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Biomedical subjects

J Isner

Publications and source records attributed to J Isner.

14 recordsLinked to original sources
PubMed2001

Chronic ischemic monomelic neuropathy from critical limb ischemia.

OBJECTIVE: To describe the peripheral neuropathy resulting from chronic and critical arterial leg ischemia. METHODS: The authors evaluated 19 patients on entry to a gene therapy treatment trial for chronic and critical leg ischemia. Measurements included medical history, examination, neurologic symptom (NSS) and neurologic examination (NES) scores, motor and sensory nerve conduction studies, and quantitative sensory testing. The critically ischemic leg was compared with the less affected contralateral limb. RESULTS: All patients experienced pain from skin ulceration or vascular claudication, but many also had rest pain (58%), numbness (58%), burning (42%), and paresthesias (37%) in the ischemic foot that were consistent with peripheral nerve ischemia. Only three patients (16%) were free of neuropathic symptoms. The most common asymmetric neurologic signs included hypalgesia (74%), toe weakness (64%), hyperesthesia (63%), and pallanesthesia (53%) in the distal leg. NSS and NES were more abnormal in the critically ischemic leg, as were distal motor, total motor, and sensory examination subscores (p < 0.01 for each). Sural sensory potentials were reduced or absent, frequently on both sides. The symptomatic limb had reduced tibial motor amplitudes and increased thermal (cold) sensory thresholds (p < 0.01 for both) whereas the distal latencies, conduction velocities, and vibration thresholds were similar in the two legs. CONCLUSIONS: There is a predominantly sensory neuropathy associated with chronic and critical limb ischemia. Neuropathic symptoms are often obscured by the effects of ischemia on other tissues. The neurophysiologic changes suggest that the underlying pathophysiology is a distal axonopathy affecting nerve fibers of all sizes. Measures of blood flow in the leg correlate with neurologic symptom scores, examination scores, and electrophysiologic testing.

Adult↗
PubMed2001

Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication.

PURPOSE: We tested the hypothesis that propionyl-L-carnitine would improve peak walking time in patients with claudication. Secondary aims of the study were to evaluate the effects of propionyl-L-carnitine on claudication onset time, functional status, and safety. SUBJECTS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 155 patients with disabling claudication from the United States (n = 72) or Russia (n = 83) received either placebo or propionyl-L-carnitine (2g/day orally) for 6 months. Subjects were evaluated at baseline and 3 and 6 months after randomization with a graded treadmill protocol at a constant speed of 2 miles per hour, beginning at 0% grade, with increments in the grade of 2% every 2 minutes until maximal symptoms of claudication forced cessation of exercise. Questionnaires were used to determine changes in functional status. RESULTS: At baseline, peak walking time was 331 +/- 171 seconds in the placebo group and 331 +/- 187 seconds in the propionyl-L-carnitine group. After 6 months of treatment, subjects randomly assigned to propionyl-L-carnitine increased their peak walking time by 162 +/- 222 seconds (a 54% increase) as compared with an improvement of 75 +/- 191 seconds (a 25% increase) for those on placebo (P <0.001). Similar improvements were observed for claudication onset time. Propionyl-L-carnitine treatment significantly improved walking distance and walking speed (by the Walking Impairment Questionnaire), and enhanced physical role functioning, reduced bodily pain, and resulted in a better health transition score (by the Medical Outcome Study SF-36 Questionnaire). The incidence of adverse events and study discontinuations were similar in the two treatment groups. CONCLUSIONS: Propionyl-L-carnitine safely improved treadmill exercise performance and enhanced functional status in patients with claudication.

Adult↗
PubMed2001

Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels at sites of adult neovascularization.

The transmembrane ligand ephrinB2 and its receptor tyrosine kinase EphB4 are molecular markers of embryonic arterial and venous endothelial cells, respectively, and are essential for angiogenesis. Here we show that expression of ephrinB2 persists in adult arteries where it extends into some of the smallest diameter microvessels, challenging the classical view that capillaries have neither arterial nor venous identity. EphrinB2 also identifies arterial microvessels in several settings of adult neovascularization, including tumor angiogenesis, contravening the dogma that tumor vessels arise exclusively from postcapillary venules. Unexpectedly, expression of ephrinB2 also defines a stable genetic difference between arterial and venous vascular smooth muscle cells. These observations argue for revisions of classical concepts of capillary identity and the topography of neovascularization. They also imply that ephrinB2 may be functionally important in neovascularization and in arterial smooth muscle, as well as in embryonic angiogenesis.

