Internists, Geriatric Specialist (elderly care), Sleep Medicine Specialist
12 years of experience

North Hills West
16111 Plummer St
North Hills, CA 91343
310-478-3711
Locations and availability (1)

Education ?

Medical School Score Rankings
University of California at Los Angeles (1998)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
American Board of Internal Medicine

Affiliations ?

Dr. Fung is affiliated with 1 hospitals.

Hospital Affilations

  • Veterans Affairs Greater Los Angeles Healthcare Center
    11301 Wilshire Blvd, Los Angeles, CA 90073
  • Publications & Research

    Dr. Fung has contributed to 57 publications.
    Title Is Patient-perceived Severity of a Geriatric Condition Related to Better Quality of Care?
    Date January 2011
    Journal Medical Care
    Excerpt

    Care for falls and urinary incontinence (UI) among older patients is inadequate. One possible explanation is that physicians provide less recommended care to patients who are not as concerned about their falls and UI.

    Title The Relationship Between Multimorbidity and Patients' Ratings of Communication.
    Date July 2008
    Journal Journal of General Internal Medicine
    Excerpt

    BACKGROUND: The growing interest in pay-for-performance and other quality improvement programs has generated concerns about potential performance measurement penalties for providers who care for more complex patients, such as patients with more chronic conditions. Few data are available on how multimorbidity affects common performance metrics. OBJECTIVE: To examine the relationship between multimorbidity and patients' ratings of communication, a common performance metric. DESIGN: Cross-sectional study SETTING: Nationally representative sample of U.S. residents PARTICIPANTS: A total of 15,709 noninstitutionalized adults living in the United States participated in a telephone interview. MEASUREMENTS: We used 2 different measures of multimorbidity: 1) "individual conditions" approach disregards similarities/concordance among chronic conditions and 2) "condition-groups" approach considers similarities/concordance among conditions. We used a composite measure of patients' ratings of patient-physician communication. RESULTS: A higher number of individual conditions is associated with lower ratings of communication, although the magnitude of the relationship is small (adjusted average communication scores: 0 conditions, 12.20; 1-2 conditions, 12.06; 3+ conditions, 11.90; scale range 5 = worst, 15 = best). This relationship remains statistically significant when concordant relationships among conditions are considered (0 condition groups 12.19; 1-2 condition groups 12.03; 3+ condition groups 11.94). CONCLUSIONS: In our nationally representative sample, patients with more chronic conditions gave their doctors modestly lower patient-doctor communication scores than their healthier counterparts. Accounting for concordance among conditions does not widen the difference in communication scores. Concerns about performance measurement penalty related to patient complexity cannot be entirely addressed by adjusting for multimorbidity. Future studies should focus on other aspects of clinical complexity (e.g., severity, specific combinations of conditions).

    Title An Evaluation of the Veterans Health Administration's Clinical Reminders System: a National Survey of Generalists.
    Date May 2008
    Journal Journal of General Internal Medicine
    Excerpt

    BACKGROUND: The Veterans Health Administration (VHA) is a leader in developing computerized clinical reminders (CCRs). Primary care physicians' (PCPs) evaluation of VHA CCRs could influence their future development and use within and outside the VHA. OBJECTIVE: Survey PCPs about usefulness and usability of VHA CCRs. DESIGN AND PARTICIPANTS: In a national survey, VHA PCPs rated on a 7-point scale usefulness and usability of VHA CCRs, and standardized scales (0-100) were constructed. A hierarchical linear mixed (HLM) model predicted physician- and facility-level variables associated with more positive global assessment of CCRs. RESULTS: Four hundred sixty-one PCPs participated (response rate, 69%). Scale Cronbach's alpha ranged from 0.62 to 0.82. Perceptions of VHA CCRs were primarily in the midrange, where higher ratings indicate more favorable attitudes (weighted standardized median, IQR): global assessment (50, 28-61), clinical/situational specificity (29, 17-42), integration with workflow/workload (39, 17-50), training (50, 33-67), VHA's management of CCR use (67, 50-83), design/interface (53, 40-67), perceived role in CCR use (67, 50-83), and self-efficacy (67, 57-78). In a HLM model, design/interface (p < .001), self-efficacy (p < .001), integration with workflow/workload (p < .001), and training (p < .001) were associated with more favorable global assessments of CCRs. Facilities in the west as compared to the south (p = .033), and physicians with academic affiliation (p = .045) had less favorable global assessment of CCRs. CONCLUSIONS: Our systematic assessment of end-users' perceptions of VHA CCRs suggests that CCRs need to be developed and implemented with a continual focus on improvement based on end-user feedback. Potential target areas include better integration into the primary care clinic workflow/workload.

