Stanghellini, V; Cogliandro, R F; De Giorgio, R; Barbara, G; Cremon, C; Antonucci, A; Fronzoni, L; Cogliandro, L; Naponelli, V; Serra, M; Corinaldesi, R
Chronic intestinal pseudo-obstruction is a severe, often unrecognized disease characterized by disabling and potentially life-threatening complications over time. The diagnosis is based on the evidence of typical clinical manifestations, radiological evidence of distended bowel loops with air-fluid levels, and the exclusion of any organic obstruction of the gut lumen. The radiological sign of intestinal occlusion allows the distinction from enteric dysmotility, which is characterized by better outcomes. Manometry can play a supportive role in defining the diagnosis, and differences in the manometric pattern of chronic intestinal pseudo-obstruction and enteric dysmotility have been shown. The disease is often unrecognized, and the diagnosis, therefore, delayed by several years. Thus, the majority of patients undergo useless and potentially dangerous surgeries. Long-term outcomes are generally poor despite surgical and medical therapies characterized by disabling and potentially life-threatening complications over time. A substantial percentage of patients requires parenteral nutrition. Failure of this nutritional support represents an indication for small bowel transplantation.
Lee, Byoung Hwan; Kang, Sung-Bum; Lee, Kyoung-Ho; Oh, Jane C.; Kim, Sun-Mi; Park, Young Soo; Lee, Dong Ho
Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by a severe impairment of gastrointestinal propulsion in the absence of mechanical obstruction. We experienced a case of chronic pseudo-obstruction in the initial phase mimicking acute pseudo-obstruction, which was treated medically. This ongoing case was compared to another recurrent and intractable case successfully treated with surgery and diagnosed as hypoganglionosis. These two cases showed different clinical features and therapeutic approaches for CIPO; one with the first episode of CIPO mimicking Ogilvie's syndrome; the other with recurrent episodes of CIPO with typical features. In conclusion, CIPO is a difficult disorder with various clinical manifestations and different treatment modalities, therefore individualized diagnostic and therapeutic approaches are needed. PMID:20535331
Lee, Byoung Hwan; Kim, Nayoung; Kang, Sung-Bum; Lee, Kyoung-Ho; Oh, Jane C; Kim, Sun-Mi; Park, Young Soo; Lee, Dong Ho
Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by a severe impairment of gastrointestinal propulsion in the absence of mechanical obstruction. We experienced a case of chronic pseudo-obstruction in the initial phase mimicking acute pseudo-obstruction, which was treated medically. This ongoing case was compared to another recurrent and intractable case successfully treated with surgery and diagnosed as hypoganglionosis. These two cases showed different clinical features and therapeutic approaches for CIPO; one with the first episode of CIPO mimicking Ogilvie's syndrome; the other with recurrent episodes of CIPO with typical features. In conclusion, CIPO is a difficult disorder with various clinical manifestations and different treatment modalities, therefore individualized diagnostic and therapeutic approaches are needed.
Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna F; Caputo, Carla; Giorgio, Roberto De; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo
Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases. PMID:18494042
Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna-F; Caputo, Carla; De Giorgio, Roberto; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo
Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.
Andrés, A M; Miguel, M; De la Torre, C; Barrena, S; Ramírez, M; Hernández, F; Martínez, L; Leal, N; Ramos, E; Prieto, G; López Santamaría, M; Tovar, J A
Chronic Intestinal Pseudo Obstruction (CIPO) and Berdon Syndrome (BS) are motility disorders with still unclear pathophysiology, and challenging diagnosis and management. Patient and methods. 26 patients (8M/18F) treated of CIPO (21) or BS (5) at our institution between 1982-2009 were retrospectively reviewed and clinical, diagnostic, therapeutic and follow-up data were analyzed. 77% had a neonatal onset by the 3rd month of life (5 had a prenatal diagnosis of megacystis). Abdominal distension (87%), recurrent suboclusive episodes (70%) and malnourishment (60%) were the main symptoms followed by vomits, chronic diarrhea, constipation and dysfagia. The urinary tract was involved in 12 patients (46%): 8 had megacystis, 8 had vesicoureteral reflux. Arrythmias were seen in 2, deafness in 1, hydrocephalia in 1 and malrotation in 5. Radiological studies were consistent for CIPO in all of them: the disease was limited to the esophagus in 1, 3 had segmentary involvement of the small bowel, 6 had microcolon, and the rest had all the digestive tract involved. Anorectal manometry ruled out aganglionosis in 12, esophageal manometry showed aperistalsis in 9 and antro-duodenal manometry confirmed the diagnosis in 9 (visceral myopathy in 4 y neuropathy in 5). Rectal biopsies (16) and muscular biopsies (5) were normal in all of them. Full thickness biopsies (in 18, after surgery) showed myopathy in 12 and neuropathy in 6. Prokinetics and antibiotics for bacterial overgrowth were employed in 100%, 17 required long-time parenteral nutrition (PN), 21 required surgery and 7 were transplanted (4 isolated small bowel, 3 multivisceral). Symptoms improved in 9/15 with an ileostomy. 19 weaned from PN. After a median follow-up of 7.9 years (range 5m-17a), 3 were lost, 17/23 patients are alive and only 2 on home PN. Six died, 3 after being transplanted. CIPO and/or BS have a wide clinical spectrum and a complex diagnosis; however, the knowledge of the disease and an appropriate treatment
Movahedi, Masoud; Tavakol, Marzieh; Hirbod-Mobarakeh, Armin; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Tavakol, Zahra; Momenzadeh, Kaveh; Nabavi, Mohammad; Dabbaghzade, Abbas; Mosallanejad, Asieh; Rezaei, Nima
Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.
Serrano-Munuera, C; Rojas-García, R; Gallardo, E; De Luna, N; Buenaventura, I; Ferrero, M; García, T; García-Merino, J A; González-Rodríguez, C; Guerriero, A; Marco, M; Márquez, C; Grau, J M; Graus, F; Illa, I
Antidisialosyl antibodies were found in two out of 13 patients with chronic idiopathic ataxic neuropathy (CIAN) and not in 32 patients with different sensory neuropathies of known cause. This finding confirms the association of antidisialosyl antibodies and CIAN regardless of the absence of the M band. These antibodies may have pathogenic relevance; however, larger series are needed to establish their clinical significance.
Effect of the herbal medicine dai-kenchu-to on gastrointestinal motility in patients with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) and chronic idiopathic intestinal pseudo-obstruction (CIIP): report of two cases.
Hirakawa, Hitoshi; Ueno, Shigeru; Matuda, Hiromitu; Hinoki, Tomoya; Kato, Yuko
Dai-kenchu-to (DKT), a traditional Japanese herbal medicine (Kampo medicine), composed of zanthoxylum fruit, ginseng root, dried ginger rhizome and malt sugar, is clinically effective for postoperative ileus and chronic constipation. MMIHS and CIIP are severe motility disorder associated with high morbidity. The aim of this study was to evaluate the effect of DKT on functional intestinal obstruction. DKT was clinically effective for gastrointestinal motility in a case with MMIHS, but not effective in one with CIIP. MMIHS and CIIP are speculated to have different pathogenesis regarding gastrointestinal pseudo-obstruction based upon the effect of this drug.
Looijer–van Langen, Mirjam A.C.; Dieleman, Levinus A.
Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn’s disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials. PMID:18831524
Mori, P G; Mancuso, G; del Principe, D; Duse, M; Miniero, R; Tovo, R; Bardare, M; Carnelli, V; de Mattia, D
Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed. PMID:6685997
Muñoz, M T; Solís Herruzo, J A
Chronic intestinal pseudo-obstruction (CIPO) is a syndrome characterized by the presence of recurrent episodes of clinical intestinal obstruction in the absence of obstructive lesions. Although this syndrome is rare, it causes a high morbidity. It is caused by a disturbance of the intestinal motility, that results in a failure of the progression of the intestinal content. Basically, the failure of the intestinal motility is a consequence of muscular disorder, neurological disorder or both. Usually, CIPO is secondary to other systemic disease; however, in the last years, many cases of primary CIPO have been described. The use of new manometric tecniques and specific histological procedures have allowed to clarify the pathogenesis of some of these entities including mitochondrial diseases and paraneoplasic syndromes. Clinical manifestations of CIPO are diverse, depending on the location and extension of the motility disorder. As the diagnosis of this disease is usually not an easy task, patients frecuently undergo unnecesary surgical interventions, are diagnosed of psyquiatric disorders, or the correct diagnosis is delayed several years after the first symptoms arise. The aims of the treatment are to maintain the nutritional condition and to improve symptoms using nutritional measures, drugs or, eventually, endoscopical or surgical procedures.
Joly, Francisca; Amiot, Aurélien; Coffin, Benoît; Lavergne-Slove, Anne; Messing, Bernard; Bouhnik, Yoram
Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.
Ruggeri, R M; Imbesi, S; Saitta, S; Campennì, A; Cannavò, S; Trimarchi, F; Gangemi, S
Chronic urticaria is a common condition characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions lasting for more than 6 weeks. In about 75% of cases, the underlying causes remain unknown, and the term chronic idiopathic urticaria (CIU) is used to emphasize that wheals develop independently of identified external stimuli. Although CIU affects about 1.0% of the general population, its etiopathogenesis is not yet well understood. It is now widely accepted that in many cases CIU should be regarded as an autoimmune disorder caused by circulating and functionally active IgG autoantibodies specific for the IgE receptor (FceRI) present on mast cells and basophils or for IgE itself. The well-known association of CIU with other autoimmune processes/diseases represents further indirect evidence of its autoimmune origin. Autoimmune thyroid diseases, especially autoimmune thyroiditis, represent the most frequently investigated diseases in association with CIU. Here we review this topic with particular regard to the association between Graves' disease and CIU. The possible pathogenetic mechanisms and the clinical implications of such an association are discussed.
Ohkubo, Hidenori; Inoh, Yumi; Fuyuki, Akiko; Nakajima, Atsushi
Chronic intestinal pseudo-obstruction(CIPO) is a rare severe digestive disease in which clinical symptoms of intestinal obstruction appear without any mechanical cause. Pathophysiologically, CIPO shows ineffective intestinal propulsion due to an impairment of intestinal smooth muscle, enteric nervous system, and interstitial cells of Cajal(ICC). Sustained increased intra-bowel pressure often causes small intestinal malabsorption and bacterial translocation, and leads to malnutrition and blood stream infection (sepsis). Key points of the medical approach for CIPO are to improve nutritional status and reduce abdominal symptoms. Dietary cure and defecation control are the main options in mild cases, whereas home-parenteral-nutrition(HPN) and decompression therapy are often needed in severe cases. Stimulant laxatives, prokinetics and herbal medicine are usually used but often in fail. Percutaneous endoscopic gastrojejunostomy(PEG-J) tube may be burdenless compared to conventional ileus tube. Most important points in the management of this disease are to make a correct diagnosis as early as possible and avoid unnecessary surgery. However, no clear diagnostic criteria have been established so far. Manometry, scintigraphy, and full-thickness biopsy are the major examination for the CIPO diagnosis in the Western countries; however these specialized examinations are not popular in Japan. Therefore the Research Group(chief investigator, Atsushi Nakajima) proposed Japanese diagnostic criteria in 2009 to facilitate the diagnosis of this rare disease by the general physician. In 2013, we have reported that cine-MRI is a non-invasive diagnostic method for CIPO. Although further data are eagerly awaited, it can become a promising diagnostic tool in CIPO patients. Furthermore the Japanese criteria have been revised, and in 2014, the comprehensive criteria from a child to an adult have been devised. In 2015, CIPO is newly certified as Specified Rare and Intractable Disease which is
Seyer, J M; Hutcheson, E T; Kang, A H
Collagens in normal human lung and in idiopathic chronic fibrosis were investigated in terms of their covalent structure and compared for possible alterations in the diseased state. Collagens were solubilized by limited digestion with pepsin under nondenaturing conditions, and after purification they, were fractionated into types I and III. Carboxymethylcellulose and agarose chromatography of both types I and III collagens, and amino acid and carbohydrate analyses of the resulting alpha-chains indicated that the alpha 1 (I), alpha 2, and alpha 1 (III) chains of normal human lung were identical with the human skin alpha-chains in all respects examined except that the normal lung chains contained higher levels of hydroxylysine. Examination of collagens obtained from the diseased lung revealed that the content of hydroxylysine of the alpha 1 (I) and the alpha 1 (III) chains appeared to be diminished as compared to the normal lung chains. The values, expressed as residues per 1,000 residues, are 7.1 and 8.3 for the alpha 1 (I) and the alpha 1 (III) chains, respectively, as compared to 10.0 and 11.1 for the alpha-chains from the normal tissue. The chromatographic properties and amino acid and carbohydrate composition of the alpha-chains from the diseased tissue were otherwise indistinguishable from those of normal lung. In addition, isolation and characterization of the CNBr peptides of alpha 1 (I), alpha 2 and alpha 1 (III) from the diseased lung revealed no significant differences from the CNBr peptides from other human tissues reported previously. Normal and diseased lungs were also digested with CNBr, and the resultant alpha 1 (I) and alpha 1 (III) peptides were separated chromatographically. The relative quantities of these peptides indicate that type III collagen constitutes 33% of the total collagen in normal human lung, with the remainder being type I, whereas in idiopathic chronic pulmonary fibrosis, the relative content of type III collagen is markedly
Castillo, T; Navarrete, J; Celestina, A
Much has been written about gastric mucosae behavior and the occurrence of intestinal metaplasia. The aim of this paper is to learn something more about these matters in peruvian population. We selected 100 patients with endoscopically no localized lesions between 30 to 70 years of age. We took 8 samples of gastric mucosae in each patient which were carefully examined for the presence of inflammatory changes, settle the line type between antral and fundic mucosae and the frequency of intestinal metaplasia finding. The results showed disagreement between endoscopic and histological findings, so we conclude it is better to diagnose chronic gastritis on the basis of histological parameters. The line between antral and fundic mucosae was of the close type one found in 87% of all cases and it advanced proximally with increasing age. Intestinal metaplasia was present in 46% of the whole number of patients and the rate of occurrence increased in 50% over 50 years age. These findings will let us compare future investigations of gastric mucosae behavior with localized benign or malign lesions.
Azzoulai, C; Djeddi, J; Chapoy, V; Boudailliez, B; Bovin, E; Pripis, C; Buisson, P; Guilé, J-M
Chronic idiopathic intestinal pseudo-obstruction is a rare and serious chronic disease starting in childhood, which can affect the entire digestive tract. It is caused by a peristalsis intestinal disorder that leads to occlusions without any obvious obstruction. Few studies have been carried out regarding the prognosis of this illness. This disease is often diagnosed by a process of elimination, but some histological anomalies have been present in the digestive wall of certain patients. This clinical case concerns a 17-year-old girl affected by CIPO and eating disorders. It seems difficult to discriminate between digestive disorders and eating disorders. What psychological effects can this severe pathology have? Are eating disorders induced by CIPO? These questions are raised in this article through the example of this patient's somatopsychic complexity and the ensuing difficulties in her overall care.
Guarino, M P L; Carotti, S; Cogliandro, R; Stanghellini, V; De Giorgio, R; Barbara, G; Alloni, R; Altomare, A; Tarquini, E; Coppola, R; Corinaldesi, R; Cicala, M
Chronic intestinal pseudo-obstruction represents a cause of persistent functional intestinal failure either "secondary" to specific conditions or "chronic intestinal idiopathic pseudo-obstruction" in origin. The diagnosis is mainly clinical, supported by radiological and/or endoscopic findings excluding any mechanical cause of intestinal obstruction. We reported a case of a 39-year-old woman with chronic intestinal idiopathic pseudo-obstruction, who underwent colectomy with ileorectal anastomosis; histological examination of the surgical specimen did not reveal myogenic or neurogenic defects or other pathological abnormalities indicative of an underlying neuromuscular impairment. Because of the apparent integrity of the gut neuromuscular layer, we tested whether a functional impairment affected colonic single smooth muscle cells. Muscle cells were isolated from the right colon and their contractile response to a receptor-dependent agonist evaluated in comparison to that obtained from controls. The cell contraction induced by acetylcholine in a dose response manner was markedly decreased in the patient affected by chronic intestinal idiopathic pseudo-obstruction compared with cells from controls (percentage of cell shortening with maximal dose of acetylcholine [10(-6)M]: 10.7+/-3% versus 34.2+/-4%, respectively). The present findings indicate a specific defect of colonic smooth muscle cells likely related to an ineffective response to acetylcholine.
Gabbard, Scott L; Lacy, Brian E
Chronic intestinal pseudo-obstruction (CIP) is a rare and serious disorder of the gastrointestinal (GI) tract characterized as a motility disorder with the primary defect of impaired peristalsis; symptoms are consistent with a bowel obstruction, although mechanical obstruction cannot be identified. CIP is classified as a neuropathy, myopathy, or mesenchymopathy; it is a neuropathic process in the majority of patients. The natural history of CIP is generally that of a progressive disorder, although occasional patients with secondary CIP note significant symptomatic improvement when the underlying disorder is identified and treated. Symptoms vary from patient to patient depending on the location of the luminal GI tract involved and the degree of involvement; however, the small intestine is nearly always involved. Common symptoms include dysphagia, gastroesophageal reflux, abdominal pain, nausea, vomiting, bloating, abdominal distension, constipation or diarrhea, and involuntary weight loss. Unfortunately, these symptoms are nonspecific, which can contribute to misdiagnosis or a delay in diagnosis and treatment. Since many of the symptoms and signs suggest a mechanical bowel obstruction, diagnostic tests typically focus on uncovering a mechanical obstruction, although routine tests do not identify an obstructive process. Nutrition supplementation is required for many patients with CIP due to symptoms of dysphagia, nausea, vomiting, and weight loss. This review discusses the epidemiology, etiology, pathogenesis, diagnosis, and treatment of patients with CIP, with an emphasis on nutrition assessment and treatment options for patients with nutrition compromise.
Lucas, Katherine E; Rowe, Peter C; Coresh, Josef; Klag, Michael J; Meoni, Lucy A; Ford, Daniel E
To determine whether there is an association between hypotension and incident cases of idiopathic chronic fatigue. A prospective study. Johns Hopkins Precursors Study. Medical students (n = 876) in graduating classes from 1948 to 1964. 'Easy fatigability' reported by participants at 5- or 10-year follow-up after graduation. The unadjusted risk in women was 5.0 (95% exact confidence interval = 1.4 to 17.4) and in men was 1.7 (95% exact confidence interval = 0.8, to 3.5). These preliminary findings suggest that hypotension may be a risk factor for the development of idiopathic chronic fatigue in women.
Muñoz-Yagüe, M T; Solís-Muñoz, P; Salces, I; Ballestín, C; Colina, F; Ibarrola, C; López-Alonso, G; Carreira, P; Cruz Vigo, F; Solís Herruzo, J A
Chronic intestinal pseudoobstruction (CIPO) is a rare entity characterized by recurrent clinical episodes of intestinal obstruction in which no mechanical cause is identified. There are multiple causes for this syndrome but two main groups can be distinguished: a) secondary to a systemic non-gastrointestinal disease; and b) primary or idiopathic originated from alterations in the components of the intestinal wall. The latter forms are the most uncommon and their diagnosis is generally difficult. In the present article, we describe nine patients with CIPO that were diagnosed in our center over the last six years. Four of them were diagnosed with primary or idiopathic form of CIPO and another four were clearly secondary to a systemic disease. The ninth case, which was initially diagnosed as secondary, is probably also a primary form of the disease. The number of patients diagnosed in our center, even thought small, makes us to hypothesize that the prevalence of CIPO is probably greater than is generally believed and that the reasons of its rarity are the incomplete understanding of its physiopathology and the difficulties to achieve a correct diagnosis.
Kar, P K; Chari, Kvr
In a prospective study a comparison has been made between the clinical efficacy and safety of cetirizine, a third generation H1 receptor antagonist with chlorpheniramine and cyprohepatadine, the most widely used antithistamines in the treatment of chronic idiopathic urticaria. One hundred and five patients with chronic idiopathic urticaria were studied where the effects of chlorpheniramine, 4 mg and cyproheptadine, 4 mg administered twice daily were compared with cetirizine, 10 mg given once daily for 4 weeks or earlier till the relief of symptoms and regression of lesions. Local therapy consisted of calamine lotion in all cases. Out of 35 patients receiving chlorpheniramine excellent response was achieved in 9 (25.7%) cases by subjective evaluation (SE) and 11 (31.4%) by objective evaluation (OE). Out of 35 cases, 7 (20%) and 10 (28.5%) cases treated with cyproheptadine have shown excellent response by SE and OE respectively. Out of 35 patients taking cetirizine 25 (71.4%) had shown excellent response by SE and 22 (62.8%) cases by OE. Drowsiness was an important side effect observed in 19 (54.2%) cases receiving chlorpheniramine, 22 (62.8%) patients taking cyproheptadine and 1 (2.8%) case getting cetirizine. These results suggest that cetirizine has got superior antiallergic activity than chlorpheniramine and cyproheptadine in the treatment of chronic idiopathic urticaria.
Heineman, Thomas E; Kacker, Ashutosh; Kutler, David I
The purpose of this study was to correlate imaging and sialendoscopic findings to therapeutic response in patients with idiopathic chronic parotitis. We retrospectively reviewed 122 consecutive sialendoscopies performed in an academic medical center by two surgeons between 2008 and 2013. Forty-one (34%) and 54 (44%) patients were excluded on the basis of having parotid or submandibular sialolith, respectively. Nineteen cases were included in the study with idiopathic chronic parotitis. There was a median follow-up of 5 months. Computed tomography (CT) imaging had a sensitivity and specificity of 80.0 and 71.4%, respectively, for predicting abnormal findings on sialendoscopy, while magnetic resonance imaging (MRI) had 100% accuracy in a small set of cases. In glands with noticeable pathology present on preoperative imaging or sialendoscopy, 11 out of 12 glands (92%) treated experienced symptomatic improvement, while 3 out of 7 glands (43%) without pathology on imaging or endoscopy experienced symptomatic improvement (p = 0.038). Sialendoscopy for the treatment of idiopathic chronic parotid disease can improve pain and swelling with a higher frequency of success in patients with abnormalities noted on endoscopy. CT and MRI have a moderate degree of accuracy in predicting which patients will benefit from therapeutic sialendoscopy. © 2015 S. Karger AG, Basel.
Mao, Weiming; Liao, Xiujun; Wu, Wenjing; Yu, Yanyan; Yang, Guangen
Abstract The aim of this study was to investigate the clinical characteristics, treatment outcomes and psychological distress in patients with chronic idiopathic anal pain. The study was conducted on patients referred to Hangzhou Third Hospital for chronic anal pain from January, 2010 to December, 2014. Patient demographics, clinical history, anorectal physiology, and radiological imaging data were recorded for all patients. The treatment outcome was noted for patients treated and followed up for more than 6 month at the present unit. Ninety-six patients with mean age of 45.1 years (range, 17-82) were studied. Seventy-one patients (74.0%) had functional anorectal pain(FARP). The main complaints were dull, sharp, stabbing, or spasm pain. Among all patients, 34.3% reported that their pain radiated into other locations. Fifty-one patients (53.1%) had bowel dysfunction, while 28.1% patients had urinary dysfunction. The common factors associated with pain relief were day time, lying down and warm water baths; the factors that contributed to aggravated pain were night time, defecation or sitting. 92.7% (89/96) of patients reported symptoms of psychological disturbance. FARP patients exhibited increased depression than non-FARP patients(P<0.05). In addition, female patients were more likely to have depression than male patients (P<0.05). The overall pain treatment success rate was 55.2% (53/96). The pain treatment outcome was better in non-FARP patients than in FARP patients(χ2=3.85, P<0.05). Conclusively, chronic idiopathic anal pain is a complex clinical symptom, involving pelvic floor muscles, the nervous system, endocrine system, and the patients’ psychological conditions. Further research is needed to improve diagnosis and treatment for patients with chronic idiopathic anal pain. PMID:28730167
Zoppi, G; Cinquetti, M; Luciano, A; Benini, A; Muner, A; Bertazzoni Minelli, E
Chronic functional constipation is common in infants, and the bacterial composition of stools in this condition is not known. The study aims were to: (i) investigate the composition of the intestinal ecosystem in chronic functional constipation; (ii) establish whether the addition of the water-holding agent calcium polycarbophil to the diet induces an improvement in constipation; and (iii) determine the composition of the intestinal ecosystem after the use of this agent. In total, 42 children (20F, 22M; mean age: 8.6 +/- 2.9 y) were studied. Twenty-eight children with functional chronic constipation without anatomical disorders were treated double-blind in random sequence for 1 month with an oral preparation of calcium polycarbophil (0.62 g/twice daily) or placebo. Intestinal flora composition was evaluated by standard microbiological methods and biochemical assays on faecal samples collected before and after treatment. Fourteen healthy children were studied as controls. The results show that (i) the constipated children presented a significant increase in clostridia and bifidobacteria in faeces compared to healthy subjects--different species of clostridia and enterobacteriaceae were frequently isolated; no generalized overgrowth was observed; Clostridia outnumbered bacteroides and E. coli mean counts by 2-3log, while bacteroides and E. coli counts were similar (5-6 log10/g fresh faeces); these intestinal disturbances could be defined as a dysbiosis, i.e. a quantitative alteration in the relative proportions of certain intestinal bacterial species. (ii) Clinical resolution of constipation was achieved only in 43% of treated children and an improvement in 21% (one bowel movement every 2 d). (iii) Calcium polycarbophil treatment induced no significant changes in the composition of the intestinal ecosystem, nor in blood chemistry parameters.
Chronic idiopathic constipation is highly prevalent among adults. Bile acids (BAs) and the enterohepatic BA circulation modulate colonic secretion and motility that affect transit. BAs in the colon have a dual action as osmotic and stimulant agents. Newer agents, such as elobixibat (A3309), an inhibitor of the ileal BA transporter, have the potential to improve significantly the management of chronic constipation, with minimal adverse effects. Elobixibat modulates the enterohepatic BA circulation, enhancing the delivery of BAs to the colon where they induce secretory and motor effects. Secondary effects of the inhibition of BA absorption are reduced activation of the farnesoid X receptor, decreased secretion of fibroblast growth factor-19 into the portal circulation, and increased BA synthesis. This review focuses on the role of BAs, the enterohepatic BA circulation, and an ileal BA transporter inhibitor (elobixibat) in chronic constipation. PMID:25057297
Guarneri, Fabrizio; Guarneri, Claudio; Cannavò, Serafinella Patrizia
Chronic urticaria (CU) is frequent, remains often idiopathic despite diagnostic efforts, and sometimes poorly responds to oral antihistamines and/or corticosteroids. We noticed that hyposideremia is often found in patients with chronic idiopathic urticaria poorly responsive to usual treatments (prCIU), and oral iron therapy is frequently associated to improvement or resolution of urticaria. Between 2003 and 2012, we observed 122 patients with prCIU, of which 81 had moderate hyposideremia at our first visit. They continued the antihistamines already practiced and received oral iron therapy for 30 or 45 days. Two months after our first visit, all had normal serum iron levels; 64 reported complete remission of urticaria and 17 reported improvement superior to 80%. No adverse reactions to treatment were observed. Follow-up visits confirmed stability of results over 6 months. Our preliminary data show that hyposideremia is the only abnormality in many patients with prCIU, and restoration of normal iron serum levels is associated to remission or remarkable clinical improvement of urticaria. In consideration of low cost and potential benefits for some patients, determination of serum levels of iron could be introduced in the diagnostic workup of chronic urticaria, maybe as a second-level exam in patients without other relevant clinical or laboratory abnormalities.
De Giorgio, R; Ricciardiello, L; Naponelli, V; Selgrad, M; Piazzi, G; Felicani, C; Serra, M; Fronzoni, L; Antonucci, A; Cogliandro, R F; Barbara, G; Corinaldesi, R; Tonini, M; Knowles, C H; Stanghellini, V
Chronic intestinal pseudo-obstruction (CIPO), one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Analysis of full-thickness biopsy samples may unravel structural changes of the neuromuscular layer involving the whole gut, although the midgut is usually worst affected. Intestinal pseudo-obstruction can occur in association with systemic neurological, endocrine, and connective tissue diseases or malignancy but, when no recognizable etiology is found, CIPO is referred to as idiopathic (CIIPO). The latter form can be diagnosed early in life due to a genetic etiology or in adulthood when a viral origin may be considered. This review addresses the hypothesis that some systemic neurotrophic viral infections can affect the enteric nervous system thereby altering normal peristaltic activity. Available data are reviewed, focusing specifically on herpesviruses or polyomaviruses (JC virus). These suggest that in comparison to a proportion of CIIPO patients, healthy controls rarely harbor viral DNA in the myenteric plexus, leaving open the possibility that a viral infection might have an etiologic role in the development of CIIPO. The review thus provides some new perspectives in the pathophysiology and perhaps targeted treatment of CIIPO.
Kinnear, D. G.; Johns, D. G.; MacIntosh, P. C.; Burgen, A. S. V.; Cameron, D. G.
The intestinal absorption of folic acid in patients with idiopathic steatorrhea was studied by the oral administration of tritium-labelled folic acid in a dosage of 15 μg./kg. Results were expressed as a percentage of the orally administered folic acid radioactivity excreted in the urine over 24 hours. The mean excretion of radioactivity in 38 normal subjects was 48.2 ± 16.6% (mean ± SD), whereas eight patients with untreated idiopathic steatorrhea excreted only 16.7 ± 3.4% (mean ± SE). The ability of the gluten-free diet to correct this absorptive defect was demonstrated by the finding of normal values in 11 patients in complete clinical remission for periods exceeding six months after institution of the diet. Serial studies in individual patients indicated that a significant improvement was obtainable in as short a period as two weeks following exclusion of gluten from the diet. PMID:14077269
Objectives This report describes the case of a patient with chronic idiopathic meralgia paresthetica associated with bilateral sacroiliac joint dysfunction who was managed with chiropractic care. Clinical Features A 35-year-old white woman presented to a private chiropractic clinic with a complaint of numbness in the right anterolateral thigh region. Neurological assessment revealed a diminution of sensibility and discrimination on the right lateral femoral cutaneous nerve territory. Pain was rated as 8.5 on a numeric pain scale of 0 to 10. Musculoskeletal examination of the pelvic region disclosed bilateral sacroiliac joint dysfunction. Intervention and Outcomes Chiropractic management included pelvic mobilizations, myofascial therapy, transverse friction massage, and stretching exercises. After 3 visits (2 weeks later), result of neurological evaluation was normal, with no residual numbness over the lateral thigh. Conclusion In the present case, chiropractic management with standard and applied kinesiology techniques resulted in recovery of meralgia paresthetica symptoms for this patient. PMID:22942840
Canan, Fatih; Karakaş, Ayşe Akman; Geçici, Nihal
Introduction Psychosocial factors have been implicated as being important in the onset and/or exacerbation of urticaria. Aim To examine both personality factors of patients with chronic idiopathic urticaria (CIU) and the correlations between illness duration, severity of itching, urticaria activity score (UAS) and temperament-character dimensions. Material and methods A total number of 70 CIU patients and 60 healthy individuals were included in the study. The Temperament and Character Inventory (TCI) was administered individually. The relationship between UAS, illness duration and severity of pruritus and TCI subscales were evaluated. Results The CIU group had significantly higher scores of novelty seeking and lower scores of cooperativeness, reward dependence and self-directedness than the control group. Conclusions The current study shows that CIU patients have distinctive temperament and character dimensions when compared with the control group. We suggest that evaluation and treatment of CIU should also include psychosomatic approaches in clinical practice. PMID:26161056
This report describes the case of a patient with chronic idiopathic meralgia paresthetica associated with bilateral sacroiliac joint dysfunction who was managed with chiropractic care. A 35-year-old white woman presented to a private chiropractic clinic with a complaint of numbness in the right anterolateral thigh region. Neurological assessment revealed a diminution of sensibility and discrimination on the right lateral femoral cutaneous nerve territory. Pain was rated as 8.5 on a numeric pain scale of 0 to 10. Musculoskeletal examination of the pelvic region disclosed bilateral sacroiliac joint dysfunction. Chiropractic management included pelvic mobilizations, myofascial therapy, transverse friction massage, and stretching exercises. After 3 visits (2 weeks later), result of neurological evaluation was normal, with no residual numbness over the lateral thigh. In the present case, chiropractic management with standard and applied kinesiology techniques resulted in recovery of meralgia paresthetica symptoms for this patient.
Cornaggia, Matteo; Leutner, Monica; Mescoli, Claudia; Sturniolo, Giacomo Carlo; Gullotta, Renzo
The incidence of chronic idiopathic inflammatory bowel diseases (IBD) is growing in western countries, making their histological diagnosis an everyday task for all pathologists. Reviews from the literature strongly suggest that such diagnosis cannot be performed on the histological ground alone but requires a clinical-pathological approach. Moreover, bewildering variations can be observed in the terminology employed to report either individual lesions or diagnostic categories. The aim of the present paper is to suggest a practical diagnostic algorithm summarizing the main data from the literature. Particular emphasis has been placed on minimum clinical information required and the accurate definition of individual lesions. Diagnostic categories to employ and to avoid in daily practice have furthermore been stressed.
de Vries, J; Baarsma, G S; Zaal, M J; Boen-Tan, T N; Rothova, A; Buitenhuis, H J; Schweitzer, C M; de Keizer, R J; Kijlstra, A
In a randomised double-masked study of 27 patients with a severe chronic idiopathic uveitis we evaluated the efficacy, safety, and tolerability of cyclosporin. All received prednisone in a low dose (0.3 mg/kg/day). In 14 patients this was combined with cyclosporin in a single daily dose of 10 mg/kg/day, while 13 patients received a placebo. The dosages were tapered off in accordance with a protocol, and we compared the number of months of successful therapy before the uveitis relapsed. The efficacy results, as expressed in a Kaplan-Meier curve, were in favour of cyclosporin. Owing to the small sample size, however, this difference did not reach statistical significance. The immunosuppressive effect of cyclosporin was not permanent, and in all but one patient the intraocular inflammation relapsed on reduction of dosage. Rather small cumulative doses of cyclosporin proved to be nephrotoxic, but subjective tolerability for cyclosporin was good. PMID:2198928
Mosińska, Paula; Fichna, Jakub; Storr, Martin
Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.
Khairullah, S; Jasmin, R; Yahya, F; Cheah, T E; Ng, C T; Sockalingam, S
Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome of ineffective intestinal motility characterised by clinical and radiological evidence of intestinal obstruction with no identifiable mechanical lesion. CIPO can either be idiopathic or secondary to a systemic disease, like systemic lupus erythematosus (SLE). Fewer than 30 cases of CIPO secondary to SLE have been reported so far. Here we describe a case of SLE with the initial presentation of CIPO. In SLE-related CIPO, treatment includes a combination of high-dose intravenous corticosteroids, immunosuppressants and supportive care. With awareness of this condition, unnecessary surgical intervention and repeated invasive procedures could be avoided. Early initiation of treatment would avoid complications and bring about resolution of symptoms.
Fan, X; Sellin, J H
Chronic watery diarrhoea is one of the most common symptoms prompting GI evaluation. Recently, new diagnostic considerations have emerged as possible factors in chronic diarrhoea. To review available data regarding diagnosis and treatment of chronic diarrhoea with an emphasis on bacterial overgrowth and bile acid malabsorption. A systematic search of the English language literature of chronic diarrhoea was performed focused on three possible aetiologies of diarrhoea: small intestinal bacterial overgrowth (SIBO), idiopathic bile salt malabsorption (IBAM), gluten responsive enteropathy. Recent studies suggest that SIBO and bile acid malabsorption may have been underestimated as possible causes of chronic watery diarrhoea. Gluten intolerance with negative coeliac serology is a contentious possible cause of watery diarrhoea, but requires further research before acceptance as an entity. In patients with otherwise unexplained chronic watery diarrhoea, small intestinal bacterial overgrowth and bile salt malabsorption should be considered and investigated.
Hoeper, Marius M.; Behr, Juergen; Held, Matthias; Grunig, Ekkehard; Vizza, C. Dario; Vonk-Noordegraaf, Anton; Lange, Tobias J.; Claussen, Martin; Grohé, Christian; Klose, Hans; Olsson, Karen M.; Zelniker, Thomas; Neurohr, Claus; Distler, Oliver; Wirtz, Hubert; Opitz, Christian; Huscher, Doerte; Pittrow, David; Gibbs, J. Simon R.
Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP. Conclusions Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival. Trial Registration clinicaltrials.gov NCT01347216 PMID:26630396
Illuminati, G; Caliò, F G; D'Urso, A; Papaspyropoulos, V; Mancini, P; Ceccanei, G; Vietri, F
Due to the rarity of the condition, large and prospective series defining the optimal method of digestive arteries revascularization, for the treatment of chronic intestinal ischemia, are lacking. The aim of this consecutive sample clinical study was to test the hypothesis that flexible application of different revascularization methods, according to individual cases, will yield the best results in the management of chronic intestinal ischemia. Eleven patients, of a mean age of 57 years, underwent revascularization of 11 digestive arteries for symptomatic chronic mesenteric occlusive disease. Eleven superior mesenteric arteries and one celiac axis were revascularized. The revascularization techniques included retrograde bypass grafting in 7 cases, antegrade bypass grafting in 2, percutaneous arterial angioplasty in 1, and arterial reimplantation in one case. The donor axis for either reimplantation or bypass grafting was the infrarenal aorta in 4 cases, an infrarenal Dacron graft in 4, and the celiac aorta in one case. Grafting materials included 5 polytetrafluoroethylene (PTFE) and 3 Dacron grafts. Concomitant procedures included 3 aorto-ilio-femoral grafts and one renal artery revascularization. Mean follow-up length was 31 months. There was no operative mortality. Cumulative survival rate was 88.9% at 36 months (SE 12.1%). Primary patency rate was 90% at 36 months (SE 11.6%). The symptom free rate was 90% at 36 months (SE 11.6%). Direct reimplantation, antegrade and retrograde bypass grafting, all allow good mid-term results: the choice of the optimal method depends on the anatomic and general patients status. Associated infrarenal and renal arterial lesions can be safely treated in the same time of digestive revascularization. Angioplasty alone yields poor results and should be limited to patients at poor risk for surgery.
Wilders, M M; Drexhage, H A; Kokjé, M; Verspaget, H W; Meuwissen, S G
Antigen presenting veiled cells have recently been described in cell suspensions prepared from the gut wall of patients with chronic idiopathic inflammatory bowel disease (CIBD). The normal gut wall is virtually devoid of these cells. In this report we describe a phenomenon known as peripolesis studied by phase contrast cinematography. This is a process in which lymphocytes are seen to wander around larger target cells. These could be identified ultrastructurally as Ia positive veiled cells. In most cases peripolesis was followed by lysis of the target cell. Peripolesis was recorded in cell suspensions of three out of seven patients with ulcerative colitis and in three out of nine patients with Crohn's disease; furthermore peripolesis was observed in one out of two patients with non-classifiable CIBD. In four cell suspensions showing peripolesis, cell lysis could be recorded and was especially striking in ulcerative colitis. Peripolesis involving veiled cells was previously described in delayed hypersensitivity reactions. This study lends support to the concept that delayed allergic reactivity plays a part in chronic inflammatory bowel disease. The antigens involved are, however, completely unknown. Images Fig. 1 Fig. 2 Fig. 3 PMID:6380839
Volkmann, M; Wirtherle, N C; Beddies, G F; Kohn, B
Chronic idiopathic enteropathies (CIE) in dogs are complex diseases of unknown origin. AST-120 is a spherical carbon adsorbent preparation with a high adsorption ability for low molecular substances. Evaluation of the clinical efficacy of AST-120 in dogs with CIE. Ten client-owned dogs with mild (n = 7) to moderate (n = 3) CIE. Explorative, prospective, randomized, placebo-controlled, double-blinded pilot study. Dogs with chronic diarrhea and no or insufficient response to an elimination diet were included. The dogs received either AST-120 (n = 5) or placebo (n = 5) for a duration of 21 days. The canine inflammatory bowel disease activity index (CIBDAI) was used to assess disease severity at baseline and clinical outcome after 3 weeks of treatment. Furthermore, changes in body weight and the parameters stool consistency and frequency were compared within and between groups. The mean CIBDAI score decreased from 5.6 (SD 1.5) to 2.0 (SD 1.2) in the AST-120 group (P = .125) and from 4.8 (SD .8) to 3.6 (SD 2.3) in the placebo group (P = .688). Compared with baseline, posttreatment CIBDAI scores decreased more than 60% in 4/5 dogs treated with AST-120 and in 1/5 dogs treated with placebo (P = .206). Changes in CIBDAI scores, body weights, stool consistency, and frequency within and between groups did not achieve statistical significance after 3 weeks of treatment. No adverse effects of AST-120 were noted. This study investigated potential efficacy of AST-120 as an alternative therapy in dogs with mild-to-moderate CIE. Copyright © 2013 by the American College of Veterinary Internal Medicine.
Cohn, Jonathan A; Neoptolemos, John P; Feng, Jinong; Yan, Jin; Jiang, Zefei; Greenhalf, William; McFaul, Christopher; Mountford, Roger; Sommer, Steve S
Cystic fibrosis (CF) is a recessive disease caused by mutations of the CF transmembrane conductance regulator (CFTR) gene. The risk of idiopathic chronic pancreatitis (ICP) is increased in individuals who have CFTR genotypes containing a CF-causing mutation plus a second pathogenic allele. It is unknown whether the risk of ICP is increased in CF carriers who have one CF-causing mutation plus one normal allele. In this study, 52 sporadic cases of ICP were ascertained through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer. Individuals with pathogenic cationic trypsinogen mutations were excluded. DNA was comprehensively tested for CFTR mutations using a robotically enhanced, multiplexed, and highly redundant form of single-strand conformation polymorphism (SSCP) analysis followed by DNA sequencing. Fifteen subjects had a total of 18 pathogenic CFTR alleles. Eight subjects had common CF-causing mutations. This group included seven CF carriers in whom the second CFTR allele was normal (4.3 times the expected frequency, P=0.0002). Three subjects had compound heterozygotes genotypes containing two pathogenic alleles (31 times the expected frequency, P<0.0001). A variant allele of uncertain significance (p.R75Q) was detected in eight of the 52 ICP subjects and at a similar frequency (13/96) in random donors. ICP differs from other established CFTR-related conditions in that ICP risk is increased in CF carriers who have one documented normal CFTR allele. Having two CFTR mutations imparts a higher relative risk, while having only one mutation imparts a higher attributable risk.
Hawe, Emma; McBride, Doreen; Balp, Maria-Magdalena; Tian, Haijun; Halliday, Anna; Stull, Donald E
To obtain utility estimates suitable for use in economic models for chronic spontaneous (idiopathic) urticaria (CSU). Patient-level data from three randomized clinical trials-ASTERIA I, ASTERIA II and GLACIAL-were analysed. Health states were derived from the Urticaria Activity Score over 7 days (UAS7); higher scores denote greater activity. The health state score ranges were urticaria free: 0; well-controlled urticaria: 1-6; mild urticaria: 7-15; moderate urticaria: 16-27; and severe urticaria: 28-42. The mean EQ-5D utilities were calculated for each health state. A mixed model was used to predict the EQ-5D according to UAS7 health states in a pooled data set containing all treatment arms and time points from the three trials. Pooled trial data were validated through visual comparisons and interaction terms. Fixed and random effects for trials and patients were included, along with the following covariates: UAS7 health state at baseline (moderate or severe); presence of angioedema at baseline and during follow-up; duration of CSU; number of previous CSU medications; visit; current treatment; and patient age and sex. There was a consistent improvement in EQ-5D utilities as urticaria activity decreased. The mean utilities ranged from 0.710 (severe urticaria) to 0.780 (moderate urticaria), 0.829 (mild urticaria), 0.862 (well-controlled urticaria) and 0.894 (urticaria free). Sensitivity and subgroup analyses confirmed the robustness of the results. The results suggest that EQ-5D utility scores increase with decreasing urticaria activity. EQ-5D utility scores enable the health-related quality of life of CSU patients to be compared with that of patients with other diseases.
Chrobák, L; Voglová, J
Idiopathic hypereosinophilic syndrome is a heterogenous group of hematological disorders characterized by eosinophilia (> 1.5 x 10(9)/l) persistent for more than 6 months, exclusion of reactive eosinophilia from other causes, such as parasitic infections or allergy, and evidence of end-organ damage. According to World Health Organization the exclusion includes all neoplastic disorders in which eosinophils are part of the neoplastic clone. Excluded should be also T cell population with aberant phenotype and abnormal cytokine production, recently considert also as "lymphocytic" variants of the HES . HES has to be reclassified as chronic eosinophilic leukemia (CEL) when there is evidence for clonality based on the presence of chromosomal abnormalities or inactivation of X-chromosome in female patients. The successful empiric treatment of patients with tyrosine kinase inhibitor imatinib (Glivec) suggested the presence of an imatinib-sensitive tyrosine kinase inhibitor. The identification of a specific intersticial chromosome deletion del(4)(q12;q12) creating the FIP1L1-PDGFRA fusion gene confirmed this hypothesis. Patients carrying this gene should be reclassified as CEL and detection of this gene is a positive predictor for response to imatinib therapy. Effective doses of imatinib are 100 mg/day. The side effects are minimal. The only exception is an acute left ventricular dysfunction which has been reported in three patients within the first week of treatment with imatinib. Imatinib has been successfully used also in some patients with the constitutively activated thyrosine kinase ETV6-PDGFRbeta  and in systemic mast cell disease associated with eosinophilia. Other therapeutical options for HES/CEL have been mentioned. The resistence to imatinib and the possibilities how to overcome it are discussed.
Schiller, L.R.; Hogan, R.B.; Morawski, S.G.; Santa Ana, C.A.; Bern, M.J.; Norgaard, R.P.; Bo-Linn, G.W.; Fordtran, J.S.
We studied radiolabeled fecal bile acid excretion in 11 normal subjects and 17 patients with idiopathic chronic diarrhea for three major purposes: to establish normal values for this test in the presence of increased stool volumes (induced in normal subjects by ingestion of poorly absorbable solutions); to test for bile acid malabsorption in the patients and to correlate this with an independent test of ileal function, the Schilling test; and to compare the results of the bile acid excretion test with the subsequent effect of a bile acid binding agent (cholestyramine) on stool weight. In normal subjects fecal excretion of the radiolabel was increased with increasing stool volumes. As a group, patients with idiopathic chronic diarrhea excreted radiolabeled bile acid more rapidly than normal subjects with induced diarrhea (t1/2 56 +/- 8 vs. 236 +/- 60 h, respectively, p less than 0.005). There was a statistically significant positive correlation between t1/2 of radiolabeled bile acid and Schilling test results in these patients. Although 14 of 17 patients absorbed labeled taurocholic acid less well than any of the normal subjects with comparable volumes of induced diarrhea, cholestyramine had no statistically significant effect on stool weight in the patient group, and in none of the patients was stool weight reduced to within the normal range. In summary, most patients with idiopathic chronic diarrhea have bile acid malabsorption (as measured by fecal excretion of labeled bile acid), but they do not respond to cholestyramine therapy with a significant reduction in stool weight. Although the significance of these findings was not clearly established, the most likely interpretation is that bile acid malabsorption is a manifestation of an underlying intestinal motility or absorptive defect rather than the primary cause of diarrhea.
Saad, Richard; Chey, William D
Lubiprostone, a locally acting highly selective type-2 chloride channel activator, has been US FDA approved since January 2006 for the treatment of adults with chronic idiopathic constipation and FDA approved since April 2008 for the treatment of woman aged 18 years or older suffering from irritable bowel syndrome (IBS) with constipation. Through activation of the type-2 chloride channels located on the luminal side of intestinal epithelial cells, it promotes fluid secretion, increasing the liquid content of stool and accelerating small bowel as well as colonic transit. Lubiprostone has demonstrated efficacy with respect to increasing weekly spontaneous bowel movements and improving stool consistency, straining and constipation severity, both in short- and long-term studies. It has also demonstrated efficacy in the treatment of IBS with constipation, with beneficial effects on global symptoms, abdominal pain, constipation-related symptoms and overall quality of life. There is no evidence of a rebound in constipation or IBS symptoms following cessation of lubiprostone. In general, lubiprostone is well tolerated, with the most common side effects including nausea, headache and diarrhea.
Phillips, A D; Thomas, A G; Walker-Smith, J A
The association between Cryptosporidium, chronic diarrhoea and a proximal small intestinal mucosal enteropathy was reviewed over a six and a half year period. One hundred and twenty three children with cryptosporidiosis and no clinical evidence of immune deficiency were identified. 50% of children excreting only Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea occurred in the first two years of life. A mild to moderate enteropathy was present in all nine children undergoing a small intestinal biopsy and seven showed the presence of Cryptosporidium adhering to villous epithelium. All patients eventually recovered spontaneously. Cryptosporidium is a cause of chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children without immune deficiency. Screening for the parasite should be part of the investigative procedures in children with chronic diarrhoea. Images Figure 4 PMID:1398230
Muñoz-Yagüe, M T; Marín, J C; Colina, F; Ibarrola, C; López-Alonso, G; Martín, M A; Solís-Herruzo, J A
Chronic intestinal pseudo-obstruction is an uncommon syndrome characterized by relapsing episodes suggesting intestinal obstruction during which no mechanical causes are identified to account for symptoms. Etiologic factors may be manifold. Among them a number of neurologic conditions, gastrointestinal smooth muscle myopathies, endocrino-metabolic and autoimmune diseases, and the use of selected drugs stand out. We report a case of chronic intestinal pseudo-obstruction originating in a sporadic, primary intestinal myopathy that corresponds to no type thus far described. A histological study of the intestinal wall showed disrupted muscle bundles and the presence of interstitial edema. Myocytes had severe degenerative changes, and no alterations were seen in submucosal and myenteric plexus neurons. The activity of enzyme complexes in the mitochondrial respiratory chain, and of thymidine phosphorylase was normal. No mitochondrial DNA changes were seen.
Uchida, Keiichi; Otake, Kohei; Inoue, Mikihiro; Koike, Yuhki; Matsushita, Kohei; Araki, Toshimitsu; Okita, Yoshiki; Tanaka, Koji; Uchida, Katsunori; Yodoya, Noriko; Iwamoto, Shotaro; Arai, Katsuhiro; Kusunoki, Masato
Lymphocytic intestinal leiomyositis is a rare entity, which causes chronic intestinal pseudo-obstruction (CIPO) in children. We present the first case of a boy who had pure red cell anemia 1 year before onset. Prolonged ileus developed after gastroenteritis and the patient was diagnosed using a biopsy of the intestinal wall. Findings from the present case indicate that there are three important factors for accurate diagnosis: history of enteritis, positive serum smooth muscle antibody, and lymphocyte infiltration with muscle destruction in the muscularis propria in the intestinal wall. Earlier diagnosis and induction of immunosuppressive therapy may be essential for a better outcome.
Sabatino, Alice; Regolisti, Giuseppe; Cosola, Carmela; Gesualdo, Loreto; Fiaccadori, Enrico
Diabetes mellitus is a major cause of kidney disease [chronic kidney disease (CKD) and end-stage renal disease (ESRD)] and are both characterized by an increased risk of cardiovascular events. Diabetes and kidney disease are also commonly associated with a chronic inflammatory state, which is now considered a non-traditional risk factor for atherosclerosis. In the case of type 2 diabetes mellitus (T2DM), inflammation is mainly a consequence of visceral obesity, while in the case of CKD or ESRD patients on dialysis, inflammation is caused by multiple factors, classically grouped as dialysis-related and non-dialysis-related. More recently, a key role has been credited to the intestinal microbiota in the pathogenesis of chronic inflammation present in both disease states. While many recent data on the intestinal microbiota and its relationship to chronic inflammation are available for CKD patients, very little is known regarding T2DM and patients with diabetic nephropathy. The aim of this review is to summarize and discuss the main pathophysiological issues of intestinal microbiota in patients with T2DM and CKD/ESRD. The presence of intestinal dysbiosis, along with increased intestinal permeability and high circulating levels of lipopolysaccharides, a condition known as "endotoxemia," characterize T2DM, CKD, and ESRD on dialysis. The hallmark of intestinal dysbiosis is a reduction of saccharolytic microbes mainly producing short-chain fatty acids (SCFA) and, in the case of CKD/ESRD, an increase in proteolytic microbes that produce different substances possibly related to uremic toxicity. Dysbiosis is associated with endotoxemia and chronic inflammation, with disruption of the intestinal barrier and depletion of beneficial bacteria producing SCFAs. T2DM and CKD/ESRD, whose coexistence is increasingly found in clinical practice, share similar negative effects on both intestinal microbiota and function. More studies are needed to characterize specific alterations of the
Chronic idiopathic urticaria (CIU) is a disabling affliction that considerably limits patients' daily activities and interferes with sleep. Clinical studies have shown that histamine H1-receptor antagonists (antihistamines) are highly effective for inhibiting the hives/wheals and pruritus associated with CIU, as well as improving patients' quality of life. Desloratadine is a rapid-acting, once-daily, nonsedating selective H1-receptor antagonist/inverse receptor agonist with proven clinical efficacy in patients with CIU. It has 10-20 times the in vivo H1 receptor-binding affinity of loratadine, its parent compound, and 52-194 times the H1 receptor-binding affinity of cetirizine, ebastine, loratadine, and fexofenadine. Desloratadine displays linear pharmacokinetics after oral administration. Age and sex have no apparent effect on the drug's metabolism and elimination, and food does not affect its bioavailability or absorption. Desloratadine also exerts anti-inflammatory effects via mechanisms that are independent of H1-receptor antagonism. Results from randomized, double-blind, placebo-controlled studies of 6 weeks' duration in adults and adolescents with moderate-to-severe CIU indicate that desloratadine significantly minimizes the severity of pruritus, reduces the number and size of hives, and improves disease-impaired sleep and daily activities. Improvements were noted after a single dose of desloratadine and were maintained over 6 weeks of treatment. Desloratadine was safe and well tolerated in clinical trials of patients with CIU. The adverse effect profile of desloratadine in adults, as well as in children aged from 6 months to 11 years, is comparable to that of placebo. Evaluations of cognitive and psychomotor performance in adults indicate no impairment of function with dosages of desloratadine 5 mg/day. In conclusion, desloratadine is an important therapeutic option for prompt and enduring symptom relief in patients with moderate-to-severe CIU. In addition
Hohmann, Nicole; Walker, Charlotte
Focus Areas: Integrative Approaches to Care, Pediatrics, Alleviating Pain Juvenile idiopathic arthritis (JIA) patients and their parents have a high propensity to use complementary therapies to relieve pain. Medications and exercise therapy are a cornerstone of conventional treatment with a substantial rate of inadequate pain relief and the potential of side effects from pharmaceuticals. This session will highlight the evidence behind treating intestinal permeability to reduce pain from JIA.
Tonacci, Alessandro; Billeci, Lucia; Pioggia, Giovanni; Navarra, Michele; Gangemi, Sebastiano
Omalizumab is recombinant humanized monoclonal antibody to immunoglobulin E. Guidelines for the treatment of chronic idiopathic urticaria (also known as chronic spontaneous urticaria) recommend the use of omalizumab as third-line therapy in addition to high doses of histamine receptor type 1 (H1 ) antihistamines when they are unsuccessful as first- and second-line therapy. We performed a systematic review of the literature to identify studies that evaluated the efficacy of omalizumab for the treatment of chronic idiopathic urticaria, in both controlled and real-world settings, to assess its potential role as a preferred therapy. The PubMed, ScienceDirect, LILACS (Latin American and Caribbean Health Sciences Literature), and Google Scholar databases were searched between January 1, 2000, and November 21, 2016. The search was limited to articles published in peer-reviewed journals in the English language, and 29 studies were included in this review. Omalizumab 300 mg administered every 4 weeks appears to be the most effective and safe dosage, with a rapid response time, for the treatment of chronic idiopathic urticaria, with few minor adverse effects, and appears to be safe in the offspring of pregnant patients who received the drug. However, as published studies of omalizumab are sparse, future studies are warranted. When findings are confirmed in larger studies, due to its efficacy, safety, and increased benefit/cost ratio, omalizumab could become the preferred method of treatment for chronic idiopathic urticaria in patients unresponsive to H1 antihistamines.
