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J P Raufman

Publications and source records attributed to J P Raufman.

At least 19 recordsLinked to original sources

Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial.

CONTEXT: Severe gastroesophageal reflux disease (GERD) is a lifelong problem that can be complicated by peptic esophageal stricture and adenocarcinoma of the esophagus. OBJECTIVE: To determine the long-term outcome of medical and surgical therapies for GERD. DESIGN AND SETTING: Follow-up study conducted from October 1997 through October 1999 of a prospective randomized trial of medical and surgical antireflux treatments in patients with complicated GERD. Mean (median) duration of follow-up was 10.6 years (7.3 years) for medical patients and 9.1 years (6.3 years) for surgical patients. PARTICIPANTS: Two hundred thirty-nine (97%) of the original 247 study patients were found (79 were confirmed dead). Among the 160 survivors (157 men and 3 women; mean [SD] age, 67 [12] years), 129 (91 in the medical treatment group and 38 in the surgical treatment group) participated in the follow-up. MAIN OUTCOME MEASURES: Use of antireflux medication, Gastroesophageal Reflux Disease Activity Index (GRACI) scores, grade of esophagitis, frequency of treatment of esophageal stricture, frequency of subsequent antireflux operations, 36-item Short Form health survey (SF-36) scores, satisfaction with antireflux therapy, survival, and incidence of esophageal adenocarcinoma, compared between the medical antireflux therapy group and the fundoplication surgery group. Information on cause of death was obtained from autopsy results, hospital records, and death certificates. RESULTS: Eighty-three (92%) of 90 medical patients and 23 (62%) of 37 surgical patients reported that they used antireflux medications regularly (P<.001). During a 1-week period after discontinuation of medication, mean (SD) GRACI symptom scores were significantly lower in the surgical treatment group (82.6 [17.5] vs 96.7 [21.4] in the medical treatment group; P =.003). However, no significant differences between the groups were found in grade of esophagitis, frequency of treatment of esophageal stricture and subsequent antireflux operations, SF-36 standardized physical and mental component scale scores, and overall satisfaction with antireflux therapy. Survival during a period of 140 months was decreased significantly in the surgical vs the medical treatment group (relative risk of death in the medical group, 1.57; 95% confidence interval, 1.01-2.46; P =.047), largely because of excess deaths from heart disease. Patients with Barrett esophagus at baseline developed esophageal adenocarcinomas at an annual rate of 0.4%, whereas these cancers developed in patients without Barrett esophagus at an annual rate of only 0.07%. There was no significant difference between groups in incidence of esophageal cancer. CONCLUSION: This study suggests that antireflux surgery should not be advised with the expectation that patients with GERD will no longer need to take antisecretory medications or that the procedure will prevent esophageal cancer among those with GERD and Barrett esophagus.

Adenocarcinoma↗

The role of liver biopsy in the evaluation of liver test abnormalities.

Percutaneous liver biopsy, first performed by Paul Ehrlich in 1883, remains an important diagnostic procedure for the management of hepatobiliary disorders. Modern biochemical, immunologic, and radiographic techniques have facilitated the diagnosis of liver disease but have not made biopsy obsolete. Indeed, examination of liver histology remains the "gold standard" for many diagnoses. This article reviews current indications for liver biopsy and the role biopsy plays in managing a variety of disorders.

Biopsy↗

Treatment of hepatitis C.

With > 100 million people infected worldwide and > or = 4 million people infected in the United States, hepatitis C virus (HCV) is a major public health concern. In the United States, HCV is the most common cause of chronic liver disease. End-stage liver disease from chronic HCV is the most common indication for liver transplantation.

Algorithms↗

Changing trends in gastric carcinoma at a university medical center: a twelve-year retrospective analysis.

Over the past 60 years, the epidemiology of gastric adenocarcinoma has changed considerably. The most striking change in the epidemiology of gastric adenocarcinoma has been the rapid increase in cancers of the proximal stomach. We performed a retrospective analysis of all gastric adenocarcinomas diagnosed at two hospitals in Little Rock, Arkansas, U.S.A., between 1985 and 1996. Two hundred seventeen patients were diagnosed with gastric adenocarcinoma. Patients were divided into three 4-year cohorts. We found that the proportions of gastric cardia adenocarcinoma in cohorts 1, 2, and 3 were 31%, 36%, and 42%, respectively (p = 0.52). Median survival in the three cohorts was 5, 8, and 8 months, respectively (p = 0.22). Median survival (stages 1-4) was 41.5, 11.5, 10, and 3 months, respectively (p < 0.0001). Well-, moderately-, and poorly- differentiated adenocarcinoma had median survivals of 18, 7.5, and 6 months, respectively (p = 0.07). We concluded that patients with gastric adenocarcinoma continue to be diagnosed at late stages. There has been a trend toward an increasing proportion of cardia adenocarcinoma. Stage at presentation was the only significant predictor of survival.

