[Fibrillary glomerulonephritis]. / La glomérulonéphrite fibrillaire.

Fibrillary glomerulonephritis (FGN) is a glomerular disease described since 1977, with a prevalence in renal biopsies of less than 1%. It presents as renal failure, proteinuria, haematuria and hypertension in middle-aged adults. It is defined histologically, using light microscopy, which reveals organised deposits of fibrils measuring around 20nm, which are negative for Congo red staining. Electron microscopy, the first gold standard for diagnosis, has now been superseded by immunohistochemistry using the anti-DNAJB9 antibody. The discovery of this molecule has revolutionised the diagnosis of GNF, thanks to its excellent sensitivity and specificity (98% and 99% respectively). The association of GNF with hepatitis C virus, autoimmune diseases, neoplasia or haemopathy is debated. Renal prognosis is guarded, with 50% of patients progressing to end-stage renal failure within 2 to 4years of diagnosis. In the absence of randomised controlled trials, the recommended treatment is based on nephroprotective measures, corticosteroid therapy and possibly a second-line immunosuppressant such as rituximab. After renal transplantation, recovery or recurrence is possible. The pathophysiology of the disease is still poorly understood, and further studies are needed.

[Cholesterol crystal embolism mimicking a DRESS]. / Des embolies de cristaux de cholestérol mimant un DRESS.

INTRODUCTION: Clinical presentation of cholesterol crystal embolism (CCE) can be dermatologic when cholesterol crystals become lodged in small cutaneous arteries resulting in ischemia. We report a case of CCE with erythroderma misleading to a diagnostic of drug reaction with eosinophilia and systemic symptoms (DRESS). CASE REPORT: A 66 year-old woman presented with erythroderma few months after initiation of allopurinol. Acute renal failure was present with elevation in plasma creatinine concentration (523µmol/L) and hypereosinophilia (HE) (5666/mm3). Finally, the REGISCAR score helped to rule out DRESS diagnostic. Past blood-count tests were analyzed revealing chronic HE present before allopurinol initiation. Renal biopsy identified CCE. CONCLUSION: This case is the first to report a DRESS like presentation of CCE. Clinical findings are secondary to HE and not to occlusion of cutaneous arteries.

Urinary mRNA for the Diagnosis of Renal Allograft Rejection: The Issue of Normalization.

Urinary messenger RNA (mRNA) quantification is a promising method for noninvasive diagnosis of renal allograft rejection (AR), but the quantification of mRNAs in urine remains challenging due to degradation. RNA normalization may be warranted to overcome these issues, but the strategies of gene normalization have been poorly evaluated. Herein, we address this issue in a case-control study of 108 urine samples collected at time of allograft biopsy in kidney recipients with (n = 52) or without (n = 56) AR by comparing the diagnostic value of IP-10 and CD3ε mRNAs-two biomarkers of AR-after normalization by the total amount of RNA, normalization by one of the three widely used reference RNAs-18S, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Hypoxanthine-guanine phosphoribosyltransferase (HPRT)-or normalization using uroplakin 1A (UPK) mRNA as a possible urine-specific reference mRNA. Our results show that normalization based on the total quantity of RNA is not substantially improved by additional normalization and may even be worsened with some classical reference genes that are overexpressed during rejection. However, considering that normalization by a reference gene is necessary to ensure polymerase chain reaction (PCR) quality and reproducibility and to suppress the effect of RNA degradation, we suggest that GAPDH and UPK1A are preferable to 18S or HPRT RNA.

[Warfarin-related nephropathy: a case report]. / Néphropathie aux anti-vitamine K : à propos d'une observation.

INTRODUCTION: Warfarin-related nephropathy (WRN) is a newly recognized entity, which is characterized by the occlusion of renal tubules by red blood cells following glomerular hemorrhage in a patient overexposed to warfarin (international normalized ratio>3). CASE REPORT: We report a 70-year-old man with no previous renal condition who developed WRN when his INR was>12. He did not fully recover his previous renal function. CONCLUSION: The diagnosis of WRN should be considered whenever INR exceeds 3 in patients exposed to warfarin, particularly in the presence of hematuria. Vitamin K is the only therapeutic option.

Crystalline ultrastructures, inflammatory elements, and neoangiogenesis are present in inconspicuous aortic valve tissue.

