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Although strong epidemiologic evidence suggests an important role for adaptive immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis (JRA), there remain many aspects of the disease that suggest equally important contributions of the innate immune system. We used gene expression arrays and computer modeling to examine the function in neutrophils of 25 children with polyarticular JRA. Computer analysis identified 712 genes that were differentially expressed between patients and healthy controls. Computer-assisted analysis of the differentially expressed genes demonstrated functional connections linked to both interleukin (IL)-8- and interferon-gamma (IFN-gamma)-regulated processes. Of special note is that the gene expression fingerprint of children with active JRA remained essentially unchanged even after they had responded to therapy. This result differed markedly from our previously reported work, in which gene expression profiles in buffy coats of children with polyarticular JRA reverted to normal after disease control was achieved pharmacologically. These findings suggest that JRA neutrophils remain in an activated state even during disease quiescence. Computer modeling of array data further demonstrated disruption of gene regulatory networks in clusters of genes modulated by IFN-gamma and IL-8. These cytokines have previously been shown to independently regulate the frequency (IFN-gamma) and amplitude (IL-8) of the oscillations of key metabolites in neutrophils, including nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and superoxide ion. Using real-time, high-speed, single-cell photoimaging, we observed that 6/6 JRA patients displayed a characteristic defect in 12% to 23% of the neutrophils tested. Reagents known to induce only frequency fluctuations of NAD(P)H and superoxide ion induced both frequency and amplitude fluctuations in JRA neutrophils. This is a novel finding that was observed in children with both active (n = 4) and inactive (n = 2) JRA. A subpopulation of polyarticular JRA neutrophils are in a chronic, activated state, a state that persists when the disease is well controlled pharmacologically. Furthermore, polyarticular JRA neutrophils exhibit an intrinsic defect in the regulation of metabolic oscillations and superoxide ion production. Our data are consistent with the hypothesis that neutrophils play an essential role in the pathogenesis of polyarticular JRA.

Purpose: To retrospectively evaluate the radiographic features of extraluminal leak after Roux-en-Y gastric bypass (RYGBP) surgery at upper gastrointestinal (GI) examinations in a large series of patients and to determine morbidity and mortality in those patients with leak., Materials and Methods: The investigational review board approved this HIPAA-compliant study, and the need for patient informed consent was waived. Radiologic database review revealed 1202 upper GI studies performed over a 4-year period in 906 patients after RYGBP. Extraluminal leak was identified in 50 patients. Two patients with leaks that occurred before the study period were excluded. Of the remaining 48 patients, 12 were men and 36 were women (mean age, 45 years; range, 26-64 years). Surgery had been laparoscopic in 23 patients and open in 25. Upper GI studies were analyzed by two radiologists in consensus for the origin, extent, and severity of leaks and associated findings. Chart review was performed to determine clinical course, treatment, and outcome., Results: Fifty extraluminal leaks were detected in 48 of 904 patients (5.3%) at upper GI examinations. All leaks were identified within 28 days, and, in 37 of 48 patients (77%), leakage was diagnosed within 1 week of surgery. The majority of leaks (n = 37) originated from the gastrojejunal anastomosis. Leaks also occurred at the distal portion of the esophagus (n = 5), the gastric pouch (n = 5), the oversewn jejunum (n = 2), and the distal anastomosis (n = 1). Leaks extended into the left upper quadrant in 30 patients. Obstruction or ileus was present in 35 of 48 patients (73%). Leak into the excluded stomach was observed in 15 of 48 patients. The occurrence of extraluminal leak prolonged hospital stays; organ failure occurred in 14 (29%) and death in three (6%) of the 48 patients., Conclusion: Extraluminal leak was identified on upper GI series in 48 of 904 patients (5.3%) after RYGBP for morbid obesity. Extraluminal leak most commonly arises from the gastrojejunal anastomosis and extends into the left upper quadrant. Extraluminal leak affects morbidity and mortality., (RSNA, 2006.)

