Arthroscopic Anterior and Posterior Glenoid Bone Augmentation With Capsular Plication for Ehlers-Danlos Syndrome With Multidirectional Instability.

Recurrent multidirectional shoulder instability is a difficult clinical problem. This can be compounded in patients with connective tissue diseases such as Ehlers-Danlos syndrome. We present an all-arthroscopic technique involving extra-articular anterior and posterior glenoid bone grafting to augment a capsular repair in a patient with Ehlers-Danlos syndrome and recurrent multidirectional shoulder instability. Graft options include either distal tibial allograft or iliac crest autograft. Anterior graft placement uses a dilated far medial portal using an inside-out technique. The posterior graft is placed through a dilated posterior portal. A 1-mm edge of anterior and posterior glenoid rim is denuded of cartilage for later capsular repair, and grafts are secured flush to the osseous surface. A capsular plication is then completed and repaired to the prepared native glenoid surface, using the grafts as extra-articular osseous bumpers.

Tertiary care centre adherence to unified guidelines for management of periprosthetic joint infections: a gap analysis.

BACKGROUND: The success rate of surgical treatment for periprosthetic joint infection (PJI) remains inconsistent in the literature. Variability in PJI clinical guidelines and surgeon adherence to guidelines could affect treatment success. The objectives of this study were to appraise current recommendations for PJI management and develop a unified clinical standard of care, to perform a gap analysis of PJI cases in a tertiary institution to determine the rate of guideline adherence, and to determine if adherence to unified PJI guidelines affected 2-year treatment outcomes. METHODS: We appraised the PJI guidelines from 3 academic medical societies, and consistent statements were aggregated. We retrospectively reviewed all PJI cases in a tertiary care institution. We defined PJI based on Musculoskeletal Infection Society PJI criteria. Surgeon adherence to preoperative, intraoperative, surgical and medical management guidelines was calculated, and we evaluated the association between guideline adherence and 2-year treatment outcomes. RESULTS: The institutional rate of PJI was 1.13% (38 of 3368). Treatment success was 57.8% at 2 years. Unified guideline adherence percentages varied substantially: 92% of patients had preoperative erythrocyte sedimentation rate and C-reactive protein, 97% had intraoperative tissue cultures, 42% had appropriate preoperative arthrocentesis, and 74% underwent guideline-appropriate surgery. Performing appropriate preoperative arthrocentesis significantly correlated with positive treatment outcomes at 2 years (p = 0.028). CONCLUSION: Adherence to PJI guidelines varies considerably, indicating that clinicians are either unaware of them or do not recognize their value for PJI treatment. This study shows the need for institution-based PJI treatment pathways that are consistent with published guidelines and the need to monitor adherence.

CONTEXTE: Les études ne concordent pas quant au taux de réussite du traitement chirurgical des infections de prothèses articulaires (IPA). Une certaine variabilité dans les lignes directrices sur ces infections et dans l'adhésion des chirurgiens à celles-ci pourrait nuire à la réussite du traitement. La présente étude visait à évaluer les recommandations actuelles sur la prise en charge des IPA afin d'élaborer une norme de soins uniforme, à effectuer une analyse des lacunes entourant les cas d'IPA dans un établissement de soins tertiaires pour déterminer le taux d'adhésion aux lignes directrices, et à déterminer si l'adhésion à des lignes directrices uniformes influençait les issues de traitement après 2 ans. MÉTHODES: Nous avons évalué les lignes directrices sur les IPA de 3 sociétés médicales universitaires, et agrégé des énoncés cohérents. Nous avons également examiné de façon rétrospective tous les cas d'IPA dans un établissement de soins tertiaires. Aux fins de notre étude, l'IPA était définie selon les critères de la Musculoskeletal Infection Society. Nous avons calculé l'adhésion des chirurgiens aux lignes directrices de prise en charge préopératoire, peropératoire, chirurgicale et médicale, puis nous avons évalué l'association entre ce paramètre et les issues de traitement après 2 ans. RÉSULTATS: Le taux d'IPA dans l'établissement était de 1,13 % (38 sur 3368), et le taux de réussite du traitement était de 57,8 % après 2 ans. Les pourcentages d'adhésion aux lignes directrices variaient considérablement : 92 % des patients avaient eu une analyse préopératoire de la vitesse de sédimentation érythrocytaire et de la protéine C-réactive, 97 % avaient eu des cultures tissulaires peropératoires, 42 % avaient eu une arthrocentèse préopératoire appropriée, et 74 % avaient subi une intervention chirurgicale conforme aux lignes directrices. Il y avait une corrélation significative entre l'arthrocentèse préopératoire et les issues favorables après 2 ans (p = 0,028). CONCLUSION: L'adhésion aux lignes directrices sur les IPA varie considérablement, ce qui indique que les cliniciens ne les connaissent pas ou n'en reconnaissent pas la valeur pour le traitement des IPA. La présente étude montre qu'il faut dans les établissements des protocoles de traitement conformes aux lignes directrices publiées, et qu'il est nécessaire de surveiller l'adhésion des chirurgiens à celles-ci.

