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Biomedical subjects

R D Levy

Publications and source records attributed to R D Levy.

At least 19 recordsLinked to original sources
PubMed2006

Bronchiolitis obliterans following lung transplantation: early detection using computed tomographic scanning.

BACKGROUND: Computed tomographic (CT) scanning may enable earlier diagnosis of chronic lung allograft dysfunction than forced expiratory volume in 1 second (FEV1). A study was undertaken to determine intra-observer and inter-observer agreement of composite and air trapping CT scores, to examine the association of FEV1 with the composite and air trapping CT score, and to relate the baseline composite CT score to changes in FEV1 and changes in the composite CT score over 1 year. METHODS: Lung function and baseline CT scans following transplantation and at subsequent annual follow ups were analysed in 38 lung transplant recipients. Scans were randomly scored by two observers for bronchiectasis, mucus plugging, airway wall thickening, consolidation, mosaic pattern, and air trapping, and re-scored after 1 month. CT scores were expressed on a scale of 0-100 and correlated with FEV1 as a percentage of the post-transplant baseline value. RESULTS: The mean (SD) interval between baseline and follow up CT scans was 11.2 (4.7) months. Inter-observer and intra-observer agreement was good for both the composite and air trapping CT scores. There was a significant association between FEV1 and the composite CT score, with each unit of worsening in the baseline composite CT score predicting a 1.55% and 1.37% worsening in FEV1 over the following year (p<0.0001) and a 1.25 and 1.12 unit worsening in the composite CT score (p<0.0001) for observers 1 and 2, respectively. CONCLUSION: These findings indicate a potential role for a composite CT scoring system in the early detection of bronchiolitis obliterans.

Adolescent↗
PubMed2006

Outcome in the real-world of coronary high-risk intervention with drug-eluting stents (ORCHID) -- a single-center study comparing Cypher sirolimus-eluting with Taxus paclitaxel-eluting stents.

OBJECTIVE: We present real world experience from a single center registry comparing the 6-month outcome of percutaneous coronary intervention (PCI) in unselected high-risk individuals using either sirolimus-eluting (SES) or paclitaxel-eluting stents (PES). METHODS/RESULTS: We compared clinical outcome at 6 months follow-up in two cohorts of 156 consecutive patients (total n = 312) who underwent SES (June 2002-February 2003) and PES (march 2003-July 2003) implantation. The primary endpoint was a composite of major adverse cardiac events (MACE). Baseline clinical characteristics were well matched. The 6-month target vessel revascularization (TVR) rates were 1.9% (SES) and 2.6% (PES) and MACE rates were similar in the two groups (SES 4.5% vs. PES 3.2%, P = NS). In the PES group, intervention for multivessel disease, bifurcation lesions and in small vessels was more common, and for in-stent restenosis less common, reflecting the impact of drug eluting stents on indications for PCI. The incidence of sub-acute stent thrombosis, related to inadequate antiplatelet therapy in 3 of the 6 cases, was 0.95% with no difference between the two groups. CONCLUSION: This study confirms the safety and efficacy of SES and PES in unselected high risk patients undergoing PCI. Clinical outcomes of both stents are equivalent at 6 months with low rates of MACE and TVR. These data provide important complementary information to forthcoming randomized studies.

Angioplasty, Balloon, Coronary↗
PubMed2005

Pulmonary hypertension in chronic obstructive pulmonary disease: current theories of pathogenesis and their implications for treatment.

The development of pulmonary hypertension is a poor prognostic sign in patients with chronic obstructive pulmonary disease (COPD), affecting both mortality and quality of life. Although pulmonary hypertension in COPD is traditionally viewed as a result of emphysematous destruction of the vascular bed and/or hypoxia, recent studies indicate that neither of these factors correlates very well with pulmonary artery pressures. New human and animal experimental data are beginning to show that pulmonary hypertension in this setting is probably a result of the direct effect of tobacco smoke on the intrapulmonary vessels with abnormal production of mediators that control vasoconstriction, vasodilatation, and vascular cell proliferation, ultimately leading to aberrant vascular remodelling and aberrant vascular physiology. These changes are in many ways similar to those seen in other forms of pulmonary hypertension and suggest that the treatments used for primary pulmonary hypertension may be beneficial in patients with COPD.

Animals↗
PubMed2005

Interpretation of transbronchial lung biopsies from lung transplant recipients: inter- and intraobserver agreement.

