Inhibition of LTßR signalling activates WNT-induced regeneration in lung.

Lymphotoxin ß-receptor (LTßR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTßR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTßR blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LTßR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTßR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTßR signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTßR signalling dampened epithelial non-canonical activation of NF-κB, reduced TGFß signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/ß-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTßR signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.

[Seven hour shifts versus 12 hours in intensive nursing care: going against the tide]. / Turnos de 7 horas versus 12 horas en enfermería intensiva: vivir a contratiempo.

Working in shifts has an impact on the well being of health care professionals, affecting their quality of life. The main objective of this study is to describe the consequences of 12hours work shifts versus 7hours for nursing professionals working in intensive care units. A cost-sectional, descriptive study was conducted in two tertiary hospitals of Barcelona, these being the Hospital Clínico and Hospital Vall d'Hebron (of 7hour and 12hour shifts, respectively). The data was collected through a questionnaire having 29 closed questions that was anonymous and self-administered. The questionnaire was based on two scales: Standard Shiftwork Index and Shiftwork. locus of control. Data was processed through SPSS V.18.0. The target population consisted of 85 people, for whom 52 surveys were valid: 22 in Hospital Clínico of Barcelona and 30 in Hospital Vall d'Hebron. Professionals working a 12-hour shift express higher levels of work and family conciliation, especially in the case of leisure time to enjoy (×2: 10.635 p=0.031) and family-friends time dedication as well as lower levels of perceived fatigue. No differences were found between type of shift and ease of development of professional work, even though the 12-hour shift has higher levels.

Transesophageal access to the cardiac cavities and descending thoracic aorta via echoendoscopy. An experimental study.

OBJECTIVE: The applications of endoscopic ultrasonography have diversified over recent years. The possibility of reaching cardiac territory has been successfully explored in experimental models, opening up a new field of possibilities for diagnostic and therapeutic interventions that were unthinkable until very recently. The aims set out in this study are to evaluate cardiac anatomy, its approach, the safety of the experimental procedure and the resulting morphological and histological changes after the procedure. MATERIAL AND METHODS: The study has been performed on two adult pigs. They have undergone different surgical approaches to the cardiac cavities and descending thoracic aorta with excellent results. RESULTS: Different cardiac structures have been identified and operated upon (right auricle, left auricle, left ventricle, cardiac valves), as well as major vessels. The use of contrast, both intracavitary and from a peripheral vein, enabled us to verify the anatomical spaces studied. During the procedures we monitored for arrhythmias, hemodynamic behavior, possibility of infection by obtaining sample hemocultures before and after procedures, and response to punctures. CONCLUSIONS: The present study has enabled us to evaluate access to the heart from the esophageal lumen using endoscopic ultrasonography, with results that are very similar to those described in the current bibliography. However, we offer two novelties: puncture of the right auricle through the interauricular partition and puncture of the descending thoracic aorta, both performed with ease and apparent safety.

Double-balloon enteroscopy: a descriptive study of 50 explorations.

AIM: To evaluate the utility of double-balloon enteroscopy for small-bowel disease. DESIGN: A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn's disease, tumors, and refractory celiac disease. RESULTS: We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's disease, diverticulosis, and Waldenström's disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. CONCLUSIONS: Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.

TNF induced inhibition of Cirbp expression depends on RelB NF-κB signalling pathway.

The circadian clock is required for the rhythmic expression of a plethora of genes that orchestrate metabolism, sleep-wake behaviour and the immune response to pathogens. The cold-inducible RNA binding protein (CIRBP) is required for high amplitude expression of clock genes. Moreover, CIRBP protects the expression of clock genes from the inhibitory effects of tumour necrosis factor (TNF). However, since TNF represses Cirbp expression, the protective effect of CIRBP is lost. Here, we show that the TNF effect on Cirbp requires the non-canonical NF-κB signalling pathway. While a knock down of RelA does not alter the effects of TNF on Cirbp, a knock down of RelB represses this effect. In addition, the data indicate that p50 and p52 are required in the TNF induced inhibition of Cirbp. These results show that Cirbp expression in TNF treated cells is regulated via the non-canonical NF-κB pathway.

[Gastrointestinal alterations in a female patient with common variable immunodeficiency]. / Alteraciones gastrointestinales en una paciente con inmunodeficiencia variable común.

We present the case of a 33-year-old woman who complained of intermittent diarrhea over the previous 8 years and who was diagnosed with common variable immunodeficiency. The woman presented antral atrophic gastritis, partial atrophy of the duodenal villi, nodular lymphoid hyperplasia of the small intestine and lymphocytic colitis. We also review the literature.

