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Biomedical subjects

H Oliva

Publications and source records attributed to H Oliva.

At least 37 records · Page 2Linked to original sources

Detection of hepatitis G virus from serum and liver of a patient with long-term liver dysfunction after autologous bone marrow transplantation.

Long-term effects after blood or bone marrow transplantation (BMT) are emerging as an important issue, as more patients are included in BMT programmes and as this procedure becomes more successful. Long-term liver dysfunction, mainly due to chronic graft-versus-host disease or hepatitis C virus infection, is a well-known complication. Nevertheless, the diagnosis of liver disease in this patient group is sometimes difficult and, despite adequate studies, it may remain undetected. A novel hepatitis-associated virus, hepatitis G virus (HGV), has recently been identified. The virus belongs to the Flaviviridae family and is known to be parenterally transmitted, although there is no clear evidence to implicate this agent in causing acute or chronic hepatitis. We report a patient who developed mild, but persistent, abnormalities in transaminases for 2 years after an autologous BMT. HGV RNA was detected in both serum and liver. HGV RNA persisted in serum for at least 8 months. No other known hepatitis virus was found. This report provides the first direct evidence of a patient with long-term liver abnormalities after a BMT in whom the only known hepatitis virus isolated was the HGV.

Adult↗

Pilot interferon-beta trial in children with chronic hepatitis B who had previously not responded to interferon-alpha therapy.

BACKGROUND: Recombinant interferon alpha (IFN-alpha) treatment is useful in 40% of children with chronic hepatitis B. However, nonresponder children continue to have viral replication and a progressive disease. OBJECTIVE: To administer natural IFN-beta to hepatitis B virus chronic carrier children who had not responded to a previous IFN-alpha cycle. METHODS: Twenty-two children with chronic hepatitis B, nonresponders to a previous IFN-alpha cycle, were retreated with 5 MU/m2 of body surface of natural IFN-beta, administered intramuscularly, three times per week for 24 weeks. RESULTS: At the end of treatment, 9 (41%) of 22 children became hepatitis B virus DNA negative. Hepatitis B e antibodies (anti-HBe) developed in 5 of these children, and 6 had normal alanine aminotransferase values. At the end of the posttreatment follow-up (21 months from the beginning of the study), 10 (45%) of 22 children were viral DNA negative, 7 (32%) of 22 were anti-HBe positive (none of them had viral DNA in serum), and 11 (50%) of 22 had normal alanine aminotransferase levels (10 without detectable viral DNA and 7 anti-HBe positive). CONCLUSION: IFN-beta seems to be an effective retreatment therapy for children with chronic hepatitis B who are nonresponders to a first IFN-alpha cycle; however, a controlled study should be performed to confirm these results.

Adolescent↗

Molecular analysis of the IgH gene in 212 cases of Hodgkin's disease: correlation of IgH clonality with the histologic and the immunocytochemical features.

The aims of this study are to evaluate the frequency of clonal immunoglobulin heavy chain gene rearrangements in paraffin-embedded samples of Hodgkin's disease (HD) with use of the polymerase chain reaction method and to correlate the molecular findings with the histologic and immunocytochemical features. DNA extracts from paraffin-embedded sections from 212 HD samples were used for amplification of the IgH gene by use of framework 2 and framework 3 region primers. Immunohistochemical studies were performed on paraffin sections by use of monoclonal antibodies for CD20 and latent membrane protein-1 and polyclonal antibody for CD3. With use of both primer combinations, monoclonality was detected in 18.7% of lymphocyte-predominant HD cases and in 32.2% of classical HD cases. These results suggest that immunoglobulin heavy chain gene clonal rearrangements are relatively frequent in classical HD. In addition, the statistical analyses of the genotypic and immunocytochemical data revealed that the detection of B-cell populations is significantly associated with the expression of CD20 on HRS cells. There was, however, no correlation between the histologic subtype, the percentage of HRS cells, the presence of latent membrane protein-1 expression, and the molecular analysis results.

Antigens, CD20↗

Activation of liver disease in healthy hepatitis B surface antigen carriers during interferon-alpha treatment.

Fifty percent of healthy hepatitis B surface antigen carriers may have histologically proven chronic hepatitis. Our aim was to study the benefit of interferon-alpha in healthy patients. Twenty-nine hepatitis B surface antigen carriers with normal liver enzymes and with serum hepatitis B virus DNA were randomized into two groups: Group I, 14 patients treated with 9 megaunits of interferon alpha-2a thrice weekly for six months, and Group II, 15 control patients. A liver biopsy was obtained from each patient at study initiation. A second biopsy was available in nine treated patients and six controls. During treatment, a significant increase in alanine amino transferase levels was observed in treated patients as compared with the controls (P < 0.05). After treatment, transaminase levels decreased to normal values. No differences between treated and control patients were observed in clearance of hepatitis B virus markers. A significant increase in the total histological activity index between base line and final liver biopsies was observed in treated patients (P < 0.05). It is concluded that interferon alpha treatment may induce a biochemical and histological activation of liver disease. Accordingly, interferon alpha should not be administered to healthy hepatitis B surface antigen carriers, at least with the schedule used in this work.

