[Anogenital granulomatosis as extradigestive Crohn disease: Efficiency of adalimumab therapy]. / Maladie de Crohn de localisation ano-génitale exclusive traitée par adalimumab.

INTRODUCTION: Anogenital granulomatosis is a rare disease which is actually considered as a metastatic lesion of Crohn disease (CD). OBSERVATION: A 53-year-old woman presented with intermittent vulvar and anoperineal lesions since adolescence, seeping and painful during sexual intercourse. We observed an infiltrative and asymmetric oedema of labia majora, perianal oedematous vegetative pseudo-marisca, and groin fold and perianal linear "knife-like" ulcerations. Pathological analysis revealed noncaseating giant cell granulomas. The diagnosis of CD was made. Investigations did not show any intestinal involvement. Anti-TNFα therapy with adalimumab was dramatically efficient. CONCLUSION: Anogenital granulomatosis often precedes intestinal lesions but may also be isolated as in our case. Although treatment is difficult, anti-TNFα seem promising tools.

The LAMP instrument at the Linac Coherent Light Source free-electron laser.

The Laser Applications in Materials Processing (LAMP) instrument is a new end-station for soft X-ray imaging, high-field physics, and ultrafast X-ray science experiments that is available to users at the Linac Coherent Light Source (LCLS) free-electron laser. While the instrument resides in the Atomic, Molecular and Optical science hutch, its components can be used at any LCLS beamline. The end-station has a modular design that provides high flexibility in order to meet user-defined experimental requirements and specifications. The ultra-high-vacuum environment supports different sample delivery systems, including pulsed and continuous atomic, molecular, and cluster jets; liquid and aerosols jets; and effusive metal vapor beams. It also houses movable, large-format, high-speed pnCCD X-ray detectors for detecting scattered and fluorescent photons. Multiple charged-particle spectrometer options are compatible with the LAMP chamber, including a double-sided spectrometer for simultaneous and even coincident measurements of electrons, ions, and photons produced by the interaction of the high-intensity X-ray beam with the various samples. Here we describe the design and capabilities of the spectrometers along with some general aspects of the LAMP chamber and show some results from the initial instrument commissioning.

[Multiple granular cell tumours in a patient with Noonan's syndrome and juvenile myelomonocytic leukaemia]. / Tumeurs à cellules granuleuses multiples chez un enfant atteint d'un syndrome de Noonan compliqué de leucémie myélomonocytaire juvénile.

BACKGROUND: Granular cell tumour (GCT) is a rare form of tumour comprising Schwann cells. Herein, we report a case of a child presenting Noonan syndrome complicated by juvenile myelomonocytic leukaemia (JMML) and who also developed a multiple form of GCT. We discussed the molecular mechanisms that might account for this association. PATIENTS AND METHODS: A six-year-old boy with Noonan syndrome complicated by JMML presented three asymptomatic subcutaneous nodules on his back, forearm and neck. Histological analysis revealed GCT. A literature review revealed seven cases of Noonan syndrome presenting GCT, none of which were associated with JMML. Mutation of gene PTPN11, via hyperactivation of intracellular Ras signalling may cause the development of GCT and JMML in children presenting Noonan syndrome. DISCUSSION: Detailed clinical examination is recommended in children presenting GCT to screen for multiple forms and for signs of malformation suggestive of a genetic syndrome. Ours is the first case to be described of Noonan syndrome complicated by JMML associated with multiple GCT. This association once again raises the important question of the role of the Ras-MAPK signalling pathway in the development of benign and malignant tumours of solid organs or blood, associated with genetic syndromes.

Ultrafast X-ray Auger probing of photoexcited molecular dynamics.

Molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation--X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towards high kinetic energies, resulting from a particular C-O bond stretch in the ππ* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the nπ* state.

Spectral encoding of x-ray/optical relative delay.

We present a new technique for measuring the relative delay between a soft x-ray FEL pulse and an optical laser that indicates a sub 25 fs RMS measurement error. An ultra-short x-ray pulse photo-ionizes a semiconductor (Si(3)N(4)) membrane and changes the optical transmission. An optical continuum pulse with a temporally chirped bandwidth spanning 630 nm-710 nm interacts with the membrane such that the timing of the x-ray pulse can be determined from the onset of the spectral modulation of the transmitted optical pulse. This experiment demonstrates a nearly in situ single-shot measurement of the x-ray pulse arrival time relative to the ultra-short optical pulse.

