Long-term control of choroidal neovascularization in quiescent congenital toxoplasma retinochoroiditis with photodynamic therapy: 4-year results

Purpose To evaluate the efficacy and safety of photodynamic therapy (PDT) in the long-term control of subfoveal choroidal neovascularization (CNV) associated with toxoplasmic retinochoroiditis. Methods The records of 13 patients with classic subfoveal CNV associated with toxoplasmic retinochoroiditis treated with PDT were reviewed. All patients were followed up for at least 48 months. Postoperative visual acuity was defined as a gain or loss of two or more lines of best-corrected visual acuity (BCVA), respectively. Post-treatment CNV size was dichotomized into “increased” if the major CNV diameter (CMD) had increased by ≥300 μm, and as “stable/reduced” if it had decreased by ≥300 μm or had not changed by >300 μm. Results Nine patients [four males (44.4%) and five females (55.6%)] with a mean age of 20.1 ± 4.3 years (range 14–27 years) were enrolled in the study. All had unilateral involvement. The median follow-up was 55 months (minimum 48, maximum 65 months). At the 48-month follow-up, all patients had stable/improved BCVA and a mean stable/reduced CMD (846 ± 326.5 μm), with the BCVA having improved significantly (p < 0.0001) from 0.29 ± 0.19 at baseline to 0.54 ± 0.16 at 48 months. Conclusion Photodynamic therapy seems to be a safe and effective approach to the long-term control of subfoveal CNV associated with toxoplasmic retinochoroiditis. Further trials are needed to validate these findings.     

Smoking in Italy 2005-2006: effects of a comprehensive National Tobacco Regulation

OBJECTIVE: On 10 January 2005 Italy became the first large European country adopting a comprehensive smoke-free legislation. We provide information on smoking prevalence in Italy and evaluate the effects of the 2005 regulations. METHODS: We considered data from three companion surveys on smoking, conducted in 2004, 2005 and 2006 in Italy. Each survey included more than 3000 subjects aged 15 years or over, representative of the general Italian adult population. RESULTS: Current smokers declined from 26.2% (30.0% of men, 22.5% of women) in 2004, to 25.6% (29.3% of men, 22.2% of women) in 2005 and to 24.3% (28.6% of men, 20.3% of women) in 2006. Whereas no significant difference was found comparing smoking prevalence in 2003-2004 vs. 2001-2002, the drop in smoking prevalence in 2005-2006 vs. 2003-2004 was significant (p<0.05) in the total population, in men and in subjects aged 15-44 years. Smokers consumed a mean of 15.4 cigarettes per day in 2004, 14.6 in 2005 and 13.9 cigarettes per day in 2006. Italians reported to go more frequently to restaurants and cafes. CONCLUSION: The drop in smoking prevalence and consumption is due, at least in part and particularly for younger generations, to the comprehensive smoke-free legislation adopted in Italy.     

Type-2 hepatorenal syndrome and refractory ascites: role of transjugular intrahepatic portosystemic stent-shunt in eighteen patients with advanced cirrhosis awaiting orthotopic liver transplantation