Adult↗

[Value of protein 53 expression in lymphoma. Its correlation with genetic mutations].

PURPOSE: p53 is a tumour suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation. We have tried to establish the value of expression of the p53 protein in malignant lymphomas and its correlation with the presence of structural gene abnormalities. MATERIAL AND METHODS: 230 cases of lymphomas (11 Hodgkin's disease and 219 non-Hodgkin's) were studied by immunohistochemistry using an anti-p53 monoclonal antibody (DO-7, DAKO). Sections were heated by pressure cooker in 0.01 M sodium citrate buffer pH 6 as a method for antigen unmasking. The quantification of levels of nuclear p53 protein were measured with an Image Analyzer (CAS-200, Becton-Dickinson S.A.). We have also searched for mutations in a series of 94 lymphomas using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in exons 5 to 9 of the p53 gene and the sample showing abnormal pattern were sequenced. RESULTS: p53 immunoreactivity has been detected in 82.6% of cases. The percentage of positive cells varies in a wide range which was divided into 0% (17.39%), less than 5% (57.39%), between 5-10% (13.91%) and more than 10% (11.30%). In all lymphoma subtypes, we have found the majority of cases show levels less than 10% and few more than 10%. We found abnormal bands in 9 of 94 lymphomas with different diagnosis (1 ALCL, 1 T-LNH, 2 B-LNH, 2 centroblastic, 1 lymphoblastic and 2 MALT). Two cases resulted to be a silent base change which not alter the function of the p53 protein and represent a common polymorphism. Seven cases showed single base pair missense mutations in all of them. Mutations in codons 179, 248 and 273 correspond to some of the typical hotspots described in p53 gene. CONCLUSIONS: p53 expression, is a frequent finding in malignant lymphomas, is variable and relates to histological subtype. The results suggest that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53 because the existence of cases with discrepancies between overexpression of the protein and presence of mutations.

DNA Mutational Analysis↗

Undiagnosed hepatitis C virus infection in hemodialysis patients: value of HCV RNA and liver enzyme levels.

At present, routine screening for hepatitis C virus (HCV) infection is based on the detection of antiviral antibodies. Underdiagnosis of HCV infection by using HCV antibody tests, however, still occurs. Additional diagnostic means are provided by the polymerase chain reaction (PCR). The measurement of aminotransferase (ASAT and ALAT) has served as an auxiliary, less specific test. The present research aimed to design practical and low cost strategies to diminish underdiagnosis of HCV infection in dialysis patients. With this purpose in mind, we examined whether aminotransferases values in HCV antibody-negative patients could be related to undiagnosed HCV infection, by using HCV RNA testing by PCR as the gold standard. In 112 hemodialysis patients, we found 78 negative and 34 positive for HCV antibodies. A major finding was that 222 (28.2%) out of the 78 HCV antibodies-negative patients had positive HCV RNA by PCR. In repeated samples taken at six months follow-up from 19 out of these 22 patients, only one of them was positive for anti-HCV antibodies; moreover, a positive HCV RNA by PCR was confirmed in 13 (68.5%) of them. Within the HCV antibody-negative group, the mean values of ASAT, ALAT and gammaglutamiltransferase were higher (P < 0.001, P < 0.001 and P < 0.02, respectively) in the HCV PCR-positive versus the HCV PCR-negative patients. No significant differences were found in the liver enzyme values between the HCV antibody-negative, HCV RNA positive and the HCV antibody positive, HCV RNA positive individuals. Histological samples from two HCV RNA positive, HCV antibody-negative patients disclosed the presence of a mild liver disease. In conclusion, the present study demonstrates the critical importance of HCV RNA determination by PCR in hemodialysis patients who have no detectable circulating antibodies against the HCV. Furthermore, in conditions in which PCR technology is not readily available, we have established that the existence of a moderate increase of aminotransferases is a helpful clue to detect patients with absent HCV antibodies, and might represent an useful, low cost tool for HCV screening in dialysis patients.

Adult↗

[Clinico-morphologic reconsideration of anaplastic lymphoma. Retrospective study of 60 patients with aggressive clinical course and multiple recurrences].

