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Biomedical subjects

D B Doty

Publications and source records attributed to D B Doty.

At least 55 records · Page 3Linked to original sources
PubMed1989

Efficacy of OKT3 retreatment for refractory cardiac allograft rejection.

Although OKT3 monoclonal antibody is a useful therapy for refractory cardiac allograft rejection, the use of OKT3 for prophylaxis may be limited by the potential of sensitization and subsequent loss of efficacy on retreatment. OKT3 was required for refractory rejection in 21 of 165 recipients transplanted between March 1985 and August 1988. Twelve of these patients had previously been exposed to OKT3, and the retreatment efficacy was evaluated. The study population averaged 42.1 +/- 15.3 years of age (mean +/- SEM) and had experienced 2 +/- 1 previous episodes of rejection. The prior episodes of rejection had been treated with pulse methylprednisolone and antithymocyte globulin, and in addition 3 patients (25%) also required a course of antilymphoblast globulin. Retreatment OKT3 for refractory rejection was required 120 +/- 94 days following transplantation. CD3+ lymphocytes were eliminated from the circulation within 24-48 hr in 11 of 12 patients, all of whom showed histologic improvement within the first week. Total resolution on the initial follow-up biopsy was noted in 9 (75%) during the course of therapy. Subsequent rejection episodes occurred in 9 (82%) of the survivors at 71 +/- 64 days. One-year survival was 83% in this vigorously rejecting patient population. Serious infections occurred within 3 months of therapy in 4 (36%). The side effects of OKT3 retreatment were similar to those seen with first exposure and did not require OKT3 discontinuation. Thus OKT3 may be administered with success in most patients who have previously been exposed to it.

Adult↗
PubMed1989

A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.

To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.

Antibodies, Monoclonal↗
PubMed1988

The effects of cardiopulmonary bypass and cold cardioplegia on coronary flow velocity and the reactive hyperemic response in patients and dogs.

In normal coronary arteries, reactive hyperemic responses to a 20-second occlusion, an index of coronary reserve, usually demonstrate a peak-to-resting flow velocity ratio of 4:1 or more. Most intraoperative studies that have assessed reactive hyperemic responses in bypassed vessels have reported peak-to-resting flow velocity ratios of 2:1 or less following a 20-second occlusion. These decreased reactive hyperemic responses could be due to coronary vasodilatation after cardiopulmonary bypass or to an inadequate physiological result of the surgical procedure. In 14 patients with angiographically normal coronary arteries, the peak-to-resting flow velocity ratio following a 20-second coronary occlusion decreased significantly (p less than 0.05) from 4.4 +/- 0.2 (mean +/- standard error) before bypass to 3.0 +/- 0.3 after bypass. In a similar dog model, the peak-to-resting flow velocity ratio decreased by 36 to 52% during the first hour following one hour of cardiopulmonary bypass and cardioplegia. During the same period, left ventricular perfusion increased 21 to 30%, mean arterial pressure and coronary vascular resistance decreased, and myocardial oxygen consumption was unchanged. In a second group of dogs studied for the effects of duration (200 to 240 minutes) of anesthesia and thoracotomy alone, peak-to-resting flow velocity ratio was significantly lower. These clinical and experimental studies suggest that major coronary vasodilatation occurs early following cardiopulmonary bypass and cold cardioplegia, and may contribute to the blunted coronary reactive hyperemic responses reported during this time. Consequently, an intraoperative peak-to-resting flow velocity ratio of 3:1 for bypassed coronary arteries may represent an excellent physiological result.

Adolescent↗
PubMed1987

Age-associated decline in cardiac allograft rejection.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

Actuarial Analysis↗
PubMed1987

Replacement of the aortic valve with cryopreserved aortic valve allograft: considerations and techniques in children.

