Search PubMed⌕ Search

Biomedical subjects

G Batist

Publications and source records attributed to G Batist.

107 records · Page 6Linked to original sources
PubMed1985

A phase I and pharmacokinetic study of dihydro-5-azacytidine (NSC 264880).

5,6-Dihydro-5-azacytidine (DHAC; NSC 264880) is an analogue of 5-azacytidine that does not possess the hydrolytically unstable 5,6-imino bond of the parent compound. Thus, unlike 5-azacytidine, DHAC is stable in aqueous solution and may be administered by prolonged i.v. infusion, potentially avoiding acute toxicities associated with bolus administration of 5-azacytidine. In this study, patients with advanced cancer were treated with DHAC administered as a 24-h constant i.v. infusion every 28 days. Treatment began at a dose of 1 g/sq m and was escalated to the maximum-tolerated dose of 7 g/sq m, where the limiting toxicity was pleuritic chest pain. Other toxicities included nausea and vomiting, which were not limiting. There was no evidence for myelosuppression, nephrotoxicity, or hepatotoxicity. DHAC was measured in plasma, urine, and ascites by a sensitive and specific reverse-phase high-performance liquid chromatography assay capable of detecting 50 ng of drug per ml. Steady-state plasma levels were achieved with 8 h and ranged from 10.0 to 20.5 micrograms of DHAC per ml at the maximum-tolerated dose. Total-body clearance of 311 +/- 76 ml/min/sq m and postinfusion half-lives between 1 and 2 h were observed. Between 8 and 20% of the administered dose was excreted unchanged in urine. While ascites DHAC levels in a patient with ovarian cancer were comparable to plasma levels, postinfusion elimination was slower from this compartment than from plasma. No correlation was observed between DHAC plasma levels and duration or intensity of dose-limiting pleuritic chest pain. One patient with progressive Hodgkin's lymphoma demonstrated stabilization of disease for seven treatment cycles, and two patients with aggressive lymphoma demonstrated dramatic, although transient, disease responses. A dose of 7 g/sq m is recommended for Phase II trials of DHAC using this schedule.

Adult↗
PubMed1985

Cardiac and red blood cell glutathione peroxidase: results of a prospective randomized trial in patients on total parenteral nutrition.

Oxygen derived free radicals and peroxides result from many antitumor treatments, including radiation and anthracyclines. Doxorubicin cardiotoxicity is thought to result from free radical induced lipid peroxidation. The heart has less active detoxification enzymes than does the liver and depends on selenium dependent glutathione peroxidase (GSH-PX) for this function. We did a sequential prospective trial in patients with totally controlled parenteral diets to examine the activity of red blood cell GSH-PX in patients with and without malignant disease. Decreased GSH-PX activity was found in 54% of the patients on parenteral nutrition and was more common in the older of these patients and in those with the greatest weight loss. In the absence of selenium supplementation, the RBC GSH-PX activity declines steadily, but with supplementation this was prevented or reversed. Because selenium deficiency can manifest as a cardiomyopathy, we measured the enzyme activity in the hearts of five patients who had died. The cardiac enzyme activity correlated strongly with the RBC levels. Significantly decreased GSH-PX has been shown in animals to be associated with changes in other enzymes critical both to activation and detoxification of carcinogens as well as antitumor drugs. Abnormality of selenium status might be a previously unsuspected contributor to interpatient variation in drug effects.

Adult↗
PubMed1983

Coronary bypass surgery in juvenile onset diabetes.

Atherosclerotic cardiovascular disease is the major cause of death in insulin-dependent diabetics of juvenile onset (JODM). This report summarizes our experience in coronary artery bypass surgery performed between 1971 and 1980 on 13 JODM patients. Preoperatively, 12 of 13 patients had NYHA class IV symptoms with 78% of patients having either left main or multivessel coronary artery disease. With a mean follow-up of 4 years, 12 of 13 patients are alive and 8 of 12 are either NYHA class I or II. We conclude that in a select subset of JODM, bypass surgery can be performed with a low operative morbidity and mortality and results in long-term symptomatic improvement.

Adolescent↗
PubMed1983

Implications of rapid uniform density changes on hepatic computed tomography.

Uniform hepatic density alterations may be due to fatty infiltration or hemochromatosis. Whole liver density pattern changes may occur with rapidity where there is liver fat accumulation or mobilization. Averaged hepatic densities from concomitantly increased fat and iron accumulation can result in a false impression of liver normalcy. Two cases are presented to illustrate these points and the importance of understanding the patterns in terms of pathophysiology and response to treatment.

Adult↗
PubMed1983

Small-cell carcinoma of lung: reinduction therapy after late relapse.

