A simple method to obtain the correct length of the artificial chordae in complex chordal replacement

BACKGROUND: Different techniques have been proposed to measure the correct length of artificial chordae. We herein describe a new simple method to measure the chordal length in complex chordal replacement. METHOD: Chordal replacement was used by us for two different purposes: (1) to maintain the correct chordal length for the anterior leaflet (AL) and (2) to eliminate any movement of the posterior leaflet (PL) to fix it. To reach this goal, the AL is pulled up to the maximum extent and the new chordae are tied 5 mm higher than the related border. On the contrary, in the PL the new chordae are tied at the level of the related border. RESULTS: From March 2006 to March 2007, at the University of Catania, this technique was used in 32 patients (16 for correction of PL prolapse, 6 patients for correction of AL prolapse, and in 10 patients for correction of both leaflets prolapse). The number of chordae per patients was 8.6 for the PL and 6.8 for the AL. No patient died or had major complications. After a mean follow-up of 5 +/- 2 months, two-dimensional echocardiography showed that all the patients had no or trivial mitral regurgitation (MR). The echocardiogram showed a correct movement of the new chordae. CONCLUSIONS: This technique allows to easily establish the length of the new chordae of the AL and, if necessary, of the PL in complex mitral valve repair.     

Shockwave lithotripsy and protective role of inosine: early and late evaluation in an experimental model

PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is one of the most common treatments for urinary stones. Despite technological improvements, it may cause side effects varying from minor reversible microscopic damage to severe large renal hematomas. The aim of our experimental study is to assess the efficacy of inosine in avoidance of acute renal damage after SWL. MATERIALS AND METHODS: We used 25 Wistar rats that had previously had left nephrectomy. The rats were divided into three groups: group A consisted of 10 rats undergoing renal SWL; group B consisted of 10 rats that received adjunctive treatment with IP injection of inosine 40 minutes before SWL; and group C consisted of 5 rats that served as controls. N-acetylglucosaminidase (NAG) and lactate dehydrogenase (LDH) concentrations were evaluated 24 hours before and 24 hours after SWL. All the rats were subsequently sacrificed (4 rats in group A and 4 in group B at 48 hours post-SWL, and the remaining rats were sacrificed 30 days post-SWL). Renal tissue was submitted to histologic and electron microscopic examination to assess early and late alterations. RESULTS: NAG and LDH values were significantly increased after SWL in group A (P<0.001), while no significant NAG and LDH differences were detected in group B (P<0.16). Early histologic examination revealed a considerable amount of cellular degeneration in group A with ultrastructural vacuolization and disruption of lysosomal membranes; the tubular features and cellular structures appeared to be well preserved in group B. No late histologic alterations were evident in any of the specimens. CONCLUSIONS: Inosine is helpful and protective in the prevention of early microscopic damage to renal parenchyma due to SWL.     

Laparoscopic Nissen-Rossetti Fundoplication with Routine Use of Intraoperative Endoscopy and Manometry: Technical Aspects of a Standardized Technique

Background Several different ways of fashioning a total fundoplication lead to different outcomes. This article addresses the technical details of the antireflux technique we adopted without modifications for all patients with GERD beginning in 1972. In particular it aims to discuss the relation between the mechanism of function of the wrap and the physiology of the esophagus. Methods The study population consisted of 380 patients affected by GERD with a 1-year minimum of follow-up who underwent laparoscopic Nissen-Rossetti fundoplication by a single surgeon. Results No conversion to open surgery and no mortality occurred. Major complications occurred in 4 patients (1.1%). Follow-up (median 83 months; range: 1–13 years) was achieved in 96% of the patients. Ninety-two percent of the patients were satisfied with the results of the procedure and would undergo the same operation again. Postoperative dysphagia occurred in 3.5% of the patients, and recurrent heartburn was observed in 3.8%. Conclusions Laparoscopic Nissen-Rossetti fundoplication with the routine use of intraoperative manometry and endoscopy achieved good outcomes and long-term patient satisfaction with few complications and side-effects. Appropriate preoperative investigation and a correct surgical technique are important in securing these results.     

Long-term intravenous epoetin-alpha / darbepoetin-alpha ratio in iron-replete hemodialysis patients

BACKGROUND: Equivalence of intravenous (i.v.) and subcutaneous (s.c.) dosage requirements is a notable characteristic of darbepoetin-alpha (DPO), as opposed to other epoetins (EPOs). Currently in Europe, the EPOs/DPO conversion factor (200 IU EPOs = 1 microg DPO) does not take into account the route of drugs administration. To better define this ratio we have conducted a prospective, long-term trial in a group of hemodialysis patients. SUBJECTS AND METHODS: At the start, we evaluated 40 iron-replete hemodialysis patients, but the final study was performed in the remaining 25 patients. During the first 6 months, patients were on i.v. epoetin-alpha (EPOalpha) maintenance therapy (phase 1: T-6 to T0). After conversion to i.v. DPO (initial 200:1 ratio) the observation was prolonged for a period of 12 months (phase 2: T0 to T12). DPO was administered at extended dose intervals and the EPOalpha/DPO rate was adjusted every month to maintain hemoglobin (Hgb) stability. Iron status and factors inhibiting erythropoiesis were continually checked to exclude unstable patients. RESULTS: Phase 1: EPOalpha weekly mean dose showed no significant variation. Phase 2: EPOalpha/DPO conversion factor progressively rose from 200 to 256.7 +/- 86.9 IU/microg at T7 (p<0.005) and 336.8 +/- 104.3 IU/microg at T12 (p<0.0005). DPO weekly mean dosage decreased from 40.0 +/- 12.0 microg/week at T0 to 31.6 +/- 3.7 microg/week at T7 (p<0.005) and 24.6 +/- 7.0 microg/week at T12 (p<0.0005). Mean weekly/patient acquisition cost of EPOalpha was euro 70.6 +/- 21.3 (T-6 to T0); after switching, the cost of DPO was euro 72.4 +/- 22.7 (T0) and fell to euro 53.1 +/- 11.2 during T6 to T12. CONCLUSIONS: The progressive increase of EPOalpha/DPO ratio demonstrated that i.v. DPO requires lower doses compared with i.v. EPOalpha. When drugs are administered i.v., the starting EPOalpha/DPO conversion factor should be increased over the 200:1 ratio, similar to recommendations outlined in the United States and Japan. DPO dose reduction translated to notable cost-savings.     

