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Biomedical subjects

D B Melvin

Publications and source records attributed to D B Melvin.

At least 19 recordsLinked to original sources

In vivo comparison of two enteric-pouch power transformers for circulatory support.

A defunctionalized ileal pouch is thin-walled (1-2 mm), well perfused (blood flow, 0.3-1.0 ml/g/min), and tactile-insensitive. If fixed within the abdominal wall and provided with a miniature stoma for primary wire entry, the heat dissipating capacity and achievable geometries could facilitate small efficient intra- to extracorporeal power transformers with virtually complete magnetic flux containment. Two transformers (A, weighing 102 gm with dual ferrite cores, intraluminal primary and extraluminal secondary each with 10 turns on its own crescentic ferrite core, 90 kHz, coupling coefficient k = 0.90-0.96; and B, 68 gm, a single flexible torroidal magnetic metallic tape core with attached 11 turn primary and free 14 turn serosal secondary, 14.7 kHz, k = 0.99) met the electrical and anatomic requirements. Each was implanted (minilaparotomy, coil-pouch fixation within abdominal musculature) in 4 dogs for 14-21 days to test the operative feasibility, electrical function, warming, and flux containment. For canine testing, wires were tunneled to a chewing-inaccessible site. Neither tissue necrosis, infection, provokable interference from contiguous metal, nor coil displacement were observed; secretions were retained in Group A pouches only. The mean power transmissions for the transformers were A: 24.90 +/- 1.50 W and B: 24.92 +/- 0.89 W, after operation for 7 days or more. The mean efficiencies were A: 75.6 +/- 0.1% total DC/DC, 96.2% coils and B: 80.4 +/- 0.1% total DC/DC, 96.2% coils. The peak skin surface magnetic fluxes for transformers A and B, both trivial at 1.7 and 1.2 G, respectively, were similar. Warming was 0.62 +/- 0.30 degrees C in Group A and 0.73 +/- 0.19 degrees C in Group B. The probability values were p < 0.5 (NS) for DC/DC efficiency and p > 0.10 (NS), for A versus B in all other areas of comparison. Observations for both were encouraging. Transformer B, with less mass, lower frequency, higher efficiency, and intrinsic invulnerability to displacement, was selected for longer term evaluation.

Abdominal Muscles↗

Long-term ventricular wall actuation: can and should it be systematically explored?

Hearts fail because myocardial power fails. Assist, support, or replacement devices fail, at least in part, because their blood-contacting surfaces fail. Mechanical repowering of a failing heart might circumvent these difficulties by preserving a largely healthy endocardium while correcting the basic deficit, power. Any serious consideration of doing this though must confront some difficult requirements. Effective indefinite support must be coupled with preservation or restoration of valve competence, coronary flow, rapid low-impedance refilling and independent left and right pressures; the avoidance of wall coaptation; hardware that fits in the available space; and unless muscle powered, adaptability to a deliverable form of power. Despite earlier intense interest in acute mechanical devices and later empiric study of muscle wraps, little systematic methodical work has been done on elucidating and meeting these practical requirements. Concerted efforts toward developing research tools and techniques for their study and then finding mechanisms to meet them could well yield one or more effective modalities that circumvent a major obstacle to the indefinite mechanical treatment of heart failure.

Animals↗

A physical analog of the failing left ventricle for in vitro studies of mechanical wall actuation.

Mechanical repowering of a failing heart with devices or skeletal muscle could circumvent blood-pump lining problems. Requirements are complex: indefinite support with preservation of valve competence and coronary flow, avoidance of wall coaptation, and allowance of both rapid low impedance refilling and independent left and right pressures. An accurate in vitro physical failing-heart analog could facilitate the choice and screening of surgical and engineering approaches in mock circulation experiments. Prosthetic models, transplant recipient hearts, normal animal hearts, existing in vivo animal failure models, and failing cadaver hearts all have serious limitations. One hundred and four excised porcine hearts were dilated and fixed by three iterative protocols. Geometric and passive mechanical parameters were assessed and compared with targets expected for an end-stage failing heart. For Protocol 3, Subgroup 2 (reinforcing valve support, dilatation by compliant ventricular balloon, and ethyl alcohol fixation), the left ventricular shape and capacity (ellipsoid, 201-377 ml/500 g of heart weight), passive valve function, wall flexural rigidity (Et3 range 0.101-0.331 Nm), and refilling mechanics (99 +/- 17.46 ml during 200-400 ms at < or = 10 mm Hg transmural gradient) were all within goal criteria.

