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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 55 records · Page 3Linked to original sources

Synthesis, biology, NMR and conformation studies of the topographically constrained delta-opioid selective peptide analogs of [beta-iPrPhe(3)]deltorphin I.

Replacement of Phe3 in the endogenous delta-opioid selective peptide deltorphin I with four optically pure stereoisomers of the topographically constrained, highly hydrophobic novel amino acid beta-isopropylphenylalanine (beta-iPrPhe) produced four pharmacologically different deltorphin I peptidomimetics. Radiolabeled ligand-binding assays and in vitro biological evaluation indicate that the stereoconfiguration of the iPrPhe residue plays a crucial role in determining the binding affinity, bioactivity and selectivity of [beta-iPrPhe3]deltorphin I analogs: a (2S,3R) configuration of the iPrPhe3 residue in [beta-iPrPhe3]deltorphin I provided the most desirable biological properties with binding affinity (IC50 = 2 nM), bioassay potency (IC50 = 1.23 nM in MVD assay) and exceptional selectivity for the delta-opioid receptor over the mu-opioid receptor (30 000). Further conformational studies based on two-dimensional NMR and computer-assisted molecular modeling suggested a model for the possible bioactive conformation in which the Tyr1 and (2S,3R)-beta-iPrPhe3 residues adopt trans side-chain conformations, and the linear peptide backbone favors a distorted beta-turn conformation.

Analgesics, Opioid↗

Best practice in psychogeriatric care.

This paper presents a best practice model for psychogeriatric care. Best practice is becoming one of the most common expressions used in the area of health care, and is often referred to in government reports and documents. The definition of 'best practice', however, is still evolving. What then, is best practice? And how can the principles of best practice be applied and integrated into the clinical speciality of psychogeriatrics? The article emphasizes the importance of evidence-based interventions and the need to focus on the pragmatic aspects of providing best practice in the clinical area of psychogeriatrics; that is, what works best in practice? The position taken by the authors of this paper is that the conceptualization of a best practice model in psychogeriatrics is necessary in order to describe and explain the different components involved in the service provided. This conceptualization also communicates and articulates the role of the major stakeholders, and the key players in the achievement of best practice. A psychogeriatric service may become more coherent, more goal-orientated and more efficient if a model is utilized. This paper outlines a proposed model of best practice in psychogeriatrics, and discusses the potential implications for achieving desirable clinical outcomes.

Aged↗

Orbital myiasis: a case report.

Myiasis; a term first introduced by HOPE refers to invasion of living tissue of humans and other mammals by the eggs or larvae of flies of the order of Diptera. Orbital involvement occurs in approximately 5% of all cases of myiasis. A 72 year old patient is presented with orbital myiasis that was successfully treated by enucleation and grafted with split thickness of skin.

Aged↗

A microscopic and biochemical study of fragmentation phenotypes in stage-appropriate human embryos.

The occurrence of a pleiomorphic population of cytoplasmic fragments is a common characteristic of early human embryos fertilized in vitro. Here, temporal, spatial, fine structural, and biochemical aspects of fragmentation were examined in fragmented monospermic and dispermic pronuclear to early cleavage stages human embryos classified as stage-appropriate during the first 3.5 days of culture. The morphodynamics of certain common patterns of fragmentation and the movement and composition of fragments were analysed by time-lapse video, mitochondrial fluorescent probes, and transmission electron microscopy. Plasma membrane and nuclear DNA integrity were assessed by annexin V staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and single-cell alkaline gel electrophoresis ('comet') assays respectively. Developmental competence for affected embryos was related to outcome after embryo transfer. The results demonstrate that certain common forms of spontaneous fragmentation affecting early human embryos are not lethal, and that clusters of apparent fragments are often transient structures, which disappear by resorption or lysis. The findings suggest that the occurrence and fate of fragments characteristic of these phenotypes may be related to oncosis-like processes associated with transient and focal ATP deficiencies in blastomeres and mitochondrial deficiencies or absence in extracellular fragments.

Blastomeres↗

Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro.

