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Shaik MR, Shaik NA, Mikdashi J. Autoimmune Dysphagia Related to Rheumatologic Disorders: A Focused Review on Diagnosis and Treatment. Cureus 2023; 15:e41883. [PMID: 37581141 PMCID: PMC10423619 DOI: 10.7759/cureus.41883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2023] [Indexed: 08/16/2023] Open
Abstract
Autoimmune dysphagia is defined as dysphagia caused by autoimmune processes affecting various components of the swallowing process such as muscle, neuromuscular junction, nerves, roots, brainstem, or cortex. These autoimmune causes can be classified into gastroenterological, dermatological, rheumatologic, and neurologic. Rheumatological disorders, such as scleroderma, Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, Behcet's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, or granulomatosis with polyangiitis, have been associated with dysphagia. Autoimmune dysphagia in the context of rheumatological disorders is particularly significant because it can occur as a sole manifestation or as part of a symptom complex associated with the underlying disorder and often responds to immunosuppressive therapies. However, diagnosing autoimmune dysphagia can be challenging as it requires the exclusion of structural and primary motility disorders through procedures such as endoscopy and manometry. Early diagnosis is important to improve the quality of life and prevent significant mortality and morbidity. Management focuses on treating the underlying disease activity, and a multidisciplinary approach involving various medical specialties may be necessary to achieve success. This article aims to review the autoimmune rheumatological conditions that can lead to dysphagia and discuss the associated pathophysiological mechanisms. We also outline the clinical clues and laboratory testing methods that facilitate early diagnosis, with the goal of improving patient outcomes through timely intervention and appropriate management.
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Affiliation(s)
- Mohammed Rifat Shaik
- Department of Internal Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, USA
| | - Nishat Anjum Shaik
- Department of Internal Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, USA
| | - Jamal Mikdashi
- Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, USA
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Qureshi A, Jehangir A, Malik Z, Parkman HP. Rheumatologic disorders in patients undergoing esophageal manometry: prevalence, symptom characteristics, and manometric findings. Dis Esophagus 2021; 34:6131381. [PMID: 33558877 DOI: 10.1093/dote/doaa135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/01/2020] [Accepted: 12/19/2020] [Indexed: 12/11/2022]
Abstract
Rheumatologic disorders (RDs) can have gastrointestinal (GI) manifestations. Systemic sclerosis (SSc) patients often have upper GI symptoms from absent esophageal contractility (AC). Upper GI symptom characteristics and high-resolution esophageal manometry with impedance (HREMI) findings of other RDs have not been well studied. We aimed to: (i) determine the prevalence of RD in patients undergoing HREMI and (ii) assess the symptom characteristics and manometric findings of these patients. Patients undergoing HREMI (July 2018 to March 2020) rated their GI symptoms' severity. Healthy volunteers (HVs) also underwent HREMI. Of the 1,003 patients, 90 (9%) had RD (mean age: 55.3 ± 1.4 years, 73.3% females), most commonly SSc (n = 27), rheumatoid arthritis (RA, n = 20), and systemic lupus erythematosus (SLE, n = 11). The most severe upper GI symptoms in patients with RD were heartburn, regurgitation, nausea, and dysphagia, with no significant differences in their severities between SSc, RA, and SLE. RD patients had higher upper esophageal sphincter (UES) pressures, lower distal contractile integral (DCI), lower bolus clearance, and more frequent hiatal hernia (HH) on HREMI (all P < 0.05) than HVs. Over half (61.1%) of patients with RD had esophageal motility disorders, most commonly AC (n = 25), ineffective esophageal motility (IEM; n = 18), and esophagogastric junction (EGJ) obstructive disorders (n = 11). Among patients undergoing HREMI, 9% had RD. Upper GI symptom severities did not distinguish different RDs. Patients with RD had higher UES pressures, weaker DCI, lower bolus clearance, and more frequent HH than HVs. Although AC and IEM were most common motility disorders, a considerable minority (12.2%) of our RD patients had EGJ obstructive disorders.
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Affiliation(s)
- Anam Qureshi
- Gastroenterology Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Asad Jehangir
- Gastroenterology Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Zubair Malik
- Gastroenterology Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Henry P Parkman
- Gastroenterology Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
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Dehghan M, Ahmadi A, Yousefghahari B, Kiakojouri K, Gholinia H. Effects of Rheumatoid Arthritis on the Larynx. IRANIAN JOURNAL OF OTORHINOLARYNGOLOGY 2020; 32:147-153. [PMID: 32596173 PMCID: PMC7302527 DOI: 10.22038/ijorl.2020.43213.2418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Introduction: The aim of the present study was to compare the videolaryngostroboscopic findings between patients with rheumatoid arthritis and vocally healthy controls. Materials and Methods: This case-control descriptive study was performed on 113 people, including 50 patients with rheumatoid arthritis and 63 controls. The participants were subjected to videolaryngostroboscopic examinations in order to evaluate fundamental frequency, different structural vocal lesions, patterns of glottal closure, subglottal changes, supraglottis appearance, and movement patterns of the arytenoid cartilage. The obtained results were compared between the two research groups. Data analysis was performed in the Statistical Package for the Social Sciences, version 24.0. A p-value less than 0.05 was considered statistically significant. Results: The results revealed a statistically significant difference between the two groups in terms of the complete pattern (P=0.00) and strained state of glottal closure (P=0.00), pattern of subglottal changes (χ2=25.98, df=2; P<0.001), and movement patterns of the arytenoid (χ2=21.16, df=1; P<0.001). Additionally, based on the obtained frequencies, the two groups showed significant differences regarding the normal state of the larynx (P=0.00), hypertrophy of vocal fold (P=0.007), epithelial change (P=0.007), and Reinke's edema (P=0.001). However, the videolaryngostroboscopic examination results revealed no significant difference between the two groups in terms of polyp (P=0.20), nodule (P=0.57), sulcus vocalis (P=0.08), cyst (P=0.45), and atrophy of vocal folds (P=0.45). Conclusion: It seems that rheumatoid arthritis affects the patterns of arytenoids movement, some kinds of glottal closure patterns, and subglottal changes. As the results indicated, the occurrence of some laryngeal structural changes was higher in patients with rheumatoid arthritis than in individuals without this disorder.
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Affiliation(s)
- Mehdi Dehghan
- Department of Speech Therapy, School of Rehabilitation, Babol University of Medical Sciences, Babol, IR, Iran
| | - Akram Ahmadi
- Department of Speech Therapy, School of Rehabilitation, Babol University of Medical Sciences, Babol, IR, Iran
| | - Behnaz Yousefghahari
- Clinical Research Development Unite of Rouhani Hospital, Babol University of Medical Sciences, Babol, IR, Iran
| | - Keyvan Kiakojouri
- Clinical Research Development Unite of Rouhani Hospital, Babol University of Medical Sciences, Babol, IR, Iran
| | - Hemmat Gholinia
- Clinical Research Development Unite of Rouhani Hospital, Babol University of Medical Sciences, Babol, IR, Iran
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Abstract
Gastrointestinal (GI) manifestations of rheumatoid arthritis (RA) are rare, but can be impactful for patients. Some GI processes are directly related to RA, whereas others may be sequelae of treatment or caused by concomitant autoimmune diseases. This article discusses the role of the GI tract in RA pathogenesis; the presentation, epidemiology, and diagnosis of RA-related GI manifestations; concomitant GI autoimmune diseases that may affect those with RA; and GI side effects of RA treatment. The importance of appropriately considering conditions unrelated to RA in the differential diagnosis when evaluating new GI symptoms in patients with RA is noted.