Animals↗
PubMed1997

Embryonic expression of the Gax homeodomain protein in cardiac, smooth, and skeletal muscle.

Gax is a homeobox-containing gene that has been detected in adult cardiovascular tissues and exhibits a growth arrest-specific pattern of expression in cultured vascular myocytes. To study the regulation of gax during development, we performed immunohistochemistry and in situ hybridization on mouse embryos. Gax was present in mesodermally and, as with other homeobox genes, neuroectodermally derived tissues. Early mesodermal protein expression was limited to the lateral plate and somitic mesoderm. Gax in the cardiac muscle lineage exhibited a biphasic pattern of expression. Expression was prominent in the heart tube of the earliest cardiomyocytes and remained prominent through the looping stage (day 12.5 post coitum [pc]) but fell below the threshold of detection in atria and ventricles by day 13.5 pc. At day 15.5 pc, Gax protein was again detectable but restricted to cells within the compact layer of the ventricular myocardium. Gax expression was also noted in smooth muscle cells as early as day 9.5 pc. In the skeletal muscle lineage, Gax protein was expressed at the onset of somitogenesis before the expression of the myogenic basic helix-loop-helix and MEF2/RSRF family proteins. Subsequently, it was noted at day 9.5 pc in premyogenic cells migrating into head, trunk, and limb buds. Gax was detected in myotomes, premuscle masses, and mature muscle groups. These data suggest an important developmental role for Gax in all muscle lineages.

Animals↗
PubMed1997

Selective deposits of versican in the extracellular matrix of restenotic lesions from human peripheral arteries.

Although a large percentage of the volume of human restenotic arterial lesions is occupied by extracellular matrix (ECM), the composition and organization of this ECM are not well characterized. In this study, restenotic segments taken from 30 human peripheral arteries by directional atherectomy at times ranging from 13 days to 36 months after angioplasty were analyzed for specific patterns of ECM composition and organization by light and electron microscopic histochemistry and immunohistochemistry. Histochemical analysis revealed the presence of distinct zones, enriched either in proteoglycans or fibrillar collagen. Most sections contained these regions juxtaposed to each other. The frequency of these two distinct ECMs did not change as a function of time after angioplasty. The collagen-rich zone usually contained elongated smooth muscle cells spaced close together except in regions resembling fibrous plaques. The proteoglycan-rich ECM contained both elongated and stellate-shaped smooth muscle cells randomly arranged and separated by wide distances. This region resembled the loose-connective-tissue-containing myxoid region typical of restenotic lesions. Immunohistochemical analysis of these regions revealed that the proteoglycan-containing zone stained intensely for versican, a large interstitial chondroitin sulfate proteoglycan, whereas the collagen-containing areas were mostly negative for versican but positive for type I collagen. The versican-positive regions also immunostained for biglycan, a small leucine-rich dermatan sulfate proteoglycan, and sparsely for elastin. However, both of these ECM molecules were present in the versican-negative type I collagen-positive regions of the lesions. These results suggest that the development of restenotic lesions involves localized deposits of specific ECM molecules that may play a role in the asymmetric renarrowing of this tissue after angioplasty.

Angioplasty, Balloon↗
PubMed1995

Inoue balloon mitral valvotomy in patients with severe valvular and subvalvular deformity.

