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Biomedical subjects

M L Hall

Publications and source records attributed to M L Hall.

At least 19 recordsLinked to original sources
PubMed2006

An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C).

The driving forces for the regulation of cell morphology are the Rho family GTPases that coordinate the assembly of the actin cytoskeleton. This dynamic feature is a result of tight coupling between the cytoskeleton and signal transduction and is facilitated by actin-binding proteins (ABPs). Mutations in the actin bundling and PDZ domain-containing protein harmonin are the causes of Usher syndrome type 1C (USH1C), a syndrome of congenital deafness and progressive blindness, as well as certain forms of non-syndromic deafness. Here, we have used the yeast two-hybrid assay to isolate molecular partners of harmonin and identified DOCK4, an unconventional guanine exchange factor for the Rho family of guanosine triphosphatases (Rho GEF GTPases), as a protein interacting with harmonin. Detailed molecular analysis revealed that a novel DOCK4 isoform (DOCK4-Ex49) is expressed in the brain, eye and inner ear tissues. We have further provided evidence that the DOCK4-Ex49 binds to nucleotide free Rac as effectively as DOCK2 and DOCK4 and it is a potent Rac activator. By immunostaining using a peptide antibody specific to DOCK4-Ex49, we showed its localization in the inner ear within the hair bundles along the stereocilia (SC). Together, our data indicate a possible Rac-DOCK4-ABP harmonin-activated signaling pathway in regulating actin cytoskeleton organization in stereocilia.

Actins↗
PubMed2001

A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation.

BACKGROUND: Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids. METHODS: Serial blood samples (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation from 184 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. Demographic-clinical covariates were explored with regression methods. RESULTS: Basiliximab clearance was 55 +/- 26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/- 6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C seropositivity, and notable postoperative bleeding had no clinically relevant influences on basiliximab disposition; however, the cumulative volume of drained ascites fluid in the first week was positively correlated with clearance. Receptor-saturating basiliximab concentrations (> or =0.1 microg/mL) were maintained for 38 +/- 16 days, and this was negatively correlated with the cumulative volume of drained ascites fluid in week 1. Patients who experienced an acute rejection episode did not clear basiliximab at a faster rate than their rejection-free peers nor did they maintain CD25-saturating concentrations for a shorter period. CONCLUSIONS: Although the standard dose regimen of 20 mg of basiliximab on days 0 and 4 after transplantation appears to be appropriate for the majority of patients with liver transplants, a supplemental dose at the end of the first week may be considered for those with substantial (>10 L) postoperative ascites fluid drainage.

Antibodies, Anti-Idiotypic↗
PubMed2001

Private practitioners' perceptions of the changes in their use of treatment modalities following participation in managed care panels.

Private practicing social workers, psychologists, and psychiatrists were surveyed to assess their perceptions of how their use of treatment modalities has changed since joining managed care panels. Social work respondents report that they perceive managed care organizations as certifying them to practice individual therapy more since joining managed care panels than they practiced individual therapy prior to joining managed care panels. However, they perceive managed care organizations as certifying them to practice group and family therapy less often since joining managed care panels. Psychologist respondents report that they perceive managed care organizations as certifying them less often for all treatment modalities except individual therapy. Likewise psychiatrist respondents report they perceive managed care organizations as certifying them less often for all treatment modalities except medication management. These results have potential implications for educators and practitioners interested in pursuing careers in solo or group practice.

Journal Article↗
PubMed2000

A prospective economic evaluation of basiliximab (Simulect) therapy following renal transplantation.

BACKGROUND: Immunoprophylaxis with basiliximab (Simulect), an anti-interleukin-2-receptor (anti-IL-2R; CD25) chimeric monoclonal antibody, has been demonstrated to significantly reduce the incidence of acute cellular rejection in adult renal allograft recipients (32% vs. placebo, p < 0.01). METHODS: An economic evaluation was conducted as part of a U.S. multi-center, randomized, double-blind, placebo-controlled clinical trial comparing basiliximab plus dual immunosuppressive therapy (cyclosporine modified [Neoral] and corticosteroids) to dual therapy alone. Healthcare resources utilized by the 346 subjects in the 'intent-to-treat' population were prospectively collected over the 1-yr study period. Direct medical costs were determined for all hospitalizations, outpatient provider visits, procedures (excluding the initial transplant procedure), laboratory and diagnostic tests, and immunosuppressants, including basiliximab when administered. RESULTS: Total first-year medical costs were lower for the basiliximab group than for the placebo group ($28 927 vs. $32 300, difference = $3373). although this difference was not statistically significant. First-year hospital costs for treating acute rejection were also lower for the basiliximab group ($9328 vs. $10761, difference = $1433); however, this difference did not achieve statistical significance. Importantly, the efficacy analysis demonstrated a significant reduction in the incidence of acute rejection (38 vs. 55%, p < 0.01) in the basiliximab arm, and this was accomplished without increasing the overall cost of care. Fewer basiliximab-treated patients (8 vs. 15%,, p = 0.03) were hospitalized. This observation suggested less serious illness and reduced treatment costs among basiliximab-treated patients, because the overall incidence of infection was similar between the groups. The adverse event profile of patients receiving basiliximab was clinically and economically indistinguishable from that of those treated with placebo. CONCLUSION: Induction immunosuppression with basiliximab, combined with cyclosporine modified and corticosteroids, was therapeutically beneficial and contained medical costs during the initial post-transplant year.