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Affiliation(s)
- Ethan Craig
- Johns Hopkins University School of Medicine, Division of Rheumatology, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
| | - Laura C Cappelli
- Johns Hopkins University School of Medicine, Division of Rheumatology, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
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Di Piazza A, Vernuccio F, Costanzo M, Scopelliti L, Picone D, Midiri F, Salvaggi F, Cupido F, Galia M, Salerno S, Lo Casto A, Midiri M, Lo Re G, Lagalla R. The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review. Gastroenterol Res Pract 2017; 2017:7659273. [PMID: 28706536 PMCID: PMC5494561 DOI: 10.1155/2017/7659273] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 04/11/2017] [Indexed: 02/01/2023] Open
Abstract
Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%-80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients.
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Affiliation(s)
- Ambra Di Piazza
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | | | - Massimo Costanzo
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Laura Scopelliti
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Dario Picone
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Federico Midiri
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Francesco Salvaggi
- Unit of Colorectal Surgery, Department of Medical, Surgical, Neurological, Metabolic and Ageing Sciences, Second University of Naples, Naples, Italy
| | - Francesco Cupido
- Department of Surgical, Oncologic and Stomatologic Diseases, University of Palermo, Palermo, Italy
| | - Massimo Galia
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Sergio Salerno
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Antonio Lo Casto
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Massimo Midiri
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Giuseppe Lo Re
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
| | - Roberto Lagalla
- Section of Radiology-Di.Bi.Med., University of Palermo, Palermo, Italy
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Mandl T, Ekberg O. Dysphagia in Systemic Disease. Dysphagia 2017. [DOI: 10.1007/174_2017_61] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Rainsford KD. Comparative Studies of Gastric Ulcerogenesis by Non-steroid Anti-inflammatory Drugs: Effects of Fenclofenac. Proc R Soc Med 2016. [DOI: 10.1177/00359157770700s602] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- K D Rainsford
- Department of Biochemistry, University of Tasmania Medical School, GPO Box 252 C, Hobart, Tasmania, Australia 7001
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9
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Roth SH, Fuller P. Pooled safety analysis of diclofenac sodium topical solution 1.5% (w/w) in the treatment of osteoarthritis in patients aged 75 years or older. Clin Interv Aging 2012; 7:127-37. [PMID: 22791985 PMCID: PMC3393357 DOI: 10.2147/cia.s30884] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background This study aimed to determine the safety of diclofenac sodium topical solution 1.5% (w/w) in 45.5% dimethyl sulfoxide (TDiclo) for the treatment of knee or hand osteoarthritis in persons aged 75 years or older. Methods A pooled analysis of safety data from seven multicenter, randomized, blinded, Phase III clinical trials (4–12 weeks’ duration) of TDiclo was conducted. The analysis focused on a subset of patients (n = 280) aged 75 years or older with a primary diagnosis of osteoarthritis of the knee (six trials) or hand (one trial). Patients received one of three topical treatments: TDiclo (n = 138); placebo (2.33% or 4.55% dimethyl sulfoxide, n = 39); or control (45.5% dimethyl sulfoxide, n = 103). Treatment groups were compared using Chi-square analysis, Fisher’s Exact test, or analysis of variance. Results The most common adverse events involved the skin or subcutaneous tissue, primarily at the application site. The incidence of dry skin was higher in the TDiclo (36.2%; P < 0.0001) and dimethyl sulfoxide control (18.4%; P = 0.0142) groups than in the placebo group (2.6%); the incidence of other skin or subcutaneous tissue adverse events was similar between the groups. Relatively few patients (<18%) experienced gastrointestinal adverse events, and group differences were not detected. In the TDiclo group, constipation (3.6%), diarrhea (3.6%), and nausea (3.6%) were the most common gastrointestinal adverse events. Cardiovascular and renal/ urinary adverse events were rare, and group differences were not detected. There was one case (0.7%) each of hypertension, spider veins, and vasodilation in the TDiclo group. Changes from baseline to the final visit in blood pressure and hepatic/renal enzyme levels were also similar between the groups. Conclusion TDiclo appears to be well tolerated for the treatment of osteoarthritis in persons aged 75 years or older.
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Dysphagia in Systemic Disease. Dysphagia 2012. [DOI: 10.1007/174_2012_584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Roth SH. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety. Clin Interv Aging 2011; 6:125-31. [PMID: 21753867 PMCID: PMC3131982 DOI: 10.2147/cia.s21107] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2011] [Indexed: 12/13/2022] Open
Abstract
Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.
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Affiliation(s)
- Sanford H Roth
- Arizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, USA.
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13
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Ebert EC, Hagspiel KD. Gastrointestinal and hepatic manifestations of rheumatoid arthritis. Dig Dis Sci 2011; 56:295-302. [PMID: 21203902 DOI: 10.1007/s10620-010-1508-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2010] [Accepted: 11/15/2010] [Indexed: 12/11/2022]
Abstract
Rheumatoid arthritis (RA), characterized by inflammation of the synovium and surrounding structures, has a prevalence of 0.5-1%. Rheumatoid vasculitis (RV) is an inflammatory condition of the small- and medium-sized vessels that affects up to 5% of patients with RA with intestinal involvement in 10-38% of these cases. Clinically apparent RV of the gastrointestinal (GI) tract, while rare, is often catastrophic, resulting in ischemic ulcers and bowel infarction. Vasculitis of the colon may present as pancolitis clinically similar to ulcerative colitis. Rectal biopsies that include submucosal vessels are positive for vasculitis in up to 40% of cases. Abnormal esophageal motility in RA may result in heartburn and dysphagia. Chronic atrophic gastritis may be associated with hypergastrinemia and hypo- or achlorhydria, promoting small bowel bacterial overgrowth. RA is the most common cause of secondary amyloidosis with GI symptoms in 22% of affected patients. Although amyloid is usually found in the liver, it is rarely evident clinically. Felty's syndrome occurs in less than 1% of patients with RA and is characterized by neutropenia and splenomegaly. The liver may be involved with portal fibrosis or nodular regenerative hyperplasia. Liver histology is abnormal in 92% of RA patients at autopsy, although the changes are usually mild without associated hepatomegaly. Drug-induced liver disease may occur with aspirin, sulfasalazine, and methotrexate. Significant liver damage is rare if the drug is discontinued or the patient is properly monitored. RA can affect both the GI tract and the liver; changes are usually mild except with RV.
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Affiliation(s)
- Ellen C Ebert
- Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
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Jain R, L. Thiele D. Gastrointestinal and Hepatic Manifestations of Systemic Diseases. SLEISENGER AND FORDTRAN'S GASTROINTESTINAL AND LIVER DISEASE 2010:557-592.e11. [DOI: 10.1016/b978-1-4160-6189-2.00035-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Bijlsma JW. Treatment of NSAID-induced gastrointestinal lesions with cimetidine: an international multicentre collaborative study. Aliment Pharmacol Ther 2007; 2 Suppl 1:85-95. [PMID: 2979287 DOI: 10.1111/j.1365-2036.1988.tb00768.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The efficacy of cimetidine 800 mg nocte in the treatment of erosions or ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) was evaluated in an uncontrolled multicentre study of 187 patients requiring continuation of their NSAID therapy. After 4 weeks of treatment, endoscopic healing was achieved in 62% of patients. After 8 weeks of therapy, 88% of patients were lesion-free. Patients with ulcer had a healing rate of 49% at week 4, which increased to 81% at the completion of 8 weeks. The majority of patients (82%) with erosions healed in 4 weeks. By week 8, erosions were healed in 97% of patients. Following endoscopically verified lesion healing, 113 patients entered a maintenance phase of the study, which assessed the efficacy of cimetidine 400 mg nocte in preventing recurrence of erosions or ulcers while continuing NSAID therapy. During a 6-month observation period, the cumulative probability of endoscopically observed recurrence of lesions was 12% (with a mean time to recurrence of 116 days), which is similar to the incidence of relapse achieved with cimetidine 400 mg nocte in patients with uncomplicated peptic ulcer. The results of this study suggest that cimetidine 800 mg nocte is effective in healing NSAID-induced lesions despite continued NSAID use, and that maintenance treatment with cimetidine 400 mg nocte can prevent lesions and reduce lesion recurrence during chronic NSAID administration.
