Fermi surfaces, fermi liquids, and high-temperature superconductors.

Recent experimental results are beginning to limit seriously the theories that can be considered to explain high-temperature superconductivity. The unmistakable observations of a Fermi surface, by several groups and methods, make it the focus of realistic theories of the metallic phases. Data from angle-resolved photoemission, positron annihilaton, and de Haas-van Alphen experiments are in agreement with band theory predictions, implying that the metallic phases cannot be pictured as doped insulators. The character of the low energy excitations ("quasiparticles"), which interact strongly with atomic motions, with magnetic fluctuations, and possibly with charge fluctuations, must be sorted out before the superconducting pairing mechanism can be given a microscopic basis.

Isolation and characterization of a monoclonal antibody specific for epithelial cells.

Monoclonal antibodies were generated to antigens on human foreskin keratinocytes to identify epithelial-specific molecules. Spleen cells from BALB/c mice, immunized with membrane preparations from primary explants of foreskin epithelial cells, were fused with the NS-1 mouse myeloma line. Hybridoma supernatants were screened for the desired immunological reactivity using enzyme-linked immunosorbant binding assays. Hybridomas secreting antibodies reacting with epithelial cells, but not fibroblasts or lymphocytes, were cloned by limiting dilution, and two stable clones producing immunoglobulin M K antibodies were selected for study. Evaluation of fixed paraffin-embedded human tissue by an indirect immunoperoxidase technique revealed that the antibodies bound most strongly to normal stratified squamous and transitional epithelium, and squamous and transitional cell carcinomas. Antibodies from the cloned hybridomas also reacted with primary cell cultures of foreskin keratinocytes, pulmonary epithelium, fetal liver, and amnion cells, but not with primary cultures of nonepithelial cells. Further testing by enzyme-linked immunosorbent assays revealed that the antibodies reacted with some long-term cell lines derived from epithelial tumors. Nonepithelial cell lines were not stained by the antibodies. Indirect immunofluorescent studies indicated that staining was confined to the cell surface. These antibodies may prove useful in studies of differentiation markers of human epithelial cells.

A method for the quantitative analysis and standardization of interleukin-1 bioactivity.

A method is presented for the reproducible quantitation of the biological activity of interleukin 1 (IL-1). This method provides diagnostic tools which give insights into the qualitative aspects of the binding of IL-1 and of the resulting activation of the responder thymocytes; for example, whether the lymphokine and/or the responder population is heterogeneous, or whether a threshold level exists. It establishes under what circumstances the assumptions on which it is based are reasonably adhered to and, consequently, quantitative estimation in the manner it prescribes is justified. It also gives a simple way to calculate both the maximal response attainable for each preparation in an assay and the dilution of a particular preparation that would produce a half-maximal response, the accepted unit of activity of IL-1. This empirical technique provides an improved means of comparing the activities of various preparations of IL-1 in bioassays using various stocks of responder cells and reagents. It should also be applicable to the evaluation of the biological activity of lymphokines in general.

Analysis of the heterogeneity of the biological responses to native and mutant human interleukin-6.

The structure-function relationships of the biological activities of mutant varieties of the pleiotropic cytokine interleukin-6 (human) were measured by three assays: induction of immunoglobulin M (IgM) secretion from an Epstein-Barr virus-transformed human B cell line and induction of fibrinogen secretion from either a human hepatoma cell line or a rat hepatoma cell line. The biological effects of the cytokine were characterized by three parameters as determined by a novel analysis: effectiveness (the maximal response attainable), efficiency (the concentration yielding a half-maximal response), and complexity (a measure of heterogeneity and feedback control). Substitution of serine for cysteine was associated with a reduction in the effectiveness of interleukin-6 in both fibrinogen secretion assays. In the assay with human hepatoma cells, there was also a profound reduction in efficiency. Serine substitution in the human IgM synthesis assay appears mainly to reduce the efficiency. Deletion of amino acids 4 to 23 increased the efficiency in the rat hepatoma assay. The complexity parameter suggests the presence of multiple receptor classes or negative feedback in all three assays. Use of the proposed sequential approach to the analysis of dose-response relations in bioassays provides a more useful quantitative assessment of activities as well as more insight into the complexity of the reactions.

