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Biomedical subjects

W R Scott

Publications and source records attributed to W R Scott.

At least 19 recordsLinked to original sources
PubMed2000

Curling of flap tips in HIV-1 protease as a mechanism for substrate entry and tolerance of drug resistance.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible. RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from the unliganded crystal structure. This movement is on the time scale observed by Nuclear Magnetic Resonance (NMR) relaxation data. The highly flexible tips of the flaps, with the sequence Gly-Gly-Ile-Gly-Gly, are seen curling back into the protein and thereby burying many hydrophobic residues. CONCLUSIONS: This curled-in conformational change has never been previously described. Previous models of this movement, with the flaps as rigid levers, are not consistent with the experimental data. The residues that participate in this hydrophobic cluster as a result of the conformational change are highly sensitive to mutation and often contribute to drug resistance when they do change. However, several of these residues are not part of the active site cavity, and their essential role in causing drug resistance could possibly be rationalized if this conformational change actually occurs. Trapping HIV-1 protease in this inactive conformation would provide a unique opportunity for future drug design.

Binding Sites↗
PubMed2000

Sharing ideas.

Explore the source record for details and available documents.

Color↗
PubMed2000

Ocular injuries due to projectile impacts.

An animal model has been developed using enucleated porcine eyes to evaluate ocular trauma. The eyes were pressurized to approximately 18 mmHg and mounted in a container with a 10% gelatin mixture. The corneas of sixteen pressurized eyes were impacted by a blunt metal projectile (mass of 2.6 gm, 3.5 gm or 45.5 gm) at velocities of 4.0 to 38.1 m/s. The impacted eyes were evaluated by an ophthalmologist. A numerical classification scheme was used to categorize the severity of the ocular injury. A chi-squared test indicates that the injury level is associated with the kinetic energy (KE) and not the momentum of the projectile. The enucleated eyes began to experience lens dislocations when the KE of the projectile was approximately 0.75 Nm, and retinal injuries when the KE was approximately 1.20 Nm.

Acceleration↗
PubMed1998

Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix.

PURPOSE: To evaluate the efficacy and toxicity of intravenous vinorelbine as single-agent chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between August 1993 and July 1995, 35 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Patients had received no prior therapeutic chemotherapy. The initial dose of vinorelbine 30 mg/m2 was administered as a weekly intravenous infusion. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group (GOG) and World Health Organization criteria, respectively. RESULTS: Thirty-three of 35 patients were assessable for response and 35 of 35 for toxicity. The overall response rate was 18% (one complete response [CR], five partial responses [PR]). The mean response duration was 5.2 months and the median survival from treatment for all patients was 11.0 months. The major toxicity was leukopenia, with 61% of patients who had grade 3 or 4. Gastrointestinal and neurotoxicity were infrequent and mild. CONCLUSION: Vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Further studies of combination regimens with this agent are justified in this patient population.

Adult↗
PubMed1998

An organizational field approach to resource environments in healthcare: comparing entries of hospitals and home health agencies in the San Francisco Bay region.

OBJECTIVE: To draw together insights from three perspectives (health economics, organizational ecology, and institutional theory) in order to clarify the factors that influence entries of providers into healthcare markets. A model centered on the concept of an organizational field is advanced as the level of analysis best suited to examining the assortment and interdependence of organizational populations and the institutional forces that shape this co-evolution. In particular, the model argues that: (1) different populations of healthcare providers partition fiscal, geographic, and demographic resource environments in order to ameliorate competition and introduce service complementarities; and (2) competitive barriers to entry within populations of providers vary systematically with regulatory regimens. DATA SOURCES: County-level entries of hospitals and home health agencies in the San Francisco Bay Area using data from the American Hospital Association (1945-1991) and California's Office of Statewide Health Planning and Development (1976-1991). Characteristics of the resource environment are derived from the Area Resource File (ARF) and selected government censuses. METHODS OF ANALYSIS: A comparative design is applied to contrast influences on hospital and home health agency entries during the post-World War II period. Empirical estimates are obtained using Poisson and negative binomial regression models. RESULTS: Hospital and HHA markets are partitioned primarily by the age and education of consumers and, to a lesser extent, by urbanization levels and public funding expenditures. Such resource partitioning allows independent HHAs to exist comfortably in concentrated hospital markets. For both hospitals and HHAs, the barriers to entry once generated by oligopolistic concentration have declined noticeably with the market-oriented reforms of the past 15 years. CONCLUSION: A field-level perspective demonstrates that characteristics of local resource environments interact with interdependencies of provider populations and broader regulatory regimes to affect significantly the types of provider organizations likely to enter a given healthcare market.

