Impacto de la contaminación aérea por incendios forestales en la morbimortalidad de la población expuesta / Impact of air pollution by forest fires and the morbidity of the exposed population

La exposición a las emanaciones de incendios forestales es un importante problema de salud pública nacional e internacional. El cambio climático que conlleva sequía y aumento de la temperatura estival aumenta el riesgo y magnitud de los episodios de incendios forestales, generándose grandes incendios cuyas emanaciones pueden afectar a poblaciones distanciadas del epicentro. La asociación entre la exposición a las emanaciones de los incendios forestales, el aumento de las concentraciones de material particulado aéreo y la morbilidad respiratoria (exacerbación de asma y enfermedades respiratorias crónicas) ha sido evidenciada en diversos estudios. Sin embargo, es difícil realizar un metaanálisis de ellos, ya que la metodología empleada es muy disímil. Entre los principales mecanismos de morbilidad se encontrarían: la producción de citoquinas proinflamatorias, la activación endotelial y la disfunción del sistema nervioso autónomo. Ante la exposición al humo de incendios forestales, se produce daño tisular, aumento de los mecanismos protrombóticos, aumento de la presión arterial y cambios en el ritmo cardiaco, que explicaría los efectos cardiovasculares. Los sujetos con patología cardiovascular preexistente podrían tener mayor riesgo cardiovascular; sin embargo, existen factores confundentes en esta asociación. Por otra parte, el posible riesgo cancerígeno con la exposición a estas emanaciones requiere mayores estudios poblacionales.

Exposure to forest fire fumes is a major national and international public health issue. Climate change that leads to drought and increased summer temperature increases the risk and magnitude of wildfires episodes, generating mega-fires whose fumes not only affect the boundary population, but they may become transcontinental. Association between exposure to forest fire fumes, mainly increased concentrations of air born particulate matter and respiratory morbidity (exacerbation of asthma and chronic respiratory diseases) has been evidenced by diverse studies. However, it is difficult to carry out meta-analysis with them since the methodology used is dissimilar. Among the main causes of morbidity have been postulated the production of pro-inflammatory cytokines, endothelial activation and dysfunction of the autonomic nervous system. Occurrence of tissue damage, increased prothrombotic mechanisms, increased blood pressure and changes in heart rate, would explain the cardiovascular effects associated with exposure to smoke from these fires. However, epidemiological outcomes have not been entirely consistent, as the association between cardiovascular morbidity and exposure to wildfire fumes may be mixed with confounding factors. Despite this, patients with pre-existing cardiovascular pathology may be at increased risk. Finally, the potential risk of carcinogen with exposure to these fumes requires further population studies.

Effect of sedation on fore- and hindlimb lameness evaluation using body-mounted inertial sensors.

REASONS FOR PERFORMING STUDY: Diagnostic analgesia is an integral part of equine lameness examinations, but is challenging to perform in uncooperative horses. Using sedation to facilitate this might, because of analgesic and ataxia-inducing effects, interfere with lameness evaluation. OBJECTIVES: To evaluate whether sedation with low-dose xylazine would alter lameness amplitude as measured by body-mounted inertial sensors. STUDY DESIGN: Controlled experiment. METHODS: Forty-four horses were randomly split into 2 groups. Lameness was measured using body-mounted inertial sensors before and after injection of xylazine (0.3 mg/kg bwt) or saline. Sedation was measured at 5, 20 and 60 min following treatment, and lameness evaluations were performed before (Time 0) and at 20 and 60 min after treatment. Forelimb lameness was determined by measuring the vector sum of mean head height maximum and minimum differences between all right and left forelimb strides (n>25) collected with the horse trotting in a straight line. Hindlimb lameness amplitude was determined by measuring mean pelvic height maximum and minimum differences between right and left hindlimb strides. Numbers of horses staying the same, improving or worsening were compared between groups at each time interval. RESULTS: There were no significant differences in head or pelvic movement asymmetry between xylazine and saline treatment groups. However, a few horses with forelimb lameness in the xylazine treatment group showed a large decrease in head movement asymmetry (decrease in forelimb lameness) at 60 min following sedation. CONCLUSIONS: Low-dose sedation with xylazine may be used without the concern of potential lameness-masking effects for hindlimb lameness evaluation, but caution should be used in some horses with forelimb lameness of mild severity. The Summary is available in German - see Supporting information.

Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4.

Successful hematopoietic stem cell transplant requires the infusion of a sufficient number of hematopoietic stem/progenitor cells (HSPCs) that are capable of homing to the bone marrow cavity and regenerating durable trilineage hematopoiesis in a timely manner. Stem cells harvested from peripheral blood are the most commonly used graft source in HSCT. Although granulocyte colony-stimulating factor (G-CSF) is the most frequently used agent for stem cell mobilization, the use of G-CSF alone results in suboptimal stem cell yields in a significant proportion of patients. Both the chemokine receptor CXCR4 and the integrin α(4)ß(1) (very late antigen 4 (VLA-4)) have important roles in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of CXCR4 or VLA-4 with their ligands results in the rapid and reversible mobilization of hematopoietic stem cells into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the development of small-molecule CXCR4 and VLA-4 inhibitors and how they may improve the utility and convenience of peripheral blood stem cell transplantation.

Preclinical evaluation of Mab CC188 for ovarian cancer imaging.

Cancer stem cells (CSCs) have been successfully isolated from solid tumors and are believed to be initiating cells of primary, metastatic and recurrent tumors. Imaging and therapeutic reagents targeted to CSCs have potential to detect subclinical tumors and completely eradicate the disease. Previously, we have demonstrated that Mab CC188 binds to colon cancer CD133- and CD133+ (CSCs) cells. In this study, we examined the reactivity of Mab CC188 to ovarian cancer cells including CD133+ cells and primary tumor tissues using immunofluorescence staining methods and tissue microarray technique. We also explored the feasibility of using NIR dye-labeled Mab CC188 probe to image ovarian tumors in vivo. Mab CC188 stains both CD133- and CD133+ cells of ovarian cancer. Tissue microarray analysis reveals that 75% (92/123) of ovarian cancer cases are positively stained with Mab CC188. Weak positive (±), positive (+), strong positive (++) and very strong positive (+++) stains are 14.8, 3.7, 11 and 24.4%, respectively. In contrast, Mab CC188 staining is low in normal cells and tissues. In vivo study show that significant amounts of the probe accumulates in the excretion organs in the early period postinjection. At 24 hr, the imaging probes have largely accumulates in the tumor, while the intensity of the imaging probe decreases in the liver. The tumor uptake was still evident at 120-hr postinjection. Our work suggests that Mab CC188-based imaging and therapeutic reagents are capable of detecting early stage ovarian tumors and effectively treating the tumor.

Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas.

Primary effusion lymphomas (PELs) are a rare type of non-Hodgkin's lymphoma that are resistant to cytotoxic chemotherapy. PELs manifest constitutive activation of nuclear factor kappa B (NF-kappaB), and inhibition of NF-kappaB induces apoptosis of PELs and sensitizes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced death. Bortezomib (PS-341), a peptidyl boronic acid inhibitor of the proteasome, is a potent agent against a wide range of hematologic malignancies and has been shown to inhibit NF-kappaB. Thus, we examined the cytotoxic effects of bortezomib alone and in combination with various drugs. Bortezomib potently inhibited NF-kappaB in PEL cells in a dose-dependent manner. In addition, bortezomib inhibited growth and induced apoptosis of PEL cell lines (IC(50) values of 3.4-5.0 nM). Results of drug interactions between bortezomib and chemotherapy (doxorubicin and Taxol) were schedule-dependent: synergistic interactions were generally observed when PEL cells were pretreated with bortezomib prior to chemotherapy, whereas additive or even antagonistic interactions occurred with chemotherapy pretreatment or simultaneous treatment with bortezomib and chemotherapy. Most schedules of bortezomib and dexamethasone were synergistic, although pretreatment with dexamethasone resulted in additive interactions. Effects of combinations of bortezomib and TRAIL were generally additive. Thus, bortezomib represents a promising potential therapy for the treatment of PEL.

