[Critical assessment of long-term proton pump inhibitor use in the elderly]. / Approche critique du traitement prolongé par inhibiteurs de la pompe à protons chez les personnes âgées.

Proton pump inhibitors (PPI) are drugs frequently used for gastric acid-induced conditions. Their use is constantly increasing and due to the apparent absence of side-effects, the treatment is not reassessed, even for the elderly. However, there are many cases of misprescribing while concerns about some side-effects are rising. Old people are weakened by their particular homeostasis and their associated medical conditions. Therefore, it seems useful to particularly insist on side-effects of the PPI, their indications and the ways of withdrawal, first of all for the elderly.

Les inhibiteurs de la pompe à protons (IPP) sont des médicaments fréquemment prescrits pour la prise en charge de pathologies secondaires à l'acidité gastrique. Leur utilisation est en constante augmentation et la question d'un éventuel sevrage, notamment chez les personnes âgées, est rarement soulevée en raison de leur bonne tolérance clinique apparente. Pourtant, leur utilisation est régulièrement injustifiée et il existe de plus en plus de preuves d'effets secondaires variés et potentiellement sévères. Les personnes âgées étant fragiles en raison de leur homéostasie particulière et de leurs comorbidités, il semble intéressant d'insister, dans cette population, sur les manifestations indésirables potentiellement médiées par les IPP, les indications reconnues de traitement et les méthodes de sevrage disponibles, le cas échéant.

[Alcool and pancreatic complications]. / Alcool et complications pancréatiques.

Alcohol consumption is the main cause of development of chronic pancreatitis and the second etiology of acute pancreatitis. The mortality of acute pancreatitis depends on its necrotic haemorrhagic character and the initial inflammatory response, while pain, malnutrition and diabetes are the main issues in the management of chronic pancreatitis. As medical and endoscopic techniques progress, surgical indications have become increasingly rare but remain indispensable for some patients. The multidisciplinary approach of these patients is the key to the success of care.

La consommation d'alcool est la cause principale de développement d'une pancréatite chronique et la seconde étiologie de la pancréatite aiguë. La mortalité de la pancréatite aiguë dépend de son caractère nécrotico-hémorragique et de la réponse inflammatoire initiale tandis que les complications de type douleur, dénutrition et diabète sont les principaux enjeux de la prise en charge de la pancréatite chronique. Au fur et à mesure de l'avancée des techniques médicales et endoscopiques, les indications chirurgicales sont devenues de plus en plus rares, mais restent indispensables pour certains patients. L'approche pluridisciplinaire de ces patients est la clé du succès de la prise en charge.

Intravenous infusion of lidocaine significantly reduces propofol dose for colonoscopy: a randomised placebo-controlled study.

BACKGROUND: Propofol use during sedation for colonoscopy can result in cardiopulmonary complications. Intravenous lidocaine can alleviate visceral pain and decrease propofol requirements during surgery. We tested the hypothesis that i.v. lidocaine reduces propofol requirements during colonoscopy and improves post-colonoscopy recovery. METHODS: Forty patients undergoing colonoscopy were included in this randomised placebo-controlled study. After titration of propofol to produce unconsciousness, patients were given i.v. lidocaine (1.5 mg kg-1 then 4 mg kg-1 h-1) or the same volume of saline. Sedation was standardised and combined propofol and ketamine. The primary endpoint was propofol requirements. Secondary endpoints were: number of oxygen desaturation episodes, endoscopists' working conditions, discharge time to the recovery room, post-colonoscopy pain, fatigue. RESULTS: Lidocaine infusion resulted in a significant reduction in propofol requirements: 58 (47) vs 121 (109) mg (P=0.02). Doses of ketamine were similar in the two groups: 19 (2) vs 20 (3) mg in the lidocaine and saline groups, respectively. Number of episodes of oxygen desaturation, endoscopists' comfort, and times for discharge to the recovery room were similar in both groups. Post-colonoscopy pain (P<0.01) and fatigue (P=0.03) were significantly lower in the lidocaine group. CONCLUSIONS: Intravenous infusion of lidocaine resulted in a 50% reduction in propofol dose requirements during colonoscopy. Immediate post-colonoscopy pain and fatigue were also improved by lidocaine. CLINICAL TRIAL REGISTRATION: NCT 02784860.

The Belgian national registry on chronic pancreatitis: A prospective multi-centre study covering more than 800 patients in one year.

