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Biomedical subjects

T Menzel

Publications and source records attributed to T Menzel.

At least 73 records · Page 4Linked to original sources
PubMed1992

Biologic and therapeutic efficacy of mafosfamide in patients with metastatic renal cell carcinoma.

It is well known that oxazaphosphorines [e.g., cyclophosphamide and 4-hydroperoxycyclophosphamide (mafosfamide)] are potent immunosuppressive agents. Under the proper conditions, they can potentiate immune responses as well. Immunomodulation represents a major breakthrough in the management of chemotherapy-resistant tumors. Thus, we evaluated the clinical and laboratory sequelae of low to intermediate doses (100-1000 mg/m2) of mafosfamide administered to 16 patients. Four weeks after therapy, one patient had a complete remission, eight patients presented with stable disease, and seven patients did not respond. Clinical and laboratory toxicity was mild and totally reversible, and therapy was well tolerated in all patients. Analyses of phenotypic cell surface antigens on circulating peripheral blood mononuclear cells showed inconsistent alterations of the CD4/CD8 ratio, initial depletion with later rebound of CD8+ cells, increase of CD20+ cells, and a mafosfamide dose-dependent regulation of natural killer-like cells as characterized by CD16 and CD56 positivity. Cell-mediated cytotoxicity against K562 target cells peaked 1 day after therapy and was most pronounced in patients who had received 300 mg/m2 mafosfamide, whereas cytotoxicity against Daudi targets was essentially unchanged, consistent with an increase in natural killing activity without augmentation of lymphokine activated killing. We conclude that mafosfamide administration at low to intermediate doses can be performed with good safety and tolerance; immunophenotypic analyses and cytotoxicity assays showed most pronounced alterations in patients receiving low doses of mafosfamide. These observations support the use of mafosfamide in the attempt to augment antitumor immune responses.

Adjuvants, Immunologic↗
PubMed1991

Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes.

Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.

Carcinoma, Renal Cell↗
PubMed1991

Increased serum levels of granulocyte colony-stimulating factor in patients with severe congenital neutropenia.

Severe congenital neutropenia (SCN), also known as Kostmann Syndrome, is characterized by a maturation arrest of myelopoiesis at the level of promyelocytes with absence of neutrophils in bone marrow (BM) and blood. Hypotheses of the pathophysiology of SCN include (1) defective production of granulocyte colony-stimulating factor (G-CSF), and/or (2) defective response to G-CSF. To exclude defective G-CSF production we tested sera from patients with SCN for the presence of G-CSF using Western blot analysis and NFS-60 proliferation assay. Using these assays we were able to detect increased G-CSF serum levels in SCN patients (150 to 910 pg/mL) as compared with normal controls (between undetectable and 100 pg/mL). These results suggest that patients with SCN have no defect in G-CSF production but a defective response of neutrophil precursors to endogenous G-CSF.

Adult↗
PubMed1991

Blood mononuclear cells from patients with severe congenital neutropenia are capable of producing granulocyte colony-stimulating factor.

Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia or absence of blood neutrophils secondary to a maturational arrest at the level of promyelocytes. We examined peripheral blood mononuclear cells (PBMC) of SCN patients who demonstrated normalization of their blood neutrophil counts in a phase II clinical study with recombinant human granulocyte colony-stimulating factor (rhG-CSF). When stimulated in vitro with bacterial lipopolysaccharides (LPS), PBMC of those SCN patients produced G-CSF activity, as judged by proliferation induction of the murine leukemia cell line, NFS-60. Western and Northern blot analysis showed G-CSF protein and G-CSF-mRNA indistinguishable in size from those of normal controls. We conclude that PBMC of the SCN patients tested are capable of synthesizing and secreting biologically active G-CSF in vitro.

Adult↗
PubMed1991

New nomenclature and computerized programme of graphics for the description and recording of aortocoronary bypasses.

In the process of drawing up a computerized operation reporting system, a nomenclature for the precise description of recently fitted or existing aortocoronary bypasses has been developed. This is based on a sequence of letters showing in one line which type of bypass has been fitted, the graft material used, the central anastomosis (source) as well as the peripheral anastomoses on the coronary arteries (objective). For this purpose, abbreviations of the customary terms in use in cardiac surgery have been used. A computer graphics programme has been created in parallel, enabling all bypasses (existing and/or new) to be sketched into the diagram of a heart with the aid of a mouse. The bypass nomenclature is automatically generated from the diagram, which can also be printed out as a sketch of the operation. The complete diagram of the heart plus data input forms enable the operation report to be compiled automatically. The nomenclature and the graphics programme are easily learnt, simplify work, can readily be incorporated into a computerized hospital organization and enhance documentation quality.

Abbreviations as Topic↗
PubMed1991

Diminished expression of interleukin-2 receptors in vivo after prior chemotherapy in advanced cancer patients receiving recombinant interleukin-2.

