into three groups. RESULTS: A statistically significant correlation was found between the NVC patterns and the durations of both RP and SSc (P<0.001). Enlarged and giant capillaries, together with haemorrhages, constituted the earliest NVC finding in SSc (early NVC pattern). These abnormalities were mostly expressed in the active NVC pattern. Loss of capillaries, ramified capillaries and vascular architectural disorganization were increased in the late NVC pattern. Age and the duration of both RP and SSc were lower in 24 patients complaining of RP alone. Anti-Scl70 antibodies were statistically less frequent in the early vs both the active and the late NVC pattern, whereas no significant correlation was found between the presence of anti-Scl70 antibodies and the duration of either RP or SSc. ACA positivity was more frequent in patients with longer RP duration. Patients with lSSc had shorter SSc duration and showed the early or active NVC pattern more frequently. Conversely, patients with dSSc showed longer disease duration and mostly showed the late NVC pattern. CONCLUSIONS: NVC is an appropriate tool for differential diagnosis between primary and secondary RP through the clear recognition of the early NVC scleroderma pattern. This study confirms, in a large number of SSc patients, the existence of three distinct NVC patterns that might reflect the evolution of SSc microangiopathy. The presence of anti-Scl70 antibodies seems be related to earlier expression of the active and late NVC patterns of SSc microvascular damage. The presence of ACA seems to be related to delayed expression of the late NVC pattern.

Adult↗
PubMed2004

Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.

BACKGROUND/AIMS: Lamivudine efficiently inhibits hepatitis B virus replication and has been used to treat hepatitis B virus recurrence after orthotopic liver transplantation. Although effective, its use is hampered by viral breakthrough due to the appearance of hepatitis B virus drug-resistant strains. Aims of this work were to evaluate the inter- and intra-individual variations of lamivudine serum levels and the effects on the drug levels of the lamivudine-resistant hepatitis B virus mutant infection. METHODS: Serum lamivudine concentration was measured by high-performance liquid chromatography. Polymerase chain reaction analysis and sequencing analysis of the reverse transcriptase area of the polymerase was performed on each sample using specific primers. A polymerase chain reaction-enzyme-linked immunosorbent assay was used to differentiate between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus strain. RESULTS: Lamivudine serum levels presented minor inter- and intra-individual fluctuations along time, with an important increase at the time of the hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild-type hepatitis B virus briefly reappeared as a mixed population, the titre of lamivudine dropped to below the detection level. CONCLUSIONS: While lamivudine serum levels appears stable when the anti-viral efficacy is fully achieved, important fluctuations are present according to the type of viral population, with a considerable decrease possibly due to the presence of the wild-type virus.

Anti-HIV Agents↗
PubMed2004

[Intra-prosthetic dislocation of the Bousquet dual mobility socket].

PURPOSE OF THE STUDY: The Bousquet system is a dual mobility head-polyethylene polyethylene-metal cup socket. The polyethylene insert retaining the femoral head moves in the noncemented metal cup, increasing both mobility and stability. MATERIAL AND METHOD: Between 1989 and 1997, seven cases of intra-prosthetic dislocation (six patients) were observed. The femoral head escaped from the polyethylene insert due to wear. On the average, this complication occurred ten Years after implantation. Risk of dislocation was high in six of the seven hips. All patients had a large sized stem screwed into the femoral neck. There was a characteristic radiological aspect with loss of the concentric head metal cup configuration. The head was applied against the upper wall of the metal cup. RESULTS: Surgical replacement was undertaken early in six patients by simply changing the insert without modifying the other stable components. Outcome remained good at three to eight Years. One patient underwent late surgery. The insert and the cup were replaced with a classical implant. Functional outcome was good but recurrent dislocation occurred. DISCUSSION: At mid-term, intra-prosthetic dislocation of dual mobility sockets appears to be exceptional. Dislocation results from polyethylene wear leading to failure of the insert to retain the prosthetic head. Wear is favored by direct phenomena (direct contact between neck and insert which can occur early if there is a small difference in the head and neck diameters) or indirect phenomena (factors limiting polyethylene metal-cup mobility). Surgical treatment is necessary. If undertaken early, replacement with a modular head and insert can be sufficient if the prosthesis has not loosened but the metal cup may have to be replaced in the event of metal-metal contact between the head and the cup. Prosthesis loosening, wear of the metal cup, or an identified cause of dislocation imply replacing the failing implants. Implantation of the dual mobility system is particularly interesting for patients with a high risk of dislocation or a chronically unstable hip prosthesis. Careful technique is required to reduce or retard the risk of intra-prosthetic dislocation. CONCLUSION: Intra-prosthetic dislocation of a dual mobility socket is an exceptional complication at mid-term. Surgical treatment is required but may be limited to simple insert replacement. Systematic use of this type of implant in young subjects must be carefully examined, but for us, the risk of dislocation does not outweigh the advantages of this original concept of dual mobility. This type of socket remains an useful preventive technique for high-risk hips or for curative treatment of recurrent dislocation.

Adult↗
PubMed2004

Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients.

