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Biomedical subjects

V Diehl

Publications and source records attributed to V Diehl.

At least 235 records · Page 13Linked to original sources

[Disseminated infection with Mycobacterium avium complex (MAC) in HIV infection].

EPIDEMIOLOGY: Disseminated MAC-infection is one of the most frequent opportunistic infections occurring in HIV-infected patients. Severely immunocompromised patients with CD4-counts < 50/microliter are at greatest risk for the disease. Survival of untreated infection is very poor (5 to 6 months). With therapy survival is prolonged by about 4 months. CLINICAL PRESENTATION AND DIAGNOSTIC PROCEDURES: The leading symptom of MAC-infection is fever eventually accompanied by weight lost, night sweats, enlarged lymph nodes, hepatosplenomegaly, abdominal pain and anemia. Blood cultures are very sensitive and the most appropriate examination. Other diagnostic procedures include bone marrow cultures, biopsies of the gastrointestinal tract, lymph nodes and the liver. Detection of MAC in sputum and stool samples only proves colonisation but not dissemination. However, colonisation of the gastrointestinal tract frequently precedes disseminated disease. THERAPY: Combination of clarithromycin, rifabutin and ethambutol has proven to be the most efficacious therapy and therefore has to be considered as standard therapy for disseminted MAC-infection. Problems most frequently encountered with this medication include uveitis (rifabutin) gastrointestinal disturbances (clarithromycin) and leucopenia (rifabutin) as well as drug interactions with protease-inhibitors (rifabutin). PROPHYLAXIS: Clarithromycin, rifabutin and azithromycin given as primary prophylaxis can diminish the risk of disseminated MAC-infection. Although a survival benefit has been seen with clarithromycin, primary prophylaxis of MAC-infection is not standard care in many centers. Reasons to withhold MAC-prophylaxis include lower incidence rates in some countries as well as possible side effects and drug interactions. CONCLUSION: Disseminated MAC-infection is a frequent opportunistic disease in HIV-infected persons who are severely immunocompromised. Antibiotic combination therapy with clarithromycin, rifabutin and ethambutol improves clinical symptoms and survival. Primary prophylaxis with different regimens is efficacious but the specific epidemiologic situation in each country has to be considered.

AIDS-Related Opportunistic Infections↗

Asymptomatic pneumatosis intestinalis and free abdominal air in a patient with AIDS.

Detection of free abdominal air requires in most cases immediate surgical intervention. However, there may be situations, where invasive procedures are not indicated. We present a case of asymptomatic pneumatosis intestinalis and free abdominal air in a patient with Aids. Pneumatosis intestinalis is a rare entity with accumulation of subserosal or submucosal gas occurring in the small or large bowel. It has been reported in a variety of gastrointestinal disorders, in Aids, after transplantation, with steroid use, and in association with leukemia, lymphoma, vasculitis, collagen vascular disease and chronic obstructive pulmonary disease.

Abdomen↗

[Strongyloides stercoralis infection in a patient with AIDS and non-Hodgkin lymphoma].

HISTORY AND CLINICAL FINDINGS: The patient, now 50 years old, an immigrant miner from the former Yugoslavia who was known to have AIDS, was in 1992 found to have non-Hodgkin lymphoma of the oesophagus and given five cycles of multiple chemotherapy (CHOP) with complete remission. Subsequently he complained of retrosternal pain, dysphagia, dry cough and upper abdominal discomfort. On admission he had slight fever of 39.1 degrees C, but physical examination was unremarkable. LABORATORY TESTS: Blood count revealed an eosinophilia of 41%. IgE concentration was raised to 432IU/ml. The CD4+ T-cell count was reduced to 10/microliter, that of CD8+ to 89/microliter. ADDITIONAL TESTS: Blood culture, fecal and sputum samples and bronchoalveolar lavage demonstrated Mycobacterium avium intracellulare. TREATMENT AND COURSE: Treatment of the disseminated atypical mycobacterial infection was started with clarithromycin, rifabutin, ciprofloxacin and ethambutol. There was no improvement of the upper abdominal discomfort, but the fever subsided. Oesophagogastroscopy excluded recurrence of the lymphoma. Biopsy and examination of the duodenal juice revealed worms and larvae of Strongyloides stercoralis. Stool samples contained no mycobacteria, but strongyloides larvae were demonstrated. Albendazole was given (2 x 400 mg daily for 6 days, followed by a maintenance dose of 1 x 400 mg daily). Repeat endoscopy and stool sample after a month no longer showed any parasites. CONCLUSION: Even in Western Europe, persons coming from endemic areas who, as this patient, have various risk factors that may facilitate the occurrence of strongyloidiasis. With early diagnosis and treatment albendazole is an efficacious drug.

