Search PubMed⌕ Search

Biomedical subjects

R D Clark

Publications and source records attributed to R D Clark.

105 records · Page 6Linked to original sources
PubMed1975

Fibrinogen metabolism in acute hepatitis and active chronic hepatitis.

Coagulation studies, including those of radioactive fibrinogen metabolism, were performed in seven patients with acute viral hepatitis and 12 patients with active chronic hepatitis. An increased fractional catabolic rate for fibrinogen was observed in four patients from the first group, and seven from the second. The catabolic rate was increased in those patients with the greatest degree of hepatic necrosis as demonstrated by the raised serum aminotransferase levels. There was no correlation between the rate of fibrinogen catabolism and the standard clotting tests, but the SDPS test (indicating the presence of fibrin monomers in the circulation) was consistently positive in those cases where the catabolic rate was increased.

Acute Disease↗
PubMed1967

Poloxalene as an anti-bloat compound and its effect on milk yield and composition.

Poloxalene, a nonionic surfactant, was fed to beef cattle on a legume ration or a high grain ration to observe its effect on bloat. It was also fed to lactating dairy cows to note any effect on yield or composition of milk. Poloxalene was beneficial in the prevention of bloat with both legume and grain rations. It had no effect on per cent fat, protein, solids-not-fat, or yield of milk.

Animals↗
PubMed1965

Effect of injectable iron-dextran on dairy calves and lambs.

Ten Holstein calves, 10 Jersey calves, 7 single lambs, and one lamb from each of ten sets of twins were injected with an iron-dextran solution shortly after birth. These were paired with an equal number of untreated animals that formed the control groups. Percentage of hemoglobin and body weights were recorded periodically up to 16 weeks of age for the calves and 21 weeks for the lambs. Percentage of hemoglobin in the blood of treated calves was generally higher than that of untreated calves but body weights between groups were not significantly different. In the lambs there was no significant difference in percentage of hemoglobin or body weights between the treated and control groups. The results indicate that under the confined system of management as outlined, there was no advantage in administering iron-dextran to young calves or lambs.

Animals↗
PubMedDate not supplied

Treatment patterns among adult patients with asthma: factors associated with overuse of inhaled beta-agonists and underuse of inhaled corticosteroids.

BACKGROUND: Overuse of inhaled beta-agonists and underuse of inhaled corticosteroids by patients with asthma may have adverse consequences. This study was performed to identify factors associated with misuse of these types of asthma medication. METHODS: We examined baseline data from a longitudinal survey of adult patients with asthma. The setting was a consortium of 15 national managed care organizations serving 11 large employers. Baseline surveys were completed by 6612 health plan enrollees at least 18 years old who had had at least 2 visits with a diagnostic code for asthma in the preceding 2 years. The main outcome measures were the overuse of inhaled beta-agonists and the underuse of inhaled corticosteroids. Independent variables were patient and process of care factors. RESULTS: Among patients with moderate or severe asthma, 16% of users of inhaled beta-agonists reported overuse (>8 puffs per day on days of use), and 64% of users of inhaled corticosteroids reported underuse (use on < or =4 days/wk or < or =4 puffs per day). Overuse of inhaled beta-agonists was most strongly associated with concomitant treatment with inhaled corticosteroids or anticholinergic agents, increased asthma symptom severity, problems in obtaining asthma medication, and male sex. Underuse of inhaled corticosteroids was associated with nonwhite race, younger age (18 to 34 years), lower use of inhaled beta-agonist, lower symptom severity, and not possessing a peak flow meter. Rates of misuse of medication also varied by speciality of the patient's provider (generalist, allergist, or pulmonologist). CONCLUSIONS: Overuse of inhaled beta-agonists may be caused by symptom severity, while underusers of corticosteroids may interrupt use as symptoms abate. This study demonstrated an important opportunity to improve medication use among patients with asthma.

Administration, Inhalation↗
PubMedDate not supplied

(R) and (S) RS 56532: mixed 5-HT3 and 5-HT4 receptor ligands with opposing enantiomeric selectivity.

The pharmacological properties of the (R) and (S) enantiomers of RS 56532 have been studied in vitro and in vivo. In radioligand binding studies at 5-HT4 receptors in guinea-pig striatum, (S) RS 56532 exhibited a higher affinity than (R) RS 56532 (-log Ki = 7.6 and 6.5, respectively). (S) RS 56532 acted as a potent agonist at 5-HT4 receptors mediating relaxation of rat oesophageal muscularis mucosae (-log EC50 = 7.9) while (R) RS 56532 acted as a weaker agonist at this receptor (-log EC50 < 6.0). These data suggest that at 5-HT4 receptors, the enantiomeric selectivity of RS 56532 was (S) > (R). In binding studies at 5-HT3 receptors in rat cortex, (R) RS 56532, conversely, exhibited a higher affinity than (R) RS 56532 (-log Ki = 9.1 and 8.0, respectively). At 5-HT3 receptors in guinea-pig isolated ileum, (R) RS 56532 exhibited an affinity (-log KB) of 7.9, whereas (S) RS 56532 (1 nM-1 microM) was inactive. No agonism was observed at ileal 5-HT3 receptors with either enantiomers. These data suggest that at 5-HT3 receptors in rat and guinea-pig, both enantiomers acted as antagonists, with (R) > (S) RS 56532. At the non-5-HT3, high affinity '(R) zacopride' site, (R) RS 56532 exhibited a higher affinity than (S) RS 56532 (-log Ki = 6.1 and 4.9). This site was insensitive to potent 5-HT3 antagonists such as (R) YM 060 or ondansetron. However, it was recognized with relatively high affinity (-log Ki = 7.5) by the (R), but not (S) enantiomer, of RS 42358 (-log Ki = 4.7). Since (S) RS 42358 is a high affinity 5-HT3 receptor antagonist, these data further highlight the dissimilarity between the 5-HT3 receptor and the '(R) zacopride' site. The '(R) zacopride' site also appeared to be pharmacologically distinct from the 5-HT4 receptor, since 5-HT4 ligands such as renzapride, SDZ 205,557 or RS 23597-190 exhibited low affinities. The enantiomeric selectivity of (R) and (S) RS 56532 in vivo was consistent with findings in vitro. At 5-HT4 receptors mediating tachycardia in the pig, 5-HT induced a dose-dependent tachycardia (ED50 = 3 micrograms kg-1, i.v.; maximum response = 90-100 beats min-1). (S) RS 56532 increased heart rate by 88 min-1 with a potency of (ED50) of 3 micrograms kg-1, i.v.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

