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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 73 records · Page 4Linked to original sources
PubMed1997

Changing structure to improve function: one academic health center's experience.

Academic health centers (AHCs) have been under siege for the past few years, with decreased federal and state funding for educational and research programs and increasing competition in the health care marketplace. In addition, many AHCs are burdened with the bureaucratic red tape of large educational institutions, which makes agility in responding to a demanding health care market difficult. The authors describe the response to these threats by Oregon Health Sciences University (OHSU), an approach that has been different from those of most similar institutions. OHSU chose to change its structure from being part of the state system of higher education to being an independent public corporation. The authors outline the political process of building widespread support for the legislation passed in 1995, the key features of the restructuring, the challenges faced before and after the transition to a public corporation, and lessons learned in this metamorphosis to a new form.

Academic Medical Centers↗
PubMed1997

Cholinesterase. Its significance in anaesthetic practice.

Plasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its role in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.

Anesthesia↗
PubMed1997

Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells.

Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which mediate the conversion of arachidonate to prostaglandin H2. COX1 is the predominant constitutive isoform, whereas COX2 expression is typically low. In the present studies we cloned rabbit COX2 and determined its distribution in unstimulated tissues. Screening rabbit eye and uterine libraries yielded two cDNAs containing identical inserts with a 1,812-nucleotide open-reading frame. This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary bladder. COX2 expression was primarily in renal outer medullary interstitial cells with cortical expression in macula densa. In cultured medullary interstitial cells, COX2 mRNA predominated, with little COX1 expression. Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone. Phorbol ester also upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important implications for side effects of COX2-selective inhibitors.

Amino Acid Sequence↗
PubMed1997

Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans.

Peroxisome proliferator-activated receptors (PPARs, alpha, beta/delta, and gamma) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs regulate the expression of genes involved in lipid metabolism. 8(S)-hydroxyeicosatetraenoic acid (8-S-HETE), leukotriene B4 (LTB4), and hypolipidemic fibrates activate PPAR alpha, whereas PPAR gamma is activated by prostaglandin metabolites. The present studies examined the intrarenal and tissue distribution of rabbit and human PPAR alpha, -beta/delta, and -gamma mRNAs. Nuclease protection showed PPAR alpha predominated in liver, heart, and kidney, whereas PPAR gamma, a putative adipose-specific transcription factor, was in white adipose tissue, bladder, and ileum, followed by kidney and spleen. Lower expression levels of PPAR beta/delta were observed in several tissues. In situ hybridization of kidney showed PPAR alpha mRNA predominated in proximal tubules and medullary thick ascending limbs of both rabbit and human. PPAR gamma was exclusively expressed in medullary collecting duct and papillary urothelium. Immunoblot confirmed the expression of PPAR gamma protein in freshly isolated inner medullary collecting ducts. mRNAs for all the PPARs were expressed in the ureter and bladder in both rabbit and human, but PPAR gamma expression was greatest. This distinct distribution of PPAR isoforms has important implications for lipid-activated gene transcription in urinary epithelia.

Animals↗
PubMed1997

Protein extract as a surrogate mother.

Brief dynamic psychotherapy, carried out by an resident in training, can bring significant improvement to a patient who does not necessarily meet ideal selection criteria. S. had experienced early childhood deprivation resulting in adult psychosomatic manifestations of feeling hypoglycemic under pressure of responsibility or during fear of abandonment. He soothed himself with the aid of a bottle of "protein extract," which he carried at all times on his belt. The 21-week therapy resulted in his increased ability to differentiate the sources of his anxiety and allowed him to find new and more mature ways of coping with stress. Although still confronting internal conflicts and anxiety, he relinquished the protein-extract bottle and began to take a more active role in work and relationships. With the help of brief dynamic psychotherapy, this patient was able to start moving forward in his personal growth. Finally, although requiring ongoing supervision and training, resident therapists should be encouraged to treat difficult patients with brief dynamic psychotherapy despite their limited experience with such a promising therapeutic technique.

Adaptation, Psychological↗
PubMed1997

Race, finding meaning, and caregiver distress.

This study investigated the relationship between race, finding meaning (as a positive psychological resource variable), and the outcomes of caregiver depression and global role strain among 77 African American and 138 White spouse caregivers of persons with dementia. Finding provisional meaning had a direct negative relationship with depression and global role strain. Although African American caregivers were less likely to report depression and role strain, there was no interaction by race in the process influencing caregiver distress.

Black or African American↗
PubMed1997

Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study.

