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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↗
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↗
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↗
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↗
PubMedDate not supplied

Spontaneous whole blood platelet aggregation, hematological variables and complications in insulin-dependent diabetes mellitus: the Pittsburgh Epidemiology of Diabetes Complications Study.

The role of platelet aggregation in the pathogenesis of diabetes complications remains unclear despite a number of reports suggesting associations in univariate analyses. The Pittsburgh Epidemiology of Diabetes Complications Study is a prospective study initiated in 1985 to determine risk factors for the development of complications in insulin-dependent diabetes mellitus (IDDM). This report focuses on the cross-sectional correlation between platelet count and aggregation and IDDM complications, in 563 participants aged 18 years and older seen at baseline. Spontaneous whole blood platelet aggregation (SWBPA) and other hematological variables [hematocrit, total platelet count (TPC), red blood cell count (RBC), fibrinogen and white blood cell count (WBC)] were evaluated as risk factors for IDDM complications (nephropathy, neuropathy, and retinopathy) in the baseline cross-sectional data of the Pittsburgh Epidemiology of Diabetes Complications Study. SWBPA was determined by a method based on the percentage fall in platelet count after shaking a fresh citrated blood sample kept at 37 degrees C. Subjects with chronic aspirin use or on dialysis were excluded from analysis. An increased TPC was observed in subjects with overt nephropathy (291.4 +/- 65.1 versus 261.2 +/- 64.9, p less than 0.001) compared with subjects without nephropathy. Similar results were found for proliferative retinopathy. The association with nephropathy (but not with retinopathy) persisted in multivariate analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
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↗
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↗
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↗
PubMed1975

Demography and evolution of an urban ethnic community: Polish Hill, Pittsburgh.

Polish Hill is an urban, ethnic enclave of approximately 3000 residents residing in a 25-block area of Pittsburgh. This paper documents changes in the fertility, morbidity, and mortality patterns in the community from the turn of the century to the present. The demographic reconstruction is based upon baptismal and marriage records, the administration of demographic proformae and population censuses. The high mortality, morbidity, and fertility variance suggest that the immigrant population has experienced a period of high opportunity for selection in the early 1900's and that Crow's index was gradually reduced to its present level.

Adolescent↗
PubMed1992

The impact of the apolipoprotein E polymorphism on the lipoprotein profile in insulin-dependent diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study IX.

The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.

Adult↗
PubMed1989

The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research.

Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.

Adult↗
PubMed1988

An epidemiologic approach to the study of retinopathy: the Pittsburgh diabetic morbidity and retinopathy studies.

Diabetic retinopathy was studied in two cohorts of insulin-dependent diabetics (IDDs) from the Children's Hospital of Pittsburgh. The first cohort (n = 696) consisted of IDDs of long duration. Severe retinopathy was self-reported in 70% of this cohort by 30 years duration of diabetes. Associations between severe retinopathy, hypertension and smoking were observed. In order to examine the relationship between metabolic control and early diabetic retinopathy, a second cohort of adolescent IDDs (n = 58) were referred for standardized fluorescein angiography. Sixty-four percent had early retinopathy. None had proliferative changes. Significant differences in individual mean whole blood glycosylated hemoglobin (GHb), averaged over 3 years before angiography, were consistently seen between those with and without early retinopathy. Also, the number of microaneurysms was positively correlated with individual mean GHb. Before the advent of GHb testing, those IDDs who later had retinopathy were more likely to have experienced at least one hospitalization for diabetic ketoacidosis. These observations provide strong support that poor metabolic control preceded the development of diabetic retinopathy. Results are consistent with the hypothesis that improvement of metabolic control early in the course of IDDM may prevent or delay the development of the early changes of diabetic retinopathy.

Adolescent↗
PubMed1979

Opportunistic lung infection due to "Pittsburgh Pneumonia Agent".

Eight immunosuppressed patients had pneumonia due to Pittsburgh Pneumonia Agent (PPA), a gram-negative, weakly acid-fast bacterium cultivatable only in embryonated eggs and guinea pigs and distinct from Legionella pneumophila. The diagnosis was established by isolation of the agent from lung or visualization of the organism in lung tissue. The clinical presentations, radiographic abnormalities and pathology were not specific. The most consistent feature associated with the disease was the recent institution of daily high-dose corticosteriod therapy in all patients. Five of the eight patients died despite broad-spectrum antibiotic and antituberculous therapy. Anti-microbial activity against PPA was demonstrated for sulfamethoxazole combined with trimethoprim, for rifampin and for erythromycin with an egg-protection assay. Serologic studies with an indirect fluorescent-antibody technic suggested that seroconversion or high titers may be a sensitive test for PPA disease. PPA appears to be a newly recognized cause of life-threatening bacterial pneumonia in immunosupressed patients.

Adrenal Cortex Hormones↗
PubMed1987

Assessment of neuropsychological dysfunction in the workplace: normative data from the Pittsburgh Occupational Exposures Test Battery.

Neuropsychologists are being increasingly called upon to assess the neurobehavioral status of adults who have been exposed to toxic chemicals or heavy metals in the workplace. Unfortunately, the evaluation of blue-collar workers has been hampered by the absence of a brief yet comprehensive battery of sensitive neuropsychological tests that have been administered to a large cohort of demographically similar adults with no prior history of occupational exposure. In this paper we describe the development of the Pittsburgh Occupational Exposures Test Battery. We detail the procedures used to collect appropriate age-scaled norms from 182 blue-collar males, and delineate the factor structure of the test battery. We also examine the interrelationships among test scores and certain demographic variables, and discuss the epidemiologic and clinical relevance of these data.

Adult↗