The role of serum visfatin and vaspin in hepatocellular carcinoma in hepatitis C-related liver cirrhosis.

Aim of the study: To investigate the role of the novel adipokines visfatin and vaspin in hepatitis C virus (HCV)-cirrhotic patients with and without hepatocellular carcinoma (HCC) and their association with tumour characteristics and liver dysfunction. Material and methods: This case-control study was carried out between March 2021 and September 2021. Serum visfatin and vaspin were measured in 67 HCV-cirrhotic patients (37 had HCC, and 30 did not) and 20 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results: Serum visfatin and vaspin were substantially elevated in HCC patients compared to those without HCC and healthy controls (p = 0.001, < 0.0001, respectively) and significantly associated with hepatic dysfunction. At a cut-off value of 12.1 ng/ml, the sensitivity and specificity of the serum visfatin in detecting HCC were 67.6% and 83.3%, respectively. Serum vaspin at a cut-off value of 321 ng/dl had a sensitivity of 94.6% and specificity of 66.7%. In multivariate regression analysis, serum vaspin and albumin were independent risk factors for HCC development. Patients with Barcelona Clinic Liver Cancer (BCLC) stage D had significantly the highest serum levels of visfatin and vaspin (p = 0.03, 0.008, respectively). Conclusions: Serum visfatin and vaspin were substantially higher in HCC patients, associated with tumour stage, and might be considered as potential biomarkers of HCC, but this should be confirmed in larger independent cohorts of patients with liver cirrhosis. Serum vaspin and albumin were independent risk factors for HCC development. There was a substantial association between visfatin, vaspin, and the severity of the underlying liver dysfunction.

Hepatitis D virus infection among hepatitis B virus surface antigen positive individuals in Upper Egypt: Prevalence and clinical features.

BACKGROUND/PURPOSE: About 248 million people are chronic HBV surface antigen carriers in the world. Hepatitis D virus (HDV) infection present in more than 15 million people worldwide. HDV needs hepatitis B surface antigen (HBsAg) to help its replication. We aimed to estimate the prevalence of HDV infection among HBsAg positive individuals and to determine the clinical, laboratory and virological characters of HDV infected patients. METHODS: This study was prospective cross-sectional analytic one including 186 HBsAg positive cases. Anti-HBc total, IgM and HBV PCR were done for all of these cases. Anti-HDV ELISA analysis was done for all cases. Positive samples for Anti-HDV by ELISA were then tested by HDV PCR. RESULTS: Of the 186 HBsAg positive cases, 80 were reactive for anti-HDV antibodies, resulting in an overall anti-HDV seropositivity of 43%. Higher prevalence of liver cirrhosis (43.8%), HCC on top of cirrhosis (8.8%) were found in anti-HDV positive compared to anti-HDV negative cases (17.9%) and (3.8%) respectively (p value<0.001). Portal hypertension and Child-Pugh grade B, C were significantly higher in anti-HDV-positive cases as compared to the anti-HDV-negative ones (47.5% versus 18.9%) and (11.3% versus 6.6%); (16.3% versus 3.8%) respectively (p value<0.001 for each). HDV RNA was positive in 25 out of 80 anti-HDV-positive cases (31.3%). CONCLUSION: Anti-HDV was seropositive in 43% among HBsAg positive cases in Upper Egypt. HDV RNA was positive by PCR in 25 out of 80 anti-HDV-positive cases (31.3%). HDV prevalence using PCR was 25/186 (13.4%) in Upper Egypt.

Prevalence and predictors of occult hepatitis C virus infection among Egyptian patients who achieved sustained virologic response to sofosbuvir/daclatasvir therapy: a multi-center study.

