Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model

PURPOSE: To investigate the morphologic and functional effects of verteporfin ciliary body photodynamic therapy (PDT) in a murine glaucoma model and normal mouse eyes. METHODS: A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57BL/6) were used in the study. Verteporfin was injected intravenously at doses of 1.0 (DBA/2J) or 2.0 or 4.0 (C57BL/6) mg/kg. Transscleral irradiation of the ciliary body was performed with light at a wavelength of 689 nm delivered through an optical fiber, with irradiance of 1800 mW/cm2 and fluence of 100 J/cm2. Laser irradiation was applied for 360 degrees of the corneoscleral limbus in C57BL/6 normal mice and for 180 degrees in DBA/2J mice. Retreatment was performed in C57BL/6 normal mice that had been treated with 2.0 mg/kg of verteporfin at post-PDT day 7. One eye of each animal was treated, and the fellow eye served as the control. The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy. The IOP was measured using an applanation tonometer with a fiber-optic pressure sensor. Surviving retinal ganglion cells (RGCs) in DBA/2J mice eyes were retrogradely labeled with a neurotracer dye at 12 weeks after PDT. RESULTS: In all groups, almost all ciliary body blood vessels in the treated area were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT. The mean IOP in treated eyes was significantly reduced compared with that in the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, although the mean IOP in normal mouse eyes treated with 2 or 4.0 mg/kg verteporfin returned to the level of the fellow control eyes by 7 and 17 days after treatment, respectively. The mean number of RGCs in the DBA/2J treated eyes was significantly higher than in control eyes. CONCLUSIONS: Ciliary body PDT resulted in morphologic changes in the ciliary body, significant reduction of IOP, and prevention of ganglion cell loss in a mouse glaucoma model. These results suggest that ciliary body PDT is a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma.     

Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure

Purpose of the study was to investigate whether short-term atorvastatin treatment improves endothelial function and affects inflammatory process in patients with heart failure (HF) and normal cholesterol levels. HF is characterized by endothelial dysfunction and increased inflammatory process, while statins restore endothelial function having also anti-inflammatory effects in hypercholesterolemic patients. We investigated the effect of 4-week atorvastatin treatment (10 mg/day) on endothelial function and inflammatory markers in patients with HF and cholesterol levels <220 mg/dl. Patients were randomly allocated into groups and received atorvastatin (n=19) or no statin (n=19). Forearm blood flow was measured using gauge-strain plethysmography. Serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule (sVCAM-1) were determined with ELISA. Data are expressed as median [25th-75th percentile]. Forearm vasodilatory response to reactive hyperemia was significantly improved in atorvastatin-treated patients (from 38.1% [32.0-59.1] to 70.0% [61.1-106.3], P<0.01), while it remained unaffected in the control group. Levels of IL-6, TNF-alpha and sVCAM-1 were decreased in atorvastatin-treated group (from 7.8 pg/ml [4.8-9.5], 3.2 pg/ml [2.7-4.8] and 595 ng/ml [440-810] to 5.6 pg/ml [2.5-9.0], 2.8 pg/ml [2.0-3.6] and 289 ng/ml [169-368], respectively, P<0.05 for all) but not in the control group. These findings indicate that atorvastatin may improve forearm vasodilatory response to reactive hyperemia and depress inflammatory process in patients with heart failure and normal baseline cholesterol levels.     

Direct assessment of adherence and drug interactions in patients with hypertensive crisis—A cross‐sectional study in the Emergency Department

Though drug adherence is supposed to be low in hypertensive crisis (HTN‐C), there are no data available from direct adherence assessments. The aim of the present study was to evaluate adherence to prescribed antihypertensives and potential interactions of concomitant drugs and foods with prescribed antihypertensives in patients with HTN‐C by a direct evaluation via biochemical urine analysis. In the present cross‐sectional study, 100 patients with HTN‐C, admitted to the emergency department (ED), were included. A biochemical urine analysis using gas chromatography‐tandem mass spectrometry was performed. Out of 100 patients, 86 received antihypertensives. Urine analyses could be evaluated unambiguously in 62 patients. In 15 of these 62 patients (24%), a nonadherence could be demonstrated, and in 21 patients (34%), a partial nonadherence could be demonstrated. Patients with nonadherence or partial nonadherence showed a longer hypertension history (15[5‐22] vs 10[3‐15] years, P = 0.04) were prescribed more general medication (number 7.1 ± 3.4 vs 3.4 ± 1.8; P < 0.01) as well as antihypertensive drugs (number 2.8 ± 1.1 vs 1.5 ± 0.7, P < 0.01). A potential BP‐raising trigger by medications or food interaction was frequently detectable, predominantly with nonsteroidal anti‐inflammatory drugs (NSAIDs; n = 38), glucocorticoids (n = 8), antidepressants (n = 10), and licorice (n = 10). Nonadherence and partial nonadherence to prescribed antihypertensives might play a crucial role for the occurrence of HTN‐C. However, further case‐controlled studies are needed to confirm the present findings. Ingestion of concurrent over‐the‐counter drugs such as NSAIDs but also prescribed drugs as well as aliments may lead to critical BP elevation. In order to prevent HTN‐C, the present findings emphasize the importance for clinicians to pay attention to the issue of adherence and co‐medication.     

