Association of polymorphisms in myeloperoxidase and catalase genes with precancerous changes in the gastric mucosa of patients at inner-city hospitals in New York.

Gastric carcinogenesis is a multistep process progressing from chronic gastritis, through glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia. We have previously demonstrated that minority patients at New York City hospitals are infected with a relatively virulent strain of H. pylori (Hp) and that Hp infection is associated with an increased incidence of precancerous changes in the gastric mucosa. Nevertheless, precancerous changes are not observed in every Hp-infected individual, suggesting that environmental and genetic factors may also play a role in the formation and appearance of precancerous lesions. In the present study, the association between polymorphisms in the promoter regions of human myeloperoxidase (MPO -463G--> A) and catalase (CAT -262C-->T) genes and the appearance of precancerous changes in the gastric mucosa of our patient population were examined. Patients enrolled in this study were undergoing endoscopy for gastrointestinal complaints. Samples were collected from 126 patients at Kings County Hospital in Brooklyn and St. John's Episcopal Hospital in Queens. One antral biopsy was taken for genotyping, while additional biopsies were taken from the antrum and fundic region for histological analysis and were scored with respect to acute and chronic inflammation, GA, IM and Hp infestation according to the Sydney classification. MPO and CAT genotypes were determined by PCR and RFLP. CAT genotypes did not influence the incidence or severity of precancerous lesions in the fundic or antral regions of the stomach, whereas the MPO -463A allele was associated with an increase in intensity of gastric atrophy in the fundic mucosa. In Hp-infected individuals, the MPO -463G/G genotype was associated with an increase in the incidence of IM in the antrum, whereas the A allele was associated with an increase in IM in the fundic region. These paradoxical findings suggest that different MPO genotypes are associated with the appearance of IM in distinct anatomical regions of the stomach. However, since the majority of gastric cancer (GC) cases in our patient population occurred in the antrum, the MPO -463G/G genotype, which is associated with increased MPO expression and antral IM, may be considered a risk factor for GC.

Helicobacter pylori infection is associated with a high incidence of intestinal metaplasia in the gastric mucosa of patients at inner-city hospitals in New York.

Gastric carcinogenesis is a multistep process progressing from chronic gastritis, through glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia. Infection of the stomach with H. pylori increases the risk of developing gastric cancer. Few studies have examined the degree to which Hp-induced changes occur in specific populations. In the present study, we examined the association between Hp infection and histological changes in the gastric mucosa of patients at two inner-city hospitals in New York. Patients enrolled in this study were undergoing endoscopy for gastrointestinal complaints. One antral biopsy was taken for detecting and genotyping Hp by PCR. Additional biopsies were taken from the antrum and fundic region for histological analysis and were scored with respect to acute and chronic inflammation, GA, IM and Hp infestation according to the Sydney classification. Hp strains infecting these patients were genotyped with respect to the expression of Hp virulence factors including VacA, CagA, and BabA2. Samples were collected from 126 patients at Kings County Hospital in Brooklyn and St. John's Episcopal Hospital in Queens. Hp infection rates were highest in Blacks (41.6%) and Hispanics (29.4%) and lowest in Caucasians (18.8%). Scores for acute and chronic inflammation and IM were higher in Hp-infected individuals in both the antrum and fundic regions, whereas Hp infection did not affect the incidence or intensity of GA. In Hp-infected individuals, the incidence of IM was greater in the antrum (Hp-infected 37.8% vs. non-infected 9.2%, p < 0.05) and fundic region (Hp-infected 15.1% vs. noninfected 1.8%, p < 0.05). Genotyping of the Hp strains infecting these patients revealed that the predominant VacA allele was s1 bm 1 and that the CagA gene was present in 69.8% of Hp-infected samples. Interestingly, the BabA2 gene was detected in only four samples (9.3%). The incidence of IM in the antrum was higher in CagA + samples when compared with CagA- samples (52.2% vs. 15.4%, respectively). Our findings indicate that the virulent Hp strain infecting minority patients treated at inner-city hospitals in New York City is associated with a high incidence of IM and that these patients may be at greater risk for developing gastric cancer than the general population.