Effect of pH on the self-association of erythrocyte band 3 in situ.

The human erythrocyte anion exchanger (band 3) contains a cytoplasmic domain (cdb3) that exists in a reversible, pH-dependent structural equilibrium among three native conformations. To understand how this conformational equilibrium might influence the association state of band 3, we have incubated stripped erythrocyte membranes in solutions ranging from pH 6.0 to pH 10.5 and have examined the oligomeric state of the protein by size exclusion high performance liquid chromatography. We demonstrate that incubation of membranes in slightly acidic conditions favors dimer formation, whereas extended incubation at higher pHs (pH>9) leads to irreversible formation of an oligomeric species larger than the tetramer. Since the pH dependence of the conformational state of the cytoplasmic domain exhibits a similar pH profile, we suggest that the conformation of the cytoplasmic domain can modulate the self-association of band 3. Importantly, this modulation would appear to require the structural interactions present within the intact protein, since the isolated membrane-spanning domain does not display any pH dependence of association. The irreversible nature of the alkali-induced aggregation further suggests that a secondary reaction subsequent to band 3 association is required to stabilize the high molecular weight aggregate. Although we were able to eliminate covalent bond formation in this irreversible aggregation process, the exact nature of the secondary reaction remains to be elucidated.

Volar plate arthroplasty of the distal interphalangeal joint.

Ten patients with chronic dorsal fracture subluxation of the distal interphalangeal joint were managed over 5 years with volar plate advancement arthroplasty. The mean time from injury to definitive surgical treatment was 8 weeks (range, 2 weeks to 4 months). All injuries were characterized by volar comminution and impaction of the distal phalanx, with associated dorsal subluxation. Surgical treatment included volar plate advancement arthroplasty and K-wire fixation of the reduced joint for 4 weeks. All patients were evaluated at an average postoperative duration of 25 months (range, 10-60 months). The average arc of motion of the distal interphalangeal joint of the 4 fingers (6) was 42 degrees and of the interphalangeal joint of the thumb (4) was 51 degrees. All patients had a residual flexion contracture averaging 12 degrees (range, 6 degrees to 25 degrees ). Volar plate advancement arthroplasty is an effective treatment for chronic distal interphalangeal joint dorsal fracture subluxation.

Galeazzi fracture-dislocation: a new treatment-oriented classification.

Forty patients with Galeazzi fracture-dislocations were treated with open reduction and internal fixation of the radial shaft fracture. Intraoperative distal radioulnar joint (DRUJ) instability after anatomic reduction was managed with supplemental wire transfixion of the DRUJ (10 patients) or open reduction and triangular fibrocartilage complex repair (3 patients). Two patterns of fracture-dislocation were identified based on the location of the radial shaft fracture. Twenty-two type I fractures were in the distal third of the radius within 7.5 cm of the midarticular surface of the distal radius; 12 of these cases were associated with intraoperative DRUJ instability. Eighteen type II fractures were in the middle third of the radial shaft more than 7.5 cm from the midarticular surface of the distal radius. Only one of these fractures had intraoperative DRUJ instability after open reduction and internal fixation of the radial shaft fracture. A high index of suspicion, early recognition, and acute treatment of DRUJ instability will avoid chronic problems in this complex injury.

Open reduction and internal fixation of acute displaced scaphoid waist fractures.

Fourteen consecutive patients with acute displaced scaphoid waist fractures were treated with open reduction and internal fixation. The operative technique consisted of anatomic reduction of the displaced scaphoid waist fracture, correction of carpal instability, radial bone grafting for comminution, and internal fixation with K-wires or Herbert screw. The patients were evaluated an average of 26 months (range, 4-48 months) after surgery. Thirteen of the 14 (93%) fractures united. The average time to union was 11.5 weeks (range, 8-20 weeks). Fracture union was confirmed with trispiral tomography. Final radiographic assessment consistently revealed a healed scaphoid fracture, restored intrascaphoid alignment, and no evidence of carpal instability. All patients regained functional wrist range of motion (wrist extension, 57 degrees; wrist flexion, 52 degrees ) and grip strength. Open reduction and internal fixation of acute displaced scaphoid waist fractures restores scaphoid alignment and leads to predictable union. Early operative intervention avoids malunion and carpal instability that often occurs with closed management of these complex fractures.

A Phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease.

BACKGROUND: Bone metastases typically are associated with osteolytic bone destruction, resulting in bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. Bisphosphonates are potent inhibitors of normal and pathologic bone resorption and represent a significant therapeutic improvement in the management of patients with lytic bone metastases. Zoledronic acid is a new-generation, highly potent, nitrogen-containing bisphosphonate that to the authors knowledge is the most potent inhibitor of bone resorption currently in clinical trials. The objectives of the current study were to assess the safety and tolerability of increasing doses of zoledronic acid and to determine its activity with respect to reducing biochemical markers of bone resorption in cancer patients with bone metastases. METHODS: Forty-four cancer patients with bone metastases or primary bone lesions were enrolled sequentially into 1 of 5 fixed ascending-dose treatment groups. Each patient received a single intravenous bolus injection of 1, 2, 4, 8, or 16 mg of zoledronic acid over 30-60 seconds. Patients were monitored for 8 weeks for the evaluation of clinical findings, adverse events, vital signs, electrocardiograms, markers of bone resorption, and urinary N-acetyl-beta-D-glucosaminidase. RESULTS: Zoledronic acid was safe and well tolerated at all dose levels tested. Commonly reported adverse events included bone pain, fever, anorexia, constipation, and nausea, which were experienced by a similar proportion of patients in each treatment group. Seven patients reported serious adverse events, none of which appeared to be related to the study drug. Zoledronic acid effectively suppressed biochemical markers of bone resorption, including the highly specific markers N-telopeptide and deoxypyridinoline, for up to 8 weeks in the 2-16-mg dose groups and for a shorter duration in the 1-mg group. CONCLUSIONS: In the current study, zoledronic acid was safe and well tolerated and demonstrated potent inhibition of bone resorption. The authors believe it may improve the treatment of metastatic bone disease.

Dorsal open repair of proximal pole scaphoid fractures.

Proximal pole fractures of the scaphoid are well suited for comprehension screw fixation. A dorsal approach allows for direct visualization of the fracture site, accurate reduction, and internal fixation. Bone grafting can also be achieved through the same incision without additional significant dissection. Successful uncomplicated union in the majority of cases with a considerably shortened period of immobilization has lead to a growing interest in this surgical procedure.

Lack of serologic association of human herpesvirus-8 (KSHV) in patients with monoclonal gammopathy of undetermined significance with and without progression to multiple myeloma.

Because human herpesvirus-8 (HHV-8) DNA has been found in multiple myeloma (MM) patients by polymerase chain reaction, it was suggested that HHV-8 may play a role in the transformation of monoclonal gammopathy of undetermined significance (MGUS) to MM. Therefore, 362 MGUS sera with and without progression to MM were tested for IgG antibody to HHV-8. Only 7.8% of the MGUS sera contained HHV-8 antibody to lytic proteins, and IgG antibody to HHV-8 latent antigen was even lower than lytic antibody (2.9%). No differences were observed in the distribution of antibody to HHV-8 in sera from MGUS patients who progressed to MM. The seroprevalences of HHV-8 in MGUS (7.8%), MM (5.4%), and healthy donors (5.9%) were similar, thus arguing for the lack of epidemiologic evidence of HHV-8 participation in the pathogenesis of MM. MGUS patients were immune competent in response to Epstein-Barr virus (EBV) infection because 97% contained antibody to EBV virus capsid antigen.

Acute fractures of the distal radius.

Distal radius fractures commonly are sustained by athletes during competition. Typically, these are high energy injuries with severe displacement, metaphyseal comminution, and articular surface disruption. Each fracture is distinguished by its degree of articular displacement, stability, and reducibility. Management is contingent on recognition of the variable magnitude of articular disruption and skillful treatment based on specific fracture configuration.

The digital extensor mechanism of the hand.

In summary, there is a complex interplay between the extrinsic and intrinsic components of the digital extensor mechanism. Numerous examples of dynamic anatomy and pathology of the extensor mechanism in common clinical settings have been described. Treatment principles have been outlined. This review should provide the orthopaedic surgeon with a framework for management of common hand problems.

