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Biomedical subjects

V Diehl

Publications and source records attributed to V Diehl.

At least 307 records · Page 17Linked to original sources
PubMed1996

Molecular single cell analysis demonstrates the derivation of a peripheral blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin's lymphoma patient.

A novel cell line, L1236, was established from the peripheral blood of a patient with Hodgkin's disease (HD). Two Ig VH and one Vkappa gene rearrangements were amplified by polymerase chain reaction (PCR) from the DNA of this cell line, demonstrating its derivation from the B-cell lineage. To test the cell line for its clonal relationship to the Hodgkin/Reed-Sternberg (H-RS) cells in the patient, single H-RS cells were micromanipulated from tissue sections of a tumor-infiltrated bone marrow specimen from that patient and analyzed by PCR for Ig gene rearrangements. The same rearrangements detected in the cell line were also found repeatedly in H-RS cells of the biopsy material. Thus, L1236 is the first cell line established from a case of HD for which a derivation from the H-RS cells of the patient could be demonstrated. Furthermore, the selective isolation of identical V gene rearrangements from multiple single H-RS cells demonstrates that these cells represented a clonal population in the patient.

Adult↗
PubMed1996

[Paraproteins and lymphoma in HIV positive patients].

BACKGROUND AND AIM: Compared to healthy subjects there is a higher incidence of monoclonal immunoglobulins (= paraproteins = PP) in patients infected with the human immunodeficiency virus (HIV). High-grade B-cell non-Hodgkin's lymphomas (NHL) are the second most common neoplasms in these patients. Our aim was to determine whether paraproteins would be of diagnostic significance regarding an underlying or developing NHL. PATIENTS AND METHODS: The sera of 202 HIV-positive patients were tested for the presence of monoclonal or oligoclonal bands by using high-resolution-electrophoresis (HRE) and immunofixation (IFX). We also examined immunoglobulin concentrations, leucocyte count, lymphocyte count, CD4 lymphocyte count and CD4/CD8-ratio and collected clinical data. RESULTS: Paraproteins were detected in 26 (12.8%) of the patients. 84.6% of PP were IgG, in 80.7% associated with a kappa light chain. Patients with monoclonal or oligoclonal bands developed NHL significantly more often compared to those without PP (16.7% and 2.8%, respectively (p < 0.05%)). The CD4 count was significantly higher in patients with PP. There was no difference in levels of immunoglobulins, leucocyte count, lymphocyte count and CD4/CD8-ratio. The prevalence of PP was equally distributed in patients at different CDC-stages of HIV-infection. Common acute systemic infections like pneumocystis carinii pneumonia (PCP), toxoplasmosis, mycobacteriosis or cytomegalovirus (CMV) infection were not associated with paraproteins. CONCLUSION: We conclude that paraproteins could indicate the presence of a non-Hodgkin's-lymphoma.

AIDS-Related Opportunistic Infections↗
PubMed1996

CMV-antigenemia in peripheral blood for the diagnosis of CMV disease in HIV-infected patients.

In a prospective study of HIV patients with suspected cytomegalovirus (CMV) disease (n = 144; 140 men, four women; aged 23-69 years, median 38 years; CD4 cells 0-400, median 20/microliters), 242 blood samples were examined for the presence of CMV-pp65 antigen in peripheral blood polymorphonuclear leucocytes by use of monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase staining. All patients were thoroughly examined for existing CMV disease at first visit and during follow-up (at least 2 months or until death: 0-24 months, median 14 months). In 43/486 samples of patients with CMV disease, the antigen-test was positive and in 179/194 samples of patients without CMV disease the test was negative, resulting in a sensitivity of 90% and a specificity of 93% for the presence of CMV disease in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Clinical aspects and primary therapy of Hodgkin's lymphomas].