PURPOSE: To identify anaplastic large cell lymphoma Ki-1+ (ALCL-Ki-1+) among a group of patients with aggressive Hodgkin's disease (HD) and to know the biological behaviour of the neoplasia (ALCL-Ki-1+). PATIENTS AND METHODS: Biopsies and clinical data of sixty patients with previous morphological diagnosis of HD lymphocytic depletion (LD), syncytial variant of nodular esclerosis (NE-II) and other subtypes of HD with aggressive clinical features were reviewed. A morphological, immunohistochemical (IHQ), proliferative and flow cytometric (FCM) studies were performed in lymph node biopsies. RESULTS: Morphological study and IHQ identify three groups: 15 patients (25%) lymphocytic predominance (LP) HD, 36 (60%) ALCL-Ki-1+ and 9 (15%) of non-Hodgkin's lymphoma (NHL) and unclassifiable cases. Nine cases of LP show anaplastic and variable immunophenotype being the rest of B-cell nature. 75% of LP patients showed long survival and frequent second neoplasias (47%). ALCL-Ki-1+ group had good initial response to therapy (84%) and multiple relapses, 67% showed CD15 positive marker (the so-called ALCL-HD related). CONCLUSIONS: A retrospective study of a selected group of patients previously diagnosed of aggressive HD showed different pathological subtypes: LP, LP with anaplastic areas, ALCL-Ki-1+ Hr (Hodgkin's related) and ALCL-Ki-1+ (classical type), all of them were CD30+, which could represent different stages of the same neoplasia.

Adolescent↗

Evaluation of clonal immunoglobulin heavy chain rearrangements in Hodgkin's disease using the polymerase chain reaction (PCR).

We have correlated histologic type of Hodgkin's disease, degree of Hodgkin and Reed-Sternberg cell infiltration, percentage of Hodgkin and Reed-Sternberg cell positivity for latent membrane protein, immunophenotype of Hodgkin and Reed-Sternberg cells, and immunoglobulin heavy chain (IgH) gene rearrangements detected by polymerase chain reaction (PCR) in 56 unselected Hodgkin's disease cases. Two protocols were used for amplification of IgH gene using Fr2 or Fr3 V-region primers, in conjunction with nested primers directed to the JH region. PCR products were run on polyacrylamide gels. Immunohistochemical studies were performed on paraffin sections using monoclonal antibodies for CD20 and latent membrane protein, and polyclonal antibody to CD3. Using both primer combinations we detected a definitive clonal band in 23.2% of the Hodgkin's disease cases. Clonal IgH rearrangements were detected in 23.6% of nodular sclerosis type and in 28.5% of mixed cellularity type. Using a highly sensitive method such as PCR, more than 20% of unselected cases of Hodgkin's disease were found to contain B-cell clonal proliferations, but there was no correlation between histological and immunological parameters and molecular analysis results.

Antigens, Viral↗

Waldeyer ring lymphomas. A clinicopathological study of 79 cases.

Waldeyer ring lymphomas belong to a category of tumours which has not yet been fully defined. Their relation to mucosa-associated lymphoid tissue (MALT) and other extranodal lymphomas remains largely unknown. We performed a clinicopathological retrospective study of 79 patients, and compared them with a series of MALT and nodal lymphomas. Tumours from the nasopharynx and palatine tonsil showed similar histological profiles, with a predominance of large B-cells. Centroblastic lymphomas constituted the largest group (n = 45), followed by those of centrocytic type (9) with smaller groups of centroblastic-centrocytic (5) and Hodgkin's lymphomas (2). Three monocytoid B-cell lymphomas were identified. Only one case could be classified as MALT lymphoma. The frequency of bcl-2 expression in large B-cell tumours of Waldeyer's ring has an intermediate range between large B-cell lymphomas occurring in mucosal and nodal locations. Epitheliotropism was present in all low-grade cases, and was therefore not a useful marker in the identification of potential MALT lymphomas in contrast with other mucosal sites. Comparative survival studies showed significant overall differences between Waldeyer ring lymphomas, MALT and nodal cases. These disappeared after taking stage and histological grade into account. We conclude that Waldeyer ring lymphomas show distinctive features, mainly in terms of histological distribution and immunophenotype. The key factor determining their behaviour could be their different spreading capability. These findings suggest that extranodal lymphomas are heterogeneous, and indicate the need for additional efforts to clarify this.

Adolescent↗

Primary pleomorphic T-cell lymphoma of the spleen.

We report a case of primary splenic T-cell lymphoma that posed difficult problems in differential diagnosis with erythrophagocytic T-gamma lymphoma and inflammatory pseudotumor of the spleen. The need for immunophenotypic and molecular studies for establishing the correct diagnosis and the importance of early detection and treatment, is emphasized in the light of the relatively good prognosis of splenic lymphoma, diagnosed in the early stages of disease.

Aged↗

Pneumothorax in AIDS patients: operative management.

