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Biomedical subjects

K M Davis

Publications and source records attributed to K M Davis.

At least 19 recordsLinked to original sources
PubMed2001

Using clinical practice analysis to improve care.

BACKGROUND: Improving clinical outcomes requires that physicians examine and change their clinical practice. Sustaining outcome improvements requires a dedicated and dynamic program of analyzing and improving patient care. In 1992 North Mississippi Health Services (NMHS) implemented a program to improve physicians' clinical efficiency. CLINICAL PRACTICE ANALYSIS ( CPA): CPA uses evidenced-based guidelines and examines each physician's resource utilization, processes, and outcomes for a diagnosis or procedure. Clinical practice profiles are developed, and individual performance is compared to local and national benchmarks and presented to physicians. The CPA process is used on its own or as a component of more comprehensive performance improvements projects. Physicians have been engaged in outcome improvement by more than 55 CPA projects. RESULTS: NHMS has progressively reduced its Medicare loss and its length of stay (LOS) to 4.9 days. Mortality and readmission rates have been reduced in specific diagnoses. The community-acquired pneumonia project reduced the LOS from 7.7 to 5.1 days, decreaesed the mortality rate from 8.9% to 5.0%, and decreased the cost of care from $4,269 to $3,834. The ischemic stroke project reduced the aspiration pneumonia rate from 6.4% to 0% and mortality from 11.0% to 4.6%. Patients' average LOS decreased from 10.7 days to 6.5 days, and their cost of care was reduced by $1,100 per patient. DISCUSSION: Providing individualized data has engaged physicians in improving outcomes. The program has evolved from improving efficiency to managing outcomes and from simple CPA projects to integrated performance improvement projects; however, the CPA process remains the cornerstone of the current process.

Anti-Bacterial Agents↗
PubMed2000

Association of L-glutamic acid decarboxylase to the 70-kDa heat shock protein as a potential anchoring mechanism to synaptic vesicles.

Recently we have reported that the membrane-associated form of the gamma-aminobutyric acid-synthesizing enzyme, l-glutamate decarboxylase (MGAD), is regulated by the vesicular proton gradient (Hsu, C. C., Thomas, C., Chen, W., Davis, K. M., Foos, T., Chen, J. L., Wu, E., Floor, E., Schloss, J. V., and Wu, J. Y. (1999) J. Biol. Chem. 274, 24366-24371). In this report, several lines of evidence are presented to indicate that l-glutamate decarboxylase (GAD) can become membrane-associated to synaptic vesicles first through complex formation with the heat shock protein 70 family, specifically heat shock cognate 70 (HSC70), followed by interaction with cysteine string protein (CSP), an integral protein of the synaptic vesicle. The first line of evidence comes from purification of MGAD in which HSC70, as identified from amino acid sequencing, co-purified with GAD. Second, in reconstitution studies, HSC70 was found to form complex with GAD(65) as shown by gel mobility shift in non-denaturing gradient gel electrophoresis. Third, in immunoprecipitation studies, again, HSC70 was co-immunoprecipitated with GAD by a GAD(65)-specific monoclonal antibody. Fourth, HSC70 and CSP were co-purified with GAD by specific anti-GAD immunoaffinity columns. Furthermore, studies here suggest that both GAD(65) and GAD(67) are associated with synaptic vesicles along with HSC70 and CSP. Based on these findings, a model is proposed to link anchorage of MGAD to synaptic vesicles in relation to its role in gamma-aminobutyric acid neurotransmission.

Animals↗
PubMed2000

Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.

