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Biomedical subjects

D Ukena

Publications and source records attributed to D Ukena.

At least 55 records · Page 3Linked to original sources
PubMed1996

A palliative accelerated irradiation regimen (PAIR) for advanced non-small-cell lung cancer (NSCLC).

In order to avoid overtreatment in advanced NSCLC we developed a palliative accelerated irradiation regimen (PAIR) applying a total dose of 32 Gy in 10 days with two daily fractions of 2 Gy. This paper reports on a 1-year pilot study carried out in preparation of a randomised trial. Data for the 34 patients receiving PAIR were compared to 179 conventionally irradiated historical controls selected from a pre-existing database according to identical inclusion criteria. Statistical analysis showed that PAIR patients had a significantly longer survival than controls (P = 0.0029). Median survival was 11.8 and 5.8 months, respectively, while 1-year survival was 45.6% vs. 21.2%. Compared to the subgroup of controls who had received the full planned dose of 60 Gy (n = 104) PAIR patients showed no significant difference in survival. In order to adjust for possible imbalances we used a comprehensive blinded prognostic rating design creating one score value per patient out of several known prognostic factors. After adjustment for the resulting prognostic score by means of the Cox proportional hazards model PAIR patients still showed significantly longer survival. We conclude that in advanced NSCLC survival after a palliative short-term regimen appears to be at least equivalent to that following conventional high-dose irradiation.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial.

Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug's pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound: therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.

Administration, Oral↗
PubMed1995

Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction.

Zardaverine is a selective inhibitor of phosphodiesterase (PDE) III and IV isozymes. It has been shown to exert potent bronchodilator effects in animals. In order to study the efficacy and safety in man, a phase II clinical trial in 10 patients with partially reversible chronic airflow obstruction was carried out. The trial was designed as a double-blind, randomized, five-period change-over study. Zardaverine (at single doses of 1.5 mg, 3.0 mg, or 6.0 mg), salbutamol (0.3 mg) and placebo were administered by metered dose inhaler on separate days. As evaluated by spirometry over a time period of 4 h, salbutamol induced a significant bronchodilatation. In contrast, zardaverine did not improve airway function in these patients. Unwanted effects of the study medication were not observed.

Aged↗
PubMed1995

[18FDG in the primary staging of lung tumors. Results with a gamma camera and a 511 keV collimator].

The diagnosis of primary lung tumors requires a precise staging according to the TNM classification. In contrast to established imaging methods 18FDG describes the functional metabolic processes in the tumor tissue due to increased glycolysis. This paper describes the use of 18FDG in the primary staging of lung tumors and metastases. 44 patients were studied with a gamma camera and a 511 keV collimator. In comparison to pulmonary tumors and metastases detected by other imaging methods (107) the accumulation of 18FDG has a sensitivity of 85%, in lesions verified by histology (50) of 89%, in primary tumors (35) of 100% and in metastases (63) of 76%. As an alternative to FDG PET studies, primary staging of lung tumors is possible with a gamma camera, suitable for ECT and fitted with a 511 keV collimator.

Adult↗
PubMed1995

[Tumor markers as prognostic factors in non-small-cell bronchial carcinoma].

PURPOSE: Considerations of different therapeutic approaches require a realistic estimation of the prognosis. The usefulness of tumor markers as prognostic indicators was evaluated by means of a multivariate analysis. PATIENTS AND METHODS: The data of 300 patients who had been irradiated for their primary tumor were analysed retrospectively. The serum concentrations of CEA, SCCA, NSE, and LDH were available before treatment and 3 months thereafter in a sufficient number of cases. The prognostic factors for survival and progression-free survival resulting from univariate tests were further evaluated by a Cox-proportional-hazards model. RESULTS: The serum levels of the particular tumor markers were pathologically elevated in 25 to 36.5% of the cases. Their values correlated with the stage of the disease and separately the N-stage too. A normalization of increased marker levels after irradiation occurred in 37.5 to 67% of the cases. Survival of patients with increased pretherapeutic values of CEA, SCCA, and LDH was significantly worse compared to those with normal values. In the case of a post-therapeutic return to normal levels, prognosis was significantly better than for those where the elevation persisted. However, after inclusion of all other parameters in multivariate analysis the tumor markers were meaningless. Karnofsky-performance status, total dose of radiotherapy, stage of the disease, and weight-loss evolved as independent prognostic factors for survival. For progression-free survival only stage of the disease was important. All subgroup analyses (restriction on patients with favorable prognosis) showed the same results. CONCLUSIONS: A prognostic importance of NSE could not be demonstrated. CEA, SCCA, and LDH were univariate predictors for survival and progression-free survival. But they proved to be dependent on the stage of the disease and were not confirmed as independent variables in the Cox-model. Their importance during the follow-up is diminished by the frequent lack of therapeutic approaches in the case of disease progression. Certainly a more favorable prognosis in case of a post-therapeutic normalization of previously elevated values was found.

Biomarkers, Tumor↗
PubMed1994

Prevention of chemotherapy-induced nausea and vomiting by tropisetron (Navoban) alone or in combination with other antiemetic agents.