[McArdle disease: report of four brothers with myophosphorylase deficiency]. / Enfermedad de McArdle: descripción de cuatro hermanos con déficit de miofosforilasa.

Myophosphorylase deficiency, or McArdle disease, is an uncommon entity. The gene for human myophosphorylase has been cloned and is located on chromosome 11, in keeping with the autosomal recessive nature of the disease and there is an excess of male patients. The diagnosis is established by documentation of elevated glycogen content and reduced phosphorylase activity in biopsied muscle tissue. We report four cases with McArdle disease which were 16, 15, 11 and 5 years old. They were brothers, and they came to the hospital because of pain, cramps and myoglobinuria after exercise or infection; in the first case, a male patient, myoglobinuria caused acute renal failure. Three of them showed reduced phosphorylase activity in biopsied muscle tissue. We discuss the different therapeutic possibilities.

Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors.

PURPOSE: Kahalalide F (KF) is a dehydroaminobutyric acid-containing peptide from marine origin with activity against several human malignant cell lines. This dose-escalating phase I clinical trial evaluated the maximum tolerated dose (MTD), and the recommended dose for further phase II studies (RD) of weekly KF given as a prolonged (3- to 24-h) intravenous (i.v.) infusion. METHODS: Eligible patients with advanced solid tumors and adequate performance status, hematologic, renal, and hepatic function were recruited into this study. RESULTS: A total of 106 patients were treated with KF at four different weekly schedules: 3-h (n = 40), 24-h (n = 59), and two transitional schedules [6-h (n = 4) and 12-h (n = 3)]. For the 3-h weekly schedule, the MTD was 1,200 µg/m² and the RD was 1,000 µg/m². For the 24-h weekly schedule, the MTD was reached (6,650 µg/m²), but the RD could not be confirmed. Asymptomatic and reversible grade 3/4 transaminase increase was the most common dose-limiting toxicity in both schedules. Fatigue, paresthesia, pruritus, nausea, vomiting, and rash were the most common KF-related adverse events. No major deviations from linearity were detected in the pharmacokinetic (PK) profiles of both schedules, which showed a narrow distribution and short body residence. Prolonged disease stabilization (≥3 months) occurred in eight patients: two with the 3-h schedule and six with the 24-h schedule. CONCLUSIONS: Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.

A 1.2-V 140-nW 10-bit Sigma-Delta Modulator for Electroencephalogram Applications.

This paper presents a second-order Sigma-Delta modulator for electroencephalogram applications with 10 bits of resolution, 1.2 V of supply voltage, and only 140 nW of power consumption over a bandwidth of 25 Hz. Low-voltage operation has been achieved using quasi-floating-gate-based circuits. The use of a new class-AB operational amplifier in weak inversion allows very low power consumption. Experimental results show an energy efficiency of 1.6 pJ per quantization level, making it the most energy-efficient converter reported to date in the very low signal bandwidth range.

Phase II trial of cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors.

The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC), and outcome parameters were correlated with the expression of thymidine phosphorylase (TP), thymidilate syntetase (TS), vascular endothelial growth factor receptor (VEGFR) 1-3, and microvessel density (MVD). Patients with recurrent or unresectable HNSCC were eligible if they had received prior neoadjuvant chemotherapy, concurrent chemo-radiotherapy, or no prior systemic therapy. Patients received cisplatin (75 mg m(-2) day 1), and capecitabine (2000 mg m(-2) day 1-14) every 3 weeks. A total of 41 patients received 194 cycles. In all, 16 complete responses (39%) and 12 partial responses (29%) were documented, for an overall response rate of 68% (95% CI, 53-80%). Grade 3-4 uncomplicated neutropenia was documented in five subjects. Asthenia, anorexia, hand-foot syndrome, and constipation were the most frequent nonhaematologic events. Median progression-free and overall survival were 6.4 and 12.6 months. Cytoplasmic TP expression was more prevalent in patients with a laryngeal location vs other, and in patients with a recurrence vs primary disease. Microvessel density count was higher in patients with recurrent vs primary disease. The combination of cisplatin and capecitabine is effective in recurrent or unresectable HNSCC, and shows a manageable toxicity.

[Brucella hepatic abscess. Report of a case and review of the literature]. / Absceso hepático por Brucella. Descripción de un caso y revision de la literatura.

Hepatic involvement in infections caused by Brucella organisms is common but the production of liver abscess is exceptional. Therefore, the most appropriate therapeutic approach is unclear. The use of antibiotics can be effective but in some cases abscess drainage is required. We report here a case of brucellar hepatic abscess and a review of fourteen cases reported in the literature. An emphasis is laid on the clinical, laboratory and radiological findings, treatment, and patient evolution. On the basis of the reported cases a therapeutic approach is proposed.