PURPOSE: The present intergroup phase III randomized study compared combined chemotherapy (CT) plus radiotherapy (RT) treatment versus RT only in patients with locally advanced esophageal cancer. MATERIALS AND METHODS: Two courses of chemotherapy during 50 Gy RT followed by additional two courses of the same CT, versus 64 Gy RT alone were investigated. CT consisted of cisplatin 75 mg/m2 on day 1 [corrected] and fluorouracil (5FU) 1,000 mg/m2/d on days 1 to 4 every 4 weeks with RT and every 3 weeks post-RT. The main objective of the study was to compare overall survival between the two randomized treatment groups. Patients were stratified by tumor size, histology, and degree of weight loss. RESULTS: Sixty-two assessable patients were randomized to receive RT alone, and 61 to the combined arm. Patients characteristics were as follows: squamous cell cancer, 90% versus 85%; weight loss greater than 10 lb, 61% versus 69%; and tumor size, > or = 5 cm, 82% versus 80% on the RT and CT-RT arms, respectively. Systemic side effects, which consisted of nausea, vomiting, and renal and myelosuppression, occurred more frequently on the combined arm, while local side effects were similar in both groups. With a minimum follow-up time of 5 years for all patients, the median survival duration was 14.1 months and the 5-year survival rate was 27% in the combined treatment group, while the median survival duration was 9.3 months with no patients alive at 5 years in the RT-alone group (P < .0001). Additional patients (69) were treated with the same combined therapy and were analyzed. The results of the last group confirmed all of the results obtained with combined CT-RT in the randomized trial, with a median survival duration of 17.2 months and 3-year survival rate of 30%. CONCLUSION: We conclude that cisplatin and 5FU infusion given during and post-RT of 50 Gy is statistically superior to standard 64-Gy RT alone in patients with locally advanced esophageal cancer.

Adult↗
PubMed1997

Pharmacological activity and safety profile of P10358, a novel, orally active acetylcholinesterase inhibitor for Alzheimer's disease.

1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-1(H)-indol-5-yl methyl carbamate (P10358) is a potent, reversible acetylcholinesterase inhibitor that produces central cholinergic stimulation after oral and parental administration in rats and mice. P10358 is a 2.5 times more potent acetylcholinesterase inhibitor than THA in vitro (IC50 = 0.10 +/- 0.02 microM vs. IC50 = 0.25 +/- 0.03 microM). It also inhibits butyrylcholinesterase activity as potently as THA (IC50 = 0.08 +/- 0.05 microM vs. IC50 = 0.07 +/- 0.01 microM). Ex vivo, P10358 (0.2 - 20 mg/kg, p.o.) produced dose-dependent inhibition of brain acetylcholinesterase activity. At 10 and 20 mg/ kg, it produced profound and long-lasting hypothermia in mice. P10358 enhanced performance in rats in a step-down passive avoidance task (0.62 and 1.25 mg/kg) and in a social recognition paradigm (0.32, 0.64 and 1.25 mg/kg) in mice. It reversed scopolamine-induced deficits in the Morris Water maze in rats (1.25 and 2.5 mg/kg) and a higher dose elevated striatal homovanillic acid levels. These behavioral and biochemical effects are consistent with central cholinergic stimulation. Hemodynamic studies in the rat demonstrated a 16-fold separation between behaviorally active doses (1.25 mg/kg) and those that elevated arterial pressure (20 mg/kg). Lethality in rats occurred at an oral dose of 80 mg/kg, but not at lower doses. Chemically, P10358 is an N-aminoindole and may not have the hepatotoxic liability associated with aminoacridine structure of tacrine. P10358 had weak affinity (>10 microM) at a variety of aminergic and peptidergic receptors and uptake carriers. These properties suggest that P10358 may be a safe and promising symptomatic treatment for Alzheimer's disease.

Acetylcholinesterase↗
PubMed1996

Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeutic agents for Alzheimer's disease.

A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs was synthesized and evaluated in tests to determine potential utility for the treatment of Alzheimer's disease. From these compounds, N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on in-depth biological evaluation. In addition to cholinomimetic properties based initially on in vitro inhibition of [3H]quinuclidinyl benzilate binding, in vivo reversal of scopolamine-induced behavioral deficits, and subsequently on other results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in vitro by inhibition of [3H] clonidine binding and synaptosomal biogenic amine uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis, structure-activity relationships for this series, and the biological profile of 4c are reported.

Alzheimer Disease↗
PubMed1996

Substituted (pyrroloamino)pyridines: potential agents for the treatment of Alzheimer's disease.

A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure-activity relationships for this series is presented, along with the biological profiles of selected compounds.

Alzheimer Disease↗
PubMed1996

A comparison of hyperthermia cisplatin sensitization in human ovarian carcinoma and glioma cell lines sensitive and resistant to cisplatin treatment.

Two pairs of human tumor cell lines (glioma and ovarian carcinoma (OvCa) each having a parental cell line and cisplatin-resistant variant, were evaluated for (a) cisplatin response, (b) hyperthermia response, and (c) combined hyperthermia and cisplatin response. The two resistant lines had comparable resistant responses while for the parental lines, the OvCa was more sensitive than the glioma to cisplatin doses up to 14 microgram/ml. For the hyperthermia response, the OvCa parental line was more resistant than the variant line at low-temperature hyperthermia (41 degrees C or 42 degrees C) but became more sensitive at high temperature (45 degree C). For the glioma, the parental line was more sensitive to hyperthermia at all temperatures tested. Hyperthermia caused sensitization to cisplatin in all cell lines but was generally greater in the glioma cell lines. In the OvCa system, hyperthermia had a slightly greater sensitizing effect on the resistant cell lines, while in the glioma the opposite was true. The degree of sensitization increased with hyperthermia temperature. In summary, the results showed that there is no cross- resistance for hyperthermia and cisplatin, that the degree of thermal sensitization is not reduced in cisplatin- resistant cell lines, and that cisplatin thermal sensitization is cell-line and temperature dependent. Thus, hyperthermia can effectively improve tumor cell response to cisplatin and may be useful in overcoming resistance to cisplatin.

