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Biomedical subjects

B D Paul

Publications and source records attributed to B D Paul.

At least 37 records · Page 2Linked to original sources

Nasal carriage of Staphylococcus aureus in a population of healthy Nigerian students.

The nasal carrier-rate of Staphylococcus aureus in 548 Nigerians aged 9-32 years and attending various educational establishments was 56.4%. This rate decreased with increasing age. A significantly greater proportion of females (65.0%) than males (46.5%) were carriers, but the excess in females was apparent only in subjects aged greater than 20 years. Mucoid strains of S. aureus, which gave a negative slide-coagulase reaction, were found in 21.5% of carriers aged 10-15 years, but were absent from members of other age-groups. A considerable proportion of all the strains tested were resistant to commonly used antibiotics.

Adolescent↗

Citizen participation overplanned: the case of a health project in the Guatemalan community of San Pedro la Laguna.

Citizen involvement is a widely endorsed but often elusive goal in community betterment projects. An initiative by the major of San Pedro attracted funds to build a clinic and hire a doctor and attracted an American health educator to direct the project. Contrary to plan, the director's insistence on creating a representative community committee discouraged rather than increased participation. The case chronicles the interplay of interests and strategies and points toward potentially more productive approaches to issues of leadership, factionalism and public participation.

Community Health Services↗

In the search for new anticancer drugs. 9. Synthesis and anticancer activity of spin-labeled analogues of N,N:N',N':N",N"-Tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N",N"-tri-1,2-ethanediylphosphorothioic triamide.

A number of N,N:N',N':N",N"-tri-1,2- ethanediylphosphoric triamide (TEPA) and N,N:N',N':N",N"-tri-1,2- ethanediylphosphorothioic triamide (thio-TEPA) derivatives containing either two aziridine moieties (1a) or two (2-chloroethyl)amino functions (1b) and either a 2,2,6,6-tetramethylpiperidine, 1-oxy-2,2,6,6-tetramethylpiperidine or 1-hydroxy-2,2,6,6-tetramethylpiperidine component were synthesized and tested against lymphocytic leukemia P388 in mice. In a structure-activity comparison it was found that at optimum dose all compounds containing the nitroxyl radical were more active than the corresponding hydroxylamine derivatives. The open-chain compounds (1b) were less active than the corresponding aziridine ring compounds (1a). The replacement of the X = bridge in 1a with the X = N(CH3) group resulted in lowering of the anticancer activity.

Animals↗

Comparative sero-epidemiologic observations of rubella infection in pregnant women and female university students.

Sera from 58 pregnant women and 34 female university students were tested by a haemagglutination-inhibition (HI) method to determine the levels of immunity to rubella and to assess factors important in its epidemiology. Ages of women ranged from 15 to 35 years. Pregnant women were from the lower socio-economic groups, whilst students came from middle and upper income families. In both groups immunity to rubella increased with age. Students were more susceptible to the infection than pregnant women (21% compared with 3% respectively) - p less than 0.05 and the geometric mean titre was significantly higher in pregnant women than in students. Since women were of the same ages and essentially from the same geographical location, it is suggested that differences in susceptibility rates to rubella were due to differences in the socio-economic status of the two groups.

Adolescent↗

D-Ephedrinephosphate, DEP: a new substrate with specificity for prostatic acid phosphatase (PAP).

This report describes the synthesis and physical (including spectral) properties of a new substrate, D-ephedrinephosphate, DEP1, which is histochemically highly specific for a secreted non-lysosomal prostatic acid phosphatase, PAP. This specificity is in contrast to other substrates which are nonspecific, i.e., which demonstrate acid phosphatases that originate from various cell types and are mainly lysosomal. When this substrate is used for light and electron microscopic histochemistry in a modified Gomori medium, PAP is demonstrated mainly in secretory granules and in the Golgi apparatus (and its related vacuoles) of prostatic epithelial cells of several species of mammals including man. This corroborates our previous suggestion that PAP is not a lysosomal enzyme as are many of the other acid phosphatases. This high degree of specificity of DEP for PAP supports the usefulness of this compound in the histochemical and biochemical characterization of PAP, and in the diagnosis of localized or disseminated prostatic disease.

Acid Phosphatase↗

The histochemical demonstration of human prostatic acid phosphatase with phosphorylcholine.

