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Biomedical subjects

G Cariti

Publications and source records attributed to G Cariti.

At least 19 recordsLinked to original sources

Antiretroviral activity of pegylated interferon alfa-2a in patients co-infected with HIV/hepatitis C virus.

OBJECTIVES: To evaluate the early anti-HIV activity of pegylated interferon (PEG-IFN) alfa-2a and ribavirin in HIV/hepatitis C virus (HCV) co-infected patients not receiving antiretroviral therapy. PATIENTS AND METHODS: In 19 patients with baseline plasma HIV load (HIV-RNA) >1000 copies/mL treated with PEG-IFN alfa-2a and ribavirin, HIV-RNA and T-cell subsets were measured at baseline and 2, 4 and 12 weeks after initiation of anti-HCV therapy. RESULTS: We observed a significant HIV-RNA decrease (>1 log(10) copies/mL) through week 12 of anti-HCV treatment. The magnitude of HIV-RNA decline was associated with baseline HIV-RNA, CD4 count and PEG-IFN weight-adjusted dose. CONCLUSIONS: A significant early anti-HIV activity of PEG-IFN alfa-2a was observed. Such an effect warrants further clinical evaluation in the management of co-infected patients.

Adult↗

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↗

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy.

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment.

Acute Disease↗

Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients.

BACKGROUND/AIMS: To evaluate the efficacy and tolerance of amantadine in combination with interferon in the treatment of chronic hepatitis C. METHODS: Multi-centre trial including 180 chronic hepatitis C patients without cirrhosis, randomly enrolled to receive interferon 6 MU every other day for 6 months followed by 3 MU for further 6 months (group A, 90 patients), or the same schedule plus amantadine 200 mg/day (group B, 90 patients). Primary end-point was a sustained virological and biochemical response, secondary end-points were on-treatment (third month) and end-of-treatment response rates. RESULTS: The two groups had similar demographic, biochemical and virological characteristics. A sustained response after 6 months follow-up was observed in 17% of group A and 24% of group B patients (P not significant), an end-of-treatment response was observed in 37% in group A and 47% in group B (P not significant), an on-treatment response was observed in 46% in group A and 61% in group B patients (P < 0.05). No major side effects due to amantadine administration were observed. CONCLUSIONS: Adding amantadine to interferon did not improve the sustained treatment efficacy. However, the rate of early response at the third month of therapy was significantly higher in the combination therapy group.

Adult↗

A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone.

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-alpha2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P =.04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P =.03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.

Adult↗

Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study. The North West Italian Hepatological Group.

OBJECTIVE: To establish whether tailoring the dosage of interferon (IFN)-alpha2b in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of sustained response (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the end of therapy). PATIENTS: A total of 538 consecutively collected HCV-positive patients with non-cirrhotic chronic hepatitis who had not been previously treated. METHODS: Quantitative viraemia and genotype were determined in each patient by a core laboratory. The patients were randomized to: Group 1, 86 patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4, 85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a further 10 months. RESULTS: According to an intention-to-treat analysis, a sustained virological response (negative HCV-RNA by polymerase chain reaction 6 months after the end of therapy) was observed in 42% of Group 1 patients, in 21% of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in 28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of Group 6 patients versus 12% of Group 7 patients (P = NS). CONCLUSIONS: Even though a trend towards a therapeutic improvement is observed, the adoption of more aggressive IFN protocols, such as induction therapy, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and highly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when treated with high doses of IFN.

Adult↗

Hepatitis C virus genotypes in a non-cirrhotic Italian population with chronic hepatitis C: correlation with clinical, virological and histological parameters. Results of a prospective multicentre study.

To identify correlations between the distribution of hepatitis C virus (HCV) genotypes and demographic, pathological and virological parameters of HCV-infected patients, we prospectively recruited 650 patients with biopsy-proven chronic hepatitis C without histological aspects of cirrhosis; none had been treated with antiviral therapy. Data regarding gender, age, mode of HCV transmission, alanine aminotransferase (ALT) and HCV RNA levels, immunoglobulin M (IgM) anticore values, liver histology and histological activity were obtained from each patient and correlated on multivariate analysis with infecting HCV genotype. Fifty-five per cent of the patients were infected with HCV genotype 1, 20% with HCV genotype 2, 18% with HCV genotype 3 and 7% with HCV genotype 4. Non-transfusional HCV transmission, low ALT levels, IgM anticore reactivity and a low histological grading score were independent variables associated with HCV genotype 1. Older age, female gender, post-transfusional transmission and a high histological grading score were related to HCV genotype 2, whilst younger age, history of current/previous drug abuse, high ALT values, low IgM anticore reactivity and high viraemic levels were associated with HCV genotype 3. History of illicit use of intravenous drugs and low HCV RNA levels were the only independent variables correlated with HCV genotype 4. Genotype 1 remains predominant in Italy but the prevalence of HCV genotypes is changing in relation to age and mode of transmission: Italian patients with HCV genotype 3 are younger and exhibit higher levels of ALT and HCV RNA than patients with other genotypes.

