Search PubMed⌕ Search

Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 271 records · Page 15Linked to original sources
PubMed1992

Setting national health goals and targets in the context of a fiscal crisis: the politics of social choice in New Zealand.

The setting of national health goals and targets in New Zealand has taken place in the context of fiscal crisis. The mandate for State intervention for social goals has also been under a sustained ideological challenge. These circumstances, together with other developments within the New Zealand health service, prepared the way for the development of the first set of health goals and targets. Six criteria were used to identify health problems for which goals and targets could be set. Ten areas were included, and specific, timed and quantified targets were set in each area for the year 2000 with shorter term targets for 1995. The Minister of Health gave priority to three areas: tobacco control, secondary prevention of cervical cancer, and reduction of road accident injury and death. An important aspect of the program is that the goals and targets are to be the focus of the annual contract between the Minister of Health (the primary funder of health care) and the Area Health Boards (the primary providers of health care). A matrix of policy options is presented for resource allocation and public health. The case study described represents one solution to the set of policy choices presented by fiscal and ideological challenge; the "new managerialism" has been allied with the "new public health." The authors argue that a combination of ideological renewal and fiscal probity has preserved a vigorous role for the State in health and health care. This matrix of policy options also underlines the necessity to consider health outcomes, as well as organizational goals, in the evaluation of the performance of health systems.

Cost Control↗
PubMed1992

Viral infections, acquired immunodeficiency syndrome, and rheumatic diseases.

There is increasing evidence of a role for viruses in the pathogenesis and etiology of rheumatic diseases. Although definitive evidence of any involvement in diseases such as rheumatic arthritis and systemic lupus erythematosus is currently lacking, there is increasing evidence that viruses may be involved in the pathogenesis of related diseases. In particular, the recent world-wide epidemic of human immunodeficiency virus infection has been associated with the identification of a wide variety of rheumatic manifestations, most notably oligoarthropathies, psoriatic arthropathies, and Reiter's-like syndromes. The spectrum of rheumatic diseases associated with human immunodeficiency virus infection appears to be expanding at a considerable rate. Other viruses have also been shown to be associated with rheumatic disorders, most notably hepatitis viruses, human T lymphotropic virus type I, and parvoviruses. In the latter case, acute arthropathies and those resembling rheumatoid arthritis and Lyme arthritis have recently been identified. This review presents some of the evidence in the recently published literature on the role of different viruses and their implications in the pathogenesis of various rheumatic diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1992

A high proportion of early response genes are constitutively activated in T cells by HTLV-I.

Immortalization of T cells by HTLV-I is mediated by the X region of the virus and probably involves transactivation of cellular genes. We show that T cells transformed by HTLV-I constitutively express a high proportion of early response genes that are normally transiently induced following antigenic or mitogenic activation of T cells. Thus, HTLV-I-infected T cells display an 'early activation' phenotype that is distinct from the gene expression pattern of continuously dividing T cells. Ten early response genes representing a diverse array of functional categories were assayed. Four DNA-binding proteins/transcription factors including the p50 subunit of NF-kappa B were evaluated. A protein(s) encoded by the X region of HTLV-I appeared to contribute to up-regulated expression of most, if not all, of the early response genes. For those genes that could be assayed, increased transcriptional rates, but not substantial changes in mRNA half-life, were demonstrated in the presence of pX-encoded proteins, suggesting that the transcriptional transactivator, Tax, affects the induction or maintenance of transcription for these mitogen-inducible genes. Therefore, Tax may mimic or interact with a component(s) of the signal transduction pathway activated by antigen or mitogen treatment. These data demonstrate that early response genes, some of which probably play roles in initiating or maintaining cellular proliferation, are frequent targets of HTLV-I activation.

Blotting, Northern↗
PubMed1991

Topographical requirements for delta opioid ligands: presence of a carboxyl group in position 4 is not critical for deltorphin high delta receptor affinity and analgesic activity.

To investigate the role of the carboxyl group in deltorphin molecules, we have synthesized three new analogues in which the acidic amino acid residues in position 4 of the deltorphins were replaced by non-acidic but hydrophilic amino acids residues. The three analogues, [Ser4]-, [Gln4]-, and [Cys4]-deltorphin, all are as potent or more potent than either deltorphin I or II at delta opioid receptors and possess good delta selectivities. The excellent correlation between their in vitro delta receptor potencies and their intrathecal antinociception activity forms a strong argument for involvement of those receptors in spinal nociceptive modulation in the rats.

