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Biomedical subjects

R F Palmer

Publications and source records attributed to R F Palmer.

At least 19 recordsLinked to original sources
PubMed1981

Effects of inhaled diesel emissions and coal dust in rats.

Rats were exposed to coal dust and diesel exhaust emissions, separately and in combination, for 20 months to evaluate the potential health effects of these specific mine air materials. The diesel exhaust was produced by an engine operated in a load, no-load mode and acceleration, deceleration cycle. It was also modified to simulate an inefficiently tuned engine. Exposure to coal dust was performed in a whole-body rodent inhalation system. Mortality, body weight and hematologic parameters examined were normal compared with those of control rats. Lesions observed were primarily restricted to the lungs and were similar to those described for simple coal workers' pneumoconiosis (CWP). Lesion progression and severity was related to exposure duration and exposure material. Alveolar bronchiolization, though not reported in human CWP, was present in the lungs of some rats in all exposure groups except the control animals.

Animals↗
PubMed1980

The effects of amrinone on contractility, Ca2+ uptake and cAMP in smooth muscle.

Amrinone, a known positive inotropic agent in the heart, was found to cause a dose-dependent (10--100 micrograms/ml) inhibition of norepinephrine (NE) or high-K+-induced contractions of rabbit aorta. Amrinone also inhibited carbachol or high-K+-induced contractions of guinea-pig taenia coli. Neither total tissue 45Ca uptake nor the rate of 45Ca uptake induced by 80 mM K+ in rabbit aorta was altered by pretreatment with amrinone. On the other hand, a similar pretreatment with amrinone inhibited NE (10(-6) or 10(-5) M) induced tissue 45Ca uptake. Amrinone (100 micrograms/ml) caused about a 70% increase in cAMP concentration over resting levels. It is concluded that amrinone causes a nonspecific inhibition of smooth muscle contractility by acting probably at multiple sites to decrease the availability of Ca2+ required for activation. One or more of these mechanisms may involve cAMP.

Aminopyridines↗
PubMed1980

A stable isotope dilution assay for disopyramide and its [13C, 15N]labelled analogue in biological fluids.

The mass spectra of disopyramide phosphate and two stable isotopically labelled analogues have been obtained using electron impact and chemical ionization. The low isotopic purity of [13C, 15N)disopyramide phosphate was shown to be due to the low isotopic purity of the 15N label. A stable isotope dilution assay for disopyramide and [13C, 15N]disopyramide in biological fluids has been developed using [2H14]disopyramide phosphate as the internal standard. This assay will be used to analyse samples obtained after the co-administration of disopyramide phosphate intravenously and [13C, 15N]disopyramide phosphate orally to several animal species.

Animals↗
PubMed1979

Bioavailability and pharmacokinetics of norethisterone in women after oral doses of ethynodiol diacetate.

Measurement by radioimmunoassay of plasma norethisterone (NE) has been used to compare the bioavailability of tablets containing ethynodiol diacetate (EDA) with that of a standard oral solution of this progestogen in 12 normal women. The tablets investigated were from three batches which showed different in vitro dissolution rates. There were no significant differences in the bioavailability of the tablet formulations, which were essentially bioequivalent to the solution. Peak blood levels of NE were reached within 4h of EDA administration in solution or tablets. After the peak, NE plasma levels declined in two phases, with a mean terminal elimination half lives of 4 to 6.9h. The pharmacokinetics of NE after EDA administration showed some similarity to those observed by other workers after oral doses of NE itself.

Adult↗
PubMed1979

The use of 22Na as a tracer for long-term bone mineral turnover studies.

Sodium-22 has been studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with 22Na, which is released through the metabolic turnover of the bone. The 22Na not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high, but nontoxic levels of NaCl. The 22Na tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

Adult↗
PubMed1978

Application of ion-exchange and lipophilic-gel chromatography to the purification and group fractionation of steroidal spirolactones, isolated from biological fluids.

Chromatography of steroidal spirolactones on DEAE-Sephadex A-25 under selected pH conditions allowed efficient separation of these compounds from other steroids and many of the endogenous components of human urine. The spirolactones were recovered in high yield, mostly over 90%. Lipophilic-gel chromatography provided a useful method for group fractionation of mixtures of these spirolactones with high recoveries (generally over 90%), unaffected by the presence of endogenous material from normal human urine.

Canrenoic Acid↗
PubMed1978

Electron impact and chemical ionization mass spectrometry of steroidal spirolactones.

