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At least 19 recordsLinked to original sources
PubMed1990

Evolution of the Pittsburgh studies of the epidemiology of insulin-dependent diabetes mellitus. Pittsburgh Diabetes Epidemiology and Etiology Research Group.

The Pittsburgh project evaluating the epidemiology and etiology of insulin-dependent diabetes mellitus (IDDM) is currently one of the large ongoing studies of childhood diabetes. This paper traces the evolution of the project, from the initial basic epidemiologic approach in the early 1980s, to the current thrust where complex molecular genetic approaches are being incorporated into population-based research. The epidemiology models employed in the Pittsburgh project are similar to those that could be used in many areas of chronic disease research. The integration of immunogenetics into epidemiology produces a powerful approach for understanding the complex interaction of host susceptibility and environmental agents that contribute to the development of IDDM.

Adolescent↗
PubMed1985

Tatlockia micdadei (Pittsburgh pneumonia agent) growth kinetics may explain its infrequent isolation from water and the low prevalence of Pittsburgh pneumonia.

Sediment and indigenous microflora taken from water distribution systems has been shown to promote the survival of Legionella pneumophila. The effect of sediment and indigenous microflora on Tatlockia micdadei (Pittsburgh pneumonia agent, PPA) was evaluated by growth curve experiments. Symbiosis between PPA and environmental bacteria was demonstrated by satellitism experiments. Unlike L. pneumophila, the concentration of PPA remained stationary in test tube suspensions containing both microflora and sediment. The difference in the ecology between the two organisms may explain the infrequent environmental recovery of PPA and, ultimately, the epidemiologic differences between Legionnaires disease and Pittsburgh pneumonia.

Bacteria↗
PubMed1998

Recombinant antitrypsin Pittsburgh undergoes proteolytic cleavage during E. coli sepsis and fails to prevent the associated coagulopathy in a primate model.

During severe sepsis there is dramatic activation of both contact proteases and the coagulation pathway. These processes contribute to the development of shock and disseminated intravascular coagulation (DIC) respectively. The Pittsburgh mutant of antitrypsin (358Met-Arg) is a novel protease inhibitor with activity against both thrombin and the contact proteases and should therefore prove beneficial as a therapeutic agent in the management of septic shock. This hypothesis was supported by an earlier study in a pig model where recombinant antitrypsin Pittsburgh (rAT Pittsburgh) at a concentration of 1 microM alleviated some of the features of shock, but did not improve survival. In order to reduce the lethal effects of E. coli sepsis we postulated that a higher concentration of antitrypsin Pittsburgh would be necessary. To test this hypothesis we used rAT Pittsburgh in a primate model. This was chosen in preference to another species as E. coli sepsis in the primate has been well characterised and closely resembles the changes seen in man. Surprisingly this treatment did not alleviate the features of shock and unexpectedly appeared to exacerbate the associated coagulopathy. We propose two possible mechanisms for this unforeseen outcome. The first results from the broad spectrum of activity of antitrypsin Pittsburgh. As well as inhibiting thrombin and the contact proteases, the Pittsburgh mutant also inhibits activated protein C. Inhibition of the protein C system is known to exacerbate septic shock. Secondly, a significant quantity of inactive antitrypsin Pittsburgh, cleaved at the reactive centre, was detected in the plasma of the treated animals. Proteolytically altered serpins, including antitrypsin. have been shown to enhance the inflammatory process. Therefore the accumulation of cleaved rAT Pittsburgh might be expected to exacerbate septic shock.

Animals↗
PubMed1986

Alpha-1-antitrypsin-Pittsburgh. A potent inhibitor of human plasma factor XIa, kallikrein, and factor XIIf.

