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Biomedical subjects

J Roboz

Publications and source records attributed to J Roboz.

At least 55 records · Page 3Linked to original sources
PubMed1981

Intraperitoneal infusion of doxorubicin in the treatment of gynecologic carcinomas.

Intraperitoneally administered doxorubicin yields high local concentrations that are expected to deliver higher doses to clinically important peritoneal and lymphatic metastatic sites. Two infusions of 20 mg and 30 mg in a patient with residual microscopic intraperitoneal ovarian cancer eradicated her disease. Quantification of serum doxorubicin by HPLC revealed significant levels of the drug and its major metabolite lasting 72 hours. A 50-mg infusion induced complete remission in endometrial carcinoma; the patient died in 6 months without evidence of abdominal tumor. Complications due to subcutaneous infiltration of doxorubicin and possible systemic effects of sustained high levels of the drug need further investigation to enable the full exploitation of this modality.

Adenocarcinoma↗
PubMed1981

Long-term follow-up of incorporation of 15N from glycine into uric acid in gout.

The incorporation of 15N-glycine into urinary uric acid was studied in three gouty patients, repeating a study carried out 13 to 27 years ago. The 15N incorporation attained a lower maximum and declined less rapidly in the repeat study in all three patients. The cumulative 15N incorporation into uric acid was reduced to one half of that determined previously. Similarly, urinary uric acid excretion was less, along with a lower uric acid nitrogen to total nitrogen ratio. The data indicate changes in the nature of the metabolic aberrations, which are apparently related to long-term drug therapy, changes in lifestyle, aging and associated medical complications.

Adult↗
PubMed1980

Mass spectrometric technique for the determination of N-phosphonoacetyl-L-aspartic acid in serum.

N-Phosphonoacetyl-L-aspartic acid (PALA), a potent inhibitor of aspartic acid transcarbamylase, is now undergoing Phase I clinical trials. Initial experiments revealed that PALA is not metabolized to phosphonoacetic acid (PAA) in humans. Thus PALA may be quantified in serum after in vitro conversion to PAA. Serum is deproteinized with perchloric acid, lipid extracted with methylene chloride, hydrolyzed with 8 N hydrochloric acid at 100 degrees for 3 h, and evaporated to dryness with nitrogen. The residue is silylated, and PAA is quantified by monitoring the (M + 1)+ ions of the protonated molecular ions of trimethylsilyl derivatives of PAA and phosphonopropionic acid (internal standard) obtained in chemical ionization with methane. Limit of detection is 0.5 microM (150 ng/ml) PALA using 1 ml serum. PALA was given by continuous infusion to cancer patients at various doses. Maximum levels of PALA (50-500 microM range) were obtained at the end of infusion, followed in most cases by biexponential decay. Persistent residual PALA levels (5 microM for 48 h after infusion) correlated with increased toxicity.

Antineoplastic Agents↗
PubMed1980

Quantification of arabinitol in serum by selected ion monitoring as a diagnostic technique in invasive candidiasis.

D-Arabinitol was identified by mass spectrometry as a metabolite of Candida albicans and Candida tropicalis. For quantification, serum was deproteinized with acetone, the supernatant was evaporated to dryness, the silyl derivative was formed, and a portion was injected into a combined gas chromatograph-mass spectrometer system. Erythritol or 2-deoxy-galactitol was the internal standard. The protonated molecular ions, obtained in chemical ionization with isobutane, were monitored. For 39 normal subjects the mean endogenous arabinitol concentration was 0.52 microgram/ml (standard deviation, +/- 0.34). An increment of 0.2 microgram of arabinitol per ml could be quantified. Of 11 cases with diagnosed invasive candidiasis, 9 had arabinitol levels > 1.2 microgram/ml (8 microM) in the range of 1.2 to 25.0 micrograms/ml; the remaining 2 cases had levels in the normal range. Six cases of diagnosed colonized candidiasis showed normal arabinitol levels.

Adolescent↗
PubMed1980

Competitive fluorescence polarization study of the binding of 1,4-dihydroxy-5,8-bis[(2-[(2-hydroxyethyl) amino] ethyl]amino] 9-10-anthracenedione to DNA.

The title compound is now undergoing Phase I clinical trials as an experimental antitumor agent. Fluorescent polarization was used to determine the extent of inhibition of the binding of acridine orange to DNA. Displacement of 50% of the acridine orange was achieved by 0.21 microM of the title compound, 0.32 microM daunorubicin, 0.41 microM doxorubicin, 0.61 microM dactinomycin, and 7.8 microM cis-platinum. Binding inhibition was essentially equivalent with natural DNAs (calf thymus and Micrococcus luteus) and synthetic polymers [poly d(A):d(T) and poly d(G):d(C)] of widely differing adenine plus thymidine content.

Acridine Orange↗
PubMed1980

Clinical pharmacologic effects of thymidine plus 5-FU.

