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Machado RS, Tavares FN, Sousa IP. Global landscape of coxsackieviruses in human health. Virus Res 2024; 344:199367. [PMID: 38561065 PMCID: PMC11002681 DOI: 10.1016/j.virusres.2024.199367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 04/04/2024]
Abstract
Coxsackieviruses-induced infections, particularly in infants and young children, are one of the most important public health issues in low- and middle-income countries, where the surveillance system varies substantially, and these manifestations have been disregarded. They are widespread throughout the world and are responsible for a broad spectrum of human diseases, from mildly symptomatic conditions to severe acute and chronic disorders. Coxsackieviruses (CV) have been found to have 27 identified genotypes, with overlaps in clinical phenotypes between genotypes. In this review, we present a concise overview of the most recent studies and findings of coxsackieviruses-associated disorders, along with epidemiological data that provides comprehensive details on the distribution, variability, and clinical manifestations of different CV types. We also highlight the significant roles that CV infections play in the emergence of neurodegenerative illnesses and their effects on neurocognition. The current role of CVs in oncolytic virotherapy is also mentioned. This review provides readers with a better understanding of coxsackieviruses-associated disorders and pointing the impact that CV infections can have on different organs with variable pathogenicity. A deeper knowledge of these infections could have implications in designing current surveillance and prevention strategies related to severe CVs-caused infections, as well as encourage studies to identify the emergence of more pathogenic types and the etiology of the most common and most severe disorders associated with coxsackievirus infection.
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Affiliation(s)
- Raiana S Machado
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia e Parasitologia Molecular, Rio de Janeiro, 21040-900, Brasil; Programa de Pós-Graduação em Medicina Tropical, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brasil; Laboratório de Referência Regional em Enteroviroses, Seção de Virologia, Instituto Evandro Chagas, Rodovia BR 316‑ KM 07, S/N Bairro Levilândia, Ananindeua, PA 67030000, Brasil
| | - Fernando N Tavares
- Laboratório de Referência Regional em Enteroviroses, Seção de Virologia, Instituto Evandro Chagas, Rodovia BR 316‑ KM 07, S/N Bairro Levilândia, Ananindeua, PA 67030000, Brasil
| | - Ivanildo P Sousa
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia e Parasitologia Molecular, Rio de Janeiro, 21040-900, Brasil.
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Simons-Linares CR, Imam Z, Chahal P. Viral-Attributed Acute Pancreatitis: A Systematic Review. Dig Dis Sci 2021; 66:2162-2172. [PMID: 32789532 DOI: 10.1007/s10620-020-06531-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 07/31/2020] [Indexed: 01/18/2023]
Abstract
Infectious etiologies are rare cause of acute pancreatitis (AP). We sought to investigate the frequency of viral-attributed AP (VIAP) and describe its natural course and clinical features. Comprehensive review of PubMed and EMBASE in English until December 31, 2019, was performed. AP diagnosis and severity were defined per the Revised Atlanta Classification. Viral infections were diagnosed by serology and/or histology. A diagnosis of viral infection, with a concurrent AP diagnosis, a temporal resolution of both entities, and the attempt to exclude the most common etiologies of AP defined VIAP. Two independent reviewers reviewed eligible publications. Bias risk was assessed with the Murad tool. A total of 209 cases identified in 128 publications met inclusion criteria. Mean age was 38.9 ± 1.28 years. Male-to-female ratio was 2.2:1, and 28% of patients were immunocompromised. Viral hepatitis (A, B, C, D and E) was the most common virus and accounted for 34.4% of cases, followed by coxsackie and echoviruses (14.8%), hemorrhagic fever viruses (12.4%), CMV (12.0%), VZV (10.5%), mumps and measles (3.8%), primary HIV infection (3.8%), HSV (1.9%), EBV (1.9%), and the remainder of cases (2.9%) attributed to adenovirus, influenza H1N1, and multiple viruses. Severity of AP was: 43.1% mild, 11.7% moderately severe, 32.4% severe. Death occurred in 42 (20.1%) patients. A significant portion of VIAP patients were immunocompromised (28.0%) and accounted for 71.4% of mortality cases. Mortality was higher than that reported for AP from other etiologies in the literature.
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Affiliation(s)
- C Roberto Simons-Linares
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
| | - Zaid Imam
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - Prabhleen Chahal
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
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Imam Z, Simons-Linares CR, Chahal P. Infectious causes of acute pancreatitis: A systematic review. Pancreatology 2020; 20:1312-1322. [PMID: 32938554 DOI: 10.1016/j.pan.2020.08.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/21/2020] [Accepted: 08/24/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Infectious etiologies of acute pancreatitis (AP) are rare and include viruses, bacteria, mycobacteria, parasites, and fungi. We aimed to conduct a comprehensive review on infectious etiologies of AP analyzing the frequency, clinical features, and outcomes of individuals presenting with this condition. METHODS Eligible articles reporting on AP attributed to infectious etiologies were included. A comprehensive literature search of PubMed from time of inception and until September 6,2019 was performed using all relevant MeSH (medical subject heading) keywords. Articles were assessed for eligibility and independently reviewed by two reviewers for clinical features of AP, local complications, and mortality. Methodological quality of included studies was evaluated using the Murad tool. RESULTS A total of 212 articles were included, of which 168 (79.2%) were at high risk of bias. 320 cases of AP were identified. Viruses were the leading etiology of infection attributed AP (65.3%) followed by helminths (19.1%), and bacteria (12.5%). Protozoa, mycobacteria, and fungi accounted for the remaining 3.1% of cases. Mean age was 40.5 ± 18.4 years and M:F ratio was 1.94:1. Mortality occurred in 50 patients. Mortality rate was higher in the virus attributed AP patients than AP from other infectious etiologies (21.8% vs. 7.0%, p < 0.0005). INTERPRETATION Literature quality on infection attributed AP is limited. Virus attributed AP appears to carry a higher mortality than other etiologies of infection attributed AP.
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Affiliation(s)
- Zaid Imam
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - C Roberto Simons-Linares
- Department of Gastroenterology, Hepatology, and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
| | - Prabhleen Chahal
- Department of Gastroenterology, Hepatology, and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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Gupta A, Vuan Z, Balaskas EV, Khanna R, Oreopoulos DG. CAPD and Pancreatitis: No Connection. Perit Dial Int 2020. [DOI: 10.1177/089686089201200308] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Autopsy studies have shown that approximately 56% of patients on long-term continuous ambulatory peritoneal dialysis (CAPD) develop various pancreatic abnormalities, such as acute and chronic pancreatitis, fibrosis, and acinar dilatation. This prevalence of anatomical abnormalities is similar to that observed in patients on hemodialysis and higher than that in those with normal renal function. However, clinical acute pancreatitis is an uncommon complication of CAPD (0.9%), and this prevalence is similar to that (1.7%) of patient son hemodialysis. We can attribute acute pancreatitis in CAPD patients to no single factor. Perhaps preexisting anatomical abnormalities of the pancreas make the CAPD patient susceptible to acute pancreatitis when exposed to a variety of physiological and non physiological influences. The diagnosis of acute pancreatitis in CAPD patients is difficult, because symptoms and signs are similar to those of dialysis-associated peritonitis. Serum amylase values three times greater than the upper limit of normal and effluent amylase greater than 100 U/L suggest the diagnosis of acute pancreatitis. Serum lipase, isoamylase, and pancreatic secretory trypsin inhibitor are not helpful. In confirming the diagnosis, a computed tomography (CT) scan is more helpful than ultrasound, although it is positive in only 50–60% of cases. One should harbor a high index of suspicion concerning acute pancreatitis if a CAPD patient presenting with suspected peritonitis has either a negative effluent culture or does not respond to antibiotic therapy.