H. pylori infection and genotyping in patients undergoing upper endoscopy at inner city hospitals.

Kings County Hospital (KCH), and St. John's Episcopal Hospital (SJH) are inner-city hospitals in New York City serving predominantly minority populations. Staten Island University Hospital (SIUH) serves a predominantly middle-class Caucasian population. We examined H. pylori (HP) infection in patients undergoing upper endoscopy at these hospitals. Two gastric biopsies were obtained from each patient. One biopsy was examined by histology or the rapid urease test for the presence of HP. The other was subjected to analysis by PCR to detect HP DNA and to identify putative HP virulence factors. Of 200 subjects, 54% were African-American, 10% were Hispanic, and 36% were Caucasian. HP infection rates in African-American, Hispanic, and Caucasian patients were 43%, 20%, and 11%, respectively. Many of the African-American patients are recent immigrants from the Caribbean Islands. In these patients, an inverse relationship was observed between HP infection and the number of years living in the United States. Higher levels of HP infection were observed in patients with duodenitis and peptic ulcer disease. With respect to HP virulence factors, the vacA s1b and m1 alleles, as well as the iceA2 allele were the predominant alleles expressed in HP-positive samples obtained from African-Americans. The cagA gene was detected in 81% of HP-positive samples. However, CagA positivity was not related to any specific gastrointestinal disorder. Our findings indicate that among several ethnic groups served by three hospitals, African-American patients have the highest rate of HP infection. Moreover, in AfricanAmerican patients undergoing endoscopy: (1) HP infection was inversely related to the number of years the patients have been living in the USA; (2) HP infection rates were higher in patients diagnosed with duodenitis and peptic ulcer disease versus other disorders; (3) expression of the CagA gene was not associated with any specific gastroduodenal disorder; and (4) there was little allelic heterogeneity with respect to VacA and IceA subtypes. These findings suggest that inner-city African-Americans are more likely to be infected with HP and suffer from more serious gastroduodenal disorders than other ethnic groups.

Accuracy and precision of serum gastrin measurements in commercial laboratories.

Patients referred to us with "positive" secretin tests and the diagnosis of Zollinger-Ellison syndrome were found to be achlorhydric. This observation led us to study prospectively the accuracy and precision of serum gastrin determinations from commercial laboratories. Synthetic gastrin (G17) was added to serum to achieve gastrin concentrations of 50, 100, 250, 500, 750, 1000, 3000, and 5000 pg/mL after subtraction of the basal value (24 pg/mL). Three aliquots of each concentration were analyzed by radioimmunoassay in our laboratory (Health Science Center at Brooklyn) and sent to four major commercial laboratories that perform 5000 to 25,000 gastrin assays per year. The reported gastrin concentrations of the triplicate samples demonstrate that many commercial laboratories failed to accurately measure gastrin. Commercial laboratories generally reported higher-than-actual gastrin concentrations in samples containing less than 500 pg/mL and lower-than-actual gastrin concentrations in samples containing more than 500 pg/mL. Of all aliquots containing 100 pg/mL or less, 14 of 24 samples (58%) were reported by commercial laboratories to contain elevated gastrin concentrations. At gastrin concentrations from 250 to 5000 pg/mL, the range of values (highest- to lowest-reported value for each concentration) was greater than 200 pg/mL in 62% of triplicate samples reported by commercial laboratories. These data indicate that determinations by some commercial laboratories lack the precision required to satisfy the current diagnostic criterion (a postsecretin rise from basal gastrin of 200 pg/mL or greater) for Zollinger-Ellison syndrome. Clinicians should be aware of this problem and obtain more basal serum gastrin samples to allow for an analysis of the range of baseline values prior to secretin injection.

Histamine-2 receptor antagonists do not alter serum ethanol levels in fed, nonalcoholic men.

