[Sarcoidosis and chronic idiopathic thrombocytopenic purpura].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
V Diehl
Publications and source records attributed to V Diehl.
Hodgkin's disease--environmental or genetic?
Explore the source record for details and available documents.
Adult↗
Suppression of Burkitt's lymphoma tumorigenicity in nude mice by co-inoculation of EBV-immortalized lymphoblastoid cells.
EBV-immortalized B-lymphoblastoid cell lines (LCL) inoculated s.c. into T-cell-deficient nude mice regress completely after a short initial growth period. We tested whether the putative host response underlying this phenomenon might also be directed against progressively growing Burkitt's lymphoma (BL) tumors in nude mice. Outgrowth of BL tumors was suppressed when cells of the highly tumorigenic BL cell line BL 60 were mixed with cells of the autologous LCL IARC 277 before s.c. inoculation into nude mice. Even when the cells were inoculated separately and simultaneously into contralateral flanks of the mice, regression of initially growing BL tumors could be observed, albeit with reduced frequency and dependent on the dose of LCL cells. Tumor growth of BL 60 cells could also be suppressed by co-inoculation with the non-autologous LCL IARC 174 and IARC 277 cells could suppress growth of the non-autologous BL cell line Eli. Pronounced infiltration with murine (m)CD-11b-positive mouse macrophages and mCD-8a-positive mouse lymphoid cells, most probably natural killer cells, was seen in histological tissue sections of regressing BL 60 tumors when LCL cells were inoculated contralaterally. In regressing BL tumors, these mouse cells were present not only in necrotic areas but also in vital BL tissue, indicating that infiltration of mouse cells had taken place before the development of necrosis. Since tumor-infiltrating mouse cells can be activated at least by some human cytokines, we measured cytokine production of BL 60 and IARC 277. High amounts of IL 6 and IL 10 were produced by the LCL cells, whereas IL-6 and IL-10 production by the BL 60 cells was beyond or close to the detection threshold. In addition, IL 8 was secreted up to 5-fold more by the LCL than by the BL cells. The results presented here thus suggest a host response of the nude mouse, which is triggered by cytokines released from the LCL but, once induced, is directed also against BL cells.
Animals↗
The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML--a comparative morphometric study on sequential trephine biopsies.
To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph(1+)-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
Adolescent↗
Biology and therapy of Hodgkin's disease.
Explore the source record for details and available documents.
Combined Modality Therapy↗
Molecular single-cell analysis of Hodgkin and Reed-Sternberg cells.
In Hodgkin's disease, the malignant Hodgkin and Reed-Sternberg (HRS) cells are present in very small numbers in the diseased tissue, thus making molecular analysis of these cells very difficult. Using micromanipulation and single-cell polymerase chain reaction (PCR), rearranged immunoglobulin genes can be amplified and sequenced from single HRS cells. Oligonucleotides chosen from the variable (V)-gene sequences identified in the HRS cells can be used as specific markers for the tumour clone. This technique will allow one to search for members of the tumour clone in various compartments of the patient's body, to follow disease progression during therapy, and to analyse stem-cell populations for contamination by tumour cells before autologous bone-marrow transplantation.
Animals↗
Intestinal microsporidiosis with Septata intestinalis in a patient with AIDS--response to albendazole.
Microsporidiosis is a common finding in HIV-infected patients who have diarrhoea. The species most commonly causing gastrointestinal disease is Enterocytozoon bieneusi. Recently Septata intestinalis has been described as a cause of diarrhoea and disseminated infection in patients with AIDS. A 44-year-old homosexual man with severe immunodeficiency (CD4 cell count 40/microliters) had a history of watery diarrhoea for 2 weeks. Microsporidian spores measuring 1.2 to 1.5 x 2.5 to 3.0 microns were found in stool samples. Electron microscopy of duodenal biopsies confirmed the diagnosis of intestinal microsporidiosis and showed parasitophorous vacuoles with the typical ultrastructure of S. intestinalis. The patient was treated with albendazole (400 mg twice daily) and became asymptomatic within 4 days. No spores could be detected in stool samples after a treatment period of 14 days. About 25 infections with S. intestinalis have been reported to date, and the case presented here is the first in a German patient.
