Are PR3 positive and MPO positive GPA the same disease?

Granulomatosis with Polyangiitis is a necrotising systemic vasculitis predominantly affecting small and medium sized vessels. It is predominantly associated with antibodies directed against proteinase 3, but a small number of individuals with this disease have antibodies directed against myeloperoxidase. The premise of this paper is to explore the possibility that these two serotypes maybe two separate diseases. There is evidence that the same single nucleotide polymorphisms in the TLR 9 gene is associated with increased risk for PR3 ANCA positivity but protects against MPO ANCA positivity. There is some evidence that MPO ANCA positive GPA disease may be ‘limited’ in its expression and be associated with the more indolent phenotype. The genotype may affect the serotype, and the serotype might affect the phenotype. There has been limited success in identifying how the difference in phenotype might affect outcomes. We are at a very early stage in our understanding of how these serotypes might be treated differently. This paper attempts to critically appraise the evidence available so far.     

Trends on gastrointestinal bleeding and mortality: Where are we standing?

Bleeding from the gastrointestinal tract and its management are associated with significant morbidity and mortality. The predisposing factors that led to the occurrence of these hemorrhagic instances are largely linked to the life style of the affected persons. Designing a new strategy aimed at educating the publics and improving their awareness of the problem could effectively help in eradicating this problem with no associated risks and in bringing the mortality rates down to almost zero.     

Hypertension in the elderly: Are we all on the same wavelength?

Hypertension is of frequent occurrence in the elderly population.Isolated systolic hypertension(ISH) accounts for the majority of cases of hypertension in the elderly.ISH is associated with a 2-4-fold increase in the risk of myocardial infarction,left ventricular hypertrophy,renal dysfunction,stroke,and cardiovascular mortality.There have been many studies to determine the optimal treatment for hypertension in the elderly. Why,when and how to treat hypertension in the elderly was the scope of the majority of these trials.Despite countless efforts many aspects remain obscure.While a number of novel drugs are being developed,the issue of whether all antihypertensive drugs bestow parallel benefits or whether some agents offer a therapeutic advantage beyond blood pressure control remains of crucial importance.Furthermore,the response of theelderly to different antihypertensive agents also differs from that of younger patients and may explain some of the disparities in outcomes of trials conducted in elderly patients with hypertension.     

OSA and cardiometabolic risk: What's the bottom line?

Obstructive sleep apnoea (OSA) is a common condition characterized by repetitive upper airway obstruction during sleep. OSA promotes wide intrathoracic pressure swings, intermittent hypoxia and sleep fragmentation. Growing evidence derived from animal models mimicking the oxygen profile observed in patients with OSA as well as clinical studies support that this important sleep‐disordered breathing is associated with increased cardiovascular risk. Although the precise mechanisms are not fully established, it is conceivable that the metabolic deregulation promoted by the components of OSA may have an important causal role in the poor cardiovascular prognosis. In this review, we summarize the potential role of OSA and its components on cardiometabolic disease. We also summarize evidence evaluating the impact of OSA treatment (notably continuous positive airway pressure) on reversing the metabolic deregulation promoted by OSA. Finally, we discuss the research agenda and perspectives for this important research area.     

Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities?

PURPOSE OF THE REVIEW: One of the most perplexing features of systemic-onset juvenile rheumatoid arthritis is the association with macrophage activation syndrome, a life-threatening complication caused by excessive activation and proliferation of T cells and macrophages. The main purpose of the review is to summarize current understanding of the relation between macrophage activation syndrome and other clinically similar hemophagocytic disorders. RECENT FINDINGS: Clinically, macrophage activation syndrome has strong similarities with familial and virus-associated reactive hemophagocytic lymphohistiocytosis. The better understood familial hemophagocytic lymphohistiocytosis is a constellation of rare, autosomal recessive immune disorders. The most consistent immunologic abnormalities in patients with familial hemophagocytic lymphohistiocytosis are decreased natural killer and cytotoxic cell functions. In approximately one third of familial hemophagocytic lymphohistiocytosis patients, these immunologic abnormalities are secondary to mutations in the gene encoding perforin, a protein that mediates cytotoxic activity of natural killer and cytotoxic CD8+ T cells. Several recent studies have suggested that profoundly depressed natural killer cell activity and abnormal levels of perforin expression may be a feature of macrophage activation syndrome in systemic-onset juvenile rheumatoid arthritis as well. Although it has been proposed that in both hemophagocytic lymphohistiocytosis and macrophage activation syndrome, natural killer and cytotoxic cell dysfunction may lead to inadequate control of cellular immune responses, the exact nature of such dysregulation and the relation between macrophage activation syndrome and hemophagocytic lymphohistiocytosis still remain to be determined.     