    Title Systematic Review: the Evidence That Publishing Patient Care Performance Data Improves Quality of Care.
    Date January 2008
    Journal Annals of Internal Medicine
    Excerpt

    BACKGROUND: Previous reviews have shown inconsistent effects of publicly reported performance data on quality of care, but many new studies have become available in the 7 years since the last systematic review. PURPOSE: To synthesize the evidence for using publicly reported performance data to improve quality. DATA SOURCES: Web of Science, MEDLINE, EconLit, and Wilson Business Periodicals (1999-2006) and independent review of articles (1986-1999) identified in a previous systematic review. Only sources published in English were included. STUDY SELECTION: Peer-reviewed articles assessing the effects of public release of performance data on selection of providers, quality improvement activity, clinical outcomes (effectiveness, patient safety, and patient-centeredness), and unintended consequences. DATA EXTRACTION: Data on study participants, reporting system or level, study design, selection of providers, quality improvement activity, outcomes, and unintended consequences were extracted. DATA SYNTHESIS: Forty-five articles published since 1986 (27 of which were published since 1999) evaluated the impact of public reporting on quality. Many focus on a select few reporting systems. Synthesis of data from 8 health plan-level studies suggests modest association between public reporting and plan selection. Synthesis of 11 studies, all hospital-level, suggests stimulation of quality improvement activity. Review of 9 hospital-level and 7 individual provider-level studies shows inconsistent association between public reporting and selection of hospitals and individual providers. Synthesis of 11 studies, primarily hospital-level, indicates inconsistent association between public reporting and improved effectiveness. Evidence on the impact of public reporting on patient safety and patient-centeredness is scant. LIMITATIONS: Heterogeneity made comparisons across studies challenging. Only peer-reviewed, English-language articles were included. CONCLUSION: Evidence is scant, particularly about individual providers and practices. Rigorous evaluation of many major public reporting systems is lacking. Evidence suggests that publicly releasing performance data stimulates quality improvement activity at the hospital level. The effect of public reporting on effectiveness, safety, and patient-centeredness remains uncertain.

    Title Quality Indicators for Hospitalization and Surgery in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Quality Indicators for the Care of Hypertension in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Quality Indicators for the Care of Ischemic Heart Disease in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Quality Indicators for Screening and Prevention in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Quality Indicators for the Care of Sleep Disorders in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Quality Indicators for the Care of Stroke and Atrial Fibrillation in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Quality Indicators for the Screening and Care of Urinary Incontinence in Vulnerable Elders.
    Date December 2007
    Journal Journal of the American Geriatrics Society
    Title Computerized Condition-specific Templates for Improving Care of Geriatric Syndromes in a Primary Care Setting.
    Date September 2006
    Journal Journal of General Internal Medicine
    Excerpt

    INTRODUCTION: As the U.S. population ages, primary care clinicians (PCCs) will encounter more patients with geriatric syndromes, such as urinary incontinence (UI) and falls. Yet, current evidence suggests that care of these conditions does not meet expected standards and that PCCs would benefit from tools to improve care of these conditions. Little is known about the role of computerized condition-specific templates for improving care of geriatric syndromes. AIM: We sought to develop and assess the usefulness of condition-specific computerized templates in a primary care setting. SETTING: A large academic Veterans Affairs medical center. PROGRAM DESCRIPTION: We developed and tested the usefulness of 2 condition-specific computerized templates (UI and falls) that could be added on to an existing electronic health record system. PROGRAM EVALUATION: Semistructured interviews were used to identify barriers to use of computerized templates. Usefulness and usability were assessed through a randomized-controlled trial involving standardized patients. DISCUSSION: Use of condition-specific templates resulted in improved history and physical exam assessment for both UI and falls (P < .05). Our computerized, condition-specific templates are a promising method for improving care of geriatric conditions in a primary care setting, but require improvement in usability before widespread implementation.

    Title Geographic Variation Across Veterans Affairs Medical Centers in the Treatment of Early Stage Prostate Cancer.
    Date April 2006
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We investigated geographic variation in the treatment of early stage prostate cancer in a national sample of veterans after widespread adoption of the prostate specific antigen test. MATERIALS AND METHODS: Our sample consisted of 16,352 cases from the Veterans Affairs Central Cancer Registry that were diagnosed between January 1997 and December 1999 with stage I or II prostate cancer. We used a 2-stage nested logit model to compare surgery, radiation therapy and noncurative treatment among 4 geographic regions of the United States. RESULTS: Multivariate analysis showed that patients in the West (referent group) had a higher OR of undergoing surgery than radiation compared with the Northeast, South or Midwest (OR 0.77, 95% CI 0.67 to 0.87, OR 0.86, 95% CI 0.76 to 0.98 and OR 0.75, 95% CI 0.64 to 0.87, respectively. Black men, men with lower grade and higher stage tumors, and unmarried men were less likely to undergo curative treatment and less likely to undergo surgery than radiation. CONCLUSIONS: Geographic variation persists in patterns of care in men with early stage prostate cancer. However, this variation is limited to the choice between surgery and radiation rather than to the choice between curative and noncurative treatment.

    Title Laboratory Suggestion. Interpretation of Plasma Protamine Paracoagulation Test.
    Date April 2006
    Journal American Journal of Clinical Pathology
    Excerpt

    The reliability of the plasma protamine paracoagulation test has been questioned because of the controversy surrounding its interpretation and because of false positives reported with high frequency in some series. To minimize the frequency of false positives, it is recommended that when the test is done at room temperature, clot or fibrin strand formation be considered a positive result and precipitates be considered negative. Use of the wire hook to distinguish fibrin strands from precipitates is suggested. Nascent clotting and blood drawn from indwelling catheters should be avoided.

