Arterial Wall Inflammation and Increased Hematopoietic Activity in Patients With Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) confers an increased risk of cardiovascular disease (CVD), independent of blood pressure. Animal models have shown that aldosterone accelerates atherosclerosis through proinflammatory changes in innate immune cells; human data are scarce. OBJECTIVE: The objective of this article is to explore whether patients with PA have increased arterial wall inflammation, systemic inflammation, and reprogramming of monocytes. DESIGN: A cross-sectional cohort study compared vascular inflammation on 2'-deoxy-2'-(18F)fluoro-D-glucose; (18F-FDG) positron emission tomography-computed tomography, systemic inflammation, and monocyte phenotypes and transcriptome between PA patients and controls. SETTING: This study took place at Radboudumc and Rijnstate Hospital, the Netherlands. PATIENTS: Fifteen patients with PA and 15 age-, sex-, and blood pressure-matched controls with essential hypertension (EHT) participated. MAIN OUTCOME MEASURES AND RESULTS: PA patients displayed a higher arterial 18F-FDG uptake in the descending and abdominal aorta (P < .01, P < .05) and carotid and iliac arteries (both P < .01). In addition, bone marrow uptake was higher in PA patients (P < .05). Although PA patients had a higher monocyte-to-lymphocyte ratio (P < .05), systemic inflammatory markers, cytokine production capacity, and transcriptome of circulating monocytes did not differ. Monocyte-derived macrophages from PA patients expressed more TNFA; monocyte-derived macrophages of healthy donors cultured in PA serum displayed increased interleukin-6 and tumor necrosis factor-α production. CONCLUSIONS: Because increased arterial wall inflammation is associated with accelerated atherogenesis and unstable plaques, this might importantly contribute to the increased CVD risk in PA patients. We did not observe inflammatory reprogramming of circulating monocytes. However, subtle inflammatory changes are present in the peripheral blood cell composition and monocyte transcriptome of PA patients, and in their monocyte-derived macrophages. Most likely, arterial inflammation in PA requires interaction between various cell types.

Mitochondrial DNA: A new driver for sex differences in spontaneous hypertension.

The prevalence of arterial hypertension (AH) is higher in men than in premenopausal women of the same age. AH has been characterized as a chronic inflammatory disease and activation of Toll-like receptors (TLR) by damage-associated molecular patterns (DAMPs) is involved. Mitochondrial DNA (mtDNA) may be released by end-organ damage, which is recognized and activates TLR9. The serum level of mtDNA is increased in AH. The aim of this study was to compare the serum mtDNA levels between male and female spontaneously hypertensive rats (SHR) and to evaluate the sex differences in the effect of mtDNA on the function, inflammation and signaling pathway related to TLR9 in the vasculature. Male and female 15-week-old SHR and Wistar rats were used to evaluate the arterial blood pressure, serum mtDNA, contractile response, inflammatory markers and signaling pathway related to TLR9. Male SHR had higher arterial blood pressure values and serum mtDNA compared to female SHR and to male and female normotensive Wistar rats. In male SHR aorta, mtDNA incubation increased the contractile response to phenylephrine, which was blunted by inhibition of TLR9, and also increased pro-inflammatory molecules IL-6 and TNF-α. However, in female SHR aorta, mtDNA incubation did not change the contractile response, reduced pro-inflammatory molecules and prevented oxidative stress. mtDNA incubation did not change the expression of TLR9, MyD88 and eNOS neither in male nor in female SHR aorta, but it increased the phosphorylation of ERK1/2 in male and reduced in female SHR aorta. The mtDNA differential modulation of vascular response in male and female SHR might contribute to sex differences in AH. This study contributes to the understanding of a need for more personalized therapeutic strategies for men and women with hypertension. Keywords: Sex differences, Arterial hypertension, Mitochondrial DNA, Toll-Like receptor 9.

Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans.

