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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 127 records · Page 7Linked to original sources
PubMed1998

Membrane depolarization and depletion of intracellular calcium stores are associated with delay of apoptosis in human neutrophils.

Apoptosis occurs rapidly in human polymorphonuclear leukocytes (PMN) after exposure to 1 mM cycloheximide (CHX). We examined whether this form of stimulated apoptosis altered either resting cytosolic free Ca2+ concentrations ([free Ca]) or membrane potential (psi) in PMN and found no significant effects. However, manipulation of either PMN intracellular Ca2+ stores or psi was found to delay CHX-induced apoptosis. Depletion of PMN intracellular Ca2+ stores with thapsigargin caused membrane depolarization and significantly delayed CHX-induced apoptosis based on both morphological and annexin-V-fluorescein isothiocyanate binding criteria. Short-term suspension (4 h) of PMN in Ca2+-free buffer depleted internal Ca2+ stores, induced membrane depolarization at 2.5 h, and delayed spontaneous (24 h) apoptosis but had no effect on CHX-induced apoptosis. Rapid membrane depolarization with 150 mM KCl buffer significantly delayed CHX-induced apoptosis, suggesting that depolarization rather than Ca2+ stores depletion was the crucial event. Timing experiments revealed that depolarization within 12 min of CHX exposure significantly delayed apoptosis. Collectively, these observations suggest an early psi-sensitive step in the apoptosis pathway initiated by CHX. CHX exposure alone does not alter either resting PMN [free Ca] or psi; accompanying depolarization of plasma membrane (either electrochemically or via depletion of internal Ca2+ stores) delays CHX-induced apoptosis in a time-dependent manner.

Annexin A5↗
PubMed1998

Pharmacokinetics and relative bioavailability of carboxyamido-triazole with respect to food and time of administration: use of a single model for simultaneous determination of changing parameters.

Carboxyamido-triazole (CAI) is an anti-invasive, antimetastatic, antiangiogenic agent in clinical development for cancer treatment. It has been postulated that food might enhance the oral absorption of micronized CAI based on an apparent discrepancy in steady state maximum concentrations when taken without regard to meals vs. fasting. The purpose of this study was to determine if a standardized meal affects the absorption and pharmacokinetics of this agent. Twelve patients with refractory cancers and good end organ function were randomized to receive two doses of CAI (250 mg/m2) with and without a standardized high fat meal. One cohort of 6 patients received these doses at 9 AM, and the remaining 6 patients received CAI at 9 PM. Blood was obtained prior to each dose, and serially thereafter. A series of pharmacokinetic (PK) models were fit to the concentration-time data. PK parameters were ultimately calculated using a model which allows simultaneous estimation of parameters from both test doses using nonlinear least squares analysis with ADAPT II. This model estimates independent absorption rate constants and relative fraction absorbed for each condition. AUC0-t was determined using the trapezoidal method, extrapolated to infinity, and used to calculate the relative bioavailability. No significant differences in PK parameters were noted between the morning and evening cohorts. However, the relative bioavailability, as measured by AUC0-infinity, of CAI was significantly increased when administered with a high fat meal compared to fasting (138.9 vs. 52.2 micrograms * hr/ml; p = 0.0005). The magnitude of the increase in relative bioavailability of CAI taken with food could have profound implications for patients who may inadvertently take this medication shortly after eating.

Adult↗
PubMed1998

Disproportionate consumption of ventilator resources by very preterm survivors persists in the 1990s.

The aim of this study of consecutive livebirths between 23 and 30 weeks of gestational age was to determine the changes over time in the relationship between gestational age and the consumption of nursery resources by surviving preterm infants. Three discrete eras, comprising the years 1977-1985, 1986-1990, and 1991-1995, were identified, based on availability of ventilators and changes in perinatal care. The survival rate rose dramatically with each week's increase in gestational age, and increased significantly between successive eras. Overall, consumption of resources for assisted ventilation by survivors increased over time. In infants born before 28 weeks, for each week of decrease in gestational age, survivors averaged an extra 12.9 days of assisted ventilation in 1977-1985, 13.4 days in 1986-1990, and 13.5 days in 1991-1995, while infants born between 28-30 weeks of gestational age needed only an extra 2.3 days, 3.3 days, and 4.6 days of assisted ventilation for each week of decrease in gestational age in successive eras, respectively. There was no indication that improvements in perinatal care over time shortened the duration of assisted ventilation for surviving preterm infants.

Gestational Age↗
PubMed1998

Preliminary findings from a teleultrasound study in Alberta.

