Biomedical subjects
Publications and source records attributed to T Menzel.
In 20 patients, the serum level and urinary output of zinc, magnesium, copper, calcium and anorganic phosphate were examined during postoperative parenteral feeding. The parenteral feeding was standardized. In addition, the above mentioned bioelements were systematically substituted. Effects of this substitution therapy on serum level and urinary output are discussed.
In 52 adult patients, serum levels and renal loss of zinc, magnesium, calcium, copper and anorganic phosphate were examined during the period of parenteral postoperative nutrition. Simultaneously performed analyses of applied infusion and protein solutions, as well as of conserved blood, yielded a markedly differing content of these bioelements. Particularly pronounced are the differences in zinc concentrations of individual infusion solutions. A random substitution of zinc and anorganic phosphate is insufficient since it does not correspond with the demand. For this reason, anorganic phosphate and zinc should only be purposively substituted.
Following a short presentation of the physiological changes in respiration of pregnant women, we report our own experience with the development and therapy of a case of pneumonia during the last month of pregnancy. In this case, the spontaneous birth of a healthy child occurred after four days of mechanical ventilation. We discuss the advantages and disadvantages of waiting for spontaneous birth, taking under consideration the conditions previously described.
In 45 patients serum levels and urinary excretion of zinc, magnesium, calcium and phosphate were examined during postoperative parenteral nutrition. The patients received the same parenteral nutrition and were divided in groups according to different types of operations. Serum levels of calcium and magnesium were found to be normal in all groups at highly varying degrees of urinary excretion. Zinc and phosphate serum levels, as well as urinary excretion, show a markedly different behavior.
Clinical observations during postoperative feeding (observation period 10 to 30 days) are reported. We compared glucose and fructose intake at different intake rates to glucose and fructose urinary output. Insulin admixture per 100 g of glucose is not constant. It can be progressively reduced following operation.
44 patients are analysed for the frequency of postoperative vomiting and the amount of gastroatonia following aorto-femoral bypass operations during neuroleptanaesthesia and halothane combination anasthesia. More than 60% of patients develop gastroatonia during both methods of anaesthesia. However it is less apparent on the first postoperative day after neuroleptanaesthesia and does not affect as many patients as after halothane combination anaesthesia. Postoperative vomiting is significantly more frequent after halothan combination anaesthesia than after neuroleptanaesthesia.
When judging a probable therapeutic success for antibiotic management of bioprosthetic endocarditis, sufficient drug levels in heterologous valve tissues play a very important role. The pharmacokinetic behavior of ciprofloxacin was investigated in native and porcine valvular tissues and compared with plasma levels during a 90- to 120-min period of surgery. Analysis was carried out by HPLC using excised valvular tissues (Hancock T 505). In all, 15-20 patients were investigated in each group. The antibiotics were administered intravenously or per os. Tissue concentrations after onset of the procedures showed ciprofloxacin plasma concentrations of 2.09-0.47 micrograms g in the native and 3.98-1.99 micrograms/g in the heterologous valvular tissues.
A subset of patients have substantial discomfort on examination with transesophageal echocardiography with the conventional probe, whereby the dimensions of the probe play a decisive role. Miniaturized biplane transducers have recently become available (2 x 32 channels, dimensions 9.5 x 8.7 mm, and circumference approximately 30% less than the conventional echoscope) and allow ultrasound examination at 3.5, 5.0 and 7.0 MHz. A prospective study was carried out in 90 patients to compare difficulties on insertion of the probe, subjective evaluation by the patient during examination, and the two-dimensional image, as well as Doppler and color-coded Doppler quality of the miniaturized biplane versus the conventional probe. In 62 patients, intubation of the esophagus proved less difficult with the smaller instrument and more difficult in nine cases. Seventy-six patients reported that they suffered less discomfort on use of the narrow instrument. Concomitant parasympatholytic medication was needed with the smaller probe in seven cases and 17 times with the conventional probe. As anticipated, quality of the two-dimensional image attained by the miniaturized probe was lower. With transmit/receive frequency of 7.0 MHz, however, image resolution was excellent in the near field of 5 cm and nearly equivalent to that of the conventional probe (5.0 MHz). Pulsed-wave and continuous wave Doppler and color-coded Doppler information from both probes was similar in quality. Whenever examination with a conventional transesophageal transducer promises to be difficult, or when sedation is contraindicated because of a severe illness or respiratory insufficiency, transesophageal echocardiography should be considered with a smaller biplane probe at higher transmit-receive frequencies.
Granulocyte colony-stimulating factor (G-CSF) was previously shown to be produced constitutively by malignant epithelial cells and by monocytes/macrophages, fibroblasts and endothelial cells following stimulation. In this study we investigated the ability of medulloblastoma cells, representing malignant embryonal neuroectodermal cells, to produce G-CSF. Conditioned medium was freshly prepared from unstimulated explanted tumor tissue from two patients with medulloblastoma as well as from the medulloblastoma cell lines TE-671 and DAOY, and as controls normal glial cells. Following 72 hours of culture at a density of 5 x 10(5) cells/ml in RPMI 1640 with 10% FCS, the supernatants were harvested and tested for the presence of G-CSF in (1) the CFU-GM asay, (2) proliferation assay using the G-CSF dependent cell line NFS-60, and (3) Western blot analysis using an anti-G-CSF monoclonal antibody. Biological active and immunological detectable G-CSF was secreted by the medulloblastoma cell line DAOY and by one of the explanted tumor biopsies. The cell line TE-671 as well as normal glial cells did not produce G-CSF under identical culture conditions. We conclude that in addition to previously described sources of G-CSF, neuroectodermally derived medulloblastoma cells are also able to produce G-CSF constitutively. The G-CSF production was increased after stimulation with IL-1 alpha or TNF alpha. The role of G-CSF in neuroectodermal tissues remains to be further investigated.
