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M Fraga

Publications and source records attributed to M Fraga.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Epidural abscess secondary to the implantation of a thoracic catheter].

Spinal compression related to the formation of an epidural abscess after epidural blockade is a rare but serious complication. We report the case of a male patient in whom a thoracic epidural catheter was implanted to provide analgesia after trauma involving fracture ribs. The patient developed an epidural abscess within one week of implantation. Delay in diagnosis led to persistent neurogenic bladder symptoms in spite of aggressive treatment. We review causal factors, mechanisms of formation, pathogenesis, diagnosis and management, as well as possible relation between injury and abscess formation. We also emphasize the importance of adequate vigilance as well as rapid diagnosis and adoption of therapeutic measures in order to avoid permanent sequelae such as paresis, sensory deficits or mechanical sphincter dysfunction.

Abscess↗
PubMed1997

Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression.

Previous studies have shown that in non-Hodgkin's lymphomas and others neoplasms, tumoral progression, treatment response, and outcome are related to the expression of different oncogenic and tumor suppressor proteins. This study aimed to determine the prognostic significance of the expression of p53, bcl2, retinoblastoma protein (Rb), Ki67, CD15, and latent membrane protein 1-Epstein-Barr Virus (LMP1-EBV) proteins in Hodgkin's disease. A retrospective study was performed on 140 patients collected at the 11 participating centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. A highly sensitive immunohistochemical method with previous microwave-induced antigen retrieval technique was used for the demonstration of the above-mentioned proteins. A Cox's multivariate analysis was performed to evaluate the impact of the variables in the overall survival, together with a logistic regression model for the achievement of complete remission. Univariate statistical analysis confirmed the prognostic significance of the alredy known clinical parameters: stage, age over 60 years, and B symptoms. High proliferation index (Ki67) and loss of Rb expression were also found to be adverse prognostic factors influencing respectively lower overall survival and failure to achieve complete remission. Multivariate analysis confirmed the independent significance of these two parameters and additionally identifies LMP1-EBV expression as a favorable prognostic marker, in relation with overall survival. Histopathological type, p53, bcl2, and CD15 expression lack significant influence on the outcome of this series. The progression of the disease or the response to treatment in HD patients is the consequence of the interrelationship of different factors, among which LMP1 expression, loss of Rb, and high growth fraction seems to play a more relevant role.

Adolescent↗
PubMed1997

Cellular and subcellular distribution of 7B2 in porcine Merkel cells.

BACKGROUND: Merkel cells are neuroendocrine cells located in the skin and oral mucosa of various mammalian species. These cells express multiple peptides as well as serotonin. Although the precise function of Merkel cells is still unknown, different studies support its role as mechano-electric transducer. 7B2 granin (secretogranin V) is a polypeptide isolated from the pituitary gland and present in the dense-cored granules of neuronal and paraneuronal cells. METHODS: The expression of the 7B2 in Merkel cells of pig snout skin was analysed by immunohistochemical techniques. The streptavidin-biotin peroxidase complex procedure was employed for light microscopy. A postembedding method using immunoglobulin-colloidal gold complexes was employed for the ultrastructural studies. RESULTS: Immunoreactivity for 7B2 was observed in virtually all Merkel cells, both in epidermis and vibrissae. The immunostaining was shown in the basal side of cytoplasms where neuroendocrine granules were accumulated. Immunoelectron microscopy allowed us to demonstrate that 7B2 labelling was located on the electrondense granules. Nuclei and epidermal nerve terminals associated with merkel cells did not show immunoreactivity. CONCLUSIONS: The polypeptide 7B2 is present in the dense-cored granules of Merkel cells. This result is consistent with the possible role for 7B2 in secretory granules' processing. To our knowledge this is the first evidence of 7B2 protein in Merkel cells.

Animals↗
PubMed1997

Long-term treatment with recombinant interferon alpha-2b prolongs survival of asymptomatic HIV-infected individuals.