BACKGROUND: The aim of this study was to observe the effects of neoadjuvant therapy with irinotecan and 5-fluorouracil (5-FU)/folinic acid (FA) on the resection rate and survival of colorectal cancer patients with initially unresectable hepatic metastases. PATIENTS AND METHODS: Forty patients received neoadjuvant chemotherapy comprising irinotecan 180 mg/m(2) administered intravenously (i.v.) on day 1, FA 200 mg/m(2) i.v. on days 1 and 2, 5-FU 400 mg/m(2) i.v. bolus on days 1 and 2, and 5-FU 1200 mg/m(2) as a continuous 48-h i.v. infusion on day 1. The treatment was repeated every 2 weeks and response was assessed every 12 weeks (six cycles). RESULTS: The objective response rate to chemotherapy was 47.5% (n = 19), with two complete responses and disease stabilization in 11 (27.5.%) patients. Responses were unconfirmed for 11 patients undergoing surgery within 2 weeks. Treatment was well tolerated and adverse events were typical of the chemotherapy agents used. Twenty-seven (67.5%) patients reported hematological toxicity (35.0% grade 3/4) and 14 (35.0%) reported gastrointestinal toxicity (12.5% grade 3/4). Thirteen patients (32.5%) underwent potentially curative liver resection following chemotherapy. Chemotherapy was particularly effective in patients with large metastases on entry to the study. The median time to progression is 14.3 months and, at a median follow-up of 19 months, all patients are alive. CONCLUSIONS: Neoadjuvant therapy with irinotecan combined with 5-FU/FA enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. The effects of treatment on survival have yet to be determined.

Adult↗
PubMed2004

Kinetics of soluble tumour necrosis factor (TNF)-alpha receptors and cytokines in the early phase of treatment for chronic hepatitis C: comparison between interferon (IFN)-alpha alone, IFN-alpha plus amantadine or plus ribavirin.

We have previously studied the effect of three different treatment regimens with interferon (IFN)-alpha alone or in combination with amantadine or ribavirin on viral kinetics in the first month of therapy. To understand the regulation of cytokine immune response during early inhibition of HCV replication, we analysed the longitudinal profile of proinflammatory markers (soluble TNFRs), of type 1 cytokines [IFN-gamma and interleukin (IL-12)], and of a type 2 cytokine (IL-10). Twenty-two chronic hepatitis C patients received daily therapy for 6 months. Sera were collected at baseline, at 6, 12, 24, 30 and 48 h and at the 3rd, 7th, 15th and 30th days of treatment. All cytokines and receptors were evaluated by enzyme linked immunosorbent assay (ELISA). At baseline, a correlation was found between the two soluble TNFRs (P < 0.0001) and between the soluble TNFRs and ALT levels (P < 0.003), as shown previously. Regardless of the type of treatment, lower levels of soluble TNFR-p75 were present from day 3 in patients who had significant virus decay at day 30 (P < 0.01). Baseline IL-10 levels correlated with TNFR-p75 (P < 0.01) and with treatment response (P < 0.05) and a significant IL-10 reduction from baseline was observed from day 3 among responders, irrespective of the type of treatments (P < 0.05). IL-12 and IFN-gamma levels did not differ according to treatment or outcome. These findings suggest a pivotal role for IL-10 in orchestrating the antiviral immune response. Its early decline can favour the shift from a Th2 to a Th1 immune response, which has been shown to be associated with a long-term virological response to treatment.

Adult↗
PubMed2004

Long-term follow-up of a pilot phase II study with neoadjuvant epidoxorubicin, etoposide and cisplatin in gastric cancer.

OBJECTIVE: The prognosis in T3-T4 or N+ gastric cancer is dismal, and the role of adjuvant therapy remains uncertain. Neoadjuvant chemotherapy could improve both resectability and survival. Here, we report the results of the long-term follow-up of a pilot study aimed at evaluating a neoadjuvant treatment in a group of patients carefully staged by computed tomography (CT), endoscopic ultrasound and laparoscopy. METHODS: Twenty-five stage II-III patients with histologically proven gastric adenocarcinoma were enrolled in the study. All patients gave informed consent and were thoroughly staged. Patients were treated with epidoxorubicin (40 mg/m2 i.v.) on days 1 and 4, etoposide (VP-16; 100 mg/m2) on days 1, 3 and 4 and cisplatinum (80 mg/m2) on day 2, every 21-28 days for 3 pre-operative cycles before CT clinical restaging followed by laparotomy and D2 gastrectomy. Three further cycles of chemotherapy were planned after radical surgery. RESULTS: Twenty-four patients received the planned pre-operative chemotherapy and underwent surgical resection; total (13 patients) or subtotal (7 patients) R0 D2 gastrectomy was possible in 20 patients. One patient died as a result of gastric bleeding. Perioperative complications occurred in 5 patients (failure of anastomosis in 1 patient and wound infection in the other 4). The pathologic response rate included 7 partial responses (29.1%) and 10 patients with stable disease (41.7%). The main toxicity was grade 3/4 neutropenia (68%), which occurred more frequently during the postoperative chemotherapy, and fatigue (68%). Fever or infection, however, were never observed. The median disease-free survival was 37 months, and median survival has not been reached after 40 months of median follow-up. One-, 2- and 3-year survival rates were 80, 64 and 60%, respectively. CONCLUSION: The notable long-term survival in the present study suggests a comparison between the neoadjuvant approach, including new drug combinations, and adjuvant chemo- or chemoradio-therapy in locally advanced gastric cancer.

Adenocarcinoma↗
PubMed2003

Proteome analysis of mesencephalic tissues: evidence for Parkinson's disease.

Proteome analysis is a powerful methodology to investigate protein expression in tissues involved in diseases not linked to particular genetic defects. To date, this technique has a limited number of applications in the field of neurodegenerative disorders. We decided therefore to investigate by this approach autoptic mesencephalic tissues of patients with idiopathic Parkinson's disease as well as control specimens from healthy subjects.

Blotting, Western↗