Some patients with small-cell carcinoma of lung can be expected to achieve long-term disease-free survival. However, relapses may occur even after 2 years. Information on the treatment of these patients is sparse, although response rates to "salvage" therapy in patients with progressive disease while receiving treatment are poor. We report six patients who had relapses after more than 2 years in complete remission. Five patients were retreated with chemotherapy including some or all of the drugs in the initial treatment, and four had responses with a median duration of 10 months (range, 2 to 18 months). Thus retreatment with chemotherapy similar to the initial treatment can occasionally achieve second responses persisting up to 1 year or longer. The high incidence of patients who have relapses after 2 years confirms previous data on relatively slow growth rates in small-cell carcinoma.

Adult↗
PubMed1983

Effects of low-dose warfarin on antithrombin III levels in morbidly obese patients.

Morbid obesity has been associated with increased risks for thrombotic diseases. Patients with morbid obesity are shown to have decreased activity and decreased concentration of antithrombin (AT) III. This deficit can be corrected by giving the patients low doses of the oral anticoagulant warfarin. The same beneficial effect was not observed in normal lean control volunteers in whom the levels of AT III were normal at all times. Thus, it may be possible to offer prophylactic protection against the effects of having depressed levels of AT III in patients at increased risk for thrombotic diseases without using full anticoagulant doses of warfarin, including morbidly obese patients.

Antithrombin III↗
PubMed1982

Altered amino acid kinetics in rats with progressive tumor growth.

The present study was designed to determine whether alterations in host metabolism associated with progressive tumor growth were a result of the anorexia frequently observed with cancer or could be attributed to other direct tumor effects. Rates of tyrosine flux, oxidation, and incorporation into protein, as well as fractional protein-synthetic rates in nonsecretory liver, muscle, and tumor, were determined in overnight-fasted rats, 5 to 6 (Stage I), 10 to 11 (Stage II), and 15 to 16 (Stage III) days following s.c. implantation of RNC-254 fibrosarcoma. Tumor-bearing rats were allowed to consume a purified diet containing 20% protein ad libitum, and results were compared to non-tumor-bearing rats pair fed quantities of food equivalent to tumor-bearing animals or allowed to consume the diet ad libitum. Results demonstrate that during later stages of tumor growth (Stage III) calorie intake and nontumor body weight gain were reduced in tumor-bearing rats (p less than 0.05). Fifteen and 16 days following implantation, there were significant changes in amino acid kinetics that were not observed after earlier periods of tumor growth and that could not be explained by any reduction in dietary intake. Rates of tyrosine appearance in the plasma and subsequent incorporation into whole-body protein were increased 33 and 34%, respectively (p less than 0.05), when compared to non-tumor-bearing rats fed equivalent quantities of food. Whole-body tyrosine oxidation rates were unchanged. Skeletal protein synthesis, as reflected by gastrocnemius or rectus abdominus muscle, was reduced from 10.5 and 10.1%/day to 7.4 and 6.0%/day, respectively (p less than 0.05), in tumor-bearing compared to pair-fed animals. The findings suggest that significant alterations in protein metabolism occur in advanced stages of experimental neoplastic disease which cannot be explained by reductions in dietary intake and are aimed at providing adequate quantities of endogenous amino acids for net tumor growth.

Animals↗
PubMed1981

Pulmonary toxicity of antineoplastic drugs.

Pulmonary toxicity caused by antineoplastic drugs is becoming a more frequently recognized entity, and the number of drugs known or suspected of causing this disease is steadily increasing. In general, the initial clinical appearance includes both constitutional signs of malaise and fever, as well as pulmonary complaints. Some clinical signs may suggest a particular drug as the cause. The pathological condition also is generally nonspecific, but some clues may be present histologically that help define the causal agent. This is a review of the antineoplastic drugs that are associated with pulmonary toxicity. Clinical, laboratory, and pathological data are presented as useful information for practicing physicians. Although therapeutic maneuvers are limited, these are discussed with regard to each drug.

Alkylating Agents↗
PubMed1981

Aorticopulmonary paraganglioma and gastric leiomyoblastoma in a young woman.

The 16th report of a patient with "Carney's triad" is presented. The triad consists of an extra-adrenal paraganglioma, gastric leiomyoblastomas and a pulmonary chondroma. The diagnosis is made by discovery of the presence of at least two of these individually rare tumors. The patient described as 15 year old girl who presented with a pericardial effusion caused by an invasive mediastinal paraganglioma. She was subsequently found to have multiple gastric leiomyoblastomas. The leiomyoblastomas have been resected. The paraganglioma was unresectable, and the patient underwent sequential radiation therapy and chemotherapy without response. Concomitant 5-fluorouracil chemotherapy with radiation resulted in an objective regression of tumor mass.

Adolescent↗
PubMedDate not supplied

Selenium. Preclinical studies of anticancer therapeutic potential.

Selenium is a trace element that is essential to the human diet. Deficiency states have been described in both animals and humans. In addition, selenium compounds have demonstrated toxicity in humans, as well as in human tissues in culture. As early as 1956, one form of selenium was used as an antineoplastic agent in humans with some demonstrated activity. Recently, evidence in both tumor-bearing animals and human tumor cells in culture have confirmed an antitumor effect of potential clinical benefit. The mechanism of this cytoxic effect appears, at least in part, to relate to the property of some forms of selenium to oxidize critical sulfhydral groups in the cell. Evidence for this, and the resulting implications for the use of selenium in anticancer treatment, is presented in this manuscript.