RATIONALE AND OBJECTIVE: Early long-term treatment with recombinant interferon (IFN) alpha-2b delayed disease progression in asymptomatic Human Immunodeficiency Virus (HIV) carriers in a randomized trial that lasted from October 1987 to February 1992 (14). The aim of the work reported in this paper was to observe if there was also an effect on survival when the same patients were followed-up further. DESIGN AND INTERVENTIONS: IFN alpha-2b was given 3 x 10(6) IU, 3 times weekly. The control group did not receive any treatment. The main end-point for this evaluation was death due to any cause. The deadline was August 1995. POPULATION: Subjects were anti-HIV-1 seropositive, Western blot-confirmed, asymptomatic (CDC group II), or with generalized lymphadenopathies (CDC group III). The groups had 79 (control) and 83 (IFN) patients. MAIN RESULTS: Mean survival was longer in the IFN group (95% CI: 127-152 vs. 101-120 months since infection or 80-90 vs. 70-82 months since the start of treatment). Survival rates were higher in IFN-treated individuals (61-77% vs. 24-54% at 10 years of infection or 53-69% vs. 34-52% at 7 years of treatment or follow-up). It was also confirmed that disease progression is significantly slower in IFN-treated patients. There were 23.4 vs. 3.2% long-term survivors in the IFN and control groups, respectively (p = 0.005). IFN-treated patients had fewer AIDS-related malignancies (5 vs. 11), mainly Kaposi's sarcomas (1 vs. 5). This difference was not statistically significant, but clinically interesting. There was no difference in survival if measured since the onset of AIDS. CONCLUSION: IFN alpha treatment given from the early stages of infection, but not after the appearance of AIDS symptoms, can prolong survival.

Adult↗
PubMed1996

Cellular distribution of prolactin receptors in human digestive tissues.

In the present study we analyzed the expression of prolactin receptors (PRLR) in human digestive tissues by immunohistochemistry. PRLR immunoreactivity was primarily localized in the cytoplasm. However, in some organs (liver and salivary glands) a nuclear positivity was also found. The liver was used as control and showed a diffuse immunostaining in the parenchymal cells. In the gastrointestinal tract, PRLR immunoreactivity was observed in the mucosa, muscularis layer, and nervous plexuses. The more intense immunostaining in the mucosa of the different segments was as follows: esophagus, superficial layers of the stratified squamous epithelium and mucous glands; stomach, parietal cells; small intestine, absorptive and Paneth cells; and colon, surface epithelium and superficial half of the crypts of Lieberkühn. In the salivary glands, immunoreactivity was strong in the mucous tubules, moderate in the ducts, and weak in the serous cells. Endocrine pancreas showed a more intense immunoreactivity than the pancreatic acini. By serial sections of the islets of Langerhans we showed that immunostaining was confined to B cells. These findings demonstrate the widespread distribution of PRLR in human digestive tissues and its localization both in cytoplasms and nuclei.

Cell Nucleus↗
PubMed1996

S-100 immunoreactivity in pulmonary neuroendocrine cells of newborn infants.

S-100 protein was demonstrated by immunohistochemical techniques in occasional solitary neuroendocrine cells of the lungs of newborn infants. The S-100 immunoreactivity was located in both the nucleus and the cytoplasm; its distribution in the cytoplasm was diffuse, there being no differences in staining intensity between the apical and basal poles. This homogeneus distribution of immunoreactivity argues against the S-100 being located in the dense-core granules, since these organelles are concentrated towards the basal pole. Double immunohistochemical techniques revealed that S-100 immunoreactive cells were also chromogranin A immunoreactive. Our results indicate that the S-100 positive population is a subset of the chromogranin A positive neuroendocrine cells. S-100 immunoreactivity was not detected in neuroepithelial bodies.

Female↗
PubMed1995

Neural cell adhesion molecule immunoreactivity in Merkel cells and Merkel cell tumours.

