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Biomedical subjects

E Neumann

Publications and source records attributed to E Neumann.

At least 37 records · Page 2Linked to original sources
PubMed1989

[Differential therapy of myocardial ischemia in females].

Peripheral perfusion abnormalities are considered a possible reason for myocardial ischemia in the absence of visible coronary artery stenoses. In 85 women (age: 41-58 years, mean age: 46 +/- 8) with pathological exercise ECG (precordial mapping: 50 leads), hemodynamic studies were performed without medication, after sublingual nitroglycerin (NTG, 0.8 mg), sublingual Nifedipin (N, 30 mg), and intravenous Dipyridamol (D, 0.5 mg/kg). Eighteen women showed normal coronary arteries and a normal myocardial perfusion (group I), 21 an impaired perfusion due to coronary stenoses (Group II), and 46 women a reduced perfusion without visible changes (Group III). Reference methods were measurement of pulmonary artery pressure, 201-TI-scintigraphy, and coronary angiography. In group II, enddiastolic and endsystolic left ventricular volume (EDV, ESV) as well as enddiastolic pulmonary artery pressure (pAd) were increased, the ejection fraction (EF) was reduced, and cardiac output (CO) was normal. In group III, ESV, EDV, EF, and CO were significantly reduced, while pAd increased. In group II, N led to a normalization of ESV, EDV, EF, and pAd. In group III, NTG led to a reduction of pAd and EDV, and concomitantly to a further reduction of the already low CO. In both groups the reduction of ST-segment depressions after NTG was significant. N led to a moderate reduction of pAd and ST-segment depression, but to an increase of CO in both groups. D exhibited a comparable effect in group III. In group II an increase of ST-segment changes and of pAd with unchanged CO was observed. With regard to longterm treatment of women in group III, N and D seemed to be more efficacious than nitrates due to a beneficial effect on cardiac output.

Administration, Sublingual↗
PubMed1988

[High dosage and intermediate dosage cytosine arabinoside in the treatment of secondary leukemias].

Patients with secondary acute myeloid leukaemia (AML) following treatment with alkylating agents and/or radiation show a poor response to standard induction therapy. Between 1983-1987 8 consecutive patients were treated with high-dose cytosine arabinoside (HD-ARA C; 3 g/sqm twice daily for 6 days) or intermediate-dose cytosine arabinoside (ID-ARA C; 0.5 g/sqm twice daily for 6 days). Complete remission was achieved in 3 patients (HD-ARA C: 2/3l; ID-ARA C: 1/5) and partial remission in 3 patients (ID-ARA C: 3/5). One patient (HD-ARA C) died during prolonged aplasia, one patient (ID-ARA C) proved refractory to treatment. The respective duration of remission in the 3 responsive patients was 3, 7 and 8 months. The probability of survival of the whole group was 50% after 12 months and 25% after 24 months. Our results confirm the efficacy of monotherapy with ARA C in the treatment of secondary AML. Consolidation therapy with ID-ARA C for 4 days seems to prolong remission.

Adult↗
PubMed1988

Recombinant alpha-interferon (alpha-IFN) for progressive hairy-cell leukemia (HCL): a study in previously untreated nonsplenectomized patients.

Ten nonsplenectomized patients (5 males, 5 females) with hairy-cell leukemia were treated with recombinant alpha-IFN. The median age of patients was 54 years (32-76 years). The time between diagnosis and onset of treatment ranged from 1-120 months. Initially the patients received 5 x 10(6) I.U. daily by intramuscular or subcutaneous injections for 10 weeks. Thereafter the dose of IFN was reduced to 5 x 10(6) I.U. 3 x weekly and after 6 months to 5 x 10(6) I.U. 2 x weekly for at least 6 months. The median time of patient follow-up is 23 months (4-28 months). Three complete remissions were achieved after 3-24 months and five partial remissions after 4-18 months. One patient showed improvement after 3 months, and one patient died from cerebral hemorrhage after 5 weeks. In eight of ten patients peripheral blood cell counts normalized after a median of 7 months (1.5-11 months). A marked reduction in spleen size was observed in all seven patients who had splenomegaly at study entry. Two of three patients who interrupted therapy have relapsed after 2 and 6 months. We conclude that alpha-interferon is an effective method of first-line treatment in patients with HCL.

Adult↗
PubMed1988

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes.

Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n = 3; RA with ring sideroblasts (RARS), n = 3; RA with excess of blasts (RAEB), n = 8; RA with excess of blasts in transformation (RAEBt), n = 7; chronic myelomonocytic leukemia (CMML), n = 2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.

Aged↗
PubMed1988

Diagnosis of silent myocardial ischemia in women.

