Background Hypoxia may contribute to the pathogenesis of various diseases of the vascular wall. Hypoxia-inducible factors (HIFs) are nuclear transcriptional factors that regulate the transcription of ...genes that mediate cellular and tissue homeostatic responses to altered oxygenation. This article reviews the published literature on and discusses the role of the HIF pathway in diseases involving the vascular wall, including atherosclerosis, arterial aneurysms, pulmonary hypertension, vascular graft failure, chronic venous diseases, and vascular malformation. Methods PubMed was searched with the terms “hypoxia-inducible factor” or “HIF” and “atherosclerosis,” “carotid stenosis,” “aneurysm,” “pulmonary artery hypertension,” “varicose veins,” “venous thrombosis,” “graft thrombosis,” and “vascular malformation.” Results In atherosclerotic plaque, HIF-1α was localized in macrophages and smooth muscle cells bordering the necrotic core. Increased HIF-1α may contribute to atherosclerosis through alteration of smooth muscle cell proliferation and migration, angiogenesis, and lipid metabolism. The expression of HIF-1α is significantly elevated in aortic aneurysms compared with nonaneurysmal arteries. In pulmonary hypertension, HIF-1α contributes to the increase of intracellular K+ and Ca2+ leading to vasoconstriction of pulmonary smooth muscle cells. Alteration of the HIF pathway may contribute to vascular graft failure through the formation of intimal hyperplasia. In chronic venous disease, HIF pathway dysregulation contributes to formation of varicose veins and venous thromboembolism. However, whether the activation of the HIF pathway is protective or destructive to the venous wall is unclear. Increased activation of the HIF pathway causes aberrant expression of angiogenic factors contributing to the formation and maintenance of vascular malformations. Conclusions Pathologic vascular wall remodelling of many common diseases of the blood vessels has been found to be associated with altered activity of the HIF pathway. Therefore, understanding the role of the HIF pathway in diseases of the vascular wall is important to identify novel therapeutic strategies in the management of these pathologies.
In the recently published 5th Edition of the World Health Organisation Classification of Head and Neck Tumours, there are relatively few changes to report in terms of nomenclature in lesions of ear ...and temporal bone and fewer developments in molecular pathogenesis in comparison to other sites, particularly in sinonasal tract. Ear and temporal bone tumours are rare and biopsy material is limited. As a result, resources in the literature are scarce with few large series, no controlled clinical trials and the approaches to staging and management are not standardised. New entities are difficult to characterise. The number of entries has, however, increased for tumours of the ear and temporal bone (thirteen) compared to the 4th Edition (eleven). Some lesions previously included in the 4th Edition considered to have no site-specific features have been excluded to be discussed elsewhere and other benign lesions that are specific to this site have been included. The tumours and tumour-like entities of ear and temporal bone are discussed here mindful that the chapter in the 5th edition better correlates disease processes with clinical information and imaging and as far as possible standardises nomenclature.
Corynebacterium ulcerans cutaneous diphtheria Moore, Luke S P, Dr; Leslie, Asuka, MFPH; Meltzer, Margie, FFPH ...
The Lancet infectious diseases,
09/2015, Letnik:
15, Številka:
9
Journal Article
Recenzirano
Summary We describe the case of a patient with cutaneous diphtheria caused by toxigenic Corynebacterium ulcerans who developed a right hand flexor sheath infection and symptoms of sepsis such as ...fever, tachycardia, and elevated C-reactive protein, after contact with domestic cats and dogs, and a fox. We summarise the epidemiology, clinical presentation, microbiology, diagnosis, therapy, and public health aspects of this disease, with emphasis on improving recognition. In many European countries, C ulcerans has become the organism commonly associated with cutaneous diphtheria, usually seen as an imported tropical disease or resulting from contact with domestic and agricultural animals. Diagnosis relies on bacterial culture and confirmation of toxin production, with management requiring appropriate antimicrobial therapy and prompt administration of antitoxin, if necessary. Early diagnosis is essential for implementation of control measures and clear guidelines are needed to assist clinicians in managing clinical diphtheria. This case was a catalyst to the redrafting of the 2014 national UK interim guidelines for the public health management of diphtheria, released as final guidelines in March, 2015.
Aims
To verify the applicability, reproducibility and predictive value of a proposed unified classification (amended Ljubljana classification) for laryngeal squamous intraepithelial lesions (SILs).
...Methods and results
Six internationally recognized experts and three pathologists from Ljubljana contributed to this study by evaluating a set of laryngeal SILs using the new system: low‐grade SIL, high‐grade SIL, and carcinoma in situ (CIS). The overall agreement among reviewers was good. Overall unweighted and weighted κ‐values and 95% confidence intervals were 0.75 (0.65–0.84) and 0.80 (0.71–0.87), respectively. The results were stratified between the international reviewers and the Ljubljana pathologists. The former had good overall agreement, and the latter had very good agreement. Kaplan–Meier survival curves showed a significant difference (P < 0.0001) between patients with low‐grade and high‐grade SILs; 19 of 1204 patients with low‐grade SILs and 30 of 240 patients with high‐grade SILs progressed to malignancy in 2–15 years and in 2–26 years, respectively.
Conclusions
The proposed modification to the Ljubljana classification provides clear morphological criteria for defining the prognostic groups. The criteria facilitate better interobserver agreement than previous systems, and the retrospective follow‐up study demonstrates a highly significant difference in the risk of malignant progression between low‐grade and high‐grade SILs.
