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Biomedical subjects

E Soffer

Publications and source records attributed to E Soffer.

16 recordsLinked to original sources

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions.

BACKGROUND: Zollinger-Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long-term maintenance. AIMS: The safety and efficacy data for short-term (6-month) treatment of Zollinger-Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years. METHODS: The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid-reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h. RESULTS: Twenty-four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90-100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported. CONCLUSIONS: Maintenance oral pantoprazole therapy up to 3 years at dosages of 40-120 mg b.d. was effective and well tolerated in patients with Zollinger-Ellison syndrome and other hypersecretory conditions.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of autologous platelet lysates on ceramic particle resorption and new bone formation in critical size defects: the role of anatomical sites.

This study investigated the effects of rabbit autologous platelet lysates (APL) on the performance of fillers consisting of calcium carbonate ceramic particles (CP) pertinent to new bone formation and repair. Critical-size defects in rabbit femurs and calvaria were filled with CP alone, CP plus APL, and CP plus APL with or without thrombin (THR). After 6 weeks, resorption of CP occurred under all conditions tested in the present study. Compared with respective CP alone controls, addition of APL resulted in significantly higher ceramic resorption, as evidenced by decreased ceramic particle diameter (p < 0.01) and number (p < 0.01) at both defect sites. The presence of THR prevented reduction of both CP diameter and number in the femoral defect sites. Addition of APL to the CP resulted in a significant (p < 0.03) decrease in new bone area at the calvarial sites, but not at the femoral sites; moreover, when THR was added to the CP plus APL fillers, bone formation in the femoral defects was significantly (p < 0.05) reduced. In addition to differences in the respective anatomical and cellular milieu, the biochemical events induced by mechanical loading at the femurs may explain the reduced ceramic particle resorption as well as the enhanced new bone formation when compared with the results obtained at the calvarial defect sites.

Animals↗

Gastric electrical stimulation at proximal stomach induces gastric relaxation in dogs.

Gastric electrical stimulation (GES) improves symptoms in patients with gastroparesis. However, the underlying mechanisms remain unclear. To determine if GES at proximal and distal stomach could affect the biomechanical properties of the stomach, thus contributing to the beneficial effect of GES. Four pairs of electrodes were implanted along the greater curvature of the stomach in seven dogs. Gastric tone and compliance was assessed with a barostat. Measurements were obtained randomly during control and proximal and distal stimulation (4 mA, 375 ms and 6/18 cpm). Data as mean or median (25-75th percentiles). Gastric compliance was not affected by proximal and distal GES. Gastric tone was significantly reduced during proximal GES: 82.0 (66.8, 89.1) mL vs control 49.7 (39.6,75.9) mL at 6 cpm (P = 0.016), and 90.6 (54.5, 117.9) mL vs control 62.8 (39.6, 75.9) mL at 18 cpm (P = 0.031). Tone was not affected by distal GES at 6 cpm: 95.8 (46.3, 106.7) mL vs control 75.2 (49.7, 86.1) mL (P = 0.47) and at 18 cpm: 80.4 (38.1, 170.3) mL vs control 62.8 (44.6, 156.3) mL (P = 0.44). Proximal GES induces gastric relaxation. This effect, if seen also in humans, may explain, in part, the symptomatic improvement associated with GES therapy in patients with gastroparesis.

Animals↗

Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation.

BACKGROUND: Interstitial cells of Cajal (ICC) are required for normal intestinal motility. ICC are found throughout the human colon and are decreased in the sigmoid colon of patients with slow transit constipation. AIMS: The aims of this study were to determine the normal distribution of ICC within the human colon and to determine if ICC are decreased throughout the colon in slow transit constipation. PATIENTS: The caecum, ascending, transverse, and sigmoid colons from six patients with slow transit constipation and colonic tissue from patients with resected colon cancer were used for this study. METHODS: ICC cells were identified with a polyclonal antibody to c-Kit, serial 0.5 microm sections were obtained by confocal microscopy, and three dimensional software was employed to reconstruct the entire thickness of the colonic muscularis propria and submucosa. RESULTS: ICC were located within both the longitudinal and circular muscle layers. Two networks of ICC were identified, one in the myenteric plexus region and another, less defined network, in the submucosal border. Caecum, ascending colon, transverse colon, and sigmoid colon displayed similar ICC volumes. ICC volume was significantly lower in the slow transit constipation patients across all colonic regions. CONCLUSIONS: The data suggest that ICC distribution is relatively uniform throughout the human colon and that decreased ICC volume is pan-colonic in idiopathic slow transit constipation.

Adolescent↗

The challenge of irritable bowel syndrome: creating an alliance between patient and physician.

