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C Wenzel

Publications and source records attributed to C Wenzel.

36 records · Page 2Linked to original sources
PubMed2000

Relation of pro- and anti-inflammatory cytokines and the production of nitric oxide in patients receiving high-dose immunotherapy with interleukin-2.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sTNFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL-10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.

Adult↗
PubMed1999

[Clinical phase II-evaluation of neoadjuvant, cytostatic combination chemotherapy with docetaxel and epidoxorubicin in female breast cancer patients (T1-4, N0-2, M0)].

BACKGROUND: Preoperative (neo-adjuvant) chemotherapy is very effective in downstaging primary tumors and moreover is able to prevent advancing metastatic growth early in the course of the disease. METHODS: We report on 38 patients with a median age of 54 years (range, 33-70 years) suffering from biopsy-proven breast cancer (T1-T4). Mastectomy had been considered the treatment of choice in all cases. The patients received 194 cycles of chemotherapy with docetaxel (75 mg/m2) and epidoxorubicin (75 mg/m2) on day 1, every 21 days, together with 30 million IU of G-CSF from days 3 to 10. Three to 8 cycles (median 5 cycles) of the treatment were administered until best response was achieved on mammography and clinical assessment. RESULTS: The neo-adjuvant chemotherapy was well tolerated and all patients completed the treatment regimen on an out-patient basis. During 194 cycles we observed leukopenia WHO grade IV only at one occasion (0.5%). WHO-grade III toxicity consisted of leukopenia (0.5%), diarrhoea (2%), and stomatitis (0.5%). Response to treatment was present in 85%, with 4 patients (11%) experiencing a pathological complete response (pCR) of the invasive tumor (T0: n = 2, DCIS: n = 2) and 28 patients (74%) showing a partial pathological response. In 21 patients (52%) a breast-conserving surgical procedure was possible. SUMMARY: We conclude that neo-adjuvant treatment of primary breast cancer with docetaxel and epidoxorubicin is safe and effective. By applying more chemotherapy cycles preoperatively it might even be possible to raise the rate of pCR and prolong survival.

Adult↗
PubMed1998

Clinical outcome at six months of coronary stenting followed by ticlopidine monotherapy.

Antiplatelet therapy has been shown to be superior to oral anticoagulation after coronary stent implantation. Different regimens for postinterventional antiplatelet therapy have been proposed. A combination of ticlopidine and aspirin has gained the most widespread use. The relative merit of the different compounds in this combination remains unclear. There are several, partly conflicting, reports on coronary stent implantation followed by aspirin alone, but data on ticlopidine monotherapy are scarce. We conducted a prospective trial of elective coronary stenting followed by ticlopidine monotherapy in 263 consecutive, unselected patients. One-, 2-, and 3-vessel disease was present in 42.9%, 42.6%, and 14.5% of patients, respectively. We deployed a total of 322 stents. All patients received 250 mg of ticlopidine twice daily for up to 6 months. The clinical end points encountered during the hospital stay and at 5.9+/-2.9 months, respectively, were: death (2 [0.8%] and 2 [0.8%]); myocardial infarction (5 [1.9%] and 4 [1.5%]); target vessel occlusion (2 [0.8%] and 4 [1.5%]); bypass surgery (0 and 2 [0.8%]); and repeat angioplasty (2 [0.8%] and 52 [19.8%]). There was 1 vascular surgery (0.4%) and 4 (1.5%) non-procedure-related ischemic cerebrovascular events at follow-up. We conclude that coronary stent deployment followed by ticlopidine monotherapy is safe and effective in an unselected population. The overall clinical outcome at 6 months is good and comparable to that of patients treated with combined antiplatelet therapy. Ticlopidine monotherapy may be a safe alternative for patients with contraindications to aspirin.

Adult↗
PubMed1997

How accurate is the assessment of thyroid volume by palpation? A prospective study of 316 patients.

