Clarisa Alvarez

Plexogenic Arteriopathy Associated with Pulmonary Vasculitis in Systemic Lupus Erythematosus

Pulmonary arterial hypertension and compulmonale were found in a woman with inactive systemic lupus erythematosus (SLE). The patient died of right heart failure 5 years later. Postmortem study showed SLE reparative lesions, plexogenic arteriopathy and vasculitis in the lung vessels. Since no active SLE was found, the pulmonary vasculitis was attributed to plexogenic arteriopathy.

Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia.

This study investigated the involvement of chemokines including stromal derived factor 1 (SDF‐1), interleukin 8 (IL‐8), growth‐related oncogene alpha (GRO‐α) and their receptors, CXCR4, CXCR2 and CXCR1 in essential thrombocythemia (ET), a chronic myeloproliferative disease characterized by megakaryocytic hyperplasia and high platelet count. Fifty‐three ET patients were studied. Plasma levels of SDF‐1, IL‐8 and GRO‐α, evaluated by enzyme‐linked immunosorbent assay, and flow cytometric analysis of CXCR1 and CXCR2 on the platelet membrane, were found to be normal in ET patients. CXCR4 expression on platelet surface as well as platelet CXCR4 mRNA detected by real‐time reverse transcription polymerase chain reaction, were decreased. Platelet CXCR4 internalization rate was normal while SDF‐1‐induced platelet aggregation was delayed, decreased or absent. Immunohistochemical staining revealed that megakaryocytes were also affected. CXCR4 decrease was not observed either in peripheral white blood cells or in circulating CD34+ precursors. These results show that CXCR4 is decreased in the megakaryocytic lineage in ET, mainly due to a reduced CXCR4 production, and an abnormal platelet response to SDF‐1. This report is the first to describe platelet and megakaryocytic CXCR4 deficiency in a human disease and the presence of this abnormality in a megakaryocytic‐related illness highlights the important role of SDF‐1/CXCR4 axis in platelet development.

Long-term Outcome of Lupus Nephritis Class II in Argentine Patients: An Open Retrospective Analysis.

BackgroundThere is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. MethodsA retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. ResultsForty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133).In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). ConclusionsThis series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect.

Accelerated Recovery from Toxic Acute Renal Failure with Thyroxin: Stimulation of Renal Phospholipid Biosynthesis

Thyroxine (T4) seems to accelerate recovery from various forms of acute renal failure. The mechanisms of this effect are still debated. We decided to evaluate if thyroxine enhances the recovery of HgCl2 renal failure through an increment in the mitotic activity or through an increase in membrane phospholipid biosynthesis of the regenerating tubular cells. Male Wistar rats were allocated to four groups: one group received 0.4 mg/100 g BW HgCl2 SC and saline IP (HgCl2 group); the second received the toxin and 24 and 48 h after it, T4 15 micrograms/100 g BW IP (HgCl2 + T4 group); a third group received saline SC and T4 IP (T4 group), and the last group received saline SC and IP (control group). On the third day GFR was evaluated by 24-h creatinine clearance and afterward rats were sacrificed and the kidneys removed. Some of them were studied histologically, evaluating the severity of the tubular lesion using a semiquantitative score (0-4) and the mitotic index (N mitotic figures per 10 high-power fields). In the other kidneys we studied phospholipid synthesis through the incorporation of 32 P into the different renal phospholipids of the several kidney regions. The T4-treated group had a better recovery of GFR after the toxin (HgCl2 + T4: 0.44 +/- .09 vs. HgCl2: 0.23 +/- .06, p < .05). Both HgCl2-treated groups had similar lesional scores and mitotic indexes.(ABSTRACT TRUNCATED AT 250 WORDS)