OBJECTIVE: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). APPROACH AND RESULTS: Arterial wall inflammation and bone marrow activity were measured using 18F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of 18F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07-5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27-0.40]; P<0.001). Monocytes from patients with FD showed increased lipid accumulation (lipid-positive monocytes: Patients with FD 92% [86-95], controls 76% [66-81], P=0.001, with an increase in lipid droplets per monocyte), and a higher expression of surface integrins (CD11b, CD11c, and CD18). Patients with FD also exhibited monocytosis and leukocytosis, accompanied by a 1.2-fold increase of 18F-FDG uptake in bone marrow. In addition, we found a strong correlation between remnant levels and leukocyte counts in the CGPS (n=103 953, P for trend 5×10-276). In vitro experiments substantiated that remnant cholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. CONCLUSIONS: Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD.

iMAP™ imaging of tumorous lesions surrounding the coronary arteries in a patient with an elevated serum level of immunoglobulin G4.

A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAP™, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252-427 mg/dL (8 measurements) (reference range, 4.8-105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4.

Inflammation and congenital heart disease associated pulmonary hypertension.

BACKGROUND: Increased blood flow may trigger pulmonary arterial wall inflammation, which may influence progression of pulmonary artery hypertension in patients with congenital heart disease. In this study, we aimed to investigate the correlation between preoperative inflammation markers and pulmonary arterial hypertension. METHODS: A total of 201 patients with pulmonary hypertension were enrolled in this study retrospectively; they had undergone open heart surgery between January 2012 and December 2013. Patients' preoperative C-reactive protein (CRP), neutrophil to lymphocyte ratio, red blood cell distribution width, pulmonary pressures, and postoperative outcomes were evaluated. RESULTS: Patient age, neutrophil to lymphocyte ratio, red blood cell distribution width, and CRP were found to be significantly correlated with both preoperative peak and mean pulmonary artery pressures. These data were entered into a linear logistic regression analysis. Patient age, neutrophil to lymphocyte ratio, and CRP were found to be independently correlated with peak pulmonary pressure (P < .001, P < .001, and P = .004) and mean pulmonary artery pressure (P < .001, P < .001, and P = .001), whereas preoperative mean pulmonary artery pressure was found to be independently correlated with intensive care unit stay (P < .001). No parameter was found to be significantly correlated with extubation time and mortality. Eighteen patients had experienced pulmonary hypertensive crisis; in this subgroup, patients' mean pulmonary artery pressure and neutrophil to lymphocyte ratio were found to be significant (P = .047, P = .003). CONCLUSIONS: Preoperative inflammation markers may be correlated with the progression of pulmonary hypertensive disease, but further studies with larger sample size are needed to determine the predictive role of these markers for postoperative outcomes.

Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis.

BACKGROUND: Steroid Responsive Meningitis-Arteritis (SRMA) is a common cause of inflammation of the canine central nervous system (CNS). To investigate if transforming growth factor beta 1 (TGF-ß1), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) are involved in the production of excessive immunoglobulin A (IgA), the induction of acute phase proteins and in the development of a systemic necrotizing vasculitis, characteristic of SRMA, these three signalling proteins were evaluated. RESULTS: Cerebrospinal fluid (CSF) and serum samples of dogs during the acute phase of SRMA (SRMA) were tested for IL-6, VEGF and TGF- ß1. Results were compared to those of dogs affected with SRMA during treatment (SRMA Th) and during relapse (SRMA R), to dogs with other meningoencephalomyelitides (ME), with miscellaneous non-inflammatory diseases of the CNS (CNS-Mix), with idiopathic epilepsy (IE), with systemic inflammatory diseases (Syst. Infl.) and with healthy dogs (Healthy). Concentrations of IL-6 and VEGF in CSF were significantly elevated in the SRMA group compared to the other disease categories (p<0.05). The CSF concentrations of TGF-ß1 were increased in SRMA group, but statistically significant differences were found only in comparison with Healthy and CNS-Mix groups. No differences were detected in the serum concentrations of TGF-ß1 between the different groups. In untreated SRMA patients, a positive correlation (rSpear = 0.3549; P=0.0337) between concentrations of TGF-ß1 and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (rSpear=0.8323; P<0.0001 and rSpear=0.5711; P=0.0166, respectively). CONCLUSIONS: Our results suggest that these three signalling proteins are biomarkers of disease activity in SRMA. VEGF might play an important role in the development of a systemic arteritis. TGF-ß1 is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis. The combined intrathecal increase of TGF-ß1 and IL-6 detected in SRMA could possibly force CD4 progenitors to differentiate towards the newly described Th17 lymphocyte subset and enhance the autoimmune response.

