Utility of a repeated EUS at a tertiary-referral center

BACKGROUND: The utility of a repeated EUS by experts is not known. OBJECTIVE: To define the utility of a repeated EUS for the same indication. DESIGN: A retrospective case series. SETTING: Tertiary-referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive subjects, with and without cancer, who, between January 2000 and September 2006, underwent an initial EUS elsewhere within 6 and 12 weeks of a repeated EUS at our hospital. INTERVENTIONS: A repeated EUS. MAIN OUTCOME MEASUREMENTS: Clinical impact of a repeated EUS. RESULTS: Of 8936 EUS examinations, 73 repeated procedures (0.8%) were identified, and 24 were excluded. The 49 initial EUS procedures (26 men, median age 59 years) were done in Indiana (n = 44) or another state (n = 5) by one of 15 physicians in private practice (n = 48) or at a teaching hospital (n = 1). An EUS-guided FNA (EUS-FNA) was performed during an initial EUS in 21 patients (no biopsy diagnostic for cancer) and was not attempted in 14 patients. The principle indication for a repeated EUS (n = 35) was for an EUS-FNA after the initial tissue sampling was benign, nondiagnostic, or not done. A second EUS had no clinical impact in 18 patients (37%). In the remaining 31 patients (63%), a repeated EUS provided a new or changed clinical diagnosis (n = 12), the initial diagnosis of primary pancreatic cancer (n = 5) or GI stromal tumor (GIST) (n = 1) after a previous nondiagnostic biopsy; or the initial diagnosis of primary (n = 4) or metastatic (n = 2) pancreatic cancer, metastatic esophageal cancer (n = 1), hilar cholangiocarcinoma (n = 1), GIST (n = 1), or pancreatic neuroendocrine tumor (n = 1), or an initial aspiration of a pancreatic cyst (n = 3) after a previous EUS-FNA was not able to be performed. LIMITATIONS: A retrospective design; a small number of nonpancreatic indications. CONCLUSIONS: In this study, a repeated EUS at a tertiary-referral center had a clinical impact in 63% of patients when performed by experts for a similar clinical indication.     

Percutaneous aspiration of a thromboembolus

Percutaneous aspiration of a thromboembolus was successfully performed in 12 out of 13 patients with in situ thrombosis (4 patients), distal embolization (7 patients), or both (2 patients). The flow was improved from TIMI 0 (10 patients, no flow) or TIMI 1 (2 patients, impaired flow) to TIMI 3 (10 patients, normal flow) or TIMI 2 (2 patients, normal but slower flow). A custom-made 8 F Teflon-coated sheath was introduced in the superficial femoral and proximal below-the-knee arteries to aspirate the debris. Distal embolization in below-the-knee arteries was concomitantly treated with short-term intraarterial Urokinase in nine patients. Complications included one in-hospital (not procedure related) death, two patients with below-the-knee amputations (above-the-knee amputation averted), and one transmetatarsal amputation (prior established gangrene present and below-the-knee amputation avoided). The remaining nine patients left the hospital with improved limb status and peripheral pulses. This technique is a rapid, reliable, and efficient method to treat in-situ clot or procedure-related distal embolization as an adjuvant or complement to lytic treatment.     

Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25–77) years. Sixty-three patients (78.8 %) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3–15,732) and 16 (0.3–1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2–60) and 12.5 (2–39) respectively, with an interval of 2.9 (0.3–9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5 %) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.     

Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan.

