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At least 1,423 records · Page 79Linked to original sources
PubMed1989

[Topographical differences in cellular DNA content between the radial growth phase and the vertical growth phase of superficial spreading melanoma].

The nuclear DNA content of tumor cells was measured during the radial growth (RGP) and vertical growth (VGP) phases of three cases of superficial spreading melanoma. To compare these two phases, the DNA distribution histogram was analyzed and the DNA index was calculated. A aneuploid population appeared histographically in all specimens of VGP; however, no such abnormal population could be detected in RGP. VGP cells contained greater numbers of polyploid cells and had a higher DNA index value than RGP cells in all cases. These findings support Clark's postulation that the appearance of a new clonal cell population contributes to the development of VGP from RGP in malignant melanoma.

Adult↗
PubMed1989

[Solid phase clean up and determination of theophylline in plasma by reversed phase high performance liquid chromatography].

Theophylline is the drug of choice in the prevention and treatment of asthmatic symptoms. A plasma sample clean up procedure using alumina solid phase to eliminate the interference of plasma impurities and some other drugs and a RP-HPLC method to determine plasma theophylline concentration were developed. The system used a Zorbax-C18 (5 microns) column. The mobile phase consists of a mixture of methanol and sodium acetate (50:50) buffer (pH 3.0). Detection at a wavelength of 254 nm showed no interfering peaks. Caffeine was used as an internal standard. The clean up procedure is simple, rapid and satisfactory. The detection limit of theophylline is 0.2 ng (R/N, 3:1), the minimal detectable concentration of theophylline in plasma is 20 ng/ml. Calibration curve is linear (r = 0.9995) in the concentration range of 4 micrograms/ml to 30/micrograms/ml. Within-day precision and day-to-day precision (CV) were 1.89% and 2.41% respectively. The average recovery of the method is 98.44 +/- 0.89%.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

The pharmacokinetics of all-trans-retinoic acid and N-(2-hydroxyethyl)retinamide in mice as determined with a sensitive and convenient procedure. Solid-phase extraction and reverse-phase high performance liquid chromatography.

An improved method for the analysis of retinoids in mouse plasma allows quantification of all-trans-retinoic acid (RA) and N-(2-hydroxyethyl)retinamide (NHERA) in amounts as low as 2 ng/ml (7 X 10(-9) M), the approximate endogenous concentration of RA. The procedure, involving solid-phase extraction and reverse-phase HPLC, can be used for rapid processing of large numbers of samples. With this procedure, we have determined the terminal half-life for RA (0.5 hr) and have confirmed the half-life for NHERA (3.6 hr) in the plasma of mice dosed orally. We have also noted that the serum content of retinol is temporarily reduced following dosing with RA, but not with NHERA.

Animals↗
PubMed1988

Solid-phase extraction and ion-pair reversed-phase HPLC of isometamidium in bovine serum and tissues.

An analytical method has been developed for the determination of isometamidium in bovine serum and tissues. Samples were enzymatically hydrolysed and cleaned up on a solid-phase system (C8 Bond Elut column). The drug was chromatographed by an ion-pair reversed-phase technique using heptane sulphonate as a pairing-ion and triethylamine as a counter-ion reagent. Detection was by fluorescence at 593 nm (excitation = 380 nm). The method is more sensitive and specific than existing methods and it is currently being used in evaluating the pharmacokinetics of isometamidium in cattle.

Animals↗
PubMedDate not supplied

Determination of vitamin D3 in liquid multivitamin preparation, using reverse phase, solid phase extraction liquid chromatography.

A method is described for the determination of vitamin D3 in a liquid multivitamin preparation by liquid chromatography. Samples are purified on a disposable reverse phase extraction (SPE) column with a mobile phase of methanol-2-propanol (97 + 3) and are analyzed on a Zorbax ODS (5 micron) column with an acetonitrile-2-propanol-water (90 + 8 + 2) solvent system. Vitamin D3 is completely resolved from other interfering compounds within approximately 21 min and is detected with a UV detector at 254 nm. A mean of 98.5% of theory with a coefficient of variation of 3.8% was found for determination of vitamin D3 in a commercial preparation.

