Rome IV. Gallbladder and Sphincter of Oddi Disorders.

The concept that motor disorders of the gallbladder, cystic duct and sphincter of Oddi can cause painful syndromes is attractive and popular, at least in the USA. However, the results of commonly performed ablative treatments (cholecystectomy and sphincterotomy) are not uniformly good. The predictive value of tests that are often used to diagnose dysfunction (dynamic gallbladder scintigraphy and sphincter manometry) is controversial. Evaluation and management of these patients is made difficult by the fluctuating symptoms and the placebo effect of invasive interventions. A recent stringent study has shown that sphincterotomy is no better than sham treatment in patients with post-cholecystectomy pain and little or no objective abnormalities on investigation, so that the old concept of sphincter of Oddi dysfunction (SOD) type III is discarded. ERCP approaches are no longer appropriate in that context. There is a pressing need for similar prospective studies to provide better guidance for clinicians dealing with these patients. We need to clarify the indications for cholecystectomy in patients with Functional Gallbladder Disorder (FGBD) and the relevance of sphincter dysfunction in patients with some evidence for biliary obstruction (previously SOD type II, now called "Functional Biliary Sphincter Disorder - FBSD") and with idiopathic acute recurrent pancreatitis.

Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.

A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis.

BACKGROUND: Several pharmacological agents for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been studied. Clinical trials evaluating the protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. AIM: To perform a meta-analysis of studies evaluating the effect of prophylactic rectal NSAIDs on PEP. METHODS: By searching Medline, Embase, meeting abstracts and bibliographies, two independent reviewers systematically identified prospective randomised controlled trials (RCTs) examining the effect of rectally administered prophylactic NSAIDs on the incidence of PEP pancreatitis. A meta-analysis of these clinical trials was performed. RESULTS: Four RCTs, enrolling a total of 912 patients, have been published. Meta-analysis of these studies demonstrates a pooled relative risk for PEP after prophylactic administration of NSAIDs of 0.36 (95% CI 0.22 to 0.60); patients who received NSAIDs in the periprocedural period were 64% less likely to develop pancreatitis and 90% less likely to develop moderate to severe pancreatitis. The pooled number needed to treat with NSAIDs to prevent one episode of pancreatitis is 15 patients. No adverse events attributable to the use of NSAIDs were reported in any of the clinical trials. CONCLUSION: In this meta-analysis, prophylactic NSAIDs were effective in preventing PEP. Widespread prophylactic administration of these agents may significantly reduce the incidence of PEP, resulting in major clinical and economic benefit. Given current scepticism regarding the efficacy of any prophylactic medication for ERCP, additional multicentre studies are needed for confirmation prior to widespread adoption of this strategy.

Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans.

Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection.

BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection. METHODS: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary. RESULTS: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects. CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

Utility of a linear array ultrasound endoscope in the evaluation of suspected pancreatic disease.

Endoscopic ultrasonography (EUS) is currently being used to evaluate and stage pancreaticobiliary malignancies and neuroendocrine tumors, and to perform aspiration for cytologic diagnosis. There are currently two different commercially available EUS systems for clinical use. One system uses a mechanical radial sector scanner oriented in a plane perpendicular to the long axis of the endoscope, and the other uses an electronic convex scanner that is oriented in the long axis of the endoscope. The vast majority of the current literature reports experience using the radial scanning device in the evaluation of pancreaticobiliary abnormalities. We prospectively evaluated the linear probe as the sole instrument for EUS in 26 patients with suspected pancreatic disease. The results of the endoscopic ultrasound examination were compared with the results of surgery or long-term clinical follow-up. The sensitivity and specificity of linear array EUS for benign pancreatic disease were 93.8% and 88.2%, respectively. The sensitivity and specificity for malignant disease of the pancreas were 80.0% and 88.9%, respectively. The linear array echoendoscope, employed as the only instrument for evaluation of the pancreas, is accurate in the evaluation of pancreatic disease. The addition of EUS-guided pancreatic biopsy would be anticipated to improve the sensitivity of the linear array instrument for detecting malignancy.

Injection sclerotherapy-induced esophageal strictures. Risk factors and prognosis.

