The 24-hour rhythm of blood pressure differs from that of leg hemodynamics in orthotopic heart transplant recipients

BACKGROUND: This study was aimed at investigating whether a circadian rhythm of peripheral resistance exists in patients with orthotopic cardiac transplantation (OCT) and whether it parallels that of blood pressure (BP). METHODS: BP and leg flow and resistance (plethysmography) were monitored for 24 hours in 13 denervated OCT recipients and 13 control patients with native heart, matched for casual blood pressure. RESULTS: On the basis of BP trend, control patients showed a BP reduction during sleep, whereas OCT recipients did not. Leg resistance was significantly lower and leg flow significantly higher during sleep than during waking in all patients, and the extent of the nocturnal decrease was similar in the two categories. CONCLUSIONS: The decrease in leg resistance in patients confined to bed for 24 hours is caused by peripheral mechanisms and does not depend on the autonomic control of the heart. The nocturnal decline in BP depends, on the contrary, on cardiac control and is lost in patients with denervated heart.     

Outcome in ulcerative colitis after switch from adalimumab/golimumab to infliximab: A multicenter retrospective study

Background

Anti-TNF therapies infliximab (IFX), adalimumab (ADA), and golimumab (GOL) are approved for treating moderate to severe ulcerative colitis (UC). In UC, only the switch from IFX to ADA has been investigated, reaching no more than 10–43% remission rates at 12 months.

Molecular discrimination of atypical bovine spongiform encephalopathy strains from a geographical region spanning a wide area in Europe

Transmissible spongiform encephalopathy strains can be differentiated by their behavior in bioassays and by molecular analyses of the disease-associated prion protein (PrP) in a posttranslationally transformed conformation (PrPSc). Until recently, isolates from cases of bovine spongiform encephalopathy (BSE) appeared to be very homogeneous. However, a limited number of atypical BSE isolates have recently been identified upon analyses of the disease-associated proteinase K (PK) resistance-associated moiety of PrPSc (PrPres), suggesting the existence of at least two additional BSE PrPres variants. These are defined here as the H type and the L type, according to the higher and lower positions of the nonglycosylated PrPres band in Western blots, respectively, compared to the position of the band in classical BSE (C-type) isolates. These molecular PrPres variants, which originated from six different European countries, were investigated together. In addition to the migration properties and glycosylation profiles (glycoprofiles), the H- and L-type isolates exhibited enhanced PK sensitivities at pH 8 compared to those of the C-type isolates. Moreover, H-type BSE isolates exhibited differences in the binding of antibodies specific for N- and more C-terminal PrP regions and principally contained two aglycosylated PrPres moieties which can both be glycosylated and which is thus indicative of the existence of two PrPres populations or intermediate cleavage sites. These properties appear to be consistent within each BSE type and independent of the geographical origin, suggesting the existence of different BSE strains in cattle. The choice of three antibodies and the application of two pHs during the digestion of brain homogenates provide practical and diverse tools for the discriminative detection of these three molecular BSE types and might assist with the recognition of other variants.     

Influence of nitric oxide-donating nonsteroidal anti-inflammatory drugs on the evolution of acute pancreatitis

Microcirculatory disturbances and leukocyte activation are main events in the pathogenesis of acute pancreatitis (AP) that is characterized by inflammatory up-regulation. Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) regulate vascular function and mitigate inflammation. To investigate the influence of NO-NSAIDs on AP. AP was induced by the biliopancreatic duct outlet exclusion-closed duodenal loops model. Treatment with NO-flurbiprofen, NO-ibuprofen, NO-aspirin, or their parental drugs was done (i) 1 h before, (ii) 1 h after, (iii) 1 h before and 4 h after, or (iv) 4 h after surgery. The degree of severity was evaluated using biochemical and histopathological analyses. NO-NSAIDs given before and during the first hour of the noxia decreased blood levels of amylase, lipase, C-reactive protein, IL-6, IL-10, heat shock protein 72, prostaglandin E2 inactive metabolite, and 8-isoprostane, as well as pancreatic and lung myeloperoxidase and cyclooxygenase. Acinar and fat necrosis, hemorrhage, and leukocyte infiltrate were also reduced. The best protection was achieved when treatment was performed 1 h before and 4 h after triggering AP. NO-flurbiprofen was the most effective drug. AP severity was significantly ameliorated by NO-NSAIDs being the administration time essential to achieve optimal pancreatic protection that may result to be useful in the prevention of postendoscopic severe AP.     

