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Biomedical subjects

B Misra

Publications and source records attributed to B Misra.

At least 19 recordsLinked to original sources

Variation in routine electrocardiogram use in academic primary care practice.

BACKGROUND: Lack of practical consensus regarding routine electrocardiogram (ECG) ordering in primary care led us to hypothesize that nonclinical variations in ordering would exist among primary care providers. METHODS: We used 2 computerized billing systems to measure ECG ordering at visits to providers in 10 internal medicine group practices affiliated with a large, urban teaching hospital from October 1, 1996, to September 30, 1997. To focus on screening or routine ECGs, patients with known cardiac disease or suggestive symptoms were excluded, as were providers with fewer than 200 annual patient visits. Included were 69 921 patients making 190 238 visits to 125 primary care providers. Adjusted rates of ECG ordering accounted for patient age, sex, and 5 key diagnoses. Logistic regression evaluated additional predictors of ECG ordering. RESULTS: Electrocardiograms were ordered in 4.4% of visits to patients without reported cardiac disease. Among the 10 group practices, ECG ordering varied from 0.5% to 9.6% of visits (adjusted rates, 0.8%-8.6%). Variations between individual providers were even more dramatic: adjusted rates ranged from 0.0% to 24% of visits, with an interquartile range of 1.4% to 4.7% and a coefficient of variation of 88%. Significant predictors of ECG use were older patient age, male sex, and the presence of clinical comorbidities. Additional nonclinical predictors included Medicare as a payment source, older male providers, and providers who billed for ECG interpretation. CONCLUSIONS: Variations in ECG ordering are not explained by patient characteristics. The tremendous nonclinical variations in ECG test ordering suggest a need for greater consensus about use of screening ECGs in primary care.

Academic Medical Centers↗

National patterns of physician activities related to obesity management.

CONTEXT: National physician practices related to the clinical recognition and management of obesity are unknown. OBJECTIVES: To estimate national patterns of office-based, obesity-related practices and to determine the independent predictors of these practices. DESIGN: Serial cross-sectional surveys of physician office visits. SETTING: Ambulatory medical care in the United States. PATIENTS: We analyzed 55,858 adult physician office visits sampled in the 1995-1996 National Ambulatory Medical Care Surveys. Data from the Third National Health and Nutrition Examination Surveys, 1988-1994 were used to assess and, then, adjust for the underreporting of obesity. MAIN OUTCOME MEASURES: Reporting of obesity at office visits and physician counseling for weight loss, exercise, and diet among patients identified as obese. RESULTS: Physicians reported obesity in only 8.6% of 1995-1996 National Ambulatory Medical Care Surveys visits. The 22.7% prevalence rate of the Third National Health and Nutrition Examination Surveys, 1988-1994 suggests that physicians reported obesity in only 38% of their obese patients. Among visits by patients identified as obese, physicians frequently provided counseling for weight loss (35.5%), exercise (32.8%), and diet (41.5%). Adjusted for population prevalence; however, each service was provided to no more than one quarter of all obese patients. While patients with obesity-related comorbidities were treated more aggressively, in these patients, weight loss counseling occurred at only 52% of the visits. CONCLUSIONS: Specific interventions to address obesity are infrequent in visits to US physicians. Obesity is underreported and interventions are only moderately likely among patients identified as obese, even for those with serious obesity-related comorbidities.

Adult↗

Stress testing: national patterns and predictors of test ordering.

OBJECTIVE: To determine predictors of ordering of exercise stress tests. BACKGROUND: Because exercise stress testing is routinely used and widely available and may have an effect on subsequent evaluation of and therapy for heart disease, understanding current patterns of ordering exercise stress tests may have important implications for national health care costs. We hypothesized that factors other than clinical condition exert an influence on ordering of exercise stress tests. METHODS: Data from the 1991 and 1992 National Ambulatory Medical Care Surveys conducted by the National Center for Health Statistics were analyzed by means of multivariate logistic regression. RESULTS: In an estimated 1.12 billion adult visits to office-based physicians in the United States (95% confidence interval [CI], 1.07-1.16 billion), 6.2 million (95% CI, 4.8-7.6 million) exercise stress tests were ordered. After adjustment for clinical and nonclinical variables associated with the office visit, cardiologists were 3.7 (95% CI, 2.7-5.1) times more likely to order exercise stress tests than were internists, who were more likely to order an exercise stress test than were family and general practitioners (0.5, 95% CI, 0.3-0.7). Nonclinical factors associated with increased ordering of exercise stress tests included male sex (odds ratio 2.5; 95% CI, 2.0-3.2), white race (odds ratio 1.6; 95% CI, 1.1-2.3), new referral status (odds ratio 3.8; 95% CI, 2.5-5.8), and private insurance (odds ratio 1.4; 95% CI, 1.1-1.8). Medicare recipients were about half (95% CI, 0.4-0.9) as likely as other patients to have an exercise stress test ordered. CONCLUSIONS: Factors other than clinical condition exert an influence on ordering of exercise stress tests and may represent modifiable elements associated with appropriate practice.