AIDS-Related Opportunistic Infections↗

An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30.

Hodgkin's lymphoma patients fail to establish an efficient cellular response against CD30+ Hodgkin/Reed-Sternberg cells. An impaired T-cell receptor/CD3-zeta-mediated activation of T cells is thought to be involved in this situation. We here present a chimeric anti-CD30 receptor that mediates MHC and T-cell receptor/CD3-zeta-independent T-cell activation against CD30+ lymphoma cells even in the presence of soluble CD30. The receptor consists of the binding domain of the monoclonal antibody HRS3 and the signaling unit of the Fc epsilonRI-receptor gamma-chain. After expression in MD45 T cells, receptor cross-linking with immobilized anti-idiotypic monoclonal antibody and CD30+ cells, respectively, results in increased interleukin 2 secretion and specific cytolysis of CD30+ Hodgkin's lymphoma cells. Soluble CD30 in concentrations up to 6000 units/ml did not interfere with cellular activation induced by membrane-bound antigen. This demonstrates the feasibility of the chimeric anti-CD30-scFv-gamma receptor in CD30+ lymphoma cell targeting, even in the presence of as high concentrations of soluble CD30 as are found in patients during progression of the disease.

CD3 Complex↗

Raynaud's phenomenon and acral necrosis after chemotherapy for AIDS-related Kaposi's sarcoma.

Raynaud's phenomenon is a common vascular side effect of chemotherapy drug regimens. Chemotherapy-induced Raynaud's phenomenon leading to acral gangrene has rarely been reported. In this report, one patient who developed gangrene after bleomycin and vincristine/vinblastine chemotherapy for AIDS-related Kaposi's sarcoma and another HIV-infected patient who exhibited symptoms of severe Raynaud's phenomenon related to the same regimen are presented. Because the combination of bleomycin and vinca alkaloids is commonly used for the treatment of AIDS-related Kaposi's sarcoma, clinicians should be aware of the risk of provoking acral necrosis in patients who develop Raynaud's phenomenon under chemotherapy. The literature is reviewed, and clinical symptoms, pathophysiology, and treatment options are discussed.

AIDS-Related Opportunistic Infections↗

Intracerebellar tuberculoma in a patient with AIDS. A case report.

The incidence of tuberculosis in HIV-infected patients has increased continuously over the past ten years. Extrapulmonary manifestations have become more frequent in AIDS patients than in immunocompetent hosts. Here we report about a patient with an unusual presentation of extrapulmonary tuberculosis. Our case report indicates that differential diagnosis of brain lesions in HIV-infected patients should include tuberculosis. In uncertain cases, it is indispensable to obtain specimens by craniotomy or stereotactic biopsy.

AIDS-Related Opportunistic Infections↗

Cytosine arabinoside, etoposide and aclarubicin (AVA) for the treatment of acute myeloid leukemia (AML) in elderly patients.

