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Joseph A Murray

Publications and source records attributed to Joseph A Murray.

15 recordsLinked to original sources
PubMed2003

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.

Adolescent↗
PubMed2003

Streamlining 24-hour pH study for GERD: Use of a 3-hour postprandial test.

At present, the ambulatory 24-hr pH test has been used as a diagnostic tool to assess gastroesophageal reflux disease (GERD) in those patients with reflux symptoms and a normal endoscopy. However, patients poorly tolerate the prolonged nature of the 24-hr test. The aim of this study was to determine whether analyzing a 3-hr postprandial period from a full 24-hr study would be as sensitive as the longer test. Data were analyzed from a standard ambulatory 24-hr pH recording. A positive test was determined if the pH was < 4 for more than 4% of the study period with the probe placed 5 cm above the lower esophageal sphincter for both groups. The data were then reanalyzed by determining the percent time of pH < 4 during a 3-hr postprandial period. The results of 50 patients with a positive 24-hr test were compared with 50 patients with normal tests. The meal that was used to study the 3-hr postprandial period occurred in the late afternoon or early evening. The 3-hr postprandial test had a sensitivity of 88% when compared to the 24-hour test and a specificity of 98%. The positive predictive value was 100% for the 3-hr test, and the accuracy of this shorter test when compared with the standard 24-hour test was 95%. In conclusion the 3-hr postprandial analysis is a highly sensitive and specific test for demonstrating GERD. By using the shorter test, patient discomfort may be reduced and compliance enhanced.

Case-Control Studies↗
PubMed2003

Temporal correlation between chronic cough and gastroesophageal reflux disease.

Reflux disease (GERD) and chronic cough often coexist, but a temporal correlation using the symptom association probability has not been reported. Our aim was to determine if a temporal correlation exists between cough and GERD. Sixty-one patients with chronic cough had esophageal pH monitoring with sensors 5 and 20 cm above the LES. The symptom (SI) and symptom sensitivity (SSI) indices and the symptom association probability (SAP) were used to test cough-reflux association. Pathological reflux was defined as the percentage of time pH < 4 exceeded 4.2%. A significant temporal association between cough and distal reflux was made in 35% of patients by SAP compared with only 14.8% by SI and SSI alone (P < 0.002). Patients with pathologic reflux had a greater likelihood of a temporal symptom correlation (57.1%) when not on acid-blocking medications. In conclusion, a temporal association between cough and distal reflux exists in one third of patients, especially those with pathological reflux. The SAP is a more sensitive measure of temporal association than SI or SSI.

Cough↗
PubMed2002

HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice.

We have investigated the genetic basis of the immune response to dietary gluten in HCD4/DQ8 and HCD4/DQ6 double transgenic mice. Mice were immunized with gluten i.p. or individual peptides s.c. and spleen or draining lymph node T cells were challenged in vitro. Strong proliferative responses to gluten were seen in the HCD4/DQ8 mice, whereas the HCD4/DQ6 mice responded to gluten poorly. A series of overlapping peptides spanning gliadin were synthesized. The HCD4/DQ8 mice reacted to many of the individual peptides of gliadin, while the HCD4/DQ6 mice were relatively unresponsive. T cells isolated from HCD4/DQ8 mice also responded well to modified (deamidated) versions of the gliadin peptides, whereas HCD4DQ6 mice did not. The T cell response to gluten was CD4 dependent and DQ restricted and led to the production of cytokines IL-6, TGF-beta, and IL-10. Finally, intestinal lymphocytes isolated from gluten-fed HCD4/DQ8 mice displayed an activated phenotype. These data suggest that this HLA class II transgenic murine model of gluten sensitivity may provide insight into the initiation of the MHC class II-restricted gluten sensitivity in celiac disease.

Animals↗
PubMed2002

Esophageal manifestations of dermatologic disease.

This review describes those skin conditions, or conditions where skin involvement is a prominent feature, that may present with esophageal manifestations. These conditions have been categorized in many different ways. For the purposes of this review, esophageal manifestations of skin conditions are classified as bullous diseases, hyperkeratotic diseases, collagen vascular diseases, syndromes associated with cancer, and miscellaneous diseases.

Epidermolysis Bullosa Acquisita↗
PubMed2002

Clinical features of patients with novel Yersinia species.

