Drug delivery options and therapeutic advances in the management of erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. It is estimated that 20-30% of adult men will have at least one episode of ED during their lifetime and the prevalence increases with age. ED is known to have significant negative psychological implications for men, resulting in impaired functional status and a greater prevalence of anxiety and depression. AREAS COVERED: Medications for the treatment of erectile dysfunction largely revolve around oral, injection, and topical therapies. Though all three modalities are widely used, each delivery option has its own advantages and specific indications. Likewise, there are several new developing treatments for ED that may change the landscape of treatment. The goal of this review is to summarize contemporary drug delivery options used in the treatment of ED and highlight future promising pharmacological developments. EXPERT OPINION: There are a myriad of new developments on the horizon including new PDE5Is and drug targets, nanotechnology enhancements, stem cell and gene therapy, shockwave therapy, and platelet-rich plasma injections. These are all promising new methods to not only treat ED but also to address the pathology and prevent or eliminate further damage.

Should assessment of penetrative sexual activity be used as the treatment arbiter in the management of Peyronie's disease?

Peyronie's disease is an inflammatory disorder, which causes thickening of the tunica albuginea of the penis. Peyronie's disease has a variable natural history and the assessment and management of the disease has yet to be standardised. The case notes of 97 patients with a diagnosis of Peyronie's disease were retrospectively reviewed at a single tertiary referral centre. Patients who were able to achieve sexual penetrative activity to the satisfaction of both partners were managed conservatively. Patients who were unable to achieve penetrative sexual activity were given intra-cavernosal prostaglandin, with those achieving a satisfactory erection being offered appropriate surgical intervention. The mean age at presentation was 50 years (range 18-82). A total of 59 (61%) men were able to have penetrative sex at the time of presentation. Following initial conservative management, only five (8%) of this group had disease progression, which stopped them from being able to penetrate. In all 38 (39%) men who were not able to penetrate at presentation were offered surgical intervention. In all 24 (63%) of these men chose to have surgical intervention. Tunical plication resulted in the ability to penetrate in 77% of men choosing this option whereas only 46% of men undergoing autologous saphenous vein grafting were able to have penetrative sex. Assessment of penetrative sexual function is an essential component of the management of patients with Peyronie's disease. This enables appropriate counselling with respect to possible conservative management or the most appropriate surgical intervention. The majority of patients with Peyronie's disease can achieve sexual penetrative activity, many without surgical intervention.

Ketamine-induced vesicopathy: a literature review.

Ketamine consumption in on the increase as a recreational abuse substance. It is reported to cause lower urinary tract symptoms (LUTS), and published accounts of its deleterious effects are increasing. We reviewed the available literature regarding the urological impact of ketamine abuse and its management. Twenty-two publications were found in total after a search of all databases including Pubmed, Medline and Google Scholar using the words 'ketamine', 'bladder' and 'cystitis' with no limits imposed. There are approximately 110 cases reported in the literature in the form of case series, case reports and letters. The effect of ketamine abuse on the bladder is universally similar; however, there is no uniform method adopted in reporting the symptoms, diagnosis and management. Very little is known regarding the pathogenesis of its effects on the urinary tract. Patients with severe irritative LUTS, a positive history of ketamine abuse and the absence of any other aetiology should be considered to have ketamine-induced vesicopathy. Effort must be made to elicit the history of drug abuse in those with no found cause of LUTS, especially in the young. Presently, ketamine cessation is the only effective treatment modality to prevent deterioration of the renal function and indeed offer the possibility of symptom resolution. Management akin to that formulated for interstitial cystitis patients would appear to offer the greatest opportunity for effective treatment.

Incidence of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation.

AIMS: The aim of this study is to describe the incidence and characteristics of neovascularization in the fellow eye of patients with retinal angiomatous proliferation (RAP). METHODS: This is a retrospective study conducted on all patients with a diagnosis of unilateral RAP commencing treatment in a single centre between November 2002 and January 2010. Clinical biomicroscopic examination, fluorescein angiography, and if required, indocyanine green angiography, and optical coherence tomography were used to evaluate all patients. RESULTS: In all, 37 patients had a follow-up of ≥1 year, 28 ≥2 years, and 11 ≥3. Patients who developed RAP in the fellow eye were: 2 of 37 (5.4%) within 1 year of follow-up, 4 of 28 (14.2%) within 2 years, and 4 of 11 (36.3%) within 3 years. CONCLUSION: In our case series, the risk of neovascularization in the fellow eye of patients with unilateral RAP increased with time. Approximately one-third of patients with a 3-year follow-up developed a bilateral disease. Our findings warrant further large-scale investigation.

