Mechanisms of Penile Fibrosis Gonzalez‐Cadavid, Nestor F.
Journal of sexual medicine,
March 2009, Letnik:
6, Številka:
S3
Journal Article
Recenzirano
Penile fibrosis has been conceptually identified with the plaque that develops in the tunica albuginea in Peyronie's disease (PD), or with localized processes induced in the corpora cavernosa by ...ischemic or traumatic events. Recently, it has been proposed that a diffuse, progressive, and milder intracorporal fibrosis, which affects also the media of the penile arteries, is responsible for vasculogenic erectile dysfunction (ED) associated with aging, smoking, diabetes, hypertension, and post‐radical prostatectomy. These processes differ in etiology, time course, target cells, and treatment, but have many features in common.
To review the literature pertaining to fibrosis in the penis, related to PD and ED.
PubMed search for pertinent publications mainly during 2001–2008.
This review focuses initially on PD and then deals with studies on ED in animal and cell culture models, discussing some of the pathophysiological similarities between tunical fibrosis in PD and corporal fibrosis in corporal veno‐occlusive dysfunction (CVOD), and emerging therapeutic strategies. The role of profibrotic factors, the excessive deposit of collagen fibers and other extracellular matrix, the appearance of a synthetic cell phenotype in smooth muscle cells or the onset of a fibroblast–myofibroblast transition, and in the case of the corporal or penile arterial tissue the reduction of the smooth muscle cellular compartment, are discussed. This histopathology leads either to localized plaques or nodules in penile tissues, or to the diffuse fibrosis causing impairment of tissue compliance that underlies CVOD and arteriogenic ED. The antifibrotic role of the sustained stimulation of the nitric oxide/cyclic guanosine monophosphate pathway in the penis and its possible relevance to exogenous and endogenous stem cell differentiation is also briefly presented.
Fibrotic processes in penile tissues share a similar cellular and molecular pathophysiology and common endogenous mechanisms of defense that have inspired novel pharmacological experimental approaches. Gonzalez‐Cadavid NF. Mechanisms of penile fibrosis.
Stroke is the third leading cause of death in developed nations. Up to 88% of strokes are ischemic in nature. Extracranial carotid artery atherosclerotic disease is the third leading cause of ...ischemic stroke in the general population and the second most common nontraumatic cause among adults younger than 45 years. This article provides comprehensive, evidence-based recommendations for the management of extracranial atherosclerotic disease, including imaging for screening and diagnosis, medical management, and interventional management.
Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of ...circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants’ serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4–34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (
p
= 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (
p
= 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.
To characterize the relationship between aneurysm size and epidemiologic risk factors with growth and rupture by using computed tomographic (CT) angiography.
In this HIPAA-compliant, institutional ...review board approved study, patients with known asymptomatic unruptured intracerebral aneurysms were followed up longitudinally with CT angiographic examinations. Growth was defined as an increase in one or more dimensions above the measurement error, and at least 5% volume by using the ABC/2 method. Associations of epidemiologic factors with aneurysm growth and rupture were analyzed by using logistic regression analysis. Intra- and interobserver agreement coefficients for dimension, volume, and growth were evaluated by using the Pearson correlation coefficient and difference of means with 95% confidence intervals, the agreement statistic, and the McNemar χ(2).
Patients (n = 165) with aneurysms (n = 258) had a mean follow-up time of 2.24 years from time of diagnosis. Forty-six of 258 (18%) aneurysms in 38 patients grew larger. Spontaneous rupture occurred in four of 228 (1.8%) intradural aneurysms of average size (6.2 mm). Risk of aneurysm rupture per patient-year was 2.4% (95% CI: 0.5%, 7.12%) with growth and 0.2% (95% CI: 0.006%, 1.22%) without growth (P = .034). There was a 12-fold higher risk of rupture for growing aneurysms (P < .002), with high intra- and interobserver correlation coefficients for size, volume, and growth. Tobacco smoking (3.806, one degree of freedom; P < .015,) and initial size (5.895, two degrees of freedom; P < .051) were independent covariates, predicting 78.4% of growing aneurysms.