Our purpose was to describe the clinical features of patients with novel Yersinia species. Between 1985 and 1999; 194 patients had yersinia species isolated from stool specimens, 38 (20%) had non-Yersinia enterocolitica species; 12 (32%) had Yersinia intermedia, 7 (18%) Yersinia fredericksenii, 3 (8%) Yersinia kristensenii, and the remaining 16 (42%) were unclassified non-Yersinia enterocolitica species. The most common presenting symptom was diarrhea alone in 10 (26.3%) patients. Symptoms persisted for >1 month in 54% of cases; 21% had symptoms for <1 week; 18 (47%) patients were taking corticosteroids, acid suppressants, and/or antibiotics when Yersinia was isolated. An immunocompromised state was present in 11 (29%) patients. An immunocompromised host and administration of acid suppressants predicted persistence of symptoms for >1 month. Most [27 (71%)] patients received no treatment; 5 (13%) received antibiotics. In conclusion, novel non-Yersinia enterocolitica species, including Yersinia intermedia, Y. fredericksenii, and Y. kristensenii may represent up to 20% of all Yersinia isolates. Diarrhea is the most common symptom.

Adolescent↗
PubMed2002

Helicobacter pylori infection and monoclonal gammopathy of undetermined significance.

A recent report found resolution of monoclonal gammopathy of undetermined significance (MGUS) in nearly 30% of patients upon eradication of concomitant Helicobacter pylori (H. pylori) infection. We performed serologicalal testing for H. pylori on 93 MGUS patients and 98 control subjects. Seroprevalence of H. pylori was not significantly different between the two groups, 30% and 32% respectively. A retrospective review of Mayo Clinic records revealed identical diagnosis rates of H. pylori infection (33%) by serology, breath or stool testing between patients with MGUS and those with negative monoclonal protein studies. There was no evidence of resolution of MGUS with H. pylori therapy.

Aged↗
PubMed2002

The insensitivity of endoscopic markers in celiac disease.

OBJECTIVES: Celiac disease (CD) is characterized by small intestinal inflammation and mucosal atrophy. Endoscopic markers of villous atrophy are reported to be present in 88-100% of untreated celiac patients. In patients being evaluated for iron deficiency anemia (IDA), we examined whether endoscopic markers could predict histological results consistent with CD. METHODS: One hundred thirteen patients without histories of CD had small bowel biopsies to evaluate IDA using videoendoscopy. Markers suggesting villous atrophy were noted at endoscopy. Biopsy specimens were reviewed for consistency with CD. Endoscopic and histological findings were compared. RESULTS: Seventeen patients were diagnosed with CD, both clinically and histologically. Loss of folds was the most sensitive marker of villous atrophy, present in 47% with CD, with 97% specificity. The mosaic pattern was much less sensitive (12%), with 100% specificity. Nodularity and scalloping had low sensitivities (6%), but specificities of 95% and 100%, respectively. A finding of any endoscopic marker yielded a sensitivity of 59% and specificity of 92% for CD. CONCLUSIONS: Although endoscopic markers have been guides for directing small bowel biopsies in patients suspected of having CD, we found sensitivities of these markers to be low and conclude that they should not be relied upon for detecting CD in patients presenting with IDA.

Adult↗
PubMed2002

Barrett's esophagus: prevalence in symptomatic relatives.

OBJECTIVES: Relatives of patients with Barrett's esophagus have an increased prevalence of reflux symptoms. Our aim was to find if these relatives were at increased risk of having Barrett's esophagus. METHODS: First degree relatives of patients with Barrett's esophagus completed the Reflux Symptom Questionnaire. Relatives with reflux symptoms, never previously investigated. were invited for endoscopy. Controls were patients with similar reflux symptoms and no family histories of Barrett's esophagus. RESULTS: We found previously undiagnosed Barrett's esophagus (>3 cm) in eight of 100 relatives (8%) from 53 families and in five of 100 controls (5%) (adjusted OR = 1.58, 95% CI = 0.46-5.45). Including another 27 previously investigated cases, 10 of the 53 families had two or more cases of Barrett's esophagus. Barrett's esophagus prevalence increased with age (p = 0.014) and was associated with reflux symptoms of >10 yr (p = 0.020), and Barrett's esophagus was twice as common in males (p = 0.28). Reflux esophagitis was found in 74% of relatives and 57% of controls without Barrett's (p = 0.04). CONCLUSIONS: The risk of Barrett's esophagus in any one symptomatic relative of a patient with Barrett's esophagus was not statistically higher than in other persons with reflux symptoms. However, more relatives of Barrett's esophagus patients have reflux symptoms, so the overall prevalence of Barrett's esophagus and reflux esophagitis in relatives may also be greater than in the general population. In considering whether to screen patients with reflux symptoms for Barrett's esophagus, age and duration of symptoms are stronger predictors than having a relative with Barrett's esophagus.

Adult↗
PubMed2002

Etiology of nonresponsive celiac disease: results of a systematic approach.

