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Biomedical subjects

P Fabris

Publications and source records attributed to P Fabris.

At least 55 records · Page 3Linked to original sources

Organ-specific autoimmunity and genetic predisposition in interferon-treated HCV-related chronic hepatitis patients.

AIMS: Interferon alpha has been reported to enhance autoantibody production and to increase the risk of autoimmunity particularly against thyroid tissue. We designed a study with the following aims: 1) to assess the incidence of organ- and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate whether these autoantibodies have any clinical relevance; 3) to establish whether the development of autoimmune disorders can be related to a genetic predisposition. METHODS: A panel of 5 non-organ-specific and 6 organ-specific autoantibodies was evaluated in serum samples collected before treatment and then at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b-recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part of the study we explored genetic predisposition for autoimmune disorders in 31 patients by DNA-HLA class II typing using Restriction Fragment Length Polymorphism (RFPL). RESULTS: Non-organ-specific autoantibodies were absent in all patients before and after Interferon. During follow-up 6 patients showed an increment in thyroid microsomal antibody titres; 3 of these also developed thyroglobulin autoantibodies; 3 of the 6 patients developed persistent hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth had a transient subclinical hyperthyroidism. Two patients with initial positivity for ICA and PCA maintained their reactivity during treatment without impairment of the respective target organs. Eight out of 39 initially negative patients developed one or more organ-specific autoantibodies during follow-up. One of these developed a persistent hypothyroidism, and another developed insulin-dependent diabetes. HLA-typing did not reveal any particular allele frequency in patients with thyroid antibody positivity as compared with those without autoantibodies and controls. Moreover, four of the 6 patients positive for islet-cell antibodies were carrying the non-Asp 57 allele which is considered a marker of a genetic predisposition for insulin-dependent diabetes. CONCLUSIONS: These findings suggest that, besides the thyroid gland, pancreatic beta-cells could be a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A genetic predisposition may be important, though insufficient alone, in the development of Interferon-induced autoimmune phenomena.

Adolescent↗

H. pylori infection in HIV-positive patients. A serohistological study.

Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H. pylori infection. The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H. pylori IgG antibodies. The H. pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS). Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy. Low CD4+ counts were also apparently associated with low-grade H. pylori infection. Serological testing was positive for anti-H. pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81%. The discrepancy between histological and serological positive results for H. pylori was noted to be higher in the more advanced phases of HIV infection. Based upon our results, the serological testing for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

Acquired Immunodeficiency Syndrome↗

The role of anthracyclines in adult acute lymphoblastic leukaemia.

The role of anthracyclines (ANT) in the treatment of adult acute lymphoblastic leukaemia (ALL) is poorly defined as regards drug dosage, schedule, preferable compound, and indications for use in specific treatment phases or disease subset. We therefore reviewed ANT treatment results in adult ALL. Altogether, an early and intensive use of ANT would improve both initial response rate and long-term disease-free survival; idarubicin (IDR) exhibits a considerable antileukaemic activity deserving further evaluation as possible reference drug; and the prognosis of CD10+ t(9;22)/BCR-ABL- ALL can be particularly good following an early dose-intensive ANT consolidation program.

Adolescent↗

Target value tailored (TVT) apheresis approach for blood progenitor cell collection after high-dose chemotherapy and rh-G-CSF.

Twenty-eight patients with different hematological diseases (17 non-Hodgkin's lymphoma, one Hodgkin's disease and 10 multiple myeloma) underwent peripheral blood progenitor cell (PBPC) collection after cyclophosphamide 7 g/m2 and rh-G-CSF. Fifty-eight leukaphereses were carried out with a fully automated PBPC collection procedure. Progenitor cell release was monitored by standardized determination of CD34+ cells in the peripheral blood. After a profound aplasia, a continuous increase in CD34+ cells in the peripheral blood was seen for at least 3-4 days. In 82% of our patients more than 2.5 x 10(6) CD34/kg could be collected using a standard apheresis of 10 l. There was a high correlation between the CD34+ cells in the peripheral blood and CD34+ cells/kg harvested. (r2 = 0.91). A relatively constant ratio (median 14.3, range 3.2-22.6) was found between CD34+ cells/kg and CFU-GM/kg. Based on the CD34 values of the pre-apheresis blood and the body weight of an individual patient and using the mathematical model of regression analysis (y = mx + b) for the correlation between the CD34+ cells/microliter in the pre-apheresis blood and the CD34+ cells/kg, it was possible to create a formula allowing for target value tailored apheresis. Using this formula, the blood volume which needs to be processed in order to harvest a desired number of CD34+ cells/kg can be calculated. This strategy can be applied to reduce the time for and the number of aphereses. Nineteen leukaphereses were carried out applying the formula. In 18 of 19 leukaphereses the expected CD34+/kg values were correctly achieved or exceeded. The formula was most reliable when the CD34 value was higher than 15/microliter and when the WBC count was below 20 x 10(9)/l in the pre-apheresis blood. For mobilizations using hematopoietic growth factors alone our formula is not applicable, because in most cases the pre-apheresis white blood cell count is higher than 20 x 10(9)/l and the collection efficacy of lymphomonocytoid cells decreases with a high pre-apheresis white blood cell count. The formula also works with other mobilization regimens that induce a pronounced aplasia.

