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Biomedical subjects

Jonathan M Weiswasser

Publications and source records attributed to Jonathan M Weiswasser.

12 recordsLinked to original sources
PubMed2006

Thiamine (vitamin B1) improves endothelium-dependent vasodilatation in the presence of hyperglycemia.

Brachial artery vasoactivity (BAVA) is a reliable, noninvasive method of assessing endothelium-dependent vasodilatation (EDV) in vivo. Acute hyperglycemia, impaired glucose tolerance (IGT), and diabetes mellitus impair EDV, a precursor to atherosclerosis. Thiamine is a coenzyme important in intracellular glucose metabolism. The purpose of this study was to evaluate the effect of thiamine on BAVA in the presence of hyperglycemia. Ten healthy subjects (group H, mean age 27 years), 10 patients with impaired glucose tolerance by World Health Organization criteria (group IGT, mean age 65 years), and 10 patients with non-insulin-dependent diabetes mellitus (group NIDDM, mean age 50 years) were studied. Duplex ultrasound was used to measure brachial artery flow changes in response to reactive hyperemia following brachial artery tourniquet occlusion for 5 min. This test was performed after a 10 hr fast and at 30, 60, and 120 min after a 75 g oral glucose challenge along with measurements of blood glucose level (BGL). A week later, BAVA evaluation was repeated after administration of 100 mg of intravenous thiamine. BAVA (% increased blood flow) at peak and trough BGL was compared with and without thiamine. BAVA at peak glucose improved from 69.0 +/- 6.4% to 152.8 +/- 22.9% in group H (p < 0.005), from 57.6 +/- 12.6% to 139.7 +/- 12.4% in group IGT (p < 0.005), and from 57.8 +/- 8.3% to 167.8 +/- 11.6% in group NIDDM (p < 0.005) following administration of thiamine. On the other hand, at trough glucose levels, BAVA remained essentially unchanged in group H (prethiamine 83.8 +/- 6.5% vs. post-thiamine 83.8 +/- 17.0%, p > 0.05) as well as group IGT (prethiamine 96.7 +/- 8.5% vs. post-thiamine 104.0 +/- 17.4%, p > 0.05). BAVA at trough glucose was not measured in group NIDDM secondary to trough BGL > 140 mg/dL. EDV was improved by thiamine in the presence of hyperglycemia in healthy subjects and in patients with IGT and NIDDM. The mechanism by which thiamine improves EDV is not due to a glucose-lowering effect as thiamine had no effect on EDV under normoglycemic conditions. Routine administration of thiamine might improve endothelial function and therefore slow the development and progression of atherosclerosis, especially in patients with IGT and NIDDM who are prone to develop accelerated atherosclerosis.

Adult↗
PubMed2006

Hypoxia attenuates insulin-induced proliferation and migration of human diabetic infrapopliteal vascular smooth muscle cells.

The proliferative effects of insulin on infrapopliteal vascular smooth muscle cells (VSMCs) have been established. We examined the effect of hypoxia in the presence and absence of insulin on the proliferation and migration of human diabetic infrapopliteal VSMCs in vitro. VSMCs isolated from the infrapopliteal arteries of male diabetic patients of identical disease and clinical patterns undergoing below-knee amputation were harvested and grown to subconfluence. Cells were then exposed to control medium (M199/1% fetal bovine serum/2% antibiotic-antimycotic) or control medium with 100 ng/mL insulin in oxygen concentrations of 17% (normoxia), 5%, and 1%. Cellular proliferation was assayed using [methyl-3H]-thymidine incorporation. Migration assays were performed using the Corning Costar Transwell system. Lactate dehydrogenase was assayed and compared among groups as a marker for cytotoxicity. VSMCs in normoxic conditions (17%) had a significant increase in both proliferation (100 +/- 6.5% vs. 124 +/- 4.7%, p = 0.007) and migration [73.2 +/- 9.3 vs. 118.1 +/- 14.9 cells/4 high-power fields (HPF), p = 0.03] when exposed to insulin. Of cells exposed to insulin, those at both 5% (75.9 +/- 7.9%, p = 0.0001) and 1% (73.6 +/- 4%, p < 0.0001) hypoxia proliferated at a significantly decreased rate compared with cells at normoxia (124 +/- 4.7%). Migration of these insulin-exposed cells was significantly decreased at 1% hypoxia (63.1 +/- 9.0 cells/4HPF) compared to those at normoxia (118.1 +/- 14.9 cells/4HPF, p = 0.006) and 5% hypoxia (101.2 +/- 10.0 cells/4HPF, p = 0.01). There were no significant differences in migration between cells at normoxia and 5% hypoxia. Finally, hypoxia and insulin exerted no significant effect on cytotoxicity. The proliferative and promigratory effects of insulin on diabetic VSMCs are attenuated in hypoxic conditions in a manner unrelated to cytotoxicity.