BACKGROUND: Transbronchial lung biopsy results are crucial for the management of lung transplant recipients. Little information is available regarding the reliability and reproducibility of the interpretation of transbronchial lung biopsies. OBJECTIVE: To examine the inter-reader variability between two lung pathologists with expertise in lung transplantation. METHODS: Fifty-nine transbronchial lung biopsy specimens were randomly selected. Active infection had been excluded in all cases. The original interpretations (as per the Lung Rejection Study Group) for acute rejection grade included 19 biopsies scored as A0 (none), 14 scored as A1 (minimal), 12 as A2 (mild), 11 as A3 (moderate) and three as A4 (severe). The pathologists worked independently without clinical information or knowledge of the original interpretation. The specimens were graded using the Lung Rejection Study Group criteria for acute rejection (grades A0 to A4), airway inflammation (grades B0 to B4) and bronchiolitis obliterans (C0 absent and C1 present). Between-reader agreement for each category was analyzed using a Kappa statistic. RESULTS: Because many transplant specialists initiate augmented immunosuppression with biopsy grades of A2 or higher, results for each reader were dichotomized as A0/A1 versus A2/A3/A4. Using this dichotomy, there was only moderate agreement (kappa 0.470, P < 0.001) between readers. For categories B and C, the results were dichotomized for the absence or presence of airway inflammation and bronchiolitis obliterans, respectively. The level of agreement between readers was fair for category B (kappa 0.333, P = 0.014) and poor for category C (kappa 0.166, P = 0.108). The intrareader agreement for acute rejection was substantial (kappa 0.795, P = 0.0001; kappa 0.676, P = 0.0001). CONCLUSIONS: Because the agreement between expert pathologists is only modest, optimum clinical decision-making requires that transbronchial lung biopsy results be used in an integrated clinical context.

Biopsy↗
PubMed2004

Lung transplant outcomes: a review of survival, graft function, physiology, health-related quality of life and cost-effectiveness.

The success of lung transplantation has improved over time as evidenced by better long-term survival and functional outcomes. Despite the success of this procedure, there are numerous problems and complications that may develop over the life of a lung transplant recipient. With proper monitoring and treatment, the frequency and severity of these problems can be decreased. However, significant improvement for the overall outcomes of lung transplantation will only occur when better methods exist to prevent or effectively treat chronic rejection.

Cost-Benefit Analysis↗
PubMed2004

Plasma concentrations of tumour dimeric pyruvate kinase are increased in patients with chronic cardiac failure.

BACKGROUND: The aim of the study was to assess the effect of chronic cardiac failure (CCF) on circulating plasma concentrations of tumour metabolic marker dimeric pyruvate kinase type M2 (M2-PK). METHODS: Fifty patients with clinically stable CCF were studied. Patients with a history of past or ongoing malignancy were excluded. Dimeric M2-PK was measured by enzyme-linked immunosorbent assay in EDTA plasma. RESULTS: Dimeric M2-PK concentration increased significantly (P = 0.005) with increasing clinical severity of CCF as assessed by the New York Heart Association classification grade. CONCLUSIONS: Chronic cardiac failure results in an increased circulating plasma concentration of M2-PK, probably related to increased glycolytic flux. The physiological significance of the results is at present unclear but may relate to maintaining a balance between energy production and the supply of glycolytic intermediates to maintain synthetic processes. The results of this investigation will also have significance in the clinical interpretation of M2-PK concentrations.

Adult↗
PubMed2001

Impaired exercise performance after successful liver transplantation.

BACKGROUND: Recipients of heart, lung, and kidney transplants have impaired peak exercise performance (peak Vo2 40% to 60% predicted, reduced anaerobic threshold [AT]) without evidence of ventilatory or cardiac limitations. The aim of this study was to determine whether similar exercise impairment occurs in liver transplant recipients. METHODS: We studied eight healthy liver transplant recipients (age 42+/-9 [SD] years, 6 male, 31+/-13 months posttransplant). Immunosuppression included FK506 or cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Subjects underwent lung function testing and cardiopulmonary exercise testing on a cycle ergometer. RESULTS: Peak exercise oxygen consumption (Vo2) was 22+/-8 ml/min/kg (66+/-20% predicted maximum). No subject demonstrated exercise desaturation or ventilatory limitation (peak minute ventilation 55+/-8% predicted maximum voluntary ventilation). Peak heart rate was 87+/-8% of predicted maximum. Early AT was evident (1.2+/-0.34 L/min, 48+/-11% predicted Vo2max). CONCLUSIONS: Liver transplant recipients exhibit impaired peak exercise performance similar to that observed after other solid organ transplants, possibly as a result of chronic deconditioning or myopathy related to immunosuppressive medications.