Animals↗

Concomitant cardiac and pulmonary operation: the role of cardiopulmonary bypass.

To assess the safety and efficacy of concomitant pulmonary resection and cardiac operation requiring cardiopulmonary bypass, the records of 19 patients were reviewed. Eighteen patients (94.7%) presented with cardiac symptoms and were found to have pulmonary pathology of indeterminate etiology. Pulmonary resections were performed through a median sternotomy in all but 1 patient, who underwent posterolateral thoracotomy and right middle lobectomy after repositioning because dense adhesions prevented adequate dissection through the initial incision. A total of 24 resections were performed. Sixteen (66.7%) were performed on cardiopulmonary bypass. Six wedge resections (25.0%) were performed before bypass. Two lobectomies (8.3%) were performed after infusion of protamine sulfate. Nine patients (47.4%) had benign pathology, 7 (36.8%) had primary carcinoma, and 3 (15.8%) had metastatic disease. Bleeding complications occurred in 15.8% of patients (3/19). There was 1 perioperative death (5.3%), which was due to adult respiratory distress syndrome after intraoperative hemorrhage followed lobectomy for bullous disease. Another patient required lateral extension of the sternotomy during an episode of exsanguinating intraparenchymal pulmonary hemorrhage, which resulted in lobectomy, as well as costochondral and sternal osteomyelitis. A third patient required exploration for bleeding at the staple line. Postoperative complications occurred in 7 patients (36.8%) and were predominantly respiratory (5/7, 71.4%) (p = 0.006). The median postoperative hospitalization was 15 days. Although comparison of patients who underwent pulmonary resection during bypass with those who had resection either before heparinization or after protamine infusion showed no significant difference with respect to age, incidence of malignancy, operation performed, complications, postoperative hospitalization, or survival, this was probably due to the small number of patients in the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Antimurine antibody formation following OKT3 therapy.

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Successful retreatment of allograft rejection with OKT3.

OKT3 is a murine monoclonal antibody to the CD3 antigen of human T lymphocytes. The production of human antimurine antibodies after treatment with OKT3 has been perceived as a major limitation to its extended use and reuse. Treatment of 142 patients with 168 courses of OKT3 resulted in the development of antimouse antibody in 28% of the patients. Twenty-six patients (16 kidney, 6 liver, 3 heart, 1 pancreas) have been retreated with 27 courses of OKT3. Eighteen patients had no antimurine antibodies present, and the rejection reversal rate was 83% (15/18). Six patients had a low-titer antimurine antibody present, and rejection reversal occurred in 5 (83%). Rejection was not reversed in 2 patients with a high-titer antibody. Development of antimurine antibody was more frequent in renal transplant recipients (33%) than in hepatic (12%) or cardiac transplant recipients (18%). We believe that this reflects the fact that concomitant immunosuppressive therapy is more likely to be reduced during OKT3 therapy in renal transplant recipients than in hepatic or cardiac transplant recipients. Retreatment of patients with no anti-OKT3 antibody resulted in depletion of CD3+ cells from the peripheral blood, but it took longer than in patients being treated with OKT3 for the first time. Similarly, serum OKT3 levels rose more slowly in retreated patients compared to first treatment. In retreating patients with a low-titer antimurine antibody, it often was necessary to increase the dose of OKT3 in order to achieve adequate serum OKT3 levels and to deplete CD3+ cells. De novo antimurine antibody developed in 4 of the 18 (22%) antibody-negative patients who were retreated. In conclusion, retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low-titer antibodies does not preclude successful retreatment with OKT3; however, alternate antirejection therapy should be used in patients with high-titer antimurine responses.

Antibodies, Anti-Idiotypic↗

Functional evidence in diseased human heart fibers for multiple sensitivities of the inotropic ouabain receptor Na+,K+-ATPase (NKA).

Through contributions of many investigators from our group at the University of Cincinnati Medical Center, several facts emerged. It is clear that the rat ventricle has 2 inotropic sensitivities to ouabain (Grupp et al., 1981), related to high and low affinity ouabain binding sites (Adams et al., 1982) and the presence of an appropriate abundance of alpha and alpha + catalytic subunits of NKA (Young and Lingrel, 1987). The rat atria which demonstrate only the low affinity inotropic response (Grupp et al., 1981) also show the alpha catalytic subunit in vast predominance, with little or no alpha + (Young and Lingrel, 1987). This scheme has now also been confirmed in the ferret (Ng and Akera, 1987). By analogy, we suggest that the possibility exists that in diseased hearts part of the normally prevailing alpha catalytic subunit (sensitivity in normal human fibers about 140 nM ouabain) is converted to a more sensitive alpha + catalytic subunit leading to an increase of the ouabain sensitivity to about 50 nM. There is also an earlier occurrence of toxic effects and a reduction of the number of low affinity (alpha) ouabain binding sites, resulting in a decrease of the maximally achievable contractile force effect of ouabain. This hypothesis is presently being tested in the genetics laboratory of the University of Cincinnati Medical Center where the relative abundance of the alpha, alpha + and perhaps other isoforms of the NKA are being determined in the tissues of the same hearts from which the trabeculae used in this study were obtained.