DetectTLC: Automated Reaction Mixture Screening Utilizing Quantitative Mass Spectrometry Image Features.

Full characterization of complex reaction mixtures is necessary to understand mechanisms, optimize yields, and elucidate secondary reaction pathways. Molecular-level information for species in such mixtures can be readily obtained by coupling mass spectrometry imaging (MSI) with thin layer chromatography (TLC) separations. User-guided investigation of imaging data for mixture components with known m/z values is generally straightforward; however, spot detection for unknowns is highly tedious, and limits the applicability of MSI in conjunction with TLC. To accelerate imaging data mining, we developed DetectTLC, an approach that automatically identifies m/z values exhibiting TLC spot-like regions in MS molecular images. Furthermore, DetectTLC can also spatially match m/z values for spots acquired during alternating high and low collision-energy scans, pairing product ions with precursors to enhance structural identification. As an example, DetectTLC is applied to the identification and structural confirmation of unknown, yet significant, products of abiotic pyrazinone and aminopyrazine nucleoside analog synthesis. Graphical Abstract ᅟ.

Estilos sanos de vida en adultos con discapacidad intelectual: qué conocen, factores que los benefician y dificultan / No disponible

Las personas con discapacidad intelectual son más propensas a tener problemas de salud que las que no la tienen. Hasta ahora se ha investigado poco la salud desde la perspectiva de las propias personas con discapacidad intelectual. Intentamos centrarnos sobre qué es lo que estas personas entienden por estar sanos, y cuáles son sus experiencias sobre los estilos sanos de vida. Se llevaron a cabo entrevistas semiestructuradas a 13 adultos con discapacidad intelectual para preguntarles sobre su salud y estilos sanos de vida. Los datos fueron analizados por los temas recogidos. Los participantes demostraron comprender el significado de estar sanos, llevar una dieta sana, los peligros del uso de sustancias y los beneficios del ejercicio. Mostraron cierto conocimiento sobre las razones para embarcarse en conductas sanas. Surgió la idea de la moderación, así como la existencia de factores que benefician y dificultan la implicación en un estilo sano de vida. Estos resultados sugieren que las personas con discapacidad intelectual demuestran tener cierta comprensión de lo que constituye estar sano y ser conscientes de los estilos sanos de vida, las consecuencias de conductas poco sanas y la necesidad de tener moderación (AU)

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Myoepithelioma of the skull: a case report.

BACKGROUND AND IMPORTANCE: Myoepithelioma of bone is a rare osseous tumor thought to be related to myoepithelial lesions found at other anatomic sites such as the salivary gland and skin. These tumors are composed of varying proportions of epithelial and myoepithelial cells and exhibit a spectrum of biologic behavior ranging from benign to malignant. We present the first reported case of myoepithelioma of the skull. CLINICAL PRESENTATION: A 20-year-old white woman presented with a persistent right parieto-occipital skull nodule, relating its presence to a fall on the site 2 years previously. The nodule had become painful in the past 2 months. Her past medical history and workup were otherwise unremarkable. The initial biopsy was inconclusive for diagnosis. The lytic bone lesion was subsequently resected, and histopathological examination showed a proliferation of epithelioid cells in a myxochondroid background. Fluorescence in situ hybridization studies revealed a rearrangement of the EWSR1 locus. The morphologic and molecular findings were consistent with the diagnosis of myoepithelioma of bone. CONCLUSION: Six months after surgery, the patient is doing well with no evidence of recurrence. This case illustrates the clinical presentation, histopathology, and molecular findings of a myoepithelioma of the skull with successful surgical treatment. Because myoepitheliomas with benign morphological appearance may rarely act aggressively, long-term clinical follow-up is warranted.

The human cerebrospinal fluid metabolome.

With continuing improvements in analytical technology and an increased interest in comprehensive metabolic profiling of biofluids and tissues, there is a growing need to develop comprehensive reference resources for certain clinically important biofluids, such as blood, urine and cerebrospinal fluid (CSF). As part of our effort to systematically characterize the human metabolome we have chosen to characterize CSF as the first biofluid to be intensively scrutinized. In doing so, we combined comprehensive NMR, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) Fourier transform-mass spectrometry (FTMS) methods with computer-aided literature mining to identify and quantify essentially all of the metabolites that can be commonly detected (with today's technology) in the human CSF metabolome. Tables containing the compounds, concentrations, spectra, protocols and links to disease associations that we have found for the human CSF metabolome are freely available at http://www.csfmetabolome.ca.