In spite of intensive research, the etiology and the pathogenesis of Hodgkin's lymphoma are still unclear. Hodgkin's lymphoma is clinically characterized by the appearance of enlarged lymph nodes and systemic symptoms. The diagnosis is exclusively based on the identification of the typical Reed-Sternberg cells surrounded by a mixture of reactive cells. Careful staging aims at determining disease extent and other risk factors which have therapeutic relevance. The appropriate use of modern radio- and chemotherapy results in the cure of approximately 75% of all patients with Hodgkin's lymphoma. The prognosis of patients in limited or intermediate stages is particularly favourable. New treatment strategies aim at reducing therapy related long-term toxicity while preserving the high chance of cure. In contrast, the prognosis of patients in advanced stages is still unsatisfactory. The main goal of the clinical research is to improve treatment results for these patients.

Adolescent↗
PubMed1996

Promotion of IL8, IL10, TNF alpha and TNF beta production by EBV infection.

Burkitt's lymphoma (BL) represents a high malignant B cell tumour. It has been proposed that cytokines are responsible for some of the characteristics of BL. We have analysed a panel of different BL and lymphoblastoid cell lines (LCLs) for the expression of cytokines, including: IL 1 alpha, IL 1 beta, IL2, IL3, IL4, IL6, IL8, IL10, TNF alpha and TNF beta and for the soluble cytokine receptor for IL2 (slL2R). Our results show that expression of IL8, IL10, TNF alpha or TNF beta was detected frequently in several of the Burkitt or lymphoblastoid cell lines. There was a correlation between Epstein-Barr virus (EBV) infection and cytokine protein production. Our results suggest that EBV promote the expression of IL8, IL10, TNF alpha and TNF beta.

Burkitt Lymphoma↗
PubMed1996

Resting energy expenditure, weight loss, and altered body composition in HIV infection.

Failure to downregulate resting energy expenditure (REE) as an adaption to anorexia or malabsorption is often stated as the major cause of weight loss in individuals with AIDS. In a prospective study, REE was compared with weight changes in HIV-infected patients. The impact of altered body composition on REE was reassessed by critical review of the literature. Patients were 65 male HIV-infected patients, 28 with recent weight loss (WL), and 37 who were weight stable (WS); 50/65 patients had AIDS, and 29/65 had acute infections; 29 male healthy persons served as controls. Indirect calorimetry, prospective intake protocol, and bioelectrical impedance analysis were performed. Absolute REE was lower in WL patients than in controls (1459 +/- 309 versus 1711 +/- 151 kcal/d, p < 0.001) and in WS patients (1625 +/- 402 kcal/d, p < 0.05). REE/kg body cell mass (BCM) was higher in WL and WS than in controls (both p < 0.01) due to lower BCM in both patient groups (p < 0.001). REE (%Harris-Benedict) was not different among the three groups. Weight changes around the measurement were not correlated to REE (r2 = 0.0008, p = 0.82). REE was independent of diarrhea, acute infection, fever, or caloric intake. REE had a stronger correlation to body weight and to Harris-Benedict's prediction than to fat-free mass or BCM. REE explains < 1% of weight changes. Many patients can downregulate REE as an adaption to anorexia and/or malabsorption. Higher REE/kg BCM does not signify hypermetabolism at the cellular level but can be explained by the maintenance of energy-consuming visceral tissue within the BCM during BCM loss.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Hodgkin's disease. Treatment of intermediate stages.

Intermediate stage Hodgkin's disease (HD) is defined as nodal disease with certain clinical risk factors. Patients with intermediate stage HD qualify for a combination of chemo- and radiotherapy, since radiotherapy alone results in a high relapse rate. The precise definition of this group varies between trial groups. It is generally believed that such patients should receive 4-6 cycles of modern multidrug chemotherapy and in addition radiotherapy of the involved field or the extended field. With modern combination therapy, about 70-80% of the patients in this group can be cured. However, the combination of the number of chemotherapy cycles, the field sizes and the dosage of radiation within these fields are not clear. Current clinical studies try to reduce radiation dose and field without compromising treatment efficacy in order to reduce late toxicities.

Combined Modality Therapy↗
PubMed1996

Hodgkin's disease. Future treatment strategies: fact or fiction?