Heart Atria↗

Clinical variability of cyclosporine pharmacokinetics in adult and pediatric patients after renal, cardiac, hepatic, and bone-marrow transplants.

The most important limitation associated with the clinical use of cyclosporine is the narrow therapeutic range between its efficacy and toxicity. Effective treatment is further complicated by significant variation in intrapatient and interpatient pharmacokinetics of the drug. We describe a practical approach to pharmacokinetic analysis that does not interfere with the cyclosporine dosage regimen or with clinical management of the patient. To optimize therapy, we individualized patient management by using noncompartmental pharmacokinetic analysis. Mean residence time (MRT) and volume of distribution at steady-state were calculated from data on concentration vs time after dose. We applied this approach to 24 kidney, 12 heart, 8 bone-marrow, 7 liver, and 5 pancreas transplants. Individualized requirements for cyclosporine dose and dosage interval can be predicted from these parameters. MRT is the most useful pharmacokinetic parameter, because it allows prediction of the optimal dosage interval.

Adult↗

Coronary bypass without angiography: an unusual circumstance.

This paper presents an unusual case of an individual with myocardial ischemia, angina pectoris, and myocardial infarction who also had an anaphylactic reaction to angiographic dye. The coronary bypass operation was guided by the use of intraoperative coronary reactive hyperemia assessed by Doppler ultrasound. The patient has had a good response to the operation without additional angina or difficulties.

Angina Pectoris↗

The cost of simultaneous surgical standby for percutaneous transluminal coronary angioplasty.

From November, 1980, to May 1985, 699 patients have undergone percutaneous transluminal coronary angioplasty of 784 lesions at our institutions. Simultaneous surgical standby was available on all cases. One hundred twenty-four patients (18%) underwent immediate myocardial revascularization; 45 (6%) were operated on because the lesion could not be dilated. Seventy-nine patients (11%) underwent immediate operation for an acute complication of angioplasty: coronary occlusion in 45, dissection in 29, coronary perforation in three, and atrial perforation in one. Fourteen patients (18%) required cardiopulmonary resuscitation en route to the operating room, and 10 patients (20%) had insertion of an intra-aortic balloon pump in the cardiac catheterization laboratory. The average time from complication to reperfusion was 87 minutes, ranging from 40 to 165 minutes. An average of 2.0 grafts per patient (ranging from one to five grafts per patient) were performed. Of those 79 patients who underwent operation for an acute complication, one died (1.3%), 31 patients (39%) had a myocardial infarction according to enzyme criteria (creatine kinase-myocardial band greater than 40 IU), and 17 patients (22%) had new Q waves on the electrocardiogram. Good results are related to minimizing the time the myocardium is ischemic. No patient in whom reperfusion was begun in less than 75 minutes had a Q wave infarction or a creatine kinase-myocardial band level greater than 40 IU. Simultaneous surgical standby is the only method allowing immediate access to surgical facilities. A standby team of eight persons and equipment were immediately available for emergency bypass grafting for an average of 3.6 hours (range 1.3 to 5.4 hours per angioplasty attempt). The patient charges for this simultaneous standby were $632.00 per angioplasty attempt, or $442,278.00 for the entire series. The actual cost of the standby was over $1,700.00 per attempt totaling $1,188,843.00 for the 699 patients. This underestimation of the cost of surgical standby has occurred in other series, because little mention has been made of this cost in the published reports on the cost effectiveness of angioplasty. In terms of time demands, over 2,500 hours were spent by surgeons standing by for the 699 attempts. Simultaneous surgical standby is the most effective means of limiting the time the myocardium is ischemic after an angioplasty complication. However, this method is costly, necessitating more of a financial and time commitment than generally anticipated. Future studies of the cost effectiveness of angioplasty should include the cost of surgical standby with accurate per-patient cost accountability.

Adult↗

Coronary artery bypass surgery following thrombolytic therapy for acute coronary thrombosis.