Objective: The purpose of this study was to describe the abdominal imaging features associated with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, a complication of pregnancy., Conclusion: The abdominal imaging features of HELLP syndrome include intraparenchymal and perihepatic hematomas and hemoperitoneum as noted on sonography, CT, and angiography.

Minocycline is neuroprotective in animal models of a number of acute CNS injuries and neurodegenerative diseases. While anti-inflammatory and anti-apoptotic effects of minocycline have been characterized, the molecular basis for the neuroprotective effects of minocycline remains unclear. We report here that minocycline and a number of antioxidant compounds protect mixed neuronal cultures in an oxidative stress assay. To evaluate the role of minocycline's direct antioxidant properties in neuroprotection, we determined potencies for minocycline, other tetracycline antibiotics, and reference antioxidant compounds using a panel of in vitro radical scavenging assays. Data from in vitro rat brain homogenate lipid peroxidation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays show that minocycline, in contrast to tetracycline, is an effective antioxidant with radical scavenging potency similar to vitamin E. Our findings suggest that the direct antioxidant activity of minocycline may contribute to its neuroprotective effects in some cell-based assays and animal models of neuronal injury.

The generation of long-range three-dimensional nanoscopic patterns is a major goal in materials chemistry. Here we report a strategy for creating such systems using virus crystals as scaffolds which can be infiltrated with metal specifically palladium and platinum. The inorganic component effectively packs within the porous macromolecular crystal architecture, providing a route for patterning these materials on the nanometer length scale. To verify the quality of the metal infiltration, SEM-EDX was used to determine the homogeneous distribution of metal across the crystal, and TEM was used to confirm that the metal was confined within the porous structure of the crystal.

Objective: The purpose of our pictorial essay is to highlight the helical CT features of uncommon mimics of appendicitis and to provide clues to differentiate them from appendicitis., Conclusion: Uncommon mimics of appendicitis create a diagnostic challenge in patients with right lower quadrant pain. Recognition of the helical CT features of uncommon mimics of appendicitis is important in clinical management and avoiding unnecessary laparotomy.

Objective: The purpose of our pictorial essay is to present common mimics of appendicitis as noted on helical CT in patients with right lower quadrant pain and to highlight the features that provide clues to the diagnosis., Conclusion: Recognition of the findings of common diseases that simulate acute appendicitis on helical CT, along with features that help to differentiate these entities from appendicitis, is important in establishing a correct diagnosis and in guiding appropriate therapy.

Morbid obesity is an increasing health problem, and bariatric surgery is becoming a popular treatment option. Radiologists must be familiar with performing and interpreting studies in this patient population. The typical postoperative findings of the Roux-en-Y gastric bypass (RYGBP) procedure for morbid obesity on upper gastrointestinal (UGI) series are presented. An overview of the potential complications that may be diagnosed with contrast studies and computed tomography (CT) is provided in addition to a description of potential pitfalls in interpreting these studies.

A primary pathological feature of Alzheimer's disease is beta-amyloid (Abeta)-containing plaques in brain and cerebral vasculature. Reductions in the formation of Abeta peptides by gamma-secretase inhibitors may be a viable therapy for reducing Abeta in Alzheimer's disease. Here we report on the effects of two orally active gamma-secretase inhibitors. BMS-289948 (4-chloro-N-(2,5-difluorophenyl)-N-((1R)-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide hydrochloride) and BMS-299897 (4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid) markedly reduced both brain and plasma Abeta(1-40) in APP-YAC mice with ED(50) values of 86 and 22 mg/kg per os (po), respectively, for BMS-289948, and 30 and 16 mg/kg po, respectively, for BMS-299897. Both compounds also dose-dependently increased brain concentrations of APP carboxy-terminal fragments, consistent with inhibition of gamma-secretase. BMS-289948 and BMS-299897 (100 mg/kg po) reduced brain and plasma Abeta(1-40) rapidly (within 20min) and maximally within 3 h. BMS-299897 also dose-dependently reduced cortical, cerebrospinal fluid (CSF), and plasma Abeta in guinea pigs with ED(50) values of 30 mg/kg intraperitoneally, without affecting CSF levels of alpha-sAPP. The reductions in cortical Abeta correlated significantly with the reductions in both plasma (r(2) = 0.77) and CSF (r(2) = 0.61) Abeta. The decreases in Abeta were apparent at 3 and 6 h post-administration of BMS-299897, but not at 12h. These results demonstrate that BMS-289948 and BMS-299897 are orally bioavailable, functional gamma-secretase inhibitors with the ability to markedly reduce Abeta peptide concentrations in APP-YAC transgenic mice and in guinea pigs. These compounds may be useful pharmacologically for examining the effects of reductions in beta-amyloid peptides in both animal models and in Alzheimer's disease.