BACKGROUND/OBJECTIVES: The epidemiology, natural history, complications, and therapeutic management of chronic pancreatitis (CP) are not well described at the national level. This multi-centre prospective observational study involving eight Belgian hospitals aimed to improve the understanding of these aspects of CP in Belgium. METHODS: All patients with a diagnosis of CP based on imaging were eligible for this study. Data were gathered regarding epidemiology, etiology, CP complications, and treatment modalities. RESULTS: A total of 809 patients were included between 1/9/2014 and 31/8/2015. Most patients (794) were adults ≥16-years old, 74% were male, the median age at symptom onset was 47 (38-57) years, the median disease duration was 7 (3-13) years, and the median Izbicki pain score (IPS) was 96 (0-195). The main etiological risk factors according to the TIGAR-O classification were alcohol and tobacco (67%). Current drinkers had lower body mass index (BMI) (21.4 kg/m2 vs 24.1 kg/m2), higher IPS (110 vs 56), and longer inability to work than non-drinkers. Current smokers had lower BMI (21.5 kg/m2 vs 25 kg/m2) and higher IPS (120 vs 30) than non-smokers. Endocrine insufficiency and/or clinical steatorrhea was recorded in 41% and 36% of patients, respectively. The highest IPS was reported in patients with ongoing endotherapy (166 vs 50 for patients who completed endoscopy). CONCLUSION: This multicentric study on CP patients showed that current alcohol drinking and smoking are associated with pain and malnutrition. Pain scores were higher in patients with ongoing endotherapy, independently of surgery.

A tailored multi-frequency EPR approach to accurately determine the magnetic resonance parameters of dynamic nuclear polarization agents: application to AMUPol.

To understand the dynamic nuclear polarization (DNP) enhancements of biradical polarizing agents, the magnetic resonance parameters need to be known. We describe a tailored EPR approach to accurately determine electron spin-spin coupling parameters using a combination of standard (9 GHz), high (95 GHz) and ultra-high (275 GHz) frequency EPR. Comparing liquid- and frozen-solution continuous-wave EPR spectra provides accurate anisotropic dipolar interaction D and isotropic exchange interaction J parameters of the DNP biradical AMUPol. We found that D was larger by as much as 30% compared to earlier estimates, and that J is 43 MHz, whereas before it was considered to be negligible. With the refined data, quantum mechanical calculations confirm that an increase in dipolar electron-electron couplings leads to higher cross-effect DNP efficiencies. Moreover, the DNP calculations qualitatively reproduce the difference of TOTAPOL and AMUPol DNP efficiencies found experimentally and suggest that AMUPol is particularly effective in improving the DNP efficiency at magnetic fields higher than 500 MHz. The multi-frequency EPR approach will aid in predicting the optimal structures for future DNP agents.

[INITIAL MANAGEMENT IN ACUTE PANCREATITIS]. / Prise en charge initiale de la pancréatite aiguë.

Basic steps of acute pancreatitis initial management are diagnostic assessment, severity prediction, search for concomitant abnormalities being part of the etiologic work up or requiring an early treatment. Adequate volume perfusion is certainly the most important therapeutic measure.

[CRITICAL VIEWPOINT ON THE CURRENT APPROACH OF LOCALIZED PANCREATIC DUCTAL ADENOCARCINOMA]. / COMMENT JE TRAITE ... Point de vue critique sur l'approche actuelle du cancer du pancréas localize.

Surgical resection followed by chemotherapy is the actual standard of care for localized, deemed resectable, pancreatic ductal adenocarcinoma. Despite a better selection of surgical candidates and the actual performance of expert teams, the proportion of patients with a prolonged survival has not been ameliorated during the last three decades. The morphological determinants of resectability are the subject of limitations. In the future, only a better understanding of the biological process, an earlier diagnosis of purely localized disease and more efficient systemic therapies may lead to a better prognosis. Meanwhile, taking into account the prognostic factors associated with a lower chance of cure is currently a matter of debate. The optimal therapeutic sequence, being a surgery-first or a neoadjuvant approach is controversial. The theoretical advantages of preoperative chemotherapy eventually associated with chemo-radiation are demonstrated in other tumours and applicable to pancreatic cancer without any excess of operative mortality, early progression rates and, on the contrary with positive survival data. The completion rates of multi-modal therapy are in favour of the preoperative approach, which also gives the opportunity to select the best candidates for surgical resection.