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Affiliation(s)
- Amit Gupta
- Division of Nephrology, The Toronto Hospital and University of Toronto, Missouri
| | - Zheng Vuan
- Division of Nephrology, The Toronto Hospital and University of Toronto, Missouri
| | - Elias V. Balaskas
- Division of Nephrology, The Toronto Hospital and University of Toronto, Missouri
| | - Ramesh Khanna
- Division of Nephrology, University of Missouri, School of Medicine, Missouri
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Li X, Xia Y, Huang S, Liu F, Ying Y, Xu Q, Liu X, Jin G, Papasian CJ, Chen J, Fu M, Huang X. Identification of the interaction of VP1 with GM130 which may implicate in the pathogenesis of CVB3-induced acute pancreatitis. Sci Rep 2015; 5:13324. [PMID: 26314804 PMCID: PMC4551966 DOI: 10.1038/srep13324] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2015] [Accepted: 07/21/2015] [Indexed: 11/09/2022] Open
Abstract
Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, pancreatitis, and meningitis in humans. Although the susceptibility of CVB3-induced acute pancreatitis is age-dependent, the underlying mechanisms remain unclear. Here we identified the host factor Golgi matrix protein 130 (GM130) as a novel target of CVB3 during CVB3-induced acute pancreatitis. The viral protein VP1 interacted with GM130, disrupted GM130-GRASP65 complexes, and caused GM130 degradation, which may lead to disruption of the Golgi ribbon and development of acute pancreatitis in mice. Interestingly, the expression level of GM130 in mouse pancreas was age-dependent, which was nicely correlated with the age-associated susceptibility of CVB3-induced acute pancreatitis. Furthermore, interference RNA-mediated knockdown of GM130 significantly reduced CVB3 replication in HeLa cells. Taken together, the study identified GM130 as a novel target of CVB3, which may implicate in the pathogenesis of CVB3-induced acute pancreatitis.
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Affiliation(s)
- Xiuzhen Li
- Department of Medical Microbiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China
| | - Yanhua Xia
- Department of Medical Microbiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China
| | - Shengping Huang
- Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO, USA
| | - Fadi Liu
- Children’s Hospital of Jiangxi Province, Nanchang, Jiangxi, China
| | - Ying Ying
- Department of Pathophysiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China
| | - Qiufang Xu
- Shanghai Qingpu Center for Disease Control and Prevention, Shanghai, China
| | - Xin Liu
- Children’s Hospital of Jiangxi Province, Nanchang, Jiangxi, China
| | - Guili Jin
- The affiliated hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China
| | - Christopher J. Papasian
- Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO, USA
| | - Jack Chen
- Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK, USA
| | - Mingui Fu
- Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO, USA
| | - Xiaotian Huang
- Department of Medical Microbiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China
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Yang L, He D, Tang M, Li Z, Liu C, Xu L, Chen Y, Du H, Zhao Q, Zhang J, Cheng T, Xia N. Development of an enzyme-linked immunosorbent spot assay to measure serum-neutralizing antibodies against coxsackievirus B3. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2014; 21:312-20. [PMID: 24391137 PMCID: PMC3957675 DOI: 10.1128/cvi.00359-13] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 12/23/2013] [Indexed: 11/20/2022]
Abstract
Coxsackievirus B3 (CVB3) is the most common pathogen that induces acute and chronic viral myocarditis in children. The cytopathic effect (CPE)-based neutralization test (Nt-CPE) and the plaque reduction neutralization test (PRNT) are the most common methods for measuring neutralizing antibody titers against CVB3 in blood serum samples. However, these two methods are inefficient for CVB3 vaccine clinical trials, which require the testing of a large number of serum specimens. In this study, we developed an efficient neutralization test based on the enzyme-linked immunospot (Nt-ELISPOT) assay for measuring CVB3-neutralizing antibodies. This modified ELISPOT assay was based on the use of a monoclonal antibody against the viral capsid protein VP1 to detect the cells that are infected with CVB3, which, after immunoperoxidase staining, are counted as spots using an automated ELISPOT analyzer. Using the modified ELISPOT assay, we characterized the infection kinetics of CVB3 and divided the infection process of CVB3 on a cluster of cells into four phases. The stability of the Nt-ELISPOT was then evaluated. We found that over a wide range of infectious doses (10(2) to 10(6.5)× 50% tissue culture infectious dose [TCID(50)] per well), the neutralizing titers of the sera were steady as long as they were tested during the log phase or the first half of the stationary phase of growth of the spots. We successfully shortened the testing period from 7 days to approximately 20 h. We also found that there was a good correlation (R(2) = 0.9462) between the Nt-ELISPOT and the Nt-CPE assays. Overall, the Nt-ELISPOT assay is a reliable and efficient method for measuring neutralizing antibodies in serum.
