Showing papers on "Fibrinoid necrosis published in 2001"

Small‐vessel vasculitis surrounding a spared temporal artery: Clinical and pathologic findings in a series of twenty‐eight patients

Abstract: Objective Occasionally, a temporal artery biopsy reveals small-vessel vasculitis (SVV) surrounding a spared temporal artery, the significance of which is unclear. We analyzed the final diagnosis in a series of patients with this condition and tried to identify histopathologic features with potential usefulness in predicting the ultimate diagnosis. Methods We performed a clinical and histopathologic review of 28 patients in whom SVV surrounding a spared temporal artery was the first histologic finding that led to the diagnosis of vasculitis. For comparison purposes, we analyzed the pattern of small vessel involvement in 30 patients with biopsy-proven giant cell arteritis (GCA). Results GCA was considered the most likely diagnosis in 12 patients, based on the absence of clinical evidence of additional organ involvement and normal findings on muscle biopsy and electrophysiologic study. Three patients had systemic necrotizing vasculitis (SNV), based on the demonstration of typical lesions on subsequent muscle, nerve, or kidney biopsy. After extensive evaluation, 4 patients remained unclassifiable. Nine patients were incompletely studied. Fibrinoid necrosis was significantly more frequent in patients with SNV (P = 0.0022), whereas involvement of vasa vasorum was more frequent in patients classified as having GCA (P = 0.022). No differences in the pattern of small vessel involvement were found in patients with SVV surrounding a spared temporal artery who were classified as having GCA compared with patients with biopsy-proven GCA. Granulocytes were observed at similar frequency in all conditions. Conclusion SVV may be the only abnormal feature in a temporal artery biopsy and the only histologic evidence of vasculitis. The diagnosis of GCA can be reasonably established in most of these patients when there is no apparent evidence of additional organ involvement. However, when fibrinoid necrosis is observed or the temporal artery vasa vasorum are not involved, SNV must be extensively excluded.

Prevention and treatment of experimental crescentic glomerulonephritis by blocking tumour necrosis factor‐α

Abstract: Background. The mechanisms controlling progression of glomerulonephritis are poorly understood, but there is increasing evidence that tumour necrosis factor-a (TNF-a) plays a central role in many aspects of glomerular inflammation and scarring. We investigated the role of TNF-α in an experimental model of crescentic glomerulonephritis in Wistar Kyoto (WKY) rats by continuously blocking endogenous TNF-a, using its soluble receptor sTNFr p55, both before and after establishment of nephritis. Methods. Glomerulonephritis was induced by a single intravenous injection of 0.1 ml nephrotoxic serum. In the first experiment, rats were pre-treated with sTNFr p55 2 mg/kg intraperitoneally 1 hour before induction of nephritis and on a daily basis thereafter until day 4. In the second experiment, a similar protocol was followed, but treatment with sTNFr p55 was continued until day 10. In the third experiment, treatment with sTNFr p55 was delayed until 4 days after induction of nephritis and continued until day 10. The effects of treatment on renal function, renal histology, cellular infiltration, activation and proliferation, and IL-1β expression were assessed by standard methods. Results. In the first experiment, short-term treatment with sTNFr p55 caused a marked reduction in albuminuria and fibrinoid necrosis. It also reduced glomerular cell infiltration, activation and proliferation. In the second experiment, prolonged treatment with sTNFr p55 caused a sustained reduction in albuminuria and all histological and cellular parameters of glomerular inflammation; in particular it completely prevented the development of crescents. In the third experiment, delayed therapy of established nephritis with sTNFr p55 significantly reduced albuminuria and glomerular inflammation, including the prevalence of crescent formation. In both long-term experiments, there was less glomerular expression of IL-1β and lower serum concentrations of IL-β in sTNFr p55-treated rats. Conclusions. This study shows that neutralization of endogenous TNF-α is effective in preventing acute glomerular inflammation and crescent formation, and in treating established disease, in a rat model of crescentic nephritis. These results may have therapeutic implications for human glomerulonephritis.

Acute hemorrhage in late radiation necrosis of the temporal lobe: report of five cases and review of the literature.