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Affiliation(s)
- J W Bijlsma
- Department of Rheumatology, University Hospital Utrecht, The Netherlands
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Turnbull CM, Rossi AG, Megson IL. Therapeutic effects of nitric oxide-aspirin hybrid drugs. Expert Opin Ther Targets 2007; 10:911-22. [PMID: 17105376 DOI: 10.1517/14728222.10.6.911] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
This review examines the therapeutic potential and mechanisms of action of drugs known as nitric oxide (NO)-aspirins. Drugs of this class have an NO-releasing moiety joined by ester linkage to the aspirin molecule. NO-aspirins have the capability to release NO in addition to retaining the cyclooxygenase-inhibitory action of aspirin. The protective nature of NO led to the development of NO-aspirins in the hope that they might avoid the gastric side effects associated with aspirin. However, it has become apparent that the drug-derived NO instills potential for a wide range of added beneficial effects over the parent compound. In this review, the authors focus on the analgesic, anti-inflammatory, cardiovascular and chemopreventative actions of compounds of this emerging drug class.
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Affiliation(s)
- Catriona M Turnbull
- Queen's Medical Research Institute, University of Edinburgh, Centre for Cardiovascular Science, Edinburgh, EH16 4TJ, UK.
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Abstract
The developing popularity of non-steroidal anti-inflammatory drugs (NSAIDs) over the last 100 years has been paralleled by an increase in associated complications, particularly affecting the gastrointestinal (GI) tract [1]. Over this period, there have been several attempts to develop less toxic NSAIDs, most of which have been unsuccessful. Since the discovery that the enzyme cyclooxygenase (COX) exists as two isoforms, the largely constitutive COX-1 and the mainly inducible COX-2, much interest has centred on the development of drugs capable of selectively inhibiting COX-2. Early studies that investigated specific COX-2 inhibitors (with no effect on the COX-1 isoform over the whole range of concentrations achieved in clinical usage) are encouraging, as they demonstrate that these drugs have fewer effects on gastroduodenal mucosa than standard NSAIDs given at equivalent doses. Further clinical experience with these agents outside trial settings and additional studies to assess the role of COX-2 when induced in the GI tract are needed, before such agents can be safely recommended for widespread prescribing.
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Affiliation(s)
- L M Jackson
- Division of Gastroenterology, Department of Medicine, University Hospital Nottingham, Nottingham, NG72UH, UK
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Hagiwara M, Kataoka K, Arimochi H, Kuwahara T, Nakayama H, Ohnishi Y. Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by nonsteroidal antiinflammatory drug. World J Gastroenterol 2005; 11:1040-3. [PMID: 15742411 PMCID: PMC4250768 DOI: 10.3748/wjg.v11.i7.1040] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the ulceration in small intestines of rats.
METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4- methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.
RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin) did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others (pravastatin, atorvastatin).
CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.
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Affiliation(s)
- Mari Hagiwara
- Department of Molecular Bacteriology, Graduate School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan
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Machado WM, Freire BFA, Rocha OM, Azambuja CAP, Oliveira MEC. [Proposal of a questionnaire for the characterization of the prevalence of digestive symptoms in connective tissue diseases]. ARQUIVOS DE GASTROENTEROLOGIA 2004; 41:64-70. [PMID: 15499428 DOI: 10.1590/s0004-28032004000100013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND Connective tissue diseases may damage multiple organic systems, including digestive system. In this one, the degree of injury vary according to the associated disease. Despite the significant frequency of gastrointestinal involvement, there are few studies characterizing the prevalence of digestive symptoms in connective tissue diseases. Furthermore, most of the studies available are less detailed and based in personal experiences or reviews of records. AIM To establish a reliable list of gastrointestinal symptoms found in the progressive systemic sclerosis, rheumatoid arthritis, polymyositis/dermatomyositis, mixed connective tissue disease and systemic lupus erythematosus, through a medical interview and a predefined questionnaire of symptoms. PATIENTS AND METHODS There were studied 99 patients, 90% females, mean age 45 years. The whole group were composed of 35 rheumatoid arthritis, 26 progressive systemic sclerosis, 21 systemic lupus erythematosus, 12 polymyositis/dermatomyositis and 5 mixed connective tissue disease. Each patient was submitted to an interview with a well trained doctor and answered a structured questionnaire, containing 17 questions. RESULTS It was found a high prevalence of digestive symptoms in all five connective tissue diseases searched. Many of them were present in more than 50% of the patients. Called special attention the detection of some manifestations neglected by the literature like, for example, fecal incontinence. Also, disagreeing with other authors, was the finding of multiple gastrointestinal manifestations associated with rheumatoid arthritis. It was particularly surprising the occurrence of dysphagia in one third of the rheumatoid arthritis group. CONCLUSIONS The connective tissue diseases are usual causes of many gastrointestinal complaints. The use of an interview plus predefined questionnaire seems a very effective way to identify and characterize symptoms and is even sometimes able to uncover features unknown before. Finally, the lack of studies, specially updated studies, did not allow more comprehensive comparisons.
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Affiliation(s)
- Wellington M Machado
- Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, UNESP, Botucatu, SP.
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Fries JF, Murtagh KN, Bennett M, Zatarain E, Lingala B, Bruce B. The rise and decline of nonsteroidal antiinflammatory drug-associated gastropathy in rheumatoid arthritis. ACTA ACUST UNITED AC 2004; 50:2433-40. [PMID: 15334455 DOI: 10.1002/art.20440] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Nonsteroidal antiinflammatory drug (NSAID)-associated gastropathy is a major cause of hospitalization and death. This study was undertaken to examine whether recent preventive approaches have been associated with a declining incidence of NSAID gastropathy, and, if so, what measures may have caused the decline. METHODS We studied 5,598 patients with rheumatoid arthritis (RA) over 31,262 patient-years at 8 sites. We obtained standardized longitudinal information on the patients that had been previously used to establish the incidence of NSAID gastropathy, and also information on patient risk factors and differences in toxicity between NSAIDs. Consecutive patients were followed up with biannual Health Assessment Questionnaires and medical record audits between 1981 and 2000. The major outcome measure was the annual rate of hospitalization involving bleeding, obstruction, or perforation of the gastrointestinal (GI) tract and related conditions. RESULTS Rates of GI-related hospitalizations rose from 0.6% in 1981 to 1.5% in 1992 (P < 0.001), and then declined to 0.5% in 2000 (P < 0.001). The fitted spline curve fit the data well (R2 = 0.70). The period of rise was mainly associated with increasing patient age and the GI risk propensity score. The period of decline was associated with lower doses of ibuprofen and aspirin, a decline in the use of "more toxic" NSAIDs from 52% to 42% of patients, a rise in the use of "safer" NSAIDs from 19% to 48% of patients, and increasing use of proton-pump inhibitors, but not with change in age, NSAID exposure, or GI risk propensity score. CONCLUSION The risk of serious NSAID gastropathy has declined by 67% in these cohorts since 1992. We estimate that 24% of this decline was the result of lower doses of NSAIDs, while 18% was associated with the use of proton-pump inhibitors and 14% with the use of less toxic NSAIDs. These declines in the incidence of NSAID gastropathy are likely to continue.
