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Biomedical subjects

J A Lopez

Publications and source records attributed to J A Lopez.

102 records · Page 6Linked to original sources
PubMed1983

Cerebrospinal fluid and plasma pharmacokinetics of high doses of 1-beta-D-arabinofuranosylcytosine in nonhuman primates.

The pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C) in plasma, cerebrospinal fluid (CSF), and urine was studied in nonhuman primates. Conventional and high-dose schedules of ara-C were administered i.v. and intraventricularly through indwelling Ommaya reservoirs. ara-C and its metabolite 1-beta-D-arabinofuranosyluracil (ara-U) were measured by high-pressure liquid chromatography. Due to rapid peripheral deamination (230 nm ara-C/hr/ml plasma), the half-life of ara-C in plasma after a 140-mg/kg i.v. 1-hr infusion was short (3.7 min). Peak plasma concentrations of ara-C, ranging between less than 0.1 and 49 micrograms/ml, were dose dependent (ara-C, 15 to 140 mg/kg). Under these conditions, ara-C was undetectable in CSF. About 53% of the administered dose (140 mg/kg) was excreted in urine during the first 5 hr mostly as ara-U. Intraventricular administration of 50 and 250 mg of ara-C resulted in peak lumbar CSF levels of 435 and 2235 micrograms/ml, respectively, at about 155 and 80 min postinjection. Concomitant ara-U levels were one-tenth of those of ara-C and increased progressively, suggesting deamination of the drug in the central nervous system. The half-life of ara-C in CSF ranged between 50 and 60 min. Administration of 50 mg of ara-U intraventricularly resulted in peak lumbar ara-U levels of 595 micrograms/ml at about 180 min with a prolonged clearance. Concomitant plasma levels throughout the study were less than 0.1 micrograms/ml, suggesting slower equilibrium. No hematological or nervous system toxicity was observed during these studies. The clinical implications of these findings are discussed.

Animals↗
PubMed1982

Errors in measurement and reporting of serum markers in patients with germ cell tumors.

Elevation of the serum value of either human chorionic gonadotropin or alpha-fetoprotein in patients with germ cell testicular tumors is often accepted as evidence for persistent malignancy in the absence of histologic confirmation. These laboratory values are not subject to review and confirmation, unlike histologic diagnosis. We report 3 cases in which serum marker values were incorrectly reported to be elevated by commercial laboratories over a thirteen-month period and suggest a method for handling serum samples to avoid errors in diagnosis.

Adult↗
PubMed1980

Infection prevention in patients with cancer: microbiological evaluation of portable laminar air flow isolation, topical chlorhexidine, and oral non-absorbable antibiotics.

The increasing use of intensive cytotoxic chemotherapy for patients with solid tumours enhances the risk of opportunistic infection to levels formerly seen only in patients with acute leukaemia, and prevention of infection is a major concern. A relatively simple regimen of isolation, topical antisepsis, and orally administered non-absorbable antibiotics was studied in 18 patients. Sixteen of 21 studies were performed using portable laminar air flow apparatus and five with isolation only. All patients became severely neutropenic but there were no major infections. Microbiological results showed effective decontamination of the skin, which was maintained without recolonization or acquisition of new organisms. The ears, nose and throat were effectively decontaminated only when the regimen was intensified. Colonization with Pseudomonas aeruginosa, a major pathogen in compromised hosts, did not occur. The protective regimen is less expensive than regimens previously described, is acceptable to patients, and requires no modification of existing hospital rooms. It merits further evaluation in patients with common cancers who receive intensive cytotoxic drug therapy.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparative survival analysis of p53 gene mutations and protein accumulation in colorectal cancer.

Immunohistochemical reactivity for p53 protein is common in various human malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 alterations, we screened a series of 72 colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations in exons 5-9 of the p53 gene were assayed by single-strand conformation polymorphism and direct DNA sequencing, whereas p53 protein accumulation was detected in 10-microm frozen tissue by immunostaining using 2 different monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexpression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivariate survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation emerged as risk factors, but only the stage was significant. In univariate analysis, stage, differentiation and p53 immunoreactivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.

Colorectal Neoplasms↗
PubMedDate not supplied

Vascular responses to endothelin-1 in atherosclerotic primates.

Endothelin-1 (ET-1) is a vasoactive peptide that is released by endothelial cells. This study was performed to determine whether vascular responses to ET-1 are altered by atherosclerosis. ET-1 (1 or 10 nmol) was injected intra-arterially into the perfused hind limb of normal cynomolgus monkeys and monkeys fed an atherogenic diet for 19 months. We calculated the resistance of the total limb and large arteries and estimated the resistance of the small vessels. The major finding was that ET-1 had minimal effects on large arteries in normal monkeys but produced pronounced constriction of large arteries in atherosclerotic monkeys. In both groups, ET-1 produced dilatation of small vessels at 1 nmol and constriction at 10 nmol. Indomethacin (6 mg/kg intravenously) did not affect the responses to ET-1 in normal or atherosclerotic monkeys. In summary, the major finding is that the constrictor responses of large arteries to ET-1 are potentiated by atherosclerosis.

Animals↗
PubMedDate not supplied

Vascular responses to platelet activation in normal and atherosclerotic primates in vivo.

Platelets release vasoactive substances that may contribute to augmented vasoconstriction. In this study, we examined vascular responses to activation of platelets in vivo by infusion of collagen. Purified bovine collagen was infused into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys. Resistance of the total limb and large arteries was measured at constant flow. In normal monkeys, collagen produced a decrease in total limb resistance, with a modest constrictor response of the large arteries. In atherosclerotic monkeys, collagen produced a transient, small decrease in total limb resistance, with pronounced constriction of large arteries. Indomethacin (5 mg/kg i.v.) and the thromboxane A2/prostaglandin H2 receptor antagonist SQ29,548 (2 mg/kg i.v.) virtually abolished the large-artery constrictor response to collagen in atherosclerotic monkeys. The 5-HT2-serotonergic receptor antagonist ketanserin (0.6 mg/kg i.v.) had no effect on the vasoconstrictor response. We conclude that 1) large arteries constrict and small vessels dilate in response to collagen-mediated activation of platelets in vivo in normal and atherosclerotic monkeys, 2) large-artery constriction in response to activation of platelets is augmented in atherosclerotic monkeys, and 3) the augmented large-artery constriction in atherosclerotic monkeys may be mediated primarily by thromboxane. The findings provide evidence that platelets may contribute to augmented constrictor responses of atherosclerotic arteries.

Adenosine↗