Abstract: Hemorrhage in late cerebral radiation necrosis is a rare complication after radiotherapy for intracranial and extracranial neoplasms. We report 5 cases of acute hemorrhage in late radiation necrosis of the temporal lobe following radiation therapy for nasopharyngeal carcinoma. In a review of the literature, the authors identified a total of 27 such cases. The interval period between the onset of hemorrhage and cranial irradiation is long (mean = 7.8 years). The most prominent histological feature was the proliferation of large, dilated and thin-walled new blood vessels in a background of gliosis and fibrinoid necrosis of vessels. Rupture of these thin-walled new blood vessels is the proposed mechanism of hemorrhage in this condition.

Acute vasculitis after endovascular brachytherapy.

Abstract: Purpose: Angioplasty effectively relieves coronary artery stenosis but is often followed by restenosis. Endovascular radiation (β or γ) at the time of angioplasty prevents restenosis in a large proportion of vessels in swine (short term) and humans (short and long term). Little information is available about the effects of this radiation exposure beyond the wall of the coronary arteries. Methods and Materials: Samples were obtained from 76 minipigs in the course of several experiments designed to evaluate endovascular brachytherapy: 76 of 114 coronary arteries and 6 of 12 iliac arteries were exposed to endovascular radiation from 32 P sources (35 Gy at 0.5 mm from the intima). Two-thirds of the vessels had angioplasty or stenting. The vessels were systematically examined either at 28 days or at 6 months after radiation. Results: We found an unexpected lesion: acute necrotizing vasculitis in arterioles located ≤2.05 mm from the target artery. It was characterized by fibrinoid necrosis of the wall, often associated with lymphocytic exudates or thrombosis. Based on the review of perpendicular sections of tissue samples, the arterioles had received between 6 and 40 Gy. This arteriolar vasculitis occurred at 28 days in samples from 51% of irradiated coronary arteries and 100% of irradiated iliac arteries. By 6 months, the incidence of acute vasculitis decreased to 24% around the coronary arteries. However, at that time, healing vasculitis was evident, often with luminal narrowing, in 46% of samples. Vasculitis was not seen in any of 44 samples from unirradiated vessels (0%) and had no relation to angioplasty, stenting, or their sequelae. This radiation-associated vasculitis in the swine resembles the localized lymphocytic vasculitis that we have reported in tissues of humans exposed to external radiation. On the other hand, it is quite different from the various types of systemic vasculitis that occur in nonirradiated humans. Conclusion: Endoarterial brachytherapy using 32 P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis is causally related to radiation, but its mechanism is unclear and a dose effect is not evident. Quite possibly, local upregulation of inflammatory cytokines contributes to this radiation-associated vasculitis, which only involved some of the arterioles in each sample. It is likely that radiation-associated vasculitis also occurs around human coronary arteries and may result in foci of ischemia. To our knowledge, this lesion has not been previously recognized, either in experimental models or in human specimens examined after angioplasty/brachytherapy.

Immunopathological aspects of systemic vasculitis.

Abstract: A number of obvious questions that are still largely unanswered form the basis of current research in ANCA-associated vasculitis. Do ANCA have pathogenic potential in the development of the vasculitic lesion? Why are anti-Pr3-antibodies found predominantly in WG? Does this have pathogenetic significance? How is glomerular fibrinoid necrosis related to the development of extracapillary proliferation? How specific are these lesions of systemic vasculitis syndromes? And are ANCA directly involved in the development of the histopathological lesions that are typically found in ANCA-associated vasculitis? These and other questions will hopefully be answered in the near future, enabling us to offer a more specific therapy for patients with systemic vasculitis syndromes.

Polyarteritis nodosa complicated by thrombotic thrombocytopenic purpura

Abstract: A 56 year old woman was diagnosed with polyarteritis nodosa (PAN) in June 1998 based on the presence of fibrinoid necrosis and infiltration of polymorphonuclear cells into medium and small sized arteries on a skin biopsy specimen. She presented with erythema on her arms and legs, with fever and body weight loss. Tender masses were palpable on her right abdomen. Small erythematous lesions and livedo reticularis were seen on the arms and legs. Laboratory investigation on admission disclosed anaemia (haemoglobin 73 g/l) and leucocytosis (22.5×109/l) consisting mainly of neutrophils (85%). Creatinine clearance was 39 ml/min. Serological examination showed raised levels of C reactive protein (88.6 mg/l). Serological tests for syphilis, hepatitis B virus antigen, and antibody for hepatitis C virus were negative. …