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Hagiwara M, Kataoka K, Arimochi H, Kuwahara T, Ohnishi Y. Role of unbalanced growth of gram-negative bacteria in ileal ulcer formation in rats treated with a nonsteroidal anti-inflammatory drug. THE JOURNAL OF MEDICAL INVESTIGATION 2004; 51:43-51. [PMID: 15000255 DOI: 10.2152/jmi.51.43] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) induced formation of intestinal ulcers as side effects, in which an unbalanced increase in the number of gram-negative bacteria in the small intestine plays an important role. To clarify how intestinal microflora are influenced by NSAIDs, we examined the effects of 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT), an NSAID, on intestinal motility and on the growth of Escherichia coli and Lactobacillus acidophilus. Transit index, a marker of peristalsis, was not different in BFMeT-treated and solvent-treated rats, indicating that BFMeT increased the number of gram-negative bacteria without suppression of peristalsis. The factors that affect the growth of intestinal bacteria were not found in intestinal contents of BFMeT-treated rats, because the growth of E. coli and that of L. acidophilus in the supernatants of small intestinal contents of BFMeT-treated rats and solvent-treated rats were not different. The mechanism of the increase in the number of gram-negative bacteria is still unclear, but heat-killed E. coli cells and their purified lipopolysaccharide (LPS) caused deterioration of BFMeT-induced ileal ulcers, while they could not cause the ulcers by themselves without the NSAID. Concentration of LPS and myeloperoxidase activity level were elevated correlatively in the intestinal mucosa of rats treated with LPS and BFMeT. These results suggest that an increase in the number of gram-negative bacteria and their LPS in the mucosa induces activation of neutrophils together with the help of NSAID action and causes ulcer formation.
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Affiliation(s)
- Mari Hagiwara
- Department of Molecular Bacteriology, Graduate School of Medicine, The University of Tokushima, Tokushima, Japan
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Abstract
Medication-induced oesophageal distress and injury have become increasingly common conditions. First, smooth muscle relaxants may worsen or produce symptoms of pre-existing gastro-oesophageal reflux disease; notable examples include certain calcium antagonists (nifedipine), nitrates, sildenafil, nicotine, theophylline, and substances with antimuscarinic potential. Second, drugs with local toxicity may produce de novo damage including inflammation, strictures, ulcers, and bleeding. Notorious examples are alendronate, certain antibiotics including tetracyclines and clindamycin, all NSAIDs/aspirin, quinidine, potassium chloride, and ferrous sulfate. Cyclooxygenase-2 inhibitors may be devoid of such toxicity, but may damage the mucosa by interfering with regenerative cell proliferation. The galenic formulation can modulate the risk of oesophageal injury. For this reason, medicines containing the same potentially toxic ingredient may be less exchangeable than commonly thought. Diagnostic gold standard is endoscopy. The best treatment is removal of the offending drug and supportive care. Prevention requires a re-appraisal of the drug's indication and adherence to guidelines of optimal drug intake including ingestion in an upright position and swallowing with enough fluid. The clinical relevance of drug-induced oesophageal injury and the feasibility of therapeutic alternatives are individually addressed.
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Affiliation(s)
- Karl-Uwe Petersen
- Institut für Pharmakologie und Toxikologie, Rheinisch-Westfälische Technische Hochschule Aachen, Wendlingweg 2, 52057 Germany.
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Cozzarini W, Rath J, Bauer A, Györög I, Györög M, Prenner M, Trianto T, Maderbacher H, Höller E, Grusch B, Sebesta C. [Mucosa protective therapy with long-term nonsteroidal antirheumatic drugs]. Wien Med Wochenschr 2003; 153:295-303. [PMID: 12924104 DOI: 10.1046/j.1563-258x.2003.03035.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Due to the extraordinary high prevalence of peptic lesions in the upper gastrointestine in the long-term treatment with nonsteroidal anti-inflammatory drugs, a prophylaxis in patients belonging to high-risk groups is essential. Misoprostol, proton pump inhibitors and histamine 2-receptor antagonists have been evaluated in prospective studies. The efficacy of Misoprostol is well documented, though its use in prevention is frequently limited due to side effects. Proton pump inhibitors are also well established, especially in the therapy of nonsteroidal anti-inflammatory drugs associated peptic ulcers and in consecutive secondary prevention. The histamine 2-receptor antagonist Famotidine in a high oral dosage is able to reduce the frequency of peptic lesions too, but not to the same degree as Misoprostol and proton pump inhibitors. It is very likely that helicobacter pylori eradication without any further mucosaprotective therapy will only decrease the incidence of upper gastrointestinal bleeding in low dose Aspirin application. In spite of controversial studies this eradication seems to be a useful additional therapy for ulcer prophylaxis in high risk groups. Selective Cyclooxygenase-2 inhibitors may become a promising alternative, from a pathophysiological perspective. However, to date there has been a lack of clear comparative studies with common nonsteroidal anti-inflammatory drugs plus mucosaprotecting agents. Daily therapy costs are higher with a Cyclooxygenase-2 inhibitor than using the traditional nonsteroidal anti-inflammatory drugs together with either proton pump inhibitors, histamine 2-receptor antagonists or Misoprostol--a fact that should be considered in primary therapeutic decisions. In the following review we will present the most important results of the different prophylactic and therapeutic modalities. On the basis of placebo-controlled, prospective studies on the one hand and the recommendations of the scientific societies on the other, a guideline for daily clinical practice will be suggested.
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Affiliation(s)
- Wolfgang Cozzarini
- 1. Medizinischen Abteilung, NO Zentrum für Rheumatologie, Humanisklinikum Niederösterreich, Stockerau
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López-Cepero Andrada JM, Jiménez Arjona J, Amaya Vidal A, Rubio Garrido J, Navas Relinque C, Soria de la Cruz MJ, Benítez Roldán A. [Pseudoachalasia and secondary amyloidosis in a patient with rheumatoid arthritis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2002; 25:398-400. [PMID: 12069703 DOI: 10.1016/s0210-5705(02)70274-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Rheumatic diseases cover a wide spectrum of clinical syndromes and frequently present with gastrointestinal alterations. Systemic amyloidosis is associated with infectious diseases or chronic inflammatory processes such as rheumatoid arthritis and it can also affect the gastrointestinal tract. Although esophageal involvement is difficult to quantify because its course is frequently asymptomatic, systemic amyloidosis is recognized as a cause of motor disorders of the esophagus. Typical manometric patterns, including achalasia, are usually absent. Esophageal involvement due to amyloid deposits usually corresponds to primary amyloidosis as only a few cases of secondary esophageal deposits (type AA) have been described. We describe a new case of this exceptional association that first presented as dysphagia in a patient with rheumatoid arthritis. The initial suspicion of pseudoachalasia led to the definitive diagnosis of secondary amyloidosis.
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Abstract
Most peptic ulcers not due to Helicobacter pylori are caused by non-steroidal anti-inflammatory drugs (NSAID), among which an important subset are due to vascular protective ("low-dose") aspirin therapy. Non-steroidal anti-inflammatory drugs ulcers heal quite quickly when treated with a proton pump inhibitor (PPI), even though the NSAID is continued. If the NSAID can be stopped, the ulcers heal readily with either a PPI or a histamine H2-receptor antagonist (H2-RA). If anti-inflammatory treatment is still needed after ulcers are healed, prophylactic co-therapy with a PPI or misoprostol will reduce the risk of ulcer recurrence by about 60-80%. The alternative of switching to a highly selective cyclooxygenase-2 inhibitor has been shown to reduce the risk of a complicated ulcer by about 50-60%, unless low-dose aspirin treatment needs to be given as well for vascular disease. Idiopathic ulcers are becoming more frequent as H. pylori prevalence falls. Some may be sequelae of previous NSAID ulceration even though the NSAID has been ceased and the original ulcer had healed. These are best treated with an H2-RA or a PPI, followed by long-term maintenance with either of these (often in half the healing dosage) to prevent recurrence. Ulcers due to Zollinger-Ellison syndrome and other hypergastrinemia syndromes are rare, and largely beyond the scope of this review.
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Affiliation(s)
- Neville D Yeomans
- Department of Medicine, The University of Melbourne at Western Hospital, Footscray, Melbourne, Victoria 3011, Australia.
