Biomedical subjects
T J Ryan
Publications and source records attributed to T J Ryan.
The relationship between operator volume and outcomes after percutaneous coronary interventions in high volume hospitals in 1994-1996: the northern New England experience. Northern New England Cardiovascular Disease Study Group.
OBJECTIVES: The purpose of this study was to examine the relationship between annual operator volume and outcomes of percutaneous coronary interventions (PCIs) using contemporaneous data. BACKGROUND: The 1997 American College of Cardiology (ACC)/American Heart Association task force based their recommendation that interventionists perform > or = 75 procedures per year to maintain competency in PCI on data collected largely in the early 1990s. The practice of interventional cardiology has since changed with the availability of new devices and drugs. METHODS: Data were collected from 1994 through 1996 on 15,080 PCIs performed during 14,498 hospitalizations by 47 interventional cardiologists practicing at the five high volume (>600 procedures per hospital per year) hospitals in northern New England and one Massachusetts-based institution that support these procedures. Operators were categorized into terciles based on their annualized volume of procedures. Multivariate regression analysis was used to control for case-mix. In-hospital outcomes included death, emergency coronary artery bypass graft surgery (eCABG), non-emergency CABG (non-eCABG), myocardial infarction (MI), death and clinical success (> or = 1 attempted lesion dilated to < 50% residual stenosis and no death, CABG or MI). RESULTS: Average annual procedure rates varied across terciles from low = 68, middle = 115 and high = 209. After adjusting for case-mix, clinical success rates were comparable across terciles (low, middle and high terciles: 90.9%, 88.8% and 90.7%, Ptrend = 0.237), as were all the adverse outcomes including death (low-risk patients = 0.45%, 0.41%, 0.71%, Ptrend = 0.086; high-risk patients = 5.68%, 5.99%, 7.23%, Ptrend = 0.324), eCABG (1.74%, 2.05%, 1.75%, Ptrend = 0.733) and MI (2.57%, 1.90%, 1.86%, Ptrend = 0.065). CONCLUSIONS: Using current data, there is no significant relationship between operator volumes averaging > or = 68 per year and outcomes at high volume hospitals. Future efforts should be directed at determining the generalizability of these results.
Site-directed mutagenesis establishes cysteine-110 as essential for enzyme activity in human gamma-glutamyl hydrolase.
Gamma-glutamyl hydrolase (GH), which hydrolyses the gamma-glutamyl conjugates of folic acid, is a key enzyme in the maintenance of cellular folylpolyglutamate concentrations. The catalytic mechanism of GH is not known. Consistent with earlier reports that GH is sulphydryl-sensitive, we found that recombinant human GH is inhibited by iodoacetic acid, suggesting that at least one cysteine is important for activity [Rhee, Lindau-Shepard, Chave, Galivan and Ryan (1998) Mol. Pharmacol. 53, 1040-1046]. Using site-directed mutagenesis, the cDNA for human GH was altered to encode four different proteins each with one of four cysteine residues changed to alanine. Three of the mutant proteins had activities similar to wild-type GH and were inhibited by iodoacetic acid, whereas the C110A mutant had no activity. Cys-110 is conserved among the human, rat and mouse GH amino acid sequences. The wild-type protein and all four mutants had similar intrinsic fluorescence spectra, indicating no major structural changes had been introduced. These results indicate that Cys-110 is essential for enzyme activity and suggest that GH is a cysteine peptidase. These studies represent the first identification of the essential Cys residue in this enzyme and provide the beginning of a framework to determine the catalytic mechanism, important in defining GH as a therapeutic target.
ACC/AHA guidelines for coronary artery bypass graft surgery: executive summary and recommendations : A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1991 guidelines for coronary artery bypass graft surgery).
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1999 update: ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction: Executive Summary and Recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction).
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Early revascularization in cardiogenic shock--a positive view of a negative trial.
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ACC/AHA guidelines for ambulatory electrocardiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the guidelines for ambulatory electrocardiography).
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ACC/AHA guidelines for coronary angiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography) developed in collaboration with the Society for Cardiac Angiography and Interventions.
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Management issues in vasculitis.
In a Congress devoted to both rheumatic disease and skin disease, vasculitis is an appropriate topic for discussion. Many dermatologists believe that rheumatology has made a mess of the classification of vasculitis and with respect to management it is too drug orientated. When vasculitis is uncomplicated and affects only a single organ it behaves benignly and needs only attention to protection and decreasing the vulnerability of the skin to gravitational 'stasis', pressure, cooling and immobility. Complicated, multi-system vasculitis frequently needs much of the same skin care plus additional drug therapies. Unfortunately, there is no evidence that vasculitis of the skin is responsive to such drugs other than single case reports and uncontrolled trials. Where the cause of the vasculitis is a known infection, food or drug, autoimmune process or neoplasm, removal of the cause is an appropriate policy.
