Propofol versus midazolam for conscious sedation guided by processed EEG during endoscopic retrograde cholangiopancreatography: a prospective, randomized, double-blind study.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure, which requires appropriate sedation. The aim of this prospective, randomized, double-blind study was to compare the quality and characteristics of sedation with midazolam or propofol in patients undergoing ERCP. PATIENTS AND METHODS: A total of 32 patients undergoing ERCP were randomly allocated for sedation with propofol (n = 15) or midazolam (n = 17). Blood pressure, heart rate, and O2 saturation were monitored. Sedation was maintained at near constant levels by use of the spectral edge frequency (SEF) technique, an EEG-based method for measuring the depth of sedation. Clinical variables, patient cooperation, time to recovery, and amnesia served as outcome variables. RESULTS: There was no significant difference between the two study groups in patient characteristics. The "target SEF" was 13.6 +/- 0.7 Hz for the propofol group and 14.8 +/- 1.1 Hz for the midazolam group (n.s.). The only clinical parameter with a significant difference between the groups was the percent of time in which the heart rate deviated more than 20% from baseline for at least 2 minutes, i.e. 14.6 +/- 2.0 % for propofol and 48.2 +/- 38.0% for midazolam (P<0.01). Patient cooperation was better in the propofol group than in the midazolam group (full cooperation, 13/15 vs. 1/17, respectively; P<0.001). Patient recovery was significantly quicker in the propofol group (P<0.001). The degree of amnesia was similar in both groups; no patient in either group remembered details of the procedure. CONCLUSIONS: ERCP is better tolerated by patients sedated with propofol compared with midazolam, with a shorter recovery time and lesser hemodynamic side effects. Propofol should be considered to be the sedative drug of choice for ERCP.

Premedication with Xylocaine spray does not lead to a false positive rapid urease test.

Rapid urease tests are used for quick identification of Helicobacter pylori during upper gastrointestinal endoscopy. Rapid urease test solutions contain urea, which in the presence of H. pylori urease, generates ammonia, which changes the test medium color to indicate a positive result. Theoretically, Xylocaine spray (ASTRA, Södertalje, Sweden), which has a basic pH value, could cause a similar positive reaction in the test medium. To determine whether patients premedicated with Xylocaine spray have a higher rate of false positive urease tests, we compared the results of a rapid urease test and histologic stains in 107 patients, 54 premedicated with Xylocaine spray and 53 premedicated with intravenous midazolam but not Xylocaine spray. There were no significant differences in test sensitivity, specificity, or predictive values between the study groups. We conclude that patients can be premedicated with Xylocaine spray without concern that the false positive rate of rapid urease tests will increase.

Open access endoscopy for hospitalized patients.

OBJECTIVES: Most requests for gastroenterology consultations for hospitalized patients are for endoscopic procedures. Open access endoscopy has been evaluated in several institutions for outpatients. Our aim was to evaluate an open access policy for hospitalized patients. METHODS: Since April of 1996, patients hospitalized in the Soroka Medical Center have been referred directly for upper endoscopy (esophagogastroduodenoscopy, EGD) and flexible sigmoidoscopy (FS). The numbers of procedures and consultation requests between July 1, 1996, and September 30, 1996, were compared with the corresponding months of 1995. A survey of physician satisfaction with the new open access system was conducted. RESULTS: The mean number of monthly consultations during the study period was 30.7 +/- 2.4, compared with 119.3 +/- 5.4 during the same months in 1995 (p = 0.006). Open access endoscopy was performed on 114 patients during the study period. Upper GI bleeding (n = 41) and abdominal pain (n = 33) were the most common indications for EGD. There were nine duodenal ulcers, five gastric ulcers, and eight gastric carcinomas. Sixteen patients (21%) had normal EGDs. The most common indications for FS were rectal bleeding (n = 24) and diarrhea (n = 13). Seven patients had colorectal cancer; 12 FSs were normal. In all, 286 EGDs and FSs were conducted in the study period compared with 253 in 1995 (not significant). All physicians expressed satisfaction with the new system and favored its continuation. CONCLUSIONS: The open access policy for hospitalized patients led to a considerable reduction in requests for consultations, with no significant increase in the number of endoscopies. The majority of patients referred directly for endoscopy had appropriate indications.