Many new approaches involving biological agents have given promising results in experimental HD models. Clinical trials with immunotoxins, IL-2, Bi-Moabs or radioimmunoconjugates have demonstrated some clinical efficacy in patients with advanced refractory HD. Although it looks very unlikely to cure patients with larger tumour masses by either of these approaches, it might be feasible to treat bulky disease by conventional therapy first and then administer biological drugs to kill residual H-RS cells. Future phase-III trials will have to prove a possible superior effect of this combined immuno-/chemotherapy. In the meantime, the search for the most promising approach continues.

Antibodies, Anti-Idiotypic↗
PubMed1996

Model analysis of the contrasting effects of GM-CSF and G-CSF treatment on peripheral blood neutrophils observed in three patients with childhood-onset cyclic neutropenia.

Human cyclic neutropenia (CN) is a rare haematological disorder characterized by regular fluctuation in the serial count of blood neutrophils. The oscillations occur at subnormal levels with a stable 3-week period. To reduce the risk of serious infections during the severe neutropenic nadir phases (< 0.25 x 10(9) neutrophils/l) patients are usually treated with recombinant growth factors. Compared with G-CSF, which has been shown to enhance the amplitudes substantially, the response to GM-CSF is poor: neutrophil numbers are not amplified, the cycles remain unchanged or are dampened. However, two cases with a modest neutrophil increase have been reported in the literature. In a recently published clinical study the different effects of GM-CSF and G-CSF application have been investigated in the same patients. Based on a mathematical model of CN we previously proposed, the detailed neutrophil data measured in this study are analysed by simulation. The contrasting clinical results can be quantitatively explained by the model concept of regulatory control together with possible individual feedback defects, i.e. abnormally reduced mitotic responsiveness of granulopoietic progenitor cells to GM-CSF and G-CSF.

Cell Division↗
PubMed1996

Current clinical trials in Hodgkin's disease.

With the advent of modern polychemotherapy and radiation techniques, cure rates in Hodgkin's disease (HD) have improved substantially. This article summarises current concepts of treatment for early, intermediate and advanced stage HD. Current strategies focus on the balance between cure rate and toxicity. In early stages, cure rates approach 90% and new strategies mainly try to avoid toxicities. Possible approaches comprise the use of less CT or RT or leaving laparotomy. In advanced stages, polychemotherapy with 8 courses of either M(C)OPP or ABVD or M(C)OPP/ABVD is considered to be the treatment of choice, but unsatisfactory low complete remission rates, progression-free survival or freedom from treatment failure rates have to be improved. The role of additional radiotherapy after extensive chemotherapy in the treatment of advanced stages is uncertain. To achieve a better tumour control, new regimens have been developed. The Stanford group initiated the 12-week intensified hybrid protocol Stanford V. The German Hodgkin's Lymphoma Study Group (GHSG) introduced the BEACOPP protocol with time intensification and dose escalation of cyclophosphamide and etoposide. The Milan Cancer Institute tries to improve treatment outcome using high doses of single agents. One problem to be addressed in ongoing and future trials is the identification of high-risk groups allowing an early stratification of patients into more aggressive but effective regimens. Risk-adapted therapy might allow further reduction of doses in patients with early-stage Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Development of immunotoxins for potential clinical use in Hodgkin's disease.

During the last decade, immunotoxins (ITs) consisting of a cell-binding moiety and a potent toxin were developed as a new class of biological anti-tumor agents. Hodgkin's disease has shown to be one of the best targets for immunotoxins, as lymphocyte activation markers such as CD25 and CD30 are expressed on Hodgkin and Reed-Sternberg (H-RS)-cells in large numbers. Several immunotoxins against these antigens, which are expressed physiologically only on a small subset of activated hematopoietic cells have demonstrated potent anti-tumor effects both, in vitro and in animal models. Here we summarize the experimental and recent clinical data of using ITs in Hodgkin's disease.

Clinical Trials as Topic↗
PubMed1996

Report on the workshop biology of the Third International Symposium on Hodgkin's Lymphoma in Cologne 1995.

