Pregnancy termination might affect the pathogenesis of adenomyosis. The number of foci and their myometrial depths correlated to each other and to dysmenorrhea, but only myometrial depth correlated to menorrhagia.

Five of 10 patients who commenced successful highly active antiretroviral therapy (HAART) for infection with human immunodeficiency virus type 1 (HIV-1) concurrent with or soon after a diagnosis of cryptococcal infection experienced clinical events characterized by sterile inflammation. Two patients developed aseptic meningitis with elevated intracranial pressure, 1 developed intrathoracic lyphadenopathy with hypercalcemia, 1 developed cavitary pneumonia at the site of a cryptococcal nodule, and 1 developed a supraclavicular abscess. These events occurred 2-11 months after initiation of HAART. For 3 patients, biopsy demonstrated findings atypical for acquired immunodeficiency syndrome-associated cryptococcosis. Results of fungal cultures were negative for all 5 patients, and cryptococcal antigen levels had declined markedly in 4 patients. The timing and clinical features of and biopsy findings for these cases of cryptococcosis suggest the existence of a paradoxical reaction to Cryptococcus infection that occurs in the context of HIV immune restoration.

BackgroundPodocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.Methodology/Principal FindingsProtein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = −0.48, p<0.0001) and eGFR (rho = −0.33, p = 0.005).Conclusions/SignificanceThese data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.

Previously it was shown that the TNF superfamily member TWEAK (TNFSF12) acts through its receptor, Fn14, to promote proinflammatory responses in kidney cells, including the production of MCP-1, RANTES, IP-10 and KC. In addition, the TWEAK/Fn14 pathway promotes mesangial cell proliferation, vascular cell activation, and renal cell death. To study the relevance of the TWEAK/Fn14 pathway in the pathogenesis of antibody-induced nephritis using the mouse model of nephrotoxic serum nephritis (NTN), we induced NTN by passive transfer of rabbit anti-glomerular antibodies into Fn14 knockout (KO) and wild type (WT) mice. Severe proteinuria as well as renal histopathology were induced in WT but not in Fn14 KO mice. Similarly, a pharmacologic approach of anti-TWEAK mAb administration into WT mice in the NTN model significantly ameliorated proteinuria and improved kidney histology. Anti-TWEAK treatment did not affect the generation of mouse anti-rabbit antibodies; however, within the kidney there was a significant decrease in glomerular immunoglobulin deposition, as well as macrophage infiltrates and tubulointerstitial fibrosis. The mechanism of action is most likely due to reductions in downstream targets of TWEAK/Fn14 signaling, including reduced renal expression of MCP-1, VCAM-1, IP-10, RANTES as well as Fn14 itself, and other molecular pathways associated with fibrosis in anti-TWEAK treated mice. Thus, TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the NTN model, apparently mediating a cascade of pathologic events locally in the kidney rather than by impacting the systemic immune response. Disrupting TWEAK/Fn14 interactions may be an innovative kidney-protective approach for the treatment of lupus nephritis and other antibody-induced renal diseases.

In order to describe the clinical and serologic features of a cutaneous vasculitis due to cocaine contaminated with the adulterant levamisole, we report four new cases of this syndrome along with 12 previously reported cases identified through a PubMed Literature search (1964 to March 2011). Of the 16 patients described, the average age was 43, with a female predominance (81% of patients). Over half of patients had involvement of the earlobes, and the rash frequently affected the extremities in a "retiform" pattern. Leukopenia or neutropenia was reported in 56% of patients. Ninety-three percent were anti-neutrophil cytoplasmic antibody positive, and 63% tested positive for anti-phospholipid antibodies. The predominant pattern seen on histopathological examination of the skin was small vessel vasculitis and/or a thrombotic vasculopathy. Treatment in these patients varied widely, with several patients showing improvement or resolution of the rash without specific therapy following cessation of illicit drug use. This new cutaneous vasculitis syndrome can be recognized by its characteristic rash and skin pathology, together with leukopenia and autoantibody production. Certain clinical features can be attributed to the adulterant levamisole, though cocaine as well may play a role in its pathogenesis.