An analysis of liver transplant experience from 37 transplant centers as reported to Medicare.

Analysis of 5180 liver transplant cases from 37 liver transplant centers in the United States (1982-1991) shows an overall one-year survival rate of 79.4 +/- 0.6% and a five-year survival rate of 69.2 +/- 0.9%. There was marked improvement in the one-year survival rate after liver transplantation from 36.0 +/- 9.6% in 1982 to 85.0 +/- 1.8% in 1991. One-year survival rates after liver transplantation for postnecrotic cirrhosis, primary biliary cirrhosis, alcoholic cirrhosis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, and Wilson's disease ranged from 78.4 +/- 1.0% to 84.2 +/- 1.5% and five-year survival rates from 68.6 +/- 3.8% to 79.2 +/- 5.3%. Survival rates after liver transplantation for hemochromatosis were poor--a one-year survival rate of 53.8 +/- 6.8% and a five year survival rate of 43.1 +/- 11%. One- and five-year survival rates for the 0-13 years age group were 74.6 +/- 2.8% and 66.7 +/- 3.4%; for the 14-37 years age group, 83.3 +/- 1.2% and 73.8 +/- 1.8%; for the 38-54 years age group, 79.6 +/- 0.8% and 69.7 +/- 1.3%; for the 55-63 years age group, 76.0 +/- 1.4% and 63.0 +/- 3.1%; and for the 64-77 years age group, 76.5 +/- 3.0% and 65.4 +/- 4.6%.

The relationship of clinical outcomes to status as a Medicare-approved heart transplant center.

This study reports the evaluation of the validity and utility of the Medicare heart transplant center selection process, as outlined in its 1986 Heart Coverage Regulations. A total of 9401 heart transplants performed in the U.S. between 1986 and 1991 were analyzed. The outcomes assessed were mortality and the occurrence of infection during the hospital stay. Outcomes experienced by centers with and without Medicare approval were compared directly and following adjustment for patient risk factors. Patients at centers that satisfied the Medicare criteria experienced lower mortality. The risk-adjusted hazard ratio for death over the five years of observation was 0.874 (P = 0.005). The probability of death following a transplant at a Medicare-approved center was 7.0 +/- 0.4% at 30 days and 16.2 +/- 0.6% at one year, and 9.2 +/- 0.4% and 19.2 +/- 0.6%, respectively, at centers without Medicare approval (P = 0.001). The difference appeared to be principally associated with death within 30 days of admission due to nonspecific graft failure. The posttransplant infection rate at Medicare-approved centers was 0.743 (P < 0.001) but this result is strongly confounded with differences in reporting patterns of the two types of centers. Criteria used by HCFA identify medical centers where outcomes of heart transplantation, as measured by mortality, are superior. This difference is established early, persists over time, and is not attributable to the numerous risk factors considered in our models. Overall, the results of the present study suggest that "centers of excellence" can be identified through the evaluation of center characteristics and outcomes, and that this approach chosen by HCFA may have broad health care systems applications.

Assessment of prognostic factors and projection of outcomes in renal transplantation.

Analysis of data on renal transplantation collected in two large multicenter observational studies resulted in the concordant identification of five factors that correlated highly and at a substantial level of statistical significance with the outcome of unrelated cadaveric donor transplantation (i.e., they were associated with differences in one-year graft survivals of 0.07-0.21 and P values less than 0.05). These factors were: blood transfusions prior to the transplant, race of the recipient (white or black), prior failure in transplantation, level of sensitization to lymphocyte alloantigens, and diabetes as the cause of end-stage renal failure. Multivariate analysis with a mathematical survival model confirmed the importance and independence of these prognostic factors. Matching of HLA antigens appeared to be beneficial in both studies, but failed to attain high statistical significance in one. Systematic differences in the use of pretransplant splenectomy and, probably, in the nature of the antilymphocyte serum or globulin led to discordance in assessment of the importance of these factors in the two studies. Although advanced age (greater than 45 years) of the recipient was associated with reduced graft survival in both studies, analysis by means of the model failed to detect a significant correlation between the recipient's age and the outcome in one of the studies because the relation was not monotonic. In an illustration of their utility in the detailed assessment of performance, the prognostic factors were found to substantially account for the markedly superior results at one center and partly for lower graft survivals at another. These prognostic factors may be used to predict probable outcomes for populations and for individual patients subjected to particular arrays of conditioning strategies.