    Title Patients' Preferences for Technical Versus Interpersonal Quality when Selecting a Primary Care Physician.
    Date September 2005
    Journal Health Services Research
    Excerpt

    OBJECTIVE: To assess patients' use of and preferences for information about technical and interpersonal quality when using simulated, computerized health care report cards to select a primary care provider (PCP). DATA SOURCES/STUDY SETTING: Primary data collected from 304 adult consumers living in Los Angeles County in January and February 2003. STUDY DESIGN/DATA COLLECTION: We constructed computerized report cards for seven pairs of hypothetical individual PCPs (two internal validity check pairs included). Participants selected the physician that they preferred. A questionnaire collected demographic information and assessed participant attitudes towards different sources of report card information. The relationship between patient characteristics and number of times the participant selected the physician who excelled in technical quality are estimated using an ordered logit model. PRINCIPAL FINDINGS: Ninety percent of the sample selected the dominant physician for both validity checks, indicating a level of attention to task comparable with prior studies. When presented with pairs of physicians who varied in technical and interpersonal quality, two-thirds of the sample (95 percent CI: 62, 72 percent) chose the physician who was higher in technical quality at least three out of five times (one-sample binomial test of proportion). Age, gender, and ethnicity were not significant predictors of choosing the physician who was higher in technical quality. CONCLUSIONS: These participants showed a strong preference for physicians of high technical quality when forced to make tradeoffs, but a substantial proportion of the sample preferred physicians of high interpersonal quality. Individual physician report cards should contain ample information in both domains to be most useful to patients.

    Title Identifying Barriers to the Effective Use of Clinical Reminders: Bootstrapping Multiple Methods.
    Date August 2005
    Journal Journal of Biomedical Informatics
    Excerpt

    Advances in electronic medical record capabilities enable clinical reminders to inform providers when recommended actions are "due" for a patient. Despite evidence that they improve adherence to guidelines, the Veteran's Health Administration (VHA) has experienced challenges in having providers consistently use clinical reminders as intended. In this paper, we describe how multiple methods were used to opportunistically triangulate, or "bootstrap," an understanding of barriers to the effective use of clinical reminders in the VHA. In an initial study using ethnographic observations and semi-structured interviews of HIV clinical reminders, we identified six barriers to effective use: workload, time to remove inapplicable reminders, false alarms, training, reduced eye contact, and the use of paper forms rather than software. In a second study, we collected open-ended and closed-ended data regarding barriers and facilitators to the use of clinical reminders in general in the VHA through a survey of 261 participants at a national informatics meeting, where 104 of 142 VHA health care facilities were represented. The findings from the second study extended our understanding of the previously identified barriers. In addition, four new barriers were identified: ease of use issues, accessibility of workstations, resident physicians and trainees, and administration benefiting more than providers from clinical reminder use. We discuss potential implications regarding the similarities and differences in study findings for factors to consider in planning interventions to improve clinical reminder use.

    Title Variation in Implementation and Use of Computerized Clinical Reminders in an Integrated Healthcare System.
    Date February 2005
    Journal The American Journal of Managed Care
    Excerpt

    OBJECTIVES: To identify patterns of use of computerized clinical reminders (CCRs) across an integrated healthcare system and describe institutional factors associated with their implementation. STUDY DESIGN: Cross-sectional study. METHODS: At a national electronic health record (EHR) meeting, we surveyed 261 participants from 104 Veterans Health Administration (VHA) healthcare facilities regarding the number and types of CCRs available at each facility. Potential explanatory measures included perceived utility and ease of use of CCRs, training and personnel support for computer use, EHR functionalities, and performance data feedback to providers at each facility. RESULTS: The number of conditions with CCRs in use at a facility ranged from 1 to 15; most reported implementation of reminders for 10 of the 15 conditions surveyed. The most commonly implemented CCRs, used in more than 85% of facilities, were for conditions with VHA national performance measures (eg, tobacco cessation, immunizations, diabetes mellitus). The least commonly implemented CCRs were for post-deployment health evaluation and management, medically unexplained symptoms, and erectile dysfunction. Facilities that had implemented greater numbers of clinical reminders had providers who reported greater ease of use and utility of the reminders (P= .01). CONCLUSIONS: VHA facilities vary markedly in their implementation of CCRs. This effect may be partly explained by greater incorporation of clinical reminders for conditions with performance measures. Further study is needed to determine how to best implement clinical reminders and the institutional factors important in their use.

    Title Controversies and Legal Issues of Prescribing and Dispensing Medications Using the Internet.
    Date February 2004
    Journal Mayo Clinic Proceedings. Mayo Clinic
    Excerpt

    Online pharmacies fall into 3 major categories: independent Internet-only sites, online branches of "brick-and-mortar" pharmacies, and sites representing partnership among neighborhood pharmacies. Potential benefits of online pharmacies include increased access, lower transaction and product costs, and greater anonymity. However, online pharmacies have generated controversies, including the use of "cyberdoctors" on some sites, the dispensing of drugs without prescriptions from other sites, and the importation of prescription medications. Although some online pharmacies are legitimate and likely provide benefits to patients, other online pharmacies engage in questionable practices. Numerous state and federal regulations and laws have tried to address controversies surrounding rogue Internet pharmacies. Because online pharmacies are increasingly common, clinicians may encounter patients asking for advice and information about online pharmacies. We review the regulatory framework governing online pharmacies and the potential risks and benefits of using online pharmacies.

    Title Simple Basic Program for Calculating the Cervicovaginal Fnp and for Estimating the Sample Size of the Number of Cervicovaginal Smears to Be Rescreened.
    Date December 1999
    Journal Acta Cytologica
    Excerpt

    OBJECTIVE: To guide cytotechnologists and pathologists in calculating the false negative proportion, or rate, and the number of Papanicolaou smears to be reevaluated for a meaningful assessment of screening performance, a computer program written in BASIC was prepared, based on several recent publications in the field of cytopathology. RESULTS: A complete program listing and sample runs to help users be cognizant of the necessary inputs to run the program. The output from the program gives the results of the various calculations. CONCLUSION: Since the tedious manual calculations are handled by the computer program, it is more likely for those involved in the interpretation of Papanicolaou smears to follow the approaches suggested by experts in these two areas.