The effects of four rounds of ovarian stimulation spaced 1-6 weeks apart on the normality of metaphase II (MII) spindle formation, chromosomal alignment and cytoplasmic organization were examined in intact ovulated mouse oocytes and at MII for oocytes obtained at the germinal vesicle stage from the same ovaries and matured in vitro. The terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling assay was used to identify DNA strand breaks in chromosomes, and histological studies of ovaries between and at each round of ovarian stimulation were performed. The results demonstrate a progressive and significant increase in the frequency of spindle defects with each round of ovarian stimulation, including those spaced weeks apart. Oocytes with spindle defects were also characterized by the occurrence of detached chromosomes and cytoplasmic asters. In contrast, in-vitro matured oocytes derived from the same ovaries were normal. No evidence of DNA strand breaks with repeated rounds of ovarian stimulation was detected in ovulated or in-vitro matured oocytes. The development and persistence of nodules of hypertrophied granulosa in regions where follicular growth occurs suggest that a progressively increasing proportion of oocytes in the ovulatory pathway may experience an intrafollicular milieu that has negative consequences for competence. The results are discussed with respect to ovarian and oocyte biological ageing and possible adverse implications for human oocyte competence with repeated hyperstimulation.

Animals↗

A randomised controlled trial of two methods of delivering nasal continuous positive airway pressure after extubation to infants weighing less than 1000 g: binasal (Hudson) versus single nasal prongs.

OBJECTIVES: Primary: to determine whether nasal continuous positive airway pressure (CPAP) delivered through binasal prongs results in a greater proportion of extremely low birthweight infants being successfully extubated, after a period of intermittent positive pressure ventilation, than nasal CPAP delivered by a single nasal prong. Secondary: to evaluate the effect of mode of delivery of nasal CPAP after extubation on the need for endotracheal reintubation, weight gain, rates of feeding intolerance, sepsis, suspected sepsis, cranial ultrasound abnormalities, retinopathy of prematurity, chronic lung disease, and the duration of assisted ventilation and care in the tertiary neonatal unit. DESIGN AND SETTING: Randomised, controlled, clinical trial conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, Australia. PATIENTS: Infants of birth weight less than 1000 g, ventilated, requiring < 50% oxygen and ventilator rate less than or equal to 20/minute, and considered by the clinical management team to be ready for extubation. INTERVENTION: Infants were randomly allocated to receive nasal CPAP delivered through binasal (Hudson) prongs or a single nasal prong. PRIMARY OUTCOME MEASURE: Failure of extubation as defined by the following criteria: (a) apnoea (more than one episode/hour over a six hour period or one episode requiring bag and mask ventilation); (b) absolute increase in oxygen requirement greater than 15% above that required before extubation; (c) respiratory acidosis (pH < 7.25 with PCO(2) > 6.67 kPa). RESULTS: Ten of the 41 (24%) infants randomised to binasal prongs reached predetermined failure criteria compared with 26 of the 46 (57%) infants randomised to a single nasal prong (p = 0.005). Four of 17 (24%) infants of birth weight less than 800 g extubated to binasal prongs reached failure criteria compared with 14 of 16 (88%) extubated to a single nasal prong (p < 0.001). There were no significant differences in any of the secondary outcomes. CONCLUSIONS: For extremely low birthweight infants ventilated using an endotracheal tube, nasal CPAP delivered through binasal (Hudson) prongs is more effective in preventing failure of extubation than that delivered through a single nasal prong.

Device Removal↗

Telehealth consultations in rheumatology: cost-effectiveness and user satisfaction.

We conducted a feasibility study to assess user satisfaction with and the cost-effectiveness of a rheumatology telehealth clinic in northern Alberta. Six telehealth clinics were organized between a rural health centre and the specialist rheumatology centre, which was about a 4 h drive away. Fifty-two new patients were seen. Their median age was 54 years (range 7-81 years). After the teleconsultation, no patient required a conventional face-to-face consultation. Overall, patients agreed that the teleconsultation met their needs and that the care they received was as good as conventional care. The physicians involved in the study thought the process practical and effective. The total costs of service delivery would be equal for teleconsultation and for traditional consultation at a workload of 247 consultations a year.

