Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/ß dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study.

OBJECTIVE: To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1ß, in patients with knee osteoarthritis (OA). METHOD: This was a randomized, double-blind, placebo-controlled, single-center study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate OA of the knee (NCT01668511). Three cohorts received ABT-981 (0.3, 1, or 3 mg/kg) or placebo every other week for a total of four SC injections, and one cohort received ABT-981 (3 mg/kg) or placebo every 4 weeks for a total of three SC injections. Assessment of safety and tolerability were the primary objectives. A panel of serum and urine biomarkers of inflammation and joint degradation were evaluated. RESULTS: A total of 36 patients were randomized (ABT-981, n = 28; placebo, n = 8); 31 (86%) completed the study. Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%). The most common AE reported with ABT-981 vs placebo was injection site erythema (14% vs 0%). ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1ß, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen. Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein demonstrated decreasing trends with ABT-981. Antidrug antibodies were found in 37% of patients but were not associated with the incidence or severity of AEs. CONCLUSION: ABT-981 was generally well tolerated in patients with knee OA and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven OA.

Tratamiento no quirúrgico de la contractura de Dupuytren con colagenasa de Clostridium hystoliticum / Non surgical treatment in Dupuytren´s contracture with collagenase from Clostridium hystoliticum

La contractura de Dupuytren origina una pérdida progresiva de la función de la mano. Su tratamiento de elección es quirúrgico. La inyección de una solución compuesta por dos colagenasas distintas aisladas y purificadas a partir de la bacteria Clostridium histolyticum realiza lisis selectiva del colágeno en la cuerda pretendinosa. Presentamos nuestra experiencia en el tratamiento de la enfermedad mediante la inyección de dicha colagenasa en 15 pacientes como opción no quirúrgica. Se trata de un tratamiento mínimamente invasivo, eficaz y seguro en la reducción de las contracturas de Dupuytren, tanto en las articulación metacarpofalángica como en la interfalángica proximal, al tiempo que elimina los gastos de ingreso hospitalario y las complicaciones del postoperatorio (AU)

Dupuytren's contracture causes a progressive loss of hand function, being surgery the treatment of choice. The injection of a solution composed by two different collagenases, isolated and purified by Clostridium histolyticum bacteria, performs a selective lysis of collagen in the pretendinous cord. We show our experience in the treatment of the disease, by injecting collagenase in 15 patients as a non-surgical option. This treatment has proven to be a minimally invasive, effective and safe in reducing contractures in the joints metacarpophalangeal, proximal interphalangeal or both. It also eliminates the cost of hospitalization and postoperative complications (AU)

Hysteroscopic diagnosis of uterine sarcomas at the Department of Gynaecology, Sant Joan de Déu University Hospital.

Uterine sarcomas are rare and the clinical diagnosis of sarcoma is difficult. Diagnostic and surgical hysteroscopy is a minimally invasive outpatient procedure that makes an accurate diagnosis of malignant intrauterine pathology and could play a role in the diagnosis of the uterine sarcomas. Uterine sarcomas diagnosed at the Department of Gynecology of Sant Joan University Hospital by hysteroscopy between January 2004 and August 2010 are described. In this period 2,441 hysteroscopies were performed; a total of 67 adenocarcinomas of the endometrium and five sarcomas were diagnosed by hysteroscopy. The data are presented with a review of the literature, focusing on the diagnostic value of hysteroscopy in these tumors.

Consulta hepatología pediátrica pretrasplante: importancia de la misma en el programa de trasplante hepático pediátrico / Check pretransplant pediatric hepatology: importance of it in the pediatric liver transplant program