Effect of Carmeda BioActive Surface coating versus Trillium Biopassive Surface coating of the oxygenator on circulating platelet count drop during cardiopulmonary bypass.

An investigation was conducted to evaluate the effect that surface coating of the hollow-fiber membrane oxygenator had on circulating platelet count drop during cardiopulmonary bypass (CPB). Sixty patients undergoing non-emergency myocardial revascularization for coronary artery disease were randomly divided into two groups. Group one (n = 32) received the Carmeda-coated Maxima-Plus PRF oxygenator while the patients in Group two (n=28) received the Trillium-coated Affinity oxygenator during CPB. The net platelet count drops for the pump specimen (15-20 min after the initiation of bypass) for the Carmeda and the Trillium groups were 3.6 +/- 15.8% and 6.2 +/- 10.2%, respectively. The net platelet count drop for the warming specimen for the Carmeda and the Trillium groups were 2.9 +/- 19.4% and 0.5 +/- 11.0%, respectively. There were no statistically significant differences between the groups. The authors conclude that using either the Carmeda-coated Maxima-Plus PRF oxygenator or the Trillium-coated Affinity oxygenator afford similar benefits in regards to preserving circulating platelet counts during bypass.

Effect of Trillium Biopassive Surface coating of the oxygenator on platelet count drop during cardiopulmonary bypass.

The new Trillium Biopassive Surface is a coating designed to minimize the adsorption of protein and the attachment of cells. In previous studies, we were able to demonstrate that, by coating the bypass circuit with small amounts of albumin, the drop in circulating platelet count seen with the newer low-prime hollow-fiber membrane oxygenators is eliminated. A study was undertaken to compare the Avecor Affinity oxygenator with albumin in the prime with the Trillium-coated Affinity. Fifty-six patients undergoing nonemergency open-heart surgery were randomly divided into two groups. One group (Albumin) received the Affinity oxygenator with 10 ml of 25% albumin added to the pump prime. The other group (Trillium) received the Trillium-coated Affinity oxygenator. To normalize the data for the effects of hemodilution, the mean net platelet count drop on bypass was calculated for each group. The Albumin group had a net platelet count drop of 0.81+/-9.78%, while the Trillium group had a drop of 1.58+/-13.0%. There was no significant statistical difference between the two groups. From our investigation, we concluded that Trillium Biopassive Surface coating affords the Affinity oxygenator the same protective effects on circulating platelet counts as adding albumin to the prime.

Protein microcrystals and the design of a microdiffractometer: current experience and plans at EMBL and ESRF/ID13.

There is a growing demand for the examination of protein microcrystals at third-generation synchrotron sources. After successful pilot experiments at EMBL/ESRF, which proved that protein microcrystals are often suitable for data collection, operation of the microfocus beamline ID13 was made more user-friendly and suitable for macromolecular crystallography experiments. Given the excellent quality of the beamline microfocusing optics, the key element for successful experiments becomes the handling and visualization of microcrystals. To address this, a microdiffractometer has been designed to allow maximum precision combined with ease of usage and is currently under construction.

Neutron Laue diffractometry with an imaging plate provides an effective data collection regime for neutron protein crystallography.

Neutron quasi-Laue diffraction data (2 A resolution) from tetragonal hen egg-white lysozyme were collected in ten days with neutron imaging plates. The data processing Laue software, LAUEGEN, developed for X-ray Laue diffractometry, was adapted for neutron diffractometry with a cylindrical detector. The data analysis software, X-PLOR, was modified and used for the refinement of hydrogen atoms, and the positions of 960 hydrogen atoms in the protein and 157 bound water molecules, were determined. Several examples are given of the methods used to identify hydrogen atoms and water molecules.

A neutron image plate quasi-Laue diffractometer for protein crystallography.

An instrument which is based on image plate technology has been constructed to perform cold neutron Laue crystallography on protein structures. The crystal is mounted at the center of a cylindrical detector which is 400mm long and has a circumference of 1000mm, with gadolinium oxide-containing image plates mounted on its exterior surface. Laue images registered on the plate are read out by rotating the drum and translating a laser read head parallel to the cylinder axis, giving a pixel size of 200 microm x 200 microm and a total read time of 5 minutes. Preliminary results indicate that it should be possible to obtain a complete data set from a protein crystal to atomic resolution in about two weeks.