Injection sclerotherapy (IS) has become an effective modality for the treatment of bleeding esophageal varices. Despite improvements in equipment, sclerosant solutions and operator technique, injection sclerotherapy-induced esophageal strictures (ISES) remain a significant cause of patient morbidity. To analyze the risk factors and prognosis of ISES, the records of 117 patients who underwent IS over a 6-year period at a single teaching institute were reviewed. The predictive value of multiple risk factors including the patient's age, Child's risk classification, previous bleeding episodes, etiology of varices, cumulative amount of sclerosant used, and the number of IS treatments were determined using ANOVA. A P value of less than 0.05 was considered significant. In all cases, a free-hand injection technique, flexible endoscopes and sodium morrhuate were used. During a mean follow-up period of 228 days (1-1,469 days), 41 patients (35%) died and 24 patients (20.5%) developed symptomatic strictures. The cumulative amount of sclerosant used (81.4 +/- 9.5 ml) and the number of IS treatments (6.5 +/- 0.7) required in the stricture group was significantly greater than in the nonstricture group (49.1 +/- 2.7 and 4.0 +/- 0.3, respectively). The risk of stricture formation did not correlate with the volume of sclerosant injected per treatment, cause of varices, number of previous bleeds, or Child's hepatic risk class. A mean of 3.6 +/- 4.5 dilations was required for treatment of established strictures and 18 patients (75%) required r 4 dilations. One esophageal perforation occurred following dilation. Mortality correlated with hepatic risk class as 30/41 (73%) of deaths occurred in Child's C patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Helicobacter pylori in patients with nonulcer dyspepsia.

The relationship between endoscopically diagnosed gastroduodenitis, histologically confirmed gastritis, and symptoms of dyspepsia remains unclear. Marked histologically confirmed inflammation of gastric mucosa often occurs in a stomach that appears normal by endoscopy. Both histologically confirmed and endoscopically diagnosed gastritis are commonly blamed as causes of nonulcer dyspepsia (NUD), although neither disease has been convincingly shown to cause NUD. Helicobacter pylori infection of gastric mucosa is a common cause of histologically confirmed inflammation. It is unclear whether this infection with H. pylori and the resultant gastric mucosal inflammation cause symptoms since inflamed mucosae are also common in asymptomatic controls. The reported increased prevalence of H. pylori in patients with NUD compared with controls suggests a possible causative role in at least a subset of patients with NUD. In addition, three controlled studies of treatment with bismuth demonstrated a significant trend toward improvement of symptoms after clearance of H. pylori. However, two studies of therapy with bismuth failed to demonstrate improvement of symptoms. Further study of patients with NUD is needed to clarify this possible association.

Home study course: spring 2001.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1 credit hour in Category 1 of the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

Meperidine need not be proscribed during sphincter of Oddi manometry.

Meperidine is routinely proscribed during sphincter of Oddi manometry because narcotics have been associated with spasm of the sphincter of Oddi. We have performed a prospective study of the effect of meperidine on sphincter of Oddi manometry in 18 patients undergoing manometry for suspected sphincter dysfunction. After diagnostic manometry using only intravenous diazepam sedation, the endoscope remained in the duodenum while 1 mg/kg intravenous meperidine was given. Five minutes later sphincter manometry was repeated. There was no difference in the baseline sphincter pressure before and after meperidine in all patients. The frequency of phasic contractions increased after meperidine (p = 0.001). Baseline sphincter pressure is generally the only manometric criteria used to diagnose sphincter dysfunction and this did not change after meperidine. We conclude that meperidine may be used for additional analgesia during sphincter manometry. This may improve patient tolerance and the success rate of this procedure.

Esophageal dysphagia as the sole symptom in type I Chiari malformation.

Chiari malformation, also called Arnold-Chiari deformities, are rare hindbrain herniations that may present in children or adults. The most common symptoms include headache, syncope, disordered eye movement, sensory loss, weakness, and cerebellar features such as ataxia. Dysphagia occurs in 5-15% of patients, although only a few reports describe dysphagia as the only presenting symptom. We report a case of a 27-year-old woman who presented with a three-year history of dysphagia, chest pain, and weight loss. Esophageal manometrics revealed markedly disordered esophageal motility and gastroesophageal reflux. Her symptoms failed to respond to high doses of omeprazole, prokinetics, and eventually surgical fundoplication. The subsequent onset of neurological symptoms led to the diagnosis of Chiari type I malformation. Following posterior craniotomy with decompression, her dysphagia and chest discomfort completely resolved. Repeat esophageal manometrics revealed complete resolution of prior abnormalities.