BACKGROUND/AIMS: TIPS (transjugular intrahepatic portosystemic stent-shunt) has been used increasingly in the management of refractory variceal bleeding. Its role in the management of refractory ascites and hepatorenal syndrome still awaits further prospective studies. Type-2 hepatorenal syndrome is a moderate steady renal impairment. It arises spontaneously and it is the main mechanism of refractory ascites. Precipitating factors may lead to type-1 hepatorenal syndrome. Hepatorenal syndrome is a common complication of advanced cirrhosis with a 3-month mortality of more than 90% unless treated by orthotopic liver transplantation. However, because of the short survival of patients with hepatorenal syndrome and the limited availability of organs, only a small percentage of patients with hepatorenal syndrome can actually reach orthotopic liver transplantation. That is why awaiting orthotopic liver transplantation we have submitted some suitable patients to a TIPS setting. METHODOLOGY: We have considered eighteen consecutive patients affected by advanced cirrhosis (Child-Pugh 10-12) awaiting orthotopic liver transplantation and suitable for TIPS treatment for the presence of type-2 hepatorenal syndrome (10 males, average age 44.5). The criteria for the diagnosis of hepatorenal syndrome and refractory ascites have been effected according to a consensus recommendation. Organic kidney disease was excluded. After mild intravenous sedation and analgesia a puncture needle was advanced transjugular in a catheter through the inferior cava into one of the three hepatic veins. Subsequently, an intrahepatic branch of the portal vein was punctured and the shunt was established by the implantation of Wallstent (diameter 10 mm; Boston, Scientific, Natick, MA). In all patients, we compared serum creatinine, creatinine-clearance, sodium excretion and urine volume before the intervention and 12 weeks after TIPS. The differences among groups were analyzed using paired Student's t-test. RESULTS: The stent shunt was successfully established in all eighteen patients. Complications occurred in 4 patients (temperature above 38 degrees C or vomiting). No patients have developed hepatic encephalopathy resistant to medical treatment. As for the ascites a complete response with total remission of ascites was obtained in eight patients, while a partial response with the presence of sonographically detectable ascites--without the need of paracentesis--was obtained in ten patients. As regards renal functional parameters we have evidenced a significant improvement after TIPS. CONCLUSIONS: We can notice how the setting of TIPS, at least in the presented case, has allowed the treatment of ascites and, furthermore, has lead to improvement of the renal functional parameters. It all implies the enormous advantage of a better management of the patient waiting for orthotopic liver transplantation and, most of all, the advantage of preparing the patient for the surgical intervention with normal renal functional parameters: in fact, it is well known that the increase of serum creatinine influences the pre- and post-orthotopic liver transplantation course, and in particular can modify the mortality rate of the patient list. The lack of effective alternative treatment modalities and the almost universally fatal outcome of hepatorenal syndrome make TIPS an attractive option in the treatment of hepatorenal syndrome as a bridge to orthotopic liver transplantation.     

Effect of Sildenafil on Reperfusion Function,Infarct Size,and Cyclic Nucleotide Levels in the Isolated Rat Heart Model

We have previously shown that NO-donor induced elevation in myocardial cGMP levels is associated with improved reperfusion function of the isolated rat heart. The phosphodiesterase 5 (PDE 5) inhibitor, sildenafil could potentially increase myocardial cGMP levels and thus protect the heart against ischaemic/reperfusion injury.Methods: To test our hypothesis we treated the isolated working rat heart with vehicle, OR sildenafil (10, 20, 50, 100, 200 nM), OR sildenafil (50 nM) plus a sarcolemmal (HMR 1098) or a mitochondrial (5-Hydroxydecanoate (5-HD)) K_ATP channel blocker. Hearts were then subjected to 20 min global, or 35 min regional ischaemia at 37C before reperfusion function (aortic output, coronary flow and aortic pressure) and infarct size were documented. Pre-ischaemic, ischaemic and reperfusion myocardial cAMP and cGMP concentrations were determined.Results: Low concentrations of sildenafil (10, 20 and 50 nM) improved reperfusion aortic output (AO) recovery (61.4± 4.5%, 64.8 ± 5.2% and 62.3 ± 5.0% vs. 45.4 ± 3.8% for controls (p < 0.05)) and infarct size, while high concentrations (200 nM) worsened AO recovery (24.9 ± 4.9.0%, p < 0.05). Myocardial cGMP levels of ischaemic tissue were elevated (34.7 ± 2.4 vs. 27.3 ± 2.2 pmol/g ww) and cAMP levels were suppressed (0.59 ± 0.03 vs. 0.87 ± 0.06 nmol/g ww) in the sildenafil (50 nM) treated hearts. Co-perfusion with sildenafil plus HMR 1098 decreased AO recovery (21.7 ± 7.6% vs. 62.3 ± 5.0% for sildenafil alone, p < 0.05) and increased infarct size (29.7 ± 2.04% vs. 8.6 ± 2.39% for sildenafil alone, p < 0.05).Similarly, sildenafil plus 5-HD decreased reperfusion AO recovery (44.4 ± 6.0% vs. 62.3 ± 5.0% for sildenafil alone, p < 0.05) and increased infarct size (33.8 ± 1.62% vs. 8.6 ± 2.39% for sildenafil alone, p < 0.05).Conclusions: (1) Pretreatment with low concentrations of sildenafil (20–50 nM) improves, while higher concentrations (200 nM) worsen reperfusion function in this model. (2) Low concentrations of sildenafil (20–50 nM) decrease infarct size while the higher concentrations had no effect. (3) These protective properties of low concentrations of sildenafil may be related to its cGMP elevating and cAMP suppressing effects in the ischaemic heart. (4) Possible end-effectors for sildenafil in the ischaemic heart include the mitochondrial and sarcolemmal K_ATP channel.     

