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E C Schreiber

Publications and source records attributed to E C Schreiber.

At least 19 recordsLinked to original sources
PubMed2005

Sensitivity of large-field electron beams to variations in a Monte Carlo accelerator model.

Adjustments made to Monte Carlo models during the commissioning of the simulation should be physically realistic and correspond to actual machine characteristics. Large electron fields, with the jaws fully open and the applicator removed, are sensitive to important source and geometry parameters and may provide the most accurate beam models, including those collimated by an applicator. We report on the results of a comprehensive Monte Carlo sensitivity study documenting the response of these large fields to changes in the configuration of a Siemens Primus linear accelerator. The study was performed for 6, 9 12, 15, 18 and 21 MeV configurations, and included variations of thickness, position and lateral alignment of all treatment head components. Variations of electron beam characteristics were also included in the study. Results were classified by their impact on central-axis depth dose distributions, including the bremsstrahlung tail, and on beam profiles near D(max) and in the bremsstrahlung region. Low-energy results show an increased sensitivity to electron beam properties. High-energy bremsstrahlung profiles are shown to be useful in determining misalignments between the beam axis and mechanical isocentre. For all energies, the alignment of the secondary scattering foil and monitor chamber are shown to be critical for correctly modelling beam asymmetries. The results suggest a methodology for commissioning of electron beams using Monte Carlo treatment head simulation.

Electrons↗
PubMed1983

Phencyclidine exposure and the developing mouse: behavioral teratological implications.

The effects of perinatal exposure to phencyclidine (PCP) on the reflex development of the offspring of mothers given PCP during gestation and/or lactation were determined. ICR Swiss mice received daily injections of either PCP (5, 10, 20 mg/kg, PO) or saline during gestation and/or lactation. Thus, four groups of animals were studied; those exposed only prenatally, postnatally, both pre- and postnatally, or control. After birth, these offspring were observed daily until weaning for the appearance of certain reflexes, using a modification of the Fox battery. There was a delay in the disappearance of the cross extensor reflex and delayed appearance of reflexes, such as walking, crawling, vibrissal placement and vibrissal stroking in the offspring of PCP-treated mothers. Treated animals also showed slower righting times than control animals. Growth rate was decreased in PCP-exposed animals beginning at 3 days of age and continuing through 15 days of age. These results indicate that PCP exposure during gestation or nursing adversely affects the development of behavioral reflexes in mice and suggest that regular observation of reflex ontogeny in neonates may be a sensitive indicator of behavioral teratology.

Abnormalities, Drug-Induced↗
PubMed1982

Phencyclidine: its transfer across the placenta as well as into breast milk.

Phencyclidine (PCP) is a dangerous and unpredictable drug which is widely abused among young people. Acute placental transfer of this drug was studied in pregnant rabbits and mice where it was shown to cross the placenta readily. Rabbit fetal levels of radioactivity reached their peak 2 hours after parenteral administration of PCP to the doe. In the mouse, where actual PCP levels were determined, there was a tenfold higher concentration of PCP in fetal tissue than in maternal blood. In lactating mice, the drug was found to cross rapidly into breast milk where it reached concentrations which were 10 times that of plasma. As PCP may be teratogenic and has been shown to be harmful to the infant during the postnatal period, those treating pregnant women should be aware to these possible routes of exposure for the developing infant and should counsel their patients accordingly.

Animals↗
PubMed1980

N-Acetyltransferases of rat liver and blood: substrate specificities.

The substrate specificities of N-acetyltransferases (NAT) were investigated by measuring Vmax and Km values with p-aminobenzoic acid (I), p-aminobenzamide (II), p-amino-benzamidopyridine (III), 2-(p-aminobenzamido)-4,6-dimethylpyrimidine (VI), and the corresponding p-aminobenzenesulfonamides (VII, VIII and XI) using at rat liver and blood preparations. With liver NAT, II, III and VI had lower Km and higher Vmax values than did their corresponding sulfonyl analogs (VII, VIII, XI). III was extraordinarily active (Vmax 854 nmol/mg protein/h); in contrast, II gave a Vmax of 22.4. Sulfadiazine (IX) and sulfamerazine (X) were acetylated at a very slow rate. The activities of the blood enzymes on these compounds were very different. The Vmax values obtained with blood NAT for II, VI and VII were sharply decreased. Surprisingly, acetylation of III, VIII, IX and X could not be detected. In contrast to liver, the blood NAT gave lower values of both Vmax and Km for the S analog of II and a much higher Km for I. While p-aminobenzoic acid was the best substrate for blood NAT, substitution of the amido nitrogen of p-aminobenzamide with an aromatic substituent enhanced the substrate potential for liver NAT, III may be useful as a substrate for the rapid classification of slow and fast acetylators.