Comparison of coffee intake and coffee-induced symptoms in patients with duodenal ulcer, nonulcer dyspepsia, and normal controls.

Coffee and decaffeinated coffee stimulate acid secretion. In addition, many patients experience dyspepsia after coffee ingestion. Therefore, coffee is often prohibited by physicians in patients with peptic diseases. However, the association between peptic disease and symptoms remains unclear. This study compares coffee intake and the induction of symptoms by coffee in patients with duodenal ulcer disease, nonulcer dyspepsia, and normal controls. We have studied the coffee drinking habits of 58 duodenal ulcer patients, 55 nonulcer dyspepsia patients, and 55 normal controls. The use of coffee on a daily basis was not significantly different between duodenal ulcer patients (64%) and controls (56%), or between nonulcer dyspepsia patients (55%) and controls. There was also no difference between the three groups in the use of decaffeinated coffee, the number of cups per day, the method of preparation, the length of time of coffee use, or any change in coffee intake in the previous year. The intake of tea, caffeinated carbonated beverages, and aspirin or nonsteroidal anti-inflammatory drugs was also similar in the three groups. The duodenal ulcer patients were more likely to be cigarette smokers (45%) than either the controls (16%) or the nonulcer dyspepsia patients (24%). Daily alcohol intake was not significantly different in the three groups. The prevalence of coffee induction of dyspeptic symptoms was similar in duodenal ulcer patients (29%) and controls (22%), but was much more common in nonulcer dyspepsia patients (53%) than in controls (22%), p = 0.0036. In conclusion, there was no difference in coffee intake between patients with duodenal ulcer, nonulcer dyspepsia, or normal controls. However, patients with nonulcer dyspepsia, but not duodenal ulcer, were more likely to experience dyspeptic symptoms after coffee ingestion.

Persistent immune deficiency in patients with alcoholic hepatitis.

T-lymphocyte subset numbers, recall-antigen skin test responses and mitogen-induced lymphocyte proliferation assays were investigated in 12 patients with severe alcoholic hepatitis (AH). Serial studies of these parameters were obtained at intervals of 1 or 2 wk. Patients with AH had lower peripheral blood lymphocyte counts with corresponding decreases in T-cell subset numbers that were persistent in the serial evaluations. T8 cells were disproportionately decreased, with a significant resultant increase in the T4:T8 ratios. Compared with controls, AH patients had significantly smaller cutaneous responses to Candida albicans antigen (p less than 0.05) and mumps antigen (p less than 0.005). Fifty-eight percent of patients were anergic when tested with a battery of four antigens. Patients with AH had increased concanavalin A-, but not phytohemagglutinin-induced lymphocyte proliferative responses. These serial analyses confirm previous observations of cell-mediated immune dysfunction in patients with severe AH. Moreover, there is a persistence of these abnormalities for at least 6 wk after withdrawal from alcohol.

Elevation of gastric pH with ranitidine does not affect the release characteristics of sustained release ibuprofen tablets.

The effect of elevating gastric pH on the release characteristics of a single unit sustained release (SR) ibuprofen tablet (MOTRIN-SR, Upjohn) was evaluated in 12 young, healthy men. Using a randomized crossover-type design, each subject received three treatments--ibuprofen SR 800 mg, ranitidine 300 mg followed by ibuprofen SR 800 mg, and conventional ibuprofen tablets (2 x 400 mg). Gastric pH, which was monitored radiotelemetrically, was maintained above pH 6 for at least 4 h after pretreatment with ranitidine. In absence of ranitidine, the pH remained mostly below pH 3. Serum levels of ibuprofen were measured for 24 h and urine was collected for 48 h after each treatment. Similarity of the serum levels after the two treatments with ibuprofen SR 800 mg indicated that the release of ibuprofen was unaffected by elevation in gastric pH. Comparison of profiles with the immediate release dosage form indicated that dose dumping did not occur in any subject.

