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1.
Surgeon ; 21(5): 308-313, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36935272

ABSTRACT

BACKGROUND: There is underrepresentation of women at surgical conferences. We examine the representation of women in Irish urology by looking at gender balance within the Irish Society of Urology (ISU) conference. AIMS: ISU programmes over thirteen years from 2008 to 2020 were assessed and female representation in session chairs, guest speakers, poster and oral presentations identified. Gender distributions of authors for each year was examined. To investigate changes in female representation temporally, the period of this study (2008-2020) was subdivided and compared: 2008-2013 and 2014-2020. RESULTS: 76 sessions were presided over by 138 chairs, of which 6 (4.3%) were female. Eight conferences had zero female chairs. 62 guest lectures were given, 6 (9.6%) by women. Of total 340 poster and 434 oral presentations, women delivered 24.9% (0-47.5%) of posters and 31.6% (10.3-59.4%) of oral presentations. We found no significant difference in the percentage of female poster presentations between the time periods 2008-2013 (m = 18.2, sd = 13.7) and 2014-2020 (m = 34.3, sd = 17.8), t(11) = -1.4, p > 0.05. However, we found a significant difference in the percentage of female oral presentations between the periods 2008-2013 (m = 18.7, sd = 14.2) and 2014-2020 (m = 40.6, sd = 14.5), t(11) = -2.8, p < 0.05. CONCLUSIONS: Our study is the second to examine female representation in Irish urology. Session chairs and guest speakers were grossly overrepresented by males as were oral and poster presentations. Despite lacking female influence overall, in more recent years there was an increased representation of women. Societies should strive to increase female representation, as this perpetuates a positive feedback loop, encouraging future female trainees to pursue urological surgery.


Subject(s)
Specialties, Surgical , Urology , Female , Humans , Male
2.
Surgeon ; 20(4): e100-e104, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34130889

ABSTRACT

INTRODUCTION: Undescended testis (UDT) is a clinical diagnosis and a common reason for referral to paediatric urology outpatients. Our aim was to assess current referral patterns at our unit and to identify predictive factors that may better aid primary care physicians (PCP) in diagnosing UDT based on history and physical exam. METHODS: A retrospective analysis of referrals to outpatients from 2014 to 2016 was performed to assess current referral patterns including referral source, age, reason for referral and outcome following assessment by a single consultant paediatric urologist.A prospective analysis of new referrals was performed to identify predictive factors which may aid in the diagnosis of UDT including gestational age, presence of scrotal asymmetry and previously obtained imaging. RESULTS: From 2014 to 2016, 259 boys were referred with suspected UDT. The majority of referrals were received from PCPs (62%) followed by Neonatology (29%), Paediatrics (8%) and general surgery (1%). Median age at time of assessment was 29 (5-180) months. One hundred and eight (41.7%) boys were diagnosed with UDT.There were 74 boys assessed prospectively. Median age at assessment was 24.5 (6-171) months. We identified 3 predictors of a diagnosis of UDT; history of prematurity (p = 0.001), UDT mentioned to the parents at birth (p = 0.027) and scrotal asymmetry on examination (p < 0.001). Greatest diagnostic inaccuracy was found in boys referred beyond one year of age (27.7%). In this cohort, the absence of all three risk factors was associated with a negative predictive value of 94.1%. CONCLUSION: The majority of boys with suspected UDT are referred beyond the age recommended for orchidopexy (6-12 months). The majority of boys referred for assessment did not have UDT. We have identified three predictive factors that may aid referring physicians when assessing boys, particularly those older than 1 year.