Cell Hypoxia↗
PubMed2006

Carotid plaque morphologic characteristics.

Carotid artery atherosclerosis is predominantly believed to mirror atherosclerosis elsewhere in the body. Endothelial injury results in expression of cell surface adhesion molecules with expression of sequence of genes involved in the inflammatory pathway and expression of proinflammatory cytokines. The combination of the inflammatory mediators and contribution by monocytes infiltrating the intima and vascular smooth muscle cell proliferation result in the development of atheromatous plaque with a lipid-rich necrotic core. Complications of these atheromatous plaques can lead to plaque instability, rupture, and subsequent hemorrhage or ulceration. The significant risk factors, characteristics associated with symptoms, and available diagnostic imaging modalities are also discussed with review of the relevant literature.

Carotid Artery Diseases↗
PubMed2005

Aortic angiosarcoma presenting as distal arterial embolization.

Aortic angiosarcoma is a rare, malignant neoplasm of the vasculature, with 24 case reports in the literature. Patients usually present with either aneurysmal or occlusive disease. Treatment consists of en bloc resection of the vessel and contiguous structures with postoperative chemoradiation therapy. Despite surgery and adjunctive measures, prognosis remains dismal as a result of early metastasis and late diagnosis. We report a case of aortic angiosarcoma that presented with distal thromboembolic phenomenon.

Aged↗
PubMed2005

Evaluation of the microcirculation in vascular disease.

Insufficient blood flow through end-resistance arteries leads to symptoms associated with peripheral vascular disease. This may be caused in part by poor macrocirculatory inflow or impaired microcirculatory function. Dysfunction of the microcirculation occurs in a similar fashion in multiple tissue beds long before the onset of atherosclerotic symptoms. Impaired microcirculatory vasodilatation has been shown to occur in certain disease states including peripheral vascular disease, diabetes mellitus, hypercholesterolemia, hypertension, chronic renal failure, abdominal aortic aneurysmal disease, and venous insufficiency, as well as in menopause, advanced age, and obesity. Microcirculatory structure and function can be evaluated with transcutaneous oxygen, pulp skin flow, iontophoresis, and capillaroscopy. We discuss the importance of the microcirculation, investigative methods for evaluating its function, and clinical applications and review the literature of the microcirculation in these different states.

Humans↗
PubMed2005

Evaluation of macrocirculatory endothelium-dependent and endothelium-independent vasoreactivity in vascular disease.

Macrocirculatory endothelium-dependent and independent vasodilatation is integral to tissue-bed oxygen delivery and homeostasis. Dysfunction of macrocirculatory vasoreactivity is a precursor to atherosclerosis and occurs in a similar fashion in multiple tissue beds long before the onset of symptoms. Impaired macrocirculatory vasodilatation has been shown to occur in certain disease states including diabetes mellitus, hypercholesterolemia, chronic renal failure, peripheral arterial atherosclerosis, and abdominal aortic aneurysms, as well as secondary to smoking, advanced age, menopause, high-fat diet, and sedentary lifestyle. Brachial artery vasoreactivity is a noninvasive means of assessing macrocirculatory vasodilatory capacity that may help identify patients at increased risk for peripheral and cardiovascular disease and allow for objective assessment and monitoring of treatment. Endothelium-dependent vasoreactivity, or flow-mediated dilatation, is measured after brachial artery occlusion with a pneumatic blood pressure cuff, and endothelium-independent vasoreactivity is measured after the administration of sublingual nitroglycerin. The accuracy of brachial artery vasoreactivity is dependent on hematologic variables, as well as diurnal, day-to-day, ultrasound operator, and reader variations; however, the overall coefficient of variation is only 1.8%. We discuss the importance of the macrocirculation, investigative methods for evaluating macrocirculatory vasoreactivity, and review the literature of vasoreactivity in these different states.