These results support imaging follow-up of all patients with aneurysms, including those whose aneurysms are smaller than the current 7-mm treatment threshold. Aneurysm growth, size, and smoking were associated with increased rupture risk.
Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current ...knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.
Intracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole-brain vessel wall imaging, we sought to study the differences in plaque features among various types of ...plaques in patients with a recent unilateral anterior circulation ischemic stroke.
Sixty-one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole-brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque-wall contrast ratio, high signal on T1-weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole-brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1-weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9-44.1;
=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8-164.9;
=0.013), and type 2 (≥50% cross-sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3-82.2;
=0.030) were independently associated with culprit lesions.
High signal on T1-weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.
Purpose
To propose and evaluate a parameter tune‐up solution to expedite a three‐dimensional (3D) variable‐flip‐angle turbo spin‐echo (TSE) sequence for whole‐brain intracranial vessel wall (IVW) ...imaging.
Materials and Methods
Elliptical k‐space sampling and prolonged echo train length (ETL), were used to expedite a 3D variable‐flip‐angle TSE‐based sequence. To compensate for the potential loss in vessel wall signal, optimal combination of prescribed T2 and ETL was experimentally investigated on 22 healthy volunteers at 3 Tesla. The optimized protocol (7–8 min) was then compared with a previous protocol (reference protocol, 11–12 min) in terms of signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR), vessel wall sharpness, and wall delineation quality on a 4‐point scale (0:poor; 3:excellent) in 10 healthy volunteers. A pilot study of five patients was performed and lesion delineation score was used to demonstrate the diagnostic quality.
Results
A protocol with ETL = 52 and prescribed T2 = 170 ms was deemed an optimized one, which, compared with the reference protocol, provided significantly improved wall SNR (12.0 ± 1.3 versus 10.0 ± 1.1; P = 0.002), wall–lumen CNR (9.7 ± 1.2 versus 8.0 ± 0.9; P = 0.002), wall–CSF CNR (2.8 ± 1.0 versus 1.7 ± 1.0; P = 0.026), similar vessel wall sharpness at both inner (1.59 ± 0.18 versus 1.58 ± 0.14, P = 0.87) and outer (1.71 ± 0.25 versus 1.83 ± 0.30; P = 0.18) boundaries, and comparable vessel wall delineation score for individual segments (1.95–3; P > 0.06). In all patients, atherosclerotic plaques (10) or wall dissection (5) were identified with a delineation score of 3 or 2.
Conclusion
A parameter tune‐up solution can accelerate 3D variable‐flip‐angle TSE acquisitions, particularly allowed for expedited whole‐brain IVW imaging with preserved wall delineation quality.
Level of Evidence: 2.
Technical Efficacy: Stage 1
J. MAGN. RESON. IMAGING 2017;46:751–757
Abstract
BACKGROUND:
Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby a sublethal ischemic stimulus confers a protective benefit against a subsequent severe ischemic ...insult. RIC has significant potential clinical implications for the prevention of delayed ischemic neurological deficit after aneurysmal subarachnoid hemorrhage (aSAH). Although RIC has been extensively investigated in animal models, it has not been fully evaluated in humans.
OBJECTIVE:
To assess the feasibility and safety of RIC for aSAH in a phase I clinical trial.
METHODS:
Consecutive patients hospitalized for treatment of an aSAH who met the inclusion/exclusion criteria were approached for consent. Enrolled patients received up to 4 RIC sessions on nonconsecutive days. Primary end points were the development of a symptomatic deep venous thrombosis, bruising, or injury to the limb and request to stop by the patient or surrogate. The secondary end points were the development of new neurological deficits or cerebral infarct, demonstrated by brain imaging after enrollment, and neurological deficit and condition at follow-up.
RESULTS:
Twenty patients were enrolled and underwent 76 RIC sessions, 75 of which were completed successfully. One session was discontinued when the patient became confused. No patient developed a deep venous thrombosis or injury to the preconditioned limb. No patient developed delayed ischemic neurological deficit during enrollment. At follow-up, median modified Rankin Scale score was 1 and Glasgow Outcome Scale score was 5.
CONCLUSION:
The RIC procedure was well tolerated and did not cause any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical trial.
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