Acquired immunodeficiency syndrome (AIDS) is a devastating disease. Pneumocystis carinii pneumonia (PCP) is a major clinical manifestation of AIDS. A 2-year experience with eight operations for PCP-associated pneumothorax in seven AIDS patients was reviewed. Initial treatment was tube thoracostomy in all cases. Operation was performed because of inability to expand the lung and/or persistent air-leak. Time from insertion of the initial chest tube to operation was 9-66 days (mean, 33 days). Pulmonary air leaks were closed with surgical staples and/or sutures. Chest tubes were removed 3-16 days after surgery (mean, 8.5 days). There were no cases of postoperative respiratory insufficiency and there were no deaths. Patients were discharged from the hospital 6-18 days after surgery (mean, 13 days). The postoperative hospital stay was substantially shorter than the preoperative period of nonoperative therapy (13 vs. 33 days). Follow-up is complete in six of the seven patients. Three patients died of AIDS 4-8 months after surgery (mean, 6 months). Three patients are alive 7-14 months after operation (mean, 11 months). Operative management of PCP-associated pneumothorax is effective and can be performed with low morbidity and mortality. We conclude that surgery should be considered as an early option in AIDS patients with PCP-associated pneumothorax.

AIDS-Related Opportunistic Infections↗

A multiparametric study of malignant lymphoma of mucosa associated lymphoid tissue (MALT).

A morphological, immunophenotypic and ultrastructural study, cell cycle estimation, DNA and cytogenetic analysis were performed in ten cases of B-MALT lymphomas. Five had low grade lymphoma and five had high grade. Low and high grade cases showed the same cells but in different percentages: These included centrocyte-like cells with occasional monocytoid cytoplasmic changes, and centroblast-like cells. However, in high grade cases more dysplastic and large cells were present. All cellular types showed an important development of rough endoplasmic reticulum. In all cases a large panel of monoclonal antibodies was employed to study the B-cell immunophenotype. Ki-67 positivity ranged from 5% to 30% in low-grade cases and from 50% to 70% in high-grade cases. Gene rearrangement analysis showed rearrangement with Jh probe and half of the cases were also rearranged with the Kde probe (Kappa constant chain gene). A rearrangement banding pattern with TCR genes was not present in any of the cases. Cytogenetic study showed complex alterations in high grade cases and a normal karyotype in low grade lymphomas. Only one case had rearrangement for the bcl-2 probe.

Female↗

[Castleman's disease. A multifactorial study].

A case of Castleman's disease (hialino-vascular subtype) in a female patient 15-years-old is considered. Clinically there were isolated lymphadenopathies which relapsed after surgery and absence of general syndrome. Histoimmunological and electron microscopic studies were performed as DNA rearrangement and cytogenetics in order to exclude genetic abnormalities and monoclonality of this disorder. The role of follicular dendritic component in discussed.

Adolescent↗

Lymphocyte predominance Hodgkin's disease (nodular paragranuloma)--a bcl-2 negative germinal centre lymphoma.

Hodgkin's disease, lymphocyte predominance type (nodular paragranuloma), is of germinal centre origin and the tumour cells have a B-cell phenotype. As the T(14;18) translocation, and the subsequent expression of bcl-2 protein by germinal centre cells, is the most characteristic finding of centroblastic-centrocytic lymphoma, we have tested a series of 11 cases of lymphocyte predominance Hodgkin's disease, using Southern blot analysis for the major breakpoint region and the minor breakpoint cluster region, polymerase chain reaction with primers for the major and minor breakpoint cluster region, and immunohistological studies with a monoclonal antibody specific for the bcl-2 protein. All three techniques gave negative results in the cases of Hodgkin's disease, establishing a clear differentiation from centroblastic-centrocytic lymphoma. These findings are useful in the differential diagnosis between the two entities and raise the question of the non-clonal nature of lymphocyte predominance Hodgkin's disease.

Antibodies, Monoclonal↗

[Low-grade B cell gastric lymphoma originated in mucosa-associated lymphoid tissue. Relationship of tumor cells with the marginal zone and monocytoid B lymphocytes. An immunohistochemical and ultrastructural study].

Seven cases of gastric B-cell low-grade lymphomas were characterized by morphology, immunohistology and electron microscopy. All them were immunophenotyped with a panel of monoclonal antibodies against immunoglobulins and other B-cell determinants. Histologic study of gastric B-cell low-grade lymphomas showed germinal centers of lobated shape and polyclonal nature, mainly polyclonal subepithelial plasma cell (except in one case) and neoplastic interfollicular B-cells of monoclonal character. Light-chain restriction supports the neoplastic nature of gastric lymphoma of low-grade malignancy, a distinctive tumour of extranodal B-cell origin. Interfollicular B-cells share with marginal zone cells a perifollicular localization, morphology and phenotype, suggesting a possible relation between these two cellular subtypes. In two cases, the tumour appears constituted by monocytoid B-lymphocytes (MBL), which suggests a relation of tumoral interfollicular B-cells with this subpopulation.

Adult↗