    Title False Negative Proportion: a Complementary Form of Sensitivity.
    Date June 1999
    Journal Acta Cytologica
    Title Meta-analysis of Studies of the Diagnostic Accuracy of Laboratory Tests.
    Date May 1999
    Journal Archives of Pathology & Laboratory Medicine
    Title Treatment for Hemophilia: Gene Therapy Vs Transplantation.
    Date June 1994
    Journal Jama : the Journal of the American Medical Association
    Title Fetal-tissue Transplantation for Parkinson's Disease.
    Date November 1993
    Journal The New England Journal of Medicine
    Title Actin-positive Spindle Cell Lymphoma.
    Date November 1993
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    We report an unusual case of malignant lymphoma, large noncleaved B-cell type, exhibiting sarcomatoid and myxoid patterns and strong positive staining for muscle-specific actin. Despite vigorous chemotherapy, the 64-year-old male patient, who had lymphoma involving his right inguinal area, retroperitoneum, and anterior chest wall at the time of presentation, died 3 months later.

    Title Autofluorescent Charcot-leyden Crystals.
    Date December 1992
    Journal Archives of Pathology & Laboratory Medicine
    Title Postoperative Spindle-cell Nodule of Urinary Bladder with Unusual Intracytoplasmic Inclusions.
    Date May 1992
    Journal Diagnostic Cytopathology
    Excerpt

    Postoperative spindle-cell nodule of the urinary bladder (or in the absence of previous surgical procedure, inflammatory pseudotumor) is a reactive process of unknown etiology mimicking a sarcoma. Intracytoplasmic inclusion bodies were noted inside the atypical spindle cells on Diff-Quik stained smears in a recent case of this entity. Although fluorescence was noted in the inclusion bodies with monoclonal antibodies against the major outer membrane protein of the Chlamydia species, the exact nature of these inclusion bodies remains unknown.

    Title Basic Microcomputer Program for Generating Percentile Values, Based on Age and Serum Cholesterol Levels.
    Date March 1991
    Journal Archives of Pathology & Laboratory Medicine
    Title The Effects of Triiodothyronine, Hydrocortisone and Insulin on Lipid Synthesis by Cultured Fibroblasts Preincubated in a Serum-free Medium.
    Date April 1984
    Journal Biochimica Et Biophysica Acta
    Excerpt

    Studies of lipid metabolism in cell cultures are usually carried out after preincubation of cells in media containing lipoprotein-deficient or delipidated serum. The artifacts produced during delipidation prevent the standardization of assays and the study of the role of hormones on lipid metabolism. We studied the effects of triiodothyronine, hydrocortisone, insulin and their combination on cholesterol and fatty acid synthesis in cultured human skin fibroblasts preincubated for 24 h in an artificial medium (medium A) consisting of equal volumes of Dulbecco's modified Eagle's and Ham's F-12 media enriched with transferrin, biotin and calcium pantothenate. In cells preincubated in medium A the incorporation of acetate to cholesterol and the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase were much lower than in cells preincubated in standard medium containing lipoprotein-deficient serum. Addition of the three hormones caused a marked stimulation of the incorporation of acetate to cholesterol (from 3.1 to 17.7 pmol/min per mg protein), an activity similar to that in cells preincubated in lipoprotein-deficient serum plus hormones. The stimulatory effect of the hormones on HMG-CoA reductase activity was smaller, from 11 to 26 pmol/min per mg protein compared to 83 pmol/min per mg protein in cells preincubated in lipoprotein-deficient serum plus hormones. Most of the stimulatory effect was due to insulin. The lack of coordinate response between these two parameters in cells preincubated in artificial medium could not be explained by (a) stimulation of a post-mevalonate step as measured by the incorporation of mevalonate to cholesterol; (b) the in vitro inactivation of HMG-CoA reductase by phosphorylation: incubation of fibroblast microsomes with Escherichia coli alkaline phosphatase resulted in a decrease in HMG-CoA reductase activity, in contrast to an increase in hepatic microsomes; (c) the presence of inhibitors of HMG-CoA reductase in the microsomal extract. In cells preincubated in medium A the incorporation of acetate to fatty acids and the activities of acetyl-CoA carboxylase and fatty acid synthetase were approximately equal to that of cells preincubated in standard medium containing lipoprotein-deficient serum. Hormones added to medium A caused a stimulation of incorporation of acetate to fatty acids (from 5.1 to 19.8 pmol/min per mg protein), the activity of acetyl-CoA carboxylase (from 494 to 820 pmol/min per mg protein) and of fatty acid synthetase (from 300 to 678 pmol/mg protein). These values were significantly higher than those obtained in cells preincubated with lipoprotein-deficient serum with or without hormones.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title The Utility of Low- and Intermediate-magnification Apochromatic Objectives.
    Date March 1984
    Journal Human Pathology
    Title Polyoxyethylated Cholesterol Derivatives. Organic Synthesis, Cellular Uptake and Effect on Lipid Metabolism in Cultured Skin Fibroblasts.
    Date January 1982
    Journal Biochimica Et Biophysica Acta
    Title 'rhabdoid' Wilms' Tumor: an Ultrastructural Study.
    Date November 1981
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    We studied a 5-week-old infant who had a "rhabdoid" Wilms' tumor. Ultrastructural studies disclosed aggregates of cytoplasmic filaments that seemed to correspond with the eosinophilic cytoplasmic bodies seen by light microscopy, but did not uncover evidence of rhabdomyoblastic differentiation. The histogenesis of this subtype was not established, but origin from the metanephric blastema could not be ruled out.