PURPOSE: Previous studies have examined the effects of hospitalists in urban academic hospitals. We compared the outcomes of patients treated by hospitalists with those of patients treated by internists at a 647-bed rural community hospital. SUBJECTS AND METHODS: The 443 patients in the hospitalists' 10 most common diagnosis-related groups (DRGs) were compared with 1,681 patients in the same DRGs who were cared for by internists in fiscal year 1998. Length of stay, cost of care, patient illness severity, patient satisfaction, 30-day readmission rate, inpatient mortality, discharge status, and resource utilization were compared. RESULTS: The hospitalists' patients had a shorter mean (+/- SD) length of stay (4.1 +/- 3.0 days versus 5.5 +/- 4.9 days, P <0.001) and their cost of care was less than that of the internists' patients ($4,098 +/- $2,455 versus $4,658 +/- $4,084, P <0.001). Analyses that adjusted for patient age, race, sex, insurance status, severity of illness, and specific medical comorbidities confirmed these differences. The differences between hospitalists and internists were most apparent among very ill patients. Mortality rates were similar (4.5% for hospitalists versus 4.9% for internists, P = 0.80), as were the readmission rates (4.5% for hospitalists versus 5.6% for internists, P = 0.41). Patient satisfaction was similar for both groups. The internists used more resources in 8 of 11 categories. CONCLUSIONS: The hospitalists provided cost-effective care, particularly for the sickest patients, with good outcomes and patient satisfaction.

Health Resources↗
PubMed2000

A novel method for expression and large-scale production of human brain l-glutamate decarboxylase.

l-Glutamate decarboxylase (GAD; EC 4.1.1.15) is the rate-limiting enzyme involved in the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain. Imbalance in the conversion of glutamate to GABA has been implicated in a host of human diseases. Studies on the structure, function, and therapeutic use of GAD have been precluded by insufficient quantities of purified active enzyme. Here we report a novel methodology for the expression and large-scale production of enzymatically active, pure, recombinant human GAD65 and GAD67. This method circumvents the sequestering of expressed protein into insoluble inclusion bodies and reduces production of truncated proteins. The availability of sufficient quantities of purified HGAD65 and HGAD67 has allowed for the production of specific polyclonal antibodies that discriminate between the two isoforms. This methodology, in addition to providing key human brain enzymes, may be generally applicable to other systems.

Brain↗
PubMed1999

Role of synaptic vesicle proton gradient and protein phosphorylation on ATP-mediated activation of membrane-associated brain glutamate decarboxylase.

Previously, we have shown that the soluble form of brain glutamic acid decarboxylase (GAD) is inhibited by ATP through protein phosphorylation and is activated by calcineurin-mediated protein dephosphorylation (Bao, J., Cheung, W. Y., and Wu, J. Y. (1995) J. Biol. Chem. 270, 6464-6467). Here we report that the membrane-associated form of GAD (MGAD) is greatly activated by ATP, whereas adenosine 5'-[beta,gamma-imido]triphosphate (AMP-PNP), a non-hydrolyzable ATP analog, has no effect on MGAD activity. ATP activation of MGAD is abolished by conditions that disrupt the proton gradient of synaptic vesicles, e.g. the presence of vesicular proton pump inhibitor, bafilomycin A1, the protonophore carbonyl cyanide m-chorophenylhydrazone or the ionophore gramicidin, indicating that the synaptic vesicle proton gradient is essential in ATP activation of MGAD. Furthermore, direct incorporation of (32)P from [gamma-(32)P]ATP into MGAD has been demonstrated. In addition, MGAD (presumably GAD65, since it is recognized by specific monoclonal antibody, GAD6, as well as specific anti-GAD65) has been reported to be associated with synaptic vesicles. Based on these results, a model linking gamma-aminobutyric acid (GABA) synthesis by MGAD to GABA packaging into synaptic vesicles by proton gradient-mediated GABA transport is presented. Activation of MGAD by phosphorylation appears to be mediated by a vesicular protein kinase that is controlled by the vesicular proton gradient.

Adenosine Triphosphate↗
PubMed1999

Atrial natriuretic peptide and the development of congestive heart failure in the oldest old: a seven-year prospective study.

BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic heart failure and correlate with invasively measured left heart pressures. OBJECTIVE: To examine the association between plasma ANP level and the subsequent development of congestive heart failure (CHF) in older subjects with no history of CHF. DESIGN: A 7-year, prospective, blinded, cohort study. SETTING: A life care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred fifty-six frail older subjects (mean age 88 +/- 7) with no history of CHF at study entry. MAIN OUTCOME MEASURE: Clinical episodes of CHF with confirmatory chest roentgenogram findings. Cox proportional hazard analyses were performed to examine the relationship between ANP levels and the development of CHF while controlling for 19 clinical, physical, and laboratory parameters. A Kaplan-Meier estimator (log-rank test) was used to determine if the development of CHF differed by tertile of ANP. RESULTS: During the follow-up period, 32% of the cohort developed CHF. The mean ANP level in the CHF group was 95 pmol/L +/- 11 pmol/L versus 60 pmol/L +/- 5 pmol/L in the no CHF group (two tailed t test P = .005). On multivariate analysis, a high ANP level was found to be associated significantly (P = .01) with the development of CHF. CONCLUSIONS: There is a statistically significant association between ANP level and the subsequent development of CHF in frail older individuals with no history of CHF.

Aged↗
PubMed1998

Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes.

Our purpose is to assess whether genotypes of the vitamin D receptor (VDR) and estrogen receptor (ER) and their interaction influence changes in bone mass in postmenopausal Caucasian women with and without hormone replacement therapy (HRT). A population of 108 US Mid-West women who participated in a study of low-dose continuous estrogen/progestin was genotyped at the VDR BsmI site and the ER XbaI and PvuII sites. Adequate vitamin D and calcium nutritional intakes were assured in all the study subjects. For the 3.5-year duration of the study, we analyzed changes in bone mineral density (BMD) at the spine, femoral neck, distal radius, and the total body (total body bone mineral content, tbBMC). We adjusted for confounding factors, such as age and weight, in the analysis. We found that VDR and/or ER genotypes and/or their interaction generally had significant effects on the changes in the bone mass measurements in both the placebo and HRT groups. When a significant gene-by-gene interaction exists between VDR and ER genotypes, failure to account for them in analyses may yield nonsignificant results, even if significant genotypic effects exist. The amount of variation in changes in bone mass measurements explained by the total genotypic effects of the VDR and ER loci varies from approximately 1.0% (for the tbBMC changes in combined placebo and HRT groups) to approximately 18.7% (for the spine BMD changes in the HRT group). These results suggest that individual genotypes are important factors in determining changes in bone mass in the elderly with and without HRT and thus may need to be considered with respect to the treatment to preserve bone mass in elderly Caucasian women.

Aged↗
PubMed1998

Clinical efficiency tools improve stroke management in a rural southern health system.

BACKGROUND AND PURPOSE: Ischemic stroke is a high-volume and financially draining diagnosis at this rural health system. The purpose of this clinical practice analysis was to identify resource utilization and clinical process inefficiencies and to promote clinically efficient, evidence-based improvements. METHODS: A retrospective analysis of medical record and financial databases of 356 patients with ischemic stroke was performed. The medical record data were adjusted for severity, and outliers were eliminated. The resources utilized by each physician were determined. Comparative graphs were prepared, presented, and discussed. The physicians implemented two types of changes: (1) alteration of resource utilization and consultation patterns and (2) support of clinical process improvement. In 1997, a follow-up analysis of 399 patients was performed. RESULTS: The initial comparison of internists' to neurologists' patient populations found the following: patient age (75 versus 65 years), patient severity ratings (2.8 versus 2.5), length of stay (10.7 versus 8.8 days), costs ($7360 versus $6862), mortality rates (12.5% versus 8.9%), and aspiration pneumonia rate (8.5% versus 3.8%). A comparison of the 1995 analysis to the 1997 analysis revealed the following per patient resource utilization decreases (all P < 0.05): chemistry laboratory, 2.65 to 1.95 studies; intravenous fluids, 2.85 to 1.85 L; oxygen use, 6.06 to 2.75 U; and nifedipine use, 1.62 to 0.33 capsules. The clinical process improvements resulted in the following overall outcomes (all P < 0.05 except mortality): length of stay (7.2 days), nonadjusted costs ($6246), mortality (6.5%), and rates of pneumonia (2.7%). CONCLUSIONS: Objective analysis of resource utilization resulted in physicians changing their individual management of stroke and collectively supporting clinical process changes that improved clinical and financial outcomes.

