Biomedical subjects

M Raphael

Publications and source records attributed to M Raphael.

At least 37 records · Page 2Linked to original sources

PubMed1997

Thrombosis and restenosis after peripheral angioplasty: does acute 111indium-platelet accumulation predict angioplasty outcome?

OBJECTIVES: Use of platelet deposition to predict failure following angioplasty. DESIGN: Prospective study of angioplasty patients in a 9 months surveillance period. MATERIALS: Thirty-eight successful angioplasty patients. METHODS: Autologous 111indium-labelled platelets were re-injected immediately after angioplasty. Gamma camera and probe measures of radioactivity were obtained daily for 2-4 days and compared to a reference site to obtain a radioactivity ratio. Patient follow up was with duplex and arteriography from day 0 to 9 months or at angioplasty failure. RESULTS: Thirty-one patients remained asymptomatic; two developed acute occlusion and five developed restenosis. Platelet accumulation (increased mean radioactivity ratio) occurred at all angioplasty sites and was significantly higher after acute occlusion (camera: 2.93 and probe: 1.93) compared to asymptomatic patients (camera: 1.25 and probe: 1.15) and restenotic patients (camera: 1.31 and probe: 1.23). Radioactivity ratio was not different in patients who later developed restenosis. CONCLUSION: 111Indium platelet radioactivity effectively detected acute angioplasty reocclusions, but was unable to predict subsequent angioplasty restenosis.

Adult↗

PubMed1997

Pleomorphic medium-sized T-cell lymphoma following Hodgkin's disease (nodular sclerosis type).

We describe a 32-year-old woman who presented with Hodgkin's disease, nodular sclerosis type II, subtype I, which necessitated several treatments over 11 years. The patient then developed pleomorphic, medium-sized T-cell lymphoma, which had a fatal outcome within 13 months. The role of radiotherapy, splenectomy, and chemotherapy in second tumor induction is compared with other sequential T-cell lymphomas. The significance of rare Epstein-Barr virus-infected cells during the T-cell lymphoma extension is discussed.

Adult↗

PubMed1997

A hidden complication of out-patient arteriography.

Rapid progression of arterial disease may occur between out-patient diagnostic arteriography and therapeutic angioplasty. We have studied the incidence of this complication in our institution. Sixty-seven consecutive out-patient arteriograms were assessed. Thirty-four patients were re-admitted for angioplasty within a median interval of 4 weeks (range 5 days-3 months). We compared immediate pre-angioplasty arteriograms with the out-patient images. Twenty-five pairs of films showed disease progression. Three patients showed new disease, one remote from the site of the arterial lesion and two in the opposite limb. Six patients showed marked progression of the original disease. The policy of delayed treatment after out-patient arteriography may require reconsideration in the light of our complication rate of 18%.

Aged↗

PubMed1997

Lymphomas associated with HIV infection.

Lymphomagenesis in HIV positive patients is a complex phenomenon not yet completely understood (Karp and Broder, 1992). The great majority of NHL are of the B cell type. Burkitt lymphoma seems to develop early during the evolution of HIV infection in patients with a CD4 count above 200/microliter. MYC is rearranged in the majority of the cases. EBV latent infection is observed in 30-45%. EBV status is characterized by a negativity for EBNA2 and LMP1 The main sites of the tumour are the lymph node and the bone marrow. Diffuse large cell lymphomas, mostly represented by immunoblastic lymphomas with plasmacytoid differentiation and by centroblastic lymphomas rich in immunoblasts, are a late event in HIV infection, in patients with a low CD4 count (often below 50/microliter). The prognosis is worse than in Burkitt and Burkitt like lymphoma. MYC is rearranged in about 30-40% of the cases, whereas more than 70% are EBV positive. EBV status is characterized by a positivity for both EBNA2 and LMP1. B type ALC lymphomas are more frequently associated with EBV than in the general population and exhibit the same EBV status as diffuse large cell lymphomas. HD occurs at any stage of HIV infection. The majority of patients are in clinical stage III or IV at the time of diagnosis, and HIV associated HD shows a more aggressive course than non-HIV HD. Many cases remain difficult to classify; instead, the immunophenotype of neoplastic cells is similar to that in HD occurring in the general population. Histiocytes and epithelioid cells are even more numerous than T lymphocytes, and the CD4:CD8 ratio is low. Neoplastic cells are EBV positive in most or all cases, although they are consistently HIV negative by in situ hybridization. Lymphomagenesis seems to be very complex, with multiple agents acting together or successively. EBV, other viruses, rearrangement of various genes and production of cytokines all seem to have major roles in addition to immune deficiency.