BACKGROUND: Occult hepatitis C virus (HCV) infection (OCI) is characterized by the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA or antibodies in the serum. In this study, we tried to evaluate the prevalence and possible predictors of OCI in patients who achieved sustained virologic response (SVR) post sofosbuvir/daclatasvir (SOF/DCV) therapy. PATIENTS AND METHODS: A cross-sectional multicenter study was designed to enroll 1,280 HCV-infected patients who received SOF (400 mg) plus DCV (60 mg) once daily ± ribavirin regimen for 12 weeks and achieved SVR 12 weeks post treatment. They were randomly recruited from three dedicated Egyptian centers for management of HCV. Real-time PCR was performed to detect HCV-RNA in serum and PBMCs and to evaluate the different risk factors pertaining to the existence of OCI. RESULTS: HCV-RNA was detected in PBMCs of 50 (3.9%) of them. All OCI cases exhibited significant fibrosis score and raised pre-treatment alanine aminotransferase (ALT) levels. Logistic regression analysis comparing OCI with non-OCI revealed that high pre-treatment viral load, raised ALT, advanced fibrosis score, prolonged prothrombin time, low albumin, Child B score, antiviral experienced patients, and raised bilirubin are the most significant predictor for the possibility of OCI presence with Odds Ratio as 7.03, 5.13, 4.4, 2.68, 2.52, 1.9, 1.5, and 1.2, respectively. CONCLUSION: In spite of its remote possibility, OCI post SOF/DCV therapy may be present in some cases, and this may entail a re-auditing for the definition of SVR by dual testing in both serum and PBMCs.

Efficacy of ombitasvir/paritaprevir/ritonavir/ribavirin in management of HCV genotype 4 and end-stage kidney disease.

BACKGROUND: Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation. AIM: To evaluate a real-life experience of the efficacy and safety of ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r plus RIB) in patients with end-stage kidney disease (ESKD). PATIENTS AND METHODS: Between January 2017 and January 2018, an open-label multicenter prospective study was designed to enroll all consecutive patients with proven CHC genotype 4 infections and concomitant ESKD based on estimated glomerular filtration rate (eGFR) with (HD group) or without hemodialysis (non-HD group). Patients were given a co-formula of OBV/PTV/r (25/150/100 mg) once-daily plus RIB was given for 12 weeks. Sustained virologic response (SVR 12) was the primary endpoint. RESULTS: A total of 110 patients were enrolled. An overall SVR 12 was reported in 104 (94.5%) patients, and treatment failure were reported in 6 patients [2 patients (1.8%) were relapsed, and 4 patients (3.6%) patients were non-responders]. SVR12 was 96% in HD and 91.4% in non-HD patients (P = 0.286). There were no reported serious adverse events. Anemia was reported in 66.6% (n = 50) in HD group and in 31.4% (n = 11) in non-HD group. CONCLUSION: Although it is still challenging, achievement of SVR12 in patients with chronic HCV and concomitant end-stage kidney disease in the era of DAAs became possible with a 12 weeks course of a co-formula of ombitasvir/paritaprevir /ritonavir plus ribavirin. CLINICALTRIALS. GOV ID: NCT03341988.

Effect of percutaneous and open tenotomy on continuity of tendoachillis in relapsed clubfoot

Background: Tenotomy of tendon Achilles is one of the major components of Ponseti method and necessary to complete correction in about 80 to 90 % of patients, it is safely procedure can be done in outpatient office as percutaneous technique under local anesthesia or in operative room under general anesthesia as mini-open technique. This study was designed to evaluate effect of tendoachillis tenotomy either percutaneous or open on continuity of tendoachillis by open evaluation in relapsed club foot. Patient & method: This study was conducted on 18 individuals. They were divided into 2 equal groups: Group I: containing 9 patients both sex had previously percutaneous tenotomy is done and Group II: 9 patients both sex had previously open tenotomy is done. Results: percutaneous technique found easy dissection in 6 patients (66.7%) and difficult dissection in 3 patients (33.3%) and continuity found central and regular contour in 7 patients (77.8%) and fibrotic mass in 2 patients (22.2%), open technique found easy dissection in 5 patients (55.6%) and difficult dissection in 4 patients (44.4%) and continuity found central and regular contour in 5 patients (55.6%) and fibrotic mass in 4 patients (44.4%), Conclusion: the techniques tenotomy of tendoachillis had no effect on continuity of tendoachillis either open or closed techniques in management of club foot

Serum Level of IL17a among Cirrhotic Hepatitis C Virus Infected Patients with Incidence of Diabetes Mellitus.