Purpose: To determine the usefulness and potential pitfalls of helical computed tomography (CT) for depiction of normal anatomy and diagnosis of complications after gastric bypass surgery., Materials and Methods: From March 1998 to July 2002, 100 abdominal and pelvic CT examinations were performed in 72 patients after gastric bypass surgery for treatment of morbid obesity. Two of four attending abdominal radiologists retrospectively assessed the CT images in consensus for normal postoperative gastrointestinal anatomy and complications such as leaks, staple line dehiscence, bowel obstruction, abscess, hepatic or splenic infarction, and hernia. CT findings were compared with clinical, surgical, and other imaging findings., Results: The gastric pouch, excluded stomach, proximal efferent loop, oversewn jejunal loop, and distal jejunojejunal anastomosis were identified in 96 (96%) of 100 studies and 69 (96%) of 72 patients, 100 (100%) of 100 studies and 72 (100%) of 72 patients, 99 (99%) of 100 studies and 71 (99%) of 72 patients, 88 (88%) of 100 studies and 61 (85%) of 72 patients, and 67 (67%) of 100 studies and 46 (64%) of 72 patients, respectively. The fundus of the excluded stomach was filled with a combination of air, fluid, and contrast material, which mimicked a loculated fluid collection in 15 (15%) of 100 studies and 13 (18%) of 72 patients. Sixty-two abnormalities, detected in 41 patients, included leak (n = 12), loculated fluid collection unrelated to leak (n = 9), markedly distended excluded stomach (n = 6), small-bowel obstruction (n = 6), gastric staple line dehiscence (n = 6), splenic infarction (n = 5), hematoma (n = 5), left hepatic lobe infarction (n = 3), and hernia related to gastric bypass (n = 10, including three internal hernias, three incisional hernias, and four nonincisional ventral hernias). Seventeen patients required a total of 21 CT-guided interventional procedures., Conclusion: Helical CT is useful for identifying normal postoperative anatomy and complications after gastric bypass surgery., (Copyright RSNA, 2004)

Context: Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers., Objective: To assess the accuracy of CTC in a large number of participants across multiple centers., Design, Setting, and Participants: A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results., Main Outcome Measures: The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience., Results: A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique., Conclusions: Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

