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Biomedical subjects

J B Young

Publications and source records attributed to J B Young.

At least 55 records · Page 3Linked to original sources

Perspectives on cardiac allograft vasculopathy.

Allograft arteriopathy, the slowly progressive, diffuse, atherosclerosis noted often after heart transplant, and also called chronic rejection, is the most common cause of late cardiac graft failure and patient death. The process is multifactorial, rooted in both immune and nonimmune factors that can be coupled to passenger atherosclerosis moved with the donor heart, as well as initially nondiseased endothelium. Great insight has emerged from experimental models and intravascular ultrasound study of patients, but treatments are still crude and produce less than optimal results. Nonetheless, it has been demonstrated that diltiazem, pravastatin, ganciclovir, newer immunosuppressive agents, and photophoresis may be helpful. In the future, better control of the allograft immunologic response will likely be the key to attenuating development of this form of atherosclerosis.

Coronary Artery Disease↗

Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies.

OBJECTIVES: This study sought to evaluate the effects of postmenopausal estrogen use on mortality in aging women with congestive heart failure (CHF). BACKGROUND: The age-related increase in CHF mortality in women may be related to a menopause-associated increased incidence of coronary artery disease. In addition to inhibiting coronary atherosclerosis, estrogen may also have protective effects on cardiac myocytes independent of the coronary vasculature. We hypothesized that estrogen use is associated with improved survival in elderly women with CHF. METHODS: Associations between survival, estrogen use and patient characteristics were assessed in 1,134 women who were at least 50 years of age, had CHF and left ventricular ejection fraction (EF) < or =30% and were enrolled in one of three clinical trials of vesnarinone. RESULTS: All-cause 12-month mortality was 15.0% among the 237 estrogen users versus 27.1% among the 897 estrogen nonusers (p = 0.004 for unadjusted comparison of survival). Similar results were observed for cardiac mortality. Regression analysis demonstrated that estrogen use was independently associated with improved survival (relative risk of mortality = 0.68, 95% confidence interval 0.48 to 0.96, p = 0.03). Advanced age, low EF, New York Heart Association class IV CHF, Caucasian race and abnormal serum creatinine, sodium, potassium and transaminase were independently associated with increased mortality. CONCLUSIONS: Estrogen use among older women with CHF is associated with decreased overall and cardiac mortality.

Aged↗

Results of partial left ventriculectomy for dilated cardiomyopathy: hemodynamic, clinical and echocardiographic observations.

OBJECTIVES: The study was done to prospectively measure the echocardiographic, hemodynamic and clinical outcomes after partial left ventriculectomy (PLV). BACKGROUND: Although PLV can improve symptoms of advanced heart failure, immediate postoperative echocardiographic findings remain abnormal. METHODS: Fifty-nine patients with cardiomyopathy and advanced heart failure underwent PLV and concomitant mitral valve surgery between May 1996 and December 1997. Thirty-nine percent were on inotropic therapy. All were New York Heart Association (NYHA) functional class III or IV. Mechanical circulatory support (LVAD) and transplant were provided for rescue therapy when hemodynamic compromise occurred. Patients were followed for a mean of 405+/-168 days, and clinical, echocardiographic and hemodynamic measures were obtained preoperatively, immediately postoperatively, and at 3 and 12 months prospectively. RESULTS: Comparing preoperative and 12-month postoperative values in event-free survivors, we found: NYHA functional class improved from 3.6 to 2.1, p < 0.0001; peak oxygen consumption increased from 10.8 to 16.0 ml/kg/min, p < 0.0001; LV ejection fraction increased from 13+/-6.0% to 24+/-6.9%, p < 0.0001; LV end diastolic diameter decreased from 8.2+/-1.03 to 6.2+/-0.64 cm, p < 0.0001, and volume was reduced from 167+/-60 to 105+/-38 ml/m2, p = 0.02. Central hemodynamics did not normalize after surgery. CONCLUSIONS: Partial left ventriculectomy can provide structural remodeling of the heart that may result in temporary improvement in clinical compensation. However, perioperative failures and the return of heart failure limit the propriety of this procedure.