Adolescent↗

Comparative practice patterns of emergency medicine physicians and pediatric emergency medicine physicians managing fever in young children.

BACKGROUND/OBJECTIVE: The management of fever in young children is a controversial topic. This study seeks to compare the management approaches between general emergency medicine physicians (GEMPs) and pediatric emergency medicine physicians (PEMPs) and correlate them to existing practice guidelines. DESIGN/METHODS: All charts of children age 3 to 36 months presenting with the complaint of fever at both a children's hospital emergency department (ED) and a general ED from June 1, 1998 to September 1, 1998; December 1, 1998 to April 1, 1999; and June 1, 1999 to September 1, 1999 were retrospectively reviewed. Fever was defined as >/=39 degrees C. Patients with a history of immunodeficiency, chronic illness, ventriculoperitoneal shunt, antibiotic use in the past 48 hours, or focal infection noted on examination were excluded. Data collected included focal exam findings, laboratory tests, diagnosis, treatment, and disposition. Variances from the practice guidelines were tabulated and compared. RESULTS: One thousand three hundred twenty-three eligible children met exclusion criteria and were seen by PEMPs; 755 were eliminated because of exclusion criteria (526 because of focal infection). Twenty-two (4%) of 568 remaining patients were admitted to the hospital. Two hundred twenty-eight eligible children were seen by GEMPs; 147 were excluded (109 because of focal infection). No patients were admitted to the hospital. PEMPs ordered more complete blood counts (324/568 vs 27/81), more blood cultures (321/568 vs 27/81), and more urine cultures (208/568 vs 20/81) than GEMPs. GEMPs ordered more chest radiographs and cerebrospinal fluid analyses than PEMPs; GEMPs ordered less complete blood counts, blood cultures, and urine cultures than PEMPs. GEMPs diagnosed more focal infections (109/228 vs 526/1323), and conflicted more often with the practice guidelines (66/79 vs 225/498) than PEMPs. Patients spent an average of 2.26 +/- 0.16 hours in the pediatric ED versus 3.0 hours +/- 0.18 hours in the general ED. CONCLUSIONS: Significant differences in the management of the young child with fever and no source exist between these two groups of physicians. These variations affect both cost and standard of care. Future studies assessing whether these strategies affect patient outcomes would further elucidate their clinical implication.

Bacterial Infections↗

The interface between primary and secondary care.

The interface between primary and secondary care in the UK has been affected by a number of recent changes, particularly in provision of out-of-hours care and advice. This paper reviews some current measures of healthcare quality and argues that many do not adequately measure contributions in primary care. To overcome these deficiencies the Royal College of General Practitioners (RCGP) has published guidelines on issues of quality in primary care.

Continuity of Patient Care↗

An evaluation of telehealth in the provision of rheumatologic consults to a remote area.

OBJECTIVE: To evaluate the feasibility and acceptability of providing telehealth consultations in rheumatology. METHODS: A prospective review of new consults from a rural area assessed by a rheumatologist in an urban area using telehealth. Patient demographics were recorded along with a self-administered questionnaire reporting assessment of the acceptability of the process. Referring physician and consultant provided open ended feedback as to relative strengths and weaknesses of telehealth versus traditional consult. A simple cost and time benefit analysis was undertaken. RESULTS: The spectrum of patients with rheumatic disease assessed was similar to a traditional consultation clinic. Patients found the overall process to be acceptable and effective. Apart from accessibility to specialist consultation, the greatest benefit was improved communication among patient, referring physician, and consultant. The process was determined to be efficient in both time and cost savings. CONCLUSION: Telehealth rheumatology consultations are feasible, acceptable, and cost/time effective and are therefore advocated for those geographic areas where traditional consultations are not readily available.

Adolescent↗

Wealthy nations called on to boost support efforts. Five-year plan estimated to cost $9.2 billion.

Using the 20-year mark in the history of AIDS as a catalyst, the United Nations and other international organizations have called upon the world's wealthier nations to increase attention, support, and funding to HIV/AIDS prevention and treatment efforts. This call to action included a series of meetings with business and political leaders and culminated in the first United Nations General Assembly Special Session on HIV/AIDS, held in June.