S-Adenosylhomocysteine hydrolase (AdoHcy hydrolase) crystallizes from solutions containing the intermediate analogue neplanocin A with the analogue bound in its 3'-keto form at the active sites of all of its four subunits and the four tightly bound cofactors in their reduced (NADH) state. The enzyme is in the closed conformation, which corresponds to the structure in which the catalytic chemistry occurs. Examination of the structure in the light of available, very detailed kinetic studies [Porter, D. J., Boyd, F. L. (1991) J. Biol. Chem. 266, 21616-21625. Porter, D. J., Boyd, F. L. (1992) J. Biol. Chem. 267, 3205-3213. Porter, D. J. (1998) J. Biol. Chem. 268, 66-73] suggests elements of the catalytic strategy of AdoHcy hydrolase for acceleration of the reversible conversion of AdoHcy to adenosine (Ado) and homocysteine (Hcy). The enzyme, each subunit of which possesses a substrate-binding domain that in the absence of substrate is in rapid motion relative to the tetrameric core of the enzyme, first binds substrate and ceases motion. Probably concurrently with oxidation of the substrate to its 3'-keto form, the closed active site is "sealed off" from the environment, as indicated by a large (10(8)(-)(9)-fold) reduction in the rate of departure of ligands, a feature that prevents exposure of the labile 3'-keto intermediates to the aqueous environment. Elimination of the 5'-substituent (Hcy in the hydrolytic direction, water in the synthetic direction) generates the central intermediate 4',5'-didehydro-5'-deoxy-3'-ketoadenosine. Abortive 3'-reduction of the central intermediate is prevented by a temporary suspension of all or part of the redox catalytic power of the enzyme during the existence of the central intermediate. The abortive reduction is 10(4)-fold slower than the productive reductions at the ends of the catalytic cycle and has a rate constant similar to those of nonenzymic intramolecular model reactions. The mechanism for suspending the redox catalytic power appears to be a conformationally induced increase in the distance across which hydride transfer must occur between cofactor and substrate, the responsible conformational change again being that which "seals" the active site. The crystal structure reveals a well-defined chain of three water molecules leading from the active site to the subunit surface, which may serve as a relay for proton exchange between solvent and active site in the closed form of the enzyme, permitting maintenance of active-site functional groups in catalytically suitable protonation states.

The goal of the quality improvement project reported here was to increase the proportion of peritoneal dialysis (PD) patients receiving adequate dialysis as defined by the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) guidelines. Our approach was to increase the frequency with which we measured PD adequacy and changed prescriptions in response to low adequacy values. We developed 3 indicators, each one subdivided to reflect differences by type of PD and time on PD. Our improvement goal was to achieve the midpoint between baseline performance on those indicators and 100%, equating to a 50% reduction in failure rate (RFR). At baseline, the project included 122 facilities with 1,517 patients (data from October 1999 to March 2000). At re-measurement, we had 117 facilities with 1,372 patients (data from January 2001 to June 2001). In addition to obtaining facility-specific feedback reports, we conducted educational intervention workshops to which all PD providers were invited. After the workshops, "mandatory intervention" facilities submitted improvement plans that were reviewed by the PD Adequacy Work Group to determine if improvement actions were appropriately focused on identified root causes. Not all intervention facilities attended the workshops, and some facilities attended voluntarily. Overall, the Network 5 results showed a statistically significant improvement in measuring PD adequacy (84% baseline to 92% re-measurement), with a corresponding 51% RFR. Improvement in desired levels of adequacy was also statistically significant (55% baseline to 64% re-measurement), with a 21% RFR. Analysis by the intervention group showed that "mandatory intervention" facilities improved more than did "voluntary" facilities in measuring adequacy and in reaching desired levels, and that the differences were statistically significant. Quality improvement efforts that focused on improving the adequacy of PD in Network 5 were accomplished.

Two soil profiles were collected from undisturbed areas near the Nevada Test Site (NTS). The activity of 137Cs in the surface layer of the downwind Queen City Summit profile is three times higher than at the upwind site at Searchlight, NV (41.1+/-0.6 mBq/g vs. 13.0+/-0.4 mBq/g), and the 239,240Pu activity is 100 times greater (51+/-2 mBq/g vs. 0.52+/-0.03 mBq/g). An examination of the literature suggests that the 137Cs/239,240Pu and the 239,240Pu/238Pu activity ratios in soils and sediments from the northern hemisphere, due to fallout from atmospheric atomic weapons testing, have generalized values of 36+/-4 and 30+/-4, respectively (as of 1 July 1995). Deviations from these values may indicate possible contamination by sources other than fallout. Data from the surface soil of the downwind Queen City Summit profile yield a 137Cs/239,240Pu ratio of 0.81+/-0.02 and a 239,240Pu/238Pu ratio of 78+/-6. Clearly, an increase in 239,240Pu relative to 137Cs or 238Pu can account for these observations. There is compelling evidence that this "excess" 239,240Pu came from activities at the NTS during the aboveground testing of nuclear devices, more than likely from safety tests, some 40 years ago, and/or during the interim by the wind-driven resuspension of contaminated surface soil on the NTS and its transport off-site. Moreover, the two concentration profiles show that high percentages of both of these elements are retained for decades in the upper few centimeters of soil in Nevada's desert environment.

