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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 163 records · Page 9Linked to original sources
PubMed1997

Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy.

A new cyclic opioid peptide of sequence Tyr-D-Pen-Gly-Phe-Cys-Phe (HBP2) was examined in the mouse isolated vas deferens (MVD) bioassay. Studies with receptor-selective opioid antagonists showed the peptide to be highly selective for delta opioid receptors. HBP2 and the standard delta agonist DPDPE were simultaneously compared using the technique of partial irreversible receptor blockade; data were analyzed using the operational model of pharmacologic agonism. HBP2 was approximately 160 times as potent as DPDPE; estimation of the affinity and efficacy of the two peptides revealed that the potency increase was due to a 5.3-fold increase in efficacy, as well as a 37-fold increase affinity. This contrasts with our previous findings with other cyclic enkephalin analogs, in which increased affinity was achieved without a change in apparent efficacy. Analysis of concentration-response curve shape suggested in addition the possibility of heterogeneity in transduction mechanisms for MVD delta receptors.

Animals↗
PubMed1997

Opioid peptides: simultaneous delta agonism and mu antagonism in somatostatin analogues.

Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were made with beta-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. The analogues displayed varying potencies and biological activities including: simultaneous delta receptor agonism/mu receptor antagonism, mu receptor antagonism, and delta receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues my represent leads to therapeutic agents that yield analgesia via delta agonist effects, yet lack side effects associated with mu activity.

Analgesics↗
PubMed1997

Clinical outcome of ulcerative proctitis in children.

BACKGROUND: Although the course of ulcerative proctitis in adults has been well described, little data are available concerning its clinical behavior in children and adolescents. This study sought to characterize the presentation, response to therapy, and long-term course of ulcerative proctitis in the pediatric population. METHODS: A retrospective chart review was conducted at five pediatric gastroenterology centers. RESULTS: A total of 38 subjects (mean age 11.6 years) were identified with ulcerative proctitis (mean follow-up 4.3 years). Symptoms were mild at diagnosis in 74% and moderate or severe in 26%. Thirty-two percent had a complaint of constipation at presentation. Cessation of symptoms was noted in 68% within 3 months of therapy, an additional 24% within 6 months, and 8% were still symptomatic despite 6 months of therapy. During any subsequent yearly follow-up interval, -55% of patients were asymptomatic, 40% had a chronic intermittent course, and < 5% were continuously symptomatic despite therapy. Eight subjects were treated with oral corticosteroids, one with 6-mercaptopurine, and one with cyclosporine. Extension of inflammation proximal to the rectosigmoid occurred in 11 of 38 subjects (29%), 0.5-11.3 years postdiagnosis. Seven of the 13 subjects (54%) followed for > or = 5 years had proximal extension of disease, and two had undergone colectomy. CONCLUSIONS: Despite a mild presentation in most subjects, ulcerative proctitis seems to have a high risk of proximal extension of disease. The overall response to therapy seems to be similar to that reported for ulcerative colitis in children. Follow-up endoscopic evaluation of patients with ulcerative proctitis seems warranted, especially in the setting of recurrent or recalcitrant symptoms.

Adolescent↗
PubMed1997

Synthesis and biological properties of beta-MePhe3 analogues of deltorphin I and dermenkephalin: influence of biased chi 1 Phe3 residues on peptide recognition for delta-opioid receptors.

Using the method of conformational constraint, we have designed and synthesized analogues of deltorphin I and dermenkephalin containing each of the four stereoisomers (2S,3S; 2S,3R; 2R,3S; 2R,3R) of the unusual amino acid beta-methylphenylalanine in position three. The potency and selectivity of these analogues were evaluated by radioreceptor binding assays in the rat brain using [3H]CTOP (mu-ligand) and[3H]p-C1Phe4]DPDPE (delta-ligand), and by bioassay using the mouse vas deferens (delta-receptor assay) and guinea pig ileum (mu-receptor assay) assays. The substitution of a beta-MePhe for Phe3 in deltorphin I and dermenkephalin has a large and variable effect on the bioactivities of the synthesized analogues. The synthesized analogues are somewhat less potent than the native peptides. Both [(2S,3R)-beta-MePhe3]deltorphin and [(2S,3R)-beta-MePhe3] dermenkephalin are more selective, however, and interact essentially specifically with the receptor in the binding assays and bioassays. The bioassay data in vitro of the synthesized analogues of deltorphin I and dermenkephalin follow the same general trends as the receptor binding data. These results demonstrate that topographical modifications of the side-chain conformation of critical structural moieties in a ligand can significantly modulate both the potency and receptor selectivity for ligands that have multiple sites of biological activity, and they illustrate that this approach has general application to peptide and peptidomimetic ligand design.

