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Biomedical subjects

R C Daly

Publications and source records attributed to R C Daly.

At least 19 recordsLinked to original sources

Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings.

BACKGROUND: Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. SUBJECTS AND METHODS: We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. RESULTS: Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. CONCLUSIONS: Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.

Adolescent↗

Valvular heart operation in patients with previous mediastinal radiation therapy.

BACKGROUND: The outcome of valvular heart operations in patients with previous mediastinal radiation therapy was studied. METHODS: This is a single center retrospective study of 60 patients (37 females, 23 males) with a mean age of 62 +/- 15 years (28 to 88 years old) operated on from January 1976 to December 1998. Valvular heart operations performed included aortic valve replacements (n = 26), mitral valve procedures (n = 16), tricuspid valve procedures (n = 6), and multiple valve procedures (n = 12). A total of 264 clinical, hemodynamic, electrocardiographic and echocardiographic variables were analyzed. RESULTS: Total follow-up was 199 patient-years with a mean of 3.3 +/- 3.1 years and a range of 0 to 12.4 years old. Early mortality was 7 patients (12%). Early mortality in patients with constrictive pericarditis was 40% (4 of 10) compared with 6% (3 of 50) in patients without constrictive pericarditis. By univariate analysis, early mortality was associated with constrictive pericarditis (p = 0.011), reduced preoperative ejection fraction (p = 0.015), and longer cardiopulmonary bypass times (p = 0.037). A total of 14 patients (23%) required permanent pacemaker placement before (n = 7), during (n = 1), or early (n = 6) after valvular heart operations. There were 19 late deaths (malignancies, 7; heart failures, 5; other cardiac, 4; and other noncardiac, 3). Overall survival and freedom from late cardiac death and cardiac reoperation at 5 years for hospital survivors were 66% +/- 8%, 82% +/- 7%, and 93% +/- 4%, respectively. By univariate analysis, late cardiac death was associated with low ejection fraction (p = 0.002), New York Heart Association (NYHA) functional class IV (p = 0.004), preoperative congestive heart failure (p = 0.02), and preoperative atrial fibrillation (p = 0.038). Eighty-five percent of the discharged patients were in NYHA functional class I or II at follow-up. CONCLUSIONS: Early results of valve replacement after mediastinal radiation therapy were good except in the presence of constrictive pericarditis. Long-term outcome was limited by malignancy and heart failure. Early surgical intervention is recommended before the development of risk factors for late death, namely, severe symptoms, left ventricular dysfunction, and atrial fibrillation.

Adult↗

Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls.

BACKGROUND: GABA receptor-modifying neurosteroids may play a role in premenstrual syndrome (PMS). The peripheral benzodiazepine receptor (PBR) both regulates the formation of neurosteroids and is, in animals, regulated by ovarian steroids. Alterations in PBR density have been observed in association with several psychiatric disorders. METHODS: We examined the effects of gonadal steroids on lymphocytic PBR density in nine women with prospectively confirmed PMS and nine controls. PBR densities were measured during three pharmacologically controlled conditions: gonadotropin releasing hormone agonist (Lupron)-induced hypogonadism, Lupron plus estradiol, and Lupron plus progesterone replacement. Blood samples were obtained after six weeks of Lupron alone and after 3-4 weeks of estradiol and progesterone replacement. RESULTS: No significant hormone state-related changes in PBR density were observed (ANOVA-R: phase-F(2,32)=1.5, P=0.2). Despite mood symptom development in the subjects with PMS, PBR density did not differ in women with PMS compared to controls across hormonal states (ANOVA-R: F(1,16)=0.6, P=0.4). CONCLUSIONS: PBR densities are not altered in women with PMS and are not changed significantly by selective gonadal steroid administration. Changes in PBR density would not appear to underlie the differential sensitivity to the mood destabilizing effects of ovarian steroids in PMS.

Affect↗

Heart transplantation for radiation-associated end-stage heart failure.

Radiation-induced heart disease is an increasingly recognized late sequela of mediastinal radiation therapy for malignant neoplasms. We report four cases of heart transplantation for end-stage heart failure induced by mediastinal radiation therapy. Short-term and intermediate-term results are excellent with all four patients currently surviving a mean of 48 months after transplantation. Neither a second malignancy nor recurrence of the primary malignancy has been observed to date. The early results of heart transplantation for end-stage, radiation-induced heart disease are encouraging.

Adult↗

Posterior pericardial approach for ascending aorta-to-descending aorta bypass through a median sternotomy.

