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Biomedical subjects

P H Green

Publications and source records attributed to P H Green.

At least 19 recordsLinked to original sources

CCR9-positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease.

BACKGROUND & AIMS: Thymus-expressed chemokine (TECK) or CCL25) is selectively expressed in the small bowel (SB), where lamina propria lymphocytes (LPL) and intraepithelial leukocyte expressing the cognate chemokine receptor CCR9 predominate. We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease. METHODS: CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL. TECK expression was analyzed in inflamed SB and colon by reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS: The fraction of CCR9(+) T cells in inflamed SB was significantly lower than in uninvolved SB mucosa. In contrast, in peripheral blood lymphocytes, CCR9(+) lymphocytes were markedly elevated in patients with small bowel Crohn's or celiac disease, but not in patients with purely colonic Crohn's. Also, TECK expression is altered in inflamed small bowel, being intensely expressed in a patchy distribution in crypt epithelial cells in proximity to lymphocytic infiltrates. TECK is not expressed in either normal or inflamed colon. CONCLUSIONS: In SB immune-mediated diseases, there is repartitioning of CCR9(+) lymphocytes between SB and blood and an altered pattern of TECK expression in SB Crohn's. The TECK/CCR9 ligand/receptor pair may play an important role in the pathogenesis of SB Crohn's disease.

Chemokines, CC↗

Osteoporosis in a north american adult population with celiac disease.

OBJECTIVE: Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States. METHODS: Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21-83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr). RESULTS: Osteoporosis (T score < -2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between -1.0 and -2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 +/- 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation. CONCLUSIONS: Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease.

Absorptiometry, Photon↗

Macroamylasemia in patients with celiac disease.

OBJECTIVE: Macroamylasemia is considered to be rarely associated with celiac disease (CD). We have evaluated patients in whom macroamylasemia or elevated total amylase (TA) led to the diagnosis of CD. These cases served as a catalyst for examining the prevalence of elevated TA and macroamylase (MA) in patients with active CD. METHOD: Total amylase and MA measurements were performed in the sera of 124 celiac patients with positive antiendomysium and tissue transglutaminase tests, in 100 patients on gluten-free diet (GFD) with negative serology test results, and in the sera of 89 healthy controls. Macroamylasemia was measured by using the PEG precipitation method. RESULTS: Twenty-three newly diagnosed celiac patients had elevated serum amylase levels (>2 SD above the controls). The average TA and MA levels were significantly elevated in both celiac groups. The nonprecipitated amylase levels (pancreatic and salivary amylase fractions) were not different from those of the controls. Three controls (3.4%), 21 newly diagnosed celiac (16.8%), and seven patients on GFD (7%) had significantly elevated MA activity in their sera. CONCLUSIONS: A significant percentage of the newly diagnosed patients with CD have macroamylasemia. Serum MA remained elevated in some patients on strict GFD. In addition, in the presence of an elevated amylase or MA the possibility of CD should be considered.

Amylases↗

Significance of unsuspected celiac disease detected at endoscopy.

BACKGROUND: Endoscopy provides an opportunity to diagnose unsuspected celiac disease. METHODS: We prospectively identified patients undergoing endoscopy for reasons other than the evaluation of diarrhea or suspected malabsorption, who had endoscopic signs in the duodenum suggestive of celiac disease and in whom villous atrophy was confirmed. Patients were assessed for nutritional deficiencies, reduced bone density, parameters of calcium metabolism, and malignancies. RESULTS: Nine patients (3 women and 6 men) were identified among 1749 patients undergoing endoscopy between January 1990 and May 1998, representing a rate of unsuspected celiac disease of 1 per 194 endoscopies. The duodenal abnormalities were as follows: reduced or absent folds in 6, scalloped folds in 5, mosaic appearance in 3, and mucosal fissures in 2. Assessment revealed iron deficiency in 5, folate deficiency in 1, osteopenia in 4, osteoporosis in 1, and hypocalciuria in 4. Three had malignancies associated with celiac disease, 2 esophageal squamous carcinomas, and 1 jejunal adenocarcinoma. CONCLUSIONS: Unsuspected celiac disease can be diagnosed at endoscopy by recognition of changes in the duodenum. When detected, patients have one or more manifestations of the disease. Celiac disease is more common in the United States than previously considered and endoscopy provides an opportunity to establish the diagnosis.

Adult↗

All that scallops is not celiac disease.

