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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 145 records · Page 8Linked to original sources
PubMed1998

Clinical outcome of 149 patients with polymyalgia rheumatica and giant cell arteritis.

OBJECTIVE: To assess the clinical outcome of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: All charts of consecutive patients with a diagnosis of PMR and/or GCA attending a tertiary referral center from June 1989 to February 1996 were reviewed following a predetermined protocol. Subsequently, the majority of patients (90%) were assessed clinically or by telephone interview. Registered variables included demographic data, disease characteristics, prednisone dosage and duration, comorbidities, and clinical outcomes. RESULTS: There were 149 patients (133 with PMR alone, 7 with GCA alone, 9 with both); 94 (63%) were females; the mean age was 68 +/- 9 years, and the mean disease duration from the first symptom to the rheumatology consultation was 13 +/- 12 weeks (1-99). Typical clinical features of PMR were present in patients with PMR. Synovitis was observed in 26 patients. The presenting symptoms for GCA were typical features in 13 patients and blindness in 3 (2%) patients. Mean followup was 3.7 +/- 2 years. Comorbid conditions were present in 71 patients: 12 patients had hypertension, 13 had fractures, 8 diabetes, 29 cataract, 8 major infection, and 37 had other complications. Cancer was diagnosed in 4 patients and 6 patients had died. Prednisone was prescribed in 148 patients (mean dose 23 +/- 14 mg) for a mean time of 28 +/- 29 mo. Nonsteroidal antiinflammatory drugs were prescribed in 51 (34%) patients and methotrexate in 2. Disease remission was achieved in 81 (54%) patients (72 remissions, 9 presumed remissions) in whom steroid therapy had been stopped. Another 54 (36%) patients were still taking prednisone at the time of the interview, all were in clinical remission. Seventeen patients developed rheumatoid arthritis subsequent to the diagnosis of PMR. CONCLUSION: PMR and GCA should not necessarily be considered diseases with favorable outcome. In many of our patients, steroids were required for a prolonged period. Some patients developed significant complications attributable to steroid therapy. A significant number of patients progressed to rheumatoid arthritis.

Aged↗
PubMed1998

Prevalence and disease associations of certain autoantibodies in elderly patients.

OBJECTIVE: To determine the prevalence and association with various diseases of certain autoantibodies among elderly patients, in order to challenge the hypothesis that these autoantibodies are elevated generally in these patients as a result of immunosenescence. DESIGN: Prospective prevalence study. PATIENTS: A total of 399 elderly patients: 63 aging successfully (without chronic illness), 301 with a variety of chronic general illnesses (frail elderly) and 35 with a clinical diagnosis of rheumatoid arthritis. These were compared with 250 healthy adult blood donors. INTERVENTIONS: Measurement of autoantibodies to rheumatoid factor, antinuclear antibody, double-stranded (native) DNA (nDNA), extractable nuclear antigens and anticardiolipin antibodies. OUTCOME MEASURES: Prevalence of these autoantibodies and correlation with disease states. RESULTS: Antibodies to rheumatoid factor and antinuclear antibody were significantly more prevalent in the elderly patients with chronic illness or rheumatoid arthritis but were not disease-specific. The prevalence of nDNA and extractable nuclear antigens was not increased in either the healthy or frail elderly groups. Anticardiolipin antibodies were significantly more prevalent in the frail elderly group when compared with normal controls and the healthy elderly group. The prevalence of anticardiolipin antibodies correlated with clinical features of cerebrovascular disease, in particular multi-infarct dementia and stroke, but not with Alzheimer's disease. CONCLUSIONS: The prevalence of the autoantibodies measured was not elevated in healthy elderly subjects, and autoantibodies such as nDNA and extractable nuclear antigens are specific to disease states in all groups of elderly patients. Anticardiolipin antibodies correlate with cerebrovascular events. Therefore, the clinical significance of autoantibodies in elderly patients is related more to global health status than to the effects of aging.

Age Factors↗
PubMed1998

Utilization and predictive value of laboratory tests in patients referred to rheumatologists by primary care physicians.