Cholecalciferol↗
PubMed1986

Characterization of outer membrane proteins of virulent phase I Shigella sonnei strains and their avirulent phase I derivatives.

Comparison of polyacrylamide gel electrophoretic protein profiles of four isogenic sets of virulent phase I Sh. sonnei strains and their avirulent phase I cells revealed no differences in outer membrane protein composition between virulent and avirulent derivatives. However, significant qualitative and quantitative differences were found in composition of major outer membrane proteins between strains of different origin. All four strains tested contained one major protein of 33K. This protein was susceptible to proteolytic enzymes and was found to be heat modifiable. Other major proteins of 35K and 37K present in three strains and 36K present in one strain were identified as peptidoglycan associated proteins.

Bacterial Outer Membrane Proteins↗
PubMed1987

Phase 3 and phase 4 block of the accessory pathway in Wolff-Parkinson-White syndrome--a case report.

A 12-year-old girl presented with recurrent episodes of supraventricular tachycardia. A 12 lead electrocardiogram showed normal sinus rhythm with a normal PR interval and no evidence of preexcitation. A 24 h Holter monitor showed intermittent preexcitation. Both phase 3 and phase 4 block in the accessory pathway were demonstrated with introduction of atrial extrastimuli during sinus rhythm at electrophysiology study. However, Holter recording failed to reveal a consistent relationship between coupling intervals and accessory pathway conduction. The discrepancy between the Holter monitor and the electrophysiologic study can be explained by variability of factors such as autonomic tone during the Holter recording. This case illustrates a potential mechanism for intermittent preexcitation in the Wolff-Parkinson-White syndrome.

Bradycardia↗
PubMed1986

[Phase I study of 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). Phase I Study Group].

A phase I study on TA-077, a water-soluble nitrosourea, was performed by a 9-institution clinical group using 89 patients with various malignant tumors. The study consisted of single-dose i.v. administration and daily i.v. administration for 3-6 consecutive days. The dose-limiting factor was delayed leukopenia and thrombocytopenia which reached nadirs about 5 weeks and about 4 weeks after the initiation of administration and recovered in 2 to 3 weeks, respectively. Gastrointestinal toxicity, such as nausea, vomiting and anorexia, appeared in the early stage of treatment, although most of these symptoms were mild or moderate. Other side effects, including transient liver and renal dysfunctions observed in a few cases, were mild and appeared not to be dose-dependent. M.T.D. in single administration was considered to be more than 3,000 mg/m2 and M.T.D. in 5-day consecutive administration was considered to be 1,000 mg/m2/day. The recommended dose schedule for initiation of the phase II study was assumed to be 700 to 900 mg/m2/day for 5 consecutive days.

Antineoplastic Agents↗
PubMed1979

Novel 125I-labeled nortriptyline derivatives and their use in liquid-phase or magnetizable solid-phase second-antibody radioimmunoassays.

Nortriptyline derivatives prepared by reaction with fluorescein isothiocyanate or conjugation to N-acetyl-L-histidine were radioiodinated and the products purified with Sephadex LH-20 columns to obtain two novel nortriptyline radioligands. Antisera were raised in rabbits by immunization with nortriptyline conjugated to succinylated ovine albumin. By use of the iodinated fluorescein derivative we developed a liquid-phase second-antibody radioimmunoassay that gives results correlating closely (r = 0.98) with those by an established radioimmunoassay of similar specificity in the assay of apparent total amitriptyline and its metabolite nortriptyline in serum or plasma from patients being treated with these drugs. With the iodinated N-acetyl-L-histidine derivative we developed a magnetizable solid-phase second-antibody radioimmunoassay. The cross reactivities of amitriptyline and nortriptyline could be made equal by performing the assay at pH 9.0, which makes it possible to measure true total active drug concentrations in patients receiving amitriptyline.

Amitriptyline↗
PubMed1982

Phase I-phase II trial of N-phosphonacetyl-L-aspartic acid given by intravenous infusion and 5-fluorouracil given by bolus injection.