The most important component of the treatment of irritable bowel syndrome (IBS) is to establish a therapeutic physician-patient relationship, coupled with patient education. We describe a stepwise approach to management, including judicious use of invasive tests, and setting realistic treatment goals that address the dominant symptoms, their severity, and psychosocial factors.

Abdominal Pain↗

Manometric tests of anorectal function in healthy adults.

OBJECTIVE: Although tests of anorectal function are useful in the assessment of defecation disorders, there is inadequate and inconsistent information regarding normative data. Also, there are discrepancies in manometric techniques and data interpretation. Our aim was to perform a comprehensive evaluation of anorectal function in healthy adults. METHODS: We used a 6-mm diameter probe containing six radially arrayed microtransducers, and a 4-cm-long latex balloon for performing anorectal manometry in 45 healthy subjects who were controlled for gender and age. Sequentially, subjects were asked to squeeze, bear down, or blow up a party balloon. Subsequently, rectal sensation, rectal compliance, and rectoanal reflexes were assessed simultaneously by performing intermittent phasic balloon distentions. Additionally, balloon defecation, pudendal nerve latency, and saline continence tests were performed. RESULTS: In men, the anal sphincter was longer (p < 0.05) and squeeze sphincter pressure and squeeze duration were higher (p < 0.01), but resting sphincter pressure was similar to that in women. When bearing down, although not significant, the defecation index was higher in men. Distinct thresholds for rectal sensation were identified but there was no gender difference. Likewise, rectal compliance and balloon expulsion time were similar. However, during saline infusion, the onset of first leak and total volume retained were higher (p < 0.001) and pudendal nerve latency was shorter (p < 0.05) in men. Overall, parity or age did not influence anorectal function. CONCLUSIONS: This study represents the most comprehensive age- and gender-controlled assessment of anorectal function using solid state technology. Gender influences some parameters of anorectal function. Our results could serve as a valuable resource of normative data.

Action Potentials↗

Measurement of gastrointestinal motility in the GI laboratory.

Current tests of gastric and small intestinal motor function provide relevant physiological information, but their clinical utility is controversial. This article reviews the current procedures, indications, significance, pitfalls, and guidelines for gastrointestinal motility measurements by scintigraphy, gastroduodenojejunal manometry, and surface electrogastrography in humans. Methods included review of literature and discussions in closed and open fora among investigators, including presentations for peer review at focused (Iowa City American Motility Society Symposium, December 1995) and national meetings (American Gastroenterological Association, May 1996, and American Motility Society, September 1996). The current tests are generally complementary; scintigraphy is typically the first test in the evaluation of gastric motor function and often confirms the clinical suspicion of dysmotility. Manometry identifies patterns suggestive of myopathy, neuropathy, or obstruction but may be most helpful when it shows entirely normal findings, because manometry helps in part to exclude dysmotility as a cause of symptoms. Electrogastrography may identify dysrhythmias or failure of signal power to increase postprandially; rhythm abnormalities may be independent of impaired emptying among dyspeptic patients. The best validated and clinically most significant results pertain to transit tests; manometry may contribute importantly to the diagnostic process; and the significance of electrogastrography remains to be fully elucidated.

Digestive System↗

Clinical value of duodenojejunal manometry. Its usefulness in diagnosis and management of patients with gastrointestinal symptoms.

The records of all patients who had duodenojejunal manometry (DJM) from 1989 to 1995 were retrospectively reviewed. We evaluated the main symptoms of the patients, the indication for the study, its result, and the impact on therapy and management. One hundred sixteen patients out of 154 were included in the study, of whom 96 were women and 20 were men, with a mean age of 41.2 years. Twenty-five had perfused tube studies, and 91 had prolonged ambulatory recordings. Forty-one patients were referred for evaluation of abdominal pain, 34 for chronic constipation, 24 for nausea and vomiting, 8 for pseudoobstruction, and the remaining 9 for other reasons. All patients had appropriate endoscopic, radiographic, or scintigraphic studies prior to manometry. Forty-seven (40.5%) had abnormal manometry: 20 of 41 (48.8%) for abdominal pain, 7 of 34 (20.6%) for chronic constipation, 10 of 24 (41.7%) for nausea and vomiting, 5 of 8 (62.5%) for pseudoobstruction, and 5 of 9 (55.6%) for the miscellaneous group. The various subgroups did not have specific patterns of motor abnormalities. In 22 patients (18.9%) manometry helped in the choice of therapy: in 15 patients by affecting surgical approach, particularly in the constipation group, and in 7 patients by affecting feeding options and prokinetic agents. Detection of motor abnormalities was helpful in patients with severe symptoms thought to have functional disease even when no specific therapy was rendered. Thus, DJM was abnormal in 2/5 patients referred for evaluation of suspected motility disorders. It directly affected therapy in approximately 1/5 patients, particularly in those with constipation. It is helpful in the management of patients even when specific therapy is not rendered, particularly in those with abdominal pain. The modest impact on specific therapy is related to limited availability of effective prokinetic drugs and the limited specificity and predictive value of tests results.