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Schreiber J, Langhorst H, Jüttner R, Rathjen FG. The IgCAMs CAR, BT-IgSF, and CLMP: Structure, Function, and Diseases. ADVANCES IN NEUROBIOLOGY 2014; 8:21-45. [DOI: 10.1007/978-1-4614-8090-7_2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Souii A, M’hadheb-Gharbi MB, Sargueil B, Brossard A, Chamond N, Aouni M, Gharbi J. Ribosomal Initiation Complex Assembly within the Wild-Strain of Coxsackievirus B3 and Live-Attenuated Sabin3-like IRESes during the Initiation of Translation. Int J Mol Sci 2013; 14:4400-4418. [PMID: 23439549 PMCID: PMC3634407 DOI: 10.3390/ijms14034400] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Revised: 02/16/2013] [Accepted: 02/19/2013] [Indexed: 12/18/2022] Open
Abstract
Coxsackievirus B3 (CVB3) is an enterovirus of the family of Picornaviridae. The Group B coxsackieviruses include six serotypes (B1 to B6) that cause a variety of human diseases, including myocarditis, meningitis, and diabetes. Among the group B, the B3 strain is mostly studied for its cardiovirulence and its ability to cause acute and persistent infections. Translation initiation of CVB3 RNA has been shown to be mediated by a highly ordered structure of the 5'-untranslated region (5'UTR), which harbors an internal ribosome entry site (IRES). Translation initiation is a complex process in which initiator tRNA, 40S and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the initiation codon of the mRNA. We have previously addressed the question of whether the attenuating mutations of domain V of the poliovirus IRES were specific for a given genomic context or whether they could be transposed and extrapolated to a genomic related virus, i.e., CVB3 wild-type strain. In this context, we have described that Sabin3-like mutation (U473→C) introduced in CVB3 genome led to a defective mutant with a serious reduction in translation efficiency. In this study, we analyzed the efficiency of formation of ribosomal initiation complexes 48S and 80S through 10%-30% and 10%-50% sucrose gradients using rabbit reticulocyte lysates (RRLs) and stage-specific translation inhibitors: 5'-Guanylyl-imidodiphosphate (GMP-PNP) and Cycloheximide (CHX), respectively. We demonstrated that the interaction of 48S and 80S ribosomal complexes within the mutant CVB3 RNA was abolished compared with the wild-type RNA by ribosome assembly analysis. Taken together, it is possible that the mutant RNA was unable to interact with some trans-acting factors critical for enhanced IRES function.
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Affiliation(s)
- Amira Souii
- Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives (LR99-ES27), Faculté de Pharmacie de Monastir, Avenue Avicenne, Monastir 5000, Tunisia; E-Mails: (M.B.M.-G.); (M.A.); (J.G.)
| | - Manel Ben M’hadheb-Gharbi
- Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives (LR99-ES27), Faculté de Pharmacie de Monastir, Avenue Avicenne, Monastir 5000, Tunisia; E-Mails: (M.B.M.-G.); (M.A.); (J.G.)
- Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Avenue Tahar Hadded, BP 74, Monastir 5000, Tunisia
| | - Bruno Sargueil
- Laboratoire de Cristallographie et RMN Biologiques (UMR 8015), Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l’Observatoire, Paris 75270 Cedex 06, France; E-Mails: (B.S.); (A.B.); (N.C.)
| | - Audrey Brossard
- Laboratoire de Cristallographie et RMN Biologiques (UMR 8015), Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l’Observatoire, Paris 75270 Cedex 06, France; E-Mails: (B.S.); (A.B.); (N.C.)
| | - Nathalie Chamond
- Laboratoire de Cristallographie et RMN Biologiques (UMR 8015), Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l’Observatoire, Paris 75270 Cedex 06, France; E-Mails: (B.S.); (A.B.); (N.C.)
| | - Mahjoub Aouni
- Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives (LR99-ES27), Faculté de Pharmacie de Monastir, Avenue Avicenne, Monastir 5000, Tunisia; E-Mails: (M.B.M.-G.); (M.A.); (J.G.)
| | - Jawhar Gharbi
- Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives (LR99-ES27), Faculté de Pharmacie de Monastir, Avenue Avicenne, Monastir 5000, Tunisia; E-Mails: (M.B.M.-G.); (M.A.); (J.G.)
- Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Avenue Tahar Hadded, BP 74, Monastir 5000, Tunisia
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Abstract
OBJECTIVES Alcohol abuse is one of the most common factors associated with acute and chronic pancreatitis. Although it is evident that alcohol abuse can have an important role in the development of pancreatitis, it does not seem that alcohol abuse alone is responsible for this disease. We investigated the involvement of ethanol in the impairment of pancreatic repair after induction of pancreatitis. METHODS A biologically relevant mouse model of alcoholic pancreatitis, combining long-term ethanol consumption and coxsackievirus infection, was used to investigate the effects of ethanol on pancreatic regeneration. Tissues were harvested and analyzed by reverse transcription-polymerase chain reaction and immunoblot. RESULTS These studies demonstrate that long-term ethanol consumption impairs the structural repair of the exocrine pancreas. This is accompanied by a delay in the restitution of lipase expression. In addition, impaired expression of the critical pancreatic transcription factors, PDX1 and PTF1, and the mediator of Notch signaling, HES1, was observed. CONCLUSIONS Long-term ethanol consumption impairs the structural repair and functional restitution of the pancreas after severe injury. These impairments may, in part, be explained by the impaired expression of factors important in the development and maintenance of the exocrine pancreas. Impaired pancreatic regeneration may have a role in the pathogenesis of alcoholic pancreatitis.
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Affiliation(s)
| | - Marc Scheer
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
| | - Mallory Suhr
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
| | - Dahn L. Clemens
- Nebraska and Western Iowa Veterans Administration Medical Center, Omaha, Nebraska 68105,Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105,Corresponding Author: Dahn L. Clemens, PhD., Associate Professor Department of Internal Medicine, University of Nebraska Medical Center, Omaha Nebraska 68198-8098, (402) 995-3738,
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Lucas-Herald A, Jamieson N, Roxburgh C. A case of acute pancreatitis: could this be caused by dermal filler injections? J Surg Case Rep 2012; 2012:5. [PMID: 24960763 PMCID: PMC3649574 DOI: 10.1093/jscr/2012.8.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The use of dermal fillers is increasingly common. Side effects associated with their use are usually limited to local reactions. Acute pancreatitis is also a common condition with a wide range of aetiologies. To date, no potential associations between acute pancreatitis and dermal filler injections have been reported. A 58-year-old lady was admitted with an acute onset of epigastric pain and vomiting. She was diagnosed with acute severe pancreatitis. No cause could be found for her pancreatitis. She did, however, have dermal filler injection 24 hours previous to her initial symptoms. Causality is difficult to prove beyond doubt in the present isolated case report. However, given the exponential rise in accessible and affordable cosmetic procedures such as dermal filler injections such case reporting is necessary to establish whether such associations truly exist and to examine underlying mechanisms.
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Affiliation(s)
| | - Nb Jamieson
- Department of Academic Surgery, University of Glasgow, UK
| | - Cs Roxburgh
- Department of Academic Surgery, University of Glasgow, UK
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12
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Pönkä A, Kosunen TU. Pancreas affection in association with enteritis due to Campylobacter fetus ssp. jejuni. ACTA MEDICA SCANDINAVICA 2009; 209:239-40. [PMID: 7223520 DOI: 10.1111/j.0954-6820.1981.tb11584.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
A woman with pancreas affection during diarrhoea due to Campylobacter fetus ssp. jejuni is presented. The patient recovered within 8 days without specific treatment. In addition, 5 other cases with pancreas affection associated with Campylobacter infection are cited.