4-Aminobenzoic Acid↗
PubMed1978

Pharmacokinetics of cephalosporin antibiotics: protein-binding considerations.

The therapeutic activity of antibiotics depends on several factors including absorption, elimination kinetics, distribution in the body, minimal inhibitory concentrations (MIC), stability against enzymes, and plasma-protein binding. Some of these factors are interrelated, for example, the extent of protein binding of an antibiotic influences its elimination kinetics, distribution into tissues, MIC, and antibacterial activity. To evaluate the potential efficacy of an antibiotic, it is important to know the extent of its binding to plasma proteins especially since the protein-bound fraction of the antibiotic is devoid of antibacterial activity. Cephalosporins are a new class of broad-spectrum antibiotics that bind to plasma proteins in different degrees. Reported values for protein binding range from 6% for cephradine to 92% for cefazolin. The effects of protein binding of some of the commonly used cephalosporins on antibacterial activity and several pharmacokinetic parameters are discussed in this communication.

Cefazolin↗
PubMed1977

Metabolism of the (+)-, (+/-)-, and (-)-enantiomers of alpha-methylfluorene-2-acetic acid (cicloprofen) in rats.

1. After oral or intraperitoneal administration of (+/-)-[14C]cicloprofen to rats, the peak plasma concentrations of radioactivity and the areas under the plasma concentration/time curves did not increase proportionally with dose; total urinary and faecal excretions of radioactivity did increase with dose, suggesting saturation of plasma protein binding of drug and faster elimination of unbound drug at higher doses. 2. [14C]Cicloprofen and its metabolites were eliminated mainly via biliary excretion. Ratios of faecal to urinary excretion ranged from 2 to 3 and depended on dose administered. 3. Rats with cannulated bile ducts excreted the drug almost exclusively in bile, whereas intact rats excreted up to 32% of the dose in urine in 6 days, suggesting that [14C]cicloprofen or its metabolites or both undergo extensive enterohepatic recirculation in the rats. 4. The major metabolites of [14C]cicloprofen excreted in urine or bile were the 7-hydroxy, 9-hydroxy-, 7,9-dihydroxy-, and 9-hydroxy-9-methoxy-derivatives and their glucuronide or sulphate conjugates. 5. The (+)-enantiomer of [14C]cicloprofen was hydroxylated and excreted by rats at a faster rate than its (-)-antipode; no qualitative stereoselective metabolism of the individual enantiomers of [14C]cicloprofen was observed.

Administration, Oral↗
PubMed1976

Release and elimination of 14C-fluphenazine enanthate and decanoate esters administered in sesame oil to dogs.

The rates of release of 14C-fluphenazine enanthate and 14C-fluphenazine decanoate were compared in two groups of five male dogs. Each dog was given a single dose (2 mg/kg im) of either the enanthate or decanoate ester in sesame oil. The times required to attain maximum concentrations of radioactivity in plasma were 3.8 +/- 0.5 days (+/-SE) for the enanthate ester and 10.6 +/- 1.1 days for the decanoate ester (p less than 0.001); maximum concentrations of radioactivity in the plasma at these times were 16.7 +/- 1.1 and 11.1 +/- 1.2 ng/ml, respectively (p less than 0.01). However, 35 days after dosing, the concentrations of radioactivity in plasma were greater for the decanoate ester than for the enanthate ester. The times required for 50% of the dose to be excreted in the urine and feces were 7.8 +/- 0.5 days for the enanthate ester and 22.6 +/- 4.4 days for the decanoate ester (p less than 0.05). The total amounts excreted in 35 days were 85.4 +/- 1.8 and 68.8 +/- 6.6% of the dose for the enanthate and decanoate esters, respectively; the average half-times for the rates of release of radioactivity from depot and body, as calculated from the data for total excretion, were 5.55 days for the enanthate ester and 15.4 days for the decanoate ester. Thirty-five days after dosing, the amount of the dose present in the injection site was 4.6 +/- 1.6% for the enanthate ester and 18.6 +/- 5.7% for the decanoate ester. Two groups of six dogs each were protected against the emetic effects of apomorphine more than twice as long by the decanoate ester than by the enanthate ester after the subcutaneous administration of single 8-mg/kg doses of either drug in sesame oil (p less than 0.05). Based on measurements of total radioactivity, it was concluded that the decanoate ester was released from the depot at less than one-half the rate of the enanthate ester.

