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Gantzel RH, Møller EE, Aagaard NK, Watson H, Jepsen P, Grønbæk H. Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites. Hepatol Commun 2024; 8:e0481. [PMID: 38934679 PMCID: PMC11213594 DOI: 10.1097/hc9.0000000000000481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/16/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites. METHODS We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30 ng/kg/min, though later reduced to 20 for safety reasons. RESULTS In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5 mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. -6.2 mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2-35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness. CONCLUSIONS Ularitide in doses of 20-30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.
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Affiliation(s)
- Rasmus H. Gantzel
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Medicine, Regional Hospital Gødstrup, Herning, Denmark
| | - Emilie E. Møller
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Niels K. Aagaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Hugh Watson
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
- Medical Development and Translational Sciences, Evotec ID, Lyon, France
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Wu HHL, Rakisheva A, Ponnusamy A, Chinnadurai R. Hepatocardiorenal syndrome in liver cirrhosis: Recognition of a new entity? World J Gastroenterol 2024; 30:128-136. [PMID: 38312119 PMCID: PMC10835518 DOI: 10.3748/wjg.v30.i2.128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/05/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome (HRS), outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context. In the absence of established heart disease, cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease. It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities. Despite the clinical description of these potential cardiac-related complications of the liver, the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS. Yet from a physiological sense, temporality (prior onset) of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients. In this review, we discuss current concepts surrounding how the heart may influence the development and progression of HRS, and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting. The temporality of heart and kidney dysfunction in HRS will be discussed. For a subgroup of patients who receive portosystemic shunting, the dynamics of cardiorenal interactions following treatment is reviewed. Continued research to determine the unknowns in this topic is anticipated, hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital & The University of Sydney, St. Leonards (Sydney) 2065, New South Wales, Australia
| | - Amina Rakisheva
- Department of Cardiology, City Cardiological Center, Almaty 050000, Kazakhstan
| | - Arvind Ponnusamy
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Rajkumar Chinnadurai
- Donal O’Donoghue Renal Research Centre & Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [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: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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Gantzel RH, Kjær MB, Jepsen P, Aagaard NK, Watson H, Gluud LL, Grønbæk H. Effects and safety of natriuretic peptides as treatment of cirrhotic ascites: A systematic review and meta-analysis. World J Hepatol 2022; 14:827-845. [PMID: 35646272 PMCID: PMC9099106 DOI: 10.4254/wjh.v14.i4.827] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/22/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis, counterbalancing vasoconstriction and anti-natriuretic factors. The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies, and definitive results are lacking. AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites. METHODS We searched MEDLINE, Web of Science, Scopus, Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites. Inclusion was not limited by treatment duration or dose, or by follow-up duration. Both randomised controlled trials and non-randomised studies were eligible for inclusion. The primary outcome was change in renal sodium excretion. Secondary outcomes included safety measures and changes in renal water excretion, plasma aldosterone concentration, and plasma renin activity. RESULTS Twenty-two studies were included. Atrial natriuretic peptide (ANP) was the only intensively studied treatment. Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of > 30 ng/kg/min were administered compared with ≤ 30 ng/kg/min (P < 0.01). Moreover, natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites (P < 0.01). ANP infusions increased renal water excretion, although without reaching a statistically significant dose-response gradient. Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders (P < 0.01). Blood pressure decreases occurred less frequently when ANP doses ≤ 30 ng/kg/min were applied. The quality of evidence for a natriuretic response to ANP was low, mainly due to small sample sizes and considerable between-study heterogeneity. Data were sparse for the other natriuretic peptides; B-type natriuretic peptide and urodilatin. CONCLUSION Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites. Continuous infusion rates > 30 ng/kg/min are the most effective. However, safety increases with infusion rates ≤ 30 ng/kg/min.
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Affiliation(s)
- Rasmus Hvidbjerg Gantzel
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark
| | - Mikkel Breinholt Kjær
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark
| | - Niels Kristian Aagaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark
| | - Hugh Watson
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark
| | - Lise Lotte Gluud
- Gastroenterology Unit, Copenhagen University Hospital, Hvidovre 2650, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark.