Phase III randomized, double-blind study of maintenance CAI or placebo in patients with advanced non-small cell lung cancer (NSCLC) after completion of initial therapy (NCCTG 97-24-51).

PURPOSE: This study assessed whether maintenance therapy with carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen. METHODS: After completion of chemotherapy, patients were randomized to receive daily oral CAI at 250mg or placebo. Treatment continued until patient refusal, disease progression or unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L). RESULTS: Registration was halted early for slow accrual (targeted 360, randomized 186: 94 CAI, 92 placebo). All patients were off active treatment at time of analyses. Non-haematologic AEs (primarily grade 1, 2) observed significantly more often in the CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%), nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0% versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment for AEs, death on study or refusal more often in the CAI group (36.0% versus 8.7%, p<0.0001). No significant differences in survival or time to progression were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log rank p=0.54; 2.8 months versus 2.4 months, log rank p=0.50). More patients receiving CAI reported a clinically significant (10-point) decline in QOL particularly on the functional (58% versus 37%, p=0.05) construct of FACT-L and UNISCALE (72% versus 51%, p=0.04). CONCLUSION: The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC.

A heuristic technique for CTIS image reconstruction.

An iterative method is presented for computed tomography imaging spectrometer (CTIS) image reconstruction in the presence of both photon noise in the image and postdetection Gaussian system noise. The new algorithm, which assumes the transfer matrix of the system has a particular structure, is evaluated experimentally with the result that it is significantly better, for larger problems, than both the multiplicative algebraic reconstruction technique (MART) and the mixed-expectation image-reconstruction technique (MERT) with respect to accuracy and computation time.

Crystal structure of LL-diaminopimelate aminotransferase from Arabidopsis thaliana: a recently discovered enzyme in the biosynthesis of L-lysine by plants and Chlamydia.

The essential biosynthetic pathway to l-Lysine in bacteria and plants is an attractive target for the development of new antibiotics or herbicides because it is absent in humans, who must acquire this amino acid in their diet. Plants use a shortcut of a bacterial pathway to l-Lysine in which the pyridoxal-5'-phosphate (PLP)-dependent enzyme ll-diaminopimelate aminotransferase (LL-DAP-AT) transforms l-tetrahydrodipicolinic acid (L-THDP) directly to LL-DAP. In addition, LL-DAP-AT was recently found in Chlamydia sp., suggesting that inhibitors of this enzyme may also be effective against such organisms. In order to understand the mechanism of this enzyme and to assist in the design of inhibitors, the three-dimensional crystal structure of LL-DAP-AT was determined at 1.95 A resolution. The cDNA sequence of LL-DAP-AT from Arabidopsis thaliana (AtDAP-AT) was optimized for expression in bacteria and cloned in Escherichia coli without its leader sequence but with a C-terminal hexahistidine affinity tag to aid protein purification. The structure of AtDAP-AT was determined using the multiple-wavelength anomalous dispersion (MAD) method with a seleno-methionine derivative. AtDAP-AT is active as a homodimer with each subunit having PLP in the active site. It belongs to the family of type I fold PLP-dependent enzymes. Comparison of the active site residues of AtDAP-AT and aspartate aminotransferases revealed that the PLP binding residues in AtDAP-AT are well conserved in both enzymes. However, Glu97* and Asn309* in the active site of AtDAP-AT are not found at similar positions in aspartate aminotransferases, suggesting that specific substrate recognition may require these residues from the other monomer. A malate-bound structure of AtDAP-AT allowed LL-DAP and L-glutamate to be modelled into the active site. These initial three-dimensional structures of LL-DAP-AT provide insight into its substrate specificity and catalytic mechanism.

Hemoglobin and hematocrit values after saline infusion and tourniquet.

