In this population-based study, PVT was found to be more common than indicated by previous clinical series. The markedly excess risk in cirrhosis and hepatic carcinoma should warrant an increased awareness in these patients for whom prospective studies of directed intervention might be considered.
Objective-To determine the incidence of venous thromboembolism in all necropsy reports over 30 years.Design-Study of all necropsies in one hospital in 1987 and longitudinal analysis of results of necropsy in 1957, 1964, 1975, and 1987. Setting-Departments of general surgery, infectious diseases, internal medicine, oncology, and orthopaedics in a Swedish general hospital.Main outcome measure-Number of cases of venous thromboembolism.Results 32-2% in 1987 (p<005), although there were only a few patients.Conclusions-The overall incidence of venous thromboembolism has not changed over 30 years. During this period the proportion of the population aged over 65 has doubled, and this may have masked the beneficial effects of prophylaxis and early mobilisation. Prevalences corrected for age are needed.
Early recognition and revascularization would have been a prerequisite for survival in at least half of the patients, since the jejunum, ileum, and colon were affected by infarction. A minority of all patients were under surgical care. AMI, cardiac thrombi, and synchronous emboli were common findings among patients with embolic occlusions.
Abstract. Acosta S, Ö gren M, Sternby N-H, Bergqvist D, Björck M (Malmö University Hospital, Malmö; and Uppsala University Hospital, Uppsala; Sweden). Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors. J Intern Med 2006; 259: 305-313.Objectives. To estimate the incidence and extension of visceral organ infarction, and to evaluate potential causes, in patients with autopsy-verified nonocclusive mesenteric ischaemia (NOMI) and transmural intestinal infarction. Setting. In Malmö, Sweden, the autopsy rate between 1970 and 1982 was 87%, creating possibilities for a population-based study. Design. Amongst 23 446 clinical autopsies, 997 cases were coded for intestinal ischaemia in a database. In addition, 7569 forensic autopsy protocols were analysed. In a nested case-control study within the clinical autopsy cohort, four NOMIfree controls, matched for gender, age at death and year of death, were identified for each fatal NOMI case to evaluate risk factors.Results. The overall incidence of autopsy-verified fatal NOMI was 2.0/100 000 person-years, increasing with age up to 40/100 000 personyears in octogenarians. Patients with stenosis of the superior mesenteric artery (SMA; n ¼ 25) were older (P ¼ 0.002) than those without (n ¼ 37), and had more often a concomitant stenosis of the coeliac trunk (P < 0.001). Synchronous infarction in the liver, spleen or kidney occurred in one-fifth of all patients. Fatal cardiac failure 2)], history of atrial fibrillation [OR 2.2 (1.2-4.0)] and recent surgery )] were risk factors for fatal NOMI. Conclusions. Fatal heart failure was the leading cause of intestinal hypoperfusion, although stenosis of the SMA and coeliac trunk, atrial fibrillation and recent surgery contributed significantly. Collaboration across specialties seems to be of utmost importance to improve the prognosis.
Globular inclusions of abnormal ␣1-antitrypsin (AAT)in the endoplasmic reticulum of hepatocytes are a characteristic feature of AAT deficiency of the PiZZ phenotype. Monoclonal antibodies, which contain constant specificity and affinity, are often used for the identification of Z-mutation carriers. A mouse monoclonal antibody (ATZ11) raised against PiZZ hepatocytic AAT was successfully used in enzyme-linked immunosorbent assays (ELISA) and in identification of Z-related AAT globular inclusions by immunohistochemical techniques. Using electrophoresis, Western blotting, and ELISA procedures, we have shown in the present study that this monoclonal antibody specifically detects a conformationdependent neoepitope on both polymerized and elastase-complexed molecular forms of AAT. The antibody has no apparent affinity for native, latent, or cleaved forms of AAT. The antibody ATZ11 illustrates the structural resemblance between the polymerized form of AAT and its complex with elastase and provides evidence that Z-homozygotes beyond the native form may have at least one more circulating molecular form of AAT, i.e. its polymerized form. In addition, staining of endothelial cells with ATZ11 antibody in both M-and Z-AAT individuals shows that AAT attached to endothelial cells is in a polymerized form. The antibody can be a powerful tool for the study of the molecular profile of AAT, not only in Z-deficiency cases but also in other (patho)physiological conditions.The capacity to undergo conformational changes is crucial for the physiological function of many proteins; the serine proteinase inhibitors (serpins) 1 are a clear case for such changes having been exploited during evolution as a means of modulating inhibitory activity (1). Serpins possess two structural elements that are conformationally labile and are essential for efficient proteinase inhibition: a reactive center loop and a -sheet (-sheet A) that is able to open and accommodate the reactive center loop after its cleavage by the attacking proteases (2-5). The x-ray crystal structures of native, cleaved, cleaved in complex with protease, and polymerized forms of serpins have confirmed the abilities of these proteins to undergo profound conformational changes under certain environmental conditions (6 -8). The crystal structure of the ␣1-antitrypsin-trypsin complex showed complete insertion of the reactive site loop, which substantially increases thermal and conformational stability of the serpin and results in the irreversible inhibition and then the structural destruction of the proteinase (9).The conformational changes that occur in the serpin molecule during the formation of the enzyme-serpin complexes, interaction with other molecules, polymerization, cleavage, and oxidation lead to the generation of conformation-dependent neoepitopes (10). Immunochemical analysis by means of monoclonal antibodies is a useful approach for study of the formation of new epitopes that occur as a result of the conformational polymorphism of serpins (11,12). For example, the sugge...
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