Alpha-1-antitrypsin-Pittsburgh is a human variant that resulted from a point mutation in the plasma protease inhibitor, alpha 1-antitrypsin (358 Met----Arg). This defect in the alpha 1-antitrypsin molecule causes it to have greatly diminished anti-elastase activity but markedly increased antithrombin activity. In this report, we demonstrate that this variant protein also has greatly increased inhibitory activity towards the arginine-specific enzymes of the contact system of plasma proteolysis (Factor XIa, kallikrein, and Factor XIIf), in contrast to normal alpha 1-antitrypsin, which has modest to no inhibitory activity towards these enzymes. We determined the second-order-inactivation rate constant (k'') of purified, human Factor XIa by purified alpha 1-antitrypsin-Pittsburgh and found it to be 5.1 X 10(5) M-1 s-1 (23 degrees C), which is a 7,700-fold increase over the k'' for Factor XIa by its major inhibitor, normal purified alpha 1-antitrypsin (i.e., 6.6 X 10(1) M-1 s-1). Human plasma kallikrein, which is poorly inhibited by alpha 1-antitrypsin (k'' = 4.2 M-1 s-1), exhibited a k'' for alpha 1-antitrypsin-Pittsburgh of 8.9 X 10(4) M-1 s-1 (a 21,000-fold increase), making it a more efficient inhibitor than either of the naturally occurring major inhibitors of kallikrein (C-1-inhibitor and alpha 2-macroglobulin). Factor XIIf, which is not inhibited by normal alpha 1-antitrypsin, displayed a k'' for alpha 1-antitrypsin-Pittsburgh of 2.5 X 10(4) M-1 s-1. This enhanced inhibitory activity is similar to the effect of alpha 1-antitrypsin-Pittsburgh that has been reported for thrombin. In addition to its potential as an anticoagulant, this recently cloned protein may prove to be clinically valuable in the management of septic shock, hereditary angioedema, or other syndromes involving activation of the surface-mediated plasma proteolytic system.

Factor IX↗
PubMed1983

Simultaneous infection with Legionella pneumophila and Pittsburgh pneumonia agent. Clinical features and epidemiologic implications.

Nosocomial pneumonia caused simultaneously by two organisms, Legionella pneumophila and the Pittsburgh pneumonia agent, was documented in seven patients in one institution. In all seven cases, both organisms were demonstrated by isolation from culture or visualization by direct immunofluorescence. Four patients died as a result of pneumonia, including two who received erythromycin therapy. The hospital water distribution system appeared to be the reservoir for both L. pneumophila and Pittsburgh pneumonia agent. These seven cases constituted 26.9 percent and 17.9 percent of the cases of Pittsburgh pneumonia agent and Legionnaires' disease, respectively, at one institution. Given this relatively high incidence of dual infection, it is likely that the mode of transmission for both organisms is identical. Dual infection may account for some cases of antibody response to more than one Legionella species. Historical parallels of the discovery of L. pneumophila and Pittsburgh pneumonia agent are reviewed.

Cross Infection↗
PubMed1993

Circulating proalbumin associated with a second case of antitrypsin Pittsburgh.

We report here the conclusive identification of circulating proalbumin of normal N-terminal sequence (Arg Gly Val Phe Arg Arg Asp Ala) in a second child with the alpha 1-antitrypsin Pittsburgh 358 Met-->Arg mutation. As in the first case, the proalbumin made up 3-5% of the total serum albumin. The finding of proalbumin associated with a second de novo mutation at the inhibitory site bait of antitrypsin confirms our earlier hypothesis; that antitrypsin Pittsburgh was acting as a specific intracellular inhibitor of the hepatic proalbumin convertase and that antitrypsin Pittsburgh could be used as a probe to identify the proprotein convertase.

Amino Acid Sequence↗
PubMed1983

Legionellaceae in the hospital water-supply. Epidemiological link with disease and evaluation of a method for control of nosocomial legionnaires' disease and Pittsburgh pneumonia.

An epidemiological link was found between contamination of a hospital water-supply by Legionella pneumophila and by Pittsburgh pneumonia agent (PPA) and subsequent cases of nosocomial legionnaires' disease and Pittsburgh pneumonia. The extent of L pneumophila isolation from the water-supply paralleled the occurrence of disease. Whenever L pneumophila was isolated from more than 30% of ten selected water sites, nosocomial legionellosis occurred. The temperature of the hot water tanks was raised to 60-77 degrees C for 72 h, and water outlets were flushed for 30 min with hot water. A decline in numbers of L pneumophila and PPA in the water-supply was followed by a fall in the incidence of legionnaires' disease and Pittsburgh pneumonia. In addition, intermittent raising of the temperature in the hot water system decreased both the number of months in which disease occurred and the proportion of nosocomial pneumonias caused by these organisms.