Li, Qiurong; Zhang, Qiang; Wang, Chenyang; Tang, Chun; Zhang, Yanmei; Li, Ning; Li, Jieshou
The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.
Kadowaki, H; Ouchi, M; Kaga, M; Motegi, T; Yanagawa, Y; Hayakawa, H; Hashimoto, G; Furuya, K
An 8-year-old girl with chronic idiopathic intestinal pseudo-obstruction (CIIP), who is the first case of CIIP in Japan, has been receiving total parenteral nutrition (TPN) for more than 6 years. During this time, she experienced deficiencies of copper, zinc, vitamin A, vitamin B12, folic acid, and biotin, and an excess of vitamin A; she exhibited a series of signs and symptoms due to these deficiencies and vitamin A overdosage. Nevertheless, careful monitoring of serum levels of trace elements and vitamins and appropriate therapy have almost solved these problems. She has achieved normal physical and mental development and goes to school, while receiving home parenteral nutrition with an ambulatory infusion system.
Leake, Hayley B.; Chalmers, K. Jane; Moseley, G. Lorimer
Background Despite common use of proprioceptive retraining interventions in people with chronic, idiopathic neck pain, evidence that proprioceptive dysfunction exists in this population is lacking. Determining whether proprioceptive dysfunction exists in people with chronic neck pain has clear implications for treatment prescription. Purpose The aim of this study was to synthesize and critically appraise all evidence evaluating proprioceptive dysfunction in people with chronic, idiopathic neck pain by completing a systematic review and meta-analysis. Data Sources MEDLINE, CINAHL, PubMed, Allied and Complementary Medicine, EMBASE, Academic Search Premier, Scopus, Physiotherapy Evidence Database (PEDro), and Cochrane Collaboration databases were searched. Study Selection All published studies that compared neck proprioception (joint position sense) between a chronic, idiopathic neck pain sample and asymptomatic controls were included. Data Extraction Two independent reviewers extracted relevant population and proprioception data and assessed methodological quality using a modified Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Data Synthesis Thirteen studies were included in the present review. Meta-analysis on 10 studies demonstrated that people with chronic neck pain perform significantly worse on head-to-neutral repositioning tests, with a moderate standardized mean difference of 0.44 (95% confidence interval=0.25, 0.63). Two studies evaluated head repositioning using trunk movement (no active head movement thus hypothesized to remove vestibular input) and showed conflicting results. Three studies evaluated complex or postural repositioning tests; postural repositioning was no different between groups, and complex movement tests were impaired only in participants with chronic neck pain if error was continuously evaluated throughout the movement. Limitations A paucity of studies evaluating complex or postural repositioning
Ahn, Jung Yong; Kwon, Seong Oh; Shin, Moon Soo; Joo, Jin Yang; Kim, Tai Sung
Idiopathic trigeminal sensory neuropathy is a clinically benign disorder in which the main feature is facial numbness limited to the territory of one or more divisions of the trigeminal nerve; the disorder persists for a few weeks to several years. and no underlying disease can be identified. Magnetic resonance (MR) imaging findings are occasionally consistent with a small trigeminal neuroma of the left gasserian ganglion associated with idiopathic trigeminal sensory neuropathy. The authors report on two patients who were treated using a skull base approach in which the gasserian ganglion was exposed and the lesion was removed. The pathological diagnosis was chronic granulomatous neuritis. The authors conclude that, in patients with MR findings suggestive of a small trigeminal neuroma, benign idiopathic trigeminal sensory neuropathy should also be considered in the differential diagnosis. A conservative approach featuring sequential MR imaging studies may avoid an unnecessary surgical exploration.
Heneyke, S; Smith, V; Spitz, L; Milla, P
AIMS—To document the long term course of chronic idiopathic intestinal pseudo-obstruction syndrome (CIIPS) in children with defined enteric neuromuscular disease, and the place and type of surgery used in their management; in addition, to identify prognostic factors. METHODS—Children with CIIPS were investigated and treated prospectively. RESULTS—Twenty four children presented congenitally, eight during the 1st year of life, and 10 later. Twenty two had myopathy and 16 neuropathy (11 familial). Malrotation was present in 16 patients, 10 had short small intestine, six had non-hypertrophic pyloric stenosis, and 16 had urinary tract involvement. Thirty two patients needed long term parenteral nutrition (TPN): for less than six months in 19 and for more than six months in 13, 10 of whom are TPN dependent; 14 are now enteral feeding. Prokinetic treatment improved six of 22. Intestinal decompression stomas were used in 36, colostomy relieved symptoms in five of 11, and ileostomy in 16 of 31. A poor outcome (death (14) or TPN dependence (10)) was seen with malrotation (13 of 16), short small bowel (eight of nine), urinary tract involvement (12 of 16), and myopathic histology (15 of 22). CONCLUSIONS—In CIIPS drugs are not helpful but decompression stomas are. Outcome was poor in 24 of 44 children (15 muscle disorder, 10nerve disease). PMID:10373127
Izzi, Jessica M; Beck, Sarah E; Adams, Robert J; Metcalf Pate, Kelly A; Hutchinson, Eric K
Chronic diarrhea poses a significant threat to the health of NHP research colonies, and its primary etiology remains unclear. In macaques, the clinical presentation of intractable diarrhea and weight loss that are accompanied by inflammatory infiltrates within the gastrointestinal tract closely resembles inflammatory bowel disease of humans, dogs, and cats, in which low serum and tissue cobalamin (vitamin B12) levels are due to intestinal malabsorption. We therefore hypothesized that macaques with chronic idiopathic diarrhea (CID) have lower serum cobalamin concentrations than do healthy macaques. Here we measured serum cobalamin concentrations in both rhesus and pigtailed macaques with CID and compared them with those of healthy controls. Serum cobalamin levels were 2.5-fold lower in pigtailed macaques with CID than control animals but did not differ between rhesus macaques with CID and their controls. This finding supports the use of serum cobalamin concentration as an adjunct diagnostic tool in pigtailed macaques that present with clinical symptoms of chronic gastrointestinal disease. This use of serum vitamin B12 levels has implications for the future use of parenteral cobalamin supplementation to improve clinical outcomes in this species. PMID:27538863
DuPont, Andrew W; DuPont, Herbert L
Mucosal surfaces of the gut are colonized by large numbers of heterogeneous bacteria that contribute to intestinal health and disease. In genetically susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut flora contributes to alterations in the mucosa and local immune system leading to gastrointestinal disease. These diseases include enteric infections, such as Clostridium difficile infection, small intestinal bacterial overgrowth, functional gastrointestinal disorders (including IBS), IBD and colorectal cancer. Prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) have the capacity to reverse pathologic changes in gut flora and local immunity. Intestinal health and disease need to be thoroughly characterized to understand the interplay between the indigenous microbiota, the immune system and genetic host factors. This Review provides a broad overview of the importance of the intestinal microbiota in chronic disorders of the gut.
Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A. )
Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.
Li, Qiurong; Zhang, Qiang; Wang, Chenyang; Tang, Chun; Zhang, Yanmei; Li, Ning; Li, Jieshou
Background The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. Methods/Principal Findings The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. Conclusions/Significance Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation. PMID:21698145
Bisset, W M; Stapleford, P; Long, S; Chamberlain, A; Sokel, B; Milla, P J
In children with severe failure of intestinal function, intravenous nutrition is at present the only treatment able to maintain adequate nutrition for prolonged periods of time. Over the last five years we have discharged 10 patients home on parenteral nutrition for a total of 25 patient years and here the outcome of these children is presented. Of the 10 patients, one has discontinued home parenteral nutrition (HPN), seven patients remain well, one patient has recently moved to the USA, and one patient has died after major abdominal surgery. All children had either normal or an accelerated rate of growth on HPN and developmentally all have progressed well. All the children over 5 years attend normal schools. The major complication of treatment was line sepsis with an overall rate of one episode in 476 days and a total of nine central lines (five patients) have required replacement giving an average line life of 680 days. For those children unfortunate enough to suffer from severe intestinal failure, HPN is preferable to prolonged hospital treatment and offers the chance of a good quality of life with prolonged survival. PMID:1739322
Sabatino, Alice; Regolisti, Giuseppe; Brusasco, Irene; Cabassi, Aderville; Morabito, Santo; Fiaccadori, Enrico
Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.
Baker, Danial E
Lubiprostone offers an additional alternative for patients with chronic idiopathic constipation. Lubiprostone is more efficacious than placebo in the treatment of chronic idiopathic constipation. In placebo-controlled clinical trials, lubiprostone therapy was generally well tolerated and was not associated with severe adverse effects; however, the high incidence of nausea may be problematic for some patients. The nausea may be alleviated or minimized by administering the dose with food, and some patients may require a dosage reduction to 24 mug once daily. The key limitations of the placebo-controlled clinical trials include the absence of information regarding the duration of the constipation and previous types of therapies that had been used to treat the constipation and the absence of an active control group. Comparative studies with other therapies (eg, saline laxatives, polyethylene glycol) used for constipation are necessary to determine the clinical and economic value of this agent relative to other forms of therapy.
Kim, Jung-Eun; Seo, Byung-Kwan; Choi, Jin-Bong; Kim, Hyeong-Jun; Kim, Tae-Hun; Lee, Min-Hee; Kang, Kyung-Won; Kim, Joo-Hee; Shin, Kyung-Min; Lee, Seunghoon; Jung, So-Young; Kim, Ae-Ran; Shin, Mi-Suk; Jung, Hee-Jung; Park, Hyo-Ju; Kim, Sung-Phil; Baek, Yong-Hyeon; Hong, Kwon-Eui; Choi, Sun-Mi
The causes of chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) are not clearly known, and there are no definitive treatments for them. Therefore, patients with CFS and ICF are interested in Oriental medicine or complementary and alternative medicine. For this reason, the effectiveness of complementary and alternative treatments should be verified. We investigated the effectiveness of two forms of acupuncture added to usual care for CFS and ICF compared to usual care alone. A three-arm parallel, non-blinded, randomized controlled trial was performed in four hospitals. We divided 150 participants into treatment and control groups at the same ratio. The treatment groups (Group A, body acupuncture; Group B, Sa-am acupuncture) received 10 sessions for 4 weeks. The control group (Group C) continued usual care alone. The primary outcome was the Fatigue Severity Scale (FSS) at 5 weeks after randomization. Secondary outcomes were the FSS at 13 weeks and a short form of the Stress Response Inventory (SRI), the Beck Depression Inventory (BDI), the Numeric Rating Scale (NRS), and the EuroQol-5 Dimension (EQ-5D) at 5 and 13 weeks. Group A showed significantly lower FSS scores than Group C at 5 weeks (P = 0.023). SRI scores were significantly lower in the treatment groups than in the control group at 5 (Group A, P = 0.032; B, P <0.001) and 13 weeks (Group A, P = 0.037; B, P <0.001). Group B showed significantly lower BDI scores than Group C at 13 weeks (P = 0.007). NRS scores from the treatment groups were significantly reduced compared to control at 5 (Group A and B, P <0.001) and 13 weeks (Group A, P = 0.011; B, P = 0.002). Body acupuncture for 4 weeks in addition to usual care may help improve fatigue in CFS and ICF patients. Clinical Research Information Service (CRIS) KCT0000508; Registered on 12 August 2012.
Pironi, Loris; Arends, Jann; Bozzetti, Federico; Cuerda, Cristina; Gillanders, Lyn; Jeppesen, Palle Bekker; Joly, Francisca; Kelly, Darlene; Lal, Simon; Staun, Michael; Szczepanek, Kinga; Van Gossum, André; Wanten, Geert; Schneider, Stéphane Michel
Chronic Intestinal Failure (CIF) is the long-lasting reduction of gut function, below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. CIF is the rarest organ failure. Home parenteral nutrition (HPN) is the primary treatment for CIF. No guidelines (GLs) have been developed that address the global management of CIF. These GLs have been devised to generate comprehensive recommendations for safe and effective management of adult patients with CIF. The GLs were developed by the Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds, and accepted in an online survey of ESPEN members. The following topics were addressed: management of HPN; parenteral nutrition formulation; intestinal rehabilitation, medical therapies, and non-transplant surgery, for short bowel syndrome, chronic intestinal pseudo-obstruction, and radiation enteritis; intestinal transplantation; prevention/treatment of CVC-related infection, CVC-related occlusion/thrombosis; intestinal failure-associated liver disease, gallbladder sludge and stones, renal failure and metabolic bone disease. Literature search provided 623 full papers. Only 12% were controlled studies or meta-analyses. A total of 112 recommendations are given: grade of evidence, very low for 51%, low for 39%, moderate for 8%, and high for 2%; strength of recommendation: strong for 63%, weak for 37%. CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for both the underlying gastrointestinal disease and to provide HPN support. The rarity of the condition impairs the development of RCTs. As a consequence, most of the recommendations have a low or very low grade of evidence. However, two-thirds of the
Conti, Valentina; Calia, Nunzio; Pasquini, Claudio; Zardi, Silvia; Finetti, Cinzia; Stomeo, Francesco; Ravenna, Franco
We report a case of idiopathic tracheal stenosis in a 75-year-old woman, who presented to our observation with a diagnosis of asthmatic bronchitis characterized by cough and exertional dyspnea, later complicated by the appearance of tirage. Biopsy of the lesion showed focal squamous metaplasia of the epithelium lining, multiple sclerosis and chronic inflammatory infiltration of the corium. The patient was treated with endoscopic destruction via rigid bronchoscopy, through the combined action of YAG laser and mechanical debulking.
Obrador, D.; Ballester, M.; Carrio, I.; Berna, L.; Pons-Llado, G.
Monoclonal antimyosin antibody studies were undertaken to assess the presence of myocardial uptake in patients with chronic idiopathic dilated cardiomyopathy. Three groups were studied: 17 patients with chronic (greater than 12 months) idiopathic dilated cardiomyopathy, 12 patients with a large, poorly contracting left ventricle not due to dilated cardiomyopathy (control patients) and 8 normal individuals. The patients in the cardiomyopathy and control groups showed a similar degree of clinical and functional impairment. Imaging was undertaken 48 h after antimyosin injection. The heart/lung ratio of antimyosin uptake was used to assess the results. The mean ratio in the cardiomyopathy group was 1.83 +/- 0.36 (range 1.40 to 2.80), a value significantly higher than that obtained in the control patients without cardiomyopathy (mean 1.46 +/- 0.04, range 1.38 to 1.50) or normal subjects (mean 1.46 +/- 0.13, range 1.31 to 1.6) (p less than 0.01). No difference in the ratio was noted between the normal subjects and control patients. Abnormal antimyosin uptake was seen in 12 (70%) of the 17 patients with cardiomyopathy and in only 1 (8%) of the 12 control patients. Positive monoclonal antimyosin antibody studies are highly prevalent in chronic idiopathic dilated cardiomyopathy.
Marchand, E; Etienne-Mastroianni, B; Chanez, P; Lauque, D; Leclerc, P; Cordier, J F
Since idiopathic chronic eosinophilic pneumonia (ICEP) and asthma are frequently associated, their possible reciprocal influence on clinical presentation and evolution were investigated. The clinical and follow-up features of 53 cases of ICEP, of which 41 (77%) had asthma, were reviewed retrospectively. Asthma preceded the diagnosis of ICEP in 26 patients, was contemporaneous in eight patients, and developed 17 +/- 12 months after ICEP in seven patients. Presentation of ICEP was similar in asthmatics and nonasthmatics with the exception of a higher level of total immunoglobulin E in the former group. Patients with asthma at the time of diagnosis of ICEP were more likely to remain free of relapse of ICEP (56 versus 23%) and had a lower number of relapses per year of follow-up (median 0 versus 0.24). Moreover, they were treated more frequently with long-term inhaled corticosteroids (88 versus 31%) at last follow-up. Asthma got worse after the diagnosis of ICEP and frequently required long-term oral corticosteroids. To conclude, among patients with idiopathic chronic eosinophilic pneumonia, asthmatics have a lower frequency of relapse than nonasthmatics, possibly because of a higher use of inhaled corticosteroids. The occurrence of idiopathic chronic eosinophilic pneumonia in asthmatics is often associated with the development of severe asthma.
Jeican, Ionuţ Isaia; Ichim, Gabriela; Gheban, Dan
The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison's disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis.
Background Juvenile idiopathic arthritis is the most common rheumatic disease in children. Chronic uveitis is a common and serious comorbid condition of juvenile idiopathic arthritis, with insidious presentation and potential to cause blindness. Knowledge of clinical associations will improve risk stratification. Based on clinical observation, we hypothesized that allergic conditions are associated with chronic uveitis in juvenile idiopathic arthritis patients. Methods This study is a retrospective cohort study using Stanford’s clinical data warehouse containing data from Lucile Packard Children’s Hospital from 2000–2011 to analyze patient characteristics associated with chronic uveitis in a large juvenile idiopathic arthritis cohort. Clinical notes in patients under 16 years of age were processed via a validated text analytics pipeline. Bivariate-associated variables were used in a multivariate logistic regression adjusted for age, gender, and race. Previously reported associations were evaluated to validate our methods. The main outcome measure was presence of terms indicating allergy or allergy medications use overrepresented in juvenile idiopathic arthritis patients with chronic uveitis. Residual text features were then used in unsupervised hierarchical clustering to compare clinical text similarity between patients with and without uveitis. Results Previously reported associations with uveitis in juvenile idiopathic arthritis patients (earlier age at arthritis diagnosis, oligoarticular-onset disease, antinuclear antibody status, history of psoriasis) were reproduced in our study. Use of allergy medications and terms describing allergic conditions were independently associated with chronic uveitis. The association with allergy drugs when adjusted for known associations remained significant (OR 2.54, 95% CI 1.22–5.4). Conclusions This study shows the potential of using a validated text analytics pipeline on clinical data warehouses to examine practice
Broides, Arnon; Sagi, Orli; Pinsk, Vered; Levy, Jacov; Yerushalmi, Baruch
Chronic granulomatous disease is a primary immunodeficiency caused by impaired neutrophil production of reactive oxygen species. Non-infectious colitis is common in chronic granulomatous disease, and high levels of antimicrobial antibodies that are associated with Crohn's disease are common even without colitis. Fecal calprotectin concentration is a marker for intestinal inflammation. We sought to determine whether subclinical intestinal inflammation occurs in asymptomatic chronic granulomatous disease patients. Asymptomatic chronic granulomatous disease patients without overt gastrointestinal symptoms suggestive of colitis at the time of enrollment were studied for fecal calprotectin concentration, antibodies associated with Crohn's disease and systemic inflammatory markers. Eight patients were included, aged 54-176 months. In 7/8 (87.5 %) fecal calprotectin concentration was normal (<50) and elevated (137 mg/kg) in only one patient. This patient later developed colitis. In 7/8 (87.5 %) anti-Saccharomyces cerevisiae antibody was positive. C-reactive protein, albumin, complete blood count and p-anti-neutrophil cytoplasmic antibody were normal in all 8 patients. Subclinical colitis is not evident in most asymptomatic chronic granulomatous disease patients; however, in some patients, fecal calprotectin concentration may be elevated, possibly indicating the presence of subclinical colitis and predicting the occurrence of clinically relevant colitis. Serum anti-Saccharomyces cerevisiae antibody concentrations do not seem to correlate with fecal calprotectin concentration in asymptomatic chronic granulomatous disease patients.
Terpstra, Matty L; Singh, Ramandeep; Geerlings, Suzanne E; Bemelman, Frederike J
AIM: To evaluate methods measuring the intestinal per-meability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD. METHODS: We reviewed the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and performed a systematic literature search through MEDline and EMBASE. All controlled trials and cohort studies using non-invasive methods to assess intestinal permeability in CKD patients were included. Excluded were: Conference abstracts and studies including patients younger than 18 years or animals. From the included studies we summarized the used methods and their advantages and disadvantages. For the comparison of their results we divided the included studies in two categories based on their included patient population, either assessing the intestinal permeability in mild to moderate CKD patients or in end stage renal disease (ESRD) patients. Results were graphically displayed in two plots, one comparing the intestinal permeability in mild to moderate CKD patients to healthy controls and one comparing the intestinal permeability in ESRD patients to healthy controls. RESULTS: From the 480 identified reports, 15 met our inclusion criteria. Methods that were used to assess the intestinal permeability varied from markers measured in plasma to methods based on calculating the urinary excretion of an orally administered test substance. None of the applied methods has been validated in CKD patients and the influence of decreased renal function on the different methods remains unclear to a certain extent. Methods that seem the least likely to be influenced by decreased renal function are the quantitative PCR (qPCR) for bacterial DNA in blood and D-lactate. Considering the results published by the included studies; the studies including patients with mild to moderate CKD conducted conflicting results. Some studies did report an increase in intestinal
Tanizaki, Hideaki; Yamamoto, Yosuke; Nakamizo, Satoshi; Otsuka, Atsushi; Miyachi, Yoshiki; Kabashima, Kenji
Olopatadine is one of the second-generation H1 antihistamines that were used for treating allergic disorders initially in Asia, and now also in Western countries. Whereas several trials compared the efficacy on chronic urticaria among second-generation H1 antihistamines, no study has directly compared the clinical efficacy between olopatadine and other H1 antihistamines in patients with chronic idiopathic urticaria (CIU). In this study, we address this issue for the first time and conclude that olopatadine is a good candidate for the treatment of CIU. © 2015 S. Karger AG, Basel.
Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.
Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.
Nenci, Arianna; Becker, Christoph; Wullaert, Andy; Gareus, Ralph; van Loo, Geert; Danese, Silvio; Huth, Marion; Nikolaev, Alexei; Neufert, Clemens; Madison, Blair; Gumucio, Deborah; Neurath, Markus F; Pasparakis, Manolis
Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease. The gut epithelium is critically involved in the maintenance of intestinal immune homeostasis-acting as a physical barrier separating luminal bacteria and immune cells, and also expressing antimicrobial peptides. However, the molecular mechanisms that control this function of gut epithelial cells are poorly understood. Here we show that the transcription factor NF-kappaB, a master regulator of pro-inflammatory responses, functions in gut epithelial cells to control epithelial integrity and the interaction between the mucosal immune system and gut microflora. Intestinal epithelial-cell-specific inhibition of NF-kappaB through conditional ablation of NEMO (also called IkappaB kinase-gamma (IKKgamma)) or both IKK1 (IKKalpha) and IKK2 (IKKbeta)-IKK subunits essential for NF-kappaB activation-spontaneously caused severe chronic intestinal inflammation in mice. NF-kappaB deficiency led to apoptosis of colonic epithelial cells, impaired expression of antimicrobial peptides and translocation of bacteria into the mucosa. Concurrently, this epithelial defect triggered a chronic inflammatory response in the colon, initially dominated by innate immune cells but later also involving T lymphocytes. Deficiency of the gene encoding the adaptor protein MyD88 prevented the development of intestinal inflammation, demonstrating that Toll-like receptor activation by intestinal bacteria is essential for disease pathogenesis in this mouse model. Furthermore, NEMO deficiency sensitized epithelial cells to tumour-necrosis factor (TNF)-induced apoptosis, whereas TNF receptor-1 inactivation inhibited intestinal inflammation, demonstrating that TNF receptor-1 signalling is crucial for disease induction. These findings demonstrate that a primary NF-kappaB signalling defect in intestinal epithelial cells disrupts immune homeostasis in the gastrointestinal tract
Szema, Anthony M.; Forsyth, Edward; Ying, Benjamin; Hamidi, Sayyed A.; Chen, John J.; Hwang, Sonya; Li, Jonathan C.; Sabatini Dwyer, Debra; Ramiro-Diaz, Juan M.; Giermakowska, Wieslawa; Gonzalez Bosc, Laura V.
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In
Szema, Anthony M; Forsyth, Edward; Ying, Benjamin; Hamidi, Sayyed A; Chen, John J; Hwang, Sonya; Li, Jonathan C; Sabatini Dwyer, Debra; Ramiro-Diaz, Juan M; Giermakowska, Wieslawa; Gonzalez Bosc, Laura V
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In
Gauci, Julia L; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A
A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described.
Gauci, Julia L.; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A.
A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described. PMID:24975870
Nauta, Sjoukje; Feibig, Doreen; Wanten, Geert
Telemedicine is a valuable extension of the ways in which patients with chronic diseases can be contacted. Patients can easily contact their caregivers within the safe environment of the digital waiting room. Telemedicine especially offers an advantage for those forms of care where the visual aspect is important. Care should be taken with respect to its implementation into the disease management process with careful synchronisation between all involved parties, e.g. patient, caregiver, and organisation. The effectiveness of telemedicine and the savings that can be achieved should be properly established in order to justify the funding of a telemedicine project. Rather than focusing on the possible drawbacks of telemedicine, e.g. safety concerns and the user-friendliness of the system, we should highlight the possibilities that information technology offers.
Chiò, A; Cocito, D; Bottacchi, E; Buffa, C; Leone, M; Plano, F; Mutani, R; Calvo, A
Aim The clinical and epidemiological characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in an Italian population were assessed. Subjects and methods All subjects with a diagnosis of demyelinating neuropathy after 1990 in Piemonte and Valle d'Aosta (4 334 225 inhabitants) were considered. The diagnosis of CIDP was based on the research criteria of the American Academy of Neurology. 165 of 294 patients met the diagnostic criteria. Results The crude prevalence rate was 3.58/100 000 population (95% CI 3.02 to 4.20). At the prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%) possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%) and severe in 18 (11.6%). The course was remitting–relapsing in 40 cases (25.8%), chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the 95 patients whose disorder presented in the period 1995–2001, the mean annual crude incidence rate was 0.36/100 000 population (95% CI 0.29 to 0.44), with a male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In multivariate analysis, factors related to severe disability at the prevalence day were: age>60 years; failure of immunomodulating therapies at the time of diagnosis; worse disability at nadir; and chronic course. Conclusion Incidence and prevalence rates of CIDP in Italy were higher than those observed in most previous studies. At the prevalence day, more than 80% of cases had a mild or moderate disability, indicating either a good response to immunomodulating therapy or a tendency of CIDP to have a mild course in most cases. PMID:17494979
Asmundson, Gordon J. G.; Hadjistavropolous, Heather D.
Wicksell and colleagues (2005) addressed the important and currently understudied realm of chronic idiopathic musculoskeletal pain treatment in children. They presented a brief overview of empirically supported treatments for children with chronic pain, detailed their case and intervention strategy, and offered conclusions regarding the potential…
Asmundson, Gordon J. G.; Hadjistavropolous, Heather D.
Wicksell and colleagues (2005) addressed the important and currently understudied realm of chronic idiopathic musculoskeletal pain treatment in children. They presented a brief overview of empirically supported treatments for children with chronic pain, detailed their case and intervention strategy, and offered conclusions regarding the potential…
Lacy, Brian E.; Schey, Ron; Shiff, Steven J.; Lavins, Bernard J.; Fox, Susan M.; Jia, Xinwei D.; Blakesley, Rick E.; Hao, Xinming; Cronin, Jacquelyn A.; Currie, Mark G.; Kurtz, Caroline B.; Johnston, Jeffrey M.; Lembo, Anthony J.
Background Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation. The objective of this trial was to evaluate the efficacy and safety of linaclotide in patients with chronic idiopathic constipation and concomitant moderate-to-severe abdominal bloating. Methods This Phase 3b, randomized, double-blind, placebo-controlled clinical trial randomized patients to oral linaclotide (145 or 290 μg) or placebo once daily for 12 weeks. Eligible patients met Rome II criteria for chronic constipation upon entry with an average abdominal bloating score ≥5 (self-assessment: 0 10-point numerical rating scale) during the 14-day baseline period. Patients reported abdominal symptoms (including bloating) and bowel symptoms daily; adverse events were monitored. The primary responder endpoint required patients to have ≥3 complete spontaneous bowel movements/week with an increase of ≥1 from baseline, for ≥9 of 12 weeks. The primary endpoint compared linaclotide 145 μg vs. placebo. Results The intent-to-treat population included 483 patients (mean age=47.3 years, female=91.5%, white=67.7%). The primary endpoint was met by 15.7% of linaclotide 145 μg patients vs. 7.6% of placebo patients (P<0.05). Both linaclotide doses significantly improved abdominal bloating vs. placebo (P<0.05 for all secondary endpoints, controlling for multiplicity). Approximately one-third of linaclotide patients (each group) had ≥50% mean decrease from baseline in abdominal bloating vs. 18% of placebo patients (P<0.01). Diarrhea was reported in 6% and 17% of linaclotide 145 and 290 μg patients, respectively, and 2% of placebo patients. AEs resulted in premature discontinuation of 5% and 9% of linaclotide 145 μg and 290 μg patients, respectively, and 6% of placebo patients. Conclusions Once-daily linaclotide (145 and 290 μg) significantly improved bowel and abdominal symptoms in chronic idiopathic constipation patients with moderate-to-severe baseline abdominal
Krieger, J N; Riley, D E; Roberts, M C; Berger, R E
Half of all men experience symptoms of prostatitis at some time in their lives, but the etiology is unknown for more than 90% of patients. Optimal clinical and culture methods were used to select 135 men with chronic prostatitis refractory to multiple previous courses of antimicrobial therapy. The subjects had no evidence of structural or functional lower genitourinary tract abnormalities of bacteriuria or bacterial prostatitis by traditional clinical tests, or of urethritis or urethral pathogens by culture. Specific PCR assays detected Mycoplasma genitalium, Chlamydia trachomatis, or Trichomonas vaginalis in 10 patients (8%). Broad-spectrum PCR tests detected tetracycline resistance-encoding genes, tetM-tetO-tetS, in 25% of patients and 16S rRNA in 77% of subjects. The tetM-tetO-tetS-positive cases constituted a subset of the 16S rRNA-positive cases. Patients with 16S rRNA were more likely to have > or = 1,000 leukocytes per mm3 in their expressed prostatic secretion than men whose prostate biopsy specimens were negative for 16S rRNA (P < 0.001). Based on direct sequencing and repetitive cloning, multiple sources of 16S rRNA were observed in individual patients. Sequences of 29 cloned PCR products revealed 16S rRNAs distinct from those of common skin and gut flora. These findings suggest that the prostate can harbor microorganisms that are not detectable by traditional approaches. These organisms may be associated with inflammation in the expressed prostatic secretions. Molecular methods hold great promise for identifying culture-resistant microorganisms in patients with chronic prostatitis.
Krieger, J N; Riley, D E; Roberts, M C; Berger, R E
Half of all men experience symptoms of prostatitis at some time in their lives, but the etiology is unknown for more than 90% of patients. Optimal clinical and culture methods were used to select 135 men with chronic prostatitis refractory to multiple previous courses of antimicrobial therapy. The subjects had no evidence of structural or functional lower genitourinary tract abnormalities of bacteriuria or bacterial prostatitis by traditional clinical tests, or of urethritis or urethral pathogens by culture. Specific PCR assays detected Mycoplasma genitalium, Chlamydia trachomatis, or Trichomonas vaginalis in 10 patients (8%). Broad-spectrum PCR tests detected tetracycline resistance-encoding genes, tetM-tetO-tetS, in 25% of patients and 16S rRNA in 77% of subjects. The tetM-tetO-tetS-positive cases constituted a subset of the 16S rRNA-positive cases. Patients with 16S rRNA were more likely to have > or = 1,000 leukocytes per mm3 in their expressed prostatic secretion than men whose prostate biopsy specimens were negative for 16S rRNA (P < 0.001). Based on direct sequencing and repetitive cloning, multiple sources of 16S rRNA were observed in individual patients. Sequences of 29 cloned PCR products revealed 16S rRNAs distinct from those of common skin and gut flora. These findings suggest that the prostate can harbor microorganisms that are not detectable by traditional approaches. These organisms may be associated with inflammation in the expressed prostatic secretions. Molecular methods hold great promise for identifying culture-resistant microorganisms in patients with chronic prostatitis. PMID:8940458
Asymmetric ventriculomegly due to idiopathic occlusion of the foramen of Monro is rare. Such patients present with clinical features of raised intracranial pressure (ICP). Presentation as chronic headache has not been previously described. In the absence of raised ICP, pursuing surgical treatment raises a clinical dilemma as the headache may be a primary headache with no improvement after surgery. A 21-year-old woman presented with chronic headache. She was found to have asymmetric ventriculomegaly due to the occlusion of the foramen of Monro. She underwent endoscopic septostomy and widening of the foramen of Monro. Her headache subsided after surgery. At 15 months of follow-up, she was free from headache without medications. Unilateral occlusion of the foramen of Monro can present with asymmetric ventriculomegaly resulting in chronic headache. Though the symptoms of raised ICP may not be present, still endoscopic relief of ventriculomegaly leads to cure of headache.
Kurmaeva, Elvira; Bhattacharya, Dhruva; Goodman, Wendy; Omenetti, Sara; Merendino, Amber; Berney, Seth; Pizarro, Theresa; Ostanin, Dmitry V.
Chronic colitis is accompanied by extensive myelopoiesis and accumulation of CD11b+Gr-1+ cells in spleens and secondary lymphoid tissues. Although cells with similar phenotype have been described in cancer, chronic infection, or autoimmunity, where they were associated with suppression of T cell responses, little is known regarding how these cells affect CD4 T cell responses in the context of chronic intestinal inflammation. Therefore, we undertook this study to characterize the interplay between colitis-induced myeloid cells and CD4 T cell. Within the CD11b+Gr-1+ population, only monocytes (Ly6GnegLy6Chigh) but not other myeloid cell subsets suppressed proliferation and production of cytokines by CD4 T cells. Suppression was mediated by cell-contact, NO and partially by IFN-γ and PGs. Interestingly, Ly6Chigh MDCs, isolated from colitic colons, showed up-regulation of iNOS and arginase-1 and were more potent suppressors than those isolated from spleen. On a single-cell level, MDCs inhibited Th1 responses but enhanced generation of foxp3+ T cells. MDCs, cocultured with activated/Teffs, isolated from inflamed colons under hypoxic (1% O2) conditions typical for the inflamed intestine, suppressed proliferation but not their production of proinflammatory cytokines and chemokines. Taken together, expansion of monocytes and MDCs and activation of their suppressive properties may represent a homeostatic mechanism aimed at restraining excessive T cell activation during chronic inflammatory settings. The contribution of immunosuppressive monocytes/MDCs to chronic colitis and their role in shaping T cell responses in vivo require further investigation. PMID:24696357
Zacho, Helle D
A redundant collateral network between the intestinal arteries is present at all times. In case of ischaemia in the gastrointestinal tract, the collateral blood supply can develop further, thus accommodating the demand for oxygen even in the presence of significant stenosis or occlusion of the intestinal arteries without clinical symptoms of intestinal ischaemia. Symptoms of ischemia develop when the genuine and collateral blood supply no longer can accommodate the need for oxygen. Atherosclerosis is the most common cause of obliteration in the intestinal arteries. In chronic intestinal ischaemia (CII), the fasting splanchnic blood flow (SBF) is sufficient, but the postprandial increase in SBF is inadequate and abdominal pain will therefore develop in relation to food intake causing the patient to eat smaller meals at larger intervals with a resulting weight loss. Traditionally, the CII-diagnosis has exclusively been based upon morphology (angiography) of the intestinal arteries; however, substantial discrepancies between CII-symptoms and the presence of atherosclerosis/stenosis in the intestinal arteries have been described repeatedly in the literature impeding the diagnosis of CII. This PhD thesis explores a method to determine the total SBF and its potential use as a diagnostic tool in patients suspected to suffer from CII. The SBF can be measured using a continuous infusion of a tracer and catheterisation of a hepatic vein and an artery. By measuring the SBF before and after a standard meal it is possible to assess the ability or inability to enhance the SBF and thereby diagnosing CII. In Study I, measurement of SBF was tested against angiography in a group of patients suspected to suffer from CII due to pain and weight loss. A very good agreement between the postprandial increase in SBF and angiography was found. The method was validated against a well-established method independent of the hepatic extraction of tracer using pAH in a porcine model (study II
Minty, Ian; Bain, Iain M.; Cundall, Jeremy; Yiannakou, Yan
Background. Transanal irrigation (TAI) can successfully treat neurogenic bowel dysfunction (NBD), but patient perception of its use in chronic idiopathic constipation (CIC) is unknown. Objective. To evaluate patient perceptions of the efficacy and safety of TAI for CIC and whether there are predictive factors of perceived treatment response. Methods. Prospective data collection of baseline physiology and symptom severity; retrospective evaluation of efficacy and safety perceptions using a snapshot survey. All patients fulfilling the Rome III criteria for functional constipation with chronic idiopathic aetiology were included. The main outcome measure was the duration of patients' usage of TAI. Results. 102 patients reported 21,476 irrigations over 119 patient years, with a mean duration of therapy use of 60.5 weeks [SD 73.2 : SE 7.3]. Overall symptom improvement included general well-being (65%), rectal clearance (63%), bloating (49%), abdominal pain (48%), and bowel frequency (42%). 68 patients (67%) were “moderately better” or “very much better” on a satisfaction question. Reported complications were minor. No correlation was demonstrated between duration of therapy use and baseline measures. Conclusion. A significant proportion of CIC sufferers use TAI as a long-term or bridging therapy and perceive it as safe. This therapy demands a prospective investigation of efficacy and safety. PMID:28115930
Peterlana, D; Puccetti, A; Simeoni, S; Tinazzi, E; Corrocher, R; Lunardi, C
Human intravenous immunoglobulins (hIVIgs) are used in two broad categories of diseases: immunodeficiency and autoimmunity. Among the immune-mediated diseases hIVIgs are of benefit in idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and dermatomyositis. Chronic idiopathic pericarditis (CIP) is a chronic disease of unknown origin characterized by recurrent episodes of pericardial inflammation. The cause of the recurrence is unknown, although in some cases it may be traced to a viral infection and to the presence of antimyocardial antibodies. Since a viral infection can induce an autoimmune process through a mechanism of molecular mimicry, and since the optimal therapy for prevention of the recurrences has not been established, we reasoned that treatment with hIVIgs could be beneficial in our patients unresponsive to previous immunosuppressive therapies. We describe four patients affected by CIP treated with monthly high-dose hIVIgs (0.4 g/kg daily for 5 consecutive days) for five times followed by administration every 2 months. Three of the four patients could permanently discontinue steroid therapy and are still in remission after years of follow-up. Our experience suggests that hIVIgs therapy may be a useful and safe treatment for CIP in steroid-dependent patients.
Pomper, Jörn K; Gebert, Lena; Fischer, Matthias; Bunjes, Friedemann; Thier, Peter
Most patients suffering from chronic idiopathic dizziness do not present signs of vestibular dysfunction or organic failures of other kinds. Hence, this kind of dizziness is commonly seen as psychogenic in nature, sharing commonalities with specific phobias, panic disorder, and generalized anxiety. A more specific concept put forward by Brandt and Dieterich (1) states that these patients suffer from dizziness because of an inadequate compensation of self-induced sensory stimulation. According to this hypothesis self-motion-induced reafferent visual stimulation is interpreted as motion in the world since a predictive signal reflecting the consequences of self-motion, needed to compensate the reafferent stimulus, is inadequate. While conceptually intriguing, experimental evidence supporting the idea of an inadequate prediction of the sensory consequences of own movements has as yet been lacking. Here we tested this hypothesis by applying it to the perception of background motion induced by smooth pursuit eye movements. As a matter of fact, we found the same mildly undercompensating prediction, responsible for the perception of slight illusory world motion ("Filehne illusion") in the 15 patients tested and their age-matched controls. Likewise, the ability to adapt this prediction to the needs of the visual context was not deteriorated in patients. Finally, we could not find any correlation between measures of the individual severity of dizziness and the ability to predict. In sum, our results do not support the concept of a deviant prediction of self-induced sensory stimulation as cause of chronic idiopathic dizziness.
Tatterton, M; El-Khatib, C
Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterised by recurrent symptoms and signs of intestinal obstruction without an underlying mechanical cause. Caecal volvulus remains a rare cause of intestinal obstruction that often requires operative intervention. We describe the previously unreported case of caecal volvulus occurring in an adult patient with CIPO, together with his subsequent management.
Arvonen, M; Vähäsalo, P; Turunen, S; Salo, H M; Mäki, M; Laurila, K; Vaarala, O; Karttunen, T J
We aimed to study intestinal immune activation status in juvenile idiopathic arthritis (JIA) by assessing intestinal human leucocyte antigen (HLA) class II expression and the mRNA expression levels of the pro- and anti-inflammatory mediators and pattern recognition receptors. HLA-D-related (HLA-DR) expression was assessed using immunohistochemical staining of frozen sections in 11 children with JIA and 17 controls. The gene expression levels of the anti- and proinflammatory cytokines, lymphocyte recognition receptors and pattern recognition receptors were studied with reverse transcription–polymerase chain reaction (RT–PCR) in 14 children with JIA and 12 controls. All subjects had various gastrointestinal (GI) symptoms indicating endoscopic examinations, but eventually were not diagnosed with GI disease. In JIA patients, the expression of HLA-DR was increased in the crypt epithelial cells and in the epithelial basement membrane of the ileum when compared with the controls. Positive HLA-DR staining in the ileal mucosa was associated with the presence of high clinical disease activity of JIA and low mRNA expression of anti-inflammatory mediators, such as forkhead box protein P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and transforming growth factor (TGF)-beta. Low ileal expression of interleukin (IL)-10, TGF-β, FoxP3, Toll-like receptor 2 (TLR-2) and TLR-4 transcripts correlated significantly with a high clinical disease activity in the JIA patients. The increased HLA-DR expression suggests enhanced intestinal antigen presentation in JIA. A correlation between clinical disease activity and low gene expression of tolerogenic mediators in the ileum supports the hypothesis that a link exists between the gut immune system and JIA. PMID:23121667
... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...
Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran
Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.
Baicus, Cristian; Baicus, Anda
Idiopathic chronic fatigue is an exclusion diagnosis established when no chronic disease is found. Spirulina platensis is an alga with a rich content of proteins, vitamins, minerals and amino acids and is considered as a bioactive additive with multiple effects, among them being effects against fatigue. However, despite the worldwide utilization of Spirulina, there are only a few quality studies with it and none concerning fatigue. The N-of-1 randomized trials are made on one patient, and by this kind of study the efficacy of a treatment on that particular patient can be assessed. A series of four N-of-1 double-blind, randomized trials were performed on four physicians who complained of chronic fatigue. Each patient was his own control and received three pairs of treatments comprising 4 weeks of spirulina and 4 weeks of placebo. Spirulina platensis was administered in a dose of 3 g/day. For each pair, the order of treatments was randomized. Outcome measures were severity of fatigue measured on a 10-point scale. The scores of fatigue were not significantly different between spirulina and placebo. Spirulina administered in a dose of 3 g/day did not ameliorate fatigue more than the placebo in any of the four subjects, and possibly it has no effect on chronic fatigue.
Sarosiek, Irene; Bashashati, Mohammad; Alvarez, Alicia; Hall, Mark; Shankar, Nagasri; Gomez, Yvette; McCallum, Richard W; Sarosiek, Jerzy
Lubiprostone is an effective treatment for chronic constipation (CC). The mechanism of action of lubiprostone is through increasing fluid secretion and lubrication of the intestinal lumen. The effects of lubiprostone on gastrointestinal transit and small intestinal bacterial overgrowth (SIBO) have not been adequately explored. The current study was designed to investigate whether lubiprostone (1) alters gastrointestinal transit and (2) affects SIBO in patients with constipation. A total of 29 female patients (mean age = 39 years; range: 19-64) with CC received 2 weeks of lubiprostone (24mcg b.i.d., P.O.). Stool consistency based on Bristol stool scale and the frequency of bowel movements (BMs) were recorded. Gastric emptying time, small bowel transit time, colon transit time (CTT), combined small and large bowel transit time (SLBTT) and whole gut transit time were measured using wireless motility capsule. The SIBO status was assessed by the lactulose breath test. Data were analyzed using Wilcoxon rank, Mann-Whitney U, Spearman׳s rank correlation and Chi-square tests. Lubiprostone significantly softened the stool and increased the frequency of BM from median of 2 to 4times per week. The CTT and SLBTT were significantly shorter in responders to lubiprostone (i.e., those with ≥ 2 times increase in the number of their weekly BM) compared with nonresponders. The higher frequency of BM after treatment was significantly correlated with the acceleration of CTT, SLBTT and whole gut transit time. In all, 17 out of 25 (68%) patients, who were tested for SIBO at baseline, were positive. In addition, 7 out of 17 (41%) SIBO-positive patients became SIBO-negative after lubiprostone treatment (P < 0.05). In CC, lubiprostone improves the frequency of BMs, softens the stool, accelerates intestinal transit and decreases accompanying SIBO. The improvement of SIBO could be explained by the cleansing effect of increased intestinal fluid and mucus combined with enhanced intestinal
Camera, Luigi; Calabrese, Milena; Sarnelli, Giovanni; Longobardi, Margaret; Rocco, Alba; Cuomo, Rosario; Salvatore, Marco
Chronic intestinal pseudo-obstruction (CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic, on both clinical and radiological grounds, mechanical obstruction. We report a case of a 26-year-old woman who presented to our institution for plain abdominal radiography for referred long-lasting constipation with recurrent episodes of abdominal pain and distension. At X-ray, performed both in the upright and supine position, an isolated air-fluid level was depicted in the left flank, together with a number of radiological signs suggestive of pneumoperitoneum. First, subphrenic radiolucency could be observed in the upright film. Second, the intestinal wall of some jejunal loops appeared to be outlined in the right flank. Third, the inferior cardiac border was clearly depicted in the upright film. The patient however had no evidence of peritoneal signs but only hypoactive bowel movements. Unenhanced multi-detector computed tomography (MDCT) of the abdomen and pelvis was therefore performed. MDCT revealed abnormal air-driven distension of the small and large bowel, without evidence of extra-luminal air. All radiological signs of pneumoperitoneum turned out to be false-positive results. The patient was submitted to pan-colonoscopy and to anorectal manometry to rule out Hirshprung's disease, and was finally discharged with a diagnosis of CIPO.
Higgins, J Nicholas P; Pickard, John D; Lever, Andrew M L
Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each - fatigue and headache - are common in the other and their multiple other symptoms are frequently seen in both. The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations? We suggest that it is a quirk of clinical measurement that has created this discrepancy. Specifically, that the criteria put in place to define IIH have led to a failure to appreciate the existence, clinical significance or numerical importance of patients with lower level disturbances of intracranial pressure. We argue that this has led to a grossly implausible distortion of the epidemiology of IIH such that the milder form of the illness (IIHWOP) is seen as less common than the more severe and that this would be resolved by recognising a connection with chronic fatigue syndrome. We hypothesise, therefore, that IIH, IIHWOP, lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Pollak, Martin R
In children, chronic kidney disease (CKD) that results from structural abnormalities and glomerular injury is readily diagnosed; however, most cases of pediatric CKD are of unknown etiology. In this issue of the JCI, Verbitsky and colleagues used chromosomal microarrays to evaluate genomic variation in children with CKD. Compared with control individuals, a substantial proportion of children with idiopathic CKD had clearly identifiable genomic imbalances. Moreover, in some cases, detailed analysis of these imbalances identified pathogenic alterations that were unsuspected based on clinical presentation. The results of this study support genome-wide evaluation for pediatric cases of CKD; however, more work will need to be done before such an approach is widely available in the clinic.
Finucane, David; Fleming, Padraig; Smith, Owen
A case is presented of a 13-year-old boy with chronic idiopathic thrombocytopenic purpura (ITP) who sustained traumatic labial luxation of both lower central incisors, with partial alveolar fracture resulting in displacement of the labial alveolar plate. Intravenous immunoglobulin (Fleibogamma, 1 g/kg body weight x 2 days) was administered, resulting in the patient's platelet count rising from 15,000/mm3 to 70,000/mm3. Under general anesthesia, the displaced lower labial alveolus and luxated teeth were repositioned and splinted 2 days following trauma. Healing was uneventful. Subsequently, both lower central incisors became nonvital and were endodontically treated. The dental treatment of this patient with ITP is discussed in terms of emergency management, and subsequent care.
Carpenter, M.; Musacchia, X. J.
The study examines intestinal transport of sugars (D-glucose and D-galactose) in vitro and assesses organ maintenance in chronically heat-exposed rats. The results suggest that the response of intestinal absorption to heat exposure in the rat involves changes in intestinal weight and in glucose utilization. Despite the reduction in total intestinal weight, the ability of intestinal tissue to transport hexose per unit weight remains stable. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function of the amount of food consumed. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity.
Rowell, Robert M; Rylander, Steven J
The purpose of this article is to report the case of a patient who had low-back pain, leg pain, and idiopathic chronic testicular pain and who sought chiropractic care for his low-back and leg pain and received pain relief including his testicular pain. A 36-year-old male patient had low-back pain, right leg pain, and testicular pain that was worsening. All had been present for 5 years. He had been seen by several medical physicians and had lumbar magnetic resonance imaging and x-rays performed. All were read as normal. Examination revealed tenderness of the testicles bilaterally with no masses or other abnormality of the testicles or scrotum. Orthopedic and neurological testing was unremarkable. Tenderness rated 8 out of 10 was noted at the L4 spinous process. The patient was treated with Cox Technic (flexion-distraction) of the lumbar spine, receiving a total of 19 treatments over an 8-week time period. After 4 weeks, the patient's low-back pain was decreased and his leg pain was gone. The testicular pain was improved after the first treatment and gone after 3 weeks of care. The patient was followed up by telephone at 3 and 6 months after discharge to find out if the testicle pain had returned, which it had not. This case was one of chronic idiopathic testicular pain. The patient was treated with the Cox Technic, and his low-back pain improved with complete remission of his leg and testicular pain. The testicular pain had not returned 6 months following his discharge from care.
Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael
Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Illa, I; Rojas, R; Gallardo, E; Serrano, C; Graus, F
Sensory ataxic neuropathies (SANs) are characterized by loss of proprioceptive sensations and preservation of muscle strength. They may be idiopathic or associated with different toxic, infectious or autoimmune causes. Reactivity against gangliosides containing disialosyl groups, particularly GD1b, has been reported in isolated cases of acute and chronic idiopathic ataxic neuropathies (iSAN) and different experimental findings (in vivo animal models and in vitro preparations) suggest that antidisialosyl or antiGD1b antibodies could play a role in the pathogenesis of some ataxic neuropathies. We present the clinical, immunological and immunohistochemical characteristics of 17 patients who had a chronic iSAN without gammopathy. Patients were selected from a large group of 130 subjects with SAN: 93 with known etiology and 37 with iSAN. IgM and IgG antibodies to GM1, GM2, GM3, aGM1, GD1a, GD1b, GD3, GT1b and GQ1b were investigated by ELISA (INCAT protocol) and thin layer chromatography. Immunohistochemistry, using biotinylated Ig extracted from the patientś serum, was performed on human dorsal root ganglia (DRG), spinal cord, anterior and posterior roots, sural nerve and muscle tissue. The mean age of the 17 patients was 62 (37-80 years). The most disabling features were unsteadiness and severe ataxia of gait. Only one patient of this group was wheelchair-bound. The clinical data of these 17 patients were similar to those of the other patients with SAN, except that progression was slower. Antibodies to GD1b, GD3 and GT1b were found in 1/17. Two more patients (one with an acute iSAN and one with chronic iSAN and gammopathy), also had antibodies to disialosyl or GD1b. No immunohistochemical pattern of reactivity was found in any of the tissues tested with the 17 sera. In summary, this study demonstrates antidisialosyl or anti GD1b antibodies only in 3/37 (8.1p. cent) of patients with iSAN, either acute, chronic, or with gammopathy. However, their value seems to be
Kawanishi, Koki; Moribata, Kosaku; Kato, Jun; Murata, Kenya; Fukatsu, Kazuhiro; Tamaki, Hidehiko; Itou, Daisaku; Wada, Yuki; Ichinose, Masao
A 37-year-old woman who had previously been diagnosed with idiopathic chronic intestinal pseudo-obstruction (CIPO) at another hospital was admitted to our institution with severe abdominal pain. She had a history of several abdominal surgeries to treat ileus at the previous hospital, and contrast-enhanced computed tomography on admission revealed subileus without any apparent causes of obstruction. Total parenteral nutrition, a gastrointestinal prokinetic agent, and opiates reduced persistent pain;however, breakthrough pain continued. A neurologist at our hospital suggested autoimmune autonomic ganglionopathy (AAG) as a potential cause of CIPO. The patient was diagnosed with suspected AAG on the basis of seropositive results for anti-ganglionic acetylcholine receptor antibody. Intravenous immunoglobulin administration and plasma exchange were performed in combination with immunosuppressive drugs;however, her symptoms barely improved. Although percutaneous endoscopic gastrostomy and enterostomy were subsequently performed to reduce internal intestinal pressure, her pain relief was insufficient.
Huang, Yuanyuan; Chen, Jun; Gui, Li
Abstract Rationale: Idiopathic hypertrophic pachymeningitis (IHP) is a rare condition, characterized by a chronic fibrosing inflammatory process usually involving either the intracranial or spinal dura mater, but rarely both. Here, we report a rare case of IHP affecting both the intracranial and spinal dura mater. We also discussed the diagnosis, management, and outcome of IHP. Patient concerns: We reviewed the case of a 60-year-old woman presenting with chronic headache, multiple cranial nerve palsies and gait disturbance. Magnetic resonance imaging (MRI) of her head revealed thickened and contrast-enhanced dura in the craniocervical region as well as obstructive hydrocephalus and cerebellar tonsillar herniation. The patient had a suboccipital craniectomy and posterior decompression through C1 plus a total laminectomy. The dura was partially resected to the extent of the bony decompression, and a duroplasty was performed. Diagnoses: Microscopic examination of the surgically resected sample showed chronic inflammatory changes, lymphoplasmacytic cell infiltration, fibrous tissue hyperplasia, and hyaline degeneration. Blood tests to evaluate the secondary causes of hypertrophic pachymeningitis (HP) were unremarkable. Interventions: Steroid was used to treat suspected IHP. Outcomes: Postoperatively, the patient showed gradual improvement in her headache, glossolalia, and bucking. Prior to discharge, a follow-up MRI showed improvement of the dura mater thickening. Lessons: IHP is a chronic inflammatory disorder of the dura mater that usually causes neurological deficits. Clinical manifestations of IHP, MRI findings, and laboratory abnormalities are the essential components for making an accurate diagnosis. When the radiological or laboratory evaluation is uncertain, but neurological deficits are present, a prompt surgical approach should be considered. Postoperative steroid therapy and close observation for recurrence are necessary to ensure a good long-term outcome
Samuelsson, Kristin; Osman, Ayman A M; Angeria, Maria; Risling, Mårten; Mohseni, Simin; Press, Rayomand
Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy.