Subject(s)
Cryptorchidism , Child , Cryptorchidism/complications , Cryptorchidism/diagnosis , Cryptorchidism/surgery , Female , Humans , Infant , Infant, Newborn , Male , Orchiopexy , Referral and Consultation , Retrospective Studies , Risk Factors
3.
Ir J Med Sci ; 190(4): 1553-1559, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33449326

ABSTRACT

OBJECTIVE: To assess whether instillation of lidocaine gel both before and after flexible cystoscopy is more effective at reducing post procedural symptoms than instillation of lidocaine gel pre flexible cystoscopy alone. We hypothesise that inadequate urethral dwell time and dilution of lidocaine gel by the irrigation fluid during flexible cystoscopy limits its anaesthetic efficacy. Only one other study has attempted to reduce bothersome urinary symptoms through an intervention after flexible cystoscopy. METHODS: This was a randomised controlled trial in which patients were randomised 1:1 to receive lidocaine gel pre and post flexible cystoscopy (treatment) or lidocaine gel pre flexible cystoscopy only (control). Patient-reported outcome measures were used to assess symptoms and quality of life prior to cystoscopy, on day 2 and day 7 post cystoscopy. RESULT: Fifty patients were divided equally between the treatment and control groups. There were no significant differences in baseline characteristics between the groups (p = 1.000). An overall symptoms variable was measured, though no significant difference was found in the distribution of responses between the groups at baseline, 2 or 7 days after the flexible cystoscopy (p = 0.423, 0.651,0.735). In the treatment group, 1 patient (4.0%) presented to a doctor for review following flexible cystoscopy, and 4 patients (16.0%) presented in the control group (p = 0.349). CONCLUSION: Initial study results suggest that post-operative lidocaine does not significantly limit the exacerbation of urinary symptoms following flexible cystoscopy; however, our results are not powered to detect a small difference. We do not recommend a change in practice based on our results.


Subject(s)
Cystoscopy , Lidocaine , Anesthetics, Local , Gels , Humans , Male , Quality of Life
4.
Ir J Med Sci ; 187(4): 1109-1113, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29423823

ABSTRACT

OBJECTIVES: EAU and AUA guidelines recommend urgent surgical exploration in cases of suspected testicular rupture. However, the management of rupture to other encapsulated organs (e.g. kidney) is primarily non-operative. The aim of this study was to evaluate the conservative management of blunt scrotal trauma. METHODS: Standard practice in our Level II trauma centre is to manage all blunt scrotal injuries conservatively with analgesia, antibiotics and scrotal support. Ultrasonography is performed where testicular injury or haematocoele is suspected clinically. All patients are offered a 3 month follow-up appointment. A retrospective chart review was performed on all patients who underwent ultrasonography for blunt scrotal trauma between 1998 and 2014. Each patient was contacted by telephone to assess for testicular atrophy. RESULTS: Thirty-seven consecutive patients were identified for inclusion in the study. Twenty-three patients (62%) were diagnosed with significant testicular injury (rupture of tunica albuginea or large haematocele). All were managed conservatively regardless of ultrasound findings. Four patients had evidence of testicular atrophy at their three month follow up appointment. None reported chronic pain or required delayed orchidectomy. Four patients later underwent repair of an asymptomatic post-traumatic hydrocoele. CONCLUSIONS: Our experience shows that blunt scrotal trauma can be safely managed conservatively and may reduce the risk of atrophy compared to case series where the testis was surgically explored.


Subject(s)
Testis/injuries , Wounds, Nonpenetrating/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Child , Humans , Male , Middle Aged , Orchiectomy , Retrospective Studies , Rupture , Scrotum/diagnostic imaging , Scrotum/injuries , Trauma Centers , Ultrasonography , Wounds, Nonpenetrating/diagnostic imaging , Young Adult
6.
Ir J Med Sci ; 187(2): 323-326, 2018 May.
Article in English | MEDLINE | ID: mdl-28726031

