We present a full 3D numerical simulation of the acoustic streaming observed in full-image micro-particle velocimetry by Hagsäter et al., Lab Chip 7, 1336 (2007) in a 2 mm by 2 mm by 0.2 mm ...microcavity embedded in a 49 mm by 15 mm by 2 mm chip excited by 2-MHz ultrasound. The model takes into account the piezo-electric transducer, the silicon base with the water-filled cavity, the viscous boundary layers in the water, and the Pyrex lid. The model predicts well the experimental results.
Heparan sulfate proteoglycan associated with endothelial cells in normal blood vessels inhibits intravascular coagulation and egress of blood cells and plasma proteins, key features of hyperacute ...rejection. It was shown herein that exposure of cultured porcine endothelium to human serum as a source of natural antibodies and complement caused cleavage and release of 5% of endothelial cell proteoglycans within 4 min and greater than 50% within 1 h. Proteoglycan release depended on activation of the classical complement pathway and preceded irreversible cell injury. These findings suggest that loss of endothelial cell proteoglycan may be a critical step in the pathogenesis of hyperacute rejection and in diseases involving humoral injury to endothelial cells.
F. Hayashi, S. K. Coles, K. B. Bach, G. S. Mitchell and D. R. McCrimmon
Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611-3008.
The objectives were to ...determine 1) respiratory responses to carotid
chemoreceptor inputs in anesthetized rats and 2) whether the cerebellar
vermis plays a role in these responses. A carotid sinus nerve was
stimulated (20 Hz) with five 2-min trains, each separated by approximately
3 min. During stimulation, respiratory frequency (f), peak amplitude of
integrated phrenic nerve activity (integral of Phr), and their product (f x
integral of Phr) immediately increased. As stimulation continued, integral
of Phr progressively increased to a plateau short-term potentiation
(STP), but f and f x integral of Phr decreased short-term depression
(STD) to a value still above control. Upon stimulus termination, integral
of Phr progressively decreased but remained above control; f and f x
integral of Phr transiently decreased below baseline. After the final
stimulation, integral of Phr remained above control for at least 30 min
long-term facilitation (LTF). Repeated 5-min episodes of isocapnic
hypoxia also elicited STP, STD, and LTF. Vermalectomy lowered the
CO2-apneic threshold and eliminated LTF. In conclusion, carotid
chemoreceptor activation in rats elicits STP and LTF similar to that in
cats; the vermis may play a role in LTF. A new response, STD, was observed.
La nécrose médullaire est une manifestation rare essentiellement retrouvée au cours d’hémopathies malignes (60 %) ou de cancer solide (30 %). Nous rapportons le cas d’un patient de 71 ans dont le ...diagnostic de nécrose médullaire a été porté sur un tableau initialement proche d’une pseudo-polyarthrite rhizomélique (PPR).
Un patient de 71 ans sans antécédent notable nous est adressé en hospitalisation complète pour AEG fébrile avec syndrome inflammatoire inexpliqué évoluant depuis un mois malgré l’administration de 2 lignes d’antibiothérapie probabiliste. Il présentait alors des douleurs inflammatoires prédominant aux ceintures, sans autres anomalies à l’examen clinique en dehors d’une fièvre oscillante. Le bilan biologique retrouvait : une hémoglobine à 11g/dL normocytaire arégénérative, une thrombopénie à 146000/mm3, une lymphopénie à 450/mm3. On retrouvait un important syndrome inflammatoire biologique avec un fibrinogène à 6g/L, une CRP à 157mg/L. L’électrophorèse des protéines avec immunofixation, l’immunophénotypage lymphocytaire, la recherche d’ANA, d’ANCA, de cryoglobulinémie, le dosage des fractions C3 C4 CH50 du complément sont tous revenus normaux, tout comme les hémocultures. La calcémie était normale, les triglycérides à 2,54mmol/L. Une PPR a été tout d’abord suspectée, un scanner TAP et une biopsie d’artère temporale demandée. Le scanner ne retrouvait aucune anomalie particulière. Une corticothérapie a été débutée dans l’attente des résultats de la biopsie temporale.
