Perceptual independence of whole length, partial length, and hand position in wielding a rod.

Previous investigations of dynamic touch have shown that, in wielding an occluded rod, the nonvisible perceptions of total rod length, hand position, and fractional rod length above or below the hand are different functions of the eigenvalues and eigenvectors of the inertia tensor. The implication that the 3 perceptions are independent covariants of the inertia tensor of a wielded object was tested with the complete identification experimental procedure using the statistical prescriptions of F. G. Ashby and J. T. Townsend (1986). The confirmed independence is discussed in the context of the generalized psychological or perception-information hypothesis.

Alterations in the cardiopulmonary effects and pharmacokinetics of a bisphosphonate drug by a cytochrome P-450 inhibitor in conscious rats.

U-91502, a bisphosphonate for arthritic inflammation treatment, was evaluated for its parental toxicity. The objective was to differentiate between the parent drug and a reactive metabolite(s) as the proximate cause of the toxic effects using two methods. The first method was to block the metabolism of U-91502 with a broad-spectrum cytochrome P-450 inhibitor, 1-aminobenzotriazole (ABT), to increase its toxicity. The second method was to scavenge any electrophilic intermediates of U-91502 with supplemental nucleophiles, L-methionine (LM) and N-acetylcysteine (NaLc) to decrease its toxicity. Two groups of rats each were given an i.v. injection of saline or ABT followed by an i.v. infusion of U-91502 at a constant dose rate. A third group was given two oral doses of LM followed by a co-infusion of U-91502 and NaLc. The breathing rate (BR) and electrocardiogram (ECG) of the rats were monitored. Blood samples were taken at specified time points for plasma drug concentration analyses (PDC) and pharmacokinetics determination. Each rat was infused until its BR was depressed by approximately 30% from the rates prior to injection of saline or ABT, or the second oral dose of LM. Thereafter, half of the rats in each group were sacrificed immediately and the remaining half at 180 min post infusion. All infused rats, except for those of the co-infusion group, and a group of untreated rats were analyzed for hepatic non-protein sulfhydryl for indication of glutathione depletion. The results indicated that ABT pretreatment expedited the elevation of PDC to a critical level that caused BR and then heart rate (HR) depression and ECG alterations. There was no unusual depletion of glutathione. The maximum concentration and the area under the curve were significantly increased while the total clearance was significantly reduced. Consequently, the postinfusion PDC remained high and the BR and HR depressions persisted. LM and NaLc did not alleviate the toxicity or alter the pharmacokinetics of U-91502. It was concluded that the toxic effects of U-91502 were due mainly to the parent drug and not the metabolites.

Red pepper-induced dermatitis in breast-fed infants.

We report a transient, erythematous dermatitis that formed in 2 infants shortly after breast-feeding from their mothers who had ingested food flavored with red pepper, although the mothers did not display any signs of dermatitis.

Pulmonary atresia and ventricular septal defect with coronary artery to pulmonary artery fistula: case report and review of the literature.

The pulmonary blood supply in patients with pulmonary atresia and ventricular septal defect is highly variable. Several cases have been reported in the literature in which a coronary artery to pulmonary artery fistula, alone or in combination with additional vessels, supplies the pulmonary circulation. We report a case of successful repair during early infancy, with unique hemodynamic, clinical, and anatomic features. The literature is reviewed.

Exposure of the intramyocardial left anterior descending artery.

A systematic approach incorporating several discrete technical maneuvers is described that facilitates localization of the intramyocardial left anterior descending coronary artery. These simple maneuvers reliably afford localization of the initially hidden intramyocardial vessel and are easily incorporated into one's technical armamentarium.

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.

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.

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.

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.

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.

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.

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.

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)

Monitoring of somatosensory evoked potentials during surgical procedures on the thoracoabdominal aorta. I. Relationship of aortic cross-clamp duration, changes in somatosensory evoked potentials, and incidence of neurologic dysfunction.

To determine if intraoperative monitoring of somatosensory evoked potentials detects spinal cord ischemia, we subjected 21 dogs to aortic cross-clamping distal to the left subclavian artery. Group I animals (short-term studies, n = 6) demonstrated decay and loss of somatosensory evoked potentials at 8.5 +/- 1.1 minutes after aortic cross-clamping. During loss of somatosensory evoked potentials, significant decreases in spinal cord blood flow occurred in cord segments below T6. Significant reactive hyperemia occurred without normalization of somatosensory evoked potentials after reperfusion. Fifteen Group II animals (long-term studies) were studied to determine the relationship between duration of spinal cord ischemia (evoked potential loss) and subsequent incidence of paraplegia. Extension of aortic cross-clamping for 5 minutes after loss of somatosensory evoked potentials in six dogs resulted in no paraplegia (mean cross-clamp time 12.7 +/- 0.6 minutes). Prolongation of aortic cross-clamping for 10 minutes after evoked potential loss in nine dogs (mean cross-clamp time 17.6 +/- 0.6 minutes) resulted in a 67% (6/9) incidence of paraplegia 7 days postoperatively (p = 0.02 versus 10 minutes of aortic cross-clamping). These findings demonstrate that simple aortic cross-clamping uniformly results in spinal cord ischemia and that such ischemia is detectable by monitoring of somatosensory evoked potentials. Duration of ischemia, as measured by the time of evoked potential loss during the cross-clamp interval, is related to the incidence of postoperative neurologic injury.

Monitoring of somatosensory evoked potentials during surgical procedures on the thoracoabdominal aorta. III. Intraoperative identification of vessels critical to spinal cord blood supply.

Somatosensory evoked potentials were used to locate intercostal arteries critical to spinal cord blood flow in nine dogs. To mimic a clinical situation, the proximal descending thoracic aorta (left subclavian artery to T7) was excluded with cross-clamps, and partial pulsatile left atrial-femoral artery bypass was instituted to maintain distal aortic pressure at 100 mm Hg. Progressively lower aortic segments were excluded (T7-10, T10-L1, L1-3, L3-6, L6-7) until loss of somatosensory evolved potentials occurred. Spinal cord blood flow measurements at the time of evoked potential loss revealed significant ischemia (p less than 0.02 versus baseline) in the excluded segment in seven animals but normal spinal cord blood flow in the remainder of the cord. Upon reperfusion, significant reactive hyperemia (p less than 0.02) was noted only in previously ischemic cord segments. Two animals exhibited no change in somatosensory evoked potentials or spinal cord blood flow despite exclusion of the entire thoracoabdominal aorta, presumably as a result of spinal collaterals. Loss of somatosensory evoked potentials despite adequate distal perfusion indicates that critical intercostal vessels have been excluded from systemic and bypass circulations. Use of evoked potential measurements in both experimental and clinical situations provides a means for assessing adequacy of spinal cord blood flow during cross-clamping and can alert the surgeon to the need for reimplantation of critical intercostal arteries during surgical resection of the thoracoabdominal aorta.