Glutamyl hydrolase and the multitargeted antifolate LY231514.
PURPOSE: To examine the activity of glutamyl hydrolase (GH) on the poly-gamma-glutamates of multitargeted antifolate (MTA) (LY231514) and the effect of enhanced GH on the pharmacological activity of MTA. METHODS: Expressed and purified GH were used to study the enzymatic cleavage of MTA poly-gamma-glutamates and wild-type and GH-enhanced H35 hepatoma cell lines to evaluate growth inhibition. RESULTS: MTA tri- and penta-gamma-glutamates were good substrates for human GH, having higher rates than MTX tri- and penta-gamma-glutamates. Preferential hydrolysis with human enzyme occurred at the two gamma-glutamyl bonds at the carboxyl end of the molecule, whereas the rat enzyme preferred the innermost gamma-linkage. Incubation of rat H35 hepatoma cell lines with MTA resulted in the intracellular accumulation of primarily tetra-, penta-, and hexa-gamma-glutamate. The formation of these were markedly reduced in H35D cells, which is a line resistant to antifolates chiefly through enhanced cellular levels of GH activity. CONCLUSIONS: MTA poly-gamma-glutamates are effective substrates for GH and their pharmacological effectiveness bears an inverse relationship to cellular GH activity. This observation, along with enhanced resistance to MTA of thymidylate synthase-amplified cells, substantiates the importance of the poly-gamma-glutamates of MTA inhibiting TS as the primary target. Further evidence for the inverse relationship of GH to classical antifolate pharmacological activity is established.
Clinical correlates of the initial and long-term cost of coronary bypass surgery and coronary angioplasty.
BACKGROUND: Medical costs vary substantially among patients. Understanding the baseline factors that predict subsequent cost may allow better selection of therapy for individual patients. Understanding the postprocedure events that increase cost should help to improve efficiency and effectiveness of coronary revascularization. METHODS: Data on 4-year costs were collected from patients randomly assigned to coronary angioplasty or bypass surgery as part of the BARI (Bypass Angioplasty Revascularization Investigation) trial. Regression models first examined factors known at the time of randomization that prospectively predicted initial procedure cost and long-term cost. Subsequent models tested the value of postrandomization events as explanatory variables for cost. RESULTS: The independent baseline predictors of higher initial percutaneous transluminal coronary angioplasty cost included 3-vessel disease (+12%) and acute presentations (+22%), whereas the independent predictors of higher initial coronary artery bypass grafting cost included the number of comorbid conditions (+5% per condition) and female sex (+7%). The independent baseline predictors of 4-year cost included heart failure (+26%), diabetes (+22%), comorbidity (+10%), and angioplasty assignment in patients with 2-vessel disease (-15%). Postrandomization models showed higher initial and long-term costs were strongly correlated with the number of repeat revascularization procedures (+30% to +128%) and the occurrence of clinical complications (+8% to +131%). CONCLUSIONS: Two-vessel disease identifies patients likely to have lower costs after angioplasty, whereas heart failure, comorbid conditions, and diabetes identify patients likely to accrue higher costs after either angioplasty or bypass surgery. Long-term costs can be potentially reduced by interventions that decrease procedural complications or reduce the need for repeat revascularization.
Primary PTCA versus thrombolytic therapy: an evidence-based summary.
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Coronary heart disease. Stable and unstable syndromes.