Several epidemiological studies have shown a positive association between serum uric acid levels and the risk of hypertension. However, subjects in these studies were mostly men, or were incompletely examined for lifestyle-related variables. We prospectively examined the relation between hyperuricemia and the risk of developing hypertension with consideration for alcohol consumption and smoking habits in a large screened cohort of men and women. A total of 4,489 individuals (2,927 men and 1,562 women) who did not have hypertension and were not currently using antihypertensive medication were examined at the Okinawa General Health Maintenance Association in 1977. Subjects were re-examined in 2000. Hyperuricemia was defined as a serum uric acid level >or=7.0 mg/dl in men and >or=6.0 mg/dl in women. Hypertension was defined as systolic blood pressure (SBP) >or=140 mmHg, and/or diastolic blood pressure (DBP) >or=90 mmHg. A total of 289 subjects (201 men and 88 women) were hypertensive (SBP >or=140 mmHg, and/or DBP >or=90 mmHg) in 2000. Multivariate analysis was performed for development of hypertension in hyperuricemic subjects, adjusted for age, family history of hypertension, alcohol consumption, cigarette smoking, obesity, hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol, and diabetes mellitus. The adjusted odds ratio (95% confidence interval) in men was 1.48 (1.08-2.02) and in women was 1.90 (1.03-3.51) (p <0.05, respectively). The results showed hyperuricemia to be a new predictor of hypertension development in both men and women.     

Repeat coronary angioplasty: efficacy of a third angioplasty for a second restenosis

To determine the efficacy of repeat percutaneous transluminal coronary angioplasty, 74 patients were studied who underwent a third angioplasty for a second restenosis of one coronary artery segment. The procedure was successful in 93% of patients. Procedural complications included emergency bypass surgery (three patients) and in-hospital death (two patients). At late follow-up (mean 18 months, range 7 to 49), 30 patients (43%) had a third restenosis treated with either a fourth angioplasty (16 patients), coronary bypass surgery (11 patients) or medical management (1 patient). Thirty-nine patients (57%) had no restenosis on the basis of follow-up angiography or absence of symptoms previously attributed to restenosis. Factors associated with a third restenosis included a shorter time interval (less than 3 months) between previous angioplasty procedures and dilation of the left anterior descending coronary artery. Among the 16 patients undergoing a fourth angioplasty for a third restenosis, the procedural success rate was 94%. One patient required emergency bypass surgery. At late follow-up (mean 16 months, range 7 to 38), eight patients (53%) had a fourth restenosis treated with either a fifth angioplasty (one patient), bypass surgery (five patients) or medical management (two patients). Considering all 74 patients undergoing a third angioplasty for a second restenosis, 27% had bypass surgery, 5% died, 4% were managed medically and 64% were free of angina at late follow-up after either a third, fourth or fifth angioplasty. Restenosis rates after a third or fourth angioplasty procedure for recurrent restenosis are higher than those for the initial procedures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of chest CT in a pediatric ICU: a prospective study

STUDY OBJECTIVES: (1) To determine whether chest CT provides additional information compared with chest radiography regarding the nature of intrathoracic disease in critically ill children, (2) to determine whether such information alters clinical management, (3) to assess the role of a low-dose high-resolution CT (HRCT) protocol in pediatric ICU (PICU) patients. DESIGN: Prospective study. SETTING: Specialized PICU in a teaching hospital serving London and the south of England. PATIENTS: Twenty children (age range, 3 weeks to 12 years; median, 11 months) underwent chest CT during a 33-month period. Inclusion criteria were (1) inconclusive diagnosis from chest radiograph (CXR) or (2) CXR appearances inconsistent with high oxygenation or ventilatory requirements (PaO(2) to fraction of inspired oxygen ratio < 30 or mean airway pressure > 15 cm H(2)O). INTERVENTIONS: Low-dose HRCT scans (50 mA, 2-mm slice thickness at intervals of 10 or 15 mm) were performed on 12 patients, and helical CT (50 to 250 mA; pitch, 1 to 1.5) performed on 8 patients. MEASUREMENTS AND RESULTS: CT provided additional information regarding the nature of intrathoracic disease in 17 of 20 patients (85%) and resulted in changes to subsequent clinical management in 12 of 20 patients (60%). CONCLUSIONS: Chest CT can add to the accuracy of intrathoracic diagnosis provided by the CXR and may directly influence the acute management of critically ill children. The CT protocol should be tailored to the clinical and radiologic question posed for each individual patient. Noncontiguous HRCT can often provide accurate assessment of pulmonary parenchymal and pleural disease at a reduced radiation dose compared with helical CT.     