Adult↗
PubMed2001

A limited sampling strategy for cyclosporine area under the curve monitoring in lung transplant recipients.

We developed a limited sampling strategy (LSS) for predicting cyclosporine (Neoral) area under the curve from concentration-time data obtained specifically from lung transplant recipients. The optimal and most clinically convenient LSS for lung transplant recipients, based on patient wait time, number of blood samples required, percent prediction error, and assessment of predictive performance is one that requires 2 blood samples collected at 1 and 3 hours post-dose: AUC = 1.75 x C(1) + 4.91 x C(3) + 185.62.

Adult↗
PubMed2001

Myositis associated graft-versus-host-disease presenting as respiratory muscle weakness.

Myositis associated with graft-versus-host-disease (GVHD) typically presents with proximal muscle weakness, myalgias, and a raised creatinine phosphokinase (CPK) level. We report a case of a 51 year old man who developed respiratory muscle weakness five years after an allogeneic bone marrow transplant for multiple myeloma. His symptoms included tachypnoea, abdominal paradox, and orthopnoea. Pulmonary function tests revealed diminished vital capacity and maximal inspiratory and expiratory pressures. Serum CPK levels were raised and a peripheral muscle biopsy specimen was consistent with GVHD. He improved with immunosuppressive therapy.

Bone Marrow Transplantation↗
PubMed2000

The real cost of aspirin.

Aspirin is a widely used drug and perceived by most physicians to be inexpensive. High rates of concurrent gastroprotective agents are reported from a study of cardiology outpatients. Aspirin takers are more likely to also be taking a proton pump inhibitor, H(2) antagonist, or antacid than non-aspirin takers. They are more than 10 times as likely to be experiencing upper gastrointestinal symptoms. Although aspirin is inexpensive, it is emphasised that the overall cost implications for therapy can be significant and it is suggested that it may be more appropriate to consider the use of alternative antiplatelet agents in patients who tolerate aspirin poorly.

Aged↗
PubMed1999

Glutathione-linked enzymes in benign and malignant oesophageal tissue.

Oxyradicals are involved in multiple mutational events and can contribute to the conversion of healthy cells to cancer cells. Glutathione (GSH) and the GSH-replenishing enzymes keep the antioxidant status of normal cells at a level where they can avert oxyradical derived mutations. The aim of this study was to determine whether in cancer cells the GSH-replenishing, GSH antioxidant and GSH-depleting enzymes were not at appropriate levels and therefore not able to protect cancer cells adequately against oxyradical-induced mutations. Cancer of the oesophagus was chosen since it is the most common gastrointestinal malignancy in South African Blacks. Biopsies and blood from 31 patients with cancer of the oesophagus and 29 non-cancer patients were assessed for these enzymes. The mean activity of the antioxidant and depleting enzyme GSH-peroxidase was elevated significantly by twofold in the cancer tissue compared to normal tissue. However, the activity of the replenishing enzyme GSSG-reductase and the level of the depleting enzyme GSH-s-transferase P1-isoenzyme were significantly reduced by 23% and 33% respectively. As in a previous paper we found that GSH was depleted and gamma-glutamine transpeptidase was diminished in oesophageal cancer. There can be two reasons for GSH depletion. Firstly, elevated GSH-peroxidase will use more GSH in an attempt to cope with the excessive production of oxyradicals as revealed by elevated lipid peroxidation; this was, as shown by us before, elevated sixfold in oesophageal cancer. Secondly, if little replenishment of GSH occurred the level of GSH would become lower. This was confirmed by our findings that the activities of the replenishing enzymes were significantly diminished in oesophageal cancer tissue. Contrary to what was expected, the other depleting enzyme GSH-s-transferase P1 was not elevated in cancer tissue but was significantly lower. However, in the blood of the same patients it was significantly elevated. An explanation for this phenomenon is that, although the production of GST-P1 was enhanced in cancer, it did not show because it was rapidly extruded into the blood by an unknown mechanism operational only in cancer cells.

Esophageal Neoplasms↗
PubMed1999

Porcine endotoxemic shock is associated with increased expired nitric oxide.