This study attempted to contribute to standardization of blood testing in sport, and to investigate the effect of artificial dilution with saline. In 10 healthy, physically active males and 3 healthy physically active females hemoglobin (Hb), hematocrit (Ht), and % reticulocytes (%retics) were measured at different time points to look for possible fluctuations during day time, while the subjects had regular coffee breaks and lunch. In 7 of the subjects in a separate experiment 500 ml of saline were infused around 8 am and Hb, Ht, and %retics were measured before and every hour thereafter until 7 hours after infusion. In addition Ht was measured on a hematological analyzer as well as with a centrifuge. In a separate experiment the effect of tourniquet duration on Hb and Ht was studied in 9 of the subjects. The results show that Hb, Ht, and %retics are stable from 8 am to 4 pm, but that infusion of 500 ml of saline induces an acute decrease in Hb and Ht within one hour (Hb decreased from 15.2+/-0.9 g/dl to 14.5+/-1.0 g/dl, and Ht from 45.6+/-2.8 % to 44.0+/-2.5 %). The decline in Hb and Ht was maintained during the 7-hour observation period. Ht values of the same samples measured with a hematological analyzer and a centrifuge were not different. Application of the tourniquet did significantly affect Hb and Ht values only from two minutes, and thereafter Hb and Ht remained stable during the rest of the 5-minute tourniquet. With blood testing in sport these results have to be taken into consideration.

Liquid chromatographic determination including simultaneous "on-cartridge" separation of ranitidine cisapride drug combinations from paediatric plasma samples using an automated solid-phase extraction procedure.

HPLC methodology was investigated for the simultaneous determination of cisapride and ranitidine in small volume paediatric plasma samples. Such a simultaneous determination proved difficult due to the small sample volumes, the low concentrations of the drugs and the different log P values of the two compounds. The two drugs and their respective internal standards were separated "on-cartridge" using HLB Solid Phase Extraction cartridges and the samples quantified by individual HPLC methodologies. The technique has been applied successfully to 60 paediatric plasma samples containing both cisapride and ranitidine.

Modification of cysteine 111 in Cu/Zn superoxide dismutase results in altered spectroscopic and biophysical properties.

Cu/Zn superoxide dismutase (SOD) mutations are involved in about 20% of all cases of familial amyotrophic lateral sclerosis (FALS). Recently, it has been proposed that aberrant copper activity may be occurring within SOD at an alternative binding, and cysteine 111 has been identified as a potential copper ligand. Using a commercial source of human SOD isolated from erythrocytes, an anomalous absorbance at 325 nm was identified. This unusual property, which does not compromise SOD activity, had previously been shown to be consistent with a sulfhydryl modification at a cysteine residue. Here, we utilized limited trypsin proteolysis and mass spectrometry to show that the modification has a mass of 32 daltons and is located at cysteine 111. The reaction of SOD with sodium sulfide, which can react with cysteine to form a persulfide group, and with potassium cyanide, which can selectively remove persulfide bonds, confirmed the addition of a persulfide group at cysteine 111. Gel electrophoresis and glutaraldehyde cross-linking revealed that this modification makes the acid-induced denaturation of SOD fully irreversible. Furthermore, the modified protein exhibits a slower acid-induced unfolding, and is more resistant to oxidation-induced aggregation caused by copper and hydrogen peroxide. Thus, these results suggest that cysteine 111 can have a biochemical and biophysical impact on SOD, and suggest that it can interact with copper, potentially mediating the copper-induced oxidative damage of SOD. It will be of interest to study the role of cysteine 111 in the oxidative damage and aggregation of toxic SOD mutants.

Cu/Zn superoxide dismutase can form pore-like structures.

Mutations in Cu/Zn superoxide dismutase (SOD) are associated with familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease that is characterized by the selective death of motor neurons. Despite the genetic association made between the protein and the disease, the mechanism by which the mutant SOD proteins become toxic is still a mystery. Using wild-type SOD and three pathogenic mutants (A4V, G37R, and G85R), we show that the copper-induced oxidation of metal-depleted SOD causes its in vitro aggregation into pore-like structures, as determined by atomic force microscopy. Because toxic pores have been recently implicated in the pathogenic mechanism of other neurodegenerative diseases, these results raise the possibility that the aberrant self-assembly of oxidatively damaged SOD mutants into toxic oligomers or pores may have a pathological role in FALS.

Prevalence and Prognostic Significance of Neuroendocrine Differentiation in Colorectal Carcinomas.

The prognostic significance of neuroendocrine differentiation in colorectal carcinoma is uncertain. We analyzed 289 moderately differentiated (grades II and Ill) colorectal carcinomas for neuroendocrine differentiation by immunohistochemistry and in situ hybridization. The tumors were divided into three groups based on the presence of and the numbers of neuroendocrine cells, with group I having no neuroendocrine cells, group II having <1 positive cell/mm(2), and group Ill with >1 positive cell/mm(2). In situ hybridization with probes for chromogranin A and B detected almost twice as many neuroendocrine cells as did immunostaining with an antibody for chromogranin A. There was no prognostic difference associated with the presence or absence of neuroendocrine differentiation in this group of moderately differentiated carcinomas. These results indicate that the presence of neuroendocrine cells detected by expression of chromogranin protein or mRNA does not influence prognosis in moderately differentiated colorectal carcinomas.