Effects of cilostazol on human venous smooth muscle.

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10(-2) M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 microg/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15 +/- 1.9% (mean +/- SEM) at low cilostazol doses (680 microg/L) to 37+/-3% at high cilostazol doses (2,720 microg/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n = 52) or hypercholesterolemia (n = 18) did not affect the amount of relaxation of the venous rings. Smokers (n = 46) had less relaxation 16 +/- 2.4% (680 microg/L) to 41 +/- 3.6% (2,720 microg/L) compared to nonsmokers (n = 53) who relaxed 22 +/- 3.5% (680 microg/L) to 48 +/- 5.7% (2720 microg/L). This did not reach statistical significance at any concentration cilostazol (p = 0.11-0.18). Diabetics (n = 53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n = 11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.

Current concepts in lymphedema management.

PURPOSE: To provide physicians and nurses with an overview of the pathophysiology, assessment and diagnosis, and treatment of lymphedema. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in managing patients with lymphedema. OBJECTIVES: After reading the article and taking the test, the participant will be able to: 1. Describe the pathophysiology of lymphedema and the difference between transient and chronic lymphedema. 2. Describe the assessment and diagnosis of lymphedema. 3. Identify treatment options and teaching considerations for patients with lymphedema.

Recognizing and managing venous leg ulcers.

PURPOSE: To provide physicians and nurses with an overview of the pathophysiology, assessment, diagnosis, and treatment of venous insufficiency and ulceration. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in managing patients with venous insufficiency and ulceration. OBJECTIVES: After reading the article and taking the test, the participant will be able to: describe the anatomy, physiology, and pathophysiology of the lower extremity venous system; describe the assessment and diagnosis of venous insufficiency and ulceration; identify treatment options and teaching considerations for patients with venous insufficiency and ulceration.

Arterial insufficiency and ulceration: diagnosis and treatment options.

PURPOSE: To provide physicians and nurses with an overview of the pathophysiology, assessment, diagnosis, and treatment of arterial insufficiency and ulceration. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in managing patients with arterial insufficiency and ulceration. OBJECTIVES: After reading the article and taking the test, the participant will be able to: 1. Describe the anatomy and physiology of the lower extremity arterial system and the pathophysiology of arterial ulcers. 2. Describe the assessment and diagnosis of arterial insufficiency and ulceration. 3. Identify treatment options and teaching considerations for patients with arterial insufficiency and ulceration.

Elevated expression of matrix metalloproteinase-13 in abdominal aortic aneurysms.

Destructive remodeling of extracellular matrix has been shown to be present in aneurysmal abdominal aorta. We used real-time quantitative reverse transcriptase polymerase chain reaction to determine the relative expression of matrix metalloproteinase-13 (MMP13) in aortic tissue samples from patients who underwent abdominal aortic aneurysm repair operations (n = 36) and from nonaneurysmal autopsy samples (n = 20). The assays were carried out simultaneously in the same reaction tubes for ribosomal 18S RNA to correct for different amounts of input RNA. MMP13 was expressed in all parts of aorta and its expression was elevated in aneurysmal sac. In further studies using MMP13-specific antibody we demonstrated that MMP13 protein was present in the aneurysmal wall.

Familial abdominal aortic aneurysms: collection of 233 multiplex families.

OBJECTIVE: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. SUBJECTS AND METHODS: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags). RESULTS: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively. CONCLUSION: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors.