Erectile dysfunction, penile atherosclerosis, and coronary artery vasculopathy in heart transplant recipients.

INTRODUCTION: Vascular erectile dysfunction (ED) is the expression of a systemic vascular disease and in particular of endothelial dysfunction. Dysfunctional endothelium plays also a significant role in the onset and progression of coronary artery vasculopathy (CAV). AIM: This pilot study was designed to evaluate the prevalence and pathogenesis of ED and its correlation with CAV in heart transplanted male. METHODS: A total of 77 male heart transplanted patients (HTx) evaluated in our center (mean age 61.6 + 10.6 years) were enrolled in the study. MAIN OUTCOME MEASURES: All subjects underwent accurate medical history collection, including lifestyle (cigarette smoking, dietary and sedentary habits, drug intake, and erectile function before cardiac transplantation), physical examination (body mass index and arterial pressure), biochemical blood tests (fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides), and hormones (prolactin, luteinizing hormone and total testosterone). Furthermore, they were studied with penile, carotid, femoral echo-color Doppler ultrasonography and coronary angiogram. RESULTS: Incidence of ED was 24% before HTx and increased up to 65% after. Postischemic cardiomiopathy was an indication to HTx in ED group more frequently than in patients without ED (No-ED group) (45.1% vs. 20%). ED patients showed a lower peak systolic velocity, a higher cavernosal intima-media thickness (IMT), a higher prevalence of cavernosal plaques (26.7% vs. 5.2%, P < 0.05), peripheral vascular disease (60.87% vs. 26.1%, P < 0.05) and CAV (45.8% vs. 25.8%, P < 0.05) with respect to No-ED patients. Coronary flow reserve was significantly reduced in ED vs. No-ED patients (2.43 + 0.7 vs. 2.9 + 0.8, P < 0.04). Finally, cavernous plaque and testosterone plasma levels were statistically associated with CAV. CONCLUSIONS: We showed that ED is a frequent disease in HTx patients, more common when the original pathology is postischemic cardiomiopathy and associated with higher prevalence of cavernous plaques and CAV. Its evaluation should be integral to an HTx rehab program.

Monoclonal gammopathy after liver transplantation: a risk factor for long-term medical complications other than malignancies.

The aims of the study were to evaluate (i) the prevalence of MGUS in patients after liver transplantation (LT), (ii) the role of MGUS as a risk factor for malignancy and other medical complications after LT. One hundred and fifty consecutive patients were included in the study and followed prospectively after LT for more than 18 months. Eighteen patients had MGUS before LT, whereas 49 patients developed MGUS after LT ('de novo' MGUS). Thirty-six of these patients showed a MGUS along all the follow up after LT ('permanent' MGUS). In 31 patients, MGUS disappeared after LT ('transient' MGUS). No patient with MGUS developed B-malignant lymphoproliferative disorder and only one patient developed a myeloma after LT. Comparing patients with 'permanent' MGUS to patients with 'transient' MGUS or without MGUS after LT, the former group showed a higher rate of serious infections (30% versus 13%, P = 0.01), chronic kidney disease (CKD) (75% versus 44%, P = 0.001) and mortality (33% versus 17%, P = 0.04). Permanent MGUS was confirmed as an independent risk factor for serious infections and CKD by multivariate analysis. Permanent MGUS after LT does not entail a significant risk of malignancy, but it is associated with a higher risk of serious infections and CKD.

Metabolic syndrome and erectile dysfunction: the ultrasound evaluation of cavernosal atherosclerosis.