Aminobutyrates↗
PubMed1997

Para-substituted phenylalanine-4 analogues of [L-Ala3]DPDPE: highly selective delta opioid receptor ligands.

Several para-substituted Phe4 analogues of the delta 1-selective antagonist [L-Ala3]DPDPE (DPADPE) were prepared and evaluated for their brain-binding and in vitro pharmacological effects. Unlike the p-haloPhe4 analogues of DPDPE and the deltorphins, similar analogues of DPADPE with electron-withdrawing groups substituted at the para-position of the Phe4 aromatic ring did not all have increased potency and selectivity for delta opioid receptors, but all retained high potency and selectivity for delta opioid receptors greater than DPDPE.

Animals↗
PubMed1997

Changes over time in attitudes to treatment and survival rates for extremely preterm infants (23-27 weeks' gestational age).

We determined the changes over time in attitude to treatment of very preterm infants (23-27 weeks of gestational age) born at the Royal Women's Hospital, Melbourne, and their survival rate. The subjects were consecutive livebirths at 23-27 weeks' gestational age born from 1983-1994, inclusive. The main outcomes measured were the proportions of livebirths treated intensively and survival rates to hospital discharge, both excluding lethal abnormalities. Over the 12 years of the study there were 788 livebirths free of lethal abnormalities born at 23-27 week's gestational age. Overall 669 (85%) were treated intensively; the proportions treated intensively rose significantly over time from 74% in 1983-1985 to 91% in 1992-1994, and with increasing gestational age, from 19% at 23 weeks to 100% at 27 weeks. Overall 439 (56%) survived their primary hospitalization; the survival rate rose significantly over time, from 43% in 1983-1985 to 70% in 1992-1994, and with increasing gestational age, from 3% at 23 weeks to 78% at 27 weeks. In 1992-1994, the survival rates were 11% at 23 weeks, 53% at 24 weeks, 70% at 25 weeks, 81% at 26 weeks, and 87% at 27 weeks. For infants treated intensively, the survival rate rose significantly from 53% in 1983-1985 to 76% in 1992-1994. The largest increases in survival have occurred in the 1990s, and at 24 and 25 weeks' gestational age. The proportions of very preterm infants treated intensively and their survival rates have increased over time, and have always been higher with increasing gestational age.

Attitude of Health Personnel↗
PubMed1997

SIDS: parental awareness and infant care practices in contrasting socioeconomic areas in Cardiff.

Parental awareness of risk factors for sudden infant death syndrome (SIDS) and infant care practices were compared in an area of relative deprivation and one of relative affluence in Cardiff. Awareness was high in both areas. More infants slept on the side in the deprived area (p < 0.02). One in three babies was exposed to cigarette smoking, significantly more in the deprived area (p < 0.001). Health professionals should discourage side sleeping and smoking, especially in areas of deprivation.

Awareness↗
PubMed1997

The effect on risk estimates of excluding cases from a case-control study of ischemic stroke.

There is limited information about the effect on stroke risk estimates of excluding cases who are unable to respond to interviews. A case-control study of ischemic stroke between 1988 and 1990 in Shreveport, La., USA, provided a basis for studying this question. Of 197 consecutively admitted cases of ischemic stroke, 77 were excluded due to dementia, aphasia or impaired consciousness. Information about risk factors and stroke characteristics was obtained from hospital records. Excluded cases had more left hemispheric (52 versus 19%) and fewer vertebrobasilar (12 versus 29%) and lacunar (5 versus 13%) infarcts than included cases. Excluded cases were also older (p < 0.01), and they had larger infarcts (p < 0.01), multiple strokes (p < 0.01) and congestive heart failure (p < 0.01) more often than included cases. Cases were matched to hospital controls by age, sex, race, and date of admission. Odds ratios (ORs) were higher for excluded cases for 5 of 6 exposures with a significantly higher OR for congestive heart failure (p < 0.01). The ORs changed by as much as 63% when excluded cases were added. These results emphasize the importance of acquiring information about excluded cases and considering selection bias when interpreting stroke studies that exclude cases who are unable to respond to interviews.

Adult↗
PubMed1997

Attitudes and beliefs of family physicians and gynecologists in relation to the prevention and treatment of osteoporosis.

