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Biomedical subjects

J E Morin

Publications and source records attributed to J E Morin.

At least 37 records · Page 2Linked to original sources
PubMed1989

Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus.

As a major cause of acute and chronic liver disease as well as hepatocellular carcinoma, hepatitis B virus (HBV) continues to pose significant health problems world-wide. Recombinant hepatitis B vaccines based on adenovirus vectors have been developed to address global needs for effective control of hepatitis B infection. Although considerable progress has been made in the construction of recombinant adenoviruses that express large amounts of HBV gene products, preclinical immunogenicity and efficacy testing of candidate vaccines has remained difficult due to the lack of a suitable animal model. We demonstrate here that chimpanzees are susceptible to enteric infection by human adenoviruses type 7 (Ad7) and type 4 (Ad4) following oral administration of live virus. Moreover, after sequential oral immunization with Ad7- and Ad4-vectored vaccines containing the hepatitis B surface antigen (HBsAg) gene, significant antibody responses to HBsAg (anti-HBs) were induced in two chimpanzees. After challenge with heterologous HBV, one chimpanzee was protected from acute hepatitis and the other chimpanzee experienced modified HBV-induced disease. These data demonstrate the feasibility of using orally administered recombinant adenoviruses as a general approach to vaccination.

Adenoviruses, Human↗
PubMed1988

Expression of HBV surface antigen or HIV envelope protein using recombinant adenovirus vectors.

Recombinant adenoviruses were constructed that contained either the HBsAg coding sequence or the HIV envelope protein coding sequence. The recombinant adenoviruses can replicate normally in cultured human cells. Cells infected with the adenovirus-HBV recombinant secreted HBsAg into the tissue culture medium. This HBsAg had immunological and physical properties similar to those of the 22-nm particles found in human serum. Expression of HIV envelope protein in cells infected with the adenovirus-HIV recombinant was demonstrated using cytoimmunofluorescence and immunoprecipitation. A hamster model was developed to evaluate the immunogenic properties of adenovirus-HBV recombinants. Hamsters inoculated intranasally with live adenovirus-HBV recombinant produced antibody against both adenovirus and hepatitis B virus surface antigen.

Adenoviridae↗
PubMed1987

Recombinant adenovirus induces antibody response to hepatitis B virus surface antigen in hamsters.

Recombinant adenoviruses carrying the hepatitis B virus surface antigen coding sequence in the adenovirus E3 region were constructed using DNA from either adenovirus type 5 or an adenovirus type 5 E3-region deletion mutant. Both of these recombinant adenoviruses replicated as efficiently as wild-type adenovirus in all human cells tested, including the human diploid cell strain WI-38. This indicates that insertion of the hepatitis B virus surface antigen gene into the E3 region does not significantly affect viral replication. Human cells infected with these recombinant adenoviruses secreted immunoreactive hepatitis B virus surface antigen. Since a practical small animal model for human adenoviruses was lacking, a hamster model was developed to evaluate the immunogenic potential of these recombinant adenoviruses. Upon intranasal inoculation, both wild-type adenovirus and the adenovirus E3-region deletion mutant replicated in the lungs of these animals and induced an antibody response against adenovirus. Hamsters similarly immunized with the live recombinant adenoviruses produced antibody against both adenovirus and hepatitis B virus surface antigen.

Adenoviruses, Human↗
PubMed1986

The use of temporary atrial electrodes to improve diagnostic capabilities with Holter monitoring after cardiac surgery.

The use of temporary atrial electrodes implanted during cardiac surgery has been advocated for diagnosis and treatment of cardiac arrhythmias in the postoperative period. We have adapted this technique to allow continuous ambulatory electrocardiographic (Holter) recording of atrial activity in patients after coronary artery surgery. The electrodes of one of the two leads of the Holter recorder were attached as a surface electrocardiographic lead, while the electrodes of the other were each attached to one of the two implanted atrial wires. The Holter record was then obtained in the usual way. A satisfactory recording of the atrial electrocardiogram and the simultaneous surface electrocardiogram was obtained in all 6 patients and resulted in improved diagnostic capabilities, specifically in differentiating supraventricular and ventricular arrhythmia. As has proven to be true in the post-myocardial infarction setting, arrhythmias that were not noted clinically despite continuous electrocardiographic monitoring were demonstrated on Holter records.