ABSTRACT

BACKGROUND: Leydig cell tumour (LCT) of the testis is a rare histological subtype of stromal tumours, accounting for 1 to 3% of testicular neoplasms. The natural history of LCT is poorly understood. AIMS: The aim of this study was to assess the incidence and natural history of Leydig cell tumours (LCT) of the testes. METHODS: A search of the National Cancer Registry of Ireland database was performed regarding Leydig cell testicular tumours. Recurrence free survival (RFS) and disease-specific survival (DSS) were analysed. RESULTS: Between 1994 and 2013, 2755 new cases of testicular cancer were diagnosed in Ireland. Of these, 22 (0.79%) were Leydig cell tumours. Nineteen were invasive (stage T1) and three were in situ (stage Tis). One patient developed a local recurrence following an organ preserving procedure and underwent a completion orchidectomy 107 days after initial diagnosis. No further treatment was required. There have been no disease-specific deaths. The 1-, 3- and 5-year overall survival (OS) rates were 95.5, 88.2 and 73.3%, respectively. The 5-year disease-specific survival (DSS) was 100% and the 5-year recurrence free survival (RFS) was 93.3%. CONCLUSION: From the National Cancer Registry, LCT has been shown to be a rare subtype of testicular tumour. Due to the relatively favourable natural history, it may be possible to tailor less aggressive surveillance regimens in these patients.


Subject(s)
Leydig Cell Tumor , Testicular Neoplasms , Adult , Female , Humans , Ireland , Leydig Cells/pathology , Male , Middle Aged
7.
Public Health ; 153: 25-35, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28822850

ABSTRACT

OBJECTIVES: Given the increased risk of foodborne infection to cancer patients receiving chemotherapy treatment, and the risk of listeriosis reportedly five-times greater to this immunocompromised patient group, there is a need to ensure the implementation of domestic food safety practices among chemotherapy patients and their family caregivers. However, information regarding the adequacy of resources to inform and enable patients to implement domestic food safety practices to reduce the risk of foodborne infection is limited. Consequently, this study aimed to evaluate the provision of food safety information available to UK chemotherapy patients. STUDY DESIGN: In-depth semi-structured interviews and content analysis of online patient information resources. METHODS: Interviews with patients and family caregivers (n = 15) were conducted to explore food-related experiences during chemotherapy treatment. Online food-related information resources for chemotherapy patients (n = 45) were obtained from 35 of 154 National Health Service chemotherapy providers in England, Scotland, and Wales, the Department of Health (DoH) and three of 184 identified UK cancer charities. Identified food-related information resources were reviewed using a content-analysis approach to assess the inclusion of food safety information for chemotherapy patients. RESULTS: In-depth interviews established that many patients indicated awareness of immunosuppression during treatment. Although patients reported practicing caution to reduce the risk of communicable diseases by avoiding crowded spaces/public transport, food safety was reported to be of minimal concern during treatment and the risk of foodborne infection was often underestimated. The review of online food-related patient information resources established that many resources failed to highlight the increased risk of foodborne infection and emphasize the importance of food safety for patients during chemotherapy treatment. Considerable information gaps exist, particularly in relation to listeriosis prevention practices. Cumulatively, information was inconsistent, insufficient, and varied between resources. CONCLUSION: The study has identified the need for an effective, standardized food safety resource specifically targeting chemotherapy patients and family caregivers. Such intervention is essential to assist efforts in reducing the risks associated with foodborne infection among chemotherapy patients.


Subject(s)
Food Safety , Foodborne Diseases/prevention & control , Neoplasms/drug therapy , Patient Education as Topic , Health Knowledge, Attitudes, Practice , Humans , Immunocompromised Host , Listeriosis/prevention & control , Risk , United Kingdom
8.
Ir J Med Sci ; 185(1): 165-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25673163