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Abstract
On the basis of their reduced potential to cause injury to the gastroduodenal mucosa, cyclo-oxygenase (COX)-2-selective inhibitors were developed and marketed as a safer alternative to traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This manuscript reviews the major steps leading to the introduction of COX-2-selective inhibitors into clinical practice, from the identification of the COX isoenzymes to their various roles in physiological and pathological processes. The available data show that COX-2 inhibitors have a favourable safety profile and are at least as effective as traditional NSAIDs for the treatment of pain and inflammatory conditions with a reduced incidence of gastrointestinal complications. Emerging evidence points to new and unanticipated effects from these agents. COX-2 inhibition appears to play an important role in the modulation of intestinal polyposis and colorectal carcinogenesis. Additionally, COX-2 expression may be associated with inflammatory responses leading to the occurrence of Alzheimer's disease and potentially, COX-2 inhibitors could be used to retard the progression of this condition. However, by decreasing prostacyclin production, COX-2 inhibitors may lead to increased prothrombotic activity and increase the risk of cardiovascular events. Until further large-scale prospective studies are performed, and the magnitude of these potential risks is quantified, COX-2 inhibitors should be used with caution in patients at risk for cardiovascular morbidity.
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Affiliation(s)
- J A Oviedo
- Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA
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Jones JI, Hawkey CJ. Physiology and organ-related pathology of the elderly: stomach ulcers. Best Pract Res Clin Gastroenterol 2001; 15:943-61. [PMID: 11866486 DOI: 10.1053/bega.2001.0251] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Peptic ulcer disease, particularly as a result of its complications, is a burden that is focused on the elderly through their higher Helicobacter pylori prevalence and use of non-steroidal anti-inflammatory drugs (NSAIDs). In these patients, senescence may further increase ulcer susceptibility, particularly in the stomach, by the loss of mucosal protection and repair mechanisms. Age is mainly a marker for the increased prevalence of other complicated ulcer risk factors such as previous ulcer history and use of anti-coagulants, steroids and aspirin. The development of selective cyclo-oxygenase inhibitors (coxibs) has reduced the specific risk of NSAID ulceration, but the residual incidence in high risk patients remains substantially higher than that in young patients without other risk factors. The argument for early surgery versus endoscopic therapy in high risk patients with bleeding ulcers has not been resolved, both having a high mortality. There is still potential for the development of new strategies to prevent primary and secondary ulcers, either by new drug development or by expanding existing co-prescription strategies.
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Affiliation(s)
- J I Jones
- Divison of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK
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30
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Abstract
By inhibiting prostaglandin synthesis, nonsteroidal anti-inflammatory drugs (NSAIDs) compromise gastroduodenal defense mechanism including blood flow and mucus/bicarbonate secretion. This has led to NSAIDs being the most widely reported drug cause of adverse events. While NSAIDs also cause dyspepsia, inhibition of prostaglandin synthesis may reduce this from even higher levels that would otherwise prevail and mask ulcer-related dyspepsia, making anticipatory management difficult. On average, the risk of ulcer complications increases 4-fold, resulting in 1.25 additional hospitalizations per 100 patient-years according to one estimate. Older patients, those with a past history, and those taking anticoagulants or corticosteroids are at higher risk. Risk is dose dependent and is lower with ibuprofen at low doses than with other NSAIDs. It is unlikely that Helicobacter pylori increases the risk, and under some circumstances it may be protective. Selective inhibitors of the inducible cyclooxygenase 2 spare gastric mucosal prostaglandin synthesis and do not damage the gastric mucosa. Their place in therapy, compared with use of misoprostol or proton pump inhibitors, is currently emerging. Future competitors may include nitric oxide-donating, zwitterionic, or R-enantiomer NSAIDs.
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Affiliation(s)
- C J Hawkey
- Division of Gastroenterology, University Hospital Nottingham, Queen's Medical Centre, Nottingham, England.
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Püspök A, Kiener HP, Oberhuber G. Clinical, endoscopic, and histologic spectrum of nonsteroidal anti-inflammatory drug-induced lesions in the colon. Dis Colon Rectum 2000; 43:685-91. [PMID: 10826432 DOI: 10.1007/bf02235589] [Citation(s) in RCA: 128] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE It has become increasingly clear that nonsteroidal anti-inflammatory drugs may cause damage not only to the upper gastrointestinal tract but also to the small and large intestine. Although the colon may be readily investigated by endoscopy, drug-induced lesions are not well known, probably because they are considered to occur only rarely. In the present study we describe endoscopic, histologic, and gross characteristics of nonsteroidal anti-inflammatory drug-induced colonic damage. Furthermore, pathogenetic mechanisms and therapeutic options are discussed. METHODS The histories of all patients diagnosed as having nonsteroidal anti-inflammatory drug colitis during the last two years at the department of gastroenterology or the department of pathology at our hospital were reviewed. Endoscopic, histologic, and gross pathologic findings were systematically recorded. In addition, data on duration and type of nonsteroidal anti-inflammatory drug intake and time from onset of symptoms to diagnosis were collected. Therapy and outcome of our patients, if available, are reported. RESULTS During the study period 11 patients were diagnosed as having nonsteroidal anti-inflammatory drug colitis. Most patients presented with diarrhea with or without blood loss and complained about diffuse abdominal pain. Endoscopy revealed flat ulcers in the entire colon being more severe in the right colon in the three cases with acute onset of diarrhea. In four cases concentric "diaphragm-like" strictures were seen, all located in the right colon. In the remainder endoscopy showed nonspecific erosions and was normal in one patient. Histology revealed findings similar to ischemic colitis. Additionally, in two cases collagenous colitis was found. Diclofenac slow release was the most commonly involved drug. The median time from onset of symptoms to diagnosis was 1.8 (range, 0-11.5) years. CONCLUSIONS Nonsteroidal anti-inflammatory drug colitis is a clinically significant disease, which may present with diarrhea, anemia, and nonspecific abdominal complaints. Careful history taking, together with awareness of endoscopic and histologic findings, allows a timely diagnosis of this disease.
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Affiliation(s)
- A Püspök
- Clinic of Internal Medicine IV, AKH, Vienna, Austria
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32
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Abstract
Drug-induced injury of the oesophagus is a common cause of oesophageal complaints. 'Pill-induced' oesophagitis is associated with the ingestion of certain drugs and accounts for many cases of erosive oesophagitis. To date, more than 70 drugs have been reported to induce oesophageal disorders. Antibacterials such as doxycycline, tetracycline and clindamycin are the offending agents in more than 50% of cases. Other commonly prescribed drugs that cause oesophageal injury include aspirin (acetylsalicylic acid), potassium chloride, ferrous sulfate, quinidine, alprenolol and various steroidal and nonsteroidal anti-inflammatory agents. However, many physicians and even more patients are not aware of this problem. Capsules or tablets are commonly delayed in their passage through the oesophagus. Highly caustic coatings, direct medication injury and poor oesophageal clearance of pills can lead to acute inflammation. Oesophageal damage occurs when the caustic contents of a drug remain in the oesophagus long enough to produce mucosal lesions. Taking medications at bedtime or without fluids is a common cause of oesophagitis. The possibility of drug-related damage should be suspected in all cases of oesophagitis, chest pain and dysphagia. History and gastrointestinal endoscopy will confirm the diagnosis. Treatment is supportive, although acid reduction is used frequently as an adjunct. This review reflects the current state of knowledge in this field.
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Affiliation(s)
- D Jaspersen
- Department of Gastroenterology, Academic Medical Hospital, Fulda, Germany.
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Affiliation(s)
- M M Wolfe
- Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, MA 02118-2393, USA.
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Bailey M, Chapin W, Licht H, Reynolds JC. The effects of vasculitis on the gastrointestinal tract and liver. Gastroenterol Clin North Am 1998; 27:747-82, v-vi. [PMID: 9890113 DOI: 10.1016/s0889-8553(05)70032-7] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Vasculitis can affect every organ of the digestive system. In many cases, it may first present with gastrointestinal symptoms. In several forms of vasculitis, including Churg Strauss syndrome, Henoch-Schönlein purpura, and lupus, the majority of patients have gastrointestinal involvement. The astute gastroenterologist should consider vasculitic causes of the symptoms seen in many patients. Making the correct diagnosis requires a thorough understanding of the potential role of vasculitis in causing these symptoms and the appropriate path to making a diagnosis. This article reviews the variety of manifestations of vasculitis on the digestive system, and emphasizes diagnosis and clinical manifestations.
