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Biomedical subjects

M P Schwartz

Publications and source records attributed to M P Schwartz.

At least 19 recordsLinked to original sources

Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial.

BACKGROUND: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. DESIGN AND SETTING: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. PATIENTS AND INTERVENTIONS: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. OUTCOME MEASURES: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. RESULTS: At 3 months, the percentage of patients who had reduced drug use by > or =50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. CONCLUSIONS: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.

Antacids↗

Value of magnification endoscopy in current clinical practice.

Ongoing technological developments in endoscopy have led to an ever improving evaluation and management of digestive diseases. The recent development of a new range of high-power magnification, or zoom, endoscopes has boosted interest in this technique, which has become increasingly available to the modern gastroenterologist. Magnification is often used in conjunction with chromoendoscopy in order to improve the detection and diagnosis of neoplastic tissue. Currently, the main clinical indications are the diagnosis of Barrett oesophagus, the colonoscopic surveillance of colonic polyps and the assessment of disease severity or the presence of dysplasia in inflammatory bowel disease. In this article we present an overview of the clinical implementations of magnification endoscopy in current and future gastroenterological practice.

Barrett Esophagus↗

Small intestinal glucose absorption and duodenal motility in type 1 diabetes mellitus.

OBJECTIVE: Small intestinal glucose absorption is increased in animal models of diabetes mellitus, but little data are available in humans. Small intestinal motility is reported to be frequently abnormal in patients with diabetes and could potentially affect glucose absorption. Our aim was to evaluate small intestinal glucose absorption and duodenal motor responses to intraduodenal nutrients, in patients with type 1 diabetes and controls. METHODS: Eight type 1 patients (two with autonomic neuropathy) and nine controls were studied during euglycemia. A manometric catheter was positioned across the pylorus, and nutrient infused intraduodenally (90 kcal over 30 min), followed by a bolus of 3-O-methylglucose (3-OMG). Blood was sampled to measure glucose and 3-OMG concentrations. RESULTS: During nutrient infusion, the number of duodenal waves did not differ between patients and controls. After the infusion, patients with diabetes had more propagated duodenal wave sequences (p < 0.05). The area under the plasma 3-OMG curve did not differ between the groups but correlated with both the blood glucose concentration at the time of 3-OMG administration (r = 0.64, p < 0.005) and the number of duodenal waves (r = 0.52, p < 0.05) and antegrade propagated duodenal sequences (r = 0.51, p < 0.05) preceding the 3-OMG bolus. CONCLUSIONS: During euglycemia, duodenal motor responses to small intestinal nutrient are comparable in patients with relatively uncomplicated type 1 diabetes and healthy subjects, but duodenal motility after nutrient infusion is increased in patients. Small intestinal glucose absorption is similar in patients and controls, but may be dependent on the blood glucose concentration and duodenal motor activity.

3-O-Methylglucose↗

ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal.

Protein unfolding is a key step in several cellular processes, including protein translocation across some membranes and protein degradation by ATP-dependent proteases. ClpAP protease and the proteasome can actively unfold proteins in a process that hydrolyzes ATP. Here we show that these proteases seem to catalyze unfolding by processively unraveling their substrates from the attachment point of the degradation signal. As a consequence, the ability of a protein to be degraded depends on its structure as well as its stability. In multidomain proteins, independently stable domains are unfolded sequentially. We show that these results can explain the limited degradation by the proteasome that occurs in the processing of the precursor of the transcription factor NF-kappaB.

Adenosine Triphosphatases↗

Human duodenal motor activity in response to acid and different nutrients.

Duodenal motor activity in response to intraduodenal infusion of small volumes of acid and nutrients of different chemical composition was studied in 10 healthy humans, using a water-perfused catheter incorporating 20 antropyloroduodenal sideholes. Saline and dextrose did not affect motility. Acid very rapidly (in 39 +/- 11 sec) increased the number of pressure waves (P = 0.035) and antegradely propagated pressure waves (P = 0.02). After lipid infusion a considerable lag time (163 +/- 81 sec) was observed, followed by a prominent increase in duodenal pressure waves (P = 0.02) and antegradely propagated pressure waves (P = 0.002). Furthermore, lipid-induced propagated pressure waves traveled over significantly longer distances (4.5 to 6 cm) than those induced by acid infusion (3 cm). We conclude that the motor response to small amounts of intraduodenal nutrients and acid is dependent on the chemical composition of the stimulus. The findings suggest that chemoreceptors in the duodenal wall provide input to local or regional control mechanisms involved in the regulation of duodenal motility.

