PubMed Health⌕ Search

Biomedical subjects

J R Carpenter

Publications and source records attributed to J R Carpenter.

At least 19 recordsLinked to original sources
PubMed2005

Phosphorus in Hawaiian kikuyugrass pastures and potential phosphorus release to water.

Pasture systems in Hawaii are based primarily on kikuyugrass (Pennisetum clandestinum Hochst. ex Chiov.). Relationships among kikuyugrass P concentration, animal P requirements, and various soil P determinations are needed to help identify source areas for implementing pasture management strategies to limit P loss via overland flow. A total of 51 rotationally stocked kikuyugrass pastures (>20 yr old) with contrasting soil chemical properties were sampled. A satisfactory predictive relationship between modified-Truog (MT)-extractable phosphorus (P(MT)) and dissolved (<0.45-mum pore diameter), molybdate-reactive phosphorus (DRP) desorbed from soil in a water extract (DRP(WE)) was found when 0- to 4-cm-depth data for the soil orders with medium to high DRP(WE) (two Mollisols and an Inceptisol) were pooled separately from those with low DRP(WE) (five Andisols, three Ultisols, and an Oxisol). The oxalate phosphorus saturation index (PSI(ox)) procedure was the best predictor of DRP(WE) across soil orders when oxalate-extractable molybdate-reactive phosphorus (RP(ox)) was used to calculate PSI(ox) (PSI(ox)RP) rather than when total oxalate-extractable phosphorus (TP(ox)) was used (PSI(ox)TP). There was little DRP(WE) until PSI(ox)RP exceeded 6% or PSI(ox)TP exceeded 8%. A more empirical dilute-acid phosphorus saturation index (PSI(MT)) was also calculated using P(MT) and MT-extractable iron (Fe(MT)) and aluminum (Al(MT)). The PSI(MT) procedure showed some utility in predicting DRP(WE), was positively related to the PSI(ox) procedures, and can be more readily performed in agronomic soil testing laboratories than PSI(ox). The present research suggests that while Hawaiian kikuyugrass pastures tend to be sufficient to high in forage P, potential soil P release to water only appeared to be a possible environmental concern for the Mollisol and Inceptisol sites.

Animals↗
PubMed2005

Long-term ursodeoxycholic acid therapy for primary biliary cirrhosis: a follow-up to 12 years.

BACKGROUND: It is uncertain whether ursodeoxycholic acid therapy slows down the progression of primary biliary cirrhosis, according to two meta-analyses. However, the randomized trials evaluated had only a median of 24 months of follow-up. AIM: To evaluate long-term ursodeoxycholic acid therapy in primary biliary cirrhosis. METHODS: We evaluated 209 consecutive primary biliary cirrhosis patients, 69 compliant with ursodeoxycholic acid and 140 untreated [mean follow-up 5.79 (s.d. = 4.73) and 4.87 (s.d. = 5.21) years, respectively] with onset of all complications documented. Comparison was made following adjustment for baseline differences according to Cox modelling, Mayo and Royal Free prognostic models. RESULTS: Bilirubin and alkaline phosphatase concentrations improved with ursodeoxycholic acid (at 36 months, P = 0.007 and 0.018, respectively). Unadjusted Kaplan-Meier analysis showed benefit (P = 0.028), as 44 (31%) untreated and 15 (22%) ursodeoxycholic acid patients died or had liver transplantation. However, there was no difference when adjusted by Cox modelling (P = 0.267), Mayo (P = 0.698) and Royal Free models (P = 0.559). New pruritus or fatigue or other complications were not different, either before or after adjustment for baseline characteristics. CONCLUSIONS: Long-term ursodeoxycholic acid therapy did not alter disease progression in primary biliary cirrhosis patients despite a significant improvement in serum bilirubin and alkaline phosphatase consistent with, and similar to, those seen in ursodeoxycholic acid cohorts in randomized trials.

Adult↗
PubMed2000

Bootstrap confidence intervals for relative risk parameters in affected-sib-pair data.