Hydrogen bonding of nitroxide spin labels in membrane proteins.

On the basis of experiments at 275 GHz, we reconsider the dependence of the continuous-wave EPR spectra of nitroxide spin-labeled protein sites in sensory- and bacteriorhodopsin on the micro-environment. The high magnetic field provides the resolution necessary to disentangle the effects of hydrogen bonding and polarity. In the gxx region of the 275 GHz EPR spectrum, bands are resolved that derive from spin-label populations carrying no, one or two hydrogen bonds. The gxx value of each population varies hardly from site to site, significantly less than deduced previously from studies at lower microwave frequencies. The fractions of the populations vary strongly, which provides a consistent description of the variation of the average gxx and the average nitrogen-hyperfine interaction Azz from site to site. These variations reflect the difference in the proticity of the micro-environment, and differences in polarity contribute marginally. Concomitant W-band ELDOR-detected NMR experiments on the corresponding nitroxide in perdeuterated water resolve population-specific nitrogen-hyperfine bands, which underlies the interpretation for the proteins.

[Clinical vignette. Diagnosis of acute cholangitis]. / La vignette diagnostique de l'étudiant. Approche diagnostique d'une angiocholite.

Acute cholangitis develops as the result of infection by enteric organisms and obstruction of the biliary tract, mainly by stones. Diagnosis is highly probable if patient complains of biliary pain, fever and jaundice. Almost 10% of patients will develop a life-threatening disease. Clinical, biological and radiological features relevant for the diagnosis and management will be discussed.

[Management of acute cholangitis]. / La vignette thérapeutique de l'étudiant. Prise en charge de l'angiocholite.

Treatment of acute cholangitis requires antibiotics and biliary drainage. Some patients develop a life threatening form requiring intensive care and urgent drainage. It is important to identify those patients as soon as possible.

Abundance of alkali metals, alkaline and rare earths, and strontium-87/ strontium-86 ratios in lunar samples.

The variation in trace element abundance patterns indicates that lunar igneous rocks are the product of extensive igneous fractionation. Variations in the Sr(87)/ Sr(86) ratio indicate that these rocks crystallized 3.5+/-0.3 x 10(9) years ago.

Chemistry of lunar basalts with very high alumina contents.

A chemically distinct group of lunar rocks with the trace element characteristics of basaltic lunar rocks is apparently ubiquitous on the lunar surface. Such rocks have been found at the Apollo 15, Apollo 16, and Luna 20 landing sites. They may be derived from the plains-forming material that has been designated Cayley Formation.

[Eosinophilic esophagitis in adults: report of a case]. / Le cas clinique du mois. L'oesophagite à éosinophiles chez l'adulte: à propos d'un cas.

Eosinophilic esophagitis is a chronic inflammatory disease. The most typical symptoms are recurrent dysphagia and episodes of food impactions. This pathology is quite frequently associated with atopy. We report the case of a 39-year-old patient, suffering from allergic asthma, admitted to hospital for an episode of food impaction. Clinical, endoscopic and histological findings lead to the diagnosis of eosinophilic esophagitis. From data of the litterature, we discuss the diagnosis, the pathogeny and the treatment of this pathology.

WITHDRAWN: A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

The article has been withdrawn at the request of the authors and editor because of incorrect authorship, which is considered a form of unethical publication. The Publisher apologizes for any inconvenience this may cause.

[On the mechanism of photoinduced electron transfer in photosystem II reaction centers].

The EPR spectrum of the triplet state of photosystem II reaction centers has been studied in the case of the singly reduced primary acceptor complex QAFe2+. It was demonstrated that the shape of the spectrum does not change much when the relaxation of the primary acceptor is accelerated and when magnetic interaction between the reduced quinone molecule QA and the non-heme iron Fe2+ is disrupted. This observation confirms the earlier conclusion that the anomalous shape of the EPR spectrum is due mainly to the anisotropy of the quatum yield of the triplet state. A scheme of primary events in photosystem II is discussed, which is consistent with the observed properties of the EPR spectrum of the triplet state.

A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

BACKGROUND AND STUDY AIMS: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. PATIENTS METHODS: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. RESULTS: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. CONCLUSIONS: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

Transfer of light-induced electron-spin polarization from the intermediary acceptor to the prereduced primary acceptor in the reaction center of photosynthetic bacteria.