Carcinoma↗
PubMed1996

Interactive effects of depression symptoms, nicotine dependence, and weight change on late smoking relapse.

Signal detection methods were used to develop an algorithm useful in distinguishing those at risk for late relapse from those likely to maintain abstinence. Four subgroups with 24-month survival (nonrelapse) rates ranging from 79% to 33% were identified. Among participants whose depression symptoms decreased from baseline to the end of treatment, lower levels of nicotine dependence were associated with less relapse at the 24-month follow-up (odds ratio = 2.77; 95% confidence interval: 1.36-5.62). Among participants whose depression symptoms increased from baseline to the end of treatment, greater weight gain was associated with less relapse at follow-up (odds ratio = 2.90; 95% confidence interval: 1.41-5.96). This study suggested that it may become possible to use both baseline and treatment information to "titrate" interventions.

Algorithms↗
PubMed1996

Minority use of community long-term care services: a comparative analysis.

A series of national surveys since 1982 have examined health needs of elders. Small proportions of minority elders in each sample have limited our understanding of service use by minorities. This research sought to determine (1) the extent to which minorities have restricted use of community long-term care services as a result of socioeconomic status, family structure, and health status, and (2) the replicability and validity of results across three national surveys: Supplement on Aging, National Long-Term Care, and National Medical Expenditure. Results indicate no bivariate or multivariate differences between African American, Hispanic, or White frail older persons in use of community long-term services. Living arrangements, Medicaid use, and overall health and functional status were primary predictors of service use. Taking methodological limitations into account, the results suggest similarity in processes influencing use of community long-term care services for African American and White older persons.

Black or African American↗
PubMed1996

Feasibility of fitting contact lenses with apical clearance in keratoconus.

Despite the wide variety of rigid contact lens fitting philosophies for the visual correction of keratoconus, questions remain, including which approach-flat, divided support, or steep-contributes the most toward the preservation of a clear cornea. One goal of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Pilot Study was to determine the feasibility of managing early keratoconus patients with apical clearance rigid contact lenses. Of 30 keratoconus patients identified with at least 1 nonscarred cornea, 17 patients (30 eyes) were randomly assigned to a steep lens fitting protocol. After trial fitting with a standardized lens design demonstrating minimum apical clearance, lenses were dispensed whose base curve was 0.2 mm steeper than the minimum apical clearance lens. Patients were re-evaluated on a quarterly schedule concluding at 12 months. Changes in keratometry between baseline and 12 months identified unequal steepening of the flat and steep corneal curvatures, suggestive of corneal molding. Best corrected rigid lens visual acuity measures illustrated no significant changes over the course of the study. Clinically significant corneal compromise was transiently observed in some patients. Only 1 of 22 eyes completing the pilot study and fitted with apical clearance developed mild corneal scarring.

Adolescent↗
PubMed1996

Cytomegalovirus infections in Toronto child-care centers: a prospective study of viral excretion in children and seroconversion among day-care providers.

OBJECTIVES: To prospectively determine the rate of cytomegalovirus shedding in children and the rate of seroconversion to cytomegalovirus in providers at 38 infant-toddler day care centers in Toronto, Canada. METHODS: Urine was collected for shell vial assay in 471 children between the ages of 3 and 42 months. Providers (n = 206) were tested for the presence of cytomegalovirus antibody by latex agglutination. Of the 68 providers who were seronegative, 56 were retested approximately 1 year later. RESULTS: Viruria was documented in 79 (17%) children and antibody in 67% of providers. Seropositivity was significantly related to country of birth outside Canada, presence of children at home < 5 years of age and increased household size. Seroconversion was documented in 12.5% (n = 7). Of these providers 71% worked at centers where workers never wore gloves for diaper changing vs. 33% of those who did not seroconvert (P = 0.06), and all were younger than 30 years vs. 59% of those who did not seroconvert (P = 0.04). In centers with viruria the association of seroconversion with lack of glove use was enhanced (P = 0.04). Seroconversion was marginally more likely in providers working with infants only than with infants and toddlers or with toddlers alone. Logistic regression confirmed that seroprevalence was more likely in providers who were born outside Canada, had children younger than age 5 years in the household and with an increased number of people in the household. Seroconversion was more likely if the provider worked at centers not using gloves for diaper changes, worked with infants only rather than with toddlers and infants and was < 30 years old, with each factor contributing independently to the model. CONCLUSIONS: Cytomegalovirus infection is common in children and providers in Toronto day-care centers.

Adolescent↗