AIDS-Related Opportunistic Infections↗
Immunologically confirmed disseminated, asymptomatic Encephalitozoon cuniculi infection of the gastrointestinal tract in a patient with AIDS.
Microsporidia are obligate intracellular protozoan parasites that infect a broad range of vertebrates and invertebrates. They are increasingly recognized as human pathogens, especially in patients infected with human immunodeficiency virus (HIV). Organisms of the genus Encephalitozoon have been implicated as a major cause of disseminated microsporidian infections in persons with AIDS. Until recently, E. hellem was the only Encephalitozoon species confirmed by antigenic or nucleic acid methods to have infected humans. We describe the clinical course and morphological features of a case of disseminated microsporidian infection with Encephalitozoon cuniculi in an HIV-infected patient with chronic sinusitis, rhinitis, and keratoconjunctivitis. Parasites were found in conjunctival swab, nasal discharge, sputum, urine, stool, and duodenal biopsy specimens, but no pulmonary, renal, or gastrointestinal symptoms were documented. The patient was treated with albendazole (400 mg po b.i.d.), resulting in complete remission of his ocular and nasal symptoms, and microsporidian spores disappeared from all sites. To our knowledge, this case is only the second of E. cuniculi infection in humans that has been confirmed by either antibody- or nucleic acid-based methods, and it is the first in which an Encephalitozoon species has been found in the intestinal tract of a human. Microsporidiosis is an important emerging opportunistic infection in HIV-infected patients and, as documented in this report, has an expanding clinicopathologic spectrum.
Acquired Immunodeficiency Syndrome↗
Increase in interleukin-6 serum level preceding fever in granulocytopenia and correlation with death from sepsis.
Serum interleukin (IL)-6 levels measured by ELISA were correlated with the clinical course of 53 adults with hematologic malignancies in 95 episodes of chemotherapy-induced leukocytopenia (< 1000/microL). The median IL-6 level was 15 pg/mL (range, < 3-123) in 27 episodes without fever. This level was 14.5 pg/mL (range, < 3-187) 72-48 h before onset of fever, 78 pg/mL (range, < 3-170) 24 h before fever in episodes with unexplained fever (FUO), and 182 pg/mL (range, 63-1076) 24 h before fever in episodes with positive blood cultures (P < .001). Within 24 h after onset of fever, median IL-6 level was 171 pg/mL (range, 53-1134) in episodes of FUO, 444 pg/mL (range, 38-7973) in episodes with gram-negative bacteremia, and 2017 pg/mL (range, 76-7253) with gram-positive bacteremia (P < .01). IL-6 levels increased before death in all 13 patients who died of sepsis. Median level was 7253 pg/mL (range, 445-95,906) within 3 days of death. Determination of IL-6 may be useful for early assessment and as a prognostic tool in leukocytopenic fever.
Adult↗
Serum cytokine levels correlate with clinical parameters in Hodgkin's disease.
BACKGROUND: It has been suggested that cytokines are involved in the pathogenesis of Hodgkin's disease. Enhanced expression of various cytokines has been demonstrated in cell lines and biopsy specimens from patients with Hodgkin's disease (HD). PATIENTS AND METHODS: In this investigation 14 cytokines were analysed by ELISA in sera of a large panel of patients with HD and compared with clinical and serological parameters. RESULTS: Increased levels of soluble IL-2 receptors (sIL-2R), IL-6, IL-7, IL-8 and G-CSF, were found in many patients with HD as opposed to healthy individuals. In contrast, IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, TNF alpha, TNF beta and GM-CSF were rarely detectable. Serum concentrations of sIL-2R, IL-6 and IL-7 were significantly correlated with advanced stage of HD and, together with G-CSF levels, with the presence of B-symptoms. In addition, elevated cytokines correlated with several laboratory parameters. In the majority of patients the serum levels of cytokines decreased after therapy. However, elevated cytokine levels persisted in some patients in complete remission. Patients with normal IL-6 levels had better event-free survivals than patients with elevated IL-6 levels but this difference has not reached significance. CONCLUSION: Our results indicate that enhanced levels of sIL-2R, IL-6, IL-7, IL-8 and G-CSF, are correlated with disease activity and clinical symptoms in HD.