L’évolution initialement franchement favorable s’est rapidement dégradée et la corticothérapie stoppée au bout de 10jours. Les douleurs initiales se sont étendues, le patient rapportait alors des douleurs osseuses diffuses moyennement calmées par des antalgiques de palier III. La ferritinémie était à 6907ug/L. Un PET-scanner a finalement été réalisé retrouvant un hypermétabolisme ostéomédullaire extrêmement intense et hétérogène de tout le squelette. C’est la biopsie ostéomédullaire qui va permettre de faire le diagnostic, retrouvant une infiltration lymphomateuse massive associée à des plages de nécroses étendues du tissu hématopoïétique. Au final le diagnostic de lymphome non hodgkinien diffus à grandes cellules de localisation osseuse et ostéomédullaire exclusive compliqué de nécrose médullaire a été retenu. Un traitement de « de Bulky » a été débuté associant endoxan, étoposide et solumédrol. Ce traitement s’est compliqué d’une aggravation rapide des cytopénies avec survenue actuelle d’une infection de CIP.
Cette présentation est originale de par l’errance diagnostic initiale notamment liée à la présentation clinique et la normalité des examens scanographiques initiaux : la principale plainte du patient en dehors de cette AEG fébrile était des douleurs des ceintures d’horaires inflammatoires. La discordance entre les résultats du scanner et du PET-scanner est remarquable.
La nécrose médullaire est une affection rare et grave associée dans 90 % des cas à un processus néoplasique en particulier hématologique. La présentation clinique comprend dans 80 % des cas des douleurs osseuses sévères particulièrement au niveau lombaire, une altération de l’état général quasi-systématique, ainsi qu’une fièvre ou un ictère dans 55 à 70 % des cas. Sur le plan biologique, l’hémogramme retrouve dans 90 % des cas une anémie arégénérative typiquement normocytaire ou une thrombopénie voire une pancytopénie mais les leucocytes peuvent rester normaux. On observe constamment un syndrome inflammatoire biologique. Aucune de ces anomalies n’est spécifique du diagnostic. Le médullogramme est rarement contributif et la biopsie ostéomédullaire reste indispensable pour poser le diagnostic retrouvant une nécrose recouvrant plus de 50 % du tissu hématopoïétique. Le pronostic de cette pathologie est sombre lié à la pathologie sous-jacente.
Coupling of C9 - 14 (4) and C15 - 21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to ...4/Cs2CO3/Pd(dppf)2). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki−Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric β-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8 - 9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still−Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7 - 24 (7) ready to be coupled with the C1 - 6 fragment, which is described in Part 2 of this series.
Objectives: To evaluate the effects of MK‐0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals.
Design: ...Placebo‐controlled, randomized, double‐blind trial.
Setting: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers.
Participants: One hundred sixty‐one hip‐fracture patients were enrolled. Entry criteria included consenting hip‐fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity.
Intervention: Random assignment to 6 months of daily treatment with MK‐0677 or placebo. Patients were followed for an additional 6 months after completion of therapy.
Measurements: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP‐NH), the ability to live independently, and insulin‐like growth factor I (IGF‐I) levels.
Results: MK‐0677 treatment increased serum IGF‐I levels by 84% (95% confidence interval (CI)=63–107), compared with an increase of 17% (95% CI=8–28) on placebo. There were no significant differences between MK‐0677 and placebo in improvement in functional performance measures or in the overall SIP‐NH score. Although MK‐0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant.
Conclusion: Although MK‐0677 treatment increased serum IGF‐I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip‐fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.
The Knee Society Total Knee Arthroplasty Radiographic Evaluation and Scoring System was introduced to encourage uniform reporting of radiographic outcome. However, the method for evaluation of ...radiolucent lines has been shown to be unreliable. Because it has been shown that reducing the complexity of classification systems increases reliability and reproducibility, we questioned whether a simplification of the Radiographic Evaluation and Scoring System would improve reliability and reproducibility. A new system for assessment of radiolucent lines was introduced, and the interobserver reliability and intraobserver reproducibility were studied in 100 patients with 120 total knee replacements. For the new system the mean kappa intraobserver reproducibility coefficient was 0.71 (range, 0.62-0.85) for the femoral component, 0.86 (range, 0.80-0.96) for the tibial component, and 0.58 (range, 0.46-0.75) for the patella prosthesis. The mean interobserver reliability coefficient among three observers was 0.61 (range, 0.45-0.72) for the femoral component, 0.82 (range, 0.73-0.88) for the tibial component, and 0.58 (range, 0.43-0.72) for the patella prosthesis. The new system for assessment of radiolucent lines increased reliability and reproducibility and should supplement the Knee Society's Radiographic Evaluation and Scoring System.
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