OBJECTIVES: Nitric oxide (NO) is believed to decrease systemic vascular resistance in sepsis, but the data are mainly from studies on rats and mice. We tested this hypothesis in pigs and also whether there is induction of the inducible form of nitric oxide synthase (iNOS). DESIGN: Animal study. SETTING: University center. SUBJECTS: Ten pigs. INTERVENTIONS: The pigs were anesthetized and mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: Pulmonary and systemic hemodynamics were monitored and mixed expired NO was measured by chemiluminescence. Animals received 20 microg/kg of endotoxin over 2 hrs. We then infused 25 mg/kg of N(omega)-nitro-L-arginine methyl ester (L-NAME) over 10 mins, followed by 0.5 g/kg of L-arginine, the precursor of NO, for 30 mins more to reverse the effects of L-NAME. Five additional pigs were treated with 20 microg/kg of endotoxin for 2 hrs and followed for another hour. Plasma nitrite/nitrate was measured by Greiss reaction. The animals were then killed and tissues were sampled for iNOS by Western blot, and iNOS messenger RNA by reverse transcriptase polymerase chain reaction. After endotoxin infusion, arterial pressure (BP) initially increased, then decreased to 62+/-1 mm Hg from the baseline of 115+/-4 mm Hg (p<.001). Cardiac output initially decreased, then increased slightly from the baseline of 3.7+/-0.2 to 4.2 +/-0.3 L/min (p<.05). The BP pattern was mirrored by an increase in expired NO concentration from 6.4+/-0.8 to 10.4+/-1.4 parts per billion (p<.05) and increased rate of pulmonary NO excretion in expired gas (VeNO) from 71+/-10 to 146+/-24 pmol/kg/min (p<.05). Inhibition of NOS with L-NAME decreased expired NO concentration and VeNO and increased BP; however, cardiac output decreased. The vasoconstriction produced by L-NAME was partially reversed by L-arginine, and this also increased VeNO from 80+/-18 after L-NAME to 132+/-31 pmol/kg/min (p<.05). Plasma nitrite (n = 5) did not change and there was no iNOS by Western blot analysis in multiple tissues. However, there was a small increase in messenger RNA by reverse transcriptase polymerase chain reaction. CONCLUSIONS: The time course and pattern of changes in expired NO during endotoxemia followed the change in systemic hemodynamics, which supports a causal role for NO in sepsis. However, this is not due to a large production of NO by iNOS induction. The hemodynamic pattern, nitrite in blood, and changes in expired NO also differed markedly from those findings in rodent models and caution should be used in extrapolating from rodents to higher order animals.

Analysis of Variance↗
PubMed1999

Maximal exercise testing for the selection of heart transplantation candidates: limitation of peak oxygen consumption.

BACKGROUND: Peak exercise oxygen consumption (peak VO2), which is considered an indicator of prognosis in advanced heart failure, is currently being used as a major criterion in many centers for the selection of candidates for heart transplantation. Available studies suggest that patients with peak VO2 < 14 mL/min/kg have improved survival and significant functional benefit with transplantation. Since patients may terminate symptom-limited exercise tests for a variety of reasons, peak VO2 does not necessarily reflect maximal VO2, leading to the possibility of inappropriate selection for transplantation. Therefore, we investigated the proportion of transplant candidates referred for exercise testing considered to have achieved maximal results from studies. METHODS: Fifty-five patients with heart failure, aged 51+/-9 years, (mean +/- SD) underwent maximum symptom-limited exercise tests on a cycle ergometer utilizing a Jones stage 1 incremental protocol. Tests were considered maximal if subjects achieved peak heart rate (HR) > 85% predicted ("cardiocirculatory limitation") or peak minute ventilation (VE) > 85% predicted ("ventilatory limitation"), and achieved an anaerobic threshold (AT) by noninvasive measures. RESULTS: Seven tests were terminated because of chest pain, ST-segment abnormalities, or ventricular arrhythmias. Of the remaining 48 studies, the reasons for stopping exercise were leg fatigue in 52%, dyspnea in 16%, and both symptoms in 23%. Sixteen of the 48 patients (33%) had peak VO2 < 14 mL/min/kg. In 8 of these 16 patients, both peak HR and VE were < 85% predicted. Of these eight without apparent HR or ventilatory limitation, none had oxygen desaturation below 90% or fall in BP, two were in atrial fibrillation, and only three had evidence that an AT was achieved. CONCLUSIONS: Among the patients with peak VO2 < 14 mL/min/kg, there were no objective signs of a cardiocirculatory or a respiratory limitation to exercise in half of them, and 31% did not achieve an AT either, thus not meeting any criteria to support evidence of maximal exercise. Exercise tests without objective evidence of cardiocirculatory or ventilatory limitation may not represent maximal performance. Consequently, peak VO2 may misclassify an appreciable proportion of candidates if the test results are submaximal. CLINICAL IMPLICATIONS: Clinical exercise studies indicating low peak VO2 must be interpreted in the context of whether a defined objective exercise limitation is evident to avoid biasing the selection of heart transplant candidates.

