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Biomedical subjects

M M Cooper

Publications and source records attributed to M M Cooper.

12 recordsLinked to original sources

Recurrent intravenous leiomyomatosis with cardiac extension.

A case of recurrent intravenous leiomyomatosis with cardiac extension and a temporally extended presentation is described. Complete excision was achieved employing simultaneous sternotomy and laparotomy and deep hypothermia with circulatory arrest. Coronary revascularization was performed concomitantly with complete tumor resection. Diagnostic, operative, and pathologic considerations are reviewed and a preferred surgical approach discussed.

Female

Permanent pacing following cardiac transplantation.

Permanent pacemakers were inserted in 20 of 439 patients who had received 453 orthotopic cardiac allografts since 1980 at the Columbia-Presbyterian Medical Center. Mean age at transplantation was 45 +/- 4 (SEM) years (range 10 to 64). Pacemakers were inserted an average of 2.4 +/- 1 months after transplantation (range 0.4 to 29), 16 of 20 (80%) within the first month. Indications included sinus bradycardia or sinus arrest in 15 (75%), third-degree heart block in 2 (10%), and both sinus node and atrioventricular node dysfunction in 3 (15%). Rejection episodes and pacemaker insertion were associated in 8 patients (40%). Pacing modes included DDD (7 patients, 35%), AAI,R (7 patients, 35%), VVI,R (3 patients, 15%), DDD,R (2 patients, 10%), and VVI (1 patient, 5%). There was no pacing-related morbidity or mortality. Fourteen of 20 patients (70%) are alive and well 3 to 48 months (mean 24 +/- 4) after transplantation. Late follow-up indicated that atrioventricular node dysfunction resolved in one of two patients, sinoatrial node dysfunction improved or resolved in 7/13 patients, and no atrioventricular block developed in 11 (8 to 37 months, mean 22 +/- 3). Permanent pacing can be safely performed following orthotopic cardiac transplantation, predominantly for sinus node dysfunction. The requirement for pacing may reflect ongoing or new onset rejection and patients should therefore be evaluated accordingly. Dual-chamber pacing is probably not necessary unless atrioventricular node dysfunction is coexistent. Further, as most transplant recipients return to an active life-style, AAI,R may be the preferred mode of pacing.

Adolescent

Pediatric heart transplantation after operations involving the pulmonary arteries.

A prohibitive perioperative mortality has been previously ascribed to pediatric heart transplantation after palliative operations for congenital heart disease involving the pulmonary arteries. Of 46 children who have undergone heart transplantation at our institution between June 1984 and February 1990, 7 (15%; mean age 8 +/- 3 years; range 1 to 18 years) have previously undergone such operations: right ventricle to pulmonary artery conduit/homograft for levo-transposition of the great arteries (2), Waterston shunt for tricuspid and pulmonary atresia (1), pulmonary artery banding for single ventricle (1), Fontan procedure for single ventricle (1), first-stage Norwood procedure for hypoplastic left heart syndrome (1), and classic right Blalock-Taussig shunt for atrioventricular canal with pulmonic stenosis (1). Three categories of pulmonary artery anatomy that require different approaches to reconstruction at the time of transplantation are recognized: abnormalities of position, pulmonary outflow obstruction, and previous systemic- or atrial-pulmonary connections. At operation, individualized pulmonary arterial reconstruction was employed, including use of previously created right ventricular-pulmonary artery conduits/homografts and angioplasty (with and without pericardial patches). Transplantation was successful in all patients. Posttransplant right ventricular-pulmonary artery pressure gradients and pulmonary vascular resistance indices were acceptable, with a tendency to decrease with time. Two patients had critical right ventricular failure postoperatively; one of them required support with extracorporeal membrane oxygenation. There was no perioperative mortality, with three deaths occurring from 5 to 39 months after transplantation. All surviving patients are in New York Heart Association functional class I. Techniques borrowed from the repair of congenital cardiac lesions can be applied to subgroups of children undergoing heart transplantation. Additional length of donor aorta and pulmonary artery should be harvested for possible use in designing pulmonary artery connections. Previous palliative operations involving the pulmonary arteries with associated complex pulmonary artery anatomy are not of themselves an insurmountable obstacle to successful heart transplantation.

Actuarial Analysis

Planning the purification process of active cDNA in expression cloning strategies.

In principle, it is possible to clone the gene for any receptor that can be expressed in the Xenopus laevis frog oocyte and assayed electrophysiologically (E. S. Levitan, 1988, TINS 11, 41-43). Repeated fractionation of a lambda vector cDNA library made from mRNA which encodes the receptor protein will eventually lead to a single cDNA clone. This strategy poses the question as to how large should a lambda vector cDNA aliquot be at any fractionation stage in order that one may be relatively certain that the aliquot contains the clone of interest, and how many times should the fractionation be repeated in order that one isolate the single clone of interest? The purification of active cDNA is an iterative process. At each fractionation stage we specify the probability of at least one active cDNA in the total aliquot to be high. The required size of the aliquot taken depends upon this specified probability and the additional probability of selecting at random an individual cDNA which is active. We require an estimate of the latter probability for the initial stage. For subsequent stages Baye's estimators of these probabilities are used in the formula for calculating the aliquot size at each stage. We show how to perform this calculation when there is equal amplification of the active and remaining sequences and when the active sequence has a non-representative (unequal) amplification. When equal amplification holds a relatively simple formula is provided for calculating the expected number of stages needed in the process. When unequal amplification holds there is no simple calculation for this quantity and the entire sequence of calculations leading to termination of the process must be performed. In either case the minimum lambda vector amplification (growth) factor required at each stage to yield an adequate amount of cDNA for analysis is calculable.