OBJECTIVE: To determine whether the four histamine-2 receptor antagonists currently available for the treatment of acid-peptic disorders in the United States alter serum ethanol levels after moderate alcohol consumption. DESIGN: Prospective, randomized crossover design comparing the effects of histamine-2 receptor antagonists and no treatment on serum ethanol levels. Each participant served as his own control. PARTICIPANTS: Twenty-five healthy nonalcoholic men (21 to 35 years old); two participants were withdrawn before starting the study. SETTING: University medical center. INTERVENTION: Cimetidine (400 mg twice daily), famotidine (20 mg twice daily), nizatidine (150 mg twice daily), ranitidine (150 mg twice daily), and no treatment for 7 days. After the last dose of medication, participants ate a standard meal; 1 hour later they drank ethanol (0.3 g/kg body weight in 500 mL of orange juice) over 8 minutes. MEASUREMENTS: Simultaneous measurements of breath and serum (headspace gas chromatography) ethanol were made before and 10, 20, 30, 45, 60, 90, 120, 150, and 180 minutes after ingestion of ethanol. RESULTS: Peak ethanol levels did not differ (mmol/L; mean +/- SE) after cimetidine (3.0 +/- 0.3), famotidine (2.9 +/- 0.3), nizatidine (2.9 +/- 0.3), ranitidine (3.1 +/- 0.4), and no treatment (2.9 +/- 0.4). Similarly, there was no difference in the area under the curve (mmol/L.h; mean +/- SE) after cimetidine (4.3 +/- 0.5), famotidine (3.8 +/- 0.4), nizatidine (4.2 +/- 0.5), ranitidine (3.9 +/- 0.4), and no treatment (4.0 +/- 0.5). CONCLUSIONS: In healthy nonalcoholic men, the histamine-2 receptor antagonists currently available in the United States do not alter serum ethanol levels following moderate alcohol consumption after an evening meal.

Meal-stimulated gastrin release in normal men and women.

Due to the importance of possible differences in gastrin and parietal cell secretory functions related to gender, we attempted to determine whether normal men and women release gastrin differently in response to a standard meal. Eight male and 9 female volunteers (mean age 25 and 23 years) ingested a standard meal consisting of 15g of protein, 13g of fat, and 36g of carbohydrates. Plasma for gastrin determination was drawn at baseline and at 5, 10, 15, 20, 30, 40, 60, 90 and 120 minutes after eating. No significant differences were found in basal or meal-stimulated gastrin of males or females.

Clinical significance and pathogenesis of hyperbilirubinemia associated with Staphylococcus aureus septicemia.

PURPOSE: Our goal was to examine the clinical significance of hyperbilirubinemia in patients with Staphylococcus aureus endocarditis. In addition, preliminary data concerning the possible mechanism of cholestasis observed during S. aureus septicemia are presented. PATIENTS AND METHODS: This study had two parts: a clinical investigation and a laboratory investigation. In the former, patients with endocarditis were identified through chart review. Those with admission total serum bilirubin levels of 2.0 mg/dl or greater were considered to have hyperbilirubinemia. In the latter investigation, the hepatic storage capacity and transport maximum for sulfobromophthalein (BSP), an organic dye that is rapidly taken up and excreted by the liver, were determined by measuring the change in serum concentration and the corresponding hepatic removal rate at various BSP infusion rates. Measurements were conducted before and after the infusion of Escherichia coli-derived lipopolysaccharide in some rabbits, after the infusion of resuspended S. aureus in others, and after the infusion of lipoteichoic acid in the remainder. RESULTS: Eleven of 47 consecutive patients with S. aureus endocarditis were noted to have hyperbilirubinemia without clinical or laboratory evidence of hepatic bacterial infection. Compared with the remaining 36 patients, these 11 patients had a significantly lower mean platelet count and a higher serum creatinine level and white blood cell count. Although none of the 47 patients were hypotensive on admission, four of the 11 hyperbilirubinemic patients died of overwhelming sepsis, compared with two of the 36 remaining patients (p less than 0.05). When one of the clinical isolates of S. aureus or lipoteichoic acid was infused into conscious rabbits, there was a marked decrease in the hepatic transport maximum and an increase in the relative hepatic storage capacity of sulfobromophthalein. Similar changes were noted following the administration of lipopolysaccharide. CONCLUSION: Our data suggest that the presence of hyperbilirubinemia in patients with S. aureus sepsis may identify persons at high risk of dying from overwhelming sepsis. It further suggests that lipoteichoic acid may play an important role in causing defective hepatic excretory function that is responsible for hyperbilirubinemia.

Endoscopic procedures in the AIDS patient: risks, precautions, indications, and obligations.