PKC-delta and PKC-epsilon: foes of the same family or strangers?

Protein kinase C (PKC) is a family of 10 serine/threonine kinases divided into 3 subfamilies, classical, novel and atypical classes. Two PKC isozymes of the novel group, PKCε and PKCδ, have different and sometimes opposite effects. PKCε stimulates cell growth and differentiation while PKCδ is apoptotic. In the heart, they are among the most expressed PKC isozymes and they are opposed in the preconditioning process with a positive role of PKCε and an inhibiting role of PKCδ. The goal of this review is to analyze the structural differences of these 2 enzymes that may explain their different behaviors and properties.     

Bifocal lung cancer: the same histology?

Whereas synchronous lung cancer is rare, synchronous small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are exceptional. The authors report the case of a 61-year-old man with synchronous unilateral adenocarcinoma and small cell lung cancer, raising the question as to the need for the histology of all of the lesions in the same lobe or same lung as well as the treatment. The medical history, biology, CT and (18)F-FDG TEP-CT did not support a diagnosis of synchronous lung cancer. The prognosis was poor and only surgery could improve the prognosis. This is a rare case and illustrates the difficulty in the diagnosis of multiple lung cancer and the difficulty in treating synchronous lung cancer with different histologies (SCLC and NSCLC).     

Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?

BACKGROUND: There is a difference in the location of colorectal mucosal lesions and invasive cancers. AIMS: To ascertain whether the location of colorectal neoplasms reflects the carcinogenesis pathway. METHODS: The subject material consisted of 4147 neoplastic lesions that had been resected endoscopically or surgically from 5025 patients. Mucosal lesions and submucosal cancers were classified into depressed and non-depressed types endoscopically or histologically. The relations between macroscopic type, size, histology, and location were investigated. RESULTS: (a) Non-depressed type. A total of 1774 of 3454 (51%) mucosal lesions were located in the right colon, 1212 (35%) in the left colon, and 468 (14%) in the rectum. The incidence of mucosal lesions larger than 10 mm was 10% (185/1774) in the right colon, 21% (254/1212) in the left colon, and 27% (127/468) in the rectum. The incidence of mucosal lesions with villous components was 2% (32/1774) in the right colon, 5% (63/1212) in the left colon, and 13% (62/468) in the rectum. The ratio of submucosal cancers to mucosal lesions was significantly higher in the rectum (0.064, 30/469) than in the left (0.034, 43/1279) or right (0.010, 18/1857) colon. (b) Depressed type. The incidences of depressed type mucosal lesions and submucosal cancers were 5% (83/1857) and 17% (3/18) in the right colon, 5% (67/1279) and 5% (2/43) in the left colon, and 0.2% (1/469) and 0% (0/30) in the rectum, respectively. CONCLUSION: There may be some mechanisms that promote the progression of mucosal lesions to invasive cancers in the left colon and rectum, whereas a de novo pathway from depressed type lesions may be implicated in some cancers of the right colon.     

Systolic and diastolic heart failure: Different phenotypes of the same disease?

Traditional pathophysiological concepts of chronic heart failure have largely focused on the haemodynamic consequences of ventricular systolic dysfunction. How these concepts relate to the pathophysiology of diastolic heart failure, i.e., heart failure with a preserved ejection fraction is, however, unclear, causing uncertainty about pathophysiology, diagnosis and management. Recent measurements of regional myocardial systolic function in patients with diastolic heart failure indicate that systolic and diastolic heart failure may be more closely related than previously anticipated. Rather than being considered as separate diseases with a distinct pathophysiology, systolic and diastolic heart failure may be merely different clinical presentations within a phenotypic spectrum of one and the same disease. In this review, we will interpret these new insights in a broader conceptual context of chronic heart failure and design novel paradigms in which systolic and diastolic heart failure jointly progress in a pathophysiological time trajectory of only one disease.     

Visceral obesity and metabolic syndrome: two faces of the same medal?

In this review, we have analyzed the role of visceral obesity in the occurrence of metabolic syndrome (MetS). MetS is a common metabolic disorder that has been related recently to the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) should be applicable worldwide. The pathophysiology has been largely attributed, in the past years, to insulin resistance, although several epidemiological and pathophysiological data now indicate visceral obesity as a main factor in the occurrence of all the components of MetS. In view of this, relationships among visceral obesity, free fatty acids, dyslipidemia and insulin resistance have been reported. In addition, the effects of some adipocytokines and other proinflammatory factors produced by fat accumulation on the occurrence of MetS have been also emphasized. Accordingly, the “hypoadiponectinemia hypothesis” has been proposed as the most interesting to explain the pathophysiology of MetS. The epidemiologic, pathophysiologic and clinical data reported seem to indicate that MetS might be considered a fatal consequence of visceral obesity.