The diagnosis of silent ischaemic heart disease may be important in men as well as in women. However, diagnosing women by exercise ECG is limited due to the higher rate of false positive results. For improving diagnostic validity the following investigations were done. In 310 women, aged 41-63 years (mean age 47 years', revealing 'pathological' exercise ECG, further testing was performed using nitroglycerin (NTG 0.8 mg). As a reference method, pulmonary artery (PA) pressure measurement was used. As a result of NTG testing, two groups could be separated: (a) those in whom ST segment depression remained constant (N = 217, NTG negatives = 70%). Since the end-diastolic PA pressure was found normal, these results were interpreted to be false-positive. (b) NTG effected a reduction or normalization of exercise induced ST segment changes (N = 93, NTG positives = 30%). There was a correspondence with exercise inducible end-diastolic PA pressure decrease. Consequently, true positives were assumed. Analysis of angina pectoris history indicated typical chest pain in 2% of NTG negatives only, but in 16% of NTG positives. In agreement with this during exercise, angina was reported by NTG negatives in 3% of cases and by NTG positive in 17%. The rest of this group (83%) is considered having exercise induceable silent myocardial ischaemia. When checking-up after five years, exercised-induced angina could be found in 4% of NTG negatives again, but in 36% of NTG positives. It was concluded that exercise testing by additionally using nitroglycerin is a rather important approach for diagnosing myocardial ischaemia in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Phosphorylation of phosphatidylinositol associated with the nicotinic acetylcholine receptor of Torpedo californica.

When isolated, detergent solubilized and affinity chromatographically purified nicotinic acetylcholine receptor of Torpedo californica electric organ is incubated with [gamma-32P]ATP/Mg2+, phosphatidylinositol 4-phosphate (PIP) is formed from receptor associated phosphatidylinositol (PI). This receptor associated endogenous kinase activity is enhanced by orthovanadate and, remarkably, also by acetylcholine. Exogenously added PI-kinase only increases the phosphorylation rate if vanadate is present. PIP as the main phosphorylation product (up to 95%) remains bound to the beta-, gamma- and delta-subunits of the receptor and to the receptor associated v-protein. The alpha-subunits do not carry 32p phosphate; no phosphatidylinositol 4,5-bisphosphate formation has been observed. Concomitant to lipid phosphorylation tyrosine and serine residues are phosphorylated (5% of total incorporated 32P phosphate).

1-Phosphatidylinositol 4-Kinase↗
PubMed1987

Model of cell electrofusion. Membrane electroporation, pore coalescence and percolation.

High electric field impulses (1-20 kV/cm, 1-20 microseconds) may trigger fusion between adhering cells or lipid vesicles (electrofusion). In this paper a qualitative model of electrofusion is proposed consistent with both electron and light microscopic data. Electrofusion is considered as a multistep process comprising tight membrane-contact formation, membrane electroporation as well as an alternating series of subsequent fast collective and slow diffusive fusion stages. The following sequence of steps is suggested: The electric field pulse enforces (via polarization) a tight contact between the membranes of the cells or vesicles to be fused. During tight-contact formation between the opposing membrane surfaces the membrane-adherent water layers are partially squeezed out from the intermembraneous space. Pores are formed in the double membrane contact area (electroporation) involving lateral diffusion and rotation of the lipid molecules in both adhering membrane parts. With increasing pore density, pore-pore interactions lead to short-range coalescence of double membrane pores resulting in ramified cracks; especially small tongues and loops are formed. At supercritical pore density long-range coalescence of the pores occurs (percolation) producing one large double membrane loop (or tongue) and subsequently one large hole in the contact area. After switching off the electric field, the smaller pores, tongues and loops reseal and water flows back into the intermembraneous space of the double membrane in the contact area. As a consequence of the increasing membrane-membrane separation due to water backflow, cooperative rounding of the edges of remaining larger tongues and holes occurs. This results in the formation of an intercellular cytoplasm bridge (channel) concomitant with the disappearance of the contact line between the fusing cells. The membrane parts surrounded by continuous loop-like cracks may separate from the system and may finally form vesicles. Our electrofusion model comprises a strong linkage between the membrane pore formation by high electric fields (electroporation) and the process of electrofusion. Additionally, both pore-pore interactions as well as protein-protein interactions in the contact area of the fusing cells are explicitly introduced. The model provides a qualitative molecular description of basic experimental observations such as the production of membrane fragments, of smaller inside-out vesicles and the formation of larger intercellular cytoplasm bridges.

Cell Membrane Permeability↗
PubMed1987

[Allogeneic bone marrow transplantation in acute myeloid leukemia (AML): results in 14 patients].

Between February 1982 and August 1986 14 patients with AML (median age 24 years, range 10-41) underwent allogeneic bone marrow transplantation. 9 patients were grafted in first complete remission, 4 in first relapse, 1 in second relapse and 1 patient with refractory AML. Conditioning consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad). The patients received methotrexate (n = 12) or methotrexate and cyclosporine (n = 2) for prevention of graft versus host disease. Of the 14 patients, 7 are alive, 7 patients died. Causes of death were recurrence of leukaemia (n = 2), veno occlusive disease of the liver (n = 1), CMV-pneumonitis (n = 1), septicaemia (1), cerebral haemorrhage (1), acute graft versus host disease of the gut (1), necrotizing encephalopathy (n = 1). 7 patients are alive between 124 and 1784 days (median 671) in continuous complete remission. All patients but 1 have a Karnofsky-index of more than 80%.