Gastroenterologists are frequently asked to perform endoscopy on patients with AIDS. A survey of university-based endoscopy units in the United States indicates that at the majority of these centers, endoscopic personnel are concerned about the risk of contracting AIDS and that these concerns have altered endoscopic practices. The actual risks are difficult to determine, but appear to be very low. Nevertheless, a variety of precautions are warranted to decrease the risk of transmitting AIDS virus or other pathogens to endoscopic personnel and patients. These precautions include the wearing of protective attire (gloves, gowns, masks, eye protection), careful handling of biological specimens, and adequate decontamination of equipment and surfaces. Indications for endoscopy in patients with AIDS are generally the same as those for other patients, but special diagnostic considerations include esophageal candidiasis, enteric Kaposi's sarcoma, cytomegalovirus infection, and a variant of sclerosing cholangitis. Patients with AIDS are entitled to the same consideration and medical care as other patients. This includes the performance of indicated endoscopic procedures.

Gastrointestinal endoscopy in patients with acquired immune deficiency syndrome: an evaluation of current practices.

To determine attitudes and practices associated with gastrointestinal endoscopy in patients with acquired immune deficiency syndrome (AIDS), we surveyed the chiefs of gastroenterology at 196 medical centers in the United States. The response rate was 61% overall and 100% from New York and San Francisco. Our results revealed a broad spectrum of perceived risk and precautions. Seventy-three percent of respondents believed that endoscopy places personnel at risk for contracting AIDS. At 35% of institutions endoscopic procedures are exclusively or frequently performed at the bedside of the patient with AIDS. At 46% of institutions procedures on patients with AIDS are performed with instruments used only in these patients. Endoscopic equipment used in patients with AIDS is gas sterilized at 85% of institutions. One third of respondents noted reluctance of personnel to participate in endoscopy for patients with AIDS. Reluctance was related to the respondent's perception of risk and did not differ among nurses, fellows, attendings, and gastrointestinal assistants. These data indicate that concern regarding transmission of the AIDS virus during endoscopy has resulted in costly and inefficient endoscopic practices.

Fasting- and meal-stimulated peptide hormone concentrations before and after gastric surgery for morbid obesity.

The influence of morbid obesity and of gastric surgery operation in circulating peptide hormone concentrations was studied in 26 patients. Plasma hormone levels were determined in the fasting state and after a standardized test meal before and six to nine months after gastric surgery. Before surgery fasting and postprandial blood glucose and hormone levels did not significantly differ in morbidly obese subjects from those in obese or normal subjects, except that in morbidly obese subjects, postprandial gastrin concentration remained at peak levels and did not return to fasting levels 120 minutes after the test meal. An average weight loss of 92 lb following the gastric surgery operation was accompanied by a decrease of fasting glucose and insulin levels and a decreased postprandial insulin response. There were no significant differences in plasma levels of pancreatic glucagon, of pancreatic polypeptide in the basal state, or of pancreatic glucagon after the test meal between the preoperative and postoperative groups. As compared to preoperative values, fasting gastrin levels decreased after surgery, the postprandial release of gastrin was virtually absent, and that of pancreatic polypeptide reduced. The significance of altered postprandial pancreatic polypeptide response and of the reversal of prolonged postprandial hypergastrinemia to a state of low circulating gastrin levels following gastric surgery on gastrointestinal secretion and mucosa remain to be determined.

Pancreatic polypeptide, pancreatic glucagon and enteroglucagon in morbid obesity and following gastric bypass operation.

The influence of morbid obesity and gastric bypass operation on pancreatic polypeptide (PP), pancreatic glucagon and enteroglucagon was studied in six morbidly obese patients before and 6-9 months after surgery. Hormone plasma levels were determined in the fasting state and after a standardized test meal. Fasting levels of PP, pancreatic glucagon and enteroglucagon were not significantly different between the pre- and post-operative state as well as compared to normal controls. The postprandial response showed a significant reduction of PP, a significant increase of enteroglucagon and no change of pancreatic glucagon after surgery compared with the preoperative values.

Granulomatous involvement of the liver in patients with AIDS.

During a one month period liver biopsy was carried out on eight patients with established acquired immune deficiency syndrome (AIDS) and two suspected of having AIDS to evaluate raised liver enzymes or unexplained fever and weight loss. Each of the 10 patients were found to have hepatic granulomas. Appropriate staining techniques showed acid-fast bacilli in seven of the liver specimens. One specimen contained numerous Cryptococcal organisms. Two biopsies showed granulomas but no organisms. Liver biopsy was found to be a high yield and rapid diagnostic procedure in patients with AIDS. Our results suggest that hepatic mycobacterial infection may be more common in the syndrome than previously recognised and that liver biopsy specimens should be examined routinely for the presence of acid-fast bacilli.