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Hunziker IP, Cornell CT, Whitton JL. Deletions within the 5'UTR of coxsackievirus B3: consequences for virus translation and replication. Virology 2006; 360:120-8. [PMID: 17084431 PMCID: PMC2190293 DOI: 10.1016/j.virol.2006.09.041] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2006] [Revised: 09/12/2006] [Accepted: 09/22/2006] [Indexed: 10/23/2022]
Abstract
Key features of an ideal RNA-based vaccine against coxsackievirus B3 (CVB3) are (i) limited genome replication/virus production (to minimize vaccine-related pathology) and (ii) abundant virus protein synthesis (to maximize immunogenicity). These attributes may apply to CVB3 RNAs lacking up to 250 nucleotides (nt) from their 5' terminus; these RNAs do not give rise to infectious progeny, but they have been reported to retain the entire CVB3 IRES (mapped to nt approximately 432-639) and to produce large quantities of viral protein in transfected cells. Here, we constructed five 5' RNA deletion variants that, to our surprise, failed to protect against CVB3 challenge. We investigated the reasons for this failure and conclude that (i) a 5' terminal deletion as short as 32 nt abolishes CVB3 RNA replication in transfected cells; (ii) this deleted RNA, and others with longer deletions, do not direct abundant protein synthesis in transfected cells, probably as a consequence of their replicative incapacity; and (iii) the CVB3 IRES is substantially larger than previously thought, and its 5' boundary lies between residues 76 and 125, very closely approximating that of the poliovirus IRES.
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Affiliation(s)
| | | | - J. Lindsay Whitton
- Corresponding author: Molecular and Integrative Neurosciences Department, SP30-2110, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA, Tel: 858-784-7090, FAX: 858-784-7380,
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Tracy S, Chapman NM, Drescher KM, Kono K, Tapprich W. Evolution of virulence in picornaviruses. Curr Top Microbiol Immunol 2006; 299:193-209. [PMID: 16568900 DOI: 10.1007/3-540-26397-7_7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The Picornaviridae encompass many positive-strand RNA viruses, all of which share a generally similar genome design and capsid structure, but which induce quite diverse diseases in humans and other animals. Picornavirus strains of the same serotype have been shown to express different virulence (or pathogenic) phenotypes when studied in animal models, demonstrating that key elements of pathogenesis reside in the viral genome. However, the genetics that determine the virulence phenotype of any picornavirus are poorly understood. Picornaviruses do not have virulence genes per se, but the design ofthe capsid andhow it interacts with the virus receptor expressed on the host cell surface, specific sequences within the nontranslated regions of the viral genome, as well as coding sequences that result in different protein sequences may all have a part in determining the virulence phenotype. Virulence may be better understood as a continuum from an apparent inability to induce disease to the ability to cause severe pathogenic changes. Ultimately, the ability of a picornavirus to induce disease depends upon viral genetics and how they are modulated by the host environment.
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Affiliation(s)
- S Tracy
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-6495, USA.
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Hegyi P, Ordog B, Rakonczai Z, Takács T, Lonovics J, Szabolcs A, Sári R, Tóth A, Papp JG, Varró A, Kovács MK, Gray MA, Argent BE, Boldogköi Z. Effect of herpesvirus infection on pancreatic duct cell secretion. World J Gastroenterol 2005; 11:5997-6002. [PMID: 16273613 PMCID: PMC4436723 DOI: 10.3748/wjg.v11.i38.5997] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2004] [Revised: 02/13/2005] [Accepted: 02/18/2005] [Indexed: 02/06/2023] Open
Abstract
AIM To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion. METHODS The virulent Ba-DupGreen (BDG) and non-virulent Ka-RREp0lacgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/interlobular ducts were infected with BDG virus (10(7) PFU/mL for 6 h) or with KEG virus (10(10) PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h. The rate of HCO(3)(-) secretion (base efflux -J(B-)) was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4-diisothiocyanatostilbene-2,2-disulfonic acid (500 micromol/L) and amiloride (200 micromol/L), and (2) after alkali loading the ducts by exposure to NH(4)Cl. All the experiments were performed in HCO(3)(-)-buffered Ringer solution at 37 degrees (n = 5 ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virally-encoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope. RESULTS The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral antigens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -J(B-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -J(B-). After alkali loading the ducts, -J(B-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group. CONCLUSION Incubation with the BDG or KEG strains of PRV results in an effective infection of ductal epithelial cells. The BDG strain of PRV, which is able to initiate a lytic viral cycle, stimulates HCO(3)(-) secretion in guinea pig pancreatic duct by about four- to fivefold, 24 h after the infection. However, the KEG strain of PRV, which can infect, but fails to replicate, has no effect on HCO(3)(-) secretion. We suggest that this response of pancreatic ducts to virulent PRV infection may represent a defense mechanism against invasive pathogens to avoid pancreatic injury.
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Affiliation(s)
- Péter Hegyi
- Department of Biology, Faculty of Medicine, University of Szeged, Somogyi Bela str. 4, H-6720 Szeged, Hungary
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Hunziker IP, Harkins S, Feuer R, Cornell CT, Whitton JL. Generation and analysis of an RNA vaccine that protects against coxsackievirus B3 challenge. Virology 2005; 330:196-208. [PMID: 15527846 DOI: 10.1016/j.virol.2004.09.035] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2004] [Accepted: 09/26/2004] [Indexed: 01/25/2023]
Abstract
Coxsackievirus B3 (CVB3) is an important human pathogen that causes substantial morbidity and mortality but, to date, no vaccine is available. We have generated an RNA-based vaccine against CVB3 and have evaluated it in the murine model of infection. The vaccine was designed to allow production of the viral polyprotein, which should be cleaved to generate most of the viral proteins in their mature form; but infectious virus should not be produced. In vitro translation studies indicated that the mutant polyprotein was efficiently translated and was processed as expected. The mutant RNA was not amplified in transfected cells, and infectious particles were not produced. Furthermore, the candidate RNA vaccine appeared safe in vivo, causing no detectable pathology following injection. Finally, despite failing to induce detectable neutralizing antibodies, the candidate RNA vaccine conferred substantial protection against virus challenge, either with an attenuated recombinant CVB3, or with the highly pathogenic wt virus.
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Affiliation(s)
- Isabelle P Hunziker
- Department of Neuropharmacology, CVN-9, The Scripps Research Institute, La Jolla, CA 92037, USA
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17
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Reimund JM, Muller CD, Finck G, Escalin G, Duclos B, Baumann R. Factors contributing to infectious diarrhea-associated pancreatic enzyme alterations. ACTA ACUST UNITED AC 2005; 29:247-53. [PMID: 15864174 DOI: 10.1016/s0399-8320(05)80757-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
OBJECTIVES Several pathogens have been involved as etiologic agents of acute pancreatitis. We studied 59 patients presenting acute infectious diarrhea in order to determine the incidence as well as to identify factors which may contribute to the occurrence of pancreatic enzyme alteration or true acute pancreatitis. METHODS Patients were evaluated for serum lipase and amylase, and 24-hours urinary amylase. Clinical and biological parameters were noted. Abdominal sonography and rectosigmoidoscopy were performed. RESULTS Pancreatic enzyme alteration was found in 24% of patients. Twelve had salmonellosis and 2 Campylobacter jejuni infection. They had more prolonged diarrhea, more frequent renal impairment and increased triglyceridemia. Triglyceridemia was correlated to blood amylase, inflammatory syndrome and renal impairment. Serum amylase was linked to serum urea and creatinine and to biological markers of inflammation. Three patients had true acute pancreatitis. CONCLUSION Patients presenting dysentery-like infectious diarrhea and upper abdominal pain should be investigated for concomitant pancreatic reaction or acute pancreatitis which seems more frequent in patients with enterocolitis due to enteroinvasive microbes, mostly non-typhoidal Salmonella. Pancreatic disturbances are related to the severity of these infections. However, overt infectious diarrhea-associated pancreatitis is a rare event.
