Search PubMed⌕ Search

Biomedical subjects

E Tucker

Publications and source records attributed to E Tucker.

At least 19 recordsLinked to original sources
PubMed1998

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia.

BACKGROUND: In homozygous familial hypercholesterolemia (HFH), the aortic root is prone to develop atherosclerotic plaque at an early age. However, the aortic wall and plaque have not yet been assessed in this condition by MRI. We evaluated the aortic root by use of MRI in 17 HFH patients and 12 normal control subjects in a prospective, blinded, controlled study. METHODS AND RESULTS: Morphological assessment of the aortic root was done with spin-echo and gradient-echo MRI scanning. Comparisons were made with a number of measures of disease severity, including cholesterol-year score, calcium score on electron-beam CT (EBCT), and size of Achilles tendon xanthomas. Atherosclerotic plaque, visible on fat-suppressed images but never on water-suppressed images, was present in 9 HFH patients (53%). Supravalvular aortic stenosis was present in 7 patients with HFH (41%). Maximum supravalvular aortic wall thickness was significantly greater and OD and lumen cross-sectional area (CSA) were smaller in patients than in control subjects (P=0.006, 0.0005, and 0.06, respectively). Maximum wall thickness was associated with a greater calcium score on electron-beam CT (P=0.02). Although the cumulative exposure of the aortic root to cholesterol (the cholesterol-year score) was significantly correlated with the Achilles tendon CSA and vascular calcification, this score did not correlate with the wall thickness or aortic CSA. CONCLUSIONS: This study not only demonstrates the utility of MRI for detecting and characterizing aortic root atherosclerotic plaque and supravalvular aortic stenosis in HFH patients but also suggests that the LDL receptor plays a direct or indirect role in aortic mural development and vascular growth.

Achilles Tendon↗
PubMed1995

A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer.

Increasing evidence suggests that P-glycoprotein (Pgp) expression can mediate drug resistance in refractory breast cancer. We studied 33 patients with refractory breast cancer enrolled in a pilot study of oral amiodarone as a Pgp antagonist given in combination with infusional doxorubicin or vinblastine. Whenever possible, tumors were biopsied and Pgp expression was assayed. Patients received either 60 mg/m2 doxorubicin over 96 h or 8.5 mg/m2 vinblastine over 120 h by continuous intravenous infusion. Beginning with the second cycle of chemotherapy, 600-800 mg amiodarone was given orally each day. Patients who experienced toxicity due to amiodarone but were responding to chemotherapy were placed on quinidine. Partial responses were observed in 9 of 33 patients on study and were sometimes observed after the first cycle of chemotherapy, before amiodarone was given, suggesting that some patients may have responded to treatment because of the infusional schedule. Toxicities were primarily the known side effects of the antineoplastic agents and of amiodarone. The major amiodarone toxicity was gastrointestinal, with nausea, vomiting, anorexia, or diarrhea being noted in 21 patients. Biopsy samples were obtained from 29 patients and in 21 cases, viable tumor tissue was present and the results were interpretable. Of the 21 samples, 9 had Pgp expression as determined by immunohistochemical staining; 12 were considered negative. The presence of Pgp expression was associated with an acceleration of the time to treatment failure. Whereas normal-tissue toxicities related to the combination of a Pgp antagonist with chemotherapy were not observed, amiodarone was associated with too many untoward effects to be utilized as a drug resistance-reversing agent.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents.

