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Biomedical subjects

J J Leonard

Publications and source records attributed to J J Leonard.

At least 19 recordsLinked to original sources
PubMed1999

Effect of peptide concentration and temperature on leuprolide stability in dimethyl sulfoxide.

The effects of temperature and concentration on leuprolide degradation in dimethyl sulfoxide (DMSO) were explored. Leuprolide degradation products were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC) and structurally characterized by mass spectrometry. Leuprolide solution stability in DMSO was characterized at 50, 100, 200, 400 mg/ml at 37-80 degrees C for 2 months to 3 years. Leuprolide degradation products were identified by mass spectrometry and could generally be attributed to isomerization, hydrolysis, oxidation, or aggregation. The hydrolytic degradation products consisted primarily of backbone cleavage C-terminal to Trp(3), Ser(4), Tyr(5), Leu(6) and Leu(7), and oxidation of Trp(3) and beta-elimination of Ser(4) were identified. Leuprolide degradation at 50 degrees C, 65 degrees C and 80 degrees C proceeded in an exponential fashion (E(a)=22. 6+/-1.2 kcal/mol); however, leuprolide degradation plateau'd after approximately 6 months at 37 degrees C. Upon closer examination, degradation product peak areas were seen to vary with temperature. For example, aggregation products did not increase with time at 37 degrees C, but aggregation peak intensities increased sharply with time at 80 degrees C. Increasing the temperature also increased the proportion of leuprolide degrading via isomerization/hydrolytic pathways, and decreased the proportion degrading via oxidation. These variations suggested that solvent dielectric, free H(+) in an aprotic solvent, oxygen solubility, impurities and residual moisture may play a role. Leuprolide solubilized in DMSO yields adequate stabililty for a 1 year implantable osmotic delivery system, where use of a dry aprotic solvent results in conditions similar to solid state stability.

Chromatography, Gel↗
PubMed1999

Characterization and comparison of leuprolide degradation profiles in water and dimethyl sulfoxide.

The effect of solvent on the rate of leuprolide degradation and on the structure of the degradation products was explored. Leuprolide solutions (370 mg/mL) were prepared in water and dimethyl sulfoxide (DMSO) for delivery in DUROS osmotic implants. Both solvent systems demonstrated better than 90% stability after 1 year at 37 degrees C, where the DMSO formulation afforded better stability than the aqueous formulation and was used in subsequent clinical trials. The rate of leuprolide degradation in DMSO was also observed to accelerate with increasing moisture content, indicating that the aprotic solvent minimized chemical degradation. Interestingly, leuprolide degradation products varied with formulation vehicle. The proportions of leuprolide degradation products observed to form in water and DMSO at 37 degrees C were hydrolysis > aggregation > isomerization > oxidation and aggregation > oxidation > hydrolysis > isomerization, respectively. Specifically, more N-terminal hydrolysis and acetylation were observed under aqueous conditions, and increased Trp oxidation and Ser beta-elimination were seen under non-aqueous conditions. Furthermore, the major chemical degradation pathway changed with temperature in the DMSO formulation (decreasing oxidation with increasing temperature), but not in the aqueous formulation.

Acetylation↗
PubMed1995

Surgical intervention in acute myocardial infarction: an historical perspective.

Acute myocardial infarction is an evolving event that lends itself well to surgical intervention. An historical review of surgery of acute myocardial infarction, with specific emphasis on the Spokane data, shows that this can be done safely and efficiently with myocardial salvage. Those people who were operated on within 6 hours of the onset of symptoms of acute myocardial infarction had a clear reduction in hospital mortality incidence and a better long-term result. The conclusion of our review is that emergency coronary artery bypass grafting for acute evolving myocardial infarction should be considered as a therapeutic option in every patient. All other modalities of therapy should be compared with the results of acute bypass surgery.

Coronary Artery Bypass↗
PubMed1988

Adult cardiology and the expanding supply of physicians.

The number of cardiologists can be projected with considerable accuracy into the next century. The total cardiology pool of physicians will increase until the year 2015 at which time those entering and leaving the pool will come into equilibrium. At that time the ratio of active cardiologists to the population will have greatly increased. This nation's future need for cardiologists is difficult to assess with any degree of precision. Therefore, this is the time for updating practice profile studies. Such studies today could be formulated in a manner to provide more detailed information on the cardiologist's daily activities. In addition, a data base developed through methodology such as the consensus formation approach must be developed and updated on a periodic basis. Through such analyses it will be possible to quantitate the future needs of cardiovascular manpower.

Adult↗
PubMed1987

Prevalence of systolic anterior motion of the mural (posterior) leaflet of the mitral valve in hypertrophic cardiomyopathy: an echocardiographic study.

Cross-sectional echocardiography was used to identify systolic anterior motion of the mural (posterior) leaflet of the mitral valve from a group of 53 patients with hypertrophic cardiomyopathy. This type of systolic anterior motion was identified in parasternal long axis, apical four-chamber and/or long-axis cross-sections and was characterized by an elongation of the mural leaflet and an abnormal coaptation with the aortic (anterior) leaflet. At end-diastole, the aortic leaflet coapted at the basal or mid portion of the mural leaflet, leaving its distal "residual" segment in the left ventricle. Subsequently, during systole this "residual" segment approached or touched the ventricular septum. Systolic anterior motion of the mural leaflet was present in 6 (12%) of our patients with hypertrophic cardiomyopathy. Lengthening of the leaflet and an abnormal coaptation were associated with increased thickening of the posterior wall of the left ventricle and narrowing of the left ventricular outflow tract. All these elements contribute to the occurrence of systolic anterior motion and left ventricular tract obstruction.