BACKGROUND AND OBJECTIVES: Ultrasound practice in Alberta requires direct supervision by an ultrasound-accredited specialist physician (sonologist). This requirement limits access to ultrasound examinations in many rural communities. A prospective study was performed to evaluate the adequacy of teleultrasound service in High Level, Alberta, with remote sonologist supervision from Edmonton, Alberta. METHODS: A total of 146 patients were evaluated in two groups. Group A (72 patients) was evaluated by both an on-site radiologist in High Level and a remote supervising radiologist in Edmonton. Group B (74 patients) was evaluated only by the remote supervising radiologist in Edmonton. The teleultrasound service included digital store-and-forward capabilities using a commercially available teleradiology system, with videoconferencing review for real-time scanning. RESULTS: The teleultrasound service was helpful to the referring physician. It made transfer unnecessary in 42% of patients, and the results of the ultrasound assessment influenced management in 59% of patients. The sonographer on site and the remote radiologists agreed on the quality of the images. The information required for diagnosis was available from the sonographer's study in the majority of cases, with second-look scanning by the on-site radiologist or videoconferencing by the remote radiologist providing a major new diagnosis in only 1% of patients. CONCLUSION: Teleultrasound service to High Level could be provided reliably with remote supervision, comparable to direct on-site supervision.

Alberta↗
PubMed1998

Mitochondrial transfer between oocytes: potential applications of mitochondrial donation and the issue of heteroplasmy.

The developmental competence of mouse and human early embryos appears to be directly related to the metabolic capacity of a finite complement of maternally inherited mitochondria that appear to begin to replicate after implantation. Mitochondrial dysfunctions resulting from a variety of intrinsic and extrinsic influences, including genetic abnormalities, hypoxia and oxidative stress, can profoundly influence the level of ATP generation in oocytes and early embryos, which in turn may result in aberrant chromosomal segregation or developmental arrest. Deletions and mutations in oocyte mitochondrial DNA may subtend metabolic deficiencies or replication disorders in some infertile women and in women of increased reproductive age. Here, we describe methods for (i) the compartmentalization of mouse and human oocyte mitochondria into unique cytoplasts enriched for these organelles, and (ii) their transfer by microinjection into intact recipient oocytes. Metabolically active mitochondria in donor and recipient metaphase II stage oocytes were labelled with mitochondria-specific fluorescent probes, and the fate and location of donated mitochondria in recipient oocytes were followed by conventional epifluorescence and scanning laser confocal fluorescence microscopy. The net ATP content of undisturbed and recipient oocytes from the same cohort(s) was measured quantitatively at timed intervals after mitochondrial injection. The results demonstrate the feasibility of isolating and transferring mitochondria between oocytes, an apparent increase in net ATP production in the recipients, and the persistence of activity in the transferred mitochondria. The findings are discussed with respect to mitochondrial function and dysfunction in mammalian oocytes and embryos, and to the potential clinical applications of mitochondrial donation as they relate to the creation of heteroplasmic embryos.

Adenosine Triphosphate↗
PubMed1998

Referral and diagnosis of common rheumatic diseases by primary care physicians.

OBJECTIVE: To describe primary care patterns of referral and diagnoses of patients with rheumatic diseases referred to rheumatologists. METHODS: The medical records of all consecutive patients referred in 1994 by >300 primary care physicians to two rheumatologists at an academic centre were reviewed. The referring physician diagnosis was compared with the rheumatologist's diagnosis. Sensitivity, specificity and predictive values of primary care diagnoses were estimated using the rheumatologist diagnosis as the 'gold standard'. SETTING: University-based rheumatology out-patient clinic. RESULTS: Over half of the patients referred had a rheumatologist diagnosis of soft-tissue rheumatism or a spinal pain syndrome. Three hundred and forty-seven patients (49%) had a primary care diagnosis of a defined rheumatic disease. Of these, 142 (41%) of the primary care diagnoses were subsequently modified by the rheumatologist. The highest agreement between primary care physician and rheumatologist was observed for crystal-induced arthritis (kappa = 0.86), and the lowest agreement for polymyalgia rheumatica (kappa = 0.39) and systemic lupus (kappa = 0.46). Sensitivity was lowest for a primary care diagnosis of fibromyalgia (48%) and highest for ankylosing spondylitis (94%). Positive predictive values were generally low, in particular for systemic lupus erythematosus (33%) and polymyalgia rheumatica (30%). CONCLUSION: Most patients referred to an academic rheumatology centre had soft-tissue rheumatism or other pain syndromes. In general, diagnostic agreement between rheumatologists and primary care physicians was low. Increased emphasis on musculoskeletal disorders should be encouraged in medical education to increase the efficiency of rheumatology referrals.