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Busquets-Cortés C, Bennasar-Veny M, López-González AA, Fresneda S, Aguiló A, Yanez A. Fatty liver index and progression to type 2 diabetes: a 5-year longitudinal study in Spanish workers with pre-diabetes. BMJ Open 2021; 11:e045498. [PMID: 34433590 PMCID: PMC8388308 DOI: 10.1136/bmjopen-2020-045498] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE The main aim of the study was to evaluate the association between non-alcoholic fatty liver disease (NAFLD), estimated by fatty liver index (FLI), and the development of type 2 diabetes (T2D) in a large cohort of adult workers with pre-diabetes. DESIGN Prospective cohort study. SETTING Occupational health services from Spain. PARTICIPANTS 16 648 adult workers (aged 20-65 years) with pre-diabetes (fasting plasma glucose (FPG) of 100-125 mg/dL). OUTCOME AND MEASURES FLI was calculated based on measurements of triglycerides, body mass index, waist circumference and γ-glutamyltransferase. The population was classified into three categories: FLI<30 (no hepatic steatosis), FLI 30-60 (intermediate status) and FLI>60 (hepatic steatosis). Sociodemographic, anthropometric, dietary habits, physical activity and clinical data were collected from all subjects. The incidence rate of T2D was determined after 5 years of follow-up. RESULTS After 5 years of follow-up, 3706 of the 16 648 participants (22.2%) were diagnosed with T2D, corresponding to an annual rate of progression of 4.5%. FLI was strongly associated with T2D conversion. The incidence rates of T2D in the FLI<30, FLI 30-60 and FLI>60 groups were significantly different after 5 years of follow-up were 19/6,421 (0.3%), 338/4,318 (7.8%) and 3,349/5,909 (56.7%), respectively. This association remained significant for FLI>60 after adjustment for, age, diet, physical activity, FPG, blood pressure, social class and smoking habits (adjusted HR=6.879; 95% CI 5.873 to 8.057 for men, and HR=5.806; 95% CI 4.863 to 6.932 for women). CONCLUSION NAFLD assessed by FLI independently predicted the risk of conversion to T2D among people with pre-diabetes. FLI may be an easily determined and valuable early predictor for T2D in people with pre-diabetes. FLI-based assessment of NAFLD in subjects with pre-diabetes in routine clinical practice could allow the adoption of effective measures to prevent and reduce their progression to T2D.
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Affiliation(s)
- Carla Busquets-Cortés
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Escuela Universitaria ADEMA, Palma, Illes Balears, Spain
| | - Miquel Bennasar-Veny
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Angel-Arturo López-González
- Escuela Universitaria ADEMA, Palma, Illes Balears, Spain
- Prevention of Occupational Risks in Health Services, Balearic Islands Health Services, Palma de Mallorca, Illes Balears, Spain
| | - Sergio Fresneda
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
| | - Antoni Aguiló
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
| | - Aina Yanez
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
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Mahalingam S, Shaikh OH, Kumbhar US, Mohan A. Cystic artery pseudoaneurysm due to carcinoma of the gallbladder. BMJ Case Rep 2021; 14:14/6/e241714. [PMID: 34083192 DOI: 10.1136/bcr-2021-241714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 52-year-old man, with known case of hypertension and stroke, presented to us with an upper gastrointestinal bleed and abdominal pain. Ultrasonography of the abdomen showed haematoma within the gallbladder (GB), and Doppler ultrasound was suggestive of an aneurysm arising from the cystic artery (CA). CT of the abdomen showed a well-enhancing thick-walled GB suggestive of malignancy. It also showed the presence of a double CA along with an aneurysm of one of the cystic arteries, haematoma within the GB and haemoperitoneum. Digital subtraction angiography confirmed the presence of double CA and CA pseudoaneurysm. The CA was selective catheterised and embolised with N-butyl cyanoacrylate glue. The patient underwent extended radical cholecystectomy later and was reported to have adenocarcinoma of the GB.