Abnormalities of kidney function as a cause and a consequence of cardiovascular disease

Hypertension, left ventricular hypertrophy (LVH), hypercreatininemia, and microalbuminuria (MA) are independent risk factors for cardiovascular disease (CVD). Hypertension increases the risk of CVD by two- to three-fold and LVH (especially concentric) is a risk factor for coronary heart disease, heart failure, stroke, and peripheral arterial disease. In people with hypertension, a serum creatinine level of 1.7 mg/dL or more may be an even stronger CVD risk factor than diabetes, smoking, LVH, or systolic blood pressure. Similarly, MA is a strong and independent predictor of CVD morbidity and mortality in people with and without diabetes and/or hypertension. Impaired renal sodium handling and sodium retention are physiological hallmarks of the very early stages of heart failure. Heart failure is a physiologically delicate condition that can decompensate with excess dietary salt intake or over diuresis, or compensate with cautious therapy designed to block the sodium retention and simultaneously interrupt excessively activated neurohumoral mechanisms.     

Effect of a nonrebreathing exhalation valve on long-term nasal ventilation using a bilevel device

STUDY OBJECTIVE: To determine whether an exhalation valve designed to minimize rebreathing improves daytime or nocturnal gas exchange or improves symptoms compared with a traditional valve during nocturnal nasal ventilation delivered using a bilevel pressure ventilation device. DESIGN: Prospective direct comparison trial with each patient sequentially using both valves, during a 2-week run-in period with a traditional valve, a 2-week trial with the nonrebreathing valve, and a 2-week washout period with the traditional valve. SETTING: Outpatient pulmonary function laboratory and home nocturnal monitoring. PATIENTS: Seven patients who received long-term (> 1 year) nocturnal nasal bilevel pressure ventilation with an expiratory pressure of 相似文献   

Electrocardiographic changes in a cohort of hypertensive patients in a community intervention program

A pilot project for the control of hypertension in the Community was carried out in Italy as a part of the WHO Programme "Community Control of Hypertension". 1190 subjects identified as hypertensive (BP greater than or equal to 160 and/or 95 mmHg at two subsequent measurements, or under treatment) during the screening of a random sample of the population between 20 and 64 years in the District of Camposampiero (Padova) were enrolled in a Hypertension Register during a subsequent visit (Registration Visit: VR) carried out two months after the screening. In the following 5 years they were recalled about once a year at a Hypertension Clinic for a complete visit (VA). On both the VR and the VAs a resting electrocardiogram (ECG) was recorded and subsequently assessed according to the Minnesota Code (MC). Out of the 1190 registered hypertensive subjects, 872 (400 males and 472 females) participated in the last VA visit after 5 years, which corresponds to an overall participation rate of 69.4% in males (M) and 76.9% in females (F). Among subjects with normal and abnormal ECG at the VR, the participation rates at the last VA were, respectively, 67.9 and 71.5% in M (not significant difference); 80.0% and 70.8% in F (significant difference: P less than 0.001). Between the VR and the last VA the mean BP values of the 872 subjects investigated decreased from 162. 9/102.2 mmHg to 148. 6/90.4 mmHg in M and from 168. 7/102.2 mmHg to 155. 3/91.7 mmHg in F. The rate of abnormal ECGs increased from 44.0% to 50.3% in M and from 36.4% to 47.9% in F, involving most single items and all the classes of the MC with the exception of classes 8 and 9. The items which diminished generally had a rather low prevalence or were those indicating minor abnormalities. The apparent regression of some pathological patterns could actually be accounted for by a shift towards more severe abnormalities. The most remarkable changes occurred in codes indicating respectively left ventricular hypertrophy (3: 1 or 3: 3) and myocardial ischaemia (4: 1-3 or 5: 1-3 or 7: 1).(ABSTRACT TRUNCATED AT 400 WORDS)     