Arrhythmias, Cardiac↗
PubMed1986

Host defense mechanisms in elective and emergency vascular surgery: predicting septic-related mortality.

This study examines host defense mechanisms in vascular surgery patients when admitted to the hospital to determine the frequency of abnormal host defense and the predictability of this information for septic-related mortality in affected patients. Sixty-four patients undergoing elective surgery (indications: 35 with aneurysms, 27 with aortoiliac disease, and two with renovascular disease) and nine patients undergoing emergency operation (indications: two with ruptured aneurysms, seven with aortoenteric fistulas) were skin tested when admitted to the hospital with five ubiquitous antigens (Candida, mumps, tuberculin, Trichophyton, and streptokinase-streptodornase [Varidase]) and read at 24 and 48 hours. Patients were anergic with none, relatively anergic with one, or reactive with two or more antigen responses (induration 5 mm). Eighty-nine percent of elective surgery patients were reactive, 5% were relatively anergic, and 6% were anergic. This compared with 64% reactive, 13% relatively anergic, and 17% anergic patients in a separate concurrent study of 565 surgical patients with gastrointestinal malignancies (p less than 0.001, chi 2). There were two septic-related deaths in the elective surgery group and both patients were anergic at admission, which resulted in a mortality rate of 50%. Two deaths not related to sepsis occurred in two reactive patients (4%). Logistic regression analysis predicted 3.9 deaths in the elective surgery group and four deaths were observed. Both patients with ruptured aneurysms were unreactive and both died of septic-related complications. Only one of seven patients admitted with an infected graft was reactive. All had surgery. Using the admission data of these seven patients, we predicted 2.3 deaths. Two deaths were observed 21 and 48 days after operation. Both patients were anergic and scored high probabilities of mortality (more than 0.6) at admission. The remaining emergency procedure patients scored lower probabilities of mortality (less than 0.4) at admission and none died.2+.

Adult↗
PubMed1986

Long-term prognosis of surgical treatment of renovascular hypertension: a fifteen-year experience.

To determine the long-term prognosis for hypertension control, mortality, renal function, and maintenance of renal blood flow in patients operated on to control renovascular hypertension, we studied 60 patients managed surgically between 1969 and 1984. Thirty-six patients had atherosclerotic disease, 22 had fibromuscular dysplasia, one had neurofibromatosis, and one had a combination of atherosclerosis and pyelonephritis. We confined the analysis to the 58 patients with pure atherosclerosis or fibromuscular dysplasia. In the atherosclerosis group 14 patients died and the results of hypertension control in the remaining 22 were classified as cured, three (14%); improved, 15 (68%); failed, one (5%); and unknown, three (14%). In the fibromuscular dysplasia group one patient died and results of hypertension control in the remaining 21 patients were (1) cured, 10 (48%); improved, 10 (48%); and failed, one (5%). The 5- and 10-year survival rates were 79% and 40%, respectively, for the atherosclerosis group and 95% and 89%, respectively, for the fibromuscular dysplasia group. Renal function was well maintained for patients in both groups. The mean serum creatinine value was 1.4 mg/dl in the atherosclerosis group and 1.0 mg/dl in the fibromuscular dysplasia group. To evaluate the effect of operation on the maintenance of renal blood flow we compared the blood flow of the operated and unoperated sides in patients who had a unilateral operation and had a second kidney for comparison. Eight of these patients had scans in each of the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

A microcomputer system for the practising cardiac surgeon.

The authors present a computer program designed for the practising cardiac surgeon who wishes to computerize patient data. The program is efficient, versatile and can be adapted to individual needs. It can be used with any IBM PC-compatible machine and requires little knowledge of computer science. More than 250 items on 30 000 patients can be stored and all this information analysed simultaneously. The program can chart a patient's profile and tabulate the information of the entire registry. It can generate lists of patients with their surgeons, cardiologists, diagnoses, operations and dates of intervention. It can also be used for mailing purposes.

Cardiac Surgical Procedures↗
PubMed1985

Improvement in resting ventricular performance following coronary bypass surgery.