In summary, over the past decade, MRCP has evolved not only as a feasible means of noninvasively evaluating the pancreaticobiliary tract but also as a technique with documented clinical utility. With the evolution of MRCP, there has been, by necessity, an evolution of ERCP. In fact, at some institutions MRCP has replaced diagnostic ERCP such that ERCP is reserved primarily for therapeutic interventions. When MRCP is performed in conjunction with abdominal MR and MRA, a comprehensive examination results that permits evaluation of the solid organs and vessels of the abdomen as well as the ductal systems.

A study was made of 19 adults with situs anomalies (situs inversus [n = 10], situs ambiguous with polysplenia [n = 8], situs ambiguous with asplenia [n = 1]). No patient had congenital heart disease, bowel obstruction related to malrotation, or immune deficiency disorders. All 10 patients with situs inversus had mirror-image location of the abdominal organs relative to situs solitus; nine had dextrocardia, and one had levocardia. The eight adults with situs ambiguous with polysplenia demonstrated a spectrum of abnormalities. All had some degree of abdominal heterotaxy, including midline livers and gallbladders (n = 5), right-sided stomachs and spleens (n = 3), and rotational abnormalities of the small bowel and colon (n = 7). Other findings included multiple spleens (n = 7), interruption of the inferior vena cava (IVC) with azygous or hemiazygous continuation (n = 7), truncation of the pancreas (n = 6), and ipsilateral location of the aorta and IVC (n = 1). In the one patient with asplenia, a midline liver, right-sided stomach, bowel rotation abnormality, IVC interruption, and pancreatic truncation were noted. Recognition of the spectrum of situs anomalies is important because the altered anatomy associated with these anomalies may result in confusing imaging findings when seen in conjunction with acquired diseases., (Copyright RSNA, 2002)

Rho-kinase II (ROCK-II) is a serine/threonine kinase that is involved in regulation of smooth muscle contraction and has been shown to contribute to the early stages of axon formation in neurons and the regulation of the neuronal cytoskeleton. Much of what is known about Rho-kinase function comes from cell-biological studies, whereas a paucity of biochemical characterization exists for the enzyme. In an effort to characterize ROCK-II biochemically we have cloned a truncated form of human ROCK-II comprising amino acids 1-543 and overexpressed it in Sf-21 cells. Utilizing the Sf-21/baculovirus expression system we isolated milligram quantities of ROCK-II (1-543) and purified the enzyme to near homogeneity. Optimal expression conditions revealed that infection of Sf-21 cells at a multiplicity of infection of 10 for 72h yielded maximal protein expression. Expression of ROCK-II (1-543) as an N-terminal Flag fusion protein allowed a single-step purification yielding greater than 90% homogeneous protein as assessed by SDS-PAGE. Enzyme activity was linear over a range of enzyme concentrations and times. Capture of phosphorylated, biotinylated peptides on streptavidin membrane allowed assessment of peptide substrate preference and measurement of steady-state rate constants. The data indicated that an 11-mer peptide containing Ser235/Ser236 of the S6 ribosomal protein and a 12-mer peptide containing Thr508 of LIM kinase were preferred substrates for ROCK-II (1-543). Finally, staurosporine had an IC(50) value 215-fold more potent than that of the ROCK inhibitor Y-27632. Collectively these data lay the foundation for the beginning of a biochemical characterization for this enzyme and provide methodology for more detailed biochemical, biophysical, and kinetic analysis.

