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Joseph A Murray

Publications and source records attributed to Joseph A Murray.

At least 19 recordsLinked to original sources
PubMed2006

Allergen-specific in vitro cytokine production in adult patients with eosinophilic esophagitis.

Although the pathogenesis of eosinophilic esophagitis (EE) likely involves hypersensitivity reactions against exogenous allergens, allergen-specific cellular immune responses have not been studied. We investigated allergen-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in adult patients with EE (n=15) and healthy controls (HC; n=9). PBMCs were incubated with nine common food and environmental allergens or a nonspecific mitogen, and the levels of interleukin (IL)-5, IL-10, IL-13, and interferon-gamma in the cell-free supernatants were determined. Spontaneous and mitogen-stimulated cytokine production did not differ between EE and HC. House dust mite, ragweed, Aspergillus, milk, and soy induced significantly higher IL-5 production in EE (P < 0.05). House dust mite also augmented IL-13 production in EE (P < 0.05). Furthermore, PBMCs from three EE patients without allergen-specific IgE vigorously produced IL-5 and IL-13 on allergen stimulation. Thus, immune responses in EE are characterized by enhanced production of Th2-like cytokines against both food and environmental allergens.

Adult↗
PubMed2006

Hematologic manifestations of celiac disease.

Celiac disease is a common systemic disorder that can have multiple hematologic manifestations. Patients with celiac disease may present to hematologists for evaluation of various hematologic problems prior to receiving a diagnosis of celiac disease. Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication of celiac disease and many patients have anemia at the time of diagnosis. Celiac disease may also be associated with thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency. Patients with celiac disease are at increased risk of being diagnosed with lymphoma, especially of the T-cell type. The risk is highest for enteropathy-type T-cell lymphoma (ETL) and B-cell lymphoma of the gut, but extraintestinal lymphomas can also be seen. ETL is an aggressive disease with poor prognosis, but strict adherence to a gluten-free diet may prevent its occurrence.

Anemia↗
PubMed2006

Cognitive impairment and celiac disease.

OBJECTIVE: To characterize the clinical, radiological, and electrophysiological laboratory profiles and histological features of patients who developed cognitive impairment temporally associated with celiac disease. DESIGN: Case series. SETTING: Referral center. PATIENTS: Patients with the onset of progressive cognitive decline within 2 years of symptomatic onset or with a severe exacerbation of biopsy-proved adult celiac disease were identified from the Mayo Clinic medical records from January 1, 1970, to December 31, 2005. Patients were excluded if an alternate cause of their cognitive impairment was identified. RESULTS: Thirteen patients (5 women) were identified. The median age at cognitive impairment onset was 64 years (range, 45-79 years), which coincided with symptom onset or exacerbation of diarrhea, steatorrhea, and abdominal cramping in 5 patients. Amnesia, acalculia, confusion, and personality changes were the most common presenting features. The average initial Short Test of Mental Status score was 28 of a total of 38 (range, 18-34), which was in the moderately impaired range. The results of neuropsychological testing suggested a trend of a frontosubcortical pattern of impairment. Ten patients had ataxia, and 4 of them also had peripheral neuropathy. Magnetic resonance imaging of the head showed nonspecific T2 hyperintensities, and electroencephalography showed nonspecific diffuse slowing. Deficiencies in folate, vitamin B(12), vitamin E, or a combination were identified in 4 patients, yet supplementation did not improve their neurological symptoms. Three patients improved or stabilized cognitively with gluten withdrawal. A detailed histological analysis revealed nonspecific gliosis. CONCLUSIONS: A possible association exists between progressive cognitive impairment and celiac disease, given the temporal relationship and the relatively high frequency of ataxia and peripheral neuropathy, more commonly associated with celiac disease. Given the impact for potential treatment of similar cases, recognition of this possible association and additional studies are warranted.

Aged↗
PubMed2006

Atrophic autoimmune pangastritis: A distinctive form of antral and fundic gastritis associated with systemic autoimmune disease.