Samuelsson, Kristin; Osman, Ayman A. M.; Angeria, Maria; Risling, Mårten; Mohseni, Simin; Press, Rayomand
Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy. PMID:27662650
Sofia, Valentina Maria; Da Sacco, Letizia; Surace, Cecilia; Tomaiuolo, Anna Cristina; Genovese, Silvia; Grotta, Simona; Gnazzo, Maria; Petrocchi, Stefano; Ciocca, Laura; Alghisi, Federico; Montemitro, Enza; Martemucci, Luigi; Elce, Ausilia; Lucidi, Vincenzina; Castaldo, Giuseppe; Angioni, Adriano
Genetic features of chronic pancreatitis (CP) have been investigated extensively, mainly by testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. A total of 80 patients with idiopathic chronic pancreatitis (ICP) were investigated using a Next-Generation Sequencing (NGS) approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen, modifier genes of cystic fibrosis phenotype, pancreatic secretion and ion homeostasis, calcium signaling and zymogen granules (ZG) exocytosis, autophagy and autoimmune pancreatitis-related genes. We detected mutations in 34 out of 70 genes examined; of the 80 patients, 64 (80.0%) were positive for mutations in one or more genes and 16 (20.0%) had no mutations. Mutations in CFTR were detected in 32 of the 80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38 (59.3%) of the 64 patients positive for mutations showed variants in two or more genes. Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in CP and that trans-heterozygosity may predispose to the ICP phenotype. PMID:27264265
Finnerup, Nanna Brix; Christensen, Peter
Introduction. Most spinal-cord-injured patients have constipation. One-third develop chronic abdominal pain 10 years or more after injury. Nevertheless, very little is known about the nature of abdominal pain after spinal cord injury (SCI). It may be neuropathic or caused by constipation. Aim. To compare characteristics of abdominal pain in SCI with able-bodied with chronic idiopathic constipation (CIC). Subjects and Methods. 21 SCI and 15 CIC patients were referred for treatment of bowel symptoms. Constipation-related symptoms were assessed with the Cleveland Constipation Scoring System and the International Spinal Cord Injury Basic Bowel Function Data Set. Characteristics of abdominal pain were described using the Brief Danish Pain Questionnaire. Total gastrointestinal transit times (GITT) were measured by radiopaque markers. Results. Seventeen (81%) SCI and 14 (93%) CIC patients reported abdominal pain or discomfort within the last month (P = 0.38). Pain was considered more intense by CIC than by SCI patients (P < 0.05). Only minor differences were found in patient's qualitative description of abdominal pain or in the location of pain. In neither SCI nor CIC was pain associated with GITT. Conclusion. Most characteristics of abdominal pain among SCI patients resemble those of CIC. This indicates that constipation is a major cause of pain after SCI. PMID:24159329
Sina, Christian; Lipinski, Simone; Gavrilova, Olga; Aden, Konrad; Rehman, Ateequr; Till, Andreas; Rittger, Andrea; Podschun, Rainer; Meyer-Hoffert, Ulf; Haesler, Robert; Midtling, Emilie; Pütsep, Katrin; McGuckin, Michael A; Schreiber, Stefan; Saftig, Paul; Rosenstiel, Philip
Cathepsin K is a lysosomal cysteine protease that has pleiotropic roles in bone resorption, arthritis, atherosclerosis, blood pressure regulation, obesity and cancer. Recently, it was demonstrated that cathepsin K-deficient (Ctsk(-/-) ) mice are less susceptible to experimental autoimmune arthritis and encephalomyelitis, which implies a functional role for cathepsin K in chronic inflammatory responses. Here, the authors address the relevance of cathepsin K in the intestinal immune response during chronic intestinal inflammation. Chronic colitis was induced by administration of 2% dextran sodium sulphate (DSS) in distilled water. Mice were assessed for disease severity, histopathology and endoscopic appearance. Furthermore, DSS-exposed Ctsk(-/-) mice were treated by rectal administration of recombinant cathepsin K. Intestinal microflora was assessed by real-time PCR and 16srDNA molecular fingerprinting of ileal and colonic mucosal and faecal samples. Using Ctsk(-/-) mice, the authors demonstrate a protective role of cathepsin K against chronic DSS colitis. Dissecting the underlying mechanisms the authors found cathepsin K to be present in intestinal goblet cells and the mucin layer. Furthermore, a direct cathepsin K-mediated bactericidal activity against intestinal bacteria was demonstrated, which potentially explains the alteration of intestinal microbiota observed in Ctsk(-/-) mice. Rectal administration of recombinant cathepsin K in DSS-treated Ctsk(-/-) mice ameliorates the severity of intestinal inflammation. These data identify extracellular cathepsin K as an intestinal antibacterial factor with anti-inflammatory potential and suggest that topical administration of cathepsin K might provide a therapeutic option for patients with inflammatory bowel disease.
Chénier, Sonia; Macieira, Susana M; Sylvestre, Doris; Jean, Daniel
An 11-year-old Quarter horse mare was presented for recurrent episodes of colic. A chronic intestinal pseudo-obstruction was diagnosed. Medical treatment and surgical resection of the colon were performed but the condition did not improve and the horse was euthanized. Histopathological examination revealed a myenteric ganglionitis of the small intestine and ascending colon.
Taverna, Josephine A; Babiker, Hani M; Yun, Seongseok; Bishop, Maria C; Lau-Braunhut, Sarah; Meyer, Paul N; Enzler, Thomas
Paraneoplastic syndromes can precede the initial manifestation and diagnosis of cancer. Paraneoplastic syndromes are a heterogeneous group of disorders caused by mechanisms other than the local presence of tumor cells. These phenomena are mediated by humoral factors secreted by tumor cells or by tumor mediated immune responses. Among paraneoplastic syndromes, chronic intestinal pseudo-obstruction (CIPO) is rare and represents a particularly difficult clinical challenge. Paraneoplastic CIPO is a highly morbid syndrome characterized by impaired gastrointestinal propulsion with symptoms and signs of mechanical bowel obstruction. Clinical outcomes of paraneoplastic CIPO are often deleterious. The current standard of care for the management of CIPO includes supportive treatment with promotility and anti-secretory agents. However, the majority of patients with CIPO eventually require the resection of the non-functioning gut segment. Here, we present a 62-year-old patient with anti-Hu antibody associated paraneoplastic CIPO and underlying small cell lung cancer who underwent treatment with cisplatin and etoposide. Herein, we discuss diagnosis, prognosis, proposed mechanisms, treatment options, and future potential therapeutic strategies of paraneoplastic CIPO.
Papadaki, H A; Eliopoulos, D G; Valatas, V; Eliopoulos, G D
This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.
Lecker, Jaime L; Froberg-Fejko, Karen
Idiopathic chronic diarrhea of nonhuman primates is a major gastrointestinal disorder and a leading cause of serious morbidity in nonhuman primates kept in captivity. Many animals are not responsive to traditional treatments. Millions of dollars are spent annually on diagnosis and supportive care of these animals. Probiotics like Bio-Serv's PrimiOtic and PrimiOtic Plus can help to reduce the incidence of diarrhea in captive nonhuman primates by supporting the natural microflora in the gut.
Zenner, Hans-Peter; Delb, Wolfgang; Kröner-Herwig, Birgit; Jäger, Burkhard; Peroz, Ingrid; Hesse, Gerhard; Mazurek, Birgit; Goebel, Gerhard; Gerloff, Christian; Trollmann, Regina; Biesinger, Eberhard; Seidler, Harald; Langguth, Berthold
The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation.
Gale, Jeremy D
Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (C-IBS) are commonly reported gastrointestinal (GI) disorders that have a major impact on health and quality of life. Patients experience a range of symptoms of which infrequency of bowel movement is but one and report that straining, the production of hard stools, and unproductive urges are more bothersome than stool infrequency. Additionally, in C-IBS, patients report abdominal pain and bloating as particularly troubling. Traditional treatments, such as laxatives, are often ineffective, especially in more severe constipation over the long term. In a population-based survey of constipation sufferers, half were not satisfied with their current treatment, due predominantly to poor efficacy. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists stimulate GI motility and intestinal secretion, and tegaserod has demonstrated efficacy in improving bowel habit. Tegaserod also improves constipation-associated symptoms including bloating, abdominal discomfort, stool consistency, and straining in patients with both CIC and C-IBS. However, tegaserod has been withdrawn due to an association with serious adverse cardiovascular effects. Further 5-HT(4) receptor agonists, including prucalopride and TD-5108 are in development and show exciting results in clinical studies in CIC patients, suggesting further product approvals are likely. Headache and diarrhea are the most commonly reported adverse event with this class of agent. Recently a novel prosecretory agent has been approved for the treatment of both CIC and C-IBS. Lubiprostone stimulates chloride secretion through activation of type-2 chloride channels, increasing intestinal secretion and transit, and its use has been associated with improvements in bowel habit and symptoms of constipation. Nausea, diarrhea, and headache are the most commonly reported adverse events. Linaclotide also stimulates intestinal chloride secretion, but this molecule
Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.
Busby, Robert W; Kessler, Marco M; Bartolini, Wilmin P; Bryant, Alexander P; Hannig, Gerhard; Higgins, Carolyn S; Solinga, Robert M; Tobin, Jenny V; Wakefield, James D; Kurtz, Caroline B; Currie, Mark G
Linaclotide, a potent guanylate cyclase C agonist, is a therapeutic peptide approved in the United States for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. We present for the first time the metabolism, degradation, and disposition of linaclotide in animals and humans. We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide. Systemic exposure to these active peptides is low in rats and humans, and the low systemic and portal vein concentrations of linaclotide and MM-419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration. Linaclotide is stable in the acidic environment of the stomach and is converted to MM-419447 in the small intestine. The disulfide bonds of both peptides are reduced in the small intestine, where they are subsequently proteolyzed and degraded. After oral administration of linaclotide, <1% of the dose was excreted as active peptide in rat feces and a mean of 3-5% in human feces; in both cases MM-419447 was the predominant peptide recovered. MM-419447 exhibits high-affinity binding in vitro to T84 cells, resulting in a significant, concentration-dependent accumulation of intracellular cyclic guanosine-3',5'-monophosphate (cGMP). In rat models of gastrointestinal function, orally dosed MM-419447 significantly increased fluid secretion into small intestinal loops, increased intraluminal cGMP, and caused a dose-dependent acceleration in gastrointestinal transit. These results demonstrate the importance of the active metabolite in contributing to linaclotide's pharmacology.
Schröder, Carin; Johnston, Marie; Teunissen, Laurien; Notermans, Nicolette; Helders, Paul; van Meeteren, Nico
To investigate (1) whether control perceptions (person's perception of ease or difficulty of performing behavior) and emotions contribute to activity limitations and if so (2) whether these variables mediate the relation between impairment and activity limitations in patients with chronic idiopathic axonal polyneuropathy (CIAP). Cross-sectional study. Outpatient clinics of a university medical center. Fifty-six patients diagnosed with CIAP. Not applicable. Control perceptions about performing activities (questionnaire based on the theory of planned behavior), emotions (Hospital Anxiety and Depression Scale), activity limitations (performance: Shuttle Walk Test [SWT]; self-report: Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36] physical functioning subscale, self-reported ability to walk), and physical impairments (muscle strength, sensory function). Control perceptions significantly (P<.01) correlated with all measures of activity limitations (r range, .58-.69). Hierarchical multiple regression analyses showed that perceived control explained 9% of the variance in the SWT (beta=.34, P<.01), 12% in the SF-36 (beta=.40, P<.01), and 24% in ability to walk (beta=.54, P<.01). In all measures of activity limitations, perceived control significantly mediated the effect of impairment. Perceived control explained and mediated variance in activity limitations, whereas emotions did not. This suggests that increasing patients' perceptions of control might enhance performance of activities, even without changes in impairment.
Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver
Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.
Garmendia, Jenny V; Zabaleta, Mercedes; Aldrey, Oscar; Rivera, Henry; De Sanctis, Juan B; Bianco, Nicolás E; Blanca, Isaac
The pathogenesis of chronic idiopathic urticaria (CIU) is not completely understood although autoimmunity has been proposed. The aim of the study was to assess the expression of different leukocyte antigens, by flow cytometry, assaying total blood of 29 patients with CIU and of 20 sex and age matched controls. Moreover, we assessed soluble CD154 a marker of immune cell activation, predominantly memory T cells. When patients were divided depending an their response to the autologous serum skin test (ASST), three different groups were encountered: group 1 (n=11): with negative ASST-, group 2 (n=11): positive ASST (ASST+) with normal lymphocyte counts and group 3 (n=7): ASST+ with low lymphocyte counts (< 1500 cells/mm3). A significant increase in CD19+ percentage and not in the absolute count (P < 0.05) was observed in group 1 as compared to controls and to the other groups. In contrast, CD30+, CD45RO+ and CD4+/CD45RO+ percentages and biologically active soluble CD154 levels were significantly higher (P < 0.05) in group 3 as compared to group 1 or to controls. In ASST positive groups, CD45RO+ and CD4+/CD45RO+ positiveness correlates with wheal diameter. In conclusion, memory cells may play a role in these different types of patients and in understanding CIU pathogenesis.
Reboul, Marie-Pierre; Laharie, David; Amouretti, Michel; Lacombe, Didier; Iron, Albert
We report the case of a patient suffering from idiopathic chronic pancreatitis (ICP) and compound heterozygous for mutations G542X and S1235R of the cystic fibrosis transmembrane regulator (CFTR) gene. The patient had normal sweat test and no other clinical sign usually linked with a typical or moderate pathology (bronchiectasis, nasal polyposis, congenital absence of the vas deferens) of the CFTR gene. G542X is a severe mutation, which is usually found in classical cystic fibrosis when associated with other severe mutations. S1235R is a quite rare abnormality recently reported as being potentially pathogenic when combined in trans with a second CF mutation. Our case is quite similar to the only other six patients in the literature in whom only the pancreas is affected and who bear a rare mutation with moderate effect. The history and the clinical features of our patient indicate an unambiguous isolated ICP in which the presence of the S1235R mutation--in trans with regard to G542X--is likely responsible for the ICP phenotype. This case could throw light on some of the as yet poorly known abnormalities of the CFTR gene in the ICP phenotype.
Martín-Láez, R; Valle-San Román, N; Rodríguez-Rodríguez, E M; Marco-de Lucas, E; Berciano Blanco, J A; Vázquez-Barquero, A
Since its description five decades ago, the pathophysiology of idiopathic chronic adult hydrocephalus (iCAH) has been traditionally related to the effect that ventricular dilatation exerts on the structures surrounding the ventricular system. However, altered cerebral blood flow, especially a reduction in the CSF turnover rate, are starting to be considered the main pathophysiological elements of this disease. Compression of the pyramidal tract, the frontostriatal and frontoreticular circuits, and the paraventricular fibres of the superior longitudinal fasciculus have all been reported in iCAH. At the level of the corpus callosum, gliosis replaces a number of commissural tracts. Cerebral blood flow is also altered, showing a periventricular watershed region limited by the subependymal arteries and the perforating branches of the major arteries of the anterior cerebral circulation. The CSF turnover rate is decreased by 75%, leading to the reduced clearance of neurotoxins and the interruption of neuroendocrine and paracrine signalling in the CSF. iCAH presents as a complex nosological entity, in which the effects of subcortical microangiopathy and reduced CSF turnover play a key role. According to its pathophysiology, it is simpler to think of iCAH more as a neurodegenerative disease, such as Alzheimer disease or Binswanger disease than as the classical concept of hydrocephalus. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
Hube, Larissa; Dohrn, Maike F.; Karsai, Gergely; Hirshman, Sarah; Van Damme, Philip; Schulz, Jörg B.; Weis, Joachim; Hornemann, Thorsten; Claeys, Kristl G.
Aim Chronic idiopathic axonal polyneuropathy (CIAP) is a slowly progressive, predominantly sensory, axonal polyneuropathy, with no aetiology being identified despite extensive investigations. We studied the potential role of the metabolic syndrome, neurotoxic 1-deoxysphingolipids (1-deoxySLs), microangiopathy and inflammation in sural nerve biopsies. Methods We included 30 CIAP-patients, 28 with diabetic distal symmetrical polyneuropathy (DSPN) and 31 healthy controls. We assessed standardised scales, tested for the metabolic syndrome, measured 1-deoxySLs in plasma, performed electroneurography and studied 17 sural nerve biopsies (10 CIAP; 7 DSPN). Results One third of the CIAP-patients had a metabolic syndrome, significantly less frequent than DSPN-patients (89%). Although the metabolic syndrome was not significantly more prevalent in CIAP compared to healthy controls, hypercholesterolemia did occur significantly more frequent. 1-deoxySLs were significantly and equally elevated in both patient groups compared to healthy controls. Mean basal lamina thickness of small endoneurial vessels and the number of CD68- or CD8-positive cells in biopsies of CIAP- and DSPN-patients did not differ significantly. However, the number of leucocyte-common-antigen positive cells was significantly increased in CIAP. Conclusions A non-significant trend towards a higher occurrence of the metabolic syndrome in CIAP-patients compared to healthy controls was found. 1-deoxySLs were significantly increased in plasma of CIAP-patients. Microangiopathy and an inflammatory component were present in CIAP-biopsies. PMID:28114358
Adir, Yochai; Harari, Sergio
Severe pulmonary hypertension worsens the prognosis of patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). With the aim of better understanding the pathogenesis of this event and identifying the possible targets for therapeutic intervention, a great deal of clinical and translational research is now focused on this relevant field of medicine. Some studies that were published last year have helped to better define the clinical and physiological profiles of patients with COPD or IPF and severe pulmonary hypertension. The importance of pulmonary rehabilitation was confirmed, particularly in patients with pulmonary hypertension associated with IPF. Information on the use of drugs approved for the treatment of pulmonary arterial hypertension is still very limited, because of some limitations and selection biases in the studies' design. New strategies (i.e. the use of fasudil or sepiapterin in pulmonary hypertension associated with IPF) have been evaluated in animal models. Pulmonary hypertension in COPD or IPF may range from mild to severe. When pulmonary hypertension is more advanced, it can drive a poor outcome. Therefore, future studies should focus on this subset.
Tomasello, Giovanni; Bellavia, Maurizio; Palumbo, Vincenzo Davide; Gioviale, Maria Concetta; Damiani, Provvidenza; Lo Monte, Attilio Ignazio
The gut of a healthy adult harbours a myriad of different microbial species. It is estimated that approximately 10 14 are present in total bacterial colony forming units (CFU). Each colony colonizes a specific intestinal tract. In healthy adult, the main control of intestinal bacterial colonization occurs through gastric acidity but also other factors can influence the intestinal microenvironment such as pH, temperature, competition among different bacterial strains, peristalsis, drugs, radiotherapy and much more. Impaired microbial homeostasis leads to an alteration of the permeability of tissue, together with the activation of the intestinal immune system MALT (mucosal associated lymphoid tissue). In this regard we discuss the increasing experimental evidences of the role of commensal microbiota in the activation of specific intestinal immunocompetent cells. The aforementioned micro-environmental changes provide the substrate for the etiopathogenetic outbreak of numerous pathologies of gastro-intestinal tract, such as intestinal chronic inflammation (Crohn's disease and Ulcerative Colitis), together with a miscellany of extra intestinal disorders. This article is an overview of the latest scientific findings about the close causal relationship between intestinal microbial flora and inflammatory bowel diseases or other extra-intestinal diseases; it is also mentioned the possible relationship between mycobacteria and Chron's disease. Finally we analyse the beneficial role of probiotics.
Nagarale, Girish P.; Ravindra, S.; Thakur, Srinath; Setty, Swati
Background: Idiopathic gingival enlargement is a rare condition characterized by massive enlargement of the gingiva. It may be associated with other diseases/conditions characterizing a syndrome, but rarely associated with periodontitis. Case Description: This case report describes an unusual clinical form of gingival enlargement associated with chronic periodontitis. Clinical examination revealed diffuse gingival enlargement. The lesion was asymptomatic, firm, and pinkish red. Generalized periodontal pockets were observed. Radiographic evaluation revealed generalized severe alveolar bone loss. Histopathological investigations revealed atrophic epithelium with dense fibrocollagenous tissue. Lesions healed successfully following extraction and surgical excision, and no recurrence was observed after 1 year follow-up but recurrence was observed at 3 and 5-years follow-up. Clinical Implications: Successful treatment of idiopathic gingival enlargement depends on proper identification of etiologic factors and improving esthetics and function through surgical excision of the over growth. However, there may be recurrence. PMID:23869135
Cui, Yanjun; Gu, Xianhong
Acute heat stress (HS) negatively affects intestinal integrity and barrier function. In contrast, chronic mild HS poses a distinct challenge to animals. Therefore, this study integrates biochemical, histological and proteomic approaches to investigate the effects of chronic HS on the intestine in finishing pigs. Castrated male crossbreeds (79.00 ± 1.50 kg BW) were subjected to either thermal neutral (TN, 21 °C; 55% ± 5% humidity; n=8) or HS conditions (30 °C; 55% ± 5% humidity; n=8) for 3 weeks. The pigs were sacrificed after 3 weeks of high environmental exposure and the plasma hormones, the intestinal morphology, integrity, and protein profiles of the jejunum mucosa were determined. Chronic HS reduced the free triiodothyronine (FT3) and GH levels. HS damaged intestinal morphology, increased plasma d-lactate concentrations and decreased alkaline phosphatase activity of intestinal mucosa. Proteome analysis of the jejunum mucosa was conducted by 2D gel electrophoresis and mass spectrometry. Fifty-three intestinal proteins were found to be differentially abundant, 18 of which were related to cell structure and motility, and their changes in abundance could comprise intestinal integrity and function. The down-regulation of proteins involved in tricarboxylic acid cycle (TCA cycle), electron transport chain (ETC), and oxidative phosphorylation suggested that chronic HS impaired energy metabolism and thus induced oxidative stress. Moreover, the changes of ten proteins in abundance related to stress response and defense indicated pigs mediated long-term heat exposure and counteracted its negative effects of heat exposure. These findings have important implications for understanding the effect of chronic HS on intestines.
Subramanya, Sandeep B.; Subramanian, Veedamali S.; Kumar, Jeyan S.; Hoiness, Robert
The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5′-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5′-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding. PMID:21148397
Subramanya, Sandeep B; Subramanian, Veedamali S; Kumar, Jeyan S; Hoiness, Robert; Said, Hamid M
The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5'-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5'-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding.
Rajan, Jessica P; Simon, Ronald A; Bosso, John V
Chronic idiopathic urticaria (CIU) is defined as the presence of urticaria most days of the week for a period of 6 weeks or longer. There have been reports of food additive sensitivity in CIU previously, but the prevalence has not been precisely determined. To determine the prevalence of reactions to food and drug additives in patients with CIU. We challenged 100 patients in our allergy/immunology division with CIU to the 11 additives most commonly associated with reactions: tartrazine (FD&C Yellow 5), potassium metabisulfite, monosodium glutamate, aspartame, sodium benzoate, methyl paraben, butylated hydroxy anisole, butylated hydroxy toluene, FD&C Yellow 6, sodium nitrate, sodium nitrite. All of the patients had a history of CIU for longer than 6 weeks, and 43 reported possible history of food or drug additive sensitivity. Single-blind challenges to all of the additives were performed in the clinic and skin scores were recorded. Subjects with positive challenge tests underwent double-blind placebo controlled challenges. Of 100 subjects, only 2 had a positive urticarial response on single-blind challenge. Neither of these patients had a positive urticarial response on double-blind placebo-controlled challenge. There were no gastrointestinal, respiratory, or other symptom, and no patients reported late reactions. We were able to conclude, with 95% confidence intervals that sensitivity to any of the 11 food and drug additives occurs in fewer than 1% of patients with CIU. Food and drug additives appear to be a rare cause of CIU, and avoidance is not recommended. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Magen, Eli; Waitman, Dan-Andrei; Dickstein, Yoav; Davidovich, Valentina; Kahan, Natan R
Despite the established association between chronic idiopathic/spontaneous urticaria (CIU) and presence of antinuclear antibodies (ANAs), the prevalence of autoimmune comorbidities in this population has not been analyzed. Here, we aim to identify clinical and laboratory manifestations associated with ANA-positive CIU. ANA-positive patients were identified via electronic data capture from the electronic patient record database of Leumit Health care Services (LHS) of Israel. Patient characteristics, medical histories, and details of diagnostic workup, medical treatment, and follow-up were retrieved by performing a chart review of electronic patient records (EPRs). The prevalence of target diseases among ANA(+) CIU(+), ANA(+) CIU(-), and ANA(-) CIU(+) patients was calculated. A total of 91 ANA(+) CIU(+), 3131 ANA(+) CIU(-), and 478 ANA(-) CIU(+) patients were identified. The ANA(+) CIU(+) group was characterized by higher prevalence of Sjögren's syndrome (SS)-A 52 antibodies (Ab) (7.7% versus 2.4%; p = 0.008), SS-A 60 Ab (11% versus 2.8%; p = < 0.001), and SS-B Ab (14.3% versus 3.2%; p < 0.001), compared with ANA(-) CIU(+) group. Additionally, ANA(+) CIU(+) patients were more likely to be diagnosed with thyroid autoimmune diseases, higher C-reactive protein (6.4 ± 10.3 versus 4.1 ± 8.8 mg/L; p = 0.027), and more profound basopenia (0.04 ± 0.09 versus 0.15 ± 0.11 cell/mm(3); p < 0.001) than ANA(-) CIU patients. More ANA(+) CIU(+) patients were resistant to four-fold standard licensed doses of antihistamines than ANA(-) CIU(+) patients [11 (12.1%) versus 29 (6.1%); p = 0.046]. ANA-positive CIU is characterized by higher prevalence of SS-A 52, SS-A 60, and SS-B antibodies and poorer clinical response to antihistamine medications.
Eckman, John A; Hamilton, Robert G; Gober, Laura M; Sterba, Patricia M; Saini, Sarbjit S
Potentially pathogenic IgG autoantibodies to IgE or its receptor, Fc epsilonRIalpha, have been detected in approximately 40% of chronic idiopathic urticaria (CIU) patients. CIU patients' basophils display distinct altered Fc epsilonRIalpha-mediated degranulation. CIU patients with basophil histamine release in response to polyclonal goat anti-human IgE > or = 10% are classified as CIU responders (CIU-R) and < 10% are CIU non-responders (CIU-NR). We compared the presence of autoantibodies to basophil degranulation phenotypes and to disease status (active or inactive). Sera were collected from non-CIU subjects and CIU subjects who participated in a longitudinal study of disease severity and had defined basophil degranulation phenotypes. Immunoenzymetric assays (IEMA) quantified IgG anti-Fc epsilonRIalpha and anti-IgE. IgG anti-Fc epsilonRIalpha antibody was detected in 57% of CIU-R (n=35), 55% of CIU-NR (n=29), and 57% of non-CIU subjects (n=23), whereas IgG anti-IgE was present in 43% of CIU-R, 45% of CIU-NR, and 30% of non-CIU subjects. Both the autoantibody levels and the functional basophil phenotype remained stable in subjects with active disease (n=16), whereas there was an enhancement in basophil function as subjects evolved into a state of remission (n=6), which appears independent of the presence of autoantibody. IEMAs detected a similar frequency of autoantibodies in CIU-R, CIU-NR, and non-CIU subjects. Basophil function may be independent of IEMA-detected autoantibodies.
Illán-Gala, I; Pérez-Lucas, J; Martín-Montes, A; Máñez-Miró, J; Arpa, J; Ruiz-Ares, G
Adult chronic idiopathic hydrocephalus (ACIH) is a cause of dementia that can be treated by implanting a ventriculo-peritoneal shunt (VPS). We aim to study clinical and functional outcomes in patients with ACIH corrected with a VPS. Observational cohort study of patients diagnosed with probable ACIH (Japan Neurosurgical Society guidelines) and undergoing shunt placement between 2008 and 2013 in a centre of reference for neurosurgery in Spain. Clinical improvement was classified in 4 categories (resolution, partial improvement, equivocal improvement, and no improvement); functional outcome was assessed on the modified Rankin scale (mRS). The study included 29 patients with a mean age of 73.9 years; 62.1% were male and 65.5% had hypertension. Clinical improvement (complete or partial) was observed in 58% after one year and in 48% by the end of the follow-up period (mean follow-up time was 37.8 months). Older age, presence of hypertension, and surgery-related complications were more prevalent in the group responding poorly to treatment. One patient died, 20.7% experienced severe complications, and 69% were dependent (mRS ≥ 3) by the end of the follow-up period. Age at diagnosis was independently associated with poorer clinical response at one year and a higher degree of dependency by the end of follow-up. Symptomatic benefits offered by VPS were partial and transient; treatment was associated with a high complication rate and poor functional outcomes in the long term, especially in the oldest patients. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Lee, Kyung-Ah; Lee, Won-Jae
The association between deregulated intestinal microbial consortia and host diseases has been recognized since the birth of microbiology over a century ago. Intestinal dysbiosis refers to a state where living metazoans harbor harmful intestinal microflora. However, there is still an issue of whether causality arises from the host or the microbe because it is unclear whether deregulation of the gut microbiota community is the consequence or cause of the host disease. Recent studies using Drosophila and its simple microbiota have provided a valuable model system for dissecting the molecular mechanisms of intestinal dysbiosis. In this review, we examine recent exciting observations in Drosophila gut-microbiota interactions, particularly the links among the host immune genotype, the microbial community structure, and the host inflammatory phenotype. Future genetic analyses using Drosophila model system will provide a valuable outcome for understanding the evolutionarily conserved mechanisms that underlie intestinal dysbiosis and chronic inflammatory diseases.
Kang, Min Ju; Kim, Hei Sung; Kim, Hyung Ok; Park, Young Min
Chronic idiopathic urticaria (CIU) is a relatively common disease, and yet not much is known about the causative factors or its pathophysiology, which makes it difficult to cure. Due to its chronic nature, many patients have significantly reduced quality of life (QOL). The purpose of this study was to assess the impact of CIU on QOL of Korean patients, and to determine whether a relationship exists between QOL and the severity of disease. One hundred sixty three patients with CIU, who first visited our out-patient clinic between August 2005 and July 2007, were asked to complete two questionnaires: one designed to assess the clinical features of their disease; the other on the influences of CIU on their daily lives. QOL was divided into six categories: mental status (MS), daily living activities (DLA), leisure activities (LA), self-perception (SP), treatment-induced restrictions (TIR), and social functions (SF). All of the QOL scores were recalibrated to a 0~100 scale, with 100 indicating the worst QOL, and 0 the best. THE AVERAGE QOL SCORES OBTAINED FROM THE QUESTIONNAIRE WERE AS FOLLOWS: SP (13.1+/-4.6), DLA (12.0+/-4.3), MS (10.3+/-3.3), SF (8.5+/-3.4), LA (6.1+/-3.0), and TIR (5.5+/-2.6). SP was the domain that was most affected; TIR the least. There were positive correlations between pairs of the six different QOL categories (p<0.001). These results demonstrate that CIU exerts an influence on many aspects of QOL. TIR was significantly affected in longer term CIU cases (p<0.05), while SP, MS, DLA, SF, and SR scores did not correlate with disease duration. Disease severity was found to have a significant impact on SP, MS, SF, and LA (p<0.05). In patients with concurrent physical urticaria, DLA and SF scores were significantly affected (p<0.05). Based on these results, it is suggested that CIU has a negative impact on QOL in Korean patients. Therefore, it is important to recognize the effects CIU can have on QOL and consider them in evaluating the response to
Thaiwat, Supitchaya; Nakakes, Artit; Sangasapaviliya, Atik
Recent findings show food allergy is rarely the cause of chronic urticaria. However; reports showed up to 5% of chronic idiopathic urticaria (CIU) was food induced urticaria (FIU) and the remission rate with food avoidance in CIU was varied. According to recent studies, skin prick test (SPT) is not a gold standard for investigating the culprit food allergen in CIU. The clinical response for food avoidance is still unclear. The purpose of the present study is to investigate the association of food allergen and SP7 the clinical response after positive food avoidance in adult Thai patients with CIU. We conducted a prospective study that included 76 patients, who presented with CIU at the Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, between September 1, 2009 and May 31, 2010. Personal data, general physical examination, and detailed history were obtained. Twenty food allergens were used to perform SPT at the allergy clinic. The positive food allergens were enrolled to avoid the culprit food allergens for two to four weeks and evaluated the clinical response. Fifty-one of 76 patients (67.1%) gave history compatible with FIU. Shrimp (54.9%) and fish (49.0%) were the two most commonly suspected allergens by the patients. Fifteen of 76 patients (19.7%) had positive SPT In comparison to the SPT negative group in terms of clinical severity and effect on their daily lives, there was no significant difference. We then matched the SPT results with the patient's history. Five of 76 (6.6%) patients had results of SPT matching the patients' history. The five allergens in these patients were fish, milk, tomato, shrimp, and yeast. Fifty-one of 76 (67.1%) patients had negative SPT results but the patients suspected that certain foods were the cause of their urticaria. Fifteen of 76 (19.7%) patients had positive SPT results but the patients had never suspected any food allergen. Among these SPT positive patients, 13 food allergens were the culprits, the
Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L
Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
Miyakoshi, Shigesaburo; Kami, Masahiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Kusumi, Eiji; Matsumura, Tomoko; Onishi, Yasushi; Kobayashi, Kazuhiko; Kim, Sung-Won; Hamaki, Tamae; Takaue, Yoichi; Taniguchi, Shuichi
A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.
Toledo de Arruda Lourenção, Pedro Luiz; Terra, Simone Antunes; Ortolan, Erika Veruska Paiva; Rodrigues, Maria Aparecida Marchesan
Intestinal neuronal dysplasia type B (IND-B) is a controversial entity among the gastrointestinal neuromuscular disorders. It may occur alone or associated with other neuropathies, such as Hirschsprung’s disease (HD). Chronic constipation is the most common clinical manifestation of patients. IND-B primarily affects young children and mimics HD, but has its own histopathologic features characterized mainly by hyperplasia of the submucosal nerve plexus. Thus, IND-B should be included in the differential diagnoses of organic causes of constipation. In recent years, an increasing number of cases of IND-B in adults have also been described, some presenting severe constipation since childhood and others with the onset of symptoms at adulthood. Despite the intense scientific research in the last decades, there are still knowledge gaps regarding definition, pathogenesis, diagnostic criteria and therapeutic possibilities for IND-B. However, in medical practice, we continue to encounter patients with severe constipation or intestinal obstruction who undergo to diagnostic investigation for HD and their rectal biopsies present hyperganglionosis in the submucosal nerve plexus and other features, consistent with the diagnosis of IND-B. This review critically discusses aspects related to the disease definitions, pathophysiology and genetics, epidemiology distribution, clinical presentation, diagnostic criteria and therapeutic possibilities of this still little-known organic cause of intestinal chronic constipation. PMID:27602240
Cresci, Gail A; Glueck, Bryan; McMullen, Megan R; Xin, Wei; Allende, Daniella; Nagy, Laura E
Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. C57BL/6J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 h before euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction (TJ) proteins, toll-like receptors, and tumor necrosis factor-alpha were assessed. Caco-2 monolayers with or without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity. Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic toll-like receptor mRNA expression and tumor necrosis factor-alpha protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: Leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-tributyrin mice. Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury. © 2017
Lauffer, Adriana; Vanuytsel, Tim; Vanormelingen, Christophe; Vanheel, Hanne; Salim Rasoel, Shadea; Tóth, Joran; Tack, Jan; Fornari, Fernando; Farré, Ricard
Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon.
... Testing (1 link) Genetic Testing Registry: Idiopathic fibrosing alveolitis, chronic form Other Diagnosis and Management Resources (1 ... area? Other Names for This Condition cryptogenic fibrosing alveolitis idiopathic fibrosing alveolitis, chronic form IPF usual interstitial ...
Gupta, Madhulika A; Gupta, Aditya K
A large body of literature supports the role of psychologic stress in urticaria; however, the comorbidity between chronic idiopathic urticaria (CIU) and post-traumatic stress disorder (PTSD), a classic stress-mediated syndrome, has received little attention. The underlying etiology of urticaria is not identifiable in about 70% of patients, possibly because of difficulties with identification of a direct cause-and-effect relationship between a potential causative factor and the onset of urticaria. The core features of PTSD (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision [DSMIV-TR]) that are important in urticaria include (1) autonomic nervous system reactivity and state of sympathetic hyperarousal that can manifest as CIU, and (2) the persistent re-experiencing of the traumatic events in PTSD, which can manifest as urticaria or angioedema, or both, affecting a previously traumatized body region (eg, urticarial wheals affecting the body region where the patient had been stabbed years earlier). The following features of PTSD make it difficult to use the cause-and-effect model for the determination of causation: (1) PTSD may first emerge years after the initial trauma and is classified as PTSD with Delayed Onset (DSMIV-TR); and (2) the traumatic triggers that precipitate the PTSD symptoms may be unique and idiosyncratic to the patient and not even qualify as stressful or traumatic by standard criteria (eg, precipitating events for the PTSD may include smell of a certain cologne that was used by the perpetrator or witnessing a scene in a movie that was reminiscent of the location where the abuse occurred). Finally, in PTSD with Delayed Onset, patients may not make a conscious association between their recurrent urticaria and their earlier traumas because they can develop classically conditioned associations between stimuli that are reminiscent of the original abuse situation and their somatic reactions such as urticaria. The clinician
Dîrnu, Rodica; Secureanu, F A; Neamţu, Carmen; Totolici, B D; Pop, O T; Mitruţ, P; Mălăescu, D Gh; Mogoantă, L
Chronic gastritis has a high incidence in adults, causing progressive destruction of glandular structures, favoring the development of gastric atrophy. The association of chronic gastritis with intestinal type metaplasia of gastric mucosa has a poor outcome as intestinal metaplasia is regarded as a precancerous lesion. Metaplasia is common in patients with Helicobacter pylori infection and also heavy smokers. The aim of our study was to evaluate the relationship between chronic gastritis and intestinal metaplasia. The study was conducted on a total of 1218 patients, aged between 5 and 90 years, who presented for dyspeptic disorders in the period 2007-2010 and were examined clinically and endoscopically. During the gastroscopic examination, fragments of gastric mucosa were collected for the histopathological study and for highlighting the H. pylori infection. For the histopathological study, the Hematoxylin-Eosin and PAS-Alcian Blue stains were performed, while for the immunohistochemical study the anti-TAG72 and anti-PCNA antibodies were used. A diagnosis of gastritis was established in 615 patients, representing approximately 50.5% of all cases. Most cases with gastritis were found in people of middle age. Gastritis was present in almost all age groups, from teenagers to the elders. Of the 615 cases of gastritis, urease test was positive in 353 patients, representing approximately 57.40% of all patients with gastritis. Histopathological examination identified the presence of intestinal metaplasia in 61.60% of patients with chronic gastritis, mostly complete metaplasia. PCNA immunohistochemistry revealed that cell proliferation processes are intensified in intestinal metaplasia. This study highlights the importance of chronic gastritis, intestinal metaplasia, and H. pylori infection in the etiopathogeny of gastric cancer.
Pons-Guiraud, Annik; Nekam, Kristof; Lahovsky, J; Costa, Angela; Piacentini, Andrea
Emedastine difumarate (2 mg b.i.d.) was compared to loratadine (10 mg o.d.) in a randomized, double-blind, multicentre trial for 4 weeks in 192 patients with idiopathic chronic urticaria. After one week of treatment significant differences were recorded: body skin involvement diminished to 0-10% in 57.1% of emedastine patients vs. 38.2% of loratadine patients (p = 0.0019) and 83.3% had a total urticaria symptom score of 0-1 vs. 64.5% with loratadine (p = 0.0134). After 4 weeks of treatment the efficacy of the two drugs was similar in terms of mean change in total urticaria symptom score (- 5.57 +/- 3.15 with emedastine - 5.67 +/- 3.26 with loratadine), proportion of symptom-free patients (52.4% vs. 54.5%), intensity of erythema, number of hives, size of the largest hive, extent of skin area involved and overall assessment of urticaria symptoms.Twenty-three emedastine patients (23.9%) and 17 loratadine patients (17.7%) experienced an adverse event. Nineteen events in 15 emedastine patients and 9 in 9 loratadine patients were related to treatment (p = 0.0294). Only one event caused discontinuation in both treatment groups. The most common adverse event was sleepiness (7 patients with emedastine and 2 with loratadine). Emedastine is well tolerated, and as effective as loratadine in the short-term treatment of chronic idiopathic urticaria.
Politei, J; Durand, C; Schenone, A B; Torres, A; Mukdsi, J; Thurberg, B L
Chronic intestinal pseudo-obstruction results in clinical manifestations that resemble intestinal obstruction but in the absence of any physical obstructive process. Fabry disease is an X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement. We report the occurrence of chronic intestinal pseudo-obstruction in two unrelated patients with Fabry disease and the possible explanation of a direct relation of these two disorders. In Fabry disease, gastrointestinal symptoms occur in approximately 70% of male patients, but the frequency ranges from 19% to 69% in different series. In some patients, colonic dysmotility due glycolipid deposition in autonomic plexus and ganglia can lead to the pseudo-obstruction syndrome, simulating intestinal necrosis. That is why up to this date colostomy has been performed in some cases, even for children with FD without cardiac, renal or cerebrovascular compromise. Early treatment with enzyme replacement therapy in asymptomatic or mildly symptomatic patients may be justified in order to prevent disease progression. Several studies have demonstrated that enzyme replacement therapy alleviates GI manifestations. Because of the non-specific nature of the gastrointestinal symptoms, diagnosis of Fabry disease is often delayed for several years. Gastrointestinal involvement is often misdiagnosed or under-reported. It is therefore very important to consider Fabry disease in the differential diagnosis of chronic intestinal pseudo-obstruction.
Lunge, Snehal Balvant; Borkar, Milind; Pande, Sushil
Background: About 25–45% of patients of chronic urticaria (CU) have been stated to have histamine releasing autoantibodies in their blood. The term autoimmune urticaria is increasingly being accepted for this subgroup of patients. Review of the literature suggests high autologous serum skin test (ASST) positivity and presence of antithyroid microsomal antibodies in patients with autoimmune urticaria. Aims: To study prevalence of ASST positivity and antithyroid microsomal antibodies in chronic “idiopathic” urticaria and to study the correlation between the two parameters. Methods: All patients of chronic idiopathic urticaria satisfying inclusion/exclusion criteria were enrolled in the study after written informed consent. Patients of CU secondary to infections and infestations, physical urticaria including dermatographism, mastocytosis, urticarial vasculitis and those on treatment with immunosuppressive drugs for urticaria were excluded from the study. In all of these patients, complete blood count; ASST, serum T3/T4/thyroid stimulating hormone levels, antithyroid microsomal antibody (AMA) levels were done. Statistical analysis was done by Chi-square test, Fisher exact test and Kappa statistics. Results: Study included 24 males and 26 females with mean age of 39.54 years. Majority of patients belonged to 20–40 years of age. Females showed more ASST positivity. A total of 12 out of 50 (24%) patients showed positive ASST. A total of four out of 12 (33.33%) had positive ASST and raised AMA levels. Conclusion: Only 25% of patients of chronic idiopathic urticaria had positive ASST. ASST and AMA levels were positively correlated in our study. Further studies are required to authenticate this association. PMID:26225328
Le Fourn, Elodie; Giraudeau, Bruno; Chosidow, Olivier; Doutre, Marie-Sylvie; Lorette, Gérard
Background The recommended first-line therapy of chronic urticaria is second-generation antihistamines, but the modalities of treatment remains unclear. Numerous recommendations with heterogeneous conclusions have been published. We wondered whether such heterogeneous conclusions were linked to the quality of published studies and their reporting. Objective To review the study design and quality of reporting of randomized control trials investigating pharmacological treatment of autoimmune or idiopathic chronic urticaria. Methodology/Principal Findings MEDLINE and EMBASE were searched for pharmacological randomized controlled trials involving patients with chronic autoimmune or idiopathic urticaria, with the main outcome being treatment efficacy. Data were collected on general characteristics of the studies, internal validity, studied treatments, design of the trial, outcome measures and “spin” strategy in interpreting results. Spin was defined as use of specific reporting strategies to highlight that the experimental treatment is beneficial, despite statistically nonsignificant results. We evaluated 52 articles that met our criteria. Patients were reported as blinded in 42 articles (81%) and the outcome assessor was blinded in 37 (71%). A placebo was the only comparator in 13 (25%) studies. The study duration was <8 weeks in 39 articles (75%), with no follow-up after discontinuation of treatment in 37 (71%). In 4 articles (8%), blinding was clear because they described blinding of the outcome assessor, the treatment was not recognizable (identical or double-dummy) or had no major secondary effects, and computed randomization was centralized. The primary outcome was specified in 33 articles (63%) and was a score in 31. In total, 15 different scores were used. A spin strategy was used for 10 of 12 studies with a nonsignificant primary outcome. Conclusion For establishing guidelines in treatment of chronic urticaria, studies should focus on choosing clinically
Li, Koukou; Zhuo, Cheng; Teng, Chunying; Yu, Sumei; Wang, Xin; Hu, Yang; Ren, Guangming; Yu, Min; Qu, Juanjuan
This study manifested the effects of polysaccharides from Ganoderma lucidum strain S3 (GLP S3) on chronic pancreatitis (CP) therapy and intestinal microbiota modulation in mice induced by diethyldithiocarbamate (DDC). The GLPS3 was prepared from cultured mycelium and markedly alleviated the pancreatitis in mice through decreasing lipase, AMS, IFN-γ and TNF-α level as well as increasing SOD and total antioxidant activity. Furthermore, high throughput sequencing analysis revealed that GLPS3 altered the composition and diversity of intestinal microbiota, especially, decreased the relative abundance of phylum Bacteroidetes and increased that of phylum Firmictutes. At the genus level, supplementation of GLPS3 increased the relative abundance of the beneficial bacteria such as Lactobacillales, Roseburia and Lachnospiraceae. These results disclosed the potential therapy mechanism of GLPS3 on chronic pancreatitis might be intestinal microbiota dependent.
Kaplan, Allen; Ferrer, Marta; Bernstein, Jonathan A; Antonova, Evgeniya; Trzaskoma, Benjamin; Raimundo, Karina; Rosén, Karin; Omachi, Theodore A; Khalil, Sam; Zazzali, James L
Few data are available that describe response patterns in patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) treated with omalizumab. We sought to describe response patterns by using data from the 3 pivotal omalizumab CIU/CSU trials. Every 4 weeks, randomized patients received dosing with placebo or 75, 150, or 300 mg of omalizumab (ASTERIA I: n = 318, 24 weeks; ASTERIA II: n = 322, 12 weeks) or placebo or 300 mg of omalizumab (GLACIAL: n = 335, 24 weeks). Response was defined as well-controlled urticaria (weekly Urticaria Activity Score [UAS7] ≤ 6) or complete response (UAS7 = 0). Response rates were dose dependent and highest with 300 mg of omalizumab. Some patients responded early (before week 4). At week 12, a higher proportion of patients treated with 300 mg of omalizumab reported a UAS7 ≤ 6 (26.0% [75 mg of omalizumab], 40.0% [150 mg of omalizumab], 51.9% [300 mg of omalizumab], and 11.3% [placebo] for ASTERIA I; 26.8% [75 mg of omalizumab], 42.7% [150 mg of omalizumab], 65.8% [300 mg of omalizumab], and 19.0% [placebo] for ASTERIA II; and 52.4% [300 mg of omalizumab] and 12.0% [placebo] for GLACIAL) or a UAS7 = 0 (11.7% [75 mg of omalizumab], 15.0% [150 mg of omalizumab], 35.8% [300 mg of omalizumab], and 8.8% [placebo] for ASTERIA I; 15.9% [75 mg of omalizumab], 22.0% [150 mg of omalizumab], 44.3% [300 mg of omalizumab], and 5.1% [placebo] for ASTERIA II; and 33.7% [300 mg of omalizumab] and 4.8% [placebo] for GLACIAL). In patients receiving 300 mg of omalizumab with 24 weeks of treatment, median time to achieve a UAS7 ≤ 6 was 6 weeks (ASTERIA I and GLACIAL) and median time to achieve a UAS7 = 0 was 12 or 13 weeks (ASTERIA I and GLACIAL, respectively). Some patients who achieved well-controlled urticaria or complete response sustained response throughout the treatment period. Benefits of omalizumab treatment were evident early (before week 4) in some patients and persisted to week
Casirola, D M; Rifkin, B; Tsai, W; Ferraris, R P
Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.
Obermeier, Florian; Hofmann, Claudia; Falk, Werner
From numerous studies during the last years it became evident that bacteria and bacterial constituents play a decisive role both in the maintenance of intestinal immune homeostasis as well as in the development and perpetuation of chronic intestinal inflammation. In this review we focus on the role of bacterial DNA which is a potent immunomodulatory component of the bacterial flora. Bacterial DNA has been shown to be protective against experimental colitis. In contrast bacterial DNA essentially contributes to the perpetuation of an already established chronic intestinal inflammation in a Toll-like receptor (TLR)9-dependent manner. This dichotomic action may be explained by a different activation status of essential regulators of TLR signaling like Glycogen synthase kinase 3-β (GSK3-β) depending on the pre-activation status of the intestinal immune system. In this review we suggest that regulators of TLR signaling may be interesting therapeutic targets in IBD aiming at the restoration of intestinal immune homeostasis. PMID:21188217
Joly, Francisca; Baxter, Janet; Staun, Michael; Kelly, Darlene G; Hwa, Yi Lisa; Corcos, Olivier; De Francesco, Antonella; Agostini, Federica; Klek, Stanislaw; Santarpia, Lidia; Contaldo, Franco; Jonker, Cora; Wanten, Geert; Chicharro, Luisa; Burgos, Rosa; Van Gossum, Andre; Cuerda, Cristina; Virgili, Nuria; Pironi, Loris
Home parenteral nutrition (HPN) is the primary treatment for chronic intestinal failure (IF). Intestinal transplantation (ITx) is indicated when there is an increased risk of death due to HPN complications or to the underlying disease. Age, pathophysiologic conditions and underlying disease are known predictors of HPN dependency and overall survival. Although the cause of death on HPN is mostly related to underlying disease in these patients, the relationship between mortality and duration of HPN use remains unclear. The purpose of the present study is to describe factors associated with survival and HPN dependency as well as causes of death in adult patients requiring HPN for chronic intestinal failure during the first 5 years of treatment with HPN. A multicenter international (European and USA) questionnaire-based retrospective follow-up of a cohort of 472 IF patients who started HPN was conducted between June and December 2000. Study endpoint was either end of 5-year follow-up, weaned-off HPN, ITx, or death on HPN. Data were analyzed for HPN dependence and overall survival using Kaplan-Meier models and log rank tests. The overall survival probability was 88%, 74% and 64% at 1, 3 and 5 years respectively. Survival was inversely related to age (p < .001) and higher in patients with Crohn's disease or chronic idiopathic pseudo-obstruction. A total of 169 (36.5%) patients were weaned-off HPN mainly (80%) within the first year and most frequently in patients with fistulae. Five of the 14 patients who underwent ITx died. By the end of the study, 104 (23%) of patients died on HPN; 65% of deaths occurred within the first 2.5 years of HPN. Younger ages at HPN initiation and underlying pathologies are significantly predictive of survival on HPN. Risk of death is greatest during the first 2 years of HPN. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Martínez-Hernández, L; Casamian-Sorrosal, D; Barrera-Chacón, R; Cuesta-Gerveno, J M; Belinchón-Lorenzo, S; Gómez Nieto, L C; Duque-Carrasco, F J
Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD. Copyright © 2016. Published by Elsevier Ltd.
Borrelli, Silvio; Minutolo, Roberto; De Nicola, Luca; De Simone, Emanuele; De Simone, Walter; Zito, Bruno; Guastaferro, Pasquale; Nigro, Filippo; Iulianiello, Giuseppe; Credendino, Olga; Bassi, Antonio; Leone, Luigi; Capuano, Maria; Auricchio, Maria Rita; Conte, Giuseppe
Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients and is associated with poor survival. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb proinflammatory cytokines and to decrease amino acids and antioxidants loss. These features could be helpful in MHD patients affected by idiopathic chronic inflammation, but this issue remains to be elucidated. We performed a multicenter longitudinal study to assess the effect of the switching from bicarbonate HD to HFR in patients with serum C-reactive Protein (CRP) > 5 mg/L coupled with albumin <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20 patients were assessed at 4 months and 18 completed the study. We excluded 11 patients with evident causes of inflammation. At baseline, serum levels of CRP (18.7[7.0-39.4] mg/L) and albumin (3.5[3.3-3.7] g/dL) were significantly correlated (r = -0.49; P = 0.028). The effect on CRP and albumin was almost evident in the first 4 months and remained stable until to eighth month. A strict correlation (R = -0.49; 0.040) between percentage change of CRP (-35%) and albumin (+14%) after 8 months of HFR. These effects were associated with the reduction of IL-6, IL-1β, and TNF-α and the increment of pre-albumin and leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained unchanged. In MHD patients affected by idiopathic chronic inflammation the switching from BHD to HFR is associated with improvement of inflammation. Whether these favorable effects may modify the outcomes of these high-risk patients needs to be confirmed by studies ad hoc.
De Giorgio, Roberto; Cogliandro, Rosanna F; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo
CIPO is the very “tip of the iceberg” of functional gastrointestinal disorders, being a rare and frequently misdiagnosed condition characterized by an overall poor outcome. Diagnosis should be based on clinical features, natural history and radiologic findings. There is no cure for CIPO and management strategies include a wide array of nutritional, pharmacologic, and surgical options which are directed to minimize malnutrition, promote gut motility and reduce complications of stasis (ie, bacterial overgrowth). Pain may become so severe to necessitate major analgesic drugs. Underlying causes of secondary CIPO should be thoroughly investigated and, if detected, treated accordingly. Surgery should be indicated only in a highly selected, well characterized subset of patients, while isolated intestinal or multivisceral transplantation is a rescue therapy only in those patients with intestinal failure unsuitable for or unable to continue with TPN/HPN. Future perspectives in CIPO will be directed toward an accurate genomic/proteomic phenotying of these rare, challenging patients. Unveiling causative mechanisms of neuro-ICC-muscular abnormalities will pave the way for targeted therapeutic options for patients with CIPO.
Muszynski, N. D.; Cheng, L. K.; Bradshaw, L. A.; Naslund, T. C.; Richards, W. O.
Chronic mesenteric ischemia (CMI) is a challenging clinical problem that is difficult to diagnose noninvasively. Diagnosis early in the disease process would enable life-saving early surgical intervention. Previous studies established that superconducting quantum interference device (SQUID) magnetometers detect the slow wave changes in the magnetoenterogram (MENG) noninvasively following induction of mesenteric ischemia in animal models. The purpose of this study was to assess functional physiological changes in the intestinal slow wave MENG of patients with chronic mesenteric ischemia. Pre- and postoperative studies were conducted on CMI patients using MENG and intraoperative recordings using invasive serosal electromyograms (EMG). Our preoperative MENG recordings showed that patients with CMI exhibited a significant decrease in intestinal slow wave frequency from 8.9 ± 0.3 cpm preprandial to 7.4 ± 0.1 cpm postprandial (P < 0.01) that was not observed in postoperative recordings (9.3 ± 0.2 cpm preprandial and 9.4 ± 0.4 cpm postprandial, P = 0.86). Intraoperative recording detected multiple frequencies from the ischemic portion of jejunum before revascularization, whereas normal serosal intestinal slow wave frequencies were observed after revascularization. The preoperative MENG data also showed signals with multiple frequencies suggestive of uncoupling and intestinal ischemia similar to intraoperative serosal EMG. Our results showed that multichannel MENG can identify intestinal slow wave dysrhythmias in CMI patients. PMID:25930082
Somarajan, S; Muszynski, N D; Cheng, L K; Bradshaw, L A; Naslund, T C; Richards, W O
Chronic mesenteric ischemia (CMI) is a challenging clinical problem that is difficult to diagnose noninvasively. Diagnosis early in the disease process would enable life-saving early surgical intervention. Previous studies established that superconducting quantum interference device (SQUID) magnetometers detect the slow wave changes in the magnetoenterogram (MENG) noninvasively following induction of mesenteric ischemia in animal models. The purpose of this study was to assess functional physiological changes in the intestinal slow wave MENG of patients with chronic mesenteric ischemia. Pre- and postoperative studies were conducted on CMI patients using MENG and intraoperative recordings using invasive serosal electromyograms (EMG). Our preoperative MENG recordings showed that patients with CMI exhibited a significant decrease in intestinal slow wave frequency from 8.9 ± 0.3 cpm preprandial to 7.4 ± 0.1 cpm postprandial (P < 0.01) that was not observed in postoperative recordings (9.3 ± 0.2 cpm preprandial and 9.4 ± 0.4 cpm postprandial, P = 0.86). Intraoperative recording detected multiple frequencies from the ischemic portion of jejunum before revascularization, whereas normal serosal intestinal slow wave frequencies were observed after revascularization. The preoperative MENG data also showed signals with multiple frequencies suggestive of uncoupling and intestinal ischemia similar to intraoperative serosal EMG. Our results showed that multichannel MENG can identify intestinal slow wave dysrhythmias in CMI patients. Copyright © 2015 the American Physiological Society.