Adolescent↗

Effects of cisapride on salivary production in normal subjects.

Cisapride improves reflux esophagitis and enhances esophageal acid clearance. To test the effect of cisapride an salivary production, we enrolled 14 healthy volunteers in a double-blind, randomized, placebo-controlled study. Subjects received cisapride, 10mg per os four times a day, or placebo for three days. Saliva, collected during fasted and fed states, was analyzed for volume and buffer capacity. Buffer capacity was expressed as the volume of 0.01 N HCl needed to titrate 1 ml of saliva to pH 6.1. Both volume and buffer capacity significantly increased during the fed state as compared to the fasted on both cisapride and placebo. Cisapride significantly enhanced the postprandial salivary volume and buffer capacity compared to placebo: 29.6 +/- 11.3 ml vs 22.9 +/- 9.5 ml and 1.07 +/- 0.31 vs 0.89 +/- 0.28, respectively (P< 0.0001). Cisapride's enhancement of salivary flow rate and buffer capacity in the fed state may be another mechanism by which it exerts its beneficial effect in patients with reflux esophagitis.

Adult↗

Natural history of adult Hirschsprung's disease.

The natural history of adult Hirschsprung's disease was reviewed in 22 patients (four from our hospital and 18 from the literature). The diagnosis in nearly half the patients was made before age 30, and the oldest patients were 69 years of age. Male to female ratio was 4:1. Almost all patients had severe constipation since birth. Barium enema showed rectal narrowing in 77%, and colonic dilation in 100%. Anorectal manometry was performed in only four patients; three showed no relaxation with rectal distention. In all patients, rectal biopsy showed no ganglion cells. Appropriate operation for Hirschsprung's disease improved symptoms in over 80% of patients. Hirschsprung's disease should be considered in all adult patients who have had severe constipation since birth, especially if they are male.

Adult↗

Mechanism of polymeric prostaglandin PGBx for in vitro stabilization of rat liver mitochondrial oxidative phosphorylation.

The mechanism of the in vitro PGBx effect on mitochondria was studied by determining the specific requirements of the assay system composition. These studies showed that (a) rat liver mitochondria must first be exposed to hypotonic media containing PGBx under aerobic conditions, (b) oxygen, Pi, Mg++, phosphate acceptor (nucleotides), and some oxidizable substrates are essential components to yield optimal phosphorylation values. KCl and bovine serum albumin are non-essential components. With regard to nucleotide acceptor specificity, the AMP, ADP, and glucose-ADP-hexokinase systems were satisfactory. With regard to substrate specificity, only beta-hydroxybutyrate and externally reduced NAD+ were unsatisfactory. The requirement for oxygen was twofold: (a) as an absolute requirement for oxidative phosphorylation, and (b) as a requirement for the hypotonic degradation of mitochondria. These results suggest that PGBx reacts with mitochondria to "protect" against degradation during aerobic hypotonic exposure.

Anaerobiosis↗

Interaction of bovine serum albumin with PGBx (polymeric 15-keto-prostaglandin B1).

Bovine serum albumin (BSA) interacts with PGBx, a polymeric derivative of 15-keto-prostaglandin B1, to form a complex that does not exhibit the fluorescence of free BSA. The complex is soluble at pH 5.2 in contrast to free PGBx, which is insoluble. Molar ratio of the BSA-PGBx complex is 1:18. This complexing appears to suppress the ability shown by non-complexed PGBx to reactivate phosphorylation in degraded isolated rat liver mitochondria.

Animals↗

Hardware-software co-design of portable functional gastrointestinal stimulator system.

In the recent years, functional electrical stimulation has been applied to restore impaired motility in the gastrointestinal tract. Unlike other methods of electrical stimulation of the gut, microprocessor-controlled, sequential electrical stimulation has been shown to induce peristalsis and enhance emptying in acute canine gastric and colonic models. This study aims at completing the development of a portable microprocessor-based functional stimulator system consisting of a microelectronic stimulator, patient-specific computer-based real-time software and a programming interfacing device. The ultimate goals of the design are to ensure that (1) the portable stimulator can be efficiently utilized in chronic animal experiments; and (2) the device can be further miniaturized into an implantable version. The designed portable stimulator generates four channel sequential bipolar rectangular pulse trains with programmable parameters within the stimulation requirements obtained from a previously developed computer model. Real-time simulation of colonic peristalsis and a case-specific stimulation model were implemented using patient-specific computer-based software. A chronic canine case study confirmed the feasibility of this microprocessor-controlled stimulation method for future clinical applications in humans.

Algorithms↗