Animals↗
PubMed1976

Fluorometric determination of cephradine in plasma.

A fluorometric method was developed for the determination of cephradine in plasma. A fluorescent product is formed when samples of deproteinized plasma containing cephradine are heated for 3 hr at 100 degrees and pH 1. The fluorescence is determined in sodium hydroxide solution (pH 13.5) at excitation and emission wavelengths of 350 and 445 nm, respectively. Only 0.1 ml of plasma is required, and concentrations of cephradine as small as 0.1 mug/ml may be determined. In plasma samples from a dog taken over a 10-hr period after an intramuscular injection of 250 mg of cephradine, essentially similar concentrations of cephradine were obtained by the fluorometric method and a standard microbiological bioassay.

Animals↗
PubMed1976

Stereospecific inversion of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer in the dog.

1. After administration of dl-alpha-methylfluorene-2-acetic acid to dogs, the optical rotation of the drug in blood increased with time. Of the total drug in blood, the d-enantiomer increased from 61 to 80% between 3 and 24 h after administration; by 384 h it was 100%. 2. Both l- and d-enantiomers had plasma half-lives and excretion characteristics similar to those of the dl-racemic mixture, indicating that the increase in the proportion of the d-enantiomer was not due to more rapid excretion of the l-enantiomer. 3. Studies of optical rotation and circular dichroism demonstrated that the l-enantiomer was converted to the d-enantiomer in the blood of the dog, but the d-enantiomer remained unchanged. After administration of the l-enantiomer, the d-enantiomer increased from 26 to 71% of the total drug in blood between 0-3 and 2 days after administration; 14 days after dosing, almost all of the drug was present as the d-enantiomer. 4. Isomerization of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer also occurs in rat, monkey and man.

Acetates↗
PubMed1976

Metabolism of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes.

1. The metabolic dispositions of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes have been investigated, and the results compared. 2. The drug was well absorbed after oral administration to rats and was widely distributed in all tissues, which, with the exception of brain, had higher concentrations of the drug, its metabolites, or both, than did plasma. 3. Metabolism by rat-liver microsomes included N-oxidation, N-demethylation, S-oxidation and aryl hydroxylation. Metabolites hydroxylated in the aromatic ring were excreted only in bile, both by the isolated perfused rat livers and by anaesthetized bile-duct-cannulated rats. 4. Liver perfusion of the benzothiazine or its monodesmethyl analogue (V) resulted in temporary cessation of the flow of perfusate through the organ. The benzothiazine sulphoxide (IV) had only a slight effect on the flow of liver perfusate, but IV followed by I caused the flow of perfusate to cease.

Administration, Oral↗
PubMed1976

Autoradiographic and tissue distribution studies on a nitrovinylfuran derivative (SQ 18506 14C) in S. mansoni infected mice.

Autoradiographic and tissue distribution studies of SQ 18506 14C were carried out on 13 Swiss albino mice. Infection was done by I.P. route with 50 to 60 cercaria of S. mansoni (puerto Rican strain) per animal. The safe single i.v. dose of a solution containing one mg of SQ 18506 dissolved in 0.06 ml dimethylsulfoxide was 0.003 ml/g b.w. of mice. Schistosome autoradiograms were clearly demonstrated one day after that dose injected in each mouse 50 days post-infection. However, hepatic autoradiograms were visible 14 days after 2 doses of our drug to each infected mouse. The higher the concentration of SQ 18506 14C in the culture medium the darker were the schistosomes in the autoradiograms and the greater their total d.p.m/mg. Tissue distribution studies after 2 1/2 doses of our drug/mouse revealed that schistosome total d.p.m/mg dry-weight was 50 times more than that of its liver. The latter d.p.m/g wet-weight was slightly higher than that of one ml of mouse blood.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗
PubMed1976

Absorption and excretion of a new antidepressive (SQ 10,996) in humans.

A single oral dose of 10 mg of SQ 10,996-14C was absorbed slowly by 3 normal male volunteers, with peak plasma concentrations achieved 6 hr after ingestion; the plasma half-life was about 38.5 hr. On average, 82.3 +/- 3.5% of the radioactivity present in the 2 hr plasma sample was bound to plasma proteins. These volunteers excreted an average of 31 and 52% of the dose in the urine and feces, respectively. All subjects excreted minor amounts of 14CO2 in the expired air. No unchanged SQ 10,996-14C was found in the urine. Three unidentified metabolites were excreted in urine. SQ 10,996-14C was excreted in the feces only as unchanged drug, suggesting that the drug is incompletely absorbed. The volunteers tolerated the drug well and experienced no adverse effects.