In affected-sib-pair (ASP) studies, parameters such as the locus-specific sibling relative risk, lambda(s), may be estimated and used to decide whether or not to continue the search for susceptibility genes. Typically, a maximum likelihood point estimate of lambda(s) is given, but since this estimate may have substantial variability, it is of interest to obtain confidence limits for the true value of lambda(s). While a variety of methods for doing this exist, there is considerable uncertainty over their reliability. This is because the discrete nature of ASP data and the imposition of genetic "possible triangle" constraints during the likelihood maximization mean that asymptotic results may not apply. In this paper, we use simulation to evaluate the reliability of various asymptotic and simulation-based confidence intervals, the latter being based on a resampling, or bootstrap approach. We seek to identify, from the large pool of methods available, those methods that yield short intervals with accurate coverage probabilities for ASP data. Our results show that many of the most popular bootstrap confidence interval methods perform poorly for ASP data, giving coverage probabilities much lower than claimed. The test-inversion, profile-likelihood, and asymptotic methods, however, perform well, although some care is needed in choice of nuisance parameter. Overall, in simulations under a variety of different genetic hypotheses, we find that the asymptotic methods of confidence interval evaluation are the most reliable, even in small samples. We illustrate our results with a practical application to a real data set, obtaining confidence intervals for the sibling relative risks associated with several loci involved in type 1 diabetes.

Confidence Intervals↗
PubMed2000

Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations.

We describe a novel method for analysis of marker genotype data from admixed populations, based on a hybrid of Bayesian and frequentist approaches in which the posterior distribution is generated by Markov chain simulation and score tests are obtained from the missing-data likelihood. We analysed data on unrelated individuals from eight African-American populations, genotyped at ten marker loci of which two (FY and AT3) are linked (22 cM apart). Linkage between these two loci was detected by testing for association of ancestry conditional on parental admixture. The strength of this association was consistent with European gene flow into the African-American population between five and nine generations ago. To mimic the mapping of an unknown gene in an 'affecteds- only' analysis, a binary trait was constructed from the genotype at the AT3 locus and a score test was shown to detect linkage of this 'trait' with the FY locus. Mis-specification of the ancestry-specific allele frequencies - the probabilities of each allelic state given the ancestry of the allele - was detected at three of the ten marker loci. The methods described here have wide application to the analysis of data from admixed populations, allowing the effects of linkage and population structure (variation of admixture between individuals) to be distinguished. With more markers and a more complex statistical model, genes underlying ethnic differences in disease risk could be mapped by this approach.

Bayes Theorem↗
PubMed1999

Nutrient, fatty acid, amino acid and mineral analysis of natural prey of the Hawaiian monk seal, Monachus schauinslandi.

Proximate nutrients, gross energy content, mineral, amino acid and fatty acid composition were determined for teleost, cephalopod and crustacean prey of the Hawaiian monk seal. Crude protein was highest in the octopus, Octopus cyanea (80.0%), crude fat was highest in the Muraenid teleost, Gymnothorax eurostus (14.1%), whereas crude ash was highest in the lobster, Panulirus marginatus (11.6%). Gross energies ranged from 4.0 +/- 0.01 kcal g-1 in the Labrid teleost Bodianus bilulunatus to 6.0 +/- 0.12 kcal g-1 in the moray eel, Gymnothorax undulatus. Essential amino acids occurred in lower concentrations as a percentage of the total amino acids (35.8 +/- 2.6%) than non-essential amino acids (64.2 +/- 2.6%), but the ratio of individual amino acids to total amino acid concentrations were similar to those required by some monogastric terrestrial species and fingerling salmon. The fatty acid concentrations varied widely among species (range = 1.2-16.5 mg 100 mg-1); however, the teleosts had higher total fatty acids than the non-teleosts. This study indicates that, from a nutritional standpoint, some prey may be more beneficial to the Hawaiian monk seal; however, these prey are not necessarily the most abundant or available to some populations of the monk seal.

Amino Acids↗
PubMed1995

Prepartum nutrition and solar radiation in beef cattle: I. Relationships of body fluid compartments, packed cell volume, plasma urea nitrogen, and estrogens to prenatal development.

Adaptations in body fluid pools during pregnancy were monitored in cows (n = 19) assigned to either low (LO, 70% NRC total feed intake) or high (HI, 110% NRC total feed intake) nutritional level (sudangrass hay) and to either shade (S) or no shade (NS) treatments in a 2 x 2 factorial experiment. Body water distribution (empty body water [EBW] by urea dilution; extracellular water [ECW] by thiosulfate dilution; intracellular water [ICW] by difference; plasma volume by Evans Blue dilution; interstitial water [ISW] by difference) was measured at 4-wk intervals beginning at 3 mo of pregnancy until birth and then immediately after birth. Both EBW and ICW in LO cows showed a steady decline (P < or = .05), whereas HI cows tended to maintain these body pools throughout gestation. Shading did not affect the pattern of change in EBW; however, it did produce a greater (P < or = .05) ICW in the S than in the NS cows throughout gestation. Generally, other body fluid pools (ECW, ISW, and plasma) were either not affected, or were just slightly affected, by shading or nutrition. Most of the body fluid pools (EBW, ECW, ICW, and ISW) inversely followed the seasonal changes in solar radiation. Calf birth weights were not affected by treatments but were moderately correlated to EBW (r = .49; P < or = .05) and ICW (r = .50; P < or = .05). Plasma urea nitrogen change, although not affected by nutrition, was affected (P < or = .05) by shading.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1995

Prepartum nutrition and solar radiation in beef cattle: II. Residual effects on postpartum milk yield, immunoglobulin, and calf growth.