Introducción: La consulta pediátrica pretrasplante es fundamental en un programa de trasplante hepático, allí se evalúan diferentes aspectos como, la indicación del trasplante, el estadio de la enfermedad, comorbilidades asociadas y nos permite corregir las mismas ya que estas influirán en la sobrevida postrasplante. El objetivo fue conocer las características de la población pediátrica evaluada como posibles candidatos a trasplante. Pacientes y Métodos: Se realizó estudio retrospectivo. Se incluyeron todos los pacientes pediátricos que fueron referidos para valoración como posibles candidatos a trasplante hepático desde 2005 al 2010. Resultados: Se estudiaron 152 pacientes, 65 (43%) del sexo masculino y 87 (57%) del sexo femenino, con edad promedio de 6,16 + 5,24 años. Al momento del estudio 61 pacientes no tenían indicación de trasplante, 35 se encontraban en evaluación, 28 se trasplantaron, 21 fallecieron y 7 fueron referidos. Las indicaciones de trasplante fueron: disminución de la síntesis hepática 20, síndrome hepatopulmonar 2, hemorragia digestiva 3, síndrome hepatorrenal 2 y un fallo hepático subagudo. De los pacientes trasplantados 16 presentaban algún grado de desnutrición previa, 3 presentaban ascitis, 7 habían presentado hemorragias digestivas, 6 presentaban infecciones (urinarias, respiratorias y absceso dentarios), 24 tenían patologías odontológicas. Los 28 pacientes tenían esquema de inmunización incompleto durante la evaluación. Todos estos problemas fueron tratados previo al trasplante. Conclusión: La consulta pediátrica de hígado pretrasplante es de suma importancia ya que en ella se identifican los pacientes con indicación de trasplante además de valorar de forma integral al paciente, lo que nos permite conocer aquellas morbilidades asociadas a la enfermedad hepática terminal y resolverlas previo al trasplante, mejorando su posterior sobrevida.

Introduction: Pediatric liver pre-transplantation consultation is very important in a liver transplant program, there different aspects are assessed, such as the indication the transplant, disease stage, associated comorbidities and it allows us to correct them as they will affect the survival after transplantation. The objective was to determine the characteristics of the pediatric population evaluated as potential transplant candidates. Patients And Methods: A retrospective study was performed. All pediatric patients who were referred for evaluation as potential candidates for liver transplantation from 2005 to 2010 were included. RESULTS: 152 patients were studied, 65 (43%) were males and 87 (57%) females, mean age 6.16 ± 5.24 years. At the time of the study 61 patients had no indication for transplant, 35 were been evaluated, 28 were transplanted, 21 died and 7 were referred. The indications for transplantation were: decreased hepatic synthesis 20, hepatopulmonary syndrome 2, gastrointestinal bleeding 3, hepatorenal syndrome 2 and one subacute liver failure. Of the transplanted patients 16 had some degree of previous malnutrition, 3 had ascites, 7 had presented gastrointestinal bleeding, 6 had infections (urinary, respiratory and dental abscess), and 24 had dental pathologies. The 28 patients had an incomplete immunization schedule during the evaluation. All these problems were treated prior to transplantation. Conclusion: the pediatric liver pretransplantation consultation is of most importance since in it we identify patients with indication for transplantation; in addition, we can completely asses the patient allowing us to recognize morbidities associated with the end stage liver disease and resolve them before transplantation, improving subsequent survival.

Síndrome HELLP y coagulopatía / HELLP syndrome and maternal-perinatal mortality

Con este artículo se pretenden revisar las características etiológicas, fisiopatológicas y clínicas del sindrome HELLP y presentar la casuística de morbimortalidad encontrada en el Instituto Materno Infantil-IMI de Santafé de Bogotá en el período de tiempo comprendido entre enero de 1997 y diciembre de 1999

Effects of IV cyclophosphamide on HIV viral replication in a patient with systemic lupus erythematosus.

Several cases of patients with concomitant SLE and HIV infection have been reported in the literature; however, the effect of immunosuppressive therapy on HIV replication has not been described. We present the case of a 46 y/o woman with a ten-year history of HIV infection who was treated with IV cyclophosphamide for SLE nephritis. She had a positive HIV Western Blot just a few months before the diagnosis of SLE. Serum levels of HIV RNA had been persistently non-detectable since the assay became available. The patient was not receiving any antiretroviral therapy, raising doubts about the diagnosis of HIV infection. After 3 pulses of IV cyclophosphamide, HIV RNA levels went up to 135,720 copies/ml. Shortly after discontinuation of therapy viral levels were again undetectable. This case shows one of the possible clinical scenarios in patients with coexistent HIV infection and SLE. In our patient SLE appears to provide some immunologic defense against viral replication. Cross-reactivity of autoantibodies with HIV proteins may play a role in this mechanism. Effective immunosuppressive therapy suppresses this protection and leaves the immune system vulnerable to HIV reproduction. Treatment in these cases can be difficult and should be individualized in an attempt to achieve a balance between control of viral infection and SLE activity.