The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been ...implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1st diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection +/- neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1st diagnosis of the recurrence group was 59.53 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group was evaluated and found that 17 had non-cohesive invasion, 30 had dysplasia at margin, 21 had vascular invasion, 9 had nerve invasion and 3 had bony invasion. Severe dysplasia was present in 37 patients. Tumour clearance was achieved in only 8 patients. The mean depth of tumour invasion in the recurrence group was 7.6 mm.An interesting finding was that 5/11 patients who died of distant metastasis had their primary disease in the tongue. Nodal disease comparison showed that 8/10 patients who died of locoregional metastasis and 8/11 patients who died from distant metastasis had clinical nodal involvement. Comparing this to pathological nodal disease (pTNM) showed that 10/10 patients and 10/11 patients who died from locoregional and distant metastasis, respectively, had nodal disease. All patients who died from locoregional and distant metastasis were shown to have recurrence after the primary tumour resection. Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the cervical lymph nodes. Several clinicopathological parameters can be employed to assess outcome, recurrence and overall survival.
A novel DEK::AFF2 fusion carcinoma was recently described in 29 patients who originally presented with non-viral-associated nonkeratinizing squamous cell carcinoma. The tumors occurred at multiple ...sites in the head and neck including in the sinonasal tract, middle ear, and temporal bone. This tumor behaves aggressively involving adjacent vital structures, frequently recurs, and is inclined to develop lymph node and distant metastasis. This review aims to summarize the demographic, clinical, pathologic, immunophenotypic features, and pattern of molecular alterations as well as to discuss the differential diagnosis of DEK::AFF2 fusion carcinoma.
The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal ...injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b(+) Ly6C(high) inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa(-/-) mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b(+) Ly6C(high) inflammatory monocytes in C1qa(-/-) mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model.
This case report describes a unique nasal mass that was difficult to diagnose clinically and histologically. The patient was a middle-aged man employed as a metalworker, and he presented with a ...unilateral nasal obstruction and a mass arising from the right middle meatus. After a series of investigations, he underwent right-sided sphenoethmoidectomy with excision of a nasal lesion. The surgical specimen presented a major diagnostic challenge for the pathologists and clinicians involved. A series of discussions amongst two different head and neck expert teams combined with detailed clinicopathological correlation resulted in a diagnosis of a granulomatous lesion or pseudotumour related to the ingestion of water-soluble cutting oils, or “Suds oil,” as they are more commonly called. Although occupational exposures to certain inhalants, such as wood dust and formaldehyde, are well-known risk factors for sinonasal lesions, here we present a rare association between a sinonasal lesion and another inhalant, Suds oil, that has not been previously reported in the literature.
Fetal cells enter maternal blood during pregnancy and persist in women with autoimmune disease. The frequency of subsequent fetomaternal microchimerism in healthy women and its cell type is unknown. ...To test the hypothesis that fetal mesenchymal stem cells persist in maternal organs, we studied female bone marrow and ribs. Male cells were identified by XY fluorescence in-situ hybridisation in marrow-derived mesenchymal stem cells and in rib sections from all women with male pregnancies, but not in controls (9/9
vs 0/5, p=0·0005). We conclude that fetal stem cells transferred into maternal blood engraft in marrow, where they remain throughout life. This finding has implications for normal pregnancy, for obstetric complications that increase fetomaternal trafficking, and for graft survival after transplantation.
Purpose Dupuytren's tissue has typically been described as being composed of myofibroblast-rich palmar nodules and relatively acellular tendon-like cords. We aimed to determine myofibroblast ...distribution (alpha-smooth muscle actin α-SMA positive cells) within Dupuytren's tissue and to correlate histologically defined α-SMA-positive nodules with digital contracture and recurrent disease. Methods One hundred and three digital Dupuytren's cords (72 fasciectomy, 31 dermofasciectomy) were stained with anti–α-SMA antibody. The presence of α-SMA–positive nodules, their surface area, and α-SMA–positive cells were quantified throughout excised Dupuytren's tissue. Clinical data on diathesis, flexion deformity, and previous surgeries were collected. Results Cords were nodular (66%) or non-nodular (34%). Nodular cords contained 1 (55%), 2 (33%), or 3 or more nodules (12%) composed of localized collections of cells. The mean total nodule surface area was 23 mm2 (range, 1.3–105 mm2 ). Nodules contained the highest number of α-SMA–positive cells (mean 97%, 2374 cells/mm2 ) compared to peri-nodular areas (mean 32%, 763 cells/mm2 ), and more distant cord (mean 8%, 495 cells/mm2 ). Non-nodular cords contained 9% to 17% α-SMA–positive cells (mean 475–663 cells/mm2 ), with higher numbers distally. There was greater digital contracture in patients with non-nodular cords. Thirty-six of 38 proximal interphalangeal (PIP) joint–marked samples had a nodule that co-localized with the PIP joint. Nodule size did not correlate with flexion deformity or with primary or recurrent disease. Conclusions We found that two thirds of digital cords were nodular. Nodules were hypercellular, the majority being α-SMA–positive cells. Nodules varied in size and co-localized with the PIP joint. Cord was relatively cellular throughout; a proportion of these cells were α-SMA–positive and cells aligned with collagen fibers. Non-nodular cords correlated with significantly greater digital flexion contracture. We propose that cells in nodular cords contract and deposit extracellular matrix components. The matrix is then remodeled in shortened configuration, and as fixed flexion deformity develops, stress shielding eventually leads to myofibroblast apoptosis, and cord becomes less cellular.
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