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Biomedical subjects

S V Williams

Publications and source records attributed to S V Williams.

At least 19 recordsLinked to original sources
PubMed1992

Appearance of Ph negative recipient clones in chronic myeloid leukemia patients following bone marrow transplantation.

Seven patients were studied following bone marrow transplantation for chronic myeloid leukemia. Cytogenetic heteromorphisms were used to determine the origin of cells present post-BMT. Differences were found between results from blood and bone marrow samples, and between karyotype and interphase Y-body studies on the same samples. Philadelphia negative (Ph-) hematopoietic chimerism was found in 6 of 7 patients, all of whom had been Ph+ before BMT. One patient also demonstrated hematopoietic chimerism with Ph+ recipient cells following clinical evidence of relapse. In two patients who had received T-cell depleted grafts, cytogenetically rearranged Ph- clones of recipient cells were prominent in PHA-stimulated blood. In one case two clones had appeared only 1 month post BMT. The appearance of these clones so soon after transplant suggests very rapid clonal expansion, or that they were already present pre-BMT but at levels too low to have been detected. In the second patient, clones were not observed until more than 12 months post-BMT, after which four were found. These collectively expanded to occupy an increasing proportion of the total cells. These two patients with clones both remain in good health 44 and 51 months post-BMT. Further studies are needed to determine the true frequency and the significance of such findings.

Adult↗
PubMed1992

Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue.

We asked if the factors that predict overall mortality following two common surgical procedures are different from those that predict adverse occurrences (complications) during the hospitalization or death after an adverse occurrence, which we refer to as "failure to rescue." We examined 5,972 Medicare patients undergoing elective cholecystectomy or transurethral prostatectomy using three outcome measures: 1) the death rate (number of deaths/number of patients); 2) the adverse occurrence rate (number of patients who developed an adverse occurrence/number of patients); and 3) the failure rate (number of deaths in patients who developed an adverse occurrence/number of patients with an adverse occurrence). The death rate was associated with both hospital and patient characteristics. The adverse occurrence rate was associated primarily with patient characteristics. In contrast, failure to rescue was associated more with hospital characteristics, and was less influenced by patient admission severity of illness as measured by the MedisGroups score. We concluded that factors associated with hospital failure to rescue are different from factors associated with adverse occurrences or death. Understanding the reasons behind variation in mortality rates across hospitals should improve our ability to use mortality statistics to help hospitals upgrade the quality of care.

Age Factors↗
PubMed1991

Gene amplification accompanied by the loss of a chromosome containing the native allele and the appearance of the amplified DNA at a new chromosomal location.

The organization of amplified DNA in mammalian cells in the form of inverted repeats rather than tandem repeats was first observed and studied in the 3B rat cell line. The structure and chromosomal location of the amplified inverted duplications in this cell line have been further analyzed by cloning, long-range mapping, and fluorescence in situ hybridization. The amplification unit is at least 450 kilobases in size and all of the amplicons are located in a single chromosomal location of approximately 10 or 11 megabases. No heterogeneity in either size or molecular structure is detected between the 3B amplicons, indicating that the 20- to 40-fold amplification occurred in a single event and not through a series of events, which would result in heterogeneity among the amplicons. Thus the amplification in 3B cells may reflect more closely the situation seen in tumors containing amplified oncogenes/protooncogenes than the amplifications present in cell lines after multiple selections with cytotoxic drugs. The progenitor Rat-2 cell line contains three alleles of the region of DNA that is amplified in 3B cells; two are located on the two normal homologues of rat chromosome 2 and the third is at the equivalent position on a marker chromosome, der(3)t(2;3). 3B cells contain only one of the two normal homologues of chromosome 2 in addition to chromosome der(3)t(2;3). All of the amplified DNA is located on a new marker chromosome, M2, whose amplified DNA region does not resemble chromosome 2. These results are consistent with the amplification model proposed by Passananti et al. [Passananti, C., Davies, B., Ford, M. & Fried, M. (1987) EMBO J. 6, 1697-1703], in which the excision from a chromosome of the DNA to be amplified results in the loss of rearrangement of that chromosome. In this model the excised DNA can be amplified extrachromosomally during a single S phase before becoming stabilized by integration into a chromosome, probably at a different location to that of its unamplified allele.