Adrenal Cortex Hormones↗
PubMed2000

Managed behavioral health care provider practice patterns: a new item for the public policy agenda.

Managed care is a dominating issue on the public policy agenda. Difficulties in defining and operationalizing it continue to have ramifications for the nation. It is often assumed that the care being reimbursed by managed care organizations is for clients whose psychiatric conditions have been appropriately diagnosed and treated. Based on the responses of a randomly-selected group from the major behavioral health care disciplines, not all care reimbursed is for care which has been appropriately diagnosed and treated. The cost implications of managed care and the ramifications for public health policy are discussed.

Behavioral Medicine↗
PubMed1999

Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. The U.S. Simulect Renal Transplant Study Group.

BACKGROUND: Basiliximab is an interleukin-2 receptor (CD25) chimeric monoclonal antibody used for acute rejection prophylaxis in renal transplants. In the context of a randomized, double-blind efficacy trial, its population pharmacokinetics and potential exposure-response relationships were explored in de novo kidney allograft recipients receiving 40 mg basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppressive therapy with cyclosporine microemulsion and corticosteroids. METHODS: Serial blood samples (8.2+/-1.3 per patient) were collected over 12 weeks after transplant from 169 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. The duration of CD25 saturation was estimated as the time over which serum basiliximab concentrations exceeded 0.2 microg/ml. The relationships between pharmacokinetic parameters and demographic-clinical covariates were explored by regression methods and unpaired t-tests. RESULTS: Basiliximab clearance was 36.7+/-15.2 ml/hr, distribution volume 8.0+/-2.4 L, and half life 7.4+/-3.0 days. Patient weight (range, 44-131 kg) and age (range, 20-69 yrs) each contributed < or =6% to the variability in clearance and volume. Gender, ethnic group, and the presence of proteinuria had no clinically relevant influences on basiliximab disposition. Receptor-saturating basiliximab concentrations were maintained for 36+/-14 days (range, 12-91). There was no apparent relationship between the incidence or day of onset of acute rejection episodes during CD25 saturation and basiliximab concentration (range, 0.2-5.0 microg/ml). In patients who experienced a rejection episode after basiliximab was eliminated from serum (n=33), basiliximab had not been cleared faster than in their rejection-free peers (P=0.322) nor had CD25 been saturated for a shorter period of time (33+/-13 days vs. 37+/-14 days for rejection-free patients, P=0.162). CONCLUSIONS: There were no demographic or clinical subpopulations not adequately treated with the standard basiliximab dosing regimen. Over the range of CD25 suppression durations observed in this study, extended periods of receptor blockade did not seem to confer an immunoprophylactic advantage compared with shorter periods of receptor suppression.

Adult↗
PubMed1999

Private practitioners' documentation of outpatient psychiatric treatment: questioning managed care.

This study investigates how social workers, psychologists, and psychiatrists document the treatment they provide clients to managed behavioral health care organizations. The rosters of the Register of Clinical Social Workers, the American Psychological Association, and the American Psychiatric Association yielded a sample of 168 private practicing social workers, 158 psychologists, and 258 psychiatrists from across the nation. Results indicated that practitioners differed based on age, amount of time spent in private practice, racial self-identification, percentage of time with clients diminished due to communicating with managed behavioral health care organizations, and documentation of clients' prognoses. Some practitioners believe it is necessary to report treatment needs in ways to assure certification rather than in ways that accurately depict clients' clinical profiles. The ramifications for clinicians' evaluation of their own practices, reimbursement for their services, and meeting clients' needs while working under managed behavioral health care guidelines are discussed.

Adult↗
PubMed1998

Management of chronic heart failure in the outpatient.

Current management of chronic heart failure involves reducing the personal and economic burden through controlling symptoms, reducing hospital admissions, and slowing the progression of ventricular dysfunction. As healthcare providers struggle to control the rising costs of health and illness care while reducing morbidity and mortality rates associated with chronic illness, alternative practice models must be evaluated. This article describes a collaborative practice model designed to improve care of older adults with chronic heart failure. Strengths of the model include the use of evidence-based guidelines for heart failure management and for organization of the practice.

Adult↗
PubMed1998

Managed care's impact on the financial well-being of social workers in private practice.

The authors used the rosters from the Register of Clinical Social Workers, the American Psychological and American Psychiatric Associations to contrast a random sample of 167 private practicing social workers, 158 psychologists and 187 psychiatrists from across the nation with respect to changes in these practitioners' financial well-being since joining managed care organization panels. Although no statistically significant differences were found between the three groups with respect to many indicators of financial well-being, each of the groups reported that their financial well-being had been adversely affected by managed care organization guidelines. Because the social workers in this study were found to spend a greater percentage of their time in private practice than psychologists and psychiatrists, managed care organizations' policies with respect to financial reimbursement are likely to impact them more adversely than professionals in other disciplines. Other changes in overhead costs, including office staffing, record keeping and malpractice insurance, as required by managed care organizations, were considered by many of the respondents to be among the most prominent issues affecting their financial well-being.