Tissues from patients with benign prostatic hyperplasia were used for the cytochemical demonstration in light and electron microscopy of a secreted, nonlysosomal prostatic acid phosphatase (PAP) with phosphorycholine, substrate specific for PAP. The specificity of phosphorylcholine for PAP is attributable to the pentavalent nitrogen in phosphorylcholine, a feature that renders it resistant to hydrolysis by all other acid phosphatases. PAP activity was found in the Golgi cisternae and its associated vacuoles and in secretory vacuoles localized in the nuclear, Golgi, and apical areas of the prostatic epithelial cell. These results confirm the existence of two types of acid phosphatase in prostatic tissue. One is lysosomal and is prevalent in many tissues and the other, PAP, is the major enzymatic product secreted by the prostate. The specificity of PAP for phosphorylcholine, one of the natural substrates for this enzyme, validates the use of this method for the histochemical characterization of PAP and indicates the prostatic origin of cells showing PAP activity.

Acid Phosphatase↗

Carcinogenicity of Camellia sinensis (tea) and some tannin-containing folk medicinal herbs administered subcutaneously in rats.

In an attempt to correlate the high incidence of esophageal carcinoma in natives of certain places with their habit of using herbaceous folk medicines, we performed bioassays of several plant extracts and the fractions prepared from them. Fourteen extracts and fractions from 6 plants were injected sc into NIH Black rats. The tannin fractions from Quercus falcata pagodaefolia, Diospyros virginiana, and Camellia sinensis were very active and produced tumors at the injection site in 66% or more of the treated animals. Tannin fractions from 3 other plants and total aqueous extracts from 5 to 6 tested plants were also tumorigenic rats. The induced tumors were malignant fibrous histiocytomas similar, if not identical, to those encountered in humans. The experiment indicated a possibility of induction of tumor in man by the tested plant materials.

Animals↗

Detection and quantitation of urinary 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, a metabolite of tetrahydrocannabinol, by capillary gas chromatography and electron impact mass fragmentography.

A procedure for detection and quantitation of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, a major metabolite of delta-9-tetrahydrocannabinol in urine, has been described. Since the metabolite is present in both conjugated and unconjugated forms, hydrolysis of urine was carried out to increase the sensitivity of detection. The acidic metabolite was isolated by strongly basic anion exchange resin, and subsequently derivatized to methyl 1-dehydroxy-1-methoxy-11-nor-delta-9-tetrahydrocannabinol-9-carbox ylate (1a) by methyliodide in the presence of tetramethylammonium hydroxide. The derivatized product was separated in a capillary column gas chromatograph, and finally detected by a mass spectrometer under electron impact mode. Confirmation of the product was carried out by monitoring three ions that represent the major portions of the molecule and comparing their relative abundances to that of a standard. Quantitation was based on 5'-2H3-11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid as internal standard. Excellent linearity was obtained over the range of 2 to 1000 ng/mL. The overall yield of extraction using the anion exchange resin was 50 to 60%. This extraction process is rapid and suitable for a large number of sample analyses. The methylated product (1a) is stable for at least 72 hr at room temperature.

Chromatography, Gas↗

Passive inhalation of marijuana smoke: urinalysis and room air levels of delta-9-tetrahydrocannabinol.

In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [THC]) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.

Adult↗

Marijuana-laced brownies: behavioral effects, physiologic effects, and urinalysis in humans following ingestion.

Five drug-free male subjects ingested marijuana-laced brownies in a double-blind crossover study designed to test for behavioral effects, physiologic effects, and urinary cannabinoid metabolites produced as a result of consumption of marijuana plant material cooked in foodstuff. On three separate occasions, each subject consumed two brownies which contained 1.6 g of marijuana plant material. Placebo marijuana plant material (0% THC) was mixed with marijuana plant material (2.8% THC) so that each subject ingested equivalent marijuana plant material of 0, 1, and 2 marijuana cigarettes (2.8% THC). Subjects scored significantly higher on behavioral measures after consumption of brownies containing THC than with placebo; however, the effects were slow to appear and variable. Peak effects occurred 2.5 to 3.5 h after dosing. Modest changes in pulse and blood pressure also were noted. Urinalyses by EMIT d.a.u. assay and Abuscreen RIA for cannabinoids and GC/MS assay for THCCOOH indicated that substantial amounts of marijuana-related metabolites were excreted over a period of 3 to 14 days. No positives were produced as a result of ingestion of placebo brownies.

Adult↗

GC/MS analysis of phencyclidine acid metabolite in human urine.