OBJECTIVE: To study the relation between metabolic syndrome (MS), cavernosal morphological vasculopathy, and peripheral vascular alterations (carotid and femoral wall) in patients with erectile dysfunction. RESEARCH DESIGN AND METHODS: A total of 207 patients and 50 control subjects were evaluated for cardiovascular risk factors, physical examination, reproductive hormones, ultrasound analysis of cavernosal, carotid and femoral arteries (intima-media thickness), and cavernosal flow measurement (peak systolic velocity). RESULTS: A total of 28% of patients had MS, and they presented with a high prevalence of cavernosal alterations (70.3%) and systemic vascular impairment (59.3%), whereas patients with cavernosal alterations (44%) showed the higher prevalence of MS (48.9%). The number of MS components was related to the prevalence of penile vasculopathy. However, multivariate analysis showed that MS is not an independent predictor for cavernosal vasculopathy. CONCLUSIONS: Patients with cavernosal vasculopathy have an increased cardiometabolic risk, and screening for MS components might identify individuals with a higher risk for cavernosal and systemic atherosclerosis.

Blood levels, apoptosis, and homing of the endothelial progenitor cells after skin burns and escharectomy.

BACKGROUND: Skin burns are an acute trauma involving an extensive vascular damage and an intense inflammatory response. Bone marrow-derived circulating endothelial progenitor cells (EPC) are known to migrate to sites of neovascularization in response to mediators (vascular endothelial growth factor and stromal cell-derived factor-1) released after trauma and ischemia, to contribute to wound healing, and to increase neovascularization of animal prefabricated flaps. Recent data showed an increase in EPC number in burned patients and a positive correlation between EPC number and total body surface area (TBSA) burnt, but data were limited to the first 5 days after thermal injury. METHODS: By using flow cytometry, we studied EPC (CD34, CD133, CD45, and KDR cells) blood levels, apoptosis, and homing (stromal cell-derived factor-1 receptor expression and CXC chemokine receptor 4) in a 1-month follow-up postburn in 25 patients with ≥15% TBSA burnt, at least grade II burns and escharectomy performed at days 5 to 6, with respect to 31 controls. RESULTS: EPC count at admission showed a positive linear correlation with TBSA burnt. The EPC blood levels of the patients were low (50.7 cells/mL±61.8 cells/mL) immediately after thermal injury, then increased with two peaks, at day 1 (188.3 cells/mL±223.2 cells/mL) and day 12 (253.1 cells/mL±430.7 cells/mL) with respect to controls (95.2 cells/mL±28.5 cells/mL, p<0.05), and then returned to normal levels in 1 month. EPC apoptotic rate and inflammatory parameters paralleled EPC blood count. No significant variations were found in CXC chemokine receptor 4 expression. CONCLUSIONS: Thermal injury and escharectomy seem to induce an intense response in EPC production. In particular, escharectomy could improve physiologic wound repair by increasing EPC levels.

Bone mass in subjects with Klinefelter syndrome: role of testosterone levels and androgen receptor gene CAG polymorphism.

CONTEXT: Klinefelter syndrome (KS) is a chromosomal alteration characterized by supernumerary X-chromosome(s), primary hypogonadism, decreased pubertal peak bone mineral density (BMD), and accelerated bone loss during adulthood. Decreased bone mass has been traditionally related to low testosterone levels. However, testosterone replacement therapy does not necessarily increase bone mass in these patients, and low BMD can be observed also in patients with normal testosterone levels. The androgen receptor (AR) gene CAG polymorphism seems to modulate the sensitivity to testosterone and previous studies have related it to some clinical aspects of KS, to include BMD, gynecomastia, testes and prostate volume, and hemoglobin concentration. OBJECTIVE: To analyze the relation between bone mass, testosterone, and AR CAG polymorphism in men with KS. DESIGN: Cross-sectional cohort study. SETTING: University department. PATIENTS: One hundred twelve consecutive treatment-naïve 47,XXY Klinefelter patients (mean age 33.5 ± 4.7 yr) and 51 age-matched normal male controls. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry, CAG repeat length polymorphism, X-chromosome inactivation, and testosterone levels. RESULTS: Forty-nine of 112 KS subjects (42.5%) had low bone mass (osteopenia or osteoporosis). Lumbar and/or femoral T-scores were lower in KS patients compared with controls. No significant relationship was observed between testosterone levels and bone parameters, and the prevalence of osteopenia/osteoporosis was similar in subjects with normal and low testosterone levels (43.7% and 40.5%, respectively). The mean CAG repeat length calculated after X-chromosome inactivation analysis showed no differences between patients with normal and low bone mass. CONCLUSIONS: Testosterone levels and AR CAG polymorphism are not associated with bone mass phenotype in KS.