In a phase I/II dose escalation study performed at our institution, a total of 14 advanced metastatic cancer patients received between 4 and 16 weeks of subcutaneous recombinant interleukin-2. Doses were escalated at weekly intervals, starting at 1.8 million IU/m2/day up to a maximum dose of 14.4 million U/m2 daily. When comparing patients with (n = 4) and without (n = 7) prior chemotherapy on day 0 (i.e., before rIL-2), both patient groups exhibited Tac IL-2 receptor (CD25) positive peripheral blood lymphocytes at equal levels of positivity (8%). In contrast, 4-week systemic treatment with subcutaneous rIL-2 at escalating dose levels revealed a significant difference in the up-regulation by interleukin-2 of CD25 cell surface receptor. Thus, after 4 consecutive weeks of treatment, patients without previous chemotherapy showed a mean CD25 positivity of peripheral blood lymphocytes at 38%, as compared with 22% in patients who did receive prior chemotherapy (p less than 0.05). These data suggest that chemotherapy pretreatment may have a significant effect on biological response to rIL-2 in vivo.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A double-blind comparison of metoprolol CR/ZOK 50 mg and atenolol 50 mg once daily for uncomplicated hypertension.

In a double-blind study with parallel groups, the clinical bioequivalence of the antihypertensive effect of metoprolol CR/ZOK (controlled release formulation) 50 mg and atenolol 50 mg in ordinary tablets given once daily for uncomplicated hypertension was investigated. Clinical bioequivalence was defined as difference in blood pressure reduction less than 8 mmHg. The study involved 195 patients, 98 on metoprolol CR/ZOK and 97 on atenolol. All patients were taken off antihypertensive therapy during a 2-week placebo run-in period. Thereafter the patients were randomly allocated to metoprolol CR/ZOK 50 mg or atenolol 50 mg for 4 weeks. In patients with a diastolic blood pressure remaining above 90 mmHg, the dose was increased to 100 mg daily of the respective drug. After 4 weeks treatment with 50 mg of the two therapies, blood pressure and heart rate was significantly reduced in both treatment groups. At this dose, clinical bioequivalence was found regarding both blood pressure and heart rate reductions. After 8 weeks of therapy (100 mg doses given to 31 in the metoprolol group and 43 in the atenolol group), clinical bioequivalence according to stated definition was found for blood pressures and heart rate reductions, although the reductions of systolic and diastolic blood pressures at rest as well as diastolic blood pressure during exercise were significantly greater in the metoprolol group. In an evaluation of the responder rate after the 8 weeks of treatment, 89% of the patients in the metoprolol CR/ZOK group and 74% in the atenolol group (P less than .05) had a diastolic blood pressure reduction to 90 mmHg or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Parenteral tiapamil treatment of arrhythmias in cardiac patients.

27 cardiac patients with different types of arrhythmias were treated in the coronary care unit with tiapamil administered by intravenous infusion. Special attention was given to determining the antiarrhythmic effects in patients with acute coronary insufficiency. In the group of 15 patients with ventricular extrasystoles (VEs; Lown classification III-V). 9 patients had acute myocardial infarction and 1 patient had coronary artery disease. In the group with supraventricular extrasystoles (6 cases). 1 patient had experienced anterior infarction. The third group comprised 6 patients with combined ventricular (Lown V) and supraventricular extrasystoles. In 1 case, the arrhythmia was due to acute anterior infarction. 2 patients had experienced reinfarction and one patient had crescendo angina pectoris. ECG and hemodynamics were monitored continuously before, during and for 20 h following therapy. In patients with VEs alone, the median frequency fell from 612 to 459/h at the third hour of infusion. The median VE/sinus beat quotient decreased from 0.125 to 0.0108 (p less than 0.01) in the third hour of treatment, and increased to 0.1029 after the completion of therapy. VE suppression was particularly marked in the 10 patients with coronary artery disease, 7 of these demonstrating a reduction by over 90%. Similar results were obtained in patients with supraventricular arrhythmias and mixed forms. The preliminary results show that tiapamil may be an effective antiarrhythmic agent in supraventricular and particularly in ventricular extrasystoles, and that its spectrum of antiarrhythmic action merits detailed investigation in larger numbers of patients.

Adult↗
PubMed1981

[Management of supraventricular and ventricular arrhythmias with the intravenous administration of the calcium antagonist Tiapamil (Ro 11-1781) (author's transl)].