The 2 major recognized forms of atrophic gastritis are autoimmune and environmental atrophic gastritis. These differ in their topographical distribution in the stomach, histologic features, and etiology. Autoimmune atrophic gastritis results from immune-mediated destruction of specialized oxyntic glands, is restricted to the body and fundus, and shows characteristic neuroendocrine hyperplasia. Environmental atrophic gastritis is associated with long-standing Helicobacter pylori infection and preferentially involves antrum and transition zone mucosa. In this study, we describe a distinctive form of atrophic gastritis that differs markedly from both of these classic variants. This gastritis is characterized by: (1) intense mucosal inflammatory infiltrates, persisting even into the phase of severe glandular atrophy, (2) pangastric distribution with diffuse involvement of both body and antrum, (3) lack of association with H. pylori, and (4) lack of neuroendocrine hyperplasia. The 8 patients presented ranged from 1 to 75 years and showed a slight female predominance (5F:3M). All had systemic autoimmune and/or connective tissue diseases including autoimmune enterocolitis (4 cases), systemic lupus erythematosus, refractory sprue, autoimmune hemolytic anemia, and disabling fibromyalgia. Positive serum autoimmune markers were documented in 7 of 8 (87%) patients, but serologies for antiparietal cell and anti-intrinsic factor antibodies were undertaken in only 1 patient each and were negative. We propose that the distinctive histology of this form of atrophic pangastritis and its association with systemic autoimmune disease suggests an autoimmune process directed against multiple cell lineages in the stomach. The development of multifocal low-grade dysplasia in 1 patient, a 19-year-old woman, suggests that this condition might have neoplastic potential.

Adolescent↗
PubMed2006

Airway manifestations of pediatric eosinophilic esophagitis: a clinical and histopathologic report of an emerging association.

OBJECTIVES: Pediatric eosinophilic esophagitis (EE) typically presents with dysphagia, vomiting, dyspepsia, or food impaction. The purpose of this study was to highlight the emerging association of pediatric EE and airway disease. An additional goal of this study was to describe the unique histopathologic findings found in EE and specifically explore the potential role of the cytotoxic protein called eosinophil major basic protein (MBP) in the pathophysiology of the disease. METHODS: A retrospective review of 3 children with EE and airway symptoms included symptom presentation, aerodigestive tract endoscopic findings, ambulatory 24-hour dual pH-metry, allergy tests, treatment modalities, and treatment response. Esophageal tissue obtained from biopsies of each patient was evaluated by hematoxylin and eosin to determine the number of eosinophils per high-power field, by immunofluorescent anti-MBP staining to determine the presence of MBP, and by standard light and transmission electron microscopy to evaluate eosinophil migration patterns. RESULTS: All patients had airway inflammation that included nonspecific laryngeal edema and grade I or II subglottic stenosis. Allergy testing was positive in the 2 patients who were tested. All patients had symptoms refractory to standard reflux therapy. Ambulatory pH-metry findings were normal in 2 patients and abnormal in 1 patient despite maximum treatment. Two patients had visual abnormalities seen during esophageal examination. The number of eosinophils ranged from 20 to 45 per high-power field. Intracellular and extracellular MBP deposition was found in all esophageal biopsy specimens. All patients were treated with swallowed fluticasone, and 2 had symptom relapses that required repeat treatment. CONCLUSIONS: The spectrum of pediatric EE can include upper airway disease. Intracellular and extracellular MBP deposition is present in EE, which potentially releases cytotoxic mediators that explain the esophageal and airway clinical symptoms seen in those with the disease. Eosinophilic esophagitis should be considered in patients with a history of atopic diseases and unexplained upper airway findings refractory to reflux treatment. Treatment with swallowed fluticasone is successful; however, relapses are common and require repeat treatment and close follow-up.

Adolescent↗
PubMed2006

Gluten-free diet: the medical and nutrition management of celiac disease.

Celiac disease (CD) is a chronic disease causing inflammation of the proximal small intestine that occurs in genetically predisposed individuals when they eat gluten, which is the storage protein in wheat, barley, and rye. The disease injury usually resolves when gluten is excluded from the diet. Although the injury will heal, the reaction to gluten is permanent and will recur with the reintroduction of gluten. The condition is surprisingly common, affecting as many as 1% of white populations. The consequences of the disease are predominantly those of malnutrition due to maldigestion and malabsorption, such as diarrhea, weight loss, and anemia. Symptoms caused by inflammation of the small intestine are also common. CD, although it is common and its pathology is well understood, frequently goes undiagnosed, probably because of the nonspecific or vague nature of many of the symptoms that occur. The cornerstone of treatment for CD is elimination of gluten from the diet. In most patients diagnosed with CD, a strict gluten-free diet (GFD) alone should result in complete symptomatic and histologic resolution of the disease and reduce risk of complications. Noncompliance with diet is the leading cause of failure to respond in patients with CD. For these reasons, thorough assessment and counseling at the time of diagnosis and ongoing care are crucial. In this article, we address briefly what is known about the pathogenesis and diagnosis of CD and address its treatment in detail.