BACKGROUND: Bypass grafting for repeat operation or complex forms of descending aortic disease is an alternative approach to decrease potential complications of anatomic repair. METHODS: Between December 1985 and February 1998, 17 patients (13 men, 4 women; mean age, 47.6 +/- 18.5 years) underwent ascending aorta-to-descending aorta bypass through a median sternotomy and posterior pericardial approach. Indications for operation were coarctation or recoarctation of aorta in 8 patients, Takayasu's aortitis in 2, prosthetic aortic valve stenosis associated with coarctation of aorta, complex descending aortic arch aneurysm, reoperation for chronic descending aortic dissection, long-segment stenosis of descending aorta, acquired coarctation after repair of traumatic transection of descending aorta, severe aortic atherosclerosis, and false aneurysm of descending aorta after repair of coarctation in 1 patient each. Concomitant procedures were performed in 12 patients. RESULTS: No early or late mortality has occurred. Follow-up was 100% complete and extended to 12 years (mean, 2.7 +/- 3.3 years). No late graft-related complications have occurred; 1 patient had successful repair of perivalvular leak after mitral valve replacement, and 1 patient had replacement of lower descending and abdominal aorta. CONCLUSIONS: Exposure of the descending aorta through the posterior pericardium for ascending aorta-descending aorta bypass is a safe alternative and particularly useful when simultaneous intracardiac repair is necessary.

Adolescent↗

Intracardiac ectopic thyroid.

Intracardiac ectopic thyroid is a rare lesion. We present a case of successful excision of thyroid tissue obstructing the right ventricular outflow tract and provide a literature review. In all cases reported to date, the ectopic tissue arose from the ventricular septum and extended to the outflow tract.

Aged↗

Repair of anterior leaflet mitral valve prolapse: chordal replacement versus chordal shortening.

BACKGROUND: To determine the optimal method of repair for severe, segmental anterior leaflet prolapse, we analyzed outcome of 121 patients who underwent chordal shortening (n = 46) and chordal replacement (n = 75) from 1988 to 1996. METHODS: Chordae were replaced with expanded polytetrafluoroethylene sutures. Patients had an annuloplasty with either chordal replacement or shortening. Follow-up was 100% complete (mean, 3.7 years). RESULTS: Mean age was 62.1 years, 86 were men, and 60 patients had isolated valve repair. There was one hospital death and 14 late deaths for a 5-year actuarial survival of 86.4%+/-4.5%. Sixteen patients underwent reoperation, 5 in the replacement group and 11 in the shortening group. Mechanism of valve failure in the replacement group was native chordae rupture (n = 4) and neochordae dehiscence (n = 1). With chordal shortening, repair failure was attributed to rupture of shortened chordae (n = 8), leaflet prolapse with and without annuloplasty ring dehiscence (n = 2), and native chordae elongation (n = 1). Risk of reoperation because of repair failure at 3.5 years was 1.4% in the chordal replacement group and 14.8% in the chordal shortening group (p = 0.02). CONCLUSIONS: Chordal replacement is superior to chordal shortening, providing a predictable method for correction of mitral regurgitation with a low incidence of reoperation.

Actuarial Analysis↗

Cox-Maze procedure for atrial fibrillation: Mayo Clinic experience.

The Cox-Maze procedure corrects atrial fibrillation in 90% of patients, and successful operation restores sinus rhythm, thereby reducing risks of thromboembolism and anticoagulant-associated hemorrhage. Symptoms such as palpitation and fatigability also improve with restoration of atrioventricular synchrony. At the Mayo Clinic, 221 Cox-Maze procedures were performed from March 1993 through March 1999. Over 75% of patients had associated cardiac disease and concomitant operations. Overall, early mortality was 1.4%, and the incidence of postoperative pacemaker implantation was 3.2%. Limiting incisions to the right atrium simplifies the operation for patients who primarily have tricuspid valve disease, and in early follow-up, outcome appeared to be as good as that achieved with biatrial incisions. The Cox-Maze procedure has proved particularly useful for patients with preoperative atrial fibrillation who require valvuloplasty for acquired mitral valve regurgitation; 87 patients have had this combined procedure, and there have been no early deaths. Further, our experience indicates that ventricular dysfunction is not a contraindication for operation and that restoration of sinus rhythm after the Cox-Maze procedure improves left ventricular ejection fraction in most patients.

Atrial Fibrillation↗

Calcified bicuspid aortic valve mass prolapsing into the left main coronary artery.

We report a case of a mobile calcific mass on the aortic valve that prolapsed into the left main coronary artery of a 51-year-old man. This case and a review of the literature suggest that calcific embolization to coronary arteries is a rare but possibly underrecognized complication of calcified degenerative or bicuspid aortic valves. This potentially catastrophic complication of calcified aortic valves needs to be suspected and recognized in clinical practice.