Subramanian, Veedamali S.; Subramanya, Sandeep B.; Ghosal, Abhisek
Vitamin B2 (riboflavin, RF) is essential for normal human health. Mammals obtain RF from exogenous sources via intestinal absorption and prevent its urinary loss by reabsorption in the kidneys. Both of these absorptive events are carrier-mediated and involve specific RF transporters (RFVTs). Chronic alcohol consumption in humans is associated with a high prevalence of RF deficiency and suboptimal levels, but little is known about the effect of chronic alcohol exposure on physiological and molecular parameters of the intestinal and renal RF transport events. We addressed these issues using rats chronically fed an alcohol liquid diet and pair-fed controls as a model. The results showed that chronic alcohol feeding significantly inhibits carrier-mediated RF transport across the intestinal brush-border and basolateral membrane domains of the polarized enterocytes. This inhibition was associated with a parallel reduction in the expression of the rat RFVT-1 and -3 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Chronic alcohol feeding also caused a significant inhibition in RF uptake in the colon. Similarly, a significant inhibition in carrier-mediated RF transport across the renal brush-border and basolateral membrane domains was observed, which again was associated with a significant reduction in the level of expression of RFVT-1 and -3 at the protein, mRNA, and hnRNA levels. These findings demonstrate that chronic alcohol exposure impairs both intestinal absorption and renal reabsorption processes of RF and that these effects are, at least in part, mediated via transcriptional mechanism(s) involving the slc52a1 and slc52a3 genes. PMID:23804199
Subramanian, Veedamali S; Subramanya, Sandeep B; Ghosal, Abhisek; Said, Hamid M
Vitamin B2 (riboflavin, RF) is essential for normal human health. Mammals obtain RF from exogenous sources via intestinal absorption and prevent its urinary loss by reabsorption in the kidneys. Both of these absorptive events are carrier-mediated and involve specific RF transporters (RFVTs). Chronic alcohol consumption in humans is associated with a high prevalence of RF deficiency and suboptimal levels, but little is known about the effect of chronic alcohol exposure on physiological and molecular parameters of the intestinal and renal RF transport events. We addressed these issues using rats chronically fed an alcohol liquid diet and pair-fed controls as a model. The results showed that chronic alcohol feeding significantly inhibits carrier-mediated RF transport across the intestinal brush-border and basolateral membrane domains of the polarized enterocytes. This inhibition was associated with a parallel reduction in the expression of the rat RFVT-1 and -3 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Chronic alcohol feeding also caused a significant inhibition in RF uptake in the colon. Similarly, a significant inhibition in carrier-mediated RF transport across the renal brush-border and basolateral membrane domains was observed, which again was associated with a significant reduction in the level of expression of RFVT-1 and -3 at the protein, mRNA, and hnRNA levels. These findings demonstrate that chronic alcohol exposure impairs both intestinal absorption and renal reabsorption processes of RF and that these effects are, at least in part, mediated via transcriptional mechanism(s) involving the slc52a1 and slc52a3 genes.
Pohjankoski, Heini; Kautiainen, Hannu; Kotaniemi, Kaisu; Korppi, Matti; Savolainen, Anneli
To evaluate the occurrence of autoimmune diseases in first-degree relatives of children with juvenile idiopathic arthritis (JIA) and to compare the figures with published population data. Families of the 362 children with recently diagnosed JIA admitted to Rheumatism Foundation Hospital, Finland, from 1996 to 2001 were contacted by questionnaires regarding autoimmune diseases in family members. Data were collected on type 1 diabetes, coeliac disease, multiple sclerosis and chronic arthritis, consisting mainly of JIA, rheumatoid arthritis, spondyloarthropathy or psoriatic arthritis. In all, 21.4% of the 355 families with a patient with JIA had members with type 1 diabetes, coeliac disease, multiple sclerosis or chronic arthritis. Thirty-three mothers and 23 fathers had type 1 diabetes, coeliac disease, multiple sclerosis or chronic arthritis in 15.2% (95% CI 11.6-19.4) of the families, and 23 mothers and 15 fathers had chronic arthritis in 10.7% (95% CI 7.7-14.5) of the families. When compared with available research data, the prevalences of rheumatoid arthritis, spondyloarthropathy, psoriatic arthritis, paediatric type 1 diabetes and JIA (in siblings) were increased in JIA families. Coeliac disease was as prevalent as in the population. Autoimmune diseases cluster in families with a child with JIA. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
Kim, Harold; Lynde, Charles
BACKGROUND: Controlled trials have demonstrated the efficacy of antihistamines in the treatment of chronic idiopathic urticaria. Second-generation antihistamines are recommended as first-line therapy for chronic idiopathic urticaria. The purpose of this study was to determine the effect of desloratadine, a newer, nonsedating, second-generation antihistamine, on symptoms of chronic idiopathic urticaria, disease severity, and quality of life (QoL). METHODS: In an open-label, observational, multicenter study, 348 subjects with chronic idiopathic urticaria were given 5 mg of desloratadine once daily for 2 weeks. Outcome measures included change from baseline at Day 14 using the Aerius Quality of Life Questionnaire (AEQLQ); change from baseline in pruritus score, number and maximum size of hives, sleep quality, and activity impairment; and subjects' response to therapy. RESULTS: Desloratadine significantly decreased subjects' overall condition and symptom scores from baseline to Day 14 (2.19 +/- [SD] 0.66 and 1.14 +/- 0.89, respectively; P < 0.0001). Desloratadine treatment significantly improved all 10 AEQLQ domain scores from baseline to Day 7 and Day 14 (P < 0.0001). Sleep disturbance scores decreased 40% from baseline to Day 7 (1.42 +/- 1.03 to 0.85 +/- 0.89, respectively), and interference with daily outdoor activity scores showed a 41% decrease from baseline to Day 7 (1.11 +/- 0.98 to 0.66 +/- 0.90) (P < 0.0001 for both). There were significant reductions in itching, size of hives, and hive score at both Days 7 and 14. Treatment resulted in moderate, marked, or complete relief of symptoms in 76.2% of subjects. Desloratadine was well tolerated, with no adverse events reported. CONCLUSION: In an open-label, observational study, desloratadine 5 mg once daily significantly decreased symptoms of chronic idiopathic urticaria and improved subject QoL.
Ghannouchi Jaafoura, N; Khalifa, M; Atig, A; Ben Jazia, E; Alaoua, A; Braham Krifa, A; Letaief, A; Bahri, F
Intestinal pseudo-obstruction (IPO) is an uncommon and severe complication of systemic lupus erythematosus (SLE). We report a 24-year-old female with a 2 year SLE duration who presented with abdominal pain, vomiting, constipation and abdominal distention. Plain abdominal radiograph showed multiple air-fluid levels of the small bowel. Computed tomographic scan of the abdomen revealed dilated small bowel loops without mechanical obstruction. Urinary tract involvement was also demonstrated. IPO was diagnosed and the patient responded well to immunosuppressive treatment. IPO is a recently recognized manifestation of SLE that may be the presenting manifestation of the systemic disease or occur more commonly during disease course. Early recognition of IPO is necessary to institute appropriate medical treatment and to avoid inappropriate surgical intervention.
Jiminez, Janelle A; Uwiera, Trina C; Douglas Inglis, G; Uwiera, Richard R E
Acute and chronic inflammatory diseases of the intestine impart a significant and negative impact on the health and well-being of human and non-human mammalian animals. Understanding the underlying mechanisms of inflammatory disease is mandatory to develop effective treatment and prevention strategies. As inflammatory disease etiologies are multifactorial, the use of appropriate animal models and associated metrics of disease are essential. In this regard, animal models used alone or in combination to study acute and chronic inflammatory disease of the mammalian intestine paired with commonly used inflammation-inducing agents are reviewed. This includes both chemical and biological incitants of inflammation, and both non-mammalian (i.e. nematodes, insects, and fish) and mammalian (i.e. rodents, rabbits, pigs, ruminants, dogs, and non-human primates) models of intestinal inflammation including germ-free, gnotobiotic, as well as surgical, and genetically modified animals. Importantly, chemical and biological incitants induce inflammation via a multitude of mechanisms, and intestinal inflammation and injury can vary greatly according to the incitant and animal model used, allowing studies to ascertain both long-term and short-term effects of inflammation. Thus, researchers and clinicians should be aware of the relative strengths and limitations of the various animal models used to study acute and chronic inflammatory diseases of the mammalian intestine, and the scope and relevance of outcomes achievable based on this knowledge. The ability to induce inflammation to mimic common human diseases is an important factor of a successful animal model, however other mechanisms of disease such as the amount of infective agent to induce disease, invasion mechanisms, and the effect various physiologic changes can have on inducing damage are also important features. In many cases, the use of multiple animal models in combination with both chemical and biological incitants is
de Arce, Edith Pérez; Landskron, Glauben; Hirsch, Sandra; Defilippi, Carlos; Madrid, Ana María
Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by a failure of the propulsion of intraluminal contents and recurrent symptoms of partial bowel obstruction in the absence of mechanical obstruction. Regional variations of the intestinal compromise have been described. Intestinal manometry can indicate the pathophysiology and prognosis. Our objective is to establish the demographic and clinical characteristics of group Chilean patients and analyze the motility of the small intestine and its prognostic value. Methods Patients with symptoms of intestinal pseudo-obstruction with dilated bowel loops were included, in all of whom a manometry of the small intestine was performed using perfused catheters. Results Of the 64 patients included, 51 women (average age 41.5 ± 17.6 years), 54 primary and 10 secondary CIPO were included. Dilatation of the small intestine was the only finding in 38 patients; in the remaining, the compromise was associated with other segments, primarily the colon. Forty-nine patients underwent 65 surgeries, mainly exploratory laparotomies and colectomies. Intestinal manometry was performed on all patients; 4 “patterns” were observed: neuropathic (n = 26), myopathic (n = 3), mixed (n = 24), and a group without motor activity (n = 11). The most relevant findings were the complex migrating motor disorders and decreased frequency and propagation of contractions. The 9 patients who died had a severe myopathic compromise. Conclusions In our series, isolated small bowel compromise was the most common disorder. Neuropathic motor compromise was observed in most of the patients. Mortality was associated with severe myopathic compromise. PMID:27669829
Johkoh, Takeshi; Fukuoka, Junya; Tanaka, Tomonori
The new American Thoracic Society/European Respiratory Society (ATS/ERS) update to the multidisciplinary classification of idiopathic interstitial pneumonias (IIPs) defines both rare IIPs and rare histologic patterns of IIPs. Although these diseases are rare, each has some distinguishing imaging and pathologic characteristics. Common findings for IIPs in computed tomography (CT) include cysts in lymphoid interstitial pneumonia (LIP), upper lobe subpleural consolidation in pleuropulmonary fibroelastosis (PPFE), symmetrical consolidation in acute fibrinous organizing pneumonia (AFOP), and peribronchovascular consolidation or centrilobular nodules in bronchiolocentric pattern of interstitial pneumonia.
Background Serum p-cresyl sulfate (PCS) associates with cardiovascular disease in patients with chronic kidney disease. PCS concentrations are determined by intestinal uptake of p-cresol, human metabolism to PCS and renal clearance. Whether intestinal uptake of p-cresol itself is directly associated with cardiovascular disease in patients with renal dysfunction has not been studied to date. Methods We performed a prospective study in patients with chronic kidney disease stage 1 – 5 (NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24 h urinary excretion of PCS. Primary endpoint was time to first cardiovascular event, i.e., cardiac death, myocardial infarction/ischemia, ventricular arrhythmia, cardiovascular surgery, ischemic stroke or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan-Meier estimates and Cox proportional hazard analyses. Results In a cohort of 200 patients, median 24 h urinary excretion of PCS amounted to 457.47 μmol (IQR 252.68 – 697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.037). Higher urinary excretion of PCS was directly associated with cardiovascular events (univariate hazard ratio per 100 μmol increase: 1.112, P 0.002). In multivariate analysis, urinary excretion of PCS remained a predictor of cardiovascular events, independent of eGFR (hazard ratio 1.120, P 0.002). Conclusions In patients with chronic kidney disease, intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. The intestinal generation and absorption of p-cresol may be therapeutic targets to reduce cardiovascular disease risk in patients with renal dysfunction. PMID:24912660
Dewit, S; de Hertogh, G; Geboes, K; Tack, J
Chronic intestinal pseudo-obstruction (CIP) is an uncommon disorder that may be of primary or secondary origin. We report a case of a 37-year-old woman with CIP due to inflammatory disorder of unknown origin involving the skin (eosinophilic fasciitis), the lungs (decreased diffusion capacity) and the gastrointestinal tract. History, clinical examination, plain abdominal film, barium X-ray and colonoscopy established a diagnosis of recurrent pseudo-obstruction. A full-thickness biopsy was performed during explorative laparotomy, and histological examination revealed findings compatible with an inflammatory myopathy due to a dense lymphoid infiltrate and extensive loss of the muscularis propria layers. Immunosuppressive therapy with cyclosporin was initiated, with significant clinical improvement. This case illustrates another form of CIP, characterized by an inflammatory myopathy, which is histologically distinct from other known visceral myopathies and neuropathies.
Arutyunov, Gregory P; Kostyukevich, Olga I; Serov, Roman A; Rylova, Natalya V; Bylova, Nadezda A
Chronic heart failure is a systemic disease with a devastating prognosis, which affects many organ systems other than the cardiovascular system. A total of 45 Chronic heart failure patients of ischemic etiology and 18 control subjects aged 45-65 years were recruited. All subjects underwent a physical examination by a qualified physician, echocardiography, an evaluation of the trophological status (including height and weight assessment) and net-of-fat body mass (NFBM) determination, an evaluation of intestinal functional activity based on fat and protein excretion with feces, and biopsy examination from the small intestine (see below). For all of them were performed functional tests of the small intestine and morphological examination of the small intestine and biopsy collection. Staining for collagen content of the mucosal wall showed that collagen content differed significantly between the four cohorts studied. In fact, relative collagen content was highest in advanced stages of the disease. However, patients with cardiac cachexia displayed even higher relative amounts of collagen than those of the same functional class without cardiac cachexia. Both fat loss and protein loss with the feces correlated with relative collagen area.
Thomas, A G; Phillips, A D; Walker-Smith, J A
The value of proximal intestinal mucosal biopsy was reviewed in 381 children presenting with chronic diarrhoea over an eight year period. An enteropathy was detected in 44% of cases and was more frequently seen in those aged less than 6 months. A diagnosis was established in 91% of cases. The most common diagnosis was the postenteritis syndrome where the presence of an enteropathy indicated those requiring treatment with a cows' milk free diet. Other conditions where a biopsy facilitated diagnosis or treatment included giardiasis, enteropathogenic Escheriichia coli, crytosporidiosis, autoimmune enteropathy, and microvillous atrophy. Coeliac disease was considered in 55% of children and established in 8%, clearly identifying those requiring a gluten free diet. This also emphasises the important role of the biopsy procedure in the exclusion of specific diseases. Proximal small intestinal mucosal biopsy is an essential investigation in children with chronic diarrhoea in whom an enteropathy is suspected. PMID:1626996
Billiard, Michel; Sonka, Karel
Idiopathic hypersomnia continues to evolve from the concept of "sleep drunkenness" introduced by Bedrich Roth in Prague in 1956 and the description of idiopathic hypersomnia with two forms, polysymptomatic and monosymptomatic, by the same Bedrich Roth in 1976. The diagnostic criteria of idiopathic hypersomnia have varied with the successive revisions of the International classifications of sleep disorders, including the recent 3rd edition. No epidemiological studies have been conducted so far. Disease onset occurs most often during adolescence or young adulthood. A familial background is often present but rigorous studies are still lacking. The key manifestation is hypersomnolence. It is often accompanied by sleep of long duration and debilitating sleep inertia. Polysomnography (PSG) followed by a multiple sleep latency test (MSLT) is mandatory, as well as a 24 h PSG or a 2-wk actigraphy in association with a sleep log to ensure a total 24-h sleep time longer than or equal to 66O minutes, when the mean sleep latency on the MSLT is longer than 8 min. Yet, MSLT is neither sensitive nor specific and the polysomnographic diagnostic criteria require continuous readjustment and biologic markers are still lacking. Idiopathic hypersomnia is most often a chronic condition though spontaneous remission may occur. The condition is disabling, sometimes even more so than narcolepsy type 1 or 2. Based on neurochemical, genetic and immunological analyses as well as on exploration of the homeostatic and circadian processes of sleep, various pathophysiological hypotheses have been proposed. Differential diagnosis involves a number of diseases and it is not yet clear whether idiopathic hypersomnia and narcolepsy type 2 are not the same condition. Until now, the treatment of idiopathic hypersomnia has mirrored that of the sleepiness of narcolepsy type 1 or 2. The first randomized, double-blind, placebo-controlled trials of modafinil have just been published, as well as a double
The study of the gut microbiome—the collection of microbes within the intestinal tract and the genes they express—is growing in popularity as associations are found between diet, gut microbiome activity, and host health and disease. However, current metagenomic and ribosomal profiling approaches are...
Allen, Steven G; Soliman, Amr S; Toy, Kathleen; Omar, Omar S; Youssef, Tamer; Karkouri, Mehdi; Ayad, Essam; Abdel-Aziz, Azza; Hablas, Ahmed; Tahri, Ali; Oltean, Hanna N; Kleer, Celina G; Merajver, Sofia D
Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.
Huang, Yuanyuan; Chen, Jun; Gui, Li
Idiopathic hypertrophic pachymeningitis (IHP) is a rare condition, characterized by a chronic fibrosing inflammatory process usually involving either the intracranial or spinal dura mater, but rarely both. Here, we report a rare case of IHP affecting both the intracranial and spinal dura mater. We also discussed the diagnosis, management, and outcome of IHP. We reviewed the case of a 60-year-old woman presenting with chronic headache, multiple cranial nerve palsies and gait disturbance. Magnetic resonance imaging (MRI) of her head revealed thickened and contrast-enhanced dura in the craniocervical region as well as obstructive hydrocephalus and cerebellar tonsillar herniation. The patient had a suboccipital craniectomy and posterior decompression through C1 plus a total laminectomy. The dura was partially resected to the extent of the bony decompression, and a duroplasty was performed. Microscopic examination of the surgically resected sample showed chronic inflammatory changes, lymphoplasmacytic cell infiltration, fibrous tissue hyperplasia, and hyaline degeneration. Blood tests to evaluate the secondary causes of hypertrophic pachymeningitis (HP) were unremarkable. Steroid was used to treat suspected IHP. Postoperatively, the patient showed gradual improvement in her headache, glossolalia, and bucking. Prior to discharge, a follow-up MRI showed improvement of the dura mater thickening. IHP is a chronic inflammatory disorder of the dura mater that usually causes neurological deficits. Clinical manifestations of IHP, MRI findings, and laboratory abnormalities are the essential components for making an accurate diagnosis. When the radiological or laboratory evaluation is uncertain, but neurological deficits are present, a prompt surgical approach should be considered. Postoperative steroid therapy and close observation for recurrence are necessary to ensure a good long-term outcome.
Niederer, Daniel; Vogt, Lutz; Wilke, Jan; Rickert, Marcus; Banzer, Winfried
The present study aims to develop age-dependent cutoff values in a quasi-experimental, cross-sectional diagnostic test study. One hundred and twenty (120) asymptomatic subjects (n = 100, 36♀, 18 75 years, for normative values; n = 20, 23-75 years, 15♀, for selectivity analyses) and 20 patients suffering from idiopathic neck pain (selectivity analyses, 22-71 years, 15♀) were included. Subjects performed five repetitive maximal cervical flexion/extension movements in an upright sitting position. Cervical kinematic characteristics (maximal range of motion (ROM), coefficient of variation (CV) and mean conjunct movements in rotation and flexion (CM)) were calculated from raw 3D ultrasonic data. Regression analyses were conducted to reveal associations between kinematic characteristics and age and gender and thus to determine normative values for healthy subjects. Age explains 53 % of the variance in ROM (decrease 10.2° per decade), 13 % in CV (increase 0.003 per decade) and 9 % in CM (increase 0.57° per decade). Receivers operating characteristic (ROC) analyses were conducted for differences between individual values of the kinematic characteristics and normative values to optimise cutoff values for distinguishing patients from unimpaired subjects (20 patients and 20 healthy). Cutoff values distinguished asymptomatic subjects' and chronic nonspecific neck patient's movement characteristics with sufficient quality (sensitivity 70-80 %, specificity 65-70 %). By including such classifications, the present findings expand actual research stating an age-related decrease in kinematic behaviour only using categorising span widths across decades. Future study is warranted to reveal our results' potential applicability for intervention onset decision making for idiopathic neck pain patients.
Porto, Felipe; de Leeuw, Reny; Evans, Daniel R; Carlson, Charles R; Yepes, Juan F; Branscum, Adam; Okeson, Jeffrey P
To examine differences between idiopathic continuous orofacial neuropathic pain (ICONP) patients and chronic masticatory muscle pain (MMP) patients for psychosocial functioning and sleep quality. Archival data were used to compare 81 ICONP patients to 81 age- and sex-matched chronic MMP patients on pain severity, life interference, life control, and affective distress measures from the Multidimensional Pain Inventory (MPI), a global severity index of psychological symptoms from the Symptom Checklist-90-R (SCL-90-R), Posttraumatic Stress Disorder Checklist-Civilian (PCL-C), and overall sleep quality from the Pittsburgh Sleep Quality Index (PSQI). MANOVA, MANCOVA, and chi-square analysis were used to investigate differences between the two groups in the psychosocial and sleep variables. The ICONP group reported greater pain severity (P = .013) and more life interference (P = .032) than the MMP group, while the MMP group reported higher levels of global psychological symptoms (P = .005) than the ICONP group. After controlling for pain severity, however, the MMP group demonstrated greater affective distress (P = .014) than the ICONP group, and life interference was no longer significantly different between the groups. ICONP patients were more likely to report a traumatic life event (P = .007). Although ICONP patients are likely to present more intense pain and report that their pain causes more interference in their lives, MMP patients are more likely to present with higher levels of overall psychological symptoms. The greater levels of pain severity reported by ICONP patients appear to be partially responsible for their higher levels of reported life interference.
Kim, Joon Sung; Lee, Bo-In; Kim, Byung-Wook; Choi, Hwang; Lee, Yun-Seok; Maeng, Leeso
Chronic intestinal pseudo-obstruction is a rare clinical syndrome which is characterized by intestinal obstruction without occluding lesions in the intestinal lumen and pregnancy is one of the important aggravating factors. Here, we report a case of a woman with intractable intestinal pseudo-obstruction that was precipitated by pregnancy. She could not make any stool passage for more than 4 weeks until a fetal gestational age of 17 weeks was reached. However, the patient could be maintained by repetitive colonoscopic decompressions and finally total colectomy could be performed successfully at a fetal gestational age of 21 weeks.
Subramanya, Sandeep B; Subramanian, Veedamali S; Said, Hamid M
Thiamin is essential for normal cellular functions, and its deficiency leads to a variety of clinical abnormalities. Humans and other mammals obtain the vitamin via intestinal absorption. The intestine is exposed to two sources of thiamin, a dietary and a bacterial (i.e., normal microflora of the large intestine) source. Chronic alcohol consumption is associated with thiamin deficiency, which is caused (in part) by inhibition in intestinal thiamin absorption. However, little is known about the physiological and molecular aspects of the intestinal thiamin uptake process that are affected by chronic alcohol use. To address these issues, we used rats fed an alcohol-liquid diet and human intestinal epithelial HuTu-80 cells chronically exposed to ethanol as model systems. The results showed that chronic alcohol feeding to rats led to a significant inhibition in carrier-mediated thiamin transport across both the jejunal brush-border membrane and basolateral membrane domains. This was associated with a significant reduction in level of expression of thiamin transporter-1 (THTR-1), but not THTR-2, at the protein and mRNA levels. Level of expression of the heterogenous nuclear RNA of THTR-1 in the intestine of alcohol-fed rats was also decreased compared with their pair-fed controls. Chronic alcohol feeding also caused a significant inhibition in carrier-mediated thiamin uptake in rat colon. Studies with HuTu-80 cells chronically exposed to ethanol also showed a significant inhibition in carrier-mediated thiamin uptake. This inhibition was associated with a reduction in level of expression of human THTR-1 and THTR-2 at the protein, mRNA, and transcriptional (promoter activity) levels. These studies demonstrate that chronic alcohol feeding inhibits intestinal thiamin absorption via inhibition of the individual membrane transport event across the polarized absorptive epithelial cells. Furthermore, the inhibition is, at least in part, mediated via transcriptional mechanism(s).
Ghosh, Siddhartha S; Gehr, Todd W B; Ghosh, Shobha
Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides) from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP). Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.
Livingston, Robert S; Myles, Mathew H; Livingston, Beth A; Criley, Jennifer M; Franklin, Craig L
Helicobacter hepaticus is a bacterial pathogen of mice that has been reported to cause chronic intestinal inflammation in A/JCr, germfree Swiss Webster, and immunodeficient mice. To the authors' knowledge, the influence of sex on development of chronic intestinal inflammation in H. hepaticus-infected mice has not been investigated. The purposes of the study reported here were to determine whether severity of intestinal inflammation differs between male and female A/JCr mice chronically infected with H. hepaticus and to characterize the mucosal immune response in these mice. The cecum of male and female A/JCr mice infected with H. hepaticus for 1 month and 3 months was objectively evaluated histologically for intestinal disease. Also, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was done to measure interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-inducible protein of 10 kDa (IP-10), and monokine induced by gamma interferon (MIG) mRNA values in the cecal tissue of these mice. Significant differences in cecal lesion scores were not present at 1 month after infection. However, infected female mice had significantly up-regulated expression of cecal IL-10, MIP-1alpha, IP-10, and MIG mRNA compared with that in uninfected females, and expression of IL-10 and MIP-1alpha was significantly greater than that detected in infected male mice (P < or = 0.05). At 3 months after infection, cecal lesion scores were significantly (P < or = 0.05) increased in female and male mice compared with uninfected controls, and infected female mice had significantly (P < or = 0.05) higher cecal lesion scores than did infected male mice. In addition, infected females had significant (P < or = 0.05) increases in cecal IFN-gamma, TNF-alpha, IL-10, MIP-1alpha, IP-10, and MIG mRNA values compared with values in uninfected females and infected males
1. By the use of the everted jejunal sac it was shown that chronic oral treatment of rats with various drugs can either increase or decrease the mucosal transport of 14C-L-DOPA or alter its serosal/tissue ratio. 2. 14C-L-DOPA transport was significantly increased in rats that were chronically treated with L-DOPA and diminished in those that were treated with chlorpromazine and phenobarbitone. 3. Chronic treatment with amantadine and neomycin did not affect 14C-L-DOPA intestinal transport, although direct addition of amantadine to the medium, significantly increased 14C-L-DOPA transport in everted sacs of nontreated rats. Addition of neomycin directly to the medium did not affect 14C-L-DOPA transport. 4. The possible mechanisms of these findings and their clinical significance are discussed. PMID:4655269
Rieger, Kathrin; Günther, Ute; Erben, Ulrike; Kühl, Anja; Loddenkemper, Christoph; Pezzutto, Antonio; Siegmund, Britta; Bojarski, Christian
Graft-versus-host disease (GvHD) is a major complication of allogeneic stem cell transplantation. High-resolution in vivo histology of the intestine by confocal endomicroscopy (CEM) detects acute GvHD (aGvHD) with high sensitivity. This pilot study aims to evaluate the diagnostic value of CEM for intestinal chronic GvHD (cGvHD). The study included 20 patients with gastrointestinal symptoms and confirmed cGvHD in other organs as well as 20 patients with clinically suspected acute GvHD for control. Confocal endomicroscopy was performed as gastroscopy followed by sigmoidoscopy after intravenous injection of fluorescein (10%) and topical application of acriflavine (0.05%). Histopathology from H&E-stained biopsy samples throughout the intestinal tract complemented the survey. All histological features of intestinal cGvHD were predominantly mild to moderate. Stroma fibrosis detected by standard histology (16/20 patients) was not seen by CEM. Apoptosis assessed by histology in 12/20 patients was concordant with CEM (8/12 patients). Confocal endomicroscopy revealed esophageal manifestation of cGvHD in 3 patients. For each biopsy site, CEM correlated with intestinal histology (r = 0.64). Classical histology from intestinal biopsy samples taken under CEM monitoring confirmed the final diagnosis of cGvHD. The sensitivity of CEM with 40% in cGvHD was significantly lower compared to 70% in patients with aGvHD. Confocal endomicroscopy detected acute features of cGvHD and contributed to the diagnosis of esophageal cGvHD but failed to display stroma fibrosis in vivo. Although CEM represents a useful noninvasive tool in routine diagnostic of intestinal aGvHD, the method is not sufficient to fully establish the diagnosis of cGvHD within the intestinal tract. Confocal endomicroscopy allowed acquisition of targeted biopsies in patients suspected of having cGvHD. Copyright © 2017 John Wiley & Sons, Ltd.
Lotun, Kapildeo; Shetty, Ranjith; Topaz, On
Symptomatic chronic mesenteric ischemia results from intestinal hypoperfusion and is classically thought to result from involvement of two or more mesenteric arteries. The celiac artery and superior mesenteric artery are most frequently implicated in this disease process, and their involvement usually results in symptoms of small intestinal ischemia. Symptomatic chronic mesenteric ischemia resulting predominantly from inferior mesenteric artery involvement has largely been overlooked but does gives rise to its own, unique clinical presentation with symptoms resulting from large intestinal ischemia. We present four patients with atherosclerotic inferior mesenteric artery stenosis with symptomatic chronic mesenteric ischemia that have unique clinical presentations consistent with large intestinal ischemia that resolved following percutaneous endovascular treatment of the inferior mesenteric artery stenosis. These cases represent a novel approach to the diagnosis and management of this disease process and may warrant a further subclassification of chronic mesenteric ischemia into chronic small intestinal ischemia and chronic large intestinal ischemia.
Mafra, Denise; Lobo, Julie C; Barros, Amanda F; Koppe, Laetitia; Vaziri, Nosratola D; Fouque, Denis
The normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, the alteration of the intestinal microbiota has been shown to contribute to the pathogenesis of several pathological conditions, including obesity and insulin resistance, among others. Recent studies have revealed profound alterations of the gut microbial flora in patients and animals with chronic kidney disease (CKD). Alterations in the composition of the microbiome in CKD may contribute to the systemic inflammation and accumulation of gut-derived uremic toxins, which play a central role in the pathogenesis of accelerated cardiovascular disease and numerous other CKD-associated complications. This review is intended to provide a concise description of the potential role of the CKD-associated changes in the gut microbiome and its potential role the pathogenesis of inflammation and uremic toxicity. In addition, the potential efficacy of pre- and pro-biotics in the restoration of the microbiome is briefly described.
Yan, Jun-Kai; Zhou, Ke-Jun; Huang, Jian-Hu; Wu, Qing-Qing; Zhang, Tian; Wang, Chao-Chen; Cai, Wei
Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder with significant morbidity and mortality in pediatric patients. The diagnosis of CIPO is difficult, because it is clinically based on the symptoms and signs of bowel obstruction which are similar to the clinical manifestations of other gastrointestinal diseases like short bowel syndrome (SBS). Therefore, it is desirable to identify and establish new laboratory diagnostic markers for CIPO that are reliable and easily accessible. In our study we have identified the ratio of the urinary glutamine and glutamic acid as a promising biomarker for distinguishing suspected CIPO cases and simple SBS cases. The area under ROC curve was 0.83, at cutoff value = 7.04 with sensitivity of 65% and specificity of 92%.
Rubin, Deborah C.; Shaker, Anisa; Levin, Marc S.
The inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of the gastrointestinal tract, from mouth to anus, but most commonly involves the distal part of the small intestine or ileum, and colon. UC results in colonic inflammation that can affect the rectum only, or can progress proximally to involve part of or the entire colon. Clinical symptoms include diarrhea, abdominal pain, gastrointestinal bleeding, and weight loss. A serious long-term complication of chronic inflammation is the development of colorectal cancer. A genetic basis for IBD had long been recognized based on the increased familial risk. However, significant discordance for CD in twins, and a much less robust phenotypic concordance for UC, suggested additional factors play a role in disease pathogenesis, including environmental factors. In the past several years, progress in understanding the molecular basis of IBD has accelerated, beginning with the generation of animal models of colitis and progressing to the identification of specific genetic markers from candidate gene, gene linkage, and genome-wide association analyses. Genetic studies have also resulted in the recognition of the importance of environmental factors, particularly the crucial role of the gut microbiota in CD and UC. Altered immune responses to the normal intestinal flora are key factors in IBD pathogenesis. In this research topic, the genetic basis of IBD, the genetic and cellular alterations associated with colitis-associated colon cancer, and the emerging role of the intestinal microbiota and other environmental factors will be reviewed. PMID:22586430
Yue, Yunshuang; Guo, Yuming; Yang, Ying
Stress has been recognized as a critical risk factor for gastrointestinal diseases in both humans and animals. However, nutritional strategies to attenuate stress-induced intestinal barrier function and underlying mechanisms remain largely unknown. This study tested the hypothesis that L-tryptophan enhanced intestinal barrier function by regulating mucosal serotonin metabolism in chronic unpredictable stress-exposed broilers. One-day-old male broilers (Arbor Acres) were fed a basal diet supplemented with or without L-tryptophan in the absence or presence of chronic unpredictable stress. Feed intake, body weight gain, plasma corticosterone and 5-hydroxytryptamine (5-HT), intestinal permeability, mucosal secretory IgA (sIgA), and mRNA levels for tryptophan hydroxylase 1 (TPH1), IL-1β, IL-6, TNF-α, IL-10, protein abundance for claudin-1, occludin, and ZO-1 were determined. Stress exposure led to elevated plasma corticosterone (P < 0.05), increased intestinal permeability (P < 0.05), reduced growth performance (P < 0.05), and decreased sIgA secretion compared with the controls. These effects were largely reversed (P < 0.05) by L-tryptophan supplementation. Western blot analysis showed that stress exposure resulted in decreased protein abundance for occludin, claudin-1, and ZO-1, which was attenuated by L-tryptophan. mRNA levels for IL-1β, IL-6, and TNF-α were increased, but those for IL-10 were decreased, in the jejunal tissue of broilers subjected to stress. This effect of stress on cytokine expression was abolished by L-tryptophan treatment. The effects of stress were associated with decreased plasma concentration of 5-HT (P < 0.05), and reduced (P < 0.05) mRNA levels for TPH1. L-Tryptophan supplementation markedly attenuated stress-induced alterations in 5-HT and TPH1 mRNA level in jejunal tissues of broilers. Collectively, these results indicate that L-tryptophan supplementation alleviates chronic unpredictable stress-induced intestinal barrier
Wawrzyniak, Nicholas R.; Joseph, Anna-Maria; Levin, David G.; Gundermann, David M.; Leeuwenburgh, Christiaan; Sandesara, Bhanuprasad; Manini, Todd M.; Adhihetty, Peter J.
Fatigue is a symptom of many diseases, but it can also manifest as a unique medical condition, such as idiopathic chronic fatigue (ICF). While the prevalence of ICF increases with age, mitochondrial content and function decline with age, which may contribute to ICF. The purpose of this study was to determine whether skeletal muscle mitochondrial dysregulation and oxidative stress is linked to ICF in older adults. Sedentary, old adults (n = 48, age 72.4 ± 5.3 years) were categorized into ICF and non-fatigued (NF) groups based on the FACIT-Fatigue questionnaire. ICF individuals had a FACIT score one standard deviation below the mean for non-anemic adults > 65 years and were excluded according to CDC diagnostic criteria for ICF. Vastus lateralis muscle biopsies were analyzed, showing reductions in mitochondrial content and suppression of mitochondrial regulatory proteins Sirt3, PGC-1α, NRF-1, and cytochrome c in ICF compared to NF. Additionally, mitochondrial morphology proteins, antioxidant enzymes, and lipid peroxidation were unchanged in ICF individuals. Our data suggests older adults with ICF have reduced skeletal muscle mitochondrial content and biogenesis signaling that cannot be accounted for by increased oxidative damage. PMID:27447862
Stull, Donald E; McBride, Doreen; Houghton, Katherine; Finlay, Andrew Y; Gnanasakthy, Ari; Balp, Maria-Magdalena
Assessing the consequences of chronic spontaneous/idiopathic urticaria (CSU) requires the evaluation of health-related quality of life (HRQoL) associated with the severity of CSU signs and symptoms. It is important to understand how signs, symptoms, and HRQoL change over time in CSU. Evidence is lacking on how closely changes in signs and symptoms of CSU are related to changes in HRQoL. The objective of this study was to assess the correlation between changes in patient-reported outcome measures (PROMs) of signs and symptoms, dermatologic quality of life (QoL), and urticaria-specific QoL. Latent growth models (LGMs) were applied to longitudinal data from three randomized, Phase 3 clinical trials investigating the efficacy and safety of omalizumab in CSU. A near-perfect association between changes in signs and symptoms and changes in dermatologic and urticaria-specific QoLs was identified in each clinical trial when using LGMs (correlation coefficient range 0.88-0.92). Evidence showed that changes in signs and symptoms are closely related to changes in HRQoL. However, analyses were performed on clinical trial results of an extremely effective treatment; a less effective treatment with much smaller changes over time may not show such close correlations. Results suggest that any of these PROMs may be used to understand changes in CSU.
Thiele, J; Varus, E; Siebolts, U; Kvasnicka, H M; Wickenhauser, C; Metz, K A; Beelen, D W; Ditschkowski, M; Zander, A; Kröger, N
Scant knowledge exists concerning lineage-restricted mixed chimerism (mCh) after allogeneic peripheral blood stem cell transplantation (PSCT) in patients with chronic idiopathic myelofibrosis (CIMF). Following a sex-mismatched PSCT, a combined immunopheno- and genotyping by fluorescence in-situ hybridization (FISH) was performed on sequential bone marrow (BM) biopsies at standardized intervals. Results were compared with PCR analysis of corresponding peripheral blood samples in five patients. According to FISH, pretransplant specimens revealed a gender congruence of more than 99%, while in the first three months the total BM exhibited a persistent fraction of host cells (30% to 40%) with a tendency to decline after about one year. It is noteworthy that the majority of endothelial cells maintained a recipient origin, whereas CD34+ progenitors and especially CD61+ megakaryocytes exhibited only very few host-derived cells. In keeping with the prevalence of donor cells in the hematopoietic compartment, PCR analysis of peripheral blood cells displayed a non-significant degree of mCh. In conclusion, according to FISH and PCR analysis, successful PSCT in CIMF results in an almost complete chimeric (donor-derived) state of the hematopoietic cell population. The non-transplantable stromal compartment includes the vascular endothelium with a predominance of recipient cells. The minimal mCh of this population implies probably a donor-derived origin (endothelial progenitor cells).
Dubertret, Louis; Zalupca, Lavinia; Cristodoulo, Tania; Benea, Vasile; Medina, Iris; Fantin, Sara; Lahfa, Morad; Pérez, Iñaki; Izquierdo, Iñaki; Arnaiz, Eva
This randomised, double-blind, placebo-controlled, parallel-group, international, dose-ranging study investigated the effect of treatment with rupatadine 5, 10 and 20 mg once daily for 4 weeks on symptoms and interference with daily activities and sleep in 12-65 years-old patients with moderate-to-severe chronic idiopathic urticaria (CIU). Rupatadine 10 and 20 mg significantly reduced pruritus severity by 62.05% and 71.87% respectively, from baseline, over a period of 4 weeks compared to reduction with placebo by 46.59% (p < 0.05). Linear trends were noted for reductions in mean number of wheals and interference with daily activities and sleep with rupatadine 10 and 20 mg over the 4-week treatment period. The two most frequently reported AEs were somnolence (2.90% for placebo, 4.29% for 5 mg-, 5.41% for 10 mg- and 21.43% for 20 mg-rupatadine-treated group) and headache (4.35% for placebo, 2.86% for 5 mg-, 4.05% for 10 mg- and 4.29% for 20 mg-rupatadine-treated group). These findings suggest that rupatadine 10 and 20 mg is a fast-acting, efficacious and safe treatment for the management of patients with moderate-to-severe CIU. Rupatadine decreased pruritus severity, in a dose- and time-dependent manner.
Serhat Inaloz, H; Ozturk, Savas; Akcali, Cenk; Kirtak, Necmettin; Tarakcioglu, Mehmet
The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty-seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)-6, IL-8, IL-2 receptor, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-5 were measured. The mean UAS score was 32.07 +/- 7.05 and 6.22 +/- 3.84 before and after CsA treatment, respectively. The serum IL-2 receptor, TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL-2R, TNF-alpha and IL-5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting.
Hernandez, Jose C.; Rojas, Juan; Gurudu, Suryakanth R.
We reported a case of multifocal carcinoid tumor of small intestine causing chronic obscure gastrointestinal bleeding, suspected on capsule endoscopy and diagnosed on double balloon enteroscopy. PMID:27942327
Janse, A; Wiborg, J F; Bleijenberg, G; Tummers, M; Knoop, H
To determine the efficacy of a cognitive-behavioral intervention for patients meeting U.S. Centers for Disease Control and Prevention (CDC) criteria for idiopathic chronic fatigue (ICF). ICF is thought to be a less severe disorder than chronic fatigue syndrome (CFS). The intervention consisted of a booklet with self-instructions combined with e-mail contact with a therapist. Randomized controlled trial conducted at an outpatient facility. All patients suffered from severe and persistent fatigue with moderate impairment levels or fewer than 4 additional symptoms. Patients were randomly allocated to either guided self-instruction or a wait-list control group. Primary outcome measures were fatigue severity assessed with the Checklist Individual Strength and level of overall impairment assessed with the Sickness Impact Profile. Outcome measures were assessed prior to randomization and following treatment or wait-list control group. One hundred patients were randomly allocated to the intervention or a wait-list control group and 95 completed second assessment. An intention-to-treat analysis showed significant treatment effects for fatigue severity (-8.98, 95% confidence interval [CI] [-13.99, -3.97], Cohen's d = 0.68, p < .001) and for overall impairment (-317.19, 95% CI [-481.70, -152.68], Cohen's d = 0.53, p < .01) in favor of the intervention. The number of additional symptoms and overall impairment at baseline did not moderate posttreatment fatigue severity. Baseline overall impairment moderated posttreatment impairment. Patients with ICF can be treated effectively with a minimal intervention. This is relevant as ICF is more prevalent than CFS and treatment capacity is limited. (c) 2016 APA, all rights reserved).
Freeman, Hugh James
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.
Hawash, Yousry A.; Dorgham, Laila Sh.; Amir, El-Amir M.; Sharaf, Osama F.
It has been hypothesized that chronic renal failure (CRF) predisposes patients to infection with intestinal protozoa. We tested this hypothesis with a matched case-control study to determine the prevalence of these protozoa and their diarrhea associated symptoms among 50 patients with CRF (cases) from Taif, western Saudi Arabia. Fifty diarrheal patients without CRF were recruited in the study as controls. Participants were interviewed by a structured questionnaire and stool samples were collected. Samples were thoroughly examined with microscopy and three coproantigens detection kits. Enteric protozoa were detected in 21 cases and 14 controls. Blastocystis spp. were the most predominant parasite (16% in cases versus 8% in controls), followed by Giardia duodenalis (10% in cases versus 12% in controls) and Cryptosporidium spp. (10% in cases versus 6% in controls). Cyclospora cayetanensis was identified in two cases, while Entamoeba histolytica was described in one case and one control. Intestinal parasitism was positively associated with the male gender, urban residence, and travel history. Clinical symptoms of nausea/vomiting and abdominal pain were significantly varied between the parasitized cases and controls (P value ≤ 0.05). Given the results, we recommend screening all diarrheal feces for intestinal protozoa in the study's population, particularly those with CRF. PMID:26491455
Rossi, Valentina; Mosconi, Manuela; Nozza, Paolo; Murgia, Daniele; Mattioli, Girolamo; Ceccherini, Isabella; Pini Prato, Alessio
Chronic intestinal pseudo obstruction (CIPO) is a rare clinical entity characterized by symptoms and signs of intestinal obstruction without either recognizable anatomical abnormalities or intestinal aganglionosis. A Chinese female infant presented to our institution with a clinical diagnosis of CIPO. Aganglionosis was ruled out by full thickness colonic and ileal biopsies and by rectal suction biopsies. Unexpectedly, direct sequencing and PCR amplification of RET proto-oncogene from peripheral blood extracted DNA identified a RET R114H mutation. This mutation has already been reported as strongly associated with Asian patients affected by Hirschsprung's disease (HSCR) and is considered a founder mutation in Asia. The same mutation has never been reported in patients with CIPO, so far. These findings support the role of RET in the development of the enteric nervous system but underline the importance of other genetic or environmental factors contributing to the gastrointestinal phenotype of the disease. Somehow, this RET R114H mutation proved to have a role in the etiology of both CIPO and HSCR and could contribute to a more diffuse imbalance of gut dysmotility. © 2016 Wiley Periodicals, Inc.
Gökşen, Bülent; Appak, Yeliz Çağan; Girginkardeşler, Nogay; Ecemiş, Talat; Kasırga, Erhun
The aim of this study was to determine the incidence of coinfection with Helicobacter pylori and intestinal parasitosis in children with chronic abdominal pain (CAP) and to investigate the common risk factors in the development of both infections. Ninety patients with CAP were enrolled in this study. Blood samples of each case were screened for human preformed IgG (HpIgG) antibodies, and stool samples were tested for HpSA and also examined for intestinal parasites by direct wet-mount, formalin-ethyl-acetate concentration, and Trichrome staining procedures. Cellophane tape test was used for Enterobius vermicularis. Children tested positive for HpIgG and/or HpSA were accepted as H. pylori positive. The risk factors were compared with a questionnaire. The incidence of Giardia intestinalis was 14.8% in the H. pylori-positive group and was found to be statistically higher than that in the H. pylori-negative group (1.6%). The positivity rates of H. pylori were found to be statistically higher in children attending school and using drinking water from taps. The incidences of parasitosis were significantly higher in children with a low maternal education level and with a history of parasitosis treatment in the family. The most common etiologies of CAP in children are H. pylori infection and intestinal parasitosis. İmprovement of hygienic conditions would be beneficial in preventing both infections.
Holm, Jacob Bak; Sorobetea, Daniel; Kiilerich, Pia; Ramayo-Caldas, Yuliaxis; Estellé, Jordi; Ma, Tao; Madsen, Lise; Kristiansen, Karsten; Svensson-Frej, Marcus
The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.
Kiilerich, Pia; Ramayo-Caldas, Yuliaxis; Estellé, Jordi; Ma, Tao; Madsen, Lise; Kristiansen, Karsten; Svensson-Frej, Marcus
The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes. PMID:25942314
Pironi, Loris; Konrad, Denise; Brandt, Chrisoffer; Joly, Francisca; Wanten, Geert; Agostini, Federica; Chambrier, Cecile; Aimasso, Umberto; Zeraschi, Sarah; Kelly, Darlene; Szczepanek, Kinga; Jukes, Amelia; Di Caro, Simona; Theilla, Miriam; Kunecki, Marek; Daniels, Joanne; Serlie, Mireille; Poullenot, Florian; Wu, Jian; Cooper, Sheldon C; Rasmussen, Henrik H; Compher, Charlene; Seguy, David; Crivelli, Adriana; Pagano, Maria C; Hughes, Sarah-Jane; Guglielmi, Francesco W; Kozjek, Nada Rotovnik; Schneider, Stéphane M; Gillanders, Lyn; Ellegard, Lars; Thibault, Ronan; Matras, Przemysław; Zmarzly, Anna; Matysiak, Konrad; Van Gossum, Andrè; Forbes, Alastair; Wyer, Nicola; Taus, Marina; Virgili, Nuria M; O'Callaghan, Margie; Chapman, Brooke; Osland, Emma; Cuerda, Cristina; Sahin, Peter; Jones, Lynn; Lee, Andre D W; Bertasi, Valentino; Orlandoni, Paolo; Izbéki, Ferenc; Spaggiari, Corrado; Díez, Marta Bueno; Doitchinova-Simeonova, Maryana; Garde, Carmen; Serralde-Zúñiga, Aurora E; Olveira, Gabriel; Krznaric, Zeljko; Czako, Laszlo; Kekstas, Gintautas; Sanz-Paris, Alejandro; Jáuregui, Estrella Petrina; Murillo, Ana Zugasti; Schafer, Eszter; Arends, Jann; Suárez-Llanos, José P; Shaffer, Jon; Lal, Simon
The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements. ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need. Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume. Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Zhang, Edwin; Owen, Richard; Bruce, Garth; Wiebe, Sheldon
We report an unusual case of chronic mesenteric ischemia presenting in a 12-year-old girl with idiopathic infantile arterial calcinosis (IIAC). This is the first reported case in the literature of chronic mesenteric ischemia in the setting of IIAC. The girl presented with a classical history of postprandial abdominal pain. Imaging demonstrated significant stenoses of the celiac axis, superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). Angioplasty of the celiac axis and SMA was attempted, with successful dilation of the SMA only. At 3-, 6- and 12-month follow-ups, the child's symptoms had almost resolved. This case report has three important ramifications: chronic mesenteric ischemia is a possible clinical presentation in children with IACC, pre-angioplasty imaging is important in guiding treatment approach, and angioplasty was effective in this case of chronic mesenteric ischemia and offers hope for other similarly affected children.
Kim, Dae Bum; Paik, Chang-Nyol; Sung, Hea Jung; Chung, Woo Chul; Lee, Kang-Moon; Yang, Jin-Mo; Choi, Myung-Gyu
The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (≥20 ppm) or CH4 (≥10 ppm) over the baseline or (2) a baseline H2 (≥20 ppm) or CH4 (≥10 ppm) within 90 min after lactulose load. LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Meneses, F; Ehinger, B; Gerhardt, A; Meyer-Lindenberg, A; Hewicker-Trautwein, M; Amtsberg, G; Nolte, I
Aim of this study is to clinically, microbiologically and histopathologically characterize inflammatory bowel disease (IBD) in the cat. Nine cats with chronic persistent or intermitent vomitus and diarrhea were examined between 1998 and 2001. All cats had a thuorough diagnostic workup performed. Full thickness biopsies from stomach, duodenum, jejunum, ileum and colon were surgically obtained for histopathological examination. Duodenal juice was obtained by direct aspiration for microbiologic qualitative and semiquantitative examination. Seven cats euthanized for other medical reasons were used as controls. Six cats had a lymphoplasmacytic IBD and three an eosinophilic IBD. Four cats with IBD had additional diseases diagnosed. Three cats with IBD had elevated bacterial counts. Retrospectively no correlation could be found between clinical symptoms and histopathological results. Serum TLI was not able to differentiate chronic pancreatitis and IBD. Serum folic acid and cobalamin did not correlate with the distribution of lesions in the gastrointestinal tract. Finally, no correlation was found between bacterial counts in the proximal duodenum and IBD.
Nwaneri, Damia Uchechukwu; Ibadin, Michael Okoeguale; Ofovwe, Gabriel Egberue; Sadoh, Ayebo Evawere
Behavioral aberrations such as nail biting, finger sucking, and pica have been postulated as risk factors that enhance helminths ova transmission. These aberrations may present commonly in children with chronic neurological disorders and predispose them to heavy intensity of intestinal helminthiasis. This comparative cross-sectional study was to determine the prevalence, intensity, and behavioral risk factors for intestinal helminthiasis in children with chronic neurological disorders and apparently healthy controls. Fresh stool samples from 155 children (2-17 years) with chronic neurological disorders seen at the child neurology clinic and 155 age and sex matched controls from nursery and primary schools in Benin City were analyzed using the Kato-Katz technique for detection of ova of helminths from November 2008 to April 2009. The prevalence of intestinal helminthiasis (31.0%) was significantly higher in children with chronic neurological disorders compared with the controls (19.4%) (P=0.03). The intensity of infections in both groups was light ranging 24-144 eggs per gram. Ascaris lumbricoides, Trichuris trichiura and hookworm were the intestinal helminths isolated in both groups. Behavioral aberrations were significantly more represented in the subjects than in the controls (P<0.0001, OR=2.8). Nail biting and encopresis were the most significant independent predictors of intestinal helminthiasis (P=0.025 and 0.001, respectively) in the subjects only. Hand washing with water and soap after defecation and frequent de-worming exercise were practices significantly associated with decreased prevalence of intestinal helminthiasis in the subjects and controls. Behavioral modification in children with chronic neurological disorders should be an integral part of the control program for intestinal helminthiasis.
Ena, J; Simón-Aylón, A; Pasquau, F
We describe a 77-year-old patient with HIV infection suffering from chronic diarrhoea whose colonoscopy findings showed normal appearance mucosa and tissue samples revealed the presence of a dense layer of spirochetes attached to the apical cell membrane. A literature search from 1996 to April 2009 identified 19 additional cases of intestinal spirochetosis in patients with HIV infection. Analysis of cases showed that intestinal spirochetosis causes chronic diarrhoea in men who have sex with men (92% of patients with reported HIV infection risk factors) who are not severely immunosuppressed (70% with CD4 lymphocyte cells >200/microL). Colonoscopy examination often revealed normal appearance mucosa. Haematoxylin and eosin stain of biopsy samples showed the presence of spirochetes, but Warthin-Starry silver staining makes organisms easier to detect. Patients promptly responded to metronidazole or penicillin therapy. In summary, invasive intestinal spirochetosis should be considered in the differential diagnosis of patients with HIV infection and chronic diarrhoea.
Kato, Masaomi; Kashem, Mohammed Abul; Cheng, Chao
Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic – a mild and long-term – oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. PMID:27623524
Milunsky, Aubrey; Baldwin, Clinton; Zhang, Xiaoying; Primack, Daniel; Curnow, Adrian; Milunsky, Jeff
The diagnosis of chronic intestinal pseudo-obstruction has depended on clinical features, manometry, and imaging. This report aimed to determine the efficacy of sequencing the actin γ-2 (ACTG2) gene for diagnosis. In addition, the goal was to determine how often a mutation would be found in our randomly collected cohort of probands and those probands published previously. Whole exome sequencing was performed in 4 probands with chronic intestinal pseudo-obstruction. Subsequently, only the ACTG2 gene was sequenced in another 24 probands (total 28). We analyzed published data of 83 probands and our 28 (total 111) and determined how many had pathogenic variants and the precise genotype. Whole exome and Sanger sequencing revealed a pathogenic variant in the ACTG2 gene in 4 out of 28 of our probands and in 45 out of 83 published probands (49/111 [44.1%]). Moreover, a mutational hotspot in the ACTG2 gene was recognized. Genetic heterogeneity is evident. Pooled gene sequencing results from 1 individual in each of 111 families enabled a precise diagnosis of an ACTG2 mutation in 49 (44%). The benefit to patients and families of early confirmation of a motility disorder not only helps avoid unnecessary intervention, but also enables institution of appropriate treatments and avoidance of secondary disorders such as malnutrition and poor growth. Knowledge of a pathogenic variant in a parent, with a 50% risk of recurrence, provides an opportunity for genetic counseling.
Mattsson, Tomas; Roos, Robert; Sundkvist, Göran; Valind, Sven; Ohlsson, Bodil
To clarify whether disturbances in the autonomic nervous system, reflected in abnormal cardiovascular reflexes, could explain symptoms of impaired heat regulation in patients with intestinal pseudo-obstruction. Chronic intestinal pseudo-obstruction is a clinical syndrome characterized by diffuse, unspecific gastrointestinal symptoms due to damage to the enteric nervous system or the smooth muscle cells. These patients often complain of excessive sweating or feeling cold, suggesting disturbances in the autonomic nervous system. Earlier studies have pointed to a coexistence of autonomic disturbances in the enteric and cardiovascular nervous system. Thirteen consecutive patients (age range 23 to 79, mean 44 y) fulfilling the criteria for chronic intestinal pseudo-obstruction were investigated. Six of them complained of sweating or a feeling of cold. Examination of autonomic reflexes included heart rate variation to deep-breathing (expiration/inspiration index), heart rate reaction to tilt (acceleration index, brake index), and vasoconstriction (VAC) due to indirect cooling by laser doppler (VAC-index; high index indicates impaired VAC). Test results in patients were compared with healthy individuals. Patients had significantly higher (more abnormal) median VAC-index compared with healthy controls [1.79 (interquartile ranges 1.89) vs. 0.08 (interquartile ranges 1.29); P=0.0007]. However, symptoms of impaired heat regulation were not related to the VAC-index. There were no differences in expiration/inspiration, acceleration index, or brake index between patients and controls. The patients with severe gastrointestinal dysmotility showed impaired sympathetic nerve function which, however, did not seem to be associated with symptoms of impaired heat regulation.