Adult↗
PubMed1998

Cardiac versus noncardiac limits to exercise after heart transplantation.

BACKGROUND: To determine whether the reduced exercise capacity of patients after heart transplantation is primarily a result of decreased cardiac or peripheral vascular factors, we examined the cardiac output (CO) and right atrial pressure (Pra) relation during graded cycle ergometry. METHODS AND RESULTS: We studied 12 male patients (51.2+/-15.3 years [mean+/-SD]) 35.3+/-12.5 weeks after heart transplantation and 6 young healthy men. Patients had a normal increase in CO with increasing oxygen uptake (VO2) (CO = 0.00597 VO2 + 4.4, r = 0.83). Mean (+/-SEM) heart rate increased from 97.0+/-5.0 beats/min at rest to 146.9+/-6.9 beats/min at peak effort compared with the increase of 67.2+/-1.9 beats/min to 187.2+/-2.5 beats/min in the normal group. Pra in patients increased from 1.6+/-1.0 mm Hg at rest to 8.9+/-1.6 mm Hg during mild exercise but did not increase further at the highest work rates, even though CO continued to increase. In the normal group there was an initial increase in Pra from rest to exercise transition but little further change in Pra with increasing CO. Aerobic capacity (peak VO2) did not increase when cardiac function was increased with dobutamine during exercise in two patients. CONCLUSIONS: The steep increase in CO relative to Pra during severe exercise in patients who undergo heart transplantation argues against the heart as the sole limiting factor during maximal effort.

Atrial Function, Right↗
PubMed1998

Impact of stenting on coronary angioplasty procedures.

OBJECTIVE: To compare patient selection and outcome of coronary angioplasty procedures before and after the widespread availability and use of stents. SUBJECTS AND METHODS: Group 1 consisted of 252 consecutive patients and group 2 comprised 389 patients who underwent angioplasty between April 1993 and March 1994, and April 1995 and March 1996, respectively, in a tertiary cardiothoracic centre. Clinical variables were collected before the procedures. Endpoints included in-hospital death, the need for repeat coronary angiography, repeat angioplasty, and coronary artery bypass surgery. Lesions were classified under American Heart Association/American College of Cardiology criteria in 100 randomly selected patients from each group. RESULTS: 311 and 482 angioplasty procedures were performed in patients from groups 1 and 2, respectively. One or more stents were deployed in nine (4%) and 179 (46%, p < 0.01) patients, respectively. The success rate was higher in group 2 than in group 1 patients (483/523 (92%) v 274/372 (88%), respectively, p < 0.05). There were significantly more single vessel angioplasty procedures (198/252 (79%) v 272/389 (70%), p < 0.05), type A lesions (30/116 (26%) v 19/130 (15%), p < 0.05), patients with stable angina (220/252 (87%) v 311/389 (80%), p < 0.05), and fewer acute myocardial infarction patients (1/252 (0%) v 12/389 (3%), p < 0.05) treated in group 1 than in group 2, respectively. Similar numbers of angioplasty were performed in the left anterior descending, left circumflex, and right coronary arteries. There were no significant differences in the in-hospital mortality or the need for repeat coronary angiography, angioplasty, or bypass surgery at 24 hours or six months after the initial procedure. CONCLUSION: Patients undergoing angioplasty in the stenting era had features associated with an increased risk of complication. Despite this, the primary success rate was higher, and the complication rate and the need for subsequent revascularisation were similar in the two groups, supporting the widely held clinical impression that stenting has made a valuable impact on the practice of angioplasty.

Aged↗
PubMed1997

Gunshot injuries of the abdominal aorta: a continuing challenge.

This is a retrospective study of 57 patients with gunshot injuries of the abdominal aorta. The aortic repair was achieved by various means: lateral aortorraphy, patch aortoplasty and graft insertion. There was an 85 per cent mortality rate from bleeding or secondary coagulopathy directly related to the aortic injuries. The need for resuscitative thoracotomy, shock, lack of response to fluid resuscitation and intraperitoneal bleeding were directly related to mortality. We feel that shortening of prehospital transfer time will increase the absolute number of patients surviving this grave injury.

Adolescent↗