Recurrent stroke secondary to late patent foramen ovale-closure device thrombus: a case report.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure has been well established in the secondary prevention of cryptogenic stroke with overall low rates of procedural complications. One such complication is PFO closure device thrombus formation which is now rarely reported with newer generation devices. CASE SUMMARY: We present the unusual case of a 59-year-old woman with myelofibrosis who developed late-onset recurrent embolic strokes related to Amplatzer PFO closure device thrombus whilst therapeutically anticoagulated on Warfarin. Surgical management was deemed too high risk and our patient was conservatively managed with enoxaparin. Serial transthoracic echocardiography demonstrated a reduction in thrombus size and the patient had no further neurological events. DISCUSSION: Overall, the risk of serious complications following percutaneous PFO closure, such as device-associated thrombus, remains low. The risk of thrombus formation in patients with hypercoagulable states is not well characterized. Despite good evidence for the efficacy in preventing recurrent cryptogenic stroke, the role of PFO closure in addition to anticoagulation is unclear. Given this uncertain benefit of PFO closure in anticoagulated patients and the unclear risk profile, patient selection, and thorough pre-procedural evaluation are vital when assessing the appropriateness of percutaneous PFO closure.

Carcinoid heart disease of gonadal primary presenting with hypoxia: a case report.

BACKGROUND: Carcinoid heart disease is a potential sequela of metastatic neuroendocrine tumour that has characteristic valve appearances. Patients can present with symptoms of carcinoid syndrome or be relatively asymptomatic until symptoms of progressive heart failure manifest. CASE SUMMARY: We present a case of a 54-year-old male who was admitted to the hospital for investigation of hypoxia. Transthoracic echocardiogram was suggestive of carcinoid heart disease which subsequently led to a diagnosis of metastatic neuroendocrine (carcinoid) tumour of the testicular primary. Work-up revealed a patent foramen ovale with evidence of the right to left interatrial shunt from severe tricuspid regurgitation as the cause of his hypoxia. Prior to surgical excision of the primary tumour, percutaneous patent foramen ovale closure was performed resulting in improved arterial oxygen saturation and symptomatic improvement. DISCUSSION: Carcinoid heart disease typically affects the right-sided cardiac valves and the tricuspid valve appearances were critical in leading to a diagnosis of a metastatic neuroendocrine tumour in our patient. This case demonstrates that percutaneous patent foramen ovale closure can be an effective intervention for hypoxia in those not managed surgically. A high index of suspicion should be maintained for gonadal primary carcinoid tumour when there is carcinoid heart disease in the absence of liver metastases.

Dynamic echocardiography in evaluation of platypnoea-orthodeoxia.

Platypnoea-orthodeoxia is an infrequent syndrome that is usually associated with positional intracardiac right-to-left shunting. The authors report the case of a patient who presented with deteriorating severe dyspnoea and deoxygenation in the upright position that was partially relieved by recumbent repositioning. Dynamic echocardiography provided insight into the underlying anatomical and pathophysiological mechanisms as well as guidance for definitive therapy.

Androgen receptor gene expression in leucocytes is hormonally regulated: implications for gender differences in disease pathogenesis.

