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PubMed2005

Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B.

A valid quantitative imaging method for the measurement of amyloid deposition in humans could improve Alzheimer's disease (AD) diagnosis and antiamyloid therapy assessment. Our group developed Pittsburgh Compound-B (PIB), an amyloid-binding radiotracer, for positron emission tomography (PET). The current study was aimed to further validate PIB PET through quantitative imaging (arterial input) and inclusion of subjects with mild cognitive impairment (MCI). Pittsburgh Compound-B studies were performed in five AD, five MCI, and five control subjects and five subjects were retested within 20 days. Magnetic resonance images were acquired for partial volume correction and region-of-interest definition (e.g., posterior cingulate: PCG; cerebellum: CER). Data were analyzed using compartmental and graphical approaches. Regional distribution volume (DV) values were normalized to the reference region (CER) to yield DV ratios (DVRs). Good agreement was observed between compartmental and Logan DVR values (e.g., PCG: r=0.89, slope=0.91); the Logan results were less variable. Nonspecific PIB retention was similar across subjects (n=15, Logan CER DV: 3.63+/-0.48). Greater retention was observed in AD cortical areas, relative to controls (P<0.05). The PIB retention in MCI subjects appeared either 'AD-like' or 'control-like'. The mean test/retest variation was approximately 6% in primary areas-of-interest. The Logan analysis was the method-of-choice for the PIB PET data as it proved stable, valid, and promising for future larger studies and voxel-based statistical analyses. This study also showed that it is feasible to perform quantitative PIB PET imaging studies that are needed to validate simpler methods for routine use across the AD disease spectrum.

Adult↗
PubMed2006

The Online Bioinformatics Resources Collection at the University of Pittsburgh Health Sciences Library System--a one-stop gateway to online bioinformatics databases and software tools.

To bridge the gap between the rising information needs of biological and medical researchers and the rapidly growing number of online bioinformatics resources, we have created the Online Bioinformatics Resources Collection (OBRC) at the Health Sciences Library System (HSLS) at the University of Pittsburgh. The OBRC, containing 1542 major online bioinformatics databases and software tools, was constructed using the HSLS content management system built on the Zope Web application server. To enhance the output of search results, we further implemented the Vivísimo Clustering Engine, which automatically organizes the search results into categories created dynamically based on the textual information of the retrieved records. As the largest online collection of its kind and the only one with advanced search results clustering, OBRC is aimed at becoming a one-stop guided information gateway to the major bioinformatics databases and software tools on the Web. OBRC is available at the University of Pittsburgh's HSLS Web site (http://www.hsls.pitt.edu/guides/genetics/obrc).

Computational Biology↗
PubMed2006

Creating an infrastructure for training in the responsible conduct of research: the University of Pittsburgh's experience.

In response to public concerns about the consequences of research misconduct, academic institutions have become increasingly cognizant of the need to implement comprehensive, effective training in the responsible conduct of research (RCR) for faculty, staff, students, and external collaborators. The ability to meet this imperative is challenging as universities confront declining financial resources and increasing complexity of the research enterprise. The authors describe the University of Pittsburgh's design, implementation, and evaluation of a Web-based, institution-wide RCR training program called Research and Practice Fundamentals (RPF). This project, established in 2000, was embedded in the philosophy, organizational structure, and technology developed through the Integrated Advanced Information Management Systems grant from the National Library of Medicine. Utilizing a centralized, comprehensive approach, the RPF system provides an efficient mechanism for deploying content to a large, diverse cohort of learners and supports the needs of research administrators by providing access to information about who has successfully completed the training. During its first 3 years of operation, the RPF served over 17,000 users and issued more than 38,000 training certificates. The 18 modules that are currently available address issues required by regulatory mandates and other content areas important to the research community. RPF users report high levels of satisfaction with content and ease of using the system. Future efforts must explore methods to integrate non-RCR education and training into a centralized, cohesive structure. The University of Pittsburgh's experience with the RPF demonstrates the importance of developing an infrastructure for training that is comprehensive, scalable, reliable, centralized, affordable, and sustainable.

Academic Medical Centers↗
PubMed1998

The origin and evolution of the University of Pittsburgh Department of Neurological Surgery.

Neurological surgery at the University of Pittsburgh began more than 60 years ago with the arrival of Stuart Niles Rowe. During the years, the department has been led by four men, each of whom guided the department into the future in his unique way. These men and many other dedicated physicians, nurses, and staff members have contributed to this organization and created an environment where neurosurgery flourishes. This article describes the development of neurosurgery within the "Steel City" and outlines the origin and growth of the Department of Neurological Surgery at The University of Pittsburgh Medical Center.

