Overview of venous thromboembolism

Thrombosis occurs at sites of injury to the vessel wall, by inflammatory processes leading to activation of platelets, platelet adherence to the vessel wall and the formation of a fibrin network. A thrombus that goes on to occlude a blood vessel is known as a thromboembolism. Venous thromboembolism begins with deep vein thrombosis (DVT), which forms in the deep veins of the leg (calf) or pelvis. In some cases, the DVT becomes detached from the vein and is transported to the right-hand side of the heart, and from there to the pulmonary arteries, giving rise to a pulmonary embolism (PE). Certain factors predispose patients toward the development of venous thromboembolism (VTE), including surgery, trauma, hospitalization, immobilization, cancer, long-haul travel, increased age, obesity, major medical illness and previous VTE; in addition, there may also be a genetic component to VTE. VTE is responsible for a substantial number of deaths per annum in Europe. Anticoagulants are the mainstay of both VTE treatment and VTE prevention, and many professional organizations have published guidelines on the appropriate use of anticoagulant therapies for VTE. Treatment of VTE aims to prevent morbidity and mortality associated with the disease, and any long-term complications such as VTE recurrence or post-thrombotic syndrome. Generally, guidelines recommend the use of low molecular weight heparins (LMWH), unfractionated heparin (UFH) or fondaparinux for the pharmacological prevention and treatment of VTE, with the duration of therapy varying according to the baseline characteristics and risk profile of the individual. Despite evidence showing that the use of anticoagulation prevents VTE, the availability of several convenient, effective anticoagulant therapies and the existence of clear guideline recommendations, thromboprophylaxis is underused, particularly in patients not undergoing surgery. Greater adherence to guideline-recommended therapies, such as LMWH, which can be administered on an outpatient basis, should reduce the mortality associated with this preventable disease.     

Donor selection for unrelated cord blood transplants

The number of unrelated cord blood transplants is increasing, with more than 8000 patients reported worldwide. Criteria of donor choice have been identified. Cell dose measured by number of nucleated cells is the most important factor, thus increases in cell dose can partially overcome the presence of HLA incompatibilities. Overall, increasing the number of HLA incompatibilities is associated with non-engraftment, but it also decreases the risk of relapse in patients with malignant disease, resulting in an absence of effect of HLA incompatibilities on event-free survival (survival without relapse or complications related to the transplant). However, in patients with non-malignant disorders, increasing the number of HLA incompatibilities decreases the overall survival. These results show that criteria of donor choice based on number of infused cells, number of HLA incompatibilities and diagnosis improve outcomes of unrelated cord blood transplants. Currently, owing to the possibility of using a non HLA identical donor, most patients can find a donor, increasing the need for the development of the inventory of cord blood banks. Methods of improving engraftment are currently under investigation.     

Extensive central ossifying fibroma of the maxilla: a case report with description of an alternative surgical technique

Central ossifying fibroma (COF) is a fibrous-osseous lesion containing fibrous tissue and varying amounts of calcified tissue. Although the lesion is preferentially located in the jaws, it may be found elsewhere. It usually affects patients during their third and fourth decades of life, with a female predilection. The mandibular premolar-molar area is the most common site. Radiographically, COF may present a radiolucent, radiopaque or a mixed appearance. This article reports a case of an extensive COF in the maxilla of a 62-year-old patient. Intraoral examination revealed a swelling with undefined limits in the right side of the upper alveolar ridge, extending towards the palate. The lesion had invaded the maxillary sinus, nasal cavity and orbit. An incision including mucosa, periosteum, and a thin layer of the bone, was performed. The lesion was excised using a flap, and interrupted suture was utilized. The bone which was preserved in the flap was used as graft so that faster and more effective bone formation could occur. The patient has been followed-up for 5 years with no clinical or radiographic signs of recurrence. This article demonstrates that COF has a considerable growth potential. In addition, the surgical technique here in described shows very good cosmetic and functional results, especially when managing very large lesions.     