OBJECTIVES: This study evaluated the immediate and long-term results of percutaneous Inoue balloon mitral valvotomy in patients with severe valvular and subvalvular deformity. METHODS: We reviewed the prevalvotomy transthoracic echocardiograms of patients from the North American multicenter Inoue registry with total Massachusetts General Hospital (MGH) echocardiographic scores > or = 10. The echocardiograms were rescored by two investigators to assess valvular and subvalvular morphology to eliminate interinstitutional variability. Ninety patients were originally assigned scores > or = 10. After rescoring, 18 patients (20%) were eliminated, leaving 72 study patients. RESULTS: Balloon mitral valvotomy was technically successful in 69 (96%) of the 72 patients. Mean (+/- SD) mitral valve area increased from 0.9 +/- 0.3 to 1.5 +/- 0.5 cm2. An immediate optimal result, defined as > or = 50% increase in mitral valve area or a final area > or = 1.5 cm2 with no major complications, was achieved in 46 patients (64%). End points for clinical follow-up (events) included mitral valve replacement, repeat valvotomy or death. At a mean follow-up of 22.9 +/- 11.0 months, 22 patients (31%) required mitral valve replacement or a second valvotomy, 9 patients (13%) died, and 32 patients (45%) were in New York Heart Association functional class I or II. Univariate predictors of an immediate optimal result included sinus rhythm, male gender and a lower University of Southern California commissural calcium score. Only sinus rhythm predicted an optimal result by multivariate analysis. Actuarial 3-year event-free survival was 42%. Univariate predictors of event-free survival were a lower grade of mitral regurgitation, lower MGH total echocardiographic score, lower MGH leaflet thickness subscore and lower prevalvotomy left ventricular systolic pressure. Only grade of mitral regurgitation after valvotomy predicted event-free survival by multivariate analysis. CONCLUSIONS: Inoue mitral valvotomy in patients with severe valvular and subvalvular deformity has a high technical success rate and good immediate hemodynamic result but a high cardiovascular event rate in follow-up. Mitral valve replacement should be considered in surgical candidates with an MGH total echocardiographic score > or = 10 because it may be able to provide better long-term event-free survival. Balloon valvotomy remains a reasonable palliative therapeutic option for some patients with severe valvular deformity and high surgical risk.

Actuarial Analysis↗
PubMed1993

Mechanisms and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty. North American Inoue Balloon Investigators.

OBJECTIVES: The purpose of this study was to assess the incidence, mechanism and outcome of severe mitral regurgitation after treatment of mitral stenosis with percutaneous mitral valvuloplasty using the Inoue balloon. BACKGROUND: Severe mitral regurgitation occurs in up to 15% of percutaneous balloon valvuloplasty procedures for acquired mitral stenosis. The incidence and mechanism of production of mitral regurgitation with the recently introduced single-balloon Inoue technique have not been characterized. METHODS: We examined the incidence, mechanism, predictors and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty in 280 patients in the North American multicenter registry. Twenty-one patients who developed either clinically significant or angiographically severe regurgitation were identified, and their echocardiograms were reviewed to determine the mechanism of regurgitation. These patients were then compared with the remaining patients without severe regurgitation to identify predictors of this outcome. RESULTS: The incidence of severe regurgitation in this study was 7.5%, and the mean grade of angiographic regurgitation in these patients increased from 0.9 +/- 1.0 to 2.8 +/- 0.7 (p < 0.05). The most common cause of regurgitation (43%) was rupture of chordae tendineae to the anterior or posterior mitral leaflet. Tearing of a leaflet (usually the posterior one) occurred in 30% of patients; and no recognizable structural abnormality, with wide splitting of the commissures and a central regurgitant jet, was present in five patients (26%). All patients with definite posterior leaflet tears had heavily calcified leaflets. Patients who developed severe regurgitation had fewer balloon inflations and a higher grade of preexisting mitral regurgitation but were otherwise similar to the remaining patients without severe regurgitation. During 6-month follow-up, 71% of the patients with severe regurgitation were treated surgically; the grade of regurgitation decreased in four patients (19%), and five patients (24%) have not required mitral valve replacement during 18 +/- 5 months of follow-up. CONCLUSIONS: Severe mitral regurgitation is a relatively infrequent complication of Inoue balloon valvuloplasty and results from disruption of the valve integrity, including chordal rupture and leaflet tearing. Careful balloon positioning may help avoid chordal rupture, and heavily calcified posterior leaflets may be at greater risk of tearing. Most patients who develop severe regurgitation will require nonemergency mitral valve replacement.