Adult↗

Rate control and sinus rhythm maintenance in atrial fibrillation: national trends in medication use, 1980-1996.

BACKGROUND: Little is known about national patterns of pharmacological treatment of atrial fibrillation, in particular, use of medications for ventricular rate control and for restoration and maintenance of sinus rhythm. METHODS: We analyzed 1555 visits by patients with atrial fibrillation to randomly selected office-based US physicians included in National Ambulatory Medical Care surveys conducted in 1980, 1981, 1985, and 1989 through 1996. To determine national trends, we evaluated the proportion of atrial fibrillation visits with reported use of rate control medications (digoxin and antiarrhythmics in classes II and IV) and sinus rhythm medications (classes IA, IC, and III). RESULTS: The use of rate control agents decreased from 79% of atrial fibrillation visits in 1980-1981 to 62% in 1994-1996. Declining use was noted for both digoxin (76% in 1980-1981 to 53% in 1994-1996) and beta-blockers (19%-13%). After their introduction, the use of verapamil hydrochloride and diltiazem hydrochloride increased to 15% of atrial fibrillation visits in 1994-1996. Sinus rhythm agent use decreased from 18% of visits in 1980-1981 to 4% in 1992-1993 and then rose to 13% in 1994-1996. The use of class IA agents declined from 18% in 1980-1981 to 3.5% in 1992-1993 and then increased to 8% in 1994-1996. Quinidine remained the most widely used sinus rhythm medication, despite its declining share of this category. Newly available sotalol hydrochloride and amiodarone hydrochloride were used in 3.6% of visits in 1994-1996. CONCLUSIONS: Despite changes in the treatment of atrial fibrillation, digoxin remains the dominant rate control medication. Medications for sinus rhythm maintenance are not widely used. Quinidine use declined prominently in the 1980s, possibly because of concerns about proarrhythmic effects. The use of sinus rhythm agents, however, is now rising.

Adrenergic beta-Antagonists↗

Evaluation of recombinant human factor IX: pharmacokinetic studies in the rat and the dog.

The pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine, a purified human plasma-derived factor IX, after single 100 IU/kg i.v. doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine were 4-5 micrograms/ml. The mean plasma half-lives were 13.2 +/- 1.6 h for rhFIX and 13.3 +/- 1.6 h for Mononine. Dogs also received rhFIX (40 IU/kg i.v., daily) for 28 days or Mononine (40 IU/kg i.v. daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine (40 IU/kg) dogs.

Animals↗

N-ethyl-N-nitrosourea induced brain tumors in rats monitored by nuclear magnetic resonance imaging, plasma proton nuclear magnetic resonance spectroscopy and microscopy.

Characteristic slow growing brain gliomas were induced in rats by a single subcutaneous injection of N-ethyl-N-nitrosourea (ENU) within 24 h of birth. A parallel control group of rats was injected with saline. Seven treated rats developed gliomas within 2 years. Periodic nuclear magnetic resonance imaging (MRI) of the brain in 3-mm slices at 1.5 Tesla and monthly plasma sampling for proton magnetic resonance spectroscopy (MRS) at 360 MHz were started 6 months after the injection of ENU. In the MRS experiments, the Fossel index, average of the line widths of the methylene and methyl peaks at 360 MHz, was determined from half-line widths of methyl and methylene peaks at 0.8 ppm and 1.3 ppm. In five of the ENU injected animals that developed histologically verified brain tumors, these were also observed by MRI without contrast agents. There was no consistent correlation between the imaged tumors and the Fossel index obtained through MRS during the course of the study where repeated observations were performed on individual animals, nor was there any consistent statistical difference in the Fossel index between ENU-treated and control animals. The results of this study demonstrate that slowly developing carcinogen-induced brain tumors in rats can be successfully and reliably monitored noninvasively by MRI but not by MRS of plasma.

Animals↗

Comparative tumorigenicity in newborn mice of chrysene- and 5-alkylchrysene-1,2-diol-3,4-epoxides.

We determined the tumorigenicity in newborn mice of racemic anti-1,2-diol-3,4-epoxides of chrysene, 5-methylchrysene, 5-ethylchrysene and 5-propylchrysene. Among the four diol epoxides, only anti-5-methylchrysene-1,2-diol-3,4-epoxide was highly tumorigenic. It was 15-30 times more potent in induction of pulmonary tumors than the other compounds. The results demonstrate that molecular shape is critical in determining the tumorigenic activity of alkylchrysene diol epoxides. A methyl group in the same bay region as the epoxide ring leads to exceptional activity. This may be a consequence of DNA adduct conformation.