Aortic Valve↗

Surgical patent foramen ovale closure for prevention of paradoxical embolism-related cerebrovascular ischemic events.

BACKGROUND: The role of surgical closure of patent foramen ovale (PFO) for cerebral infarction (CI) or transient ischemic attack (TIA) resulting from paradoxical embolism is unclear, and its effect on recurrence is unknown. Our objective was to determine the outcome of surgical closure of PFO in patients with a prior ischemic neurological event, define the rate of CI or TIA recurrence after PFO closure, and identify risk factors for these recurrences. METHODS AND RESULTS: We retrospectively analyzed 91 patients (58 men, 33 women) with >/=1 previous cerebrovascular ischemic events who underwent surgical PFO closure between April 1982 and March 1998. The presence of a PFO with a right-to-left shunt was confirmed with transesophageal echocardiography. Mean age was 44.2+/-12.2 years. The index event was a CI in 59 and a TIA in 32; a Valsalva-like episode preceded the event in 15 patients. Deep venous thrombosis was documented in 9 patients, and a hypercoagulable state was identified in 10. Surgical closure was performed with extracorporeal circulation by either direct suture (n=82) or patch closure (n=9). Limited incisions were used in 18.7% of patients. There was no operative mortality. Morbidity included transient atrial fibrillation (n=11), pericardial drainage for effusion (n=4), exploration for bleeding (n=3), and superficial wound infection (n=1). Follow-up totaled 176.3 patient-years, and mean follow-up was 2.0 years. No one had a CI, and 8 had a TIA during follow-up, with 1 caused by temporal arteritis. Transesophageal echocardiography demonstrated all closures to be intact in these patients. The overall freedom from TIA recurrence during follow-up was 92.5+/-3.2% at 1 year and 83.4+/-6.0% at 4 years. Having multiple neurological events before PFO closure was the only significant risk factor for TIA or CI recurrence after closure by univariate analysis (P=0.05); the small number of post-PFO closure cerebral ischemic events precluded multivariate analysis. CONCLUSIONS: Surgical closure of PFO can be performed with minimal morbidity and mortality. PFO closure may decrease the risk of recurrent stroke or TIA and may avoid lifelong anticoagulation in the young adult if there is no other indication. Recurrent cerebrovascular ischemic events after surgery should prompt further evaluation to identify causes other than paradoxical embolism.

Adult↗

The role of gene therapy for intimal hyperplasia of bypass grafts.

BACKGROUND: Proliferation of the intima is an early lesion of saphenous vein graft disease. Early patency rates of radial artery grafts are acceptable, but little is known about their risk of intimal hyperplasia. METHODS AND RESULTS: To develop a model of intimal hyperplasia, we incubated human saphenous veins, internal mammary arteries, and radial arteries (n=6, 8, and 10, respectively) in an organ culture with Roswell Park Memorial Institute 1640 (30% serum) for 0, 4, 7, 10, and 14 days. Quantitative histological studies were performed, and the average intimal-to-medial (I/M) ratio was calculated for each incubation interval. After 10 and 14 days of culture, the I/M ratio increased in the saphenous veins (P=0. 03, P=0.04 versus 0 day, respectively). No significant increase occurred in the I/M ratio in either the internal mammary or radial arteries. Next, the ability of adenoviral gene transfers to inhibit intimal hyperplasia in the saphenous veins was evaluated. Adenoviral-mediated gene transfer of nitric oxide synthase significantly reduced the I/M ratio at 14 days compared with vehicle (P=0.001) and virus (P=0.004) controls. CONCLUSIONS: The human saphenous vein has a greater propensity for intimal hyperplasia than arterial grafts; the human radial artery behaves similarly to the internal mammary artery. In the future, gene therapy may augment nitric oxide synthase, limiting vein graft disease.

Adenoviridae↗

Mitral valve replacement or repair after previous coronary artery bypass grafting.

