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Biomedical subjects

V Diehl

Publications and source records attributed to V Diehl.

At least 361 records · Page 20Linked to original sources
PubMed1995

Chronic lymphocytic leukemia with an interfollicular architecture: avoiding diagnostic confusion with monocytoid B-cell lymphoma.

Certain low grade B-cell lymphoproliferative disorders can be mistaken for each other morphologically, particularly when there is partial lymph node involvement. We encountered two cases of chronic lymphocytic leukemia, in which the interfollicular growth pattern and the pale appearance of the neoplastic proliferation in the lymph nodes led to a misclassification as monocytoid B-cell lymphoma. The correct diagnosis was established, however, when the lymph node morphology was carefully reexamined, with the knowledge of the clinical history, peripheral blood findings, and bone marrow data. The immunophenotype of the neoplastic cells in the peripheral blood (CD5, CD23, weak fluorescence intensity of surface immunoglobulin and CD22) and the lymph node immunohistochemistry (weak L26 staining, strong MT1 positivity) confirmed the diagnosis of chronic lymphocytic leukemia. These two cases demonstrate the necessity of a systematic approach to lymph node morphology and the utility of a multiparameter approach in the diagnosis of lymphoproliferative disorders.

Aged↗
PubMed1994

Antidisialoganglioside ricin A-chain immunotoxins show potent antitumor effects in vitro and in a disseminated human neuroblastoma severe combined immunodeficiency mouse model.

Several monoclonal antibodies (mAbs) were screened on different neuroblastoma cell lines to evaluate ricin A-chain immunotoxins for possible use against human neuroblastoma. Four mAbs were identified that exhibited high antitumor activity against neuroblastoma cell lines as measured in an indirect cytotoxicity assay. These mAbs, including 14G2a (antidisialoganglioside), ch14.18 (a humanized switch variant), BW704 (antidisialoganglioside), and chCE7 (anti-glycoprotein of M(r) 190,000), were subsequently linked via the bivalent linker N-succinimidyloxycarbonyl-alpha-methyl-alpha-(2-piridyldithio++ +)toluene to deglycosylated ricin A chain. The most potent immunotoxin, 14G2a.dgA, inhibited the protein synthesis of neuroblastoma cell lines IMR5 and NMB by 50% at concentrations of 6 x 10(-12) M. To test the antitumor efficacy of these immunotoxins in vivo, we developed a disseminated human neuroblastoma model in severe combined immunodeficiency mice. Treatment of tumor-bearing mice with 14G2a.dgA 12 days after tumor challenge resulted in a significant prolongation of survival as compared with phosphate-buffered saline-treated controls (16.8 versus 6.5 weeks). We conclude that ricin A-chain immunotoxins might be of potential use in the treatment of human neuroblastoma.

Animals↗
PubMed1994

Oral supplements in HIV-infected patients with chronic wasting. A prospective trial.

AIM: Supplementation with polymeric formula diet was evaluated as second step of a nutritional intervention program for malnourished, but otherwise clinically stable HIV-infected patients. PATIENTS AND METHODS: 34 patients with weight loss, without opportunistic infections, diarrhea or fever, not responding to nutritional counselling as first intervention, were included. They were given 1000 kcal per day as polymeric formula. If further weight loss occurred, dose was increased to 1500 kcal per day. Nutritional status was determined by body weight and bioelectrical impedance. RESULTS: After four weeks, 7/34 patients already stopped intake. Only 10/34 patients completed three months of treatment. The average intake during three months was 496 +/- 363 kcal/d. Reasons for drop-out were intervening clinical deterioration in eight, early improvement in six, but intolerance or loss to follow-up in ten patients. On average, body weight did not change. Intake of formula diet and weight changes were not correlated. CONCLUSION: Oral supplements are a feasible, cost-effective and safe treatment of malnutrition, but they are accepted only for short time and in limited amount. To estimate efficacy of this treatment, clinical reasons for malnutrition must be considered. More effective nutritional treatments are needed for chronically malnourished HIV infected patients.

Adult↗
PubMed1994

Differentiation of cytotoxicity using target cells labelled with europium and samarium by electroporation.

We report the simultaneous use of europium-DTPA (Eu-DTPA) and samarium-DTPA (Sm-DTPA) in cytotoxicity experiments to analyze simultaneously LAK and NK cell lysis and to differentiate between specific target lysis and bystander killing. The target cells were either labelled with Eu-DTPA or Sm-DTPA chelates by electroporation, which permits the use of target cell lines or primary leukemic B cells (B-CLL) that cannot be labelled by the conventional dextran-sulphate method. The release of europium and samarium reaches a maximum at comparable time intervals (2-3 h). Due to the shorter counting interval within the samarium window the labelling efficiency is about ten times less efficient compared to europium. Using europium as label for the LAK target Daudi and samarium as label for the NK sensitive cell line K562 the differentiation of LAK versus NK activity can be performed in a single culture assay. Also, the killing of B cells and bystander cells by cytotoxic T cells was analyzed in a system where T cells were redirected to B cells through CD3 x CD19 bispecific antibodies. In fact, no bystander killing was noted when bispecific antibodies were used to bridge cytotoxic T cells to the B cells. This approach provides a simple non-radioactive method for evaluating cytotoxicity against two different cells in a single culture well.

