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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 253 records · Page 14Linked to original sources
PubMed1993

Psychopathology and relationship measures in children with inflammatory bowel disease and their parents.

Children with inflammatory bowel disease and their parents were assessed for DMS-III diagnoses, maternal attachment, marital relationship, life stresses, illness severity and cognitive/affective profile. Eleven of 15 children and 21 of 27 parents had psychiatric diagnoses. Three children were suicidal. Thirteen of 15 mothers had insecure attachment. Marital difficulties and medical severity correlated with life stress. The higher prevalence of psychiatric disorders than epidemiologically and of insecure attachment suggest at-risk relationships.

Adolescent↗
PubMed1993

Pharmaceuticals and public policy: learning from the New Zealand experience.

Pharmaceuticals provide a useful analytical prism through which to view a wider range of policy issues in the health arena. The fundamental characteristics of pharmaceuticals are shared by many other health care items and raise important policy questions in five key institutional areas: the market, science, the State, the professions, and the public. In one way or another the key policy issues raised in each one of these areas concern fundamental questions of restraint and regulation: the ability of the market to exert the normal disciplines of price competition on pharmaceuticals; the extent to which the claims of intellectual property conflict with the norms of scientific advance; the reconciliation of the different functions of the State, particularly in the management of risk; the efficacy of traditional mechanisms of self-regulation and peer review in the health professions; and the implications of pharmaceuticals for broader questions of social control. These issues are illustrated from the recent experience of a country, New Zealand, that has undergone major deregulation and restructuring of State activities. Conclusions are drawn for policy development in the pharmaceuticals area.

Drug Approval↗
PubMed1993

Labile exocyclic amine protection of nucleosides in DNA, RNA and oligonucleotide analog synthesis facilitating N-deacylation, minimizing depurination and chain degradation.

The use of tert-butylphenoxyacetyl for N-protection of nucleoside bases during oligonucleotide synthesis facilitates its removal under mild conditions. This protecting group reduces depurination of deoxyadenosine residues, and minimizes premature desilylation resulting in chain degradation during post-synthesis workup of synthetic RNA.

Acylation↗
PubMed1993

The absence of cumulative bone marrow toxicity in patients with recurrent adenocarcinoma of the ovary receiving dose-intense taxol and granulocyte colony stimulating factor.

Forty-eight patients with recurrent adenocarcinoma of the ovary were treated with taxol and granulocyte colony stimulating factor (G-CSF), with a target taxol dose intensity of 250 mg/m2 every 3 weeks (83.3 mg/m2/week). We have assessed the patterns of granulocyte and platelet toxicity seen in this cohort. Individual patients received up to nine cycles of therapy. Criteria for entry onto protocol included good end organ function, good performance status and the absence of substantial co-morbid disease. Mean taxol dose intensity was 79.0 mg/m2/week for the whole cohort and did not diminish with increased duration of therapy. Granulocytopenia and thrombocytopenia were well controlled, with the average duration of platelet and neutropenic nadirs being less than 1 day for all cycles. There was no evidence of cumulative toxicity for granulocytes nor platelets, for up to eight cycles of therapy. We conclude that taxol, when given with G-CSF support, can be safely administered in a dose-intense fashion for multiple cycles of therapy, without cumulative bone marrow toxicity.

Adenocarcinoma↗
PubMed1993

The clinical significance of autoantibody profiles in patients with systemic lupus erythematosus.

We have evaluated the autoantibody profiles in the sera of 117 patients with systemic lupus erythematosus (SLE) and compared and contrasted the clinical and laboratory features of the disease of patients segregated according to an autoantibody profile. Using this approach we are able to demonstrate that autoantibody profiles identified subsets of patients with SLE. Patients with a negative autoantibody profile had fewer clinical and laboratory features of their disease when compared to the other subsets of patients. In contrast, patients with profile A (anti-nDNA and/or anti-Sm antibodies) had a statistically significant increase in malar rash, renal and hematologic involvement and hypocomplementemia when compared to patients with a negative profile. Patients with profile B (anti-nRNP antibodies) had a clinical pattern of disease different from that of patients with profile A and had a statistically significant increase in Raynaud's phenomenon when compared to patients with a negative profile. Patients with profile C (anti-SSA and/or anti-SSB antibodies) had a statistically significant increase in lupus-related rashes and photosensitivity. None of the lupus patients reviewed in this study has profile D (antibodies to centromere and/or Scl-70), this profile being seen largely in patients with scleroderma or one of its variants. Both patients with profile E (anti-histone antibodies) had drug-induced lupus. We conclude that the use of autoantibody profiles defines subsets of patients with lupus that may have clinical, therapeutic and prognostic implications.

Antibodies, Antinuclear↗
PubMed1993

Perceptual development and early childhood injuries: a prospective pilot study.