Celiac Disease↗
PubMed2005

Celiac disease in patients with an affected member, type 1 diabetes, iron-deficiency, or osteoporosis?

Celiac disease (CD) may be a much under recognized condition, in part because it is not considered in those patients at high risk or in clinical conditions that may be a manifestation of CD. Screening high-risk groups may reveal a higher prevalence than seen in the general population. Several diseases have been described to have an association with CD that may be greater than by chance alone. The presence of autoimmune conditions such as insulin-dependent diabetes mellitus (T1DM) or a family history of CD or dermatitis herpetiformis may increase the risk of coexisting CD. The prevalence of CD may be increased in certain patient groups, including the following: osteoporosis or low bone mass or iron-deficiency anemia. Many studies, including population-based work, suggest a prevalence of CD of 3%-7% of T1DM and 4%-10% of first-degree family members. Anemia and osteoporosis are common in patients with newly diagnosed CD. Conversely, CD is common in referral populations with those conditions but makes a relatively small contribution to the overall community prevalence of anemia or postmenopausal osteoporosis. Most screen-found patients tend to have little or no gastrointestinal symptoms. In conclusion, significant reservoirs of CD can be found in some at-risk groups, such as those with T1DM, family members, and referred patients with osteoporosis and anemia. It is not clear what impact CD has on the quality of life of these individuals.

Anemia, Iron-Deficiency↗
PubMed2005

Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in children and adolescents with gastrointestinal symptoms, dermatitis herpetiformis, dental enamel defects, osteoporosis, short stature, delayed puberty and persistent iron deficiency anemia and in asymptomatic individuals with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, selective immunoglobulin (Ig)A deficiency and first degree relatives of individuals with celiac disease. The Celiac Disease Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnosis and treatment of pediatric celiac disease based on an integration of a systematic review of the medical literature combined with expert opinion. The Committee examined the indications for testing, the value of serological tests, human leukocyte antigen (HLA) typing and histopathology and the treatment and monitoring of children with celiac disease. It is recommended that children and adolescents with symptoms of celiac disease or an increased risk for celiac disease have a blood test for antibody to tissue transglutaminase (TTG), that those with an elevated TTG be referred to a pediatric gastroenterologist for an intestinal biopsy and that those with the characteristics of celiac disease on intestinal histopathology be treated with a strict gluten-free diet. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the diagnosis and treatment of celiac disease in children and adolescents.

Adolescent↗
PubMed2005

A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures.

BACKGROUND AND AIMS: The aim of the study was to examine whether endoscopic intralesional corticosteroid injection into recalcitrant peptic esophageal strictures reduces the need for repeat stricture dilation. METHODS: Patients with a peptic esophageal stricture and recurrent dysphagia having had at least one dilation in the preceding 18 months were enrolled in a prospective randomized, double-blind study comparing steroid and sham injection. After endoscopic confirmation of recurrent stricture, patients were randomized to receive either 0.5 cc/quadrant triamcinolone (40 mg/cc) or sham injection into the stricture followed by balloon dilation of the stricture. Patients were stratified by the number of dilations required in the preceding 18 months, severity of dysphagia, the presence of esophagitis, stricture severity, and prior therapy with a proton-pump inhibitor. Patients and their physicians were blinded to the type of intervention received. Baseline dysphagia questionnaires were completed. Post-procedurally all patients were placed on a standardized proton-pump inhibitor regimen and standardized telephone follow-up questionnaires were completed at 1 wk and at 1, 3, 6, 9, and 12 months. The original sample-size calculation of 60 patients could not be met in a timely fashion because of a low incidence of recalcitrant peptic stricture patients. RESULTS: A total of 30 patients were enrolled, 15 in the steroid group (10 men, mean age 66 yr) and 15 in the sham group (11 M, mean age 67 yr). Patients were followed for 1 yr, unless they underwent an antireflux operation or died. Two patients, one per group, died of non-esophageal causes at 1 and 12 months. Four patients had fundoplication, two in each group, unrelated to stricture or dysphagia. Two patients in the steroid group (13%) and nine in the sham group (60%) required repeat dilation (p= 0.011). CONCLUSIONS: In patients with recalcitrant peptic esophageal stricture, steroid injection into the stricture combined with acid suppression significantly diminishes both the need for repeat dilation and the average time to repeat dilation compared to sham injection and acid suppression alone.