Emergency ultrasound of the scrotum: a review of the commonest pathologic conditions

Ultrasound is the first imaging modality to be performed in emergency conditions of the scrotum. The commonest pathologic entities are divided into the 4 following groups: torsion, trauma, infection, and tumors. Sonographic examination should be performed as soon as possible to ensure fast diagnosis and treatment. Less acute conditions can also be noted while scanning on an emergency basis, such as anatomic variants, hydrocele, oscheocele, clinically evident varicocele, calcifications, etc. Although not threatening for scrotal integrity, they should be assessed during an emergency examination or later on. In this article, complex scrotal anatomy is reviewed and the basic examination technique is described. The commonest emergency conditions are analyzed, along with their pathophysiological basis. Nonemergent entities are also briefly mentioned. Ultrasound images of the commonest emergency conditions are demonstrated.     

MDCT angiography assessment of renal artery in-stent restenosis: Can we reduce the radiation exposure burden? A feasibility study

Aim

We explored the feasibility of renal artery multidetector computed tomography (MDCT) and detection of in-stent restenosis at low exposure settings.

Patients/methods

Sixteen patients with 19 renal artery stents underwent CT angiography. A biphasic protocol was performed including arteriographic acquisition at standard 120 kVp and a late-arterial scan at 100 kVp (n = 9) or 80 kVp (n = 7). Images were reconstructed under various algorithms. Signal-to-noise and contrast-to-noise ratios (SNR, CNR) were determined within stent, aorta and renal arteries. Image quality and the presence of restenosis were assessed. Volume CT dose-index was recorded and dose reduction (DR%) between phases was calculated.

Results

Ten patients presented with Hounsfield values >250 HU in all segments, phases and reconstructions and were further evaluated. The 120 kVp protocol performed better in all vessels and reconstruction algorithms. SNR at 120 kVp (B31f) did not differ significantly compared to 100 kVp (B31f). CNR within stent was borderline compromised at 100 kVp (p = 0.042). All but two image sets (at 80 kVp) were considered diagnostic. Minor loss of subjective image quality was noticed at 100 kVp. No difference in assessment of restenosis was observed between 120 kVp and the diagnostic low-exposure scans. Mean DR% was estimated 45% at 100 kVp and 77% at 80 kVp.

Conclusions

Renal MDCT angiography and stent-restenosis assessment are feasible at 100 kVp with minor loss of image quality and almost half radiation exposure.     

Investigation of the influence of gastric acid on the surface roughness of ceramic materials of metal-ceramic restorations. An in vitro study

The rehabilitation of eroded teeth in patients suffering from bulimia nervosa generally includes ceramics. This study compared the roughness of three ceramics before and after exposure to simulated vomit solution (SVS) with a pH of 3.8. Surface roughness parameters Ra, RMS, and AH were calculated using atomic force microscopy before and after exposure to SVS (novel peristaltic pump for 24 hours at 37°C) and were analyzed statistically. Apart from the initial high AH values of the glass-ceramic, none of the parameters evaluated were statistically significantly different after acid exposure. Under the limitations of this in vitro study, the investigated ceramics seem suitable for use in bulimia nervosa patients.     

R0 Liver Resections for Primary Malignant Liver Tumors in the Noncirrhotic Liver: A Diagnosis-Related Analysis

Background Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. Results Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. Conclusions R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.     

Periodic Therapeutic Plasma Exchange in Patients With Moderate to Severe Chronic Myasthenia Gravis Non‐Responsive to Immunosuppressive Agents: An Eight Year Follow‐Up

Few patients with moderate or severe myasthenia gravis (MG) do not respond to immunosuppressive treatment. We present our experience with periodic therapeutic plasma exchange (TPE), in 11 patients with MG resistant to intravenous immunoglobulin (IVIg) therapy, who had frequent relapses even whilst on high doses of immunosuppressive drugs, over a period of 8 years. All patients underwent TPE until control of their symptoms was achieved, and afterwards TPE sessions were continued periodically in an attempt to achieve remission of the disease, without immunosuppressant therapy. Two of the patients were progressively weaned off immunosuppressive agents, as well as TPE, and they are now symptom free. The other nine patients are still under a periodic TPE regime. Seven of them were weaned off all medications and required an average of 3.7 TPE sessions per year during the last 5 years. In the other two patients, those with the most severe form of the disease, the immunosuppressant dosage has been decreased and a TPE session every 2–3 weeks is required in order to control their symptoms. Through all these years TPE has been well tolerated and only minor side‐effects were observed in two patients. Finally, during this 8 year follow‐up period, nine of the patients treated with periodic TPE have been in good control of their symptoms over the last 5 years, and the other two patients live a normal life without any treatment in the last 3 years. Our results suggest that periodic TPE is safe and effective in the control of symptoms in patients with moderate to severe MG who do not respond to immunosuppressive therapies.