    Title Vascular Spaces in Endolymphatic Stromal Myosis.
    Date April 1981
    Journal Gynecologic Oncology
    Title Suppression of Synthesis and Esterification of Cholesterol and Stimulation of Low Density Lipoprotein Receptor Activity by Polyoxyethylated Cholesterol in Cultured Human Fibroblasts.
    Date March 1980
    Journal The Journal of Biological Chemistry
    Excerpt

    In cultured skin fibroblasts from normal and homozygous familial hypercholesterolemic subjects, a water-soluble polyoxyethylated derivative of cholesterol suppresses the incorporation of [2-14C]acetate into cholesterol and decreases the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis. The effect of this compound on low density lipoprotein (LDL) receptor-mediated activities (binding, internalization, and degradation of LDL) and on cholesterol ester formation was compared to that of LDL and 25-hydroxycholesterol. In normal fibroblasts preincubated in lipoprotein-deficient serum, LDL or 25-hydroxycholesterol decreased cholesterol synthesis and LDL receptor activity and increased cholesterol ester formation. In contrast, polyoxyethylated cholesterol stimulated LDL receptor activity, inhibited cholesterol ester formation mediated by LDL and 25-hydroxycholesterol, and inhibited the activity of acyl-CoA:cholesterol acyltransferase in cell extracts. Polyoxyethylated cholesterol had no effect on the low level of LDL receptor activity of homozygous hypercholesterolemic fibroblasts but stimulated the half-normal activity of heterozygous cells.

    Title Proton Nuclear Magnetic Resonance Study of Cobrotoxin.
    Date May 1979
    Journal Biochemistry
    Excerpt

    Cobrotoxin (Mr 6949), which binds tightly to the acetylcholine receptors, contains no phenylalanines and only two histidines, two tyrosines, and one tryptophan that result in well-resolved aromatic proton resonances in D2O at 360 MHz. His-32, Tyr-25, and the Trp are essential for toxicity and may interact with the acetylcholine receptor. We assign two titratable resonances (pKa = 5.1) at delta = 9.0 and 7.5 ppm at pH 2.5 and at 7.7 and 7.1 ppm at pH 9.5 to the C-2 and C-4 ring protons, respectively, of His-4. Two other titratable resonances (pKa = 5.7) at delta = 8.8 and 6.9 ppm at pH 2.5 and at 7.8 and 6.7 ppm at pH 9.5 are assigned to the C-2 and C-4 ring protons of His-32, respectively. The differences in delta values of the two histidines reflect chemically different microenvironments while their low pKa values could arise from nearby positive charges. A methyl resonance gradually shifts upfield to delta approximately 0.4 ppm as His-4 is deprotonated and is tentatively assigned to the methyl group of Thr-14 or Thr-15 which, from published X-ray studies of neurotoxins, are located in the vicinity of His-4. Further, we have identified the aromatic resonances of the invariant tryptophan and individual tyrosines and the methyl resonance of one of the two isoleucines in the molecule. Several broad nontitrating resonances of labile protons which disappear at pH greater than 9 may arise from amide groups of the beta sheet in cobrotoxin.

    Title Permanent Records of Microchromatography of Hemoglobins.
    Date February 1979
    Journal American Journal of Clinical Pathology
    Excerpt

    In the general hematology laboratory, quantitation of hemoglobin A2 by the microchromatographic method is superior to the method of elution from cellulose acetate membranes. A permanent record of microchromatographic patterns for the detection of hemoglobins S and C at birth can be easily obtained by using a photocopying machine and a flat mirror. These copies can be stored for comparison with definitive results when the children are retested at 6 months of age or later.

    Title Suppression of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase Activity and of Incorporation of Acetate into Cholesterol in Homozygous Hypercholesterolemic Fibroblasts by Ferritin-low Density Lipoprotein Conjugates.
    Date June 1978
    Journal Biochimica Et Biophysica Acta
    Excerpt

    Conjugates of ferritin with low density lipoproteins (LDL) were prepared and separated by sucrose gradient centrifugation. These conjugates, at cholesterol concentration of 100--132 microgram/ml, caused a greater than 90% suppression of hydroxymethylglutaryl coenzyme A reductase activity and of acetate incorporation into cholesterol in cultured skin fibroblasts from a normal subject as well as from a subject with homozygous familial hypercholesterolemia. The half maximal inhibition concentration was approx. 10 microgram/ml cholesterol for LDL and ferritin . (LDL)2 and 5 microgram/ml for (ferritin)2 . LDL in both cell lines. In contrast, native low density lipoproteins have only a minimal inhibitory effect in homozygous cells. The ability of the conjugates to stimulate the incorporation of oleate into cholesteryl esters was also equal in the two cell lines, although the conjugates were only 10% as active as low density lipoproteins in the normal cells. LDL reduced the ferritin . (LDL)2-mediated suppression of hydroxymethylglutaryl-CoA reductase activity in homozygous cells while ferritin . (LDL)2 reduced the LDL-mediated stimulation of cholesteryl ester formation in normal cells.