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Affiliation(s)
- Jean-Marie Reimund
- Service d'Hépato-Gastroentérologie et d'Assistance Nutritive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg Cedex.
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Lee CK, Kono K, Haas E, Kim KS, Drescher KM, Chapman NM, Tracy S. Characterization of an infectious cDNA copy of the genome of a naturally occurring, avirulent coxsackievirus B3 clinical isolate. J Gen Virol 2005; 86:197-210. [PMID: 15604447 DOI: 10.1099/vir.0.80424-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Group B coxsackieviruses (CVB) cause numerous diseases, including myocarditis, pancreatitis, aseptic meningitis and possibly type 1 diabetes. To date, infectious cDNA copies of CVB type 3 (CVB3) genomes have all been derived from pathogenic virus strains. An infectious cDNA copy of the well-characterized, non-pathogenic CVB3 strain GA genome was cloned in order to facilitate mapping of the CVB genes that influence expression of a virulence phenotype. Comparison of the sequence of the parental CVB3/GA population, derived by direct RT-PCR-mediated sequence analysis, to that of the infectious CVB3/GA progeny genome demonstrated that an authentic copy was cloned; numerous differences were observed in coding and non-coding sequences relative to other CVB3 strains. Progeny CVB3/GA replicated similarly to the parental strain in three different cell cultures and was avirulent when inoculated into mice, causing neither pancreatitis nor myocarditis. Inoculation of mice with CVB3/GA protected mice completely against myocarditis and pancreatitis induced by cardiovirulent CVB3 challenge. The secondary structure predicted for the CVB3/GA domain II, a region within the 5′ non-translated region that is implicated as a key site affecting the expression of a cardiovirulent phenotype, differs from those predicted for cardiovirulent and pancreovirulent CVB3 strains. This is the first report characterizing a cloned CVB3 genome from an avirulent strain.
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Affiliation(s)
- C-K Lee
- Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA
| | - K Kono
- Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA
| | - E Haas
- Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA
| | - K-S Kim
- Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA
| | - K M Drescher
- Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA
| | - N M Chapman
- Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA
| | - S Tracy
- Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA
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Drescher KM, Kono K, Bopegamage S, Carson SD, Tracy S. Coxsackievirus B3 infection and type 1 diabetes development in NOD mice: insulitis determines susceptibility of pancreatic islets to virus infection. Virology 2004; 329:381-94. [PMID: 15518817 DOI: 10.1016/j.virol.2004.06.049] [Citation(s) in RCA: 99] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2004] [Revised: 04/17/2004] [Accepted: 06/03/2004] [Indexed: 11/29/2022]
Abstract
Group B coxsackieviruses (CVB) are believed to trigger some cases of human type 1 diabetes (T1D), although the mechanism by which this may occur has not been shown. We demonstrated previously that inoculation of young nonobese diabetic (NOD) mice with any of several different CVB strains reduced T1D incidence. We also observed no evidence of CVB replication within islets of young NOD mice, suggesting no role for CVB in T1D induction in the NOD mouse model. The failure to observe CVB replication within islets of young NOD mice has been proposed to be due to interferon expression by insulin-producing beta cells or lack of expression of the CVB receptor CAR. We found that CAR protein is detectable within islets of young and older NOD mice and that a CVB3 strain, which expresses murine IL-4, can replicate in islets. Mice inoculated with the IL-4 expressing CVB3 chimeric strain were better protected from T1D onset than were mock-infected control mice despite intraislet viral replication. Having demonstrated that CVB can replicate in healthy islets of young NOD mice when the intraislet environment is suitably altered, we asked whether islets in old prediabetic mice were resistant to CVB infection. Unlike young mice in which insulitis is not yet apparent, older NOD mice demonstrate severe insulitis in all islets. Inoculating older prediabetic mice with different pathogenic CVB strains caused accelerated T1D onset relative to control mice, a phenomenon that was preceded by detection of virus within islets. Together, the results suggest a model for resolving conflicting data regarding the role of CVB in human T1D etiology.
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MESH Headings
- Age Factors
- Animals
- Cell Line, Tumor
- Coxsackie and Adenovirus Receptor-Like Membrane Protein
- Coxsackievirus Infections/complications
- Coxsackievirus Infections/virology
- Diabetes Mellitus, Experimental/etiology
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Experimental/prevention & control
- Diabetes Mellitus, Type 1/etiology
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Type 1/prevention & control
- Disease Models, Animal
- Enterovirus B, Human/genetics
- Enterovirus B, Human/metabolism
- Female
- Humans
- Interferons/biosynthesis
- Interleukin-4/biosynthesis
- Interleukin-4/genetics
- Interleukin-4/therapeutic use
- Islets of Langerhans/metabolism
- Islets of Langerhans/virology
- Mice
- Mice, Inbred NOD
- Receptors, Virus/biosynthesis
- Receptors, Virus/genetics
- Transfection
- Virulence
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Affiliation(s)
- Kristen M Drescher
- Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178, USA
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20
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Tracy S, Drescher KM, Chapman NM, Kim KS, Carson SD, Pirruccello S, Lane PH, Romero JR, Leser JS. Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence. J Virol 2002; 76:12097-111. [PMID: 12414951 PMCID: PMC136885 DOI: 10.1128/jvi.76.23.12097-12111.2002] [Citation(s) in RCA: 129] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2002] [Accepted: 08/21/2002] [Indexed: 01/28/2023] Open
Abstract
Insulin-dependent (type 1) diabetes mellitus (T1D) onset is mediated by individual human genetics as well as undefined environmental influences such as viral infections. The group B coxsackieviruses (CVB) are commonly named as putative T1D-inducing agents. We studied CVB replication in nonobese diabetic (NOD) mice to assess how infection by diverse CVB strains affected T1D incidence in a model of human T1D. Inoculation of 4- or 8-week-old NOD mice with any of nine different CVB strains significantly reduced the incidence of T1D by 2- to 10-fold over a 10-month period relative to T1D incidences in mock-infected control mice. Greater protection was conferred by more-pathogenic CVB strains relative to less-virulent or avirulent strains. Two CVB3 strains were employed to further explore the relationship of CVB virulence phenotypes to T1D onset and incidence: a pathogenic strain (CVB3/M) and a nonvirulent strain (CVB3/GA). CVB3/M replicated to four- to fivefold-higher titers than CVB3/GA in the pancreas and induced widespread pancreatitis, whereas CVB3/GA induced no pancreatitis. Apoptotic nuclei were detected by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay in CVB3/M-infected pancreata but not in CVB3/GA-infected pancreata. In situ hybridization detected CVB3 RNA in acinar tissue but not in pancreatic islets. Although islets demonstrated inflammatory infiltrates in CVB3-protected mice, insulin remained detectable by immunohistochemistry in these islets but not in those from diabetic mice. Enzyme-linked immunosorbent assay-based examination of murine sera for immunoglobulin G1 (IgG1) and IgG2a immunoreactivity against diabetic autoantigens insulin and HSP60 revealed no statistically significant relationship between CVB3-protected mice or diabetic mice and specific autoimmunity. However, when pooled sera from CVB3/M-protected mice were used to probe a Western blot of pancreatic proteins, numerous proteins were detected, whereas only one band was detected by sera from CVB3/GA-protected mice. No proteins were detected by sera from diabetic or normal mice. Cumulatively, these data do not support the hypothesis that CVB are causative agents of T1D. To the contrary, CVB infections provide significant protection from T1D onset in NOD mice. Possible mechanisms by which this virus-induced protection may occur are discussed.