BACKGROUND: Patients who have had previous CABG may subsequently develop significant mitral valve (MV) dysfunction that requires surgical intervention. METHODS AND RESULTS: We reviewed 80 consecutive patients who had had previous CABG and who underwent MV surgery between January 1972 and March 1997. Forty-seven (59%) had initial CABG elsewhere, and 5 had had previous CABG twice. The mean interval between the previous CABG and the MV surgery was 6.3 years (range, 4.4 months to -17 years). At least 15 patients had grade 1/4 to 2/4 mitral regurgitation at initial CABG. The study group included 59 men and 21 women, with a mean study group age of 65.5 years. Ninety-four percent had symptoms of congestive heart failure, 60% had angina, 96% were in NYHA class III to IV, and 37% had an ejection fraction (EF) <50%. Origin of the MV disease was ischemic in 33 patients, myxomatous in 19, combined ischemic and myxomatous in 16, rheumatic in 5, infective in 3, and unknown in 4. MV repair was performed in 46 patients (58%) and MV replacement (MVR) in 34. Concomitant repeat CABG was performed in 38 (48%) patients. In-hospital mortality was 7 of 80 (8.8%); no early death occurred among patients with myxomatous disease. EF <50% was the only significant predictor of early mortality. Overall 1-, 5-, and 10-year survival was 83.8%, 55.6%, and 34.4% respectively. Predictors of late cardiac death were preoperative NYHA class IV (P=0.0006), urgent or emergency operation (P<0.0001), use of intra-aortic balloon pump (P=0.002), and EF <50% (P=0.01). Seven patients had an additional reoperation: 4 received CABG, 2 MVR, and 2 MV repair. CONCLUSIONS: Ischemic, myxomatous, rheumatic, or infective MV dysfunction may develop subsequently after CABG. MVR or MV repair after previous CABG is associated with an acceptably low operative risk and good relief of symptoms. Left ventricular function is strongly correlated with both hospital and late mortality. Surgery should be done before LV dysfunction develops.

Aged↗

Endothelial regulation of vascular contraction in radial and internal mammary arteries.

BACKGROUND: The extent to which the endothelium regulates radial artery (RA) contractions is unknown. The goals of this study were to characterize endothelium-dependent relaxations in the RA, compare these responses with those in the internal mammary artery (IMA), and, subsequently, manipulate nitric oxide production in the RA with adenovirus-mediated gene transfer. METHODS: Segments of RA and IMA from 43 patients were studied initially in organ chambers. Endothelial function was evaluated and gene transfer, was examined. RESULTS: After precontraction to 80% maximum tension with prostaglandin F2alpha, acetylcholine produced lesser relaxations in the RA (21.5%+/-5.8%) than in the IMA (66.7%+/-10.6%); human thrombin and adenosine 5'-diphosphate yielded similar results. Reduced relaxations in the RA (16.8%+/-4.2%) compared with those in the IMA (71.6%+/-11.9%) were noted with calcium ionophore. Superfusion bioassay demonstrated a similar baseline release in both arteries but a reduced stimulated production of vasoactive substances in the RA, results confirmed by cyclic guanosine monophosphate level determination. The RA produced less 6-keto-prostaglandin F1alpha than the IMA. Light microscopy demonstrated an intact endothelium in both arteries. Adenovirus-mediated gene transfer of nitric oxide synthase augmented relaxations of the RA to acetylcholine. CONCLUSIONS: Reduced production of endothelium-derived relaxing factors suggests diminished endothelial regulation of vascular smooth muscle in the RA compared with the IMA. This finding may explain, in part, the predisposition to vasoconstriction in RA grafts.

6-Ketoprostaglandin F1 alpha↗

Coronary artery bypass grafting in patients with previous mediastinal radiation therapy.

OBJECTIVES: Our objectives were to characterize the outcome of coronary artery bypass grafting in patients with previous mediastinal radiation therapy and to identify special features of this condition that relate to surgical management. PATIENTS AND METHODS: We conducted a retrospective review of 47 patients (28 women, 19 men) with a mean age of 63.5 +/- 12.8 years (range 31.0-82. 9 years) from 1976 through December 1996 undergoing coronary artery bypass graft after mediastinal radiation therapy. RESULTS: The mean interval between mediastinal radiation therapy and coronary artery bypass grafting was 15.1 +/- 9.8 years (range 1.1-37.8 years). In the 44 patients with isolated coronary surgery, operative mortality was 3 patients (6.8%). Sternal wound infection occurred in 3 patients (6.8%). Actuarial survival at 1 and 5 years was 87.2% +/- 4. 9% and 71.6% +/- 7.1%, respectively. Total follow-up was 293.7 patient-years (mean 6.2 +/- 5.1 years). There were 17 late deaths (malignancy, n = 7; heart failure, n = 6; stroke, n = 1; other noncardiac causes, n = 2; and sudden death, n = 1). Twelve of 43 discharged patients had the development of valvular disease demonstrated by follow-up echocardiography. CONCLUSIONS: The early results of coronary artery bypass grafting for the treatment of ischemic heart disease after mediastinal radiation therapy are good. Late survival, however, is limited by malignancy, either recurrent or new, and the development of heart failure. Inasmuch as 25 other patients after radiation therapy required concomitant valve surgery and 12 of 43 (28%) discharged patients had later development of valvular disease, with 2 requiring reoperation, careful assessment of any valvular lesion is important during the initial coronary artery bypass grafting. Careful follow-up, including regular echocardiographic screening, is recommended in this patient population.

Adult↗