Adult↗
PubMed1998

Developing a nursing outcomes measurement tool.

In an era of rapidly shifting resources and changing models of care, healthcare providers must demonstrate quality and cost-effective patient care. Historically, quality of care has been described using administrative variables such as mortality, morbidity, length of stay, readmissions, and cost. Methods have not been readily available to define quality in terms of the effect of care delivery on the health of patients. Combined administrative and health-related databases are foundational to outcome infrastructures evolving with the electronic medical record. Nursing leaders in a large health maintenance organization sponsored the development of the Health Status Outcome Dimensions (HSOD) instrument. The HSOD instrument includes measures of functional status, knowledge, and engagement in healthcare and the patient and family psychosocial well-being. This article describes the processes used and the challenges faced in the development of the HSOD instrument. The current status of the HSOD instrument is described, as well as its planned future development.

California↗
PubMed1998

Preterm infants 30-36 weeks' gestation in Victoria--where should they be delivered?

There is little doubt that very preterm infants <30 weeks' gestation should be born in level-3 perinatal centres. For preterm infants 30-36 weeks' gestation, however, the optimum place of birth is not so clear-cut. The aims of this study of livebirths 30-36 weeks' gestational age born in Victoria were to determine: 1) the proportions delivered outside level-3 centres, and 2) for infants born outside level-3 centres, the proportions transferred after birth to a level-3 nursery in the first days after birth. Data on the number of livebirths 30-36 weeks' gestational age in Victoria in the 3 years 1994-1996, inclusive, were supplied by the Victorian Perinatal Data Collection Unit. Data were obtained from the Newborn Emergency Transport Service (NETS) on all transfers within the first 3 days after birth to a level-3 centre for infants born outside level-3 centres. For the 3 years 1994-1996 there were 11,375 livebirths 30-36 weeks' gestational age in Victoria. The proportion born outside a level-3 perinatal unit was 57.9% overall, and rose with increasing gestational age, from 10.9% at 30 weeks to 69.0% at 36 weeks. Of the 6,587 livebirths outside a level-3 centre, 808 (12.3%) were transferred within the first 3 days after birth by NETS to a level-3 centre, the proportions falling with increasing maturity, being 73.7%, 48.5%, 28.4%, 26.9%, 18.8%, 11.8%, and 7.0% at 30, 31, 32, 33, 34, 35, and 36 weeks, respectively. These data may help medical practitioners when determining the place of delivery for infants 30-36 weeks' gestation.

Delivery Rooms↗
PubMed1998

Procedures, placement, and risks of further abuse after Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation.

OBJECTIVES: To investigate outcome, management, and prevention in Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation. DESIGN: Ascertainment through British Paediatric Surveillance Unit and questionnaires to responding paediatricians. SETTING: The UK and Republic of Ireland, September 1992 to August 1994. SUBJECTS: Children under 14 years diagnosed with the above. MAIN OUTCOME MEASURES: Placement and child protection measures for victims and siblings; morbidity and reabuse rates for victims; abuse of siblings; prosecution of perpetrators. RESULTS: Outcome data for 119 with median follow up of 24 months (range 12 to 44 months). No previously diagnosed factitious disease was found to have been caused by genuine disease. Forty six children were allowed home without conditions at follow up. Children who had suffered from suffocation, non-accidental poisoning, direct harm, and those under 5 years were less likely to go home. Twenty seven (24%) children still had symptoms or signs as a result of the abuse at follow up; 108/120 were originally on a child protection register and 35/111 at follow up. Twenty nine per cent (34/118) of the perpetrators had been prosecuted and most convicted; 17% of the milder cases of Munchausen syndrome by proxy allowed home were reabused. Evidence in siblings suggests that in 50% of families with a suffocated child and 40% with non-accidental poisoning there would be further abuse, some fatal. CONCLUSIONS: This type of abuse is severe with high mortality, morbidity, family disruption, reabuse, and harm to siblings. A very cautious approach for child protection with reintroduction to home only if circumstances are especially favourable is advised. Paediatric follow up by an expert in child protection should also occur.

Adolescent↗
PubMed1998

Randomised, controlled trial of nasal continuous positive airway pressure in the extubation of infants weighing 600 to 1250 g.