Morbidity from calcific aortic valve disease (CAVD) is increasing. Recent studies suggest early reversible changes involving inflammation and neoangiogenesis. We hypothesized that microcalcifications, chemokines, and growth factors are present in unaffected regions of calcific aortic valves. We studied aortic valves from 4 patients with CAVD and from 1 control, using immunohistochemistry, scanning electron microscopy, and infrared spectrography. We revealed clusters of capillary neovessels in calcified (ECC), to a lesser extent in noncalcified (ECN) areas. Endothelial cells proved constant expression of SDF-1 in ECC, ECN, and endothelial cells from valvular surface (ECS). Its receptor CXCR4 was expressed in ECC. IL-6 expression correlated with CXCR4 staining and presence of lymphocytes. VEGF was expressed by ECS, its receptor by ECC and ECN. Crystalline ultrastructures were found on the surface of histologically noncalcified areas (HNCAs), spectrography revealed calcium hydroxylapatite. Our results demonstrate that crystalline ultrastructures are present in HNCAs, undergoing neoangiogenesis in an inflammatory context. These alterations could be an early witness of disease and an opening to therapy.

[Multiple aortic aneurysms in chronic atrophic polychondritis]. / Anévrysmes aortiques multiples au cours d'une polychondrite atrophiante.

BACKGROUND: Although rare, cardiovascular involvement is the second most frequent cause of mortality in chronic relapsing polychondritis behind tracheobronchial tree chondritis. The most frequent cardiovascular complications are valvulopathy and aortic aneurysm. CASE REPORT: We report a case of chronic relapsing polychondritis with multiple aortic aneurysms that were clinically silent but continued to progress despite systemic corticosteroids and immunosuppressive therapy. DISCUSSION: Progression of aortic aneurysms and extravascular disease do not appear to be correlated. Although the disease may appear to be in remission, vascular lesions can continue to progress independently. This case shows that medical treatment has little effect on the progression of these aneurysms. Consequently, it is necessary to opt for surgical therapy at the opportune moment.

Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better?

OBJECTIVE: To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis. METHODS: Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media-intima junction or in the media. RESULTS: Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age < 50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of < 0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples > or = 0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5). CONCLUSIONS: A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis.

COX-2 inhibitors and acute interstitial nephritis: case report and review of the literature.

We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days - 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 +/- 0.11 mg/dl, 5.66 +/- 3.50 mg/dl and 1.15 +/- 0.24 before treatment, at time of diagnosis and 1 - 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.

[Intracranial arteriovenous malformations: histopathological features]. / Malformations artérioveineuses intracrâniennes: aspects anatomo-pathologiques.

Arteriovenous malformations (AVM) are congenital abnormalities that consist of tangled masses of tortuous arteries, veins and abnormal connecting channels, that apparently result from the lack of development of the local capillary bed. Because of their propensity to bleed, arteriovenous malformations clinically constitute the most significant group of vascular malformations and the most frequent type in surgical specimens. On histologic study, the lesion is composed of arteries with muscular and elastic laminae, veins dilated by the pressure to which they are exposed because of the shunting and ambiguous vessels with both arterial and venous characteristics called arterialized veins. The pathological blood vessels are separated by brain parenchyma that often shows gliosis and hemosiderin pigmentation. The histologic composition of AVM generally permits confident recognition. The pathogenesis of vascular malformations likely involves the abnormal assembly, differentiation of vascular smooth muscle cells in association with dysmorphic vessel wall. AVM exhibit distinct pattern of expression of molecular markers of differentiation and maturity of VSMC as well as vascular endothelial growth factors and their receptors.

Hyperhomocysteinemia and arterial aneurysm.

Hyperhomocysteinemia (HCY) is an independent risk factor for atherosclerosis. Arterial aneurysm has rarely been described in association with heterozygous HCY. Here we report two cases of this association. Case 1 was 32-Year-old man who presented with distal trophic manifestations of the lower extremities. Upon investigation, occlusive arterial disease with fusiform aneurysm of both popliteal arteries and occlusion of the left cubital artery were found. Laboratory findings indicated HCY due to homozygous methylene tetrahydrofolate reductase (MTHFR) deficiency. Case 2 was 38-year-old man with no history of trauma who presented with repeated ischemic events involving the right hand in association with isolated aneurysm of the right cubital artery. Histological study demonstrated extensive dystrophic changes in the aneurysmal vessel wall, including sclerohyalin deposits. The only abnormality was homozygous MTHFR deficiency. Pathologic changes induced by HCY in vessel walls may be implicated in early arterial aneurysm. The association of anatomic lesions, young age, and absence of other causes suggests that the relationship between HCY and arterial aneurysm observed in these two patients was not coincidental.

Expression of platelet-activating factor receptor in human carotid atherosclerotic plaques: relevance to progression of atherosclerosis.

