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.

Surgeons and injury prevention: what you don't know can hurt you!

BACKGROUND: The most effective treatment for traumatic injuries is to prevent them from occurring. Currently, few surgeons receive any formal training in injury' control and prevention. This study was designed to test the knowledge of injury prevention principles among practicing surgeons, in order to identify areas in need of intensified educational efforts. STUDY DESIGN: Survey questions designed by members of the American College of Surgeons Committee on Trauma were programmed into a specialized touch-screen computer, which was displayed at four different surgery and trauma meetings, including the ACS Clinical Congress in 1999 and 2000. Participants were questioned about their knowledge of trauma epidemiology, bicycle helmet effectiveness, child safety seat usage, suicide, and domestic violence. RESULTS: Seventy-nine surveys were completed by surgeons, including 33 specializing in trauma care, and by 106 nurses attending trauma courses. Overall, the percentage of correct answers was 50%. There were no significant differences in survey scores between trauma surgeons and general surgeons, although both scored higher than trauma nurses. Areas where knowledge deficits were the most apparent included proper use of child safety seats, the effectiveness of airbags, the prevalence of suicide, and the annual cost of injury in America. CONCLUSIONS: The majority of practicing surgeons and nurses, including those working at trauma centers, are unaware of the basic concepts of injury prevention. Advancements in the field of injury control will require efforts to educate medical professionals and the public.

IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study.

Williams syndrome (WMS), a genetic condition resulting from a contiguous deletion on the long arm of chromosome 7, is associated with a relatively consistent profile of neurocognitive and neurobehavioral features. The distinctiveness and regularity of the profile of learning and behavioral characteristics in this genetic condition suggests that underlying neurobiological correlates may be identifiable. In this initial study, we report findings derived from a high-resolution neuroimaging study of 14 young adult subjects with WMS and an individually matched normal control group. Compared to controls, subjects with WMS were noted to have decreased overall brain and cerebral volumes, relative preservation of cerebellar and superior temporal gyrus (STG) volumes, and disproportionate volume reduction of the brainstem. Analyses also suggested that the pattern of cerebral lobe proportions in WMS may be altered compared to normal controls with a greater ratio of frontal to posterior (parietal+occipital) tissue. Assessment of tissue composition indicated that, relative to controls, individuals with WMS have relative preservation of cerebral gray matter volume and disproportionate reduction in cerebral white matter volume. However, within the cerebral gray matter tissue compartment, the right occipital lobe was noted to have excess volume loss. Combined with our growing knowledge of the function of genes in the commonly deleted region for WMS, more detailed information regarding the structure and function of the WMS brain will provide a unique opportunity for elucidating meaningful correlations amongst genetic, neurobiological, and neurobehavioral factors in humans.

Gastrointestinal hormones.

Solomon A. Berson, M.D., the first Murray M. Rosenberg Professor and Chair of the Department of Medicine at Mount Sinai from 1968 until his death in 1972, and Rosalyn S. Yalow, Ph.D., 1977 Nobel Laureate in Medicine or Physiology and Solomon A. Berson Distinguished Professor-at-Large, brought meticulous quantitation and new vistas to all of clinical medicine and biomedical science through the application of their technique of radioimmunoassay. I was fortunate to know and work with them for many years. In 1972, while I was an NIH Fellow in gastroenterology at Mount Sinai, Dr. Berson suggested that I pursue my research in their laboratory at the Bronx Veterans Administration Hospital. Dr. Berson died one month after I began my research in the Bronx. Yalow and Berson had already discovered big gastrin (G-34), but much work with gastrin remained to be done. Challenging work with secretin, cholecystokinin, and a host of other gut peptides, would keep the Mount Sinai group at the forefront of this exciting field.

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.

The Brooklyn gastrinomas.

During the past seven years we have diagnosed and treated 12 patients with the Zollinger-Ellison syndrome (ZES), some of whom have had virtually unique manifestations. Among these are a 74-year-old man who was cured after endoscopic removal of a submucosal duodenal gastrinoma, suggesting the usefulness of an operative approach using intraoperative endoscopic transillumination; a 33-year-old man in whom the manifestations of ZES brought him into conflict with the law; and a 10-year-old domestic cat who was cured surgically, the gastrinoma providing material for the first determination of the sequence of cat gastrins.

Cat gastrinoma and the sequence of cat gastrins.

Following the curative resection of a pancreatic gastrinoma in a cat, gastrin peptides were purified from the tissue and sequenced. The sequence of cat gastrinoma G17 (18-34) confirms the previously published sequence. The sequence of cat G34 (1-34) is reported for the first time. The NH2-terminal portion of cat G34 differs from that of dog by having a Q (Gln) for L (Leu) at position 10 from the NH2-terminus.