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Biomedical subjects

P Butler

Publications and source records attributed to P Butler.

At least 19 recordsLinked to original sources
PubMed2000

The in vivo pharmacological profile of eletriptan (UK-116,044): a potent and novel 5-HT(1B/1D) receptor agonist.

The anti-migraine drug, eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1 H-indole; UK-116,044], is a novel 5-HT(1B/1D) receptor agonist. In this paper, the regional vasoconstrictor profile of eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibitory actions of eletriptan on neurogenic inflammation in rat dura mater were also assessed. In the anaesthetised dog, eletriptan (1-1000 microg kg(-1) i.v.) produced a dose-dependent reduction of carotid arterial blood flow with a similar potency and maximum effect to sumatriptan (ED(50) values: eletriptan and sumatriptan, 12 and 9 microg kg(-1), i.v., respectively). However, eletriptan exhibited a significantly lower potency than sumatriptan in reducing coronary artery diameter (ED(50) values: 63 and 19 microg kg(-1), i.v., respectively, P<0.05). In the femoral circulation, sumatriptan caused a significant reduction in arterial blood flow (ED(50) 35 microg kg(-1) i.v.) whereas eletriptan (1-1000 microg kg(-1) i.v.) had no significant effect upon femoral arterial blood flow when compared to vehicle-treated animals. In rats, eletriptan (30-300 microg kg(-1) i.v.) administered prior to electrical stimulation of the trigeminal ganglion produced a dose-related and complete inhibition of plasma protein extravasation in the dura mater (mean extravasation ratio: control 1.9; eletriptan 1.0, minimum effective dose 100 microg kg(-1), P<0.05). The potency and maximum effect of eletriptan was identical to that of sumatriptan in this model. When administered during a period of continual stimulation of the trigeminal nerve, eletriptan (100 microg kg(-1) i.v.) produced a complete inhibition of plasma protein extravasation. The ability to reduce canine carotid arterial blood flow and inhibit neurogenic inflammation in rat dura mater suggests that vascular and neurogenic mechanisms may contribute to eletriptan's clinical efficacy in migraine patients. In addition, eletriptan exhibits some selectivity for reducing carotid arterial blood flow when compared with femoral arterial blood flow and coronary artery diameter, in the anaesthetised dog.

Anesthesia↗
PubMed2000

CP-101,606, an NR2B subunit selective NMDA receptor antagonist, inhibits NMDA and injury induced c-fos expression and cortical spreading depression in rodents.

(1S, 2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606) is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit. This compound was used to investigate the role of NR2B containing receptors in three responses to NMDA receptor activation in vivo. In mouse, CP-101,606 completely inhibited increases in fos-like immunoreactivity in dentate gyrus caused by a subconvulsant intraperitoneal dose of NMDA. In rat, the compound completely blocked cortical c-fos mRNA induction following focal injury in parietal cortex and the initiation and propagation of electrically induced cortical spreading depression. Inhibition of these responses by CP-101,606 indicates that c-fos induction and cortical spreading depression are dependent on activation of NMDA receptors containing the NR2B subunit. Since NMDA receptor dependent c-fos induction and cortical spreading depression may contribute to neuron loss after focal CNS injury, inhibition of these responses by CP-101,606 may contribute to the neuroprotective efficacy of the compound.

Animals↗
PubMed2000

How Do head and neck cancer patients prioritize treatment outcomes before initiating treatment?

PURPOSE: To determine, pretreatment, how head and neck cancer (HNC) patients prioritize potential treatment effects in relationship to each other and to survival and to ascertain whether patients' preferences are related to demographic or disease characteristics, performance status, or quality of life (QOL). PATIENTS AND METHODS: One hundred thirty-one patients were assessed pretreatment using standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck) and performance (Performance Status Scale for Head and Neck Cancer). Patients were also asked to rank a series of 12 potential HNC treatment effects. RESULTS: Being cured was ranked top priority by 75% of patients; another 18% ranked it second or third. Living as long as possible and having no pain were placed in the top three by 56% and 35% of patients, respectively. Items that were ranked in the top three by 10% to 24% of patients included those related to energy, swallowing, voice, and appearance. Items related to chewing, being understood, tasting, and dry mouth were placed in the top three by less than 10% of patients. Excluding the top three rankings, there was considerable variability in ratings. Rankings were generally unrelated to patient or disease characteristics, with the exception that cure and living were of slightly lower priority and pain of higher priority to older patients compared with younger patients. CONCLUSION: The data suggest that, at least pretreatment, survival is of primary importance to patients, supporting the development of aggressive treatment strategies. In addition, results highlight individual variability and warn against making assumptions about patients' attitudes vis-à-vis potential outcomes. Whether patients' priorities will change as they experience late effects is currently under investigation.

Activities of Daily Living↗
PubMed2000

Pulsatile insulin secretion.

