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Joseph A Murray

Publications and source records attributed to Joseph A Murray.

At least 37 records · Page 2Linked to original sources
PubMed2004

Patient localization of esophageal dysphagia.

The accuracy of patients' symptom localization in dysphagia is not clear. This study aims to determine the accuracy of patient localization and to determine the correlation of localization with motility disorders. We reviewed 100 patients after completion of EGD, manometry, and a dysphagia questionnaire. Proximal and midesophageal localization were rarely associated with a proximal cause of dysphagia. Distal localization correlated in 80% of cases. Fifty-seven percent of patients reporting diffuse symptoms had manometric abnormalities, but only 9% of patients with manometric abnormalities reported diffuse symptoms. In conclusion, patient localization in esophageal dysphagia is not accurate. The data suggest that proximal localization is especially inaccurate, whereas distal localization may be more accurate. Finally, there is no correlation between diffuse localization and diagnosis of motility disorders.

Adult↗
PubMed2004

Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease.

BACKGROUND: Atypical presentations of celiac disease appear to be at least as common as is the classic presentation of steatorrhea, diarrhea, and weight loss. OBJECTIVE: We examined the effect of a gluten-free diet on gastrointestinal symptoms in a cohort of US patients with celiac disease. DESIGN: A follow-up survey was conducted in 215 patients who were evaluated at the University of Iowa from 1990 through 1997 as having biopsy-confirmed celiac disease. The systematic survey asked detailed questions regarding gastrointestinal symptoms before and after the institution of a gluten-free diet in the patients, all of whom had been given the same dietary advice. RESULTS: The group consisted of 160 female and 55 male patients. Although diarrhea was the most frequent symptom in untreated celiac disease, steatorrhea occurred in only one-fifth of patients. Other complaints were common, and most responded to gluten exclusion. The benefit of gluten exclusion was equally apparent in men and women. Diarrhea responded in most patients, usually within days, and the mean time to resolution was 4 wk. Many patients had alternating diarrhea and constipation, both of which were responsive to the gluten-free diet. Most patients had abdominal pain and bloating, which resolved with the diet. CONCLUSIONS: Celiac disease causes a wide range of gastrointestinal symptoms. Clinicians must have a high level of suspicion to detect the atypical forms of celiac disease. With a gluten-free diet, patients have substantial and rapid improvement of symptoms, including symptoms other than the typical ones of diarrhea, steatorrhea, and weight loss.

Body Mass Index↗
PubMed2004

The usefulness of routine small bowel biopsies in evaluation of iron deficiency anemia.

BACKGROUND: Iron deficiency anemia (IDA) may be the sole manifestation of celiac disease. The role of routine small bowel biopsies obtained during endoscopy in the evaluation of IDA is unclear. This study assessed the usefulness of routine small bowel biopsies in patients presenting with IDA. STUDY: Evaluation of 103 consecutive patients with IDA undergoing panendoscopy with routine small bowel biopsies was performed. All patients had a diagnosis of IDA with either a ferritin less than 15 microg/L or iron saturation less than 8%. Celiac disease was defined as total or partial villous atrophy with intraepithelial lymphocytosis, histologically, and a clinical response to gluten free diet. Gastrointestinal symptoms were recorded. RESULTS: Nine patients (8.7%) were diagnosed with celiac disease. Of these patients, endoscopic lesions potentially responsible for IDA were found in 33%. We found no statistically significant difference when comparing reports of diarrhea, weight loss, abdominal pain, nausea or vomiting, aspirin or NSAID use, or menopausal status with celiac disease status. CONCLUSIONS: Routine small bowel biopsies to evaluate for celiac disease are indicated in the evaluation of patients with IDA. The finding of endoscopic lesions that may otherwise explain IDA should not preclude small bowel biopsy.

Adult↗
PubMed2004

A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice.

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. It presents as a papulovesicular rash and is often associated with enteropathy. The rash resolves when the patient is placed on a gluten-free diet and/or dapsone. DH, as well as celiac disease, is tightly associated with DQ2 and DQ8. A novel mouse model for DH is described that utilizes the NOD background and the HLA-DQ8 transgene. The addition of DQ8 contributes sensitivity to gliadin, and the addition of the NOD background contributes to autoimmunity and pathogenesis. Fifteen NOD DQ8+ mice of 90 that were sensitized to gluten developed blistering pathology similar to that seen in DH. Neutrophil infiltration of the dermis, deposition of IgA at the dermal-epidermal junction, and a complete reversal of the blistering phenomenon with the administration of a gluten-free diet with or without dapsone were observed. None of the 3 blistering mice examined had small-bowel pathology. This animal model of DH will be useful to determine the specificity of the IgA deposits, as well as the pathogenic mechanisms that occur in the skin as a result of gluten ingestion.

Animals↗
PubMed2004

Celiac disease serology in irritable bowel syndrome and dyspepsia: a population-based case-control study.