BACKGROUND: Scalloping of duodenal folds as well as a mosaic mucosal pattern, decreased folds, and increased vascularity are markers of duodenal mucosal injury, the most common cause being celiac disease. We have recognized scalloping in patients with a variety of conditions other than celiac disease. METHODS: Clinical, endoscopic and histologic data were reviewed from selected patients with endoscopically visualized scalloped folds along with testing for endomysial antibodies. Biopsy specimens were examined histologically for villous:crypt ratio, intraepithelial lymphocytes, and inflammation. RESULTS: Thirteen patients with scalloped folds underwent endoscopy for the following reasons: family history of celiac disease and osteoporosis, gastrointestinal bleeding, dyspepsia (2), B(12)/ folate deficiency (4), and diarrhea (8). Histologic examination was abnormal in all but 1 patient. Villous atrophy or flattening as evidenced by reduced villous:crypt ratio was seen in 11 of 13 patients. Other abnormalities were edematous or broadened villi (10), intraepithelial lymphocytosis (7), and infiltration of lamina propria (6). An infectious organism was identified in 6 patients (46%). Celiac disease was excluded by the lack of specific biopsy findings combined with endomysial antibody testing. Final diagnoses were normal (1), eosinophilic enteritis (1), giardiasis (1), tropical sprue (4), human immunodeficiency virus-related diseases (6) including human immunodeficiency virus enteropathy (1). CONCLUSION: We conclude that scalloping is not specific for celiac disease but rather a predictor of mucosal disease as evidenced by villous atrophy, widening, and edema.

Biopsy↗

The use of intravenous H2-receptor antagonists in a tertiary care hospital.

OBJECTIVE: The rationale for the widespread use of intravenous H2 receptor antagonists(IVH2 RA) in hospitalized patients is not clear. We therefore examined prescribing patterns and, using strict criteria, determined whether use was appropriate. Cost of administration and potential savings were also determined. METHODS: Data were obtained prospectively on 100 consecutive patients prescribed intravenous ranitidine and retrospectively on patients admitted with gastrointestinal (GI) bleeding. RESULTS: For the prospective study, various indications for prescribing intravenous ranitidine were given, including postoperative patients and patients treated with steroids. Using criteria from published literature 80% of the use was considered inappropriate. Nearly 40% of the doses were given while the patient was tolerating oral intake. Creatinine clearance was impaired in 26% of patients, though only one had dosage reduction. Estimated annual cost of intravenous ranitidine was $317,000. The retrospective study of 86 consecutive patients admitted with GI bleeding revealed that all patients received intravenous ranitidine on admission, none of which was considered appropriate. The final diagnoses were peptic ulcer (49), colonic process (11), esophagitis (seven), gastric erosions (five), esophageal varices (five), Mallory-Weiss tears (four), duodenitis (two), no diagnosis (three), and jejunal ulcer (one). CONCLUSIONS: Inappropriate use of intravenous ranitidine is common. This includes inappropriate indication, dosage, and duration of use. Large financial benefits could have been obtained if close attention was given to prescribing patterns.

Adolescent↗

Iron-rich foci in chronic viral hepatitis.

Stainable iron in the liver (hemosiderosis) is most commonly seen in individuals with homozygous genetic hemochromatosis, prior transfusion, hemolysis, porphyria cutanea tarda, and chronic alcohol-induced liver disease. In chronic viral hepatitis, however, significant hepatocellular hemosiderosis is uncommon. This report describes unusual foci of hepatocellular hemosiderosis ("iron-rich foci" or IRF) in liver biopsy specimens from three patients with chronic hepatitis with or without cirrhosis (two hepatitis C-related, one hepatitis B-related). IRF present within the lobular parenchyma or cirrhotic nodules contrasted sharply with the immediately adjacent hemosiderin-negative liver tissue. Serum iron indices were abnormal in all three patients, but homozygous hemochromatosis was ruled out based on the hepatic iron concentration and hepatic iron index for each case. These cases highlight the potential for irregular iron storage in chronic viral liver disease and possible confusion with genetic hemochromatosis. The possible pathogenesis of IRF and the relationship of iron storage to the outcome of interferon therapy in chronic viral hepatitis are discussed.

Biopsy↗

Combined magnification endoscopy with chromoendoscopy in the evaluation of patients with suspected malabsorption.

BACKGROUND: Magnification endoscopy and chromoendoscopy together have been used to evaluate mucosal detail in a number of conditions, including Barrett's esophagus and flat colonic polyps, but they have not been used to evaluate villous atrophy in the proximal small intestine. METHODS: Thirty-four patients suspected of having a malabsorption syndrome (either celiac disease or tropical sprue) were evaluated using an Olympus magnification gastroscope in both normal and high magnification settings. Indigo carmine dye spraying techniques were used to assist in evaluating duodenal mucosa for evidence of villous atrophy. The accuracy of endoscopically predicted villous atrophy was assessed by histologic evaluation of biopsy specimens taken in the descending duodenum. RESULTS: Magnification endoscopy with dye spraying was both highly sensitive (94%) and specific (88%) in identifying patients with villous atrophy. This technique was more accurate (91%) in identifying patients with partial atrophy than standard endoscopy (9%, p < 0.01) and was also useful in identifying patients with patchy villous atrophy (5 of 5) to allow directed biopsies of abnormal tissue. CONCLUSION: Magnification endoscopy with chromoendoscopy is a promising technique for the evaluation of patients with suspected malabsorption. This technique is especially valuable in patients with partial atrophy, where villous abnormalities can be patchy and the duodenum usually appears normal during standard endoscopy.

