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Showing papers by "University of Pittsburgh published in 1992"


Journal ArticleDOI
TL;DR: The Weighted Histogram Analysis Method (WHAM) as mentioned in this paper is an extension of Ferrenberg and Swendsen's multiple histogram technique for complex biomolecular Hamiltonians.
Abstract: The Weighted Histogram Analysis Method (WHAM), an extension of Ferrenberg and Swendsen's Multiple Histogram Technique, has been applied for the first time on complex biomolecular Hamiltonians. The method is presented here as an extension of the Umbrella Sampling method for free-energy and Potential of Mean Force calculations. This algorithm possesses the following advantages over methods that are currently employed: (1) It provides a built-in estimate of sampling errors thereby yielding objective estimates of the optimal location and length of additional simulations needed to achieve a desired level of precision; (2) it yields the “best” value of free energies by taking into account all the simulations so as to minimize the statistical errors; (3) in addition to optimizing the links between simulations, it also allows multiple overlaps of probability distributions for obtaining better estimates of the free-energy differences. By recasting the Ferrenberg–Swendsen Multiple Histogram equations in a form suitable for molecular mechanics type Hamiltonians, we have demonstrated the feasibility and robustness of this method by applying it to a test problem of the generation of the Potential of Mean Force profile of the pseudorotation phase angle of the sugar ring in deoxyadenosine. © 1992 by John Wiley & Sons, Inc.

5,784 citations


Journal ArticleDOI
TL;DR: This paper presents a Bayesian method for constructing probabilistic networks from databases, focusing on constructing Bayesian belief networks, and extends the basic method to handle missing data and hidden variables.
Abstract: This paper presents a Bayesian method for constructing probabilistic networks from databases. In particular, we focus on constructing Bayesian belief networks. Potential applications include computer-assisted hypothesis testing, automated scientific discovery, and automated construction of probabilistic expert systems. We extend the basic method to handle missing data and hidden (latent) variables. We show how to perform probabilistic inference by averaging over the inferences of multiple belief networks. Results are presented of a preliminary evaluation of an algorithm for constructing a belief network from a database of cases. Finally, we relate the methods in this paper to previous work, and we discuss open problems.

3,971 citations


Journal ArticleDOI
TL;DR: The current data suggest that the CIRS(G) can be successfully applied in medically and psychiatrically impaired elderly subjects, with good interrater reliability and face validity (credibility).
Abstract: Reliable quantitative ratings of chronic medical illness burden have proved to be difficult in geropsychiatric practice and research. Thus, the purpose of the study was to demonstrate the feasibility and reliability of a modified version of the Cumulative Illness Rating Scale (CIRS; Linn et al., 1968) in providing quantitative ratings of chronic illness burden. The modified CIRS was operationalized with a manual of guidelines geared toward the geriatric patient and for clarity was designated the CIRS(G). A total of 141 elderly outpatient subjects (two medical clinic groups of 20 each, 45 recurrent depressed subjects, 21 spousally bereaved subjects, and 35 healthy controls) received comprehensive physical examinations, reviews of symptoms, and laboratory testing. These data were then used by nurse practitioners, physician's assistants, and geriatric psychiatrists to compute CIRS(G) ratings of chronic illness burden. As hypothesized, analysis of variance demonstrated significant differences among groups with respect to total medical illness burden, which was highest among medical clinic patients and lowest in control subjects. Good interrater reliability (i.e., intraclass correlations of 0.78 and 0.88 in a subsample of 10 outpatients and a separate group of 10 inpatients, respectively) was achieved for CIRS(G) total scores. Among medical clinic patients, a significant correlation was found, as expected, between CIRS(G) chronic illness burden and capability as quantified by the Older Americans Activities of Daily Living Scale; and between CIRS(G) scores and physicians' global estimates of medical burden. Finally, with repeated measures of illness burden approximately 1 year from symptom baseline, significant rises were detected, as expected. The current data suggest that the CIRS(G) can be successfully applied in medically and psychiatrically impaired elderly subjects, with good interrater reliability and face validity (credibility).