To assess the changes in resting left ventricular (LV) function following coronary bypass surgery, technetium 99m-labeled multiple equilibrated blood pool gated scans were performed in 53 consecutive patients at rest, before operation, and at 24 hours and 1 week after operation. Left ventricular ejection fraction (LVEF) and end-diastolic volume (EDV) were measured. The LVEF increased significantly from a preoperative value of 49 +/- 2% to 56 +/- 2% at 24 hours after operation (p less than 0.05) and 56 +/- 2% at 1 week following operation (p less than 0.05 compared with the preoperative value). The EDV also exhibited significant changes, decreasing from a preoperative value of 148 +/- 8 ml to 91 +/- 11 ml at 24 hours (p less than 0.001) and 114 +/- 9 ml at 1 week (p less than 0.01 compared with the preoperative value). When the patients were divided into two groups according to the preoperative LVEF (Group 1, LVEF of greater than or equal to 50%; Group 2, LVEF of less than 50%), the observed changes were similar. This study demonstrates significant improvement in resting LV function 24 hours following coronary bypass surgery. This improvement persists at 1 week and is not related to the degree of preoperative impairment. We conclude that the combination of successful revascularization and optimal myocardial protection can result in significant improvement of LV function at rest.

Adult↗
PubMed1984

Recurrent or residual shunt following repair of acute postinfarctional ventricular septal defect.

Recurrent or residual ventricular septal defect following operative repair of postmyocardial infarction ventricular septal defect has been reported in many series. Most commonly, this is noted incidentally on postoperative cardiac catheterization or as a murmur in relatively asymptomatic patients in whom no further operation is required. Less frequently, its onset is a catastrophic event leading to the patient's death. On the other hand, the shunt may be sufficiently small to allow time for reoperation. With recent improvement in surgical techniques, more patients with this complication of myocardial infarction have been saved. Recurrent or residual ventricular septal defects have become less frequent, decreasing from a rate of 46% before 1970 to an overall 15% today. Few details have been published about recurrence or persistence of ventricular septal defect following operative repair. The authors report on a patient with a persistent ventricular septal defect following operation and necessitating reoperation. They describe the operative repair and review of the literature on this condition since 1973.

Acute Disease↗
PubMed1984

Surgery for postinfarction left ventricular aneurysm: prognosis and long-term follow-up.

To identify preoperative indicators of outcome following surgery for postinfarction left ventricular aneurysm, the authors have analysed the clinical course of 67 consecutive patients who underwent operation from 1970 to 1982. Follow-up extended to 12 years (mean 4.6 years) and was 97% complete. Postoperative mortality was 8.9%. Factors that were associated with a significantly (p less than 0.05) increased risk of early death included emergency surgery, the presence of ventricular arrhythmias preoperatively and a left ventricular end-diastolic pressure of more than 25 mm Hg on cardiac catheterization. Patients who underwent myocardial revascularization concomitantly had a lower mortality (7.1% v. 18.2% for aneurysmectomy alone), decreased postoperative morbidity and increased longevity. Marked functional improvement was noted in all groups. Actuarial survival (including operative mortality) was 66% at 6 years, and was significantly (p less than 0.05) better in patients operated upon for angina (83.6% +/- 8.1%) than in those operated upon for congestive heart failure (53% +/- 13%). The authors conclude that the most important predictor of outcome following postinfarction aneurysm surgery is the preoperative hemodynamic status of the left ventricle. Since functional recovery and prognosis after operation have been excellent, an aggressive surgical approach to symptomatic left ventricular aneurysms is warranted.

Adult↗
PubMed1984

Role of plasmapheresis in preparing myasthenic patients for thymectomy: initial results.

Between 1976 and 1981, one of the authors operated on 16 patients for myasthenia gravis. Plasmapheresis was carried out preoperatively on seven patients, while nine patients were operated upon without previous plasmapheresis. The seven patients who underwent plasmapheresis had a smooth course pre- and postoperatively. In the other group, there were two postoperative myasthenic complications. Both patients improved with medication and plasmapheresis. Also, the degree of myasthenia gravis was slightly more severe in this group. From their experience, the authors conclude that plasmapheresis is a worthwhile and safe adjuvant in the preparation of myasthenic patients for thymectomy, especially those in Osserman class IV.

Adolescent↗
PubMed1983

Immunological identity between bovine preparations of thiol:protein-disulphide oxidoreductase, glutathione-insulin transhydrogenase and protein-disulphide isomerase.