Academic Medical Centers↗
PubMed2002

Pittsburgh Registry of Infant Multiplets (PRIM).

This paper describes the Pittsburgh Registry of Infant Multiplets (PRIM; Pittsburgh, Pennsylvania), the results of pilot research conducted in this registry, and the plans for future studies. The main focus of the registry is on psychological development and the risk for behavioral disorders. Particularly, characteristics associated with antisociality and the risk for substance use disorders (e.g., aggressivity, hyperactivity/impulsivity), as well as language development and other traits (e.g., dental health) are among the research targets.

Child Behavior Disorders↗
PubMed1986

Kinetic studies on the interaction of alpha 1-proteinase inhibitor (Pittsburgh) with trypsin-like serine proteinases.

The rates of interaction of a number of serine proteinases with a mutant form of alpha 1-proteinase inhibitor (referred to as alpha 1-proteinase inhibitor (Pittsburgh)), in which a methionine-358 to arginine-358 mutation has occurred, have been determined. An approximately 6,000-fold increase in the second order association rate constant with human thrombin was observed (48 M-1 X s-1 for the normal protein to 3.1 X 10(5) M-1 X s-1 for the arginine mutant), confirming previously observed data using bovine thrombin (Owen, M.C., Brennan, S.O., Lewis, J.H. & Carrell, R.W. (1983) New England J. Med. 309, 694-698). However, substantial increases in the rates of association with other trypsin-like enzymes were also noted, indicating that the replacement of methionine by a basic residue affects all serine proteinases with this kind of specificity. There was a marked decrease in the rates of interaction of the Pittsburgh mutant with both human neutrophil elastase and porcine pancreatic elastase, the inhibitor being converted into lower molecular mass fragments after interaction with either enzyme. Butanedione caused a substantial loss in the inhibitory activity of the arginine mutant, while having no effect on the normal protein. These data, when compared to those previously reported for differences in reaction rates between normal and oxidized alpha 1-proteinase inhibitor (Beatty, K., Bieth, J. & Travis, J. (1980) J. Biol. Chem. 255, 3931-3934), are consistent with the interpretation that the amino acid in the P1-position at the reactive site of this protein has a marked effect on determining its primary specificity.

Blood Proteins↗
PubMed2006

The Pittsburgh Oral-Facial Cleft study: expanding the cleft phenotype. Background and justification.

The Pittsburgh Oral-Facial Cleft study was begun in 1993 with the primary goal of identifying genes involved in nonsyndromic orofacial clefts in a variety of populations worldwide. Based on the results from a number of pilot studies and preliminary genetic analyses, a new research focus was added to the Pittsburgh Oral-Facial Cleft study in 1999: to elucidate the role that associated phenotypic features play in the familial transmission patterns of orofacial clefts in order to expand the definition of the nonsyndromic cleft phenotype. The purpose of this paper is to provide a comprehensive review of phenotypic features associated with nonsyndromic orofacial clefts. These features include fluctuating and directional asymmetry, non-right-handedness, dermatoglyphic patterns, craniofacial morphology, orbicularis oris muscle defects, dental anomalies, structural brain and vertebral anomalies, minor physical anomalies, and velopharyngeal incompetence.

Brain↗
PubMed1982

The Pittsburgh study of insulin-dependent diabetes mellitus. Risk for diabetes among relatives of IDDM.

AN analysis has been made of the family histories of a survey of 1280 cases of IDDM entering Children's Hospital of Pittsburgh between December 31, 1964 and January 1, 1981, discharged on insulin and initial age of onset under 17 yr. Family histories revealed an increased occurrence of IDDM among relatives in the affected families. The risk to siblings was estimated by age-corrected proband exclusion (3.3%) by age 20 and by the Li-Mantel segregation ratio estimator (6.0%). The comparison of these risk measures is discussed. The occurrence of IDDM among the parents is 2.6% and of NIDDM among the parents is 2.4%. A comparison of risk to relatives (parents, sibs, uncles, half-sibs) observed in the Pittsburgh Study to those of six other studies reveal essentially equivalent rates. There is no increased risk to siblings of a diabetic who had an early age of onset. There is an increased risk to siblings of a diabetic (10.5%) in families where at least one parent has insulin-dependent diabetes mellitus (IDDM) and also an increased risk to siblings of a diabetic (8.8%) when at least one parent has non-insulin-dependent diabetes (NIDDM). The average age of onset for second cases in a family is significantly older than age of onset in single case families.

Adolescent↗
PubMedDate not supplied

Diabetes complications and glycemic control. The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM.