In reaction centers and chromatophores of photosynthetic bacteria strong light-induced emissive ESR signals have been found, not only after a flash but also under continuous illumination. The signal, with g = 2.0048 and delta Hpp = 7.6 G, is only present under reducing conditions in material in which the primary acceptor, ubiquinone, U and its associated high-spin ferrous ion are magnetically uncoupled. its amplitude under continuous illumination is strongly dependent on light intensity and on microwave power. The emissive signal is attributed to the prereduced primary acceptor, U-, which becomes polarized through transfer of spin polarization by a magnetic exchange interaction with the photoreduced, spin polarized intermediary acceptor, I-. A kinetic model is presented which explains the observed dependence of emissivity on light intensity and microwave power. Applying this analysis to the light saturation data, a value of the exchange rate between I- and U- of 4.10(8) s-1 is derived, corresponding to an exchange interaction of 3--5 G.

Photooxidation of chlorophyll in spinach chloroplasts between 10 and 180 K.

Electron paramagnetic resonance (EPR) and optical absorbance difference spectra and kinetics upon illumination by saturating flashes and continuous light of spinach chloroplasts frozen under various conditions were measured between 10 and 180 K. 1. At 100 K illumination with continuous light caused an EPR signal which decayed during the light in about 30 ms. This change is probably due to the reduction of P+-680, the oxidized primary electron donor of Photosystem II, by a secondary electron donor, cytochrome b-559. Flash illumination yielded the previously observed rapid (2 ms) transient. This transient has been ascribed to a back-reaction of the two primary reagents of Photosystem II (Malkin, R. and Bearden, A.J. (1975) Biochim. Biophys. Acta 396, 250-259; Visser, J.W.M. (1975) Thesis, Leiden). 2. Between 10 and 40 K, illumination with continuous light showed a transient which decayed in about 500 ms. The extent decreased with increasing temperature. However, the half time appeared to be temperature independent. This signal was also attributed to P+-680. 3. At 180 K it appeared to be impossible to observe the 2 and 30 ms components in dark frozen chloroplasts. However, they could be observed again if two short saturating flashes were given shortly before freezing. These changes seem to be dependent on the S-state of the reaction center. 4. After oxidizing the sample with ferricyanide (Eh = 540 mV), the light induced absorbance difference spectrum showed a bleaching near 676 nm. This change is ascribed to the irreversible oxidation of a dimeric chlorophyll molecule which acts as electron donor to P+-680 under these conditions. 5. Titration curves of the irreversible light-induced absorbance change at 676 nm and the irreversible light-induced EPR change near g = 2.00 provide strong evidence that these two changes reflect the same compound. Finally, a model is given to explain the observed reactions of Photosystem II at 10-180 K. The model involves three different ultimate and one intermediate electron donor to P+-680 at these temperatures.

Light-induced structural changes in photosynthetic reaction centres studied by ESEEM of spin-correlated D+QA- radical pairs.

Zn-substituted Rhodobacter sphaeroides R26 reaction centres (RCs) frozen in the dark and under illumination exhibit quite different recombination kinetics of the D+QA- radical pairs [Kleinfeld et al., Biochemistry, 23 (1984) 5780]. We have applied electron spin echo envelope modulation (ESEEM) of the spin-correlated D+QA- radical pairs to assess a possible light-induced change in the distance between the D and QA cofactors. The recombination kinetics and the field-swept spin-polarized EPR signal for the two preparations have been monitored by time-resolved EPR spectroscopy. For the samples frozen under illumination, a slight increase in the distance, 0.4+/-0.2 A, has been detected.

The triplet state of the FMO complex of the green sulfur bacterium Prosthecochloris aestuarii studied with single-crystal EPR.

Triplet-electron paramagnetic resonance (EPR) spectra were obtained of single crystals of the FMO complex of the green sulfur bacterium Prostecochloris aestuarii. The experiments support the results presented in a previous paper (Louwe et al., J. Phys. Chem. 101 (1997) 11280), which showed that the experimental optical spectra of this pigment-protein complex are best reproduced by assuming that one bacteriochlorophyll (BChl 3) is energetically isolated and that this BChl is the triplet-carrying BChl of the FMO complex at cryogenic temperatures for low excitation density. When comparing the experimental and simulated data sets of the triplet-EPR spectra in single crystals, the best fit is obtained for two triplet states, one localized at BChl 3 and the other at BChl 1. The existence of two different triplet states is traced to the relatively high excitation power necessary to observe the small triplet-EPR signal of the FMO single crystals.