OBJECTIVE: Antinuclear antibodies (ANA), rheumatoid factors (RF), and erythrocyte sedimentation rate (ESR) are among the most frequently requested tests in the diagnosis and investigation of connective tissue diseases (CTD). We evaluate the utilization patterns and predictive value of these tests in patients referred to rheumatologists by primary care physicians. METHODS: We reviewed the records of all new patients referred by primary care physicians in 1994 to 2 rheumatologists practicing at the University of Alberta. Data extracted from the records included diagnostic tests requested by referring primary care physicians, signs and symptoms at the initial rheumatology consult, and followup diagnoses. RESULTS: Seven hundred eleven new patients had been referred by over 300 primary care physicians: RF had been requested in 25%, ANA in 21%, and ESR in 29%. One hundred nine (15%) of the 711 patients had a CTD, 45 (6%) had rheumatoid arthritis (RA), and 8 (1%) systemic lupus erythematosus (SLE). The predictive values of positive tests for the diagnosis of CTD were low: 49% for RF, 29% for ANA, and 35% for ESR. For RA, the positive predictive values were 44% for RF, 8% for ANA, 17% for ESR; for SLE, 2, 12, and 3%, respectively. Diffuse musculoskeletal pain and fatigue were significantly associated with test utilization, although most patients with these symptoms had fibromyalgia or localized soft tissue rheumatism. CONCLUSION: Primary care physicians frequently requested autoantibodies in patients referred to rheumatologists. Most tests were negative, and were often requested in patients without CTD, resulting in low positive predictive values and questionable clinical utility. These findings suggest inappropriate overuse and lack of understanding of the use of autoantibody tests in diagnosing rheumatic diseases. A decrease in inappropriate use could be achieved by emphasizing that fatigue and diffuse musculoskeletal pain are not indicative of CTD in the absence of other features such as joint swelling, typical rash, or organ involvement.

Adult↗
PubMed1998

A protocol for coadministration of i.v. iron dextran and heparin in chronic hemodialysis patients.

The coadministration of intravenous iron dextran and heparin as a continuous infusion during hemodialysis (HD) is a safe and effective method used in maintaining and/or increasing iron stores and hematocrit levels in patients with end stage renal disease (ESRD). The technique of mixing iron dextran in low doses with heparin and infusing this mixture via the heparin syringe pump on the dialysis machine has shown to be cost effective, as well as instrumental in reducing the risk of adverse reactions due to rapid infusion or large dose infusion of iron dextran. At the Cleveland Clinic Foundation, we developed a protocol based on this methodology. A total of more than 1,000 doses of intravenous iron dextran and heparin have been administered to our HD patients using this technique, and no adverse reactions have been reported or observed.

Algorithms↗
PubMed1997

Cyclic enkephalin analogues with exceptional potency and selectivity for delta-opioid receptors.

Superpotent and highly delta-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenyl-alanine-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21,000 for delta vs mu). In the GPI and MVD bioassays the most selective and most potent analogue is the p-fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 value of 0.016 nM and a delta vs mu selectivity ratio of 45,000.

Amino Acid Sequence↗
PubMed1997

Maori/non-Maori patterns of contact, expressed morbidity and resource use in general practice: data from the Waikato Medical Care Survey 1991-2.

AIMS: To compare patterns of contact, expressed morbidity and resource use in primary care for a representative sample of patients of Maori and non-Maori background. METHODS: The data are drawn from a survey of general practice in the Waikato region representing a one per cent sample of all week day encounters. The data were recorded by participating general practitioners in four collection weeks spaced over the period of a year. In total, 12,833 patient encounter forms were completed. RESULTS: Annual rates of general practitioner contact for Maori are slightly lower than those for patients of non-Maori background. The case-mix pattern of general practitioner contact is very similar between the two groups. There is a limited correspondence between ethnic patterns of general practitioner usage and health need (as measured by mortality levels and rates of public hospital discharge). CONCLUSIONS: The near equivalence in ethnic rates of general practitioner contact revealed in this study contrasts strikingly both with the level of hospitalisation for Maori, which is nearly double that of non-Maori, and with the difference in mortality rates (30% higher for Maori). Attention devoted to improving access to general practitioner services among Maori may be necessary if important areas of ill health and hospital resource use are to be addressed effectively.

Adolescent↗
PubMed1997

Socioeconomic distribution of smoking in a population of 10,529 New Zealanders.