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Affiliation(s)
- M Bailey
- Department of Medicine, Allegheny University of the Health Sciences-Medical College of Pennsylvania, USA
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Abstract
The first clinical reports on the treatment of fever and pain with salicylate-containing natural willow bark remedies were made by the English clergyman Edward Stone in 1763. The pharmacologically active principles were isolated from natural sources by Italian, German and French scientists between 1826 and 1829. Salicylic acid was first synthesised by the German Gerland in 1852 and a year later the Frenchman Gerhardt synthesised acetylsalicylic acid. The first reports on the clinical use of salicylic acid in rheumatic disorders were made independently by the two German physicians Stricher and Reiss in 1876. Acetylsalicylic acid was rediscovered by Hoffmann in 1897 and by the turn of the century it had gained worldwide recognition in the treatment of pain and rheumatological disorders. Reports on adverse events relating to gastrointestinal intolerance and bleeding appeared early, but were largely neglected until the 1950s. Today, salicylates are still widely used as analgesic, antipyretic and anti-inflammatory drugs. New indications, such as thrombosis prophylaxis, have emerged during the last decades, and yet others are being explored.
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Affiliation(s)
- T Hedner
- Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.
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Kinouchi T, Kataoka K, Bing SR, Nakayama H, Uejima M, Shimono K, Kuwahara T, Akimoto S, Hiraoka I, Ohnishi Y. Culture supernatants of Lactobacillus acidophilus and Bifidobacterium adolescentis repress ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug by suppressing unbalanced growth of aerobic bacteria and lipid peroxidation. Microbiol Immunol 1998; 42:347-55. [PMID: 9654366 DOI: 10.1111/j.1348-0421.1998.tb02294.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
A nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT), induced ileal ulcers in rats after oral administration, while no ulcers were observed after subcutaneous injection. The ileal ulcer formation in BFMeT-treated rats was examined to correlate the administration of cultures of Lactobacillus acidophilus or Bifidobacterium adolescentis with intestinal bacteria in the ileal contents and lipid peroxidation of the small intestinal mucosa. Ileal ulcers were observed in more than 85% of the rats treated with BFMeT at a dose of 1,000 mg/kg when they were given tap water as drinking water. The incidence of ulcer formation was repressed by giving culture supernatants of L. acidophilus or B. adolescentis as drinking water, but not by giving the cell suspension as drinking water. Gram staining of the ileal contents of normal rats revealed that 97% of the stained bacteria were gram-positive rods and only 1.5% were gram-negative rods. The percentage of gram-negative rods 72 hr after BFMeT administration was 49.8% and increased over 30-fold in BFMeT-treated rats. However, the percentage of gram-negative rods was 9.7 % or 16%, respectively, in rats taking culture supernatants of L acidophilus or B. adolescentis. In addition, thiobarbituric acid-reactive substances in the ileal mucosa increased significantly in the rats given tap water for 72 hr after BFMeT treatment, but not in rats given the culture supernatants of L. acidophilus or B. adolescentis. Since BFMeT induced an unbalanced intestinal microflora, the effect of antibiotic treatment on ulcer formation in rats was examined. The magnitude of the ulcer formation in the antibiotic-treated rats was, in decreasing order, metronidazole >none > kanamycin > a mixture (bacitracin, neomycin and streptomycin). These results suggest that the intestinal microflora plays an important role in ulcer formation and that a metabolite(s) of L. acidophilus and B. adolescentis inhibits ileal ulcer formation by repressing changes in the intestinal microflora and lipid peroxidation in BFMeT-treated rats.
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Affiliation(s)
- T Kinouchi
- Department of Bacteriology, School of Medicine, The University of Tokushima, Japan
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Uejima M, Kinouchi T, Kataoka K, Hiraoka I, Ohnishi Y. Role of intestinal bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug. Microbiol Immunol 1996; 40:553-60. [PMID: 8887349 DOI: 10.1111/j.1348-0421.1996.tb01108.x] [Citation(s) in RCA: 81] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The role of intestinal bacteria in induction and repression of ulcer formation in the ileum of rats treated with one of the nonsteroidal antiinflammatory drugs (NSAIDs), 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT), was examined in this study. BFMeT was administered by intragastric gavage once at doses of 500-1,500 mg/kg of body weight to Wistar rats treated with and without antibiotics (bacitracin, neomycin, streptomycin), germ-free rats and gnotobiotic rats, and 72 hr later their gastrointestinal tracts were examined for ulcer formation. A single oral administration of BFMeT induced ileal ulcers in specific pathogen-free rats. However, the rats given antibiotics to reduce the intestinal bacteria had no ulcers. BFMeT-treated germ-free rats and gnotobiotic rats mono-associated with Bifidobacterium adolescentis or Lactobacillus acidophilus also had no intestinal ulcers. However, the drug induced ileal ulcers in gnotobiotic rats mono-associated with Eubacterium limosum or Escherichia coli. An overnight culture of B. adolescentis or L. acidophilus or yogurt containing Bifidobacterium breve and Streptococcus thermophilus, when given as drinking water, inhibited ulcer formation in the ileum of rats treated with BFMeT. Gram staining of the ileal contents of normal rats revealed that 97.4% of the stained microorganisms were Gram-positive rods and only 1.2% were Gram-negative rods. In the group of rats with ulcers induced by BFMeT, the Gram-positive rods decreased by 56.4% and the Gram-negative rods including Escherichia coli, Klebsiella, Proteus and Bacteroides increased by 37.3%. However, in the group of rats administered the Bifidobacterium culture, the Lactobacillus culture or yogurt, the percentages of the Gram-negative rods were decreased. Although Lactobacillus was a major bacterium in the ileum of normal rats, the Gram-negative facultatively anaerobic rods E.coli, Klebsiella and Proteus were increased in the ulcerated ileum of rats treated with BFMeT, suggesting that these bacteria are associated with ulcer formation in rats treated with NSAIDs, and that Lactobacillus and Bifidobacterium inhibit it by repressing the growth of ulcer-inducing bacteria.
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Affiliation(s)
- M Uejima
- Department of Bacteriology, School of Medicine, University of Tokushima, Japan
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Dowd JE, Cimaz R, Fink CW. Nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children. ARTHRITIS AND RHEUMATISM 1995; 38:1225-31. [PMID: 7575716 DOI: 10.1002/art.1780380908] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To determine the incidence of abdominal pain and gastroduodenal injury in children with arthritis taking nonsteroidal antiinflammatory drugs (NSAIDs). METHODS A retrospective review of the records of all children (570 patients) receiving followup care in an academic rheumatology clinic between 1991 and 1993 was performed. RESULTS There were 344 patients who used NSAIDs during the study period. Abdominal pain was recorded in 27.9% of patients taking NSAIDs and 14.6% of patients not taking NSAIDs. Abdominal pain in 47 patients (49%) taking NSAIDs and 14 patients (42%) not taking NSAIDs was evaluated radiographically and/or endoscopically. Among those patients evaluated, gastric or duodenal injury was found in 16 (34.0%) who were taking NSAIDs and 1 (7.1%) who were not. This represented a relative risk for gastroduodenal injury of 4.8 for patients taking NSAIDs (P = 0.09). The incidence of injury did not change when analyses were controlled for prednisone or slow-acting antirheumatic drug use. None of the children were hospitalized or died as a result of gastroduodenal injury during the 3-year period. CONCLUSION We conclude that NSAID use in children with arthritis frequently leads to gastroduodenal injury, with an estimated incidence and relative risk that are comparable to the rates found in adults with arthritis taking NSAIDs, but that hospitalization or death as a result of this injury is uncommon.
