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H Diem

Publications and source records attributed to H Diem.

15 recordsLinked to original sources
PubMed2003

[Persistent polyclonal B-cell lymphocytosis].

HISTORY AND CLINICAL FINDINGS: A 54-year-old woman was referred for ambulant checkup after an episode of acute renal failure due to severe gastroenteritis and recurrent arthralgias. Physical examination was unremarkable except for the presence of palpable small cervical lymph nodes. INVESTIGATIONS: Serum IgM levels showed a polyclonal increase. All the other routinely examined parameters were within normal limits. Microscopical blood smear examination revealed binucleated lymphocytes. Immunophenotyping of peripheral blood showed a polyclonal B-cell lymphocytosis despite normal numbers of leukocytes and lymphocytes. PCR analysis identified cells with a t(14;18) translocation (bcl-2/IgH rearrangement). DIAGNOSIS: A routine medical checkup disclosed the diagnosis of persistent polyclonal B-cell lymphocytosis. This rare benign lymphoproliferative disorder is characterized by binucleated lymphocytes, polyclonal expansion of B-cells, and a polyclonal increase in serum IgM. The diagnosis was established despite the lack of leukocytosis or lymphocytosis in the peripheral blood. CONCLUSIONS: Because of its benign and indolent course without the need for chemotherapy, it is important to discriminate the disorder of persistent polyclonal B-cell lymphocytosis from other malignant lymphoproliferative diseases.

Acute Kidney Injury↗
PubMed2002

Cryopreservation of reduced cytochrome C for determination of N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion production in human whole blood.

Various methods are available for measuring the production of reactive oxygen species by phagocytes, but they are limited in their use by the need for their immediate application, cell isolation and of cell-activation by unphysiological stimuli. In addition, after measurement of reactive oxygen metabolites using oxidizing agents, the reduced compounds formed have to be determined during or immediately after their formation. In the present study, an improved cytochrome C assay was investigated which allowed measurements of superoxide anions in whole blood samples following activation of phagocytes by physiological stimuli such as the bacterial tripeptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). The fMLP-stimulated production of superoxide anion (O(2)(-)) showed a sigmoidal-shaped fMLP dose-response curve, and constant O(2)(-) production rates (nmol.1(-1)x10(6) granulocytes) could be determined reliably up to a blood granulocyte concentration of 1 x 10(4) x microl(-1). To allow the determination of reduced cytochrome C later after its formation, the effect of long-term storage at -20 degrees C on the stability of reduced cytochrome C was tested up to 16 weeks. The results obtained show that the determination of reduced cytochrome C in whole blood represents a simple and reliable method. Most importantly, O(2)(-)-reduced cytochrome C can be frozen and stored without any alterations, at least up to 2 weeks. Thus the method seems to be superior to other methods of detection, especially when the experimental conditions do not allow immediate spectrophotometry (e.g. mountain medicine, space medicine). Under such conditions the present assay would allow reliable measurement of reduced cytochrome C, even after weeks of cryopreservation.

Cell Separation↗
PubMed2002

Performance of the XE-2100 leucocyte differential.

The XE-2100 trade mark was evaluated in a multicentre study following a previously established protocol. In this paper, we demonstrate the results of analytical performance studies, including comparison of the leucocyte differential with the NCCLS H20-A method and evaluation of flagging sensitivity. Linearity of the leucocyte count over a wide clinical range, low imprecision in clinically important ranges and no measurable carry over were confirmed. For comparability studies, 4 x 200 cell microscopic differential leucocyte counts were correlated with the automated five-part-differential counts. No significant differences were detected in (1) a group without morphological abnormality and in (2) a leukopenic group. The sensitivity of flags for the detection of immature granulocytes and myeloid blasts was very good. Only few samples containing blast cells remained unrecognized but these would have been examined microscopically in any event because of other abnormalities indicated by the instrument. Atypical/abnormal lymphocytes/and lymphoblasts were detected very reliably when the total lymphocyte count and the flags were evaluated in combination. A similar procedure is recommended for the detection of left shift. When the neutrophil count is elevated, the sensitivity of the left shift flag is improved. The absolute immature granulocyte (IG) count by the instrument correlates well with that of myeloid precursor cells by microscopy.