Pathophysiology of Pre-eclampsia/eclampsia Syndrome

Abstract: Sirs: We have been reading the letter from Friese et al. with great interest that described a women with eclampsia-syndrome in whom diffusion-weighted MRI revealed vasogenic oedema [4]. Their findings are of great pathophysiological relevance and are in line with other reports [11, 13, 14]. The new finding is the pattern of the MRI-abnormalities in their case. We here discuss with the authors the underlying pathophysiology of the observed vasogenic oedema, and their interpretation, that ‘blood pressure exceeds the range of autoregulation, and hyperperfusion creates vasogenic oedema’ [3]. If the blood pressure exceeds the upper limit of autoregulation for a long time, a ‘breakthrough’ of cerebral autoregulation with forced vasodilatation of the cerebral resistance vessels and subsequent hyperperfusion has been documented under experimental conditions [5, 12, 13]. The high blood pressure and increased blood flow induces a weakening of the tight junctions between the endothelial cells [5, 7, 13]. This results in a destruction of the blood-brain barrier (BBB) with an extravasation of fluid and proteins, diapedesis of red cells, and fibrinoid necrosis of cerebral arterioles [5]. Auer has found an early extravasation of Evans blue in the venules during acute hypertension [1], which is attributed to a venular congestion by an overload of a venous outflow. These pathophysiological conditions are in generally found in the hypertensive encephalopathy (HTE). In eclamptic women, the situation is much more complex and the clear pathophysiological concept of HTE cannot be transferred without several major limitations. Firstly, an endothelial dysfunction in preeclampsia/eclampsia with implications on vascular permeability, coagulation and altered response of the vasculature to pressor agents has been reported that is independent of damage of the BBB by high arterial pressure [8, 9]. Increased levels of factor VIII and fibronectin (which are considered as markers for an endothelial lesion) antedate the clinical disorder by days or weeks [8, 9]. Secondly, high concentrations of atrial natriuretic peptide (ANP) in the first week postpartum may have an impact of the permeability of the BBB for water [2, 17]. Brust and co-workers showed that ANP selectively increased the permeability of the BBB for water but not for amino acids [2]. Other mechanisms like low angiotensin II levels, altered concentrations of prostacyclin, sympathetic overactivity, may account for an additional difference between ‘pure’ HTE and the preeclampsia/eclampsia syndrome [5, 8–10]. These factors may be the reason for a ‘dissociation’ between the development of cerebral vasogenic oedema on MRI and the increase of cerebral blood flow velocities in transcranial ultrasound examinations. The latter most probably reflects cerebral hyperperfusion in patients with eclampsia [15, 16, 18]. We could observe severe vasogenic oedema in women with eclampsia within the first two days after the seizures with an almost complete resolution after 6, and 10 days, respectively, whereas flow velocities were peaking between day 3 and 7 and still highly elevated between 8 and 12 days [16]. These results are in keeping with an observation of Morriss et al. who measured cerebral blood flow within 24 h after delivery or after seizure and compared it with that found 4–5 weeks postpartum. There was no significant difference in the flow velocities. However, initial T2-weighted images were markedly abnormal in all eight women with eclampsia and in 2 of ten patients with severe preeclampsia [6]. These data suggest that the development of vasogenic oedema antedate the peak of cerebral hyperperfusion in eclamptic women, which again seems to be a difference from patients with HTE. Thus, despite the similarity in the clinical and radiological presentation of the patients with preeclampsia/eclampsia syndrome and HTE, one has to consider relevant pathophysiological differences which have not yet been clearly evaluated and understood.

Clinical picture of arteriolosclerosis

Abstract: Arteriolosclerosis is a generalised systemic vascular disease which is characterised by hyalinisation of intima (hyalinosis) as well as proliferation and hypertrophy of the media in the arteriolar part of the arterial system (so-called benign arteriolosclerosis). However, the patients suffering from accelerated and malign hypertension develop also fibrinoid necrosis (so-called malign arteriolosclerosis, arteriolonecrosis). Arteriolosclerosis as well as other similar stenotic (obliterating, obstructive, occlusive) diseases of the arterial system, have one single common consequence--ischemia. Currently, angio-organic ischemic syndromes in the whole world most frequently result from atherosclerosis which, however, is not the only nosologic unit of the group of arterial diseases having the tendency to develop arterial wall sclerosis. The latter group is briefly referred to as arteriosclerosis. In addition to atherosclerosis, this group includes also Monckeberg's medial arteriosclerosis, diabetic angiopathy and arteriolosclerosis. The authors of this study, on the basis of their analysis of their own large set of patients (71,662 angiologic consultant examinations performed during the period of 25 years of the existence of the Angiologic Department of the Medical Faculty Hospital of Comenius University in Bratislava) attract attention to the fact that the clinical picture of this disease is multiform, and that it occurs frequently in clinical practice. Therefore, angiology is a separate specialisation which is above the structure of internal medicine.

