Search PubMed⌕ Search

Biomedical subjects

S L Olsen

Publications and source records attributed to S L Olsen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effects of carvedilol on systolic and diastolic left ventricular performance in idiopathic dilated cardiomyopathy or ischemic cardiomyopathy.

Recent evidence has shown that improvement in left ventricular (LV) systolic function in patients with New York Heart Association class II to III heart failure occurs with beta-adrenergic blocking agents. However the specific effects on LV diastolic function have been subjected to only limited examination. This study investigated the effects of the combined beta blocker/vasodilator, carvedilol, on systolic and diastolic LV performance in dilated cardiomyopathy. Thirty-six patients with New York Heart Association II to III heart failure and LV ejection fraction < or = 0.35 were entered into either arm of this placebo-controlled, double-blind 4-month trial. Twenty-one subjects were entered into the carvedilol treatment arm and 15 patients were entered into the placebo arm in a 3:2 ratio. Carvedilol therapy resulted in a significant improvement in LV ejection fraction, from 0.22 +/- 0.02 to 0.30 +/- 0.02 when compared with the placebo group (0.19 +/- 0.02 to 0.21 +/- 0.02 at baseline and after 4 months of therapy, respectively; p = 0.0001). However, no significant change in radionuclide parameters of LV diastolic function, including peak filling rate or time to peak filling rate, was observed. LV end-diastolic volume index did not change with carvedilol therapy, whereas end-diastolic volume index increased in the placebo group, although the difference between groups at 4 months was significant (p = 0.02). In conjunction with these changes, end-systolic volume index was smaller at 4 months after carvedilol treatment compared with that of the placebo group (p = 0.04). Thus, these results demonstrate that in moderate chronic heart failure, systolic LV performance improves but diastolic LV function does not improve when compared with placebo after treatment with carvedilol.

Adrenergic beta-Antagonists↗
PubMed1996

Cyclophosphamide in cardiac transplant recipients with frequent rejection: a six-year retrospective review.

Allograft rejection remains a major cause of morbidity and mortality. Cyclophosphamide, a nitrogen mustard, is a potent immunosuppressive agent with effects on both T- and B-lymphocytes, and thus may be effective in preventing further cellular and/or humoral rejection in cardiac transplant recipients with recurrent or recalcitrant rejection. We retrospectively reviewed the records of 320 surviving cardiac transplant recipients. Cyclophosphamide was substituted for azathioprine in 28 patients because of frequent allograft rejection. We then reviewed the rejection history of these 28 patients, specifically looking at rejection frequency, type (cellular, vascular or mixed), and treatment. Cyclophosphamide was substituted for azathioprine at an average of 8.4 +/- 2.8 months after transplantation. Despite a 56.0% reduction in prednisone dose (p < 0.001), at least a threefold reduction in rejection frequency (p < 0.001) was observed, while cyclosporine levels were unchanged. Twenty-eight percent of the patients did not experience even mild rejection after beginning therapy with cyclophosphamide, 55% had 1 or 2 subsequent mild or moderate rejection episodes, and only 17% had more than two subsequent episodes of mild or moderate rejection. Overall, the number of treated rejection episodes decreased from 0.37 episodes per patient month with azathioprine to 0.10 episodes per patient month on therapy with cyclophosphamide. Separating the patients into two groups based on the predominant rejection type (cellular vs. vascular) occurring at the time of cyclophosphamide substitution revealed a similar reduction in cellular and vascular rejection in each respective group. While white blood cell count decreased by 16%, cyclophosphamide was not discontinued in any patient due to leukopenia, and no change was noted in hematocrit. Cyclophosphamide appears to be safe and effective in maintenance immunosuppression and may reduce rejection frequency in some patients with frequently occurring allograft rejection without necessitating the augmentation of either corticosteroids or cyclosporine.

Azathioprine↗
PubMed1995

Tricuspid valve dysfunction in the transplanted heart.

Mild degrees of tricuspid regurgitation are common in the orthotopically transplanted heart, probably secondary to the geometry of the right atrial anastomosis. At the University of Utah, 5 (0.95%) of 526 patients with transplantations performed from March 1985 to December 1993 have presented with severe tricuspid regurgitation requiring operative intervention. Echocardiographic findings confirmed at the time of operation consisted of ruptured chordae to the tricuspid valve. Standard tricuspid valve repair and replacement techniques were used with good results. We postulate the chordal disruption found in these patients is secondary to injuries incurred at the time of endomyocardial biopsy.