Atrophy↗

Increased expression of the cyclin D1 gene in Barrett's esophagus.

Previous studies have found a 3-10-fold amplification and overexpression of the cyclin D1 gene in about 32% of human esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of increased expression of the cyclin D1 protein in Barrett's esophagus. Using 69 formalin-fixed and paraffin-embedded human esophageal specimens, which had been removed endoscopically or obtained at surgery during 1993 and 1994, all immunohistochemical analyses were performed using an avidin-biotin complex immunoperoxidase technique. Increased nuclear expression of the cyclin D1 protein was noted in 32 of 69 samples (46%; 44% of the samples from males and 50% of the samples from females). Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women. Nuclear accumulation of the cyclin D1 protein was also found in both dysplastic and nondysplastic lesions, and it was not associated with sex, age, or cigarette or alcohol consumption. Samples from patients taking proton pump inhibitors tended to be less frequently positive (32%) for cyclin D1 nuclear staining when compared to patients taking H2 antagonists (45%) or antacids (55%). These studies suggest that increased expression of cyclin D1 is an early event in the tumorigenic process of esophageal adenocarcinomas and that the increased expression of this gene might predispose the epithelium to malignant transformation.

Adenocarcinoma↗

Gastric duplication cyst communicating with the pancreatic duct: a rare cause of recurrent abdominal pain.

A 41-year-old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct. Celiotomy demonstrated a noncontiguous gastric duplication cyst. Internal drainage was curative.

Abdominal Pain↗

Prevalence of cryptosporidiosis in patients undergoing endoscopy: evidence for an asymptomatic carrier state.

PURPOSE: We sought to determine the presence of the parasite cryptosporidium in the duodenal aspirates of patients undergoing routine upper gastrointestinal endoscopy. PATIENTS AND METHODS: The study consisted of 169 patients undergoing upper endoscopy or endoscopic retrograde cholangiopancreatography. Immunocompromised patients were not included in the study population. Samples were aspirated from the second portion of the duodenum. Biopsy specimens were also obtained. Three randomly passed stool samples were obtained from 75% of the patients who were found to have cryptosporidium in the duodenum. RESULTS: Overall, cryptosporidium oocysts were identified in 12.7% of patients. There was no significant difference in the prevalence of the parasite in any subgroup of procedure or symptom complex. Half of those (46.7%) with positive aspirates had demonstrable cryptosporidium in stool samples, although none of the patients had diarrhea. No patient had detectable cryptosporidium in biopsy samples of the duodenum. CONCLUSION: The findings suggest a surprisingly high asymptomatic carrier rate for cryptosporidium.

Carrier State↗

Neoplasia in chronic erosive (varioliform) gastritis.

Chronic erosive gastritis is a gastric mucosal lesion characterized by multiple, small, sessile elevations with central erosions. Symptoms typically resemble those in peptic ulcer disease. The elevations may persist and appear as sessile polyps after the erosions heal and symptoms resolve with therapy. Adenomatous transformation is reported in a patient with chronic erosive gastritis who had serial gastroscopies. This report suggests a possible association between chronic erosive gastritis and gastric neoplasia.

Aged↗

Isolated ventral pancreatitis in an alcoholic with pancreas divisum.

An alcoholic with no history of clinical pancreatitis was found to have pancreas divisum and marked changes of chronic pancreatitis isolated to the ventral pancreas. Pancreas divisum has been suggested to cause recurrent pancreatitis in some patients. Gross and histologic changes of pancreatitis in only the dorsal pancreas of surgically resected specimens from patients with pancreas divisum is thought to support the concept that obstruction at the minor papilla produces dorsal pancreatitis. Alternative explanations for the occurrence of segmental pancreatitis and the possible synergistic role of ethanol and bile are reviewed.

Adult↗

Giardia lamblia in patients undergoing endoscopy: lack of evidence for a role in nonulcer dyspepsia.

Previous studies have suggested that Giardia lamblia may cause nonulcer dyspepsia as the sole manifestation of infection. To explore this premise, duodenal aspirates from patients undergoing upper endoscopy were examined for Giardia and results were correlated with endoscopic findings and symptoms. Of 155 patients, 15.5% had Giardia. Patients with dyspepsia, with or without obvious lesions at endoscopy, had a similar prevalence. Patients with vomiting and diarrhea had an increased prevalence (38.5%) (p less than 0.05). The prevalence of Giardia lamblia in this patient population is surprisingly high. This study suggests that Giardia lamblia infection is not a major cause of nonulcer dyspepsia.

Adolescent↗