Aged↗
PubMed1998

Clinical applications of computer-based health information.

Competitive health care systems are improving their clinical and cost efficiency by performing clinical practice analyses. Large numbers of severity-adjusted cases provide the most objective data for making clinical efficiency decisions. The most cost-effective way to perform these analyses is to utilize well-coded, computer-based health information. This requires consistent coding of patients' comorbidities and complications as well as an interactive working relationship between coders and clinicians providing the clinical practice analysis. The article describes one hospital's evolving clinical efficiency information needs, how its health information system met them, the clinical practice analysis procedure, and the outcomes of this clinical practice analysis.

Abstracting and Indexing↗
PubMed1998

Pharmacologic management of depression in the elderly.

Depression, the most common geriatric psychiatric disorder, is a disabling mood disorder that impairs one's well-being and may even threaten a sufferer's life. Severely depressed elderly persons are more likely to kill themselves than individuals in any other age group. However, geriatric depression is, for the most part, a treatable and manageable illness. Antidepressant medication can be very effective in treating major depressive disorder (MDD). Because age-related physical changes in the elderly produce pharmacokinetics that are often different than that experienced by younger adults, different doses are often necessary. This article summarizes recommendations for selecting and initiating appropriate antidepressant therapy in elderly persons suffering from MDD. The benefits and drawbacks of tricyclic antidepressant agents, and other atypical antidepressant agents are discussed. Phases of treatment, drug selection, dosing, and educational tips for pharmacotherapy are presented.

Aged↗
PubMed1997

Effects of hypertonicity on water intake in the elderly: an age-related failure.

Dehydration is a common clinical syndrome associated with many illnesses and treatments in the elderly. Prior studies have shown diminished sensation of thirst during water deprivation. It is currently unclear whether age-related decreases in thirst perception impair the defense against a hyperosmolar challenge. To examine the impact of water ingestion during hyperosmolality, young and old subjects were allowed free access to water during and after an intravenous infusion of 5% hypertonic saline. Cumulative water intake and serum osmolality were compared between seven healthy young (20-28 yrs) and seven healthy old (72-89 yrs) volunteers during and following a two hour hypertonic saline infusion at a rate of 0.06 mlxkg(-1) min(-1). Serum osmolality and water intake were markedly different between the two groups. In the old group, serum osmolality increased by 17 mosmol/kg above baseline despite free access to water. In contrast, serum osmolality increased to only 7 mosmol/kg above baseline in the young group and did not rise further. By ingesting water, the young were able to defend against an additional increase in serum osmolality. The young drank approximately twice that of the old during the infusion period. Healthy older individuals drink less than young despite a significantly increased serum osmolality. This hypodipsia in old individuals increases their susceptibility to hypertonicity.

Adult↗
PubMed1997

Developing a rural primary care practice network.

Establishing and managing a primary care practice in rural communities is particularly challenging. Many rural practices are closing, and relatively few new practices are initiated independently. The integrated health system can provide at least part of the solution to the lack of physicians in the rural setting. The following article describes the objectives, methods, and results of an integrated health system's development of a rural primary care provider network.