AIMS: This study aimed to investigate the associations of several smoking variables with socioeconomic status. METHODS: Cross-sectional analyses of data about smoking behaviour and socioeconomic status (education, occupation and neighbourhood income) were performed using baseline data from the Fletcher Challenge-University of Auckland Heart and Health Study (10,529 participants). RESULTS: After adjustment for age and sex, lower educational level was associated with: (1) higher frequency of ever having smoked (65% of participants who had attended secondary school for fewer than two years, versus 43% of participants who had attended university; 2p < 0.0001); (2) lower likelihood of having quit (46% versus 71%; 2p < 0.0001); (3) higher likelihood of being a current smoker (35% versus 12%; 2p < 0.0001); (4) higher tobacco consumption per smoker (13 manufactured cigarettes/day versus 8 manufactured cigarettes/day; 2p < 0.0001); and (5) higher tobacco consumption per participant (1980 cigarette-equivalents/year versus 450 cigarette-equivalents/year; 2p < 0.0001). Similar, but shallower, associations of these smoking variables were observed with occupation and neighbourhood income (with the exception that tobacco consumption per smoker was not associated with neighbourhood income). The socioeconomic gradients of tobacco consumption per study participant with all three socioeconomic indicators were particularly steep among younger participants, men and Maori. CONCLUSIONS: Participants of low socioeconomic status consumed a disproportionately large amount of tobacco. Policies that prevent smoking initiation and promote smoking cessation in low socioeconomic groups are therefore needed. These should include targeting of mass media messages to low socioeconomic groups, public subsidisation of nicotine replacement therapy and higher taxes on tobacco.

Adult↗
PubMed1997

Patterns of general practitioner usage among Pacific people: indicative results from the Waikato Medical Care Survey 1991-2.

AIMS: To report patterns of medical contact in a representative sample of Pacific people attending the general practitioner. METHODS: The data were drawn from a survey of general practice in the Waikato region representing a one per cent sample of all weekday encounters. In total, 12,833 patient encounter forms were completed. Just over one per cent of all encounters were recorded for patients of Pacific Islands background. RESULTS: Rates of medical contact for Pacific patients were lower-3.4 visits per year versus 4.5 for the whole sample-fewer follow up visits were requested (71% versus 76.2%), presentation was delayed (4.9 days from onset versus 3.7 for the sample) and there was an apparently lower level of rapport achieved. CONCLUSION: Overall levels of medical contact and return visits among Pacific patients appear to be lower and presentation delayed in this Waikato sample.

Adolescent↗
PubMed1997

Probes for narcotic receptor-mediated phenomena. 25. Synthesis and evaluation of N-alkyl-substituted (alpha-piperazinylbenzyl)benzamides as novel, highly selective delta opioid receptor agonists.

A series of N-alkyl- and N,N-dialkyl-4-[alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl] benzyl]-benzamides were synthesized and evaluated for binding affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were in the micromolar or greater range indicating excellent delta opioid receptor subtype selectivities. In this series, two important structure-activity relationships were found for the delta receptor binding affinity. First, the spatial orientation of the alpha-benzylic position influenced the affinities with the alpha R derivatives 2a-n generally showing more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the binding affinities were strongly influenced by the number of alkyl substituents on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted benzamide derivative 2a had the lowest affinity for the delta receptor in the series. The dramatic effect of the amide group substitution pattern on the binding affinity for the delta receptor strongly suggests that the amide function is an important structural element in the interaction of this series of compounds at the delta receptor. Selective compounds in this series were examined for binding affinity in cloned human mu and delta receptors. The results obtained generally paralleled those from the rat brain binding assay. Compounds 2e,f with potent delta binding affinities and high delta selectivities were shown to be delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Compound 2f was the most selective compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu selectivity, respectively.

Alkylation↗
PubMed1997

Probes for narcotic receptor mediated phenomena. 23. Synthesis, opioid receptor binding, and bioassay of the highly selective delta agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide (SNC 80) and related novel nonpeptide delta opioid receptor ligands.

The highly selective delta (delta) opioid receptor agonist SNC 80 [(+)-4- [(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N ,N- diethylbenzamide, (+)-21] and novel optically pure derivatives were synthesized from the enantiomers of 1-allyl-trans-2,5-dimethylpiperazine (2). The piperazine (+/-)-2 was synthesized, and its enantiomers were obtained on a multigram scale in > 99% optical purity by optical resolution of the racemate with the camphoric acids. The absolute configuration of (+)-2 was determined to be 2S,5R by X-ray analysis of the salt with (+)-camphoric acid. Since the chirality of the starting material was known, and the relative configuration of compounds (-)-21, (-)-22, and (+)-23 were obtained by single-crystal X-ray analysis, the assignment of the absolute stereochemistry of the entire series could be made. Radioreceptor binding studies in rat brain preparations showed that methyl ethers (+)-21 (SNC 80) and (-)-25 exhibited strong selectivity for rat delta receptors with low nanomolar affinity to delta receptors and only micromolar affinity for rat mu (mu) opioid receptors. Compounds (-)-21, (-)-22, and (-)-23 showed micromolar affinities for delta opioid receptors. The unsubstituted derivative (+)-22 and the fluorinated derivative (-)-27 showed > 2659- and > 2105-fold delta/mu binding selectivity, respectively. The latter derivatives are the most selective ligands described in the new series. Studies with some of the compounds described in the isolated mouse vas deferens and guinea pig ileum bioassays revealed that all were agonists with different degrees of selectivity for the delta opioid receptor. These data show that (+)-21 and (+)-22 are potent delta receptor agonists and suggest that these compounds will be valuable tools for further study of the delta opioid receptor at the molecular level, including its function and role in analgesia and drug abuse.

