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Biomedical subjects

L Lambert

Publications and source records attributed to L Lambert.

At least 55 records · Page 3Linked to original sources

Enhanced immunogenicity of a T cell immunogenic peptide by modifications of its N and C termini.

The modification of the terminal ionizable charges of an immunogenic peptide, HEL (46-61), was found to greatly increase the immunogenicity of the peptide. The modified peptide had 100- to 1000-fold enhanced activity in both in vitro and in vivo T cell assays. The mechanism of the enhancement was investigated by determining the binding affinities to I-Ak as well as circular dichroism (CD) studies. The native and enhanced peptides had indistinguishable binding affinities, as well as similar kinetics. The CD studies revealed that in aqueous solution, neither peptide had any detectable helicity; however, the addition of trifluoroethanol did result in significant helicity; with the two peptides being indistinguishable. These same modifications were also shown to enhance other immunogenic peptides if they contained a basic carboxy-terminal amino acid residue. Thus, by modifying the termini of T cell epitopes, their immunogenicity can be dramatically increased, but the molecular basis for this enhancement is still unclear.

Amino Acid Sequence↗

Zacopride, a potent 5-HT3 antagonist.

The substituted benzamide derivative zacopride was found to antagonize competitively the effects of 5-hydroxytryptamine (5-HT) on the guinea-pig ileum, the rabbit vagus nerve and the von Bezold Jarisch reflex in the rat. The potency of zacopride was comparable with that of ICS 205-930 and it is concluded that zacopride possesses 5-HT3 receptor antagonizing properties.

Animals↗

Enhanced late survival following coronary artery bypass graft operation for unstable versus chronic angina.

Late survival following coronary artery bypass operation is time-frame dependent, with a major improvement occurring by 1974. In the cohort of patients undergoing operation between 1974 and mid-1982, subsets were present with further enhanced survival. In this study of 3,575 patients, the urgency of clinical presentation is examined as a survival determinant, and the results are seemingly paradoxical. Among the 1,404 patients with chronic angina, survival at 1 month was 98.3%; at 5 years, 88%; and at 8 years, 79%. Among the 1,008 patients with progressive angina, survival at 1 month was 97.8%; at 5 years, 90%; and at 8 years, 80%. Among the 1,163 patients with unstable angina, 1-month survival was 98.3%; 5-year survival, 92%; and 8-year survival, 89%. The best long-term results were obtained in patients with an acute clinical presentation. Ventricular function was an important determinant of late survival for the groups with chronic (p less than 0.001) and progressive (p less than 0.001) angina, but it had no effect in the group with unstable angina (p = 0.803). For the patients with chronic angina and good left ventricular (LV) function, survival was 99.5% at 1 month; 92% at 5 years; and 86% at 8 years. For those with poor LV function, the respective survival was 96%, 84%, and 71%. For the patients with progressive angina and good LV function, 1-month survival was 98.9%; 5-year survival, 94%; and 8-year survival, 83%. For those with poor LV function, the respective figures were 96.3%, 85%, and 76%. For the patients with unstable angina and good LV function, survival at 1 month was 97.8%; at 5 years, 92%; and at 8 years, 89%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Ten-year survival after coronary bypass surgery for unstable angina.

We have assessed the long-term results of coronary bypass surgery performed for unstable angina in 1282 patients from 1970 to 1982. The operative mortality was 1.8 per cent; in the first 4 years it was 2.5 per cent, and in the last 8 1/2 years it was 1.7 per cent. Using actuarial techniques, we determined that the 5-year and 10-year survival rates (mean +/- S.E.) were 92 +/- 1 per cent and 83 +/- 2 per cent, respectively, for the whole group. For patients with "normal" left ventricular function, they were 92 +/- 2 per cent and 86 +/- 3 per cent, and for patients with "abnormal" left ventricular function 91 +/- 2 per cent and 79 +/- 4 per cent (P = 0.14). No significant differences were observed in the long-term survival for any of the three clinical subgroups of patients with unstable angina--angina at rest, angina after recovery from acute myocardial infarction, and progressive angina of recent onset (P = 0.49). The reoperation rates at 5 and 10 years were 6 +/- per cent and 17 +/- 3 per cent. Currently, 61 per cent of the survivors have no angina; angina occurs on severe exertion in 20 per cent, on ordinary exertion in 14 per cent, and on mild exertion in 5 per cent. We conclude that coronary bypass surgery is an effective form of therapy (for up to 10 years) in patients with unstable angina.

Actuarial Analysis↗

Detecting ductal shunting in premature infants by range-gated Doppler echocardiography.

Range-gated pulsed Doppler echocardiography has been reported to be a useful noninvasive bedside technic for detecting ductal left-to-right shunting in premature infants. We studied 30 premature infants with a birth weight of less than 1,500 gm, using a 5 MHz system developed by Advanced Technology Laboratories. An umbilical artery catheter was used to obtain a contrast aortogram. Twenty-three infants had both a positive flush aortogram and a continuous turbulence documented by Doppler echocardiography. A clinically audible murmur was present in 17 of these patients. In six infants there was no Doppler evidence of PDA. In five of this last group there was also a negative flush aortogram. The excellent correlation found between the Doppler and aortographic studies suggests that this noninvasive technic is very sensitive for detecting ductal left-to-right shunting, even in the absence of an audible murmur.