Aged↗

Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft cellular rejection.

BACKGROUND: Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant cellular myocardial rejection. METHODS: We retrospectively analyzed the incidence of rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant cellular rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent rejection. RESULTS: Eighty five percent (56/66) of the episodes of rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2. 4 +/- 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 +/- 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute rejection per patient (3.14 +/- 0.85-0.57 +/- 0.87, p < 0.0001), and the incidence of acute rejection per 100 patient-days (6.39 +/- 3.96-0. 25 +/- 0.47, p < 0.0001). In comparison, OKT3 was started 5.25 +/- 9. 20 months post-transplant. Similarly, there was a significant decrease in the incidence of acute rejection per 100 patient-days (8. 69 +/- 5.65-0.20 +/- 0.23, p < 0.0001). The average hospital charges per patient for the OKT3-treated group was $33,339 +/- $10,511. There was no significant difference in the actuarial 1-year survival between the tacrolimus and OKT3-treated groups (93% vs 80%, p = 0.5). CONCLUSIONS: Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant cellular rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.

Adult↗

Fluorescence spectroscopy of endomyocardial tissue post-human heart transplantation: does it correlate with histopathology?

BACKGROUND: A significant correlation between autofluorescence spectroscopy and heart allograft rejection has been described in the rat heterotropic allograft model. However, the use of this technique in human heart transplants has not been validate. METHODS: We obtained fluorescence and reflectance spectra on 37 human endomyocardial biopsy specimens and correlated the spectra with International Society Heart and Lung Transplantation grade for histologic rejection. RESULTS: Using different excitation wavelengths (ultraviolet, lambda = 337 nm; blue, lambda = 440 nm, and green, lambda = 486 nm), we found no significant difference in the fluorescence spectra among the different grades of rejection. CONCLUSIONS: Fluorescence spectroscopy is not a sensitive method for detecting rejection in human heart transplant recipients.

Adult↗

Left ventricular reduction surgery with mitral valve repair.

The echocardiographic changes and functional outcome from mitral valve repair, combined with partial left ventriculectomy (PLV), the Batista procedure, were investigated. From May 1996 to August 1997 the operation was performed on 57 patients, primarily (95%) transplant candidates with idiopathic dilated cardiomyopathy. All had been Class IV (36.8% had improved to Class III by the time of surgery) on medical therapy, including 40% hospitalized on inotropes and 3 patients on intra-aortic balloon pumps. The mean cardiac index was 2.1+/-0.6 L/min/m2, with a wedge pressure of 24+/-8 mm Hg, and norepinephrine levels of 855+/-500 pg/mL (normal 80-526 pg/mL). There were 2 in-hospital mortalities (3.5%). At 3 months there were significant persistent changes in LV end-diastolic diameter (8.1+/-1.0 cm-6.3+/-0.9 cm) and ejection fraction (13.6+/-6%-23+/-7.7%). Subjective improvement included a mean change in NYHA functional class from 3.7 to 2.2, and objective changes included improvement in peak oxygen consumption from 10.6+/-4 mL/kg/min to 15.4+/-4.5 mL/kg/min. Actuarial survival at 1 year was 82.1%; and freedom from death, relisting for transplantation, and need for LVAD support was 58%. The earliest "learning curve" experience with this relatively unstudied operation warrants careful investigation. Many questions remain to be answered, but many patients have demonstrated early subjective and objective improvement.

Cardiac Surgical Procedures↗

Outpatient parenteral inotropic therapy for advanced heart failure.