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Affiliation(s)
- S Tracy
- Enterovirus Research Laboratory, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
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21
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22
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Abstract
Acute pancreatitis has multiple causes, an unpredictable course, and myriad complications. The diagnosis relies on a combination of history, physical examination, serologic markers, and radiologic findings. The mainstay of therapy includes aggressive hydration, maintenance of NPO, and adequate analgesia with narcotics. Antibiotic and nutritional support with total parenteral nutrition should be used when appropriate.
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Affiliation(s)
- J Vlodov
- Division of Gastroenterology, Maimonides Medical Center, Brooklyn, New York 11219, USA
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23
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Tracy S, H�fling K, Pirruccello S, Lane PH, Reyna SM, Gauntt CJ. Group B coxsackievirus myocarditis and pancreatitis: Connection between viral virulence phenotypes in mice. J Med Virol 2000. [DOI: 10.1002/1096-9071(200009)62:1%3c70::aid-jmv11%3e3.0.co;2-r] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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24
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Tracy S, Höfling K, Pirruccello S, Lane PH, Reyna SM, Gauntt CJ. Group B coxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypes in mice. J Med Virol 2000; 62:70-81. [PMID: 10935991 DOI: 10.1002/1096-9071(200009)62:1<70::aid-jmv11>3.0.co;2-r] [Citation(s) in RCA: 106] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The group B coxsackieviruses (CVB) induce experimental pancreatitis and myocarditis in mice and are established agents of human myocarditis, especially in children. We tested the hypothesis that the development of CVB-induced myocarditis is linked to CVB-induced pancreatitis by studying the replication of different CVB strains in mice. Eight of nine genotypically different type 3 CVB (CVB3) strains induced acute pancreatitis in mice; of these, three viruses also induced acute myocarditis. One CVB3 strain was avirulent for both organs. Myocarditis was not observed in the absence of pancreatitis. The results obtained by inoculation of mice with strains of other CVB serotypes were consistent with these data. Infectious virus titers were measured in serum, pancreas, and heart as a function of time after inoculation of mice with three CVB3 strains. Each strain was representative of one of the three viral virulence phenotypes: avirulent, pancreovirulent only, and cardiovirulent. All strains replicated well and persisted in the pancreas through 8 days post-inoculation, but the cardiovirulent CVB3 strain tended to replicate to higher titer earlier and persist longer in sera, pancreatic, and cardiac tissues than the noncardiovirulent strains. Replication of the CVB3 strains were studied in two human pancreatic tumor lines and in primary human endothelial cell cultures derived from cardiac artery. Cardiovirulent strains, both individually and as a group, tended to replicate to titers as high as, or higher than, noncardiovirulent strains did in cell culture. The data are consistent with the possibility of an etiologic link between CVB-induced pancreatic and heart disease.
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Affiliation(s)
- S Tracy
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-6495, USA.
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25
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26
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Bergelson JM, Krithivas A, Celi L, Droguett G, Horwitz MS, Wickham T, Crowell RL, Finberg RW. The murine CAR homolog is a receptor for coxsackie B viruses and adenoviruses. J Virol 1998; 72:415-9. [PMID: 9420240 PMCID: PMC109389 DOI: 10.1128/jvi.72.1.415-419.1998] [Citation(s) in RCA: 273] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Complementary DNA clones encoding the murine homolog (mCAR) of the human coxsackievirus and adenovirus receptor (CAR) were isolated. Nonpermissive CHO cells transfected with mCAR cDNA became susceptible to infection by coxsackieviruses B3 and B4 and showed increased susceptibility to adenovirus-mediated gene transfer. These results indicate that the same receptor is responsible for virus interactions with both murine and human cells. Analysis of receptor expression in human and murine tissues should be useful in defining factors governing virus tropism in vivo.
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Affiliation(s)
- J M Bergelson
- Division of Infectious Diseases, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
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27
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Andersson R, Deng XM, Wang XD. Role of macrophage overactivation in the development of acute pancreatic injury in rats. Br J Surg 1997; 84:775-780. [PMID: 9189083 DOI: 10.1002/bjs.1800840610] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND An increase in systemic inflammatory mediators from stimulated leucocytes and macrophages has been noted during acute pancreatitis. The role of cytolytic inflammatory macrophages and potential mechanisms in the development of acute pancreatic injury and endothelial barrier dysfunction are less well defined. METHODS Rats were challenged by an intraperitoneal injection of cytolytic or non-cytolytic inflammatory macrophage stimulators at various concentrations. The effects of oxygen free radicals, prostaglandin and extracellular calcium influx on macrophage-associated pancreatic endothelial compromise, measured by pancreatic intravascular plasma volume, pancreatic interstitial fluid volume, and the pancreatic extravascular human serum albumin distribution volume, were explored. RESULTS Zymosan-induced overactivation of cytolytic inflammatory macrophages resulted in the development of acute pancreatic endothelial dysfunction in a dose- and time-dependent pattern. An increase in pancreatic water content and interstitial fluid volume was observed following a higher dose (0.5 mg/g) of concanavalin A without alteration in plasma lipase level, while thioglycollate medium did not compromise pancreatic endothelial barrier function. Oxygen free radicals, but also prostaglandins and extracellular calcium influx, seemed to be involved in macrophage overactivation-induced pancreatic injury. CONCLUSION Overactivation of cytolytic macrophages plays a role in the pathogenesis of pancreatic injury by initiating the development of endothelial barrier dysfunction. Multiple inflammatory mediators from overactivated macrophages act as intercellular signals between macrophages and the endothelium during acute pancreatic injury.