Five preparations of bovine thiol:protein-disulphide oxidoreductase/glutathione-insulin transhydrogenase (EC 1.8.4.2) and one preparation of bovine liver protein-disulphide isomerase (EC 5.3.4.1) from four different laboratories showed immunological identity in double immunodiffusion and rocket-line immunoelectrophoresis. Consequently, thiol:protein-disulphide oxidoreductase/glutathione-insulin transhydrogenase and protein-disulphide isomerase, formerly classified as two separate enzymes, should be considered as alternative activities of the same enzyme.

Animals↗
PubMed1983

Identification of thiol:protein disulfide oxidoreductase activity in cultured human fibroblasts: dependence of enzyme activity on growth conditions.

Thiol:protein disulfide oxidoreductase activity was assayed in extracts of cultured normal human skin fibroblasts. Enzyme activity in confluent fibroblasts was dependent on growth conditions. In serum-deprived fibroblasts grown in minimal medium enzyme activity was approximately 40% of that observed in fibroblasts maintained in medium supplemented with 10% fetal calf serum. In fibroblasts cultured in medium supplemented only with insulin, activity was 35% greater than that in fibroblasts cultured in unsupplemented defined medium. Antibodies raised against purified bovine liver thiol:protein disulfide oxidoreductase immunoprecipitated all of the activity present in fibroblast extracts. The thiol:protein disulfide oxidoreductase from human fibroblasts thus appears to share antigenic determinants with the bovine liver enzyme. The human fibroblast may serve as an in vitro model to study the regulation of the oxidoreductase.

Blood↗
PubMed1983

Electrical behavior of the heart following high-potassium cardioplegia.

The electrical activity of the heart was studied in 25 patients undergoing elective coronary artery bypass grafting. Simultaneous surface electrocardiograms and bipolar atrial electrograms were monitored continuously from the onset of cardioplegic arrest until normal sinus rhythm was reestablished. Several observations were made. (1) Administration of cardioplegia promptly induced and maintained ventricular arrest in all patients. (2) Atrial activity was seen in 23 patients during global ischemia. (3) Following unclamping, the first sustained rhythm was atrial in 22 patients and was associated initially with high-grade atrioventricular block progressing to 1:1 conduction after a mean reperfusion time of 23 minutes. (4) The time required for complete electrical recovery varied directly with the cross-clamp time and the amount of cardioplegic solution used. (5) Only 3 patients required ventricular defibrillation. (6) In the postoperative period, supraventricular tachyarrhythmias developed in 6 patients. Their occurrence appeared to be related to prolonged atrial activity during the cross-clamp period. Although cardioplegia administration maintained ventricular arrest, sustained atrial activity often was present, perhaps implying inadequate atrial protection and predisposing to atrial arrhythmias. Normal sinus rhythm was reestablished spontaneously in all patients. The atrial electrogram proved essential in the precise intraoperative recognition of cardiac rhythm.

Adult↗
PubMed1983

Persistent atrial activity during cardioplegic arrest: a possible factor in the etiology of postoperative supraventricular tachyarrhythmias.

We assessed the relationship between the duration of atrial activity during the cross-clamp period and the postoperative occurrence of supraventricular tachyarrhythmias in 50 patients undergoing elective coronary bypass operation. The atrial electrical activity was monitored continuously by means of a bipolar atrial electrogram from the onset of cardioplegic administration until removal of the aortic cross-clamp. While ventricular arrest was induced promptly and maintained in all patients, sustained atrial activity was observed in 44 out of 50 patients during the cross-clamp period. In the postoperative period, supraventricular tachyarrhythmias developed in 15 patients (Group 1). Thirty-five patients (Group 2) were free from such tachyarrhythmias. There was no significant difference between the two groups with respect to cross-clamp time, bypass time, amount of cardioplegic solution used, or number of grafts per patient. The mean duration of atrial activity during cardioplegic arrest, however, was significantly longer in Group 1 than in Group 2 (46 +/- 4.7 minutes versus 22.6 +/- 4.0 minutes, respectively, p less than 0.001). None of the 6 patients in whom atrial activity was completely abolished experienced supraventricular tachyarrhythmias. The strong correlation observed between the duration of atrial activity during cardioplegic arrest and the incidence of postoperative supraventricular tachyarrhythmias suggests the possibility that these arrhythmias may be a manifestation of inadequate atrial protection during global myocardial ischemia.

Arrhythmias, Cardiac↗