Circulating elevated levels of soluble CD23, interleukin-4, and CD20+CD23+ lymphocytes in atopic subjects with elevated serum IgE concentrations.

Circulating IgE protein levels, leukocyte counts, lymphocyte subsets, IL-4, and soluble CD23 levels were quantitated in 43 atopic and 19 nonatopic subjects. Mean values of IgE protein levels, total eosinophil counts, CD20+CD23+ cells (B cells with low-affinity IgE receptor), IL-4 and sCD23 levels were elevated in atopic patients compared with nonatopic controls. The results suggest that sCD23, IL-4, and CD20+CD23+ lymphocytes may play a role in the increased production of IgE in atopic subjects in a manner similar to that observed by other investigators in prior in vitro studies.     

Absence of myocardial dysfunction during cold pressor stress echocardiography in patients with endothelial dysfunction

Background: Several methods are available for the assessment of coronary endothelial function, but there are no reports to date regarding the usefulness of cold pressor stress echocardiography (CPSE). Objective: To assess regional systolic and diastolic left ventricular function using CPSE in patients with endothelial dysfunction. Methods: We studied 24 patients, of whom 10 were men, aged 27 to 68 years, who had coronary risk factors and a normal exercise MP-SPECT test. They were compared with 10 normal subjects (6 men), aged 21 to 44 years. All patients underwent a CPSE. Results: The cold pressor-MP-SPECT revealed myocardial ischemia in 10 patients (Group I) and was normal in 14 patients (Group II). All normal subjects (Group III) had normal cold pressor-MP-SPECT. The cold pressor test caused a significant increase in systolic BP in the three groups (baseline 117 ± 17 mmHg vs. postcold test 137 ± 16 mmHg, P < 0.05), without changes in heart rate, PR interval, or the corrected QT interval. During the CPSE, no patient developed WMA in 2D echo or changes in regional systolic or diastolic LV function in the pulsed Doppler tissue imaging. Conclusions: In patients with endothelial dysfunction and no known coronary artery disease, the ischemic response to the cold pressor-MP-SPECT is not accompanied by WMA or changes in regional systolic or diastolic LV function during CPSE. Such negative findings indicate that the amount of ischemia that occurs secondarily to endothelial dysfunction does not involve sufficient myocardial mass to cause contractile dysfunction.     

Adjuvant radio-chemotherapy after extended or simple cholecystectomy in gallbladder cancer

Purpose  

To analyse results of combined treatment of adjuvant radio-chemotherapy (RT-CT) in patients diagnosed with gallbladder cancer (GBC) after complete resection. Methods and material From June 1993 until July 2006, 67 patients with a diagnosis of GBC who underwent R0 surgical resection and were staged as T1b-2-3N0-1M0 received adjuvant RT-CT. Radiotherapy consisted of whole abdominal irradiation (20 Gy at 100 cGy daily) plus a boost to the tumour bed for a total of 45–59.4 Gy. Concomitant chemotherapy (fluoropyrimidines) was given. Overall survival (OS) and median survival were analysed in relation to different prognostic factors.     

Development of a Novel Human Cell-Derived Tissue-Engineered Heart Valve for Transcatheter Aortic Valve Replacement: an In Vitro and In Vivo Feasibility Study

Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n?=?4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n?=?5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.