AIM: To determine whether extubation to nasal continuous airway pressure (NCPAP) results in a greater proportion of infants remaining free of additional ventilatory support for one week after extubation compared with those extubated directly to headbox oxygen. METHODS: A randomised, controlled, clinical trial was conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, of infants with birthweights between 600 and 1250 g, ventilated via an endotracheal tube for more than 12 hours, requiring less than 50% oxygen, a ventilator rate < or = 20/minute, considered by the clinical management team to be ready for extubation. Infants were randomly allocated either to NCPAP or to oxygen administered via a headbox. Success was defined by no requirement for additional ventilatory support over the week following extubation. Failure criteria were (i) apnoea; (ii) absolute increase in oxygen requirement greater than 15% above than required before extubation; or (iii) respiratory acidosis (pH < 7.25 with pCO2 > 6.67 kPa). RESULTS: Thirty one of 47 (66%) infants were successfully extubated to NCPAP compared with 18 of 45 (40%) for headbox oxygen. The increase in failure rate in the headbox group was due primarily to increased oxygen requirements in this group. Of the 27 who failed headbox oxygen, 26 were given a trial of NCPAP and 13 did not require endotracheal reintubation. There was no significant difference between the groups in the total number of days of assisted ventilation or the duration of inpatient stay. CONCLUSIONS: NCPAP applied prophylactically after endotracheal extubation reduces the incidence of adverse clinical events that lead to failure of extubation in the seven days after extubation. This reduction is clinically important. The benefits of NCPAP do not seem to be associated with an increased incidence of unwanted side effects.

Female↗
PubMed1998

Association of environmental tobacco smoke exposure with socioeconomic status in a population of 7725 New Zealanders.

OBJECTIVE: To test the hypothesis that environmental tobacco smoke (ETS) exposure is inversely associated with socioeconomic status. DESIGN: Survey. SETTING: General community, New Zealand. PARTICIPANTS: 7725 non-smoking adults (volunteer sample of a multi-industry workforce, n = 5564; and a random sample of urban electoral rolls, n = 2161), including 5408 males; mean age 45 years. MAIN OUTCOME MEASURES: ETS exposure was assessed as self-reported number of hours per week spent near someone who is smoking, and as prevalence of regular exposure to some ETS. Socioeconomic status was assessed as educational level, occupational status, and median neighbourhood household income. RESULTS: Both measures of ETS exposure were steeply and inversely associated with all three indicators of socioeconomic status (all p < 0.0001). Geometric mean ETS exposure ranged from 16 minutes per week among university-educated participants to 59 minutes per week in the second lowest occupational quintile (95% confidence intervals: 14-18 minutes per week and 54-66 minutes per week). The associations with occupational status and educational level were steeper than those with neighbourhood income. The socioeconomic gradients of ETS exposure were steeper among participants aged less than 35 years than among participants aged over 50 years, among men than women, and among Maori than Europeans. CONCLUSIONS: In this study population, ETS exposure was inversely associated with socioeconomic status. Greater ETS exposure might therefore contribute to the higher risks of disease and death among low socioeconomic groups. These results provide a further rationale for targeting tobacco control measures to people in low socioeconomic groups.

Adult↗
PubMed1998

Axon conduction and survival in CNS white matter during energy deprivation: a developmental study.

We investigated the postnatal development of axon sensitivity to the withdrawal of oxygen, glucose, or the combined withdrawal of oxygen + glucose in the isolated rat optic nerve (a CNS white matter tract). Removal of either oxygen or glucose for 60 min resulted in irreversible injury in optic nerves from adult rats, assessed by loss of the evoked compound action potential (CAP). Optic nerves at ages 45 min caused the selective loss of late CAP components; this was not seen with oxygen deprivation. The amplitude of the early component recovered to 94.8% of control after 60 min of glucose withdrawal, although total CAP area recovered to only 42.3%. Combined oxygen + glucose withdrawal for 60 min produced a greater degree of permanent CAP loss than 60 min of glucose or oxygen withdrawal individually in optic nerves from rats older than P4. Younger than P4 optic nerves showed no permanent loss of function from 60 min of combined oxygen + glucose withdrawal. Unexpectedly, optic nerves from P21-P49 rats recovered significantly less after all three conditions than adult opticnerves (>P50). It is probable that this period of final myelination corresponds to a time of heightened metabolic activity in white matter. The tolerance of CNS white matter to energy deprivation can be categorized into four stages that are correlated with specific developmental features: premyelination (P0-P4), highly tolerant to anoxia, aglycemia and combined anoxia/aglycemia; early myelination (P5-P20), partially tolerant of anoxia and aglycemia but not to combined anoxia/aglycemia; late myelination (P21-P49), very low tolerance of anoxia, aglycemia and combined anoxia/aglycemia; and mature (>P50), low tolerance of anoxia, aglycemia and combined anoxia/aglycemia. The relative resistance of optic nerve function to glucose withdrawal in the presence of oxygen, compared with glucose withdrawal in the absence of oxygen, is presumably due to the presence of oxygen-dependent energy reserves such as astrocytic glycogen, amino acids. and phospholipids.