Adult↗
PubMed1995

Carvedilol improves left ventricular function and symptoms in chronic heart failure: a double-blind randomized study.

OBJECTIVES: This study assessed the safety and efficacy of carvedilol in patients with heart failure caused by idiopathic or ischemic cardiomyopathy. BACKGROUND: Carvedilol is a mildly beta 1-selective beta-adrenergic blocking agent with vasodilator properties. Beta-blockade may be beneficial in patients with heart failure, but the effects of carvedilol are not known. METHODS: Sixty patients with heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction < or = 0.35 were enrolled in the study. All patients tolerated challenge with carvedilol, 3.125 mg twice a day, and were randomized to receive carvedilol (n = 36) versus placebo (n = 24). Study medication was titrated over 1 month from 6.25 to 25 mg twice a day (< 75 kg) or 50 mg twice a day (> 75 kg) and continued for 3 months. One placebo-treated and two carvedilol-treated patients did not complete the study. RESULTS: Carvedilol therapy resulted in a significant reduction in heart rate and mean pulmonary artery and pulmonary capillary wedge pressures and a significant increase in stroke volume and left ventricular stroke work. Left ventricular ejection fraction increased 52% in the carvedilol group (from 0.21 to 0.32, p < 0.0001 vs. placebo group). Carvedilol-treated patients also reported a significant lessening of heart failure symptoms (p < 0.05 vs. placebo group). Submaximal exercise duration tended to increase with carvedilol therapy (from 688 +/- 31 s to 871 +/- 32 s), but this change was not significantly different from that with placebo therapy by between-group analysis. Peak oxygen consumption during maximal exercise did not change. CONCLUSIONS: Long-term carvedilol therapy improves rest cardiac function and lessens symptoms in patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed1994

A prospective, randomized comparison of cyclophosphamide and azathioprine for early rejection prophylaxis after cardiac transplantation. Decreased sensitization to OKT3.

Humoral immune responses have been implicated in the pathogenesis of vascular rejection, allograft coronary artery disease, and sensitization to OKT3. Because cyclophosphamide (CP) is a potent suppressor of humoral immunity, we postulated that substituting cyclophosphamide for azathioprine (AZA) would be associated with a decrease in acute vascular rejection and sensitization to OKT3 in cardiac transplant recipients also receiving cyclosporine, corticosteroids, and perioperative OKT3. We prospectively randomized 119 patients to receive azathioprine (n = 61) or cyclophosphamide (n = 58) from the time of transplantation. Dosage was adjusted to target white blood cell (WBC) counts. At six weeks posttransplantation, cyclophosphamide was converted to azathioprine. Patients were followed for a mean of 321 +/- 16 days. At four weeks WBC (1000/mm3) was 9.2 +/- 0.4 (SEM) in the AZA group and 9.7 +/- 0.6 for the CP group (P = 0.4). No differences were noted between the CP and AZA groups in mean cellular grades of rejection (1.8 +/- 0.1 vs. 1.7 +/- 0.1), mean vascular grades of rejection (2.0 +/- 0.1 vs. 1.8 +/- 0.1), early treated rejection episodes (1.9 +/- 0.1 vs. 2.2 +/- 0.1) days to first treated cellular rejection (38 +/- 3 vs. 41 +/- 3), or the number of patients manifesting primarily vascular rejection (18 vs. 19). Major infections and survival did not differ between the two groups. Eight patients in the AZA group developed anti-OKT3 antibodies, whereas only one patient in the CP group did (P = 0.04). In the early posttransplant period cyclophosphamide decreases the incidence of sensitization to OKT3 and appears to be as effective as azathioprine in preventing both cellular and vascular rejection.

Antibody Formation↗
PubMed1994

Paternity by cardiac transplant recipients.