    Title Regulation of Lipid Synthesis by Low Density Lipoproteins in Cultured Skin Fibroblasts in Homozygous Familial Hypercholesterolemia.
    Date September 1977
    Journal Biochimica Et Biophysica Acta
    Title Cystadenoma of the Pancreas. An Ultrastructural Study.
    Date August 1977
    Journal Cancer
    Excerpt

    A case of cystadenoma of the pancreas was studied at the light (LM) and the ultrastructural (EM) levels. The observation made under LM that the flattened epithelial cells lining the cystic spaces were similar to the centroacinar cells of a normal pancreas was supported by EM findings. Numerous glycogen granules were demonstrated in the cells, a feature characteristic of fetal but not adult centroacinar cells. A few epithelial cells contained occasional membrane bound dense granules of unknown nature. This observation and the finding of normally appearing islets of Langerhans raise the possibility that this may be an example of a mixed insular-duct cystadenoma. However, if the islets of Langerhans were considered entrapped structures, this tumor should be labelled as a simple serous cystadenoma.

    Title Pulmonary Blastoma: an Ultrastructural Study with a Brief Review of Literature and a Discussion of Pathogenesis.
    Date March 1977
    Journal Cancer
    Excerpt

    A pulmonary blastoma is reported in a 19-year-old black female. The light and electron microscopic characterics are described; they are found to be similar to those of the fetal lung prior to the fourth gestational month. Although the ultrastructural features do not favor any particular theory of histogenesis of this unique tumor, evidence for the commonly held theory that the tumor arises from pluipotential pulmonary blastema seems tenuous. A brief review of the literature disclosed 38 other similar cases. There was a male predominance with an average age of detection at 39 years. Sputum cytology was rarely positive. Among tumors larger than 5 cm in diameter, survival was usually less than 2 years. Metastases were present in approximately half of the cases.

    Title Chromium(iii)-adenosine Triphosphate As a Paramagnetic Probe to Determine Intersubstrate Distances on Pyruvate Kinase. Detection of an Active Enzyme-metal-atp-metal Complex.
    Date July 1976
    Journal The Journal of Biological Chemistry
    Excerpt

    The interaction of CrATP, a stable, substitution-inert, paramagnetic tridentate complex of ATP, with muscle pyruvate kinase has been studied by measuring the effects of CrATP on the kinetics of pyruvate enolization and on the longitudinal nuclear magnetic relaxation rate (1/T1) of the protons of water and the protons and carbon atoms of pyruvate to investigate the existence and activity of bimetallic enzyme-M(II)-CrATP complexes and to determine intersubstrate distances on a kinase. The paramagnetic effect of CrATP on 1/T1 of water protons is enhanced upon complexation with the enzyme. Titrations of the enzyme with CrATP yielded characteristic enhancements of 1/T1 for the binary enzyme-CrATP, ternary enzyme-Mg(II)-crATP, and quaternary enzyme-Mg(II)-crATP-pyruvate complexes of 3.5, 1.7, and 1.2 and dissociation constants of CrATP of 400, 200, and 200 muM, respectively. From the frequency dependence of 1/T1, the number of fast exchanging water protons in the coordination spheres of Cr(III) is approximately 6 in CrATP and in both the ternary enzyme-Mg(II)-CrATP complex and the quaternary enzyme-Mg(II)-CrATP-pyruvate complex. The paramagnetic effect of enzyme-bound Mn(II) on 1/T1 of water protons decreases upon the addition of CrATP. Titration of the binary enzyme-Mn(II) complex with CrATP decreases the characteristic enhancement due to Mn(II) from 24 +/- 3 to 6 +/- 1. Titration of the ternary eznyme-Mn(II)-pyruvate complex with CrATP decreases the enhancement from 6 +/- 1 to 0.5 +/- 0.1. The affinity of the enzyme for Mn(II) is increased 2-fold upon binding of CrATP as indicated by decreases in the amplitude of the EPR spectrum of free Mn(II). The dissociation constants of CrATP from the enzyme-Mn(II)-CrATP complex, the enzyme-CrATP-pyruvate complex, and the enzyme-Mn(II)-CrATP-pyruvate complex are all 200 muM. The observed titration behavior, the characteristic enhancement values, the tightening by Mg(II) of the binding of CrATP to the enzyme, and the tightening of the binding of Mn(II) to the enzyme by CrATP establish the existence of enzyme-M(II)-CrATP and enzyme-M(II)-CrATP-pyruvate complexes containing two cations, Mg(II) or Mn(II) and Cr(III), at the active site.

    Title Arrangement and Conformations of Substrates at the Active Site of Pyruvate Kinase from Model Building Studies Based on Magnetic Resonance Data.
    Date July 1976
    Journal The Journal of Biological Chemistry
    Excerpt

    Seventeen distances from two paramagnetic reference points, as determined by nuclear relaxation studies of six active complexes of rabbit muscle pyruvate kinase, have been used to construct molecular models of two composite enzyme complexes. In the model of the hypothetical pyruvate kinase-M(I)-M(II)-ATP-Cr(III)-P-enolpyruvate complex, overlap of the transferred phosphoryl groups of the two substrates, which is required to explain the observed competition, is incomplete, allowing greater than or equal to 1 A for the transition state to form. In the active enzyme-M(I)-M(II)-ATP-Cr(III)-pyruvate complex, the gamma-phosphoryl phosphorus of ATP is in molecular contact (3.0 +/- 0.5 A) with the carbonyl oxygen of pyruvate, consistent with direct phosphoryl transfer, indicating no need for intermediate phosphorylation of the enzyme. The enzyme-bound divalent cation, which forms second sphere complexes with the phosphoryl groups of P-enolpyruvate and ATP, may activate the transferred phosphoryl group indirectly, through a water ligand. By analogy with the position of Cr(III), a second divalent cation may participate more directly by coordination of the triphosphate chain of ATP.