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Affiliation(s)
- R Andersson
- Department of Surgery, Lund University Hospital, Sweden
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28
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Andersson R, Deng XM, Wang XD. Role of macrophage overactivation in the development of acute pancreatic injury in rats. Br J Surg 1997. [DOI: 10.1046/j.1365-2168.1997.02794.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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29
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Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997; 275:1320-3. [PMID: 9036860 DOI: 10.1126/science.275.5304.1320] [Citation(s) in RCA: 2313] [Impact Index Per Article: 82.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
A complementary DNA clone has been isolated that encodes a coxsackievirus and adenovirus receptor (CAR). When transfected with CAR complementary DNA, nonpermissive hamster cells became susceptible to coxsackie B virus attachment and infection. Furthermore, consistent with previous studies demonstrating that adenovirus infection depends on attachment of a viral fiber to the target cell, CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and showed a 100-fold increase in susceptibility to virus-mediated gene transfer. Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.
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MESH Headings
- Adenoviruses, Human/genetics
- Adenoviruses, Human/metabolism
- Adenoviruses, Human/physiology
- Amino Acid Sequence
- Animals
- CHO Cells
- Coxsackie and Adenovirus Receptor-Like Membrane Protein
- Cricetinae
- Cytopathogenic Effect, Viral
- Enterovirus B, Human/metabolism
- Enterovirus B, Human/physiology
- Gene Transfer Techniques
- Genetic Vectors
- HeLa Cells
- Humans
- Molecular Sequence Data
- Receptors, Virus/chemistry
- Receptors, Virus/genetics
- Receptors, Virus/isolation & purification
- Receptors, Virus/metabolism
- Sequence Alignment
- Transfection
- Virus Replication
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Affiliation(s)
- J M Bergelson
- Division of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
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Affiliation(s)
- W Steinberg
- Department of Medicine, George Washington University Medical Center, Washington, DC 20037
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31
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Ozsvár Z, Deák J, Pap A. Possible role of Coxsackie-B virus infection in pancreatitis. INTERNATIONAL JOURNAL OF PANCREATOLOGY : OFFICIAL JOURNAL OF THE INTERNATIONAL ASSOCIATION OF PANCREATOLOGY 1992; 11:105-8. [PMID: 1318913 DOI: 10.1007/bf02925981] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Coxsackie-B antibodies were examined in a study of 118 patients with acute and relapsing chronic pancreatitis. The rise in antibody titers was significant in 40 cases. Fourteen had acute, five relapsing acute, and 21 chronic pancreatitis. Among patients with acute pancreatitis, we detected infectious hepatitis in six cases. Two patients with persisting acute pancreatitis received levamisole as an immune adjuvant, which promoted their recovery. It seems that Coxsackie-B virus can cause acute pancreatitis, and it can also worsen chronic pancreatitis.
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Affiliation(s)
- Z Ozsvár
- Municipal Hospital of Szeged, Department of Infectious Disease, Hungary
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32
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Lászik ZG, Kallajoki M, Hyypiä T, Rima B, Aho HJ, Nevalainen TJ. Mumps, enteroviruses, and human acute pancreatitis. Scand J Gastroenterol 1990; 25:906-10. [PMID: 2171134 DOI: 10.3109/00365529008997611] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The presence of mumps virus and enterovirus RNA was studied by in situ hybridization in 15 surgical biopsy specimens from patients with acute pancreatitis. 35S-Labeled cRNA probes, detecting the 5' end of the poliovirus type 3, a 1.1-kb fragment of the polymerase gene region of coxsackievirus B3, and mumps virus mRNA, encoding the nucleocapsid protein, were used. The controls consisted of mumps virus-infected and uninfected cultured cells, normal human and mouse pancreatic tissue, and mouse tissue from experimental coxsackievirus B3-induced pancreatitis. No specific hybridization signal was observed in any of the acute pancreatitis cases. It is concluded that neither mumps virus nor enteroviruses tested were present in pancreatic tissue of advanced human acute pancreatitis.
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Affiliation(s)
- Z G Lászik
- Dept. of Pathology, University of Turku, Finland
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33
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Abstract
Full functional and morphologic restitution of the pancreas is possible after an attack of acute pancreatitis if the initiating agent or process is removed, whereas chronic pancreatitis is associated with irreversible changes. Most attacks of acute pancreatitis are related to biliary tract stone disease, and it is likely that the offending stone causes obstruction of the pancreatic duct with ductal hypertension. Some recent experimental observations suggest that acute pancreatitis may involve intra-acinar cell activation of digestive enzymes by lysosomal hydrolases. Most patients with chronic pancreatitis develop their disease after many years of ethanol abuse, but the events underlying the pathogenesis of chronic pancreatitis are not known.
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Affiliation(s)
- M L Steer
- Harvard Medical School, Boston, Massachusetts
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34
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Kirschner S, Raufman JP. Varicella pancreatitis complicated by pancreatic pseudocyst and duodenal obstruction. Dig Dis Sci 1988; 33:1192-5. [PMID: 3409805 DOI: 10.1007/bf01535799] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Several viral infections, including mumps, coxsackie B, and infectious mononucleosis, have been associated with acute pancreatitis; however, varicella infection has not previously been associated with this complication. A 29-year-old man was admitted to the hospital with severe abdominal pain and hyperamylasemia several days following the onset of a characteristic varicella skin rash. His son had been diagnosed with varicella one week earlier. The hospital course was complicated by the development of pseudocysts in the head and tail of the pancreas which caused partial obstruction of the common bile duct and duodenum. The pancreatitis, pseudocysts, and duodenal obstruction resolved with conservative medical management. This is the first report of acute pancreatitis associated with varicella infection.
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Affiliation(s)
- S Kirschner
- Department of Medicine, State University of New York-Health Science Center, Brooklyn 11203
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Alexander JA, Demetrius AJ, Gavaler JS, Makowka L, Starzl TE, Van Thiel DH. Pancreatitis following liver transplantation. Transplantation 1988; 45:1062-5. [PMID: 2454520 PMCID: PMC3035837 DOI: 10.1097/00007890-198806000-00012] [Citation(s) in RCA: 30] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.
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Affiliation(s)
- J A Alexander
- University of Pittsburgh School of Medicine, Pennsylvania 15261
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Lal SM, Fowler D, Losasso CJ, Berg GG. Coxsackie virus-induced acute pancreatitis in a long-term dialysis patient. Am J Kidney Dis 1988; 11:434-6. [PMID: 2835903 DOI: 10.1016/s0272-6386(88)80058-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
This report describes a patient on continuous ambulatory peritoneal dialysis (CAPD) who developed acute pancreatitis with pseudocyst formation and cloudy dialysate with pleocytosis in the absence of bacterial or fungal organisms. To our knowledge, pancreatitis, in the absence of hypertriglyceridemia in a CAPD patient, has not been previously reported. There was a significant increase in Coxsackie B1 and B6 viral titers by complement fixation test, suggesting Coxsackie virus-induced pancreatitis.