ABSTRACT

INTRODUCTION: The majority of patients with scrotal problems or urinary symptoms will first present to their general practitioner (GP). The importance of the initial examination performed by the GP is often underestimated; however, it frequently determines the course of investigation and ultimately treatment. Unfortunately, medical schools have devoted increasingly less time to teaching urology over the past decade. The impact of this decline in teaching on a GP trainee's assessment of urological complaints remains unclear. The aim of this study was to investigate the self-reported competency of GP trainees in assessing urological presentations. METHODS: A questionnaire was circulated to 101 GP trainees from five separate training programmes. Respondents rated their confidence in evaluating four different urological presentations. They were also invited to give their opinion regarding the teaching of urology on their current scheme and whether they would be in favour of the addition of urology as an optional rotation. RESULTS: Only 18 trainees (19 %) felt urology was adequately covered on their curriculum. A small yet significant number of respondents felt uncomfortable in their assessment of testicular (28 %, 28/101) or prostate (35 %, 35/101) pathology and male (17 %, 17/101) or female (10 %, 10/101) urinary symptoms. Twenty-six trainees (26 %) would choose a rotation in urology if available. Another ten trainees felt that attending urology outpatient clinics would benefit training. CONCLUSION: This study highlights a number of concerns among GP trainees in relation to their training in urology. These issues should be addressed to ensure that the training scheme sufficiently prepares GPs to manage common urological conditions.


Subject(s)
Attitude of Health Personnel , Female Urogenital Diseases/diagnosis , General Practice/education , Male Urogenital Diseases/diagnosis , Urology/education , Adult , Clinical Competence , Curriculum , Female , Humans , Male , Surveys and Questionnaires , Symptom Assessment , Young Adult
10.
Int Urogynecol J ; 26(3): 313-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25216630

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data assessing the effectiveness of trigonal BoNT-A are limited. This study evaluates adverse events (AEs) and short-term efficacy associated with trigonal and extratrigonal BoNT-A. METHODS: Electronic databases (PubMed, EMBASE, and the Cochrane database) were searched for studies comparing trigonal and extratrigonal BoNT-A for DO. Meta-analyses were performed using the random effects model. Outcome measures included incidence of AEs and short-term efficacy. RESULTS: Six studies describing 258 patients met the inclusion criteria. The meta-analysis did not show significant differences between trigonal and extratrigonal BoNT-A for acute urinary retention (AUR; 4.2 vs 3.7 %; odds ratio [OR]: 1.068, 95 % confidence interval [CI]: 0.239-4.773; P = 0.931) or high post-void residual (PVR; 25.8 vs 22.2 %; OR: 0.979; 95 % CI: 0.459-2.088; P = 0.956). The incidence of urinary tract infection (UTI; 7.5 vs 21.0 %; OR: 0.670; 95 % CI: 0.312-1.439; P = 0.305), haematuria (15.8 vs 25.9 %; OR: 0.547; 95 % CI: 0.264-1.134; P = 0.105) and post-operative muscle weakness (9.2 vs 11.3 %; OR: 0.587; 95 % CI: 0.205-1.680, P = 0.320) was similar in both groups. Finally, differences in short-term cure rates between two study arms were not statistically significant (52.9 vs 56.9 %; OR: 1.438; 95 % CI: 0.448-4.610; P = 0.542). CONCLUSIONS: Although data are limited, no significant differences between trigonal and extratrigonal BoNT-A in terms of AEs and short-term efficacy were observed. Additional randomised controlled trials are required to define optimal injection techniques and sites for administering intra-vesical BoNT-A.


Subject(s)
Acetylcholine Release Inhibitors/administration & dosage , Acetylcholine Release Inhibitors/adverse effects , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/adverse effects , Urinary Bladder, Overactive/drug therapy , Administration, Intravesical , Humans
11.
Ir J Med Sci ; 184(2): 493-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24903123