Comparative therapeutic use of Risedronate and Calcarea phosphorica--allopathy versus homeopathy--in bone repair in castrated rats

Osteoporosis, a disease characterized by progressive bone loss, has been the target of several studies in the past few years. It results in a much higher risk for fractures and might cause slower bone lesion healing. The aim of this work was to study the effects of Risedronate (allopathic medicine) and Calcarea phosphorica 6CH (homeopathic medicine) on the repair of bone lesions in male rats with osteoporosis induced by castration. Eighty-four three-month-old rats were used divided into four groups of twenty-one animals each. Three groups where castrated and one group was submitted to Sham surgery. One month later, cortical lesions were made in all animals' tibiae and, after one day, the different experimental treatments began according to the following groups: CR--castrated/Risedronate (1 mg/kg/day); CCp--castrated/Calcarea phosphorica 6CH (3 drops/day); CP--castrated/placebo and SP--Sham/placebo. The animals were sacrificed at seven, fourteen and twenty-eight days after the beginning of the treatments and had their tibiae removed. Digital radiographs of the tibiae were taken and analyzed in order to evaluate the optical density of the defect area. Then, they were decalcified and processed for histological and histomorphometrical analysis. The data were submitted to ANOVA, and to the Tukey and Dunnett tests (5%). The allopathic and homeopathic treatments led to different bone formation as regards remodeling and maturation aspects. Further research is necessary to access the resistance and quality of the newly formed bone.     

Bioactive constituents of brazilian red propolis

In a new propolis type, red Brazilian propolis, 14 compounds were identified (six of them new for propolis), among them simple phenolics, triterepenoids, isoflavonoids, prenylated benzophenones and a naphthoquinone epoxide (isolated for the first time from a natural source). Three of the major components demonstrated significant antimicrobial activity, and two (obtained as inseparable mixture) possessed radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH).     

Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination

To assess the role of NOD2/CARD15 variants on the long-term outcome of allogeneic stem cell transplantation in a genetically homogeneous group, we extended our previous study (cohort I, n = 78) and typed DNA for NOD2/CARD15 single nucleotide polymorphisms (SNPs) from an additional 225 recipients and their HLA-identical sibling donors (cohort II) treated at four other European centers. Results of genotyping were compared with clinical outcome. The strong association of NOD2/CARD15 variants with transplantation-related mortality (TRM) was confirmed in univariate and multivariate analysis; TRM increased from 20% in cohort I/22% in cohort II in recipient/donor pairs without any NOD2/CARD15 variants to 47% in cohort I/32% in cohort II in the presence of one variant in either donor or recipient and further to 57% in cohort I/74% in cohort II in the presence of 2 or more variants (P < .002 in both cohorts). NOD2/CARD15 SNPs were not associated with relapse rate but had a strong impact on overall survival. In an analysis of center effects, the type of gastrointestinal decontamination was the only factor interfering with the prognostic significance of NOD2/CARD15 SNPs. Our data further support an interaction between gastrointestinal defense mechanisms, activation of the innate immune system, and specific transplant-related complications.     