OBJECTIVE: To determine whether undiagnosed celiac disease is associated with irritable bowel syndrome (IBS) or dyspepsia in the community. SUBJECTS AND METHODS: A self-report bowel disease questionnaire was mailed to a random sample of Olmsted County, Minnesota, residents aged 20 to 50 years. All respondents who reported symptoms of dyspepsia or IBS (cases) and all respondents without notable gastrointestinal symptoms (controls) were invited to participate (260 eligible subjects; 150 [58%] were studied). Each respondent was examined by a physician, and the medical records of each were reviewed (3 subjects did not meet the criteria for dyspepsia or IBS at the time of the physician interview). Serum was obtained to measure antiendomysial antibodies and tissue transglutaminase (TTg) IgA antibodies using validated assays. RESULTS: A total of 34 subjects had dyspepsia (20 had ulcerlike dyspepsia), 50 had IBS (19 had diarrhea-predominant IBS), and 15 met criteria for both dyspepsia and IBS; 78 were asymptomatic healthy controls. The overall prevalence of positive TTg serology was 4% (95% confidence interval [CI], 1.5%-8.5%). The number of subjects who were seropositive for TTg was 2 of 34 (5.9%) with dyspepsia (95% CI, 0.7%-19.7%), 2 of 50 (4.0%) with IBS (95% CI, 0.5%-13.7%), and 2 of 78 (2.6%) of asymptomatic controls (95% CI, 03%-9.0%) (P = .64 IBS vs controls; P = .58 dyspepsia vs controls). No subjects had positive antiendomysial antibodies. CONCLUSION: In this community, celiac disease did not explain the presence of either IBS or dyspepsia.

Adult↗
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↗
PubMed2003

Esophageal function testing with combined multichannel intraluminal impedance and manometry: multicenter study in healthy volunteers.

BACKGROUND & AIMS: Combined multichannel intraluminal impedance and manometry (MII-EM) assesses esophageal function by simultaneous measurement of both pressure and bolus transit. Normative data for this method have not been published. The aim of this study was to establish normative data for combined MII-EM and to correlate liquid and viscous bolus transit by impedance with esophageal contractions by manometry. METHODS: Forty-three normal volunteers recruited from 4 centers (15 women, 28 men; age range, 21-72 years) underwent combined MII-EM with a catheter containing 4 impedance-measuring segments and 4 solid-state pressure transducers. Each center recruited and analyzed subjects independently, according to pre-established criteria. Each subject received 20 x 5 mL swallows, 10 liquid and 10 viscous material. Tracings were analyzed manually for bolus presence time, bolus head advance time, segmental transit times, total bolus transit time, contraction amplitude, duration, and onset velocity. RESULTS: Ninety-seven and four-tenths percent of manometrically normal liquid and 96.1% of manometrically normal viscous swallows had complete bolus transit by impedance. Almost half (47.2%) of manometrically ineffective liquid and 34.7% of ineffective viscous swallows had complete bolus transit, whereas 91.7% of manometric simultaneous liquid swallows and 54.5% of simultaneous viscous swallows had complete bolus transit. More than 93% of normal individuals had at least 80% complete liquid or at least 70% complete viscous bolus transit. CONCLUSIONS: This study establishes normative data for combined MII-EM. Combined MII-EM may be a more sensitive tool in assessing esophageal function compared to standard manometry because impedance can distinguish different bolus transit patterns. Studies in patients with manometrically defined esophageal motility abnormalities should help clarify the functional importance of manometric ineffective and simultaneous swallows.

Adult↗
PubMed2003

Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001.

BACKGROUND AND AIMS: Celiac disease is considered rare in North America. However, an increasing incidence and widening clinical spectrum have been reported in many countries, and serologic screening suggests a higher prevalence of minimally symptomatic disease. This study reports temporal trends in the incidence of celiac disease in Olmsted County, Minnesota. METHODS: All county residents diagnosed with celiac disease between 1950 and 2001 were identified through the Rochester Epidemiology Project. Incidence rates were calculated assuming a Poisson distribution, and changes in incidence by calendar year, age, and gender were assessed by using Poisson regression. RESULTS: Altogether, 82 new cases of celiac disease were identified during the 50-year period. There was a marked female predominance (P < 0.005), and the incidence rates increased with age (P < 0.001) and calendar period (P < 0.001). The overall annual incidence of celiac disease was 2.1 per 100,000 (95% confidence interval [CI], 1.7-2.6) but increased from 0.9 per 100,000 (CI, 0.5-1.2) in 1950-1989 to 3.3 per 100,000 (95% CI, 2.2-4.4) in the 1990s. The incidence was 9.1 per 100,000 (95% CI, 5.2-13.0) in the final 2 years of the study. Serology prompted biopsy in a substantial proportion of recent diagnoses. Clinical features also changed over time, with less diarrhea and weight loss at presentation. CONCLUSIONS: Celiac disease has increased recently in this well-characterized population. Milder clinical features and use of serology suggest an increased detection rate, although a true increase in incidence may have also occurred. Celiac disease is not rare in North America.

Adolescent↗
PubMed2003

Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture.