Goitre is the cardinal symptom of most thyroid diseases and treatment is often influenced by the evaluation of thyroid size. Quantitative palpation of the thyroid gland could offer a quick and easy initial examination method for discovering most thyroid diseases. However, this clinical technique is frequently underestimated and its accuracy is not evaluated. Therefore, we examined the question whether thyroid volume can be determined with sufficient precision by manual palpation. 316 patients with suspected thyroid diseases were selected at random at our hospital and prospectively studied. Thyroid volume of each patient was assessed by palpation followed by ultrasonically scanning. The examinations were performed by two physicians: an endocrinologist (A) and a resident (B) who had undergone a structured palpation training. Ultrasonic scanning of 99 thyroid glands revealed a high level of agreement (r2 = 0.87) between both physicians. Examiner A evaluated 111 patients by palpation and ultrasonic scanning. The mean volume determined by ultrasound was 35.9 ml (SD = 27.1 ml) with a range of 4-152 ml. This correlated well with the results of palpation (r2 = 0.872). Examiner B evaluated 215 patients. These ultrasonically determined volumes had a mean value of 37.3 ml (SD = 24.2 ml; range 4-145 ml) and correlated well with the results obtained by palpation (r2 = 0.856). A total of 53 patients were examined by both physicians. The interobservers' comparison of the palpation results yielded an excellent correspondence (r2 = 0.893). We conclude that the manual palpation technique yields sufficiently precise quantitative results for clinical purposes and can be taught. Clinical assessment of thyroid size on a routine basis should result in better diagnostic strategies for thyroid diseases and in cost savings.

Adolescent↗
PubMed1996

The suitability of oiled guillemots (Uria aalge) as monitoring organisms for geographical comparisons of trace element contaminants.

The influence of the nutritional state (condition factor), age, and sex of Common Guillemots (Uria aalge) on trace element levels was examined to investigate the validity of geographical comparisons of metal accumulations in dying and dead oiled seabirds. A quotient of liver mass to kidney mass was calculated as a condition factor. Condition factors ranged from 0.85-4.74. Sex did not alter the distribution of any of the elements analyzed in immature or adult birds. Cadmium concentrations in soft tissues were strongly influenced by the age of the birds, with adult birds containing significantly higher amounts (0.025-88.28 ppm) than immature ones (0. 004-17.9 ppm). When simultaneously considering age and nutritional condition of the birds, selenium levels were highest in liver samples in immature guillemots (7.37-41.27 ppm) as compared to adult birds (7.22-36.84 ppm). Mercury, copper, and zinc were independent of age. The condition factor had no effect on cadmium levels in birds. In contrast, copper and zinc concentrations in kidney, liver and feathers were negatively correlated with the nutritional condition. In the case of mercury a similar relationship was found only in feathers. On the basis of these results guillemots collected in the German Bight showed significantly higher mercury values (0. 81-20.87 ppm) in soft tissues than birds collected in Brittany (0. 85-17.95 ppm). In general, cadmium levels were higher in the liver of immature birds from the German Bight than in those from Brittany. With regard to copper and zinc only kidney samples had higher values in the German Bight than in Brittany. Selenium levels were lower in feathers of birds from the German Bight (0.09-2.20 ppm) than in those from Brittany (0.67-6.64 ppm). The results indicate that beached guillemots can be used to monitor geographical differences in the contamination with certain metals provided that birds of the same age and/or nutritional condition are compared.

Aging↗
PubMed1996

[CAA 19-9 and carcinoembryonic antigen in gallbladder cancer].

The aim of this work was to assess the diagnostic yield of serum tumoral markers, Ca 19-9 and carcinoembryonic antigen, in patients with gallbladder cancer. We studied 54 patients of whom 33 had gallbladder cancer and in 21 the tumor was removed previously and were presently free of disease. Twenty one patients with cholelithiasis were used as controls. Ca 19-9 was over 37 U/ml in 22 (65%) patients with cancer, in two patients free of disease and in two controls. The sensitivity and specificity of Ca 19-9 was 0.66 and 0.90 respectively. Carcinoembryonic antigen was over 2.5 ng/ml in 25 patients with cancer (56%) and its sensitivity and specificity was 0.75 and 0.71 respectively. Using a cutoff point of 4 ng/ml, these figures were 0.51 and 0.9 respectively. The better predictive capacity was given by a Ca 19-9 over 37 U/ml or a carcinoembryonic antigen over 4 ng/ml. It is concluded that, although the sensitivity and specificity of these markers was adequate in this work, one must bear in mind that studied patients had advanced tumors.

Adult↗
PubMed1995

[Gallbladder cancer. Case-control study].

Gallbladder cancer is the principal oncological cause of death in chilean women and cholelithiasis is a well recognized risk factor. Aiming to unravel other risk factors for gallbladder cancer, we compared 50 patients subjected to cholecystectomy in whom a gallbladder cancer was found with 50 age and sex matched operated controls without cancer. Subjects were clinically assessed and interrogated about demographic, obstetrical features and feeding features. Multiples and early pregnancies were factors significantly associated to the development of gallbladder cancer. Twenty subjects (44%) with cancer knew that they had cholelithiasis and 41 patients in each group were symptomatic. It is concluded that pregnancy may be a risk factor for gallbladder cancer probably due to the lithogenic effect of its hormonal changes. Also, early cholecystectomy in symptomatic individuals may be an effective preventive measure.

