Circulating microparticles in patients with benign and malignant ovarian tumors.

BACKGROUND: Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. PATIENTS AND METHODS: Microparticles from platelets/megakaryocytes, activated platelets and endothelial cells, tissue factor exposing microparticles and D-dimer values were examined in patients with newly diagnosed ovarian lesions before surgery, and were correlated with tumor histology. RESULTS: Higher counts of CD63-positive microparticles were detected in patients with ovarian cancer [mean=276×10(6) (range: 64-948)/l; n=12] as compared to patients with benign ovarian tumors [146×10(6) (45-390)/l; n=21; p=0.014]. D-dimer values were also increased in patients with cancer [860 (180-4500) ng/l versus 280 (170-2720) ng/l; p=0.001]. CONCLUSION: Elevated levels of CD63-positive microparticles and D-dimer reflect the procoagulant phenotype of these patients. However, for the discrimination between benign and malignant ovarian tumors, measuring preoperative levels of microparticles does not seem to be helpful.

Clearance of platelet microparticles in vivo.

At present, little is known about the clearance of platelet-derived microparticles (PMP) in human blood, as due to ethical considerations infusion experiments with labeled microparticles are delicate. Therefore, we investigated the kinetics of PMP, which are abundantly present in apheresis platelet concentrates (PC), following platelet transfusion in severe thrombocytopenic patients (n=11). PMP were double-stained with annexin V and cell-specific antibodies (anti-CD61, anti-CD63 or anti-CD62P, respectively) and detected by flow cytometry before and after transfusion of a single PC at fixed time intervals. Upon transfusion, the plasma levels of MP binding annexin V (2.5-fold), PMP (CD61+; 2.9-fold), and PMP from activated platelets (CD63+; 1.9-fold) or P-selectin (2.5-fold) increased immediately. The plasma levels of MP decreased with a half life of 5.8 hours (annexin V; 95% CI: 1.8?18.3) and 5.3 hours (CD61; 95% CI: 2.0?14.2). This is the first report in which the half life time of transfused PMP has been investigated in humans.

Apheresis platelet concentrates contain platelet-derived and endothelial cell-derived microparticles.

BACKGROUND AND OBJECTIVES: Microparticles (MP) are membrane vesicles with thrombogenic and immunomodulatory properties. We determined MP subgroups from resting platelets, activated platelets and endothelial cells in donors and apheresis platelet concentrates (PC). MATERIAL AND METHODS: MP were double stained with annexin V and CD61 (platelet-derived MP; PMP), P-selectin or CD63 (MP from activated platelets) and CD144 plus E-selectin (endothelial cell-derived MP; EMP) and detected by flow cytometry in platelet donors (n=36) and apheresis PC (n=11; Trima™). RESULTS: PC contained MP, mainly from resting platelets [93% (90-95)], and minor fractions of PMP from activated platelets [P-selectin(+) or CD63(+); 4·8% (3·2-7·7) and 2·6% (2·0-4·0)]. Compared to donors, levels of annexin V+ MP, PMP, P-selectin(+) and CD63(+) MP were 1·7-, 2·3-, 8·6- and 3·1-fold higher in PC (all P<0·05). During storage (1-5 days), levels of annexin V+ MP and PMP did not increase, although small increases in the fraction of P-selectin(+) or CD63(+) MP occurred (both P<0·05). PC also contained EMP, which were 2·6- to 3·7-fold enriched in PC compared to donors (P<0·05). CONCLUSIONS: Transfusion of apheresis PC also results in transfusion of HLA-carrying PMP and EMP. This might counteract the aim of reducing transfused HLA load by leucodepletion. The increases in PMP exposing P-selectin or CD63 reflect mild platelet activation during storage. We conclude that in leucodepleted platelet apheresis using fluidized particle bed technology, MP are harvested mainly from the donor by apheresis. Improvement in apheresis technology might reduce MP load.