OBJECTIVE: With the increased use of tricyclic antidepressants in children, and several reports of several sudden deaths associated with desipramine (DMI) treatment, systematic study of their cardiac effects is indicated. In the present study, DMI's and clomipramine's (CMI) short-term effects on the electrocardiogram (ECG) were compared, as well as the long-term effects of CMI. METHOD: The ECGs of 47 children and adolescents in treatment trials were examined at baseline, after 5 weeks of CMI and of DMI treatment, and during CMI maintenance (mean duration 24.6 months). RESULTS: At 5 weeks of CMI and of DMI treatment, the heart rate, PR, QRS, and QT-corrected (QTc) intervals on ECG were significantly increased from baseline (p < .05); DMI increased PR and QRS intervals more than CMI (p < .05), and CMI increased QTc more (p < .05). Tachycardia was the most common change (36%). More patients experienced an incomplete intraventricular conduction delay during DMI treatment (23%, 9/39) than during CMI (2%, 1/47) (p < .05). Four patients (9%) acutely developed a prolonged QTc during either DMI or CMI. Long-term maintenance ECGs during CMI treatment (n = 25) were not significantly different from that at week 5, although some individuals developed or resolved specific ECG changes. CONCLUSION: CMI and DMI both produced ECG changes typically reported for tricyclic antidepressants, and they differed on specific ECG changes. Changes in ECG measures for individuals from short to long term suggest that continued monitoring is required.

Adolescent↗
PubMed1994

Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma.

BACKGROUND: Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed. METHODS: The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity. RESULTS: One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037). CONCLUSIONS: Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible.

Adolescent↗
PubMed1992

Impact of surgical relief of outflow obstruction on thallium perfusion abnormalities in hypertrophic cardiomyopathy.

BACKGROUND: To assess the impact of surgical relief of left ventricular outflow obstruction on myocardial perfusion abnormalities in patients with obstructive hypertrophic cardiomyopathy, 20 symptomatic patients who underwent a septal myectomy or mitral valve replacement were studied with assessment of myocardial perfusion during exercise by 201Tl emission computed tomography before and 6 months after surgery. METHODS AND RESULTS: Before surgery, 15 patients had myocardial perfusion defects during exercise that completely normalized at rest, one patient had both reversible and fixed perfusion defects, two patients had fixed defects only, and two patients had normal exercise and rest thallium scans. After surgical relief of left ventricular outflow obstruction (basal gradient reduced from 62 +/- 40 to 7 +/- 12 mm Hg, p less than 0.001; peak provokable gradient reduced from 131 +/- 27 to 49 +/- 36 mm Hg, p less than 0.001), repeat exercise thallium studies showed complete normalization of perfusion defects in 11 patients, including the two patients with fixed defects alone before surgery, and improvement in the magnitude and distribution of perfusion defects in five additional patients. This was associated with a significant reduction in the number of patients with reversible regional defects (five patients compared with 13 patients before surgery, p = 0.026) and of patients with endocardial hypoperfusion (four patients compared with 12 patients before surgery, p = 0.024). Furthermore, increased lung uptake of thallium was noted in five patients after surgery, compared with 12 patients before surgery (p = 0.055). Only two patients with reversible perfusion defects before surgery had unchanged postoperative studies. However, four patients acquired new fixed defects as a consequence of surgery, and two of these four had the greatest severity and distribution of left ventricular hypertrophy by echocardiography. These four patients experienced a substantially greater decrease in ejection fraction (-26 +/- 15%) after surgery than the remaining patients (-3 +/- 14%, p less than 0.01). CONCLUSIONS: Surgical relief of left ventricular outflow obstruction results in normalization or improvement of myocardial perfusion in the majority of patients with reversible and fixed perfusion defects by 201Tl scintigraphy. However, surgery may result in myocardial injury and scarring, with consequent decreased left ventricular ejection fraction in some patients.

Cardiac Catheterization↗
PubMed1991

Late recurrent Candida endocarditis.

Late recurrent Candida endocarditis (LRCE) developed on a prosthetic mitral valve 22 months after treatment for primary native mitral valve endocarditis. The LRCE was difficult to diagnose; results of two dimensional echocardiography and repeated blood cultures were negative. Only transesophageal echocardiography revealed a vegetation and only lysis centrifugation blood cultures demonstrated candidemia. Postmortem examination revealed a large Candida vegetation on the prosthetic valve and Candida in the mitral valve ring. This case and a review of the literature indicate that Candida endocarditis treated with amphotericin B and prosthetic valve replacement may recur months after treatment, and that LRCE, which is difficult to diagnose and treat, may be best prevented by lifelong antifungal suppressive therapy.