Adenoma↗

Phototoxicity involving the ocular lens: in vivo and in vitro studies.

Our laboratory has demonstrated the cataractogenic potential of UV radiation and several photosensitizing drugs in laboratory animals and in humans. We have utilized lens fluorescence measurements (which we have demonstrated to be a reliable marker for pre-cataractous and early cataractous changes), NMR pulse relaxation techniques, and our recently developed magnetic resonance imaging method to measure lens T2 values in the normal and UV exposed Degus lens (in vivo and in vitro) to detect pre-cataractous changes in the lens. These approaches will permit us to employ two parameters (increased non-tryptophan fluorescence and a decrease in T2 values) to monitor for such changes months before the lens opacities become manifest by conventional slit lamp examinations.

Animals↗

Chromatographic conditions for separation of 32P-labeled phosphates of major polynuclear aromatic hydrocarbon--deoxyribonucleoside adducts.

The 3'-monophosphates of the major deoxyribonucleoside adducts of five representative polynuclear aromatic hydrocarbons (PAH)-benzo[a]pyrene, benz[a]anthracene, chrysene, 5-methylchrysene and 6-methylchrysene--were prepared by reaction with DNA of the appropriate bay-region diol epoxides followed by enzymatic hydrolysis and HPLC purification. These standards were converted to 3',[32P]-5'-bisphosphates as in the Randerath 32P-postlabeling assay. TLC and HPLC systems for their separation are described. HPLC conditions for separation of the corresponding 3'- and 5'-monophosphates are also reported. These data will be useful for determining whether unknown DNA adducts detected by the 32P-postlabeling assay may have resulted from reactions of DNA with PAH diol epoxides.

DNA↗

Diagnostic value of immunological leukemia phenotyping.

The diagnostic value of immunological leukemia phenotyping using a panel of reagents in immunofluorescence assays was assessed in 309 consecutive patients. The cells from 307 patients could be clearly phenotyped and assigned to one of the subgroups with a definite immunophenotype. Each phenotype was characterized by a distinct marker profile. A simplified classification scheme based on surface antigen expression is presented. A combination of complementary reagents ('first panel') was used for the first-line screening. The application of selected reagents from the 'second panel' allowed for further subtyping and confirmation of the primary diagnosis. The contribution of different key reagents to the identification of distinct immunophenotypes is discussed. Multiple marker analysis, i.e. the combination of information from several disciplines, is a necessary and very useful tool in the routine investigation of patients with hematopoietic malignancies.

Antigens, Neoplasm↗

High concordance between marker profiles of 22 human leukemia-lymphoma cell lines tested with the same monoclonal antibodies before and during the second international workshop on human differentiation antigens.

Our laboratory participated in the Second International Workshop and Conference on Human Leucocyte Differentiation Antigens. In this international study the reactivity profiles of monoclonal antibodies were analyzed on normal and malignant hematopoietic cells. The Workshop was divided into three categories: the T-cell, B-cell and myelomonocytic cell studies. We blindly tested 159 coded monoclonal antibodies of the panel for the T-cell study on 22 permanently established leukemia cell lines. The monoclonal antibodies were provided by the Workshop Committee and their reactivity with the target cells was visualized by standardized indirect immunofluorescence. After decoding it was recognized that 11 monoclonal antibodies had been examined on these cell lines prior to the Workshop. The reactivity of these 11 monoclonal antibodies was analyzed and compared with the earlier results. From a total of 217 paired tests done blindly in the Workshop study and prior to the Workshop, 191 tests (88%) did not show significantly different data. The possible reasons for discrepancies include nonspecific Fc-receptor-binding on some cell lines and a relatively nonspecific reactivity of some monoclonal antibodies. This analysis demonstrates the stability of the antigen expression on human leukemia-lymphoma cell lines grown at consistently optimal conditions, for the tests, using the same monoclonal antibodies as in the Workshop, had been performed 0.5-5 years prior to the Workshop study. On the other hand, nonspecific Fc-binding, wide "specificity" of monoclonal antibodies and a shift in antigen expression of the cells (due to poor growth conditions, involuntary induction of differentiation and other factors) must be taken into consideration upon immunological analysis.

Antibodies, Monoclonal↗

Antigens specified by the Tla locus are expressed on the surface of murine Langerhans cells.

A monoclonal antibody against the murine thymus leukemia antigen TL, was employed to demonstrate the presence of the antigen on the surface of dendritic cells in murine epidermis of Tla-positive strains, B.10A and A.TH. Immunofluorescence and immunoperoxidase staining of EDTA-separated epidermal sheets demonstrated dendritic cells with a distribution pattern and density comparable to that noted for anti-IAk staining. Tla-negative mouse strains such as A.TL, C3H/HeJ, and C57BL/6 did not show any staining of dendritic epidermal cells. Epidermal cell suspensions similarly contained 2-4% cells with discrete surface staining with anti-TL antibody. Capping was noted in these cells. Once again positive results were noted only in appropriate Tla-positive strains. Control staining was carried out in all cases on frozen sections of thymii from mice. Thymocytes in the cortical zones and some dendritic cells at the corticomedullary junction were stained. TL antigen in mouse appears to be analogous to T-6 antigen previously detected on human Langerhans cells.