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Affiliation(s)
- J E Dowd
- University of Texas Southwestern Medical Center, Dallas, USA
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Abstract
Nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy is an important clinical entity, most commonly encountered in elderly female patients. The expanding use of NSAIDs in the elderly population has led to an increased incidence of NSAID-induced gastropathy. The risk of gastric bleeding in these patients is 7-fold higher than in the younger population. Long term NSAID therapy in the elderly is apparently associated with failure of normal gastric mucosal adaptation. Silent unidentified gastric lesions are likely to be common with long term NSAID therapy, as symptomatology does not parallel pathological progression. This gastropathy, in contrast to peptic ulcer disease, is responsive to prostaglandins and other cytoprotective agents. A new generation of prostaglandin-sparing NSAIDs (e.g. nabumetone), in addition to the older nonacetylated salicylates, may represent less gastrotoxic alternatives. Therefore, these agents may substantially reduce the risk of NSAID-induced gastropathy. The debate continues as to whether to use NSAIDs, and under which circumstances. More importantly, the cost-benefit implications and justification for concomitant therapy with gastroprotective agents cloud the picture. Currently, there is a definite consensus that NSAIDs should not be casually used on a chronic basis, especially in patients at risk for serious gastropathy complications. In all cases, where possible, gastric prostaglandin-sparing NSAIDs or nonacetylated salicylates should be used in lowest effective dosages. In special circumstances, gastroprotective co-therapy can be considered. NSAID therapy probably should not be used or continued in elderly patients with a history of bleeding ulcers or recent major gastric ulcer activity.
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Affiliation(s)
- S H Roth
- Arthritis Center, Phoenix, Arizona, USA
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Carryl OR, Spangler RS. Comparative effects of nabumetone, naproxen, piroxicam, and diclofenac on rat gastric irritancy following acute exposure to OTC non-steroidal anti-inflammatory agents and other gastric irritants. Scand J Rheumatol 1995; 24:336-41. [PMID: 8610216 DOI: 10.3109/03009749509095177] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This study examined the relative effects of equally-effective anti-inflammatory doses of nabumetone, naproxen, piroxicam and diclofenac on gastric irritancy induced by over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs) aspirin and ibuprofen and a variety of necrotizing agents (0.6 N HCl, 0.2 N NaOH and 25% NaCl). Within one hour, aspirin 100 and 200 mg/kg and ibuprofen up to 15 mg/kg produced significant gastric mucosal injury. Aspirin 50 mg/kg produced only minimal damage that was enhanced by 5 x ID25 piroxicam and naproxen, but not by nabumetone or diclofenac. 5 x ID25 naproxen, piroxicam, and diclofenac significantly enhanced mucosal damage produced by ibuprofen 2.5 mg/kg. An equivalent anti-inflammatory dose of nabumetone failed to enhance the gastric irritancy produced by ibuprofen 2.5 mg/kg. Similarly, naproxen, piroxicam, and diclofenac enhanced the susceptibility of the gastric mucosa to the necrotizing actions of 0.6 N HCl, 0.2 N NaOH or 25% NaCl. Naproxen, piroxicam, or diclofenac are more likely than nabumetone to enhance gastric mucosal injury produced by OTC NSAIDs (aspirin and ibuprofen) or other gastric irritants.
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Affiliation(s)
- O R Carryl
- Procter and Gamble Company, Cincinnati, Ohio, USA
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Dijkmans BA, Janssen M, Vandenbroucke JP, Lamers CB. NSAID-associated upper gastrointestinal damage in patients with rheumatoid arthritis. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1995; 212:105-8. [PMID: 8578222 DOI: 10.3109/00365529509090308] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
AIM OF THE STUDY The main aim of the present study was to identify the patient with rheumatoid arthritis (RA) taking non-steroidal anti-inflammatory drugs (NSAIDs) at risk for peptic ulcer disease (PUD) and its life-threatening complications. PATIENTS AND METHODS During a retrospective study in which more than 1000 patients were interviewed, current gastrointestinal (GI) complaints were of no use in detecting current PUD. RESULTS A history of PUD was an important predictor of current PUD, while the predictive value of serologic parameters, such as serum values of pepsinogen and antibodies to Helicobacter pylori, was disappointingly low. A prospective study in which 81 consecutive RA patients underwent a gastroscopy revealed 16% PUD; again a history of PUD was the most important predictive parameter. Since no study had been undertaken into the effects of a NSAID on intragastric pH we performed such a study, the main conclusion being that indomethacin does not influence the intragastric pH of RA patients. A placebo-controlled study of ranitidine 300 mg b.i.d. for the prevention of recurrent PUD in RA patients on NSAIDs is underway.
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Affiliation(s)
- B A Dijkmans
- Dept. of Rheumatology, University Hospital, Leiden, The Netherlands
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Elliott SL, Yeomans ND, Buchanan RR, Smallwood RA. Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial. Scand J Rheumatol 1994; 23:171-6. [PMID: 8091141 DOI: 10.3109/03009749409103056] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
We performed a 12-month, double-blind, randomised, placebo-controlled study to determine the long term effect of misoprostol (600-800 micrograms/d) in the prevention of gastric ulcers and gastroduodenal erosions in 83 arthritis patients on chronic NSAID therapy. Patients underwent endoscopy at 0, 3, 6 and 12 months. At the initial endoscopy, 12 patients had an ulcer (11 gastric), which was healed prior to randomization. Seventy eligible patients reached the 3 month endoscopy. Four (12.5%) of the 32 patients given misoprostol developed a gastric ulcer compared with 11 (28.9%) of the 38 on placebo (p < 0.05, life-table analysis). Six of the 11 patients with an initial gastric ulcer developed a further gastric ulcer, compared to 9 of 58 patients without an initial ulcer (p < 0.05). We conclude that misoprostol decreases the cumulative development of NSAID-induced gastric ulcers. Patients with a previous NSAID-ulcer have a higher risk of further ulceration.
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Affiliation(s)
- S L Elliott
- University of Melbourne Department of Medicine, Austin Repatriation Hospital, Australia
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Bjarnason I, Hayllar J, MacPherson AJ, Russell AS. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993; 104:1832-47. [PMID: 8500743 DOI: 10.1016/0016-5085(93)90667-2] [Citation(s) in RCA: 671] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND It is not widely appreciated that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause damage distal to the duodenum. We reviewed the adverse effects of NSAIDs on the large and small intestine, the clinical implications and pathogenesis. METHODS A systematic search was made through Medline and Embase to identify possible adverse effects of NSAIDs on the large and small intestine. RESULTS Ingested NSAIDs may cause a nonspecific colitis (in particular, fenemates), and many patients with collagenous colitis are taking NSAIDs. Large intestinal ulcers, bleeding, and perforation are occasionally due to NSAIDs. NSAIDs may cause relapse of classic inflammatory bowel disease and contribute to serious complications of diverticular disease (fistula and perforation). NSAIDs may occasionally cause small intestinal perforation, ulcers, and strictures requiring surgery. NSAIDs, however, frequently cause small intestinal inflammation, and the associated complications of blood loss and protein loss may lead to difficult management problems. The pathogenesis of NSAID enteropathy is a multistage process involving specific biochemical and subcellular organelle damage followed by a relatively nonspecific tissue reaction. The various possible treatments of NSAID-induced enteropathy (sulphasalazine, misoprostol, metronidazole) have yet to undergo rigorous trials. CONCLUSIONS The adverse effects of NSAIDs distal to the duodenum represent a range of pathologies that may be asymptomatic, but some are life threatening.