Adolescent↗

[Breast neoplasms detected only with ultrasonography: incidental finding or clinical evidence?].

INTRODUCTION: Mammography is the only technique of proven efficacy in the early diagnosis of breast cancer, even though its sensitivity is much lower in breasts that are dense or with a high parenchymal-stromal component. In the past malignant breast nodules detected at US in patients with negative mammographic and physical findings were considered incidental findings, but more recent papers report increasing numbers of breast cancers detected only at US. PURPOSE: We investigated the yield of US performed as a diagnostic complement in asymptomatic women with mammographic findings that were either negative or poorly readable because of dense breast. MATERIAL AND METHODS: We examined 13 women 37 to 55 years old (mean 47): 9 of them were asymptomatic and 4 had poorly specific physical findings. The patients underwent physical examination, mammography, US, microhistologic biopsy with 14G needles under US guidance and surgery. RESULTS: Fourteen breast lesions 7.0-15 mm in diameter were detected only by US. Mammography (2 or 3 standard views) was negative in all cases. The lesions detected only by US (10% of all carcinomas) were typified with US-guided needle biopsy and finally confirmed surgically. DISCUSSION AND CONCLUSIONS: Though obtained in a small series, our results seem to suggest that US should be included in the diagnostic work-up, especially of women with dense breast. Also, any hypoechoic lesion detected at breast US in clinically asymptomatic women with negative mammographic findings should be further investigated with US, needle aspiration or core biopsy to make the final diagnosis.

Adult↗

Natural beta interferon in acute type-C hepatitis patients: a randomized controlled trial.

AIM OF THE STUDY: A multicentre randomized controlled trial to assess whether a short course of beta-interferon could reduce the rate of chronic evolution of acute hepatitis C, in line with recent observations, was started in Northern Italy in 1991. METHODS: Forty acute hepatitis C patients were randomized to receive natural beta interferon 3,000,000 international units intramuscularly three times a week for 4 weeks or symptomatic drugs, and were followed up for a median period of 22.5 months. RESULTS: The chronicity rate was 75% (15/20 patients) in the interferon-treated group, and 80% (16/20) in the untreated group. No difference in the duration of the acute phase of hepatitis was observed. Hepatitis C virus ribonucleic acid was determined in 21 cases and was positive in 19 cases at baseline and in 15/17 chronic and 1/4 non chronic cases at the end of follow-up. Side effects of therapy (flu-like syndrome in 40% of cases) were mild and short-lasting. No aminotransferase flare-ups were observed during treatment. CONCLUSIONS: Beta interferon at the suggested regimen is well tolerated but does not seem to significantly influence the natural course of acute hepatitis C.

Acute Disease↗

[Percutaneous biopsy in the definition of breast lesions: fine needle vs. 14-gauge].

INTRODUCTION: Any breast lesion/abnormality detected at mammography must be characterized as (non)-neoplastic before surgery. Fine needle aspiration cytology (FNAC) permits a precise diagnosis in over 70% of cases but exhibits many inadequate, false negatives or questionable findings. This makes surgical biopsy mandatory in many cases. An alternative is offered by fine needle biopsy (FNB: 16-18 G needles) or by large core biopsy (LCB: 14 G needles), which procedures can reduce the number of questionable diagnoses with no major discomfort or side-effects for the patient. MATERIAL AND METHODS: January, 1996, to October, 1997, we performed 422 microhistologic biopsies on breast lesions at the Unità Integrata di Senologia, Azienda Ospedaliera Careggi, Florence, Italy. 383 of these lesions were nonpalpable. FNB was performed in 221 cases and LCB in 201. Most biopsies (65%) were carried out under US guidance and some others (25%) under stereotactic guidance. RESULTS: Microhistologic biopsy allowed accurate lesion characterization in most cases, even though LCB obviously performed much better. Samples were inadequate in 5.88% of cases with FNB and only in 2.98% of cases with LCB. The false negative rate was 1.92% for FNB and 0.99% for LCB. Surgical biopsy was needed for an unquestionable diagnosis only in 9.5% of FNB and 3.9% of LCB cases. CONCLUSIONS: Our results confirm the literature data on how LCB can be considered a valid alternative to surgical biopsy (and, to some extent, to FNAC); in particular, its advantages are: moderate invasiveness, little patient discomfort and high diagnostic accuracy. Moreover, the procedure is short (5-10 minutes) and costs much less than surgical biopsies (1/2 to 1/4).

Adult↗

[Atypical hepatitis].

Acute viral hepatitis has a rather homogeneous clinical pattern, excepting a few features which are related to the specific viral agent. However, a few cases may be defined "atypical", as fas as clinical features, transmission pattern, serology are concerned. These include cholestatic hepatitis syndrome, fulminant HEV hepatitis during pregnancy, neonatal hepatitis. Non-typical aspects may be observed when extrahepatic manifestations are present (cryoglobulinemia, bone marrow aplasia, guillain-Barré syndrome, peripheral neuropathy, skin involvement, etc.). Finally, viral hepatitis may be "atypical" when associated with other infections (malaria, typhoid fever, etc.), mostly in patients from tropical Countries.