Flow Cytometry↗
PubMed2001

Levels of insulin-like growth factor after stem cell transplantation.

Some cytokines, i.e. tumor necrosis factor-, interleukin-6 and soluble interleukin-2 receptors are associated with complications of stem cell transplantation. Insulin-like growth factors (IGFs) are a family of peptides essential for the proliferation of normal and malignant cells. Recently increased levels of IGFs have been associated with the development of malignant tumors. In this communication we report on 96 measurements of insulin-like growth factor-I (IGF-1), insulin-like growth factor-II (IGF-2), and insulin-like growth factor-binding protein-3 (IGFBP-3) performed in 19 patients following stem cell transplants. Seventeen patients had allogeneic and 2 patients autologous transplants. Most IGF determinations were made at days 0, 7, 14, 21 and 28, some at other time points. The baseline values (day 0) of IGF-1 and IGFBP-3 were not different from controls. IGF-2 values were slightly lower than controls. Following transplantation, a consistent increase of IGF-1 was observed in 9/16 patients at days 7 and 14. Later the values decreased again. IGF-2 and IGFBP-3 did not change significantly after transplantation. No direct correlation could be established with the severity of graft-versus-host disease, levels of interleukin-6 and the time to hematopoietic recovery. A potential relevance of IGFs following stem cell transplantation may be the early diagnosis of liver damage and the development of second malignancies. More studies are necessary to investigate the pathophysiology and the clinical relevance of the increase of IGF-1 following stem cell transplantation.

Adolescent↗
PubMed1997

Idarubicin monotherapy in multiply pretreated leukemia patients: response in relation to P-glycoprotein expression.

The aim of the study was to test whether fractionated (weekly) idarubicin administration to multiply pretreated leukemia patients is effective and tolerable for outpatient treatment, and whether idarubicin alone can overcome P-glycoprotein (P-gp)-related resistance. P-gp was assessed with an immunocytological technique using the monoclonal antibody 4E3.16. P-gp. expression was characterized as a percentage of P-gp-positive blasts. Additionally, the function of P-gp was determined with the rhodamine-123 (R-123) accumulation test in combination with or without verapamil and expressed as the R123 accumulation ratio. Fractionated idarubicin (12 mg/m2/week) was given to 36 acute myelogenous leukemia (AML) patients, 12 acute lymphoblastic leukemia (ALL) patients, and eight chronic myelogenous leukemia (CML) patients in blast crisis. Furthermore, 11 AML and four ALL patients were treated with fractionated daunorubicin at a dose of 50 mg/m2/week. All patients had been pretreated with drugs inducing P-gp-related resistance including daunorubicin and/or doxorubicin or vindesine (CML patients). Of 71 pretreated patients, 51 (72%) had a P-gp value between 25 and 98%. Six of these patients with increased P-gp expression had a nonpumping P-gp; four of them were CD34 positive. Of 51 patients with increased P-gp expression, 30 (59%) were CD34 positive. With regard to idarubicin monotherapy, overall response was 33/56 (59%) patients, and 23/33 (70%) responding patients showed a P-gp expression between 25 and 95%. All idarubicin-responding patients with high P-gp expression before treatment showed a clear reduction of P-gp-positive blasts. No patients with P-gp expression between 34 and 85% treated with fractionated daunorubicin showed response or reduction of P-gp-positive blasts in bone marrow. This study demonstrates that P-gp-related resistance can be overcome in multiply pretreated leukemia patients with idarubicin alone, and that the protocol used here is tolerable for outpatient treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

P-glycoprotein expression in patients with acute leukemia-clinical relevance.