[Densiron-68 heavy silicone oil in cases of PVR. Anatomic and functional outcomes]. / Schweres Silikonöl bei PVR. Anatomische und funktionelle Ergebnisse.

PURPOSE: To evaluate the safety and efficacy of Densiron-68 heavy silicone oil in the clinical management of complex retinal detachments with proliferative vitreoretinopathy (PVR). METHODS: We present a prospective, interventional noncomparative case series of 80 eyes of 79 consecutive patients. The primary end point was anatomical reattachment of the retina, defined as retinal reattachment in the absence of any tamponade agent. The secondary end point was to record the visual function and surgical complications. Inclusion criteria were PVR stages B-CA4, including posterior or inferior retinal breaks and the patient's inability to posture. RESULTS: Patients were 59.1 (+/-18.1) years old, male:female =48:32, R:L=40:40. Fifty-six patients (70%) had previous unsuccessful retinal surgery, and 24 (30%) received heavy silicone oil at their first procedure. The extent of the detachments was 2.46 quadrants (+/-0.83) with macular involvement in 49 cases (61%). Fifty-six (67.5%) patients achieved retinal reattachment with one retinal operation and no tamponade, 64 (80%) achieved retinal reattachment with more than one operation and no tamponade, and 72 (90%) achieved a flat retina with tamponade in situ. Visual acuity rose from 1.48 LogMar (+/-0.91) to 1.12 (+/-0.82; p=0.009). Densiron was removed after 126 days (+/-55.1). CONCLUSION: The treatment of PVR remains challenging. No tamponade agent can provide simultaneous support for the superior as well as the inferior retina; therefore, a tamponade agent that "sinks" is a welcome new tool for the surgeon. We regard the use of heavy as well as conventional silicone oil as complementary to each other.

Observational prospective study of the effectiveness in routine clinical practice of verteporfin photodynamic therapy in patients with neovascular age-related macular degeneration.

AIMS: To investigate effectiveness in routine clinical practice of verteporfin photodynamic therapy (PDT) for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: Patients commencing PDT for nAMD in a single UK centre entered a prospective observational 7-year study and were followed for 2 years. Best-corrected visual acuity (BCVA) and contrast sensitivity (CS) were measured at each visit by accredited technicians after full protocol refraction on standardised charts. Reasons for failure to complete the course of therapy were documented. RESULTS: 1008 patients entered the study between 1999 and 2006. 81% and 52% completed 12 and 24 months' follow-up respectively (excluding administrative censoring). Results at 12 and 24 months respectively were: maintenance of BCVA 62%, 63%; drop in mean BCVA (letters) 10.1, 9.4; numbers of treatments 2.9, 3.5. The mean CS remained stable. No correlation of change in BCVA outcome between first and second treated eyes in 82 bilateral cases was detected. Loss to follow-up was significantly associated with age, CS and distance from the treating centre. CONCLUSIONS: PDT delivered in clinical practice is at least as effective as that reported in randomised clinical trials and uses fewer treatments.

Cytomegalovirus retinitis in the absence of HIV or immunosuppression.

PURPOSE: Cytomegalovirus (CMV) retinitis classically occurs in advanced human immunodeficiencyvirus (HIV) infection but is rare in other forms of immunosuppression. The authors report a case of CMV retinitis in an HIV-negative man with idiopathic CD4 lymphocytopenia (ICL). This is the first such case to be confirmed by polymerase chain reaction (PCR) of aqueous humor. METHODS: Case report. RESULTS: A 69-year-old retired Chinese seaman presented with gradual visual deterioration. He was a diet controlled diabetic on regular steroids for presumed asthma. Examination showed no diabetic eye disease but confirmed acute retinal necrosis (ARN). Anterior chamber tapping of the aqueous humor was PCR positive for CMV. HIV antibody and RNA tests were negative but his full blood count revealed lymphocytopenia, with a low CD4+ subset. He responded to a 3-week course of intravenous ganciclovir therapy followed by suppressiveoral valganciclovir. CONCLUSIONS: CMV is associated with sight-threatening retinitis in HIV infection at CD4+ counts below 50 cells/microL and in transplant recipients or heavily immunosuppressed patients. Systemic steroids are a risk factor for clinical disease in these groups. It is extremely rare to report CMV eye disease in previously healthy individuals. This case illustrates that the condition does occur in association with ICL. Corticosteroids may be implicated in disease reactivation. Molecular METHODS are necessary to confirm the diagnosis.

Primary vitrectomy with Densiron-68 for rhegmatogenous retinal detachment.