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Affiliation(s)
- Sudharshan Mahalingam
- Surgery, Jawaharlal Institute of Postgraduate Medical Education, Puducherry, Puducherry, India
| | - Oseen Hajilal Shaikh
- Surgery, Jawaharlal Institute of Postgraduate Medical Education, Puducherry, Puducherry, India
| | - Uday Shamrao Kumbhar
- Surgery, Jawaharlal Institute of Postgraduate Medical Education, Puducherry, Puducherry, India
| | - Amuthabharathi Mohan
- Surgery, Jawaharlal Institute of Postgraduate Medical Education, Puducherry, Puducherry, India
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Kim JH. Influencing Factors on Depression in Stomach Cancer Patients Receiving Chemotherapy. ACTA ACUST UNITED AC 2012. [DOI: 10.7475/kjan.2012.24.6.588] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Yaghobi R, Geramizadeh B, Zamani S, Rahsaz M, Azarpira N, Karimi MH, Ayatolahi M, Hossein Aghdai M, Nikeghbalian S, Bahador A, Salahi H, Malek-Hosseini SA. The molecular and antigenic tissue impact of viral infections on liver transplant patients with neonatal hepatitis. Int J Organ Transplant Med 2011; 2:108-115. [PMID: 25013603 PMCID: PMC4089257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND Pathogenesis of neonatal hepatitis relates to various underlying causes including viral infections. Both hepatotropic and non-hepatotropic viruses may induce liver failures in infants before birth, during delivery, or shortly after birth. OBJECTIVES The tissue impact of HCMV, HSV, HBV, HCV, and rotavirus and adenovirus infections was evaluated in studied infants with neonatal hepatitis. METHODS The history of viral infections was analyzed in paraffin-embedded biopsy and autopsy tissues of 22 infants with neonatal hepatitis between years 1996 and 2007, retrospectively. The tissue molecular presentation of HBV, HCV, HCMV, HSV, adenovirus, and rotavirus was evaluated by different qualitative simple and nested PCR and RT-PCR protocols. Immunohistochemistry (IHC) method was used for studying the antigenic prevalence of HSV-1, 2; HBV, HCMV and adenovirus infections. Also the laboratory liver indices of all patients with neonatal hepatitis were analyzed. RESULTS The HBV and HSV genomes were detected in 3 (14%) of 22 infants. The rotavirus and HCV-RNA and also the HCMV-DNA were detected separately in 1 (4%) of 26 paraffin-embedded autopsy and biopsy tissues. The HBV and HSV-1 specific antigens were separately diagnosed in 1 (4%) of 26 neonatal samples by IHC protocols. Also the HSV-2 antigen was seen in 5 (23%) of 22 liver autopsy and biopsy specimens. Co-infections with HCMV, HSV, HBV, HCV, and rotavirus were detected in these infants with hepatitis. CONCLUSION Diagnosis of single and mixed molecular and antigenic traces of HCMV, HSV, HBV, HCV and rotavirus underlines the etiologic role of these viruses in clinical pathogenesis of neonatal hepatitis.
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Affiliation(s)
- R. Yaghobi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - B. Geramizadeh
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - S. Zamani
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - M. Rahsaz
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - N. Azarpira
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - M. H. Karimi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - M. Ayatolahi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - M. Hossein Aghdai
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - S. Nikeghbalian
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
- Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - A. Bahador
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - H. Salahi
- Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - S. A. Malek-Hosseini
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,
- Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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Pellissier S, Dantzer C, Canini F, Mathieu N, Bonaz B. Psychological adjustment and autonomic disturbances in inflammatory bowel diseases and irritable bowel syndrome. Psychoneuroendocrinology 2010; 35:653-62. [PMID: 19910123 DOI: 10.1016/j.psyneuen.2009.10.004] [Citation(s) in RCA: 140] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2008] [Revised: 09/12/2009] [Accepted: 10/09/2009] [Indexed: 02/07/2023]
Abstract
Psychological factors and the autonomic nervous system (ANS) are implicated in the pathogenesis of inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). This study aimed to assess, firstly the way IBS and IBD patients cope with their pathology according to their affective adjustment and secondly the possible links between these affective adjustments and ANS reactivity. Patients with Crohn's disease (CD; n=26), ulcerative colitis (UC; n=22), or IBS (n=27) were recruited and compared to 21 healthy subjects based on psychological variables (trait- and state anxiety, depressive symptomatology, negative mood, perceived stress, coping, health locus of control) and sympatho-vagal balance through heart-rate variability monitored at rest. A principal component analysis, performed on all affective variables, isolated a leading factor labelled as "affective adjustment". In each disease, patients were distributed into positive and negative affective adjustment. In all the diseases, a positive affect was associated with problem-focused coping, and a negative affect with emotion-focused coping and external health locus of control. Results show that the sympatho-vagal balance varied according to the disease. In CD presenting positive affectivity, an adapted high sympathetic activity was observed. In UC, a parasympathetic blunt was observed in the presence of negative affectivity and an equilibrated sympatho-vagal balance in the presence of positive affectivity. In contrast, in IBS, an important dysautonomia (with high sympathetic and low parasympathetic tone) was constantly observed whatever the affective adjustment. In conclusion, this study suggests that the equilibrium of the ANS is differentially adapted according to the disease. This equilibrium is conjugated with positive affective and cognitive adjustment in IBD (CD and UC) but not in IBS.