Insulin is secreted in a pulsatile manner. Recently it has been shown that almost all (approximately 70-100%) of insulin is secreted in discrete insulin secretory bursts occurring approximately every 6 min. Furthermore, it has been revealed that regulation of the rate of insulin secretion is achieved primarily through modulation of the mass of these discrete insulin bursts. Thus meal ingestion increases insulin secretion by enhancing insulin burst mass by approximately 50% but also increases pulse frequency by approximately 50%. Interestingly, the hepatic clearance of insulin is also apparently closely related to the pattern of insulin delivery to the liver. It has been known for many years that the pattern of insulin delivery is abnormal in patients with type 2 diabetes. Recently, with new more sensitive insulin assays (ELISA) and validated methods for pulse detection, it has been possible to examine more precisely the abnormalities of pulsatile insulin in patients with type 2 diabetes. These recent studies suggest that the principal defect of insulin secretion is a deficient pulse mass of insulin with no changes in pulse frequency, and that this defect can be overcome by a period of beta cell rest.

Diabetes Mellitus↗
PubMed2000

Child development services in Medicaid managed care organizations: what does it take?

OBJECTIVE: We sought to understand why certain Medicaid managed care organizations (MMCOs) implemented child development services or programs and how they had done so. We also sought to identify barriers and facilitators to successful initiation and implementation of child development programs. METHODS: We conducted 9 key informant interviews and 4 site visits, and performed qualitative analyses to identify major themes across responses. RESULTS: We identified a small number of MMCOs with child development services. High-level support was crucial for program initiation; physician buy-in, staff support, and strong working relationships with outside health professionals or agencies were principal factors in successful program implementation. CONCLUSIONS: MMCOs that were committed to implementing child development services were successful in doing so, without external funding or regulatory mandate. The results provide valuable strategies for MMCOs interested in developing programs and for researchers and advocates interested in promoting child development services for low-income children.

Child Development↗
PubMed1999

Lights out.

Explore the source record for details and available documents.

Ambulances↗
PubMed1999

Leadership 99. Interview by Terese Hudson.

Cost control, customer service and collaboration among health care sectors rank as top concerns with panelists in H&HN's annual Leadership Report. Efforts to improve community health are a priority, too, but are often frustrated by financial and other constraints. The 16 panelists represent managed care, physicians, and hospitals and health systems.

Attitude of Health Personnel↗
PubMed1998

Reality cheque.

Explore the source record for details and available documents.

Data Collection↗
PubMed1998

(3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol: a conformationally restricted analogue of the NR2B subtype-selective NMDA antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)- 1-propanol.

(1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606, 1) is a recently described antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit. In the present study, the optimal orientation of compounds of this structural type for their receptor was explored. Tethering of the pendent methyl group of 1 to the phenolic aromatic ring via an oxygen atom prevents rotation about the central portion of the molecule. Several of the new chromanol compounds have high affinity for the racemic [3H]CP-101,606 binding site on the NMDA receptor and protect against glutamate toxicity in cultured hippocampal neurons. The new ring caused a change in the stereochemical preference of the receptor-cis (erythro) compounds had better affinity for the receptor than the trans isomers. Computational studies suggest that steric interactions between the pendent methyl group and the phenol ring in the acyclic series determine which structures can best fit the receptor. The chromanol analogue, (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1- yl]chroman-4,7-diol (12a, CP-283,097), was found to possess potency and selectivity comparable to CP-101,606. Thus 12a is a new tool to explore the function of the NR2B-containing NMDA receptors.

Animals↗
PubMed1998

Alpha-glutathione-S-transferase in acute rejection of liver transplant recipients.

BACKGROUND: Alpha-glutathione-S-transferase (alphaGST) has been suggested as a sensitive marker of acute cellular rejection in liver transplantation. This study evaluated the usefulness of alphaGST as a marker of acute rejection in comparison with standard liver function tests. METHODS: Daily measurements of liver function tests and alphaGST (enzyme immunometric assay, Biotrin) were prospectively recorded in 23 consecutive liver transplant recipients up to the time of discharge. Liver biopsies were performed as protocol biopsies or after clinical or biochemical deterioration in liver function, 38 of 56 showed acute rejection. RESULTS: AlphaGST peaked on the second day (median, 125 microg/L; interquartile [IQ] range, 75-321 microg/L) and preceded the alanine transaminase (ALT) peak by 1 day. AlphaGST levels then steadily declined, reaching baseline by day 6, plateauing until day 8. After the initial peak, alphaGST still correlated well with the ALT (median correlation coefficient, 0.6; IQ range, 0.45-0.77) and with bilirubin concentration (median correlation coefficient, 0.47; IQ range, 0.14-0.6). There was no significant difference in alphaGST levels between those with rejection compared with other causes of hepatic dysfunction. The sensitivity and specificity of alphaGST for diagnosing acute rejection was 63.1% and 38.8%, respectively, compared with 97.4% and 16.7% for ALT. In 14 of the 16 patients treated for moderate or severe rejection, the improvement in the histological score of rejection was not associated with a consistent change in the alphaGST. CONCLUSIONS: AlphaGST is not more useful than ALT in diagnosing rejection or determining response to treatment, but is a sensitive marker of liver injury.

Adult↗