1,769 citations


Journal ArticleDOI
17 Jul 1992-Science
TL;DR: The findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase, and the regulation of pro-inflammatory cytokines and myocardia nitricoxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.
Abstract: The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.

1,641 citations


Journal ArticleDOI
TL;DR: This paper surveys the different approaches to software reuse found in the research literature and uses a taxonomy to describe and compare the different approach and make generalizations about the field of software reuse.
Abstract: Software reuse is the process of creating software systems from existing software rather than building software systems from scratch. This simple yet powerful vision was introduced in 1968. Software reuse has, however, failed to become a standard software engineering practice. In an attempt to understand why, researchers have renewed their interest in software reuse and in the obstacles to implementing it.This paper surveys the different approaches to software reuse found in the research literature. It uses a taxonomy to describe and compare the different approaches and make generalizations about the field of software reuse. The taxonomy characterizes each reuse approach in terms of its reusable artifacts and the way these artifacts are abstracted, selected, specialized, and integrated.Abstraction plays a central role in software reuse. Concise and expressive abstractions are essential if software artifacts are to be effectively reused. The effectiveness of a reuse technique can be evaluated in terms of cognitive distance—an intuitive gauge of the intellectual effort required to use the technique. Cognitive distance is reduced in two ways: (1) Higher level abstractions in a reuse technique reduce the effort required to go from the initial concept of a software system to representations in the reuse technique, and (2) automation reduces the effort required to go from abstractions in a reuse technique to an executable implementation.This survey will help answer the following questions: What is software reuse? Why reuse software? What are the different approaches to reusing software? How effective are the different approaches? What is required to implement a software reuse technology? Why is software reuse difficult? What are the open areas for research in software reuse?

1,592 citations


Journal ArticleDOI
TL;DR: Teacher ratings obtained for 931 boys in regular classrooms in grades K through 8 from around North America revealed that several hallmark symptoms of ADHD had very poor predictive power, whereas combinations of symptoms from the two ADHD factors had good predictive power.
Abstract: Ratings were collected on a rating scale comprised of the DSM-III-R diagnostic criteria for disruptive behavior disorders. Teacher ratings were obtained for 364 boys in special education classrooms...

1,290 citations


Journal ArticleDOI
TL;DR: In this paper, the authors collected teacher ratings for 931 boys in regular classrooms in grades K through 8 from around North America and collected ratings on a rating scale comprised of the DSM-III-R diagnostic criteria for disruptive behavior disorders.
Abstract: Ratings were collected on a rating scale comprised of the DSM-III-R diagnostic criteria for disruptive behavior disorders Teacher ratings were obtained for 931 boys in regular classrooms in grades K through 8 from around North America Means and standard deviations for attention-deficit hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), and conduct disorder (CD) scales are reported by age Frequencies of DSM-III-R symptoms are reported by age, and suggested diagnostic cutoffs are discussed A factor analysis revealed three factors: one reflecting ODD and several CD symptoms, one on which ADHD symptoms of inattention loaded, and one comprised of ADHD impulsivity/overactivity symptoms Conditional probability analyses revealed that several hallmark symptoms of ADHD had very poor predictive power, whereas combinations of symptoms from the two ADHD factors had good predictive power Combinations of ODD symptoms also had very high predictive power The limited utility of teacher ratings in assessing symptoms of conduct disorder in this age range is discussed

1,219 citations


Journal ArticleDOI
01 May 1992-Pain
TL;DR: The results tend to support the efficacy of multidisciplinary pain treatment; however, these results must be interpreted cautiously as the quality of the study designs and study descriptions is marginal.
Abstract: Sixty-five studies that evaluated the efficacy of multidisciplinary treatments for chronic back pain were included in a meta-analysis. Within- and between-group effect sizes revealed that multidisciplinary treatments for chronic pain are superior to no treatment, waiting list, as well as single-discipline treatments such as medical treatment or physical therapy. Moreover, the effects appeared to be stable over time. The beneficial effects of multidisciplinary treatment were not limited to improvements in pain, mood and interference but also extended to behavioral variables such as return to work or use of the health care system. These results tend to support the efficacy of multidisciplinary pain treatment; however, these results must be interpreted cautiously as the quality of the study designs and study descriptions is marginal. Suggestions for improvement in research designs as well as appropriate reports of research completed are provided.