To assess whether children fathered by cardiac transplant recipients are at high risk of teratogenicity, cardiac transplant centers listed with the International Society for Heart and Lung Transplantation were surveyed. Paternities after transplantation by heart (n = 35) and heart-lung (n = 1) allograft recipients have resulted in 42 pregnancies (children's age 3.3 +/- 0.3 years). The fathers' age at conception was < 45 years in 40 (95%) and > 45 years in 2 (5%). Most fathers (86%) were enjoying an active and healthy lifestyle at the time of conception; one (2%) was on dialysis and listed for kidney transplantation due to nephrotic syndrome, 1 (2%) had asthma, 4 (10%) had allograft coronary disease (1 died while waiting for second heart transplant when the child was 2 months old), and 2 (5%) were retransplanted after the pregnancies. Immunosuppressive regimens were reported for 37 paternities; drug protocols at the time of conception were as follows: 25 (60%) CsA/prednisone/AZA, 6 (14%) CsA/prednisone, 4 (10%) CsA/AZA, and 2 (5%) AZA/prednisone. Twenty-six (62%) had received treatment for rejection episodes before conception; seven (17%) had received treatment for rejections since conception. Of the 42 children fathered by these recipients, 3 (7%) were preterm, 1 (2%) had a cleft palate and lip that have subsequently been corrected, 1 (2%) died from interruption of umbilical cord circulation at 24 weeks, and 1 (2%) whose father had familial cardiomyopathy was born with a cardiomyopathy that improved with time. Although the numbers are small, the available data suggest that paternity by cardiac transplant recipients may be safe.

Adult↗
PubMed1993

beta-adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy.

Alterations in the myocardial receptor-G protein-adenylate cyclase (RGC) complex and cardiac adrenergic neurons in the failing human heart result in subsensitivity to beta-adrenergic stimulation. Pharmacologic interventions such as beta blockade may modify critical components of the RGC complex and partially restore the sensitivity of the beta-adrenergic pathway. Among the receptors coupled to the stimulatory (Gs) protein are the beta 1 and beta 2 receptors. Because of differences in receptor population and agonist (i.e., norepinephrine) affinity, the beta 1-receptor is the predominate adrenergic subtype regulating contractility in the nonfailing myocardium. Down-regulation occurs in the myocardial beta-receptor component of the RGC complex with mild-to-moderate and severe left ventricular dysfunction. However, abnormalities of the RGC complex vary with the etiology of heart failure; beta 1-receptor down-regulation is greater in idiopathic dilated cardiomyopathy than in post-infarction cardiomyopathy, while beta-receptor uncoupling is greater in post-infarction disease. In chronic heart failure, the adrenergic nervous system is activated in the heart and kidney. There is evidence that an increased cardiac norepinephrine concentration contributes to the decrease in beta 1-receptor density in heart failure. However, norepinephrine exposure is not the only factor responsible for regulating beta-adrenergic receptors in heart failure. Chronic beta blockade may improve hemodynamic and clinical response in patients with idiopathic dilated cardiomyopathy by protecting the myocardium from the cardiotoxic effects of increased catecholamines and by up-regulating the beta 1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

The use of mycophenolate mofetil (RS-61443) in human heart transplant recipients.

Mycophenolate mofetil is a potent inhibitor of de novo guanine nucleotide synthesis that selectively blocks lymphocyte proliferative responses. In animal models, mycophenolate mofetil has been shown to prolong allograft survival, reverse ongoing rejection, and induce strain-specific tolerance. To assess the safety and efficacy of mycophenolate mofetil in cardiac transplantation, 30 recipients with mild rejection were enrolled in an 8-week phase I trial. Mycophenolate mofetil in doses from 500 to 3000 mg/day orally was substituted for azathioprine, while baseline cyclosporine levels and corticosteroid doses were maintained. Rejection resolved in the majority of patients, with a significant decrease in mean biopsy score. By protocol, mycophenolate mofetil was discontinued in 4 patients due to persistent mild rejection, and in 4 patients due to progression to moderate rejection. The rate of progression to moderate rejection compared favorably with that observed in patients with mild rejection maintained on azathioprine without augmentation of immunosuppression. Significant increases were observed in hematocrit, total white blood cell count, and absolute neutrophil count. Absolute lymphocyte count remained unchanged. No nephrotoxicity or hepatotoxicity was observed. Gastrointestinal side effects prompted discontinuation of mycophenolate mofetil in one patient. Two major infections occurred. Mycophenolate mofetil remained well tolerated during long-term maintenance immunosuppression, with a rate of rejection similar to that in patients receiving azathioprine. We conclude that mycophenolate mofetil is safe and well tolerated in cardiac transplant recipients, is less myelosuppressive than azathioprine, and appears to be at least equipotent to azathioprine.

Adult↗
PubMed1993

Prevention of Pneumocystis carinii pneumonia in cardiac transplant recipients by trimethoprim sulfamethoxazole.

