Giant right atrial thrombus in hepatocellular carcinoma: real-time characterization by cardiac magnetic resonance and real time three-dimensional echocardiography.

Hepatocellular carcinoma (HCC) with extension to the right atrium is an uncommon form of cardiac involvement. We report a case of a 67-year-old man admitted to our Department for the incidental findings of a mass in the right atrium. Physical examination revealed leg edema, distention of external jugular vein and ascites. The anamnestic collection revealed HCC occurred on post-alcoholic liver cirrhosis 3 years earlier. Transthoracic echocardiography revealed a dilated RA containing a mass, with superficial apposition of a thrombotic material. Bi-dimensional echocardiography is the most commonly used noninvasive tool for evaluating intracardiac masses. Although MRI is considered the gold standard, real-time three-dimensional echocardiography has the capability to obtain the entire volume reconstruction of an intracardiac mass, even with an irregular shape. Moreover, it permits an hemodynamic evaluation of the potential obstructive effects visualized from different angles and planes.

A p70 killer cell inhibitory receptor specific for several HLA-B allotypes discriminates among peptides bound to HLA-B*2705.

Natural killer (NK) cells express a repertoire of killer cell inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I molecules. KIR specificity for MHC class I can be broad, as in the case of a single p70 KIR that can recognize several HLA-B allotypes, including HLA-B*2705. On the other hand, recognition of MHC class I can also be highly specific, as in the case of NK clones that recognize HLA-B*2705 in a peptide-specific manner. Most NK cells express multiple KIR sequences. To determine whether the broad and specific types of HLA-B recognition by NK cells reflect the use of different receptors or a property of a single KIR we analyzed the recognition of HLA-B*2705 by the p70 KIR-11, known to recognize several HLA-B allotypes. Vaccinia virus-mediated expression of KIR-11 in NK clones resulted in inhibition by HLA-B*2705 molecules on wild type but not on target cells deficient in the transporter for antigen presentation (TAP). Two peptides (FRYNGLIHR and RRSKEITVR) loaded onto HLA-B*2705 molecules on TAP-deficient cells provided protection from lysis by NK cells expressing KIR-11 but three other B27-specific peptides did not. As the five peptides bound to HLA-B*2705 with similar stability, these data demonstrate that a single KIR specific for several HLA-B allotypes recognizes a subset of peptides bound to HLA-B*2705.

Comparative Evaluation of Two Different Post-Operative Analgesia after Hallux Valgus Correction in Day Surgery Patients.

INTRODUCTION: The aim of this study was the evaluation of two different techniques on post-operative analgesia and motor recovery after hallux valgus correction in one-day surgery patients. MATERIAL AND METHODS: We enrolled 26 patients scheduled for hallux valgus surgery and treated with the same surgical technique (SCARF osteotomy). After subgluteal sciatic nerve block with a short acting local anaesthetic (Mepivacaine 1.5%, 15ml), each patient received an ultrasound-guided Posterior Tibialis Nerve Block (PTNB) with Levobupivacaine 0.5% (7-8ml). We measured the postoperative intensity of pain using a Visual Analogue Scale (VAS), the consumption of oxycodone after operative treatment and the motor recovery. VAS was detected at baseline (time 0, before the surgery) and at 3, 6, 12 and 24 hours after the operative procedure (T1, T2, T3, T4 respectively). Control group of 26 patients were treated with another post-operative analgesia technique: local infiltration (Local Infiltration Anaesthesia, LIA) with Levobupivacaine 0.5% (15ml) performed by the surgeon. RESULTS: PTNB group showed a significant reduction of VAS score from the sixth hour after surgery compared to LIA group (p<0.028 at T2, p<0.05 at T3 and p<0.002 at T4, respectively). Instead, no significant differences were found in terms of post-operative oxycodone consumption and motor recovery after surgery.Conclusions: PTNB resulted in a valid alternative to LIA approach for post-operative pain control due to its better control of post-operative pain along the first 24 hours. In a multimodal pain management according to ERAS protocol, both PTNB and LIA should be considered as clinically effective analgesic techniques.

Peptide specificity in the recognition of MHC class I by natural killer cell clones.

Recognition by natural killer (NK) cells of major histocompatibility complex (MHC) class I molecules on target cells inhibits NK-mediated lysis. Here, inhibition of NK clones by HLA-B*2705 molecules mutated at single amino acids in the peptide binding site varied among HLA-B*2705-specific NK clones. In addition, a subset of such NK clones was inhibited by only one of several self peptides loaded onto HLA-B*2705 molecules expressed in peptide transporter-deficient cells, showing that recognition was peptide-specific. These data demonstrate that specific self peptides, complexed with MHC class I, provide protection from NK-mediated lysis.

Intramedullary nailing of tibial shaft fractures in the semi-extended position using a suprapatellar approach: A retrospective case series.