Normal structure and function of the aortic valve requires not only the basic three-cusp architecture but also the dynamic action and shape of the aortic sinuses and correct diameter relationships at the left ventricular outlet and at the aortic sinus rim. Congenital malformation of the aortic valve implies abnormality of the aortic cusps and, additionally, there may be deformity of the aortic sinuses or the subvalvular left ventricular outflow tract or the supravalvular aorta. Aortic valve replacement in children using an aortic valve allograft often requires enlargement of the left ventricular outflow tract or restoration of aortic sinus configuration. Careful consideration of the malformations of the aortic root and planning of reconstructive operation is required lest the malformation be recreated in the allograft valve replacement. Even the best execution of known aortic root reconstructive or left ventricular outflow tract enlarging operations has limitations in restoration of normal structure and compliance of the aortic root. Consequently, there remain many unknown factors that could affect late results of aortic valve allograft operations in children compared to those results observed in adult patients.

Aorta↗
PubMed1987

Pulmonic valve.

Explore the source record for details and available documents.

Heart Valve Diseases↗
PubMed1986

Cerebral infarction complicating Fontan surgery for cyanotic congenital heart disease.

We report on four children who had cerebral vascular events in the first three months after the Fontan procedure for complex cyanotic congenital heart disease. Potential risk factors in these children included congestive heart failure, postoperative thrombocytosis, and cardiac arrhythmias. These cases suggest that children who undergo Fontan surgery may be at increased risk for cerebral infarction.

Adolescent↗
PubMed1986

Morphologic characteristics of aortic atresia: implications for fetal hemodynamics.

We studied hearts with aortic atresia to determine the relationship between cardiac morphology and fetal cardiac blood flow. We compared measurements of aortic, pulmonary, and tricuspid valve circumference and right ventricular wall thickness among 37 hearts with aortic atresia and mitral hypoplasia, 14 hearts with aortic atresia together with mitral atresia and 24 normal hearts. Right ventricular free wall thickness and tricuspid and pulmonary valve annular circumferences were greater and aortic circumferences were smaller in hearts with aortic atresia than in normal hearts (P less than 0.05). Between the subgroups of aortic atresia, the aortic circumference was 5 +/- 1 mm in those with mitral atresia compared to 7 +/- 2 mm in association with mitral hypoplasia (P less than 0.05). The morphologic differences between the subgroups of aortic atresia are consistent with differences in fetal blood flow. Left heart blood flow was likely to be greater during development in those hearts with aortic atresia and mitral hypoplasia than in those with the combination of aortic and mitral atresia.

Aorta↗
PubMed1986

The role of venography and surgery in the management of patients with superior vena cava obstruction.

Venacavography proved to be an excellent guide for the design of patient management programs. Type 1 patients with incomplete obstruction of the superior vena cava (SVC) are best managed by irradiation and chemotherapy regimens and usually do not require operation to bypass the SVC. Types II and IV patients are treated by operation when symptoms of airway obstruction or cerebral venous hypertension are present. Type III patients should be considered for SVC bypass as an initial therapeutic intervention. This group is more likely to have cerebral or airway symptoms and would benefit most from the bypass operation. In terms of operative considerations, type III patients are ideal for operation because the left brachiocephalic vein is usually available for bypass. Type IV patients may also be considered, but operation is more difficult and may require venous thrombectomy or extension of the bypass graft above the thoracic inlet to obtain head and neck decompression.

Adult↗
PubMed1986

Coronary obstructive lesions: assessing their physiological significance in humans.

For more than two decades cardiologists and cardiac surgeons have estimated the physiologic significance of coronary lesions by measuring percent stenosis of the obstructive vascular segment from coronary angiograms. Such measurements, when performed without computer-based analysis, are associated with substantial variability between observers, as well as within a single observer. In addition, recent intraoperative measurements of coronary reserve in individual obstructed vessels of patients with multivessel coronary disease performed with a suction Doppler probe indicate that, in the intermediate range (10% to 90% diameter stenosis), percent stenosis measurements of coronary lesions by angiography correlates poorly with coronary reserve. These studies suggest that the physiologic significance of coronary obstructions cannot be accurately assessed by visual interpretation of coronary angiograms. More sophisticated and accurate approaches are needed for assessing the physiologic significance of coronary obstructions preoperatively.

Coronary Disease↗
PubMed1986

Correction of Taussig-Bing malformation by intraventricular conduit.