We have analysed the expression of the neural cell adhesion molecule (NCAM) in normal Merkel cells of pig and human skin, and in nine neuroendocrine carcinomas of the skin (Merkel cell carcinomas). NCAM immunoreactivity was observed in virtually all Merkel cells, both in epidermis and vibrissae of pig snout skin and in human epidermis. Immunostaining surrounded the entire surface of Merkel cells and was not restricted to the contact areas between Merkel cells and nerve terminals. All Merkel cell carcinomas studied were also positive for NCAM. The immunostaining pattern of the tumour cells was similar to that observed in normal Merkel cells; the immunoreactivity was confined to the cell membranes. These results suggest that NCAM may be used as an immunohistochemical marker for both Merkel cells and Merkel cell tumours.

Animals↗
PubMed1995

Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance.

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.

Adolescent↗
PubMed1995

Mucosal mantle cell (centrocytic) lymphomas.

The morphology, phenotype, genotype and clinical behaviour of four cases of mantle cell lymphoma (centrocytic lymphoma) presenting primarily in mucosa (two gastric, one in large bowel and one tonsillar) are reviewed. Their relationship with the broader group of mantle cell and mucosa-associated lymphoid tissue (MALT) lymphomas is also discussed. All four tumours showed a monomorphic picture of mantle cells (centrocytes) arranged in a diffuse, or vaguely nodular, pattern. Scattered non-neoplastic germinal centres were entrapped within the tumour cells, although there was no follicular colonization. In two cases distinct epithelial infiltration by tumour cells was observed. All four tumours had a CD19, CD20, CD5, IgD, Leu8 immunophenotype, whereas KiM1P and CD10 expression were absent. DRC antibody showed loose aggregates of dendritic cells in three of four cases. Three cases showed PRAD-1/Cyclin D1 overexpression by Northern blot analysis. Although we were not able to detect bcl-1 rearrangement in the major translocation cluster (MTC) breakpoint, the possibility of bcl-1 rearrangement involving other cluster breakpoints cannot be ruled out. The four cases evolved as a disseminated disease, involving either peripheral lymph nodes, spleen or bone marrow. The biological behaviour of mantle cell lymphoma presenting in mucosa appears, irrespective of localization or macroscopic presentation, similar to that of nodal mantle cell lymphoma. Their tendency to dissemination contrasts with MALT lymphomas, which tend to remain localized, and from which mucosa mantle cell lymphoma must be distinguished. The presence of lymphoepithelial lesions does not seem to be a useful differential feature, since occasional epithelial infiltration was seen in two cases. Reactivity with CD5 appears to be especially useful in distinguishing these, since all four cases were clearly positive, in contrast with what is usually found in MALT lymphomas.

Aged↗
PubMed1994

Use of recombinant interferon-alpha in human immunodeficiency virus (HIV)-infected individuals.

RATIONALE AND OBJECTIVE: Interferon alpha (IFN-alpha) has anti-retroviral activity and is a possible HIV infection-limiting factor. The aim of this work is to prevent or delay disease progression in asymptomatic Human Immunodeficiency Virus (HIV) carriers. DESIGN AND INTERVENTIONS: Recombinant IFN alpha-2b (3 x 10(6) IU 3 times weekly) was compared to no treatment (control) in a randomized trial. Endpoints were: (i) appearance of any CDC group IV symptoms and (ii) disease progression (which excluded shifts to group IVC2 or reversible IVA, or IVB). The trial lasted from October 1987 to February 1992. SETTING: The trial was performed at the "Santiago de las Vegas" sanatorium, a specialized institution for the care of HIV-infected and AIDS patients. POPULATION: Subjects were anti-HIV-1 seropositive, Western blot-confirmed, asymptomatic (CDC group II), or with generalized lymphadenopathies (CDC group III). The groups had 79 (control) and 71 (IFN) patients. MAIN RESULTS: Long-term IFN-alpha treatments significantly reduced the proportion of patients who shifted to any group IV (control: 46/79; IFN: 14/71; p < 0.001) or developed AIDS (control: 27/79; IFN: 12/71; p < 0.05). IFN also delayed progression to AIDS (95% confidence interval for 0.5 probability of progression) from 67-83 to 116-180 months after infection. The IFN group had significantly less opportunistic infections and non-infectious complications. CD4 cell count and hemoglobin decreased in the control but not in the IFN group. Fewer IFN-treated patients developed positive serum HIV antigen detection. CONCLUSION: IFN alpha treatment during the early stages of infection seems to be beneficial to the patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