IL17a is the key inflammatory cytokine of TH17 and contributes to the pathogenesis of diabetes mellitus which is a common endocrine disorder associated with HCV infection. Herein, 183 cirrhotic HCV infected patients were screened for ANA by ELISA and positive cases (n=40) were screened for ICA by Immunofluorescence and IL17a serum levels were measured by ELISA and compared to a control group (n=24). Out of 40 cirrhotic HCV, ANA (+) infected patients, 16 patients (40 %) were type 2 diabetic and 13 (32.5%) were non-diabetic. On the other hand, 17 positive ICA (42.5%) and 23 negative ICA (57.5%) patients were reported. IL17a serum level was significantly elevated in cirrhotic HCV infected patients who were positive for ICA than negative ICA (P < 0.0001) and was significantly higher in type 2 diabetic than both non-diabetic patients (P=0.04) and controls (P=0.0005). In conclusion, IL17 serum levels were elevated in diabetic HCV infected patients.

Variceal bleeding in cirrhotic patients: What is the best prognostic score?

BACKGROUND/AIMS: To find the most accurate, suitable, and applicable scoring system for the prediction of outcome in cirrhotic patients with bleeding varices. MATERIALS AND METHODS: A prospective study was conducted comprising 120 cirrhotic patients with acute variceal bleeding who were admitted to Tropical Medicine and Gastroenterology Department in Sohag University Hospital, over a 1-year period (1/2015 to 1/2016). The clinical, laboratory, and endoscopic parameters were studied. Child-Turcotte-Pugh (CTP) classification score, Model for end-stage liver disease (MELD) score, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, and AIMS65 score were calculated for all patients. Univariate and multivariate analyses were performed for all the measured parameters and scores. RESULTS: Of the 120 patients (92 male) admitted during the study period, eight patients (6.67%) died in the hospital. Advanced age, the presence of encephalopathy, rebleeding, and higher serum bilirubin were independent factors associated with higher hospital mortality. The largest area under the receiver operator curve (AUROC) was obtained for the AIMS65 score and SOFA score, followed by the MELD score and APACHEII score, then CTP score, all of which achieved very good performance (AUROC>0.8). AIMS65 score showed the best sensitivity, specificity, and negative and positive predictive values. Although the AIMS65 score was not significantly different from the MELD, SOFA, and APACHEII scores, it was the optimum among them in terms of the prediction of mortality. CONCLUSION: AIMS65 score is the best simple and applicable scoring system for independently predicting mortality in cirrhotic patients with acute variceal bleeding.

The NADH:flavin oxidoreductase Nox from Rhodococcus erythropolis MI2 is the key enzyme of 4,4'-dithiodibutyric acid degradation.

The reduction of the disulphide bond is the initial catabolic step of the microbial degradation of the organic disulphide 4,4'-dithiodibutyric acid (DTDB). Previously, an NADH:flavin oxidoreductase from Rhodococcus erythropolis MI2 designated as NoxMI2 , which belongs to the old yellow enzyme (OYE) family, was identified. In the present study, it was proven that NoxMI2 has the ability to cleave the sulphur-sulphur bond in DTDB. In silico analysis revealed high sequence similarities to proteins of the flavin mononucleotide (FMN) reductase family identified in many strains of R. erythropolis. Therefore, nox was heterologously expressed in the pET23a(+) expression system using Escherichia coli strain BL21(DE3) pLysS, which effectively produces soluble active NoxMI2 . NoxMI2 showed a maximum specific activity (Vmax ) of 3·36 µmol min-1  mg-1 corresponding to a kcat of 2·5 s-1 and an apparent substrate Km of 0·6 mmol l-1 , when different DTDB concentrations were applied. No metal cofactors were required. Moreover, NoxMI2 had very low activity with other sulphur-containing compounds like 3,3'-dithiodipropionic acid (8·0%), 3,3'-thiodipropionic acid (7·6%) and 5,5'-dithiobis(2-nitrobenzoic acid) (8·0%). The UV/VIS spectrum of NoxMI2 revealed the presence of the cofactor FMN. Based on results obtained, NoxMI2 adds a new physiological substrate and mode of action to OYE members. SIGNIFICANCE AND IMPACT OF THE STUDY: It was unequivocally demonstrated in this study that an NADH:flavin oxidoreductase from Rhodococcus erythropolis MI2 (NoxMI2 ) is able to cleave the xenobiotic disulphide 4,4'-dithiodibutyric acid (DTDB) into two molecules of 4-mercaptobutyric acid (4MB) with concomitant consumption of NADH. NoxMI2 showed a high substrate specificity as well as high heat stability. This study provides the first detailed characterization of the initial cleavage of DTDB, which is considered as a promising polythioester precursor.