Antineoplastic Agents↗
PubMedDate not supplied

Phase II study of troxacitabine (BCH-4556) in patients with advanced non-small-cell lung cancer.

Troxacitabine. a promising new L-nucleoside, inhibits DNA polymerase and leads to complete DNA chain termination. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of troxacitabine in untreated patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients were eligible if they had inoperable stage IIIB or IV NSCLC, ECOG PS < or = 2, adequate hematology and biochemistry, and at least one bidimensionally measurable lesion. Patients with prior malignancy or brain metastases were excluded. Troxacitabine (10 mg/m(2)) was administered intravenously over 30 minutes every 3 weeks. Between June 1999 and May 2000, 17 eligible patients received treatment. Patient characteristics included: median age 64 years; female 41%; stage IV (94%); PS 0 (12%), 1 (59%), and 2 (29 %), 3 or more disease sites (59%). In 17 patients, there were 8 stable disease, 9 disease progression, and no objective responses. Median duration of stable disease was 3.6 months (range = 2.0-7.1). A total of 56 cycles were administered (median = 3), and 88% of patients received 90% or more of the planned dose intensity. The majority (82%) of patients experienced skin rash. Hematologic and biochemical toxicities, grade 3/4 (%) were: granulocytopenia (41), anemia (12), thrombocytopenia (6), and hyperglycemia (6). Troxacitabine appears to have little activity in NSCLC in the dose and schedule tested.

Aged↗
PubMedDate not supplied

Low antithrombin III in morbid obesity: return to normal with weight reduction.

Morbidly obese adults are at increased risk for perioperative thrombotic complications. Antithrombin III (AT III) is a major endogenous anticoagulant and its deficiency is associated with more frequent thrombotic diseases. We measured AT III quantity and function in 23 morbidly obese adults and in 19 otherwise identical people who had reduced their mean weight to 160% of ideal body weight. Both groups were compared to normal weight controls (less than 120% ideal body weight). Serum and plasma AT III function and serum AT III antigenic concentration were significantly lower in the morbidly obese people compared to the weight reduced group in all three assays. The reduced group had values within the normal range of the normal weight group. In addition, three patients studied both before and after weight loss had similar significant changes in their AT III. We conclude that AT III is reduced in morbidly obese adults and normalizes as weight is reduced. Possible mechanisms of this deficiency and therapeutic approaches are considered.

Adult↗
PubMedDate not supplied

Overexpression of cytochrome P-450 isoforms involved in aflatoxin B1 bioactivation in human liver with cirrhosis and hepatitis.

Studies were carried out to test the hypothesis that inflammatory liver disease increases the expression of specific cytochrome P-450 isoenzymes involved in aflatoxin B1 (AFB) activation. The immunohistochemical expression and localization of various human cytochrome P-450 isoforms, including CYP2A6, CYP1A2, CYP3A4, and CYP2B1, were examined in normal human liver and liver with hepatitis and cirrhosis. The constitutive expression of CYP3A4 in normal liver showed a characteristic pattern of distribution in centrilobular hepatocytes, whereas CYP1A2, CYP2A6, and CYP2B1 were expressed uniformly throughout the liver acinus. In sections of liver infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), the expression of CYP2A6 was markedly increased in hepatocytes immediately adjacent to areas of fibrosis and inflammation. CYP3A4 and CYP2B1 were induced to a lesser degree, and expression of CYP1A2 was unaffected. In HBV-infected liver, double immunostaining revealed that overexpression of CYP2A6 occurred in hepatocytes expressing the HBV core antigen. In HCV-infected liver, CYP2A6, CYP3A4, and CYP2B1 were overexpressed in hepatocytes with hemosiderin pigmentation. These results suggest that alterations in phenotypic expression of specific P-450 isoenzymes in hepatocytes associated with hepatic inflammation and cirrhosis might increase susceptibility to AFB genotoxicity.

Adult↗
PubMedDate not supplied

Identification of a novel steroid derivative, NSC12983, as a paclitaxel-like tubulin assembly promoter by 3-D virtual screening.

By flexibly docking 9593 compounds of the NCI-3D database against the refined structure of beta-tubulin using DOCK 4.0, a long-forgotten synthetic steroid derivative, NSC12983, has been identified as a microtubule-stabilizing agent. The 32 top scorers includes NSC12983 and the three added references: paclitaxel, docetaxel and IDN5109. That is, 12.5% of the 0.33% top scorers are active. In addition, NSC12983 is active on Mycobacterium tuberculosis in vitro and in vivo, which might be due to its ability to promote the assembly of essential cell division protein.

Antineoplastic Agents, Phytogenic↗