Alleles↗
PubMed1991

Differences in mortality from coronary artery bypass graft surgery at five teaching hospitals.

OBJECTIVE: To measure hospital- and surgeon-specific mortality rates for patients with coronary artery bypass graft (CABG) surgery and to examine possible reasons for any differences. DESIGN: Cohort study using hospital discharge abstracts and itemized bills. SETTING: Five major teaching hospitals in Philadelphia, Pa. PATIENTS: Consecutive sample of all 4613 patients over a 30-month period. MAIN OUTCOME MEASURE: In hospital mortality rates. RESULTS: We observed differences in hospital mortality rates for patients who underwent coronary artery catheterization and CABG surgery during the same admission (diagnosis related group 106) but not for patients who underwent only CABG surgery during the admission (diagnosis related group 107). There were threefold differences in surgeon-specific mortality rates. The hospital mortality rates for coronary artery catheterization and CABG surgery during the same admission changed during the study and coincided with moves of surgeons among study hospitals. Our measures of illness severity did identify patients who were more likely to die, but differences in severity of illness did not explain differences in hospital- or surgeon-specific mortality rates. Patient mortality rates were not associated with the volume of procedures performed by individual surgeons. We found inconclusive evidence for an association with surgeons' clinical skills, and to a lesser extent, with the hospital's volume of procedures and the hospital's organization and staffing. A greater intensity of hospital services was not necessary for a lower mortality rate. CONCLUSIONS: We conclude that studies of CABG mortality should examine mortality rates by diagnosis related group, collect data from more than 1 year, examine associations with surgeons' clinical skills, include information on hospital organization and staffing, and cautiously explore more efficient ways of providing care.

Age Factors↗
PubMed1991

Molecular cloning and analysis of the fragile X region in man.

The fragile X syndrome (FraX), the most common inherited form of mental retardation, has been located to Xq27.3. As a step in the molecular analysis of this mutation, we have cloned a contiguous 1.8 Mb region containing the entire fragile X region in YAC and cosmid clones. The cloned area defines a region of 50 kb containing a CpG island, found to be selectively methylated in patients expressing the fragile X phenotype. In this 50kb area we have localised the breakpoints of four somatic cell hybrids selected to break at the position of the fragile site. Fluorescence in-situ hybridisation of cosmids flanking this area shows that the breakpoints, the CpG island and the fragile site coincide.

Chromosomes, Fungal↗
PubMed1991

Fine mapping of probes in the adenomatous polyposis coli region of chromosome 5 by in situ hybridization.

The gene for adenomatous polyposis coli has been localized to 5q21-22. We have mapped six probes from this region using isotopic or nonisotopic in situ hybridization. Using tritium-labeled probes we localized II227 (D5S37) to 5q14-15 and ECB27 (D5S98) to 5q21. Following hybridization with biotin-labeled probes, the positions of signals along the chromosomes were measured as fractional length relative to the length of the chromosome arm from centromere to qter (FLcen-qter). Ninety-five percent confidence limits, compared with standard karyotypes, provided the corresponding band localization. By this method we localized Cllpll (D5S71) to FLcen-qter 0.407-0.452 (5q21.1-21.3), ECB27 to FLcen-qter 0.426-0.473 (5q21.3), YN5.48 (D5S81) to FLcen-qter 0.459-0.496 (5q21.3-22.2), and ECB134 (D5S97) to FLcen-qter 0.509-0.533 (5q22.3-23.1). ECB220 had three sites of hybridization, a major site at FLcen-qter 0.460-0.492 (5q21.3-22.1) and minor sites at FLcen-qter 0.299-0.339 (5q14.3-15) and FLcen-qter 0.629-0.691 (5q23.3-31.2). We have shown that the chromosome 5 breakpoint in a t(5;15) translocation from a patient with Gardner's syndrome (GM03314) is between Cllpll and ECB27. Linkage data are presented suggesting that ECB27 is located on the same side of the APC locus as II227. These and published results including data on several constitutional deletions (M, SD, and brothers PW and ND) give a probable order of [cen] - [II227, proximal SD breakpoint] - [Cllpll] - [proximal PW/ND, M breakpoint(s), GM03314 breakpoint] - [ECB27] - [APC] - [YN5.48] - [distal PW/ND breakpoint] - [ECB134] - [distal M breakpoint] - [qter]. The major site of ECB220 appears to be between ECB27 and the distal PW/ND breakpoint; the distal SD breakpoint is distal to YN5.48.