Tibial shaft fractures are extremely common injuries. High rate of union, acceptable alignment in all planes, and a low complication rate have been reported when diaphyseal fractures are treated by intramedullary nailing. However, knee pain after tibial nailing has historically been problematic. While the exact aetiology of the knee pain is still unknown, surgical approach relative to the patellar tendon, nerve transection, violation of the fat pad or joint capsule as well as nail diameter and implant prominence have been claimed as possible causes. Therefore, establishing an appropriate starting point remains a crucial step in the surgical procedure. Recently, suprapatellar nailing in the semi-extended position has been suggested as a safe and effective surgical technique. Literature is lacking on this topic, therefore the present article discusses clinical outcomes of 25 patients treated by suprapatellar nailing at 2 years follow up and a literature review.

Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study.

PURPOSE: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l(-1)), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms(-1)), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg(-1) min(-1), p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

A combined therapeutic approach in progressive idiopathic pulmonary fibrosis-pirfenidone as bridge therapy for ex vivo lung transplantation: a case report.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF.

Inhibition of natural killer cell cytotoxicity and interferon gamma production by the envelope protein of HIV and prevention by vasoactive intestinal peptide.

Natural killer (NK) cell dysfunction is common in human immunodeficiency virus (HIV)-infected subjects, although its mechanisms are poorly understood. A direct effect of HIV envelope glycoprotein gp120 may be involved. We investigated the in vitro effects of gp120 on the major NK cell effector functions, natural cytotoxicity and cytokine production. In addition, the ability of the vasoactive intestinal peptide (VIP) to modulate these effects was investigated. Our results indicated that gp120 inhibits NK natural cytotoxicity and showed, for the first time, that the inhibition affects also the production of the proinflammatory cytokine interferon-gamma (IFN-gamma). Interestingly, the inhibitory effect on NK cell functions was obtained with gp120 at concentrations within the range measured in the serum of HIV-infected subjects. Furthermore, we showed that the inhibitory activity of gp120 can be prevented by coincubation with VIP, even if VIP has no stimulatory activity by itself. Taken together these data suggest that (1) an inhibitory effect of gp120 may account for the NK cell dysfunction in HIV-infected subjects; (2) the gp120-mediated decrease in IFN-gamma production by NK cells may contribute to the cytokine imbalance observed in HIV infection; and (3) VIP counteracts the inhibitory effect of gp120 on NK cell functions.

Determination of phenoxyalkanoic acids and other herbicides at the ng/ml level in water by solid-phase extraction with poly(divinylbenzene-co-N-vinylpyrrolidone) sorbent and high-performance liquid chromatography--diode-array detection.

A method for the determination of phenoxyalkanoic acids and other polar compounds in environmental water samples without pH adjustment before extraction has been developed. Recoveries were calculated from 500 ml of milliQ water spiked at the level of 0.5 ng/ml using solid-phase extraction (SPE) and HPLC-DAD. Different SPE materials (RP-C18, ENV+, ENV+-C8, SAX and Oasis HLB) were tested. After method optimization, 15 of the 16 compounds studied could be extracted with recoveries better than 70% on the most suitable copolymeric poly(divinylbenzene-co-N-vinylpyrrolidone) material (Oasis HLB cartridges).

Commercial and laboratory extracts from artichoke leaves: estimation of caffeoyl esters and flavonoidic compounds content.

Artichoke leaf extracts are widely used alone or in association with other herbs for embittering alcoholic and soft drinks and to prepare herbal teas or herbal medicinal products. Despite this wide diffusion, the European Pharmacopoeia does not report an official method for the determination of the active principles of artichoke leaf extracts. This work reports a quali-quantitative determination by HPLC/DAD and HPLC/MS techniques of both cynnamic acids and flavonoids present in some artichoke leaf commercial extracts (Com) compared with two different laboratory extracts (Lab). Most of the commercial extracts showed a similar quali-quantitative pattern with a single exception having five-six times higher value. The quantitative data from the Italian Pharmacopoeia(IP) official method does not evaluate the flavonoidic fraction and showed an overestimation of the caffeoyl esters with respect to the HPLC/DAD results. The proposed HPLC/DAD method was able to completely characterize and quantify this matrix and represents a contribution to better quality control of these herbal extracts.

Absorption of iron from iron succinyl-protein complexes by mouse small intestine.

The absorption of iron from iron succinyl-protein complexes was investigated in mice. 59Fe-labelled succinyl-casein and -albumin complexes, [59Fe]ferritin and 59FeSO4, at doses of 20 or 200 micrograms of iron, were administered orally to normal mice or mice with absorption enhanced by chronic hypoxia. 59Fe from iron succinyl-protein was well absorbed in normal mice (greater than 10% of dose) and showed enhanced absorption in hypoxic mice (greater than 40% of dose). Intestinal uptake was predominantly by the duodenum for all compounds studied. In-vivo absorption of 59Fe from an iron succinyl-protein complex was studied using tied-off segments of mouse duodenum, jejunum or ileum of normal or hypoxic mice. Incubation for up to 15 min in duodenum or 60 min in ileum showed very little absorption of 59Fe. No enhancement of absorption was seen in hypoxic mice. It was concluded that absorption of the intact iron succinyl-protein complex cannot explain absorption seen after oral dosing.