Antigens, CD34↗

Amphotericin B as primary therapy for cryptococcosis in patients with AIDS: reliability of relatively high doses administered over a relatively short period.

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.

AIDS-Related Opportunistic Infections↗

Serological survey of hepatitis B infection in Tanzania.

In 1992, the prevalence of hepatitis B virus (HBV) markers was evaluated in 1004 subjects aged one to 76 years living in urban and rural areas in Tanzania. The overall prevalence rates of hepatitis B surface antigen (HBsAg) and of any HBV marker were 4.4% and 37.0%, respectively. No statistically significant difference by sex was found. The HBsAg prevalence among pregnant women was 4.3% (20/463). The proportion of HBeAg positive among HBsAg positive pregnant women was 10% (2/20). The HBsAg age-specific prevalence was 2.1% in the 1-5 year age-group; peak prevalence (12.1%) occurred in the 6-15 year age-group. Markers of HBV infection were 4.1% by age five years; they increased with advancing age (P < 0.01). Subjects residing in urban areas had statistically significant higher HBV exposure than those residing in rural areas (43.9% vs 27.4%, P < 0.01). Subjects belonging to the largest family size (seven or more members) showed increasing risk (OR 2.9; 95% CI = 1.96-4.28) of HBV exposure. Because maternal HBV transmission early in life appears to be of minor impact and children are mostly infected later in infancy, HBV vaccination at birth is not indicated, while vaccination of all infants at 2-3 months of age with other paediatric vaccinations is the first priority.

Adolescent↗

Impact of interferon at induction chemotherapy and maintenance treatment for multiple myeloma. Preliminary results of a multicenter study by the Italian non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG).

In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG) started a multicenter study on the role of interferon (IFN) in multiple myeloma (MM). The schedule of treatment was based on the assumption that melphalan plus prednisone (MP) would be better for good-prognosis patients, whereas poor-prognosis patients would benefit from polychemotherapy. Accordingly, IFN was included randomly for the induction treatment of good-prognosis patients and randomly as maintenance of the response achieved in both groups. Up to now 78 patients of the 124 enrolled have completed the induction treatment and are evaluable for response and response duration. The overall response rate was 59%. Sixty-two percent of good-prognosis patients obtained objective response, 9/14 (64%) with MP and 9/15 (60%) with MP+IFN. Up to now, with a median follow-up of 9 months from the evaluation of response, no difference has been recorded between the maintenance and no maintenance groups on relapse rate, neither in good- nor in poor-prognosis patients.

Aged↗

Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL).

Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985 and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1, were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily for a median of 5.7 months, produced a response of 93%, complete+partial response (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment variables were associated with the rate of response to IFN. However maintenance treatment of 3 MU/mq weekly given randomly had a slightly significant effect on failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%) obtained a new response with IFN. No differences in FFS were recorded between first and second response. At the third induction 7/11 patients were treated again with IFN, 4/7 obtaining some response, but the FFS was significantly worse. The overall survival is still 85%. We conclude that (1) IFN should be used as chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to prolong the disease free status and (3) continuous lymphoblastoid IFN administration seems not to be associated with the development of resistance to retreatment.

Aged↗

Hepatitis C virus infection in homosexual men: a seroepidemiological study in gay clubs in north-east Italy.

Seroprevalence of Hepatitis C virus (HCV), Hepatitis B virus (HBV) and HIV antibodies was studied in a group of 259 apparently healthy homosexual men of the Veneto Region (Italy). Subjects were recruited between 1987 and 1989 from homosexual men's clubs. Seropositivity was evaluated in relation to main risk factors associated with the lifestyle and sexual behaviours of this population. Serological evaluation revealed an overall prevalence of HCV infection of 18.9% in the study population as a whole, but on breaking the samples down into three subgroups according to optical density (O.D.) values and to the year of sera collection, different seroprevalences were observed. Prevalence of anti-HCV was higher in 1987 and steadily decreased in 1988 and 1989; 4.1% of subjects gave positive results at O.D. greater than 2.0, while 6.2% were positive at O.D. between 0.8 and 2.0 and 9.6% at O.D. between cut-off and 0.8. Anti-HCV positivity was not correlated with HIV nor HBV positivity. No correlation was found between HCV seropositivity and either the type of anogenital intercourse or sexual promiscuity, but the prevalence increased (p = n.s.), as observed for HIV (p less than 0.05) and HBV (p = n.s.), with the number of intercourses per month. Epidemiological and preventive aspects arising from the investigation are discussed herein.