A phase I clinical trial of N-phosphonacetyl-L-aspartic acid (PALA) and 5-fluorouracil (FUra) was performed on 30 patients. PALA was given as a 15-minute iv infusion once daily for 5 days, and FUra was given as a bolus injection on days 2, 3, 4, and 5. Cycles of treatment were repeated every 3 weeks. Dose-limiting toxicity was manifested by stomatitis and diarrhea. Skin rash was observed also but was not dose limiting. No consistent hematopoietic or renal toxicity was observed. Seventeen patients with disseminated metastatic melanoma and measurable disease were evaluated for response. One partial response was seen; however, the response was associated with significant toxicity, and the treatment could not be repeated. Stable disease was observed in 3 patients with melanoma, 1 patient with colon carcinoma, and 1 patient with ovarian carcinoma. Our findings suggest that the clinical activity of PALA and FUra given according to the above schedule for melanoma is less than 25% (P less than 0.05). Pharmacokinetic studies of FUra revealed no consistent effect of PALA pretreatment on FUra disappearance in plasma. The mean FUra elimination half-line in plasma was 7.11 +/- 0.84 minutes (SEM), which is no different from that reported for FUra alone. The recommended doses on this schedule for phase II studies are 1,000 mg PALA/m2/day iv daily for 5 days and 200 mg FUra/m2/day iv on days 2, 3, 4, and 5.

Adult↗
PubMed1980

Outer membrane proteins of Shigella sonnei. I. Characterization of phase I, phase II and R-form Shigella sonnei.

The cell envelope of Shigella sonnei phase I, phase II and R-form was fractionated inot outer and cytoplasmic membrane components by means of sucrose density gradient centrifugation. The protein composition of the outer membrane has been analyzed by SDS-polyacrylamide gel electrophoresis. The outer membrane preparations contained 15-17 proteins. The major proteins of the outer membrane were of apparent molecular weights: 27,000, 28,000 and 31,000. Their amount varied depending on the structural defects of lipopolysaccharide.

Bacterial Proteins↗
PubMedDate not supplied

Phase I and preliminary phase II observations of high-dose intermittent 6-thioguanine.

6-Thioguanine was administered iv or orally to 66 patients on an intermittent schedule, one dose every 3 weeks. Doses were gradually escalated until moderate toxicity was observed. The dose-limiting toxic effects were myelosuppression and azotemia. The recommended starting doses for phase II or III studies were 700 mg/m2 iv and 1400 mg/m2 orally. Nephrotoxicity and myelosuppression were reversible in all clearly drug-related instances. Myelosuppression was transient, with nadir blood cell counts observed 10-14 days after drug administration. No cumulative toxicity was observed. Antitumor responses were observed in five of 21 evaluable patients with metastatic colorectal carcinoma including two of four previously untreated patients with that disease. Other than a transient response in a patient with endometrial carcinoma, who received her drug orally, all other responses were observed in patients treated iv with 6-thioguanine. Further phase II trials, particularly in colorectal carcinoma, are recommended.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Analysis of phase I and phase II metabolites of tamoxifen in breast cancer patients.

This study describes the application of LC/MS/MS to the determination of phase I and phase II metabolites of tamoxifen in urine and plasma samples of breast cancer patients. In the plasma extracts, in addition to the parent drug and N-desmethyltamoxifen, a minor metabolite tamoxifen N-oxide was identified for the first time in human. Four intact glucuronides of tamoxifen metabolites were isolated in the 24-hr posttreatment urine sample. They were the glucuronides of 4-hydroxytamoxifen, 4-hydroxy-N-desmethyltamoxifen, dihydroxytamoxifen, and a monohydroxy-N-desmethyltamoxifen. Hydroxylation followed by glucuronidation is a well-established metabolic route of tamoxifen, and this study describes for the first time direct analyses of these metabolites in human urine samples using on-line LC tandem MS.

Breast Neoplasms↗
PubMed1993

Clinical measurement of serum amiodarone and desethylamiodarone by using solid-phase extraction followed by HPLC with a high-carbon reversed-phase column.