1,167 citations


Journal ArticleDOI
TL;DR: Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.
Abstract: Background and Methods. Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a doubleblind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. Results. By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P<0.001). Systemic fungal in...

1,116 citations


Journal ArticleDOI
TL;DR: The chimeric nature of the transplanted liver was first shown in long-surviving human recipients of orthotopic hepatic allografts in 1969 and its continued presence was confirmed by the acquisition and maintenance in recipient blood of new donor-specific immunoglobulin (Gm) types and red-blood-cell alloantibodies.

1,001 citations


Journal ArticleDOI
TL;DR: It is indicated that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.
Abstract: An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

Book
26 Mar 1992
TL;DR: A large variety of experimental strategies have been carried out by behavioral researchers as discussed by the authors, including group-comparison designs (cf. Kazdin, 1980) and single-case experimental designs (Barlow & Hersen, 1984; Hersen & Barlow, 1976).
Abstract: Behavior modification and therapy perhaps are best distinguished from other therapeutic and educational approaches by their dependence on the experimental-empirical methods for solving human problems. Thus, in evaluating the efficacy of emerging therapeutic and educational techniques, a large variety of experimental strategies has been carried out by behavioral researchers. Included, of course, are both group-comparison designs (cf. Kazdin, 1980) and single-case experimental designs (Barlow & Hersen, 1984; Hersen & Barlow, 1976).

Journal ArticleDOI
TL;DR: The ultrastructural bases for these interactions in rat are investigated by examining the synaptic associations between prefrontal cortical terminals labeled with anterograde markers and neuronal processes containing immunoreactivity for the catecholamine synthesizing enzyme, tryosine hydroxylase.
Abstract: Physiological and pharmacological studies indicate that descending projections from the prefrontal cortex modulate dopaminergic transmission in the nucleus accumbens septi and ventral tegmental area We investigated the ultrastructural bases for these interactions in rat by examining the synaptic associations between prefrontal cortical terminals labeled with anterograde markers (lesion-induced degeneration or transport of Phaseolus vulgaris leucoagglutinin; PHA-L) and neuronal processes containing immunoreactivity for the catecholamine synthesizing enzyme, tryosine hydroxylase Prefrontal cortical terminals in the nucleus accumbens and ventral tegmental area contained clear, round vesicles and formed primarily asymmetric synapses on spines or small dendrites In the ventral tegmental area, these terminals also formed asymmetric synapses on large dendrites and a few symmetric axodendritic synapses In the nucleus accumbens septi, degenerating prefrontal cortical terminals synapsed on spiny dendrites which received convergent input from terminals containing peroxidase immunoreactivity for tyrosine hydroxylase, or from unlabeled terminals In single sections, some tyrosine hydroxylase-labeled terminals formed thin and punctate symmetric synapses with dendritic shafts, or the heads and necks of spines Close appositions, but not axo-axonic synapses, were frequently observed between degenerating prefrontal cortical afferents and tyrosine hydroxylase-labeled or unlabeled terminals In the ventral tegmental area, prefrontal cortical terminals labeled with immunoperoxidase for PHA-L were in synaptic contact with dendrites containing immunogold reaction product for tyrosine hydroxylase, or with unlabeled dendrites These results suggest that: (1) catecholaminergic (mainly dopaminergic) and prefrontal cortical terminals in the nucleus accumbens septi dually synapse on common spiny neurons; and (2) dopaminergic neurons in the ventral tegmental area receive monosynaptic input from prefrontal cortical afferents This study provides the first ultrastructural basis for multiple sites of cellular interaction between prefrontal cortical efferents and mesolimbic dopaminergic neurons