Adult↗
PubMed1989

Effect of left ventricular septal myectomy on concurrent mitral regurgitation.

To assess the impact of left ventricular septal myectomy (Morrow procedure) performed for obstructive hypertrophic subaortic stenosis on co-existing mitral regurgitation, we examined the preoperative and postoperative left ventriculograms of 35 patients (13 of them women) who underwent left ventricular septal myectomy alone or with concomitant operation. The mean age was 45 +/- 3 years (range, 19 to 74 years). Patients underwent left ventriculography at an average of 15 +/- 3 months postoperatively (range, 1 to 78 months). Severity of mitral regurgitation was evaluated by two teams of reviewers. Mitral regurgitation due to catheter entrapment or to premature ventricular contraction or other arrhythmia was excluded. Overall, 51% of patients showed improvement in the severity of mitral regurgitation, and all those with more severe mitral regurgitation (ie, 3+) demonstrated improvement. The population was subdivided for analysis into those with coronary artery disease requiring bypass grafting at the time of left ventricular septal myectomy (n = 7, 20%) and those without coronary artery bypass grafting. Among the 7 patients undergoing bypass grafting, 71% demonstrated improvement in the degree of mitral regurgitation as compared with only 46% of those without bypass grafting (p less than 0.005 by X2 analysis). Significant reductions in peak gradients at rest and in response to provocation, and in New York Heart Association functional class, also occurred in both groups.

Adult↗
PubMed1989

Cardiorespiratory effects of immunotherapy with interleukin-2.

The administration of interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells can mediate the regression of cancer. Treatment with IL-2 is associated with significant cardiorespiratory effects, as well as a leaky capillary syndrome requiring careful fluid management. A mild reversible depression of cardiac function is also associated with IL-2 treatment. All patients treated with recombinant IL-2 alone, with transfer of LAK cells, or with cyclophosphamide between December 1984 and September 1987 (total of 423 treatment courses in 317 total patients) were evaluated as to the development of significant cardiorespiratory toxicity. Of the 423 treatment courses, only 1.8% were associated with severe peripheral edema and only 2.8% and 3.1% respectively, were associated with significant ascites or pleural effusions. Thirty-nine of 423 patients (9.2%) had severe respiratory distress and 27 patients required intubation (6.4%). Cardiovascular effects included tachycardia and hypotension requiring vasopressor administration in 65% and intravenous (IV) fluid administration. Weight gain greater than or equal to 10% of body weight was noted in 32% of the 423 patients. Arrhythmias were primarily supraventricular (9.7%) and responded well to conventional medical treatments. Angina or ischemic changes were noted in 2.6% of patients and myocardial infarction in 1.2%. IL-2 caused peripheral vasodilation, with a significant decrease in peripheral vascular resistance (2,254 +/- 398 v 1,303 +/- 351 dyne.s.cm-5, P less than .0001), and an increase in heart rate (66.2 +/- 10 v 104.3 +/- 9.6 beats/min, P less than .0001). There was also evidence of mild cardiac dysfunction, with a significant decrease in the left ventricular stroke work (LVSW) index (P less than .0001) and ejection fraction (LVEF) (from 58% +/- 10% to 52% +/- 9%, P less than .03). A repeat LVEF performed after 1 to 3 months, had returned to baseline values (60% +/- 10%). A mean 64% increase in the rate of disappearance of radioactive iodine (125I) albumin (P less than .05) consistent with the development of a leaky capillary syndrome was noted. Patients with underlying cardiorespiratory diseases may be at greater risk during IL-2 administration and should not be selected to undergo this treatment.

Adult↗
PubMed1989

Preservation of brain tumor specimens for drug sensitivity testing.