Adenomatous Polyposis Coli↗
PubMed1990

Expansion of the medical intensive care unit: clinical consequences in a large urban hospital.

We examined how a permanent expansion of the medical ICU (MICU) affected resource utilization and severity of illness for intensive care admissions within a 700-bed urban teaching hospital. On our 162-bed medical service, construction of a separate cardiac care unit and the expansion of the MICU increased the number of core intensive care beds by 100%. We prospectively analyzed noncardiology MICU admissions 2 months before, immediately after, and 4 months after MICU expansion. Although the volume of MICU patients increased by 51% after MICU expansion, the severity of illness as determined by the Acute Physiology and Chronic Health Evaluation (APACHE II) score and types of admission diagnoses remained the same. Moreover, there was no change in MICU occupancy and length of stay, hospital or MICU mortality, or MICU readmission rate. The increased MICU patient volume came from the ED, transfers from other hospitals, and from other ICUs within our hospital. In contrast, the volume and severity of illness of MICU transfers from the inpatient medical floor service were constant in all time periods. These results suggest that, while MICU expansion increased patient volume, physician utilization of the MICU resources was unchanged. Our physicians used high-intensity ICU beds in a consistent fashion in response to external factors, such as ED activity, intramural ICU transfers, and referrals from other hospitals.

Bed Occupancy↗
PubMed1990

Predicting inpatient rehabilitation length of stay.

Using standardized forms and predefined criteria, information was collected on all 1,238 patients admitted to the inpatient rehabilitation facility at our university hospital between August 1, 1980 and December 30, 1986. Data from 96% of these patients were used retrospectively to create a mathematic model, based on multiple linear regression, that predicts the patient's total rehabilitation length of stay (LOS). The model requires only information about the patient's admitting diagnosis, referral source, admission functional status, and date of admission. The model compared favorably with prospective estimates of LOS made independently by attending physicians at admission to rehabilitation. We conclude that such models could be used to facilitate management of rehabilitation units, forecast patient census, schedule unit personnel, set interim goals for LOS, and facilitate discharge planning. The delivery of rehabilitation services, like the delivery of other medical services, can be defined in part by objective, measurable patient characteristics.

Adult↗
PubMed1988

Guiding individual decisions: a randomized, controlled trial of decision analysis.

In early 1983, all 1,280 faculty and resident physicians at one hospital who were eligible to be vaccinated against hepatitis B were divided randomly into three groups: Group 1 physicians received general information about the risks and benefits of alternative vaccine decisions; Group 2 physicians were additionally invited to provide personal information for an individualized decision analysis (12.6 percent responded); and Group 3 physicians, who served as controls, were not contacted. In one year's follow-up, 20 percent of physicians were screened for hepatitis B antibody or vaccinated. More Group 2 physicians whose decision analyses recommended screening or vaccination took these actions (39 percent) than any other group. Group assignment remained significantly associated with vaccine decisions after analyzing results by the "intention to treat" principle, and after adjusting for training status, exposure to blood and blood products, and pre-study intentions about the vaccine. Despite the low overall vaccine acceptance rate, it is concluded that individualized decision analysis can influence the clinical decisions taken by knowledgeable and interested patients.

Clinical Trials as Topic↗
PubMed1987

Gout and pseudogout of the temporomandibular joint.

The temporomandibular joint is rarely affected by gout or pseudogout. The following article presents two case reports that demonstrate gout and pseudogout of the temporomandibular joint. The surgical treatment and diagnostic criteria for these entities are presented and discussed.

Adult↗
PubMed1986

Comparing aggregate estimates of derived thresholds for clinical decisions.