BACKGROUND: Elderly patients (age > or = 60 years) with acute myeloid leukemia (AML) have unfavourable prognoses when polychemotherapy regimens are used, because therapy response is characterized by low remission rates, short remission duration and high toxicity. PATIENTS AND METHODS: A phase II trial in elderly AML patients was conducted to determine the efficacy of two induction courses of a moderately-dosed combination of aclarubicin (25 mg/m2, 30 min i.v., days 1-4), etoposide (100 mg/m2, 30 min i.v., days 1-3) and conventional-dose cytosine arabinoside (ara-C, 100 mg/m2, c.i.v., days 1-3 and 30 min i.v., q 12 hours, days 4-7) (AVA-7), followed by one consolidation treatment using a reduced-dose schedule over five days (AVA-5) after three months in CR. RESULTS: Thirty-two AML patients with a median age of 66.2 years (range 60-76) were included in the study: three of them had histories of preexisting myelodysplasia and one of polycythemia vera. Following 1-2 courses of AVA-7 17 patients (53%) achieved CR, two PR (6%), and nine had resistant disease (28%); the overall response rate was thus 59%. Toxicity was significant but acceptable, with an overall treatment-related death rate of five of 32 patients (16%) after 63 courses of AVA. The median disease-free survival (DFS) was 12 months, and the median survival of all patients was 16.6 months. CONCLUSIONS: These results indicate that the combination of aclarubicin, etoposide and conventional-dose ara-C is effective in elderly AML patients. The relatively brief remission duration requires new consolidation and maintenance therapy approaches.

Aclarubicin↗

Detection of identical Hodgkin-Reed Sternberg cell specific immunoglobulin gene rearrangements in a patient with Hodgkin's disease of mixed cellularity subtype at primary diagnosis and in relapse two and a half years later.

BACKGROUND: The malignant nature of Hodgkin-Reed Sternberg (H-RS) cells has been questioned due to their scarcity in lymphoma tissues. Recently, using micromanipulation of H-RS cells and single cell PCR evidence was obtained that H-RS cells represent a clonal B-cell population. In these studies H-RS cells were isolated from each one lymph node for a given case. In classical Hodgkin's disease (HD) it thus could not be ruled out that H-RS cell clonality reflected a locally restricted clonal proliferation. We analysed biopsy specimens from a patient suffering from HD for the presence of clonally related H-RS cells at primary diagnosis and during relapse of the disease. MATERIALS AND METHODS: In 1994 the H-RS cell line L1236 was generated from the peripheral blood of a patient suffering from a disseminating relapse of HD of mixed cellularity subtype. The patient had relapsed despite intensive treatment including high dose chemotherapy and autologous bone marrow transplantation. The clonal identity of this cell line with H-RS cells in situ was proven by amplifying identical Ig gene rearrangements of the cell line as well as of single H-RS cells picked from the patients bone marrow. Primers covering the CDR3 region were chosen from the H-RS cell specific VH1 gene rearrangement to detect H-RS cells of the identical clone by amplifying the rearranged VH1 genes in tissue samples obtained during disseminating relapsing disease and at primary diagnosis of HD in 1991. RESULTS: The H-RS cell specific DNA sequence was detected in all affected tissues analysed including the cervical lymph node which has been exstirpated at primary diagnosis. CONCLUSION: This finding indicates the existence of a clonal H-RS cell population during the first manifestation of HD and persistence and dissemination of this clone despite aggressive treatment. Thus, in the described case the malignant nature of H-RS cells defined by dissemination and recurrence of the identical H-RS cell clone in relapsing disease is proven.

Adult↗

Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dex-BEAM).

BACKGROUND: Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT. PATIENTS AND METHODS: Twenty-six patients (median age 30, range 20-40 years) were treated with 2-4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide). RESULTS: Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continuous CR (median follow-up 40 months, range 14-60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2-4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death. CONCLUSION: These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response.

Adult↗

Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination.

Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen.

Adolescent↗

New drugs in the treatment of Hodgkin's disease.