Practice guidelines in the management of osteoarthritis.

Osteoarthritis (OA) is the most common articular rheumatic disease. Practice guidelines have been developed to assist the practitioner in the care of patients with hip and knee OA. The guidelines divide the treatment strategy into nonpharmacologic and pharmacologic modalities. The nonpharmacologic or nonmedicinal approaches include patient education, psychosocial interventions, physical and surgical measures. Each of these are as important as the pharmacologic or medicinal measures. Medicinal measures can be subdivided into symptomatic therapy and disease modifying therapy. Even though all present therapies are aimed at symptoms, experimental therapies are being developed to alter the disease process.

The prevalence of facial acne in Peruvian adolescents and its relation to their ethnicity.

PURPOSE: This article describes the prevalence of facial acne vulgaris in adolescents of Arequipa, Peru, in relation to ethnic characteristics. METHODS: This was a cross-sectional study of 2214 healthy adolescents, 55.83% male and 44.17% female, 12-18 years old. Based on visual inspection, the severity of acne was classified into four grades. The adolescents studied were divided into three ethnic groups: whites, Mestizos, and Indians. RESULTS: Less than half of the adolescents (41.69%) had acne: 33.74% grade 1, 5.19% grade 2, 2.12% grade 3, and 0.63% grade 4. The prevalence of acne varied from 16.33% at 12 years to 71.23% at 17 years. At age 12 and 13 years, the prevalence of acne was higher in females, with the trend reversing over age 14 years. The overall prevalence of acne was significantly less in Indians (27.97%) than in Mestizos (43.08%) or whites (44.47%). More acne was found in postmenarche (39.90%) than in premenarche (20.99%). This trend was also true for the severity of acne. CONCLUSIONS: The prevalence of acne in the adolescents of Arequipa is significantly less than in Caucasians. Peruvian Indians have significantly less acne than Peruvian whites or Mestizos. It seems that ethnicity is an important predictor of not only the prevalence, but also the severity of juvenile acne vulgaris in this sample.

Reiter's syndrome among Asian shipboard immigrants: the case of The Golden Venture.

OBJECTIVE: To assess the incidence of Reiter's syndrome aboard The Golden Venture, a ship carrying illegal immigrants from China to the United States. METHODS: After identification of an index case, we conducted telephone interviews with medical staff at immigrant detention centers in Pennsylvania, New York, and Virginia. When a potential case was identified at one facility, we performed a site inspection, reviewing the medical records of all detainees and performing histories and physicals on all those with joint and/or ocular complaints. RESULTS: We identified two patients, both HLA B27 positive, with Reiter's syndrome. The observed incidence (0.87%) approximated the predicted incidence but may have underestimated the actual incidence. We review the history of shipboard Reiter's syndrome, and discuss the pathogenic roles of HLA B27 and particular infectious agents. CONCLUSION: Continued transportation of illegal immigrants from China and other parts of the world is likely to result in occasional clusters of Reiter's syndrome. Physicians treating immigrant populations should remain aware of the possibility of reactive arthritis.

Identification of C1q as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1.

To examine the role of complement components as regulators of the expression of endothelial adhesive molecules in response to immune complexes (ICs), we determined whether ICs stimulate both endothelial adhesiveness for leukocytes and expression of E-selectin and intercellular and vascular cell adhesion molecules 1 (ICAM-1 and VCAM-1). We found that ICs [bovine serum albumin (BSA)-anti-BSA] stimulated endothelial cell adhesiveness for added leukocytes in the presence of complement-sufficient normal human serum (NHS) but not in the presence of heat-inactivated serum (HIS) or in tissue culture medium alone. Depletion of complement component C3 or C8 from serum did not prevent enhanced endothelial adhesiveness stimulated by ICs. In contrast, depletion of complement component C1q markedly inhibited IC-stimulated endothelial adhesiveness for leukocytes. When the heat-labile complement component C1q was added to HIS, the capacity of ICs to stimulate endothelial adhesiveness for leukocytes was completely restored. Further evidence for the possible role of C1q in mediating the effect of ICs on endothelial cells was the discovery of the presence of the 100- to 126-kDa C1q-binding protein on the surface of endothelial cells (by cytofluorography) and of message for the 33-kDa C1q receptor in resting endothelial cells (by reverse transcription-PCR). Inhibition of protein synthesis by cycloheximide blocked endothelial adhesiveness for leukocytes stimulated by either interleukin 1 or ICs in the presence of NHS. After stimulation with ICs in the presence of NHS, endothelial cells expressed increased numbers of adhesion molecules (E-selectin, ICAM-1, and VCAM-1). Endothelial expression of adhesion molecules mediated, at least in part, endothelial adhesiveness for leukocytes, since leukocyte adhesion was blocked by monoclonal antibodies directed against E-selectin. These studies show that ICs stimulate endothelial cells to express adhesive proteins for leukocytes in the presence of a heat-labile serum factor. That factor appears to be C1q.

