[The psychosomatic correlations in bronchial asthma].

Combination of somatic symptoms with neurotic manifestations and personality's disturbances in clinical picture of bronchial asthma was established during clinical and psychological observation of 89 patients with bronchial asthma. It was shown that increase of the number of frustrating situations (when psychical vulnerability was elevated), strengthening of both anxiety and emotional tension, as well as rigidity of negative emotions, hypochondriac and anxious-depressive tendencies composed the whole correlational system with alterations in functions of external respiration, changes in blood immunoglobulins levels just as with clinical indices of bronchial asthma. This system represented different levels of psychosomatic correlations' regulation.

Individualized dosing of amonafide based on a pharmacodynamic model incorporating acetylator phenotype and gender.

Amonafide is extensively metabolized, including conversion by N-acetylation to an active metabolite. Our previous studies have shown that fast acetylators of amonafide have increased toxicity, and we have recommended doses of 250 and 375 mg m-2 day-1 for 5 days, for fast and slow acetylators, respectively. Despite phenotype-specific dosing, significant variability in leukopenia persisted.

Pharmacokinetics and pharmacodynamics of oltipraz as a chemopreventive agent.

Oral oltipraz, as a single-dose treatment, was evaluated as a chemopreventive agent in 31 normal subjects. In a subset of subjects, the relationship between plasma oltipraz concentrations and the induction of lymphocyte glutathione (GSH) and glutathione S-transferase (GST) enzyme levels was evaluated. Pharmacokinetic analysis revealed nonlinear disposition of oltipraz with disproportionate 40-fold increase and 9.

Phase I and pharmacokinetic study of a new antineoplastic agent: pyrazine diazohydroxide (NSC 361456).

Pyrazine diazohydroxide (PZDH) is a novel antineoplastic agent that appears to form DNA adducts via the reactive pyrazine diazonium ion and produces substantial antitumor activity in preclinical models. We conducted a phase I trial to determine the maximally tolerated dose of PZDH that could be administered as a 5-min i.v.

5-Fluorouracil, hydroxyurea and escalating doses of iododeoxyuridine with concomitant radiotherapy for malignant gliomas: a clinical and pharmacologic analysis.

Background: Iododeoxyuridine (IUdR) is a known radiation enhancer, and interacts biochemically with 5-fluorouracil (5-FU) and hydroxyurea (HU).

Patients And Methods: IUdR was added to the previously studied regimen of continuous infusion 5-FU at 300 mg/m2/day for 5 days, HU 500 mg every 12 hours for 11 doses and radiotherapy 200 cGy/day for 5 days, all administered for 7 consecutive weeks to patients with malignant glioma. IUdR was administered as 5-day continuous intravenous infusion during weeks 1 and 4.

Phase I study of amonafide dosing based on acetylator phenotype.

Amonafide is extensively metabolized, including N-acetylation to an active metabolite. Prior studies have demonstrated that patients who are fast acetylators of amonafide (and other drugs) have increased toxicity at standard doses of amonafide. The primary objective of this study was to define the recommended phase II dose of amonafide separately for slow and fast acetylators.

Phase I clinical and pharmacological study of iododeoxyuridine and bleomycin in patients with advanced cancer.

Studies previously performed in our laboratory demonstrated synergistic cytotoxicity and DNA strand break formation in human tumor cells following exposure to a combination of bromodeoxyuridine and bleomycin. Synergy was evident when bromodeoxyuridine was administered prior to or simultaneously with bleomycin and occurred over a wide range of concentration ratios. We therefore undertook a phase I clinical trial of the combination of iododeoxyuridine (IdUrd) and bleomycin to determine the maximally tolerated dose of IdUrd that could be administered with a standard dose of bleomycin and to determine the toxicities of the combination.

Paradoxical relationship between acetylator phenotype and amonafide toxicity.

Patients receiving the investigational antineoplastic agent amonafide underwent prospective determination of acetylator phenotype with use of caffeine as a test drug. Fast acetylators of caffeine had significantly greater toxicity (myelosuppression) after amonafide treatment than slow acetylators, presumably because of greater conversion of amonafide to the active acetylated metabolite. Furthermore, the estimated area under the plasma concentration-time curve of amonafide was significantly greater in the fast acetylators, indicating that the total plasma clearance was paradoxically lower in this group.

Pharmacologically based dosing of etoposide: a means of safely increasing dose intensity.

We have previously demonstrated that individualized dosing of etoposide (VP16) by 72-hour infusion is feasible and that the extent of leukopenia is a function of plasma concentration, pretreatment WBC (WBCp), albumin (ALB), performance status (PS), and bone marrow function (based on transfusion requirements). In the current study, 45 patients were randomized between a fixed dose of VP16 (125 mg/m2/d) versus individualized dosing to a target WBC nadir (WBCN) of 1,700/microL. The total dose was increased by an average of 22% in the latter patients (459 +/- 130 mg/m2 v 375 mg/m2, P = .

[Biochemical polymorphic systems and psychological characteristics in residents of the Soviet North-East].

15 biochemical polymorphic systems (AcP, PGM, GPT, GLO-1, EsD, PGP, Pp, AK, Gc, Hp, Tf, BO, MN, Le, P) were comparatively studied which possess psychodiagnostic features investigated by means of all-round personality study and 16-factors Kettle personality inventory in 340 healthy residents of Magadan. With the aid of computer cluster analysis, psychodiagnostic features were revealed which authentically differentiate clusters consisting of 5 combined polymorphic systems, three of them being different. Frequency of particular loci participation in differentiation of persons for psychodiagnostic tests is well-coordinated with a degree of their participation in genotype differentiation in those who left and remained in the region.

[Psychophysiological correlations in paroxysmal forms of cardiac rhythm disorders].

Fifty-two patients with paroxysmal disorders of cardiac rhythm were under observation for periods of 6 months to 3 years. Paroxysmal supraventricular tachycardia was registered in 16, ventricular tachycardia in one, paroxysmal cardiac fibrillation in 35. The method of comprehensive examination of personality (modified MMPI test, Cattell's and Hekhausen's tests) made it possible to reveal certain characteristic features of the personality and the actual psychic condition of all patients.

[Clinical pharmacokinetics of azabutyron, a new short-term action neuroleptic].

Pharmacokinetics of azabutyron--a new Soviet-made neuroleptic was studied clinically without anesthesia and also during surgery against the background of deep and surface fluorothan anesthesia in conjunction with artificial nitrous oxide and oxygen ventilation of the lungs (2:1). After intravenous administration of the drug in a dose of 4 mg/kg its maximum concentration (about 8 gamma/ml) was recorded in 5 minutes and the amount eliminated during 2 hours of observation comprised 1--2 per cent of the dose introduced. In practically healthy individuals with no anesthesia the pharmacokinetics of azabutyron lies within the limits of a bicompartment pharmacokinetics model, while surface anesthesia, blood loss changes the pharmacokinetics of the drug to such an extent that is has to be described from the standpoint of the unicompartment model system.