We report an open, three-armed, multicenter study being carried out to assess the optimum treatment for acute and delayed emesis and nausea in patients undergoing highly emetogenic chemotherapy. Eighty-seven patients were randomized to receive tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), tropisetron plus dexamethasone, or tropisetron plus metoclopramide during chemotherapy. Tropisetron in combination with dexamethasone produced the best control of both acute and delayed emesis. Acute vomiting was prevented in 69% of patients by tropisetron monotherapy, and the addition of dexamethasone significantly increased the total control of vomiting to 92% (P < .01). Similarly for delayed vomiting, total control of emesis was seen in approximately 70% of patients on tropisetron alone during days 2 and 3; this control rate increased to almost 90% with combined tropisetron/ dexamethasone treatment. In all patients receiving cisplatin, the tropisetron/dexamethasone combination produced total control of acute emesis. The tropisetron and dexamethasone combination also provided the best control of acute and delayed nausea. Tropisetron produced total control of acute nausea in 69% of patients. The addition of dexamethasone increased this control rate to 81%. Similarly for delayed nausea, on days 2 and 3 of treatment, dexamethasone plus tropisetron provided total control of nausea in more than 80% of patients compared with a control rate of more than 60% achieved using tropisetron. The combination of tropisetron and metoclopramide did not improve significantly on the control of nausea and vomiting achieved using tropisetron alone. Evaluation of quality of life events by patients indicated no appreciable change in their mental or physical condition during chemotherapy, irrespective of antiemetic therapy. In the tropisetron and tropisetron plus metoclopramide treatment groups, a decreased food intake was observed due to delayed nausea while the addition of dexamethasone prevented loss of appetite. The antiemetic treatments were similarly well tolerated. The most common adverse events were constipation (15%) and tiredness (7%).

Adult↗
PubMed1993

Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes.

The pharmacological actions of methylxanthines such as theophylline and caffeine may be due to blockade of adenosine receptors and/or inhibition of phosphodiesterase (PDE) activities. In the last years, potent xanthines have been developed that display some selectivity for A1 and A2 adenosine receptors. Little is known about the PDE inhibitory potency of these xanthines. The aim of the present study was to determine the potencies of A1 and A2 receptor selective xanthines as inhibitors of several PDE isozymes, the PDE I-V subtypes. The IC50 values of 8-phenyl- and 8-cycloalkyl-1,3-dialkylxanthines for inhibition of PDE isozymes from different sources are up to 10,000-fold higher than their antagonistic potencies at adenosine receptors. However, the A1 receptor selective antagonists 1,3-diethyl-8-phenylxanthine and 1,3-dipropyl-8-cyclopentylxanthine are comparatively potent inhibitors of PDE IV activity with IC50 values in the 10 microM range and are, therefore, nearly as potent as the PDE IV selective inhibitor, rolipram. The A2 receptor selective 1,3-dipropyl-7-methylxanthine is about 10-300-fold more potent as an adenosine receptor antagonist than as a PDE inhibitor. The results indicate that some of these novel xanthines can be used as selective adenosine receptor antagonists without interference due to inhibitory effects on PDEs.

1-Methyl-3-isobutylxanthine↗
PubMed1993

The muscarinic M1-receptor-selective antagonist, telenzepine, had no bronchodilatory effects in COPD patients.

In a double-blind, placebo-controlled, randomized, cross-over trial, we studied the effects of the muscarinic M1-receptor-selective antagonist (+/-)-telenzepine (3 mg orally at 6 p.m. for 5 days) in 21 patients with chronic obstructive pulmonary disease (COPD). At enrollment all patients showed at least a 50% decrease in airway resistance (Raw) after inhalation of 400 micrograms fenoterol or 200 micrograms oxitropium bromide. Telenzepine did not have a significant effect on forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Also, no significant changes could be detected in daily spirometric profiles or Raw. The results indicate that short-term treatment with the M1-selective antagonist, telenzepine, does not improve airway function in COPD patients, at least after administration by the oral route.

Airway Resistance↗
PubMed1991

Zardaverine as a selective inhibitor of phosphodiesterase isozymes.

The pyridazinone derivative zardaverine has recently been introduced as a potent bronchodilator in vivo and in vitro. In addition, zardaverine exerts a positive inotropic action on heart muscle in vitro. The actions of zardaverine are thought to be mediated via inhibition of phosphodiesterase (PDE) activity. Recent data suggest that there are multiple forms of phosphodiesterases and at least five different isozyme families are now recognized. In the present study, the effects of zardaverine on the different PDE isozymes were investigated in several tissues. PDE isozymes were separated by chromatography on Q-sepharose. Zardaverine inhibited the cyclic GMP-inhibitable PDE III from human platelets and the rolipram-inhibitable PDE IV from canine trachea and human polymorphonuclear (PMN) cells with IC50-values of 0.58, 0.79 and 0.17 microM, respectively. The pyridazinone derivative affected the calmodulin-stimulated PDE I, the cyclic GMP-stimulated PDE II and the cyclic GMP-specific PDE V only marginally at concentrations up to 100 microM. Zardaverine inhibits the ADP-induced aggregation of human platelets with an IC50 of 1.6 microM. This inhibition was synergistically increased by activators of adenylate cyclase such as PGE1 and forskolin. In human PMN cells, zardaverine inhibited the zymosan-induced superoxide anion generation with an IC50 of 0.40 microM. Again, this effect was increased by activators of adenylate cyclase. These data clearly demonstrate that zardaverine is a selective inhibitor of PDE III and PDE IV isozymes.

Animals↗