[Prevalence of thinness and excessive fatness in a group of school children of the city of Cordoba, Argentina]. / Prevalencia de delgadez y gordura excesiva en un grupo de escolares de la ciudad de Cordoba, Argentina.

Findings of a nutritional evaluation study, using triceps skinfold, are reported. The study was carried out in 1,615 school-children from 5 to 12 years, pertaining to the low socioeconomic status of the city of Córdoba, Argentina. Measurements were done during the years 1983 and 1984 by Center's examiners with a Lange caliper, according to international anthropometric methodology. Interintra observer technical error was found to be within tolerance limits reported by other authors. Local standards were used to determine the prevalence of thinness and excessive fatness, by comparing them to tricep skinfold of each child, and selecting those children where this parameter presented values less than or equal to 10th percentile and fatness greater than or equal to 90th percentile. Furthermore, comparison between median triceps skinfold of the examined group, the local standards and Frisancho's norms for US population was also made. Results revealed that: a) the prevalence of thinness (19.9%) was almost twice the percentage expected for a normal population; in contrast, occurrence of excessive fatness (6.4%) was found to be below the expected value; b) prevalence of thinness was not statistically associated to age nor sex; c) frequency of excessive fatness was significantly higher in the 8-11 year-old male group (8, 9%, p much less than 0.0005) and in the girls group (10.8%), P much less than 0.005) the prevalence of fatness in girls increased with age, and figures revealed that from eight years onwards this exceeded the expected percentage, and d) median triceps skinfold of the group under study was generally below local and foreign norms. It is concluded that potential or real nutrition problems as those mentioned above, may be grossly identified using the triceps skinfold as the single anthropometric indicator.

Effect of intracerebroventricular vanadate administration on salt and water intake and excretion in the rat.

The effect of vanadate (VO-3), an "in vitro" inhibitor of Na,K-ATPase activity, on sodium and water intake and excretion of Na-depleted and water deprived rats, was investigated. Injection of sodium orthovanadate Na3V04, H20 14) 1 microliter, 1.0 mM solution, 51 ng/microliter free base vanadium (V) into the 3rd brain ventricle (3BV) inhibited by 34% the sodium intake induced by peritoneal dialysis (PD). Urinary water and sodium excretion increased and potassium excretion decreased. The same concentration of vanadate administered by continuous infusion into the 3BV (1 microliter/hr, 24 hr, 51 ng/microliter, 1.2 micrograms/24 hr) during 24 hours after PD, decreased sodium intake by 69%. The same rate of infusion through the jugular vein failed to inhibit sodium intake or to increase urinary water and sodium excretion. Injections into lateral hypothalamus were also ineffective. Vanadyl (VO+2), the reduced form of vanadate, did not affect sodium intake. Similar or larger doses of vanadate injected into the 3BV of water deprived rats, did not modify water intake significantly. The present results suggest that the Na-K, active transport system is involved in salt and water balance regulation at the central nervous system level.

CT diagnosis of congenital intrapericardial masses.

Prior to the development of CT, cardiac and pericardiac masses were evaluated by chest roentgenography, angiocardiography, and echocardiography. In most cases preoperative diagnosis of a specific entity was impossible. Preoperative CT diagnosis of an intrapericardial developmental mass becomes possible because of the presence of fat, fat/fluid level, thick walled cysts, as well as globular calcifications, bones, teeth, water density fluid, and soft tissue. A report of a young woman with a ruptured and infected intrapericardial teratoma and an infant with an intrapericardial bronchial cyst is presented.