OBJECTIVE: There is evidence that male sex hormones influence the rate of progression of inflammatory and cardiovascular diseases. We have previously shown that human leucocytes and arterial cells isolated from male donors express more androgen receptor (AR) than those from female cells, with potentially pro-atherogenic effects. We now investigate whether the gender difference in AR expression is due to genetic or hormonal regulation. DESIGN AND PATIENTS: The influence of hormones on AR expression were studied in hpg mice (a mouse model of androgen deficiency) treated with testosterone, oestradiol or dihydrotestosterone (DHT). Blood samples were obtained for leucocyte AR expression and hormone levels from 53 subjects, grouped into: 12 male [six young adult (27-45 years), six elderly (71-79 years)] and six female (young adult 25-45 years) healthy controls; six male-to-female transsexuals (M2F; 20-50 years) receiving stable pharmacological oral oestrogen treatment; six female-to-male transsexuals (F2M; 31-51 years) receiving stable androgen replacement therapy; five younger men (18-56 years) who had been receiving long-term androgen replacement therapy for hypogonadal disease; six elderly men (72-88 years) who had undergone medical castration for prostate cancer treatment; and 12 male bone marrow transplant recipients (BMT; 23-65 years) from either male or female donors. MEASUREMENTS: Serum testosterone and oestradiol concentrations were measured by established immunoflurometric assays from unextracted human serum. AR mRNA levels were measured by RT-PCR and AR protein levels by western blot (cell culture) or immunohistochemistry (mouse arteries). RESULTS: We found that AR mRNA levels were significantly down-regulated in the leucocytes of hpg mice that were treated with exogenous testosterone, oestradiol or DHT. AR protein levels were also lower in aortic tissue from the same mice. In humans, we found AR expression was significantly down-regulated by exogenous treatment with testosterone in F2M (31 +/- 13%, compared with control) or oestradiol in M2F (22 +/- 5%) but was significantly up-regulated by endogenous testosterone in BMT (128 +/- 17%). Low androgen levels measured in castrated older men were associated with markedly increased AR expression (207 +/- 26%, P < 0.05) compared with age-matched older male controls (100 +/- 2%). CONCLUSIONS: Our results indicate a regulated ability of vascular cells to respond to sex hormones, with the effects of exogenous therapies differing markedly from those due to endogenous sex hormones. We conclude that the gender difference in AR expression in vascular cells is hormonally, rather than genetically, controlled.

Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway.

There exists a striking gender difference in atherosclerotic vascular disease. For decades, estrogen was considered atheroprotective; however, an alternative is that androgen exposure in early life may predispose men to earlier atherosclerosis. We recently demonstrated that the potent androgen, dihydrotestosterone (DHT), enhanced the binding of monocytes to the endothelium, a key early event in atherosclerosis, via increased expression of vascular cell adhesion molecule-1 (VCAM-1). We now show that DHT mediates its effects on VCAM-1 expression at the promoter level through a novel androgen receptor (AR)/nuclear factor-kappaB (NF-kappaB) mechanism. Human umbilical vein endothelial cells were exposed to 4-400 nm DHT. DHT increased VCAM-1 mRNA in a dose- and time-dependent manner. The DHT effect could be blocked by the AR antagonist, hydroxyflutamide. DHT increased VCAM-1 promoter activity via NF-kappaB activation without affecting VCAM-1 mRNA stability. Using 5' deletion analysis, it was determined that the NF-kappaB sites within the VCAM-1 promoter region were responsible for the DHT-mediated increase in VCAM-1 expression; however, coimmunoprecipitation studies suggested there is no direct interaction between AR and NF-kappaB. Instead, DHT treatment decreased the level of the NF-kappaB inhibitory protein. DHT did not affect VCAM-1 protein expression and monocyte adhesion when female endothelial cells were tested. AR expression was higher in male, relative to female, endothelial cells, associated with increased VCAM-1 levels. These findings highlight a novel AR/NF-kappaB mediated mechanism for VCAM-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis.

Percutaneous transcatheter patent foramen ovale closure using the right internal jugular venous approach.

Percutaneous transcatheter closure of a patent foramen ovale (PFO) is a therapeutic option in patients with paradoxical embolism. For patients in whom PFO closure is indicated when a femoral venous approach is not possible, we describe the successful closure of two PFOs using the right internal jugular venous approach.

Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.