A clinicopathologic study of immunoglobulin G4-related disease of the femoral and popliteal arteries in the spectrum of immunoglobulin G4-related periarteritis.

BACKGROUND: Immunoglobulin (Ig) G4-related disease has recently been recognized to occur in the cardiovascular system in the aorta and main branching arteries, often manifesting as aneurysms and arteritis/periarteritis. Peripheral arteries (the femoral and popliteal arteries) are frequent sites of arteriosclerosis obliterans (ASO) and occasionally show aneurysms or arteritis. This study re-examined peripheral arterial lesions from the standpoint of IgG4-related disease. METHODS: The study comprised 104 patients who underwent surgical treatment of peripheral arterial lesions, including 30 patients with peripheral arterial aneurysms (PAAs) and 74 with ASO. IgG4-related disease was identified on the basis of diffuse infiltration of numerous IgG4-positive plasmacytes as revealed by immunohistochemical examination. Clinicopathologic features were compared between IgG4-related and IgG4-unrelated lesions. RESULTS: IgG4-related disease was found in four of the 30 patients with PAAs (13.3%; two in the deep femoral artery, two in the popliteal artery) but not in any patients with ASO. IgG4-related PAA displayed clinicopathologic features resembling those of other IgG4-related diseases and a characteristic saccular appearance (P = .002). CONCLUSIONS: IgG4-related disease was detected in PAA patients but not in ASO patients. IgG4-related disease thus represents one potential etiology of aneurysm in the peripheral arteries.

[Evaluation of decreased glucose levels in the cerebrospinal fluid of dogs]. / Untersuchungen zu erniedrigten Glukosewertenim Liquor cerebrospinalis des Hundes.

OBJECTIVE: The aim of the study was to evaluate the glucose ratio (glucose level in the cerebrospinal fluid [CSF]/blood glucose level) as a quickly available marker for detecting bacterial meningoencephalomyelitis (BM). MATERIAL AND METHODS: Blood and CSF samples of 328 dogs were reviewed and evaluated retrospectively. Following the neurological diagnosis, the dogs were assigned to seven different groups: steroid-responsive meningitis-arteritis (SRMA), intervertebral disc disease (IVDD), neoplasia of the central nervous system (N), idiopathic epilepsy (IE), bacterial meningoencephalomyelitis (BM), meningoencephalomyelitis of other origin (ME) and healthy dogs. RESULTS: The median of the CSF-glucose level (mmol/l) and the median of the glucose ratio in the SRMA group displayed the lowest values and differed significantly from the CSF-glucose levels of dogs in the groups IVDD, N, IE and healthy dogs (CSF-glucose level: p<0.01; glucose ratio: p<0.05). In the BM group, both parameters did not differ significant- ly from other groups, but displayed similar low levels as in the SRMA group. There was a negative correlation between the CSF cell count and the CSF-glucose ratio (Spearman correlation coefficient -0.322, p=0.01, R²=0.108). CONCLUSION: The CSF-glucose concentration cannot be used as a distinct marker to differentiate BM from other inflammatory CNS-diseases, especially from SRMA usually accompanied by severe pleocytosis. Low CSF-glucose levels appear to be caused by elevated CSF cell counts rather than by bacterial metabolism. CLINICAL RELEVANCE: For a definitive diagnosis of bacterial meningoencephalomyelitis in dogs, the detection of microorganisms remains necessary.