Amino Acid Sequence↗
PubMed1991

Changes in opioid receptor selectivity following processing of peptide E: effect on gut motility.

Peptide E is a mu-selective opioid peptide derived from proenkephalin A which contains [Met5]-enkephalin at the amino end and [Leu5]-enkephalin at the carboxyl end. Peptide E is further processed both centrally and peripherally to a [Leu5]-enkephalin-containing fragment which was investigated to determine if processing leads to alterations in receptor selectivity. Peptide E-(15-25) inhibited electrically stimulated contractions in both the mouse vas deferens, longitudinal muscle, myenteric (IC50 = 459 nmol/L), and guinea pig ileum (IC50 = 2630 nmol/L), indicating a sixfold delta-receptor selectivity. When administered intracerebroventricularly to mice, peptide E-(15-25) also produced potent analgesia which was completely antagonized by naloxone pretreatment, but the peptide had no effect on intestinal transit as measured by the radiochromium geometric center method. This is consistent with earlier findings that intracerebroventricular delta-opioid-selective agents are analgesic but do not inhibit intestinal transit. In vitro radioligand binding assays were performed using male Sprague-Dawley rat whole brain homogenates. The IC50 for peptide E against [3H]naloxone was 1.8 nmol/L compared with the delta-opioid ligand, [3H] [D-Pen2, D-Pen5]-enkephalin of 38.8 nmol/L. The IC50 for peptide E-(15-25) against [3H]naloxone was 497 nmol/L, but for [3H] [D-Pen2, D-Pen5]-enkephalin it was 50.6 nmol/L. Therefore, peptide E loses mu-opioid receptor affinity (1.8-497 nmol/L) after proteolytic processing and the loss of the amino terminal tyrosine but maintains a high delta-opioid affinity (38.8-50.6 nmol/L). These studies demonstrate that enzymatic peptide processing of peptide E to peptide E-(15-25) leads to a shift from mu- to delta-receptor selectivity and a different spectrum of biological effects on gut motility.

Animals↗
PubMed1991

Influence of peptidase inhibitors on the apparent agonist potency of delta selective opioid peptides in vitro.

Several peptides of diverse structure, reported to possess high affinity and selectivity for the delta opioid receptor, were studied using the mouse isolated vas deferens preparation to determine the effect of peptidase inhibition on their apparent potency. The peptides evaluated included [Leu5] enkephalin, the cyclic enkephalin analogs [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Pen2,p-F-Phe4,D-Pen5]enkephalin (F-DPDPE), the linear enkephalin analogs [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Ser2(O-tBu), Leu5,Thr6]enkephalin (DSTBULET), and the naturally occurring amphibian peptides Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 (dermenkephalin), Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 (deltorphin I) and Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 (deltorphin II). Concentration-response curves were determined for each peptide in the absence and presence of a combination of the peptidase-inhibiting agents bacitracin, bestatin, and captopril. A wide range of potencies was observed, both in the control state and in the presence of peptidase inhibition. The synthetic enkephalin analogs demonstrated small increases in potency with peptidase inhibition (no increase in the case of DPDPE), whereas the naturally occurring peptides were markedly increased in potency, up to as much as 123-fold for dermenkephalin. In the presence of peptidase inhibition, deltorphin II was the most potent peptide tested (IC50 = 1.13 x 10(-10) molar), and as such is the most potent delta opioid agonist reported to date. Stability to metabolism must be considered in the design and evaluation of in vitro experiments using peptides of this type.

Amino Acid Sequence↗
PubMed1991

Delta opioid receptor-selective ligands: [D-Pen2,D-Pen5]enkephalin-dermenkephalin chimeric peptides.