Humans↗

PubMed1996

[Medication group for noncompliant patients in a psychiatric day unit--experiences during a one year period].

A group of noncompliant psychiatric patients was treated on a weekly basis over a 6-month period; 13 started but 3 dropped out. Results indicated greater feeling of security with medication; increased desire to maintain follow-up treatment in the outpatient clinic; greater likelihood of patients accepting their illness; and strong desire to discuss medication-related topics with staff. Our medication group appears to offer a convenient and organized method for addressing issues of psychiatric medication, especially for chronic patients, which we recommend to clinicians in other medical disciplines.

Adult↗

PubMed1996

VJ rearrangements of the TCR gamma locus in peripheral T-cell lymphomas: analysis by polymerase chain reaction and denaturing gradient gel electrophoresis.

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) gamma gene rearrangement was shown to be more informative than that of the TCR beta gene rearrangement. In order to amplify every VJ gamma rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged gamma alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.

Base Sequence↗

PubMed1996

Differential nuclear localization of p50, p52, and RelB proteins in human accessory cells of the immune response in situ.

The Rel/NF-kappa B proteins, p50, p52, p65, c-Rel, and RelB, constitute a family of transcription factors involved in the positive regulation of a variety of genes during the immune response. Recently, it has been shown that RelB knockout mice have no dendritic cells (DC). An overexpression of p50 has been described in follicular dendritic cells (FDC). A constitutive NF-kappa B activity has been reported in mature macrophages. This led to the hypothesis that some of the Rel/NF-kappa B proteins were key nuclear factors in functions of accessory cells of the immune response. Therefore, we investigated in situ the nuclear localization of Rel/NF-kappa B proteins in accessory cells of the immune system by immunohistochemistry and double labeling by immunofluorescence from five normal human tonsils and five lymph nodes with follicular hyperplasia. Nuclear p65 and c-Rel proteins were found in all cell types including lymphocytes. In germinal centers GC, p50, p52, and RelB were found in the nuclei of FDC only and were not detected in the nuclei of CD68+ cells. In T cell areas, p50, p52, and RelB were found in the nuclei of HLA-DR+ cells with an antigen-presenting cell (APC) morphology. p52 and RelB were detected in the nuclei in both CD1a+ and CD68+ cells from the T cell area, whereas p50 was found only in CD68- and CD1a- cells. Cells with nuclear p50 were negative for the CD38, CD20 and CD2 markers. These results show that, physiologically, high levels of nuclear of p50, p52 and RelB are restricted to accessory cells of the immune system, which include FDC in GC, and DC and macrophages in the T cell zone, that specialized scavenger macrophages from GC do not have detectable levels of p52 and RelB, whereas macrophages from the T cell area, known to present the antigen to T cells, do have both nuclear p52 and RelB, and that in the T cell zone, p52 and RelB are located in nuclei of both CD1a+, CD68+ or both, cells APC, whereas p50 is restricted to CD1a- and CD68- APC. The different patterns of p50, p52 and RelB protein nuclear localization may provide insight into their different roles during the immune response in vivo.

Adolescent↗

PubMed1996

Soft tissue sarcomas in HIV-infected adult patients.

Clinical and biological features of three HIV-infected adults with soft tissue sarcoma are reported. Epstein-Barr Virus (EBV) detection was negative using in situ hybridisation, PCR analysis and Southern blot analysis in the two cases for which tumour samples were available, contrary to all previously reported paediatric cases. All three patients developed metastases. Chemotherapy was feasible but only afforded tumour stabilisation. The cause of death in all three cases was distant spread and not AIDS. Soft tissue sarcoma associated with HIV infection are not exclusively found in children, do not appear to be EBV-related in adult patients, and fare dismally despite vigorous therapy.

Adult↗

PubMed1996

The significance of increased 111indium platelet accumulation at post-angioplasty sites.

We assessed prospectively the significance of 111indium labelled platelet accumulation following angioplasty procedures in 12 patients (9 femoral angioplasties (2 laser, 1 atherectomy) and 3 iliac stents). Autologous 111indium labelled platelets were re-injected immediately after angioplasty. Radioactivity was measured over treated and reference sites, by single probe and gamma camera, and expressed as a radioactivity ratio (RR). All patients had duplex ultrasound assessment and occlusions were confirmed by arteriography. RR was always raised after angioplasty. Three patients who had acute occlusions showed markedly raised average RRs (significant at 99% ANOVA). RR was not raised after laser assisted angioplasty, however, our numbers were small. 111Indium platelet radioactivity did not predict subsequent occlusion after angioplasty but effectively detected existing acute post-angioplasty occlusions.