ABSTRACT

INTRODUCTION: Urology cover is commonly available out-of-hours in most teaching hospitals. However, increased pressure to reduce hospital expenditure has forced many institutions to consider removing middle grade cover outside of normal working hours. The aim of this study was to audit the emergency urology activity in our institution over a 12-month period. METHODS: A prospective logbook was maintained for all urology referrals from the emergency department between August 2012 and March 2013. The diagnosis and patient outcome was recorded for each referral. The emergency theatre logbook was retrospectively evaluated for all emergency urology procedures carried out over the same time period. A basic cost analysis was performed to calculate the cost of providing the on-call service. RESULTS: A total of 752 patients were referred to the urology service over a 12-month period. The most common reasons for referral were renal colic and scrotal pain. Approximately 41 % of referrals were discharged directly from the emergency department. There were 167 emergency operations performed in total. The majority of emergency operations and referrals from the emergency department took place outside of normal working hours. A basic cost analysis revealed an associated cost saving of €58,120. CONCLUSION: Emergency urology activity constitutes a large proportion of the workload at our institution. Restricting emergency urology cover would limit essential training opportunities for urology trainees, increases length of stay and delay treatment of urological emergencies. Urology "out of hours" cover is a cost-efficient method of service provision.


Subject(s)
After-Hours Care/statistics & numerical data , Referral and Consultation/statistics & numerical data , Urologic Surgical Procedures/statistics & numerical data , Urology/statistics & numerical data , After-Hours Care/organization & administration , Costs and Cost Analysis , Emergencies , Emergency Service, Hospital/statistics & numerical data , Hospitals, University/statistics & numerical data , Humans , Male , Medical Audit , Personnel Staffing and Scheduling , Retrospective Studies , Urology/organization & administration
12.
Ir J Med Sci ; 184(3): 637-40, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25194829

ABSTRACT

BACKGROUND: Paediatric urology training is not a mandatory part of higher surgical training in urology in Ireland. It is predicted there will be a shortfall of surgeons trained in paediatric surgery in the coming years leading to a reliance on specialist paediatric surgical centres. AIM: The aim of this study was to assess the attitudes of urological trainees regarding the current state of paediatric urology training and to address the potential future changes to training structures. METHODS: A voluntary anonymous internet-based survey was emailed to all urological trainees. Parameters assessed included sex, level of training, attitudes towards paediatric urology training and levels of competence regarding core paediatric urological procedures. RESULTS: 69.2 % (n = 18) responded to the survey. 94.4 % (n = 17) would favour mandatory paediatric training-of these, 52.9 % (n = 9) would favour this in a dedicated paediatric hospital with a paediatric urologist. 66.7 % (n = 12) would like to provide a paediatric urology service as a consultant. 55.6 % (n = 10) felt they were competent to perform circumcision or scrotal exploration independently and manage all associated complications. No trainee felt themselves to be competent to perform orchidopexy independently and manage all complications. CONCLUSION: Our study demonstrates a promising desire to provide paediatric services in the future. A greater emphasis on structured paediatric urology training is required to maintain the standard currently offered by adult urologists.


Subject(s)
Circumcision, Male/education , Orchiopexy/education , Pediatrics/education , Urology/education , Attitude of Health Personnel , Child , Female , Hospitals, Pediatric , Humans , Ireland , Male , Physicians/statistics & numerical data , Specialization , Surveys and Questionnaires
13.
Am J Physiol Gastrointest Liver Physiol ; 295(5): G953-64, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18772366

ABSTRACT

Portal hypertension (PHT) is a common complication of liver cirrhosis and significantly increases morbidity and mortality. Abrogation of PHT using NSAIDs has demonstrated that prostacyclin (PGI(2)), a direct downstream metabolic product of cyclooxygenase (COX) activity, is an important mediator in the development of experimental and clinical PHT. However, the role of COX isoforms in PGI(2) biosynthesis and PHT is not fully understood. Prehepatic PHT was induced by portal vein ligation (PVL) in wild-type, COX-1(-/-), and COX-2(-/-) mice treated with and without COX-2 (NS398) or COX-1 (SC560) inhibitors. Hemodynamic measurements and PGI(2) biosynthesis were determined 1-7 days after PVL or sham surgery. Gene deletion or pharmacological inhibition of COX-1 or COX-2 attenuated but did not ameliorate PGI(2) biosynthesis after PVL or prevent PHT. In contrast, treatment of COX-1(-/-) mice with NS398 or COX-2(-/-) mice with SC560 restricted PGI(2) biosynthesis and abrogated the development of PHT following PVL. In conclusion, either COX-1 or COX-2 can mediate elevated PGI(2) biosynthesis and the development of experimental prehepatic PHT. Consequently, PGI(2) rather then COX-selective drugs are indicated in the treatment of PHT. Identification of additional target sites downstream of COX may benefit the >27,000 patients whom die annually from cirrhosis in the United States alone.