A number of DPDPE-dermenkephalin chimeric peptides have been synthesized in which the putative C-terminal delta-address of dermenkephalin has been linked to the highly delta opioid selective cyclic peptide [D-Pen2,D-Pen5]enkephalin (DPDPE). Asp, Met-Asp and Leu-Met-Asp have been added to the C-terminus of DPDPE and both the carboxyl terminal and the carboxamide terminal series have been prepared. The bioassays using the mouse vas deferens and guinea pig ileum preparations have revealed a steady decrease in potency (compared to DPDPE) at delta and mu receptors as the dermenkephalin sequences were added. Some of the analogues, however, retained high delta selectivity. Similar results were obtained using radioligand binding assays. These findings suggest that the C-terminal amino acid sequence of dermenkephalin plays a role of delta-address which is specific to dermenkephalin itself, and is not additive with another delta selective ligand such as DPDPE.

Amino Acid Sequence↗
PubMed1991

Topographically designed analogues of [D-Pen,D-Pen5]enkephalin.

The conformationally restricted, cyclic disulfide-containing delta opioid receptor selective enkephalin analogue [D-Pen2,D-Pen5]enkephalin (1, DPDPE) was systematically modified topographically by addition of a methyl group at either the pro-S or pro-R position of the beta carbon of an L-Phe4 or D-Phe4 residue to give [(2S,3S)-beta-MePhe4]DPDPE (2), [(2R,3R)-beta-MePhe4]DPDPE (3), [(2S,3R)-beta-MePhe4]DPDPE (4), and [(2R,3S)-beta-MePhe4]DPDPE (5). The four corresponding isomers were prepared in which the beta-methylphenylalanine residue was p-nitro substituted, that is with a beta-methyl-p-nitrophenylalanine (beta-Me-p-NO2Phe) residue, to give [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (6), [(2R,3R)-beta-Me-p-NO2Phe4]DPDPE (7), [(2S,3R)-beta-Me-p-NO2Phe4] DPDPE (8), and [(2R,3S)-beta-Me-p-NO2Phe4]DPDPE (9), respectively. The potency and selectivity (delta vs mu opioid receptor) were evaluated by radioreceptor binding assays in the rat brain using [3H]CTOP (mu ligand) and [3H]DPDPE (delta ligand) and by bioassay with mouse vas deferens (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay). The eight analogues of DPDPE showed highly variable binding and bioassay activities particularly at the delta opioid receptor (4 orders of magnitude), but also at the mu opioid receptor, which led to large differences (3 orders of magnitude) in receptor selectivity. For example, [(2S,3S)-beta-MePhe4]DPDPE (2) is 1800-fold selective in binding to the delta vs mu receptor, making it one of the most selective delta opioid receptor ligands in the enkephalin series as assessed by the rat brain binding assay, whereas the corresponding (2R,3R)-beta-Me-p-NO2Phe-containing analogue 9 is only 4.5-fold selective (nonselective) in this same assay. On the other hand, in the bioassay systems, [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (5) is more potent than DPDPE and 8800-fold selective for the MVD (delta receptor) vs the GPI (mu receptor), making it the most highly selective ligand in this series for the delta opioid receptor on the basis of these bioassays. In these assay systems, the (2R,3S)-beta-MePhe4-containing analogue 5 had very weak potency and virtually no receptor selectivity (4.4-fold). These results demonstrate that topographical modification alone in a conformationally restricted peptide ligand can significantly modulate both potency and receptor selectivity of peptide ligands that have multiple sites of biological activity and suggest that this approach may have general application to peptide ligand design.

Amino Acid Sequence↗
PubMed1991

Oxygen consumption during fire suppression: error of heart rate estimation.

Ten male firefighters were tested on a treadmill to determine their heart rate (HR) x oxygen consumption (VO2) relationship. These men then performed a simulated fire suppression protocol during which HR and VO2 were measured simultaneously by a portable physiological monitoring system. Average VO2 in the simulated setting was 31.0 +/- 7.0 ml.kg-1.min-1 at a HR of 176 +/- 9 bpm. This VO2 was significantly (p less than or equal to 0.05) less than the VO2 that would have been predicted by treadmill testing (38.9 +/- 5.0 ml.kg-1.min-1) at a corresponding HR. Fifty-nine per cent of this variability could be accounted for by regression analysis. Firefighters worked on average at 73 +/- 10% VO2 max with a range of 54% to 88%. There was a significant (-0.82; p less than or equal to 0.05) inverse relationship between performance time of the fire suppression protocol and the relative intensity of VO2 max at which the firefighters worked. These findings indicate that the prediction of energy expenditure from HR is not straightforward in fire suppression settings. Furthermore, the relative intensity of work firefighters self-select is variable and should be considered as an additional physiological determinant of work behaviour.