27 cardiac patients with a mean age of 58.5 years (S.D. +/- 9.43) were treated in the coronary care unit with tiapamil, a new Ca2+ antagonist, by intravenous infusion. The following arrhythmias were identified: ventricular premature complexes (VPCs, Lown class 3--5) in 15 patients, supraventricular premature complexes (SVPCs) in 6 patients, and mixed VPCs (Lown grade 5) plus SVPCs in 6 patients. ECGs and hemodynamic parameters were continuously monitored prior to, during and up to 24 hours after the therapy. In patients with VPCs, the median frequency of VPCs decreased from 612.0 to 64.0 at the 3rd hour of therapy (p less than 0.01). Between the 13th and the 24th hour after tiapamil, without therapy the median VPCs increased to 459.0. The median "VPCs/sinusal" beats ratio was decreased from 0.125 to 0.0108 (p less than 0.01) at the 3rd hour and returned to 0.1029 from the 9th to the 20th hour after stopping tiapamil. The results in the patients with SVPCs, or with VPCs + SVPCs were similar. Tiapamil did not affect the central venous pressure and decreased the median blood pressure from 130/80 to 110/75 mm Hg (p less than 0.10). The effects of tiapamil against all types of cardiac arrhythmias can therefore be defined as good. 1/27 patients presented hypotension that required therapy with dopamine, and mild subjective complaints (mainly headache) were reported in 6 patients. No complications occurred. The results show that tiapamil is effective both against SVPCs and VPCs, and thus its spectrum of action differs from that of other Ca2+ antagonists.

Adult↗
PubMed1979

The clinical usefulness of a screening test to detect static pulmonary blood using a multiple-breath analysis of diffusing capacity.

We devised a screening test to detect static blood in the lungs (e.g., with pulmonary vascular obstruction or pulmonary hemorrhage). A back pressure to CO will develop in static blood as the concentration of carboxyhemoglobin increases with time, and diffusing capacity (DLCO) will decrease. Instead of obtaining a single value for DLCO, we calculated DLCO over small decrements of the exhaled vital capacity during 4 sequential breaths using a modification of a method developed in our laboratory. In each of 5 healthy subjects there was no difference in DLCO during the 4 sequential breaths in the sitting, supine, or lateral decubitus positions. However, in a patient with a proved pulmonary embolus, DLCO decreased with sequential breaths, expecially at low lung volumes. In a patient with angiographic evidence of kinking of the left pulmonary artery when he assumed the right lateral decubitus position, DLCO showed a sequential decrease in this position only. Three patients with pulmonary hemorrhage also showed decreases in DLCO during sequential breaths during episodes of active bleeding.

Adult↗
PubMed1979

[The level of the plasma proteins transferrin, retinol-binding protein and prealbumin in the postoperative parenteral feeding by administration of varying amounts of amino acids].

38 adult patients of a surgical intensive care ward received differently large amounts of amino acids during the course of postoperative parenteral nutrition. The dose of amino acids was adapted to the preoperative nutritional condition of the patient. Changes in the serum levels of retinol-binding protein, prealbumin and transferrin were registered as well as changes in total protein and nitrogen balance up to a maximum of 10 postoperative days. Depending upon the amount of administered amino acids, the values for transferrin and nitrogen balance had changed more significantly than those of serum concentrations of retinol-binding protein and of prealbumin.

Adult↗
PubMed1979

[The behavior of bioelements during long-term parenteral feeding].

26 adult patients were investigated for 26--35 postoperative days while being fed parenterally. Serum levels and urine excretion of zinc, magnesium, calcium and phosphate were measured. From the results it can be assumed that only phosphate substitution is necessary during parenteral long-term nutrition.

Adult↗
PubMed1979

[Plasma protein levels during postoperative parenteral feeding].

In 58 adult intensive care patients, the concentration changes of some plasma proteins and of the immunoglobulins IgA, IgG and IgM were examined postoperatively under parenteral feeding. In three groups of patients with different operations (trepanation, gastrectomy, vascular surgery), the initial and subsequent values were not the same. A comparison with simultaneous nitrogen balances showed no complete agreement. Transferrin, retinol-binding protein and prealbumin seem to be suitable parameters for the measurement of catabolism.

Abdomen↗
PubMed1979

[Parameters of catabolism during long-term postoperative parenteral feeding].

In 26 adult patients of an intensive-care ward, the following parameters were controlled for 26 to 35 days under postoperative parenteral feeding: prealbumin, transferrin, and retinol-binding protein, the immunoglobulins IgA, IgM and IgG, total serum protein, Hb content, body-weight and urinary nitrogen elimination. In the early phase and also in the 2nd to 4th postoperative week, prealbumin and transferrin are apparently good indicators for the existence of a catabolic or anabolic metabolic condition.

Adult↗
PubMed1979

[Postoperative serum immunoglobulin G, prealbumin, retinol-binding protein and transferrin picture].

In 24 patients who had undergone cholecystectomy or abdominal hysterectomy the serum levels of prealbumin, transferrin, retinol-binding protein and immunoglobulin G were determined up to the 5th day after operation. Intra- and immediately postoperatively the patients received only isotonic infusion, beginning on the 3rd day after operation, they were fed increasingly orally. The observed serum levels decreased postoperatively.

Cholecystectomy↗