Mortality after coronary angioplasty and coronary artery bypass surgery (the national Medicare experience).

Mortality rates for Medicare patients who underwent coronary artery bypass surgery were compared with those who had angioplasty or angioplasty and bypass surgery. Two data sets were used for this study: The first contained information on demographic factors, co-morbidities and subsequent mortality on all 96,666 Medicare patients who had bypass surgery or angioplasty in 1985; the second contained additional detailed clinical data collected using the MedisGroups method on a random sample of 2,931 revascularization patients from 6 states. From the national data set 30-day and 1-year mortality rates were 3.8 and 8.2% for 25,423 angioplasty patients and 6.4 and 11.8% for 71,243 bypass surgery patients (p less than 0.001 for both time periods). Mortality rates for the MedisGroups data were 4.4 and 8.5% for the angioplasty patients and 6.5 and 11.9% for the bypass surgery patients. After eliminating patients admitted with a myocardial infarction, mortality rates were 1.9 and 6.0% for 632 angioplasty patients and 5.1 and 10.8% for 1,730 bypass surgery patients. The risk-adjusted relative risk of mortality for bypass surgery versus angioplasty was 1.72 (p = 0.001) for all patients, 2.15 (p less than 0.001) for low-risk patients and 0.90 (p = not significant) for high-risk patients. Results suggest that low-risk patients have better survival with angioplasty because of lower short-term mortality.

Monoclonal antibodies specific for human polymorphic cell surface antigens. I. Evaluation of methodologies. Report on a workshop.

Five techniques, the direct and the antiglobulin enhanced cytotoxicity assays, indirect immunofluorescence, the enzyme-linked immunosorbent assay, and the radioimmunoassay, were evaluated in a workshop to determine their utility in studies of the interactions of monoclonal antibodies with HLA antigens expressed on lymphocytes. Several well-defined antibodies, both cytotoxic and noncytotoxic, were tested against well-characterized human lymphoid cells. All the methods suffer from some deficiency. The enhanced cytotoxicity assay, however, is most useful as a routine screening tool because of its ease and simplicity; whereas, the enzyme-linked immunosorbent assay is most useful when dissection of antigenic structure is sought because it yields information on the quantities of the antigenic determinants expressed on the cell surface without requiring radioactive reagents.

Serum levels of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 in hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome is an acute viral disease caused by hantavirus. On the basis of clinical observation, the illness is divided into five sequential stages: febrile, hypotensive, oliguric, diuretic, and convalescent. Because interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) are mediators responsible for fever, septic shock, and acute phase protein induction, we examined, using ELISA, the presence of these three cytokines in 276 sera collected during the Korean Conflict from 110 patients. Detectable levels (> 20 pg/ml) of TNF-alpha, IL-1 beta, and IL-6 occurred in 14, 14, and 33% of these samples, respectively. There was a significant correlation between serum levels of IL-1 beta and TNF-alpha (r = 0.66, p < 0.001), IL-1 beta and IL-6 (r = 0.59, p < 0.001), and IL-6 and TNF-alpha (r = 0.71, p < 0.001). The pathophysiologic processes of HFRS do not have clear or consistent correlations with alterations in the levels of the cytokines studied.

Serum levels of alpha and gamma interferons in hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome is an acute viral disease caused by Hantavirus. On the basis of clinical observation, the illness is divided into five sequential stages: febrile, hypotensive, oliguric, diuretic, and convalescent. Because interferons can be induced by viruses, and because their stimulating effects on immune cells can alter the course of viral infections, we examined the presence of alpha interferon (IFN-alpha) and gamma interferon (IFN-gamma) in 276 serum samples collected from 110 patients during the Korean Conflict. We tested these sera for IFN-alpha by bioassay with bovine kidney MDBK cells, and for IFN-gamma by a sandwich ELISA with antibodies specific for human IFN-gamma. We found variable, but persistently elevated levels of IFN-gamma throughout the various phases of the disease, which suggested persistent immune activation through convalescence. Moderate levels of IFN-alpha were found in all stages of infection.