Immunoglobulin G4-related coronary periarteritis in a patient presenting with myocardial ischemia.

Recent studies suggest that the cardiovascular system might be a possible target of immunoglobulin G4-related disease. Here we present a 66-year-old man who was admitted to our hospital because of chest symptoms suggestive of acute coronary syndrome. Besides luminal narrowing of the coronary arteries, marked periarterial thickening around the coronary artery was observed by computed tomography coronary angiography. Serum immunoglobulin G4 levels of this patient were elevated (564 mg/dL). The patient underwent coronary bypass surgery. After incision of the pericardium, a glittery white-yellowish, elastic-hard periarterial mass surrounding the left circumflex artery could be seen. Histologic analysis of the biopsy specimen showed the formation of lymphoid follicles and the presence of immunoglobulin G4-positive plasma cells; therefore, the diagnosis was immunoglobulin G4-related coronary periarteritis accompanied by physiologically significant myocardial ischemia.

Clinicopathologic analysis of acute vascular rejection cases after renal transplantation.

INTRODUCTION: Histopathologic change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. PATIENTS: AVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. RESULTS: Among 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2-t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid-resistant rejection (SRR) requiring greater anti-rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. CONCLUSIONS: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression.

Dysregulated RANK ligand/RANK axis in hyperhomocysteinemic subjects: effect of treatment with B-vitamins.

BACKGROUND AND PURPOSE: Homocysteine has been linked to increased risk of ischemic stroke and other cardiovascular events. Matrix degradation and inflammation play an important role in these disorders, and we have demonstrated increased levels of matrix-degrading enzymes and inflammatory cytokines in hyperhomocysteinemic individuals. Recent studies suggest that RANK ligand (RANKL) through interaction with its receptor RANK can modulate matrix degradation and inflammation. The present study aimed to examine the role of the RANKL/RANK axis in hyperhomocystinemia. METHODS: RANKL/RANK was measured on protein or mRNA level before and after B-vitamin supplementation in hyperhomocysteinemic individuals. We also examined the in vitro effects of soluble RANKL in peripheral blood mononuclear cells from hyperhomocysteinemic individuals. RESULTS: Our main findings were: (1) compared to peripheral blood mononuclear cells from controls, cells from hyperhomocysteinemic individuals had significantly higher gene expression of RANKL and RANK; (2) folic acid treatment for 6 weeks in an open, uncontrolled study significantly reduced gene expression of RANKL/RANK in peripheral blood mononuclear cells from these individuals; (3) compared to placebo, treatment with folic acid, vitamin B(12), and vitamin B(6) for 3 months in a randomized, double-blind trial significantly lowered serum levels of soluble RANKL in hyperhomocysteinemic individuals; and (4) in vitro, soluble RANKL markedly increased the release of matrix metalloproteinase-9 and inflammatory cytokines from peripheral blood mononuclear cells in hyperhomocysteinemic subjects. CONCLUSIONS: Our findings suggest a dysregulated RANKL/RANK axis in hyperhomocysteinemic subjects. Based on their role in atherogenesis, this enhanced expression of RANKL and RANK could contribute to the increased risk of cardiovascular disease in hyperhomocystinemia. Moreover, treatment with B-vitamins may have beneficial implications for plaque stability in these individuals.

Susceptibility loci to coronary arteritis in animal model of Kawasaki disease induced with Candida albicans -derived substances.