Monocytoid B cells. A comparative clinical pathological study of their distribution in different types of low-grade lymphomas.

Neoplastic monocytoid B-cells (MBCs) are present in different amounts in several types of non-Hodgkin's lymphomas (NHLs), including monocytoid B-cell lymphoma (MBCL), splenic marginal zone lymphoma (SMZL), mucosa-associated lymphoid tissue (MALT) low-grade B-cell lymphomas, and follicular centroblastic-centrocytic (CB-CC) lymphomas. In an attempt to clarify the relationships between different groups of tumors with a significant monocytoid component, we studied six primary lymph node MBCL, three SMZL, seven MALT lymphomas, and four CB-CC with monocytoid differentiation. Their clinical, morphological, immunohistochemical and molecular features were compared. The results show wide overlapping between MALT and MBCL in terms of morphology, immunophenotype, and molecular features. Follicular colonization was a characteristic finding in both groups. Some MBCL revealed mucosal involvement during the course of the disease, suggesting a possible MALT origin. Our data support the suggestion that the use of the term MBCL should be discontinued in cases with mucosal involvement, as they are probably examples of lymph node involvement brought about by MALT lymphomas. Although SMZL have some overlapping features with MBCL and MALT lymphomas, some of the clinical and morphological specific findings justify their distinction from the other groups. The CB-CCs with monocytoid differentiation frequently harbored t(14;18), lacking any significant differentiating features from conventional follicular CB-CC lymphomas. Additional studies are needed to define the molecular features of MBCL and other marginal zone tumors.

Adult↗
PubMed1993

Evolution of prothymosin alpha and proliferating cell nuclear antigen (PCNA) immunoreactivity through the development of rat ovarian follicles.

The cellular distribution of prothymosin alpha (ProT) was studied in ovarian follicles of adult cycling rats. We found positive granulosa and theca cells throughout follicular maturation. When both ProT and proliferating cell nuclear antigen (PCNA) immunoreactivity was studied, we observed that both proteins were expressed in the same granulosa and theca cells, although sometimes ProT immunoreactivity was weak or absent in the mitotic (M) phase. Moreover, both peptides share the nuclear distribution, but ProT immunoreactivity was never seen in nucleoli. Therefore, we conclude that in mitotic cells ProT is expressed only in actively proliferating cells, since all ProT-positive cells were also positive for PCNA. ProT and PCNA immunoreactivities during the meiotic division were studied in oocytes. The presence of PCNA was, unlike ProT, constant throughout follicle development (except atretic oocytes). Oocytes expressed ProT from primordial follicles to the eighth generation, but more developed oocytes and atretic oocytes were not immunoreactive. In hypophysectomized rats, all oocytes were immunoreactive. Interestingly, in hypophysectomized rats treated with follicle stimulating hormone (FSH) that promoted follicle development, the more developed oocytes did not show ProT immunoreactivity. Since hypophysectomized rats were not treated with luteinizing hormone we conclude that ProT expression is not required to complete meiotic division I.

Animals↗
PubMed1993

Immunohistochemical location of prothymosin alpha in regenerating human hepatocytes and hepatocellular carcinomas.