OBJECTIVES: We sought to assess the effects of raloxifene, a selective estrogen receptor modulator, on arterial physiology and biology in postmenopausal women with coronary artery disease (CAD). BACKGROUND: Raloxifene improves endothelial function and markers of vascular health in vitro in experimental animals and in healthy postmenopausal women. In women whose arteries are affected by advanced atherosclerosis, however, the vascular effects of estrogen receptor modulation are unknown. METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled, crossover trial of raloxifene, 60 mg/day for 8 weeks, in 33 consecutively eligible and consenting postmenopausal women age 50 to 75 years with known CAD. Parameters measured at the beginning and end of each treatment period included brachial artery flow-mediated dilation (FMD), the primary end point, as well as nitroglycerin-induced dilation, peripheral artery tonometry, serum lipoprotein levels, and markers of vascular function, including urinary prostaglandin, serum endothelin-1, and fibrinogen levels. RESULTS: Baseline FMD was impaired in these women, as expected (2.84 +/- 0.60%), but there was no significant difference between the effect of raloxifene (0.26 +/- 0.66% increase) and placebo (0.01 +/- 0.63% decrease) on this marker of endothelial function (p = 0.82). No significant raloxifene-related effects were observed on derived aortic pressure, pulse pressure, augmentation index, total cholesterol or low- and high-density lipoprotein subfractions, markers of thrombosis, or vasoconstrictor or vasodilator substances. CONCLUSIONS: In postmenopausal women with treated CAD, selective estrogen receptor modulation with raloxifene does not improve a comprehensive set of parameters examining vascular function and serum lipoprotein levels.

Physiological testosterone replacement and arterial endothelial function in men.

OBJECTIVE: The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long-term physiological androgen replacement therapy, at trough and peak testosterone levels. PATIENTS AND DESIGN: We recruited nine hypogonadal men (aged 35 +/- 4 years) receiving androgen replacement therapy, each treated with 800 mg testosterone (T) depot preparations every 6 months. MEASUREMENTS: Serum lipid and hormone levels and arterial reactivity were measured, prior to (trough T) and 2-4 weeks following testosterone administration (peak T). Each subject therefore served as their own control. Vessel diameter was measured by ultrasound at rest, during reactive hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent response] and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). RESULTS: Serum T (13 +/- 2 nmvs. 27 +/- 3 nm for trough and peak serum T, respectively, P < 0.001; normal adult male range 11-35 nm), and free T (195 +/- 23 pmvs. 510 +/- 93 pm, P < 0.005) significantly increased following subcutaneous depot T administration, as did serum oestradiol (100 +/- 10 pmvs. 175 +/- 9 pm, P = 0.001; normal adult male range < 250 pm). There was a significant decrease in FMD (3.6 +/- 1.1%vs. 3.0 +/- 0.8%, P < 0.01), but GTN responses were similar (9.5 +/- 0.8%vs. 10.4 +/- 1.0%, P > 0.2). Lipid, blood pressure and vessel diameter measurements were also similar before and after testosterone administration. CONCLUSION: Physiological replacement of testosterone is associated with decreased endothelium-dependent dilatation, in hypogonadal men.

Neuropsychological and psychiatric outcomes following coronary surgery or angioplasty: a comparative study.

BACKGROUND: Medical outcomes following coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) are similar, but few studies have compared neuropsychological outcomes after these procedures. METHODS: A retrospective study compared detailed neurocognitive and psychosocial functioning in 32 patients (CABG, n = 16; PTCA, n = 16) aged 61 +/- 6 years, 9-15 months after coronary revascularisation. Subjects were tested for executive functioning, speed of processing/attention and learning/memory, significant psychopathology (General Health Questionnaire, GHQ) and psychosocial functioning (Short Form (SF)-36 health survey). In the prospective study, 55 patients completed GHQ and SF-36 surveys, the day prior to and 6 months following PTCA. RESULTS: There were no significant differences between the CABG and PTCA groups for neuropsychological or psychosocial end-points (P > 0.20). Executive functioning in both groups, however, was worse than for healthy population controls (P < 0.01). The PTCA patients were significantly more likely than CABG patients to have psychiatric abnormality (GHQ Score >4; P < 0.01). After PTCA, however, there was a significant improvement in the GHQ and SF-36 scores (P < 0.05). CONCLUSIONS: Although executive function is often impaired after coronary revascularisation, neuropsychological status appears equivalent after CABG or PTCA. Psychiatric pathology is common in patients undergoing PTCA, but improves after this intervention.