Educational Status↗
PubMed1995

Relationship between quantity of undergraduate science preparation and preclinical performance in medical school.

PURPOSE: The primary purpose of this study was to determine whether a relationship existed between the quantities of undergraduate science education completed by medical students and their subsequent preclinical performances in medical school. The secondary purpose of the study was to determine the nature of any relationship present and to re-verify standard predictors of preclinical performance in medical school. METHOD: This study was undertaken at Albany Medical College in conjunction with Sage Graduate School, Albany, New York. The analysis encompassed 120 systematically and 80 randomly selected medical student academic records (200 total cases) from the entering classes of 1977 through 1992. Twelve distinct variables were collected. Data transformations were completed as required, and the data subsequently standardized. Standard descriptive statistics, correlation between variables, t-tests between systematically and randomly selected groups, and factor analysis were performed on the data collected. RESULTS: It was determined that there was no significant relationship between total hours of undergraduate science completed and average preclinical performance in medical school. In addition, correlation between subdivisions of total hours of undergraduate science (total hours of chemistry, total hours of biology, total hours of math, and total hours of physics) and subdivisions of average preclinical performance (year-one preclinical performance and year-two preclinical performance) also proved to be nonsignificant. However, significant relationships between average preclinical performance and its subdivisions and other standard predictors of preclinical performance (Medical College Admission Test score and science grade-point average) were found to be in line with values in recent literature. In addition, significant relationships were found with the National Board of Medical Examiners Part I examination. Factor analysis of all variables yielded three underlying factors: medical school preclinical performance factor, undergraduate performance factor, and quantity of non-life-sciences factor. CONCLUSION: Quantity of science-based undergraduate premedical education, either in its entirety or in subdivisions, did not materially affect the performances of the selected medical school students in their preclinical years of medical school.

Achievement↗
PubMed1995

Pediatric emergency medicine fellow clinical work requirements.

A wide range of clinical requirements exists among PEM fellowship programs. Programs are equally split concerning the question of whether fellows should work with supervision or independently in the first year; a significant number of fellowship programs require continued supervision of fellows in subsequent years. Orientation for first year fellows and requirements for completion of PALS, advanced pediatric life support (APLS), ACLS, or ATLS courses prior to their first independent shift varied greatly. In particular, a minority of programs required ATLS completion even though a majority of overall fellowship programs operate in a hospital designated as a Level 1 Trauma Center. Programs in which first-year fellows worked independently had fewer attendings and were less likely to provide 24-hour coverage. Fellows appear to work a similar or less demanding schedule than PEM attendings in most fellowship programs, and most fellowship directors feel that their fellows should continue with their current schedule.

Education, Medical, Graduate↗
PubMed1994

Comparison of large-conductance Ca(2+)-activated K+ channels in artificial bilayer and patch-clamp experiments.

We compared the gating, ion conduction, and pharmacology of large-conductance Ca(2+)-activated K+ channels (BK channels) from canine colon in artificial lipid bilayers and in excised patches. Both protocols identified 270-pS K(+)-selective channels activated by depolarization and Ca2+ (approximately 130-mV shift of half-activation voltage per 10-fold change in Ca2+) that were inhibited by extracellular tetraethylammonium (TEA) and charybdotoxin. These similarities suggest that the same BK channels are studied in the two techniques. However, we found three quantitative differences between channels in artificial bilayers and patches. 1) Channels in artificial bilayers required fivefold higher free Ca2+ or 80-mV stronger depolarization for activation. 2) The voltage dependence of TEA block was smaller for channels in artificial bilayers. The apparent distance across the membrane field for the TEA binding site was 0.031 for channels in artificial bilayers and 0.23 for channels in patches. 3) ATP (2 mM) decreased open probability (Po) of channels in artificial bilayers, whereas channels in patches were unaffected. Neither GTP nor UTP reduced Po of channels in artificial bilayers. It is possible that these differences may be due to a lack of molecular identity between the channels studied in the two protocols. Alternatively, they may be attributed to alterations in channel properties during reconstitution or to influences of the artificial lipid environment.

Adenosine Triphosphate↗
PubMed1993

The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women.

OBJECTIVE: To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids. METHODS: One hundred ninety-five postmenopausal patients with RA were compared with 597 post-menopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x-ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex-users (18%). RESULTS: Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4-10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0-13.0%) and by 7.4% at the hip (95% CI 1.2-13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex-user and never user groups. Results were confirmed in 54 patients who had whole-body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = -0.23, P < 0.01; whole-body BMD r = -0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = -0.32, P < 0.01; whole-body BMD r = -0.72, P < 0.01). CONCLUSION: Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low-dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.

Absorptiometry, Photon↗