In the present paper we analysed the presence of prothymosin alpha (ProT) in human liver. In normal liver, ProT immunostaining was found in the nuclei of bile duct cells, but not in the hepatocytes. In contrast an intense immunoreactivity was observed in regenerative hepatocytes of chronic hepatitis, cirrhosis and in hepatocellular carcinomas. In all cases the immunostaining was restricted to the nuclei, but the nucleoli were always negative. Similar results were obtained for proliferating cell nuclear antigen. These findings confirm that ProT is related to cell proliferation and provides a new immunohistochemical proliferation marker for routinely processed samples.

Carcinoma, Hepatocellular↗
PubMed1993

Tissue concentrations of prothymosin alpha: a novel proliferation index of primary breast cancer.

In 71 patients with classic invasive ductal carcinomas, levels of prothymosin alpha (PT alpha), as assayed by a radioimmunoassay that detects thymosin alpha 1 (the NH2-terminal fragment of PT alpha), were significantly greater in tumour samples than in normal breast tissue. PT alpha levels were correlated with (a) the number of positive axillary lymph nodes (rs = 0.5384, P < 0.01), and (b) the percentage of tumour cells in the S or G2/M phase as assessed by flow cytometry (rs = 0.5027, P < 0.01). Since the beginning of this study in 1989, 21 patients have presented distant metastases, all of whom were previously shown to have tumour PT alpha levels greater than 124 ng of thymosin alpha 1/mg protein. The present report indicates that PT alpha might be used to identify breast cancer patients at high risk for distant metastases.

Adult↗
PubMed1993

A comparative immunohistochemical study of phaeochromocytomas and paragangliomas.

There is no definite morphological distinction between phaeochromocytomas and paragangliomas. We, therefore, attempted to determine the universality and differential utility of a panel of tumour markers for diagnosis in formalin-fixed, paraffin-embedded specimens. Antibodies to neuron-specific enolase (NSE), chromogranin, synaptophysin, Leu-7, neurofilaments, cytokeratins, carcinoembryonic antigen (CEA), melanoma antigen HMB-45, S-100 protein and glial fibrillary acid protein (GFAP), were used on 11 phaeochromocytomas and 8 paragangliomas. NSE reactivity was detected in 10 phaeochromocytomas and in all paragangliomas. Chromogranin reactivity was found in all but two cases (one phaeochromocytoma and one paraganglioma). Synaptophysin reactivity was present in 10 phaeochromocytomas and in the 8 paragangliomas. Ten phaeochromocytomas stained for Leu-7, but none of the paragangliomas did. S-100-positive cells (sustentacular or type II cells) were found in 8 phaeochromocytomas and 7 paragangliomas. GFAP stained sustentacular cells of only one paraganglioma. Only in 5 phaeochromocytomas was there a focal reaction by neurofilaments. Cytokeratins, CEA and HMB-45 were never detected. We conclude that NSE, chromogranin, synaptophysin and S-100 protein are useful markers of both types of tumour, whereas GFAP staining is limited to a small number of these neoplasms. Leu-7 reactivity seems to favour diagnosis of phaeochromocytoma rather than paraganglioma, but further studies with larger series are needed to confirm this. Unlike previous reports, we did not find cytokeratin or HMB-45 immunostaining in any case.

Adolescent↗
PubMed1992

Prothymosin alpha expression in lymph nodes and tonsils: an optical and ultrastructural study.

Prothymosin alpha (ProT alpha) distribution in human and rat lymph nodes and human tonsils was studied by means of immunohistochemical methods, using specific antibodies raised against thymosin alpha 1. We observed ProT alpha immunoreactivity in lymphoid cells of the germinal centers both in humans and rats. In human tonsils, positive cells were also seen in the basal layer of the surface epithelium. These results support the hypothesis that ProT alpha expression is restricted to actively proliferating cells. Immunoelectron microscopy revealed that ProT alpha was located in the nucleus, mainly in the border between euchromatin and heterochromatin.

Animals↗