Rho-Kinase is a serine/threonine kinase that is involved in the regulation of smooth muscle contraction and cytoskeletal reorganization of nonmuscle cells. While the signal transduction pathway in which Rho-Kinase participates has been and continues to be extensively studied, the kinetic mechanism of Rho-Kinase-catalyzed phosphorylation has not been investigated. We report here elucidation of the kinetic mechanism for Rho-Kinase by using steady-state kinetic studies. These studies used the kinase domain of human Rho-Kinase II (ROCK-II 1-534) with S6 peptide (biotin-AKRRRLSSLRA-NH(2)) as the phosphorylatable substrate. Double-reciprocal plots for two-substrate kinetic data yielded intersecting line patterns with either ATP or S6 peptide as the varied substrate, indicating that Rho-Kinase utilized a ternary complex (sequential) kinetic mechanism. Dead-end inhibition studies were used to investigate the order of binding for ATP and the peptide substrate. The ATP-competitive inhibitors AMP-PCP and Y-27632 were noncompetitive inhibitors versus S6 peptide, and the S6 peptide analogue S6-AA (acetyl-AKRRRLAALRA-NH(2)) was a competitive inhibitor versus S6 peptide and a noncompetitive inhibitor versus ATP. These results indicated a random order of binding for ATP and S6 peptide.

Purpose: The purpose of this work was to present the imaging findings of late biliary complications in right lobe living donor liver transplantation recipients and to describe radiologic techniques used to treat these complications., Method: A retrospective review of medical records and imaging examinations was conducted in 5 of 48 right lobe living donor recipients with known biliary obstruction treated with percutaneous biliary drainage (PBD). Two abdominal radiologists reviewed in consensus the MR cholangiopancreatography (MRCP)/MR, ultrasound (US), CT, and PBD images., Results: Biliary-enteric anastomotic strictures were detected in all five recipients. In the four recipients who underwent the procedure, MRCP detected obstruction in each. CT detected obstruction in the fifth recipient. US failed to detect obstruction in one of two recipients. PBD catheters were placed without complication and relieved the obstruction in all five recipients. In addition, in three recipients, balloon dilatation of the stricture was performed and resulted in anastomotic patency., Conclusion: Biliary-enteric anastomotic strictures accounted for all late biliary complications and were detected correctly with MRCP and CT. The strictures were treated successfully with PBD in all instances and balloon dilatation when possible.

Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition. The authors measured the time course of the inhibition and recovery of acid secretion in healthy volunteers following intravenous administration of pantoprazole to determine the rate of proton pump activation under maximally stimulated conditions. Gastric acid production was measured in 27 Helicobacter pylori negative healthy volunteers (mean age = 31 +/- 7 years; 17 men, 10 women) who received single doses of intravenous pantoprazole (20, 40, 80, or 120 mg) in the presence of a continuous intravenous infusion of 1 ug/kg/h of pentagastrin. From the time profile of acid secretion, the authors described the rate of change of acid output using an irreversible pharmacodynamic response model represented by the equation dR/dt = -k x R x Cpanto + Ln2/PPR x (Ro-R) and correlated the parameter values with demographic factors and gastric acid measurements. Mean stimulated acid output secretion was 21.6 +/- 18.4 mEq/h (range: 1.6-90.5) prior to the administration of pantoprazole and remained steady for 25 hours after placebo administration. Intravenous pantoprazole inhibited acid output in a dose-response fashion, with maximal inhibition (99.9%) occurring after an 80 mg dose. Mean proton pump recovery time was 37.1 +/- 21.0 hours (range: 6.7-75), and recovery was independent of the dose of pantoprazole. There was no association noted between proton pump recovery time and gender, age, race, body weight, or pantoprazole dose. However, there was an inverse correlation between acid output during baseline stimulation and recovery of acid secretion. Mean proton pump recovery time in stimulated normal human volunteers was 37.1 +/- 21.0 hours, with a range of 6.7 to 75 hours. The authors hypothesize that there may be a normal homeostatic mechanism that maintains acid secretory capability within a normal range by altering the rate of proton pump activation dependent on the individual's parietal cell mass. Abnormalities of this process may be responsible for the development of acid peptic disease in susceptible individuals.