[Ambulatory liver biopsy].

During 1992-1994 we performed 77 needle liver biopsies on ambulatory patients. 59 patients were observed for 6 hours and then released. 15 who lived more than 40 km away and 3 in whom complications were feared were hospitalized. All were released within 24 hours and there were no complications. We conclude that ambulatory needle biopsy of the liver is safe and cost-effective is selected patients.

Mechanism of colonic permeation of inulin: is rat colon more permeable than small intestine?

BACKGROUND/AIMS: Colonic epithelium is considered to be relatively tight. The colonic "pore" diameter is 6 A; therefore, colonic epithelium has generally been considered to be impermeable to hydrophilic probes with a cross-sectional diameter of > 6 A. This study examined whether rat colon is permeable to inulin, a large hydrophilic macromolecule having a molecular weight of 5000 g/mol and a cross-sectional diameter of 15 A (hydration diameter, 20 A). METHODS: The colonic permeation of inulin (10 mumol/L) in vivo was investigated by perfusion of rat colonic segments. RESULTS: There was significant colonic permeation of inulin, but tissue retention of inulin was low. The net colonic flux of inulin was strongly dependent on net water flux, showing a strong solvent drag effect. Addition of 16,16-dimethyl prostaglandin E2 decreased water flux with a corresponding decrease in inulin flux; this process seemed to be mediated by 5'-cyclic adenosine monophosphate because both the phosphodiesterase inhibitor aminophylline and dibutyryl adenosine 5'-cyclic adenosine monophosphate decreased water and inulin flux in a parallel manner. Chenodeoxycholic and taurocholic acids decreased net mucosal-to-serosal water flux but increased inulin flux. The net colonic permeation rate of inulin was higher than the small intestinal permeation rate. CONCLUSIONS: Rat colon is permeable to inulin. The higher net colonic permeability may be caused by differences in mucosal surface, permselectivity, solvent drag effect, and differences in net water fluxes of the colon and small intestine.

Epidemiology of Crohn's disease in southern Israel.

OBJECTIVES: Crohn's disease in Israel was described in the past as being of low incidence, more common in Europe-America-born Jews than other Jews, and of uncharacteristically low morbidity. However, recent experience has suggested that these premises are no longer correct. METHODS: The records of all hospital and outpatient cases of Crohn's disease in southern Israel for the period 1968-1992 were reviewed. Private family practitioners and specialists were contacted to assure complete case ascertainment. RESULTS: The prevalence rate of Crohn's disease among Jews on December 31, 1992, was 50.6/10(5) (Asia-Africa-born Jews 55.0/10(5), Europe-America-born Jews 58.7/10(5), and the rate was 8.2/10(5) among Bedouin Arabs. The annual incidence rate (1987-1992) was calculated as 4.2/10(5)/yr in Jews (Asia-Africa-born 4.6/10(5)/yr, Europe-America-born 3.9/10(5)/yr). The age of presentation declined progressively over the study period, was lower in Israel-born patients than immigrants, and was lower in ileocolonic versus other sites of disease. CONCLUSIONS: The data show that Crohn's disease has become more common in Jews in Israel, losing ethnic differences of frequency, and that it occurs at a younger age than before. In Arabs, the disease is more rare.

Mechanisms and sites of mannitol permeability of small and large intestine in the rat.

Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms of its penetration of the intestinal barrier are not entirely clear. Therefore, we studied mannitol's permeability of different segments of the intestine and studied the kinetics and influence of intraluminal factors on mannitol permeability in vivo in perfused intestinal segments of rats. There was linear relationship between permeability rate of mannitol and its luminal concentration (y = 7.2x + 1.7; r = 0.98), indicating that passive diffusion is involved in mannitol's permeability. Increased luminal fluid osmolarity from 0.3 to 0.6 osmol/liter resulted in decreased net water flux with a corresponding decrease in mannitol permeability in both jejunum and colon (P < 0.01), indicating the prominent influence of solvent drag on net mannitol permeability. The relationship between mannitol permeability and water absorption at different osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3 osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and 65.4% was mediated by solvent drag in the jejunum. Mannitol permeability was much more dependent on solvent drag in the colon (88.9%) than in the small intestine (65.4%). The net permeability rate of mannitol was similar in the jejunum and ileum but was much higher in the colon (P < 0.01). Addition of chenodeoxycholate (5 mM) to the perfusate resulted in a significant decrease in absorption of water (P < 0.01) with a corresponding decrease in mannitol permeability (P < 0.01). These studies indicate that mannitol permeability of the intestinal barrier is mediated by passive diffusion and solvent drag, with the latter accounting for a greater fraction of the total permeability.