To examine the feasibility of shipment of brain tumor specimens to a central laboratory for drug sensitivity testing, an experimental gliosarcoma (9L) was grown subcutaneously in rats, harvested, stored, and disaggregated. Growth of the disaggregated tumor cells in monolayer culture was evaluated after storage for various times at 2 to 6 degrees C and 37 degrees C in saline and minimum essential medium. Growth potential was maintained for 24 hours when tumor specimens were stored under refrigerated conditions and was best maintained when specimens were stored in saline. Specimens stored at 37 degrees C grew best when stored in minimum essential medium, but growth potential was lost after 12 hours unless the specimens were refrigerated. Shipment of tumor specimens to a central laboratory for drug sensitivity testing appears to be feasible, since under most circumstances, specimens should reach the laboratory for processing within 24 hours of their removal. Storage and transport of specimens in saline on wet ice appears to be optimal.

Antineoplastic Agents↗
PubMed1988

Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee.

We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4-7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens. Peak total concentrations of 1.73 and 0.86 micrograms.ml-1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively. The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.

Arthritis, Rheumatoid↗
PubMed1987

Operation for hypertrophic subaortic stenosis in the aged.

To determine if operative palliation of idiopathic hypertrophic subaortic stenosis (IHSS) is worthwhile in the elderly, hemodynamic, cardiac conduction, symptomatological, functional, and survival data were examined in 52 patients (39 women) 65 years old and older (mean age, 69 years; range, 65 to 81 years) who had a left ventricular myotomy and myectomy (LVMM) (Morrow procedure) alone or with concomitant operations. Seventy-four percent of all operative survivors underwent catheterization an average of 6 months postoperatively. The mean follow-up was 54 months (range, 5 to 120 months). The population was divided for analyses into those with coronary artery disease (CAD) (N = 11,21%) and those without (N = 41). The peak resting left ventricular outflow tract gradient was reduced from 65 +/- 16 mm Hg to 3 +/- 1 mm Hg (p less than 0.01) in the group with CAD and from 95 +/- 13 mm Hg to 17 +/- 9 mm Hg (p less than 0.001) in the group without CAD. Significant reductions in peak gradients in response to provocation also occurred in both groups. New conduction abnormalities occurred in 72% of survivors, 85% of whom showed improvement in regard to symptoms. The overall average New York Heart Association Functional Class was 3.2 +/- 0.1 preoperatively and at latest follow-up, 1.9 +/- 0.1 (p less than 0.001). The hospital mortality for LVMM alone in the absence of CAD was 8% with a 5-year actuarial survival of 75 +/- 8%. LVMM in the presence of CAD resulted in an operative mortality of 27% (N = 3); all deaths were related to an acquired ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Results of screening a large group of intercollegiate competitive athletes for cardiovascular disease.

To determine the feasibility of detecting cardiovascular disease in a large group of young competitive athletes, a prospective screening evaluation of intercollegiate student athletes was undertaken at the University of Maryland. Initial clinical screening (including personal and family history, physical examination and 12 lead electrocardiogram) was performed in 501 athletes. Ninety of these subjects had positive findings on one or more of the three studies and agreed to further cardiologic evaluation. The vast majority (75 [84%] of 90) had no definitive evidence of cardiovascular disease, although 1 athlete had mild systemic hypertension and 14 (15%) had echocardiographic evidence of relatively mild mitral valve prolapse that had not been previously suspected. In three athletes with relatively mild ventricular septal hypertrophy (14 to 15 mm), it was not possible to discern with absolute certainty whether the wall thickening was a manifestation of hypertrophic cardiomyopathy or secondary to athletic conditioning ("athlete heart"). Therefore, this screening protocol identified no athletes with definite evidence of hypertrophic cardiomyopathy, Marfan's syndrome or other cardiovascular diseases that convey a significant potential risk for sudden death or disease progression during athletic activity. This failure to identify such diseases could have been due to a lack of sensitivity of the screening tests or to the low frequency with which these diseases occur in youthful healthy athletes. A systematic preparticipation screening program (such as the present one) does not appear to be an efficient means of detecting clinically important cardiovascular disease in young athletes.