Adenocarcinoma↗

Oral pharmacokinetics of omeprazole and lansoprazole after single and repeated doses as intact capsules or as suspensions in sodium bicarbonate.

BACKGROUND: Omeprazole and lansoprazole can be given in sodium bicarbonate as, respectively, simplified omeprazole suspension and simplified lansoprazole suspension. We previously found the antisecretory effect of omeprazole 20 mg given as simplified omeprazole suspension to be lower than with intact capsules. However, lansoprazole 30 mg as simplified lansoprazole suspension produced an effect similar to that seen with intact capsules. AIM: To evaluate the absorption of both drugs when given orally as capsules or as suspensions in sodium bicarbonate. METHODS: In random order, we gave 5-day courses of omeprazole 20 mg and lansoprazole 30 mg as capsules and as suspensions in sodium bicarbonate to 12 healthy women. Serial blood samples were taken on days 1 and 5 of each course for pharmacokinetic measurements. RESULTS: There was impairment of omeprazole absorption when given as simplified omeprazole suspension. Maximum plasma concentration and area under the concentration/time curve were lower with simplified omeprazole suspension than with omeprazole capsules (P=0.034 and 0.013, respectively, on day 5). No differences were found in lansoprazole absorption when simplified lansoprazole suspension was compared with its standard capsule formulation. Relative bioavailability of omeprazole from simplified omeprazole suspension compared to the capsule was 58.4% on day 5. The corresponding value for lansoprazole was 84.7%. CONCLUSIONS: Simplified omeprazole suspension 20 mg does not supply adequate omeprazole for systemic absorption. Lansoprazole absorption from simplified lansoprazole suspension is maintained.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The effects of roasting on the allergenic properties of peanut proteins.

BACKGROUND: Because of the widespread use of peanut products, peanut allergenicity is a major health concern in the United States. The effect or effects of thermal processing (roasting) on the allergenic properties of peanut proteins have rarely been addressed. OBJECTIVE: We sought to assess the biochemical effects of roasting on the allergenic properties of peanut proteins. METHODS: Competitive inhibition ELISA was used to compare the IgE-binding properties of roasted and raw peanut extracts. A well-characterized in vitro model was used to test whether the Maillard reaction contributes to the allergenic properties of peanut proteins. The allergic properties were measured by using ELISA, digestion by gastric secretions, and stability of the proteins to heat and degradation. RESULTS: Here we report that roasted peanuts from two different sources bound IgE from patients with peanut allergy at approximately 90-fold higher levels than the raw peanuts from the same peanut cultivars. The purified major allergens Ara h 1 and Ara h 2 were subjected to the Maillard reaction in vitro and compared with corresponding unreacted samples for allergenic properties. Ara h 1 and Ara h 2 bound higher levels of IgE and were more resistant to heat and digestion by gastrointestinal enzymes once they had undergone the Maillard reaction. CONCLUSIONS: The data presented here indicate that thermal processing may play an important role in enhancing the allergenic properties of peanuts and that the protein modifications made by the Maillard reaction contribute to this effect.

Allergens↗

Survey of internal medicine residents' use of the fecal occult blood test and their understanding of colorectal cancer screening and surveillance.

OBJECTIVE: Primary care physicians have imperfect understanding of current colorectal cancer screening guidelines and recommendations. Furthermore, compliance with colorectal cancer screening by internal medicine residents has been demonstrated to be poor. We sought to identify whether current trainees in internal medicine had adequate understanding of colorectal cancer screening and surveillance and test utilization. METHODS: We applied a structured questionnaire about colorectal cancer screening and the use of fecal occult blood tests to 168 internal medicine residents at four accredited programs in the U.S. They were also asked for recommendations about six hypothetical patients who may have been candidates for screening or surveillance. RESULTS: Seventy-one percent identified 50 yr as the currently recommended age to commence screening in an average-risk individual; 64.3% would begin screening with fecal occult blood testing and flexible sigmoidoscopy and 4.8% with colonoscopy. Most perform fecal occult blood testing on stool obtained at digital rectal exam and without prior dietary restrictions. Many use fecal occult blood testing for indications other than colorectal cancer screening. Only 29% recommended colonoscopy to evaluate a positive fecal occult blood test. Most residents plan to be screened for colorectal neoplasia at the appropriate age; significantly more opted for colonoscopy than recommended it for their patients. CONCLUSIONS: Internal medicine residents have many misperceptions regarding colorectal cancer screening and the utility of the fecal occult blood test. Educational efforts should be directed at internal medicine residents, many of whom plan careers in primary care, where most colorectal cancer screening is currently performed.