Journal ArticleDOI
TL;DR: The results of a multisite field trial indicate that the binge eating disorder is common among subjects attending hospital-affiliated weight control programs, but is relatively rare in the community.
Abstract: Diagnostic criteria have been developed for a new eating disorder, binge eating disorder (BED), to describe the many individuals who have problems with recurrent binge eating but do not engage in the characteristic compensatory behaviors of bulimia nervosa, vomiting, or use of laxatives. The results of a multisite field trial involving 1,984 subjects indicate that the disorder is common (30.1%) among subjects attending hospital-affiliated weight control programs, but is relatively rare in the community (2.0%). The disorder is more common in females than in males and is associated with severity of obesity and a history of marked weight fluctuations. Based on these results, the DSM-IV Work Group on Eating Disorders has recommended that the disorder be considered for inclusion in DSM-IV, either as an official category or in an appendix of categories requiring further study.

Journal ArticleDOI
27 Aug 1992-Nature
TL;DR: The characterization of acid-eluted peptides bound to HLA-DR1 by high-performance liquid chromatography, mass spectrometry and microsequencing analyses confirmed that all of the isolated peptides had high affinity for the groove of DR1.
Abstract: PEPTIDES bound to class I molecules are 8–10 amino acids long, and possess a binding motif representative of peptides that bind to a given class I allele1–4. In the only published study of naturally processed peptides bound to class II molecules (mouse I–Ab and I–Eb), these peptides were longer (13–17 amino acids) and had heterogenous carboxy terminals but precise ammo-terminal truncations5. Here we report the characterization of acid-eluted peptides bound to HLA-DR1 by high-performance liquid chromatography, mass spectrometry and microsequencing analyses. The relative molecular masses of the peptides varied between 1,602 and 2,996 (13–25 residues), the most abundant individual Mr values being between 1,700 and 1,800, corresponding to an average peptide length of 15 residues. Complete sequence data were obtained for twenty peptides derived from five epitopes, of which all but one were from self proteins. These peptides represented sets nested at both the N- and C-terminal ends. Binding experiments confirmed that all of the isolated peptides had high affinity for the groove of DR1. Alignment of the peptides bound to HLA-DR1 and the sequences of 35 known HLA-DRl-binding peptides revealed a putative motif. Although peptides bound to class II molecules may have some related features (due to the nonpolymorphic HLA-DR α-chain), accounting for degenerate binding to different alleles6, particular amino acids in the HLA-DR β-chains presumably define allelic specificity of peptide binding.

Journal ArticleDOI
TL;DR: This paper examined the effects of brand strategy on new product market share and advertising efficiency and the degree to which these effects are mo... and the effect of brand extensions vs. individual brands.
Abstract: The authors examine the effects of brand strategy (i.e., brand extensions vs. individual brands) on new product market share and advertising efficiency, and the degree to which these effects are mo...

Journal ArticleDOI
TL;DR: The majority of longitudinal studies have determined that severity of initial depressive symptoms and the presence of a comorbid medical illness were predictors of persistence of depression.

Journal ArticleDOI
TL;DR: The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence, and further research on the determinants of low serum cholesterol level in populations and long-term follow-up of participants in clinical trials is necessary.
Abstract: Background.— With increased efforts to lower serum cholesterol levels, it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease, for which an etiologic relationship has been established. Methods.— For an average of 12 years, 350 977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single standardized measurement of serum cholesterol level and other coronary heart disease risk factors; 21 499 deaths were identified. Results.— A strong, positive, graded relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease. This relationship persisted over the 12-year follow-up period. No association was noted between serum cholesterol level and stroke. The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke. For the latter, a positive, graded association with serum cholesterol level was evident. For intracranial hemorrhage, cholesterol levels less than 4.14 mmol/L ( Conclusions.— The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence. Further research on the determinants of low serum cholesterol level in populations and long-term follow-up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease, whether serum cholesterol level and noncardiovascular disease are both consequences of other factors, or whether these associations are causal. ( Arch Intern Med . 1992;152:1490-1500)