Subject(s)
Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Epoprostenol/biosynthesis , Hypertension, Portal/metabolism , Animals , Cyclooxygenase Inhibitors/pharmacology , Epoprostenol/chemistry , Mice , Mice, Knockout , Molecular Structure , Nitrobenzenes , Protein Isoforms/metabolism , Pyrazoles , Sulfonamides
15.
Trop Anim Health Prod ; 36(3): 247-68, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15080541

ABSTRACT

This paper reviews the economic framework for the delivery of livestock services to the poor. It is argued that the demand for livestock products is likely to increase rapidly and the ability of the poor to participate in the opportunities presented by this growth is linked critically to the availability of good service support, both on the input and output side. Governments therefore have a responsibility to supply the necessary public goods (including the institutions and legal frameworks), and the market infrastructure for facilitating the emergence of efficient markets for livestock services. The paper further argues that the dynamics of public policy in developing countries are much more complex than the simple application of economic logic. It is the larger political economy that often dictates policy choices. It is therefore important to integrate political economy and governance issues into the economic debate on livestock service delivery. The paper also reviews the context in which the markets for livestock services will need to function. Different countries are facing very different sets of issues, and the identification of possible interventions in livestock service markets would require careful field research and analysis. In this context, the paper suggests the elements of a research agenda for the next few years.


Subject(s)
Animal Husbandry , Animals, Domestic/growth & development , Developing Countries/economics , Public Policy , Veterinary Medicine , Animal Diseases/prevention & control , Animal Husbandry/economics , Animal Husbandry/methods , Animal Husbandry/standards , Animals , Humans , Poverty/economics , Rural Population , Veterinary Medicine/economics , Veterinary Medicine/standards
17.
Pharmacol Ther ; 89(3): 273-93, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11516480

ABSTRACT

Portal hypertension (PHT) is a common clinical syndrome associated with chronic liver diseases; it is characterized by a pathological increase in portal pressure. Pharmacotherapy for PHT is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow. Due to the altered hemodynamic profile in PHT, dramatic changes in mechanical forces, both pressure and flow, may play a pivotal role in controlling endothelial and vascular smooth muscle cell signaling, structure, and function in cirrhotics. Nitric oxide, prostacyclin, endothelial-derived contracting factors, and endothelial-derived hyperpolarizing factor are powerful vasoactive substances released from the endothelium in response to both humoral and mechanical stimuli that can profoundly affect both the function and structure of the underlying vascular smooth muscle. This review will examine the contributory role of hormonal- and mechanical force-induced changes in endothelial function and signaling and the consequence of these changes on the structural and functional response of the underlying vascular smooth muscle. It will focus on the pivotal role of hormonal and mechanical force-induced endothelial release of vasoactive substances in dictating the reactivity of the underlying vascular smooth muscle, i.e., whether hyporeactive or hyperreactive, and will examine the extent to which these substances may exert a protective and/or detrimental influence on the structure of the underlying vascular smooth muscle in both a normal hemodynamic environment and following hemodynamic perturbations typical of PHT and cirrhosis. Finally, it will discuss the intracellular processes that regulate the release/expression of these vasoactive substances and that control the transformation of this normally protective cell to one that may promote the development of vasculopathy in PHT.