Adult↗
PubMed1993

Dam methyltransferase from Escherichia coli: sequence of a peptide segment involved in S-adenosyl-methionine binding.

DNA adenine methyltransferase (Dam methylase) has been crosslinked with its cofactor S-adenosyl methionine (AdoMet) by UV irradiation. About 3% of the enzyme was radioactively labelled after the crosslinking reaction performed either with (methyl-3H)-AdoMet or with (carboxy-14C)-AdoMet. Radiolabelled peptides were purified after trypsinolysis by high performance liquid chromatography in two steps. They could not be sequenced due to radiolysis. Therefore we performed the same experiment using non-radioactive AdoMet and were able to identify the peptide modified by the crosslinking reaction by comparison of the separation profiles obtained from two analytical control experiments performed with 3H-AdoMet and Dam methylase without crosslink, respectively. This approach was possible due to the high reproducibility of the chromatography profiles. In these three experiments only one radioactively labelled peptide was present in the tryptic digestions of the crosslinked enzyme. Its sequence was found to be XA-GGK, corresponding to amino acids 10-14 of Dam methylase. The non-identified amino acid in the first sequence cycle should be a tryptophan, which is presumably modified by the crosslinking reaction. The importance of this region near the N-terminus for the structure and function of the enzyme was also demonstrated by proteolysis and site-directed mutagenesis experiments.

Amino Acid Sequence↗
PubMed1993

Peduncular hallucinosis as a transient ischemic attack.

Peduncular hallucinosis is characterized by vivid hallucinations associated with organic midbrain disease. In the case reported here, the computed tomography brain scan showed basilar arterial atherosclerotic disease with central and cortical atrophy. Carotid imaging revealed bilateral stenosis. The electroencephalogram and magnetic resonance imaging of the midbrain revealed no abnormalities. The patient's symptoms resolved completely in 48 hours. This is believed to be the first report of peduncular hallucinosis as the manifestation of a transient ischemic attack syndrome.

Aged↗
PubMed1991

Crosslinking of Dam methyltransferase with S-adenosyl-methionine.

Highly purified DNA-adenine methyltransferase was irradiated in the presence of different concentrations of radiolabelled S-adenosyl-methionine (AdoMet) with a conventional Mineralight UV-lamp from several minutes up to 1 h while incubating in ice. Incorporation of radioactivity was monitored by electrophoresis of the crosslink between S-adenosyl-methionine and Dam methylase on SDS-polyacrylamide gels followed by fluorography. Crosslinking reached a maximum in presence of 10 microM S-adenosyl-methionine; it was inhibited in the presence of substances which competitively inhibit methylation of DNA by Dam methylase, like sinefungin or S-adenosyl-homocysteine, but not in the presence of non-inhibitors like ATP or S-isobutyl-adenosine. The crosslink obtained was resistant against a wide range of even drastic conditions commonly used in protein and peptide chemistry. Proteins, which do not bind S-adenosyl-methionine, as well as heat inactivated Dam methylase were not photolabelled. After limited proteolysis the radioactive label appeared only in certain of the peptides obtained. From Western blots carried out with polyclonal antibodies produced against a synthetic peptide corresponding in its sequence to amino acids 92-106 of the Dam methylase, the crosslinking of AdoMet could be tentatively mapped at a position after amino acid 106.

Binding, Competitive↗
PubMed1990

Volume calibration of various gasmeters using a modified Tissot spirometer.

Various methods for determinating energy expenditure by indirect calorimetry are used in laboratory and field studies such as the Douglas bag method, often used in combination with a wet gasmeter, the respirometer of Kofranyi and Michaelis (KM) and the Oxylog (OX). To calibrate the volume measurements of these pieces of apparatus a modified Tissot spirometer was built, consisting of an outer casing filled with water, a core and a bell. It was equipped with a solid counterbalance and with an additional roller chain, partly freely suspended on the side of the counterbalance. This construction allowed compensation for the varying buoyancies of the bell. The lift of the bell was measured by means of a vernier scale. From calculations of the geometric volume a revolution counter was adapted to record the moved volume in litres. By means of this spirometer volumes up to 200 l can be used for calibration at various physiological flow rates. Calibration procedures for KM, wet gasmeters and OX were developed. For OX a small inaccuracy up to 2.0% was observed within the flow range from 20 to 70 l.min-1. The inaccuracy increased at higher flow rates. Under defined calibration conditions the modified Tissot spirometer enabled repeated calibrations of different types of gasmeters.

Calibration↗
PubMed1990

A comparative study on different methods for the determination of energy expenditure.