Wandering spleen in the pelvic region in an adult man with symptoms of acute abdomen.

UNLABELLED: Wandering or ectopic spleen is a condition characterised by migration of spleen in the abdomen or pelvis. This anomaly is rare, with a reported incidence of <0.2%. It occurs mostly in women between 20 and 40years of age. Clinical diagnosis is difficult because of lack of precise signs, symptoms, and nonspecific laboratory data. Diagnosis of a wandering spleen highly depends on the results of imaging studies such as abdominal ultrasound and abdominopelvic computed tomography (CT) scanning. Treatment includes surgery with the choice between splenopexy in a noninfarcted spleen and splenectomy when infarction has occurred. We report a rare case of wandering spleen in a 27-year-old man with infarction due to torsion of its pedicle, which was diagnosed by CT and treated by splenectomy. CONCLUSION: Despite the rarity of wandering spleen, the possibility of torsion of its long pedicle with acute splenic infarction should be considered in the differential diagnosis of acute abdomen.

Can eicosapentaenoic acid maintain the original ribavirin dose or affect the response during the treatment course of chronic hepatitis C virus (HCV) patients?

BACKGROUND/AIMS: Combination therapy with peginterferon (PEG-IFN) and ribavirin (RBV) has been recommended as a standard therapy for patients with chronic hepatitis C virus (HCV). Our aim was to evaluate the efficacy of eicosapentaenoic acid (EPA) against RBV-associated hemolytic anemia. MATERIALS AND METHODS: Two hundred and forty HCV patients included in the study were randomized to either the EPA group (n=120) or non-EPA group (n=120), and they received combination therapy with or without EPA. We compare changes in hemoglobin levels with RBV dose reduction rate in each group as well as treatment response. RESULTS: Of 120 patients randomized to receive combination therapy with EPA, 15/86 (17.5%) patients required RBV dose reduction, whereas 71/86 (82.5%) patients did not require RBV dose reduction; in the non-EPA group, 22/80 (27.5%) patients required RBV dose reduction and 58/80 (72.5%) patients did not require RBV dose reduction. There was no significant difference between the two groups in the rates of virologic response. CONCLUSION: EPA can decrease the rate of RBV dose reduction and RBV-induced hemolysis during the course of combination treatment. Further trials are required to investigate the role of EPA in the current regimens of HCV treatment that include ribavirin.

Incidence, causes, and outcomes of renal failure among cirrhotic patients.

BACKGROUND/AIMS: To evaluate the incidence, risk factors of RF among cirrhotic and its impact on patient's outcome. MATERIALS AND METHODS: A total of 573 cirrhotic patients were evaluated for renal failure (RF) and its causes, 212 patients (37%) were enrolled. RESULTS: Majority of the patients had post hepatitis C liver disease (n=190, 89.6%) with Child-Pugh score C (88.2%), HCC was in 21.2% of cases baseline characteristics. Infections were observed in 45.8% (n=97) of patients whereas, spontaneous bacterial peritonitis (SBP) was the most type of infection (19.3%) among cirrhotic patients with renal failure, followed by pneumonia (9.9%). Infection-induced represents 30.2% followed by hypovolemia (29.7%), whereas HRS was in 11.3%. Reversibility of the condition was seen in 81 patients (38.2%), whereas mortality was seen in 58 (27.4%) patients of RF. The reversibility was more common in the patients with infection, followed by hypovolemia. Mortality was higher in the patients with HRS followed by parenchymal renal disease. CONCLUSION: Infection-induced and hypovolemic-induced RF represent the most common and also the most correctable causes and must be considered in management protocols for early detection and treatment that will serve for a better prognosis.