CHD in the elderly population will continue to be a source of major concern because of the increasing costs entailed and uncertainties about how the widespread array of diagnostic and therapeutic interventions, often expensive and sometimes hazardous, should be applied. Financial, political, and health policy decisions will continue to occupy much attention, but it is likely that philosophic considerations about aging and death, both from the individual and the societal perspective, will be of paramount importance of deciding how the substantial resources available to the elderly will be used. Randomized, controlled trials are unlikely to play a major role in resolution of management dilemmas in the elderly because of the extraordinary heterogeneity in this population. Registries (databases) involving carefully prospectively collected key variables are likely to be a more effective approach. Critical characterization of complications of procedures, adverse drug reactions, and collection of follow-up data on functional status are among the critical questions, and these can be answered by registry studies. Algorithms and clinical rules developed in younger cohorts are not directly transferable to the elderly cardiovascular patients, further emphasizing the need for prospectively collected, syndrome-specific data. Treatments convincingly demonstrated to reduce mortality in absolute terms more in the elderly than in the young are underused. The heterogeneity of aging emphasizes the wide variability in patients' ability to withstand the stress of procedures and complications of disease and makes clear the need to consider physiologic reserve and biologic age rather than chronology. With better characterization of biologic age and physiologic reserve, more precise estimates of outcomes of therapies and interventions can be made, and patients can be given better information and with their families have more realistic expectations. Better-informed decisions will result. Biologic age will be multifactorial, involving cognitive, emotional, physical, and nutritional attributes as well as specific organ function (lung, kidney, liver) because no single feature can characterize the total elderly patient. The concept of competing risks among the cardiovascular disease being treated, comorbidity, risks of study, and life expectancy will evolve because even the most successful therapy will have limited effect on longevity in the very old. Although important research at the cellular and molecular level will characterize and provide better understanding of the aging process, it is not likely that this basic information will be immediately useful in the management of the large number of elderly patients with major cardiovascular disease. Preventive measures, including physical exercise, mental stimulation, avoidance of depression, good nutrition, and abstinence from tobacco use, are useful approaches to postpone or ameliorate the consequences of aging and allow patients to tolerate cardiovascular diseases better when they become manifest.
A comparison of three-year survival after coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty.
OBJECTIVES: The purpose of this study was to compare 3-year risk-adjusted survival in patients undergoing coronary artery bypass graft (CABG) surgery and percutaneous transluminal coronary angioplasty. BACKGROUND: Coronary artery bypass graft surgery and angioplasty are two common treatments for coronary artery disease. For referral purposes, it is important to know the relative pattern of survival after hospital discharge for these procedures and to identify patient characteristics that are related to survival. METHODS: New York's CABG surgery and angioplasty registries were used to identify New York patients undergoing CABG surgery and angioplasty from January 1, 1993 to December 31, 1995. Mortality within 3 years of undergoing the procedure (adjusted for patient severity of illness) and subsequent revascularization within 3 years were captured. Three-year mortality rates were adjusted using proportional hazards methods to account for baseline differences in patients' severity of illness. RESULTS: Patients with one-vessel disease with the one vessel not involving the left anterior descending artery (LAD) or with less than 70% LAD stenosis had a statistically significantly longer adjusted 3-year survival with angioplasty (95.3%) than with CABG surgery (92.4%). Patients with proximal LAD stenosis of at least 70% had a statistically significantly longer adjusted 3-year survival with CABG surgery than with angioplasty regardless of the number of coronary vessels diseased. Also, patients with three-vessel disease had a statistically significantly longer adjusted 3-year survival with CABG surgery regardless of proximal LAD disease. Patients with other one-vessel or two-vessel disease had no treatment-related differences in survival. CONCLUSIONS: Treatment-related survival benefit at 3-years in patients with ischemic heart disease is predicted by the anatomic extent and specific site of the disease, as well as by the treatment chosen.
ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac Angiography and Interventions.
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ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina).
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Changing outcomes in percutaneous coronary interventions: a study of 34,752 procedures in northern New England, 1990 to 1997. Northern New England Cardiovascular Disease Study Group.
OBJECTIVES: We sought to evaluate the changing outcomes of percutaneous coronary interventions (PCIs) in recent years. BACKGROUND: The field of interventional cardiology has seen considerable growth in recent years, both in the number of patients undergoing procedures and in the development of new technology. In view of recent changes, we evaluated the experience of a large, regional registry of PCIs and outcomes over time. METHODS: Data were collected from 1990 to 1997 on 34,752 consecutive PCIs performed at all hospitals in Maine (two), New Hampshire (two) and Vermont (one) supporting these procedures, and one hospital in Massachusetts. Univariate and multivariate regression analyses were used to control for case mix. Clinical success was defined as at least one lesion dilated to <50% residual stenosis and no adverse outcomes. In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction and mortality. RESULTS: Over time, the population undergoing PCIs tended to be older with increasing comorbidity. After adjustment for case mix, clinical success continued to improve from a low of 88.2% in earlier years to a peak of 91.9% in recent years (p trend <0.001). The rate of emergency CABG after PCI fell in recent years from a peak of 2.3% to 1.3% (p trend <0.001). Mortality rates decreased slightly from 1.2% to 1.1% (p trend 0.007). CONCLUSIONS: There has been a significant improvement in clinical outcomes for patients undergoing PCIs in northern New England, including a significant decline in the need for emergency CABG.
1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction).
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