Atherosclerosis↗
PubMed2004

Medical factors affecting patency of arteriovenous access.

Arteriovenous access failure is multifactorial in nature with contributions from both medical and surgical etiologies. Medical causes of arteriovenous access failure are rare, and therefore infrequently identified as a major contributing source of malfunction. Although they account for only 10-15% of all cases of access failure, their importance should not be underestimated, especially in cases where a surgical source cannot be identified. Most medical causes are derived from Virchow's triad of endothelial cell injury, stasis, and hypercoaguability. Endothelial cell injury occurs through oxidative stress, activated platelets, increased levels of circulating tumor necrosis factor-alpha, and preexisting intimal hyperplasia. Stasis can occur through prolonged access compression, hypotension, or hypoalbuminemia. Finally, patients with renal failure requiring hemodialysis are frequently at increased risk for hypercoaguable states, except for situations of platelet dysfunction, and therefore access failure. Potential treatments include identifying and removing the offending source, as well as innovative, new medications to prevent their reoccurrence. Treatment is aimed at improving quality of life, as well as decreasing morbidity and hospital admissions in this difficult patient population.

Anticoagulants↗
PubMed2004

Strategies of arteriovenous dialysis access.

Surgical management of the patient who requires hemodialysis access, while continuing to demand more attention from the vascular surgeon, suffers from discrepancies of approach and strategy. With the increase in incidence of dialysis dependent renal failure among our population, many have attempted to present a uniform, logical strategy with which the vascular surgeon can most effectively treat the hemodialysis patient in the long term. Most notably, the multidisciplinary Dialysis Outcomes Quality Initiative (DOQI) guidelines present the surgeon with a rough outline of hemodialysis access insertion strategy, and it has become nationally recognized as an acceptable summary of treatment strategy and goals. The decision as to the most appropriate surgical access to offer a patient depends on immediate need for hemodialysis, history and physical examination findings, and suitability of available veins in the extremity. While percutaneous, catheter based access affords the luxury of immediate access, these devices suffer from several complicating factors, such as infection, and damage to large, proximal veins. For long-term access, the autogenous access, while perhaps less successful in the immediate short term, is always the preferred access type given its favorable longevity. The surgeons should focus on sites distally on the extremity, reserving proximal sites for potential future access insertions should the primary access fail. In the absence of suitable vein, prosthetic access may be considered. When both the upper and lower aspects of both upper extremities have been exhausted, the surgeon should consider access insertion elsewhere, such as the lower extremity.

Arteriovenous Shunt, Surgical↗
PubMed2002

Syndrome X and diabetes: what is the mystery?

Syndrome X describes a combination of clinical phenomena that have been statistically linked to hyperinsulinema in the absence of frank diabetes. Since its original description, Syndrome X has come to represent several phenotypes that have hemodynamic and metabolic effects on the individual, as well as major effects on the development of vascular disease. Further, this syndrome is reaching epidemic proportions, As such, a thorough understanding of this condition is becoming increasingly important for the modern vascular surgeon. The mainstay of therapy revolves around early diagnosis and management with diet changes, exercise, and reduction of cardiovascular risk factors.

Blood Glucose↗
PubMed2002

Peripheral vascular brachytherapy.

Ongoing advances in peripheral endovascular technology have been met with disappointing results because of restenosis within the treated vessel. In particular, stent balloon angioplasty of peripheral vessels has yet to achieve patency rates that approximate conventional treatment in the long term. Recent advances in stent, balloon, and wire construction include the incorporation of radioactive substances in an attempt to ameliorate the inflammatory response provoked by typical endovascular manipulation, a technique termed vascular brachytherapy. gamma- and beta-isotopes and external beam radiation target the very cell population whose activity results in the development of neointimal hyperplasia. Although most clinical research examining the efficacy of vascular brachytherapy has emerged from the coronary artery literature, the use of vascular brachytherapy also has been examined in the peripheral arterial tree and has shown promising results. Current data indicate that vascular brachytherapy is a safe and accessible adjunctive endovascular maneuver that may improve the short-term patency rate of peripheral endovascular applications. The effects on long-term patency rates remain indeterminate compared to conventional therapy.

Brachytherapy↗