In the treatment of Hodgkin's disease (HD) remission rates of 80% have been achieved with combination regimens such as COPP/ABVD; 30%-50% of these patients relapse, however, and less than 25% of those in first relapse can be cured. Although 90% of adults with advanced Hodgkin's disease (HD) achieve a complete remission with new polychemotherapy regimens such as BEACOPP, it is too early to assess how many patients ultimately can be cured. In addition, these regimens are associated with severe side effects including infertility, cardiomyopathy or second malignancies. Thus, alternative strategies for improving the outcome of patients with HD have been developed. These approaches include new cytostatic drugs and biological agents. Here, we review the most recent developments including the new vinca alkaloid vinorelbine, the anthracycline idarubicin, the nitrogen mustard bendamustine, the recently developed nucleoside analogue gemcitabine, and immunotoxins against Hodgkin/Reed-Sternberg cells. We conclude that current polychemotherapy regimens could possibly be improved by introducing new agents with a different mechanism of action such as gemcitabine. In addition, some of these new drugs including gemcitabine or vinorelbine could contribute to the reduction of toxic side effects, thus resulting in an improved quality of life for patients with HD.

Adult↗

Quality of life assessment in Hodgkin's disease: a new comprehensive approach. First experiences from the EORTC/GELA and GHSG trials. EORTC Lymphoma Cooperative Group. Groupe D'Etude des Lymphomes de L'Adulte and German Hodgkin Study Group.

Previous reports from available trials have dealt with negative long-term sequelae in Hodgkin's disease (HD) survivors. There is, however, a lack of longitudinal data showing the correlation between outcome and various treatment-related variables and the process of re-adaptation into normal life after the end of treatment. In order to investigate the quality of life (QoL) of patients with HD in different dimensions during active treatment and follow-up and to identify longitudinal patterns of QoL dimensions during re-adaptation to normal life within the EORTC Lymphoma Cooperative Group and Groupe D'Etude des Lymphomes de L'Adulte (EORTC/GELA) and the German Hodgkin Study Group (GHSG), QoL assessment strategies were put into use over the last three to five years. Furthermore, the efforts aimed at obtaining cross-cultural comparisons between the participating countries and study groups (EORTC/GELA and GHSG). Within the randomised EORTC/GELA Trial 'H8' for clinical stage I-II HD which started in September 1993, patients receive a QoL questionnaire for completion at each follow-up visit during the first 10 years after the end of active therapy. The corresponding 'HD8' study of the GHSG employs the assessment of QoL during and after active treatment periods. Within both studies, the EORTC QLQ C30 is used for QoL assessment incorporated in the QLQ-S (quality of life questionnaire for survivors), which additionally addresses the aspects of fatigue/malaise, sexuality, specific side effects, and retrospective evaluation of treatment. In total the QLQ-S includes 45 questions on 14 functional, symptom, and fatigue scales, 15 additional single items, and 3 open questions. In addition to the longitudinal QoL assessment, the GHSG carried out cross-sectional QoL trials with all cured surviving patients from the past HD1-6 studies and a matched normal control sample employing the QLQ-S and the life situation questionnaire (LSQ), an instrument covering objective data from 45 domains of life. To date, within the trials H8 and HD8 over 3000 QoL questionnaires from more than 800 patients from ten countries are available for analysis. Replication of the psychometric properties of the scales revealed satisfactory results using factor analyses and reliability testing across languages for the QLQ-S. A feasibility analysis showed generally a good acceptance of the questionnaire by the patients and physicians. QoL assessment within international multicentre trials in HD proved feasible within the two differently organised study groups of EORTC/GELA and GHSG. The use of subjective QoL data (QLQ-S) together with objective data (LSQ) in a combined cross-sectional and longitudinal trial system will give the most comprehensive insight into the problems of the re-integration process into normal life after cure. This information will provide the basis for the development of remedies/help measures and possible modifications of treatment strategies. The current approach will be further developed in close collaboration between both trial groups, and next steps will include translation of the LSQ into other languages and adaptation to various cultural circumstances.

Adult↗