Comparative absorption kinetics of imidazole and salicylic acid in volunteers after administration of ITF 182 tablets and suppositories.

Comparative absorption kinetics in volunteers of a new antiinflammatory drug (Selezen), in the form of 750 mg tablets and suppositories, were studied. The two components of the drug, imidazole and salicylic acid were found in plasma. Pharmacokinetic parameters were calculated according to a first order absorption. Salicylic acid showed a maximum concentration 59.2 +/- 5 min and 75.4 +/- 7.6 min after the administration of the tablet and suppository respectively; and imidazole after 86.3 +/- 10.8 min and 75.2 +/- 5.4 min, respectively.

Clinical and functional outcomes of internal fixation with intertrochanteric antegrade nail in older patients with proximal extracapsular femoral fractures.

PURPOSE: The intertrochanteric Trigen Intertan(®) nail (Smith & Nephew, Memphis, TN) is a popular fixation device for proximal extracapsular femoral fractures (PEFFs). We evaluated clinical and functional outcomes in patients with PEFFs treated with Trigen Intertan(®) nail. METHODS: In a single-site, prospective observational study, clinical and functional parameters were recorded for all patients admitted to the Emergency Department with PEFFs from June 2008 through June 2011. Patients with severe cognitive impairment, severe disability, neoplastic pathological fractures, or suffering from terminal illnesses were not eligible for the study. Fractures were classified according to the AO/OTA classification system. Preoperative physical fitness was assessed via the American Association of Anaesthetists (ASA) score. The Barthel index was used to quantify the level of physical function before fracture and at follow-up. RESULTS: One-hundred thirty-five patients with PEFFs were eligible for inclusion during the 3-year survey (mean age 83.2 ± 9.5 years; 82 % females). Fracture type distribution was as follows: A1.1 = 18 %, A1.2 = 7 %, A1.3 = 5 %, A2.1 = 44 %, A2.2 = 21 %, A2.3 = 5 %. All patients were treated with Trigen Intertan(®) nail. Two patients experienced a fracture of the femoral shaft during the insertion of a long nail for an A2.3 fracture. Weight-bearing was allowed between the third and tenth postoperative day depending on pain tolerance and general conditions. No loss of reduction, collapse of the femoral neck, nonunion or fixation failure were observed. Two patients died within 10 days postoperatively, and nine within 6 months after surgery. Functional status 1 month after surgery was lower than pre-fractural levels, and improved over follow-up. At 6 months, functional status was comparable to the pre-fractural level. CONCLUSIONS: Trigen Intertan(®) produces highly satisfactory clinical and functional results in older patients with PEFFs. Complete functional recovery is obtained on average 6 months after surgery.

Network meta-analysis on the comparative effectiveness and safety of transcatheter aortic valve implantation with CoreValve or Sapien devices versus surgical replacement.

INTRODUCTION: Surgical replacement for aortic stenosis is fraught with complications in high-risk patients. Transcatheter techniques may offer a minimally invasive solution, but their comparative effectiveness and safety is uncertain. We performed a network meta-analysis on this topic. METHODS: Randomized trials on transcatheter aortic valve replacement vs surgery were searched. The primary outcome was all cause death. Risk estimates were obtained with Bayesian network meta-analytic methods. RESULTS: Four trials with 1,805 patients were included. After a median of 8 months, risk of death and myocardial infarction was not different when comparing surgery versus transcatheter procedures, irrespective of device or access. Conversely, surgery was associated with higher rates of major bleeding (odds ratio vs CoreValve=3.03 [95% credible interval: 2.23-4.17]; odds ratio vs transfemoral Sapien =1.82 [1.21-2.70]; odds ratio vs transapical Sapien =2.08 [1.20-3.70]), and acute kidney injury (odds ratio vs CoreValve =2.08 [1.33-3.32]; odds ratio vs transapical Sapien =2.78 [2.21-99.80]), but lower rates of pacemaker implantation (odds ratio vs CoreValve =0.41 [0.28-0.59]), and moderate or severe aortic regurgitation (odds ratio vs CoreValve =0.06 [0.02-0.27]; odds ratio vs Sapien=0.17 [0.02-0.76]). Strokes were less frequent with CoreValve than with transfemoral Sapien (odds ratio =0.32 [0.13-0.73]) or transapical Sapien (odds ratio =0.33 [0.10-0.93]), whereas pacemaker implantation was more common with CoreValve (odds ratio vs surgery =2.46 [1.69-3.61]; odds ratio vs transfemoral Sapien =2.22 [1.27-3.85]). CONCLUSIONS: Survival after transcatheter or surgical aortic valve replacement is similar, but there might be differences in the individual safety and effectiveness profile between the treatment strategies and the individual devices used in transcatheter aortic valve implantation.

Epicatechin and catechin modulate endothelial activation induced by platelets of patients with peripheral artery disease.

Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that epicatechin plus catechin reduces endothelial activation induced by activated platelets.