Adolescent↗
Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. German Hodgkins' Study Group (GHSG).
OBJECTIVE: It was the aim of this prospective randomized multicenter study to compare chemotherapy and radiotherapy as consolidation treatments in patients achieving complete remission (CR) after 6 cycles of doxorubicin-containing chemotherapy in advanced-stage Hodgkin's disease (HD). METHODS: A total of 288 previously untreated patients aged 18-60 years with stage IIIB or IV HD received induction chemotherapy with 3 X (COPP + ABVD). Patients achieving CR were eligible for randomisation to either 20 Gy radiotherapy to initially involved fields (RT-arm) or to an additional 1 X (Copp + ABVD) (CT-arm ). Patients with nodal PR were allocated to more intense radiotherapy (IRT-arm: 20 Gy IF, 40 Gy to persisting tumor). Four patients with persisting organ involvement after induction received salvage chemotherapy. RESULTS: Of 288 patients, 171 (59%) achieved CR after induction chemotherapy. Of these, 100 patients were successfully randomized to RT or CT. In the CT arm relapses were observed on 10 of 49 patients compared with 13 of 51 patients in the RT arm (p = n.s.). Fifty patients refused randomisation and for them a treatment was chosen, and 21 patients refused any further treatment. Of these 21 patients with no consolidation therapy, 9 relapsed, indicating an approximately 3-fold increased relapse risk compared with those receiving either of the consolidation therapies. No relapse was observed in initially involved lung or liver sites. Adverse prognostic factors for freedom from treatment failure and survival were low hemoglobin and large mediastinal mass at initial presentation. CONCLUSIONS: No statistically significant differences in treatment efficacy were detected between 20 Gy IF radiotherapy and 1X (COPP + ABVD) chemotherapy following CR after six cycles of alternating chemotherapy in patients with advanced-stage HD. However, limited observations in a non-randomized cohort indicate that patients without consolidation treatment of CR after 6 cycles of chemotherapy may have an elevated risk of relapse.
Adolescent↗
Stimulated duodenal/bile juice aspiration for diagnosis of enteric pathogens in HIV-infected patients.
Gastrointestinal and biliary abnormalities are common in the acquired immunodeficiency syndrome. Although obviously related to opportunistic infections in many cases, often no infectious agent can be identified. The specific diagnosis depends on invasive methods such as endoscopic retrograde cholangiography and liver histology. To evaluate an alternative and less invasive first-line approach, we conducted a prospective study of microscopic examination of aspirated duodenal/bile juice, to try to identify microbial causes of human immunodeficiency virus (HIV)-related gastrointestinal and biliary tract disease. Sixty-four HIV-infected patients underwent upper gastrointestinal endoscopy with biopsies from the esophagus, stomach, and duodenum, and aspiration of stimulated duodenal/bile juice. Biopsies, duodenal/bile juice, and stool samples were examined for enteric pathogens. Twenty-seven intestinal infections were found in 22 of the 64 patients (34%), 12 (44%) of which were diagnosed by duodenal/bile juice examination. Seven of the 27 infections (26%) were diagnosed exclusively in duodenal/bile juice, whereas 5 were found in biopsies or stool samples as well. Twenty infections (74%) were demonstrated in intestinal biopsies and/or stool samples, 15 without any positive result in duodenal/bile juice. The proportion of patients with elevated alkaline-phosphatase and gamma-glutamyl-transpeptidase activities was higher in patients with infectious agents detected in duodenal/bile juice (5 of 11, 45%), than in patients with infectious agents found exclusively in intestinal biopsies and/or stool samples (2 of 11, 18%). Analysis of duodenal/bile juice is a simple, rapid, and effective method for the detection of enteral pathogens in HIV-related gastrointestinal and biliary dysfunction. It increases the diagnostic yield above the results of intestinal biopsies and stool examinations alone.
Adult↗
The effect of continuous G-CSF application in human cyclic neutropenia: a model analysis.