Acids↗

Effect of inhibition of gastric acid secretion on antropyloroduodenal motor activity and duodenal acid hypersensitivity in functional dyspepsia.

BACKGROUND: Heightened visceroperception and a decreased duodenal motor response to intraduodenal acid infusion have been reported in functional dyspepsia. AIM: To investigate the effect of treatment with a proton pump inhibitor on sensorimotor impairment in 19 patients with functional dyspepsia. METHODS: Patients were assigned double-blind to pantoprazole (n=10) or placebo (n=9) treatment for 2 weeks. Antropyloroduodenal manometry was performed before and after treatment, using a 21-channel catheter, and the responses to intraduodenal infusion of 5 mL of saline and acid were assessed. Nausea, fullness and epigastric pain were scored before and after each infusion. RESULTS: Acid induced a modest duodenal motor response and suppression of antral pressure waves, not altered by either treatment. However, acid evoked isolated pyloric pressure waves after pantoprazole treatment (P < 0.02), and not after placebo. Saline induced no motor response. Acid (not saline) induced nausea, both before and after treatment in both groups (all P < 0.05). Subgroup analysis of the seven acid-hypersensitive patients (37%) showed a tendency towards a decrease in nausea in all four pantoprazole-treated patients (P=0.07), in contrast to the three placebo-treated patients (P=1.0). CONCLUSIONS: In functional dyspepsia, pantoprazole influenced the acid-induced duodenogastric feedback mechanism, but not the impaired duodenal motor response. Duodenal acid hypersensitivity was decreased to some extent.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Manometric artefacts suggesting compression of the duodenum by the superior mesenteric artery in healthy humans.

Multi-channel manometry offers the opportunity to study intestinal motor activity with high spatiotemporal resolution. We report tonic and phasic intraluminal pressure changes in the mid-portion of the horizontal part of the duodenum. In 10 healthy volunteers, we recorded 2 h of interdigestive duodenal motility using a water-perfused catheter. The assembly incorporated 12 duodenal sideholes at 1.5-cm intervals (D1-D12). Measurement of the antral and duodenal transmucosal potential difference (TMPD) was used to maintain a correct position of the catheter. The incidence of pressure waves (PWs) increased gradually from proximal (D1) to distal (D12) (P < 0.0001), while the mean amplitude of PWs decreased (P < 0.0001). In eight of 10 subjects, the signals recorded from D9 showed tonic pressure elevations with superimposed phasic pressure changes at heart-rate frequency, comprising 13.8% of total recording time. In the other two subjects, this phenomenon occurred in D8 (9.9% of time). D10 showed a lower incidence of PWs compared with neighbouring sideholes (D6-D9/D11-D12) (P < 0.035), with normal amplitudes. Fluoroscopy was performed in three subjects and showed that D9 was located at the midline. In healthy subjects manometric signals recorded from the horizontal part of the duodenum showed localized artefacts, presumably caused by compression by the superior mesenteric artery. In addition, a 'silent' region was present just distal to this site, the origin of which is uncertain.

Adult↗

Chemospecific alterations in duodenal perception and motor response in functional dyspepsia.