OBJECTIVES: The aim of this study was to determine the specificity of increase in intraepithelial lymphocytes (IELs) with normal villous architecture in small bowel biopsy samples for diagnosis of gluten sensitivity (GS) and its significance in the absence of GS. METHODS: Small bowel biopsy samples from 43 patients with increased IELs and no other pathology were reviewed. Patients with prior diagnosis of GS were excluded. A group of 46 patients with normal duodenal biopsy during the same period served as controls. The clinical records of patients and controls were examined for presenting symptoms, laboratory tests, and final clinicopathological diagnosis. Immunohistochemical characterization of IELs was performed in 13 cases. RESULTS: Four (9.3%) patients had GS based on positive IgA antiendomysial antibodies (n = 3) and favorable response to gluten-free diet (n = 4). One patient (2.2%) had partially treated tropical sprue; six patients (14%) had disorders of immune regulation including Hashimoto's thyroiditis (n = 2) and one case each of Graves' disease, rheumatoid arthritis, psoriasis, and multiple sclerosis; and six patients (14%) were on nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, none of the control subjects had GS (p = 0.05), tropical sprue, or immunoregulatory disorders (p = 0.011), and one (2.2%) was on NSAIDs (p = 0.04). Increased IELs were also observed in Crohn's disease, lymphocytic/collagenous colitis, and bacterial overgrowth, but the association did not reach statistical significance. Histological features (number and distribution of IELs, crypt mitoses) and immunophenotypic analysis of IELs did not reliably distinguish GS-related from non-GS-related causes of increased IELs. CONCLUSIONS: Intraepithelial lymphocytosis in an otherwise normal small bowel biopsy is somewhat nonspecific, but in nearly 10% of cases can be the initial presentation of GS. Therefore all patients with this finding should be investigated for GS. Increased IELs may also be associated with autoimmune disorders and NSAIDs.

Adolescent↗
PubMed2003

Hepatitis B vaccine nonresponse and celiac disease.

OBJECTIVES: There is a genetic predisposition to hepatitis B vaccine nonresponse. The link between human leukocyte antigen (HLA) genotype and ineffective development of immunity to the hepatitis B vaccine has been characterized in multiple studies. Celiac disease has a strong association with a particular HLA genotype of DQ2; interestingly, this HLA genotype is seen in association with nonresponders to the hepatitis B vaccine. We report a disproportionate number of patients with celiac disease who are nonresponders to the hepatitis B vaccine series. METHODS: We reviewed the hepatitis B vaccine records, serological tests for anti-hepatitis B surface antigen antibody (anti-HBs), and HLA genotypes of celiac disease patients identified as nonresponders to hepatitis B vaccine. Subjects were identified from a database of patients diagnosed with celiac disease at our institution or referred to our center for evaluation and management of celiac disease between November, 2000, and October, 2002. RESULTS: A total of 23 subjects were reviewed. All had a clinical and pathological diagnosis of celiac disease. All subjects reported receiving the full series of hepatitis B vaccinations. Of the subjects, 19 had testing for hepatitis B vaccine response. Of these 19 subjects, 13 did not achieve long-term immunity as seen by the negative qualitative or quantitative anti-HBs antibody titer. All tested subjects were either homozygous or heterozygous for DQ2. CONCLUSIONS: We postulate that celiac disease patients may have a significant predisposition to hepatitis B vaccine nonresponse. Both celiac disease and hepatitis B vaccine nonresponse is genetically mediated. Celiac disease patients may have a failure of induction of humoral immune response needed for development of long term immunity; the mechanism for this is unclear.

Adolescent↗
PubMed2003

Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms.

BACKGROUND & AIMS: Endoscopy-negative dyspepsia is a common symptom that often is difficult to define in pathophysiologic terms. The aim of this study was to assess the frequency of disordered gastric accommodation and emptying in patients referred with unexplained upper gastrointestinal symptoms. METHODS: A computerized diagnostic index was used to identify all patients, 18-70 years old, who underwent single-photon emission computed tomography (SPECT) to assess gastric accommodation at Mayo Clinic Rochester over a 3-year period. Demographics, clinical features, and results of diagnostic testing, including scintigraphic gastric emptying, were extracted from the electronic record. RESULTS: A total of 214 patients were identified; the primary clinical diagnoses were functional dyspepsia, postfundoplication syndromes, rumination syndrome, and diabetic dyspepsia. Gastric accommodation was impaired in 43% of the whole group: 47% of functional dyspepsia, 44% of postfundoplication syndromes, and 33% of diabetic dyspepsia. Delayed gastric emptying was most prevalent in diabetic dyspepsia, and was accelerated in postfundoplication syndromes groups. Thirty-seven percent of patients had abnormal gastric emptying. The highest prevalence of delayed gastric emptying was in the diabetic dyspepsia and accelerated gastric emptying in postfundoplication syndromes groups. Twenty-five percent of patients with normal gastric emptying had impaired accommodation. Upper-gastrointestinal symptoms were not different in groups based on gastric accommodation or emptying results. CONCLUSIONS: Impaired gastric accommodation is common in patients with unexplained dyspepsia. Symptoms alone cannot predict physiologic disturbances. These noninvasive tests identify single or combined pathophysiologic disturbances and may help to identify subgroups of patients as candidates for more selective pharmacotherapy in the future.

Adolescent↗
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↗