Repair of double-outlet right ventricle with subpulmonary ventricular septal defect (Taussig-Bing malformation) was accomplished with an intraventricular conduit. The ventricular septal defect was brought into continuity with the aorta via a tubular Dacron prosthesis, which was situated anterior to the subpulmonary conus and ran transversely from the ventricular septal defect to the subaortic conus. The transverse right ventriculotomy was not closed directly, but was sutured to the external surface of the conduit.

Blood Vessel Prosthesis↗
PubMed1985

Pulmonary stenosis in infants and young children.

Twenty-four patients less than 3 years old underwent operation for pulmonary stenosis. Pulmonary dysplasia was diagnosed preoperatively in only 4 patients; in 20 patients the lesion was categorized simply as pulmonary stenosis. At operation, more severe valve deformities were often present in patients less than 2 years of age. Preoperative evaluation did not reveal the extent of the deformity in 7 additional patients. The deformities included not only valvular dysplasia (thickened redundant valve cusps) but also supravalvular and annular abnormalities. Relief of obstruction was obtained only when all components of the obstructive abnormality were relieved. Patch angioplasty of the right ventricular outflow tract was necessary in 13 patients with complex morphology. Valvotomy was effective only for pulmonary stenosis due to pure commissural fusion. A spectrum of the morphology of pulmonary stenosis is recognized, with more complex lesions than simple commissural fusion identified in younger children. The more complex lesions may require more extensive operations (outflow tract patch) to completely relieve the obstructive pathological condition in the outflow tract.

Cardiac Catheterization↗
PubMed1985

Congenital aortic stenosis with hypoplasia of the left sinus of Valsalva. Anatomic reconstruction of the aortic root.

Evaluation of the aortic root in 13 patients with congenital aortic stenosis aged 2.5 to 24 years (mean 8.3 years) has revealed morphologic characteristics of asymmetry of the aortic root caused by a small (hypoplastic) left sinus of Valsalva associated with a supravalvular ridge above the left coronary ostium and dysplasia of the aortic valve. The asymmetry resulted in folding and buckling of the left aortic cusp. The aortic valve was classified as bicuspid in 11 of the 13 patients. Preoperative aortography was characteristic and revealed the diagnosis in all patients. The average left ventricle-aorta systolic pressure gradient was 81 mm Hg. Operative repair consisted of an oblique aortotomy extended in a spiral fashion to the right and posteriorly into the left sinus of Valsalva. Seven patients had further mobilization of the posterior commissure with a second incision to the right of the commissure into the noncoronary sinus. Slightly fused valve commissures were opened in 12 patients. Aortic root reconstruction was accomplished with a spiral Dacron patch and posterior commissural repositioning. Follow-up catheterization at 9 to 35 months (mean 24 months) in five patients demonstrated an average outflow tract systolic gradient of 28 mm Hg and a more symmetrical appearance of the aortic root.

Adolescent↗
PubMed1984

Coronary reserve in volume-induced right ventricular hypertrophy from atrial septal defect.

To assess coronary reserve in patients with right ventricular (RV) hypertrophy secondary to volume overload, the quantitative characteristics of coronary reactive hyperemia were examined in 20 patients with a large atrial septal defect (ASD). The control group consisted of 13 patients who had undergone elective cardiac surgery for abnormalities that did not involve the right ventricle or its blood supply. Coronary blood flow velocity was measured in RV branches of the right coronary artery at cardiac surgery. Echocardiographic measurements of RV diameter in ASD and in control patients (2.3 +/- 0.2 and 1.1 +/- 0.2 cm, respectively, p less than 0.05) documented the presence of substantial RV enlargement in patients with ASD. In patients with ASD and in control subjects, a 20-second coronary occlusion produced maximal coronary dilation. After release of a 20 second coronary occlusion, the peak-to-resting velocity ratio in ASD and in control patients was 3.1 +/- 0.2 and 5.5 +/- 0.1, respectively (p less than 0.05). The 50% decrease in the ratio of peak-to-resting coronary blood flow velocity, a measure of relative coronary reserve, in patients with ASD suggests that coronary reserve is compromised in volume-induced RV hypertrophy. These studies support the concept that in humans, volume-induced RV hypertrophy substantially decreases coronary reserve.

Adolescent↗