Retrograde compression screw fixation of acute proximal pole scaphoid fractures.

Seventeen consecutive patients with acute unstable proximal pole scaphoid fractures were managed over the past 5 years with open reduction and internal fixation. Four fractures were displaced, with greater than 1 mm of fragment offset and intercarpal malalignment. The operative technique consisted of a dorsal approach to the scaphoid, radius bone grafting, and freehand retrograde Herbert compression screw fixation. The patients were evaluated at an average of 37 months (range, 12-63 months) after surgery. All fractures healed within 13 weeks (average, 10 weeks). Functional wrist range of motion and grip strength were achieved in all patients. No patients developed osteonecrosis or radioscaphoid arthritis. Open reduction and internal fixation rather than primary casting is a better means of reducing the complications of delayed union, nonunion, and irreparable osteonecrosis that often occur after acute proximal pole scaphoid fracture treated with cast immobilization.

Long-term assessment of proximal row carpectomy for chronic perilunate dislocations.

Twelve patients with chronic stage III or stage IV perilunate dislocations were managed over the past 7 years by proximal row carpectomy. All dislocations were untreated or incompletely reduced for a minimum of 8 weeks after injury. The mean time from injury to definitive treatment was 15 weeks (range, 8 weeks to 6 months). Surgical management was inclusive of a dual dorsal and volar approach. Median nerve decompression, lunate excision, and capsuloligament repair was performed volarly and scaphoid and triquetrum carpectomy was accomplished dorsally. Temporary radio capitate K-wire fixation during early soft tissue healing was uniformly performed. All patients were evaluated at an average postoperative duration of 40 months (range, 28 months to 7 years). Marked relief of wrist pain and median nerve dysesthesias was routinely achieved. Effective wrist range of motion and grip strength were restored. Untreated stage III and IV chronic perilunate dislocation treated by proximal row carpectomy eliminates pain and restores function to a severely injured wrist.

Evaluation of biochemical changes during in vivo erythrocyte senescence in the dog.

One hypothesis to explain the age-dependent clearance of red blood cells (RBCs) from circulation proposes that denatured/oxidized hemoglobin (hemichromes) arising late during an RBC's life span induces clustering of the integral membrane protein, band 3. In turn, band 3 clustering generates an epitope on the senescent cell surface leading to autologous IgG binding and consequent phagocytosis. Because dog RBCs have survival characteristics that closely resemble those of human RBCs (ie, low random RBC loss, approximately 115-day life span), we decided to test several aspects of the above hypothesis in the canine model, where in vivo aged cells of defined age could be evaluated for biochemical changes. For this purpose, dog RBCs were biotinylated in vivo and retrieved for biochemical analysis at various later dates using avidin-coated magnetic beads. Consistent with the above hypothesis, senescent dog RBCs were found to contain measurably elevated membrane-bound (denatured) globin and a sevenfold enhancement of surface-associated autologous IgG. Interestingly, dog RBCs that were allowed to senesce for 115 days in vivo also suffered from compromised intracellular reducing power, containing only 30% of the reduced glutathione found in unfractionated cells. Although the small quantity of cells of age >/=110 days did not allow direct quantitation of band 3 clustering, it was nevertheless possible to exploit single-cell microdeformation methods to evaluate the fraction of band 3 molecules that had lost their normal skeletal linkages and were free to cluster in response to hemichrome binding. Importantly, band 3 in RBCs >/=112 days old was found to be 25% less restrained by skeletal interactions than band 3 in control cells, indicating that the normal linkages between band 3 and the membrane skeleton had been substantially disrupted. Interestingly, the protein 4.1a/protein 4.1b ratio, commonly assumed to reflect RBC age, was found to be maximal in RBCs isolated only 58 days after labeling, implying that while this marker is useful for identifying very young populations of RBCs, it is not a very sensitive marker for canine senescent RBCs. Taken together, these data argue that several of the readily testable elements of the above hypothesis implicating band 3 in human RBC senescence can be validated in an appropriate canine model.