Adult↗

A survey of internal medicine residents' knowledge about Helicobacter pylori infection.

OBJECTIVE: Despite recently published national guidelines, many physicians have only limited knowledge about Helicobacter pylori infection. We conducted this study to assess internal medicine residents' knowledge about H. pylori. METHODS: Two hundred and nineteen residents in seven accredited internal medicine training programs completed a self-administered questionnaire on personal demographics and practices related to testing for-and treating-H. pylori infection. RESULTS: Noon conferences (82%), ward teaching (66%), journals (70%), and sponsored symposia (27%) were their major sources of H. pylori-related information. Forty-eight percent had used office-based tests for the infection. Testing for (and treatment of) Helicobacter pylori infection was recommended by 97% (97%) for newly diagnosed duodenal ulcer, but by only 61% (63%) for a past history of duodenal ulcer. Many recommended testing in unproven conditions and might not have offered treatment to an infected patient. A proton pump inhibitor-based triple-drug regimen was the treatment of first choice of 55%; 20% recommended proton pump inhibitor-based dual regimens. Sixty-six percent and 80%, respectively, underestimated the rates of resistance to clarithromycin and metronidazole. In the absence of gastrointestinal symptoms, 22% would have ordered Helicobacter pylori testing but only 33% of these would undergo treatment if positive. CONCLUSIONS: Internal medicine residents usually test for Helicobacter pylori infection in appropriate conditions, but may not always treat the infection when the result is positive. Most use efficacious treatment regimens although many have inaccurate knowledge of resistance rates, which may adversely influence prescribing. Education should focus on practical issues surrounding Helicobacter pylori testing and treatment such as those contained in the American College of Gastroenterology's 1998 practice guidelines.

Adult↗

Zinc-induced copper deficiency in a coin swallower.

In humans, acquired copper deficiency anemia is rare. This report describes a 58-yr-old man with metal pica, especially coins, who presented with symptomatic anemia. His workup led to the diagnosis of zinc-induced copper deficiency. We believe that, in this man, leaching of zinc from pennies explained the clinical and laboratory findings. This case demonstrates that health care workers should consider the possibility of zinc-induced copper deficiency when confronted with patients with unexplained anemia who have ingested coins or other zinc-containing metals.

Bezoars↗

Glucuronidation of estrogens and retinoic acid and expression of UDP-glucuronosyltransferase 2B7 in human intestinal mucosa.

We have recently shown that, in human intestine, glucuronidation of androsterone and testosterone was on the nanomolar level and increased from proximal to distal intestine. In the present study, we have characterized estrogen UDP-glucuronosyltransferase activity in microsomes from intestine of seven human subjects. Intestinal microsomes from all segments of intestine from both males and females (except for one male) glucuronidated estrone (0.2-2.6 nmol/mg x min) and estradiol (0.5-3.1 nmol/mg x min) at levels 2 to 15 times higher than found with human liver microsomes (0.04-0.1 and 0.16-0.25 nmol/mg x min, for estrone and estradiol, respectively). Only with estriol were there significant hepatic glucuronidation (2. 2-4.5 nmol/mg x min) and intestinal glucuronidation activities (0.2-2.2 nmol/mg x min) that were lower than those in liver. All-trans-retinoic acid was glucuronidated by all segments of intestine from both sexes at levels 50 to 80% of those found with human liver but quite low compared with estrogen glucuronidation. In the two subjects for whom stomach was available, there was no measurable activity in stomach microsomes toward any of the substrates. UGT2B RNA expression was examined in mucosa from stomach to colon from two subjects. There was significant expression of UGT2B7, but not of UGT2B4 or UGT2B15, in all segments of intestine. To our knowledge, this is the first direct demonstration of glucuronidation of estrogens by human intestinal microsomes. Thus, in humans, the intestine may be considered as part of the overall mechanism of detoxification via glucuronidation.

Adolescent↗

Cytosolic RAB3D is associated with RAB escort protein (REP), not RAB-GDP dissociation inhibitor (GDI), in dispersed chief cells from guinea pig stomach.