Residual effects of nutrition and solar radiation during the last two-thirds of gestation on postpartum milk yield, immunoglobulin (Ig) G and M in both colostrum and calf serum, and calf growth were determined in beef cattle. Nineteen mature, multiparous crossbred cows (Bos taurus) at d 90 of pregnancy were assigned to either low (LO, 70% NRC total energy intake) or high (HI, 110% NRC total energy intake) nutritional level (sudangrass hay) and to either shade (S) or no shade (NS) treatments in a 2 x 2 factorial experiment. After parturition, all cows were moved into a large paddock and managed uniformly. Calf weights and calf serum were collected within 1 d postpartum, thereafter at 2-wk intervals for the next 12 wk, and then at 4-wk intervals until weaning. Colostrum samples were taken from the cow and milk yields were determined by the "weigh-suckle-weigh" technique. Neither prepartum nutrition nor environment influenced lactational performance of the dam. Concentrations of IgG were elevated in the colostrum of LO cows (15.3 vs 7.8 g/100 mL, LO vs HI, respectively; P < or = .05) but were not affected by shading. The patterns of IgG concentration in the calf serum were not altered by prepartum nutrition or environment; however, the pattern of IgM concentrations was greater (P < or = .01) in calves from S cows than in those from NS cows. This difference in IgM profile did not seem to be due to any residual effect from prepartum treatments. Postnatal growth of calves from birth until weaning were similar across all prepartum treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1993

Airway response to inhaled methacholine in normal human subjects.

The individual airway responsiveness to inhaled, nebulized methacholine (MeCh) was estimated in normal volunteers, measuring specific airway conductance (sGAW). The dose of MeCh was increased logarithmically until a 60-65% reduction from baseline sGAW or an asymptotic approach to a maximal response was attained. The concentration of MeCh that caused a 35% reduction in sGAW (PC35), the dose that caused a 62.5% reduction in sGAW, the slope of the straight, central part of the log-dose-response curve (LDRC), the slope of the straight, initial part of the dose-response curve, the maximal response attainable (Emax) and the dose causing a half-maximal response (ED50) were derived. These parameters were transformed as necessary to attain normality of distribution. Relationships between them were examined by measuring the correlations between their transformed values. The ED50 was taken to represent the least biased estimate of the sensitivity to MeCh. The PC35 was the best practical estimate of sensitivity. The Emax was taken to represent the least biased estimate of the reactivity to MeCh. The slope of the LDRC was the best practical estimate of reactivity. The sensitivity and reactivity varied independently in these normal subjects. Each was also independent of the baseline sGAW.

Administration, Inhalation↗
PubMed1993

Trials of the bronchodilator activity of the xanthine analogue SDZ MKS 492 in healthy volunteers during a methacholine challenge test.

An approximately steady-state reduction of specific airway conductance was induced in healthy human subjects by means of an individualized inhaled methacholine loading dose followed by a maintenance dose regime. Tested against this background bronchoconstriction, the xanthine analogue SDZ MKS 492, when administered as a single oral dose of 40 mg, showed a significant bronchodilator action, which lasted for up to 5.5 h. Bronchodilatation was not seen after administration of 10 or 20 mg doses. SDZ MKS 492 inhaled as a dry powder had a bronchodilator action that was small, most evident with the 12 mg dose and transient. The peak relief of imposed bronchoconstriction was 29% and the apparent half-time of removal of SDZ MKS 492 from its site of action was 5-6 min. Inhaled SDZ 492 had a bitter taste that was not masked by inclusion of menthol and aspartame in the formulation. The bronchodilatation seen in laboratory animals can also be produced by SDZ MKS 492 in man when administered orally or by inhalation. Its magnitude correlates better with the plasma concentration of parent drug than with that of either of the identified metabolites. Dispositional processes in the lung abbreviate its action after administration by inhalation.

Administration, Inhalation↗
PubMed1993

Beta-adrenoceptor subtypes and the opening of plasmalemmal K(+)-channels in bovine trachealis muscle: studies of mechanical activity and ion fluxes.