BACKGROUND: To report a retrospective non-comparative interventional study on the effectiveness and ocular tolerance of a heavy silicone oil tamponade (HSO, Densiron-68) for primary inferior rhegmatogenous retinal detachment (RRD). METHODS: Forty-one eyes of 41 consecutive patients were recruited between January 2004 and August 2006. Primary vitrectomy with Densiron-68, a heavy silicone oil, was used in all cases. Inclusion criteria were primary RRD with at least one retinal break between 4 and 8 clock hours. The study protocol consisted of a minimum of eight clinic visits: baseline, surgery, 1 week, 1 month and 3 months after the initial surgery; removal of oil and 1 week, 1 month and 3 months postoperatively. The primary endpoint was anatomical re-attachment of the retina. Cases were judged successful when there was reattachment of the retina in the absence of any tamponade agent. The secondary endpoint was to record the visual function and any complications arising from the surgery. Out of 41 patients initially included in the study, 33 completed all follow-up visits. RESULTS: Anatomical success was achieved in 91% of cases (30 out of 33) with one retinal operation, and rose to 94% (31 out of 33) with additional surgery. Mean visual acuity improved from logMAR 1.19 (SD 0.9) to 0.5 (SD 0.51, p = 0.001). No significant ocular hypertension, clinically significant emulsification of the tamponade or inflammation developed during follow-up. CONCLUSION: With Densiron-68, high anatomical and functional success rates can be achieved with primary vitrectomy for RRD and predominantly inferior pathology.

Heavy tamponade 2 Densiron 68 in routine clinical practice: anatomical and functional outcomes of a consecutive case series.

PURPOSE: To evaluate the safety and efficacy of Densiron 68 in the clinical management of complex vitreoretinal cases with inferior retinal pathology. METHODS: We present a prospective interventional non-comparative case series of 122 eyes of 121 consecutive patients. The primary end point was anatomical re-attachment of the retina, defined as retinal re-attachment in the absence of any tamponade agent. The secondary end point was to record the visual function and surgical complications. Inclusion criteria were proliferative vitreoretinopathy, posterior or inferior retinal breaks, and the patient's inability to posture. RESULTS: Patients were 59.9 years (+/- 19.6), (m/f= 72:49), (R/L=65:57). Seventy-seven (63.1%) had previous unsuccessful retinal surgery and 45 had Densiron 68 at first procedure. The extent of the detachments was 2.21 quadrants (+/- 1.07) with macular involvement in 66 cases (54%). Eighty-seven (71.3%) patients achieved retinal re-attachment with one retinal operation and ultimately no tamponade, 102 (83.6%) achieved retinal re-attachment with more than one operation and ultimately no tamponade, and 112 (91.3%) patients achieved flat retina with tamponade in situ. Visual acuity rose from 1.38 LogMar (+/- 0.87) to 1.06 (+/- 0.83) (P=0.007). Densiron was removed after 135 days (+/- 73.2; range 35-405). CONCLUSION: No tamponade agent can provide simultaneous support for the superior as well as the inferior retina; therefore, a tamponade agent that 'sinks' is a welcome new tool at the surgeon's disposal. The sequential use of heavy silicone oil followed by conventional silicone oil may be an acceptable management strategy in recurrent detachment.

Peel and peel again.

AIM: To determine if the internal limiting membrane (ILM) was present in the epiretinal membrane (ERM) when we deliberately tried to perform a "double peel" for macular pucker. METHODS: Pars-plana vitrectomy and a "double peel" were carried out. The ERM and ILM were stained with Trypan Blue and peeled separately over the same area. The amount of ERM present in ILM specimens and the amount of ILM present in ERM specimens were evaluated by histological examination. RESULTS: Seventeen eyes in 17 patients were included. It was possible to double peel in all cases. Five of 17 ERM specimens (29%) contained ILM fragments. When ILM was present on the ERM, it represented less than 50% of the sample. One ILM specimen was lost as result of an administrative error; of the remaining 16 specimens, residual ERM was found in six, and cellular remnants were observed on the vitreous surface in a further six of the ILMs. Clinically, no recurrence of ERM was found. CONCLUSION: ILM was present in some ERM specimens seemingly over the same area that an intact ILM was subsequently peel. We speculate that the ILM in the ERM represent a secondary basement membrane and that the surgical plane of dissection for most ERM peel is between the ERM and the native ILM, making it feasible to double peel routinely.

Interpreting nitrogen pollution thresholds for sensitive habitats: the importance of concentration versus dose.

Nitrate and ammonium concentration in wet deposition detrimentally impacted a sensitive pollution indicator species irrespective of the nitrogen dose.

Outpatient follow up appointments; are we using the resources effectively?