We treated 14 patients with progressive metastatic colorectal cancer, using a combination of subcutaneous recombinant human interleukin-2 (4.8 x 10(6) IU/m2 three times daily on days 1 and 22, and twice daily on days 2 and 23, followed by 2.4 x 10(6) IU/m2 twice daily on days 3-5, 8-12, 24-26, and on 5 consecutive days per week, starting day 29), recombinant human interferon-alpha 2a (5.0 x 10(6) U/m2 thrice weekly), and 5-fluorouracil (750 mg/m2 i.v. bolus on days 15-19, and at weekly intervals thereafter, with a 1-week off-therapy interval every 4 weeks). Therapy was continued until disease progression occurred. Four (29%) and 8 (57%) evaluable patients achieved partial remission and stable disease, respectively; median response duration was 5.9 months. Toxicity of this regimen was moderate; the most common side effects were thrombocytopenia, leukopenia, nausea/vomiting, anorexia, malaise and fevers in all patients, along with diarrhea (63%) and mucositis (54%). Less than 10% of patients developed WHO grade IV toxicity; no toxic deaths occurred. Efficacy of this combination was not substantially different from alternative 5-fluorouracil-based regimens.
Renal cell cancer (RCC) accounts for 2-3% of all malignant tumors in adults. Due to the indolent course of disease and the few signs and symptoms in early stages the majority of patients presents with metastatic disease when diagnosed. The aims of systemic therapy of RCC are therefore palliative. Recent research shows the key role of immune mechanisms in the course of RCC. The therapeutic use of cytokines, mainly interleukin-2 (IL-2) and interferon-alpha (IFN) results in improvement of remission rates. To date it is unknown to what extent multiple cycles of chemo-immunotherapy alter the life quality (LQ) of patients with metastatic RCC. We monitored life quality during therapy in a three-armed protocol with interferon-alpha 2a, interleukin-2, 5-fluorouracil (5-FU), isotretinoin (ISO) and vinblastin (VBL). Life quality was impaired by two factors: response to chemo-immunotherapy and therapy side effects. A steep decrease of LQ-scores was seen in week 1 of therapy, LQ improved then for patients with stable disease (SD) and partial remission (PR) but not for those with progressive disease (PD).
Alterations in cell-mediated cytotoxicity levels were studied in patients receiving recombinant interleukin-2 (rIL-2) via subcutaneous injection. Fourteen outpatients, aged 36-68 years, with progressive metastatic malignancies, were treated with weekly escalated doses of rIL-2, starting at 1.8 IU/m2/day for 6 days a week, up to 14.4 IU/m2/day during the 4th week of therapy. Patients presenting with stable disease thereafter were started on maintenance therapy and received 10.8 IU/m2 once weekly for up to 12 weeks. Patient mononuclear cells were isolated from fresh peripheral blood at various times throughout the treatment. Cells were assayed prior to and after further in vitro stimulation by rIL-2 (600 IU/ml for 7 days). Natural killing (NK) activity was measured by cytolysis of K 562 target cells, and lymphokine-activated killing (LAK) was determined by cytotoxicity against Daudi targets, respectively, in four effector:target ratios (E:T), using a standard 2-hour europium3+ release assay. Spontaneous NK cell function (E:T = 25:1) of freshly isolated peripheral blood mononuclear cells (PBMC) was enhanced significantly after 28 days of therapy (27.8 vs. 9.1% on day 0). LAK activity also markedly increased during therapy (26.2 vs. 5.4% on day 0). Further in vitro culture of these PBMC in the presence of rIL-2 resulted in day 28 non-MHC-restricted cytolytic activity of 63.2% (40.3% on day 0) against K 562 targets, and 64.9% (39.6% on day 0) against Daudi targets. Activation of cytolytic function by rIL-2 appeared to be dose-dependent, as measurable lytic capability decreased throughout maintenance therapy, while neither sex nor tumor entity prior to therapy or clinical response were correlated with cytotoxicity levels. Taken together, our observations demonstrate that stimulation of the non-MHC-restricted pathway of cytolytic activation, as measured by lysis of target cells, arises in patients treated with rIL-2 doses 5- to 30-fold lower than used previously in intravenous protocols, connecting effective clinical response rates with acceptable tolerability.
The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16 patients with metastatic renal cell carcinoma. In all patients s.c. rIL-2 resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours, as determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha serum concentrations remained elevated up to 24 hours following single s.c. administration of rIL-2. Total secondary TNF-alpha release, as assessed by the area under the curve (AUC), appeared to be independent of dose distribution of rIL-2 (10 million IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2 induced TNF-alpha release was significantly higher in patients who had received prior rIL-2 immunotherapy, while steroids resulted in a significant suppression of TNF-alpha release. Secondary TNF-alpha release was statistically associated with progression-free survival of renal cell carcinoma patients and may be a prognostic factor in patients receiving rIL-2.