Riley, J W; Glickman, R M; Green, P H; Tall, A R
Chronic cholesterol feeding has been shown to produce abnormal plasma lipoproteins in a variety of experimental animals and man. In order to explore the role of the intestine in the production of these abnormal lipoproteins, rats were chronically fed a diet containing 1% cholesterol and 10% olive oil and were compared to control animals, fed either normal chow or normal chow containing 10% olive oil. Mesenteric lymph lipoproteins from fasting lymph and from lymph obtained after acutely infusing cholesterol and olive oil were examined and compared to plasma lipoproteins from these animals. There were no differences in apoA-I output, cholesterol output, or distribution in lymph lipoproteins between the two groups of controls. The cholesterol-olive oil diet produced a mild hyperlipidemia (plasma cholesterol 81 --> 95 mg/dl, plasma triglyceride 95 --> 162 mg/dl). Plasma lipoprotein electrophoresis revealed an abnormal band with broad beta mobility and a reduction in HDL. Lipid analysis of ultracentrifugally separated fractions demonstrated the appearance of an intermediate density (1.006-1.030 g/ml) lipoprotein in plasma markedly enriched in cholesteryl esters. Analysis of fasting mesenteric lymph from chronically cholesterol-fed animals revealed similar apoA-I, cholesterol, and triglyceride outputs when compared to controls. Although in both groups most of the cholesterol was transported in d < 1.006 g/ml lipoproteins, there was a redistribution of cholesterol transport in d > 1.006 g/ml lipoproteins. In the chronically cholesterol-fed animals, 19% of fasting lymph cholesterol was transported in a lipoprotein of density 1.006-1.030 g/ml, compared to 4% in this density in controls. During the acute infusion of cholesterol and olive oil, the output of lymph apoA-I (226 +/- 20 versus 374 +/- 5 micro g/hr, P < 0.025) and lymph cholesterol (970 +/- 82 +/- 1774 micro g/hr, P < 0.01) was significantly lower in the chronically cholesterol-fed group, despite no significant
Kuwano, Kazuyoshi; Araya, Jun; Hara, Hiromichi; Minagawa, Shunsuke; Takasaka, Naoki; Ito, Saburo; Kobayashi, Kenji; Nakayama, Katsutoshi
Aging is associated with impairments in homeostasis. Although aging and senescence are not equivalent, the number of senescent cells increases with aging. Cellular senescence plays important roles in tissue repair or remodeling, as well as embryonic development. Autophagy is a process of lysosomal self-degradation that maintains a homeostatic balance between the synthesis, degradation, and recycling of cellular proteins. Autophagy diminishes with aging; additionally, accelerated aging can be attributed to reduced autophagy. Cellular senescence has been widely implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease of accelerated lung aging, presumably by impairing cell repopulation and by aberrant cytokine secretion in the senescence-associated secretory phenotype. The possible participation of autophagy in the pathogenic sequence of COPD has been extensively explored. Although it has been reported that increased autophagy may induce epithelial cell death, an insufficient reserve of autophagy can induce cellular senescence in bronchial epithelial cells of COPD. Furthermore, advanced age is one of the most important risk factors for the development of idiopathic pulmonary fibrosis (IPF). Telomere shortening is found in blood leukocytes and alveolar epithelial cells from patients with IPF. Accelerated senescence of epithelial cells plays a role in IPF pathogenesis by perpetuating abnormal epithelial-mesenchymal interactions. Insufficient autophagy may be an underlying mechanism of accelerated epithelial cell senescence and myofibroblast differentiation in IPF. Herein, we review the molecular mechanisms of cellular senescence and autophagy and summarize the role of cellular senescence and autophagy in both COPD and IPF. Copyright Â© 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Thomas, Rachel H; Luthin, David R
Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are two common functional gastrointestinal disorders that impair quality of life and pose a significant economic burden to the health care system. Current therapeutic options include lifestyle modifications, over-the-counter (OTC) agents, antispasmodics, serotonin agonists, and lubiprostone and linaclotide, two prosecretory prescription drugs approved for the treatment of IBS-C and CIC. This review discusses the efficacy and safety of current treatments and emerging therapies for the treatment of IBS-C and CIC, with a focus on the prosecretory agents. A search of the PubMed database (1966-November 2014) was performed to identify relevant articles; clinical trials on emerging agents were also identified by searching the ClinicalTrials.gov registry. OTC laxatives may relieve constipation but do not treat abdominal pain and discomfort. Antispasmodics may provide short-term relief in patients with IBS-C, but their utility is limited by anticholinergic adverse effects. Tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors have shown benefit in providing global symptom relief and in improving abdominal discomfort, but further research is needed. Phase III clinical trials have demonstrated the efficacy of lubiprostone and linaclotide relative to placebo for the short-term treatment of IBS-C and CIC, with improvements reported in stool frequency, perceived constipation severity, and abdominal pain and discomfort. Relatively small response rates, higher costs, and adverse effects associated with lubiprostone and linaclotide will likely render these agents suitable as second-line therapies in the treatment of IBS-C and CIC. Emerging potential treatment options include prucalopride, plecanatide, elobixibat, and tenapanor. Several of these emerging therapies have novel mechanisms of action and may show promise in patients
Nelson, Alfred D; Camilleri, Michael; Chirapongsathorn, Sakkarin; Vijayvargiya, Priya; Valentin, Nelson; Shin, Andrea; Erwin, Patricia J; Wang, Zhen; Murad, M Hassan
To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Ford, Alexander C; Quigley, Eamonn M M; Lacy, Brian E; Lembo, Anthony J; Saito, Yuri A; Schiller, Lawrence R; Soffer, Edy E; Spiegel, Brennan M R; Moayyedi, Paul
Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI. The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn. Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain.
Illuminati, G; Caliò, F G; D'Urso, A; Papaspiropoulos, V; Mancini, P; Ceccanei, G
Due to the rarity of the condition, large and prospective series defining the optimal method of digestive arteries revascularization, for the treatment of chronic intestinal ischemia, are lacking. The aim of this consecutive sample clinical study was to test the hypothesis that flexible application of different revascularization methods, according to individual cases, will yield the best results in the management of chronic intestinal ischemia. Eleven patients, of a mean age of 56 years, underwent revascularization of 11 digestive arteries for symptomatic chronic mesenteric occlusive disease. Eleven superior mesenteric arteries and one celiac axis were revascularized. The revascularization techniques included retrograde bypass grafting in 7 cases, antegrade bypass grafting in 2, percutaneous arterial angioplasty in 1, and arterial reimplantation in one case. The donor axis for either reimplantation or bypass grafting was the infrarenal aorta in 4 cases, an infrarenal Dacron graft in 4, and the celiac aorta in one case. Grafting materials included 5 polytetrafluoroethylene (PTFE) and 3 Dacron grafts. Concomitant procedures included 3 aorto-ilio-femoral grafts and one renal artery revascularization. Mean follow-up duration was 31 months. There was no operative mortality. Cumulative survival rate was 88.9% at 36 months (SE 12.1%). Primary patency rate was 90% at 36 months (SE 11.6%). The symptom free rate was 90% at 36 months (SE 11.6%). Direct reimplantation, antegrade and retrograde bypass grafting, all allow good mid-term results: the choice of the optimal method depends on the anatomic and general patient's status. Associated infrarenal and renal arterial lesions can be safely treated in the same time of digestive revascularization. Angioplasty alone yields poor results and should be limited to patients at poor risk for surgery.
Zacho, Helle Damgaard; Henriksen, Jens Henrik; Abrahamsen, Jan
AIM: To determine the splanchnic blood flow and oxygen uptake in healthy-subjects and patients and to relate the findings to body-composition. METHODS: The total splanchnic blood flow (SBF) and oxygen uptake (SO2U) were measured in 20 healthy volunteers (10 women) and 29 patients with suspected chronic intestinal ischemia (15 women), age 40-85 years, prior to and after a standard meal. The method is based on the Fick principle using the continuous infusion of an indicator (99mTechnetium-labelled mebrofenin) and catheterization of an artery and the hepatic vein. An angiography of the intestinal arteries was performed during the same investigation. A whole-body dual-energy x-ray absorptiometry scan was performed in healthy volunteers to determine body composition. RESULTS: Angiography revealed no atherosclerotic lesions in the intestinal arteries. The mean baseline SBF was 1087 mL/min (731-1390), and this value increased significantly to 1787 mL/min after the meal in healthy volunteers (P < 0.001). The baseline SBF in patients was 1080 mL/min, which increased to 1718 mL/min postprandially (P < 0.001). The baseline SBF was independent of age, sex, lean body mass and percentage of body fat. The mean meal-induced increase in SBF was equal to 282 mL/min + 5.4 mL/min × bodyweight, (P = 0.025). The SO2U in healthy volunteers and patients was 50.7 mL/min and 48.0 mL/min, respectively, and these values increased to 77.5 mL/min and 75 mL/min postprandially, respectively. Both baseline and postprandial SO2U were directly related to lean body mass. Age and sex exerted no impact on SO2U. CONCLUSION: A direct correlation between body weight and the postprandial increase in SBF was observed. The effect of body weight should be considered in the diagnosis of chronic intestinal ischemia. PMID:23430966
Xin, Xiaofeng; Dai, Wei; Wu, Jie; Fang, Liping; Zhao, Ming; Zhang, Pengpeng; Chen, Min
The aim of the present study was to investigate intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease (COPD). Male Sprague Dawley rats (n=40) were evenly randomized into control and COPD groups and the COPD model was established by regulated exposure to cigarette smoke for 6 months. Histopathological changes of the lung and intestinal tissues were detected by hematoxylin and eosin staining. Expression of the tight junction proteins occludin and zona occludens-1 (ZO-1) in the intestinal tissues were analyzed by western blotting, serum diamine oxidase (DAO) activity was detected by spectrophotometry, the urinary lactulose to mannitol ratio (L/M) was evaluated by high performance liquid chromatography, and intestinal tissue secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-8 were detected by ELISA. Lung histopathology revealed thinned alveolar walls, ruptured alveolar septa, enlarged and deformed alveoli, and the formation of bullae and emphysema due to alveolar fusion in the COPD group, while intestinal histopathology indicated clearly swollen intestines with darkened and gray mucosa, neutrophil infiltration of the intestinal mucosal and regional epithelial shedding. The occludin and ZO-1 expression levels were significantly lower in the COPD group compared with those in the corresponding control group (P<0.05), while the urinary L/M ratio was significantly higher (P<0.05). Furthermore, the serum DAO activity and secretion of TNF-α, IFN-γ and IL-8 in the intestinal tissues were significantly higher in the COPD group than in the control group (each P<0.05). Dysfunctional and structural changes were observed in the intestinal mucosal barrier in COPD model rats, which may be associated with the increased intestinal inflammatory responses. PMID:27588054
Plaza-Díaz, Julio; Ruiz-Ojeda, Francisco Javier; Vilchez-Padial, Laura Maria; Gil, Angel
Probiotics and synbiotics are used to treat chronic diseases, principally due to their role in immune system modulation and the anti-inflammatory response. The present study reviewed the effects of probiotics and synbiotics on intestinal chronic diseases in in vitro, animal, and human studies, particularly in randomized clinical trials. The selected probiotics exhibit in vitro anti-inflammatory properties. Probiotic strains and cell-free supernatants reduced the expression of pro-inflammatory cytokines via action that is principally mediated by toll-like receptors. Probiotic administration improved the clinical symptoms, histological alterations, and mucus production in most of the evaluated animal studies, but some results suggest that caution should be taken when administering these agents in the relapse stages of IBD. In addition, no effects on chronic enteropathies were reported. Probiotic supplementation appears to be potentially well tolerated, effective, and safe in patients with IBD, in both CD and UC. Indeed, probiotics such as Bifidobacterium longum 536 improved the clinical symptoms in patients with mild to moderate active UC. Although it has been proposed that probiotics can provide benefits in certain conditions, the risks and benefits should be carefully assessed before initiating any therapy in patients with IBD. For this reason, further studies are required to understand the precise mechanism by which probiotics and synbiotics affect these diseases. PMID:28555037
Plaza-Díaz, Julio; Ruiz-Ojeda, Francisco Javier; Vilchez-Padial, Laura Maria; Gil, Angel
Probiotics and synbiotics are used to treat chronic diseases, principally due to their role in immune system modulation and the anti-inflammatory response. The present study reviewed the effects of probiotics and synbiotics on intestinal chronic diseases in in vitro, animal, and human studies, particularly in randomized clinical trials. The selected probiotics exhibit in vitro anti-inflammatory properties. Probiotic strains and cell-free supernatants reduced the expression of pro-inflammatory cytokines via action that is principally mediated by toll-like receptors. Probiotic administration improved the clinical symptoms, histological alterations, and mucus production in most of the evaluated animal studies, but some results suggest that caution should be taken when administering these agents in the relapse stages of IBD. In addition, no effects on chronic enteropathies were reported. Probiotic supplementation appears to be potentially well tolerated, effective, and safe in patients with IBD, in both CD and UC. Indeed, probiotics such as Bifidobacterium longum 536 improved the clinical symptoms in patients with mild to moderate active UC. Although it has been proposed that probiotics can provide benefits in certain conditions, the risks and benefits should be carefully assessed before initiating any therapy in patients with IBD. For this reason, further studies are required to understand the precise mechanism by which probiotics and synbiotics affect these diseases.
Nagura, Michito; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto; Uchida, Shunya
Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid. Male Wistar rats were randomly assigned to three groups consisting of Nx group, oxonic acid-treated (Ox) group and sham-operated control group, and sacrificed at 8 weeks. Creatinine and UA were measured and the mRNA expressions of UA transporters in the kidney and intestine were evaluated by a real time PCR. UA transporters in the kidney sections were also examined by immunohistochemistry. Serum creatinine elevated in the Nx group whereas serum UA increased in the Ox group. Both the mRNA expression and the immunohistochemistry of the UA transporters were decreased in the Nx group, suggesting a marginal role in UA elevation in decreased kidney function. In contrast, the mRNA expression of Abcg2 in the ileum significantly increased in the Ox group. These results suggest that the upregulation of Abcg2 mRNA in the ileum triggered by an elevation of serum UA may play a compensatory role in increasing intestinal UA excretion.
Angkathunyakul, Napat; Treepongkaruna, Suporn; Molagool, Sani; Ruangwattanapaisarn, Nichanan
Visceral myopathy is one of the causes of chronic intestinal pseudo-obstruction. Most cases pathologically reveal degenerative changes of myocytes or muscularis propia atrophy and fibrosis. Abnormal layering of muscularis propria is extremely rare. We report a case of a 9-mo-old Thai male baby who presented with chronic intestinal pseudo-obstruction. Histologic findings showed abnormal layering of small intestinal muscularis propria with an additional oblique layer and aberrant muscularization in serosa. The patient also had a short small bowel without malrotation, brachydactyly, and absence of the 2nd to 4th middle phalanges of both hands. The patient was treated with cisapride and combined parenteral and enteral nutritional support. He had gradual clinical improvement and gained body weight. Subsequently, the parenteral nutrition was discontinued. The previously reported cases are reviewed and discussed. PMID:26078585
Angkathunyakul, Napat; Treepongkaruna, Suporn; Molagool, Sani; Ruangwattanapaisarn, Nichanan
Visceral myopathy is one of the causes of chronic intestinal pseudo-obstruction. Most cases pathologically reveal degenerative changes of myocytes or muscularis propia atrophy and fibrosis. Abnormal layering of muscularis propria is extremely rare. We report a case of a 9-mo-old Thai male baby who presented with chronic intestinal pseudo-obstruction. Histologic findings showed abnormal layering of small intestinal muscularis propria with an additional oblique layer and aberrant muscularization in serosa. The patient also had a short small bowel without malrotation, brachydactyly, and absence of the 2(nd) to 4(th) middle phalanges of both hands. The patient was treated with cisapride and combined parenteral and enteral nutritional support. He had gradual clinical improvement and gained body weight. Subsequently, the parenteral nutrition was discontinued. The previously reported cases are reviewed and discussed.
van Geijlswijk, Ingeborg M; van der Heijden, Kristiaan B; Egberts, A C G; Korzilius, Hubert P L M; Smits, Marcel G
Pharmacokinetics of melatonin in children might differ from that in adults. This study aims to establish a dose-response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI). The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n = 72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL. Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (r (s) = -0.33, p = 0.022) and SO (r (s) = -0.38, p = 0.004), whereas clock TOA was correlated with SO shift (r = -0.35, p = 0.006) and not with DLMO shift. No dose-response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05-0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime.
van der Heijden, Kristiaan B.; Egberts, A. C. G.; Korzilius, Hubert P. L. M.; Smits, Marcel G.
Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives This study aims to establish a dose–response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI). Methods The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n = 72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL. Results Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (rs = −0.33, p = 0.022) and SO (rs = −0.38, p = 0.004), whereas clock TOA was correlated with SO shift (r = −0.35, p = 0.006) and not with DLMO shift. Conclusions No dose–response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05–0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime. PMID:20668840
Byun, S J; Lim, T J; Lim, Y J; Seo, J G; Chung, M J
Treatment and prevention methods for non-steroidal anti-inflammatory drug-induced enteropathy have not yet been established. We tested the preventive effects of s-pantoprazole sodium trihydrate (PAN), polaprezinc (PZ), and probiotics on an indomethacin (Indo)-induced small intestinal injury in a rat model. Rats were randomised into 6 groups to receive: normal saline (control), Indo (6 mg/kg), PZ plus Indo, PAN plus Indo, or probiotics plus Indo (at 10(8) and 10(9) cfu/head) for 2 weeks. We measured body weight, food intake, severity of small intestinal damage, haemoglobin (Hb) levels in the small intestinal fluid, intestinal inflammatory cytokines, and a few groups of faecal bacteria. The experimental groups were found to have the following survival rates: 0% for the Indo, PZ, and PAN groups; 50% for both probiotic groups; and 100% for control. Treatment with probiotics of different concentrations reduced small intestinal lesion scores and intestinal fluid Hb as compared with the Indo group, while these parameters did not reduce in the PZ and PAN groups. The anti-inflammatory marker interleukin 10 increased in both probiotic groups. Analysis of a few groups of faecal bacteria revealed that Indo-induced a significant increase in Gram-negative bacteria and decreases in Bifidobacterium and Lactobacillus. Similar changes were also observed in the PZ and PAN groups. However, opposite effects were found in both probiotic groups. The use of probiotics appeared to be beneficial in preventing Indo-induced chronic small intestinal injury.
Iwakura, Hideo; Fujii, Katsunori; Furutani, Yoshiyuki; Takatani, Tomozumi; Ebata, Ryota; Nakanishi, Toshio; Mitsunaga, Tetsuya; Saito, Takeshi; Kishimoto, Takashi; Yoshida, Hideo; Shimojo, Naoki
Ellis-van Creveld (EVC) syndrome is a rare autosomal recessive disorder characterized by hypoplastic nails, polydactyly, and achondroplasia. Patients usually exhibit normal cognitive function and no remarkable developmental delay. We herein present an unusual case of EVC syndrome. A Japanese 2-year-old boy was born at term, but immediately developed severe respiratory failure due to thorax deformity, postaxial polydactyly and nail hypoplasia. We identified a novel pattern of germinal compound heterozygous nonsense EVC2 mutations of c.1814C > A (p. S605X) and c.2653C > T (p. R885X), leading to the diagnosis of EVC syndrome. Interestingly, he also had severe developmental delay, and suddenly developed excessive abdominal distension at the age of 2. On surgery, extensive necrotic bowel with chronic intestinal pseudo-obstruction was noted. This is, to our knowledge, a most severe phenotype of EVC syndrome, illustrating that the specific pattern of EVC2 compound heterozygous mutations may cause severe developmental delay and intestinal malfunction. © 2016 Japan Pediatric Society.
Jandhyala, Sai Manasa; Madhulika, A.; Deepika, G.; Rao, G. Venkat; Reddy, D. Nageshwar; Subramanyam, Chivukula; Sasikala, Mitnala; Talukdar, Rupjyoti
Intestinal dysbiosis and its functional implications in chronic pancreatitis (CP) have not been elaborately studied. We evaluated the taxonomic and functional alterations in intestinal microbiota in 30 well-characterised patients with CP (16 without, 14 with diabetes) and 10 healthy controls. The patients with CP and diabetes had significantly longer disease duration and greater degree of malnutrition. There was increase in plasma endotoxin concentrations from controls to CP non-diabetics to CP diabetics. We observed significant differences in richness and alpha diversity between the groups. We also observed increase in the Firmicutes:Bacteroidetes ratio in CP patients without and with diabetes. There was reduction in abundance of Faecalibacterium prausnitzii and Ruminococcus bromii from controls to CP non-diabetics to CP diabetics. On the other hand, there was increase in LPS (endotoxin) synthetic pathways (KEGG orthology) in the groups. Faecalibacterium prausnitzii abundance correlated negatively with plasma endotoxin and glycemic status; while plasma endotoxin correlated positively with blood glucose and negatively with plasma insulin. Our results have important implications for future studies exploring mechanistic insights on secondary diabetes in CP. PMID:28255158
Mallick, Saumyaranjan; Prasenjit, Das; Prateek, Kinra; Shasanka, Panda S; Virender, Sekhon; Rajni, Yadav; Gaurav, Jindal; Vijay, Maneesh K; Arun, Kumar V; Mahajan, J K; Sandeep, Agarwala; Ranjan, Dash Nihar; Siddhartha, Datta Gupta
The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is critical, and the findings are often missed by the histopathologists for lack of awareness and nonavailability of standard criteria. We aimed to describe a detailed histopathological approach for working-up cases of CIP by citing our experience. Eight suspected cases of CIP were included in the study to determine and describe an approach for reaching the histopathological diagnosis collected over a period of the last 1.5 years. The Hirschsprung's disease was put apart from the scope of this study. A detailed light microscopic analysis was performed along with special and immunohistochemical stains. Transmission electron microscopy was carried out on tissue retrieved from paraffin embedded tissue blocks. Among the eight cases, three were neonates, one in the pediatric age group, two adolescent, and two adults. After following the described critical approach, we achieved the histological diagnoses in all the cases. The causes of CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4), mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in all of them along with other primary pathologies. One of the IND patients also had visceral myopathy, type IV. Histopathologists need to follow a systematic approach comprising of diligent histological examination and use of immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup. Therapy and prognosis vary depending on lesions identified by pathologists. These lesions can be seen in isolation or in combinations.
Roulis, Manolis; Armaka, Maria; Manoloukos, Menelaos; Apostolaki, Maria; Kollias, George
TNF plays a crucial role in the pathogenesis of Crohn disease. Dysregulated TNF production in mice that bear the genetic deletion of the TNF AU-rich regulatory elements (ARE) (TnfΔARE/+ mice) results in TNF receptor I (TNFRI)-dependent spontaneous Crohn-like pathology. Current concepts consider intestinal epithelial cell (IEC) responses to TNF to be critical for intestinal pathology, but the potential contribution of IEC-derived TNF in disease pathogenesis has not been addressed. In this study we examined whether IEC are sufficient as cellular targets or sources of TNF in the development of intestinal pathology. Using IEC-specific reactivation of a hypomorphic TnfΔAREneo allele in mice, we show that selective chronic overproduction of TNF by IEC suffices to cause full development of Crohn-like pathology. Epithelial TNF overexpression leads to early activation of the underlying intestinal myofibroblast, a cell type previously identified as a sufficient target of TNF for disease development in the TnfΔARE model. By contrast, restricted TNFRI expression on IEC although sufficient to confer IEC apoptosis after acute exogenous TNF administration, fails to induce pathology following chronic specific targeting of IEC by endogenous TNF in TnfΔARE/+ mice. Our results argue against IEC being early and sufficient responders to chronic TNF-mediated pathogenic signals and suggest that proinflammatory aberrations leading to chronic TNF production by IEC may initiate pathology in Crohn disease. PMID:21402942
Hashimura, Yuya; Morioka, Ichiro; Hisamatsu, Chieko; Yokoyama, Naoki; Taniguchi-Ikeda, Mariko; Yokozaki, Hiroshi; Murayama, Kei; Ohtake, Akira; Itoh, Kyoko; Takeshima, Yasuhiro; Iijima, Kazumoto
A female infant born at 36 weeks gestational age with birthweight 2135 g, and who developed respiratory disorder, hyperlactacidemia and hypertrophic cardiomyopathy after birth, was admitted to hospital at 3 days of age. After admission, bilious emesis, abdominal distention, and passage disorder of the gastrointestinal tract were resistant to various drugs. Exploratory laparotomy was performed at 93 days of age, but no organic lesions were identified and normal Meissner/Auerbach nerve plexus was confirmed, which led to a clinical diagnosis of chronic intestinal pseudo-obstruction (CIPO). She was diagnosed with mitochondrial respiratory chain complex IV deficiency on histopathology of the abdominal rectus muscle and enzyme activity measurement. This is the first report of a neonate with mitochondrial respiratory chain complex deficiency with intractable CIPO. CIPO can occur in neonates with mitochondrial respiratory chain disorder, necessitating differential diagnosis from Hirschsprung disease.
Cameron, Jean-Christy F; Vaillancourt, Régis; Major-Cook, Nathalie; Boland, Margaret; Zucker, Marc; Lariviere, Doris
Cisapride is a gastrointestinal prokinetic that facilitates or restores motility along the entire gastrointestinal tract. It has been used successfully to treat acute and chronic intestinal pseudo-obstructions (CIPs) in adults, but there is a paucity of literature surrounding the treatment of CIP in pediatric patients and therapies for CIP are limited and their impact is often unsatisfactory. This case report presents the use of cisapride in the management of pseudo-obstruction. Treatment with cisapride substantially improved the patient's symptoms and improved feeding tolerance. It improved his prognosis remarkably and prevented the need for end-of-life care. He experienced no adverse effects throughout the course of therapy. The treatment regimen is discussed in this case report.
Bonora, Elena; Bianco, Francesca; Cordeddu, Lina; Bamshad, Michael; Francescatto, Ludmila; Dowless, Dustin; Stanghellini, Vincenzo; Cogliandro, Rosanna F.; Lindberg, Greger; Mungan, Zeynel; Cefle, Kivanc; Ozcelik, Tayfun; Palanduz, Sukru; Ozturk, Sukru; Gedikbasi, Asuman; Gori, Alessandra; Pippucci, Tommaso; Graziano, Claudio; Volta, Umberto; Caio, Giacomo; Barbara, Giovanni; D'Amato, Mauro; Seri, Marco; Katsanis, Nicholas; Romeo, Giovanni; De Giorgio, Roberto
Background & Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimicks a mechanical sub-occlusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and indentify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of mRNA and proteins were analyzed by quantitative reverse transcription PCR, immunoblot, and mobility shift assays. cDNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a MO). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a MO zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 is also overexpressed in sporadic CIPO in sera and gut biopsies. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of
Allenspach, K; Bergman, P J; Sauter, S; Gröne, A; Doherr, M G; Gaschen, F
P-glycoprotein (p-gp) is a transmembrane protein functioning as a drug-efflux pump in the intestinal epithelium. Human patients with inflammatory bowel disease (IBD) who fail to respond to treatment with steroids express high levels of p-gp in lamina propria lymphocytes. The purpose of this study was to investigate p-gp expression in duodenal biopsy samples of dogs with chronic enteropathies and to evaluate the expression of p-gp after treatment with a known inducer of p-gp (prednisolone). Duodenal biopsy samples from 48 dogs were evaluated immunohistochemically with the mouse monoclonal antibody C219 for expression of p-gp in lamina propria lymphocytes. Biopsy samples were available from 15 dogs after treatment with prednisolone and 16 dogs after dietary therapy alone ("elimination diet"). Treatment with prednisolone resulted in an increase in p-gp expression (P=0.005). In contrast, dietary treatment alone produced no significant change in p-gp expression (P=0.59). A low p-gp score before initiation of steroid treatment was significantly associated with a positive response to treatment (P=0.01). These results indicate that lamina propria lymphocyte expression of p-gp is upregulated after prednisolone treatment in dogs with IBD, and that mucosal expression of p-gp may be of value in predicting the response to therapy.
Chey, William D; Camilleri, Michael; Chang, Lin; Rikner, Leif; Graffner, Hans
OBJECTIVES: A3309 is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor. We conducted an 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, phase IIb study, which evaluated A3309 in patients with chronic idiopathic constipation (CIC). METHODS: Patients with CIC (modified Rome III criteria and <3 complete (CSBM) spontaneous bowel movements (SBMs)/week during the 2-week baseline) were randomized to 5, 10, or 15 mg A3309 or placebo once daily. The primary end point was change in SBM number during week 1 compared with baseline. Other bowel and abdominal symptoms were assessed as secondary end points. Serum 7αC4 and lipids were evaluated as biomarkers of BA synthesis/loss. RESULTS: In all, 190 patients (mean 48 years, 90% female) were randomized. Mean increase (95% confidence interval) in SBM for week 1 were 1.7 (0.7–2.8) for placebo vs. 2.5 (1.5–3.5), 4.0 (2.9–5.0), and 5.4 (4.4–6.4) for 5 mg, 10 mg (P<0.002), and 15 mg (P<0.001) A3309, respectively. Increased stool frequency was maintained over 8 weeks. Time to first SBM and CSBM were significantly reduced in the 10- and 15-mg A3309 groups compared with placebo. Straining and bloating decreased with A3309 compared with placebo (P<0.05). Increased 7αC4 and reduced low-density lipoprotein cholesterol with A3309 suggested increased BA synthesis and BA loss. The most common adverse events (AEs) were abdominal pain and diarrhea, which occurred most commonly in the 15-mg A3309 group. No drug-related serious AEs were observed. CONCLUSIONS: A3309 increased stool frequency and improved constipation-related symptoms in CIC; effects were maintained over 8 weeks of treatment. PMID:21606974
Yang, Junwen; Chen, Shuijiao; Chen, Linlin; Ouyang, Miao; Li, Fujun
Abstract Rationale: Chronic diarrhea in adult patients due to various causes is very common in clinic, but patient suffering with mal-absorption due to immunoproliferative small intestinal disease was rarely reported in China. Patient concerns and Diagnoses: A 35-year-old female presented with more than three years history of chronic diarrhea, rickets, high serum value of immunoglobulin A protein, and anemia. Bone marrow aspiration suggested that the patient was in a sideropenic and megalobastic anemia stage. Duodenal and ileac biopsies revealed atrophy and blunting villi. The bowel lamina propria was infiltrated with slightly increased intraepithelial lymphocytes and mainly with diffuse plasma cells. The following enzyme labeling immunohistochemistry results were strongly positive to alpha-heavy-chain. Computed tomography manifested she had diffuse thickening of small intestine wall. At last a diagnosis of immunoproliferative small intestinal disease was made. Interventions and Outcomes: On the first month, the patient was treated with vitamin D supplements, calcium, magnesium, potassium, iron, folic acid, mecobalamin replacements and microflora probiotics. The patient frequency of water diarrhea alleviated slightly, but her weight loss, anxiety neurosis and other disorders were still severe. After taking with prednisone (40 mg per day, and gradually reduced to the lowest dose) for another month, the symptoms was gradually subsided. Lessons: The study shows that immunohistochemical staining for alpha-heavy chain proteins should be completed on small intestine biopsy specimens if the patient is suspected a diagnosis of immunoproliferative small intestinal disease. PMID:28151917
Guirl, Michael J; Högenauer, Christoph; Santa Ana, Carol A; Porter, Jack L; Little, Katherine H; Stone, Marvin J; Fordtran, John S
The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15-36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.
Tavallali, Ali; Yannuzzi, Lawrence A.
Idiopathic multifocal choroiditis (MFC) and/or punctate inner choroidopathy (PIC) describe a chronic progressive bilateral inflammatory chorioretinopathy that predominantly affect healthy myopic white women with no known associated systemic or ocular diseases. The principal sites of involvement are the retinal pigment epithelium (RPE) and outer retinal spaces; the choroid is not affected during the active phase of the disease. Idiopathic MFC with atrophy is a recently described variant. Although there is no generally accepted standard treatment, anti-inflammatory and anti-VEGF (vascular endothelial growth factor) agents are necessary in the acute stage to control the inflammation and choroidal neovascularization (CNV). PMID:27994812
Fenny, Nana; Grammer, Leslie C
Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.
Pannequin, Julie; Delaunay, Nathalie; Darido, Charbel; Maurice, Tangui; Crespy, Philippe; Frohman, Michael A; Balda, Maria S; Matter, Karl; Joubert, Dominique; Bourgaux, Jean-François; Bali, Jean-Pierre; Hollande, Frédéric
Chronic alcohol consumption is associated with increased risk of gastrointestinal cancer. High concentrations of ethanol trigger mucosal hyperregeneration, disrupt cell adhesion, and increase the sensitivity to carcinogens. Most of these effects are thought to be mediated by acetaldehyde, a genotoxic metabolite produced from ethanol by alcohol dehydrogenases. Here, we studied the role of low ethanol concentrations, more likely to mimic those found in the intestine in vivo, and used intestinal cells lacking alcohol dehydrogenase to identify the acetaldehyde-independent biological effects of ethanol. Under these conditions, ethanol did not stimulate the proliferation of nonconfluent cells, but significantly increased maximal cell density. Incorporation of phosphatidylethanol, produced from ethanol by phospholipase D, was instrumental to this effect. Phosphatidylethanol accumulation induced claudin-1 endocytosis and disrupted the claudin-1/ZO-1 association. The resulting nuclear translocation of ZONAB was shown to mediate the cell density increase in ethanol-treated cells. In vivo, incorporation of phosphatidylethanol and nuclear translocation of ZONAB correlated with increased proliferation in the colonic epithelium of ethanol-fed mice and in adenomas of chronic alcoholics. Our results show that phosphatidylethanol accumulation after chronic ethanol exposure disrupts signals that normally restrict proliferation in highly confluent intestinal cells, thus facilitating abnormal intestinal cell proliferation.
Arnold, I C; Mathisen, S; Schulthess, J; Danne, C; Hegazy, A N; Powrie, F
In inflammatory bowel diseases, a breakdown in host microbial interactions accompanies sustained activation of immune cells in the gut. Functional studies suggest a key role for interleukin-23 (IL-23) in orchestrating intestinal inflammation. IL-23 can be produced by various mononuclear phagocytes (MNPs) following acute microbial stimulation, but little is known about the key cellular sources of IL-23 that drive chronic intestinal inflammation. Here we have addressed this question using a physiological model of bacteria-driven colitis. By combining conditional gene ablation and gene expression profiling, we found that IL-23 production by CD11c(+) MNPs was essential to trigger intestinal immunopathology and identified MHCII(+) monocytes and macrophages as the major source of IL-23. Expression of IL-23 by monocytes was acquired during their differentiation in the intestine and correlated with the expression of major histocompatibility complex class II (MHCII) and CD64. In contrast, Batf3-dependent CD103(+) CD11b(-) dendritic cells were dispensable for bacteria-induced colitis in this model. These studies reinforce the pathogenic role of monocytes in dysregulated responses to intestinal bacteria and identify production of IL-23 as a key component of this response. Further understanding of the functional sources of IL-23 in diverse forms of intestinal inflammation may lead to novel therapeutic strategies aimed at interrupting IL-23-driven immune pathology.
Whittamore, Jonathan M; Hatch, Marguerite
Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine.
Eun, Chang Soo; Kim, Byung Kwon; Han, Dong Soo; Kim, Seon Young; Kim, Kyung Mo; Choi, Bo Youl; Song, Kyu Sang; Kim, Yong Sung; Kim, Jihyun F
Helicobacter pylori (H. pylori) infection plays an important role in the early stage of cancer development. However, various bacteria that promote the synthesis of reactive oxygen and nitrogen species may be involved in the later stages. We aimed to determine the microbial composition of gastric mucosa from the patients with chronic gastritis, intestinal metaplasia, and gastric cancer using 454 GS FLX Titanium. Gastric mucosal biopsy samples were collected from 31 patients during endoscopy. After the extraction of genomic DNA, variable region V5 of the 16S rRNA gene was amplified. PCR products were sequenced using 454 high-throughput sequencer. The composition, diversity, and richness of microbial communities were compared between three groups. The composition of H. pylori-containing Epsilonproteobacteria class appeared to be the most prevalent, but the relative increase in the Bacilli class in the gastric cancer group was noticed, resulting in a significant difference compared with the chronic gastritis group. By analyzing the Helicobacter-dominant group at a family level, the relative abundance of Helicobacteraceae family was significantly lower in the gastric cancer group compared with chronic gastritis and intestinal metaplasia groups, while the relative abundance of Streptococcaceae family significantly increased. In a UPGMA clustering of Helicobacter-dominant group based on UniFrac distance, the chronic gastritis group and gastric cancer group were clearly separated, while the intestinal metaplasia group was distributed in between the two groups. The evenness and diversity of gastric microbiota in the gastric cancer group was increased compared with other groups. In Helicobacter predominant patients, the microbial compositions of gastric mucosa from gastric cancer patients are significantly different to chronic gastritis and intestinal metaplasia patients. These alterations of gastric microbial composition may play an important, as-yet-undetermined role in
Junquera Bañares, S; Oria Mundín, E; Córdoba Iturriagagoitia, A; Botella-Carretero, J J
Intestinal neuronal dysplasia type B (IND B) is an infrequent disease due to hyperplasia of the parasympathetic submucous plexus which causes alteration of intestinal motility, giving rise to symptoms of constipation and subocclusive manifestations. The disease is difficult to diagnose. It requires high clinical suspicion and should include differential diagnosis of patients with repeated subocclusive manifestations in order to make an early and correct diagnosis and avoid complications derived from unnecessary surgery that worsens the prognosis. We present the case of a 33-year-old Moroccan male who was admitted to our hospital on 2 occasions in 11 months, requiring total parenteral nutrition (TPN) for five months. The immunohistochemical analysis of the ileostomy and colostomy stoma led to a diagnosis of IND B. Eighteen months later, the patients is leading a normal life and has recovered the 25 kilos lost following the dietary indications and with the enzymatic supplements.
Background Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay. Methods In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t½ therapy. Results Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogen-breath-test-positivity was associated inversely with Helicobacter-positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05). In 38 patients (untreated (17) or on stable long-t½ IP-medication), the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s-1, 89 (2, 177) Nm.10-3, per 100 cells.μl-1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). T-helper count was inversely associated with flexor-rigidity before (p=0.01) and after adjustment for natural-killer count (-36(-63, -10) Nm.10-3 per 100 cells.μl-1, p=0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effect-sizes were independent of IP
Giabicani, E; Lemale, J; Dainese, L; Boudjemaa, S; Coulomb, A; Tounian, P; Dubern, B
Treacher Collins syndrome (TCS) mainly presents with severe craniofacial developmental abnormalities characterized by a combination of bilateral downward-slanting palpebral fissures, colobomas of the lower eyelids, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. It is due to mutations in Treacher Collins syndrome 1 (TCOF1) (5q32-q33.1) and Polymerase RNA 1 polypeptides D and C (POLR1D [13q12.2], and POLR1C [6p21.1]) genes, which are responsible for increased neuroepithelial apoptosis during embryogenesis resulting in the lack of neural crest cells involved in facial bone and cartilage formation. Altered function of the upper digestive tract has been reported, whereas severe dysmotility disorders have never been reported. We describe here the first case of TCS associated with histologically proven chronic intestinal pseudo-obstruction (CIPO) in humans. Case presentatios A 12-year-old boy with TCS due to TCOF1 gene deletion experienced nutritional difficulties and digestive intolerance from birth. CIPO was suspected during childhood because of severe intestinal dysmotility leading to enteral-jejunal nutrition intolerance and dependence on total parenteral nutrition. Diagnosis of CIPO with nervous abnormalities was histologically confirmed on a surgical rectal biopsy that showed enlarged ganglionic myenteric plexus. At the age of 9 years, an isolated colonic stenosis without dilatation responsible for severe abdominal pain and altered quality of life led to digestive derivation contributing to rapid disappearance of chronic abdominal pain. At the age of 12 years, the patient was still dependent on total home parenteral nutrition 7 days a week to maintain regular growth velocity. Recently, mice studies have pointed out the role played by TCOF1 in ganglionic cell migration in the foregut, suggesting that the synergistic haploinsufficiency of Tcof1 and Pax3, a
Greenberger, Paul A
Idiopathic anaphylaxis is a prednisone-responsive condition without external cause, but it can coexist with food-, medication-, or exercise-induced anaphylaxis. Mast cell activation may occur at night or after foods that have been eaten with impunity many times previously. Idiopathic anaphylaxis can be classified into frequent (if there are six or more episodes per year or two episodes in the last 2 months) or infrequent (if episodes occur less often). Idiopathic anaphylaxis-generalized consists of urticaria or angioedema associated with severe respiratory distress, syncope or hypotension, and gastrointestinal symptoms. Idiopathic anaphylaxis-angioedema consists of massive tongue enlargement or severe pharyngeal or laryngeal swelling with urticaria or peripheral angioedema. The differential diagnosis of idiopathic anaphylaxis is reviewed, and treatment approaches are presented.
van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.
Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291
van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M
Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.
Kump, Patrizia K; Gröchenig, Hans-Peter; Lackner, Stefan; Trajanoski, Slave; Reicht, Gerhard; Hoffmann, K Martin; Deutschmann, Andrea; Wenzl, Heimo H; Petritsch, Wolfgang; Krejs, Guenter J; Gorkiewicz, Gregor; Högenauer, Christoph
In patients with ulcerative colitis (UC), alterations of the intestinal microbiota, termed dysbiosis, have been postulated to contribute to intestinal inflammation. Fecal microbiota transplantation (FMT) has been used as effective therapy for recurrent Clostridium difficile colitis also caused by dysbiosis. The aims of the present study were to investigate if patients with UC benefit from FMT and if dysbiosis can be reversed. Six patients with chronic active UC nonresponsive to standard medical therapy were treated with FMT by colonoscopic administration. Changes in the colonic microbiota were assessed by 16S rDNA-based microbial community profiling using high-throughput pyrosequencing from mucosal and stool samples. All patients experienced short-term clinical improvement within the first 2 weeks after FMT. However, none of the patients achieved clinical remission. Microbiota profiling showed differences in the modification of the intestinal microbiota between individual patients after FMT. In 3 patients, the colonic microbiota changed toward the donor microbiota; however, this did not correlate with clinical response. On phylum level, there was a significant reduction of Proteobacteria and an increase in Bacteroidetes after FMT. FMT by a single colonoscopic donor stool application is not effective in inducing remission in chronic active therapy-refractory UC. Changes in the composition of the intestinal microbiota were significant and resulted in a partial improvement of UC-associated dysbiosis. The results suggest that dysbiosis in UC is at least in part a secondary phenomenon induced by inflammation and diarrhea rather than being causative for inflammation in this disease.
Canetti, Menahem; Akhter, Mohammed W; Lerman, Amir; Karaalp, Ilyas S; Zell, Jason A; Singh, Harpreet; Mehra, Anilkumar; Elkayam, Uri
This study demonstrates a significant impairment in coronary blood flow reserve in most patients with idiopathic dilated cardiomyopathy despite normal epicardial coronary arteries. This change may prevent appropriate increases in coronary blood flow and thus lead to myocardial ischemia and progression of disease. An association between decreased response to adenosine and acetylcholine supports previous observations indicating that adenosine-induced vasodilation of coronary microcirculation is dependent on endothelial nitric oxide production.
Gu, Lili; Ding, Chao; Tian, Hongliang; Yang, Bo; Zhang, Xuelei; Hua, Yue; Zhu, Yifan; Gong, Jianfeng; Zhu, Weiming; Li, Jieshou; Li, Ning
Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a serious, life-threatening motility disorder that is often related to bacterial overgrowth. Fecal microbiota transplantation (FMT) results in restoration of the normal intestinal microbial community structure. We investigated the efficacy of FMT in the treatment of CIPO patients. Methods Nine patients (age 18–53 years) with CIPO were enrolled in this prospective, open-label study. Patients received FMT for 6 consecutive days through nasojejunal (NJ) tubes and were followed up for 8 weeks after treatment. We evaluated the rate of clinical improvement and remission, feeding tolerance of enteral nutrition, and CT imaging scores of intestinal obstructions. Lactulose hydrogen breath tests were performed before FMT and 8 weeks after FMT to evaluate for the presence small intestinal bacterial overgrowth (SIBO). Results FMT significantly alleviated bloating symptoms, and symptoms of pain were relieved 2 weeks after FMT. Enteral nutrition administered through a NJ tube after FMT was well-tolerated by 66.7% (6/9) of patients. CT scores of intestinal obstructions were significantly reduced after FMT (P = 0.014). SIBO was eliminated in 71.0% (5/7) of patients. Conclusions This pilot study demonstrated the safety of using FMT. FMT may relieve symptoms in selected patients with CIPO. FMT may also improve patient tolerance of enteral nutrition delivered via a NJ tube. PMID:27840368
Billiard, M; Merle, C; Carlander, B; Ondze, B; Alvarez, D; Besset, A
Identification of idiopathic hypersomnia dates back 20 years only. It typically consists of prolonged nocturnal sleep, great difficulty waking up in the morning or at the end of a nap, and constant or recurrent excessive daytime sleepiness. Complete and incomplete forms are encountered. Twenty-three subjects fulfilling ICSD criteria are reported with clinical, polysomnographic and immunogenetic data. Considering differential diagnosis is an important step in the diagnosis of idiopathic hypersomnia. Idiopathic hypersomnia is much less frequent than narcolepsy. A strong genetic component is suggested by the high proportion of familial cases. No association with HLA has been evidenced to date.
Giovanelli, M; Gupte, G L; Sharif, K; Mayer, D A; Mirza, D F
An 11-year-old boy with irreversible intestinal failure secondary to chronic intestinal pseudo-obstruction (CIPO) and intestinal failure-associated liver disease (IFALD) underwent a combined en bloc reduced liver and small bowel transplantation. He was discharged home after 9 weeks on full oral intake without requiring intravenous nutritional or fluid supplementation. The first episode of mild acute rejection, which occurred 18 months after transplantation, was successfully treated with steroids. An episode of rotavirus gastroenteritis led to severe exfoliative rejection of the bowel graft, which was resistant to steroid and Infliximab treatment but responded to OKT3. There was associated Epstein-Barr virus viremia with no evidence of posttransplant lymphoproliferative disease. Another episode of moderate to severe acute liver rejection occurred 5 months later. At the same time, multiple biliary strictures were diagnosed and treated. Persistent clinical symptoms of abdominal pain and increased stomal output as well as atrophy of the ileal mucosa on several biopsies, suggested the possibility of chronic rejection (CR). A second combined whole liver and small bowel transplant was performed. The diagnosis of CR was confirmed on histology of the explanted graft. The postoperative course was severely complicated and 71 days after the retransplantation, the boy died because of respiratory failure and multiorgan failure. In summary, intestinal transplantation can be successfully performed in children with CIPO, giving them the opportunity to be free from total parenteral nutrition. As survival following intestinal transplantation continues to improve, the problem of CR has become increasingly important and the only treatment available is retransplantation, which is associated with poor outcomes.
von Knorring, L; Ekselius, L
This report summarizes research on the hypothesis that idiopathic chronic pain syndromes and depressive disorders share certain common pathogenetic mechanisms. There is increasing evidence that this may be partly true. Not only do chronic pain syndromes respond to treatment with antidepressants, but there are also striking clinical similarities between these syndromes and depressive syndromes. However, important differences do exist (e.g., the courses of these disorders are usually dissimilar). Family studies show that affective disorders are common in first-degree relatives of patients with idiopathic pain syndromes, but it is impossible to conclude from this that clear-cut genetic factors are of importance. Factors common to both syndromes include common personality traits, shortened rapid eye movements in sleep EEG, hypercortisolaemia and pathological dexamethasone suppression tests, low levels of melatonin in serum and urine and high levels of endorphins and Fraction I in cerebro-spinal fluid. One important common pathogenetic mechanism seems to be disturbances in the serotoninergic system.
Avanthi, Steffie Urmila; Ravi Kanth, Vishnubhotla Venkata; Agarwal, Jaya; Lakhtakia, Sundeep; Gangineni, Karthik; Rao, Guduru Venkat; Reddy, Duvurr Nageshwar; Talukdar, Rupjyoti
Gene polymorphisms, including those recently described in the claudin2 gene, have been implicated in recurrent acute (RAP) and chronic pancreatitis (CP). In India, RAP and CP have been associated with SPINK1 polymorphism. In this study, we evaluated the association of claudin2 and PRSS1-PRSS2 polymorphisms with idiopathic RAP and CP. We included 101 prospectively followed patients with documented idiopathic RAP (IRAP) and 96 patients who presented with idiopathic chronic pancreatitis (ICP) without previous history of AP. Controls were 156 unrelated individuals undergoing master health check or with non-specific symptoms. All the samples were genotyped for the SNPs rs7057398 in the claudin2 (CLDN2) gene and rs10273639 in the PRSS1 gene on Realtime polymerase chain reaction platform. Clinical data pertaining to patient and disease characteristics were recorded. Claudin2 and PRSS1 polymorphisms were seen in a significantly higher proportion of female patients (P = 0.01 and 0.039, respectively). Thirty-three (32.7%) patients with IRAP developed features of early CP during follow-up (mean [95% confidence interval, CI] duration of 11.3 [8.9-13.7] months). Female patients with claudin2 (rs7057398) CC genotype were at significantly higher risk for IRAP (odds ratio [OR] [95% CI] 6.75 [1.82-23.67]; P = 0.004) and progression from IRAP to CP (OR [95% CI] 7.05 [1.51-33.01]; P = 0.007). CT genotype of PRSS1 (rs10273639) was associated IRAP (OR [95% CI] 2.59 [1.1-6.13]; P = 0.030), and both CT and CC genotypes with ICP in women (OR [95% CI] 2.86 [1.12-7.31]; P = 0.033 and 3.73 [1.03-13.59]; P = 0.048, respectively). In this study, we have demonstrated the association of claudin2 (rs7057398) polymorphism with IRAP and progression of IRAP to CP, and PRSS1 (rs10273639) polymorphism with IRAP and ICP. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Yeh, Ming-Han; Chang, Ya-Hui; Tsai, Yi-Chih; Chen, Su-Liang; Huang, Tze-Sing; Chiu, Jeng-Fong; Ch'ang, Hui-Ju
Bone marrow-derived cells (BMDC) have been demonstrated to play a critical role in intestine regeneration. However, organ fibrosis was one of the major side effects of bone marrow (BM) transplantation. It warrants further investigation on the mechanisms of BM cell therapy in radiation induced intestine damage. We established three murine models to evaluate BMDC within intestines after radiation, including cre-loxP system of transgenic mice. In vitro co-culture between murine BM with human intestine stromal cells was also performed to measure the level of fusion and fibrosis after treatment with anti-fibrotic agents or after macrophage depletion. Despite complete recovery of epithelial mucosa from radiation damage, we found persistent proliferation and repopulation of BMDC within the lamina propria. Fusion between BM derived monocytic and intestine stromal cells correlated with the level of fibrosis and proliferation index. Depleting macrophages genetically using CD11b-DTR mouse model or pharmacologically using clodronate liposome reduced the level of cell fusion and intestine fibrosis. Fibrotic cues from intestine enhance fusion between BM-derived monocytes/macrophages with intestine stromal cells. The fusion hybrids promote cell cycle re-entry, proliferation and reinforce fibrosis signal. Depleting macrophages interferes with cell fusion and ameliorates radiation-induced intestine fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Yaman, Onur; Dalbayrak, Sedat
Scoliosis refers to curves exceeding 10 degrees observed through posterioanterior direct radiography. In fact, the diagnosis for idiopathic scoliosis is accepted to exclude already available causes. The aim of this paper was to review the etiopathogenesis, classification systems and the treatment management of idiopathic scoliosis. A search in the National Library of Medicine (Pubmed) database using the key words 'idiopathic' and 'scoliosis' was performed. For the literature review, papers concerning the etiopathogenesis, classification and treatment were selected among these articles. A search in the National Library of Medicine (Pubmed) database using the key words 'idiopathic' and 'scoliosis' yielded 4518 articles published between 1947 and 2013. The main hypothesis put forward included genetic factors, hormonal factors, bone and connective tissue anomalies. King, Lenke, Coonrad and Peking Union Medical College (PUMC) classifications were the main classification systems for idiopathic scoliosis. Exercise, bracing and anterior, posterior or combined surgery when indicated are the choices for the treatment. Every idiopathic scoliosis case has to be managed to its own characteristics. It is the post-operative appearance that the surgeons are perhaps the least interested but the adolescent patients the most interested in. The aim of scoliosis surgery is to restore the spine without neurological deficit.
Sheedy, John R; Wettenhall, Richard E H; Scanlon, Denis; Gooley, Paul R; Lewis, Donald P; McGregor, Neil; Stapleton, David I; Butt, Henry L; DE Meirleir, Kenny L
Patients with chronic fatigue syndrome (CFS) are affected by symptoms of cognitive dysfunction and neurological impairment, the cause of which has yet to be elucidated. However, these symptoms are strikingly similar to those of patients presented with D-lactic acidosis. A significant increase of Gram positive facultative anaerobic faecal microorganisms in 108 CFS patients as compared to 177 control subjects (p<0.01) is presented in this report. The viable count of D-lactic acid producing Enterococcus and Streptococcus spp. in the faecal samples from the CFS group (3.5 x 10(7) cfu/L and 9.8 x 10(7) cfu/L respectively) were significantly higher than those for the control group (5.0 x 10(6) cfu/L and 8.9 x 10(4) cfu/L respectively). Analysis of exometabolic profiles of Enterococcus faecalis and Streptococcus sanguinis, representatives of Enterococcus and Streptococcus spp. respectively, by NMR and HPLC showed that these organisms produced significantly more lactic acid (p<0.01) from (13)C-labeled glucose, than the Gram negative Escherichia coli. Further, both E. faecalis and S. sanguinis secrete more D-lactic acid than E. coli. This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptom expressions in a subgroup of patients with CFS. Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications.
Cortés, Alba; Muñoz-Antoli, Carla; Martín-Grau, Carla; Esteban, J Guillermo; Grencis, Richard K; Toledo, Rafael
The intestinal epithelium plays a multifactorial role in mucosal defense. In this sense, augmented epithelial cell turnover appears as a potential effector mechanism for the rejection of intestinal-dwelling helminths. A BrdU pulse-chase experiment was conducted to investigate the infection-induced alterations on epithelial cell kinetics in hosts of high (mouse) and low (rat) compatibility with the intestinal trematode Echinostoma caproni. High levels of crypt-cell proliferation and tissue hyperplasia were observed in the ileum of infected mice, coinciding with the establishment of chronic infections. In contrast, the cell migration rate was about two times higher in the ileum of infected rats compared with controls, with no changes in tissue structure, indicating that an accelerated cell turnover is associated with worm expulsion. Our results indicate that E. caproni infection induces a rapid renewal of the intestinal epithelium in the low compatible host that may impair the establishment of proper, stable host-parasite interactions, facilitating worm clearance.
Pironi, L; Spinucci, G; Paganelli, F; Merli, C; Masetti, M; Miglioli, M; Pinna, A D
In 2002, the Italian guidelines for eligibility of patients for intestinal transplantation (ITx) were defined as: life-threatening complications of home parenteral nutrition (HPN), lack of venous access for HPN, locally invasive tumors of the abdomen, Chronic intestinal failure (CIF) with a high risk of mortality, primary disease-related poor quality of life (QoL) despite optimal HPN. Our aim was to identify potential candidates for ITx according to these national guidelines among patients managed by a medical referral center for CIF. Records of patients who received HPN were reviewed. CIF was considered reversible or irreversible (energy by HPN <50% or >50% basal energy expenditure). Patients with irreversible CIF were considered eligible for ITx in the absence of a contraindication, as are used for solid organs Tx. From 1986 to 2003 among 64 patients who met the entry criteria 23 showed reversible and 41 irreversible, CIF. Twenty-one patients with irreversible CIF had an indication for ITx, but eight had also contraindications; thus 13 were eligible, including intestinal pseudo-obstruction (n = 6), mesenteric ischemia (n = 3), Crohn's (n = 2), radiation enteritis (n = 1), and desmoid (n = 1). Indications for ITx included HPN liver failure (n = 2), lack of venous access (n = 2), CIF with high risk of mortality (n = 3), very poor QoL (n = 6 including 5 with pseudo-obstruction). According to the Italian guidelines for ITx, 31% of patients with irreversible CIF managed by a medical referral center were eligible for ITx. Primary disease-related poor QoL was the indication in half of them. Studies on the QoL after ITx are required to allow patients to make an educated decision.
