Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood

The platelet glycoproteins (GPs) Ib, integrin alpha(2)beta(1), and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knockout models. To examine their relationship during human thrombus formation on collagen type I fibers at high shear (1000 s(-1)), we tested a novel antibody against GPVI, an immunoglobulin single-chain variable fragment, 10B12, together with specific antagonists for GPIb alpha (12G1 Fab(2)) and alpha(2)beta(1) (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca(2+) signaling, and phosphatidylserine (PS) exposure, but not for primary adhesion, even with more than 97% receptor blockade. Inhibiting alpha(2)beta(1) revealed its involvement in regulating Ca(2+) signaling, PS exposure, and aggregate size. Both GPIb alpha and alpha(2)beta(1) contributed to primary adhesion, showing overlapping function. The coinhibition of receptors revealed synergism in thrombus formation: the coinhibition of adenosine diphosphate (ADP) receptors with collagen receptors further decreased adhesion and aggregation, and, crucially, the complete eradication of thrombus formation required the coinhibition of GPVI with either GPIb alpha or alpha(2)beta(1). In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation.     

Acute pulmonary embolism: comparison of standard axial MDCT with paddlewheel technique

PURPOSE: The purpose of this study was to evaluate the ability of rotated paddlewheel reformations for the detection of central and peripheral pulmonary embolism (PE) compared to standard axial multi detector CT (MDCT) images. MATERIAL AND METHODS: CT scans of 35 patients with PE were reviewed by three independent readers for the detection of pulmonary emboli using standard axial CT scans and reformatted paddlewheel technique. All images were evaluated in random order. MDCT examinations were performed with a collimation of 1.25 mm, a pitch of six and a reconstruction interval of 0.8mm. For each patient MIP were reformatted by using a paddlewheel arrangement with 5mm slab thickness and 5 degrees rotation. Standard of reference for PE was a consensus reading of the axial images by all three readers. RESULTS: The overall sensitivity for the axial images for the three readers ranged between 91% and 96%; for paddlewheel reformations from 78% to 83%; the specificity for both methods was 98-99%. Inter- and intraobserver agreement was also higher for axial images than for paddlewheel reformations. CONCLUSION: Comparing standard axial MDCT scans and reformatted paddlewheel images no significant difference for the detection of central PE was found, whereas for the detection of peripheral emboli standard axial images showed a significant higher percentage of detecting PE than paddlewheel reformations.     

Early glottic carcinoma: Treatment according patient's preference?

BACKGROUND: To analyze the results in early (stage I and II) glottic carcinoma of a single institution with a patient-oriented concept. METHODS: After diagnostic workup and multidisciplinary counseling, either radiotherapy or CO(2) laser surgery was chosen with respect to the patient's preference. RESULTS: Sixty-five patients underwent laser surgery and 75 had radiotherapy. For T1 tumors, the 5-year overall survival, disease-specific survival, and initial local control rate after laser surgery and radiotherapy were comparable (OS, 85% vs 88%; DSS, 96% vs 93%; LCR, 86% vs 85%). In contrast, initial local control for T2 tumors was significantly more favorable after surgery (OS, 83% vs 78%; DSS, 83% vs 88%; LCR, 89% vs 67%). Larynx preservation was significantly higher after surgery in T1 tumors (96% vs 82%) and in T2 tumors (89% vs 77%). CONCLUSIONS: Selection of the treatment modality according to patient's preference results in a comparable control of disease for T1 tumors. The initial local control for T2 tumors is significantly better after surgery. In both stages laser surgery warrants a better larynx preservation rate.     

Tracheal agenesis without esophageal fistula: genetic, resuscitative, and pathological issues

An exceptional case of tracheal agenesis with no communication with the esophagus is described. This malformation needs surgical airway approach and is hardly classifiable. We analyzed the literature and our institutional data: this resulted to be the first case of such anatomical variant. Genetic and pathological issues are reviewed: recent genetic data seem to explain this malformation. We also reviewed the available literature about prenatal presentation. Because prenatal diagnosis is difficult to achieve and current guidelines for neonatal resuscitation do not provide any recommendation, the resuscitative team may not be prepared for managing such a case. Usefulness of uncommon resuscitative maneuvers is discussed: a promptly performed surgical tracheotomy is the only mean to ventilate such a baby.     