Subject(s)
Endothelium, Vascular/physiopathology , Hypertension, Portal/physiopathology , Liver Cirrhosis/physiopathology , Muscle, Smooth, Vascular/physiopathology , Animals , Biological Factors/metabolism , Calcium Signaling , Cell Hypoxia , Cells, Cultured , Endothelins/metabolism , Endothelium, Vascular/metabolism , Epoprostenol/metabolism , Humans , Hypertension, Portal/drug therapy , Nitric Oxide/metabolism , Pressure , Receptors, Cell Surface/agonists , Regional Blood Flow/drug effects , Splanchnic Circulation/drug effects , Stress, Mechanical , Vasoconstriction , Vasodilation
18.
Circulation ; 103(4): 597-603, 2001 Jan 30.
Article in English | MEDLINE | ID: mdl-11157728

ABSTRACT

BACKGROUND: The endothelium may play a pivotal role in hemodynamic force-induced vascular remodeling. We investigated the role of endothelial cell (EC) plasminogen activator inhibitor-1 (PAI-1) in modulating flow-induced smooth muscle cell (SMC) migration. METHODS AND RESULTS: Human SMCs cocultured with or without human ECs were exposed to static (0 mL/min) or flow (26 mL/min; shear stress 23 dyne/cm(2)) conditions for 24 hours in a perfused capillary culture system. SMC migration was then assessed with a Transwell migration assay. In the absence but not in the presence of ECs, pulsatile flow significantly increased the migration of SMCs (264+/-26%) compared with SMCs under static conditions, concomitant with a 3- and 4-fold increase in PAI-1 mRNA and protein, respectively, in cocultured ECs. In the presence of PAI-1-/- ECs, flow increased wild-type SMC migration (226+/-25%), an effect that was reversed by exogenous PAI-1. To determine whether the antimigratory activity of PAI-1 was dependent primarily on inhibition of PAs or its association with vitronectin, experiments were conducted with PAI-1R (a mutant PAI-1 that binds to vitronectin but does not inhibit PA) and PAI-1K (a mutant that inhibits PA but has reduced affinity for vitronectin). PAI-1R inhibited both basal and flow-induced migration, whereas PAI-1K inhibited flow-induced migration in the absence of any effect on baseline migration. CONCLUSIONS: Flow-induced EC PAI-1 inhibits flow-induced SMC migration in vitro. EC PAI-1 expression may be one of the predominant mechanisms responsible for controlling the process of vascular remodeling.


Subject(s)
Cell Movement/physiology , Endothelium, Vascular/physiology , Muscle, Smooth, Vascular/cytology , Plasminogen Activator Inhibitor 1/physiology , Animals , Blotting, Northern , Cell Culture Techniques/methods , Cell Movement/drug effects , Cells, Cultured , Coculture Techniques , Endothelium, Vascular/chemistry , Endothelium, Vascular/cytology , Gene Deletion , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/drug effects , Plasminogen Activator Inhibitor 1/genetics , Plasminogen Activator Inhibitor 1/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism
20.
Acta Pharmacol Sin ; 21(5): 385-90, 2000 May.
Article in English | MEDLINE | ID: mdl-11324433

ABSTRACT

Epidemiological studies demonstrate a significant protective effect of moderate alcohol consumption on the incidence of cardiovascular diseases which accounts for the majority of deaths in the Western world. In this review, possible mechanisms to explain the cardioprotective effect of ethanol are discussed. While the prevailing theory supported by a number of clinical and animal studies indicates that the ability of ethanol to elevate serum high-density lipoprotein (HDL) cholesterol levels is an important mechanism in ameliorating cardiovascular disease, other mechanisms whereby ethanol could exert its beneficial effect have been proposed. Namely, its ability to affect platelet function and endothelial cell and vascular smooth muscle cell function (In this review, the terms alcohol and ethanol are used interchangeably).


Subject(s)
Coronary Disease/blood , Ethanol/pharmacology , Lipoproteins, HDL/blood , Muscle, Smooth, Vascular/pathology , Animals , Cell Division/drug effects , Humans , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III , Platelet Aggregation/drug effects
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