Initial experience with stapled hemorrhoidopexy for treatment of hemorrhoids

BACKGROUND: Introduction of stapled hemorrhoidopexy by Longo in 1998 represented a radical change in the treatment of hemorrhoids. By avoiding multiple excisions and suture lines in the perianal region, stapled hemorrhoidopexy is intended to offer less postoperative pain than with conventional techniques. OBJECTIVE: To report and analyze the intra and postoperative results gained during initial experience with stapled hemorrhoidopexy. METHODS: One hundred and fifty five patients (67 males) with average age of 39.5 years (21-67 years) underwent stapled hemorrhoidopexy between June 2000 and December 2003 with symptomatic third-degree (n = 74) and fourth-degree (n = 81) hemorrhoids. Mean follow-up period was 20 months (14-60 months). RESULTS: Preoperative symptoms were prolapse (96.7%) and anal bleeding (96.1%). Overall mean operative time was 23 minutes (16-48 minutes). We observed one case of stapler failure and one case of failure to introduce the stapler occurred in a patient with previous anal surgery. Additional sutures for hemostasis were required in 103 patients (66.5%). Resection of skin tags was performed in 45 cases (29%). Postoperatively scheduled analgesia with oral dipyrone and celecoxib was enough for pain control in 131 patients (84.5%). Rescue analgesia was necessary in 24 cases (15.5%). Five patients needed opiates for pain control. Hospital discharge took place on the first postoperative day in 140 patients (90.3%). First defecation without pain was reported by 118 patients (76.1%). Postoperative complications were anal bleeding (10.3%), severe pain (3.2%), urinary retention (3.9%), fever without any signs of perianal infection (1.9%), incontinence for flatus (1.9%), hemorrhoidal thrombosis (1.3%). Two patients presented symptoms of recurrent hemorrhoidal disease and were successfully treated by conventional hemorrhoidectomy. They were no cases of anal stenosis, permanent incontinence, chronic pain or deaths in this series. CONCLUSIONS: Hemorrhoidopexy can be considered a feasible and safe alternative technique to conventional hemorroidectomy for select patients.     

Leukocyte-endothelium interactions after hemorrhagic shock/reperfusion and cecal ligation/puncture: an intravital microscopic study in rat mesentery

Hemorrhagic shock/reperfusion (HS/R) followed by sepsis triggers systemic microcirculatory disturbances that may induce multiple organ failure. The present study evaluated the effects of HS/R and cecal ligation and puncture, followed by necrotic cecal resection/peritoneal lavage (REL) on leukocyte-endothelium interactions at the mesentery. Eighty-one anesthetized Wistar rats (200-250 g) were randomly assigned to a first injury: (1) control-HS-no hemorrhagic shock/no reperfusion group, (2) HS/blood-HS/R with 25% shed blood, and (3) HS/blood + LR-HS/R with 25% of the shed blood + lactated Ringer's solution, 3x shed blood volume. Twenty-four hours post-HS/R, animals were submitted to cecal ligation and puncture and, 24 h thereafter, to REL. Leukocyte-endothelium interactions were assessed by intravital microscopy and intercellular adhesion molecule (ICAM) 1 and P-selectin expression by immunohistochemistry. Lungs were observed for ICAM-1 expression and neutrophil infiltration. Single and double injury induced significant increases in rolling (approximately 2-fold), adherent (approximately 5-fold), and migrated leukocytes (approximately 7-fold); ICAM-1 expression (approximately 1/2-fold), and P-selectin expression (approximately 1/2-fold) at the mesentery compared with control-HS group. REL normalized leukocyte-endothelium interactions at the mesentery in single-injured animals. However, in double-injured rats, adherence and migration of leukocytes decreased but did not normalize. Similar results were observed on ICAM-1 expression and neutrophil infiltration in the lungs from these animals. In conclusion, the current in vivo observation of the mesenteric microcirculation after a double injury followed by REL is a suitable model for the systematic evaluation of the inflammatory reaction at local and distant sites. In addition, data presented herein emphasized the importance of surgical removal of the septic focus in controlling the otherwise lethal sepsis-induced multiple organ dysfunction syndrome.     

The thymus exports long-lived fully committed T cell precursors that can colonize primary lymphoid organs

Thymic export of cells is believed to be restricted to mature T cells. Here we show that the thymus also exports fully committed T cell precursors that colonize primary lymphoid organs. These precursor cells exited the thymus before T cell receptor rearrangements and colonized lymphoid organs such as the thymus and the gut. Migration of the thymic T cell-committed precursors led to permanent colonization of the gut precursor compartment, improved the capacity of gut precursors to further differentiate into T cells and was sufficient for the generation of 'euthymic like' CD8alphaalpha(+) intraepithelial lymphocytes. These data demonstrate a new function for the thymus in peripheral seeding with T cell precursors that become long lived after thymus export.