Raymond, Arthur; Mercade-Loubière, Myriam; Salvador-Cartier, Christel; Ringot, Bélinda; Léonard, Renaud; Fourquaux, Isabelle; Ait-Belgnaoui, Afifa; Loubière, Pascal; Théodorou, Vassilia; Mercier-Bonin, Muriel
The present study aimed at detecting the exogenously applied probiotic Lactobacillus farciminis in rats, after exposure to IBS-like chronic stress, based on 4-day Water Avoidance Stress (WAS). The presence of L. farciminis in both ileal and colonic mucosal tissues was demonstrated by FISH and qPCR, with ileum as the preferential niche, as for the SFB population. A different spatial distribution of the probiotic was observed: in the ileum, bacteria were organized in micro-colonies more or less close to the epithelium whereas, in the colon, they were mainly visualized far away from the epithelium. When rats were submitted to WAS, the L. farciminis population substantially decreased in both intestinal regions, due to a stress-induced increase in colonic motility and defecation, rather than a modification of bacterial binding to the intestinal mucin Muc2. PMID:26367538
Dreyfus, D H
Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU.
Mueller, Tobias; Beutler, Claudia; Picó, Almudena Hurtado; Shibolet, Oren; Pratt, Daniel S; Pascher, Andreas; Neuhaus, Peter; Wiedenmann, Bertram; Berg, Thomas; Podolsky, Daniel K
Pattern recognition receptors (PRRs) orchestrate the innate immune defence in human biliary epithelial cells (BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs. We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis (PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT-PCR, Western blots and immunocytochemistry. Functional studies comprised immuno-precipitation Western blots, FACS for endotoxin uptake, and NF-κB activation assays and ELISA for secreted IL-8 and tumour necrosis factor (TNF)-α. Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-γ and TNF-α in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-α inhibition partly restored protective innate immune tolerance, endogenous TNF-α secretion probably contributed to inappropriate endotoxin responses in BECs. Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis. © 2011 John Wiley & Sons A/S.
Elriz, K; Palascak-Juif, V; Joly, F; Seguy, D; Beau, P; Chambrier, C; Boncompain, M; Fontaine, E; Laharie, D; Savoye, G; Lerebours, E
Chronic intestinal failure (CIF) is a very rare Crohn's disease (CD) complication. To determine incidence of CIF treated with home parenteral nutrition (HPN) in adult CD patients and to isolate factors associated with severe CIF. This retrospective multicentre study included 38 patients with CD-related CIF treated with HPN for at least 12 months in French HPN centres. Severe CIF was defined by a length of remnant small bowel of less than 100 cm or CIF occurrence within the 15 years following CD diagnosis. Median delay between CD diagnosis and CIF was 15 years. CIF incidence did not decrease over time (1.4/year before 1995 vs. 2.2/year after). Median number of small bowel resections per patient was three (range 1-8). Median small bowel resection, remnant and initial lengths were 160, 80 and 260 cm, respectively. Twenty-four per cent of patients developed stenosis within 1 year after CD diagnosis and 76% developed perforative complications within 2 years. In multivariate analysis, severe CIF, defined as CIF onset <15 years after CD diagnosis, was associated with a more recent CD diagnosis (odds ratio, 0.785; 95% confidence interval, 0.623-0.989). CIF occurred despite frequent use of immunosuppressants. Course of CD remained severe during HPN: immunosuppressants prescription occurred in 11 patients, surgery in six. Six patients died from CD (n = 2), HPN complications (n = 2) or other causes (n = 2). Chronic intestinal failure requiring HPN is rare during CD. Incidence remained stable over time. Surgical procedures play a minor role in the occurrence of severe chronic intestinal failure compared to CD severity. © 2011 Blackwell Publishing Ltd.
Idiopathic hypersomnia is not as well delineated as narcolepsy and its history is much more recent. There are at least two forms of the disorder: (1) a polysymptomatic form, characterized by excessive daytime sleepiness, nocturnal sleep of abnormally long duration, and signs of sleep drunkenness on awakening, and (2) a monosymptomatic form that manifests only by excessive daytime sleepiness. The most widely used laboratory procedures are nocturnal polysomnographic recording following by an MSLT demonstrating a mean sleep latency of less than 10 minutes. At least in the polysymptomatic form, however, continuous polysomnography on an ad lib protocol deserves to be performed to catch the abnormally long major sleep episode and the long unrefreshing naps. Idiopathic hypersomnia is probably one of the most overdiagnosed sleep disorders. Several other disorders must be excluded before the diagnosis can be considered conclusive. Treatment of idiopathic hypersomnia relies on stimulants, which are frequently less effective and less well tolerated than in narcolepsy.
Yamada, Chiho; Sasaki, Noriko; Kurabayashi, Takayoshi; Sasaki, Sho; Koyama, Yasushi; Wakabayashi, Takayuki; Suzuki, Yasuo
Chronic intestinal pseudoobstruction (CIPO) is a serious complication in patients with connective tissue disease (CTD) and is sometimes life-threatening or fatal despite intensive medical treatment. Here, we report a patient with dermatomyositis (DM) and anti-EJ autoantibody who developed CIPO that was improved by octreotide. Because her abdominal pain and bloatedness were so severe and persistent, we introduced octreotide to relieve symptoms. In this case, continuous intravenous administration as well as long-acting subcutaneous injection of octreotide was effective for treating CIPO. PMID:27885350
Nunokawa, Takahiro; Yokogawa, Naoto; Ohtsuka, Hideo; Shimada, Kota; Sugii, Shoji
Medical management of systemic sclerosis (SSc)-associated chronic intestinal pseudo- obstruction (CIPO) has often proved inadequate. Percutaneous endoscopic colostomy (PEC) has been proposed as a method of treatment, but it is associated with a relatively high incidence of serious complications. We report herein a very severe case of SSc-associated CIPO in which complications were successfully controlled by long tube placement via a gastrostomy. Transgastric long tube placement may offer a relatively safe alternative to PEC in treating severe SSc-associated CIPO.
Caio, Giacomo; Volta, Umberto; Cerrato, Enrico; Clavenzani, Paolo; Montali, Nicolò; Cogliandro, Rosanna; Stanghellini, Vincenzo; Golzio, Pier Giorgio; Gaita, Fiorenzo; Farrugia, Gianrico; De Giorgio, Roberto
A 26-year-old patient was diagnosed as having chronic intestinal pseudo-obstruction with manometric and histopathologic features suggestive of an intestinal myopathy. Histology was characterized by smooth muscle degeneration without inflammatory or immune cells. The severe gut dysfunction required full parenteral nutritional support. After a few months, the patient developed symptomatic tachy-brady arrhythmia episodes with syncopes. A thorough diagnostic work-up led to a diagnosis of sick sinus syndrome, which was managed by pacemaker implantation and administration of β-blockers. This led to a partial improvement in tachy-brady arrhythmia episodes. Nonetheless, the patient continued to experience sustained supraventricular tachyarrhythmia runs, poorly responsive to increasing β-blocker doses. To investigate the origin of the cardiologic impairment, the patient was tested for anticonductive tissue autoantibodies, which were positive, thus supporting a possible autoimmune origin of the dysrhythmia. Other autoantibodies were negative. On the basis of these findings, the patient was treated with high-dose steroids, which were then tapered. The patient responded to the steroid treatment and did not experience further episodes of syncope and tachyarrhythmias. The severe gut dysfunction remained unchanged. This case highlights an association between severe gut dysfunction and cardiac conductive tissue abnormalities, with autoantibodies to conductive tissue possibly causing the dysrhythmia. The severe gut and heart (likely autoimmune-mediated) dysfunction presented in this case provides a basis to further assess a link between intestinal and cardiac abnormal rhythmicity.
Amiot, A; Joly, F; Messing, B; Sokol, H; Lavergne-Slove, A; Delattre, J-Y; Bouhnik, Y
Chronic intestinal pseudo-obstruction (CIPO) is a heterogeneous group of rare disorders characterised by symptoms of intestinal obstruction with no mechanical evidence of obstruction. It is caused by ineffective intestinal contractions due to visceral neuropathy and/or neuropathy. In adults, CIPO is mostly secondary. The most common causes are metabolic disorders, connective tissue disorders, neuropathic drug related injuries, paraneoplasic and post-infectious syndromes and amyloidosis. Secondary forms of CIPO have been reported with anti-Hu antibodies. This corresponds to an antineuronal antibody that recognizes a protein expressed in the nuclei of neuron (ANNA-1) and neoplasic cells. The anti-Hu antibody must be searched for in patients over 40 years old with CIPO (associated with small cell lung cancer in 75% of cases). Recently, the association of CIPO and the anti-Hu antibody has been described without associated neoplasia. We report a case of an association of CIPO and anti-Hu antibody without cancer after 13 years of follow-up.
Molina-Infante, Javier; Mateos-Rodriguez, Jose M; Vinagre-Rodriguez, Gema; Martin-Noguerol, Elisa; Santiago, Jesus M Gonzalez
Percutaneous endoscopic colostomy (PEC), using the classic pull-through technique in the ascending or the descending colon, has been proven useful to treat chronic intestinal pseudo-obstruction. We report the case of a high-surgical risk 70-year-old male with refractory chronic intestinal pseudo-obstruction, in whom the ascending colon could not be reached due to tortuous left dolichocolon. Endoscopic-assisted colopexy and push colostomy in the proximal transverse colon was decided accordingly. Colopexy was performed under direct endoscopic vision in the proximal transverse colon using 3 preloaded T-fasteners surrounding the intended stoma site. The stoma tract was created with an introducer needle, allowing the advance of the 24 Fr 4-sleeve dilator over a guidewire. Afterwards, the dilator was removed and the peel-away sheath was left in place. Over the guidewire, a 20-Fr gastrostomy tube was advanced into the colon lumen through the covering, which was finally removed. The patient recovered uneventfully, despite postprocedure pneumoperitoneum, which was related to the technique. He died a month later due to unrelated comorbidities, without further abdominal complaints after discharge. This is the first report of PEC both using a push technique, and the first report in a different location than the ascending or the descending colon. We believe this novel push technique may be feasible for PEC, avoiding the need of reinsertion in patients with difficult colonoscopy.
Chamanara, Elham; Raeeskarami, Seyed-Reza
Children with juvenile idiopathic arthritis (JIA) are prone to the problems that can delay their psychosocial development; however, the existing literature has not reached a consensus on the psychological problems related to JIA. A total of 51 children and adolescents with JIA and 75 healthy controls aged 6 to 18 years were examined using the Child Behavioral Checklist (CBCL). Our results represented that 70 percent of JIA group reached “borderline clinical” range or “clinical” range in internalizing problems, while this percentage in the control group was 18 percent. In addition, our results indicated that JIA group has gotten significantly higher scores (more than twofold) in externalizing behaviors compared to control group. Furthermore, children with JIA showed higher rate of anxiety/depression, withdrawal/depression, somatic complaints, rule breaking behaviors, and aggressive behaviors as well as thought and social problems compared to control group (p < 0.001). As a conclusion, children and adolescents with JIA compared to healthy controls may show higher rate of both internalizing and externalizing problems. Furthermore, our novel findings on externalizing, social, and thought problems in JIA warrant further investigation on affected children who may be at greater risk of future psychopathologies. PMID:27656678
Lissner, Donata; Schumann, Michael; Batra, Arvind; Kredel, Lea-Isabel; Kühl, Anja A; Erben, Ulrike; May, Claudia; Schulzke, Jörg-Dieter; Siegmund, Britta
Macrophages are key players in inflammatory bowel diseases (IBD). This study aimed to determine site-specific effects of defined macrophage subtypes on the integrity of the intestinal epithelial barrier. Macrophage subtypes in situ in intestinal specimens of patients with IBD were visualized by immunohistochemistry. In vitro polarization of human peripheral CD14 cells yielded M1 or M2 macrophages. The influence of primary monocytes or macrophage subtypes on epithelial barrier integrity was analyzed by transepithelial resistance measurements, Western blot analysis, confocal laser scanning microscopy, and cytometric bead array in a coculture model of primary human macrophages and layers of intestinal epithelial cell lines. The lamina propria of the inflamed intestine in patients with IBD, predominantly in Crohn's disease, is massively infiltrated by CD68 cells also positive for inducible nitric oxide synthase and tumor necrosis factor (TNF) α. The presence of M1 macrophage shifted the balance in the local macrophage compartment towards a proinflammatory state. In the coculture model, monocytes and M1 macrophages reduced transepithelial resistance as a marker for epithelial barrier integrity. The mechanisms for paracellular leakage included intracellular relocalization of tight junction proteins like claudin-2 and epithelial cell apoptosis. Determined by specific cytokine blockade, M1 macrophages exerted their deleterious effect mainly through TNF-α, whereas monocyte-mediated damage was driven by the inflammasome effector cytokines, interleukin-1β and interleukin-18. Lamina propria monocytes and M1 macrophages invading intestinal tissues directly contribute to disrupting the epithelial barrier through deregulation of tight junction proteins and induction of epithelial cell apoptosis, thus driving intestinal inflammation in IBD.
Lissner, Donata; Schumann, Michael; Batra, Arvind; Kredel, Lea-Isabel; Kühl, Anja A.; Erben, Ulrike; May, Claudia; Schulzke, Jörg-Dieter
Background: Macrophages are key players in inflammatory bowel diseases (IBD). This study aimed to determine site-specific effects of defined macrophage subtypes on the integrity of the intestinal epithelial barrier. Methods: Macrophage subtypes in situ in intestinal specimens of patients with IBD were visualized by immunohistochemistry. In vitro polarization of human peripheral CD14+ cells yielded M1 or M2 macrophages. The influence of primary monocytes or macrophage subtypes on epithelial barrier integrity was analyzed by transepithelial resistance measurements, Western blot analysis, confocal laser scanning microscopy, and cytometric bead array in a coculture model of primary human macrophages and layers of intestinal epithelial cell lines. Results: The lamina propria of the inflamed intestine in patients with IBD, predominantly in Crohn's disease, is massively infiltrated by CD68+ cells also positive for inducible nitric oxide synthase and tumor necrosis factor (TNF) α. The presence of M1 macrophage shifted the balance in the local macrophage compartment towards a proinflammatory state. In the coculture model, monocytes and M1 macrophages reduced transepithelial resistance as a marker for epithelial barrier integrity. The mechanisms for paracellular leakage included intracellular relocalization of tight junction proteins like claudin-2 and epithelial cell apoptosis. Determined by specific cytokine blockade, M1 macrophages exerted their deleterious effect mainly through TNF-α, whereas monocyte-mediated damage was driven by the inflammasome effector cytokines, interleukin-1β and interleukin-18. Conclusions: Lamina propria monocytes and M1 macrophages invading intestinal tissues directly contribute to disrupting the epithelial barrier through deregulation of tight junction proteins and induction of epithelial cell apoptosis, thus driving intestinal inflammation in IBD. PMID:25901973
Takahashi, Toru; Yujiri, Toshiaki; Shinohara, Kenji; Inoue, Yusuke; Sato, Yutaka; Fujii, Yasuhiko; Okubo, Masashi; Zaitsu, Yuzuru; Ariyoshi, Koichi; Nakamura, Yukinori; Nawata, Ryouhei; Oka, Yoshitomo; Shirai, Mutsunori; Tanizawa, Yukio
The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori-positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet-associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori-positive and three H. pylori-negative) patients recognized H. pylori cytotoxin-associated gene A (CagA) protein, and in three completely responsive patients, levels of anti-CagA antibody in platelet eluates declined after eradication therapy. Cross-reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.
Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents.
Tse, Yvonne; Armstrong, David; Andrews, Christopher N; Bitton, Alain; Bressler, Brian; Marshall, John; Liu, Louis W C
Background. Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common functional lower gastrointestinal disorders that impair patients' quality of life. In a national survey, we aimed to evaluate (1) Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2) physicians satisfaction with these agents for their CIC and IBS-C patients; and (3) the usefulness of these new guidelines in their clinical practice. Methods. A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results. The response rate to the survey was 16% (n = 55). Almost all (96%) respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion. Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada.
Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents
Tse, Yvonne; Andrews, Christopher N.; Bitton, Alain
Background. Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common functional lower gastrointestinal disorders that impair patients' quality of life. In a national survey, we aimed to evaluate (1) Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2) physicians satisfaction with these agents for their CIC and IBS-C patients; and (3) the usefulness of these new guidelines in their clinical practice. Methods. A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results. The response rate to the survey was 16% (n = 55). Almost all (96%) respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion. Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada. PMID:28271055
Mešanović, S.; Šahović, H.; Perić, M.
The myeloproliferative diseases (MPDs) or myelo-proliferative neoplasms (MPNs) are a group of diseases of the bone marrow in which excess cells are produced. Chronic idiopathic myelofibrosis (CIMF) is a stem cell defect characterized by splenomegaly with multiorgan extramedullary hematopoiesis, immature peripheral blood granulocytes and erythrocytes and progressive bone marrow fibrosis. The most common chromosomal abnormalities seen in CIMF patients include numerical changes of chromosomes 7, 8 and 9, and structural changes of 1q, 5q, 13q and 20q. At least 75.0% of patients with bone marrow abnormalities have one or more of these chromosomal anomalies. Detection of the Janus kinase 2 (JAK2) mutation may be a potential major breakthrough for understanding the pathobiology of MPNs, and is an essential part of the diagnostic algorithm. In this study, we describe a JAK2V617F mutation negative CIMF patient who has the chromosomal translocation t(3;12)(q26;q21) in her karyotype. PMID:25741217
Hachulla, E; Benveniste, O; Hamidou, M; Mouthon, L; Schleinitz, N; Lozeron, P; Léger, J M; Vial, C; Viala, K
In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg.
Bech, Per; Lunde, Marianne; Møller, Stine Bjerrum
Aim. The clinimetric aspects of Eysenck's two big personality factors (neuroticism and extraversion) were originally identified by principal component analysis but have been insufficiently analysed with item response theory models. Their relationship to states of melancholia and anxiety was subsequently analysed. Method. Patients with chronic idiopathic pain disorder were included in the study. The nonparametric item response model (Mokken) was compared to the coefficient alpha to validate the anxiety and depression subscales within the neuroticism scale and the extraversion and introversion subscales within the extraversion scale. When measuring states of depression and anxiety, the Melancholia Scale and the Hamilton Anxiety Scale were used. Results. We identified acceptable subscales of anxiety and depression in the Eysenck factor of neuroticism and extraversion versus introversion subscales within the Eysenck factor of extraversion. Focusing on the item of "Does your mood often go up and down?" we showed a statistically significant association with melancholia and anxiety for patients with a positive score on this item. Conclusion. Within the Eysenck factor of neuroticism it is important to differentiate between the anxiety and depression subscales. The clinimetric analysis of the Eysenck factor of extraversion identified valid subscales.
Takei, Reoto; Arita, Machiko; Kumagai, Shogo; Ito, Yuhei; Noyama, Maki; Tokioka, Fumiaki; Ishida, Tadashi
Chronic fibrosing idiopathic interstitial pneumonia (CFIIP) has a potential risk of acute exacerbation (AE). However, the usefulness of cellular analysis of bronchoalveolar lavage fluid (BALF) has never been evaluated. This study aimed to evaluate the impact of the lymphocyte differential count > 15% in BALF on the mortality of patients with AE of CFIIP. We retrospectively analysed 37 patients with AE of CFIIP who underwent BAL on admission. Patients were divided into two groups: one group consisting of those with a lymphocyte differential count > 15% and the other consisting of those with a lymphocyte differential count ≤ 15%. We compared the 90-day mortality between the two groups as the primary outcome, using the two-tailed log-rank test. The median follow-up duration was 6.9 months. Twenty-four patients had a lymphocyte differential count > 15%. The 90-day mortality was significantly higher in the group with a lymphocyte differential count ≤ 15% than in the group with a lymphocyte differential count > 15% (long rank test, p = 0.003). In the multivariate analysis a lymphocyte differential count > 15% was shown to be an independent favourable prognostic factor for 90-day mortality (HR: 0.125; 95% CI: 0.0247-0.589; p = 0.009). A lymphocyte differential count > 15% in BALF may be associated with favourable outcomes in patients with AE of CFIIP.
... for You Healthy School Lunch Planner Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic Arthritis (JIA) ... people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people as much ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic ... can affect people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people ...
Ring, J; Hein, R; Gauger, A; Bronsky, E; Miller, B
Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12-79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained
Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao
Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis. PMID:25574083
Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao
Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.
Romanenko, E G
Study of the immune system mechanisms in chronic catarrhal gingivitis in children with gastrointestinal pathology was performed in 102 children (49 with chronic gastritis and duodenitis and 53 with no signs of gastrointestinal pathology). Forty-eight children with healthy periodontium constituted control group. Generalized chronic catarrhal gingivitis in children with gastroduodenal pathology is characterized by intense humoral response by simultaneous T-cell immunity suppression. Detection of high serum titers of circulating immune complexes in patients with chronic catarrhal gingivitis suggests a role of immune response in the pathogenesis of periodontal disease increases with concomitant diseases of the upper gastrointestinal tract.
Кhуzhnyak, S V; Bezdrobna, L K; Stepanova, L I; Morozova, V S; Voitsitskіy, V M
Objective - to investigate the intensity of oxidation and phosphorylation processes in the small intestine enterocytes mitochondria of the rats under chronic and single exposure to ionizing radiation of low power. Materials and methods. The single irradiation of the rats with X-rays was performed using the RUM-17 equipment (at the dose of 0.055 Gy/min) for absorbed doses of 0.1; 0.5 and 1.0 Gy. The functional state of mitochondria was evaluated in 1 h and 24 h after irradiation. The chronic external γ-irradiation (at the dose rate of 0.72 cGy/min to achieve a total dose of 0.3; 0.6 and 1.0 Gy was performed using the "Etalon" equipment which contained 60Co. The intensity of the oxidation and phosphorylation activity of the small intestine enterocytes mitochondria was assessed by the polarographic method. Results. The use of malate as exogenous substrate allowed to assess the functioning of all areas of the electron transport chain of mitochondria in experimental conditions. The increase in the intensity of mitochondrial respiration was found in all conditions and terms of research in response to irradiation. In chronic ionizing radiation appears partial separation of interface processes of oxidation and phosphorylation, as evidenced by the decrease in value of the index control and ADP / O and reducing efficiency phosphorylation (decrease of value Vf). For single exposure disconnection of coupling processes oxidation and phosphorylation were not accompanied by changes in the index of oxidative phosphorylation, however, was characterized by reduced ratio V4S/V4АТP. Conclusions. Single and chronic exposure to low power of ionizing radiation leads to an increase in intensity of respiration and disruption of oxidative phosphorylation as a result of separation of interface processes of oxidation and phosphorylation. In chronic exposure received changes were accompanied by inhibition of ATP from ADP and FN because no change of ATP hydrolase activity of mitochondria was
Al-Mayouf, Sulaiman M; Naji, Hamzah; Alismail, Khalid; Alazami, Anas M; Sheikh, Farrukh; Conca, Walter; Al-Mousa, Hamoud
Lipopolysaccharide-responsive, beige-like anchor protein (LRBA) deficiency causes common variable immunodeficiency (CVID) disorders and autoimmunity. LRBA deficiency has become a clinically variable syndrome with a wide spectrum of clinical manifestations. We report a patient with LRBA deficiency associated chronic non-erosive arthritis. This report highlights the spectrum of arthritis in such patients and the potential causative role of LRBA gene in juvenile arthritis.
Carreras, O; Vazquez, A L; Rubio, J M; Delgado, M J; Murillo, M L
The in vivo absorption of D-galactose by rat whole intestinal surface after 4 weeks of 30% ethanol ingestion in drinking water has been studied, and the results were compared with ad lib-fed control rats. The total serosal intestinal area was determined by integration obtaining similar values between control and alcohol-treated groups. In the caecum surface of ethanol-fed rats slight but not significant increases were found, while the jejunum area decreased with respect to control rats. Total galactose absorption during 10 min of perfusion was slightly increased in ethanol-fed rats but these results were not significant with the substrate concentrations tested. When absorption data were referred to serosal surface, the absorption/cm2 values in ethanol-fed rats were increased at the studied galactose concentrations although these results were only statistically significant at 10 mM. In conclusion, the present data indicates a slight increase in D-galactose absorptive capacity by the whole intestine in ethanol-fed rats which suggest that the tissue traditionally not evaluated such as caecum and colon could modify the functional response to the absorption nutrients.
Stern, M.; Carter, E.A.; Walker, W.A.
The effects of ethanol exposure on small intestinal handling and uptake of radiolabeled bovine serum albumin were investigated using everted gut sacs. There was less breakdown of BSA after acute ethanol administration in vitro and after acute and chronic in vivo exposure. Thus, the vascular compartment of the small intestine was confronted with more complete and potentially more antigenic material after ethanol. Changes in BSA binding and uptake after acute exposure were shown to be reversible after 4-6 hr. In all groups, there was more BSA binding when the small intestine was exposed to ethanol. This difference was most pronounced after chronic exposure. In the same group, uptake of BSA was correlated with binding and significantly increased. Combined effects of ethanol on the gut mucosal barrier may account for changes in food antigen handling and uptake.
Georgescu, Eugen Florin; Vasile, Ion; Ionescu, Reanina
Intestinal pseudo-obstruction (IPO) either acute or chronic is a condition including features of intestinal ileus in absence of mechanical obstruction. Our paper presents such a rare case of idiopathic IPO in a 53-year-old male patient with recurrent episodes of pseudo-obstruction, which were successfully resolved by anticholinesterase agents, motilin agonists or colonic decompression. However, the patient finally underwent total colectomy. Huge colonic dilatation was identified intraoperatively, while histology showed a neuropathic variant of chronic intestinal pseudo-obstruction. Etiologic mechanisms and current therapeutic methods are reviewed in this paper, which concludes that IPO is a condition in which conservative treatment usually fails. Total colectomy with ileoanal pouch may be the only solution in these situations. PMID:18240359
Pastorelli, Luca; De Salvo, Carlo; Mercado, Joseph R.; Vecchi, Maurizio; Pizarro, Theresa T.
The gut mucosa is constantly challenged by a bombardment of foreign antigens and environmental microorganisms. As such, the precise regulation of the intestinal barrier allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation. In support of this concept, emerging evidence points to defects in components of the epithelial barrier as etiologic factors in the pathogenesis of inflammatory bowel diseases (IBDs). In fact, the integrity of the intestinal barrier relies on different elements, including robust innate immune responses, epithelial paracellular permeability, epithelial cell integrity, as well as the production of mucus. The purpose of this review is to systematically evaluate how alterations in the aforementioned epithelial components can lead to the disruption of intestinal immune homeostasis, and subsequent inflammation. In this regard, the wealth of data from mouse models of intestinal inflammation and human genetics are pivotal in understanding pathogenic pathways, for example, that are initiated from the specific loss of function of a single protein leading to the onset of intestinal disease. On the other hand, several recently proposed therapeutic approaches to treat human IBD are targeted at enhancing different elements of gut barrier function, further supporting a primary role of the epithelium in the pathogenesis of chronic intestinal inflammation and emphasizing the importance of maintaining a healthy and effective intestinal barrier. PMID:24062746
Shaw, Elisabeth J; Smith, Emily E; Whittingham-Dowd, Jayde; Hodges, Matthew D; Else, Kathryn J; Rigby, Rachael J
Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor, limiting intestinal epithelial cell (IEC) proliferation in acute inflammation, and tumour growth, but little is known regarding its role in mucosal homeostasis. Resistance to the intestinal helminth Trichuris muris relies on an "epithelial escalator" to expel the parasite. IEC turnover is restricted by parasite-induced indoleamine 2,3-dioxygenase (IDO). Mice with or without conditional knockout of SOCS3 were infected with T. muris. Crypt depth, worm burden, and proliferating cells and IDO were quantified. SOCS3 knockdown was also performed in human IEC cell lines. Chronic T. muris infection increased expression of SOCS3 in wild-type mice. Lack of IEC SOCS3 led to a modest increase in epithelial turnover. This translated to a lower worm burden, but not complete elimination of the parasite suggesting a compensatory mechanism, possibly IDO, as seen in SOCS3 knockdown. We report that SOCS3 impacts on IEC turnover following T. muris infection, potentially through enhancement of IDO. IDO may dampen the immune response which can drive IEC hyperproliferation in the absence of SOCS3, demonstrating the intricate interplay of immune signals regulating mucosal homeostasis, and suggesting a novel tumour suppressor role of SOCS3. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.
Pavone, S; Sforna, M; Gialletti, R; Prato, S; Marenzoni, M L; Mandara, M T
A 7-year-old male trotter horse with a history of recurrent colic displayed clinical findings consistent with chronic intestinal pseudo-obstruction (CIP). At laparotomy, an impaction of the descending colon associated with marked atrophy of the right dorsal colon was found. The horse was humanely destroyed and tissues collected at necropsy examination revealed diffuse enteric ganglionitis comprising an infiltrate of CD3(+) T lymphocytes and plasma cells. At all levels of the intestinal tract the number of myenteric ganglia and of normal ganglion cells was decreased significantly. There were chromatolytic or necrotic neurons and the amount of connective tissue surrounding ganglia was increased. Immunohistochemical studies demonstrated slightly reduced expression of neuron-specific enolase and a moderate increase in expression of S100 and glial fibrillary acidic protein in a sample of right dorsal colon taken during the necropsy examination compared with a biopsy sample taken from the same location. Immunolabelling and semi-nested polymerase chain reaction for equine herpesvirus (EHV)-1 performed on the gut were positive, supporting an aetiological relationship between EHV-1 infection and the enteric ganglionitis.
Küllmer, Armin; Schmidt, Arthur; Caca, Karel
We report on two patients with recurrent episodes of chronic intestinal pseudo-obstruction (CIPO). A 50-year-old woman with severe multiple sclerosis and an 84-year-old man with Parkinson's disease and dementia had multiple hospital admissions because of pain and distended abdomen. Radiographic and endoscopic findings showed massive dilation of the colon without any evidence of obstruction. Conservative management resolved symptoms only for a short period of time. As these patients were poor candidates for any surgical treatment we carried out percutaneous endoscopic colostomy by placing a 20-Fr tube in the cecum with the introducer method. The procedure led to durable symptom relief without complications. We present these two cases and give a review through the existing literature of the procedure in CIPO.
Roche, Marjolaine; Neti, Prasad V S V; Kemp, Francis W; Azzam, Edouard I; Ferraris, Ronaldo P; Howell, Roger W
We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays.
Azzam, Edouard I.; Ferraris, Ronaldo P.; Howell, Roger W.
We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays. PMID:26484399
Wang, Yi; Han, Gencheng; Chen, Yu; Wang, Ke; Liu, Guijun; Wang, Renxi; Xiao, He; Li, Xinying; Hou, Chunmei; Shen, Beifen; Guo, Renfeng; Li, Yan; Chen, Guojiang
Tumor necrosis factor-α (TNF-α) acts as a key factor for the development of inflammatory bowel diseases (IBDs), whose function is known to be mediated by TNF receptor 1 (TNFR1) or TNFR2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, chronic colitis was established by oral administration of dextran sulfate sodium (DSS) in TNFR1 or TNFR2-/- mice. Unexpectedly, TNFR1 or TNFR2 deficiency led to exacerbation of signs of colitis compared with wild-type (WT) counterparts. Of note, TNFR1 ablation rendered significantly increased mortality compared with TNFR2 and WT mice after DSS. Aggravated pathology of colitis in TNFR1-/- or TNFR2-/- mice correlated with elevated colonic expression of proinflammatory cytokines and chemokines. Importantly, ablation of TNFR1 or TNFR2 increased apoptosis of colonic epithelial cells, which might be due to the heightened ratio of Bax/Bcl-2 and increased expression of caspase-8. Intriguingly, despite comparable intensity of intestinal inflammation in TNFR-deficient mice after DSS, systemic inflammatory response (including splenomegaly and myeloid expansion) was augmented dramatically in TNFR1-/- mice, instead of TNFR2-/- mice. Granulocyte-macrophage colony-stimulating factor (GMCSF) was identified as a key mediator in this process, as neutralization of GMCSF dampened peripheral inflammatory reaction and reduced mortality in TNFR1-/- mice. These data suggest that signaling via TNFR1 or TNFR2 has a protective role in chronic intestinal inflammation, and that lacking TNFR1 augments systemic inflammatory response in GMCSF-dependent manner.
Chaffin, Joanna; Lee, Jeffrey R; Rao, Satish S C; Sharma, Suash J
Chronic intestinal pseudo-obstruction (CIPO), a rare, debilitating disorder of bowel motility dysfunction, is largely a clinical diagnosis, without any universally accepted diagnostic criteria. Three subgroups are generally acknowledged based on the cell-type affected: enteric visceral myopathy (the most common subgroup), neuropathy, and mesenchymopathy. A fourth subgroup includes abnormalities of neurohormonal peptides. Although immunohistochemical staining is reportedly useful for identifying the mesenchymopathic type, its role in diagnosing enteric visceral myopathy and neuropathy has been fraught with difficulties. We present two cases of chronic intestinal pseudo-obstruction that are clinically and histopathologically suggestive of type III visceral enteric myopathy, aiming to expound upon the diagnostic and pathogenic features. We found that the outer-longitudinal layer of the muscularis propria was more severely affected as compared with the inner circular layer. To investigate the value of this finding, we performed immunostains in the one case in which a paraffin block was available. We found increased peripherin and calretinin immunopositive nerve fibers in the outer layer as compared with inner, but without any significant increase in S-100 positivity or alteration in neuronal morphology of myenteric plexus, a novel finding. This differential staining pattern was completely different from Hirschsprung disease, in which we found rare to absent peripherin and calretinin staining. It is unclear if this increase in the outer layer in visceral myopathy reflects a reactive change or dysfunctional axons. In addition, the history of volvulus in one patient and transmural inflammatory changes in the second raise concerns about the higher propensity of clinical complications secondary to the attenuated outer muscular layer. This study suggests that enteric visceral myopathy has histologic and staining characteristics different from Hirschsprung disease, a finding
Yang, Jiayin; Xu, Lili
BACKGROUND IL-23/IL-23R signaling plays a pivotal role during the course of inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut immune homeostasis and therefore are important in preventing the development of IBD. This study was performed to clarify the association between IL-23/IL-23R signaling and Foxp3+ regulatory T cells in colitis. MATERIAL AND METHODS Acute and chronic mouse colitis models were established by administering mice DSS in drinking water. IL-23R, IL-23, IL-I7, and IFN-γ expression level, as well as regulatory T cell, Th17-, and Th1-related transcription factors Foxp3, RORgt, and T-bet were assayed by real-time PCR. The frequency of Foxp3+ RORγt+ cells in a Foxp3+ cell population in colon mucosa during acute and chronic colitis was evaluated through flow cytometry. The signaling pathway mediated by IL-23R in the colon mucosa from acute colitis mice and chronic colitis mice was monitored by Western blot analysis. RESULTS We detected elevated IL-23R, IL-23, and IFN-γ expression in colon mucosa during acute and chronic colitis and found increased IL-17 in acute colitis mice. Transcription factors Foxp3 and T-bet were elevated in colon mucosa during acute and chronic colitis. Phosphorylation of Stat3 was greatly enhanced, indicating the activation of IL-23R function in colitis mice. The percentage of Foxp3+ T cells in acute and chronic colitis mice was comparable to control mice, but there was a 2-fold increase of Foxp3+ RORγt+ cells among the Foxp3+ cell population in acute and chronic colitis mice compared to control mice. CONCLUSIONS These findings indicate that the induction of Foxp3+ RORgt+ T cells could be enhanced during inflammation in the intestine where IL-23R expression is greatly induced. Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of
Yaseen, Afshan; Tresa, Vina; Lanewala, Ali Asghar; Hashmi, Seema; Ali, Irshad; Khatri, Sabeeta; Mubarak, Muhammed
Acute kidney injury (AKI) is an important complication of idiopathic nephrotic syndrome (INS) and is associated with adverse outcomes, especially the development of chronic kidney disease (CKD). We aimed to determine the clinical profile of children with INS who developed AKI and its short-term outcome. This prospective study was conducted from March 2014 to October 2015. A total of 119 children of INS (age: 2-18 years) fulfilling the pediatric RIFLE criteria for the diagnosis of AKI were enrolled and followed up for 3 months to determine the outcome. Factors predisposing to CKD were studied. The mean age at presentation was 8.8 ± 3.59 years and males were 74 (62.2%). At presentation, 61 (51.3%) children were in Risk category, 43 (36.1%) in Injury category, and 15 (12.6%) in Failure category. Most of them (41.2%) had steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) on histopathology (33.6%). Infections were the major predisposing factor for AKI in 67 (56.3%) cases. Drug toxicity was the next common, found in 52 (43.7%) children. A total of 65 (54.6%) children recovered from AKI, while 54 (45.4%) did not. CKD developed in 49 (41.2%) non-recovered cases and 5 (4.2%) children succumbed to acute illness. SRNS, cyclosporine use, FSGS on histology, and drug toxicity were significant factors associated with the development of CKD. AKI associated with INS is a reversible condition in most cases but it can progress to CKD, especially among those who have SRNS, FSGS, and drug toxicity.
Vijayalakshmi, Bodiga; Sesikeran, Boindala; Udaykumar, Putcha; Kalyanasundaram, Subramaniam; Raghunath, Manchala
AIM: To investigate if cisplatin alters vitamin status and if VR modulates cisplatin induced intestinal apoptosis and oxidative stress in Wistar/NIN (WNIN) male rats. METHODS: Weanling, WNIN male rats (n = 12 per group) received adlibitum for 17 wk: control diet (20% protein) or the same with 50% vitamin restriction. They were then sub-divided into two groups of six rats each and administered cisplatin (2.61 mg/kg bodyweight) once a week for three wk or PBS (vehicle control). Intestinal epithelial cell (IEC) apoptosis was monitored by morphometry, Annexin-V binding, M30 cytodeath assay and DNA fragmentation. Structural and functional integrity of the villus were assessed by villus height / crypt depth ratio and activities of alkaline phosphatase, lys, ala-dipeptidyl amino-peptidase, respectively. To assess the probable mechanism(s) of altered apoptosis, oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined. RESULTS: Cisplatin per se decreased plasma vitamin levels and they were the lowest in VR animals treated with cisplatin. As expected VR increased only villus apoptosis, whereas cisplatin increased stem cell apoptosis in the crypt. However, cisplatin treatment of VR rats increased apoptosis both in villus and crypt regions and was associated with higher levels of TBARS, protein carbonyls and caspase-3 activity, but lower GSH concentrations. VR induced decrease in Bcl-2 expression was further lowered by cisplatin. Bax expression, unaffected by VR was increased on cisplatin treatment. Mucosal functional integrity was severely compromised in cisplatin treated VR-rats. CONCLUSION: Low intake of vitamins increases the sensitivity of rats to cisplatin and promotes intestinal epithelial cell apoptosis. PMID:16534849
Kalogeris, T J; Painter, R G
We examined the effect of daily fat supplementation on intestinal gene expression and protein synthesis and plasma levels of apolipoprotein A-IV (apo A-IV). Rats were fasted overnight and then given intragastric bolus infusion of either saline or fat emulsion after 0, 1, 2, 4, 8, or 16 days of similar daily feedings. Four hours after the final saline or fat infusion, plasma and jejunal mucosa were harvested; plasma levels of apo A-IV, triglycerides, and leptin were measured, as well as mucosal apo A-IV mRNA levels and biosynthesis of apo A-IV protein. In response to fat, plasma apo A-IV showed an initial 40% increase compared with saline-injected control rats; with continued daily fat feeding, the plasma A-IV response showed rapid and progressive diminution such that by 4 days, plasma A-IV was not different between fat- and saline-fed groups. Jejunal mucosal apo A-IV synthesis and mRNA levels also showed time-dependent refractoriness to fat feeding. However, the kinetics of this effect were considerably slower than in the case of plasma, requiring 16 days for completion. There was no correlation between plasma leptin or triglyceride levels and intestinal apo A-IV synthesis or plasma apo A-IV. These results indicate rapid, fat-induced, posttranslational adapation of plasma apo A-IV levels and a slower, but similarly complete pretranslational adaptation of intestinal apo A-IV production, which are independent of plasma levels of leptin.
Bailey, Candice; Ruaux, Craig; Stang, Bernadette V; Valentine, Beth A
Serotonin regulates many intestinal motor and sensory functions. Altered serotonergic metabolism has been described in human gastrointestinal diseases. The objective of our study was to compare expression of several components of the serotonergic system [serotonin (5-HT), serotonin reuptake transporter protein (SERT), tryptophan hydroxylase-1 (TPH-1), 5-HT receptor2B (5-HT2B)] and the enterochromaffin cell marker chromogranin-A (CgA) in the intestinal mucosa between dogs with chronic enteropathy and healthy controls. Serotonin and CgA expression were determined by immunohistochemistry using banked and prospectively obtained, paraffin-embedded canine gastrointestinal biopsies (n = 11), and compared to a control group of canine small intestinal sections (n = 10). Expression of SERT, TPH-1, and 5-HT2B were determined via real-time reverse transcription (qRT)-PCR using prospectively collected endoscopic duodenal biopsies (n = 10) and compared to an additional control group of control duodenal biopsies (n = 8, control group 2) showing no evidence of intestinal inflammation. Dogs with chronic enteropathies showed strong staining for both 5-HT and CgA. Mean positive cells per high power field (HPF) were significantly increased for both compounds in dogs with chronic enteropathies (p < 0.001 for 5-HT; p < 0.05 for CgA). The number of 5-HT-positive and CgA-positive cells/HPF showed significant correlation in the entire group of dogs, including both diseased and healthy individuals (Pearson r(2) = 0.2433, p = 0.016). No significant differences were observed for SERT, TPH-1, or 5-HT2B expression; however, dogs with chronic enteropathy showed greater variability in expression of TPH-1 and 5-HT2B We conclude that components of the neuroendocrine system show altered expression in the intestinal mucosa of dogs with chronic enteropathy. These changes may contribute to nociception and clinical signs in these patients.
Holla, Oystein L; Bock, Gunter; Busk, Oyvind L; Isfoss, Björn Logi
A 55-year-old woman with a history of bowel dysmotility presented with abdominal distension and peritonitis. Family history included premature deaths with intestinal symptomatology, suggesting autosomal dominant inheritance. Computed tomography showed a distended small bowel. Symptoms were alleviated by enterocutaneous stomas. Initial ileal biopsy suggested neuropathy; however, exome sequencing revealed an Arg148Ser mutation in the enteric smooth muscle actin gamma 2 (ACTG2) gene. Histological reassessment showed abnormal muscularis propria and smooth muscle actin, with the same findings in sibling, confirming familial visceral myopathy. Thus, noninvasive genomic analysis can provide early and specific diagnosis of familial visceral myopathy, which may help to avoid inappropriate surgery.
Bhatt, Krupa H; Karjodkar, Freny R; Sansare, Kaustubh; Patil, Darshana
Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential.
Nacaroglu, Hikmet Tekin; Sandal, Ozlem Sarac; Bag, Ozlem; Erdem, Semiha Bahceci; Bekem Soylu, Ozlem; Diniz, Gulden; Ozturk, Aysel; Can, Demet
Introduction: Idiopathic Pulmonary Hemosiderosis (IPH) is a rare cause of alveolar hemorrhage, which is seen primarily in childhood. Celiac disease is defined as a chronic, immune-mediated enteropathy of the small intestine, caused by exposure to dietary gluten in genetically pre-disposed individuals. Association of IPH and celiac disease is known as Lane Hamilton syndrome. There are limited number of case reports of this syndrome in literature. Case Presentation: Although there were no growth and developmental delay and gastrointestinal symptoms like chronic diarrhea, chronic constipation, vomiting, abdominal bloating and pain in the two patients with IPH, they were diagnosed with Lane Hamilton Syndrome. After initiation of gluten-free diet, their IPH symptoms disappeared and hemoglobin levels were observed to return to normal. Conclusions: Even if there were no gastrointestinal symptoms in a patient with IPH, celiac disease should be investigated. These patients may benefit from gluten free diet and IPH symptoms may disappear. PMID:26495097
Kumar, Mahesh; Yadav, Krishan; Verma, Saurabh Kumar; Maheshwari, Vikas
Spontaneous chronic subdural hematoma (CSH) in infants is extremely rare. A very limited number of cases are known and reported in literature. The clinical presentation can be myriad varying from asymptomatic cases to gross neurological deficits. We report a case of a 3-month-old child who presented to us with repeated episodes of focal seizures of the left upper and lower limb of 1 month duration. Subsequent imaging revealed bilateral CSH (right > left) with left internal carotid artery infarct and midline shift to left by 8 mm. The child improved following burr hole evacuation of the right-sided CSH. The management of such case and a brief review of literature are discussed. PMID:28217168
Rosa-E-Silva, Lucilene; Troncon, Luiz E A; Gallo, Lourenço; Foss, Milton C; Passos, Afonso D C; Perdoná, Gleici C; Achcar, Jorge A; Oliveira, Ricardo B
Patients with chronic pancreatitis may have abnormal gastrointestinal transit, but the factors underlying these abnormalities are poorly understood. Gastrointestinal transit was assessed, in 40 male outpatients with alcohol-related chronic pancreatitis and 18 controls, by scintigraphy after a liquid meal labeled with (99m)technetium-phytate. Blood and urinary glucose, fecal fat excretion, nutritional status, and cardiovascular autonomic function were determined in all patients. The influence of diabetes mellitus, malabsorption, malnutrition, and autonomic neuropathy on abnormal gastrointestinal transit was assessed by univariate analysis and Bayesian multiple regression analysis. Accelerated gastrointestinal transit was found in 11 patients who showed abnormally rapid arrival of the meal marker to the cecum. Univariate and Bayesian analysis showed that diabetes mellitus and autonomic neuropathy had significant influences on rapid transit, which was not associated with either malabsorption or malnutrition. In conclusion, rapid gastrointestinal transit in patients with alcohol-related chronic pancreatitis is related to diabetes mellitus and autonomic neuropathy.
Navaneetharaja, Navena; Griffiths, Verity; Wileman, Tom; Carding, Simon R.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest. This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the “infectious” trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting. PMID:27275835
Beesley, R.C.; Jones, T.D.
Hamsters were separated into two groups and fed liquid diets ad lib. Controls were given a diet similar to that described by DeCarli and Lieber while alcoholics received the same diet containing 5% ethanol isocalorically substituted for sucrose. The volume of diet consumed daily and the gain in body weights of alcoholics were not significantly different from those of controls. After four weeks the animals were sacrificed and the upper third of the small intestine was used to prepare brush border membrane vesicles. In the presence of a Na/sup +/ gradient, uptake of proline into vesicles prepared from both groups was rapid, reaching a maximum accumulation in 1 to 2 min and then decreasing to the equilibrium level. To normalize the results, the amount of proline take up at each time point was divided by the amount present at equilibrium. From the normalized data it was concluded that both the rate of uptake and the maximum accumulation of proline into brush border membrane vesicles isolated from alcoholics were significantly less than those obtained with vesicles from controls. These results suggest that chronic ingestion of ethanol results in a reduction in Na/sup +/-dependent transport of proline across the brush border membrane and, thus, may contribute to the malnutrition which is frequently associated with chronic alcoholism.
Redan, Benjamin W; Albaugh, George P; Charron, Craig S; Novotny, Janet A; Ferruzzi, Mario G
As evidence mounts for a health-protective role of dietary phenolics, the importance of understanding factors influencing bioavailability increases. Recent evidence has suggested chronic exposure to phenolics may impact their absorption and metabolism. To explore alterations occurring from chronic dietary exposure to phenolics, Caco-2 cell monolayers were differentiated on Transwell inserts with 0-10 μM blackberry (Rubus sp.) total phenolics extracts rich in anthocyanins, flavonols, and phenolic acids. Following differentiation, apical to basolateral transport of phenolics was assessed from an acute treatment of 100 μM blackberry phenolics from 0 to 4 h. Additionally, differences in gene expression of transport and phase II metabolizing systems including ABC transporters, organic anion transporters (OATs), and uridine 5'-diphospho (UDP) glucuronosyltransferases (UGTs) were probed. After 4 h, 1 μM pretreated monolayers showed a significant (P < 0.05) decrease in the percentage of cumulative transport including less epicatechin (42.1 ± 0.53), kaempferol glucoside (23.5 ± 0.29), and dicaffeoylquinic acid (31.9 ± 0.20) compared to control. Finally, significant (P < 0.05) alterations in mRNA expression of key phase II metabolizing enzymes and transport proteins were observed with treatment. Therefore, adaptation to blackberry extract exposure may impact intestinal transport and metabolism of phenolics.
Rausch, Sebastian; Held, Josephin; Stange, Joerg; Lendner, Matthias; Hepworth, Matthew R; Klotz, Christian; Lucius, Richard; Pogonka, Thomas; Hartmann, Susanne
Infections with parasitic worms are often long lasting and associated with modulated immune responses. We analyzed the influence of the nematode Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent protozoan infection with Eimeria falciformis residing in the cecum. To dissect the effects of a nematode infection in the early versus chronic phase, we infected animals with E. falciformis 6 or 28 days post H. p. bakeri infection. Only a concurrent early nematode infection led to an increased replication of the protozoan parasite, whereas a chronic worm infection had no influence on the control of E. falciformis. Increased protozoan replication correlated with the reduced production of IFN-γ, IL-12/23, CCL4, CXCL9 and CXCL10, reduced migration of T cells and increased expression of Foxp3 at the site of protozoan infection. This was accompanied by a stronger nematode-specific Th2 response in gut-draining LN. Protection of mice against challenge infections with the protozoan parasite was not altered. Hence, the detrimental effect of a nematode infection on the control of a concurrent protozoan infection is transient and occurs only in the narrow time window of the early phase of infection.
Hayes, Kelly S; Cliffe, Laura J; Bancroft, Alison J; Forman, Simon P; Thompson, Seona; Booth, Cath; Grencis, Richard K
Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.
Obembe, Agona O.; Owu, Daniel U.; Okwari, Obem O.; Antai, Atim B.; Osim, Eme E.
Chronic ingestion of thermoxidized palm oil causes functional derangement of various tissues. This study was therefore carried out to determine the effect of chronic ingestion of thermoxidized and fresh palm oil diets on intestinal fluid and glucose absorption in rats using the everted sac technique. Thirty Wistar rats were divided into three groups of 10 rats per group. The first group was the control and was fed on normal rat chow while the second (FPO) and third groups (TPO) were fed diet containing either fresh or thermoxidized palm oil (15% wt/wt) for 14 weeks. Villus height and crypt depth were measured. The gut fluid uptake and gut glucose uptake were significantly (P < .001) lower in the TPO group than those in the FPO and control groups, respectively. The villus height in the TPO was significantly (P < .01) lower than that in FPO and control. The villus depth in TPO was significantly (P < .05) higher than that in FPO and control groups, respectively. These results suggest that ingestion of thermoxidized palm oil and not fresh palm oil may lead to distortion in villus morphology with a concomitant malabsorption of fluid and glucose in rats due to its harmful free radicals. PMID:21991537
Navaneetharaja, Navena; Griffiths, Verity; Wileman, Tom; Carding, Simon R
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest. This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the "infectious" trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting.
Iida, Hiroshi; Inamori, Masahiko; Sekino, Yusuke; Sakamoto, Yasunari; Yamato, Shigeru; Nakajima, Atsushi
Intestinal pseudo-obstruction is a clinical syndrome in which the clinical symptoms of intestinal obstruction appear without mechanical obstruction of the intestine. We searched for articles from Japana Centra Revuo Medicina for the period 1983-2009 using the keywords 'chronic' and 'intestinal pseudo-obstruction'. 124 articles were identified, and of these 121 cases were investigated using our diagnostic criteria. The patients were between 0 (just after birth) and 84 years of age, indicating that chronic intestinal pseudo-obstruction (CIP) can occur at any age. The mean age was 43.6 years and the median age was 47 years. Forty-nine patients were male and 72 were female, showing a slight tendency towards female predominance. Five cases (4.2%) had a definitive family history. Of the identified causes of secondary CIP, systemic sclerosis was the most common. Abdominal bloating was the most common initial symptom, seen in 90 (81%) patients. Patients having poor intestinal peristalsis with stagnation of the contents of the small intestines causing fatty stools and bacterial overgrowth complained of diarrhea. The interval between the initial symptoms and diagnosis ranged from 0 to 60 years, with a mean and median interval of 7.3 and 2 years, respectively. In case reports of CIP in Japan, the sensitivity of our diagnostic criteria was found to be 85.9%, indicating that the criteria are useful. For improvement in the rate of recognition of CIP and practical application of the diagnostic criteria in Japan, it is important to conduct further studies.
Marcus, E.A.; Wozniak, L.J.; Venick, R.S.; Ponthieux, S.M.; Cheng, E.Y.; Farmer, D.G.
Pregnancy after solid organ transplantation is becoming more common, with the largest recorded numbers in renal and liver transplant recipients. Intestinal transplantation is relatively new compared to other solid organs, and reports of successful pregnancy are far less frequent. All pregnancies reported to date in intestinal transplant recipients have been in women with stable graft function. The case reported here involves the first reported successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and dependence on both transplant immunosuppression and parenteral nutrition (PN) at the time of conception. Pregnancy was unplanned and unexpected in the setting of chronic illness and menstrual irregularities, discovered incidentally on abdominal ultrasound at approximately 18 weeks’ gestation. Rapamune was held, tacrolimus continued, and PN adjusted to maintain consistent weight gain. A healthy female infant was delivered vaginally at term. Medical complications during pregnancy included anemia and need for tunneled catheter replacements. Ascites and edema were improved from baseline, with recurrence of large volume ascites shortly after delivery. Successful pregnancy is possible in the setting of transplant immunosuppression, chronic intestinal graft dysfunction, and long-term PN requirement, but close monitoring is required to ensure the health of mother and child. PMID:25724255
van der Heijden, Kristiaan B; Smits, Marcel G; van Someren, Eus J W; Boudewijn Gunning, W
Research has shown efficacy of melatonin treatment to advance sleep-wake rhythms in insomnia. In healthy adults, direction and magnitude of the phase shift depends on the timing of administration relative to the phase position of the circadian system. Therefore, in the present study we investigated whether in children with chronic sleep onset insomnia (SOI) efficacy of melatonin treatment in the early evening could be predicted from dim light melatonin onset (DLMO), a phase marker of the circadian system. We combined data of two previously published double blind, randomized, placebo-controlled trials in 110 participants, aged 6-12 years. Sleep was actigraphically estimated, and saliva collected, at baseline and in the third week of a 4-week treatment period with 5 mg melatonin or placebo at 18:00 or 19:00 hours. Primary outcome measures were pre- to post-treatment changes in dim light melatonin onset (DeltaDLMO), sleep onset (DeltaSO), sleep latency (DeltaSL), and total sleep duration (DeltaTSD). Melatonin advanced DLMO with +1:12 h (P < 0.001), SO with +0:42 h (P = 0.004), SL decreased with 25 min (P = 0.019), and TSD did not change significantly, as compared with placebo. In the melatonin-treated group, but not in the placebo-treated group, pretreatment DLMO was significantly related to DeltaDLMO [F(1, 29) = 7.28, P = 0.012] and DeltaSO [F(1, 25) = 7.72, P = 0.010]. The time interval between treatment administration and pretreatment DLMO (INT) was only significantly related to DeltaSO [F(1,26) = 5.40, P = 0.028]. The results suggest that in children with SOI, the efficacy of early evening melatonin to advance sleep onset and endogenous melatonin onset increases the later the pretreatment DLMO is.