Non-CAA angiopathies and their possible interactions with cerebral amyloid angiopathy

Abstract: Cerebral amyloid angiopathy (CAA) is one of the two most common cerebral arteriopathies seen in the brains of elderly patients. The other is arteriosclerosis (AS), historically considered a consequence of chronic hypertension and also described as lipohyalinosis (LH), a clinicopathologic association that is increasingly questioned. These and other less frequently encountered degeneralions of the cerebral microvasculature (CADASIL, Binswanger subcortical leukoencephalopathy) share the common feature of degeneration of the medial smooth muscle layer within arteriolar walls. This can be dramatic in CAA, in the course of which complete replacement of medial smooth muscle by fibrillar amyloid may occur. It is a less prominent feature of CADASIL and BSLE: in the latter condition, medial smooth muscle hyperplasia, possibly a response to some kind of injury, is a more dramatic finding. In some of these "angiomyopathies", fibrinoid necrosis of the arterial wall and microaneurvsm formation may lead to stroke, manifest as cerebral hemorrhage. With CADASIL and BSLE, ischemic brain injury is more common. In the case of CAA, upregulation of the Abeta-amyloid precursor protein occurs when arteriolar smooth muscle cells in culture are exposed to prolonged hypoxia, especially with reoxygenation. Injury to arteriolar smooth muscle cells may be one mechanism by which angiomyopathies progress and become symptomatic.

SP0101 Current standard treatment for lupus nephritis

Abstract: Glomerulonephritis is a major cause for morbidity in systemic lupus erythematosus (SLE). In this disease, immune complex formation/deposition in the kidney results in intraglomerular inflammation with recruitment of leukocytes, and activation and proliferation of resident renal cells. Intense injury may destroy resident renal cells by necrosis or apoptosis resulting in fibrinoid necrosis. When injury is less intense, endocapillary cells respond by proliferating and production of extracellular matrix (proliferative lesions). Determination of disease severity: Renal biopsy, examination of the urine sediment and measurement of C3 levels (and to a lesser degree of anti-DNA titers) are essential for the management of lupus nephritis. Treatment depends on the severity of the disease. Accordingly disease severity is determined by the presence or absence of high-risk factors. These include demographic (male gender, black race), clinical (failure to acheive response or marked delay in response, multiple relapses, pregnancy), laboratory (impaired renal function, severe anaemia with hematocrit less than 26%) and histologic features (mixed membranous and proliferative or proliferative nephritis; cellular crescents and/or fibrinoid necrosis; and moderate to high degrees of interstitial fibrosis and/or tubular atrophy). Treatment: Patients with mild proliferative disease without risk factors are usually treated with corticosteroids alone or in combination with azathioprine. If the disease does not remit within 3–4 months, cytotoxic drugs such as cyclophoshamide or newer agents such as mycophenolate may be tried. For patients with moderate to severe proliferative nephritis, controlled trials have shown that pulse cyclophosphamide is the treatment of choice. Long-term follow-up of patients participating in these controlled trials suggest that combining pulse cyclophoshamide with pulse methylprednisolone increases efficacy but not toxicity. In general cytotoxic therapy continues 1 year beyond remission as shorter courses of cyclophosphamide have an increased risk for flares. Induction of response with cyclophosphamide followed by maintenance with agents such as azathioprine or cyclosporine is under investigation. For lupus membranous nephritis steroids, pulse cyclophospamide therapy or cyclosporine may be used. Relapse rates are high when cyclosporine is discontinued. In addition to immunosuppressive therapy, aggressive management of co-morbid conditions (hypertension, dyslipidemia, osteoporosis) is of paramount importance. Response rates and flares: Rates of clinical response and flares vary in different studies according to type of nephritis, treatment regimen, duration of therapy, and definition of clinical response and flare used. Flares pose a significant problem because of the risk for renal function deterioration due to cumulative damage as well as cumulative toxicities due to additional immunosuppressive therapy. Patients with nephritic flares (defined as increase in plasma creatinine level and reappearance of active nephritic urinary sediment), are more likely to progress to end-stage renal disease in spite of additional immunosuppressive therapy. Side effects: Pulse cyclophosphamide is associated with an increased risk for herpes zoster infections on the short-term and with sustained amenorrhea or azoospermia on the long-term. Gonadotropin-releasing hormone agonist (GnRH-a) may prevent accelerated recruitment and depletion of ovarian follicles (via suppression of the gonadotrophin production in the pituitary gland) and therefore protect against premature ovarian failure. In a small case series, testosterone was found to be effective in preserving fertility in patients with nephrotic syndrome treated with a short course of cyclophosphamide. New approaches: A recent controlled study reported that mycophenolate mofetil is equally effective to a regimen of oral cyclophosphamide and azathioprine used sequentially in patients with proliferative lupus nephritis However, in this study follow up was short, patients had relatively mild disease and patients with high- risk factors were not included. A controlled study comparing mycophenolate mofetil to pulse cyclophosphamide is in progress. Other investigations explore the therapeutic potential of high-dose, immunoablative cyclophosphamide therapy alone or in combination with autologous stem cell transplantation, low-dose cyclophosphamide in combination with nucleoside analogues, or biologic response modifiers. High- dose cyclophosphamide or combinations of low-doses with fludarabine may result in profound bone marrow and immune suppression. Combinations of cyclophosphamide with biologic response modifiers have shown encouraging results in preclinical animal studies and may provide a major breakthrough in the treatment of severe lupus, similar to the introduction of cytotoxic agents a few decades ago.