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Affiliation(s)
- I Bjarnason
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, England
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Morgan SL, Hine RJ, Vaughn WH, Brown A. Dietary intake and circulating vitamin levels of rheumatoid arthritis patients treated with methotrexate. ARTHRITIS CARE AND RESEARCH : THE OFFICIAL JOURNAL OF THE ARTHRITIS HEALTH PROFESSIONS ASSOCIATION 1993; 6:4-10. [PMID: 8443257 DOI: 10.1002/art.1790060103] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The nutrient intakes and circulating vitamin levels of 32 patients with rheumatoid arthritis who were treated with methotrexate were evaluated over a 6-month period. Dietary data were obtained and blood was drawn prior to the initiation of and following 12 and 24 weeks of methotrexate therapy. More than 50% of the patients had food intakes providing less than 67% of the recommended dietary allowance for zinc, vitamin E, folic acid, pyridoxine, and magnesium. Patients 51 years or older had better nutrient intakes than patients less than 51 years. Of the patients, 22% consumed vitamin supplements at the time they were recruited for the study. Mean circulating vitamin levels measured over the 6-month period were within normal limits. Our findings agree with previously published reports that patients with rheumatoid arthritis, particularly the subpopulation taking methotrexate, consume diets that are marginal in some nutrients. Additional research needs to be done to identify more sensitive nutrient assays and to establish more definitively the nutrient needs of patients with rheumatoid arthritis taking several therapeutic agents.
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al-Quorain AA, Satti MB, Marwah S, al-Nahdi M, al-Habdan I. Non-steroidal anti-inflammatory drug-induced gastropathy: a comparative endoscopic and histopathological evaluation of the effects of tenoxicam and diclofenac. J Int Med Res 1993; 21:89-97. [PMID: 8243794 DOI: 10.1177/030006059302100204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
A 4-week double-blind study compared the potential for 20 mg/day tenoxicam or 100 mg/day diclofenac sodium to induce gastropathy in 36 patients with joint disease and assessed the influence of gastric colonization by Helicobacter pylori. Endoscopic assessment at the end of 4 weeks indicated that the mucosa was normal in 79% of tenoxicam-treated patients and 59% of diclofenac-treated patients. Only 5% of patients in the tenoxicam group developed severe gastroduodenitis (> 11 haemorrhages or erosions) compared with 18% in the diclofenac group. Histological evaluation indicated that 58% and 47%, respectively, of tenoxicam-treated and diclofenac-treated patients retained normal mucosa after treatment. Diclofenac treatment was discontinued in two patients, due to a duodenal ulcer or severe erosive gastritis. Overall, 5/14 patients with moderate to severe colonization with Helicobacter pylori developed severe chronic active gastritis or ulceration, compared with the 1/22 patients in whom colonization was either absent or mild (P = 0.02). Tenoxicam and diclofenac did not show major differences in terms of gastrointestinal safety, although the trends favoured tenoxicam. The presence of severe colonization of the gastric mucosa with Helicobacter pylori appears to be an important factor for development of severe gastritis or ulceration.
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Affiliation(s)
- A A al-Quorain
- College of Medicine and Medical Sciences, King Faisal University, Dammam, Saudi Arabia
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Uribe A. Indomethacin inhibits cell proliferation in the oxyntic epithelium of the rat. PROSTAGLANDINS 1993; 45:15-26. [PMID: 8424129 DOI: 10.1016/0090-6980(93)90086-m] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The aim of this investigation was to examine the action of parenteral indomethacin and oral prostaglandin E2 on cell proliferation in the rat oxyntic mucosa. Groups of Sprague Dawley rats were treated with either 1.5 mg/kg indomethacin subcutaneously, 5 mg/kg oral prostaglandin E2 or placebo, twice daily during 5 days. All rats were killed exactly 4 hours after mitotic arrest with vincristine, and a biopsy specimen from the oxyntic mucosa was processed for routine microscopic evaluation. Mitotic figures were distributed cluster-like along the oxyntic mucosa alternating with mitosis-free areas. The total number of mitotic figures in 8 mm of mucosa was significantly reduced by administration of indomethacin (p < 0.05). In rats given indomethacin, 32.5% of the examined mucosa did not have mitotic figures, which is significantly higher than 14.3% as observed in placebo-treated rats (p < 0.05). Both rats treated with indomethacin and with prostaglandin E2 had fewer microscopic fields containing 5-6 mitotic figures than placebo-treated animals (p < 0.05). The maximal length of mitosis-free areas was 0.6 (0.6-0.9) mm in rats given indomethacin which is significantly larger than 0.4 (0.2-0.4) mm observed in controls (p < 0.05). Indomethacin produced epithelial atrophy as shown by a significant reduction of the epithelial height observed in those rats compared to controls (p < 0.05). The inhibition of cell proliferation observed in the oxyntic mucosa of rats treated with the cyclooxygenase blocker indicates that an important physiological role of endogenous prostaglandin is to maintain the proliferative activity of the epithelium at a high level.
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Affiliation(s)
- A Uribe
- Department of Medicine, Karolinska Institute Danderyd Hospital, Stockholm, Sweden
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Abstract
Peptic ulcer disease usually has periodic exacerbations and remissions. Pain can disappear without total healing of the ulcer crater and can be absent when an ulcer is present. Changes in the incidence of ulcer disease have been noted in recent years. Genetic predisposition, infection with H. pylori, and the use of anti-inflammatory drugs are involved in causation. Stress; the use of alcohol, tobacco and caffeine; and other diseases have been implicated as etiologic factors. Ulcer pain has a recognizable pattern, but the symptoms can be variable, particularly in older people and in patients taking ulcerogenic medications. The familiar complications of hemorrhage, perforation, and obstruction still occur, and nonulcer dyspepsia has not been fully explained. Duodenal ulcers have a disturbing tendency to return; new therapeutic approaches offer hope.
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Affiliation(s)
- J Katz
- Medical College of Pennsylvania, Philadelphia
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Euler AR, Safdi M, Rao J, Jaszewski R, Welsh J, Le V, Raskin J, Fleischmann R, Razzaque M, Champion C. A report of three multiclinic trials evaluating arbaprostil in arthritic patients with ASA/NSAID gastric mucosal damage. The Upjohn Company Arbaprostil ASA/NSAID Gastric Mucosal Damage Treatment Study Groups. Gastroenterology 1990; 98:1549-57. [PMID: 2186951 DOI: 10.1016/0016-5085(90)91089-o] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25- and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology.
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Marshall JB, Kretschmar JM, Gerhardt DC, Winship DH, Winn D, Treadwell EL, Sharp GC. Gastrointestinal manifestations of mixed connective tissue disease. Gastroenterology 1990; 98:1232-8. [PMID: 2323516 DOI: 10.1016/s0016-5085(12)90338-8] [Citation(s) in RCA: 84] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We examined the gastrointestinal tract abnormalities in 61 patients with mixed connective tissue disease. The first 34 were part of a prospective longitudinal study that included manometric and radiographic evaluation of the esophagus. Heartburn (48%) and dysphagia (38%) were by far the most common gastrointestinal symptoms. Seventeen percent of patients undergoing manometry had distal esophageal aperistalsis, and 43% low-amplitude peristalsis (less than 30 mmHg). Studies in 10 patients before and after treatment suggested that esophageal dysfunction in mixed connective tissue disease may be responsive to corticosteroids. Upper esophageal sphincter hypotension was also common. One patient had marked upper esophageal sphincter hypotension and recurrent aspiration, which resolved with corticosteroid therapy. Findings on radiographic studies of the stomach and small bowel in 54 patients and barium enemas in 16 patients were reviewed. Our series included one case each of malabsorption, colonic and small bowel perforations due to vasculitis, chronic active hepatitis, and acute pancreatitis. In conclusion, any area of the gastrointestinal tract may be affected by mixed connective tissue disease, although the esophagus is the most common location. The gastrointestinal aspects of mixed connective tissue disease overlap with those of progressive systemic sclerosis, polymyositis, and systemic lupus erythematosus.
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Affiliation(s)
- J B Marshall
- Department of Medicine, University of Missouri-Columbia School of Medicine
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Correction: Prophylactic antibiotics and caesarean section. West J Med 1990. [DOI: 10.1136/bmj.300.6720.284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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