Debray, M-P; Borie, R; Danel, C; Khalil, A; Majlath, M; Crestani, B
Idiopathic interstitial pneumonias comprise 8 clinicopathological entities, most of them with a chronic course and various prognosis. Idiopathic pulmonary fibrosis is the most frequent and most severe of these. Computed tomography has an important role for its diagnosis. It can identify the corresponding pathological pattern of usual interstitial pneumonia in about 50 percent of cases. It can suggest differential diagnosis in other cases, most frequently fibrosing nonspecific interstitial pneumonia and chronic hypersensitivity pneumonitis. Imaging features should be integrated to clinical and available pathologic data during multidisciplinary team meetings involving physicians with a good knowledge of interstitial diseases. Some cases may be unclassifiable, but these could later be reclassified as new data may occur or imaging features may change. Surgical lung biopsy is being less frequently performed and an emerging less invasive technique, lung cryobiopsy, is under evaluation. Pleuroparenchymal fibroelastosis is a distinct entity only recently described, with uncertain prevalence and prognosis that seems being quite often associated to another pattern of interstitial pneumonia.
Kirpich, Irina A; Feng, Wenke; Wang, Yuhua; Liu, Yanlong; Beier, Juliane I; Arteel, Gavin E; Falkner, K Cameron; Barve, Shirish S; McClain, Craig J
Alcohol and dietary fat both play an important role in alcohol-mediated multi-organ pathology, including gut and liver. In the present study we hypothesized that the combination of alcohol and dietary unsaturated fat (USF) would result in intestinal inflammatory stress and mucus layer alterations, thus contributing to disruption of intestinal barrier integrity. C57BL/6N mice were fed Lieber-DeCarli liquid diets containing EtOH and enriched in USF (corn oil/linoleic acid) or SF (medium chain triglycerides: beef tallow) for 8 weeks. Intestinal histology, morphometry, markers of inflammation, as well as levels of mucus protective factors were evaluated. Alcohol and dietary USF triggered an intestinal pro-inflammatory response, characterized by increase in Tnf-α, MCP1, and MPO activity. Further, alcohol and dietary USF, but not SF, resulted in alterations of the intestinal mucus layer, characterized by decreased expression of Muc2 in the ileum. A strong correlation was observed between down-regulation of the antimicrobial factor Cramp and increased Tnf-α mRNA. Therefore, dietary unsaturated fat (corn oil/LA enriched) is a significant contributing factor to EtOH-mediated intestinal inflammatory response and mucus layer alterations in rodents.
Bradley, E L; Clements, J L
Intestinal obstruction as a complication of pancreatitis is infrequently recognized. Only four cases of idiopathic duodenal obstruction associated with pancreatitis have been previously reported. In a three-year study of 878 patients with pancreatitis, nine cases of idiopathic duodenal obstruction associated with pancreatitis have been found. Each of the nine cases was characterized by frank obstruction in the second or third portions of the duodenum and an intact mucosa in the area of stricture. Four patients gave an abrupt history of moderately severe pancreatitis. Resolution of the duodenal obstruction occurred by three weeks in each of these four cases. Surgical exploration in one of these patients revealed marked duodenal edema with intramural hematoma. The remaining five patients reported a chronic history of obstruction. Inadequate resolution of the obstruction after four weeks of hyperalimentation led to surgical bypass. Duodenal biopsy specimens revealed inflammation, muscle destruction, and extensive fibrosis. Duodenal involvement in the inflammatory process of moderately severe pancreatitis was discovered in 25% of the upper gastrointestinal studies, but was usually self-limiting and of a mild degree. Since contiguous duodenal edema is common and fibrosing pancreatoduodenitis only occurs in an occasional patient, surgical intervention for duodenal obstruction associated with pancreatitis should only be considered after demonstrated failure of conservative management. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:7235767
Ando, Takafumi; Tsuzuki, Tomoyuki; Mizuno, Tomokazu; Minami, Masaaki; Ina, Kenji; Kusugami, Kazuo; Takamatsu, Junki; Adachi, Kouichi; El-Omar, Emad; Ohta, Michio; Goto, Hidemi
The association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been reported widely. We investigated the prevalence of H. pylori infection, its virulence profile and the effectiveness of its eradication in patients with ITP. Twenty patients with ITP, 20 with peptic ulcer (10 gastric ulcer (GU), 10 duodenal ulcer (DU)) and 20 with NUD were studied. The virulence profile of the strains was assessed by genotyping for cagA, vacA, iceA, and hpyIIIR/hrgA and by assaying for IL-8 and DNA fragmentation after incubation with AGS cells. Infected patients and two uninfected ITP patients received triple therapy and platelets were counted before and 1 month, 6 months, 1 year, and 2 years after eradication therapy. H. pylori infection was found in 17 ITP (85%), 20 ulcer (100%) and 13 NUD (65%) patients. Biopsies and strains were collected from five ITP, 20 ulcer and 13 NUD patients. The ITP patients had a pangastritis or corpus-predominant gastritis pattern. All H. pylori isolates, from ITP, ulcer and NUD patients, were cagA(+) and vacA s1/m1, and did not differ in levels of IL-8 induction or DNA fragmentation. Fifteen ITP (88%) and 17 ulcer (85%) patients had successful eradication of H. pylori. Ten of these 15 (67%) H. pylori-eradicated ITP patients had platelet recovery. There was no significant change in platelet count in the two ITP patients in whom eradication failed or in the two originally H. pylori-uninfected ITP patients, or in the treated ulcer patients. Age at onset of ITP was the main determinant of platelet recovery: 100% of patients diagnosed after the age of 60 recovered compared with only 22% of those diagnosed before 50. H. pylori-infected ITP patients have a corpus-predominant pattern of gastritis but the virulence profile of their strains does not differ from that of ulcer or NUD patients. Eradication of H. pylori infection is a good therapeutic option for some patients with chronic ITP, especially for those who
Wang, Wei; Sun, Xiao-Tian; Weng, Xiao-Ling; Zhou, Dai-Zhan; Sun, Chang; Xia, Tian; Hu, Liang-Hao; Lai, Xiao-Wei; Ye, Bo; Liu, Mu-Yun; Jiang, Fei; Gao, Jun; Bo, Lu-Min; Liu, Yun; Liao, Zhuan; Li, Zhao-Shen
Objective Genetic alterations may contribute to chronic pancreatitis (CP) in Chinese young patients. This study was designed to investigate mutations of cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor or serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin C (CTRC) and CLDN2 genes and the copy number variations (CNVs) of PRSS1 and asses associations with the development of idiopathic CP (ICP) in Chinese children. Design Retrospective. Setting A single center. Participants 75 ICP Chinese children (40 boys and 35 girls). Primary and secondary outcome measures Mutations of PRSS1, SPINK1, CFTR, CTRC and CLDN2 genes and CNVs. Results 7 patients had heterozygous mutations in PRSS1, that is, N29I (n=1), R122H or R122C (n=6). The CNVs of PRSS1 in five patients had abnormal copies (1 copy (n=4), five copies (n=1)). 43 patients had IVS3+2T>C (rs148954387) (10 homozygous and 33 heterozygous) in SPINK1. None of the PRSS1 mutation patients carried a SPINK1 mutation. Frequency of PRSS1 and SPINK1 mutations was 9.3% and 57.3%, respectively, with an overall frequency of 66.6% (50/75). In addition, one patient had a novel deletion of CFTR (GCTTCCTA from c.500 to c.508 leading to the shortened polypeptide molecule via a stop codon). Another patient had a novel missense in CLDN2 exon 2 (c.592A>C mutation). Clinically, patients with SPINK1 mutations had a higher rate of pancreatic duct stones, pancreatic pseudocyst and pancreatic calcification than those without SPINK1 mutations (p<0.05). Conclusions SPINK1 mutations were more commonly associated with Chinese children with ICP. SPINK1 IVS3+2T>C mutation may play an important role in the pathogenesis of Chinese paediatric ICP. However, further study is needed to confirm and to investigate the role of these genes in the development of Chinese ICP. PMID:24002981
Saini, Sarbjit S; Bindslev-Jensen, Carsten; Maurer, Marcus; Grob, Jean-Jacques; Bülbül Baskan, Emel; Bradley, Mary S; Canvin, Janice; Rahmaoui, Abdelkader; Georgiou, Panayiotis; Alpan, Oral; Spector, Sheldon; Rosén, Karin
ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3% P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8% P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients
Potenza, Maria Assunta; Montagnani, Monica; Nacci, Carmela; De Salvia, Maria Antonietta
Background Green tea catechins seem to contribute toward reducing body weight and fat. Objective We aimed to investigate whether chronic administration of (–)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. Design Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 µM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. Results Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle-treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05–5 µM) and increased inhibitory response to electrical field stimulation (EFS, 1–10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG
Potenza, Maria Assunta; Montagnani, Monica; Nacci, Carmela; De Salvia, Maria Antonietta
Green tea catechins seem to contribute toward reducing body weight and fat. We aimed to investigate whether chronic administration of (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 µM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle-treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05-5 µM) and increased inhibitory response to electrical field stimulation (EFS, 1-10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG incubation (100 µM, 20 min) of colonic and
Breton, Jérôme; Le Clère, Kelly; Daniel, Catherine; Sauty, Mathieu; Nakab, Lauren; Chassat, Thierry; Dewulf, Joëlle; Penet, Sylvie; Carnoy, Christophe; Thomas, Patrick; Pot, Bruno; Nesslany, Fabrice; Foligné, Benoît
Chronic ingestion of environmental heavy metals such as lead (Pb) and cadmium (Cd) causes various well-documented pathologies in specific target organs following their intestinal absorption and subsequent accumulation. However, little is known about the direct impact of the non-absorbed heavy metals on the small intestine and the colon homeostasis. The aim of our study was to compare the specific bioaccumulation and retention of Cd and Pb and their effect on the essential metal balance in primary organs, with those occurring specifically in the gastrointestinal tract of mice. Various doses of Cd (5, 20 and 100 mg l(-1)) and Pb (100 and 500 mg l(-1)) chloride salts were provided in drinking water for subchronic to chronic exposures (4, 8 and 12 weeks). In contrast to a clear dose- and time-dependent accumulation in target organs, results showed that intestines are poor accumulators for Cd and Pb. Notwithstanding, changes in gene expression of representative intestinal markers revealed that the transport-, oxidative- and inflammatory status of the gut epithelium of the duodenum, ileum and colon were specifically affected by both heavy metal species. Additionally, in vivo comet assay used to evaluate the impact of heavy metals on DNA damage showed clear genotoxic activities of Cd, on both the upper and distal parts of the gastrointestinal tract. Altogether, these results outline the resilience of the gut which balances the various effects of chronic Cd and Pb in the intestinal mucosa. Collectively, it provides useful information for the risk assessment of heavy metals in gut homeostasis and further disease's susceptibility.
Imai, D M; Miller, J L; Leonard, B C; Bach, J; Drees, R; Steinberg, H; Teixeira, L B C
An adult Bengal cat (Felis catus × Prionailurus bengalensis) with a prolonged history of partial anorexia, regurgitation, and weight loss and a clinical, radiographic, and ultrasonographic diagnosis of persistent megaesophagus and gastrointestinal ileus was submitted for necropsy. The intestinal tract was diffusely distended by gas and fluid with appreciable loss of muscle tone and an absence of luminal obstruction, consistent with the clinical history of chronic intestinal pseudo-obstruction. Histologically, the autonomic nervous system was intact, but the smooth muscle within the gastrointestinal wall exhibited a marked basophilia that was most pronounced in the jejunum. Immunohistochemistry for neurofilament, synaptophysin, CD117, and desmin demonstrated that the number of myenteric ganglia, number of interstitial cells, and leiomyocyte desmin content were similar when compared with the unaffected age- and species-matched control. Immunohistochemistry for smooth muscle α-actin demonstrated a striking loss of immunoreactivity, predominantly in the circular layer of the jejunum, that corresponded with the tinctorial change in leiomyocytes. Transmission electron microscopy revealed loss of myofibrils, loss of organelle polarity, and significantly larger central mitochondria (megamitochondria) in affected leiomyocytes, as well as nonspecific degenerative changes. Although the presence of a primary leiomyopathy and a causal relationship could not be confirmed in this case, leiomyopathies are considered a cause of chronic intestinal pseudo-obstruction in human medicine, and loss of smooth muscle α-actin immunoreactivity is one recognized marker for intestinal dysmotility.
Pantazopoulos, Harry; Dolatshad, Hamid
Evidence suggests that circadian rhythms are regulated through diffusible signals generated by the suprachiasmatic nucleus (SCN). Vasoactive intestinal peptide (VIP) is located in SCN neurons positioned to receive photic input from the retinohypothalamic tract and transmit information to other SCN cells and adjacent hypothalamic areas. Studies using knockout mice indicate that VIP is essential for synchrony among SCN cells and for the expression of normal circadian rhythms. To test the hypothesis that VIP is also an SCN output signal, we recorded wheel-running activity rhythms in hamsters and continuously infused the VIP receptor agonist BAY 55-9837 in the third ventricle for 28 days. Unlike other candidate output signals, infusion of BAY 55-9837 did not affect activity levels. Instead, BAY 55-9837 lengthened the circadian period by 0.69 ± 0.04 h (P < 0.0002 compared with controls). Period returned to baseline after infusions. We analyzed the effect of BAY 55-9837 on cultured SCN from PER2::LUC mice to determine if lengthening of the period by BAY 55-9837 is a direct effect on the SCN. Application of 10 μM BAY 55-9837 to SCN in culture lengthened the period of PER2 luciferase expression (24.73 ± 0.24 h) compared with control SCN (23.57 ± 0.26, P = 0.01). In addition, rhythm amplitude was significantly increased, consistent with increased synchronization of SCN neurons. The effect of BAY 55-9837 in vivo on period is similar to the effect of constant light. The present results suggest that VIP-VPAC2 signaling in the SCN may play two roles, synchronizing SCN neurons and setting the period of the SCN as a whole. PMID:20463182
Pareja, Juan A; Montojo, Teresa; Guerrero, Ángel L; Álvarez, Mónica; Porta-Etessam, Jesús; Cuadrado, María L
Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually. © 2015 American Headache Society.
Chandra, Lawrance C.; Kumar, Vinay; Torben, Workineh; Stouwe, Curtis Vande; Winsauer, Peter; Amedee, Angela; Molina, Patricia E.
ABSTRACT Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years. In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) inhibited viral replication and intestinal inflammation and slowed disease progression. Persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation and systemic immune activation and promote disease progression. Cannabinoids including Δ9-THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques. To determine if the anti-inflammatory effects of Δ9-THC involved differential microRNA (miRNA) modulation, we profiled miRNA expression at 14, 30, and 60 days postinfection (days p.i.) in the intestine of uninfected macaques receiving Δ9-THC (n = 3) and SIV-infected macaques administered either vehicle (VEH/SIV; n = 4) or THC (THC/SIV; n = 4). Chronic Δ9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days p.i. At 60 days p.i., ∼28% of miRNAs showed decreased expression in the VEH/SIV group compared to none showing decrease in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187, previously been shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator, was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV macaques compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage. These results support a role for differential miRNA induction in THC-mediated suppression of intestinal
Cottin, Vincent; Cordier, Jean-François
Idiopathic pulmonary fibrosis is a chronic disorder characterized histopathologically by a pattern of usual interstitial pneumonia, with heterogeneous and mutilating interstitial fibrosis with foci of proliferating fibroblasts, honeycomb lung, and little if any inflammation. The diagnosis is based on a pluridisciplinary analysis of the clinical symptoms, the chest high-resolution computerized tomography features, and pathology on video-thoracoscopic lung biopsy when indicated. In half of the cases, the typical tomodensitometric pattern allows to make a confident diagnosis without a lung biopsy. The median survival is only about 3 years and is presently not improved by any treatment. Treatment with N-acetylcysteine (antioxydant) in association with corticosteroids and azathioprine may slightly reduce the rate of functional worsening. Clinical trials are in progress to improve the treatment of this still incurable disease.
Favus, Murray J.; Walling, Marlin W.; Kimberg, Daniel V.
Previous studies have shown that chronically thyroparathyroidectomized (TPTX) rats, fed a diet with restricted calcium but adequate phosphorus and vitamin D content, have higher levels of intestinal calcium absorption than controls. The results of recent acute experiments have suggested that parathyroid hormone (PTH) may be essential for regulating the renal conversion of 25-hydroxyvitamin D3 (25-OH-D3) to 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] in response to dietary calcium deprivation. Since 1,25-(OH)2-D3 is the form of the vitamin thought to be active in the intestine, increases in calcium transport mediated by this metabolite would not be expected to occur in the absence of the parathyroid glands if the preceding model is correct. The present study was undertaken to examine the chronic effects of both dietary calcium restriction and the absence of PTH on the metabolism of [3H]25-OH-D3 and duodenal calcium-active transport in rats given thyroid replacement. These relatively long term studies confirm earlier observations which indicated that the adaptation of calcium absorption to a low calcium intake occurs in both sham-operated and TPTX animals. The present studies also demonstrated that despite reduced levels of 1,25-(OH)2-D3 in the plasma of chronically TPTX animals fed a low calcium diet, the accumulation of this metabolite in at least one target tissue, intestinal mucosa, is identical in both the sham-operated and TPTX groups. A reduced, but continued level of 1,25-(OH)2-D3 production, together with its selective accumulation by intestinal mucosa, probably explains the calcium adaptation which is observed inspite of the chronic absence of the parathyroid glands. PMID:4815079
Maier, Andrea; Mannartz, Vera; Wasmuth, Hermann; Trautwein, Christian; Neumann, Ulf-Peter; Weis, Joachim; Grosse, Joachim; Fuest, Matthias; Hilz, Max-J.; Schulz, Joerg B.; Haubrich, Christina
Abstract Chronic intestinal pseudoobstruction (CIP) can be a severe burden and even a life-threatening disorder. Typically, several years of uncertainty are passing before diagnosis. We are reporting the case of a young woman with a decade of severe, progressive gastrointestinal dysmotility. Unusually, she had also developed an autonomic neuropathy, and a stiff limb syndrome. In addition to achalasia and CIP the young woman also developed neuropathic symptoms: orthostatic intolerance, urinary retention, a Horner syndrome, and lower limb stiffness. Careful interdisciplinary diagnostics excluded underlying infectious, rheumatoid, metabolic or tumorous diseases. The detection of GAD (glutamic acid decarboxylase) antibodies, however, seemed to link CIP, autonomic neuropathy, and limb stiffness and pointed at an autoimmune origin of our patient's complaints. This was supported by the positive effects of intravenous immunoglobulin. In response to this therapy the body weight had stabilized, orthostatic tolerance had improved, and limb stiffness was reversed. The case suggested that GAD antibodies should be considered in CIP also in nondiabetic patients. This may support earlier diagnosis and immunotherapy. PMID:26252289
Tirlapur, Seema A; Priest, Lee; Daniels, Jane P; Khan, Khalid S
The term idiopathic is often used to describe a disease with no identifiable cause. It may be a diagnosis of exclusion; however, what specific minimum investigations need to be performed to define idiopathic is not always clear. This commentary describes the problems inherent in reaching a definition for the term idiopathic. There is limited literature describing methodology to define a condition with no clear diagnostic criteria. This article offers chronic pelvic pain (CPP) syndrome as an example, in which structured qualitative interviews, literature searches and group consensus discussions were undertaken to produce a working definition for idiopathic CPP. It is important to correctly develop these standardized definitions for use as outcome measures in research and as clinical indicators in healthcare.
Cardiomyopathies are certain heart diseases of unknown etiology and pathogenesis, occurring mostly in tropical and subtropical areas, where they constitute a major clinical problem and sometimes a public health problem. The need for international co-operation in the study of such forms of heart disease has long been recognized and WHO convened informal meetings of investigators on various aspects of the subject in 1964, 1965 and 1966. Out of these have arisen co-operative studies co-ordinated by WHO. In November 1967 a fourth informal meeting was held in Kingston, Jamaica, to review the following topics: the progress reports from all co-operating laboratories; the different types of cardiomyopathies; past experience with cardiac registries, and the diagnostic importance of coronary angiography. Steps were taken towards the formulation of a standard terminology, since too many confusing names are currently employed to mean “cardiomegaly of unknown origin”. A common name, “idiopathic cardiomegaly”, was therefore suggested for future use. The account presented here was prepared by Dr Z. Fejfar, Chief Medical Officer, Cardiovascular Diseases, World Health Organization, Geneva, on behalf of the other participants and is a précis of some of the information that was exchanged, some of the views that were expressed and of the suggestions that were made. PMID:4235740
Gras-Miralles, Beatriz; Cremonini, Filippo
Chronic constipation is a common disorder in the general population, with higher prevalence in the elderly, and is associated with worse quality of life and with greater health care utilization. Lubiprostone is an intestinal type-2 chloride channel activator that increases intestinal fluid secretion, small intestinal transit, and stool passage. Lubiprostone is currently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation and of irritable bowel syndrome with predominant constipation. This review outlines current approaches and limitations in the treatment of chronic constipation in the elderly and discusses the results, limitations, and applicability of randomized, controlled trials of lubiprostone that have been conducted in the general and elderly population, with additional focus on the use of lubiprostone in constipation in Parkinson's disease and in opioid-induced constipation, two clinical entities that can be comorbid in elderly patients.
Schmassmann, Adrian; Peskar, Brigitta M; Stettler, Christian; Netzer, Peter; Stroff, Thomas; Flogerzi, Beatrice; Halter, Fred
In the stomach, prostaglandins protect the gastric mucosa against injuries. One rate-limiting step in prostaglandin synthesis is mediated by prostaglandin endoperoxide synthase (PGHS), the target enzyme of non-steroidal anti-inflammatory drugs (NSAIDs). Two isoforms of PGHS exist: a constitutive (PGHS-1) and an inducible (PGHS-2) enzyme. PGHS-1 is the major source of gastric prostaglandins under physiological conditions. Inhibition of prostaglandin synthesis by traditional NSAIDs such as indomethacin and diclofenac which non-selectively inhibit both PGHS-1 and PGHS-2, causes gastric and intestinal ulceration and delays gastric ulcer healing in chronic models. It has been shown that selective PGHS-2 inhibitors such as L-745,337 (5-methanesulphonamide-6-(2,4-difluorothio-phenyl)-1-indanone) are not ulcerogenic and do not inhibit gastro-intestinal prostaglandin synthesis. However, minimal information is available on the long-term effects of PGHS-2 inhibitors on the healing of previously established gastric injuries. We assessed the cellular localization and expression of PGHS-1 and PGHS-2 during gastric ulcer healing and assessed the effects of L-745,337 on previously established cryoulcers in the rat gastric stomach.PGHS-1 and PGHS-2 were located and quantified by immunohistochemistry during experimental gastric ulcer healing. PGHS-2 immunoreactivity was only negligible in the normal gastric wall, but after gastric ulcerations, it was strongly detected in monocytes, macrophages, fibroblasts and endothelial cells below and between the regenerative glands. PGHS-1 immunoreactivity detected in normal gastric mucosa, disappeared after gastric ulceration in the mucosa adjacent to the ulcer crater. However, it reappeared in the regenerative glands from day 5 onwards. Thus, PGHS-1 and PGHS-2 were located at different sites and their maximal expression followed a different time-sequence.We assessed the effects of L-745,337, indomethacin and diclofenac on gastric ulcer healing
Dunnigan, M. G.; Denning, D. W.; Henry, J. A.; de Wolff, F. A.
Diuretic abuse has been invoked as the cause of idiopathic oedema. In this study, eight patients with idiopathic oedema were studied. Symptoms and weight variation continued despite the proven absence of diuretics in seven of them as determined by urinary chromatograms. Idiopathic oedema cannot therefore be attributed to diuretic use alone. PMID:3671223
Massoud, Ahmed M; El-Shazly, Atef M; Awad, Soha E; Morsy, Ayman T A; Sadek, Gehan S; Morsy, Tosson A
Strongyloidiasis, caused by Strongyloides stercoralis, is diagnosis considered as a challenge to clinician and laboratory technician. Because the auto-infective larvae are difficult to eradicate, one regimen dose may be in-sufficient and re-treatment of patients on two occasions, at 1 and 2 months after the initial treatment dose was recommended. This re-treatment regimen has yet to be proven in clinical trials. This study was performed on 24 patients who completed the study and having Strongyloides larvae in their stool obtained from Mansoura University Hospitals. Each stool sample was examined by direct saline smear, the formalin-ether sedimentation technique and agar plate culture. Patients were treated with Mirazid double course for a month to be followed up by stool examination by traditional method and agar plate culture for three consecutive months. In this study five cases out of 24 were asymptomatic (20.8%). Symptoms include abdominal manifestations as nausea and vomiting (16.7%), epi-gastric pain and nausea (12.5%), generalized abdominal pain (12.5%), chronic diarrhea (16.7%), irregular bowel habit (8.3%), and urticaria with abdominal pain (4.2%). Agar plate culture gave 100% positivity, even in cases were negative by coprological methods either direct smear and/or sedimenttation technique. All cases were cured by Mirazid given for one month except three resistant cases. Only one case responded to repeated course of Mirazid, while the other two cases still had larvae in their stool by agar culture plate. On combined therapy of both Mirazid and Mebendazole, larvae could be eliminated from their stool as approved by agar plate culture.
Jackson, Melinda L.; Butt, Henry; Ball, Michelle; Lewis, Donald P.; Bruck, Dorothy
Chronic Fatigue Syndrome (CFS) is a multisystem illness, which may be associated with imbalances in gut microbiota. This study builds on recent evidence that sleep may be influenced by gut microbiota, by assessing whether changes to microbiota in a clinical population known to have both poor sleep and high rates of colonization with gram-positive faecal Streptococcus, can improve sleep. Twenty-one CFS participants completed a 22- day open label trial. Faecal microbiota analysis was performed at baseline and at the end of the trial. Participants were administered erythromycin 400 mg b.d. for 6 days. Actigraphy and questionnaires were used to monitor sleep, symptoms and mood. Changes in patients who showed a clinically significant change in faecal Streptococcus after treatment (responders; defined as post-therapy distribution<6%) were compared to participants who did not respond to treatment. In the seven responders, there was a significant increase in actigraphic total sleep time (p=0.028) from baseline to follow up, compared with non-responders. Improved vigour scores were associated with a lower Streptococcus count (ρ=−0.90, p=0.037). For both the responders and the whole group, poorer mood was associated with higher Lactobacillus. Short term antibiotic treatment appears to be insufficient to effect sustainable changes in the gut ecosystem in most CFS participants. Some improvement in objective sleep parameters and mood were found in participants with reduced levels of gram-positive gut microbiota after antibiotic treatment, which is encouraging. Further study of possible links between gut microorganisms and sleep and mood disturbances is warranted. PMID:26779319
Werner, Tanja; Hoermannsperger, Gabriele; Schuemann, Klaus; Hoelzlwimmer, Gabriele; Tsuji, Shoutaro; Haller, Dirk
Environmental factors substantially contribute to the development of chronic intestinal inflammation in the genetically susceptible host. Nutritional components like iron may act as pro-oxidative mediators affecting inflammatory processes and cell stress mechanisms. To better characterize effects of dietary iron on epithelial cell responses under the pathological conditions of chronic intestinal inflammation, we characterized the protein expression profile (proteome) in primary intestinal epithelial cells (IEC) from iron-adequate and low-iron fed wild-type (WT) and TNFDeltaARE/WT mice. We performed all possible comparisons between the 4 groups according to genotype or diet. Histological analysis of iron-adequate fed TNFDeltaARE/WT mice (approximately 0.54 mg of iron/day) revealed severe ileal inflammation with a histopathology score of 8.3+/-0.91 (score range from 0-12). Interestingly, low-iron fed mice (approximately 0.03 mg of iron/day) were almost completely protected from the development of inflammatory tissue destruction (histopathology score of 2.30+/-0.73). In total, we identified 74 target proteins with significantly altered steady state expression levels in primary IEC using 2D-gel electrophoresis (2D SDS-PAGE) and peptide mass fingerprinting via MALDI-TOF mass spectrometry (MS). Interestingly, the overlap between the comparison of iron-adequate fed WT and TNFDeltaARE/WT mice (inflamed conditions) and the comparison between the iron-adequate and iron-low fed TNFDeltaARE/WT mice (absence of inflammation) revealed 4 contrarily regulated proteins including aconitase 2, catalase, intelectin 1 and fumarylacetoacetate hydrolase (FAH). These proteins are associated with energy homeostasis, host defense, oxidative and endoplasmic reticulum (ER) stress responses. In conclusion, the iron-low diet affected the epithelial cell proteome and inhibited the development of chronic intestinal inflammation, suggesting a critical role for nutritional factors in the
Suchodolski, Jan S.; Markel, Melissa E.; Garcia-Mazcorro, Jose F.; Unterer, Stefan; Heilmann, Romy M.; Dowd, Scot E.; Kachroo, Priyanka; Ivanov, Ivan; Minamoto, Yasushi; Dillman, Enricka M.; Steiner, Jörg M.; Cook, Audrey K.; Toresson, Linda
Background Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Methodology/Principal Findings Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Conclusions Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal
Suchodolski, Jan S; Markel, Melissa E; Garcia-Mazcorro, Jose F; Unterer, Stefan; Heilmann, Romy M; Dowd, Scot E; Kachroo, Priyanka; Ivanov, Ivan; Minamoto, Yasushi; Dillman, Enricka M; Steiner, Jörg M; Cook, Audrey K; Toresson, Linda
Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal microbiome of dogs with defined disease phenotypes.
Ohkubo, Hidenori; Kessoku, Takaomi; Fuyuki, Akiko; Iida, Hiroshi; Inamori, Masahiko; Fujii, Tetsuro; Kawamura, Harunobu; Hata, Yasuo; Manabe, Noriaki; Chiba, Toshimi; Kwee, Thomas C; Haruma, Ken; Matsuhashi, Nobuyuki; Nakajima, Atsushi; Takahara, Taro
Chronic intestinal pseudo-obstruction (CIPO) is a rare, serious motility disorder, with life-threatening complications over time. However, lack of an established, non-invasive diagnostic method has caused delays in the diagnosis of this intractable disease. Cine-magnetic resonance imaging (MRI) is an emerging technique, with a potential to evaluate the motility of the entire bowel. We compared small bowel motility in healthy volunteers, patients with irritable bowel syndrome (IBS), and those with CIPO, using cine-MRI, and evaluated the usefulness of cine-MRI as a novel diagnostic method for CIPO. Twelve healthy volunteers, IBS patients, and CIPO patients prospectively underwent cine-MRI at 1.5 T. Luminal diameter, contraction ratio, and contraction cycle were measured and compared between the groups. Cine-MRI provided sufficient dynamic images to assess the motility of the entire small bowel. Luminal diameter (mean±s.d.) in CIPO patients was significantly higher than that in healthy volunteers and IBS patients (43.4±14.1, 11.1±1.5, and 10.9±1.9 mm, respectively), and contraction ratio was significantly lower in CIPO patients than that in healthy volunteers and IBS patients (17.1±11.0%, 73.0±9.3%, and 74.6±9.4%, respectively). No significant differences were observed in the contraction cycle. This study is the first to assess the clinical utility of cine-MRI in CIPO patients. Cine-MRI clearly detected contractility impairments in CIPO patients. Cine-MRI is noninvasive, radiation-free, and can directly evaluate the entire small bowel peristalsis, and can detect the affected loops at a glance; therefore, it might be extremely useful for the diagnosis and follow-up of CIPO patients in clinical practice.
The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use
Nieto, Maria; Calvo, Gonzalo; Hudson, Ian; Feldschreiber, Peter; Brown, David; Lee, Ching Cheng; Lay, Geoffrey; Valeri, Anna; Abadie, Eric; Thomas, Angela; Pignatti, Francesco
On 11th March 2010, the European Commission issued a marketing authorization valid throughout the European Union for Revolade for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Revolade is an orphan medicinal product indicated for splenectomized patients with immune (idiopathic) thrombocytopenic purpura who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for non-splenectomized patients where surgery is contraindicated. The active substance of Revolade is eltrombopag (ATC code B02BX05). Eltrombopag increases platelet production through activation of the thrombopoietin receptor. The recommended oral dose is 50 mg once daily to achieve and maintain a platelet count of the 50×109/L or more necessary to reduce or prevent the risk of bleeding. The benefit of Revolade is a durable response in maintaining platelet levels. The most common side effects include headache, nausea, hepatobiliary toxicity, diarrhea, fatigue, paresthesia, constipation, rash, pruritus, cataract, arthralgia and myalgia. The decision to grant the marketing authorization was based on the favorable recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency. The objective of this paper is to describe the data submitted to the European Medicines Agency and to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (www.ema.europa.eu). PMID:21712542
Matera, Ivana; Rusmini, Marta; Guo, Yiran; Lerone, Margherita; Li, Jiankang; Zhang, Jianguo; Di Duca, Marco; Nozza, Paolo; Mosconi, Manuela; Pini Prato, Alessio; Martucciello, Giuseppe; Barabino, Arrigo; Morandi, Francesco; De Giorgio, Roberto; Stanghellini, Vincenzo; Ravazzolo, Roberto; Devoto, Marcella; Hakonarson, Hakon; Ceccherini, Isabella
Chronic intestinal pseudo-obstruction (CIPO) syndromes are heterogeneous gastrointestinal disorders, caused by either neuropathy or myopathy, resulting in compromised peristalsis and intestinal obstruction. CIPO can have a profound impact on quality of life, leading the most severely affected individuals to life-long parenteral nutrition and urinary catheterization. To search for disease causing gene(s), we performed the whole exome sequencing (WES) in both eight sporadic and two familial cases, followed by targeted sequencing in additional CIPO patients. After identifying a heterozygous missense variant in the ACTG2 gene in one of 10 patients undergone WES, targeted Sanger sequencing of this gene allowed to detect heterozygous missense variants in 9 of 23 further patients with either megacystis-microcolon-intestinal hypoperistalsis syndrome or intestinal pseudo-obstruction. Variants thus identified, one of which still unreported, affect highly conserved regions of the ACTG2 gene that encodes a protein crucial for correct enteric muscle contraction. These findings provided evidence for a correlation between the clinical phenotype and genotype at the ACTG2 locus, a first step to improve the diagnosis and prognosis of these severe conditions.
Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping
Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application.
Beckerman, R C; Taussig, L M; Pinnas, J L
Two brothers, aged 3 and 6 years, respectively, had their pulmonary conditions diagnosed as idiopathic pulmonary hemosiderosis (IPH). Both boys had severe iron-deficiency anemia, chronic cough, hemoptysis, and exertional dyspnea, and one had recurrent epistaxis. The results of light microscopic lung histopathologic studies in both patients showed numerous hemosiderinladen macrophages and chronic interstitial pneumonitis. No specific patterns of immunofluorescence of the alveolar capillary basement membranes were found. The results of electron microscopic examinations showed intact alveolar and capillary basement membranes and no evidence of electron-dense deposits. The lack of clinical or biochemical evidence for renal disease as well as the absence of serum antinuclear and antibasement membrane antibodies excluded associated autoimmune disorders. Evaluation for milk-protein allergy was negative and neither child demonstrated a clinical response to a milk-free diet. Sequential pulmonary function studies performed over four years showed episodes of acute obstructive airway disease that correlated with pulmonary hemorrhage and mild persistent restrictive lung disease. The results of this family study suggested that some cases of IPH may have a genetic basis.
Barrera, Ana Madeleine; Vargas, Leslie
Pulmonary ossification is a rare and usually asymptomatic finding reported as incidental in lung biopsies. Similarly, idiopathic pulmonary hemosiderosis is a rare cause of pulmonary infiltrates. We report the case of a 64-year old man with chronic respiratory symptoms in whom these two histopathological findings converged.
Kleinschmidt, S; Meneses, F; Nolte, I; Hewicker-Trautwein, M
An evaluation of histologic findings in full-thickness biopsies from the gastrointestinal tract (GIT) from 64 dogs with chronic GIT disease symptoms was performed. In the majority of cases (38/64; 59%), intestinal lymphangiectasia and mucosal edema of unknown etiology were present. In 10 dogs (16%) an eosinophilic colitis, either alone or together with gastritis and/or enteritis, was found. In 5 dogs (8%) lymphocytic-plasmacytic enteritis or enterocolitis was diagnosed. Five dogs (8%) had an intestinal T-cell lymphoma. Samples from the remaining cases were histologically normal or did not allow for a final diagnosis. In contrast to reports about findings in endoscopic biopsies (which often are of varying quality or inadequate for diagnosis), in the majority of cases of this study, examination of full-thickness biopsies from the GIT allowed us to make a definitive histopathologic diagnosis. Furthermore, the study revealed that transmural biopsies are very helpful for diagnosing lymphoma.
Suchodolski, Jan S.; Dowd, Scot E.; Wilke, Vicky; Steiner, Jörg M.; Jergens, Albert E.
Background Canine idiopathic inflammatory bowel disease (IBD) is believed to be caused by a complex interaction of genetic, immunologic, and microbial factors. While mucosa-associated bacteria have been implicated in the pathogenesis of canine IBD, detailed studies investigating the enteric microbiota using deep sequencing techniques are lacking. The objective of this study was to evaluate mucosa-adherent microbiota in the duodenum of dogs with spontaneous idiopathic IBD using 16 S rRNA gene pyrosequencing. Methodology/Principal Findings Biopsy samples of small intestinal mucosa were collected endoscopically from healthy dogs (n = 6) and dogs with moderate IBD (n = 7) or severe IBD (n = 7) as assessed by a clinical disease activity index. Total RNA was extracted from biopsy specimens and 454-pyrosequencing of the 16 S rRNA gene was performed on aliquots of cDNA from each dog. Intestinal inflammation was associated with significant differences in the composition of the intestinal microbiota when compared to healthy dogs. PCoA plots based on the unweighted UniFrac distance metric indicated clustering of samples between healthy dogs and dogs with IBD (ANOSIM, p<0.001). Proportions of Fusobacteria (p = 0.010), Bacteroidaceae (p = 0.015), Prevotellaceae (p = 0.022), and Clostridiales (p = 0.019) were significantly more abundant in healthy dogs. In contrast, specific bacterial genera within Proteobacteria, including Diaphorobacter (p = 0.044) and Acinetobacter (p = 0.040), were either more abundant or more frequently identified in IBD dogs. Conclusions/Significance In conclusion, dogs with spontaneous IBD exhibit alterations in microbial groups, which bear resemblance to dysbiosis reported in humans with chronic intestinal inflammation. These bacterial groups may serve as useful targets for monitoring intestinal inflammation. PMID:22720094
Ohkubo, H; Fuyuki, A; Arimoto, J; Higurashi, T; Nonaka, T; Inoh, Y; Iida, H; Inamori, M; Kaneda, T; Nakajima, A
Chronic intestinal pseudo-obstruction (CIPO) is an intractable rare digestive disease manifesting persistent small bowel distension without any mechanical cause. Intestinal decompression is a key treatment, but conventional method including a trans-nasal small intestinal tube is invasive and painful. Therefore, a less invasive and tolerable new decompression method is urgently desired. We conducted a pilot study and assessed the efficacy and safety of percutaneous endoscopic gastro-jejunostomy (PEG-J) decompression therapy in CIPO patients. Seven definitive CIPO patients (2 males and 5 females) were enrolled. All patients received PEG-J decompression therapy. The number of days with any abdominal symptoms in a month (NODASIM), body mass index (BMI), serum albumin level (Alb), and small intestinal volume before and after PEG-J were compared in all patients. Percutaneous endoscopic gastro-jejunostomy was well tolerated and oral intake improved in all patients. NODASIM has significantly decreased (24.3 vs 9.3 days/months) and BMI/Alb have significantly increased (14.9 vs 17.2 kg/m(2) and 2.6 vs 3.8 g/dL, respectively), whereas total volume of the small intestine has not significantly reduced (4.05 vs 2.59 L, P=.18). Reflux esophagitis and chemical dermatitis were observed in one case but was successfully treated conservatively. Percutaneous endoscopic gastro-jejunostomy decompression therapy can contribute greatly to improvement of abdominal symptoms and nutritional status in CIPO patients. Although sufficient attention should be paid to acid reflux symptoms, PEG-J has the potential to be a non-invasive novel decompression therapy for CIPO available at home. However, accumulation of more CIPO patients and long-term observation are needed (UMIN000017574). © 2017 John Wiley & Sons Ltd.
van Manen, Mirjam J G; Birring, Surinder S; Vancheri, Carlo; Cottin, Vincent; Renzoni, Elisabetta A; Russell, Anne-Marie; Wijsenbeek, Marlies S
Many patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably "multifactorial" and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF.
Martín-Láez, Rubén; Vázquez-Barquero, Alfonso
Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marqués de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure >15mmHg, or B-waves present in >10% of overnight recording; pressure-volume index <15ml, or resistance to cerebrospinal fluid outflow (ROUT) >4.5mmHg/ml/min in bolus infusion test; ROUT >12mmHg/ml/min, intracranial pressure >22mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high-volume cerebrospinal fluid withdrawal. The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.
Cusimano, Alessia; Abdelghany, Ahmed Mohammed Alaaeldien Beniamin; Donadini, Andrea
. Although the patient has an intestinal mal-rotation which could explain the abdominal painful symptoms, it is not possible to exclude other concomitant causes, such as perihepatitis on pelvic inflammatory disease or neuroendocrine tumors. Even if all these diseases are rarely seen in daily clinical practice, they should be considered in the differential diagnosis of chronic intermittent abdominal pain in a young woman.
Vincent, Stephen J; Lee, Graham A
Acquired limbal stem cell deficiency (LSCD) describes a condition in which the corneal limbal stem cells are altered or destroyed, typically due to ocular trauma, chronic allergy or inflammation. Idiopathic LSCD is a term used to describe limbal stem cell failure in the absence of any identifiable causative factor. While several cases of adult-onset LSCD have been identified previously, this case report describes a rare presentation of bilateral asymmetric idiopathic paediatric limbal stem cell deficiency in a sixteen-year-old male with an otherwise unremarkable ocular history.
Ben-Shlomo, Y; Sieradzan, K
Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial. PMID:7619574
KASPAREK, M. S.; FATIMA, J.; IQBAL, C. W.; DUENES, J. A.; SARR, M. G.
Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long-term effects of extrinsic denervation on functional non-adrenergic, non-cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age-matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently in both groups, greater in NC than in SBT. The VIP antagonist ([D-p-Cl-Phe6,Leu17]-VIP) and the nitric oxide synthase inhibitor L-NG-nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than in SBT. The substance P antagonist ([D-Pro2,D-Trp7,9]-substance P) inhibited effects of exogenous substance P and increased the EFS-induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT. PMID:17971029
Jäkel, J; Heise, J W; Gassler, N; Dietrich, C G
Only few case studies address pseudo-obstruction, a disorder - which often frustrates clinicians and patients due to an unclear diagnosis and limited therapeutic options. Thus, the aim of this paper is to investigate a relevant case concerning a patient presenting with symptoms of acquired chronic intestinal pseudo-obstruction (CIPO). After one year of extensive diagnostic tests and unsuccessful treatment with prokinetics, the patient underwent a subtotal ileocolectomy. The histology of the intestinal specimen revealed continuous atrophy and fibrosis mainly within the circular, inner muscle layer of muscularis propria of the ileum and colon. Even though serum markers were lacking, a subsequent skin biopsy showed signs of scleroderma supporting an initial diagnosis of intestinal involvement in systemic sclerosis. Despite treatment with steroids and methotrexate, the increasingly emaciated patient died. In conclusion, there is a bias against the publishing of pseudo-obstruction studies, in particular, due to the obscure underlying causes. To raise awareness of this problem, we call for clinicians to systematically generate comprehensive data about patients presenting these symptoms.
Leppkes, Moritz; Becker, Christoph; Ivanov, Ivaylo I; Hirth, Sebastian; Wirtz, Stefan; Neufert, Clemens; Pouly, Sandrine; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Becher, Burkhard; Littman, Dan R; Neurath, Markus F
IL-17-producing CD4(+) T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)gamma, which regulates Th17 differentiation, in chronic intestinal inflammation. Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)-, IL-17F-, IL-22-, and RORgamma-deficient CD4(+)CD25(-) T cells in RAG1-null mice. Adoptive transfer of IL-17A-, IL-17F-, or IL-22-deficient T lymphocytes into RAG1-null mice caused severe colitis that was indistinguishable from that caused by wild-type cells. In contrast, transfer of RORgamma-null T cells failed to increase mucosal IL-17 cytokine levels and did not induce colitis. Treatment with IL-17A was able to restore colitis after transfer of RORgamma-null T cells, indicating a crucial role for Th17 cells in pathogenesis. Treatment of RAG1 mice that received IL-17F-null (but not wild-type) T cells with a neutralizing anti-IL-17A antibody significantly suppressed disease, indicating redundant biological effects of IL-17A and IL-17F. We have identified a crucial role of RORgamma-expressing Th17 cells in chronic intestinal inflammation. RORgamma controls IL-17A and IL-17F production, and these cytokines have a redundant but highly pathogenic role in gut inflammation. Reagents that target RORgamma or a combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis.
... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Intestine Transplant Although it is possible for a living donor to donate an intestine segment, most intestine transplants involve a whole organ ...
Leonhardt, L; Geldszus, R; Molitor, S J
In a 39-year-old patient with chronic progressive idiopathic pulmonary fibrosis, the genetic aspects, course and therapeutic possibilities of the disease are discussed. In February, 1987, the English-born patient, Anthony V., attended for initial examination on account of progressive dyspnoea, on which occasion radiology and pulmonary function analysis revealed advanced pulmonary fibrosis. The patient's family history revealed a familial genesis, since both his father (?) and his sister had died of this disease. A comparative of the patient's chest films with original chest films of his sister revealed almost identical findings. Within the previous twelve months, follow-up examinations done on A.V. revealed an increase in the restrictive component (reduction of vital capacity from 2,400 ml to 1,500 ml), development of partial respiratory failure at rest, and global respiratory failure in response to mild ergometric exercise despite intermittent high-dose steroid administrations superimposed on long-term, low-dose steroid therapy. The unfavourable evolution observed over the past 12 months is underscored by an increase in mean pulmonary arterial pressure from 18 mmHg initially to a present 34 mmHg at rest, and 46 mmHg under submaximal ergometric loading. The only option still left to the patient is the possibility of a lung transplantation, which - probably initially unilateral - is scheduled to be carried out in the near future at the Chest Surgery Department of the Medical University at Hannover.
Gangadharan, Geethu; Criton, Sebastian; Surendran, Divya
Acquired idiopathic generalized anhidrosis is a rare condition, where the exact pathomechanism is unknown. We report a case of acquired idiopathic generalized anhidrosis in a patient who later developed lichen planus. Here an autoimmune-mediated destruction of sweat glands may be the probable pathomechanism.
Pohl, C S; Medland, J E; Mackey, E; Edwards, L L; Bagley, K D; DeWilde, M P; Williams, K J; Moeser, A J
Early life adversity (ELA) is a risk factor for development of gastrointestinal disorders later in life. The underlying mechanisms through which ELA and sex interact to influence disease susceptibility remains poorly understood. Utilizing a porcine early weaning stress (EWS) model to mimic ELA, we investigated the long-term effects of EWS on functional diarrhea, ileal permeability, mast cell activity and mast cell relationship with enteric ganglia. Juvenile and adult EWS pigs exhibited chronic, functional diarrhea (EWS 43.6% vs late wean control(LWC) 4.8%, P<.0001), increased intestinal permeability (2 fold increase EWS vs LWC, P<.0001), and mast cell numbers (at 7 weeks and 20 weeks ~1.6 fold increase EWS vs LWC, P<.05). Compared with EWS male castrates (Male-C), females EWS pigs exhibited more frequent diarrhea (58.8% vs 29.9%, P=.0016), and increased intestinal permeability (1-2 fold higher in EWS females, P<.001). Increased mast cell numbers and their enhanced co-localization with neuronal ganglia were observed in both Male-C and female EWS pigs; however, female pigs exhibited greater release of mast cell tryptase upon activation with c48/80 (~1.5 fold increase, P<.05), compared with Male-C pigs. These data demonstrate that pigs exposed to ELA exhibit increased vulnerability to functional diarrhea, intestinal permeability and mast cell activity. Further, these studies also showed that EWS female and Male-C pigs exhibited dimorphic responses to EWS with female piglets exhibited greater susceptibility and severity of diarrhea, intestinal permeability and mast cell tryptase release. Together, these findings mimic some of the key pathophysiologic findings in human functional GI disorders functional gastrointestinal disorders (FGIDs) suggesting that the EWS porcine model could be a valuable preclinical translational model for FGID research associated with ELA. © 2017 John Wiley & Sons Ltd.
Gálvez, Julio; Garrido, Margarita; Merlos, Manuel; Torres, Maria Isabel; Zarzuelo, Antonio
The present study was undertaken to investigate the intestinal anti-inflammatory effects of UR-12746 on the acute and chronic stages of a trinitrobenzene sulphonic acid (TNBS) experimental model of inflammatory bowel disease (IBD) in the rat. UR-12746 is a novel, locally-acting compound which combines, through an azo bond, 5-aminosalicylic (5-ASA) and UR-12715, a potent platelet activating factor (PAF)-antagonist. UR-12746 oral pretreatment of colitic rats (50 and 100 mg kg−1) reduced acute colonic damage when evaluated 2 days after colonic insult. Postreatment for 4 weeks with UR-12746 (50 and 100 mg kg−1) resulted in a faster recovery of the damaged colonic mucosa, which was macroscopically significant from the third week. The intestinal anti-inflammatory effect of UR-12746 was associated with a decrease in leukocyte infiltration in the colonic mucosa, which was evidenced both biochemically, by a reduction in myeloperoxidase activity, and histologically, by a lower leukocyte count after morphometric analysis. This effect was higher than that seen with sulphasalazine, when assayed at the same doses and in the same experimental conditions. Several mechanisms can be involved in the beneficial effects showed by UR-12746: inhibition of leukotriene B4 synthesis in the inflamed colon, improvement of the altered colonic oxidative status, and reduction of colonic interleukin-1β production. The results suggest that the intestinal anti-inflammatory activity of UR-12746 can be attributed to the additive effects exerted by 5-ASA and UR-12715, the PAF antagonist compound, that are released in the colonic lumen after reduction of the azo bond by the intestinal bacteria. PMID:10952687
Manoharan, Palanikumar; Gayam, Swapna; Arthur, Subha; Palaniappan, Balasubramanian; Singh, Soudamani; Dick, Gregory M.
Na-K-ATPase, an integral membrane protein in mammalian cells, is responsible for maintaining the favorable intracellular Na gradient necessary to promote Na-coupled solute cotransport processes [e.g., Na-glucose cotransport (SGLT1)]. Inhibition of brush border membrane (BBM) SGLT1 is, at least in part, due to the diminished Na-K-ATPase in villus cells from chronically inflamed rabbit intestine. The aim of the present study was to determine the effect of Na-K-ATPase inhibition on the two major BBM Na absorptive pathways, specifically Na-glucose cotransport and Na/H exchange (NHE), in intestinal epithelial (IEC-18) cells. Na-K-ATPase was inhibited using 1 mM ouabain or siRNA for Na-K-ATPase-α1 in IEC-18 cells. SGLT1 activity was determined as 3-O-methyl-d-[3H]glucose uptake. Na-K-ATPase activity was measured as the amount of inorganic phosphate released. Treatment with ouabain resulted in SGLT1 inhibition at 1 h but stimulation at 24 h. To further characterize this unexpected stimulation of SGLT1, siRNA silencing was utilized to inhibit Na-K-ATPase-α1. SGLT1 activity was significantly upregulated by Na-K-ATPase silencing, while NHE3 activity remained unaltered. Kinetics showed that the mechanism of stimulation of SGLT1 activity was secondary to an increase in affinity of the cotransporter for glucose without a change in the number of cotransporters. Molecular studies demonstrated that the mechanism of stimulation was not secondary to altered BBM SGLT1 protein levels. Chronic and direct silencing of basolateral Na-K-ATPase uniquely regulates BBM Na absorptive pathways in intestinal epithelial cells. Specifically, while BBM NHE3 is unaffected, SGLT1 is stimulated secondary to enhanced affinity of the cotransporter. PMID:25652450
Ma, Zhengwei; Zhang, Xizhong
To investigate the long-term effect of dietary fiber complex (DFC) on intestinal structure and function in hypercholesterolemic rats, 60 healthy SD rats were feed with food rich in lipids and hypercholesterolemic animal models were established. The animals were randomly divided into 5 groups. Rats were fed DFC at levels of 4%, 16%, or 64% for three month in the experimental groups. Wheat fiber was used in the hypercholesterolemic control (HC) group and rats feeding on normal food were used as normal control (NC). Morphology of the small intestine, reticum and caecum were observed by light and electron microscope examination. Intestinal function was measured physically. The results showed that (1) compared with NC group, fecal weight was significantly raised in DFC group of higher level (group D and E, P < 0.05); (2) the weights of small intestine wall in D and E group were significantly higher than those of NC and HC group and weights of caecum wall in E group were significantly higher than those of NC and HC group (P < 0.05); (3) widen villi and thickened muscle layer of small intestine were observed in DFC group of higher level. No demonstrable changes in reticulum morphology in any group of animals were found under the observation of light microscope (4) microvilla becoming short and/or absent, mitochondria swelling, impairment of the integrity of the cristae were commonly observed in DFC groups. Conclusions Long-term intake of DFC composed mainly of Hippophae rhamnoides L, Bran, oat bran and guar gum at higher levels might induce some morphological changes of intestine and caecum. Therefore, DFC might be used at low level as an effective cholesterol-lowering agent.
A multi-centre, single-arm, open-label study evaluating the safety and efficacy of fixed dose rituximab in patients with refractory, relapsed or chronic idiopathic thrombocytopenic purpura (R-ITP1000 study).
Tran, Huyen; Brighton, Tim; Grigg, Andrew; McRae, Simon; Dixon, Joanna; Thurley, Daniel; Gandhi, Maher K; Truman, Matt; Marlton, Paula; Catalano, John
The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 10(9) /l and ≤50 × 10(9) /l) idiopathic thrombocytopenic purpura (ITP). Patients received two doses of rituximab (1000 mg) on days 1 and 15 and were followed-up on weeks 1-8, 12, 26, 39 and 52. A total of 122 patients were included in the safety population; efficacy was analysed in 108 patients. Overall response rate (ORR) at week 8, defined as the proportion of patients achieving complete response (CR; platelet count >150 × 10(9) /l) or partial response (PR; platelet count >50 × 10(9) /l) was 44%. Therapeutic response, defined as achieving a response at week 8, with at least a minor response (MR; platelet count >30 × 10(9) /l), sustained up to weeks 26 and 52 and accompanied by a reduction in ITP medications, was achieved in 44% (week 26) and 35% (week 52) of patients, respectively. Treatment was well tolerated with no safety concerns. While this study failed to meet its primary endpoint of an ORR of 50%, the efficacy of two fixed doses of rituximab appear to provide similar efficacy to the standard 375 mg/m(2) four-dose schedule in relapsed/chronic ITP. © 2014 John Wiley & Sons Ltd.
Katoch, Pervez; Bhardwaj, Subhash
Intussusception is defined as telescoping of a segment of gastrointestinal tract into an adjacent one. In small children, it is the commonest cause of intestinal obstruction. More than 90% of childhood intussusceptions are idiopathic. We report a rare case of localized small intestinal lymphangiectasia, presenting as intussusception in a 6-month-old male child. The child presented with features of acute intestinal obstruction for which he was later operated. The gross examination of excised ileocecal mass revealed intussusception. Histopathologic examination revealed lymphangiectasia of small intestine, which acted as a lead point for ileocecal intussusception. Postoperative period was uneventful.