Thresholds for medical decision making are the probabilities of disease at which clinicians choose to initiate testing or therapy. A descriptive analysis of clinicians' decision making can derive their test and test-treatment thresholds and has the potential to explain variations in test utilization. A previously described method summarizes thresholds for a group of clinicians by determining the range of probability which includes the maximum number of clinicians' individual thresholds. However, there is no statistical procedure to compare the summary measure of thresholds that is derived from the distribution of clinicians' thresholds. We describe two alternative methods of developing a summary measure of the thresholds for a group of clinicians. These alternative methods enable the analyst to apply standard statistical tests when analyzing the decision-making behavior of groups of clinicians. For the "Unweighted Mean of the Midpoints" method, confidence limits of means and standard t-tests can be used to compare different groups. For the "Weighted Mean of the Midpoints" method, a weighted standard error of the mean can be calculated to determine confidence intervals, and a weighted t-test or weighted regression can be used to compare weighted means of the midpoints of threshold ranges.

Angiography↗
PubMed1985

The impact of DRG-based prospective payment on clinical decision making.

The Medicare Prospective Payment System (PPS) and the financial incentives it creates are likely to influence physician practices, as well as to offer new opportunities for research into clinical decision making. Hospital managers and physicians alike will need to look increasingly to decision analysis for answers regarding technology assessment and the cost-effectiveness of clinical practices. Areas of research in which decision analysis might contribute significantly include: the compromise between cost and quality, the comparative advantages of outpatient versus inpatient procedures, and the appropriate timing of patient discharge or transfer.

Cost Control↗
PubMed1984

Methodological limitations in case mix hospital reimbursement, with a proposal for change.

We have found five methodological limitations in the creation and implementation of the diagnosis related group (DRG) patient classification system, which is used to define a hospital's case mix. There are four methodological limitations in the system that Klastorin and Watts have proposed to identify hospital peer groups. We conclude that the effects of these limitations should be sought, and we propose studies to measure their extent. We also propose that these two approaches can be combined to create an improved hospital reimbursement program that accurately measures differences between hospitals caused by case mix and peer group characteristics.

Costs and Cost Analysis↗
PubMed1984

Health insurance under competition: would people choose what is expected?

To determine relative preferences for different cost-sharing options, we asked a 17% random sample of 2,754 nonunion employees to compare health insurance policies that differed in the level of 1) deductible amount, 2) coinsurance rate, 3) coinsurance limit, 4) maximum liability, and 5) price. Using conjoint analysis, we derived preference curves for each of the five components and measured preferences for the compromise between more coverage and the corresponding price increase. In contrast to other studies, our findings suggest that under fair market prices, respondents would choose policies with greater coverage for catastrophic illness, and they would as likely choose cost-sharing policies that contain incentives to reduce utilization as they would choose policies without these incentives.

Adult↗
PubMed1977

Computer-based audit to detect and correct overutilization of laboratory tests.

We developed a computer-bases system to detect inappropriate use of the clinical laboratory and tested a program of physician education to reduce overutilization. We modified the hospital laboratory's computerized reporting system to identify medical patients with three or more determinations of lactic dehydrogenase (LDH) or calcium during the preceding seven days. We audited the charts of these patients, using explicit criteria, to determine whether multiple studies were justified. During the control period 51 per cent of the charts audited for multiple determinations of LDH revealed overutilization. During the study period, when physicians were notified if overutilization was found, 65 per cent of the charts showed overutilization. This difference was not significant. A simultaneous, undisclosed audit of calcium determinations also showed no change between the two periods. Therefore, this method is effective in detecting and measuring overutilization of the laboratory. It is a method which is easily adaptable to a hospital's computerized laboratory reporting system, and it can be applied without a computer. However, our program of notification and education of physicians is not effective in reducing overutilization. More effective methods of modifying physicians' use of laboratory tests need to be developed.

Calcium↗
PubMed1975

Dental infection with hepatitis B.

We performed a prospective study to assess the risk of patients acquiring infection following routine professional contact with two dentists incubating type B viral hepatitis. Serum samples from patients exposed during the six weeks before onset of hepatitis in the dentists were tested for hepatitis B surface antigen and for antibody to the antigen shortly after illness developed and again six months later. Household members of exposed patients served as a control group. None of the exposed patients or controls became ill with hepititis, and none developed antigen. Three of the 237 exposed patients developed antibody, as did four of the 245 controls. The difference between exposed patients and controls was not significant. These results do not support the hypothesis that these two dentists transmitted infection to their patients.

Carrier State↗