Aortography↗

A pharmacokinetic and pharmacodynamic assessment of a combined slow-release metoprolol-chlorthalidone preparation.

Beta adrenoceptor blocking drugs and diuretics are frequently given together to control hypertension and increasingly the two agents are being combined in a single preparation. Possible interactions between the two agents are therefore of interest. In this study the addition of chlorthalidone has been shown not to influence the plasma levels or beta-blocking action of a sustained release form of metoprolol. In addition, when the combination product containing sustained release metoprolol and chlorthalidone is given over 21 days, the plasma levels of each drug are similar to those reported for each drug when given alone.

Adult↗

Early results with composite strut caged ball prostheses.

The Starr-Edwards model 6400/10 mitral and 2400/10 aortic valve prostheses incorporate metallic tracks on the inner aspects of cloth-covered struts in an attempt to preserve the favorable thromboembolic performance of cloth-covered valves while avoiding the risk of cloth wear. Two hundred severity operative survivors of mitral valve replacement with the model 6400/10 prosthesis, all on continuous anticoagulant therapy, have been followed up for a mean period of 2.3 (maximal 6) years. The late survival rate is 91 percent and the removal-free rate is 94 percent at 5 years. The rate of embolism (mean +/- standard error of the mean) is 4.6 +/- 0.9 percent per patient-year. Significant bleeding complications occurred at a rate of 1.0 +/- 0.2 percent per patient-year; there were no deaths. Two hundred forty operative survivors of aortic valve replacement with a model 2400/10 prosthesis, all on continuous anticoagulant therapy, have been followed up for a mean of 2.0 (maximal 7) years. The 5 year survival rate is 84 percent and the removal-free rate is 98 percent. Embolism occurred at a rate of 3.3 +/- 0.8 percnet per patient-year. Hemorrhagic complications occurred at a rate of 2.1 +/- 0.6 percent per patient-year; there were three families. Cloth wear and hemolysis have not been significant problems with this prosthesis, and the rates of thromboembolism are comparable with those reported for xenograft bioprostheses. The composite strut (track) valve prosthesis is a durable alternative to tissue valves in patients who are able to tolerate anticoagulant therapy.

Aortic Valve↗

Changes in behaviour ratings of a national sample of children.

The constancy of ratings of behaviour made at home and school between the ages of 7--11, 11--16 and 7--16 is examined. There were moderate correlations between ratings at the different ages (0.31--0.48) but the majority of children in the 'deviant' (top 13 per cent) group at one age had moved out of that group by a later follow-up (4, 5 or 9 years later). Certain characteristics (social class, sex, family size and birth order) of children with different patterns of ratings at the three ages are also examined.

Adolescent↗

Technical considerations in patients undergoing combined aortic valve replacement and aortocoronary bypass surgery.

Forty-nine patients have undergone combined aortic valve replacement and aortocoronary saphenous vein bypass graft surgery using a technique of distal coronary perfusion. Vein grafts are placed before replacement of the aortic valve, and continuously perfused by siting the proximal anastomoses high on the aortic root or individually perfusing the grafts before proximal anastomosis. Continuous coronary ostial perfusion is used as well during aortic valve replacement. There were 3 (6.1%) operative deaths and 1 (2%) perioperative myocardial infarction. A comparison of this technique with other reported results suggests that attention to myocardial perfusion distal to significant coronary artery stenosis may decrease the incidence of perioperative myocardial infarction in patients requiring both aortic valve replacement and coronary bypass graft operation.

Adult↗

Aortic valve replacement and aorta-coronary bypass surgery. Results with perfusion of proximal and distal coronary arteries.

The results in 80 patients undergoing simultaneous aortic valve replacement and aorta-coronary saphenous vein bypass grafting were analyzed to assess the effect of operative technique. The over-all operative mortality rate of 6.3% (five of 80) did not differ significantly from our results with aortic valve replacement alone. All patients who had isolated aortic valve replacement were operated upon with moderate hypothermia. The combined operation was performed in two ways. Thirty-one patients had aortic valve replacement prior to bypass grafting with intermittent coronary ostila perfusion. There were two deaths (6.5%), and five myocardial infarctions (16.1%) were diagnosed by standard electrocardiographic and enzyme criteria. More recently, 49 patients have undergone bypass grafting prior to aortic valve replacement. The proximal ends of the grafts were either anastomosed high on the aortic root or else individually cannulated to provide continuous distal perfusion during subsequent aortic valve replacement, with continuous coronary ostial perfusion. There were three operative deaths (6.1%) and one myocardial infarction (2.0%). The risk of combined aortic valve replacement and coronary bypass need be no greater than the risk of aortic valve replacement alone. Our experience suggests that myocardial perfusion distal to significant coronary artery stenoses reduces the risk of myocardial infarction in patients with coronary artery disease requiring aortic valve replacement.

Adult↗