Metalloproteinase expression in carotid plaque and its correlation with plasma levels before and after carotid endarterectomy

PURPOSE: To assess baseline and follow-up plasma concentrations of metalloproteinase-9 (MMP-9), MMP-2, and tissue inhibitor of metalloproteinase-2 (TIMP-2) in patients undergoing carotid thromboendarterectomy (TEA) in relation to tissue expression and diagnostic features. BASIC METHODS: Using sandwich enzyme-linked immunosorbent assay, plasma levels of enzymes were determined in 15 patients undergoing carotid TEA. Tissue sections were incubated with specific antibodies and fluorescence intensity was analyzed. PRINCIPAL FINDINGS: MMP-9 levels were higher in patients with carotid stenosis versus controls, significantly in those with cerebral lesions at neuroimaging. MMP-9 levels decreased in 93.4% of the patients at 1 month. MMP-2 levels tended to increase 30 days after surgery. TIMP-2 showed no difference. CONCLUSIONS: High concentrations of MMP-9 found in patients with carotid stenosis and cerebral lesions suggest that MMP-9 assay could be useful in the evaluation of all carotid lesions to help identify those at highest risk of a neurologic event.     

Epstein-Barr virus latent membrane protein 1 promotes concentration in multivesicular bodies of fibroblast growth factor 2 and its release through exosomes

FGF-2, a potent angiogenic factor that is involved in tumor invasion, is known to be released extracellularly by a nonclassical secretory pathway. Recently it has become clear that Epstein-Barr virus, specifically its oncoprotein LMP1, can induce expression of angiogenic factors. Among these factors is FGF-2. LMP1 not only promotes expression of FGF-2, but also the release extracellularly of its 18-kDa isoform. We analyzed the mechanism of FGF-2 release induced by LMP1. Confocal immunofluorescence microscopy revealed colocalization of FGF-2 with LMP1 in small dots also stained positively for CD63 and cathepsin D, markers of late endosomes or multivesicular bodies. Biochemical analysis and immunoelectron microscopy of purified exosomal fractions from cotransfected cells demonstrated increased release of exosomes and the concentration of LMP1 and FGF-2 in these structures. Moreover, cotransfection appeared to induce partial redistribution of the Na(+)/K(+)-ATPase, which participates in FGF-2 release, from the plasma membrane to the intracellular LMP1/FGF-2 positive dots. Treatment with ouabain, which inhibits Na(+)/K(+)-ATPase activity, partially suppressed FGF-2 secretion via exosomes in a dose-dependent manner. The results suggest that exosomes may represent a previously unrecognized mechanism for FGF-2 release mediated by LMP1, and that this pathway involves the activity of Na(+)/K(+)-ATPase.     

Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.     

The farnesyltransferase inhibitor R115777 (ZARNESTRA) enhances the pro-apoptotic activity of interferon-alpha through the inhibition of multiple survival pathways

Interferon alpha (IFNalpha) induces an EGF-Ras-->Raf-1-->Erk dependent survival pathway counteracting apoptosis induced by the cytokine. In this paper we have evaluated the effects of the combination between farnesyl-transferase inhibitor (FTI) R115777 and IFNalpha on the growth inhibition and apoptosis of cancer cells. Simultaneous exposure to R115777 and IFNalpha produced synergistic both antiproliferative and proapoptotic effects. In these experimental conditions, IFNalpha and R115777 completely antagonized the increased activity of both Ras and Erk-1/2 induced by IFNalpha and strongly reduced Akt activity. Furthermore, treatment with R115777 in combination with IFNalpha regimen induced tumor growth delay on established KB cell xenografts in nude mice, while the single agents were almost inactive. R115777 was again able to antagonize the Ras-dependent survival pathway induced by IFNalpha also in vivo. Raf-1, one of the downstream targets of Ras, has been reported to activate bcl-2 through displacement and/or phosphorylation of Bad. We have found that IFNalpha induced mitochondrial localization of Raf-1 that was antagonized by R115777. Moreover, IFNalpha increased Raf-1/bcl-2 immuno-conjugate formation and intracellular co-localization and enhanced phosphorylation of Bad at Ser 112 and again R115777 counteracted all these effects. Moreover, the use of plasmids encoding for dominant negative or dominant positive Raf-1 antagonized and potentiated, respectively, the co-immunoprecipitation between Raf-1 and bcl-2. In conclusion, FTI R115777 strongly potentiates the antitumor activity of IFNalpha both in vitro and in vivo through the inhibition of different survival pathways that are dependent from isoprenylation of intracellular proteins such as ras.