    Title Magnetic Resonance Studies of the Proximity and Spatial Arrangement of Propionyl Coenzyme A and Pyruvate on a Biotin-metalloenzyme, Transcarboxylase.
    Date April 1976
    Journal Biochemistry
    Excerpt

    A spin-labeled ester of CoA, R-CoA (3-carboxy-2,2,5,5-tetramethyl-1-pyrolidinyl-1-oxy CoA thioester), has been shown by competition studies using electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) to bind specifically to the propionyl-CoA binding sites of transcarboxylase. Titrations indicate 0.7 +/- 0.2 binding site for R-CoA per enzyme-bound biotin with a dissociation constant of 0.33 +/- 0.12 mM. Propionyl-CoA binds to this site with a 1.3-fold lower disonable agreement with kinetically determined inhibitor constants of CoA and propionyl-CoA and propionyl-CoA (D. B. Northrop (1969), J. Biol. Chem. 244, 5808). The bit of this spin-label on 1/T1 of water protons. The formation of a ternary transcarboxylase-R-CoA-pyruvate complex is suggested by the failure of pyruvate to displace R-CoA from the tight site and is established by the paramagnetic effects of enzyme-bound R-CoA on the relaxation rates of the protons and 13C atoms of enzyme-bound pyruvate. From the paramagnetic effects of R-CoA on the relaxation rates of the methyl protons of pyruvate at 40.5 and 100 MHz, and on the 13C-enriched carbonyl and carboxyl carbon atoms of pyruvate at 25.1 MHz, a correlation time of 7 nsec and distances from the bound nitroxide radical to the methyl protons, the carbonyl, and carboxyl carbon atoms of bound pyruvate of 7.9 +/- 0.7, 10.3 +/- 0.8, and 12.1 +/- 0.9 A, respectively, are calculated. These distances establish the close proximity of the CoA ester and keto acid sites on transcarboxylase. Together with the previously determined distances from the enzyme-bound (Co(II) to the methyl protons and 2 carbon atoms of bound pyruvate and to 12 protons and 3 phosphorus atoms of bound propionyl-CoA, the present distances are used to derive a composite model of the bound substrates in the overall transcarboxylation reaction. In this model the distance from the methyl carbon of pyruvate and the methylene carbon of propionyl-CoA, between which the carboxyl transfer takes place is only approximately 7 A. Depending on the detailed mechanism of the carboxyl transfer, the distance through which the carboxybiotin must migrate is therefore between 0 and 7 A. Hence the major role of the 14-A arm of carboxybiotin is not to permit a large carboxyl migration but, rather to permit carboxybiotin to traverse the gap which occurs at the interface of three subunits and to insinuate itself between the CoA and keto acid sites.

    Title 1h and 31p Fourier Transform Magnetic Resonance Studies of the Conformation of Enzyme-bound Propionyl Coenzyme A on the Transcarboxylase.
    Date April 1976
    Journal Biochemistry
    Excerpt

    The relaxation rates of the carbon-bound protons and of the three assigned phosphorus resonances of propionyl-CoA were measured in solutions of free propionyl-CoA and of the transcarboxylase-propionyl-CoA complex. In free propionyl-CoA, analysis of the 1/T1 values of 15 protons at 100 and 220 MHz and of 1/T1 and 1/T2 of the three phosphorus atoms at 40.5 MHz indicated free rotation of the propionyl region (taur approximately 3 x 10(-11) sec) but hindered motion of the remainder of the molecule with correlation times of 1-3. 5 x 10(-10) sec, approaching the tumbling time of the entire molecule (taur - 6 x 10(-10) sec. The correlation times of the three phosphorus atoms were indistinguishable from those of their nearest neighbor protons. The effects of three homogeneous enzyme preparations with varying contents of Zn(II), Co(II), and Cu(II) on 1/T1 of 12 protons and 3 phosphorus atoms of prionyl-CoA were analyzed with the help of simultaneous equations to yield the individual contributions at the three metal sites. Only diamagnetic effects were detected on the relaxation rates of the three phosphorus atoms. From the diamagnetic effects it was calculated that the motions of the prionyl side chain and of the terminal pantetheine methylene protons were hindered on the enzyme by an order of magnitude (taur approximately 6 x 10(-10) sec) and that the phosphorus atoms were hindered by two orders of magnitude (taur approximately 1 x 10(-8) sec) over the taur values found in free propionyl-CoA, but that these taur values remained well below that of the entire protein molecule (taur =6 x 10(-7) sec)...