OBJECTIVES: Nonresponse or relapse of symptoms is common in patients with celiac disease treated with gluten free diet. Refractory sprue (RS) is defined as initial or subsequent failure of a strict gluten-free diet to restore normal intestinal architecture and function in patients who have celiac-like enteropathy. The aims of this study were: 1) to identify causes of persistent symptoms in patients referred with presumed diagnosis of nonresponsive celiac disease (NCD); and 2) to characterize patients with true RS. METHODS: Patients were identified who had been systematically evaluated for NCD between January 1997, and May 2001. Patient records and small bowel biopsy results were reviewed. RESULTS: A total of 55 patients were referred with a presumed diagnosis of NCD. Six did not have celiac disease and had other diseases responsible for their symptoms. Diarrhea, abdominal pain, and weight loss were the most common reasons for evaluation in cases of NCD, whereas weight loss, steatorrhea, and diarrhea were the most common presenting features of RS (nine patients). Of the 49 patients with celiac disease, 25 were identified as having gluten contamination. Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue. CONCLUSIONS: Based on this study, we conclude the following: 1) gluten contamination is the leading reason for NCD; 2) of NCD cases, 18% are due to RS; and 3) alternative diseases or those coexistent with celiac disease and gluten contamination should be ruled out before a diagnosis of RS is made.

Adult↗
PubMedDate not supplied

Eosinophilic gastroenteritis and gluten-sensitive enteropathy in the same patient.

We report the clinical and laboratory features of a 19-year-old man with findings of both eosinophilic gastroenteritis and gluten-sensitive enteropathy. Before the onset of clinical symptoms, the patient had received a series of hepatitis B vaccinations but had not developed a measurable antibody response or any allergic reaction. Radioallergosorbent test results were positive to several foods, and the total serum immunoglobulin E (IgE) level was elevated. Adherence to a gluten-free diet caused a normalization in the endomysial antibody titer; however, the total serum IgE level continued to increase, and the total eosinophil count remained elevated. Symptoms of recurrent vomiting and abdominal pain necessitated prednisone burst therapy. The simultaneous occurrence of eosinophilic gastroenteritis and gluten-sensitive enteropathy is rare; therapy should be directed to each disorder individually.

Adult↗
PubMedDate not supplied

In-house preparation of technetium 99m-labeled human serum albumin for evaluation of protein-losing gastroenteropathy.

OBJECTIVE: To develop an in-house preparation method for technetium 99m-labeled human serum albumin (99mTc-HSA) to meet the clinical need for gastrointestinal (GI) protein loss evaluation in our institution. DESIGN/SETTING: Our in-house HSA was prepared by slowly adding 2 mL of 25% HSA to 50 mL nitrogen-purged, sterilized water. We then continued the nitrogen purging process for another 15 minutes before adding 0.5 mL of stannous chloride (SnCl2) in concentrated hydrochloride (40 mg/mL) to the HSA solution. Next, we transferred 1 mL of the mixture to a 5 mL vial containing 0.5 mL of 30 mCi (1,110 MBq) 99mTc. Using a paper chromatography method during a 6-hour postpreparation time period, we evaluated the effects of filtration (0.2 microm membrane filter versus no filtration) and storage temperature (25 degrees C versus 37 degrees C) on the in vitro stability of 99mTc-HSA. PATIENTS OR OTHER PARTICIPANTS: In this study, we employed the in-house 99mTc-HSA preparation to study GI protein loss in two patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used a radiochemical purity (RCP) value of not less than 90% as the index for determining in vitro stability of the in-house 99mTc-HSA preparation. The nuclear medicine physician interpreted the image to determine the location and extent of protein loss in the GI tract. RESULTS: Our results demonstrate that the overall RCP of 99mTc-HSA was 95.0% +/- 2.2% (mean +/- SD). We found no statistically significant difference in RCP value between filtered and nonfiltered 99mTc-HSA preparations across the sampled time points. However, RCP values tended to increase with time for each of the temperature-controlled preparations (P < .01). Storage temperature had a significant effect (P < .01), with refrigerated samples having an estimated 2.2% lower RCP value across time. However, the difference between room temperature and refrigerated samples decreased over time (P < .02) to only 1.1% at the 6-hour sampling. We noted gradual accumulation of 99mTc-HSA within the first hour in one patient, and the imaging results indicate that both patients had protein-losing enteropathy. CONCLUSION: It is relatively easy to prepare 99mTc-HSA in-house, achieving a high RCP level as well as extended in vitro stability. The clinical data further indicate that our in-house preparation of 99mTc-HSA may be useful for the study of GI protein loss; however, further clinical evaluation is needed.

Analysis of Variance↗