Cell Line↗
PubMed1994

Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells.

Tumor immunotherapy should increase both the number of T cells that kill the tumor and the likelihood that those cells are activated at the tumor site. Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell. Immunodeficient mice were cured of established human tumors when mice were treated with both the CD3-CD30 and the CD28-CD30 Bi-mAbs and then given human peripheral blood lymphocytes that had been incubated with the CD3-CD30 Bi-mAb and cells that expressed CD30. The enrichment of human T cells within the tumor and the fact that established tumors can be cured may indicate in situ activation of both the T cell receptor and the costimulatory pathway.

Animals↗
PubMed1994

Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins.

To evaluate the effects of deglycosylated ricin A-chain (dgA) immunotoxins against disseminated Hodgkin's lymphoma, we used RFT5.dgA (CD25) and IRac.dgA (70 kD) to treat L540Cy Hodgkin cells in severely immunodeficient SCID mice. In this model, more than 90% of the animals developed multiple lymphomas in various organs such as the lymph nodes, liver, bone marrow, and extranodal sites that killed untreated animals after a mean survival time (MST) of 36.3 days. A single intraperitoneal injection of 8 micrograms of either immunotoxin rendered 95% (RFT5.dgA) and 93% (IRac.dgA), respectively, of mice tumor-free when applied 1 day after tumor challenge. The MST of the RFT5.dgA-treated group was extended by more than 80 days (P < .00001). SCID mice treated 12 days after tumor challenge had lower remission rates (46%), suggesting that the antitumor effect of the immunotoxins depends on the number of tumor cells present. We conclude that ricin A-chain immunotoxins have potent antitumor effects against disseminated Hodgkin's tumors in SCID mice and that this model is ideally suited for the evaluation of different immunotoxin treatment modalities.

Animals↗
PubMed1994

Controversies in terminal cancer care.

In the long term, about 75% of all cancer patients will need palliative care, but the curricula in courses of study leading to qualifications in the caring professions take no account of this, being concerned exclusively with curative strategies. Precise definition of palliative care as a medical discipline is needed, followed by an insistence on proper funding and instruction. In addition, palliation should be integrated into the early stages of patient contact, e.g., prevention, diagnosis, treatment planning, and not only implemented when attempts at curative therapy have failed. Public and political awareness must be promoted; in particular it should be recognized that the care givers themselves need support. There is a growing need for well-run hospices with purpose-trained staff. While "mercy killing" might be considered out of charity and humanity, the death of a terminally ill patient should be neither hastened nor postponed.

Humans↗
PubMed1994

Side effects of AZT prophylaxis after occupational exposure to HIV-infected blood.

UNLABELLED: It was the objective of this study to document and evaluate AZT-induced short-term toxicity in healthy individuals. The study was designed as a longitudinal monocentric side-effect monitoring study with prospective data collection. It was carried out at the Cologne University Hospital. The study population comprised health care workers who were taking AZT prophylaxis after accidental exposure to HIV-infected blood. Fourteen individuals were included into the study; seven of them discontinued treatment prematurely, five due to severe subjective symptoms. In case of one worker AZT had to be stopped due to severe neutropenia (800 cells/microliters) with signs of upper respiratory tract infection. Four of 11 individuals taking AZT for at least 4 weeks developed neutropenia (2 WHO I, 1 WHO II, 1 WHO III). All other laboratory parameters stayed within normal range. In particular, no anemia was observed. IN CONCLUSION: Compared with other studies more neutropenias are observed. Due to side effects 50% of the workers discontinued AZT administration prematurely. The data presented herein show that AZT causes considerable side effects which must be weighed against the potential protective antiviral effect.

Adult↗
PubMed1994

The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some cases of human leukemia and lymphoma.