The neurovascular triad: mixed cavernous, capillary, and venous malformations of the brainstem

OBJECT: The four types of cerebrovascular malformations may sometimes be combined and more often occur in pairs; triads are exceptional. The authors present six patients with the clinicoradiographic profile of mixed vascular malformations of the brainstem, including cavernous malformation (CM), capillary telangiectasia, and developmental venous anomaly (DVA). METHODS: Five patients (one of whom was a child) suffered from hemorrhage, suggesting that this complex association has a high bleeding potential. Progressive growth, rebleeding, and de novo occurrence of the associated CM were documented in three cases. Magnetic resonance imaging of the brain was obtained in all patients by using one or more of the following modalities: T1-weighted sequences before and after gadolinium administration; T2-weighted sequences; T2-weighted fluid attenuated Inversion recovery; T1-weighted fast spin echo; and diffusion weighted, diffusion tensor, and perfusion imaging in three cases. RESULTS: Three patients were surgically treated with the intention of excising the hemorrhagic lesion, but only two patients had their malformations successfully removed. In the third case, diffuse pontine telangiectasia precluded the safe excision of the CM. Histological examination demonstrated a blended pathological milieu characterized by coalescent telangiectasia and venules associated with loculated endothelial chambers resembling an immature or de novo CM. Three patients were treated conservatively; recurrent minor hemorrhage occurred in one case. The authors found these malformations to be arranged in two basic relationships: CM inside the telangiectasia and CM in the radicles of the DVA. Stenosis of the main venous collector and dilation of the medullary veins were important findings. CONCLUSIONS: The pathogenesis of this malformation may be referred to a developmental deviance of the brainstem capillary-venous network associated with transitional vessels and loculated endothelial vascular spaces related to genetic and acquired origins, probably in a restrictive venous outflow milieu.     

Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not

Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12-week diets of chow or chow plus candy. The latter were randomized for 12 further weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert to chow-only diet. Energy expenditure was measured, and oral glucose tolerance tests (OGTTs) were performed. Body composition was determined by dual-energy X-ray absorptiometry scanning, and pancreatic beta-cell mass was determined by histology. Candy feeding increased weight, fat mass, and feeding-associated energy expenditure. Liraglutide or reversal to chow diet fully reversed weight and fat gains. Liraglutide was associated with decreased calorie intake and shifted food preference (increased chow/decreased candy consumption). Despite weight loss, liraglutide-treated rats did not decrease energy expenditure compared with candy-fed controls. Vildagliptin affected neither weight, food intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly suggested that both drugs increased insulin sensitivity. Liraglutide and vildagliptin inhibited obesity-associated increases in beta-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of beta-cell to body mass was low.     

Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial

OBJECTIVE: To compare unilateral and bilateral neck exploration for primary hyperparathyroidism in a prospective randomized controlled trial. SUMMARY BACKGROUND DATA: Based on the assumption that unilateral neck exploration for a solitary parathyroid adenoma should reduce operating time and morbidity, a variety of minimally invasive procedures have challenged the idea that bilateral neck exploration is the gold standard for the surgical treatment of primary hyperparathyroidism. However, to date, no open prospective randomized trial has been published comparing unilateral and bilateral neck exploration. METHODS: Ninety-one patients with the preoperative diagnosis of primary hyperparathyroidism were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. The primary end-point was the use of postoperative medication for hypocalcemic symptoms. RESULTS: Eighty-eight patients (97%) were cured. Histology and cure rate did not differ between the two groups. Patients in the bilateral group consumed more oral calcium, had lower serum calcium values on postoperative days 1 to 4, and had a higher incidence of early severe symptomatic hypocalcemia compared with patients in the unilateral group. In addition, for patients undergoing surgery for a solitary parathyroid adenoma, unilateral exploration was associated with a shorter operative time. The cost for the two procedures did not differ. CONCLUSIONS: Patients undergoing a unilateral procedure had a lower incidence of biochemical and severe symptomatic hypocalcemia in the early postoperative period compared with patients undergoing bilateral exploration. Unilateral neck exploration with intraoperative parathyroid hormone assessment is a valid surgical strategy in patients with primary hyperparathyroidism with distinct advantages, especially for patients with solitary parathyroid adenoma.     

An educational approach based on a non-injury model compared with individual symptom-based physical training in chronic LBP. A pragmatic, randomised trial with a one-year follow-up

Background  

In the treatment of chronic back pain, cognitive methods are attracting increased attention due to evidence of effectiveness similar to that of traditional therapies. The purpose of this study was to compare the effectiveness of performing a cognitive intervention based on a non-injury model with that of a symptom-based physical training method on the outcomes of low back pain (LBP), activity limitation, LBP attitudes (fear-avoidance beliefs and back beliefs), physical activity levels, sick leave, and quality of life, in chronic LBP patients.