In order to determine energy expenditure, the Douglas Bag technique (DB) and Kofranyi-Michaelis respirometers (KM) have been widely used under field conditions for several decades. Some years ago the Oxylog (OX) method was developed, measuring simultaneously the difference of partial oxygen pressure in inspired and expired air (PO2 diff.) by two polarographic oxygen sensors. In order to compare these three methods laboratory experiments (3 test subjects, 5 different bicycle ergometer work loads, 180 measurements per apparatus) were performed. Oxygen uptake (VO2) varied between about 0.9 to 3.0 l/min. The VO2 data obtained by the DB method, which were used as a reference, and those obtained by the KM method agreed fairly well. The recorded data of OX underestimated VO2 up to 21%, with the deviation increasing with work intensity. A sufficient accuracy of recorded VO2 was observed only up to moderate work intensity. OX data calculated from ventilation volume of inspired air per minute (VI) and PO2 diff., measured by OX, were always about 19% higher than those recorded by OX. This means that the calculated VO2 values of the OX corresponded fairly well with DB values at heavy work loads. The reason for the differences between recorded and calculated OX data is still unknown. Further research is urgently needed.

Adult↗
PubMed1988

Physical versus pharmacological counter-measures. Studies on febrile rabbits.

128 experiments were carried out on febrile rabbits at air temperatures of 8, 18, 24 and 30 degrees C in order to analyze the thermoregulatory effects and mechanisms of physical and/or pharmacological counter-measures. Fever was achieved by injection of 0.1 micrograms Salmonella typhi endotoxin (LPS)/kg into an ear vein. As the pharmacological counter-measure, injections of acetylsalicylic acid (ASA) into an ear vein were chosen. For the physical counter-measure, cooling thermodes (5 degrees C) were constructed for the abdominal skin, for the ear and for the rectum. ASA injections had no effect on the first fever maximum, even if applied 20 to 60 min before the LPS injection, but eliminated the second fever maximum. Of course, the additional hyperthermia observed at 30 degrees C ambient temperature could not be eliminated by the injections. On the other hand, cooling procedures can obviously not affect the pyrogen-induced temperature increase, but reduce the hyperthermic effect of a higher ambient temperature. Rectal cooling was more effective than ear or abdominal skin cooling. Abdominal cooling evoked an increase in metabolic heat production. Application of combined physical and pharmacological counter-measures achieved the strongest and quickest reduction of the second maximum, whereas the first maximum was not affected, as in all other experiments. The study emphasizes the necessity of taking into account the time course of the effector mechanisms in order to discriminate between hyperthermic and febrile components of temperature increase. In the initial phase cooling measures would evoke unwanted regulatory responses of the effectors, whereas during the second febrile maximum they would achieve a quicker reduction of core temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The role of the actin status in platelet behaviour.

The status of platelet actin has been studied analytically by the DNase-I inhibition assay. Exposure of platelets to diamide, which oxidizes sulphydryl groups, results in an increase of filamentous actin. Neutralization of the effect of diamide by addition of 2-mercaptopropionylglycine (2-MPG) or washing out the excess of diamide is associated with a normalization of the cellular actin status. These findings strongly suggest that the redox state of platelets is somehow involved in the process of actin polymerization. Alterations of the redox state in metabolically altered platelets could therefore account for changes in the G- to F-actin equilibrium. In the thrombin-induced actin polymerization the redox state of the cell seems to be not involved, since 2-MPG preincubation of platelets (1.25 mM, 30 min) does not inhibit the filament assembly.

Actins↗
PubMedDate not supplied

Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment.

Chemotherapy- and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses. The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. The prophylactic and therapeutic armamentarium for the treatment of oral mucositis consists of locally and systemically applied nonpharmacological measures and pharmacotherapeutics.

Antineoplastic Agents↗
PubMedDate not supplied

Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: results of a phase II trial.

Various cytokine combinations have been tested for efficacy in the treatment of metastatic renal cell carcinoma (MRCC). Because several immunologic synergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was conducted on the efficacy and toxicity of subcutaneous, sequentially administered, interferon-gamma (IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC were treated with 100 microg recombinant IFNgamma1b administered thrice weekly during weeks 1 and 4, followed by 400 microg GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated every 8 weeks. Five (10%) of patients experienced an objective response (complete response [CR]: 2%, partial response [PR]: 8%). Fourteen (26%) patients had stable disease with a median duration of 19 months (6-47+). The median overall survival was 12 months (range: 0.3-44 months). No toxicity greater than World Health Organization grade II was observed, with fever (43%) and erythema (43%) being the most frequent side effects. Compared with other phase II trials with IFN-gamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.

Adult↗