    Title Stereochemistry of Propionyl-coenzyme A and Pyruvate Carboxylations Catalyzed by Transcarboxylase.
    Date November 1975
    Journal Biochemistry
    Excerpt

    The stereochemistry of the two half-reactions catalyzed by the biotin-containing enzyme, transcarboxy-lase from Propionobacteria shermanii, has been determined. The pro-R hydrogen at C-2 of propionyl-coenzyme A is replaced by CO2 in formation of the S isomer of methylmalonyl-CoA, defining the process as retention of configuration. This C-2 hydrogen is abstracted at a rate identical with product formation. For the other half-reaction, pyruvate to oxalacetate, the chiral methyl group methodology of Rose (I. A. Rose (1970), J. Biol. Chem. 245, 6052) was employed. First, it was determined with [3-2-He]pyruvate that a kinetic deuterium isotope effect of 2.1 occurs at Vmax in this carboxyl transfer, indicating that the necessary requirement for discrimination against heavy isotopes of hydrogen existed. Then, 3(S)-[3-2-H,3-H]pyruvate, generated from 3(S)-]E-2-H,3-H]phosphoglycerate, was carboxylated and the oxalacetate trapped as [3030H]malate using malate dehydrogenase. Exhaustive incubation of the tritiated malate (3-H/14-C = 1.95) with fumarase to labilize the pro-R hydrogen at C-3 resulted in release of 65% of the tritium into water. Reisolation of the malate after fumarase action yielded a 30H/14-C ration of 0.67, indicating 34% retention as expected. The theoretical enantiotopic distribution for the observed k1H/k2H of 2.1 is 68:32. Selective enrichment of tritium in the pro-R position at C-3 of malate indicates enzymatic carboxylation of pyruvate with retention of configuration in this half-reaction also.

    Title Nuclear Relaxation Studies of the Role of the Divalent Cation in the Mechanism of Pyruvate Kinase and Enolase: Inner Sphere and Second Sphere Complexes.
    Date May 1974
    Journal Annals of the New York Academy of Sciences
    Title Electron and Nuclear Magnetic Resonance Studies of the Interaction of Pyruvate with Transcarboxylase.
    Date April 1974
    Journal Biochemistry
    Title Interaction of Pyruvate with Pyruvate Carboxylase and Pyruvate Kinase As Studied by Paramagnetic Effects on 13 C Relaxation Rates.
    Date May 1973
    Journal Biochemistry
    Title Pyruvate Carboxylase from Chicken Liver. Steady State Kinetic Studies Indicate a "two-site" Ping-pong Mechanism.
    Date May 1972
    Journal The Journal of Biological Chemistry
    Title Possible Control Mechanisms of Liver Pyruvate Carboxylase.
    Date July 1970
    Journal Hoppe-seyler's Zeitschrift Für Physiologische Chemie
    Title The Incidence and Significance of Villous Change in Adenomatous Polyps.
    Date February 1970
    Journal American Journal of Clinical Pathology
    Title Prospects and Challenges in Using Patient-reported Outcomes in Clinical Practice.
    Date
    Journal Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation
    Excerpt

    BACKGROUND: Patient-reported measures include preferences and reports about care received, health behaviors, and outcomes of care (patient satisfaction and health-related quality of life). These measures are a core aspect of health care, but there is much to be learned about how to use them to improve clinical practice. METHOD: We specify linkages among different patient-reported measures and focus upon the prospects and challenges for use of patient-reported outcomes in clinical practice. RESULTS: Patient-reported measures are important throughout the continuum of patient care. At the initial visit, patient-reported outcomes provide information about what is important to the patient, the patient's current behaviors, and the patient's baseline health-related quality of life. At subsequent visits, patient-reported outcomes help evaluate disease progression or regression as well as treatment effects. CONCLUSIONS: Patient-reported measures can help clinicians target interventions that will improve patient outcomes of care. However, there are a number of challenges in using patient-reported outcomes in clinical practice.

    Title Key Elements of High-quality Primary Care for Vulnerable Elders.
    Date
    Journal Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine
    Excerpt

    With the impending surge in the number of older adults, primary care clinicians will increasingly need to manage the care of vulnerable elders. Caring for vulnerable elders is complex because of their wide range of health goals and the interdependence of medical care and community supports needed to achieve those goals. In this article, we identify ways a primary care practice can reorganize to improve the care of vulnerable elders. We begin by identifying important outcomes for vulnerable elders and three key processes of care (communication, developing a personal care plan for each patient, and care coordination) needed to achieve these outcomes. We then describe two delivery models of primary care for vulnerable elders - co-management, and augmented primary care. Finally, we discuss how the physical plant, people, workflow management, and community linkages in a primary care practice can be restructured to better serve these patients.

    Title The Effectiveness of Radioactive Iodine for Treatment of Low-risk Thyroid Cancer: a Systematic Analysis of the Peer-reviewed Literature from 1966 to April 2008.
    Date
    Journal Thyroid : Official Journal of the American Thyroid Association
    Excerpt

    Radioactive iodine (RAI) remnant ablation has been used to eliminate normal thyroid tissue and may also facilitate monitoring for persistent or recurrent thyroid carcinoma. The use of RAI for low-risk patients who we define as those under age 45 with stage I disease or over age 45 with stage I or II disease based on American Joint Committee on Cancer (AJCC) 6th edition, or low risk under the metastases, age, completeness of resection, invasion, size (MACIS) staging system (value <6) is controversial. In this extensive literature review, we sought to analyze the evidence for use of RAI treatment to improve mortality and survival and to reduce recurrence in patients of various stages and disease risk, particularly for those patients who are at low risk for recurrence and death from thyroid cancer.


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