Adult↗
PubMed1987

Interobserver variability in the pathologic interpretation of endomyocardial biopsy results.

Controversy exists over the role of endomyocardial biopsy in evaluating patients with dilated cardiomyopathy, particularly in detecting myocarditis and in assessing prognosis. Interobserver variability, if high, could explain conflicting reports. To assess this possibility, we submitted biopsy specimens from 16 patients with dilated cardiomyopathy to seven cardiac pathologists. The same slides were independently reviewed by each and assessed for fibrosis, hypertrophy, nuclear changes on a 0 to 3+ scale, mean lymphocyte count per high-power field, and myocarditis. The prevalance of significant fibrosis ranged from 25% to 69%, hypertrophy from 19% to 88%, nuclear changes from 31% to 94%, and abnormal lymphocyte count from 0 to 38%. One or more pathologists diagnosed definite or possible myocarditis in 11 of the 16 patients. Of these 11 patients, three pathologists agreed about three and two pathologists agreed about five. Myocarditis was diagnosed by a single pathologist in three cases. We conclude that interobserver variability is high in interpreting biopsy specimens from patients with dilated cardiomyopathy and that quantitative and standardized methods are needed to increase diagnostic consistency.

Adult↗
PubMed1985

Correlation of B-mode ultrasound imaging and arteriography with pathologic findings at carotid endarterectomy.

Presently most noninvasive methods for assessing extracranial carotid disease have relied on hemodynamic change associated with significant stenosis. Recent evidence has suggested that both ulceration and/or plaque hemorrhage may frequently play an important role in the pathophysiology of carotid disease. To assess the ability of B-mode ultrasound to provide this anatomic information, in a prospective blinded manner we compared B-mode ultrasound and selective four-vessel arteriography to pathologic specimens obtained at the time of 89 carotid endarterectomies. The presence of ulceration, plaque characteristics (particularly hemorrhage), and luminal diameter were described for each modality. While arteriography detected only 16 of 27 ulcerations (sensitivity, 59%), B-mode ultrasound had a greater sensitivity (24/27, 89%). Both modalities had comparable specificities (arteriography, 73%; B-mode ultrasound, 87%). Moreover, B-mode ultrasound was highly sensitive for demonstrating plaque hemorrhage (27/29, 93%), as well as being quite specific (84%). Assessment of luminal reduction by B-mode ultrasound improved with technologist/interpreter experience and was significantly improved by adding real-time spectral analysis. Because of B-mode ultrasound's sensitivity for imaging ulceration and plaque hemorrhage, it offers significant advantages for the noninvasive detection of extracranial carotid disease.

Arterial Occlusive Diseases↗
PubMed1978

Aortic insufficiency requiring valve replacement in Whipple's disease.

Reviews of postmortem reports on patients with Whipple's disease (intestinal lipodystrophy) describe gross valvular deformity in more than 50% with characteristic histological findings of macrophages containing periodic acid-Schiff-positive, diastase-resistant granules. Frequently, congestive heart failure characterizes the terminal stages. In a 58-year-old man with well-documented Whipple's disease for 5 years, gastrointestinal, joint, and pericardial involvement apparently resolved with medical therapy. However, 10 years later, severe aortic insufficiency necessitated prosthetic valve replacement, at which time gross and histological examination of the excised valve demonstrated characteristic changes of Whipple's disease. Clinical recognition of the importance of cardiac valvular abnormalities and of possible late cardiac decompensation mandates close observation of patients with Whipple's disease. Corrective operation should improve the patient's chances of survival.

Angina Pectoris↗
PubMed1977

Spontaneous streptococcus pneumonia peritonitis in a patient with metastatic gastric cancer: a case report and etiologic consideration.

Spontaneous peritonitis in adults has not been previously reported to occur in association with ascites of neoplastic origin. We report a patient with metastatic gastric adenocarcinoma in whom spontaneous streptococcus pneumonia peritonitis occurred as a terminal event. Massive metastases may have resulted in significant loss of the hepatic reticuloendothelial system and impaired the capability of the liver to function as an effective bacterial filter, predisposing the patient to bacterial peritonitis.

Adenocarcinoma↗