Meta-analysis as a source of evidence in gastroenterology: a critical approach

Meta-analysis is increasingly used in hepatogastroenterology. Meta-analysis is of value to provide a systematic review of related trials and to display their results in an objective, easily understandable manner. When the trials are sufficiently homogeneous, meta-analysis can document the superiority, (a), or the lack of superiority (b) of a treatment with respect to another (e.g., (a) Interferon plus ribavirin vs Interferon for chronic hepatitis; (b) 5-ASA vs sulfasalazine for maintaining remission in ulcerative colitis). However the interpretation of meta-analysis requires caution. Meta-analysis can be unreliable or unstable if based on a few, small trials (e.g., Tamoxifen vs non-active treatment for hepatocellular carcinoma), or if distorted by confounding variables and publication bias (e.g., glucocorticoids vs standard treatment in alcoholic hepatitis). Eventually, qualitative heterogeneity makes the pooled results of meta-analysis meaningless or questionable (e.g., endoscopic sclerotherapy for prevention of first variceal bleeding in cirrhosis) and should prompt the search for its sources to plan future studies. Finally, meta-analysis of trials measuring the treatment effect of a drug vs a placebo when an active drug is available for comparison provides the limited informative content for the physician of the individual trials (e.g. 5-ASA vs placebo for maintaining remission in ulcerative colitis).     

Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injury

OBJECTIVE: Thrombin activates platelets and contributes to the occlusion of arteries following thrombolytic therapy or angioplasty. Thrombostatin (RPPGF), the angiotensin converting enzyme degradation product of bradykinin, inhibits alpha-thrombin induced platelet activation. We hypothesized that thrombostatin prevents platelet aggregation and adhesion after balloon angioplasty (BA). METHODS: Platelet-rich plasma (PRP) was obtained from 22 Beagle dogs before sacrifice and 10% of the PRP was labeled with 111In. Carotid arteries were then removed from each dog and mounted in a dual perfusion chamber and intimal injury was performed with BA. 111In-PRP with or without thrombostatin or aspirin alone was perfused through the arteries for 60 min. During perfusion, platelet volume was measured using a Coulter counter and a laser-light scattering technique. Platelet adhesion to arteries was measured by radioactivity count. RESULTS: Arterial injury alone compared to non-injury increased platelet volume in the circuit by 1.4 times (x) (P<0.05) using a Coulter counter or 1.8x (P<0.05) using laser-light scattering and increased platelet adhesion by 2.3x (P<0.01). When compared to BA injury alone, the addition of thrombostatin reduced platelet volume by 1.8x (P<0.03) as measured by Coulter counter or 1.9x (P<0.01) by laser-light scattering and platelet adhesion by 4.2x (P<0.05). Compared to BA injury alone, aspirin reduced platelet volume by 1.2x (P<0.01) as assessed by Coulter counter or 1.5x (P<0.03) using laser-light scattering and platelet adhesion by 1.8x (P<0.02). CONCLUSION: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury.     

Localization of a factor VIII binding domain on a 34 kilodalton fragment of the N-terminal portion of von Willebrand factor

Factor VIII (F.VIII) was tested for its ability to bind in solid phase system to von Willebrand Factor (vWF) or fragments obtained with Staphylococcus aureus V-8 protease, ie, SpIII (N-terminal), SpI (central), and SpII (C-terminal). Bound F.VIII was estimated in situ by clotting and chromogenic assays. F.VIII bound in a dose-dependent manner to immobilized vWF and SpIII but not to SpII or SpI. Binding was inhibited by 0.25 mol/L CaCl2 as well as by an excess of vWF or SpIII. Accordingly, immobilized F.VIII specifically bound 125I-vWF and SpIII but not SpII or SpI. Twelve monoclonal antibodies (MoAbs) directed towards SpIII, specifically blocking binding of F.VIII to vWF or SpIII, were used for the mapping of plasmic or tryptic fragments of vWF or SpIII. We thus established that a F.VIII binding domain of vWF is located on a 34 kilodalton (kd) fragment of the N-terminal portion of vWF, between residues 1 and 910, and that it is distinct from the GPIb and collagen binding domains.     