Angiography↗

PubMed1996

Non-invasive assessment of arterial stenoses in angioplasty surveillance: a comparison with angiography.

OBJECTIVES: Comparison of non-invasive arterial measurements with angiography and their use for angioplasty surveillance. DESIGN: Prospective assessments of arterial stenoses in patients undergoing angioplasty in a 9 month surveillance period. MATERIALS: Fifty consecutive patients undergoing angioplasty. METHODS: (i) One hundred and thirty-one sets of clinical assessments, ankle brachial Doppler pressure indices and colour Duplex velocities and diameters were compared to time-matched angiographic diameter stenosis. (ii) Fifty patients undergoing femoropopliteal angioplasty (32 stenoses and 18 occlusions) were studied with ankle branchial Doppler pressure indices and colour Duplex and angiography during a 9 month surveillance period. RESULTS: (i) Symptoms, pulses, resting ABPI, and exercise ABPI showed no useful correlation with angiography. Duplex velocity ratio and Duplex diameters showed correlation and agreement with angiography respectively. (ii) On surveillance, restenosis was universal but not always clinically significant. Angioplasty caused a rapid improvement in ABPI and imaging studies which worsened at later times. ABPI did not predict clinical failure however, Duplex and angiography predicted all clinical failures. CONCLUSIONS: Restenosis should be assessed with imaging of the angioplasty site during angioplasty surveillance.

Adult↗

PubMed1996

Thymocyte and thymic microenvironment alterations during a systemic HIV infection in a severe combined immunodeficient mouse model.

OBJECTIVE: A new model for systemic and multifocal HIV-1 infection was developed in severe combined immunodeficient (SCID) mice to study the alterations of thymocytes and of the thymic microenvironment that occur during a disseminated HIV infection. DESIGN AND METHODS: We grafted SCID mice with the classical human fetal thymus/liver co-implants together with fragments of autologous lungs (SCID-huLLT). These organs achieved normal differentiation and were productively infected after an intraperitoneal inoculation of two HIV-1 primary isolates. At time of sacrifice, thymic biopsies and thymic cell suspensions were analysed by immunohistochemistry, flow cytometry and lymphocyte function assays. RESULTS: At weeks 2-4 post-inoculation we observed the following thymocyte abnormalities: a minor to severe depletion of the immature CD1+CD4+CD8+ T cells (range, 0-73% thymocytes), compared with the persistence of mature CD4+ cells (11-50%) and amplification of CD8+ T cells (6-92%). The immature subset depletion was inversely related to the thymic HIV-1 viral load, suggesting the preferential infection of this subset. The residual mature thymocytes were functional as assessed by their sustained proliferative responses to CD3-triggering which contrasted with the lack of HIV-specific cytotoxic activity. A quantitative analysis of immunostained thymic sections revealed a disorganization and a densification of the thymic epithelial cells (TEC) network which occurred in all HIV-infected SCID-hu mice independently of the thymic CD1+CD4+CD8+ T-cell depletion. CONCLUSION: These results suggest that a systemic HIV infection induces in human thymuses from SCID-huLLT mice a preferential depletion of the immature thymocytes in the absence of mature CD4+ T-cell depletion, HIV-specific cytotoxic T-lymphocyte activity or thymic epithelial cell death, but is associated with dysplasia of the thymic microenvironment, and is therefore opening new perspectives for studying immune cell reconstitution strategies in HIV infection.

Animals↗

PubMed1996

Assessment tools in psychiatry.

With the advent of managed care, administrators of mental health care will need to implement outcomes measurement systems that will provide information for cost control and quality improvement. These systems must take into account the changes occurring in the delivery of mental health care, such as the broad range of settings in which mental health care occurs, and allow for the measurement of outcomes over time. A useful system must also be flexible, allowing measures to tailor the system to individual needs. Two types of systems are currently being used. Simple systems measure general outcomes, such as patient satisfaction, at baseline and discharge. More complex systems are disorder-specific and can be used to compare different types of treatments or different groups of patients. The simple systems are less costly but are not as useful to quality improvement. The disorder-specific systems are more expensive, but the information gathered with these systems can be used in quality management. As implementation of these systems becomes more commonplace, challenges such as lack of standardization, patient reluctance to fill out forms, and the need for sensitive measurement instruments will need to be addressed.

Humans↗

PubMed1996

Multicentric Castleman's disease in HIV infection: a clinical and pathological study of 20 patients.

OBJECTIVES: To describe, in a retrospective study, the clinical and pathological spectrum of multicentric Castleman's disease (MCD) in HIV infection. PATIENTS: The diagnosis of MCD was established by lymph node biopsy in 20 HIV-infected patients. All patients had been HIV-infected by sexual contact. At diagnosis, HIV infection was asymptomatic in eight patients and Kaposi's sarcoma was present in 12. Mean +/- SD CD4+ cell count was 156 +/- 99 x 10(6)/l. RESULTS: Patients were referred with a syndrome of fever and splenomegaly (100%), peripheral lymphadenopathy (90%), hepatomegaly (70%), severe weight loss (70%), respiratory symptoms (65%) and oedema (55%). Anaemia was a constant finding and seven (35%) patients presented with pancytopenia. Serum markers of inflammation were present in most patients: a high level of C reactive protein (90%), polyclonal hypergammaglobulinaemia (89%) and hypoalbuminaemia (56%). The histological pattern of the lymph nodes was characterized by small hyalinized germinal centres surrounded by concentric layers of small lymphocytes, vascular hyperplasia, hyalinized vessels and large interfollicular sheets of plasma cells. Five patients were classified as plasma cell type MCD and 15 as hyaline vascular/plasma cell (mixed) type. Immunophenotyping studies (n = 13) demonstrated a polyclonal B-cell process. No linkage with Epstein-Barr virus (EBV) could be demonstrated immunohistochemically using an anti-latent membrane protein-1 monoclonal antibody (n = 16) or by RNA in situ hybridization with an EBV-encoded RNA transcript-specific probe (n = 13). Remission was obtained with low-dose and usually single agent chemotherapy in 16 patients. During follow-up, non-Hodgkin's lymphoma developed in two patients and Kaposi's sarcoma in three. Fatal outcome occurred in 14 patients with a median survival of 14 months. CONCLUSION: MCD associated with HIV infection is a distinct clinico-pathological entity that can be differentiated from other types of HIV-associated systemic lymphoproliferative disorders. It is very similar to MCD observed in non-HIV-infected patients, except for the high prevalence of pulmonary symptoms and for the stronger association with Kaposi's sarcoma. Single-agent chemotherapy with vinblastine is effective and may prolong survival.

Adult↗

PubMed1996

Serum interleukin-10 in acquired immunodeficiency syndrome lymphoma patients. Seroco-Hemoco Study Group.

Interleukin-10 (IL-10) has multiple effects on lymphoid development, particularly as a stimulant of activated B-cell proliferation and differentiation. It is thought that IL-10 might play a role in the development of B lymphoid malignancies based on the observation that lymphomatous tissues from HIV+ patients contain numerous cells containing IL-10 mRNA as well as IL-10 protein. The aim of this study using an Elisa test was to analyze IL-10 in the serum of 18 HIV+ patients with non Hodgkin's B lymphoma (NHL) and compared the presence of this cytokine in the serum of 18 HIV+ patients without NHL. In this comparative study we also considered the different parameters such as the mode of contamination, sex, age and number of CD4 cells. 44% of the patients with HIV-related NHL had significant levels of IL-10 (> or = 12 pg/ml) in their serum, in comparison to the patients without NHL who did not show detectable serum IL-10.

Adult↗

PubMed1995

Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease.

Multicentric Castleman's disease (MCD) is an atypical lymphoproliferative disorder defined using clinical and pathologic criteria. A characteristic of the MCD is a close association with Kaposi's sarcoma (KS), which occurs during the clinical course of most human immunodeficiency virus (HIV)-associated MCD cases and also, but less frequently, in HIV-negative patients. Recently, sequences of a putative new Herpesvirus (KSHV) have been isolated and further detected in almost all the acquired immunodeficiency syndrome (AIDS) KS and in most of the non-AIDS KS samples. In this study, we searched for these Herpesvirus-like sequences in MCD samples of 31 patients. KSHV sequences were detected in 14 of 14 cases of HIV-associated MCD, including 5 cases without detectable KS. Moreover, KSHV was detected in 7 of 17 MCD cases in HIV-negative patients, including 1 case associated with a cutaneous KS. In 34 non-MCD reactive lymph nodes (follicular and/or interfollicular hyperplasia) in HIV-negative patients, KSHV was detected in only 1 case. In 1 HIV-negative case of MCD, KSHV was found in both the lymph node and peripheral blood samples. These data suggest that KSHV could play a role in the pathogenesis of MCD, especially in HIV-infected patients.

Adult↗

PubMed1995

Molecular analysis of clonality in Castleman's disease.