Human cyclic neutropenia (CN) is a rare haematological disorder characterized by oscillations of blood neutrophils at subnormal levels with a stable period of approximately 21 d. During the phase of severe neutropenia (neutrophils < 250 cells/microliters), which last 4-10 d, the patients are endangered by serious infections. Several authors report that continuous G-CSF application can elevate the blood neutrophils to such a level that the risk of infections is significantly reduced. Although the characteristic cycles are not eliminated by G-CSF, the period of the oscillations is shortened to 12-14 d. Based on a previously proposed computer-simulation model of human CN, the effects of continuous G-CSF application on CN are studied. It is shown how the known different cell-kinetic effects of G-CSF on granulopoiesis explain the clinical data in CN. The reduced length of the cycles emerges as a result of the transit time reduction of the post-mitotic granulopoietic cells by G-CSF. The measured increase of the neutrophil maxima is reproduced by the additional mitoses of the immature granulopoietic bone marrow cells induced by G-CSF. The slight elevation of the neutrophil nadirs can be attributed to a weak effect of G-CSF on the assumed underlying defect in CN (an abnormally small variance of the granulopoietic bone-marrow transit time).
Cell Cycle↗
Detection of microsporidia (Enterocytozoon bieneusi) in intestinal biopsy specimens from human immunodeficiency virus-infected patients by PCR.
Intestinal microsporidiosis has been implicated as a major cause of chronic diarrhea in human immunodeficiency virus (HIV)-infected patients. So far diagnosis depends on direct visualization of the parasites by light and transmission electron microscopy. We evaluated the diagnostic value of microsporidian DNA amplification by PCR on duodenal biopsy specimens obtained from patients with and without intestinal microsporidiosis caused by Enterocytozoon bieneusi. Thirteen HIV-infected patients (all CDC stage C3) were studied. Eight patients had intestinal microsporidiosis caused by E. bieneusi (n = 6), Septata intestinalis (n = 1), and Encephalitozoon cuniculi (n = 1); microsporidioses were diagnosed by light microscopy of stool samples and confirmed by light and electron microscopy of intestinal biopsy specimens. Five patients had no microsporidia in their stool samples or in their intestinal biopsy specimens, as examined by light and electron microscopy. Additionally, DNA prepared from Toxoplasma gondii derived from mouse ascites was used as a further control. A 353-bp DNA fragment of the small-subunit rRNA gene could be amplified from all six biopsy specimens infected with E. bieneusi, and the nature of the PCR products was confirmed by Southern blot hybridization. No amplification of DNA fragments was seen by using DNA extracted from biopsy specimens with S. intestinalis or E. cuniculi infection or without microsporidian infection and with template DNA extracted from T. gondii. The results suggest that PCR testing of intestinal biopsy specimens may be a useful approach to diagnosing microsporidiosis in HIV-infected patients.
Animals↗
Tissue diagnosis of intestinal microsporidiosis using a fluorescent stain with Uvitex 2B.
AIMS: To detect intestinal microsporidiosis in paraffin wax embedded biopsy specimens using a fluorescence technique incorporating optical brighteners. METHODS: Eight HIV infected patients with confirmed intestinal microsporidiosis (six with Enterocytozoon bieneusi, one with Encephalitozoon intestinalis and one with Encephalitozoon cuniculi infection) and 10 without infection were studied. Tissue sections of paraffin wax embedded duodenal biopsy specimens were stained with 1% Uvitex 2B, coded and analysed independently by two investigators. RESULTS: In all eight cases with confirmed intestinal microsporidian infection, spores could be detected easily in tissue sections using the fluorescence technique. Spores or other elements consistent with microsporidiosis were not found in the 10 patients without infection. CONCLUSION: Staining of tissue sections from paraffin wax embedded intestinal biopsy specimens with stains incorporating Uvitex 2B is a rapid and easy technique for the diagnosis of intestinal microsporidiosis.
AIDS-Related Opportunistic Infections↗
Bone marrow involvement in Hodgkin's disease: an analysis of 135 consecutive cases. German Hodgkin's Lymphoma Study Group.