A prospective pilot study of 172 Hispanic children was performed to identify developmental predictors of 9 maternal reports of childhood injuries that required medical attention during the following year. The 1972 McCarthy Scales of Children's Abilities was administered near the children's third birthday and maternal reports of injuries were obtained the following year. Multiple regression analysis indicated that the Verbal, Perceptual, Quantitative, Memory, and Motor Subscales of the McCarthy Scales of Children's Abilities accounted for a small but statistically significant proportion of variance. Within the model, children who showed advanced abilities on the Perceptual Subscale were more likely to reported as having an injury requiring medical attention during the subsequent 12-month period.

Child↗
PubMed1993

Serum cytidine deaminase as a measure of disease activity in rheumatoid arthritis and systemic lupus erythematosus.

Serum cytidine deaminase (CD) as a marker of disease activity was assessed in 100 patients with rheumatoid arthritis (RA) and in 102 assessments of 85 patients with systemic lupus erythematosus (SLE). In RA CD levels correlated well with clinical assessment of disease activity, but were not influenced by varying dosages of ibuprofen as therapy. In SLE significant correlations were found between CD and anti-DNA antibody titers, as well as C3 complement levels. A subset of clinically active patients with SLE with elevated CD levels but normal anti-DNA titers was identified. Serum CD levels may be a clinically useful marker in RA and in certain subgroups of patients with SLE.

Adult↗
PubMed1993

In vitro potency, affinity and agonist efficacy of highly selective delta opioid receptor ligands.

The purpose of these investigations was to estimate the relative potency, receptor affinity, and agonist efficacy of several selective delta opioid agonist peptides of diverse structure, including cyclic [D-Pen2,D-Pen5]enkephalin and its p-Phe4 halogen-substituted analogs, [D-Ser2-O-tBu,Leu5,Thr6]enkephalin, Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 (deltorphin I) and Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 (deltorphin II) in functional bioassays. The mouse-isolated vas deferens (MVD) and guinea pig-isolated ileum longitudinal muscle/myenteric plexus bioassay preparations were used; selectivity for delta opioid receptors was quantified by the relative agonist activity of the various peptides in the guinea pig-isolated ileum and MVD assays; agonist affinity and efficacy were determined using the technique of partial irreversible receptor inactivation in the MVD. Data from these experiments were analyzed both by the traditional null method and by use of the operational model of pharmacologic agonism; a comparison of these two methods, which were found to be similar, was performed. Potency determinations in MVD for the various peptides essentially matched those determined in other investigations; the relative affinity of the peptides correlated with the results of radioligand binding studies performed in other laboratories. The relative efficacies of the peptides studied were indistinguishable except for the peptide deltorphin I, which demonstrated efficacy several-fold lower than the remaining seven. All peptides were sufficiently efficacious to appear as full agonists under control conditions. These results suggest that the principle factor determining increases in potency of novel delta receptor ligands to date is an increase in receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Ring substituted and other conformationally constrained tyrosine analogues of [D-Pen2,D-Pen5]enkephalin with delta opioid receptor selectivity.

The conformationally restricted, cyclic disulfide-containing delta opioid receptor selective enkephalin analogue [D-Pen2,D-Pen5] enkephalin (DPDPE) was modified by 2' (CH3) and 3' (I, OCH3, NO2, NH2) ring substitutions and by beta-methyl conformationally constrained beta-methyltyrosine derivatives in the 1 position. The potency and selectivity of these analogues were evaluated by bioassay in the mouse vas deference (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay) assays and by radioreceptor binding assays in the rat brain using [3H]CTOP (mu ligand) and [3H][p-ClPhe4]DPDPE (delta ligand). The analogues showed highly variable potencies in the binding assays and in the bioassays. Aromatic ring substituents with positive Hammett constants had decreased potency, while substituents with negative Hammett constraints has increased potency for the opioid receptor. The most potent and most selective compound based on the binding was [2'-MeTyr1]DPDPE (IC50 = 0.89 nM and selectivity ratio 1310 in the binding assays). The 6-hydroxy-2-aminotetralin-2-carboxylic acid-containing analogue, [Hat1]DPDPE, also was highly potent and selective in both assays, demonstrating that significant modifications of tyrosine in enkephalins are possible with maintenance of high potency and delta opioid receptor selectivity. Of the beta-methyl-substituted Tyr1 analogues, [(2S,3R)-beta-MeTyr1]DPDPE was the most potent and the delta receptor selective. The results with substitution of beta-MeTyr or Hat instead of Tyr also demonstrate that topographical modification in a conformationally restricted ligand can significantly modulate both potency and receptor selectivity of peptide ligands that have multiple sites of biological activity.