Anti-HIV Agents↗

The potential for elderly suicide. . . Is health care missing it?

Assessment of elderly patients at risk for suicide, presents a unique challenge in healthcare. Assessment of residents entering long term care facilities does not end once they are admitted. Learning to identify the warning signs and situations that can precede "silent suicide" requires extraordinary sensitivity (Simon, 1989). A case study is utilized to review some of the most common risk factors for suicide in the elderly population. The impact on elderly people when they must leave their homes, is highlighted in the discussion of"relocation stress" (Harkulich, 1992) The reason why healthcare workers could misinterpret the signs and symptoms of potential elderly suicide is also included.

Activities of Daily Living↗

Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media.

The effect of antibiotic therapy on nasopharyngeal colonization by Streptococcus pneumoniae and Haemophilus influenzae was evaluated in children diagnosed with acute otitis media. Children were randomly assigned to receive either amoxicillin/clavulanate or azithromycin therapy, and nasopharyngeal swabs were obtained for culture before and after starting therapy. Amoxicillin/clavulanate therapy eradicated or suppressed all strains of S. pneumoniae susceptible to penicillin, 75% of strains with intermediate resistance, and 40% of strains resistant to penicillin. Azithromycin therapy cleared two-thirds of azithromycin-susceptible strains of S. pneumoniae but none of azithromycin-nonsusceptible strains. Selection for antibiotic-resistant strains in individual children was not observed in children who received amoxicillin/clavulanate therapy but was observed in 2 children who received azithromycin therapy. Carriage of H. influenzae was also reduced by antimicrobial therapy but more so by amoxicillin/clavulanate. Antibiotic therapy does not directly increase the number of resistant strains in the population but, by eradicating susceptible strains, allows greater opportunity for carriage and spread of resistant strains.

Acute Disease↗

Enkephalin glycopeptide analogues produce analgesia with reduced dependence liability.

Endogenous peptides (e.g. enkephalins) control many aspects of brain function, cognition, and perception. The use of these neuroactive peptides in diverse studies has led to an increased understanding of brain function. Unfortunately, the use of brain-derived peptides as pharmaceutical agents to alter brain chemistry in vivo has lagged because peptides do not readily penetrate the blood-brain barrier. Attachment of simple sugars to enkephalins increases their penetration of the blood-brain barrier and allows the resulting glycopeptide analogues to function effectively as drugs. The delta-selective glycosylated Leu-enkephalin amide 2, H(2)N-Tyr-D-Thr-Gly-Phe-Leu-Ser(beta-D-Glc)-CONH(2), produces analgesic effects similar to morphine, even when administered peripherally, yet possesses reduced dependence liability as indicated by naloxone-precipitated withdrawal studies. Similar glycopeptide-based pharmaceuticals hold forth the promise of pain relief with improved side-effect profiles over currently available opioid analgesics.

Analgesics, Opioid↗

Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491.

Neisseria meningitidis causes bacterial meningitis and is therefore responsible for considerable morbidity and mortality in both the developed and the developing world. Meningococci are opportunistic pathogens that colonize the nasopharynges and oropharynges of asymptomatic carriers. For reasons that are still mostly unknown, they occasionally gain access to the blood, and subsequently to the cerebrospinal fluid, to cause septicaemia and meningitis. N. meningitidis strains are divided into a number of serogroups on the basis of the immunochemistry of their capsular polysaccharides; serogroup A strains are responsible for major epidemics and pandemics of meningococcal disease, and therefore most of the morbidity and mortality associated with this disease. Here we have determined the complete genome sequence of a serogroup A strain of Neisseria meningitidis, Z2491. The sequence is 2,184,406 base pairs in length, with an overall G+C content of 51.8%, and contains 2,121 predicted coding sequences. The most notable feature of the genome is the presence of many hundreds of repetitive elements, ranging from short repeats, positioned either singly or in large multiple arrays, to insertion sequences and gene duplications of one kilobase or more. Many of these repeats appear to be involved in genome fluidity and antigenic variation in this important human pathogen.

Antigenic Variation↗