Electron impact and chemical ionization mass spectra are reported for several steroidal spirolactones and their TMS ethers. The electron impact spectra were characterized generally by low abundance molecular ions and large numbers of fragment ions. Methane chemical ionization spectra exhibited high intensity [M+H]+ and/or [M+H-H2O]+ or [M+H-TMSOH]+ ions with few other fragment ions. Ammonia chemical ionization spectra had intense [M+H]+ and/or [M+NH4]+ ions with a few fragment ions generally formed by loss of H2O or TMSOH from these parent ions. Ammonia chemical ionization gave intense parent ions even for polyhydroxy compounds and their TMS ethers in contrast to methane chemical ionization. The results of this study suggest that a combination of electron impact with ammonia chemical ionization mass spectrometry would offer the best techniques for detection and identification of these compounds in biological fluids.

Ammonia↗
PubMed1978

Endocrine effects of spironolactone in man.

A double blind, controlled study was carried out in order to investigate the effects of administering spironolactone, 200 mg daily, to five healthy male volunteers. The patterns of change in plasma testosterone (T) and luteinizing hormone (LH) after spironolactone were significantly different from placebo and there were significant increases in the urinary excretion of androsterone (A), aetiocholanolone (EC) and total oestrogen. Urinary dehydroepiandrosterone (DHA) excretion, after an initial rise, declined progressively during the treatment period relative to controls. The results are discussed in the light of previous observations. It is concluded that treatment with spironolactone for 2--4 days will lead to a transient rise in plasma T and urinary DHA. Continued treatment (4--10 days) is thought to cause increased LH secretion, with normalization of plasma T and DHA excretion. These changes are accompanied by increased androgen catabolism and a slightly increased conversion of androgens to oestrogens. Healthy men may therefore show alterations in sex steroid metabolism if treated for several days with high doses of spironolactone.

17-Ketosteroids↗
PubMed1978

Identification of some urinary metabolites of propantheline bromide in man.

The peak plasma concn. of total radioactivity occurred 6 h after a single oral dose of [carboxyl-14C; methyl-2H3] propantheline bromide was administered to a healthy man. At this time 10% of the dose was present in the total plasma volume. 2. A total of 71% dose of radioactivity was excreted in urine in 96 h after dosage, 59% dose being excreted in the first 24 h. About 5.3% of the orally administered propantheline bromide was excreted unchanged. 3. T.l.c. analysis and g.l.c.-mass spectrometry showed xanthanoic acid, hydroxyxanthanoic acid(s), and propantheline as urinary metabolites of the drug. 4. A glucuronide of xanthanoic acid, a hydroxylated propantheline and the (2-hydroxyethyl)diisopropylammonium ion were tentatively identified as urinary metabolites. Hydrolysis of propantheline and conjugation of the resulting xanthanoic acid appear to be the major routes of metabolism of this compound. 5. A mean elimination half-life of 9.2 h was obtained for the total radioactivity by pharmacokinetic analysis of plasma and urine levels of 14C.

Adult↗
PubMed1977

Ethanol and oral diazepam absorption.

Despite widespread use and abuse of ethanol and diazepam in combination, little is known about the effects of ethanol on diazepam absorption. We administered diazepam (0.07 mg per kilogram of body weight) with water and with 30 ml of 50 per cent ethanol to seven normal volunteers. Plasma diazepam levels were significantly higher at 60 minutes (P less than 0.05), 90 minutes (P less than 0.01), 120 minutes (P less than 0.01), and 240 minutes (P less than 0.01) when diazepam was administered with ethanol than with water alone. Since maximum mean plasma diazepam levels after combined ingestion with ethanol were nearly twice as high than after diazepam and water (373 ng per milliliter versus 197 ng per mililiter at 60 minutes) we conclude that ethanol enhanced diazepam absorption.

Administration, Oral↗
PubMed1977

The measurements of propantheline ion in biological fluids after administering propantheline bromide to man.

The measurement of propantheline ion has been accomplished in urine and plasma following administration of propantheline bromide to man. Trideuteropropantheline bromide is added to the biological fluid to act as a carrier and internal standard to quantify the propantheline ion using multiple ion monitoring. Methane was used as reactant gas but following the discovery of exchange of the trideuteromethyl group when using methane, ammonia was used for later analyses. The determination of propantheline ion in urine and plasma after administration of propantheline bromide to man is described.

Deuterium↗
PubMed1977

Factors influencing comparative bioavailability of spironolactone tablets.

The bioavailability of spironolactone from 10 tablet formulations, selected to provide a wide range of specifications and in vitro dissolution rates, was assessed from the plasma and urinary levels of its major unconjugated metabolite, canrenone, in a study of balanced incomplete block design using 11 healthy subjects. Significant but weak correlations existed between the amount of spironolactone in solution at 40 min in vitro and the area under the plasma concentration-time curve for canrenone and urinary canrenone excretion. The correlations between in vitro dissolution and bioavailability parameters appeared to be weakened by two tablet formulations, one with dibasic calcium phosphate as the principal excipient and the other formulated from micronized spironolactone bulk drug. Measurement of in vitro dissolution of spironolactone tablets is of value for quality control purposes, provided no major alteration is made in the formulation.

Adult↗