The unofficial history of drug use: a study in a Brazilian sample

Interviews were conducted with 59 former intensive users of illicit drugs with no evidence of current social or behavioural dysfunction. Data were gathered by in-depth standardized interviews through which, past and current psychoactive substance use (including alcohol, tobacco and tranquillizers) were assessed. Special attention was given to the subjects' attributions as to what had caused the change in the drug use pattern. Events attributed for ending or substantially decreasing drug use were categorised as follows: ‘physical-mental problems/disliked side effects’ (27.1% of respondents), ‘developmental/maturational/existential reasons’ (27.1%), formal or informal drug treatment system’ (11.8%), ‘interpersonal reasons’ (10.2%), ‘job or school/performance lowering’ (10.2%), “religious/spiritual involvement” (6.8%), and ‘legal/financial problems’ (6.8%). The major finding was that only 7 out of the 59 respondents (11.8%) reported having ever been in any formal or informal drug treatment system.     

Prognosis and outcome of elderly hypertensives in a Japanese community: results from a long-term prospective study

A long-term prognosis and outcome study of elderly hypertensives (aged 60 years or over) was made based on the 20-year prospective population survey conducted in a Japanese rural community (Hisayama) and the results were compared with those for younger subjects (aged 40-59 years). The risk of cardiovascular mortality related to blood pressure level increased with the elevation of either systolic or diastolic pressure in both younger and elderly groups. Cardiovascular mortality increased markedly at a systolic pressure of greater than or equal to 160 mmHg, or a diastolic pressure of greater than or equal to 100 mmHg for those aged 40-59 years. There was no cut-off level for increased risk of cardiovascular mortality for either systolic or diastolic pressures for those aged 60 years or over. Stroke mortality was seven times higher in systolic, and 10 times higher in diastolic hypertensives than in normotensives (P less than 0.01) for the group aged 40-59 years. However, deaths due to stroke and heart disease were more frequently associated with borderline (relative risk 2.3 and 2.3, respectively; P less than 0.01), systolic (relative risk 3.2 and 3.7, respectively; P less than 0.01) and diastolic hypertension (relative risk 2.1 and 4.8, respectively; P less than 0.01), compared to normotension for those aged 60 years or over. Intracerebral hemorrhage and cerebral infarction occurred more frequently in diastolic hypertensives for both young (relative risk 9.8 and 4.8, respectively; P less than 0.01) and elderly subjects (relative risk 3.4 and 1.5, respectively; P less than 0.01) than in normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of a small-caliber, variable-stiffness colonoscope as a backup in patients with difficult or incomplete colonoscopy

OBJECTIVES: Although variable-stiffness colonoscopes have been developed, difficult or incomplete colonoscopies occasionally occur. The aim of this study was to evaluate the usefulness of a small-caliber, variable-stiffness colonoscope (scVSC) as a backup in patients with difficult or incomplete colonoscopies. METHODS: First, we retrospectively reviewed the cecal intubation rate of colonoscopies in which an adult standard colonoscope (AC) was immediately switched to an scVSC in all patients in whom a colonoscopy with an AC was incomplete. Second, 374 consecutive patients were randomized to undergo colonoscopy with a pediatric variable-stiffness colonoscope (PVSC, n = 123), AC (n = 125), or scVSC (n = 126). The scVSC was used by the same endoscopist to reattempt colonoscopy immediately after colonoscopy with a PVSC or an AC had been assessed as difficult or incomplete. The cecal intubation rate and time and the ancillary maneuvers used were evaluated. RESULTS: Fifty-two (2.5%) of the 2,056 attempted colonoscopies with an AC did not reach the cecum. Fifty-one of the 52 patients (98.1%) had complete colonoscopies after the switch from the AC to the scVSC. The initial intubation rate and time were not statistically different among the groups: PVSC, 95% and 6.8 min; AC, 91% and 7.5 min; and scVSC, 98% and 8.2 min. Cecal intubation was achieved in all five patients (100%) and in 10 out of 11 (91%) patients, respectively, after the PVSC or AC was switched to the scVSC. CONCLUSIONS: The completion rate markedly improved after switching from an AC or PVSC to an scVSC in difficult or incomplete colonoscopies, although the scVSC does not appear to offer any distinct advantage over the AC or PVSC for routine colonoscopies.     