Défi cits neurológicos y aracnoiditis secundarios a anestesia neuroaxial: rol de parestesias, punciones durales, anestésicos locales y género. Protocolo para su tratamiento / Neurological defi cit and arachnoiditis secondary to neuroaxial anesthesia: role of paresthesia, dural puncture, local anesthetics and gender. Treatment protocol

Introducción: De las complicaciones de la anestesia neuroaxial, la aracnoiditis y el déficit neurológico representan uno de los problemas más serios a los que pueda enfrentarse el anestesiólogo, aun cuando la frecuencia real es desconocida las consecuencias funcionales para los pacientes y legales para el médico son devastadoras, debido principalmente al hecho que la mayor parte de los pacientes no son tratados con oportunidad y las probabilidades de un desenlace catastrófico aumentan. Material y método: Revisión de casos. Resultados: Se presenta una serie de casos en los que se analizan los factores que posiblemente influyeron en la presencia de las complicaciones, los tratamientos empleados y su eficacia para disminuir la incapacidad remanente y lograr su recuperación, así como el resultado de aplicarlo oportunamente. Discusión: Es necesario reconocer que una vez que estas complicaciones se presentan, el objetivo principal es iniciar un plan terapéutico que evite o disminuya las secuelas permanentes, para lo cual se requiere iniciar inmediatamente un tratamiento específico que permita la pronta recuperación de la función; sin embargo, en la actualidad, aún no hay un protocolo de tratamiento que haya demostrado ser eficaz en la disminución de las secuelas (AU)

Introduction: Among the complications of neuroaxial anesthesia, arachnoiditis and neurological deficit represent one of the most serious problems that anesthesiologists can face. Although the real frequency of this complication is unknown, the functional consequences for the patient and legal repercussions for the physician are devastating, mainly because most patients are not treated in a timely fashion, increasing the probability of a catastrophic outcome. Methods: Case review. Results: We reviewed a series of cases and analyzed the factors that possibly influenced the presence of complications, the treatments used and their effectiveness in reducing permanent disability and in achieving recovery, as well as the results of their timely application. Discussion: Once these complications appear, the primary objective is to initiate a therapeutic plan that avoids or reduces permanent sequels. To do this, specifi c treatment that allows functional recovery must be started immediately. However, currently there is no treatment protocol with demonstrated effectiveness in reducing sequels (AU)

[Steroid-refractory graft-versus-host disease: extracorporeal irradiation of leucocytes induces immunotolerance]. / Steroidrefraktäre Graft-versus-host-Erkrankung: Extrakorporale Bestrahlung von Leukozyten induziert Immuntoleranz.

A 42 year-old woman develops steroid refractory graft-versus-host disease (GVHD) after second allogeneic stem cell transplantation for acute myelogenous leukemia with severe GVHD of her skin with blisters, severe GVHD of her gut with watery and bloody diarrhea and GVHD of her liver with cholestasis. In a further attempt to control GVHD extracorporeal photochemotherapy is administered. The treatment exposures peripheral mononuclear cells to photoactivated psoralen before they subsequently are given back to the patient. This approach apparently offers selective immune tolerance.

Evaluación del uso de metadona en el tratamiento del dolor neuropático / Evaluation of methadone use in the treatment of neuropathic pain