Micromanipulation of single Hodgkin-Reed/Sternberg cells and subsequent nucleic acid amplification (H-RS single cell PCR) has now been established as a new and powerful method for specific genetic analysis of the tumor cells in Hodgkin's disease (HD). Although there are still some discrepancies in the results presented by different groups, most probably due to methodological problems, H-RS cells, at least in a substantial proportion of cases, seem to be B-lymphoid cells of monoclonal origin. In addition, new data were presented on the cytokine/cytokine receptor interaction in HD, on transcription factors in HD-derived cell lines and on a promising approach for identification of tumor associated antigens in HD.

Hodgkin Disease↗
PubMed1996

Lymphocyte predominant Hodgkin's disease--a workshop report. European Task Force on Lymphoma.

Since lymphocyte predominant Hodgkin's disease (LPHD) may comprise more than one entity, diagnostic criteria, clinical features, and treatment strategies are still being controversially discussed. Thus, in December 1994 a multinational project on lymphocyte predominant Hodgkin's disease was initiated by the European Task Force on Lymphoma. This project is aimed at clarifying the clinical and histopathological spectrum of LPHD, as well as its relation to T-cell- rich B-cell lymphoma and classical types of HD. 525 paraffin blocks and clinical data of 478 patients from 16 international centres were submitted. At the Third International Symposium on Hodgkin's Lymphoma in Cologne, 232 of these cases were discussed by an expert panel. The preliminary results are presented here. Most cases of LPHD were reclassified into nodular paragranuloma (NP) and lymphocyte rich classical HD. In both groups, a considerable number of cases with atypical features was observed. Few cases of NHL were found among the cohort. LPHD was generally treated according to common standards for HD. The whole group of LPHD did not have a better prognosis than NS; whereas early stage NP did perform better than early stage NS (data from the German Hodgkin's Lymphoma Study Group). There is however a striking discrepancy between good survival and the frequent relapses observed in NP which needs to be elucidated.

Hodgkin Disease↗
PubMed1996

Rationale for dose escalation of first line conventional chemotherapy in advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group.

Which strategy is more promising to improve the outcome of primary conventional chemotherapy in advanced Hodgkin's disease (HD): a moderate dose escalation or treatment intensification by shortening cycles? The answer generally depends on two factors: the tumour growth velocity and the chemosensitivity of the tumour. A simple mathematical model of tumour growth and chemotherapy effects was developed to quantify this dependency. The model allows to estimate the distribution of latency times (i.e., the time a tumour requires to grow from one cell to clinical detection) and the distribution of chemosensitivity in a patient population on the base of clinical data on tumour control and treatment given. The model was fitted to the data of 705 stage IIIB/IV HD patients of the German Hodgkin's Lymphoma Study Group (GHSG). The model reveals considerable heterogeneity in chemosensitivity and a significantly positive slope of the dose-response relationship at the standard treatment dose level. The model can be used to simulate the effect of various treatment escalation and intensification strategies. On the basis of such simulations we predict only small benefits (about 3% in 5-year tumour control rates) with shortening cycle intervals from 4 to 3 weeks. In contrast, we predict that a moderate dose escalation by 30% of a standard chemotherapy will lead to a potential benefit in the order of 10% in tumour control at 5 years. The presently ongoing HD9 trial of the GHSG is designed to demonstrate this effect.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Genetic evidence for latent Septata intestinalis infection in human immunodeficiency virus-infected patients with intestinal microsporidiosis.

Sequence data of the small subunit rRNA (SSU-rRNA) gene were used to identify Septata intestinalis in biopsies of human immunodeficiency virus-infected patients by polymerase chain reaction (PCR), southern blot hybridization, cloning, and comparative genetic sequencing. DNA products of correct size could be amplified from all examined tissues with S. intestinalis infection but also from 2 biopsies with Enterocytozoon bieneusi and from 1 biopsy with Encephalitozoon cuniculi infection. Southern blot hybridization with an S. intestinalis-specific probe and partial sequencing of the DNA fragments showed high homology with published S. intestinalis sequences and confirmed that the amplified PCR products really derived from the SSU-rRNA gene of S. intestinalis. PCR testing can detect very light infections with S. intestinalis. Thus, S. intestinalis seems to occur more frequently in the form of latent infections and the true prevalence of the parasites may be much higher than previously reported.

Animals↗