Cross Infection↗
PubMed1999

A novel mutation in the apolipoprotein E gene (APOE*4 Pittsburgh) is associated with the risk of late-onset Alzheimer's disease.

Using a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing techniques, we identified a unique missense mutation (T-->C) in exon 3 of the APOE gene which resulted in the substitution of pro-28 for leu-28. We screened 1118 White cases of late-onset (>60 years) Alzheimer's disease (AD) from three independent centers (Pittsburgh = 489, Indiana = 319, Mayo Clinic Rochester = 310) and 1123 controls (607 clinically assessed and 516 individuals randomly ascertained from the general population). Two of the 1123 control subjects had the pro-28 mutation (0.18%). However, this mutation was observed in heterozygous state in 2.66, 2.51 and 1.94% of the AD cases from Pittsburgh, Indiana and Mayo Clinic Rochester, respectively, with an overall frequency of 2.42%. All individuals with this mutation were carriers of the APOE*4 allele and hence the mutation was denoted as APOE*4 Pittsburgh (APOE*4P). Compared with the non-E*4P carriers, the E*4P carriers were associated with an increased risk of AD (odds ratio (OR) 13.2) and this risk remained significant even after adjusting for the known effect of APOE*4 (OR 5.4). The risk associated with the E*4P/E*4 combination was about five times (OR 29.1) the risk attributed to APOE*4 carriers alone (OR 5.7). Our data indicates that the new mutation most likely exists in cis-orientation with APOE*4 and is associated with increased risk of developing AD.

Adult↗
PubMed1977

Factors related to the incidence of stomach cancer in the Pittsburgh Standard Metropolitan Statistical Area.

This report presents an analysis of several demographic discriminants of stomach cancer incidence for residents of the Pittsburgh Standard Metropolitan Statistical Area (SMSA) with the use of data collected as part of the Third National Cancer Survey, 1969-71. The Pittsburgh SMSA, one of nine areas included in the Third National Cancer Survey, was of particular interest in the study of stomach cancer, since area residents showed the highest age-adjusted incidence rate for cancer of this site while showing the fifth highest rate for all sites. To examine the data in greater detail, we used the variables of sex, race, nativity, and median income level to classify the cancer patients into homogeneous subgroups of census tracts of residence to allow comparisons of the average annual age-adjusted incidence rates among the groups. The data indicated that Pittsburgh SMSA residents showed stomach cancer incidence patterns that were generally consistent with earlier published reports; particularly when contrasted with appropriate population subgroups, higher rates appeared for males, for blacks, for lower income areas, and for areas with "large" proportions of foreign-born and foreign-stock residents. Furthermore, when one considered interactions among the factors, the relationship between ethnic composition and incidence appeared to supercede that of income among white males.

Adult↗
PubMedDate not supplied

Health care cost containment: how Pittsburgh is addressing the challenge.

Rapidly escalating health care costs have the public and private sectors searching for methods to provide health care benefits in a more efficient manner. Efforts have also been underway at the community level with the development of health care coalitions created to build consensus toward a fair solution for all parties affected. With the assistance of the Robert Wood Johnson Foundation and many local co-sponsors, the Pittsburgh Program for Affordable Health Care (PPAHC) was organized to address health care cost containment issues in the greater Pittsburgh area. One of the means by which PPAHC chose to achieve this was through the development of a Model Utilization Management Program. This is a document containing community-sanctioned administrative and clinical standards for utilization review which take into consideration the needs and concerns of providers, purchasers, and consumers, and which have a goal of reducing medically unnecessary inpatient hospitalization while concurrently maintaining quality of and access to care. This article describes both the process and the product of PPAHC's efforts toward health care cost containment in Pittsburgh, specifically focusing on its utilization management component.

Community Participation↗
PubMed1988

The Presbyterian-University Hospital, Pittsburgh. The gamma knife: brain surgery without an incision.