Adolescent↗
PubMed1987

In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders.

Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.

Bone Marrow↗
PubMed1987

Changes in the oscillatory potentials of the electroretinogram in glaucoma.

Dark adapted and progressively light adapted electroretinograms (ERGs) were recorded from 34 normals and from 45 glaucoma patients. To enhance the oscillatory potentials (OP) the ERGs were highpass-filtered. The OP were characterized by two indices: their root-mean-square value and the inter-flash interval for which the maximal amplitude was obtained. In most of the glaucomatous OP, 50 of 81 eyes, both indices were abnormal, in 22 one parameter was abnormal and only in 9 were both parameters normal. In 13 of the 14 OP recorded from the opposite ('normal') eye of patients with unilateral glaucoma either one or both of the indices were abnormal. These findings indicate that the damage to the retina in glaucoma may extend more distally than the ganglion cell layer and that subclinical changes might be revealed by OP changes.

Adaptation, Physiological↗
PubMed1987

[New aspects in the diagnosis of ischemic heart disease in females].

To investigate still uncertain aspects of the diagnosis of ischemic heart disease (IHD) in women, between 1969 and 1984, repeated exercise studies were performed in 706 asymptomatic women (between the ages of 17 and 63 years). On observation of pathologic ST-segment depression of more than 0.1 mV, the exercise study was repeated after administration of 0.8 mg nitroglycerin. Pathologic ST-segment depression was seen in 310 women (44%). In 217 patients (31%), nitroglycerin had no effect (NTG negative); in 93 women (13%), there was normalization of the ST-segment changes (NTG positive). Additionally, in selected subgroups of patients, pulmonary artery pressure was measured at rest and during exercise and ECG mapping performed (n = 114); radionuclide ventriculograms (n = 64) and 201-thallium scintigrams (n = 99) were obtained and coronary angiography (n = 85) was performed. In the NTG-negative women, ejection fraction, myocardial perfusion and coronary arteries were normal. NTG-positive women had lower mean ejection fractions but still within normal limits and indications of impaired myocardial perfusion. High-grade coronary stenoses were found in 25%. No patient with pathologic ST-segment depression had mitral valve prolapse. NTG-positive women had significantly more risk factors than NTG-negative women. In the former group, pulmonary artery pressure measurements showed pathologic exercise hemodynamics, only in 25% of whom IHD with significant stenosis was found to be the cause. For this condition, differential diagnostic considerations include cardiomyopathy or small vessel disease.

Adolescent↗
PubMed1986

Indium 111-labeled platelet kinetic studies and platelet-associated IgG in hairy cell leukemia.

In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous 111In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of 111In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of 111In-labeled platelets in nonsplenectomized patients suggests "hypersplenism" with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.

Adult↗
PubMed1986

Myeloid progenitor cells in the peripheral blood of patients with hairy cell leukemia and other "leukemic" lymphoproliferative disorders.

We assayed granulocyte-macrophage committed progenitor cells (CFU-GM), erythroid committed progenitor cells (BFU-E) and pluripotent hemopoietic progenitor cells (CFU-MIX) in the peripheral blood of patients with hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). In 8 HCL patients retaining their spleens, the number of circulating CFU-GM, BFU-E and CFU-MIX were under the lower limits of normal controls in 6, 6 and 5 cases, respectively, and were in the lower normal ranges in the remaining cases. Six splenectomized HCL patients had generally more circulating progenitor cells than their nonsplenectomized counterparts. In the peripheral blood of 2 patients with ALL and 3 patients with CLL, progenitor cells of all types were markedly increased compared to their respective values in the blood of control subjects. Hairy cells from 2 HCL patients failed to inhibit CFU-GM, BFU-E and CFU-MIX derived colony growth from control peripheral blood mononuclear cells. In 3 HCL patients previously low circulating progenitor cells did not rise 5-7 months after RC-alpha 2-IFN treatment despite normalization of peripheral blood counts. Our results suggest that a reduction of the committed and pluripotent progenitor cell compartment might be at least in part responsible for the pancytopenia in the majority of patients with HCL.

Adult↗
PubMed1986

Treatment of severe aplastic anemia with combined immunosuppression (antithymocyte globulin and high-dose methylprednisolone).

Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA.

Anemia, Aplastic↗
PubMed1985

Cytogenetic findings in a case of Sézary syndrome.

Repeated cytogenetic studies were carried out on a Sézary syndrome patient during a 1-year period. The presence of a single clone of heteroploid (60-86 chromosomes) cells was a permanent finding in the PHA-stimulated blood cultures. The bone marrow was normal. Sister chromatid exchange (SCE) value was relatively lower in heteroploid cells.

Aged↗