Double-blind comparison of weekend and daily regimens of oral acyclovir for suppression of recurrent genital herpes.

The potential utility of intermittent regimens of oral acyclovir for suppression of recurrent genital herpes depends on how long the suppressive effect of the drug persists during pauses in treatment. To study this question, we admitted 38 patients in a double-blind controlled trial comparing the results of daily acyclovir treatment (200 mg t.i.d.) with treatment on weekend days only (400 mg t.i.d. on Saturday and Sunday) for suppression of recurrent genital herpes. Of the 35 patients completing the study, significantly more failures occurred in the weekend group (13/17) than in the daily group (3/18, P less than 0.001). Failures on the weekend regimen were more frequent as the week progressed (P = 0.005). The findings suggest a short-term persistence of suppression by acyclovir and hence that intermittent regimens with more closely spaced periods of treatment may be more effective than the regimen we studied. Most virus isolates studied, including all of those isolated from the patients during treatment, were sensitive to acyclovir.

National outcomes of cataract extraction. Endophthalmitis following inpatient surgery.

We analyzed the likelihood of rehospitalization for endophthalmitis in 338,141 Medicare beneficiaries over age 65 years who were admitted to US hospitals for cataract extraction in 1984. This cohort represents approximately one half of all persons who underwent cataract extraction under the Medicare program in 1984. Extracapsular extraction was performed in 195,587 (58%) of cases, intracapsular cataract extraction in 99,971 (30%), and phacoemulsification in 28,474 (8%). The risk of rehospitalization for endophthalmitis in the year following surgery was 0.17% for intracapsular cataract extraction compared with 0.12% for extracapsular extraction or phacoemulsification (P less than .002). The risk of endophthalmitis at 1 month was higher for intracapsular cataract extraction than for extracapsular extraction or phacoemulsification (0.11% vs 0.085%), although the difference did not reach statistical significance. Cataract surgery accompanied by anterior vitrectomy increased the 1-month risk of rehospitalization for endophthalmitis to 0.41%, more than a four-fold increase over that for cataract surgery alone (0.09%; P less than .05). The rates of endophthalmitis at 1 year were 0.58% and 0.13%, respectively, for cataract surgery with anterior vitrectomy and cataract surgery alone (P less than .0001). No significant differences in the rate of rehospitalization for endophthalmitis were observed based on the use of an intraocular lens, age, or race. Endophthalmitis within 1 year of surgery was 1.2 times more frequent in men than in women (0.16% vs 0.13%; P = .03). Overall, the likelihood of postoperative endophthalmitis from a national sample is consistent with case series previously reported.

Mortality and reoperation following prostatectomy: outcomes in a Medicare population.

Data from a series of pilot projects undertaken by the Health Care Financing Administration and seven peer review organizations were used to evaluate the outcomes of prostatectomy. Outcomes in both the original random sample of 3,641 patients and subsample of 2,617 patients that had a diagnosis of benign prostatic hyperplasia and did not have a diagnosis of prostatic carcinoma were examined. Patients undergoing a transurethral resection had increased probabilities of reoperation and mortality. However, the increased risk associated with having a transurethral resection was not statistically significant after controlling for other variables associated with mortality.

Light-scattering studies of the alpha-ketoglutarate dehydrogenase complex from escherichia coli. I. Characterization of the self-association of the complex.