Community Networks↗
PubMed1996

Production of glycosylated heparin-binding EGF-like growth factor in HeLa cells using vaccinia virus.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a 22-kDa, O-glycosylated protein. Because recombinant expression systems permitting a detailed analysis of the functional significance of HB-EGF glycosylation have not been described, a recombinant vaccinia virus designed to express HB-EGF was generated by homologous recombination of an intermediate plasmid vector carrying the HB-EGF cDNA and the genome of vaccinia virus and was used to infect HeLa cells. Production of immunoreactive HB-EGF was confirmed by immunofluorescence and radioimmunoprecipitation analysis. Furthermore, the expressed protein was shown to be a secreted, biologically active protein by radioreceptor and DNA synthesis assays of HeLa cell conditioned medium. The recombinant protein was purified from the conditioned medium using heparin-affinity fast protein liquid chromatography followed by C4 reverse-phase high-performance liquid chromatography (RP-HPLC). SDS-PAGE and Western blotting of the RP-HPLC-purified product showed an immunoreactive HB-EGF protein of approximately 22 kDa that was decreased to a 14-kDa protein by treatment with O-glycanase. Amino acid sequencing revealed an N-terminus that was characteristic of native, glycosylated HB-EGF. Interestingly, a Thr residue that is a putative site of O-linked glycosylation failed to be resolved. This system provides a valuable method for evaluating the role of glycosylation in HB-EGF function(s) as well as addressing other questions concerning HB-EGF structure-function relationships.

Amino Acid Sequence↗
PubMed1996

Atrial natriuretic peptide levels in the elderly: differentiating normal aging changes from disease.

BACKGROUND: Atrial natriuretic peptide (ANP) levels increase with advancing age and in patients with cardiac dysfunction. Previous studies have failed to differentiate the elevated ANP levels of normal aging from those of cardiac disease. METHODS: To differentiate the increased ANP levels seen in normal aging from that of disease, fasting supine ANP was measured in healthy young (n = 24), healthy old (n = 90), and clinically stable but cardiovascularly diseased old (n = 269) residents of a life care facility. ANP levels were correlated with physical exam findings, blood chemistries, measures of physical and cognitive function, and medications. RESULTS: ANP levels were almost fourfold higher in the healthy elderly than in the young (11.4 +/- 1.1 (SEM) vs 3 +/- 0.3 pmol/L, p < .01), and two-and-one-half times higher in the cardiovascular-diseased elderly than the healthy elderly (29 +/- 1.9 vs 11.4 +/- 1.1 pmol/L, p < .01). An ANP value of 21 pmol/L has a sensitivity of 83% and specificity of 52% in distinguishing those elders classified as healthy from those classified as having chronic cardiovascular disease. ANP levels had positive univariate correlation with age (even from 70 to 102 years) and systolic blood pressure. ANP rose progressively with increasing numbers of markers of cardiovascular comorbidity. ANP was higher in subjects with jugular venous pressure > 10 cm, presence of a third heart sound, peripheral edema, artificial cardiac pacemaker, atrial arrhythmias, and in those taking digoxin, diuretics, or nitrates. On multivariate analysis independent predictors of ANP levels were, in descending order, nitrates, age, diuretics, and atrial arrhythmias. CONCLUSION: These data suggest that ANP levels greater than 21 pmol/L are associated with cardiovascular comorbidity in a clinically stable elderly cohort.

Adult↗
PubMed1995

Pharmacokinetics of the acyl coenzyme A:cholesterol acyl transferase inhibitor CP-105,191 in dogs--the effect of food and sesame oil on systemic exposure following oral dosing.

Inhibition of acyl coenzyme A:cholesterol acyl transferase (ACAT) decreases total plasma cholesterol in animals and may be an effective therapy for atherosclerosis in man. The pharmacokinetics of CP-105,191, a potent inhibitor of ACAT, were explored in fed and fasted dogs. Following oral administration of drug, mean apparent plasma half-life ranged from 9 to 16 h. Systemic availability of CP-105,191, as determined by AUC(0-infinity), was approximately 3-4-fold higher in fed dogs than in fasted dogs when 50 mg doses were administered as aqueous suspensions. Tmax was achieved more rapidly and Cmax was lower in fasted dogs. When 50 mg doses, partially dissolved in 20 mL sesame oil, were administered to fed dogs, the availability of CP-105,191 increased by another factor of 2. A 12.5 mg dose of CP-105,191, completely dissolved in sesame oil, was administered to fed and fasted dogs. Plasma AUC's were similar for fed and fasted dogs following the 12.5 mg dose, indicating that the increased availability of drug when administered with food is related to the presence of lipid.

Administration, Oral↗