Adolescent↗
PubMed1987

Genesis of systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: an anatomical or dynamic event?

To determine the relative role of both the anatomical and dynamic components involved in the determination of systolic anterior motion (SAM) of the mitral valve, we studied 53 selected patients with hypertrophic cardiomyopathy (HCM) by M-mode and cross-sectional echocardiography (CSE). Recordings of high quality for quantitative analysis were a precondition for the inclusion in the study. Twelve of these patients had no SAM, 14 had SAM of the anterior mitral leaflet (AML), six had SAM of the posterior mitral leaflet (PML), and 21 had SAM of both the AML and PML. The length of both the AML and PML, the left ventricular outflow tract (LVOT) area and the percentage of thickening of the left ventricular posterior wall (%LVPW) were measured in 18 control subjects (group I), in patients with AML-SAM (group II), in patients with AML+ PML-SAM (Group III), in patients with PML-SAM (group IV) and in patients with HCM but without SAM (group V). The length of AML in group I (23 +/- 1.5 mm) was significantly different compared with that in groups III (28 +/- 2 mm) and IV (29 +/- 2 mm), P less than 0.001. Significant differences were present in the PML-length between group I (14 +/- 1 mm) and groups III (20 +/- 3 mm) and IV (25 +/- 4 mm), respectively (P less than 0.001), between group II (14 +/- 2 mm) and groups III and IV, respectively (P less than 0.001), and also between group V (14 +/- 1 mm) and groups III and IV (P less than 0.001). Differences were found when the %LVPW of groups II (76 +/- 17%), III (77 +/- 11%) and IV (83 +/- 19%) were compared, respectively, with groups I (42 +/- 12%) and V (54 +/- 7%), P less than 0.001; a significant difference was also found between groups I and V, P less than 0.001. The mean LVOT area was significantly reduced in groups II (3.5 +/- 1.3 cm2), III (3 +/- 1 cm2) and IV (3 +/- 1 cm2) when compared with group V (5.9 cm2), P less than 0.001. We conclude that the induction and maintenance of SAM in HCM is multifactorial, mainly depending on the length of both the AML and/or PML, the LVOT area and on the increased contractility of the LVPW.

Adult↗
PubMed1986

Doppler and two-dimensional echocardiographic observations of systolic anterior motion of the mitral valve in d-transposition of the great arteries: an explanation of the left ventricular outflow tract gradient.

Echocardiographic demonstration of systolic anterior motion of the mitral valve was seen in a 17 year old patient after the Mustard operation for d-transposition of the great arteries with intact ventricular septum. An increased flow velocity was measured by continuous wave Doppler echocardiography in the left ventricular outflow tract corresponding to an estimated peak gradient of 46 mm Hg. The presence of such a gradient had been shown earlier by the postoperative cardiac catheterization.

Adolescent↗
PubMed1984

Acute evolving myocardial infarction. A surgical emergency.

This is a report of 342 cases of acute evolving myocardial infarction treated with prompt coronary artery bypass. Myocardial infarction results from a time-related sequence of ischemic pathophysiological changes. The first hours constitute a rapidly progressive event. Prompt surgical revascularization partially prevents impending myocardial necrosis; occasionally it may even prevent it completely. The results are limited infarct size, decreased mortality and morbidity, and a striking absence of the complications associated with conventional therapy (ventricular aneurysm or perforation and septal and papillary muscle rupture).

Adult↗
PubMed1981

Changes in regional myocardial blood flow and variable development of hypertrophy after aortic banding in puppies.

Supravalvar aortic banding was performed in 6 to 12 week puppies. Sixteen animals were studied 7.3 (3.5 to 10) months later, closed-chested under morphine-chloralose, catheters being positioned in the great vessels and heart, including the left atrium for microsphere injection. Compared with 11 controls, eight dogs developed biventricular hypertrophy, four isolated left ventricular hypertrophy and four had no hypertrophy. The left ventricular systolic pressure was similar (P greater than 0.05) in these 3 banded groups (mean, 30 +/- 2 [SEM] kPa, [222 +/- 16 mmHg], n = 16). The left ventricle was divided into three coronal slices with approximately 59 samples being taken from subendocardial, midwall, and subepicardial layers and additional samples from the atria and right ventricle for regional myocardial flow measurement. As left ventricular hypertrophy increased, the subendocardial/subepicardial flow ratio decreased (r = -0.8). Heterogeneity of left ventricular regional myocardial flow, including a base-to-apex decrease in flow, present in controls, was markedly reduced in the banded dogs. Analysis of variance was found to be the most sensitive test for detecting left ventricular perfusion abnormalities since in banded dogs without hypertrophy, total and regional subendocardial/subepicardial flow ratios were not significantly different from control values, whereas the subendocardial circumferential flow pattern determined by analysis of variance was significantly different from control in these dogs (P less than 0.05).

Animals↗