Outcomes and predictors of in-hospital mortality among cirrhotic patients with non-variceal upper gastrointestinal bleeding in upper Egypt.

BACKGROUND/AIMS: Variceal bleeding is one of the most frequent causes of morbidity and mortality among cirrhotic patients. Clinical endoscopic features and outcomes of cirrhotic patients with non-variceal upper gastrointestinal bleeding (NVUGIB) have been rarely reported. Our aim is to identify treatment outcomes and predictors of in-hospital mortality among cirrhotic patients with non-variceal bleeding in Upper Egypt. MATERIALS AND METHODS: A prospective study of 93 cirrhotic patients with NVUGIB who were admitted to the Tropical Medicine and Gastroenterology Department, Assiut University Hospital (Assiut, Egypt) over a one-year period (November 2011 to October 2012). Clinical features, endoscopic findings, clinical outcomes, and in-hospital mortality rates were studied. Patient mortality during hospital stay was reported. Many independent risk factors of mortality were evaluated by means of univariate and multiple logistic regression analyses. RESULTS: Of 93 patients, 65.6% were male with a mean age of 53.3 years. The most frequent cause of bleeding was duodenal ulceration (26.9%). Endoscopic treatment was needed in 45.2% of patients, rebleeding occurred in 4.3%, and the in-hospital mortality was 14%. Hypovolemic shock was the most common cause of death (46.2%). Independent risk factors of in-hospital mortality among cirrhotic patients with NVUGIB in our study were bacterial infection during hospitalization [odds ratio (OR) =0.32, 95% confidence interval (CI) =0.03-0.89], shock (OR =1.12, 95% CI =0.68-1.54), early rebleeding (OR =2.26, 95% CI =1.85-3.21), low serum albumin (OR =3.81, 95% CI =2.35-4.67), low baseline hemoglobin (OR =0.714, 95% CI =0.32-1.24), and the need for endoscopic treatment (OR =2.96, 95% CI =0.62-3.63). CONCLUSION: Bacterial infection during hospitalization, shock, early rebleeding, low serum albumin, low baseline hemoglobin, and the need for endoscopic treatment were independent risk factors of in-hospital mortality among cirrhotic patients with NVUGIB in Upper Egypt.

Renal failure after upper-gastrointestinal bleeding among cirrhotic patients in Upper Egypt.

BACKGROUND AND STUDY AIMS: Renal dysfunction is a common and serious problem in patients with advanced liver disease. The study aims to assess the incidence, risk factors and short-term prognosis of renal failure after upper-gastrointestinal bleeding among cirrhotic patients in Upper Egypt. METHODS: We recruited 159 cirrhotic patients with 168 episodes of upper-gastrointestinal bleeding from Tropical Medicine and Gastroenterology Department, Assiut University Hospital. For all participants, the following were conducted: clinical evaluation, abdominal ultrasonography (US) examination, laboratory investigations and upper endoscopy. Risk factors of renal failure were identified using univariate, then multivariate analysis. RESULTS: The incidence of renal failure among bleeding episodes was 28%. Higher risk of renal failure among cirrhotic patients with upper-gastrointestinal bleeding was observed with shock (odds ratio (OR) 0.171, 95% confidence interval (CI) 0.047:0.624), bacterial infection (OR 0.310, 95% CI 107:897), Child-Pugh class C (OR 2.79, 95% CI 1.018:7.62), higher serum bilirubin (OR 0.122, 95% CI 0.000:0.002), lower serum albumin (OR -0.188, 95% CI -0.288:-0.056) and raised baseline blood urea (OR 0.181, 95% CI 0.003:0.017) and serum creatinine (OR 0.533, 95% CI 0.002:0.004). Mortality among patients with renal failure was 31.9%. CONCLUSION: Renal failure is a frequent event among cirrhotic patients with upper-gastrointestinal bleeding and there are many contributing factors for its development. Mortality is relatively high among patients with renal failure in cirrhotics with upper-gastrointestinal bleeding.

Clinical significance of elevated alpha-foetoprotein (AFP) in patients with chronic hepatitis C without hepatocellular carcinoma in upper EGYPT.