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder that is morphologically and clinically heterogenous and is associated with a risk of developing malignant lymphoma. We report the clonality status of CD tissues in 34 patients, including 14 patients infected by the human immunodeficiency virus (HIV). Four patients presented a localized form and 30 presented a multicentric form. Two cases were associated with B-cell lymphoma, 3 cases with Hodgkin's disease, and 9 cases (8 HIV+) with Kaposi's sarcoma. Histologically, 8 cases were of the hyaline-vascular type and 26 were of the plasma cell or mixed types. The Ig and T-cell receptor (TCR) V(D)J rearrangements were analyzed using polymerase chain reaction and Southern blot. Clonal IgH rearrangements were detected in only 4 cases, ie, 2 associated with B-cell lymphoma, 1 with Hodgkin's disease, and 1 case without malignancy. A TCR gamma rearrangement of restricted junctional size was amplified in 1 HIV+ case. Finally, polyclonal VH-JH and V gamma-J gamma rearrangements were detected in the large majority of the cases, irrespective of pathologic subtypes, clinical forms, and HIV status. The lymphoid component in CD is therefore commonly reactive, and the rare occurrence of detectable monoclonal lymphoid contingents may be caused by secondary molecular events.

Adult↗

PubMed1995

Controlled study of human herpesvirus 6 detection in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma. The French Study Group for HIV-Associated Tumors.

Human herpesvirus 6 (HHV-6) is a recently identified lymphotropic herpesvirus, which has been isolated from patients with acquired immunodeficiency syndrome (AIDS) or lymphoproliferative diseases. Two variants A and B of HHV-6 have been described, variant B being more common in children with exanthema subitum. HHV-6 infection was studied in cases of AIDS-associated non-Hodgkin's lymphoma (NHL), and in three control populations in order to evaluate the possible etiological role of HHV-6 in this lymphoproliferative disease. Tumor specimens from various organs were obtained from 27 patients with AIDS-associated NHL and 20 human immunodeficiency virus (HIV)-seronegative patients with NHL. Lymph node specimens were obtained from four HIV-seropositive and nine HIV-seronegative patients with lymph node follicular hyperplasia. A specific polymerase chain reaction (PCR) was used to detect HHV-6 DNA. Subsequently HHV-6 variant was identified by using variant-specific PCR. Human cytomegalovirus (CMV) infection was detected in parallel by means of specific PCR. HHV-6 DNA was detected in 12 of 27 tumor tissues (44%), including 8 of 15 lymph node specimens (53%) from patients with AIDS-associated NHL. The corresponding values in HIV-seronegative patients with NHL were 35% (7/20) and 36% (5/14), respectively. Lymph node specimens were positive for HHV-6 in two of four (50%) HIV-seropositive and five of nine (55%) HIV-seronegative patients with follicular hyperplasia. Variant A was detected in two cases of AIDS-associated NHL, variant B in one case, and both variants in six cases. The distribution of HHV-6 variants exhibited a similar pattern in the three control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

PubMed1995

Inefficacy of intestinal secretory immune response to Cryptosporidium in acquired immunodeficiency syndrome.

BACKGROUND/AIMS: An alteration of the secretory immune response has been forwarded to explain frequent and chronic mucosal infections in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to explore the intestinal immunoglobulin (Ig) secretions in patients with AIDS and their relationships to cryptosporidiosis. METHODS: Patients with AIDS and enteric cryptosporidiosis (n = 12), other enteric infections (n = 10), and no identifiable enteric pathogen (n = 10) and human immunodeficiency virus-seronegative controls (n = 18) were studied. The number of intestinal IgA and IgM plasma cells of the duodenal lamina propria mucosa and total and anti-Cryptosporidium IgA, IgM, and IgG were measured in serum and feces. RESULTS: Although not significantly increased, the number of IgA and IgM plasma cells was greater in patients with AIDS (n = 20) than in controls (n = 5). In feces, total IgA outputs and specific anti-Cryptosporidium IgA levels were significantly higher in patients with AIDS and cryptosporidiosis than in the two other groups of patients with AIDS (P < 0.05 and P < 0.01, respectively) and controls (P < 0.001 and P < 0.01, respectively). Total fecal IgM output and specific anti-Cryptosporidium IgM coproantibodies were increased only in the Cryptosporidium-infected patients relative to the controls (P < 0.05). CONCLUSIONS: Despite the development of pathogen-specific mucosal antibody responses, patients with AIDS and cryptosporidiosis fail to clear the parasite.

Acquired Immunodeficiency Syndrome↗