Li, Yihang; Song, Zehe; Kerr, Katelyn A; Moeser, Adam J
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0.8 fold) and colon (by 0.7 fold). Ileal sodium glucose linked transporter 1 (SGLT-1) function, measured as glucose-induced changes in short-circuit current (Isc), was diminished (by 52%) in CSS pigs, associated with reduced body weight gain and feed efficiency. Although reductions in SGLT-1 function were observed in CSS pigs, mRNA expression for SGLT-1, villus heights were increased in CSS pigs. Corticotropin releasing factor (CRF) mRNA was upregulated (by 0.9 fold) in the ileum of CSS pigs but not in the colon. Urocortin 2 (Ucn2) mRNA was upregulated (by 1.5 fold) in the colon of CSS pigs, but not in the ileum. In CSS pigs, a downregulation of pro-inflammatory cytokines mRNA (IL1B, TNFA, IL8, and IL6) was observed in both ileum and colon, compared with controls. In contrast CSS induced a marked upregulation of mRNA for IL10 and mast cell chymase gene (CMA1) in the ileum and colon. Together, these data demonstrate that chronic stress in pigs results in significant alterations in intestinal barrier and nutrient transport function and neuro-immune mediator and receptor expression.
Li, Yihang; Song, Zehe; Kerr, Katelyn A.; Moeser, Adam J.
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0.8 fold) and colon (by 0.7 fold). Ileal sodium glucose linked transporter 1 (SGLT-1) function, measured as glucose-induced changes in short-circuit current (Isc), was diminished (by 52%) in CSS pigs, associated with reduced body weight gain and feed efficiency. Although reductions in SGLT-1 function were observed in CSS pigs, mRNA expression for SGLT-1, villus heights were increased in CSS pigs. Corticotropin releasing factor (CRF) mRNA was upregulated (by 0.9 fold) in the ileum of CSS pigs but not in the colon. Urocortin 2 (Ucn2) mRNA was upregulated (by 1.5 fold) in the colon of CSS pigs, but not in the ileum. In CSS pigs, a downregulation of pro-inflammatory cytokines mRNA (IL1B, TNFA, IL8, and IL6) was observed in both ileum and colon, compared with controls. In contrast CSS induced a marked upregulation of mRNA for IL10 and mast cell chymase gene (CMA1) in the ileum and colon. Together, these data demonstrate that chronic stress in pigs results in significant alterations in intestinal barrier and nutrient transport function and neuro-immune mediator and receptor expression. PMID:28170426
Hoffmann, Micha; Kim, Sandra C; Sartor, R Balfour; Haller, Dirk
Monoassociation of germfree Interleukin 10 gene deficient (IL-10-/-) 129SvEv but not wild-type mice with Enterococcus faecalis induces severe chronic colitis. Bacterial strain-specific effects on the development of chronic intestinal inflammation are not understood. We investigated the molecular mechanisms of E. faecalis OG1RF (human clinical isolate, colitogenic) and E. faecalis ms2 (endogenous isolate from an IL-10-/- mouse) in initiating chronic experimental colitis using IL-10-/- mice. Monoassociation of IL-10-/- mice for 14 weeks revealed significant differences in colonic inflammation (3.6 +/- 0.2 and 2.4 +/- 0.6 for OG1RF and ms2, respectively) (n = 5 mice in each group) (histological scoring (0-4)). Consistent with the tissue pathology, gene expression of the pro-inflammatory chemokine interferon-gamma inducible protein-10 (IP-10) was significantly higher in intestinal epithelial cells (IEC) derived from E. faecalis OG1RF monoassociated IL-10-/- mice. We further compared the differentially E. faecalis induced colitis on the epithelial level by 2D-SDS PAGE coupled with MALDI-TOF MS. Proteome analysis identified 13 proteins which were differentially regulated during disease progression in the epithelium of E. faecalis-monoassociated IL-10-/- mice. Regulation of Alix/AIP1 protein expression and ERK1/2 phosphorylation was validated in primary IEC and epithelial cell lines, suggesting a protective role for Alix/AIP1 in the process of disease progression. Alix/AIP1 protein expression was further characterized in epithelial cell lines using siRNA-mediated knock-down. Our study demonstrates E. faecalis strain-specific induction of colitis in IL-10-/- mice after 14 weeks of monoassociation. Our study suggests that Alix/AIP1 protein expression and ERK1/2 activation are decreased in severe colitis.
Masson, Emmanuelle; Chen, Jian-Min; Audrézet, Marie-Pierre; Cooper, David N; Férec, Claude
Idiopathic chronic pancreatitis (ICP) has traditionally been defined as chronic pancreatitis in the absence of any obvious precipitating factors (e.g. alcohol abuse) and family history of the disease. Studies over the past 15 years have revealed that ICP has a highly complex genetic architecture involving multiple gene loci. Here, we have attempted to provide a conservative assessment of the major genetic causes of ICP in a sample of 253 young French ICP patients. For the first time, conventional types of mutation (comprising coding sequence variants and variants at intron/exon boundaries) and gross genomic rearrangements were screened for in all four major pancreatitis genes, PRSS1, SPINK1, CTRC and CFTR. For the purposes of the study, synonymous, intronic and 5'- or 3'-untranslated region variants were excluded from the analysis except where there was persuasive evidence of functional consequences. The remaining sequence variants/genotypes were classified into causative, contributory or neutral categories by consideration of (i) their allele frequencies in patient and normal control populations, (ii) their presumed or experimentally confirmed functional effects, (iii) the relative importance of their associated genes in the pathogenesis of chronic pancreatitis and (iv) gene-gene interactions wherever applicable. Adoption of this strategy allowed us to assess the pathogenic relevance of specific variants/genotypes to their respective carriers to an unprecedented degree. The genetic cause of ICP could be assigned in 23.7% of individuals in the study group. A strong genetic susceptibility factor was also present in an additional 24.5% of cases. Taken together, up to 48.2% of the studied ICP patients were found to display evidence of a genetic basis for their pancreatitis. Whereas these particular proportions may not be extrapolable to all ICP patients, the approach employed should serve as a useful framework for acquiring a better understanding of the role of
Sandek, Anja; Swidsinski, Alexander; Schroedl, Wieland; Watson, Alastair; Valentova, Miroslava; Herrmann, Ralph; Scherbakov, Nadja; Cramer, Larissa; Rauchhaus, Mathias; Grosse-Herrenthey, Anke; Krueger, Monika; von Haehling, Stephan; Doehner, Wolfram; Anker, Stefan D; Bauditz, Juergen
Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia. The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF. A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured. Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A-antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia. Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in
Lackeyram, D; Young, D; Kim, C J; Yang, C; Archbold, T L; Mine, Y; Fan, M Z
Intestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS treatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold higher (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF-alpha and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundance of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion, administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in the jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans Associated with chronic bowel inflammation.
Oztas, Erkin; Ozin, Yasemin; Onder, Fatih; Onal, Ibrahim Koral; Oguz, Dilek; Kocaefe, Cetin
The mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE) is a rare and life-threatening, autosomal recessive, multisystem disorder, caused by the mutations in the thymidine phosphorylase gene. Herein, we report a case of a 21 year-old male with a long history of intestinal pseudo-obstruction who was diagnosed with MNGIE syndrome after an extensive examination. In this case, our objective was to bring the gastroenterologist's attention to this difficult to diagnose syndrome in the coexistence of intestinal pseudo-obstruction and neurologic manifestations. The patient was a member of a consanguineous family of six children, in whom two sisters had died due to this disorder and one sister was affected and is still alive. The patient presented with cachexia, abdominal pain, diarrhea and muscle weakness, and was previously considered to have gluten sensitive enteropathy and treated with dietary solutions.
Wehrmann, M; Bohle, A; Bogenschütz, O; Eissele, R; Freislederer, A; Ohlschlegel, C; Schumm, G; Batz, C; Gärtner, H V
A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo-interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis.
Kajiura, Takayuki; Takeda, Tomoko; Sakata, Shinji; Sakamoto, Mitsuo; Hashimoto, Masaki; Suzuki, Hideki; Suzuki, Manabu; Benno, Yoshimi
Elemental diet (ED) has been used as an enteral nutritional therapy for Crohn's disease. However, the precise mechanisms of ED remain unclear. In interleukin-10 (IL-10)-deficient cell-transferred mice, we investigated the change of intestinal microbiota with ED using molecular terminal-restriction fragment length polymorphism (T-RFLP) analysis and culture method, and evaluated its influence on therapeutic effects of ED. ED significantly suppressed intestinal inflammation. The total amount of bacteria in colitis mice fed the regular diet was higher than in normal mice but decreased in colitis mice fed ED. T-RFLP profiles of the ED group markedly differed from those of the regular diet groups. The diversity of bacterial species in the ED group decreased to 60% of that found in the regular diet groups. Among the cultivated bacteria, the change in lactic acid bacteria composition was remarkable. Lactobacillus reuteri and L. johnsonii decreased and Enterococcus faecalis and E. durans increased in the ED group. The culture supernatant of L. reuteri isolates induced significant tumor necrosis factor-alpha (TNF-alpha) and IL-6 activity in RAW 264 cells, while the culture supernatant of E. faecalis and E. durans barely induced their activity. These data suggested that reduction in amount and diversity of intestinal microbiota and decrease of proinflammatory cytokines via a change in composition of lactic acid bacteria by ED seem to contribute to reduction of bowel inflammation in this model.
Chen, Jiun-Rong; Chen, Ya-Ling; Peng, Hsiang-Chi; Lu, Yu-An; Chuang, Hsiao-Li; Chang, Hsiao-Yun; Wang, Hsiao-Yun; Su, Yu-Ju; Yang, Suh-Ching
The aim of this study was to investigate the ameliorative effects of fish oil on hepatic injury in ethanol-fed rats based on the intestinal permeability and microbiota. Rats were assigned to 6 groups and fed either a control diet or an ethanol diet such as C (control), CF25 (control with 25% fish oil), CF57 (control with 57% fish oil), E (ethanol), EF25 (ethanol with 25% fish oil), and EF57 (ethanol with 57% fish oil) groups. Rats were sacrificed at the end of 8 weeks. Plasma aspartate aminotransferase (AST) and aminotransferase (ALT) activities, hepatic cytokines, and plasma endotoxin levels were significantly higher in the E group. In addition, hepatic histopathological analysis scores in the E group were significantly elevated. Rats in the E group also showed increased intestinal permeability and decreased numbers of fecal Bifidobacterium. However, plasma AST and ALT activities and hepatic cytokine levels were significantly lower in the EF25 and EF57 groups. Histological changes and intestinal permeability were also improved in the EF25 and EF57 groups. The fecal Escherichia coli numbers were significantly lower, but fecal Bifidobacterium numbers were significantly higher in the EF25 and EF57 groups. PMID:27143963
Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H
Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Wong, Uni; Yfantis, Harris; Xie, Guofeng
Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia. PMID:27190661
Moussaoui, Nabila; Jacobs, Jonathan P; Larauche, Muriel; Biraud, Mandy; Million, Mulugeta; Mayer, Emeran; Taché, Yvette
Background/Aims Wistar rat dams exposed to limited nesting stress (LNS) from post-natal days (PND) 2 to 10 display erratic maternal behavior, and their pups show delayed maturation of the hypothalamic-pituitary-adrenal axis and impaired epithelial barrier at PND10 and a visceral hypersensitivity at adulthood. Little is known about the impact of early life stress on the offspring before adulthood and the influence of sex. We investigated whether male and female rats previously exposed to LNS displays at weaning altered corticosterone, intestinal permeability, and microbiota. Methods Wistar rat dams and litters were maintained from PND2 to 10 with limited nesting/bedding materials and thereafter reverted to normal housing up to weaning (PND21). Control litters had normal housing. At weaning, we monitored body weight, corticosterone plasma levels (enzyme immunoassay), in vivo intestinal to colon permeability (fluorescein isothiocyanate-dextran 4 kDa) and fecal microbiota (DNA extraction and amplification of the V4 region of the 16S ribosomal RNA gene). Results At weaning, LNS pups had hypercorticosteronemia and enhanced intestinal permeability with females > males while body weights were similar. LNS decreased fecal microbial diversity and induced a distinct composition characterized by increased abundance of Gram positive cocci and reduction of fiber-degrading, butyrate-producing, and mucus-resident microbes. Conclusions These data indicate that chronic exposure to LNS during the first week post-natally has sustained effects monitored at weaning including hypercorticosteronemia, a leaky gut, and dysbiosis. These alterations may impact on the susceptibility to develop visceral hypersensitivity in adult rats and have relevance to the development of irritable bowel syndrome in childhood. PMID:27829577
Moussaoui, Nabila; Jacobs, Jonathan P; Larauche, Muriel; Biraud, Mandy; Million, Mulugeta; Mayer, Emeran; Taché, Yvette
Wistar rat dams exposed to limited nesting stress (LNS) from post-natal days (PND) 2 to 10 display erratic maternal behavior, and their pups show delayed maturation of the hypothalamic-pituitary-adrenal axis and impaired epithelial barrier at PND10 and a visceral hypersensitivity at adulthood. Little is known about the impact of early life stress on the offspring before adulthood and the influence of sex. We investigated whether male and female rats previously exposed to LNS displays at weaning altered corticosterone, intestinal permeability, and microbiota. Wistar rat dams and litters were maintained from PND2 to 10 with limited nesting/bedding materials and thereafter reverted to normal housing up to weaning (PND21). Control litters had normal housing. At weaning, we monitored body weight, corticosterone plasma levels (enzyme immunoassay), in vivo intestinal to colon permeability (fluorescein isothiocyanate-dextran 4 kDa) and fecal microbiota (DNA extraction and amplification of the V4 region of the 16S ribosomal RNA gene). At weaning, LNS pups had hypercorticosteronemia and enhanced intestinal permeability with females > males while body weights were similar. LNS decreased fecal microbial diversity and induced a distinct composition characterized by increased abundance of Gram positive cocci and reduction of fiber-degrading, butyrate-producing, and mucus-resident microbes. These data indicate that chronic exposure to LNS during the first week post-natally has sustained effects monitored at weaning including hypercorticosteronemia, a leaky gut, and dysbiosis. These alterations may impact on the susceptibility to develop visceral hypersensitivity in adult rats and have relevance to the development of irritable bowel syndrome in childhood.
Fuyuki, Akiko; Ohkubo, Hidenori; Higurashi, Takuma; Iida, Hiroshi; Inoh, Yumi; Inamori, Masahiko; Nakajima, Atsushi
Although chronic intestinal pseudo-obstruction (CIPO) is a rare and extremely severe functional digestive disorder, its clinical course and severity show various patterns. We assessed small bowel peristalsis in CIPO patients using cine-MRI (video-motion MRI) and their clinical characteristics to evaluate the clinical importance of performing cine-MRI in patients with this intractable disease. The medical records of 131 patients referred to our institution with a suspected diagnosis of CIPO between 2010 and 2015 were retrospectively evaluated. Thirty-three patients (22 female/11 male; age range 16-79 years) who met the criteria for CIPO and underwent cine-MRI were enrolled. Mean luminal diameter (MLD), contraction ratio (CR), and contraction cycle (CC) were determined and compared with these parameters in healthy volunteers. Clinical outcomes in patients with CIPO were also evaluated. The median follow-up time was 25.2 months (range, 1-65 months). Of the 33 patients with CIPO, 23 (70 %) showed apparently disturbed small intestinal peristalsis, whereas 10 (30 %) did not. The percentage of patients requiring intravenous alimentation was significantly higher (p = 0.03), and the mean serum albumin level was significantly lower (p = 0.04), in patients with than without impaired small intestinal peristalsis. Although both cine-MRI and CT findings in the latter ten cases were within the normal range, MLD and CR differed significantly from healthy volunteers. Cine-MRI is useful in predicting severe clinical features in patients with CIPO, and in detecting slightly impaired small contractility that cannot be detected on CT.
... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...
Lee, Jason Kihyuk; Enns, Robert
Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted. PMID:18081217
... rule out other conditions or infections, such as Lyme disease , that may cause similar symptoms or occur along ... ESR) Bones, Muscles, and Joints Evaluate Your Child's Lyme Disease Risk Word! Arthritis Arthritis Lupus Juvenile Idiopathic Arthritis ( ...
Peyrí Rey, E; Riverola Manzanilla, A; Cañas Tello, M A
A rare case of asymtomatic synchronous bilateral granulomatous orchitis idiopathic is decribed. In the scrotal ultrasonography are multiple hypoecoic areas, differential diagnosis between testicular tumor and granulomatous orchitis is very difficult in any examination by histological findings.
Benard, G; Costa, A N; Leopércio, A P S; Vicentini, A P; Kono, A; Shikanai-Yasuda, M A
Current knowledge on the natural history of paracoccidioidomycosis states that the chronic form of the disease results from reactivation of quiescent foci established years or decades before during the primary lung infection. Once reactivated, the fungi can disseminate to virtually any organ or system. We present herein two chronic paracoccidioidomycosis patients with a single organ involvement that points to an alternative pathogenesis of the mycosis. These patients suggest that the chronic form may also arise from reactivation of foci not confined to the lungs, due to the early dissemination of yeast cells during the primary infection.
Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).
Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal
Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.
Ohkusa, Toshifumi; Koido, Shigeo
There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
An intestinal obstruction occurs when food or stool cannot move through the intestines. The obstruction can be complete or partial. ... abdomen Inability to pass gas Constipation A complete intestinal obstruction is a medical emergency. It often requires surgery. ...
Paralytic ileus; Intestinal volvulus; Bowel obstruction; Ileus; Pseudo-obstruction - intestinal; Colonic ileus ... objects that are swallowed and block the intestines) Gallstones (rare) Hernias Impacted stool Intussusception (telescoping of 1 ...
Leiomyoma - intestine ... McLaughlin P, Maher MM. The duodenum and small intestine. In: Adam A, Dixon AK, Gillard JH, Schaefer- ... Roline CE, Reardon RF. Disorders of the small intestine. In: Marx JA, Hockberger RS, Walls RM, et ...
... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...
Julio-Pieper, M; Bravo, J A
The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses.
Ley, Brett; Collard, Harold R
Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence) and public health impact (ie, health care costs and resource utilization). Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging. PMID:24348069
Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio
Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.
Husain, Qasim; Zouzias, Alexandros; Kanumuri, Vivek V; Eloy, Jean Anderson; Liu, James K
Idiopathic granulomatous hypophysitis (IGH) is an extremely rare chronic inflammatory lesion of the pituitary gland. This condition typically presents with chronic onset of headache and slow development of visual deficits. Pituitary apoplexy is a clinical syndrome characterized by sudden onset of headache, vision loss, opthalmoplegia, and signs of meningeal irritation. Although IGH has been previously described in the literature, its presentation as clinical pituitary apoplexy is novel. We report, to our knowledge, the first patient with IGH manifesting as clinical pituitary apoplexy. Physicians involved in the treatment of pituitary disease should be aware of this rare entity. Copyright © 2013 Elsevier Ltd. All rights reserved.
Cross, J H
Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops. Images PMID:1576584
Cross, J H
Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops.
Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca; Luppi, Fabrizio
Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate. We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant. This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis.
Arenas-Pinto, A; Certad, G; Ferrara, G; Castro, J; Bello, M A; Núñez, L T
A cross sectional survey was conducted to determine the association between enteric parasites and diarrhoea in HIV-infected adults in Caracas. Three hundred and four patients were evaluated: 104 had acute diarrhoea, 113 chronic diarrhoea and 87 were controls. Isopora belli infection was associated with acute (P = 0.022) and chronic diarrhoea (P = 0.003), Entamoeba histolytica/dispar infection was also associated with both acute (P = 0.015) and chronic diarrhoea (P = 0.017). Strongyloides stercoralis (P = 0.003), and Cryptosporidium parvum (P = 0.017) infections were associated mainly with chronic episodes. Weight loss (P < 0.001), a non-infectious factor investigated, was significantly associated with diarrhoea. Eosinophilia, a laboratory parameter studied, was found to be associated with strongyloidiasis (P = 0.001), giardiasis (P = 0.001) and isoporiasis (P = 0.003). In summary, the presence of enteric parasites in HIV-infected patients from tropical urban areas with diarrhoea, with or without significant weight loss, must be considered. Similarly, eosinophilia might suggest parasitic infection in these patients.
Amato, Lauretta; Chiarini, Caterina; Berti, Samantha; Massi, Daniela; Fabbri, Paolo
A 41-year-old woman presented with a 3-year history of purpuric lesions followed by superficial, painful ulcers and development of lesions on the lower legs and on the dorsa of the feet, particularly in the summer. The patient was asymptomatic during the winter months. On physical examination she had irregular, scleroatrophic, white-ivory, coalescent lesions on a livedoid basis, with purpuric and, in some lesions, pigmented borders with numerous telangiectatic capillaries. These lesions were localized on the medial sides of the lower legs and on the dorsa of the feet (Figure 1). Laboratory investigations were normal or negative, including complete blood cell count, platelets, coagulation indexes, erythrocyte sedimentation rate, serum immunoglobulins, antinuclear antibodies, anti-double-stranded DNA, anticardiolipin, antiphospholipids, antineutrophilic cytoplasmic antibodies, circulating immunocomplexes, complement fractions (C3, C4), cryoglobulins, rheumatoid factor, and Rose-Waaler reaction. The only laboratory abnormality was an elevated fibrinogen level (472 mg/dL). Doppler velocimetry excluded a chronic venous insufficiency. Thoracic x-ray and abdominal ultrasound were normal. A digital photoplethysmograph revealed functional Raynaud's phenomenon. A biopsy specimen taken from a purpuric lesion showed an atrophic epidermis with parakeratosis and focal spongiosis. An increased number of small-sized vessels were observed within a sclerotic dermis. Most of the vessels in the upper dermis were dilated and showed endothelial swelling; some were occluded due to amorphous hyaline microthrombi (Figure 2). There were fibrinoid deposits around the vessels with thickening of the vessel walls. Extravasated erythrocytes were found throughout the upper and mid-dermis. There was a sparse perivascular lymphocytic infiltrate but no vasculitis. Direct immunofluorescence showed a perivascular microgranular deposit of IgM (+), C3 (++), and fibrinogen/fibrin (+++). On the basis of
Bäuerle, J; Egger, K; Harloff, A
This review describes the clinical findings as well as thes diagnostic and therapeutic options for idiopathic intracranial hypertension (pseudotumor cerebri). Furthermore, the pathophysiological concepts are discussed. Idiopathic intracranial hypertension is characterized by signs and symptoms of raised intracranial pressure with no established pathogenesis. Common symptoms include headaches, visual loss and pulsatile tinnitus. Treatment has two major goals: the alleviation of headaches and the preservation of vision. Weight loss and acetazolamide are the cornerstones in the treatment of the disorder. Drainage of cerebrospinal fluid, optic nerve sheath fenestration and stent angioplasty of a sinus stenosis can be employed in severe cases.
Kotwica, Tomasz; Szumarska, Joanna; Staniszewska-Marszalek, Edyta; Mazurek, Walentyna; Kosmala, Wojciech
Pulmonary artery aneurysm (PAA) is an uncommon lesion, which may be associated with different etiologies including congenital cardiovascular diseases, systemic vasculitis, connective tissue diseases, infections, and trauma. Idiopathic PAA is sporadically diagnosed by exclusion of concomitant major pathology. We report a case of a 56-year-old female with an idiopathic pulmonary artery dilatation identified fortuitously by echocardiography and confirmed by contrast-enhanced computed tomography. Neither significant pulmonary valve dysfunction nor pulmonary hypertension and other cardiac abnormalities which might contribute to the PAA development were found. Here, we describe echocardiographic and computed tomography findings and review the literature on PAA management.
Zuberbier, T; Oanta, A; Bogacka, E; Medina, I; Wesel, F; Uhl, P; Antépara, I; Jáuregui, I; Valiente, R
Bilastine is a novel nonsedative H(1)-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). The aim of this study was to compare the clinical efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg and placebo in CU patients with moderate-to-severe symptoms. Overall 525 male and female subjects aged 18-70 years were randomized to receive bilastine 20 mg, levocetirizine 5 mg or placebo, once daily for 28 days, in double-blind manner, in 46 centres across Europe and Argentina. Patients rated symptoms of pruritus, number of wheals, and maximum size of wheals (on predefined scales) as reflective (over past 12 h) symptoms twice daily, for assessment of change from baseline in the total symptoms scores (TSS) over 28 days as the primary efficacy measure. Changes in reflective and instantaneous symptoms scores, Dermatology Life Quality Index (DLQI), and CU-associated discomfort and sleep disturbance were assessed as secondary outcomes. Safety was assessed according to adverse events, laboratory tests and electrocardiograms. Bilastine reduced patients' mean reflective and instantaneous TSS from baseline to a significantly greater degree than placebo (P < 0.001); from day 2 onwards of treatment. The DLQI, general discomfort, and sleep disruption were also improved significantly in bilastine-treated patients as compared with placebo-treated patients (P < 0.001 for all parameters). Comparison with levocetirizine indicated both treatments to be equally efficacious as well as equally safe and well tolerated as compared with placebo. Bilastine 20 mg is a novel effective and safe treatment option for the management of CU.
Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d’Amati, Giulia
The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. PMID:27555800
Dianzani, C; Gaspardini, F; Persichetti, P; Brunetti, B; Pizzuti, A; Margiotti, K; Degener, A M
Scrotal elephantiasis is very rare disease in industrialized countries, where it is mainly due to surgery, irradiation or malignancies. It can be defined as idiopathic only when the possible congenital, infectious and compressive causes are excluded. We report a case of massive scrotal lymphoedema in an adult Caucasian patient, in Italy. He presented an extremely voluminous scrotal mass measuring 50 x 47 x 13 cm (weight 18 kg), which extended below his knees, invalidating all his daily activities. The patient was hospitalized in order to undergo to surgical treatment. Although genetic causes were searched and the possible role of infectious agents and compressive factors was evaluated, no etiology was ascertained. Histopathologic examination showed non-specific chronic inflammation, confirming the diagnosis of idiopathic elephantiasis. One year after surgical treatment, the patient is healthy without recurrence signs.
Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d'Amati, Giulia
The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis.
Montagnani, Marco; Abrahamsson, Anna; Gälman, Cecilia; Eggertsen, Gösta; Marschall, Hanns-Ulrich; Ravaioli, Elisa; Einarsson, Curt; Dawson, Paul A
The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM. PMID:17171805
Holschneider, A M
Motility disturbances of the small and large intestines are based on changes in the smooth-muscle potential, whereby the number of amplitudes and configuration of slow waves and of spike potentials as well as pattern, speed of propagation, and duration of the MMC are of crucial importance. Whereas the electromechanical principles of intestinal motility are sufficiently known, changes in the electromechanical activity in clinically manifest motility disturbances have as yet not been given due regard. Only recently, electromechanical measurements in the upper gastrointestinal tract and colon were performed in several gastrointestinal diseases of internal medicine. In the small intestine, changes in slow waves, spike potentials, and the MMC could be disclosed which are typical for hyperthyrosis, hypothyrosis, irritable bowel syndrome, bacterial diarrhea, primary and secondary intestinal pseudo-obstruction, short-bowel syndrome, postoperative bowel atonia, mechanical bowel obstruction, vagotomy, and diabetic enteropathy with disturbed gastric emptying. Regarding the colon, a disturbance in the electromechanical characteristics was found in irritable bowel syndrome, bacterial overgrowth in the small bowel, chronic constipation, and idiopathic intestinal pseudo-obstruction, which is probably identical with the clinical picture of adynamic ileus. Based on a thorough examination of the literature and on own results from electromechanical measurements in children, electromechanical disturbances have been narrowly defined.
Bennani, S; Ait Bolbarod, A; el Mrini, M; Kadiri, R; Benjelloun, S
The authors report a case of idiopathic renal arteriovenous fistula. The diagnosis was established angiographically in a 24 year old man presenting gross hematuria. Embolization of the fistula was performed. Efficiency of this treatment was appreciated clinically and by duplex renal ultrasonography. The characteristics of renal arteriovenous fistulas are reviewed.
Tuncer, Oğuz; Melek, Mehmet; Kaba, Sultan; Bulan, Keziban; Peker, Erdal
Though the perforation of the colon in neonates is rare, it is associated with more than 50% mortality in high-risk patients. We report a case of idiopathic neonatal perforation of the sigmoid colon in an 8-day-old, healthy, male neonate without any demonstrable cause. PMID:26023477
Brannan, Paul A; Kersten, Robert C; Kulwin, Dwight R
A 5-year-old girl referred for orbital cellulitis was found to have a right orbital mass. Computed tomography revealed a mass occupying the inferotemporal orbit, extending into the maxillary sinus. Biopsy yielded a diagnosis of sclerosing idiopathic orbital inflammation. She was successfully treated with prednisone.
Grace, Mary; Balachandran, Venu; Menon, Sooraj
Idiopathic central diabetes insipidus (CDI) is a rare disorder characterized clinically by polyuria and polydipsia, and an abnormal urinary concentration without any identified etiology. We report a case of central diabetes insipidus in a 60-year-old lady in the absence of secondary causes like trauma, infection, and infiltrative disorders of brain.
Hornberger, Brad J; Elmore, James M; Roehrborn, Claus G
Scrotal lymphedema (scrotal elephantiasis) is a condition that has historically been described in areas endemic to filariasis. We present a unique case of a 22-year-old man with idiopathic lymphedema isolated to the scrotum. After acquired causes of lymphedema were ruled out, the patient was treated with scrotectomy and scrotal reconstruction.
Bolaji, I I; Meehan, F P
Case Report--A 33-year-old woman was examined because of primary infertility. Hysterosalpingography plus laparoscopy led to a diagnosis of the extremely rare condition of pigmentosis of the fallopian tube, with complete tubal occlusion as the cause of the infertility. The condition appeared to be idiopathic.
... News) U.S. Medical Groups Sound the Alarm on Climate Change Additional Content Medical News Overview of Idiopathic Interstitial ... HealthDay U.S. Medical Groups Sound the Alarm on Climate Change WEDNESDAY, March 15, 2017 (HealthDay News) -- Climate change ...
Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L
To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.
Intestinal necrosis; Ischemic bowel - small intestine; Dead bowel - small intestine; Dead gut - small intestine; Infarcted bowel - small intestine; Atherosclerosis - small intestine; Hardening of the arteries - small intestine
Panaszek, Bernard; Pawłowicz, Robert; Grzegrzółka, Jędrzej; Obojski, Andrzej
Recent years of research have shed a new light on the role of IgE in immune reactions. It seems to be more than just a contribution to immediate type of allergic response. It appears that monomeric IgE may enhance mast cell activity without cross-linking of FcεRI by IgE specific allergen or autoreactive IgG anti-IgE antibodies. Monomeric IgE molecules are heterogeneous concerning their ability to induce survival and activation of mast cells only by binding the IgE to FcεRI, but not affecting degranulation of cells. It also turned out that IgE may react to autoantigens occurring in the blood not only in chronic spontaneous urticaria (CSU) but also in other autoimmune diseases. The aforementioned phenomena may promote the activity of mast cells/basophils in CSU that easily degranulate when influenced by various inner (autoreactive IgG against IgE and FcεRI, autoreactive IgE for self-antigens) and outer factors (cold, heat, pressure) or allergens. These findings forced the new approach to the role of autoimmunity, self-antigens and IgE autoantibodies in the pathology of CSU. CSU put in the scheme of autoreactive IgG and autoreactive IgE seems to be either a kind of an autoimmune disease or a clinical manifestation of some other defined autoimmune diseases or both.
Hoyoux, C.; Forget, P.P.; Borlee-Hermans, G.; Geubelle, F.
Intestinal permeability (IP) to /sup 51/Cr ethylenediamine tetraacetic acid was investigated in 47 children with chronic obstructive respiratory disease (CORD). Endoscopic duodenal biopsies were performed in 22 of these patients. IP was significantly increased in CORD patients when compared to either control children or adults (P less than 0.001). Mean +/- 1 SD were 4.3 +/- 1.71%, 2.5 +/- 0.78%, and 2.3 +/- 0.77% in the three groups, respectively. IP was not related to the presence of atopy. Significant differences in IP results were found between CORD children with abdominal pain (4.5 +/- 1.4%) and both control children and CORD patients without abdominal pain (2.5 +/- 0.78% and 3.2 +/- 1.49%, respectively). A significant correlation was found between small bowel injury on the one hand and IP on the other hand (P less than 0.02). Furthermore, small bowel injury was significantly related to the presence of abdominal pain (P less than 0.05). We speculate that in CORD patients with abdominal pain, a factor exists that causes small bowel injury responsible for both abdominal pain and increased small bowel permeability. Food intolerance could, presumably, play a role in the mucosal damage-linked IP increase found in the subset of CORD patients who complain of abdominal pain.
Neven, Ellen; Opdebeeck, Britt; De Maré, Annelies; Bashir-Dar, Rida; Dams, Geert; Marynissen, Rita; Behets, Geert J; Verhulst, Anja; Riser, Bruce L; D'Haese, Patrick C
Vascular calcification significantly contributes to mortality in chronic kidney disease (CKD) patients. Sevelamer and pyrophosphate (PPi) have proven to be effective in preventing vascular calcification, the former by controlling intestinal phosphate absorption, the latter by directly interfering with the hydroxyapatite crystal formation. Since most patients present with established vascular calcification, it is important to evaluate whether these compounds may also halt or reverse the progression of preexisting vascular calcification. CKD and vascular calcification were induced in male Wistar rats by a 0.75 % adenine low protein diet for 4 weeks. Treatment with PPi (30 or 120 µmol/kg/day), sevelamer carbonate (1500 mg/kg/day) or vehicle was started at the time point at which vascular calcification was present and continued for 3 weeks. Hyperphosphatemia and vascular calcification developed prior to treatment. A significant progression of aortic calcification in vehicle-treated rats with CKD was observed over the final 3-week period. Sevelamer treatment significantly reduced further progression of aortic calcification as compared to the vehicle control. No such an effect was seen for either PPi dose. Sevelamer but not PPi treatment resulted in an increase in both osteoblast and osteoid perimeter. Our study shows that sevelamer was able to reduce the progression of moderate to severe preexisting aortic calcification in a CKD rat model. Higher doses of PPi may be required to induce a similar reduction of severe established arterial calcification in this CKD model.
Waetzig, G H; Schreiber, S
Conventional treatment of chronic inflammatory disorders, including inflammatory bowel diseases, employs broad-range anti-inflammatory drugs. In order to reduce the side-effects and increase the efficacy of treatment, several strategies have been developed in the last decade to interfere with intercellular and intracellular inflammatory signalling processes. The highly conserved mitogen-activated protein kinase pathways regulate most cellular processes, particularly defence mechanisms such as stress reactions and inflammation. In this review, we provide an overview of the current knowledge of the specificity and interconnection of mitogen-activated protein kinase pathways, their functions in the gut immune system and published and ongoing studies on the role of mitogen-activated protein kinases in inflammatory bowel disease. The development of mitogen-activated protein kinase inhibitors and their use for the therapy of inflammatory disorders is a paradigm of the successful bridging of the gap between basic research and clinical practice.
... Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive ... Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive ...
Kotwicki, Tomasz; Chowanska, Joanna; Kinel, Edyta; Czaprowski, Dariusz; Tomaszewski, Marek; Janusz, Piotr
Idiopathic scoliosis is a three-dimensional deformity of the growing spine, affecting 2%–3% of adolescents. Although benign in the majority of patients, the natural course of the disease may result in significant disturbance of body morphology, reduced thoracic volume, impaired respiration, increased rates of back pain, and serious esthetic concerns. Risk of deterioration is highest during the pubertal growth spurt and increases the risk of pathologic spinal curvature, increasing angular value, trunk imbalance, and thoracic deformity. Early clinical detection of scoliosis relies on careful examination of trunk shape and is subject to screening programs in some regions. Treatment options are physiotherapy, corrective bracing, or surgery for mild, moderate, or severe scoliosis, respectively, with both the actual degree of deformity and prognosis being taken into account. Physiotherapy used in mild idiopathic scoliosis comprises general training of the trunk musculature and physical capacity, while specific physiotherapeutic techniques aim to address the spinal curvature itself, attempting to achieve self-correction with active trunk movements developed in a three-dimensional space by an instructed adolescent under visual and proprioceptive control. Moderate but progressive idiopathic scoliosis in skeletally immature adolescents can be successfully halted using a corrective brace which has to be worn full time for several months or until skeletal maturity, and is able to prevent more severe deformity and avoid the need for surgical treatment. Surgery is the treatment of choice for severe idiopathic scoliosis which is rapidly progressive, with early onset, late diagnosis, and neglected or failed conservative treatment. The psychologic impact of idiopathic scoliosis, a chronic disease occurring in the psychologically fragile period of adolescence, is important because of its body distorting character and the onerous treatment required, either conservative or surgical
Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María
Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease.
Wani, Nazir A; Parray, Fazl Q
The therapeutic effects of splenectomy in 15 patients with idiopathic hypersplenism were studied. The mean age was 43 years (range, 5-72 years). The male to female ratio was 1:1.14. The response to splenectomy was: in thrombocytopenia, complete response (CR) in 71%, partial response (PR) and no response (NR) in 14% each of patients; in anemia, CR in 83%, PR in 0%, and NR in 16% of patients; and in leukopenia, CR in 78% and PR and NR in 11% each of patients. However, the morbidity (27%) and mortality (20%) observed was quite high. Thus, we conclude that splenectomy is an excellent treatment to improve the hematological parameters in patients with idiopathic hypersplenism, but elderly patients and patients with multisystem disease should not have this surgery.
Adolescent idiopathic scoliosis is a 3D spinal deformity in frontal, sagittal and axial planes, with high relevance in the pediatric population especially in adolescents and females between 10 years of age and the end of growth spurt and skeletal maturity. The radiographic manifestation is a curve greater than 10° measured by Cobb method associated with vertebral rotation. "Idiopathic" diagnosis has to be done after neuroanatomical anomalies of the posterior cerebral fosa and spinal canal have been ruled out. The physical finding of a thoracic or lumbar hump is the clinical manifestation of vertebral rotation seen in a forward bending test (Adam's Test). It is recommended that all curves with a magnitude greater than 20° have to be controlled and treated by a spinal surgeon being observation, bracing and surgery the different treatment options based on the extent, progression of deformity and basically the clinical condition of the patient.
Samuelson, Clare; Forman, Kate M; Smith, Stuart
We present the case of an 8-year-old girl with chronic idiopathic thrombocytopenic purpura (ITP) and a short history suggestive of raised intracranial pressure. Urgent computed tomography scan of the head showed a large bleed into a left cerebellar lesion. She underwent treatment with intravenous immunoglobulin (IVIg) and steroids to increase her platelet count, followed by excision of the lesion, which was found to be a benign pilocytic astrocytoma. The patient made a complete recovery and shortly afterwards underwent splenectomy, following which there was complete resolution of her thrombocytopenia. PMID:22419950
Movva, Rajesh; Brown, Suzanne B; Morris, D Lynn; Figueredo, Vincent M
A 20-year-old pregnant woman with a history of juvenile idiopathic arthritis presented with flu-like symptoms, systemic inflammation with myocarditis, and severe cardiomyopathy. Six weeks earlier, her chronic-arthritis therapy had been changed from anakinra, an interleukin-1β receptor antagonist, to etanercept. When she resumed taking anakinra, her condition improved dramatically, including a complete recovery of ventricular function. Myocarditis is a well-recognized complication of systemic vasculitides. This unusual case emphasizes the important pathophysiologic role of interleukin receptors in the successful treatment of myocarditis. We suggest that clinical cardiologists be aware of the therapeutic usefulness of biological agents such as anakinra in patients with rheumatic conditions.
Sabato, Alessandro Fabrizio
Breakthrough pain (BTP) in treated patients with chronic pain states is neither well defined nor well understood. BTP is generally defined as a transient exacerbation of pain experienced by a patient with relatively stable and adequately controlled baseline pain. It is usually categorized as spontaneous, with no known cause, or incident, when initiated by voluntary or involuntary movements, or therapeutic procedures. Since pain is related to survival, it possibly cannot be completely and permanently controlled. It is hypothesized that glia are at least partially responsible for inducing pain spikes by attempting to reactivate unresponsive neurons. Therefore, compounds that modulate microglia may offer potential alternative therapeutic options in the control of idiopathic BTP.
Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério
Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138
Bussone, G; Grazzi, L
The aim of this paper is to review hypotheses regarding pain mechanisms in headache and relationships between headache pain and the brain's emotional network. There is evidence that chronic pain in idiopathic headaches is, in part, an emotional response induced by alterations in the homeostasis of the interoceptive system--a system that integrates nociceptive information with the emotional network (mediating emotional awareness). These findings suggest that idiopathic headaches are probably due to both an altered pain matrix on the one hand, and an altered affective-cognitive state on the other.
Cho, Min Jeng; Choi, Hyeon-Gon; Kim, Wan Seop; Yu, Yeong-Beom; Park, Kyoung Sik
Gigantomastia is a rare condition characterized by excessive breast growth. It has been reported that the majority of gigantomastia cases occur during either pregnancy or puberty. We were presented with a rare case of gigantomastia associated with neither pregnancy nor puberty, and successfully treated it with reduction mammaplasty and free nipple graft. This idiopathic gigantomastia is the very first case in Korea, and adds to the worldwide total of 9 reported cases. PMID:25741497
... the NHLBI on Twitter. What Causes Idiopathic Pulmonary Fibrosis? Sometimes doctors can find out what is causing pulmonary fibrosis (lung scarring). For example, exposure to environmental pollutants ...
Prognostic significance of surfactant protein A, surfactant protein D, Clara cell protein 16, S100 protein, trefoil factor 3, and prostatic secretory protein 94 in idiopathic pulmonary fibrosis, sarcoidosis, and chronic pulmonary obstructive disease.
Doubková, Martina; Karpíšek, Michal; Mazoch, Jiri; Skřičková, Jana; Doubek, Michael
Identification of serum and bronchoalveolar lavage fluid (BALF) biomarkers may facilitate diagnosis and prognostication in various lung disorders. Serum and BALF levels of surfactant protein A (SP-A), surfactant protein D (SP-D), Clara cell protein 16 (CC16), S100 protein, trefoil factor 3 (TFF3), and prostatic secretory protein 94 (PSP94) were evaluated in 94 consecutive patients (idiopathic pulmonary fibrosis (IPF; n=18), sarcoidosis (n=25), chronic obstructive pulmonary disease (COPD; n=51)), and in 155 healthy controls. Biomarkers were measured at diagnosis and compared with disease characteristics. Both uniparametric and multiparametric analyses were used. Seven significant correlations were found: 1) BALF PSP94 level correlated with prognosis of sarcoidosis (P=0.035); 2) BALF SP-D level with pulmonary functions in IPF (P=0.032); 3) BALF SP-D and TFF3 with IPF mortality (P=0.049 and 0.017, respectively); 4) serum TFF3 level with COPD mortality (P=0.006,); 5) serum SP-A with pulmonary functions impairment in IPF (P=0.011); 6) serum SP-D level was associated with HRCT interstitial score in IPF (P=0.0346); and 7) serum SP-A was associated with staging of COPD according to spirometry (P<0.001). Moreover, our analysis showed that some biomarker levels differed significantly among the diseases: 1) BALF SP-D level differed between sarcoidosis and IPF; 2) serum SP-A level differed among IPF, sarcoidosis, COPD and was also different from healthy controls; 3) serum S100A6, S100A11 levels differed among IPF, sarcoidosis, COPD from healthy controls 4) serum SP-D, CC16, TFF-3 levels distinguished IPF patients from healthy controls; and 5) serum CC16, TFF3, PSP94 distinguished COPD patients from healthy controls. Our study shows that some of selected biomarkers should have prognostic value in the analysed lung disorders. On the other hand, these biomarkers do not appear to be unequivocally suitable for differential diagnosis of these disorders.
Marchand, E; Reynaud-Gaubert, M; Lauque, D; Durieu, J; Tonnel, A B; Cordier, J F
Idiopathic chronic eosinophilic pneumonia (CEP) is a rare disorder of unknown cause with nonspecific respiratory and systemic symptoms but rather characteristic peripheral alveolar infiltrates on imaging, developing mainly in women and in atopic subjects. The disorder is highly responsive to oral corticosteroid therapy, but relapses are frequent on reducing or stopping treatment. The long-term course of the disease and data regarding outcome, particularly the need for prolonged oral corticosteroid therapy and the development of severe asthma, are somewhat contradictory. A multicentric retrospective study was conducted in an attempt to describe better the initial features and, above all, the later course of CEP in a large homogeneous series of 62 stringently selected patients of whom 46 were followed for more than 1 year. The prevalence of smokers was low (6.5%) and about half of our patients (51.6%) had a previous, and often prolonged, history of asthma. The clinical and roentgenographic features were in keeping with previous studies, but we found that computed tomography could disclose ground glass opacities not detected by X-ray, and that migratory infiltrates before treatment were more frequent (25.5%) than reported previously. The bronchoalveolar lavage cellular count always showed a striking eosinophilic pattern, thus allowing distinction between CEP and cryptogenic organizing pneumonia, both syndromes sharing many common clinical and imaging features. About two-thirds of the patients (68%) showed a ventilatory defect in pulmonary function tests, with about one-half of these presenting with an obstructive pattern, sometimes without previous asthma. Along with the submucosal eosinophilic infiltration noted in 2 patients without ventilatory defect, this is strong evidence to confirm that CEP is not only an alveolointerstitial but also an airway disease. The dramatic response to oral corticosteroid therapy was observed in all treated patients. Although only 1
Low, Daren; Subramaniam, Renuka; Lin, Li; Aomatsu, Tomoki; Mizoguchi, Atsushi; Ng, Aylwin; DeGruttola, Arianna K.; Lee, Chun Geun; Elias, Jack A.; Andoh, Akira; Mino-Kenudson, Mari; Mizoguchi, Emiko
Many host-factors are inducibly expressed during the development of inflammatory bowel disease (IBD), each having their unique properties, such as immune activation, bacterial clearance, and tissue repair/remodeling. Dysregulation/imbalance of these factors may have pathogenic effects that can contribute to colitis-associated cancer (CAC). Previous reports showed that IBD patients inducibly express colonic chitinase 3-like 1 (CHI3L1) that is further upregulated during CAC development. However, little is known about the direct pathogenic involvement of CHI3L1 in vivo. Here we demonstrate that CHI3L1 (aka Brp39) knockout (KO) mice treated with azoxymethane (AOM)/dextran sulphate sodium (DSS) developed severe colitis but lesser incidence of CAC as compared to that in wild-type (WT) mice. Highest CHI3L1 expression was found during the chronic phase of colitis, rather than the acute phase, and is essential to promote intestinal epithelial cell (IEC) proliferation in vivo. This CHI3L1-mediated cell proliferation/survival involves partial downregulation of the pro-apoptotic S100A9 protein that is highly expressed during the acute phase of colitis, by binding to the S100A9 receptor, RAGE (Receptor for Advanced Glycation End products). This interaction disrupts the S100A9-associated expression positive feedback loop during early immune activation, creating a CHI3L1hi S100A9low colonic environment, especially in the later phase of colitis, which promotes cell proliferation/survival of both normal IECs and tumor cells. PMID:26431492
Haley, Nicholas J; Mathiason, Candace K; Carver, Scott; Zabel, Mark; Telling, Glenn C; Hoover, Edward A
Efficient horizontal transmission is a signature trait of chronic wasting disease (CWD) in cervids. Infectious prions shed into excreta appear to play a key role in this facile transmission, as has been demonstrated by bioassays of cervid and transgenic species and serial protein misfolding cyclic amplification (sPMCA). However, the source(s) of infectious prions in these body fluids has yet to be identified. In the present study, we analyzed tissues proximate to saliva, urine, and fecal production by sPMCA in an attempt to elucidate this unique aspect of CWD pathogenesis. Oropharyngeal, urogenital, and gastrointestinal tissues along with blood and obex from CWD-exposed cervids (comprising 27 animals and >350 individual samples) were analyzed and scored based on the apparent relative CWD burden. PrP(CWD)-generating activity was detected in a range of tissues and was highest in the salivary gland, urinary bladder, and distal intestinal tract. In the same assays, blood from the same animals and unseeded normal brain homogenate controls (n = 116 of 117) remained negative. The PrP-converting activity in peripheral tissues varied from 10(-11)- to 10(0)-fold of that found in brain of the same animal. Deer with highest levels of PrP(CWD) amplification in the brain had higher and more widely disseminated prion amplification in excretory tissues. Interestingly, PrP(CWD) was not demonstrable in these excretory tissues by conventional Western blotting, suggesting a low prion burden or the presence of protease-sensitive infectious prions destroyed by harsh proteolytic treatments. These findings offer unique insights into the transmission of CWD in particular and prion infection and trafficking overall.
Margaritopoulos, George A; Harari, Sergio; Caminati, Antonella; Antoniou, Katerina M
For many years, cigarette smoking has been considered as the leading cause of chronic obstructive pulmonary disease and lung cancer. Recently, however, it has also been associated with the development of diffuse interstitial lung diseases. In the latest classification of the major idiopathic interstitial pneumonias (IIP), the term smoking-related IIP has been introduced, including two entities, namely desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-interstitial lung disease (RB-ILD). Other entities in which smoking has a definite or suggested role include pulmonary Langerhan's cell histiocytosis, smoking-related interstitial fibrosis, combined pulmonary fibrosis and emphysema syndrome and idiopathic pulmonary fibrosis. In this review, we will focus on the mechanisms of smoking-related lung damage and on the clinical aspects of these disorders with the exception of idiopathic pulmonary fibrosis, which will be reviewed elsewhere in this review series.
Shawki, Sherief; Wexner, Steven D
Fistula-in-ano is the most common form of perineal sepsis. Typically, a fistula includes an internal opening, a track, and an external opening. The external opening might acutely appear following infection and/or an abscess, or more insiduously in a chronic manner. Management includes control of infection, assessment of the fistulous track in relation to the anal sphincter muscle, and finally, definitive treatment of the fistula. Fistulotomy was the most commonly used mode of management, but concerns about post-fistulotomy incontinence prompted the use of sphincter preserving techniques such as advancement flaps, fibrin glue, collagen fistula plug, ligation of the intersphincteric fistula track, and stem cells. Many descriptive and comparative studies have evaluated these different techniques with variable outcomes. The lack of consistent results, level I evidence, or long-term follow-up, as well as the heterogeneity of fistula pathology has prevented a definitive treatment algorithm. This article will review the most commonly available modalities and techniques for managing idiopathic fistula-in-ano. PMID:21876614
Nuzzo, Alexandre; Zappa, Magaly; Cazals-Hatem, Dominique; Bouhnik, Yoram
Abstract Background: Mesenteric panniculitis (MP) is mostly an associated sign of an intra-abdominal or systemic inflammatory primary disease. Nevertheless, etiological and differential diagnosis of idiopathic MP can be challenging when an associate primary cause is not in the foreground. Methods: We report here the case of an isolated small bowel Crohn's disease, long time considered as idiopathic MP. Results: This patient presented to our department with a 10-year history of acute abdominal symptoms evolving with flare-up and remission. A diagnosis of idiopathic MP was made based on compatible CT-scan features along with normal laboratory tests and upper and lower bowel endoscopies. As symptoms recurred, a steroid course was proposed which dramatically improved his condition for years. Finally, an explorative laparoscopy was performed because of concern of malignancy when he returned to our unit with a steroid refractory flare-up and weight loss, along with MP nodes growing up to 10 mm. Crohn's disease was eventually diagnosed, based on histopathological middle-gut bowel resection and numerous granulomas in mesenteric nodes without necrosis. Conclusion: This case emphasizes the importance of excluding inflammatory intestinal lesions before making the diagnosis of idiopathic MP (fecal calprotectin, magnetic resonance enterography, wireless capsule endoscopy). PMID:27684882
Desrochers, André; Anderson, David E
A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions. Copyright © 2016 Elsevier Inc. All rights reserved.
Auricchio, A.; Brancolini, V.; Casari, G.; Milla, P. J.; Smith, V. V.; Devoto, M.; Ballabio, A.
The neuronal type of primary chronic idiopathic intestinal pseudoobstruction (CIIP) results from the developmental failure of enteric neurons to migrate or differentiate correctly. This leads to intestinal motility disorders, which are characterized by symptoms and signs of bowel obstruction in the absence of a mechanical obstacle. Most of these conditions are congenital, and among them some are inherited. One syndromic condition characterized by intestinal pseudoobstruction with morphological abnormalities of the argyrophil neurons in the myenteric plexus, associated with short small bowel, malrotation, and pyloric hypertrophy, has been previously described. We have studied a family affected by this disorder, in which the disease appeared to segregate as an X-linked recessive trait. In order to map the CIIP locus in this family, we performed linkage analysis in 26 family members by use of highly polymorphic microsatellite markers from the X chromosome. One of these markers, DXYS154, located in the distal part of Xq28, shows no recombination with a maximum lod score of 2.32. Multipoint analysis excluded linkage with markers spanning other regions of the X chromosome. Our results, integrated with the current genetic and physical map of Xq28, determine the order of loci as cen-DXS15-(CIIPX)-DXS1108/DXYS154-tel. This study establishes, for the first time, the mapping assignment of a neuropathic form of CIIP other than Hirschsprung disease. Images Figure 1 PMID:8644737
Trinchieri, Alberto; Lizzano, Renata; Castelnuovo, Chiara; Zanetti, Giampaolo; Pisani, Enrico
The aim of this study was to analyze the frequency of renal stone patients with chronic inflammatory bowel disease and their urinary patterns. During a 20-year period, 1941 consecutive patients with renal stone disease underwent routine laboratory procedures including a fasting blood sample for chemistry profile and a 24-hour urine collection for analyses of electrolytes. Thorough histories including chronic inflammatory disease or ileal resection were obtained. Patients with inflammatory bowel disease together with a control group comprising 47 idiopathic renal calcium stone formers were submitted to a xylose absorption test for evaluation of intestinal absorption. We observed 10 patients with Crohn's disease, 12 with ulcerative colitis and one patient with ileal bypass for obesity. Six patients underwent ileal resection and 10 patients total colectomy. Urinary oxalate excretion was significantly higher and urinary citrate lower in stone patients with ileal disease (Ox 60 +/- 23, Cit 113 + 7-118 mg/day) than in idiopathic stone formers (Ox 28.2 +/- 11.5, Cit 381 +/- 205) and stone patients with ulcerative colitis (Ox 20.3 +/- 14.8, Cit 369 +/- 247). Urinary volume was significantly lower in patients with ulcerative colitis. A significant inverse correlation (-0.38, p < 0.01) between oxalate urinary excretion and blood xylose level was found 2 hours after ingestion of xylose. No significant reduction of xylose absorption was demonstrated in both normoxaluric and hyperoxaluric idiopathic stone patients. Crohn's disease and ulcerative colitis are characterized by recurrent inflammatory involvement of different intestinal segments involving distinctive urinary patterns. Malabosorption associated with ileal disease causes increased oxalate absorption by increasing oxalate solubility in the intestinal lumen and permeability of the colonic mucosa; a reduced citrate excretion is associated in relation to mild acidosis due to the loss of bicarbonate in the liquid stool. In
Dani, Nitin Hemchandra; Khanna, Dinkar Parveen; Bhatt, Vaibhavi Hitesh; Joshi, Chaitanya Pradeep
Idiopathic gingival fibromatosis (IGF) is a rare hereditary condition characterized by slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva caused by increase in submucosal connective tissue elements, mostly associated with some syndrome. This case report describes a case of nonsyndromic generalized IGF in an 18-year-old male patient who presented with generalized gingival enlargement. The enlarged tissue was surgically removed by internal bevel gingivectomy and ledge and wedge procedure. The patient was regularly monitored clinically for improvement in his periodontal condition as well as for any recurrence of gingival overgrowth. PMID:26941525
Nayak, Ullal Anand; Khandelwal, Vishal; Ninave, Nupur
ABSTRACT Idiopathic gingival fibromatosis is a rare heriditary condition characterized by slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva caused by increase in submucosal connective tissue elements. This case report gives an overview of gingival fibromatosis in a 11-year-old female patient who presented with generalized gingival enlargement. Based on the history and clinical examination, the diagnosis was made and the enlarged tissue was surgically removed. The patient was being regularly monitored clinically for improvement in her periodontal condition as well as for any recurrence of gingival overgrowth. PMID:27616864