One hundred thirty-six patients underwent thrombolytic therapy for acute evolving myocardial infarction from June, 1981, through December, 1982. Of these patients, 51 underwent coronary bypass procedures from two hours to 90 days (average, 16 days) following thrombolytic therapy. Six (12%) had single-vessel disease, 15 (29%) had double-vessel disease, and 30 (59%) had triple-vessel involvement. Ejection fraction values ranged from 21 to 60%. The average number of grafts performed per patient was 3.4. There were no operative deaths in this series. Postoperative hemorrhagic problems were minimal, and the incidences were no different from those for other coronary bypass patients. In follow-up ranging from 2 to 18 months, there was no recurrence of severe angina or other clinical evidence of saphenous graft occlusion in the thrombolysed vessels. Of the 45 patients eligible to return to work, 40 (89%) have done so. The data from this series suggest that surgical myocardial revascularization after intracoronary thrombolytic infusion for acute myocardial infarction can be performed safely and that complete recovery and a high return-to-work ratio can be anticipated.

Adult↗

Extended evaluation of effects of anoxia on ventricular performance and compliance.

Eight dogs were prepared by implanting a left ventricular pressure transducer, aortic flow probe, and endocardial ultrasound crystals across the maximum transverse left ventricular diameter. In an unanesthetized state, the dogs were evaluated at rest and with acute volume loading, both before ischemic cardiac arrest and sequentially (2, 4, 6, 12, 24, and 48 hours) after 20 minutes of arrest during normothermic cardiopulmonary bypass. At a left ventricular end-diastolic diameter comparable to preoperative levels, left ventricular systolic pressure, heart rate, and rate of rise of left ventricular pressure were not changed, but at 2 to 6 hours there was a significant decrease in cardiac output (p less than 0.01), left ventricular stroke work (p less than 0.01), ejection fraction (p less than 0.05), maximum rate of systolic diameter shortening (p less than 0.05), and circumferential fiber shortening (p less than 0.05). They gradually returned to control levels by 24 hours postoperatively. Left ventricular compliance, as measured by left ventricular end-diastolic pressure at a set end-diastolic diameter and by left ventricular diastolic pressure/diameter, was reduced at 2 hours (p less than 0.01) and gradually returned to control values at 48 hours. Thus, reversible myocardial injury due to anoxia is associated with both decreased contractility and compliance, with resultant depressed left ventricular performance for 24 to 48 hours after injury.

Animals↗

Benign small bowel tumor.

The clinical record and histologic sections of 84 cases of benign small bowel tumor are reviewed. Manifestations of systemic diseases, congenital anomalies, and lesions of either the ileocecal valve or periampullary region were excluded. In the same time span there were 96 small bowel malignancies. Clinical presentation, pathologic findings, management and result are compared to the collected published experience of about 2000 cases. There were 36 leiomyomas, 22 lipomas, 9 angiomas, 6 neurofibromas and 4 fibromas. Thirty-six men and 48 women were affected; the majority in their fifth and sixth decade. Seventy-eight were operative and 6 autopsy diagnoses. The most common symptom was obstruction (42%) followed by hemorrhage (34%) and pain (22%), relative frequency differing for the various specific tumors. There were rarely significant physical findings. A diagnosis of small bowel tumor was made radiologically in 30 patients. Because of the nonspecificity of other signs and symptoms, an acute awareness of the possibility of small bowel tumor is mandatory for preoperative anticipation of the diagnosis. Local resection was performed in all with no deaths or significant postoperative complications.

Adenoma↗

Primary malignancies of the small bowel: a report of 96 cases and review of the literature.

The clinical records and histologic sections of 96 cases of primary small bowel malignancies (excluding lymphomas and periamullary lesions) were reviewed. The location, clinical presentation, pathologic findings, treatment and outcome are compared to the collected published experience, approximately 2400 cases. There were 48 adenocarcinomas, 37 carcinoids, and 11 leiomyosarcomas. Fifty-one men and 45 women ranged from 31 to 83 years old. Eighty-four caused symptoms leading to operative diagnosis; 12 carcinoids were incidental autopsy findings. The most common presentation was pain (33%) followed by weight loss (23%) obstruction (16%), hemorrhage (15%), jaundice (5%), intussusception (3%) and perforation (3%). Masses were felt in 30% of the cases, but were usually dilated bowel or intussusception rather than the tumor per se. Curative resection was attempted in 80 of 84 operatively diagnosed tumors. The 80% mortality among patients followed 5 years is attributed to the late appearance of symptoms and anatomic obstacles to a truly radical operation.

Adenocarcinoma↗