Pathogenetic aspects of persimmon bezoars. A case-control retrospective study.

To prove that ingestion of unpeeled persimmon is necessary for the development of a persimmon phytobezoar, we interviewed 15 patients, in most of whom this condition developed after peptic ulcer surgery. We compared the study group with a control group of 15 patients who had undergone peptic ulcer surgery but did not have a bezoar. In contrast with the control group, most patients with bezoars had ingested unpeeled fruits (p < 0.01). While ingestion of persimmon carried a 9.8-fold risk of bezoar development, ingestion of the unpeeled fruit increased the risk of this complication 56 times over that of age- and sex-matched controls. We recommend that patients who have undergone ulcer surgery be warned particularly against eating unpeeled persimmons.

Gastroesophageal obstruction from food in an epiphrenic esophageal diverticulum.

An epiphrenic diverticulum is usually accompanied by esophageal motor disorders, diaphragmatic hernia, or esophagitis. Symptoms are rarely attributable to the diverticulum except very rarely when no other explanation for dysphagia or chest pain is demonstrated. We describe acute esophageal obstruction from food accumulating in an epiphrenic diverticulum and compressing the gastroesophageal junction, and we confirm the mechanism with an artificial balloon.

IEC-18, a nontransformed small intestinal cell line for studying epithelial permeability.

Small intestinal epithelium is leaky and allows permeation of hydrophilic molecules of various sizes. Passively absorbed hydrophilic permeability probes have been shown to permeate across intestinal epithelium mainly through the paracellular pathways. In this study we introduce microporous filter-grown IEC-18 epithelial cells, a nontransformed small intestinal cell line, as a in vitro model of intestinal epithelium for the study of epithelial permeability. IEC-18 cells, originally derived from native rat ileal crypts, form confluent epithelium when grown on hydrated collagen-coated Millicell-CM permeable inserts (Millipore Corp., Bedford, Mass.). With scanning and transmission electron microscopy, the presence of tight junctions and desmosomes between cells and the development of microvilli at the apical surface were confirmed. Immunofluorescent labeling of ZO-1 proteins and desmoplakins verified the presence of tight-junctional proteins (ZO-1) and desmosomes in the intercellular junctions of confluent IEC-18 epithelium. The net electrical resistance of IEC-18 epithelium (28 omega-cm2) was similar to resistance values obtained from small intestinal tissue with (50 to 100 omega-cm2) or without (20 to 45 omega-cm2) muscularis and serosal layers. Assessment of mannitol and dextran permeation revealed early "maturation" of paracellular pathway, with increasing restriction of permeation to both probes through day 4. Resistance across IEC-18 epithelium also reached plateau levels between 4 and 7 days. Permeability studies with various probes indicate that cross-sectional diameter rather than molecular weight of the probe is the important determinant of permeation rate. IEC-18 epithelium selectively restricted the permeation of probes proportional to probe size; permeation of larger probes such as albumin was negligible. We conclude that cultured IEC-18 epithelial cells, because of their native crypt origin, similarity in resistance to small intestinal epithelia, retention of ability to differentiate into villus-like enterocytes, and permeability characteristics, are a useful model of intestinal epithelium for the study of permeability and paracellular transport.

[Screening for colorectal cancer and polyps].

Screening programs for the early detection of colorectal neoplasms may prevent cancer or improve its prognosis. We screened 1101 individuals (89% of whom were asymptomatic) using 3 methods. The fecal occult blood test, done in 96% of those screened, was positive in only 1.9% and was low in both sensitivity (2.1%) and positive predictive value (6.7%). However, flexible sigmoidoscopy, performed in 48%, gave positive results in 7.8% of those screened, revealing 41 cases of polyps and 1 of cancer. Colonoscopy was performed in 8% and 37 cases of polyps and 1 of cancer were detected. Of the 3 screening methods tested, sigmoidoscopy appeared to be the best because of its high diagnostic yield. The risk of colorectal neoplasm was shown for the first time to be equal in Jews of oriental and occidental origin.