Ten patients with advanced cancer were given 24 courses of thymidine (TdR) plus 5-FU. In the initial part of the study, TdR was given by continuous infusion at a dose of 8 g/m2/24 hrs x 5 days, and 5-FU was given as an iv bolus daily x 5. During the continuous TdR infusion, TdR serum levels ranged from 10(-6) to 10(-5) M, and thymine serum levels ranged from 10(-5) to 10(-4) M. 5-FU serum decay on Day 1 was rapid, and serum decay on Day 5 was slightly prolonged in two of three patients studied. The optimal dose of 5-FU with continuous infusion of TdR seemed to be between 200 and 400 mg/m2 daily x 5 in heavily pretreated patients. In the second part of the study, rapid infusion of TdR at a dose of 8 g/m2/2 1/2 hrs followed by 5-FU resulted in markedly prolonged 5-FU serum decay (initial serum half-life, approximately 240 mins) and definite increase in clinical toxicity. The dose-limiting toxic effect of both schedules was myelosuppression. Administration of TdR in one tenth of the initial infusion time resulted in a nearly 100-fold increase in peak TdR levels. Thymine was the major metabolite of TdR. 5-FU did not influence TdR blood levels. The protracted 5-FU serum decay appears to account at least in part for the increased toxicity of 5-FU when administered following TdR.

Adult↗
PubMed1979

Immunologic dysfunction among PBB-exposed Michigan dairy farmers.

In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.

Accidents↗
PubMed1979

Impaired immune function and identification of polybrominated biphenyls (PBB) in blood compartments of exposed Michigan dairy farmers and chemical workers.

In 1973 PBB's were accidentally mixed into animal feed, resulting in marked toxic effects. Meat and dairy products were widely consumed in Michigan. To determine the impact of PBB's, 55 exposed Michigan farm residents, 11 Michigan chemical workers and 46 non-exposed Wisconsin farmers were examined. Abnormalities included decreased number of T-lymphocytes with concomitant increase of lymphocytes with no detectable surface markers, "null cells", and altered lymphocyte function. Data obtained from skin testing using standard recall antigens, showed no consistent correlation between the delayed cutaneous hypersensitivity response and the impaired lymphocyte function. PBB (hexa) in separated white blood cells and red cells was positively identified and quantified by gas chromatography-mass spectrometry. PBB and immunological abnormalities were not detected in non-exposed Wisconsin dairy farm residents.

Agricultural Workers' Diseases↗
PubMed1978

Determination of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole) in blood and urine by chemical ionization-mass fragmentography.

A combined gas chromatographic-mass spectrometric technique is described for the quantification of virazole in serum and urine. Proteins are removed by molecular filtration, lipids by extraction with dichloromethane and interfering endogenous constituents by acidic and basic ion-exchange resins. Virazole is quantified by monitoring the protonated molecular ions of the fully silylated derivatives of virazole (m/e 533) and the arabinose analog (internal standard) obtained by methane chemical ionization. The detection limit is 150 pg (0.6.10(-12) mole) of virazole injected. In serum 10 ng/ml (4.10(-8) mole) can be detected, 25 ng/ml quantified. In urine 0.5 microgram/ml can be quantified without preconcentration. Virazole was detected in serum for at least 96 h at the 70-ng/ml level.

Gas Chromatography-Mass Spectrometry↗
PubMed1978

Mass fragmentographic determination of pyrazinamide and its metabolites in serum and urine.

A combined gas chromatographic-mass spectrometric technique is described for the simultaneous determination of pyrazinamide and its two main metabolites, pyrazinoic acid and 5-hydroxypyrazinoic acid. Serum (200 microliter) is deproteinized and evaporated to dryness; urine (20 microliter) is evaporated. The crude residues are silylated and selected ions are monitored in the chemical-ionization mode with isobutane as both chromatographic carrier and reagent gas. The sensitivity is 10 ng/ml for pyrazinamide and pyrazinoic acid and 20 ng/ml for the 5-hydroxy metabolite in a single analysis. Nicotinic acid and nicotinamide are internal standards. Both unchanged drug and metabolites were identified and quantified in the serum and urine of human subjects.

Gas Chromatography-Mass Spectrometry↗
PubMed1977

Preclinical toxicological study of phosphonoacetic acid: determination in blood by selected ion monitoring.

Confirmed observations of the inhibition of oncogenic viruses by phosphonoacetic acid led to preclinical trials in animal model systems. Circulating phosphonoacetic acid was detected in the blood of mouse, rabbit and monkey after oral or subcutaneous administration of the drug. Phosphonoacetic acid is quantified in blood, after removing proteins and lipids, as the trimethylsilylated derivative, by monitoring the intensity of the protonated molecular ion and also that of phosphonopropionic acid (internal standard) using chemical ionization mass spectrometry combined with gas chromatography. The detection limit is 20 ng ml-1 when 0.2 ml serum is analyzed. A dosage of 230 mg kg-1 day-1 by continuous infusion is proposed for therapeutic trials in monkeys. This dose is well tolerated and results in slowly increasing blood levels of phosphonoacetic acid which reach a maximum of approximately 50 microgram ml-1 in a four day infusion, and decrease to 2 microgram ml-1 24 h after termination.

Animals↗
PubMed1977

The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man.

Complex interactions occur between pyrazinamide (PZA) and probenecid in man involving both the metabolism and distribution of the drugs, and their effects on renal tubules. Pretreatment with PZA prolonged the half-life (T 1/2) of probenecid without changing its plasma-binding. As the rate of probenecid metabolism is decreased, its uricosuric action tends to be prolonged and the effect of PZA lessened. The PZA-suppressible urate level is increased to values well above control after the administration of probenecid; it is less after alkalinization of urine, although still larger than the value for PZA-suppressible urate after the administration of PZA alone. Urinary probenecid excretion is much greater when urine is alkalinized. These observed drug interactions, plus the known effect of probenecid to block secretion of PZA, have to be considered in evaluating the effect of the two drugs given together, compared to the effect of each drug given separately.

Adult↗