Adult↗
PubMed1991

Medications and multiple falls in elderly people: the St Louis OASIS study.

The purpose of this study was to identify associations between the use of commonly taken medications and groups of medications and the risk of falls in elderly people living in the community. A stratified random sample of 1358 persons aged 65 years and over was selected from the 15,000 members of an educational organization for functionally independent, community-dwelling elderly people in St Louis, Missouri. Twenty-seven per cent of subjects reported at least one fall in the past year and 8% reported two or more falls. After adjusting for potential confounders (including age, sex, relevant medical conditions, health status, cognitive impairment, use of alcohol, depression and use of other medications), the following medications were found to be important risk factors for multiple falls: diazepam [odds ratio (OR): 3.7, 95% confidence interval (CI): 1.5-9.3], diltiazem (OR: 1.8, 95% CI: 0.8-4.1), diuretics (OR: 1.8, 95% CI: 1.2-2.8) and laxatives (OR: 2.1, 95% CI: 1.0-4.5). We conclude that caution is needed before prescribing diuretics and psychotropics, especially diazepam, for elderly people. The safety of diltiazem in this age group should be assessed further.

Accidental Falls↗
PubMed1991

The epidemiology of acute appendicitis in California: racial, gender, and seasonal variation.

The incidence of acute appendicitis has been reported to vary substantially by country, geographic region, race, sex, season, and occupation, but the reasons for this variation are unknown. We evaluated several risk factors for appendicitis by analyzing data from hospital discharge abstracts on all cases of acute appendicitis treated surgically in nonfederal hospitals in California from 1983 to 1986 (N = 102,546). Comparison of age and sex-specific incidence rates for four racial/ethnic groups (white, Hispanic, black, and Asian/other) revealed rates in blacks and the Asian/other group one-half or less of the rates for whites and Hispanics between the ages of 5 and 29 years. Incidence rates in males were higher than rates in females in all racial/ethnic groups for most ages (RR = 1.1-1.7). Seasonal variation in incidence was modest. Peak rates occurred in July, August, and September, and the lowest rates occurred in December. Hypotheses about the etiology of appendicitis must account for substantial racial/ethnic, gender, age variation, and modest seasonal variation in the incidence.

Acute Disease↗
PubMed1991

Psychological profiles of patients with upper gastrointestinal symptomatology induced by non-steroidal anti-inflammatory drugs.

Eighty three patients with classical or definite rheumatoid arthritis taking non-steroidal anti-inflammatory drugs (NSAIDs) were studied in an attempt to determine whether a patient's personality and psychological profile might contribute to the development of NSAID induced gastrointestinal symptomatology. It was found that the personality profile of the group of 45 asymptomatic patients was similar to that of a previously reported control group. In contrast, the 37 patients with gastrointestinal symptoms attributed to NSAIDs had a significantly higher mean score for free floating anxiety, depression, and somatisation than controls, suggesting that a patient's personality may influence the development of NSAID induced gastric symptoms.

Adolescent↗
PubMed1991

Osteoarthritis 1991. Current drug treatment regimens.

Osteoarthritis, the most common rheumatic disease, presents the clinician with a major therapeutic and management task. The chronic and progressive course of the disease is punctuated by pain, declining function and escalating disability. This article attempts to deal with the pharmacological therapeutic options available to use in the management of osteoarthritis. Other non-pharmacological therapeutic modalities are also briefly discussed, including patient education, joint protection, physiotherapy, occupational therapy and surgery. Drug therapy as discussed focuses on the control of pain and inflammation. For this intermittently painful condition analgesic drugs assume a very important role. Non-steroidal anti-inflammatory drugs (NSAIDs) have combined analgesic and anti-inflammatory properties which are particularly useful in many patients who manifest inflammation in addition to pain. While systemic steroids have no role in the treatment of osteoarthritis, intra-articular steroid injections may be of benefit. In trying to slow the degenerative process chondroprotective agents such as glycosaminoglycan may also assume increasing importance in the future. Choosing one drug over another must be done after consideration of many factors including the therapeutic and toxicity profile of the drugs involved, their pharmacology and dose regimen, the patient profile, cost and the desired effect.

Analgesics↗