BACKGROUND: Patients with advanced heart failure generally have hemodynamic perturbation characterized by low cardiac output and high ventricular filling pressures. This creates a clinical milieu with profound symptomatology that includes weakness, fatigue, and fluid-retention states causing peripheral edema, mesenteric congestion, and dyspnea syndromes. Great morbidity including hospital admissions and readmissions as well as high mortality rates ensue. Though medication and/or surgical intervention often attenuate heart failure symptomatology, morbidity, and mortality, some patients reach more advanced stages despite aggressive maneuvers. Indeed, patients presenting with acute decompensation of chronic congestive heart failure frequently receive parenteral inotropic drugs during their hospitalization with clinical improvement. Because these agents generally increase cardiac output and reduce pre-load and afterload, they can be lifesaving. Some patients, however, have symptomatic and hemodynamic rebound to worsened heart failure states during or shortly after inotrope weaning. METHODS: It was, then, a logical step to segue from acute inpatient inotrope infusion to long-term administration of these drugs in the outpatient setting when patients were dependent on these agents. Dopamine, dobutamine, and milrinone are all generally available inotropes that have been used singly or in combination in a chronic outpatient infusion setting. CONCLUSIONS: Data from a few small clinical trials and anecdotal case experience suggest that these drugs result in both hemodynamic and clinical improvement that is generally sustained during chronic administration, and even noted long after discontinuation of infusions in some patients. Some reports have suggested that intermittent infusion therapy in outpatients (so-called pulsed therapy) is effective in attenuating congestive heart failure symptoms long term, with more data supporting chronic infusion of these agents. Though questions regarding safety of these agents have been raised, a reasonable compendium of data published to date supports the contention that inotropic drugs used in this fashion ameliorate symptoms. Legitimate concern may be raised regarding exacerbation of arrhythmias with subsequent sudden cardiac death syndrome; however, in severely symptomatic heart failure patients, the trade-off between symptomatic amelioration and the chance of sudden cardiac death may be worthwhile. Unfortunately, precise guidance regarding the best drug, dose, optimal administration technique, weaning protocol, and actual risk/benefit ratio are not well characterized. Practice as been guided, in large part, by anecdotal experience. However, it appears that chronic or pulsed outpatient parenteral inotropic infusion therapy is frequently prescribed and that this treatment option is an effective alternative for carefully selected patients with severely symptomatic and advanced heart failure. Formulating optimal protocols for home inotropic drug infusion therapy by conducting properly designed clinical trials will be an essential endeavor.

Adrenergic beta-Agonists↗

Sudden cardiac death syndrome and pump dysfunction: the link.

Clearly, sudden cardiac death syndrome in heart failure is linked to severely perturbed neurohumoral, hemodynamic, and mechanical systems. Routine antiarrhythmic drug therapy has not proven beneficial and, therefore, there is no justification for using these agents in unselected heart failure patients who are without significant symptomatic ventricular arrhythmia. Aggressive treatment of the failure syndrome seems most important. Because many of the problematic arrhythmias arise from triggering automaticity, which is known to occur in excessive ventricular stretch and wall stress, systemic vascular "unloading" with vasodilators and angiotensin-converting enzyme inhibitors is likely helpful. The most recent American College of Cardiology/American Heart Association Guidelines regarding therapeutic management of heart failure suggest that aggressive pharmacologic treatment of asymptomatic ventricular arrhythmias is best avoided. To be considered strongly for pharmacologic prescription or for implantation of a tachyarrhythmia termination device, a patient should have symptomatic ventricular tachycardia with an episode of syncope or sudden cardiac death syndrome rather than simply having palpitations of asymptomatic, unsustained ventricular tachycardia. Indeed, aggressively treating congestive heart failure with medication often eliminates potentially life-threatening arrhythmias. Appropriate use of vasodilators and, particularly, angiotensin-converting enzyme inhibitors is important. Correction of fluid balance and electrolyte disorders may be helpful to address symptoms and certainly is likely to decrease the potential for morbidity and mortality. On occasion it may be necessary to consider bradyarrhythmia pacemaker insertion or the use of atrioventricular nodal-ablation techniques with subsequent ventricular or atrioventricular pacer insertion. Obviously, sudden cardiac death due to sudden heart block or asystole might be attenuated with this strategy.