Rab3D, a low-molecular-weight GTP-binding protein believed to be involved with regulated exocytosis, is associated with secretory granules in gastric chief cells. Although Rab3D is predominantly membrane associated, a significant fraction is cytosolic. Rab proteins are geranylgeranylated on their C-terminal cysteine motifs by geranylgeranyltransferase (GGTase). Rab escort protein (REP) is required to present Rab proteins to GGTase and may accompany newly modified Rab proteins to their target membrane. In most tissues, cytosolic Rab proteins are complexed with rab-GDP dissociation inhibitor (rab-GDI). In the present study, we examined the interactions of Rab3D with cytosolic proteins in dispersed chief cells. Two REP isoforms and at least two GDI isoforms are present in chief cell and brain cytosol. When chief cell cytosol was fractionated by gel filtration chromatography, Rab3D eluted with REP at >150 kDa, whereas rab-GDI eluted as a separate 65-kDa peak, suggesting that Rab3D exists as a complex with REP, but not with rab-GDI. In addition, a small fraction of Rab3D eluted as a monomer at 29 kDa. As has been demonstrated previously, in brain cytosol, Rab3 proteins co-elute with rab-GDI at approx. 90 kDa, suggesting that Rab3 proteins undergo active cycling between membrane and cytosolic compartments in this tissue. In vitro experiments revealed that Rab3D remains associated with REP after geranylgeranylation. Our findings suggest that, in gastric chief cells, Rab3D remains associated with REP after geranylgeranylation until it is presented to its target membrane.

Alkyl and Aryl Transferases↗

Mesenteric venous thrombosis.

BACKGROUND: Mesenteric venous thrombosis is an uncommon but often lethal form of intestinal ischemia. METHODS: We reviewed pertinent literature on mesenteric venous thrombosis using MEDLINE search. RESULTS: We found that previous abdominal surgery and hypercoagulable states are the most common conditions associated with mesenteric venous thrombosis. The symptoms and signs related to mesenteric venous thrombosis are not specific. In the majority of cases, the diagnosis is established by a high index of clinical suspicion and noninvasive imaging techniques. Immediate operation is indicated if signs of peritonitis or intestinal infarction are present. Administration of heparin is beneficial for reducing recurrence and mortality. CONCLUSION: Clinicians should consider the possibility of acute mesenteric venous thrombosis when faced with a patient having abdominal pain out of proportion to the physical findings and with a negative workup for the common causes of abdominal pain.

Humans↗

UDP-glucuronosyltransferases in human intestinal mucosa.

While UDP-glucuronosyltransferases (UGTs) are known to be expressed at high levels in human liver, relatively little is known about extrahepatic expression. In the present study, UGT2B family isoforms involved in the glucuronidation of steroid hormones and bile acids have been characterized in microsomes prepared from jejunum, ileum and colon from six human subjects. Glucuronidation of androsterone and testosterone was highly significant and increased from proximal to distal intestine. In contrast, hyodeoxycholic acid was glucuronidated at a low level in jejunum and ileum and activity was barely detectable in colon. No significant glucuronidation of lithocholic acid was found. Small phenols were glucuronidated with much lower activity than found in liver. High levels of UGT protein were detected with polyclonal anti-rat androsterone- and testosterone-UGT antibodies, whereas UGT2B4, a major hepatic hyodeoxycholic acid-specific UGT, was undetectable using a highly specific anti-human UGT2B4 antibody. Screening for RNA expression by RT-PCR confirmed the absence of UGT2B4 and UGT1A6 and showed expression of UGT2B7, a hepatic isoform shown to glucuronidate androsterone, in all intestinal segments. To our knowledge, the presence of functional androsterone and testosterone directed isoforms in human intestine is a novel finding which supports the idea that the intestinal tract functions as a steroid-metabolizing organ and plays a significant role in steroid hormone biotransformation.

Adult↗

Protein kinase C isoform expression and function in transformed and non-transformed pancreatic acinar cell lines.

Members of the protein kinase C (PKC) family of multifunctional serine/threonine phosphorylating enzymes are believed to play a role in regulating cellular differentiation and proliferation in many cell types. In the present study, we examined the expression of PKC isoforms in non-transformed (BMRPA.430) and transformed (TUC3) rat pancreatic acinar cell lines and compared this to PKC expression in freshly dispersed acini from rat pancreas. BMRPA.430 cells maintain characteristics of normal acini and are not tumorigenic, whereas TUC3 cells do not express tight junctions or polygonal morphology and are tumorigenic. As reported previously, PKC alpha, delta, epsilon, and zeta are expressed in freshly prepared acini. Likewise, these isoforms were detected in both the BMRPA.430 and TUC3 cell lines. In addition, PKC theta, a novel isoform, was detected in all three cell types at low levels. We used two PKC inhibitors to examine the role of PKC in acinar cell proliferation. CGP 41 251, a selective PKC inhibitor, and Go 6976, an agent which specifically inhibits calcium-dependent PKC isoforms, inhibited cell proliferation of both cell lines. Translocation of PKC alpha to the membrane was not observed in either cell line. Hence, our data indicate that ras-induced transformation does not alter PKC isoform expression in pancreatic acinar cells and that activation of PKC alpha is involved with acinar cell growth.

Animals↗

Cholera.

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Adenylyl Cyclases↗