We have established an animal model of coronary arteritis which is histopathologically similar to that observed in cases of Kawasaki disease (KD), is a well-known childhood vasculitis syndrome. Coronary arteritis in this mouse model has been induced by intraperitoneal injection of Candida albicans -derived substances (CADS). Arteritis varied by mouse strain with the highest incidence by 71.1% (27/38) found in C3H/HeN mice, but absent in CBA/JN mice (0%, 0/27), suggesting association of genomic background to develop the disease. The present study aims to elucidate the susceptibility loci associated with coronary arteritis by using this animal model. The association of the onset of arteritis with polymorphic microsatellite markers between the two strains was examined using one hundred and fifteen of N1 backcross progeny [(CBAxC3H)F1xC3H]. Based on our analysis, arteritis-susceptibility loci with suggestive linkage were mapped on D1Mit171 and D1Mit245(map position 20.2 cM) on chromosome 1 (P=0.0019). These loci include several kinds of inflammatory cytokine receptors, such as interleukin 1 receptor and tumor necrosis factor receptor. We also found the cytokine response against CADS, levels of inflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 in sera increased within 24 hr after CADS injection. Our results may indicate based on genomics that ligand-receptor interaction between these inflammatory cytokines and the receptors of these cytokines may affect the onset of arteritis.

Restenosis after percutaneous angioplasty: the role of vascular inflammation.

Restenosis after endovascular treatment of atherosclerotic lesions in the peripheral, cerebrovascular, and coronary circulation is the major drawback of this minimally invasive technique. Although certain advances have been made during recent years to improve patency rates after percutaneous angioplasty, restenosis remains a challenging clinical problem. Understanding factors that contribute to the pathophysiology of late lumen loss is an effective strategy to improving patients' postangioplasty outcome. Vascular inflammation after balloon angioplasty or stent implantation has been identified as a cornerstone of the restenotic process, and several markers of inflammation have been referred to as potential predictors of outcome. This article reviews recent findings on the issue of inflammation and restenosis after percutaneous angioplasty with special attention given to the role of inflammatory parameters as markers for the restenosis risk in the peripheral vessel area.

Marked decrease in the levels of two inflammatory markers, hs-C-reactive protein and fibrinogen in patients with severe carotid atherosclerosis after eversion carotid endarterectomy.

OBJECTIVE AND DESIGN: To study changes in the levels of two acute phase proteins, plasma fibrinogen and serum C-reactive protein (hs-CRP) in patients with severe carotid stenosis after eversion endarterectomy. MATERIAL AND SUBJECTS: A total of 117 consecutive patients who underwent eversion endarterectomy were included in the study. Blood samples for acute phase protein measurement were taken before operation as well as 5.7 weeks and 13.8 months (median) post-surgery. Plasma fibrinogen and serum hs-CRP concentrations were promptly determined. RESULTS: During the follow-up period sharp, highly significant (p < 0.0001) drop occurred in the serum concentrations of both acute phase proteins. The drop in the hs-CRP levels during the follow up period was mainly due to decrease in patients with highest baseline CRP levels. CONCLUSIONS: Our present findings indicate that removal of atherosclerotic plaques from the carotid arteries markedly decreases the production of two acute phase proteins due to the decrease of the inflammatory burden or the removal of the advanced plaques able to produce these proteins.

Umbilical arteritis and phlebitis mark different stages of the fetal inflammatory response.