Screening for colorectal neoplasia: a multicenter study in Israel.

We report the design and results of the first Israeli multicenter screening program for colorectal neoplasia. The screening protocol comprised a risk questionnaire, fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. A total of 5,601 individuals were screened in five medical centers, 55% being asymptomatic with low or average risk. Colorectal tumors were found in 12.3% of screenees, the majority being adenomas. The risk for large bowel neoplasia was greatest in persons with a personal history of colorectal neoplasia (neoplasia rate 473.2/10(3)) and was increased in those with inflammatory bowel disease, a family history of colorectal tumor, or past history of cured breast cancer. European-born Jews had a 50% greater risk than non-European-born Jews. Persons at high risk were more likely to return for repeat screening than those at low or average risk. However, approximately 15% of persons at high risk actually thought that they were of average risk. Fecal occult blood testing was markedly less reliable than flexible sigmoidoscopy and had a false-negative rate of 84.4%. The results demonstrate that existing medical facilities in Israel can be used to screen at least those individuals with increased risk for colorectal neoplasia.

Effect of aging and caloric restriction on intestinal permeability.

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes--mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 +/- 0.4 and 21.0 +/- 1.1% at 3 and 28 months respectively, p less than .01) and mannitol (3.41 +/- 0.4 and 5.3 +/- 0.5% at 3 and 28 months, respectively, p less than .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 +/- 0.03 and 0.38 +/- 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.

Inflammatory bowel disease in the Bedouin Arabs of southern Israel: rarity of diagnosis and clinical features.

A prospective epidemiological and clinical study of ulcerative colitis and Crohn's disease was undertaken in the Bedouin Arabs of southern Israel between 1981 and 1990. There were six patients with ulcerative colitis and the prevalence rate in 1990 was calculated to be 9.8/10(5) (95% confidence intervals 3.6-17.4) in the total population, or 6.2/10(5) (0.8-22.5) in men and 13.7/10(5) (3.7-35.0) in women. Two cases of Crohn's disease occurred, both in women; the prevalence rate was 3.2/10(5) (0.4-11.8) in the entire population, and 6.8/10(5) (0.8-17.5) in women. The prevalence rates (age adjusted) in Arabs were significantly lower (p less than 0.01) than the corresponding rates in the local Jewish populations. The Bedouin patients were aged mean (SD) 34.0 (16.4) years at time of diagnosis. The clinical features of both diseases resembled those in the Jewish and other reported populations. It is suggested that the exposure of the Bedouin Arabs to the environmental causative factors of ulcerative colitis and Crohn's disease has hitherto been limited and thereby accounts for the rarity of these diseases in this population.

Oxygen free radical injury of IEC-18 small intestinal epithelial cell monolayers.

Oxygen radicals can cause endothelial and epithelial permeability changes and mucosal injury of the small intestine. There is no clear consensus concerning the relative injurious potential of individual oxygen radicals. In this study, the small intestinal cell line IEC-18 was used as an in vitro model to study the relative injurious effects of reactive oxygen metabolites. By introducing different combinations of oxygen metabolite-producing enzymes, xanthine oxidase, superoxide dismutase, and catalase, and an iron chelator, deferoxamine, to the fully confluent monolayers and to proliferating IEC-18 cells, the differential injurious effects of the oxygen metabolites O2-, H2O2, and OH. could be evaluated. The extent of cellular injury was assessed using [3H]thymidine uptake, 51Cr release, and morphological evaluations. Our results suggest that OH. produced as a by-product of O2- and H2O2 via the Haber-Weiss reaction was the most injurious oxygen species involved in cellular injury of IEC-18 monolayers induced by xanthine oxidase. O2- produced by xanthine oxidase appeared to be only minimally injurious, and H2O2 produced by xanthine oxidase and as a result of conversion of O2- by superoxide dismutase was moderately injurious. Superoxide dismutase and deferoxamine at appropriate concentrations were protective against xanthine/xanthine oxidase-induced monolayer injury. H2O2 added directly or produced indirectly by glucose oxidase was very injurious to the intestinal monolayers, and this injury was mitigated by catalase.