Pneumocystis carinii pneumonia (PCP) continues to cause significant morbidity in recipients of solid-organ transplants. While some programs administer trimethoprim-sulfamethoxazole (TMP-SMX) prophylactically following transplantation, a prospective determination of the safety and efficacy of TMP-SMX in cardiac transplant recipients has not previously been reported. We therefore prospectively randomized 58 cardiac transplant recipients to receive TMP (160 mg)-SMX (800 mg) twice daily either three days per week (group B), or seven days per week (group C), or to receive no treatment (group A). Treatment began 14 days after transplantation and continued for four months. Age, sex, preexisting pulmonary pathology and immunosuppressive protocols did not differ among the groups. Of 17 patients in the control group (A), 7 developed a clinical syndrome compatible with PCP, with the diagnosis histologically confirmed by bronchoalveolar lavage during the first four months following transplantation. In contrast, no patients in either the daily or intermittent therapy groups developed PCP during the study period (P < 0.005). Both doses of TMP-SMX were well tolerated, and discontinuation of therapy was not necessary in any patient. Total white blood cell count, azathioprine dose, and number of treated episodes of rejection per patient did not differ among the three groups. We conclude that TMP-SMX can safely and effectively be administered to prevent the occurrence of P carinii pneumonia during the first four months following cardiac transplantation.

Adult↗
PubMed1993

Cyclophosphamide as an alternative to azathioprine in cardiac transplant recipients with suspected azathioprine-induced hepatotoxicity.

AZA has been reported to cause liver dysfunction in some recipients of solid organ transplants. To assess the safety and efficacy of cyclophosphamide in maintenance immunosuppression in the setting of AZA-induced liver dysfunction, we retrospectively reviewed the records of 320 surviving cardiac transplant recipients in Utah. Cyclophosphamide was substituted for AZA in 29 patients due to elevated liver enzymes. Patients were switched to cyclophosphamide 689 +/- 104 days after transplantation; total follow-up after initiation of cyclophosphamide was 540 +/- 56 days. The dose of cyclophosphamide after 2 and 6 months of cyclophosphamide therapy was 62 +/- 6 mg/day (0.8 +/- 0.1 mg/kg/day) and 48 +/- 5 mg/day (0.6 +/- 0.1 mg/kg/day), respectively, compared with 233 +/- 20 mg/day (2.9 +/- 0.2 mg/kg/day) of AZA. The substitution of cyclophosphamide for AZA was associated with a significant improvement in liver function tests. Liver enzymes decreased by up to 49% (P = 0.027), while serum bilirubin decreased by 58% (P < 0.001). Rejection frequency did not increase; neither corticosteroid nor CsA dosage was altered significantly after the substitution of cyclophosphamide. Significant bone marrow suppression was not observed; specifically, no significant change in white blood cell count or hematocrit occurred. Complications of treatment with cyclophosphamide were few; only 1 patient discontinued cyclophosphamide because of alopecia. We conclude that cyclophosphamide appears to be safe in maintenance immunosuppression, permitting the discontinuation of AZA in patients with AZA-induced hepatic dysfunction without necessitating the augmentation of either corticosteroids or CsA.

Alanine Transaminase↗
PubMed1993

Increased frequency of alloantigen-reactive helper T lymphocytes is associated with human cardiac allograft rejection.

Endomyocardial biopsy (EMB) is the standard method of monitoring heart transplant recipients for the development of allograft rejection. To date, noninvasive methods to detect cardiac allograft rejection have lacked adequate sensitivity and specificity for wide clinical application. In this study, limiting dilution analysis (LDA) was used to quantitate the number of donor alloantigen-reactive helper T lymphocytes (HTLs) in the peripheral blood of cardiac transplant recipients. Cadaveric donor splenocytes were cryopreserved, providing a source of donor alloantigenic stimulation for these assays. Peripheral blood mononuclear cells were harvested from cardiac transplant recipients before transplantation and at the time of EMB. LDA of donor-reactive HTLs was conducted simultaneously on all time points to minimize experimental variation, and these data were related to EMB scores. Frequencies of donor-reactive HTLs in pretransplant samples were highly variable, ranging from 1/1381 to < 1/200,000, and correlated poorly with the degree of HLA disparity. During episodes of moderate rejection, donor-specific HTL frequencies increased an average of 6 times their post-transplant baseline frequency. Additionally, 10-fold increases in HTL frequencies were seen preceding EMB-diagnosed rejection in several individuals. These data indicate that episodes of allograft rejection are associated with increases in the number of circulating donor-reactive HTL which are frequently detected before the development of histologically defined rejection. Thus, monitoring HTL frequencies may serve as a non-invasive method for detecting and predicting cardiac allograft rejection. Furthermore, this assay may provide a valuable means of assessing the in vivo efficacy of various immunosuppressive therapies.