Cardiac Output, Low↗

Intravascular ultrasound imaging after cardiac transplantation: advantage of multi-vessel imaging.

BACKGROUND: Intravascular ultrasound is a sensitive tool to study transplant vasculopathy. However, there is no consensus regarding the methodology for imaging protocol. The impact of single versus multiple epicardial vessel imaging in determining the prevalence of transplant vasculopathy has not been determined. This study examines the benefit of three-vessel imaging versus one-vessel imaging in detecting transplant vasculopathy. METHODS AND RESULTS: One hundred eleven transplant recipients with intravascular ultrasound imaging at baseline (within 2 months of transplantation) were studied: 107 at 1-year, 53 at 2-year and 41 at 3-year follow-up. A total of 222 arteries, 519 segments and 772 sites were analyzed (94 LAD, 65 LCX and 65 RCA). The prevalence of transplant vasculopathy lesions was 27%, 41% and 58% at 1 year, 39%, 55% and 71% at 2 years and 39%, 55% and 74% at 3 years for patients with one-, two- and three-vessel imaging, respectively. Single- or two-vessel disease was present in 23% (7) and 32% (10) patients with three-vessel imaging, leading to the potential mislabeling of these 17 (55%) patients as "disease free" if they underwent only single-vessel imaging. CONCLUSIONS: Multivessel imaging is more sensitive in detecting the transplant vasculopathy lesions compared to single-vessel imaging. This important variable should be considered when designing and interpreting trials utilizing intravascular imaging derived end-point.

Adult↗

Significant post-transplant hypogammaglobulinemia in six heart transplant recipients: an emerging clinical phenomenon?

BACKGROUND: The recent development of powerful agents such as mycophenolate mofetil and tacrolimus has altered current regimens for the prevention and treatment of allograft rejection. Questions have been raised about these newer regimens in terms of susceptibility to opportunistic infections and effects on host defenses. Severe hypogammaglobulinemia has been infrequently described in solid organ transplant recipients, but has been recently noted in six heart transplant recipients at one center, of whom five were receiving a combination of tacrolimus, mycophenolate mofetil, and prednisone. METHODS: Case summaries of six recent heart transplant recipients with total immunoglobulin G (IgG) levels of less than 310 mg/dl, five of whom had cytomegalovirus (CMV) infection and three of whom had multiple infections including Nocardia, invasive Trichophyton, and Acinetobacter bacteremia. Previous literature was reviewed with the aid of a Medline search using the search terms hypogammaglobulinemia; kidney, liver, heart, lung, and organ transplantation; mycophenolate mofetil; tacrolimus; cyclosporine; azathioprine; and nocardiosis. RESULTS: We here report six cardiac transplant recipients seen over a period of one year who were found to have immunoglobulin G levels of 310 mg/dl or below (normal: 717-1400 mg/dl). The first five patients were diagnosed because of evaluation for infections; the sixth, who was asymptomatic with an IgG level of 175, was found during screening for hypogammaglobulinemia instituted as a result of these first five patients. All six patients had received steroid pulses for rejection; all received mycophenolate mofetil; and 5/6 had been switched from cyclosporine to tacrolimus because of steroid-resistant rejection. Transient neutropenia (absolute neutrophil count less than 1000) was observed in 2/6; 3/6 had received OKT3 therapy for refractory rejection. These six patients were treated with a combination of antimicrobials, immunoglobulin replacement, and decrease in immunosuppressive therapy. CONCLUSION: The finding of unexpected hypogammaglobulinemia and concomitant infectious complications in six heart transplant recipients highlights a possible complication in a subset of patients receiving newer immunosuppressive agents. A larger prospective study is underway to determine risk factors for development of post-transplant hypogammaglobulinemia and to assess pre-transplant immune status of these recipients. Monitoring of immunoglobulin levels in high-risk patients receiving intensified immunosuppressive therapy for rejection may help to prevent infectious complications.