BACKGROUND: Human monocyte-derived macrophages synthesize numerous proinflammatory and prothrombotic substances, including lipid mediators, such as platelet-activating factor (PAF), which may play a major role in the onset and perpetuation of atherosclerotic lesions. In addition, both monocytes and macrophages express PAF receptors (PAF-R). The expression of PAF-R is transcriptionally downregulated by oxidized LDL in in vitro primary cultures of monocyte/macrophages. In this study, we evaluated the expression of PAF-R in human carotid plaque tissue, in foam cells isolated from human carotid plaques, and in primary cultures of umbilical smooth muscle cells (SMCs). METHODS AND RESULTS: We show that PAF-R was expressed at low levels in foam cells compared with monocyte/macrophages in plaques, as assessed by immunohistochemical staining and in situ hybridization. In addition, low levels of mRNA were also detected by RT-PCR in isolated human carotid foam cells. A prominent finding of our study was the demonstration that contractile SMCs were positive for PAF-R, and its mRNA was extracted from primary cultures of umbilical SMCs. CONCLUSIONS: As macrophages loose their inflammatory phenotype on transformation into foam cells, they may equally loose their capacity of defense against aggression. We postulate that the diminished expression of PAF-R may be deleterious in the context of plaque formation and progression. The observation that arterial SMCs of contractile phenotype express PAF-R opens new avenues concerning the migration of these cells from media to intima and atherosclerotic plaque formation.

[Vascular manifestations of Behçet's syndrome associated with solitary ulcerations and resolved with immunosuppressants]. / Manifestations vasculaires de type angio-Behçet associées à une aphtose monopolaire isolée et résolutives sous immunosuppresseurs.

INTRODUCTION: Behçet's disease is a systemic inflammatory disorder characterized by vasculitis. Its typical features are recurrent oral and genital ulcerations with uveitis. Although vascular lesions are not listed among the criteria for diagnosis of Behçet's disease, up to 25-35% of the patients develop complications in arterial and venous large vessels. EXEGESIS: We describe the case of a 45-year-old French man with Behçet-type vasculopathy. Though only one sign of Behçet's disease, i.e., oral ulcerations, was present, the patient had to undergo emergency surgery three times. The postoperative treatment combined corticosteroids, azathioprine, and oral anticoagulants. Three years later no therapy failure was observed. CONCLUSION: On the basis of 1) recurrent aortic aneurysms, 2) large arterial and venous occlusive lesions, 3) superficial phlebitis, and 4) ulcerations of the aorta in macro- and microscopic examination of resected aortic walls, we concluded that the patient's life threatening vasculopathy was of the Behçet's type, even if several of the diagnostic features of Behçet's disease were lacking. Variations in clinical features of Behçet's disease are observed that might be due to hereditary traits, particularly to the genetic expression of an incomplete phenotype that would lead to the lack of typical clinical features.

[An unusual primary vascular tumor: intimal sarcoma of the pulmonary artery]. / Une tumeur vasculaire primitive particulière: le sarcome intimal de l'artère pulmonaire.

Primary sarcomas of great vessels are rare and involve the aorta, pulmonary artery and inferior vena cava. The pathologic classification of these tumors can be made on the location of the sarcoma in relation to the vessel wall, luminal or mural. Luminal sarcomas are usually intimal sarcoma and mural sarcoma are most frequently leiomyosarcoma. The myofibroblastic or endothelial differentiation of these tumors is still debated. We report a case of intimal sarcoma of the pulmonary artery.

Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque.

BACKGROUND: The accumulation of macrophage-derived foam cells in atherosclerotic lesions correlates with increased local release of matrix-degrading metalloproteinases (MMPs) and a thin fibrous cap. The activity of these enzymes is controlled by specific tissue inhibitors of metalloproteinases (TIMPs). METHODS AND RESULTS: Because oxidized low-density lipoprotein (OxLDL) modulates gene expression, we investigated the effect of these particles on the levels of MMP-1, MMP-3, MMP-9, TIMP-1, and TIMP-2 in the culture media of human monocyte-derived macrophages. OxLDL but not native LDL or high-density lipoprotein reduced the level of TIMP-1 in a dose-dependent manner with maximal effect (60% of control) at approximately 100 microg protein/mL. In addition, Northern blotting revealed marked reduction in the abundance of TIMP-1 mRNA in OxLDL-treated cells. Evaluation of the effect of oxysterol components of OxLDL on TIMP-1 production revealed that 25-hydroxycholesterol (1 microg/mL) was the most potent inhibitor ( approximately 30% of control). Such inhibition was partially mediated by interleukin (IL)-8. Indeed, IL-8 (2.5 ng/mL) induced maximal inhibition of TIMP-1 accumulation (30% of control) in 4 of 6 cell preparations. In addition, the inhibitory effect of OxLDL-treated cells in the presence of an anti-IL-8 neutralizing antibody was partially reversed. CONCLUSIONS: Immunohistochemical analyses of human atherosclerotic plaques revealed the expression of TIMP-1 in some but not all macrophage-rich and IL-8-rich areas. Therefore, IL-8 may play a potential atherogenic role by inhibiting local TIMP-1 expression, thereby leading to an imbalance between MMPs and TIMPs at focal sites in the atherosclerotic plaque.