The proto-oncogene c-met encodes a heterodimeric (alpha, beta) tyrosine kinase receptor which binds the hepatocyte growth factor (HGF). Recently, overexpression of the Met/HGF receptor gene has been detected in fresh samples of carcinomas and in epithelial tumor cell lines but not in cell lines derived from human leukemia and lymphoma. Our analysis of 50 primary samples of human leukemia and lymphoma and 23 hematopoietic cell lines revealed expression of mRNA and protein of the met/HGF receptor in 6 out of the 73 hematopoietic tumor samples analyzed. Four of the six samples positive for expression of the Met/HGF receptor gene were derived from patients with Hodgkin's disease. In addition, in one Burkitt's lymphoma cell line and in one acute myeloid leukemia (AML), expression of the Met/HGF receptor gene was detected. In normal unstimulated lymphocytes, granulocytes or monocytes we did not find expression of the Met/HGF receptor gene. Upon stimulation with the phorbol ester TPA we detected a weak expression of Met/HGF receptor specific transcripts of 9.0 kb in peripheral blood mononuclear cells of a healthy donor. Cytogenetic analyses of three of the four cell lines which express the Met/HGF receptor gene revealed structural or numerical abnormalities of the long arm of chromosome 7, where the Met/HGFR gene is located, in each of the three cell lines analyzed. In one of these cell lines (L540) the Met/HGFR gene is translocated to a marker chromosome. Southern blot and pulsed field gel electrophoresis experiments did not show any rearrangement in a region of 600 kb around the Met/HGF receptor gene excluding an activation of Met/HGFR by a TPR/Met oncogenic rearrangement as described for MNNG-HOS cells and for some gastric tumors. Our data indicate that the Met/HGFR gene is deregulated in a few cases of human leukemia, Burkitt's lymphoma and Hodgkin's disease possibly by chromosomal rearrangements resulting in an overexpression of the normal Met/HGF receptor mRNA and protein without formation of a hybrid gene.

Chromosome Aberrations↗
PubMed1994

Evaluation of nutritional counselling in HIV-associated malnutrition.

In HIV-infected patients, the outcome of counselling as the first step of a nutritional intervention programme was evaluated, in order to identify clinical and nutritional predictors for its efficacy. 75 HIV-infected patients were investigated, most with advanced disease. Nutritional status was determined by body weight, bioelectrical impedance and 7-day food intake record. Prior mean weight loss was 10% (range = +4% to -31%). Counselling facilitated weight gain in 40 75 patients (1-4 months later, overall mean difference +1.4 +/- 6.2%) and in 14 34 patients (8-11 months later, overall mean difference -1.4 +/- 9.0%). Weight changes correlated with changes in body cell mass (r(2) = .69, p < .001) and in body fat (r(2) = .29, p < 0.05), but not extracellular mass. Underlying conditions such as AIDS definition, fever, and diarrhoea correlated to prior weight loss (p < .001) but not to the outcome of counselling. Low energy intake (before counselling, < 31.5 kcal/kg) did not correlate to prior weight loss but it predicted further weight loss (p < 0.05 towards normal intake). High energy intake (> 38.5 kcal/kg) correlated (p < 0.05) with more prior weight loss but not with further weight changes. Nutritional counselling may be an effective first-line intervention for malnourished HIV infected patients. More than half of patients gain weight without other nutritional treatment. Whereas the severity of malnutrition is influenced by the underlying disease, fever, and diarrhoea, the course of weight change after nutritional intervention is not. Counselling may reduce the nutritional impact of these risk factors. In patients with low spontaneous intake, efficacy of counselling alone is limited, but it may help to identify those who require more invasive nutritional treatment.

Journal Article↗
PubMed1994

Is Hodgkin's disease an infectious disease?

Several lines of evidence question the concept of Hodgkin's disease (HD) starting as a true malignant disorder of the lymphatic system: (i) In early stages HD exerts pronounced clinical and biological features of an atypic immune response. (ii) Despite extensive investigations, the Hodgkin/Reed-Sternberg (H/RS) cells have not been unequivocally determined as the definite malignant cell population in HD. (iii) The epidemiological pattern of HD strongly resembles that of an infectious disease. (iv) About 50% of HD cases can be linked to infection with Epstein-Barr virus. Hodgkin's disease in early stages might thus be understood as the unsuccessful attempt of the organism to eliminate a cell expressing a putative (cellular or viral) target antigen. A stepwise transformation of this antigen-carrying cell, possibly triggered by an inherent genetic instability, might then lead to outgrowth of a malignant cell clone in late stages of the disease.

Antibody Formation↗
PubMed1994

Interleukin-7, interleukin-8, soluble TNF receptor, and p53 protein levels are elevated in the serum of patients with Hodgkin's disease.

In a search for specific serum markers with prognostic impact, we evaluated the clinical significance of IL-4, IL-7, and IL-8 as well as TNF receptor levels and soluble p53 in the serum of patients with untreated Hodgkin's lymphoma (HD). No elevations were observed for IL-4, while IL-7 and IL-8 were elevated in 15/52 (29%) and 21/78 (27%) patients, respectively. Soluble TNF receptors were detected in 16/29 patients (55%), and were significantly elevated in 6 (21%). P53 was detected in 21/33 (64%) patients. While IL-7 levels, detectable sTNF receptors, and p53 were not correlated with other obvious parameters, elevated IL-8 levels were associated with the presence of B symptoms (p < 0.002) and occurred more often in the nodular sclerosis form than in other histological subtypes (p < 0.02). Further investigations that correlate these serum parameters with the situation at the cellular level of an involved tissue will help to elucidate the enigmatic biology of HD.

Hodgkin Disease↗