Aged↗
PubMed2005

Rates of endoscopy and endoscopic findings among people with frequent symptoms of gastroesophageal reflux in the community.

BACKGROUND: Epidemiological studies have confirmed that gastroesophageal symptoms are highly prevalent. However, studies linking epidemiology with clinical or chart data are scarce. We aimed to determine the frequency of endoscopy and endoscopic findings, as well as predictors of health-care utilization, among people with reflux symptoms in the community. METHODS: A previous survey of 2,118 Olmsted County, MN, residents in 1993 identified 242 subjects with frequent reflux symptoms (at least weekly) who received care at a medical center in the county. Data were abstracted from Mayo Clinic records between 1988 and 1998. RESULTS: Overall, 130 of the 242 (54%, 95% CI 47-60%) had sought care for reflux. Twenty-five patients (10%) had visited a gastroenterologist; 47 (19%) had an upper endoscopy (EGD), 64 (26%) had an upper GI X-ray, and one had an ambulatory 24-h esophageal pH study. Long segment Barrett's esophagus was detected in 4 (9%) of those having an EGD and adenocarcinoma was found in one patient with Barrett's. Three patients had surgery for gastroesophageal reflux disease. Thirteen patients (5%) died, but no deaths were due to esophageal reflux or adenocarcinoma. Age, higher education, frequent heartburn, and dysphagia were all significant, independent predictors of consulting. CONCLUSIONS: Although many people in the community have frequent reflux symptoms, few have investigations, and deaths were unrelated to reflux disease or its complications. Data from referral clinic or endoscopy series should not be extrapolated to the large numbers of people in the community with symptoms of reflux.

Adenocarcinoma↗
PubMed2005

Ear, nose, and throat manifestations of gastroesophageal reflux disease. Complaints can be telltale signs.

GERD is one of the most common gastrointestinal conditions in the general US population. ENT become more commonly recognized or suspected by physicians, although the direct association between symptoms and acid reflux has been difficult to establish. Most patients with suspected supraesophageal GERD do not have the typical symptoms of heartburn and acid regurgitation. Possible mechanisms of GERD-mediated damage to extraesophageal structures include direct-contact damage of mucosal surfaces by acid-pepsin exposure and a vagal reflex arc between the esophagus and the upper aerodigestive tract, triggered by acid reflux. Dual-channel ambulatory pH monitoring is the most sensitive and specific diagnostic test for determining transient reflux episodes, although demonstrating the presence of acid reflux alone does not prove that it is the cause of suspected GERD-related signs or symptoms. Therefore, physicians must sometimes resort to an empirical treatment strategy for both diagnosis and treatment. High-dose PPI therapy for 9 to 12 weeks is the recognized first-line therapy; operative therapy is reserved for patients who have severe complications or whose condition incompletely responds to treatment. Complete lack of response should prompt reconsideration of alternative diagnoses. Controlled, well-designed clinical trials to assess treatment and more sophisticated techniques to quantify acid reflux are needed to help determine which patients with suspected extraesophageal complications actually have GERD as the primary cause.

Cough↗
PubMed2005

Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features.

OBJECTIVES: To estimate the prevalence of cellac disease (CD) in pediatric and adult type 1 diabetes melitus in a defined population and to describe clinical features and HLA class II genotypes predictive of CD in screened patients with type 1 diabetes. PATIENTS AND METHODS: All residents of Olmsted County, Minnesota, with type 1 diabetes mellitus on the prevalence date January 1, 2001, were identified with the use of an established medical records linkage system (Rochester Epidemiology Project) and defined clinical criteria. Consenting patients underwent serologic screening with endomyslal antibody and tissue transglutaminase antibody testing and Intestinal biopsies to confirm the diagnosis of CD. A subset of screened patients also underwent HLA class II genotyping. Quality-of-life screening (Medical Outcomes Study 36-Item Short-Form Health Survey) was completed in a subset of patients at the time of serologic screening. RESULTS: Overall, 392 Olmsted County residents with type 1 diabetes on January 1, 2001, were Identified. A total of 158 patients with type 1 diabetes were tested, representing 40% (158/392) of the enumerated diabetic population, and 11 had biopsy-proven CD for an estimated point prevalence of 7.0% (95% confidence Interval, 3.5%-12.1%). Most CD-positive diabetic patients were asymptomatic and expressed an at-risk CD haplotype with at least one of but not both HLA DQ2 or DQ8. CONCLUSIONS: Celiac disease Is not rare In North American patients with type 1 diabetes, and most CD-positive diabetic patients are asymptomatic Irrespective of age at screening.