Journal ArticleDOI
01 Sep 1992-Stroke
TL;DR: The importance of specific characteristics of a given ischemia model and of underlying stroke risk factors in determining the degree of leukocyte involvement and effectiveness of therapies directed against these cells is discussed.
Abstract: The extent to which polymorphonuclear leukocytes and monocytes/macrophages contribute to the pathobiology of cerebral ischemia and stroke is an issue of long-standing contradiction and controversy. Recent developments in the ability to selectively modify leukocyte adhesion with antiadhesion antibodies and the potential clinical application of this therapeutic approach have spurred a resurgence of experimental studies examining the role of leukocytes in cerebral ischemia and stroke.We review studies examining leukocyte accumulation, initiation of thrombosis, and exacerbation of ischemic brain injury in stroke, and we examine other proposed contributions of leukocytes to cerebrovascular pathophysiology.The importance of specific characteristics of a given ischemia model and of underlying stroke risk factors in determining the degree of leukocyte involvement and effectiveness of therapies directed against these cells is discussed.

Journal ArticleDOI
TL;DR: In this paper, a detailed derivation of a new and efficient technique based on the technology of four-dimensional heterotic strings, for computing one-loop amplitudes in gauge theories, along with expressions for the dimensionally regularized helicity amplitudes for the process with four external gluons.

Journal ArticleDOI
TL;DR: In this paper, the Gibbs sampler is proposed as a mechanism for implementing a conceptually and computationally simple solution in multivariate state-space modeling, forecasting, and smoothing, allowing for the possibilities of nonnormal errors and nonlinear functionals in the state equation, the observational equation, or both.
Abstract: A solution to multivariate state-space modeling, forecasting, and smoothing is discussed. We allow for the possibilities of nonnormal errors and nonlinear functionals in the state equation, the observational equation, or both. An adaptive Monte Carlo integration technique known as the Gibbs sampler is proposed as a mechanism for implementing a conceptually and computationally simple solution in such a framework. The methodology is a general strategy for obtaining marginal posterior densities of coefficients in the model or of any of the unknown elements of the state space. Missing data problems (including the k-step ahead prediction problem) also are easily incorporated into this framework. We illustrate the broad applicability of our approach with two examples: a problem involving nonnormal error distributions in a linear model setting and a one-step ahead prediction problem in a situation where both the state and observational equations are nonlinear and involve unknown parameters.


Journal ArticleDOI
TL;DR: Impaired glucose tolerance, the precursor of NIDDM, results primarily from reduced suppression of hepatic glucose output due to abnormal pancreatic islet-cell function.
Abstract: Background. Insulin resistance and impaired insulin secretion both occur in non-insulin-dependent diabetes (NIDDM), but their relative importance is unclear. Hyperglycemia itself has adverse effects on tissue insulin sensitivity and insulin secretion that make it difficult to distinguish between primary and secondary abnormalities. To avoid this problem we studied subjects with postprandial glucose intolerance but not sustained hyperglycemia. Methods. We compared the rate of systemic appearance and disappearance of glucose, the output of endogenous hepatic glucose, splanchnic and muscle uptake of glucose, and plasma insulin and glucagon responses after the ingestion of 1 g of glucose per kilogram of body weight in 15 subjects with impaired glucose tolerance (8 of them nonobese and 7 obese) and in 16 normal subjects (9 nonobese and 7 obese) who were matched for age and weight. Results. After glucose ingestion the mean (±SE) rate of total systemic appearance of glucose was significantly higher in b...