Catchment Area, Health↗
PubMed1990

Phase I evaluation of thio-TEPA in combination with cisplatin for advanced gynecologic malignancies.

Thirty-five patients with advanced gynecologic malignancies were entered into a phase I study evaluating thio-TEPA in combination with cisplatin (50 mg/m2) intravenously every 4 weeks. Thirty-four patients were evaluable for toxicity and response, and one was evaluable for toxicity only. Median age was 53 years (range 28-72), and performance status less than or equal to 2. Prior treatment included chemotherapy in 21 patients, radiation in 15, hormonal therapy in 3, and immunotherapy in 1. Thio-TEPA was given to three or more patients at each of the following dose levels: 15, 20, 25, 30, 40, 50, and 60 mg/m2. Thio-TEPA's primary toxicity was myelosuppression; at 50 mg/m2, grade 3 or 4 granulocytopenia occurred in 13 of 17 cycles, and grade 3 or 4 thrombocytopenia occurred in 8 of 17 cycles. The maximum tolerated dose (MTD) of thio-TEPA was 40 mg/m2; in 35 cycles at this dose, grade 3 or 4 granulocytopenia occurred in 19, and grade 3 or 4 thrombocytopenia occurred in 10 cycles; median granulocyte nadir was 1100 (range 110 to 3600) and median platelet nadir was 90,000 (range 10,000 to 289,000). Fifteen patients received three or more cycles at one dose level; cumulative myelosuppression was observed in 11. Two cases of partial alopecia occurred at 40 and 60 mg/m2 thio-TEPA. Responses were as follows: complete response, 5; partial response, 7; stable disease, 14; progressive disease, 8. In 16 patients with ovarian cancer (15 of whom had previously received cisplatin), there were 4 complete responses and 5 partial responses (overall response rate of 56%). The thio-TEPA dose recommended in combination with cisplatin (50 mg/m2) in phase II trials is 40 mg/m2. Cumulative hematologic toxicity may occur with this regimen.

Agranulocytosis↗
PubMed1989

Lumbar synovial cysts: report of eleven cases.

Over the past 18 months we have encountered 11 cases of symptomatic lumbar synovial cysts. This experience occurred during a period during which some 1,800 lumbar computed tomographic scans were done. The apparent increased incidence of these lesions is most likely due to the increased diagnostic ability made possible by the advent of high-resolution computed tomography and magnetic resonance imaging. This is a report and discussion of our 11 cases with a review of the literature. There is nothing distinctive in the physical findings or in the histories of our patients, but we have found, as have others, that high-resolution computed tomographic scanning and magnetic resonance imaging significantly enhance the diagnosis of such lesions.

Adult↗
PubMed1985

Intracerebral hemorrhage with rapid recovery.

Occasionally, patients with small supratentorial intracerebral hemorrhages exhibit the sudden onset of neurologic deficits, followed by rapid improvement during the next several days. We analyzed the computed tomographic (CT) and clinical features of a group of nine such patients, who were drawn from a series of 120 patients with intracerebral hemorrhage. The temporal pattern of illness was similar to that of a cerebral ischemic event, but the correct diagnosis of intracerebral hemorrhage was made on the basis of the CT findings.

Adult↗
PubMed1984

Does practice make perfect? Part II: The relation between volume and outcomes and other hospital characteristics.