Available methods for determining PCP use are based on the presence of the parent drug in urine. PCP, however, is very potent and is extensively metabolized; it is therefore present in urine in only small quantities. This work was undertaken to determine whether an amino acid metabolite of PCP, 5-(N-(1'-phenylcyclohexyl)amino)pentanoic acid, can be used to determine PCP use. A solid phase adsorption technique was developed to extract the amino acid metabolite from urine. Recovery averaged 93%, and subsequent GC/MS analysis was free from interference. Analysis of 67 urine samples demonstrated that the amino acid metabolite exists in human urine in significant quantities.

Gas Chromatography-Mass Spectrometry↗

Gas chromatography/electron impact mass fragmentometric determination of urinary 6-acetylmorphine, a metabolite of heroin.

A procedure for detection and quantification of urinary 6-acetylmorphine (6-AM), a metabolite of heroin, is described. After initial solvent extraction from urine, the 6-AM was purified either by acid-base liquid-liquid extraction or by solid-phase extraction techniques. The 6-AM was then derivatized to its propionyl ester, which was characterized by gas chromatography/mass spectrometry in the electron impact mode. Confirmation of 6-AM was accomplished by comparing retention times and relative abundances of selected ions with that of a standard. Quantification was based on 6-[2H3]acetyl-N-[2H3]methylnormophine (6-[2H6]AM) as internal standard. Excellent linearity was obtained in the concentration range 1-100 ng/mL. The overall yield after solvent extraction and acid-base purification ranged from 79 to 82%; for solvent extraction and solid-phase purification, it was 92 to 95%. The limit of detection was 810 pg/mL. Within-run and between-run CVs for 6-AM at concentrations in the range 1-100 ng/mL were generally less than 5% and less than 10%, respectively.

Gas Chromatography-Mass Spectrometry↗

Forensic drug testing for opiates: I. Detection of 6-acetylmorphine in urine as an indicator of recent heroin exposure; drug and assay considerations and detection times.

The urinary excretion patterns of 6-acetylmorphine (6-AM), free morphine, and total morphine were determined by GC/MS assay for six human subjects who received single doses of 3.0 and 6.0 mg of heroin hydrochloride. Clinical specimens were collected and combined with standardized drug urines into a 400 specimen/standard set. The urines were coded, randomized, and analyzed under blind conditions. The GC/MS assay had a limit of sensitivity of 0.81 ng/mL for 6-AM and displayed a linear response across a concentration range of 1-100 ng/mL. Following heroin administration, 6-AM was excreted rapidly with an average half-life of 0.6 h. This resulted in a very short detection time for 6-AM with a range of 2-8 h at the most sensitive cutoff limit. This short detection time limits the usefulness of 6-AM as a marker for identification of heroin abusers to a period immediately after drug use. In contrast, free morphine and total morphine were detectable up to approximately 24 h after heroin administration. The average half-life for free morphine was 3.6 h and for total morphine was 7.9 h. After morphine and codeine administration, no 6-AM was detected by GC/MS above the 0.81-ng/mL detection limit of the assay. It is concluded that the presence of 6-AM in urine can be interpreted with confidence to mean that heroin, or 6-AM, was administered within 24 h of specimen collection and that the presence of 6-AM in urine is not caused by morphine or codeine administration.

Gas Chromatography-Mass Spectrometry↗

Forensic drug testing for opiates. II. Metabolism and excretion rate of morphine in humans after morphine administration.

Urine levels of free and total morphine were determined by GC/MS for four male subjects who received single doses of 20 mg of morphine sulfate intramuscularly. Peak concentrations were observed within 10 h for both conjugated and free morphine; thereafter, levels declined rapidly. Initially, free morphine represented from 25 to 34% of the total amount of morphine present, but this ratio declined after 12 h to an average of only 5.9% of total morphine. Free morphine accounted for an overall mean of 6.8% of the dose excreted in urine and conjugated morphine for 58.6%. The mean excretion half-life for free morphine was 6.6 h and for conjugated morphine was 8.2 h. The lower concentration and shorter half-life of free morphine resulted in a shorter detection time for free morphine versus total morphine at a 300-ng/mL cutoff. An equivalent detection time for free morphine was obtained when its cutoff was lowered to 25 ng/mL. The possibility that morphine is metabolized to codeine was unequivocally ruled out by the finding of an absence of codeine at or above the LOD of the GC/MS assay in all clinical specimens collected after morphine administration.

Adult↗