Selective targeted delivery of TNFalpha to tumor blood vessels

We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFalpha) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFalpha) composed of mouse TNFalpha and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marker of angiogenesis. L19mTNFalpha was expressed in mammalian cells, purified, and characterized. L19mTNFalpha was an immunoreactive and biologically active homotrimer. Radiolabeled L19mTNFalpha selectively targeted tumor neovasculature in tumor-bearing mice, where it accumulated selectively and persistently (tumor-to-blood ratio of the percentage of injected dose per gram [%ID/g] of 700, 48 hours from injection). L19mTNFalpha showed a greater anticancer therapeutic activity than both mTNFalpha and TN11mTNFalpha, a control fusion protein in which an antibody fragment, irrelevant in the tumor model used, substituted for L19. This activity was further dramatically enhanced by its combination with melphalan or the recently reported fusion protein L19-IL2. In conclusion, L19mTNFalpha allows concentrating therapeutically active doses of TNFalpha at the tumor level, thus opening new possibilities for the systemic use of TNFalpha in cancer therapy.     

Hepatitis E Virus Genotype 4 Outbreak,Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.     

Impaired in vitro growth of PHA induced T lymphocyte colonies in hemodialyzed renal failure patients

Summary Using an in vitro method that allows the study of the colony forming capacity of phytohemagglutinin stimulated peripheral blood T lymphocytes, we have detected an impaired T cell colony formation in hemodialyzed renal failure patients. By contrast a near normal pattern of responses was observed in patients treated with a conservative therapy. The poor in vitro T cell responsiveness of hemodialyzed patients was not corrected by supplementing the cultures with an adherent cell contitioned medium prepared from normal donors. We conclude that an intrinsic defect of the T cell colony forming capacity exists in hemodialyzed patients.     

Endothelial dysfunction and oxidative stress in chronic renal failure

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.     

Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy

This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug‐resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty‐three consecutive patients with medically refractory epilepsy underwent out‐of‐center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post‐VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new‐onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new‐onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS‐induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS‐induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.     

Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study

The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing‐remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293–2304, 2016. © 2016 Wiley Periodicals, Inc.     

Early outcomes of colon laparoscopic resection in the elderly patients compared with the younger

Background

The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 75 years old (OP) compared with the outcomes of a younger populations (YP).

Methods

Forty elderly patients undergoing laparoscopic colectomy for colorectal cancer between 2007-2011 were studied, the patients are divided for gender, age, year of surgery, site of cancer, and comorbidity on admission and compared with 40 younger patients.

Results and discussion

Mean (standard deviation) age was 81.3 in OP and 68.3 YP Conversion rate was the same between the two groups. There was no difference in operative mean time . The overall mortality rate was 0% percent. The surgical morbidity rate was the same but there was an increased in cardiologic e bronchopneumonia complications in older population. Patients treated with laparoscopic approach had a faster recovery of bowel function and a significant reduction of the mean length of hospital stay not age related. Laparoscopy allowed a better preservation of postoperative independence status.

Conclusions

Laparoscopic colectomy for cancer in elderly patients is safe and beneficial including preservation of postoperative independence and a reduction of length of hospital stay.