OBJECTIVE: British Association of Urological Surgeons (BAUS) guidelines and government initiatives have put pressure on the effective use of outpatient resources. Follow up appointments need to be carefully managed to ensure efficient use of available resources. The aim of this study was to audit outpatient follow up service with particular attention to the appropriateness of the appointments made. METHODS: All patients attending a general urology clinic were assessed by a form completed for each individual appointment. The source of the appointment and the time interval was recorded and each follow up appointment was judged to be either appropriate or inappropriate by the person giving the consultation. For those deemed to be inappropriate, justification was sought and the notes independently reviewed by a different clinician to verify this categorisation. RESULTS: Of 164 appointments made, 143 patients attended for follow up. A total of 131 appointments were considered to be appropriate (92%) with only 12 deemed by the consulting clinician to be inappropriate (8%). The commonest cause for an inappropriate appointment was failure to appreciate that follow up had already been arranged for a different date. There was no correlation between the source of the referral and an inappropriate referral. CONCLUSION: This audit suggests an effective use of the outpatient follow up resource with respect to the appropriateness and timing of follow up consultations. Other areas of resource management such as default rates should be investigated in an attempt to improve the efficiency of a service.

A pilot study on the use of a perfluorohexyloctane/silicone oil solution as a heavier than water internal tamponade agent.

AIMS: To report a prospective two centred non-comparative interventional pilot study of a solution of perfluorohexyloctane and silicone oil (Densiron-68) as a heavier than water internal tamponade. METHODS: 42 consecutive patients were recruited. The indications include proliferative vitreoretinopathy, retinal detachments arising from inferior retinal breaks, and inability to posture. RESULTS: The success rate with one operation using Densiron was 81% and with further surgery 93%. At the end of the study all tamponade agents were removed in 90% of patients. Visual acuity improved from mean logMAR of 1.41 (SD 0.64) to 0.94 (SD 0.57), p = 0.001. There was little evidence of dispersion and excessive inflammation. CONCLUSION: This new tamponade agent is being compared to conventional silicone oil in a prospective international randomised trial.

Visual loss following removal of intraocular silicone oil.

AIM: To investigate the cause of visual loss following removal of intraocular silicone oil in patients who underwent vitrectomies for retinal detachment or giant retinal tear. METHODS: The clinical records of three cases with visual loss following removal of silicone oil were reviewed. Investigations carried out included fundus fluorescein angiogram, optical coherence tomography, and electrophysiological studies. RESULTS: Visual acuities dropped from 6/9 to 6/36 in two cases and 6/24 to 3/24 in the third. None of the three cases had macula detachment at any stage. Fundus fluorescein angiogram and optical coherence tomography were normal in all cases. Pattern electroretinogram showed reduced amplitudes of the P50 and N95 components. Multifocal electroretinogram indicated a selective damage to the central part of the macula. CONCLUSIONS: The results suggest that the abnormality arises predominantly in the central part of the macula, especially the outer and middle layers. However, the exact mechanism still remains obscure.

Environmental changes in the North Atlantic Region: SCANNET as a collaborative approach for documenting, understanding and predicting changes.

The lands surrounding the North Atlantic Region (the SCANNET Region) cover a wide range of climate regimes, physical environments and availability of natural resources. Except in the extreme North, they have supported human populations and various cultures since at least the end of the last ice age. However, the region is also important at a wider geographical scale in that it influences the global climate and supports animals that migrate between the Arctic and all the other continents of the world. Climate, environment and land use in the region are changing rapidly and projections suggest that global warming will be amplified there while increasing land use might dramatically reduce the remaining wilderness areas. Because much of the region is sparsely populated--if populated at all--observational records of past environmental changes and their impacts are both few and of short duration. However, it is becoming very important to record the changes that are now in progress, to understand the drivers of these changes, and to predict future consequences of the changes. To facilitate research into understanding impacts of global change on the lands of the North Atlantic Regions, and also to monitor changes in real time, an EU-funded network of research sites and infrastructures was formed in 2000: this was called SCANNET--SCANdinavian/North European NETwork of Terrestrial Field Bases. SCANNET currently consists of 9 core sites and 5 sites within local networks that together cover the broad range of current climate and predicted change in the region. Climate observations are well replicated across the network, whereas each site has tended to select particular environmental and ecological subjects for intensive observation. This provides diversity of both subject coverage and expertise. In this paper, we summarize the findings of SCANNET to-date and outline its information bases in order to increase awareness of data on environmental change in the North Atlantic Region. We also identify important gaps in our understanding and identify where the roles of existing infrastructures and activities represented by SCANNET can facilitate future research, monitoring and ground-truthing activities.