Effects of intra-articular administration of glucosamine and a peptidyl-glucosamine derivative in a rabbit model of experimental osteoarthritis: a pilot study

The aim of this pilot study was to analyze the effects of glucosamine (GlcN) and its N-acetyl-phenylalanine derivative (NAPA) in Vitamin A model of osteoarthritis (OA) in rabbits. GlcN or NAPA or saline solution was intra-articularly administered in rabbit OA knees. Histological analysis revealed that treatment with GlcN or NAPA was associated with more homogeneous chondrocyte cellularity, absence of fissures and fragmentation and more intense staining of the matrix with Alcian Blue compared to the articular surfaces of the knees treated with saline solution. Comparative in vitro study performed on rabbit primary chondrocytes revealed that GlcN and NAPA were also able to counteract the IL-1β-upregulation of genes coding for metalloproteases and inflammatory cytokines. Our preliminary in vivo and in vitro studies suggest that GlcN and NAPA could play a disease-modifying protective role in OA by an anti-catabolic effect and an anti-inflammatory activity on chondrocytes.     

Diagnosis of subsegmental pulmonary emboli: a multi-center study using a porcine model

We measured sensitivity, positive predictive value, and free-response receiver operating characteristic (FROC) of 20 radiologists detecting subsegmental-sized pulmonary emboli in a porcine model using either contrast-enhanced computed tomography (CT) or digital subtraction (DS) pulmonary angiography. Colored methacrylate beads (4.2 and 3.8 mm diameter) were injected into 9 anesthetized juvenile pigs. CT and DS pulmonary angiography images were obtained before and after a pulmonary infiltrate was introduced into the lower lobes. Following imaging, the pigs were euthanized, and the pulmonary arterial tree was cast using clear methacrylate allowing direct visualization of emboli. The 20 radiologists used a custom-made computer application to display the images on their personal computer and record their diagnoses. The results were mailed electronically to the coordinating center for comparison with the cast of the pulmonary vasculature. Twenty-three emboli were included in the statistical analysis. Overall sensitivity for spiral CT and angiography, respectively, was: 60 +/- 18% and 72 +/- 11% (P = 0.06). Positive predictive value for spiral CT and angiography, respectively, was: 49 +/- 24% and 58 +/- 23% (P = 0.25). There was a large variation in both sensitivity and positive predicted values between Readers. There was no difference in sensitivity or positive predictive value between radiologists from community or academic centers (P > 0.27). FROC analysis showed no significant difference between CT or DS (P = 0.27). In conclusion, in this porcine model, there is no overall diagnostic advantage to using DS pulmonary angiography rather than contrast-enhanced spiral CT for the diagnosis of PE when images are interpreted by radiologists located in either academic or community hospital settings.     

Paradoxical absence of a prothrombotic phenotype in a mouse model of severe hyperhomocysteinemia

Hyperhomocysteinemia confers a high risk for thrombotic vascular events, but homocysteine-lowering therapies have been ineffective in reducing the incidence of secondary vascular outcomes, raising questions regarding the role of homocysteine as a mediator of cardiovascular disease. Therefore, to determine the contribution of elevated homocysteine to thrombosis susceptibility, we studied Cbs(-/-) mice conditionally expressing a zinc-inducible mutated human CBS (I278T) transgene. Tg-I278T Cbs(-/-) mice exhibited severe hyperhomocysteinemia and endothelial dysfunction in cerebral arterioles. Surprisingly, however, these mice did not display increased susceptibility to arterial or venous thrombosis as measured by photochemical injury in the carotid artery, chemical injury in the carotid artery or mesenteric arterioles, or ligation of the inferior vena cava. A survey of hemostatic and hemodynamic parameters revealed no detectible differences between control and Tg-I278T Cbs(-/-) mice. Our data demonstrate that severe elevation in homocysteine leads to the development of vascular endothelial dysfunction but is not sufficient to promote thrombosis. These findings may provide insights into the failure of homocysteine-lowering trials in secondary prevention from thrombotic vascular events.