Animals

Use of yttrium-90-labeled anti-Tac antibody in primate xenograft transplantation.

The high-affinity interleukin-2 receptor (IL-2R) is expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting cells. Thus, blockade of the interaction of IL-2 with its receptor could achieve selective immunosuppression. Accordingly, anti-Tac, a murine IgG2a class monoclonal antibody specific to the IL-2R, was used alone or in a chelated form with yttrium-90 (90Y), a pure beta emitter, to inhibit rejection of cardiac xenografts from Macaca fascicularis (cynomolgus) donors transplanted to the cervical or abdominal region of Macaca mulatta (rhesus) recipients (n = 20). Animals received no immunosuppression (n = 3, group I, controls), unmodified anti-Tac (n = 5, 2 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 16 mCi, group III). To distinguish the nonspecific immunosuppressive effect of radiation, 90Y was administered bound to UPC-10 (n = 4, 16 mCi, group IV), another murine monoclonal antibody that does not specifically recognize activated immunoresponsive cells. All immunosuppression was administered in divided doses during the first 2 weeks posttransplant. Group I animals rejected their grafts at 6.7 +/- 1 days and demonstrated a rise in soluble IL-2R levels at the time of rejection, indicating the generation of Tac-expressing and -releasing cells. Graft survival in group II was not prolonged compared with controls (mean survival 6.2 +/- 1 days; P greater than 0.05). In contrast, graft survival in animals that received the designed dosage of 90Y-anti-Tac was significantly prolonged to an average of 38.4 +/- 5 days compared with groups I and II (P less than 0.005 and P les sthan 0.0005, respectively). Prolongation of graft survival occurred in animals that received 90Y-UPC-10 (mean survival 21.3 +/- 5 days, P less than 0.05 versus group I, P less than 0.01 versus group II). However, 90Y-UPC-10 was significantly less effective in prolonging graft survival than 90Y-anti-Tac, in which one-half the per-kilogram dosage of radioactivity was delivered in specific fashion via anti-Tac (P less than 0.025). Reversible nonlethal bone marrow suppression occurred without associated nephro- or hepatotoxicity, and virtually all animals developed antibodies to the murine monoclonal. Thus, the approach used in the present study, IL-2R-directed therapy with 90Y-anti-Tac, may have potential applications in organ transplantation and in the treatment of Tac-expressing neoplastic diseases.

Animals

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

Dose-dependent down-regulation of beta-adrenergic receptors after chronic intravenous infusion of antidepressants.

1. The effects of intravenous infusion of desipramine (1, 3, 10, and 60 mg/kg/day), amitriptyline, zimelidine, iprindole (3, 10, 30, 60, and 100 mg/kg/day each), imipramine (10, 30, and 100 mg/kg/day), or U-48753E (1, 3, 10, and 30 mg/kg/day) on the density of central beta-adrenergic receptors (beta-AR) were investigated in female Sprague-Dawley rats. 2. Desipramine, amitriptyline, zimelidine, iprindole, imipramine, and U-48753E dose-dependently reduced the density of beta-AR in the cerebral cortex. 3. The time of onset of down-regulation of beta-AR was negatively correlated with the doses of drugs. 4. At equipotent doses, antidepressants seem to have a similar profile for the time of onset of reduction in the density of beta-AR. 5. The results indicate that down-regulation of beta-AR may be involved in mediating the therapeutic effects of antidepressants, and this effect can be rapidly achieved by intravenous infusion of drugs.

Amitriptyline

Rapid changes in central beta-adrenergic receptors after chronic intravenous infusion of antidepressants.

The effects of intravenous infusion of desipramine (1, 3, 10, and 60 mg/kg/24 hr), amitriptyline, zimelidine, iprindole (3, 10, 30, 60, and 100 mg/kg/24 hr each), imipramine (10, 30, and 100 mg/kg/24 hr), or U-48,753E (1, 3, 10, and 30 mg/kg/24 hr) on the density of central beta-adrenergic receptors were investigated in Sprague-Dawley rats. A comparative study with oral desipramine (3 mg/kg/24 hr) for 74 hrs was also carried out. Desipramine, amitriptyline, zimelidine, iprindole, imipramine, and U-48,753E reduced the density of beta-adrenergic receptors in the cerebral cortex, and the effect seems to be dose-dependent. In the oral study, desipramine failed to down-regulate beta-adrenergic receptors. These results indicate that down-regulation of beta-adrenergic receptors can be rapidly achieved by intravenous infusion of drugs.

Administration, Oral

A computer program for testing average partial association in three-way contingency tables (PARCAT).

PARCAT is a computer program which implements alternative tests for average partial association in three-way contingency tables within the framework of the product multiple hypergeometric probability model. Primary attention is directed at the relationship between two of the variables, controlling for the effects of a covariable. This approach is essentially a multivariate extension of the Cochran/Mantel-Haenszel test to sets of (s x r) tables. A set of scores such as uniform, ridits, or probits can be assigned to categories which are ordinally scaled. In particular, if ridit scores with midranks assigned for ties are utilized, this procedure is equivalent to a partial Kruskal-Wallis test when one variable is ordinally scaled, and is equivalent to a partial Spearman rank correlation test when both variables are ordinally scaled.

Age Factors