Adolescent↗
PubMed1987

Inducible polymorphic ventricular tachycardia and ventricular fibrillation in a subgroup of patients with hypertrophic cardiomyopathy at high risk for sudden death.

This investigation was undertaken to elucidate the underlying electrophysiologic substrate in hypertrophic cardiomyopathy and to identify possible predictors of sudden death in this patient population. Programmed stimulation was performed in 18 patients aged 14 to 64 years (mean 36) believed to be at high risk for sudden death on the basis of prior cardiac arrest or syncope, nonsustained ventricular tachycardia on Holter ambulatory electrocardiographic (ECG) monitoring or a family history of frequent sudden death. Polymorphic ventricular tachycardia that deteriorated to ventricular fibrillation was reproducibly induced in 8 (44%) of the 18 patients (Group A). This rhythm was induced in all three patients with a history of cardiac arrest. No sustained monomorphic ventricular tachycardia was induced. Group B comprised the 10 patients in whom a sustained arrhythmia could not be reproducibly initiated. The electrophysiologic substrate was distinctly different in patients with, than in those without, inducible sustained arrhythmia. The refractory period was shorter at the right ventricular outflow tract (232 +/- 22 ms) compared with the apex (264 +/- 12 ms) in Group A (p less than 0.005) whereas there was no difference in Group B (271 +/- 25 ms versus 271 +/- 13 ms). The local ventricular electrogram of most patients in both groups was prolonged and markedly multiphasic. However, 5 of the 8 Group A patients exhibited a double electrogram (V-V') with premature stimulation compared with 1 of the 10 patients in Group B (p less than 0.02). A positive R wave in lead aVR of the scalar ECG and poor R wave progression in the precordial leads were more common in Group A than in Group B (p less than 0.001 and p less than 0.001, respectively). The reason for the distinctly different electrophysiologic substrate and the high prevalence of inducible polymorphic arrhythmia is unclear. It may relate to the underlying myocardial architecture in these patients, characterized by myocardial cellular disarray and fibrosis.

Adolescent↗
PubMed1987

Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis.

Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an alpha beta heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the alpha beta heterodimer, the beta beta homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrating the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, we have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the alpha beta heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the beta beta homodimer suppresses androgen production. Furthermore, similar modulatory actions of inhibin-related proteins were found in cultured ovarian theca-interstitial cells and theca explants treated with LH. In contrast, treatment with the inhibin-related proteins alone did not affect gonadal steroidogenesis. Our data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops.

Androgens↗
PubMed1986

Cardiovascular changes after bilateral upper dorsal sympathectomy. Short- and long-term effects.

The effect of bilateral upper dorsal sympathectomy (UDS) on cardiac function was investigated in two groups of young healthy patients who underwent bilateral excision of T2 and T3 ganglia for palmar hyperhidrosis. In ten patients echocardiography of left ventricular function (LVF) was performed before operation and 2 weeks after operation. Electrocardiograms (ECG) were done before operation, during operation immediately after sectioning each sympathetic chain, and at 2 weeks after operation. The mean pulse rate decreased significantly in patients after they underwent bilateral UDS. There were no clinical arrhythmias or changes in LVF in any patient. Submaximal exercise testing and ECG tracings done at rest and after effort were obtained for 29 patients before undergoing bilateral UDS, 30 days after operation, and 1-3 more times within a 2-year postoperative period. Pulse rates taken at rest and after effort were significantly lower than those taken after operation, and the blood pressure response to exercise was blunted. ECG tracings showed a significant change in the electrical frontal plane axis and shortening of the QTc interval. These changes were evident 30 days after operation and persisted for 2 years. In conclusion, bilateral UDS has no overt arrhythmogenic effect in the young, healthy heart and its beta-blocker-like effect persists for at least 2 years.

Adolescent↗