PURPOSE: To describe the incidence of primary bone marrow involvement (BMI) in Hodgkin's disease (HD) and its correlation with clinical and laboratory features present at diagnosis, and to evaluate the prognostic relevance of BMI. PATIENTS AND METHODS: Between 1983 and 1991, 2,307 patients with HD were treated according to two trial generations (HD1-3 and HD4-6) of the German Hodgkin's Lymphoma Study Group (GHSG). RESULTS: One hundred thirty-five cases of primary BMI were observed. The incidence of BMI was 4.8% in the HD4-6 study generation, which included all stages. Among stage IV patients, 32% had BMI. Among those with BMI, other organs were also involved in 33%. Among all patients, the presence of BMI was significantly associated with B symptoms, lymph nodes on both sides of the diaphragm, mixed cellularity histologic subtype, leukocytopenia, anemia, thrombocytopenia, lactate dehydrogenase (LDH) level more than 400 U/L, and erythrocyte sedimentation rate (ESR) more than 40 mm/h. BMI was negatively correlated with a large mediastinal tumor (3.7% v 20.0% in non-BMI cases). Eighty-seven of 108 (81%) assessable patients with BMI achieved a complete remission (CR). This compares favorably with the overall CR rate in all stage IIIB/IV patients. Among stage IV patients, BMI has no prognostic relevance with regard to freedom from treatment failure and overall survival. Twenty-one patients with BMI relapsed after having achieved a CR. Only five of these (24%) again had a positive bone marrow biopsy. CONCLUSION: The prognosis of patients with BMI is not worse than the prognosis of other advanced-stage HD patients. BMI alone does not define a special high-risk group in which a different treatment approach is indicated.
Adult↗
Is there a rationale for high-dose chemotherapy as first line treatment of advanced Hodgkin's disease? German Hodgkin's Lymphoma Study Group (GHSG).
Explore the source record for details and available documents.
Hodgkin Disease↗
Clinical experience with fludarabine and its immunosuppressive effects in pretreated chronic lymphocytic leukemias and low-grade lymphomas.
Fludarabine monophosphate (FAMP) is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) and low-grade non-Hodgkin lymphomas (NHLs). Here, the clinical experience and side effects with FAMP are reported in 77 patients with pretreated CLL (59 B-CLL, 2 T-CLL) and low-grade NHLs (9 immunocytic lymphomas including 5 Waldenström's macroglobulinaemia, 2 centrocytic (cc) and 5 centroblastic-centrocytic (cb-cc) NHLs). 70/77 patients are evaluable for response. All except 8 patients were pretreated with one to four different regimens and had progressive disease. FAMP was administered at a dosage of 25 mg/m2 daily for 5 days as 30 minute infusion every fifth week. Partial (PR) or complete remission (CR) was achieved in 38/56 (68%) and 3/56 (5%) of evaluable patients with CLL, respectively. In 7/8 (1 x CR, 6 x PR) evaluable patients with immunocytic lymphoma and in 3/6 (3 x PR) patients with cc or cb-cc lymphoma remissions were obtained. The probability of progression-free survival was 66% and the event-free survival was 25% and 22% at 12 and 18 months. The median progression-free survival until relapse or death, however, was only 7 months (2-20+). Major toxic effects included infections in 22 patients (grade 3 and 4 WHO), granulocytopenia (mainly grade 3) and nausea in 8 patients (mainly grade 1). 19/22 patients were in PR at the time of occurrence of infectious complications. Meanwhile, 14 patients died due to septicaemia, pneumonia or other infections. Nine patients developed severe septicaemia, 4 patients had pneumocystis carinii or aspergillus pneumonias. The high infection rate may not only be due to hypogammaglobulinaemia and granulocytopenia induced by FAMP but also to a remarkable decrease of CD4+ cells from a median of 2479 to 241 CD4+ cells/microliters after 6 cycles of FAMP. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. It is concluded that FAMP is effective even in patients with advanced CLL and low-grade NHLs refractory to multiple chemotherapy regimens. However, FAMP has a marked suppressive effect on granulocytes and T-lymphocytes, predominantly CD4+ lymphocytes.
Adult↗