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.

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.

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.