Testicular contrast harmonic imaging to evaluate intratesticular perfusion alterations in patients with varicocele.

PURPOSE: To determine whether changes in intratesticular microcirculation perfusion affect spermatogenesis in patients with left varicocele we performed testicular contrast harmonic imaging. MATERIALS AND METHODS: A total of 90 patients with left varicocele (oligospermia in 50 and normozoospermia in 40) and 36 controls without varicocele (oligospermia in 16 and normozoospermia in 20) were enrolled in the study. Before contrast harmonic imaging all participants were evaluated by clinical examination, hormonal analysis, semen sample and scrotal ultrasound. We calculated contrast material arrival time in the arteriolar circulation (wash-in), time to peak in arterial circulation, arrival time in the venular circulation (washout) and mean transit time in each testis on contrast harmonic imaging. RESULTS: We found no difference in the distribution rate of varicocele grade in patients with vs without oligospermia. All contrast harmonic imaging parameters were significantly higher in patients with varicocele plus normozoospermia or oligospermia and controls. We found no significant differences in contrast harmonic imaging parameters in patients with lower varicocele grading with respect to the higher grades. In patients with varicocele we found a negative linear correlation between total sperm count and left mean transit time (r = -0.29). In a multivariate model left mean transit time was the only independent predicting parameter of oligospermia (p <0.05). Mean transit time greater than 36 seconds predicted oligospermia in patients with left varicocele with 78% sensitivity and 58% specificity. CONCLUSIONS: To our knowledge we report for the first time that testicular contrast harmonic imaging may be a new diagnostic tool able to improve our knowledge about the influence of varicocele on intratesticular microcirculation.

Cavernous artery intima-media thickness: a new parameter in the diagnosis of vascular erectile dysfunction.

INTRODUCTION: A precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone. AIM: We performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis. METHODS: A total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study. MAIN OUTCOME MEASURES: All subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Delta-cavernous calliper]). RESULTS: Cavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT. CONCLUSIONS: An increased cavernous IMT (>or=0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase.

Asymmetric development of peripheral atherosclerosis in patients with erectile dysfunction: an ultrasonographic study.

Recent literature focused on erectile dysfunction (ED) as a reliable predictive parameter of cardiovascular diseases. ED patients have a higher prevalence of atherosclerotic lesions (increased intima-media thickness and plaques) at carotid site, but data on femoral site are still lacking. Nevertheless, there is accumulating evidence concerning a significant involvement of femoral atherosclerosis in other clinical conditions associated to ED, such as diabetes mellitus and coronary disease. Therefore, we investigated the prevalence of carotid and femoral atherosclerotic lesions and penile peak systolic velocity (PSV) in 238 ED patients by Eco-Colour Doppler ultrasonography (US). We found - irrespective of the presence of cardiovascular risk factors - a significant increase of atherosclerotic lesions in ED group with respect to 52 controls (66.4% versus 36.5%) and a higher prevalence of atherosclerosis at the femoral site (23.1% versus 5.7%), also with respect to the carotid site (8%). Moreover, PSV was significantly lower in ED patients with atherosclerosis compared to those without atherosclerotic lesions (41.9+/-15.3 cm/s versus 55.2+/-17.7 cm/s), and it was particularly low in those with combined carotid and femoral atherosclerosis (34.8+/-13.3 cm/s) and those with isolated carotid atherosclerosis (37.9+/-13.0 cm/s). These data confirm the strong relation between atherosclerosis and ED, an asymmetric development of atherosclerotic lesions in ED patients and suggest to perform an US study of both femoral and carotid district in these subjects.