Influence of the ischemic coronary bed on collateral blood flow

Summary The purpose of this study was to determine the influence of the resistance of the terminal vascular bed of an occluded coronary artery on collateral blood flow and collateral resistance. In 6 anesthetized dogs, left anterior descending coronary artery (LAD) was ligated, cannulated, and the terminal vascular bed was occluded by latex microspheres (diameter: 25). Retrograde flow was measured using a new technique, which allowed control of outflow pressure of retrograde flow (PRF) at the LAD cannula. When retrograde flow was interrupted, pressure in the occluded vessel represented collateral perfusion pressure (CPP) within the border zone of the ischemic vessel. Collateral resistance was determined dividing the pressure difference across the collateral bed (CPP-PRF) by retrograde flow. Variation of PRF was used as a model for changes in resistance of the ischemic bed. Retrograde flow fell when PRF was increased from 11.0±3.0 ml×min^–1×100 g^–1 (PRF=0) to 8.3±2.4 (p<0.01) (PRF=24.6±6 mm Hg). For the same PRF range, collateral resistance fell from 9.68±2.96 to 8.30±2.50 mm Hg×ml^–1×min×100 g (p<0.01). These results indicate that the vascular resistance of the terminal ischemic bed may considerably influence collateral blood flow and resistance.This study was supported in part by DFG grant Er 100/3-1     

Hepatitis B virus vaccine in chronic kidney disease: Improved immunogenicity by adjuvants? A meta-analysis of randomized trials

Background

Patients with chronic kidney disease typically show an impaired immune response to hepatitis B virus vaccine compared with healthy individuals. A variety of inherited or acquired factors have been implicated in this diminished response. Some authors suggested a benefit with adjuvantation to improve the immunogenicity of existing HBV vaccines.

Aim

To evaluate the efficacy and safety of adjuvantation for hepatitis B virus vaccine in patients with chronic kidney disease.

Methods

Only prospective, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird with heterogeneity and subgroups analyses. The primary end-point of interest was the seroprotection rate after HBV vaccination with recombinant vaccine plus adjuvants (study group) versus recombinant vaccine alone (control group).

Results

We identified ten studies involving 1228 unique patients with chronic kidney disease. Pooling of study results did not show a significant increase in seroprotection rate among study (HBV recombinant vaccine plus adjuvants) versus control (HBV recombinant alone) patients; the pooled odds ratio of seroprotection rate was 1.47 (95% CI: 0.88; 2.46, NS). The pooled OR for seroresponse rate after HBV vaccine (adjuvanted recombinant vaccine versus recombinant vaccine alone) did not change in the subgroup of studies based on novel adjuvant systems (i.e., HBV-AS04 or HBV-AS02), the pooled OR was 2.22 (95% CI, 0.72; 6.78), NS. Q-test for heterogeneity being 10.819 (P = 0.004).

Conclusions

Our meta-analysis showed that adjuvanted hepatitis B vaccine did not significantly improve the seroprotection rate in patients with renal insufficiency. These results do not support adjuvantation as an approach to increase the immunogenicity of existing recombinant vaccines towards HBV in this high-risk population.