The self-association of Escherichia coli alpha-ketoglutarate dehydrogenase complex (KGDC) purified by a column Chromatographic technique, was characterized by light-scattering photometry. The complex adopts a solution conformation somewhat larger than that observed in the electron microscope. The evidence suggests a nonideal indefinite self-association model for KGDC in KCl, phosphate buffer. The KGDC monomer has a molecular charge of about -3 x 10(2) at neutral pH. The self-association is promoted by increasing KCl concentrations, pH (in the range from 6.3 to 7.4) and temperature (from 20 to 30 degrees C). The effects of pH changes suggest a release of protons during the self-association and a minor 'preferential' interaction of phosphate ions. For the association of one monomer to the aggregate at neutral pH and 25 degrees C. DeltaG degrees = -7.8 kcal mol(-1). DeltaH degrees = 24 kcal mol(-1) and DeltaS degrees = 1.1 x 10(2) cal mol(-1) K(-1). These data indicate that hydrophobic interactions drive the association. Thermodynamically, the self-association of KGDC is a complex phenomenon and may serve to stabilize the enzyme complex in solution.

Physician impact on hospital admission and on mortality rates in the Medicare population.

OBJECTIVE: We assess the effect of variations in the supply and specialty distribution of physicians on admission rates for ambulatory care-sensitive conditions (ACS) and for all causes, and on mortality rates among Medicare beneficiaries of various health care service areas (HCSA). DATA SOURCES: For the Medicare beneficiaries, sources were the Health Care Financing Administration's 1992 enrollment and impatient (Part A) files for a 5 percent sample of that population; for the overall populations and for the medical resources of the HCSAs, the Area Resource File. STUDY DESIGN: This observational, cross-sectional study employed multiple linear regression to assess the influence of population characteristics and of the supply of physicians on hospital admissions, and Poisson regression in the analysis of the factors that affect mortality. PRINCIPAL FINDINGS: Physician supply levels vary nearly fourfold or more when comparing the top and bottom deciles of the HCSAs, Medicare admissions for ACS conditions vary about threefold, and admission rates for all causes and mortality rates vary about 1.5-fold. Physician supply levels and distributions have very little influence on ACS admission rates, and even less on the admissions for all causes and on mortality, except in HCSAs with very low physician supply levels (one-fourth the national average or less). However, these HCSAs account for only about 1 percent of the U.S. population. CONCLUSIONS: Physician supply levels and the proportions of specialists and generalists have negligible effects on health status as measured by mortality rates and by rates of admission for all causes and for conditions presumed to be sensitive to the adequacy of ambulatory care. Reductions in admissions for such conditions are not likely to be achieved through broadening of insurance to levels that exist under Medicare, nor through increases in the supply of physicians, nor, conversely, through a reduction in any presumed oversupply of physicians.

Evaluation of the HCFA model for the analysis of mortality following hospitalization.

From 1987 through 1990, the Health Care Financing Administration (HCFA) evaluated variations in the mortality rates experienced by patients admitted to hospitals participating in the Medicare program. This study was conducted to evaluate the adequacy of the model used for that purpose. Detailed clinical data were gathered on 42,773 patients admitted to 84 statistically selected hospitals. The effect of risk adjustment using the HCFA model, which is based on claims data, was compared to a risk-adjustment model based on physiologic and clinical data. Models that include claims data were markedly superior to those containing only demographic characteristics in predicting the probability of patient death, and the addition of clinical data resulted in further improvement. The correlation of ranks of hospitals based on a model that uses only the claims data and on one that uses, in addition, clinical data, was .91. As a screen for the identification of "high (mortality) outlier" hospitals, the claims model had moderate sensitivity (81 percent) and specificity (79 percent), a high negative predictive value (90 percent), and a low positive predictive value (64 percent) when compared to the clinical model. The two mortality models gave similar results when used to determine which structural characteristics of hospitals were related to mortality rates: hospitals with a higher proportion of registered nurses or board-certified physician specialists, or with a greater level of access to high-technology equipment had lower risk-adjusted mortality rates. These data suggest that the current claims-based risk-adjustment procedure may satisfactorily be used to characterize variations in mortality rates associated with hospitalization. The procedure could also be used as a basis for further epidemiological analyses of factors that affect the probability of patient death. However, it does not positively identify outlier hospitals as providers of problematic care.

A measure of mortality risk for elderly patients with acute myocardial infarction.