Experimental pulmonary hypertension produced by surgical and chemical denervation of the pulmonary vasculature.

The purpose of this study was to investigate the hypothesis that balloon distention of the main pulmonary artery (MPA) induces pulmonary hypertension that is produced by a neural reflex and to investigate the possible efferent components of its reflex arc. Using a specially designed triple-lumen balloon catheter, positioned under fluoroscopy in the MPA, the hemodynamic responses to MPA distention were studied before and after the following: surgical denervation of the bifurcation of the MPA, chemical sympathectomy (6-hydroxydopamine), 100 percent oxygen breathing, and vagotomy. Our findings suggest that the experimental pulmonary hypertension caused by distention of the MPA is produced by excitation of stretch receptors in or near the bifurcation of the MPA and that the efferent limb of this reflex is predominantly mediated via the adrenergic nervous system.

Ultrasonic visualization of the non-opacified gallbladder: response of the normal and obstructed canine gallbladder to C8CCK.

In vitro studies of a simulated gallbladder show that B-scan ultrasonography is as reliable as radiography in measuring changes in volume of the organ. The width or planimetric area of the sonogram correlates with the change in balloon volume and with similar radiographic measurements. In vivo measurements of the normal canine gallbladder stimulated by a carefully prescribed infusion of C8CCK in the dose range of 2.2 to 5.5 ng/kg/min over an 8 to 10 minute interval, showed a clearly defined decrease in gallbladder width. In ligation and division of the common bile duct no change in gallbladder size was demonstrated. We conclude that sonography alone can be used to measure a change in gallbladder size to better differentiate complete obstruction of the common bile duct from medical causes in the jaundiced patient.

Value of gallbladder B-scan ultrasonography.

The gallbladder B-scans of 20 patients who had subsequent surgery were separated into three categories based upon certain sonographic criteria. Our data, in this limited series, revealed gallbladder pathology in each patient who had any one or combination of the following scan characteristics: (1) internal echos, (2) irregular wall, or (3) absence of recognizable gallbladder sonolucency. The category which demonstrated a normal sonographic gallbladder, namely a smooth wall and no internal echos, contained a number of false negatives which proved to have either small stone cholelithiasis or extraphepatic ductal obstruction. Within the described limitations, the B-scan can be a valuable test in confirming the significance of a radiographically nonvisualized gallbladder or in detecting a biliary tract lesion in a patient with a disease entity that precludes radiographic visualization by conventional techniques.

Blunt injuries to branches of the aortic arch.

Blunt injuries to branches of the aortic arch are not unusual and must be considered in any patient surviving deceleration or crush injury. Review of 36 case reports, including own own case, revealed 22 injuries to the innominate artery (4 with injuries to other arch branches), seven to the right subclavian, seven to the left subclavian, and eleven associated injuries to the thoracic aorta. Thirty patients (83 per cent) survived. Mediastinal widening (92 per cent) was the most frequent manifestation of vascular injury and is an indication for immediate aortography to delineate the entire thoracic aorta. Distal circulation was clinically decreased in less than 50 per cent, with symptomatic ischemia in only a few instances. Death was due to associated head injury in 3 of 6 cases. Earlier operation would have avoided exsanguination (one death) and late complications of false aneurysm or vascular insufficiency (10 patients).

Regulation of arterial PCO2 during intravenous CO2 loading.

Increased CO2 flow to the lung produced by increasing cardiac output (with constant PVCO2) results in hyperpnea with arterial PCO2 maintained at its control value (J. Appl. Physiol. 36: 457, 1974). To study if arterial PCO2 could be similarly regulated when CO2 flow was elevated by increasing PVCO2 (without changing cardiac output), we produced graded increases in PVCO2 (up to a mean of 69 mmHg) using an extracorporeal gas exchanger in five chloralose-urethan-anesthetized dogs. CO2 output increased up to fourfold. Ventilation increased in proportion to the additional CO2 flow to the lung with consequent regulation of arterial PCO2 at its control value. Comparable increases in VE produced by "conventional" airway loading resulted in arterial hypercapnia. The resulting CO2 response curve was similar to that found in unanesthetized dogs. We conclude that intravenous delivery of CO2 to the lung results in infinite "sensitivity" when computed as Delta VE/Delta paco2. These results provide evidence for a CO2-linked hyperpnea which is not mediated by measurable increases in mean arterial PCO2.