[3H]RS 57639, a high affinity, selective 5-HT4 receptor partial agonist, specifically labels guinea-pig striatal and rat cloned (5-HT4S and 5-HT4L) receptors.

RS 57639, by being a partial agonist in rat esophagus but a competitive antagonist in guinea-pig ileum, is one of several ligands which operationally discriminate among 5-HT4 receptors in different tissues. The discovery of splice variants of the 5-HT4 receptor, 5-HT4S and 5-HT4L, raises the possibility that this functional heterogeneity among 5-HT4 receptors may be due to differences in the interaction of ligands with different isoforms of the receptor. To test this idea, the functional and binding interactions of RS 57639 with rat 5-HT4S and 5-HT4L receptors were characterized. RS 57639 stimulated adenylate cyclase in cells expressing 5-HT4S or 5-HT4L receptors with similar potency (pEC50 = 7.9 +/- 0.1 and 7.6 +/- 0.1) and efficacy (71 +/- 3 and 59 +/- 4% of 5-HT). [3H]RS 57639 also bound to 5-HT4S and 5-HT4L receptors with similar affinity (Kd = 0.09 +/- 0.01 and 0.11 +/- 0.01 nM) and specificity (SB204070 > GR113808 > SDZ 205557 > cisapride > renzapride > alpha me-5-HT > 5-CT). Therefore, the operational differences among 5-HT4 receptors, detected with RS 57639, are not explained by differences in the interaction of the ligand with 5-HT4S and 5-HT4L receptors. [3H]RS 57639 binding to guinea-pig striatal membranes was also characterized. [3H]RS 57639 bound with high affinity (Kd = 0.25 +/- 0.07 nM) and a specificity similar to that of the 5-HT4 receptor antagonist, [3H]GR113808. Therefore, while the mechanism by which RS 57639 operationally distinguishes among 5-HT4 receptors was not determined, [3H]RS 57639 was shown to specifically label native and cloned 5-HT4 receptors. As the first selective agonist radioligand to be described for this receptor, [3H]RS 57639 may prove useful in further studies of receptor coupling and ligand interactions.

Aminobenzoates↗
PubMedDate not supplied

The effects of novel, selective 5-hydroxytryptamine (5-HT)4 receptor ligands in rat spatial navigation.

Activation of central 5-hydroxytryptamine (5-HT4) receptors may enhance cognitive performance. In the present study, the effects of two novel, potent and selective 5-HT4 receptor agonists, RS 67333 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-burtl-4-piperidinyl)- 1-propanone) and RS 67506 (1-(4-amino- 5-chloro-2-methoxyphenyl)-3-[1-[2-[(methylsulfonyl)amino]ethyl]-4- piperidinyl]-1-propanone), were studied in a rat model of spatial learning and memory; the Morris water maze. RS 67333 (0.1, 10 and 1000 micrograms/kg, intraperitoneally (i.p.)), a highly potent, selective and hydrophobic 5-HT4 receptor agonist, reversed the decrements in cognitive performance induced by atropine (30 mg/kg, i.p.). By contrast, no effect was seen to RS 67506 (0.1, 10 and 1000 micrograms/kg, i.p.), a hydrophilic 5-HT4 receptor agonist, of equivalent potency and selectivity to RS 67333. This differential effect may reflect the enhanced ability of RS 67333 to enter the CNS, with respect to RS 67506. The ameliorative actions of RS 67333 on cognitive dysfunction were abolished by prior treatment with a selective 5-HT4 receptor antagonist, RS 67532 [1-(4-amino-5-chloro-2-(3, 5-dimethoxy benzyloxyphenyl)-5-(1-piperidinyl)-1-pentanone; 1 mg/kg, i.p.]. When given alone, or in naive rats, RS 67532 (0.1, 10 and 1000 micrograms/kg, i.p.), was without effect. None of the compounds tested affected the swim speed at any of the doses used. In separate locomotor studies, RS 67532 reduced activity at 1 and 10 mg/kg, i.p., although no effect was seen with RS 67333 or RS 67506 (0.01-10 mg/kg, i.p.). These data suggest that RS 67333 reversed the cognitive deficit induced by atropine and support a role of 5-HT4 receptors in rat spatial learning and memory.

Aniline Compounds↗
PubMedDate not supplied

Visualizing substructural fingerprints.

Substructural fingerprints have proven very useful for chemical library and diversity analysis, but their high dimensionality makes them poorly suited to principal components analysis and to standard nonlinear mapping methods. By using a combination of optimizable K-dissimilarity selection (OptiSim) and a modified stress function that suppresses effects of distances that fall beyond a characteristic horizon, it is possible to relax principal components analysis coordinates into more consistently meaningful projections from fingerprint space into two dimensions. The nonlinear maps so obtained are useful for characterizing combinatorial libraries, for comparing sublibraries, and for exploring the distribution of biological properties across structural space.

Combinatorial Chemistry Techniques↗