Introducción: El dolor neuropático resulta de una lesión o disfunción del sistema nervioso. Su tratamiento es básicamente farmacológico e incluye el uso de antidepresivos y anticonvulsivantes, entre otros. Existe controversia en relación con la utilidad de los opioides en el manejo del dolor neuropático. La metadona es un opioide agonista mu, que además actúa bloqueando la recaptación de norepinefrina y serotonina en el asta dorsal, y es un antagonista del receptor de N-metil-D-Aspartato (NMDA). Objetivo: Valorar la respuesta analgésica obtenida en pacientes con dolor neuropático nooncológico tratados con metadona. Material y métodos: Se realizó un estudio retrospectivo, transversal. Se revisaron expedientes clínicos y se realizó una entrevista directa a los pacientes con dolor neuropático en tratamiento con metadona, durante el período comprendido entre el 1 de enero y 31de julio de 2006, para valorar mejoría en la intensidad del dolor, la dosis del fármaco y los efectos adversos. Resultados: Se incluyó a 31 pacientes con dolor neuropático en tratamiento con metadona. La dosis diaria varió entre 2,5 y 60 mg (moda 10 mg/día). La intensidad del dolor medida por escala analógica visual fue de 8,7 ± 1,2 y 4,3 ± 1,8, antes y después de tratamiento con metadona, respectivamente, con disminución promedio del 49%. El efecto adverso más común fue la constipación (65%). Conclusiones: La metadona puede ser de utilidad en el tratamiento del dolor neuropático cuando otros fármacos no lo controlan adecuadamente (AU)

Introduction: Neuropathic pain results from nervous system injury or dysfunction. Medical treatment is the first line therapy, including antidepressants, anticonvulsants and other drugs. The analgesic efficacy of opioids in the treatment of neuropathic pain is controversial. Methadone is an Ì-opioid receptor agonist, which also acts by blocking norepinephrine and serotonin reuptake into the dorsal horn, and is an N-methyl-Daspartate (NMDA) receptor antagonist. Objective: To evaluate the clinical characteristics of patients with non-oncological neuropathic pain treated with methadone. Material and methods: We performed a retrospective, cross-sectional study. Medical records were reviewed and patients with neuropathic pain taking methadone were interviewed between January 1 and July 31, 2006 to evaluate reduction of pain intensity, dosing, and side effects. Results: We included 31 patients with neuropathic pain who received methadone treatment. The patients were taking between 2.5 mg and 60 mg per day of methadone (mode 10 mg per day). Pain intensity on the Visual Analog Scale was 8.7 ± 1.2, and 4.3 ±1.8, before and after treatment with methadone, respectively, with a mean decrease of49%. The most frequent adverse effect was constipation (65%). Conclusions: Methadone is a useful drug in the treatment of neuropathic pain when other drugs have failed (AU)

[21-year-old patient with myocardial infarct, transient cerebral ischemia and thrombocytopenia]. / 21-jährige Patientin mit Myokardinfarkt, TIA und Thrombozytopenie.

We report on a case of a young female soccer player who first experienced a transient ischemic attack at the age of 21 and then suffered an acute myocardial infarction accompanied by thrombocytopenia 6 months later. The underlying cause was antiphospholipid syndrome. This clinical picture is caused by a very heterogeneous group of antiphospholipid antibodies, which interfere with plasmatic coagulation at various sites and are able to activate thrombocytes, endothelial cells, and monocytes. This leads to a thrombophilic condition with clinical manifestation of recurrent venous thromboses, arterial embolisms, or premature birth or miscarriage. The main therapeutic options are thus anticoagulation, heparins, and aspirin. Steroids are recommended for cases of pronounced thrombocytopenias; if treatment fails, immunosuppressants are also advisable. The antiphospholipid syndrome should be kept in mind especially in cases of young patients with thromboembolic events since the presence of antiphospholipid antibodies can be detected in 10-20% of this patient group and effective therapy after diagnosis lowers the rate of recurrence.

Confidence Intervals For Maximized Alpha Coefficients: An Evaluation Of Joe And Woodward's Procedures And An Alternative Method.

The procedures yielding confidence intervals for maximized alpha coefficients of Joe and Woodward are reviewed. Confidence interval procedures of Hakstian, Whalen, and Masson are next reviewed. Results are then presented of a Monte Carlo investigation of the procedures. Of Joe and Woodward's procedures, that derived for the most general case is shown to yield confidence intervals spanning the parameter with probabilities adequately close to nominal values. This procedure is shown to perform as well as Joe and Woodward's second procedure -- for the equicorrelation case -- even with equicorrelation data. Hakstian et al's method is also shown to yield adequately precise intervals. The results are discussed, and implications for research noted.