The effect of a greater volume of patients with similar conditions being treated at a hospital on the outcomes achieved is investigated for almost 500,000 selected surgical and medical patients treated in over 1,200 nonfederal United States hospitals. In Part I the authors found strong and consistent evidence for surgical patients that high volume is associated with better outcome; evidence for medical patients was mixed. In this paper the authors include other hospital variables related both to volume and outcome--hospital size, teaching status, and expenditures--to determine whether they mask the true relationship; still, strong and consistent evidence that greater volume produces better outcome was found for both surgical and medical patients. This relation was significant for low-, medium-, and high-risk patients. Among the hospital variations added, only size was consistently and strongly related to outcome; greater size was associated with poorer outcome after accounting for volume. The potential importance of the findings for reducing deaths and days in hospital on a national level is discussed. The evidence is strongly supportive of the need for policies that would promote greater regionalization of a given service, and not greater size, to obtain better quality outcome for patients treated.

Bed Occupancy↗
PubMed1984

Does practice make perfect? Part I: The relation between hospital volume and outcomes for selected diagnostic categories.

The effect of a greater volume of patients with similar conditions being treated at a hospital on the outcomes achieved is studied using a variety of categories of patients, 15 surgical and 2 medical, and involving 550,000 patients treated in over 1,200 nonfederal United States acute care hospitals. After demonstrating that there are significant differences in the outcomes of patients, taking into account patient health status, the authors examine the impact of being treated in a hospital with a high or low volume of similar patients. Strong and consistent evidence is found that high volume is associated with better outcomes for surgical patients, which supports regionalizing patient care by procedure. Two additional variables, relative difficulty of the procedure and risk level of the patients, are analyzed to determine whether they change the relationship between volume and outcome. Some evidence is found that low-volume hospitals are associated with the poorest outcome for low-risk surgical patients. The evidence for medical patients is weak and mixed. Possible alternative explanations for the observed findings for surgical and medical patients are discussed.

Female↗
PubMed1983

Measurement of lung emptying patterns during slow exhalations.

Five subjects slowly inhaled a 200-ml bolus of sulfur hexafluoride (SF6) from residual volume (RV) followed by an O2-Ar mixture to total lung capacity, then exhaled to RV, either slowly or as rapidly as possible. Larger amounts of SF6 and N2 were recovered in fast than in slow exhalations. We calculated the gas volumes of the apical and basal halves of the parenchymal mass as functions of exhaled volume during slow exhalations from 1) the difference between SF6 recovered in slow and fast exhalations and 2) an estimate of the apex-to-base concentration profile of SF6 in the lung after inspiration. The maximal volume difference, where the apex contained 600 ml more gas than the base, occurred when 70% of the vital capacity had been exhaled. The same calculation, but using N2 data, gave unrealistically large volume differences. Apparently SF6 delivered as a bolus results in an apex-to-base gradient that is large relative to intraregional gradients, but dilution of the resident N2 by a non-N2 gas results in sizable intraregional gradients.

Humans↗
PubMed1982

Managing professional work: three models of control for health organizations.

Three arrangements for structuring the work of professional participants in professional organizations are described, contrasted and evaluated. Arguments are illustrated by application to the organization of physicians within hospitals. The primary rationale, the support structures that have fostered its development, the key structural features and the advantages and disadvantages of each arrangement are described. The effect on these arrangements of structures and forces external to any particular professional organization is emphasized.

Administrative Personnel↗
PubMed1982

Effectiveness in professional organizations: the impact of surgeons and surgical staff organizations on the quality of care in hospitals.

In this research, we examine the relative importance of different structural units in a professional organization, the hospital, as they affect organizational effectiveness. The difficulties of measuring effectiveness in a complex professional organization are discussed, and an adjusted measure of surgical outcome is developed. Data are drawn from a prospective study of over 8,000 surgical patients treated by more than 500 surgeons in 15 hospitals throughout the nation. Two different types of analyses are presented, both indicating that hospital features have more impact on surgical outcomes than do surgeon characteristics. The second analysis assesses the relative importance of specific attributes of the hospital, surgical staff organization, and surgeon characteristics on surgical outcomes.

Costs and Cost Analysis↗