Graft Rejection↗
PubMed1993

Pregnancy in heart transplant recipients: management and outcome.

OBJECTIVE: To determine the outcome of pregnancies in cardiac allograft recipients. METHODS: Thirty women who became pregnant after heart transplantation were identified from cases managed personally, questionnaires sent to all cardiac transplant centers, and review of the literature. Mothers were evaluated for evidence of rejection and for obstetric complications. The infants were observed for congenital abnormalities and perinatal morbidity or mortality. RESULTS: Frequent pregnancy complications included chronic hypertension (48%), preeclampsia (24%), and preterm labor (28%). The rate of cesarean delivery was 32%. Six episodes of rejection required treatment, and three late maternal deaths occurred. Among the 27 live births, 17 infants were born after 36 weeks' gestation and ten were preterm, five were small for gestational age, and four had neonatal complications. There were no congenital anomalies. CONCLUSION: Pregnancies in heart transplant recipients present management problems similar to those seen in patients with other allografts and should be considered high risk.

Adult↗
PubMed1992

Mediastinitis in heart transplantation.

Between March 1985 and December 1991, mediastinitis developed in 12 of 420 cardiac transplantation patients (2.8%). The mortality rate in this group of patients was 8.3% (1/12). Actuarial survival (1 year, 75%; and 5 years, 65%) was not significantly different from that of the group without mediastinitis (1 year, 88%; and 5 years, 75%). A higher percentage of the patients in the group with mediastinitis were listed as UNOS status 1 (50% versus 35%) and had a history of previous sternotomies (58% versus 44%). The presentation of mediastinitis was typical. Computed tomographic scanning with or without aspiration was a valuable adjunct in the diagnosis of mediastinitis. Induction immunotherapy with minimal steroids in the perioperative period was used in all patients. This may contribute to the patients' ability to mount an appropriate and effective response to infection, permitting earlier diagnosis. The debridement irrigation technique used in 8 of 12 patients had a low success rate of 33%, whereas the debridement muscle flap technique used in 4 of 12 was 100% successful in eliminating infection.

Actuarial Analysis↗
PubMed1990

Methotrexate as an adjunct in the treatment of persistent mild cardiac allograft rejection.

Because methotrexate arrests inflammation in autoimmune disease, we studied its efficacy in persistent low-grade cardiac allograft rejection. Seventeen patients aged 39.5 +/- 0.9 years (mean +/- SE) had persistent rejection despite previous therapy with high dose corticosteroids. Maintenance immunosuppression consisted of prednisone, azathioprine, and cyclosporine. The rejection episode treated with methotrexate occurred 180 +/- 55.4 days posttransplantation. Patients had incurred 2.7 +/- 0.3 previous episodes of rejection with the first episode occurring 30.6 +/- 6.2 days post transplant. Methotrexate was administered orally in 3 doses to an average weekly dose of 12.8 +/- 0.8 mg. The duration of methotrexate therapy was 9.0 +/- 1.1 weeks. Sixteen of the seventeen persistent rejection episodes resolved by 22.8 +/- 3.2 days of methotrexate therapy. Using methotrexate, the prednisone dose was decreased from 22.4 +/- 4.8 mg/day at initiation of methotrexate to 9.7 +/- 1.4 mg/day at the completion of methotrexate therapy (P less than 0.01). Over a 306 +/- 35-day follow-up, 9 of 17 patients (53%) have remained rejection-free. Leukopenia, necessitating reduction in azathioprine occurred in 10 patients. One patient developed herpes zoster during therapy. These data indicate that methotrexate is effective in resolving persistent cardiac allograft rejection with minimal morbidity. In addition, the use of methotrexate for treatment of rejection allows reduction in maintenance corticosteroid doses.

Adult↗
PubMed1983

Teaching treatment planning. A problem-solving model.

An effective physical therapist must be able to identify a patient's problems and the cause of the problems and to plan specific treatments with a sound rationale. This article presents a model used as a teaching tool for treatment planning may be used in both academic and clinical settings. Questions that are used in completing the model and examples of the model's application are presented. Teaching the problem-solving model and its use in one physical therapy curriculum are discussed.

Curriculum↗