Fat-soluble vitamin nutriture in primary biliary cirrhosis.

We measured serum levels of vitamins A, E, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D, as well as levels of abnormal (des-gamma-carboxy) prothrombin, in 52 patients with primary biliary cirrhosis. Decreased serum levels of retinol (vitamin A) and 25-hydroxyvitamin D and elevated levels of abnormal prothrombin were common in these patients and correlated with the histologic stage of the disease and with the clinical severity of disease as judged by elevated serum bilirubin levels and decreased serum albumin levels. The increased levels of abnormal prothrombin were due primarily to vitamin K deficiency but also, in part, to the severity of the liver disease itself. Vitamin E deficiency was rare. Only 1 patient had clinical manifestations of fat-soluble vitamin deficiency, night blindness, and gastrointestinal bleeding related to a marked prolongation of the prothrombin time. Deficiencies of fat-soluble vitamins are most likely to be present in jaundiced patients with long-standing, severe cholestasis. We suggest that fat-soluble vitamin status be determined in all patients with primary biliary cirrhosis by appropriate blood tests and that vitamin supplements be given only to those patients who require them.

Delayed biliary drainage is common in asymptomatic post-cholecystectomy volunteers.

A commonly used diagnostic criterion for sphincter of Oddi dysfunction is delayed drainage of contrast media from the bile ducts at endoscopic retrograde cholangiography (ERC), which is defined as the persistence of contrast greater than 45 min after injection. We performed ERC in 11 asymptomatic post-cholecystectomy volunteers for the purpose of evaluating biliary drainage time. In an attempt to more accurately quantify emptying, concomitant scintigraphy was performed at the time of ERC and contrast drainage. Sufficient contrast mixed with technetium-99m sulfur colloid to completely fill out the intra-hepatic tree was injected (mean volume, 9 ml) and the volunteers remained in the prone position during imaging. The length of time from cholecystectomy, bile duct size, volume of contrast injected, and scintigraphic T1/2s did not correlate with drainage time at ERC. At 45 min after injection the degree of residual contrast filling was scored as: empty in three volunteers, almost empty in one, one-fourth full in 5, and one-half full in two. Therefore, 7 of the 11 asymptomatic volunteers (63%) had delayed drainage. Even if more stringent criteria for delayed drainage were used (ducts one-half filled), 2 of the 11 (18%) had abnormal drainage. The frequent occurrence of delayed drainage in these asymptomatic post-cholecystectomy volunteers challenges the validity of the 45-min delayed drainage criterion for sphincter of Oddi dysfunction.

Campylobacter pylori is not associated with gastroparesis.

There is a high incidence of Campylobacter pylori in the gastric mucosa of patients with duodenal ulcer, gastric ulcer, and nonulcer dyspepsia. Factors that lead to development of this infection are unknown. We hypothesized that delayed solid-phase gastric emptying, a condition characterized by antral stasis, might predispose to Campylobacter pylori infection. We prospectively studied 51 patients with symptoms of gastroparesis using a solid-phase gastric emptying study and upper endoscopy. Patients were excluded if they had predominant symptoms of epigastric pain or an abnormal endoscopy. Three biopsies were obtained from the antrum and stained with H&E. When any inflammation was present, a Warthin-Starry stain was also performed. These were blindly examined for chronic inflammation, activity, and presence of Campylobacter pylori. Campylobacter pylori was not more common in patients with gastroparesis, documented by delayed gastric emptying, than in patients with a normal emptying study. On the contrary, there was a significantly lower incidence of Campylobacter pylori in those with delayed emptying compared to those with normal emptying (5% vs 31%, P less than 0.05). Gastritis activity correlated closely with Campylobacter presence. Inactive chronic gastritis with Campylobacter was equally common in those with delayed or normal gastric emptying. Diabetics were no more likely to harbor Campylobacter pylori than nondiabetics (16% vs 25%). The 5% incidence of Campylobacter in the gastroparesis group is less than, but approaches, that previously reported in asymptomatic controls. The 31% incidence of Campylobacter in the group with symptoms of gastroparesis but normal gastric emptying approaches that reported for nonulcer dyspepsia. Our data suggest that gastroparesis does not predispose to Campylobacter pylori infection or histologic chronic gastritis.