Acute Disease↗

Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection.

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are common in HIV infection. To characterize further the site of these derangements and their possible causes, eight male drug addicts with symptomatic HIV infection (stage IV C2) underwent the following investigations: repeated baseline determinations of cortisol, adrenocorticotropin (ACTH), interleukin 1 beta (IL-1 beta), IL-6 and interferon alpha (IFN-alpha); and ovine corticotropin-releasing hormone (CRH) test (100 micrograms IV) for ACTH and cortisol determinations. Baseline cortisol levels were either normal or elevated in all patients. A significant linear correlation was found between baseline levels of cortisol and both IL-6 (r = 0.955; p < 0.001) and IL-1 beta (r = 0.863; p < 0.005), but not between cortisol and ACTH or between ACTH and circulating cytokines. Both ACTH and cortisol responses to CRH were nearly absent in six out of eight patients, and delayed in the others. The areas under the curves of both ACTH and cortisol after CRH were significantly lower in HIV patients than in a group of eight healthy control subjects (p = 0.0157 for ACTH and p = 0.046 for cortisol). Out data suggest the possibility of an inappropriate stimulation of the HPA axis in symptomatic HIV infection by HIV-induced release of cytokines, with a blunted pituitary and adrenal response to CRH.

Adrenocorticotropic Hormone↗

[Use of topical methisoprinol (Viruxan) in female genital condylomatosis].

Medical therapy of genital condylomatosis seems to be the most rational strategy, since this pathology is characterised by highly frequent recurrences after destructive physical therapy alone. Successful therapy of female genital condylomatosis with methisoprinol (Viruxan), administered as ointment and/or vaginal ovules is reported. The drug proved to be efficient both in curing this viral infection and preventing its recurrences.

Administration, Topical↗

[Viral infections and neoplasms of the uterine cervix].

Since the last century, epidemiological studies of cervical carcinoma have shown a close link with sexual activity and in particular with promiscuity starting at an early age. Aetiological research has therefore concentrated on identifying sexually transmitted pathogens. In recent years studies have focused on the apparently significant role of HSV and particularly HPV in the aetiopathogenesis of this tumour. After the first cytohistological findings the HPV-cervical cancer link has been confirmed by electron microscopy, immunohistochemical studies and hybridisation of viral DNA. The identification of different HPV types presenting varying degrees of oncogenic risk offers the prospect of reaching a reliable prognosis on the basis of the particular virus identified in the lesion. The hypothesis that the virus has a decisive influence on the biology of th tumour is also intriguing: findings on the incidence and course of cervical cancer in the youngest women seems to suggest tha HPV may be a fundamental tumour growth factor.

Female↗

Non-A, non-B hepatitis; factors involved in progression to chronicity.

A cross-sectional, longitudinal study was undertaken on a group of acute non-A, non-B hepatitis patients, as well as on a control group of hepatitis B patients, in order to assess both the prevalence of the most important factors favoring infection, and the relevance of these factors in promoting evolution towards chronic liver disease. Exposures to unknown risk factors were present in 47.4% of acute non-A, non-B infections, followed by blood transfusions (17.9%), sporadic exposures (17.9%) and drug addiction (16.6%). Unknown as well as sporadic exposures showed a greater prevalence in control population if compared to non-A, non-B cases, while drug addiction was equally represented in the two groups, and blood transfusion nearly absent from control group. The risk of evolution to chronic liver disease was about 13 times greater in non-A, non-B group than in controls, with the greatest risk for drug addicts and the lowest for patients with unknown exposures. Among patients with known exposures, the lowest risk of chronic hepatitis was observed in post-transfusion and in sporadic cases, while the greatest was observed in drug addicts.

Adolescent↗

HIV infection acquired by a nurse.

We report here the history of the first case of occupationally acquired HIV infection in Italy. Results of serological investigations sequentially performed allow the investigators to outline the natural history of the infection in this case.

Acquired Immunodeficiency Syndrome↗

Pulmonary sarcoidosis associated with Leydig cell testicular neoplasm.

The first case of association between Leydig cell testicular tumor and sarcoidosis is reported. From a review of the literature, this is the ninth case of association between a testicular tumor and Besnier's disease. Lung biopsy should always be performed in patients with testicular cancer when retroperitoneal lymph node involvement cannot be demonstrated in order to avoid unnecessary antineoplastic chemotherapy.

Diagnosis, Differential↗

Relationship between circulating immune complexes, serum interferon and clinical features in sarcoidosis.

In order to assess the importance of circulating interferons and immune complexes as hypothetical mediators of some immune derangements observed in sarcoidosis, we evaluated serum interferon and immune complex levels in 45 patients with active disease. In none of our patients could circulating interferon be detected, suggesting that an infectious (viral) etiology is very unlikely, and that a great difference exists between sarcoidosis and true autoimmune diseases. On the other hand, circulating immune complexes could be found in 64.4% of our patients. A good correlation could be found with disease stage and duration, but only with 67Ga lung scan among other activity indexes.

Adult↗