1. Studies of mechanical activity and 86Rb+ efflux have been made in bovine isolated trachealis with the objectives of: (a) identifying which of the beta-adrenoceptor subtypes mediates the opening of plasmalemmal K(+)-channels, (b) gaining further insight into the properties of the novel, long-acting beta 2-adrenoceptor agonist, salmeterol and (c) clarifying the role of K(+)-channel opening in mediating the mechano-inhibitory actions of agonists at beta-adrenoceptors. 2. In bovine trachealis muscle strips precontracted with histamine (460 microM), isoprenaline (0.1 nM-1 microM), procaterol (0.1-10 nM) and salmeterol (0.1-10 nM) each caused concentration-dependent relaxation. 3. ICI 118551 (10 nM-1 microM) antagonized isoprenaline, procaterol and salmeterol in suppressing histamine-induced tone of the isolated trachealis muscle. The antagonism was concentration-dependent. In contrast, CGP 20712A (10 nM-1 microM) failed to antagonize isoprenaline, procaterol or salmeterol. 4. Salmeterol (1-10 microM) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (1 microM). 5. Cromakalim (10 microM), isoprenaline (100 nM-10 microM), procaterol (10 nM-1 microM) and salbutamol (100 nM-10 microM) each promoted the efflux of 86Rb+ from strips of bovine trachealis muscle preloaded with the radiotracer. In contrast, salmeterol (100 nM-10 microM) failed to promote 86Rb+ efflux. 6. CGP 201712A (1 microM), ICI 118551 (100 nM) and salmeterol (1 microM) did not themselves modify 86Rb+ efflux from trachealis muscle strips, nor did they affect the promotion of 86Rb+ efflux induced by cromakalim (10 microM). In contrast, CGP 20712A (1 microM) and ICI 118551 (100nM) were each able to inhibit the promotion of 86Rb+ efflux induced by isoprenaline (1 microM) or procaterol (100 nM). Furthermore,salmeterol (10 microM) inhibited isoprenaline (1 microM)-induced promotion of 86Rb+ efflux.7. It is concluded that, in bovine trachealis, activation of either beta l- or beta 2-adrenoceptors can promote the opening of 86Rb+-permeable K+-channels in the plasmalemma. The failure of salmeterol to promote plasmalemmal K+-channel opening may reflect, not its selectivity in activating beta 2- as opposed to beta 1-adrenoceptors, but rather its low intrinsic efficacy at beta 2-adrenoceptors. The opening of plasmalemmal K+-channels plays a supportive rather than a crucial role in mediating the mechano-inhibitory effects of agonists at beta-adrenoceptors acting on trachealis muscle.

Adrenergic beta-Agonists↗
PubMed1992

Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test.

1. An approximately steady-state reduction of specific airway conductance was induced in normal human subjects by means of a methacholine individualized loading+maintenance dose regime. Tested against this background bronchoconstriction, the mixed type III/IV phosphodiesterase inhibitor AH 21-132, ingested in doses up to 90 mg, had no detectable bronchodilator activity. 2. AH 21-132, infused intravenously over 15 min, evoked short-lived bronchodilatation at doses of 20 and 40 mg, without affecting blood pressure or heart rate. 3. AH 21-132, mixed 1:18.5 by weight with sucrose, dissolved in saline, nebulized and inhaled in doses between 2 and 24 mg of AH 21-132, produced dose-dependent bronchodilation. The ED50 was estimated as 9.2 mg AH 21-132. The peak relief of imposed bronchoconstriction was 80% and the apparent half-time of removal of AH 21-132 from its site of action was 25 min. 4. Inhaled, nebulized, hypertonic sucrose had a minor bronchodilator action. 5. AH 21-132, by intravenous and inhaled routes of administration, provides relief of methacholine-induced bronchoconstriction.

Administration, Inhalation↗
PubMed1991

A method for bioassay of potency and effectiveness of inhaled bronchodilators in normal subjects.