Interleukin-11 Attenuates Nephrotoxic Nephritis in Wistar

Abstract: Interleukin-11 (IL-11) is a multifuctional cytokine with anti-inflammatory activity. The effect of IL-11 was stud- ied in an experimental model of necrotizing glomerulonephritis induced in Wistar Kyoto rats by an injection of anti- glomeru- lar basement membrane antibody (nephrotoxic serum). Intra- peritoneal injection was chosen as the route of IL-11 admin- istration in all experiments. In experiment 1, recombinant human IL-11 (1360 g) was given 2 h before nephrotoxic serum, then once daily until day 6. In experiment 2, a lower dose of IL-11 (800 g/d) was used. Rats were treated either with IL-11 400 g twice daily intraperitoneally or with 800 g once daily intraperitoneally for 6 d. In experiment 3, the lower dose of IL-11 was given 2 h before nephrotoxic serum, then twice daily until day 2. In experiment 1, IL-11 significantly reduced proteinuria (13.2 3.3 versus 63.2 4.3 mg/24 h), fibrinoid necrosis (0.58 0.08 versus 1.52 0.06 quadrants/ glomerular cross section (gcs)), macrophage infiltration (ED1- positive cells, 24.4 1.8 versus 39.3 1.9 cells/gcs), apo- ptosis (1.11 0.1 versus 2.39 0.2 apoptotic bodies/gcs), and proliferating cell nuclear antigen-positive cells (24.4 2.0 versus 37.3 2.3 cells/gcs). Inducible nitric oxide synthase- positive cells were significantly increased (3.1 0.3 versus 2.0 0.2 cells/gcs). In experiment 2, a lower dose of IL-11 significantly reduced proteinuria and fibrinoid necrosis. Mac- rophage infiltration was similar in treated and control groups, although the number of sialoadhesin-positive macrophages (ED3) was significantly reduced in the IL-11-treated rats. In experiment 3, quantitative competitive reverse transcriptase- polymerase chain reaction showed that the mRNA ratio of IL-1/-actin in the treated rats was reduced compared with controls. By the use of probes designed from mouse IL-11 receptor -chain sequence, it was also shown that rat mesan- gial cells and macrophages expressed IL-11 receptor -chain, demonstrating that they were capable of responding to IL-11. In this model of necrotizing glomerulonephritis, high-dose IL-11 treatment markedly reduced both proteinuria and fibrin- oid necrosis. At the lower dose, there was a reduction in glomerular injury and macrophage sialoadhesin expression, but without an alteration of macrophage numbers, suggesting that IL-11 may be acting in part to reduce macrophage activation.