Adolescent↗

Primary biliary cirrhosis in the elderly.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with onset about menopause. To investigate its clinical features and the natural history in relation to age, we examined 86 consecutive patients with PBC (81 F, 5 M); 70 were less than 65 years (mean age 48 years) and 16 greater than 65 years (mean age 69 years). All patients were followed-up for 6 months-16 years (mean 4 years). Histological stage at presentation was comparable in the two groups, but among aged PBC subjects there was a significantly higher prevalence of asymptomatic patients (56% vs 24%, p less than 0.001). No significant differences were observed in the biochemical indices and immunological abnormalities. Survival curves showed no significant differences in PBC according to the age. Mortality was observed only in the group less than 65 years (15/70, 21.4%). In conclusion, the large proportion of asymptomatic subjects in the elderly PBC patients accounts for the similar survival in the two groups of patients.

Adult↗

Successful treatment of a steroid-resistant form of idiopathic thrombocytopenic purpura in pregnancy with high doses of intravenous immunoglobulins.

Idiopathic thrombocytopenic purpura (ITP) during pregnancy may cause serious bleeding in the mother and fetus. Therapy with high-dose intravenous immunoglobulins has caused an immediate and predictable rise in platelet count in both adults and children with chronic or acute ITP. We report our experience in managing a woman near term in pregnancy. The patient demonstrated a rapid increase in platelet count, delivered without excessive bleeding and had a normal child with normal platelet count. Intravenous immunoglobulins may offer a new and safe way to control maternal and fetal platelet counts during pregnancy, delivery and neonatal period.

Adult↗

Cytoplasmic immunoglobulins in chronic lymphocytic leukemia B cells.

It is generally assumed that chronic lymphocytic leukemia of B cell origin (B-CLL) is characterized by the presence of surface membrane immunoglobulins (SmIg) and by the absence of cytoplasmic immunoglobulins (CyIg). In a variable number of cases SmIg are not detectable because of their low density on the cellular surface. Because a constant presence of CyIg in 20 subjects suffering from B-CLL has been reported recently, we reexamined 15 SmIg-negative and 10 SmIg-positive B-CLL patients by SmIg and CyIg determinations. We used a direct immunofluorescence method on peripheral blood mononuclear cells for the detection of SmIg and, after fixation, for CyIg. CyIg were detectable in 24 out of 25 cases, with a fluorescence intensity ranging from weak to moderate. The existence of frequent negative results for CyIg determination in B-CLL reported in the literature probably depends on the low sensitivity of the method used. We conclude that CyIg determination is useful in phenotyping every B-CLL patient, especially SmIg-negative ones.

Antigens, Neoplasm↗

Bernard-Soulier syndrome: diagnosis by an ELISA method using monoclonal antibodies in 2 new unrelated patients.

Two unrelated patients with Bernard-Soulier syndrome and their relatives were studied. The patients demonstrated severe bleeding diathesis, the relatives were asymptomatic. The propositi showed the characteristic abnormalities of the syndrome: thrombocytopenia, a percentage of giant platelets higher than 65%, prolonged bleeding time and defective platelet aggregation to ristocetin and bovine plasma. On the contrary, in the heterozygotes, the typical abnormalities were not fully evident. We introduce a simple ELISA method for the precise definition of both homozygous and heterozygous states for the syndrome by the quantitation of platelet glycoprotein (GP) Ib. Specific binding of monoclonal antibodies anti-platelet GPIb was performed both by direct binding of radioiodinated antibody and by ELISA. Comparable results were obtained. In fact, we demonstrated near absence of GPIb in the 2 propositi and about half the amount in the heterozygotes studied compared to normal platelets.

Adolescent↗

Emergency splenectomy in hairy cell leukemia.

The role of splenectomy in the treatment of hairy cell leukemia (HCL) is now well established. There are however some particular situations which indicate splenectomy as a possible emergency therapy in markedly cytopenic cases with severe antibiotic-resistant infections. The aim of the emergency splenectomy in such conditions is to temporarily increase neutrophils and to permit the improvement of the infectious disease. We describe 2 cases of HCL with severe infectious disease, successfully splenectomized.

Emergencies↗

Longterm results of 38 knee prostheses.

The authors report the results obtained with 38 knee prostheses reviewed from one to 9 years after insertion and discuss the advantages and limitations of this operation relative to different types of prosthesis. Although this operation has passed the "experimental" stage it has not yet reached a stage of reliability comparable with that of hip prostheses. The sliding prostheses yielded a higher percentage of positive results (81%) than the hinged prostheses (70.5%); the latter, however, are still indicated in selected cases. Knee replacement operations are justified, however, when the only valid alternative is arthrodesis.

Adult↗

[Results of calcitonin therapy of the painful symptoms caused by osteolytic metastases of prostatic carcinoma].

Albeit within the limits imposed on us by the restricted number of cases, we can state that--in the present state of research--calcitonin constitutes a useful complement in treatment of osteolytic metastasis induced by carcinoma of the prostate. Is utilisation is justified by the effects observed: on the one hand, osteogenesis as a factor protecting against the aggressivity of the tumoural cells, and on the other the considerable antalgic strength allied with improvement in the calcium, phosphorus and phosphatase values. For some time we have replaced pig calcitonin with salmon calcitonin: the comparative results with this second product will be the subject of a subsequent paper.

Bone Neoplasms↗