Animals↗
PubMed1997

Systematic approach for detection of endocrine disorders in children treated for brain tumors.

Endocrine dysfunction can be challenging to diagnose in children treated for brain tumors. Treatments are available for hormonal replacement and when necessary, hormonal suppression. Without these endocrine treatment regimens, life can be unnecessarily difficult or unpleasant. An endocrine survey can be used to screen at-risk neuro-oncology patients once or twice a year to facilitate the recognition of endocrine dysfunction. It is hoped that through the use of a routine screening program, physicians will be able to diagnose and begin treatment of endocrine problems in a time-efficient manner.

Brain Neoplasms↗
PubMed1997

Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty minute intravenous infusion of ormaplatin.

Preclinical data suggest that ormaplatin (tetrachloro-(dl-trans)-1, 2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic profile of both the total plasma concentrations of elemental platinum and the unbound ultrafiltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultrafiltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between Cmax and dose (r2 = 0.945) and AUC and dose (r2 = 0.976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t1/2 alpha) was 0.3 h and the terminal half-life (t1/2 beta) was 39.1 h. The volume of the central compartment (V) was 68.6 L and the volume of distribution at steady state (Vdss) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t1/2 alpha) of 0.3 h and a terminal half-life (t1/2 beta) of 19.3 h. The mean volume of the central compartment (V) was 200.5 L, and the mean volume of distribution at steady state (Vdss) was 560.5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds.

Adult↗
PubMed1997

Immunogenetic similarities between patients with Felty's syndrome and those with clonal expansions of large granular lymphocytes in rheumatoid arthritis.

OBJECTIVE: Patients with chronic clonal proliferation of large granular lymphocytes (LGL leukemia) often have splenomegaly, neutropenia, and rheumatoid arthritis (RA), thereby resembling the manifestations observed in patients with Felty's syndrome. The present study sought to determine whether patients with these disorders represent 2 distinct subsets of neutropenic RA. METHODS: Prospective cohort study of outpatients attending clinics in university and private hospitals and in offices of private practice physicians. Twenty-two patients with Felty's syndrome and 22 patients with LGL leukemia, 10 of whom had RA, were studied. HLA genotyping was performed on peripheral blood mononuclear leukocyte genomic DNA. RESULTS: Nineteen of the 22 patients with Felty's syndrome (86%) were DR4 positive. Nine of the 10 patients with LGL leukemia plus RA were also DR4 positive. In contrast, only 4 of the 12 patients with LGL leukemia without RA (33%) were DR4 positive, a frequency that was within the normal range. CONCLUSION: The finding of an equally high prevalence of DR4 in patients with Felty's syndrome and in those with LGL leukemia plus RA suggests that both disorders have a similar immunogenetic basis and are parts of a single disease process rather than 2 separate disorders.

Arthritis, Rheumatoid↗
PubMed1997

Structure-activity relationship of biphalin. The synthesis and biological activities of new analogues with modifications in positions 3 and 4.

New analogues of biphalin [(Tyr-D-Ala-Gly-Phe-NH-)2] with modifications of amino acid residues in positions 3,3' and 4,4' have been synthesized. The potency and selectivity of these analogues were evaluated by competitive radioreceptor binding assay in the rat brain using [3H]CTOP (mu ligand) and [3H][p-Cl-Phe4]DPDPE (delta ligand) as ligands, and by bioassay in the mouse vas deferens (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay). The symmetrical substitution of phenylalanine in positions 4 and 4' with p-fluorophenylalanine or p-nitrophenylalanine resulted in an enhancement of the affinity at both delta and mu receptors, with some increase of the selectivity for delta opioid receptors. The analogue containing p-chlorophenylalanine in positions 4 and 4' is the most selective to the delta receptors in this series, with a selectivity ratio about 5. The symmetrical substitution of the glycine-3 residue with phenylalanine resulted in a decrease of binding affinities and biological potencies at both mu & delta receptors.

Analgesics↗