One-week therapy for Helicobacter pylori. A randomized trial of two treatment regimens.

In clinical practice, eradication of Helicobacter pylori infection may be difficult due to medication side effects and the need for 2 weeks of therapy. Because therapies of shorter duration may improve patient compliance and reduce treatment side effects, we compared the efficacy and tolerability of two anti-H. pylori treatments of 1 week's duration. Patients with H. pylori infection were randomized to treatment with either (a) short-course triple therapy, composed-of bismuth subsalicylate (Pepto-Bismol, Procter & Gamble, Cincinnati, OH, U.S.A.) two tablets four times daily, amoxicillin 1 g (two 500-mg tablets) twice daily, and metronidazole 500 mg four times daily on days 5-7 or (b) omeprazole 40 mg twice a day with amoxicillin 1 g twice a day for 1 week. At least 4 weeks posttreatment, efficacy was evaluated with either histological evaluation of antral biopsies for H. pylori or 14C urea breath testing. Patients who failed initial therapy were allowed to cross over to the alternative treatment regimen after a minimum "wash-out" period of 5 weeks. Patients completed a diary during therapy to monitor both compliance and side effects. Thirty-four patients completed the study, 10 receiving both treatment regimens. Treatment with the shortcourse triple therapy eradicated H. pylori in 78.3% of treatments compared with 38% with the high-dose omeprazole/ amoxicillin combination (p < 0.05). Patients were highly compliant with both treatments, and mild side effects, such as transient loose stools or abdominal pain, were common in both groups. This is the first report from North America confirming the success of the short-course triple therapy for the eradication of H. pylori. The high-dose omeprazole/ amoxicillin regimen's eradication rate was markedly inferior to that achieved by the short-course triple therapy regimen and should not be used. Comparative studies of the short-course triple therapy regimen with other 7-day anti-H. pylori treatment regimen therapies are indicated.

Lymphocyte subsets in primary biliary cirrhosis.

To ascertain whether abnormalities of circulating T-cell subsets are a cause or effect of primary cirrhosis, we analyzed peripheral blood lymphocytes from 44 patients at various stages of disease. The percentages of total T cells and helper/inducer cells were normal in early disease whereas the percentage of suppressor/inducer cells was increased. The percentage of all T-cell subsets fell steadily as the disease progressed histologically. The percentages in late (cirrhotic) disease were the same as those in patients with other types of cirrhosis. We conclude that most of the previously reported abnormalities of circulating T cells are secondary to the histologic progression of primary biliary cirrhosis.

Effect of iron on the guaiac reaction.

Most studies show that oral ingestion of iron does not cause a positive stool guaiac reaction. However, all in vitro studies show that iron does cause a positive guaiac reaction and some in vivo studies have shown a positive stool guaiac reaction in response to oral iron. This study examines this unresolved question. Twenty-five normal volunteers were given 900 mg of ferrous sulfate a day. Two Hemoccult II and two HemoQuant tests were obtained before and during iron therapy. All Hemoccult II tests were negative before and after oral iron. Four HemoQuant tests were slightly elevated before oral iron and one was slightly elevated after oral iron. Ferrous sulfate, 300 mg, was dissolved in 1 L of water. The solution was acidic (pH = 3.9) and produced a positive Hemoccult II test. When the solution was titrated with sodium hydroxide to a pH of greater than or equal to 6.0, iron precipitated out and the mixture no longer produced a positive Hemoccult II reaction. Our data show that ferric iron (Fe3+) in solution will give a positive guaiac reaction directly and ferrous iron (Fe2+) will give a positive guaiac reaction after hydrogen peroxide is added because it oxidizes Fe2+ to Fe3+. Iron solutions are acidic and when titrated toward a neutral pH, the iron is precipitated out and the solution is then guaiac-negative. Thus, our in vivo data confirm most previous in vivo studies; furthermore, the discrepancy between in vivo and in vitro studies can be explained as a pH-dependent phenomenon of in vitro iron solutions. Oral iron should not cause a positive guaiac reaction, and the HemoQuant results show no increase in occult blood loss in subjects on oral iron therapy.