Granulocytic sarcoma of the jejunum: a rare cause of small bowel obstruction.

We report the case of a 40-yr-old man presenting with symptoms of small bowel obstruction. Small bowel x-rays revealed a stricture of the mid-jejunum. Push enteroscopy found a polypoid mass at 1 meter of the ligament of Treitz. Histopathological examination of the biopsy and surgical specimens showed a diffuse infiltrate of the mucosa made of medium to large cells, which were stained on immunohistochemistry by the leucocyte marker CD45 and the histiocyte/monocyte marker CD68 but were negative for the B and T cell markers. Cytological examination of the ascitic fluid revealed many myelobasts with cytoplasmic Auer rods and positive myeloperoxidase staining. There was no evidence of blood or bone marrow involvement suggestive of acute leukemia or myeloproliferative disorders. These findings were consistent with the diagnosis of preleukemic granulocytic sarcoma (or chloroma). Chemotherapy led to complete remission, but 21 months later the patient developed an acute myeloid leukemia. He died from aspergillus pneumonitis, 10 months after bone marrow allograft. Preleukemic granulocytic sarcoma of the small bowel is a rare condition and its diagnosis is usually not easy, requiring histochemical or immunohistochemical studies. Most cases have progressed to acute myeloid leukemia.

[Infectious aneurysm due to Listeria monocytogenes: a new case and review of the literature]. / Anévrysme infectieux à Listeria monocytogenes: nouveau cas et revue de la littérature.

INTRODUCTION: Infections due to Listeria monocytogenes usually occur in pregnant women, in the elderly and in immunocompromised patients. Arterial aneurysms due to this germ are rare. Only 16 cases have been previously described in the literature. EXEGESIS: We report the case of a patient who had been hospitalized for recurrent fever over the past 3 months. Aortic mycotic aneurysm was diagnosed; blood and aneurysm cultures revealed Gram-positive bacilli consistent with the presence of Listeria monocytogenes. We also review previous reports focusing on infections due to Listeria monocytogenes. Mycotic aneurysms due to this germ are mainly observed in elderly male patients and occur on large arteries. In the present study, only one patient was immunocompromised. Furthermore, all patients who were not operated on died. CONCLUSION: Arterial aneurysm due to Listeria moncytogenes is best managed via surgical resection in combination with antimicrobial therapy. Immunosuppression is not necessary for the development of arterial aneurysm due to Listeria. Bacteriological and histological examinations should be done systematically when surgical resection of an aneurysm is required.

Myofibroblasts and hepatocellular carcinoma: an in vivo and in vitro study.

BACKGROUND/AIMS: The number of perisinusoidal myofibroblasts has been shown to be increased in hepatocellular carcinoma, as compared to cirrhosis. This increase might suggest a cooperative relationship between tumour cells and myofibroblasts. To assess this relationship, we undertook: (a) an immunohistochemical study to confirm the existence of an increased number of perisinusoidal myofibroblasts in human hepatocellular carcinoma, as compared to cirrhosis with or without liver cell dysplasia, (b) an in vitro study testing the role of normal or tumoral human hepatocytes in myofibroblast proliferation. METHODS: Forty explanted cirrhotic livers, including 14 with hepatocellular carcinoma and 24 with liver cell dysplasia, were studied. Myofibroblasts were detected by immunohistochemistry using an antibody directed against alpha-smooth muscle actin. Hepatic myofibroblasts in culture were obtained by outgrowth from human liver explants. RESULTS: There was a progressive increase in the number of perisinusoidal myofibroblasts, from cirrhotic nodules without dysplasia to liver cell dysplasia and hepatocellular carcinoma. Conditioned medium from isolated normal human hepatocytes had only minor mitogenic effects on myofibroblasts, as assessed by measuring DNA synthesis and cell growth. In contrast, conditioned medium from a human hepatoma cell line (HepG2 cells) markedly stimulated the proliferation of human myofibroblasts. This mitogenic activity was stored in HepG2 cells and secreted in the extracellular medium rather than being simply released following cell lysis. CONCLUSIONS: These results suggest that the increased number of myofibroblasts in hepatocellular carcinoma might be due to a paracrine mechanism involving soluble mitogenic factor(s) secreted by tumour cells.