Intravascular lymphoma: report of two autopsic cases, literature review

Intravacular large B-cell lymphoma (LIV) is a rare entity individualized in the WHO classification since 2001 as a subtype of extranodal diffuse large B-cell lymphoma. We report two autopsic cases of LIV: a 77-year-old woman presenting with fever, dyspnea, antehypophyseal failure and a 54-year-old man presenting with fever, weight-loss, night-sweats and encephalopathy. They died respectively 10 and 7 months after the beginning of symptoms, without diagnosis. Neither infectious disease nor lymphomatous proliferation had been identified. From these two cases and our literature review, we insist on the importance of histopathological diagnosis on biopsy for this rare pathology which clinical diagnosis remains difficult.     

Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3-22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.     

The PPARalpha activator fenofibrate slows down the progression of the left ventricular dysfunction in porcine tachycardia-induced cardiomyopathy

It has been reported that high intramyocardial peroxisome proliferator-activated receptor alpha (PPARalpha) stimulation or overexpression altered cardiac contractile function in mouse models of cardiac hypertrophy and heart failure. Nevertheless, it has never been demonstrated that clinically relevant doses of drugs stimulating PPARalpha activity such as fenofibrate increase the risk to develop heart failure in humans. To determine if fenofibrate accelerates the development of heart failure in large mammals, we have tested its effects on the progression of left ventricular dysfunction in pacing-induced heart failure in pigs. Fenofibrate treatment blunted reduction in left ventricular ejection fraction, reduced cardiac hypertrophy, and attenuated clinical signs of heart failure. Fenofibrate impeded the increase in atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 plasma levels. The expression of PPARalpha, fatty acyl-CoA-oxidase, and carnitine palmitoyltransferase-Ibeta was reduced at mRNA levels in the left ventricle from untreated heart failure pigs but maintained near normal values with fenofibrate. Fenofibrate prevented heart failure-induced overexpression of TNFalpha mRNA and enhanced catalase activity in left ventricle compared to placebo. These data suggest that a clinically relevant dose of fenofibrate does not accelerate but slows down heart failure development in the model of pacing-induced heart failure in large mammals.     

Caveolinopathy: Clinical,histological, and muscle imaging features and follow-up in a multicenter retrospective cohort

Background and purpose

CAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or isolated persistent high creatine kinase (CK) with a major overlapping phenotype.

Methods

Twenty-three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow-up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow-up. The results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry, and caveolin-3 Western blot analysis were also compiled.

Results

Exercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy, and only 65% of patients presented rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis, and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. Whereas a quarter of patients had normal caveolin-3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype–genotype correlation was evidenced.

Conclusions

Caveolinopathy has diverse clinical, muscle imaging, and histological presentations but often has limited functional impact. Mild forms of the disease, an atypical phenotype, and normal caveolin-3 immunostaining are pitfalls leading to misdiagnosis.     

The fraction of α-linolenic acid present in the sn-2 position of structured triacylglycerols decreases in lymph chylomicrons and plasma triacylglycerols during the course of lipid absorption in rats

Little is known about the ability of α-linolenic acid (Ln) to remain in the sn-2 position of TG during the absorption process. The goal of this study was to determine the Ln distribution in the lymph (Study 1) and plasma (Study 2) TG of rats fed a single i.g. load of structured TG [300 mg/rat of either oleic acid (O)/Ln/O TG (OLnO) or Ln/O/O TG (LnOO), n = 7 rats]. In an early fraction (3-4 h) of lymph (OLnO group; 100% Ln in the sn-2 position), 46 ± 2% Ln was maintained in this position in lymph TG. There was even less (29 ± 6%) in the last fraction (7-24 h) (P < 0.05). Ln was also found (9 ± 3%) in the sn-2 position of lymph TG in the LnOO group. The Ln content in lymph phospholipids was twice as high in rats when they were fed LnOO (4.2 ± 0.1%) than OLnO (2.3 ± 0.2%) (P < 0.005). Six hours postprandially (Study 2), 21 ± 3% of the Ln incorporated into plasma TG was located in the sn-2 position in the OLnO group compared to 13 ± 2% in the LnOO group (P < 0.001). Overall, these results indicate that the amount of Ln that moved from the sn-2 position of structured TG to the sn-1(3) position of lymph TG increased during absorption. This may account for a substantial hydrolysis of the 2-monolinolenylglycerols in enterocytes, leading to the intramolecular redistribution of Ln in lymph TG and, consequently, in plasma TG.