P-glycoprotein (P-gp) is a crucial factor in the development of chemotherapy resistance in malignant disorders. Between 1989 and 1995, P-gp expression was studied in bone marrow blast cells of 322 (239 AML; 83 ALL) acute leukemia patients. 166 AML patients with the AML-6 protocol (EORTC), containing daunorubicin, vincristine and conventional-dose cytarabine (ara-C), and 63 AML patients treated with intermediate-does Ara-C plus amsacrine. Further 71 ALL patients were treated according to a German standard polychemotherapy protocol (BMFT04/1989). P-gp was determined by using monoclonal antibodies C219 and 4E3, and the cutoff point for P-gp overexpression was set at >/= 10%. A significant (P < 0.06) difference in P-gp overexpression was demonstrated between AML (21.6%) and ALL (10.2%) patients at primary diagnosis and between primary diagnosis and relapse/refractoriness in AML (21.6%; 51.0%) and ALL (10.2%; 27.2%) patients. According to FAB classification P-gp overexpression was detected in AML patients significantly (P < 0.05) more frequently in classes M4, M5a and M5b and less frequently in M3, as compared to other types. For AML patients with P-gp overexpression at primary diagnosis or early relapse/refractoriness, the predictive value for nonresponse to the AML-6 protocol was 91 and 95%, respectively, while late-relapsed AML patients with P-gp overexpression had a significantly (P < 0.05) lower predictive value of 73% for nonresponse. Additionally, in refractory and late-relapsed P-gp--overexpressing AML patients treated with intermediate-dose ara-C plus amsacrine the predictive values for nonresponse were 44 and 39%, respectively, significantly (P < 0.05) lower as compared to AML-6 protocol-treated refractory or late-relapsed AML patients. In P-gp-overexpressing treated ALL patients the predictive values of 50 and 55% for non-response were calculated at primary diagnosis and late relapse, respectively. We conclude that P-gp overexpression is a common phenomenon in AML patients at primary diagnosis or relapse, has an inverse influence on AML-6 treatment outcome and should be taken into consideration in the development of new therapy strategies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Prognostic factors in multiple myeloma: role of beta 2-microglobulin and thymidine kinase.

Serum beta 2-microglobulin, serum thymidine kinase, and commonly used prognostic parameters were investigated for their prognostic value in a well-defined group of patients with multiple myeloma (n = 207). Multivariate analysis showed hemoglobin to be the parameter of strongest prognostic value. Only albumin, serum beta 2-microglobulin and serum thymidine kinase added further prognostic information. When tested for efficiency in recognizing patients with poor (average survival time < 1 year) and good (average survival time > 5 years) prognosis, serum beta 2-microglobulin was best (80%), followed by total urinary protein (78%), hemoglobin (76%), and albumin (75%).

Adult↗
PubMed1991

Histologic, biochemical, and clinical parameters for monitoring multiple myeloma.

In a retrospective and prospective follow-up study from 1968 to 1989, bone marrow biopsy specimens, serum beta-2-microglobulin (SB2M) levels, and the clinical features of 251 patients with multiple myeloma (MM) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS) were investigated. The main histologic variables (tumor cell type, tumor growth, tumor load, and fibrosis), SB2M level, serum thymidine kinase (STK) level, and various clinical parameters were analyzed to determine factors of value in monitoring the clinical phases of activity in MM. Our recently proposed prognostic strategy combining bone marrow histologic type, SB2M level, and signs of organ failure was tested for its ability to (1) diagnose the early and smoldering variants; (2) facilitate decisions on the time of initiation, the type and duration of initial induction therapy in the pretreatment phases (active and rapidly progressive phases); and (3) characterize variations in tumor regression and tumor-host interactions during chemotherapy (early treatment, plateau, relapse, transition, and refractory phases). The results indicate that this clinicopathologic monitoring combines information both on stage and aggressivity of MM and thus facilitates therapeutic decisions in the various clinical phases of MM.

Biomarkers, Tumor↗
PubMed1989

Bone marrow histology and serum beta 2 microglobulin in multiple myeloma--a new prognostic strategy.

Bone marrow biopsies of 720 patients with multiple myeloma (MM) were investigated from 1968-1989. Histologic variables were correlated with clinical parameters and survivals to determine prognostic factors. In 207 of these patients initial levels of serum beta 2 microglobulin (SB2M) were also measured for prognostic evaluation. Four tumour growth patterns were distinguished: interstitial (56%), interstitial/sheets (13%), nodular (15%) and packed marrow (16%) with median survivals of 46, 31, 22 and 16 months. When grouped according to the tumour cell mass in the biopsy, four histologic stages were recognized. Cellular characteristics were used to classify MM into 6 histologic types which were subsequently combined into 3 grades of malignancy: low, intermediate and high, analogous to the malignant lymphomas. With respect to tumour products, only SB2M proved to be a valuable prognostic indicator for staging and follow-up. Complications of MM such as anaemia, azotaemia, osteolytic lesions, hypercalcaemia and hypoalbuminaemia all predicted a poor prognosis, highly significant in the test statistics. We propose a new prognostic approach in MM, comprising 1) parameters defining the tumour itself, 2) the tumour products (SB2M) and 3) the tumour complications. This prognostic strategy combines information both on stage and malignancy of MM and enables definition of smouldering and of aggressive variants of MM at an early stage.