Acinetobacter Infections↗

Birth weight, climate at birth and the risk of obesity in adult life.

OBJECTIVE: To determine whether obesity in adults is related to seasonal or climatic conditions around the time of birth. SUBJECTS: 1750 men and women born in Hertfordshire between 1920 and 1930. MEASUREMENTS: Height and weight measured in the home by trained fieldworkers. RESULTS: Body mass index (BMI) rose with increasing birth weight in men and women. In men, BMI and the prevalence of obesity (BMI > or = 30 kg/m2) varied as a function of month of birth and was greater among those born in January-June than among those born in July-December. The relationship between birth weight and adult obesity was also stronger in those born in the first 6 months of the year or following cold winters than in those born in the last 6 months of the year or following mild winters. CONCLUSIONS: These findings suggest that adult obesity is linked both to high birth weight and to early cold exposure. Consequently, exposures in early life may contribute to individual variation in susceptibility to obesity in adults.

Adult↗

Clinical experience with long-term use of implantable left ventricular assist devices: indications, implantation, and outcomes.

We describe our clinical experience with 205 implantable left ventricular assist devices at the Cleveland Clinic between December 1991 and January 2000, along with manufacturers' data submitted to the Food and Drug Administration. In patients with end-stage cardiac failure who are suitable candidates for transplantation, these devices serve as excellent bridges to transplantation. Recent modifications have increased pump reliability and reduced thromboembolic rates. The vented electric HeartMate (Thermocardiosystems Inc, Woburn, MA) and the Novacor (Baxter-Novacor, Oakland, CA) left ventricular assist systems allow patients to be discharged from the hospital while awaiting a donor heart. Experience with long-term support is providing insights into permanent implantation of these devices as destination therapy. Although infection remains a major impediment to long-term support, patient-pump interactions leading to changes in the coagulation and immune systems are being recognized, and these interactions may have important implications with respect to thromboembolism, infection, and sensitization to human leukocyte antigens (HLAs). Better understanding of these factors may eventually lead to the development of permanently implantable pumps as an alternative to transplantation.

Assisted Circulation↗

Infective discitis as an uncommon but important cause of back pain in older people.

CASE REPORTS: two elderly patients (aged 70 and 80 years) presented with severe back pain and restriction of spinal movements. Inflammatory markers were raised and in each case computed tomography findings confirmed infective discitis. One patient improved with antibiotics but the second developed paraplegia, a recognized complication of discitis. CONCLUSION: the association of back pain, restricted spinal movements and raised inflammatory markers should act as 'red flags', alerting the clinician to the presence of serious, but potentially treatable pathology.

Age Factors↗

Effects of neonatal handling on sympathoadrenal activity and body composition in adult male rats.

Neonatal handling permanently alters the hypothalamic-pituitary-adrenal (HPA) response to stress. Because the sympathetic nervous system (SNS) and adrenal medulla also participate in stress responses, the impact of daily handling between birth and weaning on SNS and adrenal medullary function was examined in adult rats using techniques of [(3)H]norepinephrine ([(3)H]NE) turnover and urinary catecholamine excretion. Handled animals exhibited a 23% reduction in [(3)H]NE turnover in heart and a 53% decrease in spleen. [(3)H]NE turnover in brown adipose tissue, stomach, and kidney did not differ between handled and nonhandled animals. In contrast, urinary epinephrine (Epi) excretion was significantly greater in handled rats in response to a 3-day fast than in nonhandled animals. Although body weight, weight gain in response to dietary enrichment with sucrose or lard, or body fat content did not differ in handled and nonhandled animals, handled rats displayed heavier abdominal fat depots than nonhandled animals, implying a difference in body fat distribution. Neonatal handling thus leads to decreased sympathetic activity within specific subdivisions of the SNS and, by contrast, to increased adrenal medullary responsiveness.

Adipose Tissue↗