Amino Acid Sequence↗
PubMed1992

Morphiceptin and beta-casomorphin-5 analogues containing a reduced peptide bond: selective mu-receptor agonists and a novel mu antagonist, H-Tyr-Pro psi (CH2-NH)Phe-Pro-Gly-OH.

In order to prevent enzymatic degradation of beta-casomorphin-5 (1) and morphiceptin, reduced peptide bonds were incorporated at the 2-3 and 3-4 bonds, respectively. The analogues were synthesized by a combination of solid phase methodology and reductive alkylation of resin-bound peptide amines with Boc-amino acid aldehydes (Boc: tert-butyloxycarbonyl) in the presence of NaBH3CN. During reversed phase high pressure liquid chromatography purification, peak shape distortions could be observed. Epimerization was excluded, based on gas chromatography/mass spectroscopy analysis, which indicated acceptable levels of racemization (less than 3%) in the crude product. Instead, the phenomena could be attributed to slow cis/trans isomerizations originating from the Xxx-Pro bonds in the sequence. The presence of different conformational isomers was also established by 1H-nmr spectroscopy in DMSO-d6. All analogues showed high stability in blood plasma, enhanced binding affinity for the mu receptor, and very low binding to the delta receptor. While the Phe 3 psi(CH2-N)Pro4 analogues (3) and (5) displayed agonist activity, the Pro 2 psi(CH2-NH)Phe3 modified analogue (2) showed antagonist activity comparable to D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2.

Amino Acid Sequence↗
PubMed1992

Topographical requirements for delta opioid ligands: common structural features of dermenkephalin and deltorphin.

We propose a common topographical model for the bioactive conformation of deltorphin and dermenkephalin at the delta opioid receptor. In this model a hydrophilic surface from the N- to C-termini is surrounded by lipophilic residues ("hot dog" structure). The important element that orients the N-terminal tyramine is the interaction of the N-terminal amino group, with the carboxyl group of Asp4 in deltorphin I and with Asp7 through His4 (as a triad) in dermenkephalin. The biological properties of synthetic analogues designed to test this model demonstrate that the hydrophilic amino acid residues of these peptides are interchangeable. In addition, incorporation of Aib residues that change the lipophilic topography of these molecule, strongly reduces affinity for the delta opioid receptor.

Amino Acid Sequence↗
PubMed1992

Antinuclear and antineutrophil cytoplasmic antibodies (ANCA) in the sera of patients with Felty's syndrome.

The prevalence of antinuclear (ANA) and antineutrophil cytoplasmic antibodies (ANCA) has been studied in the sera of 62 patients with rheumatoid arthritis and 32 patients with Felty's syndrome. The presence of ANA was less in RA than Felty's syndrome (37% versus 69%). Specific autoantibody identification, where possible, was usually of SS-A or SS-B although two sera from patients with Felty's syndrome had low levels of DNA antibody. ANCA was detected in the sera of 33% of patients with Felty's syndrome and was absent in RA sera. The pattern of ANCA staining was either of a diffuse homogenous cytoplasmic or peripheral (pANCA) nature. Classical cytoplasmic granular staining (cANCA) was not identified.

Antibodies↗
PubMed1992

New horizons in the medical treatment of rheumatoid arthritis.

To date, the medical management of rheumatoid arthritis has been less than optimal for a significant number of patients. This has been manifested by progressive deformity, functional disability, and increased mortality in these patients. Alternative treatment schedules of currently available drugs, as recently advocated by some investigators and the results of both the preclinical and the applied clinical evaluations of a number of novel pharmacologic therapies are reviewed. Several effective nonpharmacologic treatments have been reported in the last year, and their significance in the treatment of rheumatoid arthritis are also discussed.

Arthritis, Rheumatoid↗
PubMed1992

Synthesis and biological activities of linear and cyclic enkephalin analogues containing a psi (E,CH = CH) or psi (CH2CH2) isosteric replacement.

The peptide CO-NH function was replaced by a trans carbon-carbon double bond or by a CH2-CH2 isostere in enkephalin analogues of DADLE, DCDCE-NH2 or DPDPE. In DADLE the 2-3 and the 3-4 peptide bond was modified, whereas in the cyclic analogues the Gly3-Phe4 bond was replaced by the isosteres Gly psi (E,CH = CH)Phe [5-amino-2-(phenylmethyl)-3(E)-pentenoic acid] or Gly psi (CH2CH2)Phe [5-amino-2-(phenylmethyl)pentanoic acid]. In general, the modification results in a drop in potency which is the largest for the flexible CH2-CH2 replacement. The Gly3 psi (E,CH = CH)Phe4 DCDCE-NH2 analogue retains considerable potency. These results confirm the importance of the peptide function at the 2-3 and 3-4 position in enkephalin analogues for biological potency.

Amino Acid Sequence↗