We describe a rapid, simple HPLC method routinely used in our clinical laboratory for determining amiodarone and its metabolite desethylamiodarone. These compounds are released from serum proteins by pretreatment with an acidic solution and then extracted onto a C2 reversed-phase clean-up column. After elution from the extraction column, the compounds are separated and quantified by HPLC with a C18 reversed-phase column and spectrophotometric detection. The standard curves for the drug and metabolite are linear up to 20.0 mg/L, with a lower limit of detection of 0.16 mg/L. The CVs for intra-assay precision were 5.0% at 0.58 mg/L and 2.9% at 5.96 mg/L; for inter-assay precision, they were 9.6% at 0.52 mg/L and 6.1% at 2.09 mg/L. Lipemia, hemoglobin, and bilirubin up to 300 mg/L do not interfere with this assay. None of > 550 cardiac patients' samples tested contained a compound that interferes with this assay.

Amiodarone↗
PubMed1996

[Sessions of a cardiac rehabilitation program in coronary disease--the hospital phase (phase I)].

Cardiac rehabilitation is nowadays an integral part of global treatment of the coronary disease. It has the goals to restore a cardiac patient to the maximum level of physical, mental and social condition, so that to achieve the best possible sociofamilial reintegration, and of secondary prevention. The cardiac rehabilitation programs integrate three major components: physical exercise, risk factor control and psychosocial intervention. They start during the period of hospitalization (Phase I), after medical stabilization. In this initial phase the aims are: risk factor education and motivation for healthier life-styles, psychological support, and physical training for early ambulation and self-care, for preventing the deleterious physiological effects of immobilization and for progressive reconditioning.

Coronary Disease↗
PubMed1996

[A case report of a left bronchial stump fistula from which the wrapped omentum was removed, because of rupture of the anastomotic aneurysm of the descending thoracic aorta--functions of the wrapped omentum in the early phase and extended phase after surgery].

The omental wrapping is a method of the choice for empyema with bronchopleural fistula. A 71-year-old woman, who had undergone graft replacement for the aneurysm of the descending thoracic aorta, underwent left pneumonectomy for lung abscess. Two months after surgery, the bronchopleural fistula in the stump was presented and successfully repaired by omentopexy. When anastomotic aneurysm rupture of the graft was presented one year later, the management was successful because mortal bleeding was prevented by the omental pedicle flap in the left thoracic cavity. Though we removed the omental flap with hematoma, the fistula didn't recurred. The omentum facilitates the healing of bronchopleural fistula in the early phase after surgery, but the healing course in the extended phase had not have any trouble without omental vascularization.

Aged↗
PubMed1997

Elucidation of phase I and phase II metabolic pathways of rhein: species differences and their potential relevance.

Because of previously observed species differences in rhein tolerability, with rabbits being very susceptible to kidney disturbances, in vivo and in vitro biotransformation studies were performed to find out whether the differences in the undesired effects of rhein are associated with qualitative, species-dependent differences in its metabolism. First hints on species-dependent biotransformation profiles were obtained from in vivo experiments with 14C-labeled rhein in rat, rabbit, dog, and man. TLC-analysis of urine samples obtained after oral administration of 14C-rhein to rabbits revealed an additional, hydrophilic metabolite fraction in rabbit urine as compared with dog and human urine, all of which contain phenolic monoglucuronide and monosulfate as major metabolites. An investigation of urine samples (obtained from dogs, rabbits, rats, and human volunteers after oral application of unlabeled rhein) was conducted by means of mass spectrometric tandem techniques including on-line HPLC-MS/MS. In vitro experiments with subcellular liver fractions of rats and rabbits revealed the presence of three monohydroxylated metabolites of rhein, their quinoid oxidation products, and a bishydroxylated derivative of rhein. The hydroxylated phase I metabolites were detected as glucuronides in urine samples of all investigated species, whereas the quinoid product was present only in rabbit urine. Moreover, two regioisomeric phenolic glucuronides and sulfates or glucosides of rhein were found as major phase II metabolites in urine of all species. Furthermore, acyl glucuronides of rhein and monohydroxylated rhein and their respective isomeric acyl migration products were identified in human urine. In rabbit urine we discovered different bisglucuronides (bisphenolic glucuronide, mixed ether/ ester glucuronides), whereas in rats only the bisether/ether glucuronide was present. In addition, the investigations of dog and human urine showed the formation of two regioisomeric phenolic glucosides. With respect to a potential reactivity with endogenous macromolecules the quinoid metabolites as well as the bisester/ether glucuronides appear most relevant.

Animals↗