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Affiliation(s)
- Sonia Pellissier
- Stress et Interactions Neuro-Digestives (SIND), Grenoble Institut des Neurosciences (GIN), Centre de Recherche INSERM 836 UJF-CEA-CHU, Grenoble F-38043, France
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Abstract
Hepatorenal syndrome (HRS) is a type of renal failure that occurs in patients with advanced cirrhosis. It is a result of splanchnic arterial vasodilation, renal vasoconstriction, reduced effective arterial volume, and potentially reduced cardiac output. Often, HRS is a fatal complication, and the only definitive treatment currently available is liver or liver-kidney transplantation. A number of other treatment modalities have been tested for the management of HRS, but most evidence is derived from small noncontrolled studies. The primary role of these treatment options is to provide a bridge to liver transplantation. Treatment may also provide acute reversal of renal failure and some symptomatic relief, but relapse is a common occurrence. The best therapeutic options appear to be those that reverse portal hypertension, splanchnic vasodilation, and/or renal vasoconstriction. Vasopressin analogs, particularly terlipressin, have emerged as the preferred pharmacologic therapies for management of HRS. Albumin is an appropriate adjunctive therapy to terlipressin and can be used to prevent HRS in patients with spontaneous bacterial peritonitis. Transjugular intrahepatic portosystemic shunt may provide a surgical option for qualified patients with HRS. Octreotide is ineffective as monotherapy but may be used as adjunctive therapy to other vasoactive agents. Dopamine agonists, endothelin antagonists, natriuretic peptides, and nitric oxide synthase inhibitors have not been effective for reversing HRS. Artificial hepatic support therapies have demonstrated the ability to improve laboratory abnormalities in patients with HRS, but their effect on clinical outcomes has not been determined. The role of renal replacement therapies or the newer artificial hepatic support therapies need further evaluation before they can be routinely recommended.
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Affiliation(s)
- Tyree H Kiser
- Department of Clinical Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80045, USA.
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Carstens J, Pedersen EB. Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin II receptor. Scand J Clin Lab Invest 2007; 68:2-10. [PMID: 17852806 DOI: 10.1080/00365510701504257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Little is known about the role of the renin-angiotensin-aldosterone system and the renal prostaglandins in modulating the renal vasoconstrictive and natriuretic effects of synthetic urodilatin (URO) in healthy humans. MATERIAL AND METHODS Twelve volunteers were pretreated in a randomized, single-blind, crossover study with losartan 50 mg a day or placebo for 5 days. Another 12 healthy subjects received indomethacin 25 mg three times a day or placebo for 4 days and a single dose on day 5. All subjects received a URO infusion (15 ng kg(-1) min(-1)) on day 5. Radioactive tracers and the lithium clearance technique were used. RESULTS The effective renal plasma flow (ERPF) decreased significantly during URO infusion: losartan pretreatment 573+/-63 to 461+/-76 mL/min versus placebo 540+/-89 to 432+/-90 mL/min. The urinary sodium excretion rate (UNa) increased significantly during URO infusion: losartan 335+/-115 to 502+/-134 umol/min (micromol/min) (UNa) versus placebo 386+/-142 to 476+/-137 umol/min (micromol/min) (UNa). In the indomethacin pretreated subjects, ERPF decreased significantly from 530+/-109 to 446+/-55 mL/min versus 533+/-89 to 449+/-69 mL/min in the placebo group. UNa increased significantly from 395+/-142 to 768+/-254 umol/min (micromol/min) (UNa) in the indomethacin group versus 282+/-117 to 552+/-242 umol/min (micromol/min) (UNa) in placebo. CONCLUSION The renal vasoconstrictive and natriuretic effects of synthetic URO are not modified by sustained inhibition of the angiotensin II receptor or the cyclooxygenase in man in a sodium replete state.
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Affiliation(s)
- Jan Carstens
- Holstebro Hospital, Aarhus University, Department of Medical Research, Holstebro, Denmark.
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