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA1) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Children's Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P less than .05). Six female subjects who had an elevated albumin excretion rate (AER; greater than or equal to 20 micrograms/min) had a higher 5-yr mean HbA1 (13.3%) than the 26 subjects with AER less than 20 micrograms/min (11.8%; P less than .05). Current HbA1 was correlated with AER (r = +.36, P less than .05) and systolic blood pressure (r = +.49, P less than .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.

Adolescent↗
PubMed2003

Training in pathology informatics: implementation at the University of Pittsburgh.

CONTEXT: Pathology informatics is generally recognized as an important component of pathology training, but the scope, form, and goals of informatics training vary substantially between pathology residency programs. The Training and Education Committee of the Association for Pathology Informatics (API TEC) has developed a standard set of knowledge and skills objectives that are recommended for inclusion in pathology informatics training and may serve to standardize and formalize training programs in this area. OBJECTIVE: The University of Pittsburgh (Pittsburgh, Pa) core rotation in pathology informatics includes most of these goals and is offered as an implementation model for pathology informatics training. DESIGN: The core rotation in pathology informatics is a 3-week, full-time rotation including didactic sessions and hands-on laboratories. Topics include general desktop computing and the Internet, but the primary focus of the rotation is vocabulary and concepts related to enterprise and pathology information systems, pathology practice, and research. The total contact time is 63 hours, and a total of 19 faculty and staff contribute. Pretests and posttests are given at the start and end of the rotation. Performance and course evaluation data were collected for 3 years (a total of 21 residents). RESULTS: The rotation implements 84% of the knowledge objectives and 94% of the skills objectives recommended by the API TEC. Residents scored an average of about 20% on the pretest and about 70% on the posttest for an average increase during the course of 50%. Posttest scores did not correlate with pretest scores or self-assessed computer skill level. The size of the pretest/posttest difference correlated negatively with the pretest scores and self-assessed computing skill level. CONCLUSIONS: Pretest scores were generally low regardless of whether residents were familiar with desktop computing and productivity applications, indicating that even residents who are computer "savvy" have limited knowledge of pathology informatics topics. Posttest scores showed that all residents' knowledge increased substantially during the course and that residents who were computing novices were not disadvantaged. In fact, novices tended to have higher pretest/posttest differences, indicating that the rotation effectively supported initially less knowledgeable residents in "catching up" to their peers and achieving an appropriate competency level. This rotation provides a formal training model that implements the API TEC recommendations with demonstrated success.

Clinical Competence↗
PubMed1980

"Pittsburgh pneumonia agent": a bacterium phenotypically similar to Legionella pneumophila and identical to the TATLOCK bacterium.

The "Pittsburgh pneumonia agent," isolated by Pasculle and co-workers from human lung tissue, has been cultured on artificial media and characterized. The "Pittsburgh" bacterium and the TATLOCK and HEBA bacteria have identical cultural, biochemical, and antigenic characteristics. They also have the same cellular fatty-acid composition, and DNA relatedness indicates that they belong to the same species.

Antigens, Bacterial↗
PubMed2005

The Pittsburgh Poison Center profile of an American poison information center.

The Pittsburgh Poison Center (PPC), a department of Children's Hospital of Pittsburgh, was established in 1971 to provide emergency poison information to the residents of western Pennsylvania, especially the children. The PPC provides comprehensive poison information center services to the lay public and to medical professionals, poison prevention education, professional education and specialized services to the business and industry sector and governmental agencies.

Adolescent↗
PubMed1989

Measurement of capsular contracture: the conventional breast implant and the Pittsburgh implant.

At present, there is no accurate, reliable method of experimentally measuring capsular contracture. This study had four goals: (1) to define the parameters of capsular contracture employing principles of biomechanics of soft tissues, (2) to develop laboratory techniques to measure the parameters, (3) to design an implant that mechanically impedes the process of encapsulation, and, (4) to test this implant against a conventional one. We have developed a breast implant (the Pittsburgh implant) with an altered surface topography. Its silicone shell is punctuated by projections 1 mm in height and 1 mm in diameter. Two techniques were devised to measure contracture. The first involved measuring the force deformation along a coronal axis. The second involved measuring hydrostatic pressures within the implant resulting from the injection of known quantities of saline. Measurements were performed in vivo on 36 animals. By both force and pressure measurements, the Pittsburgh implant showed less capsular contracture (p = 0.12 and 0.012, respectively). Histology revealed that the prototype surface alters the linear arrangement of myofibroblasts and redirects the laminar collagen into a waveform pattern. We conclude from this experimental study that an altered surface topography may serve as a means of rendering a capsule less mechanically effective. We feel that the proposed methods can be used in the laboratory to characterize the extent of capsular contracture.

Animals↗
PubMed1994

Cardiac transplantation at the University of Pittsburgh: 1994 update.