Biomarkers, Tumor↗
PubMed1989

Microvascular angina and panic disorder.

Recent cardiac studies have suggested that patients with chest pain and angiographically normal coronaries have "microvascular angina" (MVA). In contrast, prior psychiatric studies have shown that some of these patients have panic disorder (PD). We compared the clinical and psychologic characteristics of fifteen patients with MVA and fifteen patients with panic disorder (PD), and examined response to lactate infusion in a subgroup of MVA patients. Although 40 percent of MVA patients met criteria for PD and had chest pain following lactate infusion, there were psychologic and symptomatic differences between the MVA and PD groups. These results reflect either co-morbidity of MVA and PD in some patients or two types of MVA, one of primary cardiac origin and one a centrally mediated epiphenomenon of the increased autonomic arousal seen in PD.

Agoraphobia↗
PubMedDate not supplied

Expression and functional activity of P-glycoprotein in adult acute myelogenous leukemia patients.

Expression and functional activity of P-glycoprotein (P-gp) were measured in 182 acute myelogenous leukemia (AML) patients: 136 patients were treated with the AML-6 protocol (EORTC), containing daunorubicin, vincristine, and conventional-dose cytarabine (ara-C), and 21 patients received idarubicin, vepeside, and conventional-dose ara-C (ICE-AML-10 protocol/EORTC). An additional 25 patients were treated with a dose of idarubicin and ara-C, modified as compared with the ICE protocol, but with the same dose of etopside (ICE-I protocol). P-gp was determined using monoclonal antibody 4E3.16 and functional activity using the rhodamine 123 accumulation test. P-gp positivity was defined as a Kolmogorov Smirnov (KS) D value > or = 0.15, P-gp negativity as a KS D value < 0.15. P-gp activity was defined as a ratio of mean rhodamine 123 accumulation with/without verapamil. In AML patients at primary diagnosis and early relapse/refractoriness a significant (p < 0.05) difference between P-gp-positive and P-gp-negative patients was ascertained using the AML-6 protocol; the difference corresponded to the complete remission rate. For ICE- and ICE-I-treated AML patients at primary diagnosis this significance was not shown. Compared with AML patients at primary diagnosis and patients at early relapse or refractoriness, a significantly (p < 0.05) increased incidence of non-pumping P-gp and a trend (p = 0.054) to a higher percentage of non-P-gp-related mechanisms in AML patients at late relapse was determined. When the AML-6 protocol is used, age, activated P-gp, and CD34 expression are independent prognostic factors in AML patients. A test system which determines a functional P-gp overexpression is a major tool for identifying a group of AML patients with a poor prognosis. In order to effectively use so-called P-gp modulator substances, the degree of P-gp expression, the activated or nonactivated P-gp condition, and detection of non-P-gp-related resistance mechanisms are of utmost interest for optimal design and analysis of P-gp modulator trials and for understanding the complexity of chemotherapy-related resistance mechanisms in patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Neonatal hemochromatosis: a rare cause of nonimmune hydrops fetalis and fetal anemia.

Neonatal hemochromatosis is a rare inherited disorder of iron metabolism in which various tissues contain excessive amounts of iron. Only in a very few cases in which the disease is associated with fetal nonimmune hydrops is there the possibility for prenatal diagnosis. We present a case of fetal nonimmune hydrops fetalis in which severe fetal anemia and elevated liver enzymes were found. Retrospectively, according to pathological examination, these were signs of neonatal hemochromatosis. Only the knowledge of the disease entity allows antenatal diagnosis and rational perinatal management.

Adult↗