BACKGROUND AND STUDY AIMS: Egypt has the highest prevalence of hepatitis C in the world. Alpha-foetoprotein (AFP) is important in the diagnosis of hepatocellular carcinoma (HCC), but elevated AFP levels have also been observed in chronic hepatitis C (CHC) without HCC. We evaluated the clinical correlation between elevated AFP levels and CHC. We analysed data from a population-based cohort of patients with hepatitis C virus (HCV) infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. PATIENTS AND METHODS: From December 2009 to April 2011, 121 patients with no evidence of HCC with regular abdominal ultrasound or other imaging studies (multislice computed tomography (MSCT) or magnetic resonance imaging (MRI)) were controlled by a chart review. RESULTS: The prevalence of elevated AFP ≥10ngml(-1) was 11.6%. Univariate analysis revealed that fibrosis stage III/IV, alanine aminotransferase (ALT) more than 45IUl(-1) and platelet count less than 150×10(9) l(-1) were significantly associated with elevated AFP. Multivariate analysis revealed that the independent variable associated with elevated serum AFP was fibrosis stage III/IV, p=0.015. Multivariate analysis also revealed that AST>45IUl(-1) and AFP ≥10 ngml(-1) were associated with advanced fibrosis using a cut-off AFP value >10 ngml(-1). The sensitivity and specificity of diagnosing fibrosis score III/IV were 26.1% and 97.3%, respectively. CONCLUSIONS: Elevated AFP levels were observed in 11.65% of patients with CHC. Elevated AFP levels correlated positively with fibrosis stage III/IV; ALT elevation, thrombocytopenia and AFP ≥10 ngml(-1) were associated with advanced fibrosis.

Tibial angioplasty in diabetic patients: should all vessels be treated?

AIM: Patients with severe critical limb ischemia (CLI) due to tibial disease are commonly treated nowadays with tibial angioplasty. However, the benefits and complications of treating "more than one tibial vessel" have not yet been determined. This study compares the outcome of angioplasty of one vessel versus that of more than one vessel in patients with CLI due to tibial disease. METHODS: We retrospectively reviewed all consecutive diabetic patients with tibial disease with no concomitant proximal lesions who were treated by angioplasty. Among 82 patients with isolated tibial disease 48 patients were selected. All patients had to have more than one diseased tibial vessel that can be treated by angioplasty. Group A patients (N.=25) had only one tibial vessel treated while group B patients (N.=23) had more than one tibial vessel treated. We compared both groups with respect to patients' characteristics, lesion morphology, and limb salvage rate. RESULTS: Lesion morphology was worse in group A than B: anterior tibial artery showed more long lesions (17 vs. 8), more multiple lesions (22 vs. 11), and peroneal artery showed more long lesions (23 vs. 10), more multiple lesions (24 vs. 12), and more occlusions (18 vs. 10). Limb salvage rate at 12 months was similar (91%) in both groups. There were 5 complications in each group. CONCLUSION: The lesion morphology was worse in group A. Simpler lesions in group B motivated performing more than one vessel angioplasty. There was no difference in the limb salvage rate in the medium term among both groups. Additional vessels angioplasty in less diseased arteries was not associated with substantial additional morbidity.

Behcet extracranial carotid aneurysms: is there still a role for ligation?

OBJECTIVES: Aneurysm formation in Behcet's disease (BD) rarely involves extracranial carotid arteries. We report our experience of the management of extracranial carotid artery aneurysms (ECAAs) in BD. MATERIALS AND METHODS: Data of patients with Behcet ECAAs presenting from 1997 to 2008 were retrospectively collected focusing on the different treatment modalities, the indications for each modality and the outcome. RESULTS: Twelve Behcet ECAAs were managed. Seven underwent ligation of the carotid artery, where the stump pressure exceeded 70 mmHg. The remaining five patients underwent vascular reconstruction: either excision and reconstruction by an autogenous vein interposition graft (n=3), excision and end-to-end anastomosis (n=1), or direct suture of a small rent in the artery (n=1). There were no perioperative mortalities or major strokes. There was one recurrent laryngeal nerve injury and one hematoma. There was one aneurysm recurrence, which was managed by ligation and resulted in a minor stroke. CONCLUSION: Surgical repair in Behcet ECAAs should be performed with special precautions in order to prevent anastomotic pseudoaneurysm formation. Ligation can be performed when the anatomical and/or pathological circumstances are not favourable, provided that the stump pressure is adequate to maintain cerebral perfusion.

Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites.

BACKGROUND AND PURPOSE: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB(1)) and vanilloid (TRPV(1)) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB(1) and TRPV(1) may be involved. Voltage-activated Ca(2+) channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca(2+) influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses. EXPERIMENTAL APPROACH: The whole cell patch-clamp technique and fura-2 Ca(2+) imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K(+) currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons. KEY RESULTS: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 microM AEA attenuated voltage-activated K(+) currents and the recovery of KCl-evoked Ca(2+) transients. The insensitivity of these responses to the CB(1) receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB(1) receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K(+) currents and Ca(2+) influx. CONCLUSION AND IMPLICATIONS: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K(+) conductances and altered excitability of cultured sensory neurons.

Control of intraocular pressure after deep sclerectomy.

AIM: To study the long-term outcome of deep sclerectomy in patients with open angle glaucoma. METHODS: Prospective consecutive series of 43 eyes (38 patients) with medically uncontrolled open-angle glaucoma undergoing deep sclerectomy. All patients underwent clinical assessment before and after surgery at day 7 and at months 1, 3, 6, 12, 18, 24, 36. Surgical success was considered if the patient's intraocular pressure (IOP) < 22 mmHg and the IOP was lowered by more than 20% without the use of any medication. Kaplan-Meier survival curves were used to evaluate the success rate. RESULTS: The mean follow-up time was 28.1 +/- 8.2 months. Mean IOP decreased significantly from a preoperative value of 24.6 +/- 5.5 mmHg to a postoperative value of 18.5 +/- 4.6 mmHg at 36 months (P < 0.001). Microperforation of TDM occurred in three cases (7.0%) and ciliary body prolapse in one case (2.3%) but did not prevent completion of the operation. Postoperatively, hyphaema was detected in one case and shallow anterior chamber in another case and both were treated conservatively. Bleb encapsulation with elevation of IOP occurred in two cases (4.7%) and was treated with 5-fluorouracil subconjunctival injection. Goniopuncture with neodymium : YAG laser was performed in two cases (4.7%). There were no other late complications with the exception of failure of the operation. On the life-table analysis the success rate at 12, 24, and 30 months were 61.4, 36.6, and 18.9%, respectively. CONCLUSION: Deep sclerectomy reduced the IOP temporarily while minimising the risk of postoperative complications commonly encountered with standard trabeculectomy. However, after long-term follow-up surgery failed to maintain a low IOP.

Ultrasound biomicroscopy in deep sclerectomy.

PURPOSE: To evaluate by ultrasound biomicroscopy (UBM) the anatomical characteristics and the intraocular pressure (IOP) lowering mechanisms of deep sclerectomy after long-term follow-up. METHODS: In all, 22 eyes of 21 consecutive patients who had deep sclerectomy were examined by UBM. Several UBM variables were prospectively evaluated, including the presence and maximum length and height of the intrascleral space, the minimum thickness of residual trabeculo-Descemet membrane (TDM), the presence and type of subconjunctival filtering bleb, and the presence of other possible drainage sites, for example suprachoroidal. Surgical success was considered to be achieved when the IOP was <22 mmHg and the IOP was lowered by more than 20% without the use of any medication. The possible association between UBM variables and the surgical outcome was determined. RESULTS: The mean time between surgery and the UBM examination was 12.0+/-5.3 months. The mean IOP decreased significantly from a preoperative value of 23.7+/-4.0 to 16.0+/-3.9 mmHg at the time of UBM (P<0.01). There was a poor correlation between the level of IOP at the time of UBM and the length of intrascleral space (r2=0.0016), the height of the intrascleral space (r2=0.136), or the thickness of remaining TDM (r2=0.0009). The presence and type of filtering bleb were not associated with the success. CONCLUSIONS: In patients undergoing deep sclerectomy, UBM examination after long-term follow-up showed the presence of an intrascleral space and a filtering bleb in most patients. The surgical outcome was not associated with the UBM variables of the surgical area.