1. Bioassay of inhaled bronchodilator drugs for potency and effectiveness in normal human subjects is rendered difficult and imprecise because bronchomotor tone is low. When attempting to determine log dose-effect relationships for inhaled, nebulised bronchodilator drugs and measuring increased specific airways conductance (sGaw), the coefficient of variation of each mean response is likely to be so large that an intermediate response is not significantly different from either the maximum or no response. 2. A method is described by which inhaled, nebulised bronchodilator drugs can be bioassayed for potency and effectiveness with high precision. The method involves the use of inhaled, nebulised bronchoconstrictor agents (methacholine or histamine) to provide a highly reproducible, near-constant, background reduction in airway conductance in normal human subjects. The activity of bronchodilators is assessed against this background reduction in airway conductance. 3. Log specific airway conductance (log sGaw) was chosen as the response metameter on grounds of normality of distribution and relative homoscedasticity. A central straight line segment of the bronchoconstrictor drug dose-effect curve extending over a 10-fold dose multiple could be found easily; the upper end of this segment occurred near 67-75% reduction in sGaw and was reproducible. 4. The effect of a dose bronchoconstrictor drug causing 67-75% reduction in sGaw waned linearly with time at first, over the effect segment corresponding to the linear segment of the drug's log dose-effect curve. The rate constant of local elimination of bronchoconstrictor drug from its site of action, in inhaled dose equivalents, was deduced from the ratio of the slopes of the linear segments of the log dose-effect and time-effect curves. 5. The maintenance dose rate to maintain the peak effect (67-75% reduction in sGaw) of the loading dose was calculated. The repeated administration of maintenance doses at regular short intervals, at this calculated dose rate, created a steady state of bronchoconstriction equal in extent to the effect of the loading dose. This steady state bronchoconstriction occurred without undue discomfort for the subject and was reproducible. 6. Against this background bronchoconstriction, inhaled, nebulised salbutamol produced a rapidly developing and slowly waning increase in sGaw. Reproducible log dose-effect curves for the bronchodilator drugs salbutamol and reproterol allowed measurement of their potency and effectiveness; the potency of reproterol relative to salbutamol was 0.082 with 95% confidence limits of 0.0504 and 0.131. 7. Estimation of the subject's pharmacodynamic and pharmacokinetic parameters for inhaled methacholine from just three dosage individualising sessions provides estimates accurate enough to be of practical value.

Adult↗
PubMed1987

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis.

Plasma levels of hydroxychloroquine (HCQ) and its metabolites were measured, by high performance liquid chromatography, in 37 rheumatoid arthritis patients who could be clearly distinguished as responders (n = 28) or nonresponders (n = 9) to HCQ, 400 mg/day. Efficacy in both groups was determined by the patients' erythrocyte sedimentation rates, joint counts, morning stiffness, global assessments, concurrent drug therapies, and grip strength. The response rate was 76%. Responders had a mean HCQ level of 213 ng/ml, versus 306 in nonresponders (P less than 0.05). The mean level of HCQ plus total metabolites in responders was 363 ng/ml, versus 554 in nonresponders (P less than 0.01). We conclude that monitoring plasma HCQ levels is unlikely to be helpful in individualizing effective drug dosage.

Arthritis, Rheumatoid↗
PubMed1987

Effects of spasmogens on relaxant dose-response curves to full or partial agonists at beta-adrenoceptors of guinea pig isolated trachea.

When guinea pig isolated trachea is contracted with either carbachol or methacholine, relaxant concentration-response curves to isoprenaline, salmefamol and fenoterol were shifted to the right, compared with curves obtained with either spontaneous or histamine-induced tone. Carbachol and methacholine also reduced the maximal relaxation to fenoterol and abolished relaxations to the partial agonist pindolol. It is concluded that the processes linking receptor to contractile response in trachea are different for histamine receptors and muscarinic cholinoceptors.

Adrenergic beta-Agonists↗
PubMed1987

Early production of 1,4,5-inositol trisphosphate and 1,3,4,5-inositol tetrakisphosphate by histamine and carbachol in ileal smooth muscle.

We have examined the time course of the formation of inositol mono-, bis-, tris, and tetrakisphosphates (InsP1, InsP2, InsP3, and InsP4, respectively) in slices of the longitudinal muscle of guinea pig small intestine that had been prelabeled with myo-3H-inositol. The agonists employed were histamine and carbachol. InsP3 increases immediately with a time course which is similar to that of the increase in contractile force and remains elevated for the rest of the incubation period. High performance liquid chromatography analysis revealed that InsP3 is composed of two isomers, the 1,4,5- and 1,3,4-isomers. The release of 1,4,5-inositol trisphosphate [Ins(1,4,5)P3] was followed by the rapid accumulation of InsP4 and later on by the formation of 1,3,4-inositol trisphosphate [Ins(1,3,4)P3]. Ins(1,3,4)P3 and InsP4 were identified by co-chromatography with the Ins(1,3,4)P3 and 1,3,4,5-inositol tetrakisphosphate prepared from 3H-Ins(1,4,5)P3 using a kinase from rat brain. The time course of accumulation of these compounds is consistent with a second messenger role of Ins(1,4,5)P3 in initiation of smooth muscle contraction.

Animals↗