In July of 1987 a 20-ton gamma heavily shielded in a concrete "hot cell" was rolled into the basement of Presbyterian-University Hospital in Pittsburgh. Installation of the unit-one of only five in the world-and the first of its kind in the United States-was the culmination of 4.5 years of planning. It started in 1982 when the gamma knife was approved for marketing by the Food and Drug Administration. But because radioactive sources are sealed within the unit, it also had to be approved by the Nuclear Regulatory Commission (NRC), a process that required extensive and multiple levels of review within the nuclear agency. Although the device itself finally received NRC approval in 1986, the NRC Transportation Division refused to grant permission to transport a cobalt-loaded unit. So physicists at the University of Pittsburgh devised plans for on-site loading amidst the busy hospital environment in Pittsburgh! First a hot cell consisting of 3,000 lb of solid concrete block was constructed around the unit. Then, using robotic micromanipulators, the unit was loaded with 201 sources of cobalt-60, approximately 30 Ci each. The almost-6,000 Ci of cobalt provided a dosage rate of 396 cGy/min to the focal point, and patient treatment began one month later in August. Third-party reimbursement has been obtained from most major health insurance policies, and the procedure is approved for payment by Blue Shield and Medicare of Pennsylvania.

Brain Neoplasms↗
PubMed1993

Examining the range of health care reform. University of Pittsburgh Task Force on Health Care Financing.

On December 16, 1991, Senator Harris Wofford invited the president of the University of Pittsburgh Medical Center to convene a group of its leaders for a roundtable discussion of health care issues. At that meeting, J. Dennis O'Connor, Ph.D., chancellor of the University of Pittsburgh, offered to appoint a multidisciplinary group of people from western Pennsylvania to collect data to analyze future policy options relative to health care and make its findings available to the senator, other legislators, and health policy makers. The chancellor invited representatives from the community, the University of Pittsburgh Medical Center, the University's Faculty of Arts and Sciences, and other academic and health care institutions in the area to participate in the analytical process. The task force met frequently over a 10-month period to develop a report, a portion of which is excerpted here.

Health Policy↗
PubMed1995

Beyond Pittsburgh: protocols for controlled non-heart-beating cadaver organ recovery.

Much of the ethical debate about controlled non-heart-beating cadaver (NHBC) organ recovery has focused on the University of Pittsburgh Medical Center (UPMC) protocol. Some commentators have voiced serious reservations about the ethical acceptability of that protocol; others have argued that the protocol contains sufficiently stringent ethical safeguards to warrant a limited and carefully monitored trial at UPMC. UPMC is not the only organization pursuing controlled NHBC organ procurement, however. The study of organ procurement organizations described in this article suggests that controlled NHBC organ procurement is a practice that, if not yet widespread, is certainly no longer isolated to a few organizations in which it is carefully monitored. Rather, it is being carried out under a variety of circumstances, many of which are less carefully constrained ethically than at the University of Pittsburgh Medical Center. The next stage of the ethical debate should focus on issues that are arising in a variety of settings as the practice spreads.

Academic Medical Centers↗
PubMed1993

The 11-year Pittsburgh experience with liver transplantation for hepatocellular carcinoma: 1981-1991.

Experience with liver transplantation over a period of 11 years at the University of Pittsburgh is presented. The application of liver transplantation to cases of hepatocellular carcinoma has changed considerably over this 11-year period with the sequential introduction of adjuvant and, more recently, neoadjuvant chemotherapy. Results with the combination of chemotherapy plus surgery appear to be better than results with either agent alone. Moreover, the early results with neoadjuvant therapy appear to be better than those achieved with adjuvant therapy. As a result of this experience, conceptual changes in the approach to the problem of hepatic cancer and the role of both chemotherapy and liver transplantation in its management have changed at the University of Pittsburgh. These changes are identified and discussed.

Adenoma, Bile Duct↗
PubMed1989

Height at onset of insulin-dependent diabetes mellitus in high- and low-risk countries. Japan and Pittsburgh Childhood Diabetes Research Groups.

The relative height at the onset of insulin-dependent diabetes mellitus was recorded in 340 cases from Japan and 191 cases from Pittsburgh, U.S.A. In Pittsburgh, the children diagnosed after puberty were shorter than normal whereas those diagnosed prior to puberty were much taller than normal. However, in Japan, there was no association between age at onset and relative height; at every age the newly diabetic children had similar relative heights to the non-diabetic population. This discrepancy may be related to the 18-fold incidence difference between the two countries.

Adolescent↗