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Affiliation(s)
- S M Lal
- Department of Medicine and Radiology, University of Missouri, Health Sciences Center, Columbia 65212
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Leino R, Granfors K, Havia T, Heinonen R, Lampinen M, Toivanen A. Yersiniosis as a gastrointestinal disease. SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES 1987; 19:63-8. [PMID: 3551054 DOI: 10.3109/00365548709032379] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Anti-yersinia antibodies were assessed in sera from 630 patients admitted to a department of surgery for acute abdominal disease, using an enzyme-linked immunosorbent assay (ELISA). In 21 patients a high concentration of yersinia antibodies confirmed recent yersinia infection. Eight patients had an appendicectomy performed; in all patients with antibodies against Y. enterocolitica 9 or Y. pseudotuberculosis IA a true appendicitis was found at operation. Two patients with Y. enterocolitica 3 antibodies had acute terminal ileitis and mesenterial lymphadenitis. In 4 patients a diagnosis of acute pancreatitis was established; 2 of these had cholecystitis. Two further patients had cholecystitis without pancreatic affection. Two patients had colonic diverticulitis, 1 with perforation. The results demonstrate that yersinia infection may commonly give rise to a variety of acute abdominal inflammations, and stress the importance of serological and bacteriological diagnostic procedures.
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Kennedy JD, Talbot IC, Tanner MS. Severe pancreatitis and fatty liver progressing to cirrhosis associated with Coxsackie B4 infection in a three year old with alpha-1-antitrypsin deficiency. ACTA PAEDIATRICA SCANDINAVICA 1986; 75:336-9. [PMID: 3008494 DOI: 10.1111/j.1651-2227.1986.tb10211.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
A 3-year-old girl in whom severe acute pancreatitis was associated with evidence of Coxsackie B4 virus infection was alpha-1-antitrypsin deficient. Lack of this modulator of proteolysis may have been responsible for her severe course. Fatty liver at presentation progressed to cirrhosis in the ensuing 18 months.
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Toouli J, Roberts-Thomson IC, Dent J, Lee J. Sphincter of Oddi motility disorders in patients with idiopathic recurrent pancreatitis. Br J Surg 1985; 72:859-63. [PMID: 4063750 DOI: 10.1002/bjs.1800721104] [Citation(s) in RCA: 87] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Motor disorders of the sphincter of Oddi (SO) may play a role in the pathogenesis of idiopathic recurrent pancreatitis. We have compared manometric records from the SO in 28 patients with idiopathic recurrent pancreatitis with those from 10 control subjects. Patients with idiopathic recurrent pancreatitis had presented with episodes of upper abdominal pain associated with abnormal serum levels of amylase on at least two occasions, in the absence of alcohol abuse and biliary disease. Retrograde pancreatography was either normal or showed only minor changes in pancreatic ducts. A triple lumen low compliance manometric system was used to obtain a 5 min recording of spontaneous SO motor activity. From this recording were determined the SO basal pressure, SO phasic contraction amplitude, SO wave frequency and direction of wave propagation. The SO response to intravenous cholecystokinin-octapeptide (CCK-OP) 20 ng/kg was then recorded for at least 3 min. Twenty-five of the twenty-eight patients demonstrated one or more manometric abnormality when compared with data from the ten controls. The most frequent abnormality was an elevated SO basal pressure in 16 patients. In addition, excess of retrograde contractions in nine patients, high frequency of SO phasic contractions in nine patients, absence of phasic contractions in three patients, and paradoxical response to CCK-OP administration in two patients were recorded. This study has demonstrated a spectrum of sphincter of Oddi manometric disorders in patients with idiopathic recurrent pancreatitis and suggests that motility disorders of the sphincter of Oddi may be associated with episodes of pancreatitis.
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Abstract
Infection by mumps virus was found to lead to complications involving the CNS and heart in certain individuals. It is hypothesized that infection of the pancreas by mumps virus leads to the production of toxic peptides which damage the brain and heart.
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Hillemeier C, Gryboski JD. Acute pancreatitis in infants and children. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 1984; 57:149-59. [PMID: 6382834 PMCID: PMC2589812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Acute pancreatitis is being encountered more often in children due to antimetabolite therapy, accidental injury, and traumatic battering. Pancreatitis may occur in the absence of traditionally elevated serum amylase and lipase, and initial diagnosis may depend upon ultrasonography. Traditional therapy of enteric rest with nasogastric suction has been supported by the use of parenteral nutrition. Newer pharmaceutical agents have been ineffective in altering the course of the illness or in preventing complications of pseudocyst or abscess.
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Abstract
Accumulating evidence strongly suggests that viruses may play an etiologic role in some cases of diabetes mellitus. The importance of environmental factors in the pathogenesis of the disease is suggested by genetic and epidemiological observations. Group B Coxsackie viruses and mumps virus have been implicated, and the evidence suggests that several other agents also could play a role in the disease. In experimental animals, a picornavirus similar to the Coxsackie viruses exhibits specific tropism for the beta cells of the islets of Langerhans, causing a disease in mice that is similar to juvenile-onset diabetes. In these animals, genetic and metabolic factors appear to influence the severity of beta cell injury. Immunopathologic considerations also may be important. In man, histocompatibility genes are important determinants of juvenile-onset diabetes and abberations of immune responsiveness to beta cells have been demonstrated. In experimental animals, cell-mediated immunity develops subsequent to the occurrence of viral-induced lesions in the islets. Viewed in concert, the evidence supports the notion that certain "wild" viruses may possess specific tropism for beta cells and destroy them during the course of a systemic infection. Host factors clearly play a role, but their relative importance in the pathogenesis of the disease remains to be defined.
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McKay AJ, O'Neill J, Imrie CW. Pancreatitis, pregnancy and gallstones. BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY 1980; 87:47-50. [PMID: 7362789 DOI: 10.1111/j.1471-0528.1980.tb04425.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
In an 18 year hospital experience of over 500 patients with primary acute pancreatitis, 20 developed the disease either while pregnant (7 patients) or within five months of pregnancy (13 patients). Eighteen of the 20 patients had gallstones and adequate biliary surgery abolished further attacks of pancreatitis. Only two patients had surgery during the acute phase of their illness. The single fetal death was associated with early surgical intervention and there were no maternal deaths. We found no evidence of a specific link between pregnancy and pancreatitis but there is a marked association between pancreatitis and gallstones.
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Abstract
Clinical, epidemiological, and experimental observations suggest that common viruses may play an etiologic role in at least some cases of insulin dependent diabetes mellitus. The evidence is summarized and critically assessed in this presentation.
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