The objective of this study was to derive and validate a simple scoring system that predicts risk of short-term mortality in elderly patients hospitalized with acute myocardial infarction (AMI) and to compare this derived score with the MedisGroups admission severity score. A myocardial infarction severity score (MISS) was derived from a database of clinical information abstracted using MedisGroups and follow-up information on 30-day mortality status. The MISS was validated and compared with the MedisGroups Admission Severity Groups (ASGs) in a separate database. The derivation set included 2,037 Medicare patients 65 years old or older with confirmed AMI who were randomly selected from patients discharged from hospitals in seven states during 1985. The validation set consisted of 6,323 patients from the 1988 MedisGroups comparative database who were at least 65 years of age and had confirmed AMI. Multivariate logistic regression analysis found a set of nine abnormal patient characteristics that independently predict 30-day mortality. There was good agreement between mortality rates predicted by the logistic model and observed mortality rates in the validation population. This regression model was then simplified to an additive score where eight of the characteristics were weighted as one point and one characteristic was weighted as two points. The MISS is the sum of the points for each patient. In the validation dataset, the 1,373 patients with the lowest MISS scores had a mortality rate of 4.6% and the 400 patients with the highest MISS scores had a mortality rate of 64%.(ABSTRACT TRUNCATED AT 250 WORDS)

The systematic assessment of variations in medical practices and their outcomes.

The Health Care Financing Administration of the Department of Health and Human Services has carried out for several years the systematic assessment of variations over time and among geographic locales in patterns of care and patterns of outcomes experienced by Medicare beneficiaries. This routine monitoring focuses principally on hospitalizations and their outcomes (death and readmission) and is based on the Medicare enrollment file and the claims file for inpatient care. The period 1985-88 has been marked by declining adjusted post-admission risks for mortality (down 4 percent) and readmission (down 6 percent) for Medicare beneficiaries. The downward trend in mortality risks is most evident following hospitalizations for acute myocardial infarction (down 8 percent) and stroke (down 12 percent). Hospital admission and population mortality rates, adjusted for differences in demographic and socioeconomic characteristics of the populations, vary substantially among areas as large as States and Metropolitan Statistical Areas, as do risk-adjusted post admission probabilities of death among those areas and among hospitals. Thus, if overall admission and mortality rates in the upper three quartiles of Metropolitan Statistical Areas were brought down to the average of the lowest quartile, there would be 20 percent fewer admissions and 12 percent fewer deaths within 180 days of admission for hospitalized patients. Although favorable trends in the effectiveness of the hospital care received by Medicare beneficiaries appear discernible, the existence of substantial variations suggests that further improvement may be possible.

Labor epidurals improve outcomes for babies of mothers at high risk for unscheduled cesarean section.

CONTEXT: Epidural placement for labor in the general population of laboring women is associated with increased incidence of operative deliveries, prolongation of labor, and may be associated with an increased cesarean section rate. The risks and benefits associated with epidural placement for labor in the subpopulation of mothers at high risk for cesarean section have not been studied. OBJECTIVE: To determine if a population of mothers and babies at high risk for cesarean section will have improved outcomes with labor epidural placement. DESIGN: A decision and cost analysis examining epidural placement for labor on a population of women who are at high risk for unscheduled cesarean section and may benefit from scheduled cesarean section as determined by threshold analysis was performed. Outcomes and probabilities were determined through analysis of the Department of Defense's 1996 National Quality Management Program (NQMP) Birth Product Line data set containing more than 7000 deliveries. Outcomes were defined using variables comprised of all documented conditions that occurred during the peripartum and neonatal hospitalizations. The 1997 NQMP data set was used to validate the results. SETTING: Military Treatment Facilities throughout the United States and abroad and civilian facilities in the United States providing care to military dependents. PATIENT POPULATION: Active duty and dependent pregnant women and babies. RESULTS: About 8% of mothers in this patient population were found to be at high risk for cesarean section. The decision and cost analyses showed that babies of the high risk mothers who received epidurals for labor had better clinical outcomes (p<0.05) and the procedure was cost neutral (p=0.23). The procedure did not increase the frequency of cesarean section, and there was no effect on maternal outcomes scores. These results were confirmed by the validation study. CONCLUSIONS: There is a sizable subpopulation of women at high risk for cesarean section whose babies may have better outcomes with epidural placement with no sacrifice in maternal outcomes or costs.