OBJECTIVE: Funisitis, the inflammation of the umbilical cord determined by histologic examination of the placenta, is evidence of a fetal inflammatory response. The inflammatory process may involve the umbilical vein (phlebitis) and one or both umbilical arteries (arteritis) and extend into the Wharton's jelly. This study was conducted to examine whether the pattern of inflammation of the umbilical cord correlates with a biochemical marker of systemic fetal inflammation (umbilical cord plasma interleukin-6) and an adverse neonatal outcome. STUDY DESIGN: This cohort study included 636 cases of preterm delivery (<36 weeks) with or without inflammation of the umbilical cord. Umbilical cord blood was collected at the time of delivery. The aim of pathologic examination was to characterize the extent of umbilical cord inflammation and the involvement of the vein (phlebitis), the involvement of one or both arteries (arteritis), and the presence of inflammation of the Wharton's jelly. Umbilical cord plasma interleukin-6 concentrations were assayed by a sensitive and specific immunoassay. RESULTS: Neonates with umbilical arteritis had a significantly higher median concentration of cord plasma interleukin-6 (median, 111 pg/mL; range, 0.1-19,230 pg/mL) than those without umbilical arteritis (median, 22.5 pg/mL; range, 0.9-511.6 pg/mL; P <.05). Also, severe neonatal morbidity occurred more frequently in infants with arteritis than in those without arteritis (74% vs 50%; P <.05). And finally, the most severe form of inflammation, which involves both arteries, vein, and Wharton's jelly, was associated with the highest median concentration of plasma interleukin-6 observed in this study (median, 182.6 pg/mL; range, 0.1-7,400 pg/mL), whereas inflammation limited to the vein (phlebitis) was associated with a lower concentration of cord plasma interleukin-6 (median, 29.1 pg/mL; range, 0.9-511.6 pg/mL; P <.05). CONCLUSION: Neonates whose placenta demonstrates umbilical arteritis have higher concentrations of umbilical cord plasma interleukin-6 and higher rates of adverse outcome than those without umbilical arteritis.

[Eosinophilic arteritis of the scalp]. / Artérite éosinophilique du cuir chevelu.

BACKGROUND: The occurrence of recurrent peripheral arterial thromboses together with a blood eosinophilia generally suggests an occlusive vascular disease or a systemic vasculitis. CASE REPORT: In a 31-year-old woman with a 15-year history of severe smoking and a blood eosinophilia from 1,200 to 2,500/mm(3), we observed recurrent attacks of pruritus and urticaria and recurrent lesions of eosinophilic thromboangiitis of hypodermal medium-sized elastic arteries of the scalp. In spite of the persistent eosinophilia, the evolution was spontaneously regressive and no other clinical or biological sign occurred within a follow-up time of 3 years. DISCUSSION: In Buerger's disease (thromboangiitis obliterans) and in most systemic vasculitis, especially in Churg-Strauss syndrome, the first lesions may be inflammatory thromboses of the extra-cranial scalp arteries. The diagnosis of an eosinophilic arteritis of the scalp may only be considered if the examination of the other peripheral vessels is normal and if the course of the disease is benign, without any treatment, in spite of a persistent blood eosinophilia. This clinico-pathological presentation should be considered as a distinct entity.

Histo-topographic distribution of acute inflammation of the human umbilical cord.

Acute inflammation of the umbilical cord, acute funisitis, is a sign of fetal inflammatory response, and the clinicopathological need for its identification is increasing. This study was conducted in order to describe the topographic distribution of acute funisitis, and thereby to provide more information on the intrinsic nature of acute funisitis and find a better way of pathologically examining the umbilical cord. A total of 10 umbilical cords affected by acute funisitis were histopathologically examined throughout their entire lengths at 1 mm intervals. Pathological examination was done to characterize the extent of the funisitis, the involvement of the vein (phlebitis) or of one or both arteries (arteritis), and the presence of inflammation in Wharton's jelly. Umbilical cord plasma interleukin (IL)-6 was measured by specific immunoassay to assess whether or not the severity of acute funisitis correlates with fetal cytokine response. It would appear that the inflammatory reaction begins as a discrete, multifocal process which eventually becomes contiguous as the inflammatory reaction proceeds. Umbilical cord plasma IL-6 concentrations tended to correlate with the extent of umbilical cord inflammation. The initial phase of acute funisitis involves discrete and multiple foci along the length of the umbilical cord. Moreover, the extent of acute funisitis reflects the severity of systemic fetal cytokine response. Therefore, adequate sampling using multiple sections would facilitate the identification of acute funisitis. We propose a standard sampling procedure taking one section from each third of the umbilical cord.