Animals↗

Injuries of hepatic veins and retrohepatic vena cava.

Three cases of hepatic vein and retrohepatic inferior vena caval injuries are reported, and the literature is reviewed. Our experience, coupled with a critical review of the literature reveals that successful vascular isolation of the relatively inaccessible retrohepatic vena cava and/or hepatic veins is the key to optimal surgical management of major injuries to these structures. The various shunt techniques have been outlined with special emphasis made to the midline sternotomy incision as the incision of choice. This incision not only gives optimal exposure to the injured site, but also allows easy atrial-caval cannulation. If cross-clamping of the abdominal aorta is necessary, it can be easily done via a median sternotomy.

Accidents, Traffic↗

Lyapounov variable: Entropy and measurement in quantum mechanics.

We discuss the question of the dynamical meaning of the second law of thermodynamics in the framework of quantum mechanics. Previous discussion of the problem in the framework of classical dynamics has shown that the second law can be given a dynamical meaning in terms of the existence of so-called Lyapounov variables-i.e., dynamical variables varying monotonically in time without becoming contradictory. It has been found that such variables can exist in an extended framework of classical dynamics, provided that the dynamical motion is suitably unstable. In this paper we begin to extend these results to quantum mechanics. It is found that no dynamical variable with the characteristic properties of nonequilibrium entropy can be defined in the standard formulation of quantum mechanics. However, if the Hamiltonian has certain well-defined spectral properties, such variables can be defined but only as a nonfactorizable superoperator. Necessary nonfactorizability of such entropy operators M has the consequence that they cannot preserve the class of pure states. Physically, this means that the distinguishability between pure states and corresponding mixtures must be lost in the case of a quantal system for which the algebra of observables can be extended to include a new dynamical variable representing nonequilibrium entropy. We discuss how this result leads to a solution of the quantum measurement problem. It is also found that the question of existence of entropy of superoperators M is closely linked to the problem of defining an operator of time in quantum mechanics.

Journal Article↗

From deterministic dynamics to probabilistic descriptions.

THE PRESENT WORK IS DEVOTED TO THE FOLLOWING QUESTION: What is the relationship between the deterministic laws of dynamics and probabilistic description of physical processes? It is generally accepted that probabilistic processes can arise from deterministic dynamics only through a process of "coarse graining" or "contraction of description" that inevitably involves a loss of information. In this work we present an alternative point of view toward the relationship between deterministic dynamics and probabilistic descriptions. Speaking in general terms, we demonstrate the possibility of obtaining (stochastic) Markov processes from deterministic dynamics simply through a "change of representation" that involves no loss of information provided the dynamical system under consideration has a suitably high degree of instability of motion. The fundamental implications of this finding for statistical mechanics and other areas of physics are discussed. From a mathematical point of view, the theory we present is a theory of invertible, positivity-preserving, and necessarily nonunitary similarity transformations that convert the unitary groups associated with deterministic dynamics to contraction semigroups associated with stochastic Markov processes. We explicitly construct such similarity transformations for the so-called Bernoulli systems. This construction illustrates also the construction of the so-called Lyapounov variables and the operator of "internal time," which play an important role in our approach to the problem of irreversibility. The theory we present can also be viewed as a theory of entropy-increasing evolutions and their relationship to deterministic dynamics.

Journal Article↗

Nonequilibrium entropy, Lyapounov variables, and ergodic properties of classical systems.

We discuss the problem of defining (nonequilibrium) entropy in terms of the concepts of mechanics and of reconciling its monotonic increase with the Hamiltonian evolution of the dynamical system. This leads to investigating necessary and sufficient conditions for the existence of monotonically increasing quantities or the so-called Lyapounov variables of classical systems. It is found that the condition of "mixing" is necessary and the property of being K-flow is sufficient for the existence of a Lyapounov variable. The significance of the study of Lyapounov variables for the elucidation of the fundamental questions of statistical mechanics is briefly discussed. It is seen that every Lyapounov variable must fail to commute with at least some of the operators of multiplication by phase space functions. The uncertainty relations implied by this necessary noncommutativity would then set a limit on the simultaneous determination of entropy and trajectories in phase space. These considerations thus support and sharpen the view that the thermodynamical and the (microscopic) dynamical descriptions of classical systems could be consistently reconciled as being complementary descriptions analogous to the complementary descriptions encountered in quantum mechanics.

Journal Article↗