Administration, Oral↗
PubMed1975

Metabolism of triamcinolone acetonide-21-phosphate in dogs, monkeys, and rats.

The absorption, distribution and metabolic fate of triamcinolone acetonide-14C-21-phosphate were studied in the dog, monkey, and rat. A comparison of levels of radioactivity in blood or plasma, reached after intramuscular or intravenous administration, indicated that the drug was completely absorbed from the site of intramuscular injection within 10-15 min in all three species. Within 1-5 min after intramuscular or intravenous administration, the 21-phosphate ester was completely hydrolyzed to triamcinolone acetonide, which was present in the blood. The radioactivity was eliminated rapidly (t1/2 = 1-2 hr) from plasma (dogs, monkeys, and rats) and tissues (rats) after intramuscular or intravenous administration. In the three species, the major route of excretion was via the bile; however, the ratio of biliary to urinary excretion among the species varied considerably (from 1.5 to 15). In rats, excretion of radioactivity as expired carbon dioxide accounted for only 2-3 percent of the dose. 6beta-Hydroxytriamcinolone acetonide was the major metabolite in urine of the three species. Hydrolytic cleavage of the acetonide group did not appear to be significant.

Animals↗
PubMed1975

Metabolism of 8-(methylthio)cyclic 3',5'-adenosine monophosphate by rats and dogs after oral or intravenous dosing and in vitro by subcellular preparations of dog liver.

8-(Methylthio-14C or -35S)cyclic 3',5'-adenosine monophosphate (I) was given intravenously to rats (5 mg/kg) and orally and intravenously to dogs (0.25, 2.5, or 50 mg/kg). Oral doses were absorbed well but slowly. Plasma half-lives in dogs were about 3 hr after oral or intravenous doses of 0.25 or 2.5 mg/kg and ranged from 5 to 12 hr after oral or intravenous doseas of 50 mg/kg. Plasma glucose and insulin concentrations in dogs were increased by oral or intravenous doses of the compound. Regardless of the route, excretion of radioactivity by rats and dogs at all doses was chiefly in the urine (74-87% of the dose); the remainder was excreted in the feces or bile. Compound I was rapidly distributed to most tissues of dogs but entered the brain and certain portions of the eye slowly and to a limited extent. Urine and plasma of dogs and urine of rats contained I, 8-(methylthio)adenosine, and at least two other unidentified metabolites. Compound I and cyclic 3',5'-adenosine monophosphate were metabolized in vitro by the soluble fraction of dog liver to form 8-(methylthio)adenosine-5'-monophosphate and adenosine-5'-monophosphate, respectively. These compounds were further converted to 8-(methylthio)adenosine and adenosine, respectively. Compound I was metabolized in vitro more slowly than cyclic 3',5'-adenosine monophosphate.

Administration, Oral↗
PubMed1975

Absorption and biotransformation of topically applied 8-(methylthio) cyclic AMP. Studies in dogs and humans.

8-(Methylthiocyclic AMP-35S was applied topically to the intact or abraded skin of dogs at a dose of about 2-5 mg/kg. In this species, an average of 7% of the dose was absorbed through the intact and 62% through abraded skin. Half-lives for radioactivity in plasma averaged 3-6 h. After the topical application of the drug to the intact skin of dogs, the average concentration in plasma of glucose, but not of insulin, was increased by as much as 21%; after application to abraded skin, glucose and insulin were increased, on average, by as much as 84 and 221%, respectively. 8-(methylthio)adenosine and two unidentified compounds were present as metabolites in the urine of dogs; some unchanged 8-(methylthio)cyclic AMP-35S was also excreted. 8-(methylthio)cyclic AMP-35S was also applied topically (25 mg; 0-32 mg/kg) to the intact and stripped skin of normal human subjects under conditions similar to those used for dogs. Three subjects with intact skin did not absorb any of the drug, whereas three subjects with stripped skin absorbed 0-5, 8-3, and 23-3% of the dose. The half-life of radioactivity in the plasma of the subject with the greatest absorption was 0-5 h during the first 2 h, and 11 h for the next 10 h. During the first 2 h, this same subject excreted unchanged drug and 8-(methylthio)adenosine in his urine. No changes in glucose or insulin concentrations in plasma were observed in any of the subjects nor was there any apparent irritation of the skin.

Adenosine↗