The objective of this study was to evaluate the attitudes and beliefs of primary care physicians (PCPs) and obstetricians/gynecologists (O&Gs) in relation to the prevention and treatment of osteoporosis (OP) in postmenopausal women. A survey was mailed to a random sample of PCPs and to all O&Gs registered in the province of Alberta (Canada). The survey evaluated their practice patterns using closed-ended questions, Likert scaled items, and two case studies. Cases 1 and 2 were 52-year-old and 62-year-old healthy postmenopausal women, respectively, with no known risks for OP. Neither had received hormone replacement therapy (HRT). One hundred fifty-seven PCPs and 57 O&Gs participated in the study. Thirty-eight percent of the PCPs and 32% of the O&Gs stated that they never requested bone mineral density measurements (BMDm) in early postmenopausal women. Most would request BMDm only in the presence of risk factors. The most important criteria to request BMDm were chronic glucocorticoid use and recent fractures. For case 1, 7% of the PCPs and 11% of the O&Gs would request BMDm; 76% of the PCPs and 80% of the O&Gs would recommend HRT. For case 2, 29% of the PCPs and 47% of the O&Gs would request BMDm (p = 0.01); 43% of the PCPs and 49% of the O&Gs would prescribe HRT. In general, O&Gs were more inclined to intervene in relation to BMDm and HRT. O&Gs were also more likely to be influenced by clinical trials than PCPs (p < 0.001). Our findings show variations in the patterns of practice of physicians in relation to the prevention of OP. In general, use of densitometry appears to be low. The results of the case studies suggest that individual physician perceptions may be more influential than patient characteristics when requesting BMDm and prescribing HRT, particularly in older postmenopausal women. This group of healthy older women have approximately equal odds of being offered versus not being offered BMDm and HRT according to the physician they consult.

Alberta↗
PubMed1997

Radiochemical synovectomy.

Radiochemical synovectomies have been used for nearly fifty years for the treatment of persistent monoarticular synovitis refractory to antiinflammatory drugs, disease modifying drugs, and intraarticular corticosteroids. It is a therapeutic alternative to surgical synovectomy. There are controversies concerning safety, choice of appropriate agent, and logistics of administration. These concerns are discussed in addition to reviewing some of the more recent trials examining the efficacy of radiochemical synovectomy. It is clear that in properly selected patients this procedure is safe and beneficial.

Anti-Inflammatory Agents↗
PubMed1997

Yttrium-90 radiochemical synovectomy in chronic knee synovitis: a one year retrospective review of 133 treatment interventions.

OBJECTIVE: To determine treatment success rates and factors predicting successful outcome using yttrium-90 intraarticular injections for chronic knee synovitis refractory to other treatments. METHODS: A retrospective one year review of 133 treatment interventions with yttrium-90 (Y-90) with response recorded at 3, 6, 9, and 12 mo after injection. RESULTS: An excellent, good, or fair response (a treatment benefit) as evaluated by objective (degree of joint effusion, joint tenderness, range of motion) and subjective (visual analog scale, degree of pain) assessments occurred in 81, 82, 80, and 75% of joints at 3, 6, 9, and 12 mo, respectively. When only excellent and good responses were considered successful treatment then 49, 48, 57, and 46% had successful treatment at 3, 6, 9, and 12 mo, respectively. 8 of 15 joints (53%) reinjected after primary treatment failure or relapse showed a beneficial response. Patients treated successfully were more likely to have a normal radiographic appearance rather than one showing destructive changes (78 vs 54% treatment success; p < 0.05); to have localized disease or systemic disease in remission, rather than active systemic disease (66 vs 30% treatment success; p < 0.001); and shorter duration of joint disease (6.9 vs 10.2 years; p < 0.05). CONCLUSION: Y-90 synovectomy successfully treats patients with chronic knee synovitis refractory to other therapies. Primary treatment failures or relapses may be successfully treated by reinjection. Patients with less destructive radiographic changes, shorter duration of joint disease, and localized disease tend to respond more favorably.

Adolescent↗
PubMed1997

The use of standardized patients in the performance of a needs assessment and development of a CME intervention in rheumatology for primary care physicians.

OBJECTIVE: To determine the feasibility of using standardized patients in the performance of a needs assessment and subsequent development of a continuing medical education (CME) intervention in rheumatology for family physicians. METHODS: Eight family physicians and 7 rheumatologists undertook 36 encounters with standardized patients simulating 3 common rheumatologic complaints. Encounters were assessed according to a predetermined score addressing issues of communication skills, clinical diagnosis, investigations, and management. Data obtained were used to develop a small group problem based learning event. RESULTS: Mean scores differed considerably between rheumatologists and family physicians (7.2 vs 3.6; possible range -3 to +9), between individuals within the 2 groups (rheumatologists 2.5 to +9; family physicians -1 to 6.5), and between cases. Specific areas of individual and group need for the development of a subsequent CME intervention were identified and included communication skills, clinical skills in the development of a differential diagnosis, appropriate use and interpretation of investigations, and appropriate management. CONCLUSION: Standardized patients can be effectively used to undertake a needs assessment in rheumatology. Specific data can be used to develop a small group problem based learning program with objectives meeting the identified needs and using the same standardized patients.

Education, Medical, Continuing↗