During the past 14 years, 746 hearts have been transplanted at the University of Pittsburgh. Immunosuppression has evolved from a CsA-based protocol with or without lympholytic prophylaxis to a tacrolimus-based protocol. Tacrolimus offers comparable survival to the conventional immunosuppression but is associated with lesser side effects and lower recurrent rejection. It also serves as an effective rescue agent for intractable rejection in patients receiving CsA-based immunosuppression. However, the shortage of donors, chronic rejection, and the morbidity associated with chronic use of nonspecific immunosuppression remain the major limitations in clinical transplantation. Currently, research at the University of Pittsburgh focuses on the induction of donor-specific transplantation tolerance in order to eliminate the morbidity associated with nonspecific immunosuppression and on left ventricular-assist devices as a bridge and/or an alternative to cardiac transplantation.

Actuarial Analysis↗
PubMed1995

Epiglottitis and Haemophilus influenzae immunization: the Pittsburgh experience--a five-year review.

OBJECTIVE: Current trends in the clinical presentation and management of children with epiglottitis at Children's Hospital of Pittsburgh were reviewed for the years 1988 to 1993. METHODOLOGY: The medical records of all patients diagnosed as having epiglottitis between July 1988 and June 1993 at the Children's Hospital of Pittsburgh were reviewed. An additional telephone survey was conducted among the primary care physicians of those patients to collect information regarding administration of Haemophilus influenzae type b (HIB) vaccines. RESULTS: During the study period 28 children (age range, 11 months to 11 years, 10 months) were admitted with the diagnosis of epiglottitis. Cases declined remarkably in 1991. Fever, sore throat, and stridor were the usual symptoms. HIB was the most common cause of epiglottitis accounting for 21 cases. Candida albicans was recovered from the surface culture of the epiglottis in two patients. At least 11 children experienced vaccine failure: nine with polysaccharide vaccine and two with the conjugate vaccine for HIB. CONCLUSION: Cases of epiglottitis have declined dramatically since licensure of HIB conjugate vaccines for use in early infancy. At least 52% of the reported cases represent vaccine failures with the purified polysaccharide vaccine.

Bacterial Capsules↗
PubMed2003

Lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy improve the prediction of coronary artery disease in Type 1 diabetes. A prospective report from the Pittsburgh Epidemiology of Diabetes Complications Study.

AIM/HYPOTHESIS: To examine whether nuclear magnetic resonance lipoprotein spectroscopy improves the prediction of coronary artery disease in patients with Type 1 diabetes, independently of conventional lipid and other risk factors. METHODS: A prospective nested case-control design of subjects with childhood onset Type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications Study was used. 59 controls were age-, sex- and duration-matched to 59 incident cases of coronary artery disease (fatal or non-fatal myocardial infarction, angina, coronary stenosis >50%) occurring during 10 years of follow-up. Lipid mass and particle concentrations of VLDL, LDL, and HDL subclasses, grouped into three size categories (large, medium, and small), were assessed prior to event with nuclear magnetic resonance spectroscopy. RESULTS: Univariate analyses showed that both lipid mass and particle concentrations of all three VLDL subclasses, small LDL, medium LDL, and medium HDL were increased in CAD cases compared to controls, while large HDL was decreased. Mean LDL and HDL particle sizes were lower in cases. In multivariate models using conventional lipid and non-lipid risk factors, triglycerides and overt nephropathy were the strongest predictors of CAD. Nuclear magnetic resonance measures further improved the prediction, i.e. large HDL particle concentration (OR=0.43, p=0.030), medium HDL mass (OR=3.79, p=0.026) and total VLDL particle concentration (OR=2.33, p=0.033). CONCLUSION/INTERPRETATION: While these results underscore the importance of triglycerides and overt nephropathy in CAD risk in Type 1 diabetic patients, they also suggest that nuclear magnetic resonance lipoprotein spectroscopy could further refine its prediction and show novel findings concerning HDL subclasses.

Adult↗
PubMed1989

Evolution of clinical ethics teaching at the University of Pittsburgh.

The authors explain that several years of effort, by many faculty from a variety of disciplines, were required to expand medical ethics teaching at the University of Pittsburgh School of Medicine beyond the preclinical years. Since 1986, faculty associated with the school's Center for Medical Ethics have begun a comprehensive ethics teaching program for all four years and the residency period; they also are attempting to develop an ethics consultation service. The authors describe the program, its promise and plans, and the significant difficulties involved in establishing and maintaining it, not only problems of long-term funding but of the uninformed and negative attitudes of some students and faculty toward ethics teaching, especially in the clinical setting. Also discussed are the pros and cons of using cases in ethics teaching and the program's approaches to evaluation and to training clinical faculty in clinical ethics issues.

Education, Medical↗