Action Potentials↗
PubMed1998

Overproduction of the CFTR R domain leads to increased levels of asialoGM1 and increased Pseudomonas aeruginosa binding by epithelial cells.

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), particularly the common DeltaF508 mutation, have been associated with alterations in glycolipid sialylation and the availability of receptors for Pseudomonas aeruginosa binding. The surface properties of 9HTEo- tracheal epithelial cell lines transfected with plasmids that overproduce the regulatory (R) domain of CFTR (pCEP-R) and lack cyclic adenosine monophosphate-stimulated Cl- conductance were compared with control cell lines with normal CFTR function. There was increased bacterial adherence to the mutant cell lines with abnormal CFTR activity. Cell lines with overexpression of the R domain had surface properties similar to cells expressing the common DeltaF508 mutation in CF. P. aeruginosa adherence correlated with the increased numbers of asialoGM1 residues available on the surface of the epithelial cells with altered CFTR function; and antibody to asialoGM1, a P. aeruginosa pilin receptor, was able to compete with piliated bacteria for epithelial binding sites. The pCEP-R cell lines with increased bacterial binding were also associated with increased production of interleukin-8 in response to adherent P. aeruginosa compared with cells transfected with the empty vector pCEP. P. aeruginosa pil mutants that lack the adhesin specific for the asialoGM1 receptor did not discriminate between epithelial cells with normal or deficient CFTR function. These results confirm a direct relationship between aberrant CFTR function and increased levels of apical asialoGM1, and support the role of these asialylated glycolipids as P. aeruginosa receptors that initiate an epithelial proinflammatory response in response to bacterial ligands.

Bacterial Adhesion↗
PubMed1998

Pentoxifylline is not a promising treatment for multiple sclerosis in progression phase.

Fourteen MS patients took pentoxifylline at varying doses for up to 24 months. In vitro production of tumor necrosis factor alpha was reduced in patients taking 2,400 to 3,200 mg/day of pentoxifylline for 12 weeks or more. Twelve of the 14 patients experienced worsening of the disease during the study according to clinical, MRI, or visual evoked potential criteria. These results provide no hint of efficacy for pentoxifylline as a treatment for MS in progression phase.

Adult↗
PubMed1998

Topical NSAIDs for musculoskeletal conditions. A review of the literature.

In recent years a growing number of topical nonsteroidal anti-inflammatory drugs (NSAIDs) have become available. This has been prompted in large part by the high incidence of serious gastrointestinal adverse events associated with the use of systemic NSAIDs, and the premise that minimisation of plasma concentrations of active drug may result in fewer systemic adverse effects. Evidence in humans and animals with topical NSAIDs demonstrates lower plasma concentrations than with systemically administered drugs, while those in soft tissues are still of a magnitude considered consistent with exerting an anti-inflammatory effect. In joints, however, the evidence is less strong, and there is still dispute whether in this case the drug reaches the joint predominantly via the transcutaneous or systemic route. There has been a sufficient number of studies of soft tissue conditions to demonstrate the superiority of topical NSAIDs over placebo and to suggest equivalent efficacy in comparison with some oral NSAIDs. For arthropathies, however, the literature is more sparse. Although several studies claim a benefit for topical NSAIDs against placebo, the results are less conclusive and further study is required. Trials of topical agents against intra-articular corticosteroids and rubefacients are either lacking or inconclusive. The adverse event profile of topical agents is reasonable: minor cutaneous effects occur in up to 2% of patients but tend to be self-limiting. Gastrointestinal events appear from the existing literature to be infrequent and minor, although long term studies are required. Bronchospasm and renal impairment have been reported and may be more frequent in patients who have experienced these effects with oral agents. The initial costs of topical agents tend to be higher than those of oral agents but a cost-effectiveness analysis suggests an overall benefit: this issue requires further clarification.

Administration, Topical↗
PubMed1998

Prenatal alcohol exposure and communication, behavior, and nonverbal intelligence of 3 school-age children.

Associations of prenatal alcohol exposure in speech, language, behavioral, and intellectual development were investigated in three school-aged children diagnosed with Fetal Alcohol Syndrome, accompanied by Attention Deficit Hyperactivity Disorder. Each child showed similar patterns of moderate-to-severe dysfunctional behavior; however, their scores on speech, language and nonverbal intellectual measures were highly variable.

Attention Deficit Disorder with Hyperactivity↗