Journal ArticleDOI
TL;DR: Higher levels of aerobic fitness in patients with cystic fibrosis are associated with a significantly lower risk of dying, and measurement of VO2 peak appears to be valuable for predicting prognosis.
Abstract: Background. Previous studies have shown female sex, impaired pulmonary function, older age, malnutrition, and colonization of the respiratory tract by Pseudomonas cepacia to be associated with a poor prognosis in patients with cystic fibrosis. We sought to determine the prognostic value of exercise testing in addition to the other prognostic factors. Methods. A total of 109 patients with cystic fibrosis, 7 to 35 years old, underwent pulmonary-function and exercise testing in the late 1970s. They were followed for eight years to determine the factors associated with subsequent mortality. Survival rates were calculated with standard life-table methods. Cox proportional-hazards regression models were used to determine crude relative risks of mortality and relative risks adjusted for age, sex, body-mass index, forced expiratory volume in one second (FEV1), end-tidal partial pressure of carbon dioxide (PCO2) at peak exercise, and oxygen consumption at peak exercise (Vo2peak). Results. Patients with t...

Journal ArticleDOI
11 Dec 1992-Science
TL;DR: New challenges in protein electron-transfer research include identifying the role of protein dynamics, and characterizing multistep tunneling over very long distances.
Abstract: Electron-transfer (ET) reactions are key steps in photosynthisis, respiration, drug metabolism, and many other biochemical processes. The ETs are remarkably fast and proceeded with high specificity. Theoreticians have been intensely interested in long-range protein ET reactions for many years. This perspective paper discusses the tunneling-pathway model for protein ET coupling, giving the example Cytochrome c. Different coupling strength in different pathway families are mentioned and a brief overview of the future of understanding ET reactions is given.

Journal ArticleDOI
TL;DR: The most notable changes to occur during the 10-year period were a statistically significant increase in the prevalence of S. pneumoniae in patients with acute otitis media and a progressive rise in the percentage of betalactamase-producing strains of H. influenzae and Moraxella (Branhamella) catarrhalis.
Abstract: Data collected from 1980 to 1989 by investigators at the Pittsburgh Otitis Media Research Center were examined to detect changes over time in the prevalence of bacteria isolated from middle ear effusions in patients with otitis media. The organisms isolated most commonly from the 7396 effusions cultured at the center were Streptococcus pneumoniae and Haemophilus influenzae. S. pneumoniae predominated in the subgroup of patients with acute otitis media, whereas H. influenzae was isolated most frequently from patients with otitis media with effusion. The most notable changes to occur during the 10-year period were a statistically significant increase in the prevalence of S. pneumoniae in patients with acute otitis media and a progressive rise in the percentage of beta-lactamase-producing strains of H. influenzae and Moraxella (Branhamella) catarrhalis. The latter finding suggests the need for therapeutic alternatives to amoxicillin, which is not active against beta-lactamase-producing organisms, when these organisms are suspected or cultured from the middle ear.

Journal ArticleDOI
TL;DR: Evidence is provided for the existence of typical inducible NO biosynthesis in a human cell type after stimulation with interleukin 1, tumor necrosis factor, IFN- gamma, and endotoxin in freshly isolated human hepatocytes.
Abstract: Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced in various cell types and to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of the inducible type of the NO synthase (NOS). However, there is limited evidence for the existence of such inducible NOS in a human cell type. We show here the induction of NO biosynthesis in freshly isolated human hepatocytes (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN-gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in culture supernatants were associated with NADPH-dependent NOS activity in the cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L-arginine and was associated with an increase in cyclic guanylate monophosphate release. The data presented here provide evidence for the existence of typical inducible NO biosynthesis in a human cell type.

Journal ArticleDOI
TL;DR: In this paper, Monte Carlo methods are used to study the size and power of serial-correlation-corrected versions of the Dickey-Fuller (1979,1981) unit root tests appropriate when the time series has unknown mean.

Journal ArticleDOI
TL;DR: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21, and increasing use of radiation and chemotherapy suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

Journal ArticleDOI
TL;DR: Despite differences among these animals in their histories of selection and the genetic backgrounds on which selection has acted, there is a common relationship between relative hippocampal size and spatial ability.