Adolescent↗
PubMed2004

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease.

Celiac disease is associated with an increased risk of small bowel adenocarcinoma. The aims of this study were to investigate the molecular basis, assess outcomes, and identify clinicopathologic characteristics of small bowel adenocarcinoma in celiac disease. Retrospective case control cohort study of all celiac disease patients treated at our institution for small bowel adenocarcinoma and matched control patients with sporadic small bowel adenocarcinoma from July 1960 to November 2002. Mismatch repair (MMR) status was accessed by testing tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein expression. Over a 40-year time period, 18 patients with small bowel adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of 11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the celiac disease and control groups, respectively. In the celiac disease group, MSI-H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively. Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac disease status (P = 0.018), and 78% of controls were stage III or IV compared with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in the celiac disease group compared with stage-matched controls. Celiac disease patients with small bowel adenocarcinoma had a high incidence defective MMR (73%) compared with controls and had better survival compared with stage-matched controls. In addition, celiac disease patients presented more frequently with early-stage small bowel adenocarcinoma. The better survival and earlier presentation of small bowel adenocarcinoma in celiac disease appears to be biologically associated with defective MMR.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Relationship between hiatal hernia and inguinal hernia.

Several theories explain the development of hiatal hernia (HH). Since inguinal hernia (IH) is due to abdominal wall herniation, we hypothesized that if HH is caused by an excessive "push" from increased intraabdominal pressure, there would be a greater than chance association between HH and IH. The aim of this prospective case-control study was to determine the relationship between HH, identified at endoscopy, and IH, found on clinical examination. Outpatients, who were referred for elective upper GI endoscopy at the Endoscopic Unit, from January 1999 to December 1999, were evaluated. Data were collected regarding gender, age, BMI, presence or absence of HH, length of HH, and presence of IH on detailed abdominal examination of each subject. Five hundred fifty-nine outpatients were enrolled in this study. Of these, 128 (23%) had HH, whereas 431 (77%) patients did not. The average length of the HH was 2.7 +/- 0.9 cm (range, 1.5-6 cm). The overall risk of IH in patients with HH is 2.5-fold compared to those without HH (OR = 2.59). Obesity (BM, >25) was an additional risk factor for IH in patients with HH compared with normal weight (BMI, 21-25) (P < 0.05). Males with HH were more likely to have IH than females (OR = 2.86; 95% CI = 1.35-6.08). Inguinal and hiatal hernias occur together more often than expected by chance alone. Male gender and obesity increase the risk of association. These results suggest that a common etiology may exist for both IH and HH, at least in some patients, and support the hypothesis that "push" factors may contribute to the etiology of HH.

Adult↗
PubMed2004

Post-test calibration of single-use, antimony, 24-hour ambulatory esophageal pH probes is necessary.

Twenty-four-hour pH monitoring is considered the "gold standard" for detection of gastroesophageal reflux disease (GERD). However, reference pH can drift during studies using antimony pH electrodes. Posttest calibration of antimony probes to assess a "drift" has been advocated but is not routinely preformed in clinical practice. We undertook this study to determine the frequency and degree of drift that occurs during pH studies using single-use antimony pH electrodes. One hundred consecutive 24-hr ambulatory esophageal pH studies were reviewed for presence and degree of pH drift. Separately, 10 in vitro studies using antimony electrodes exposed to solution of constant pH and temperature were recorded to determine timing of drift. Drift of at least 0.1 pH unit occurred in 88 (P < 0.001). Drift of 0.1, 0.2, 0.3, 0.4, and > 0.4 pH unit occurred in 38, 28, 15, 4, and 5 of the 100 studies, respectively. In six studies the adjustment for the poststudy calibration drift changed the overall interpretation of the test. Small degrees of drift occurred at various times during the 10 in vitro studies. Drift in pH during 24-hr pH studies using antimony is common, but large degrees of drift are not. When the threshold of pH 4.0 was adjusted to reflect the drift, a small but significant number of interpretations changed. Drift artifact may impact the results of the pH study, and calibration should be repeated after all studies.

Adult↗