OBJECTIVE: Abnormal gastroduodenal motility and visceral hypersensitivity to intraduodenal acid have recently been recognized as pathophysiological factors in functional dyspepsia. The aim of this study was to assess whether these abnormalities in functional dyspepsia depend on the chemical composition of the stimulus. METHODS: In 17 patients with functional dyspepsia and 10 healthy controls 20-channel antropyloroduodenal manometry was performed. During phase II of the migrating motor complex small volumes (5 ml) of saline, acid, lipids, and dextrose were administered intraduodenally. Motility parameters and sensation scores for nausea, fullness, and epigastric pain were compared before and after each infusion and among the two groups. RESULTS: Acid induced a duodenal motor response in both groups, but less pressure waves (p < 0.05) and antegrade propagated pressure waves (p < 0.05) were observed in patients than in controls. In both groups lipids induced a similar, prominent increase in duodenal pressure waves. Acid and lipids suppressed antral-propagated pressure waves in both groups. Dextrose induced a modest increase in duodenal-propagated pressure waves in patients (p < 0.05) but not in controls. Although all infusions induced a mild increase in nausea in patients, only acid induced a significant increase in nausea after 1 min (p < 0.01). None of the infusions affected the sensations of epigastric pain or fullness in patients, nor did any infusions induce sensations in controls. CONCLUSIONS: In functional dyspepsia alterations in sensor and motor responses to intraduodenal acid and nutrients are chemospecific, suggesting an abnormality at the level of visceral afferents or mucosal chemoreceptors in these patients.

Adult↗

Cycloaddition chemistry of organic molecules with semiconductor surfaces.

Recent investigations have shown that cycloaddition reactions, widely used in organic chemistry to form ring compounds, can also be applied to link organic molecules to the (001) surfaces of crystalline silicon, germanium, and diamond. While these surfaces are comprised of Si=Si, Ge=Ge, and C=C structural units that resemble the C=C bonds of organic alkenes, the rates and mechanisms of the surface reactions show some distinct differences from those of their organic counterparts This article reviews recent studies of [2 + 2], [4 + 2] Diels-Alder, and other cycloaddition reactions of organic molecules with semiconductor surfaces and summarizes the current understanding of the reaction pathways.

Alkenes↗

Which medicines do our patients want from us?

BACKGROUND: The prescribing of medication, whether for infections or injuries, has come under the scrutiny of health maintenance organizations (HMOs). Our goal was to examine patient beliefs about the usefulness of certain classes of medications. METHODS: We surveyed 244 consecutive adult patients who presented to an urban private family medicine practice in Georgia. RESULTS: Regardless of who paid for prescriptions (an HMO or the patient), most people in the survey would be satisfied with over-the-counter medications and reassurance (84% for upper-respiratory infection, 72% for muscle strain, 56% for diarrhea). Few differences were attributable to payment status (prepaid as opposed to fee-for-service). African Americans are less likely than whites to accept reassurance as an appropriate treatment. CONCLUSIONS: Patients may be more willing to accept reassurance and over-the-counter medications than is commonly believed by physicians.

Adult↗

The dimensions of the protein import channels in the outer and inner mitochondrial membranes.

Most mitochondrial proteins are imported into mitochondria through transmembrane channels composed largely, and perhaps exclusively, of proteins. We have determined the effective internal diameter of the protein import channel in the mitochondrial outer membrane to be between 20 A and 26 A during translocation. The diameter of the import channel in the inner membrane is smaller than the diameter of the outer membrane import channel. These results were obtained by measuring the effect of rigid steric bulk introduced into precursor proteins on import.

Biological Transport↗

The structure of precursor proteins during import into mitochondria.

Precursor proteins must be at least partially unfolded during import into mitochondria, but their actual conformation during translocation is not known. Are proteins fully unfolded and threaded through the import machinery amino acid by amino acid, or do they retain some partial structure? The folding pathway of most proteins in vitro contains a partially folded intermediate known as the molten globule state, and it has been suggested that proteins are in the molten globule state during translocation across membranes. Here we show that precursors are normally fully unfolded during import into mitochondria. However, precursors containing residual structure can be imported, if less efficiently.

Biological Transport↗

Mitochondria unfold precursor proteins by unraveling them from their N-termini.

Protein unfolding is a key step in the life cycle of many proteins, including certain proteins that are degraded by ATP-dependent proteases or translocated across membranes. The detailed mechanisms of these unfolding processes are not understood. Precursor proteins are unfolded and imported into mitochondria by a macromolecular machine that spans two membranes and contains at least nine different proteins. Here we examine import of a model precursor protein derived from the ribonuclease barnase and show that mitochondria unfold this protein by unraveling it from its N-terminus. Because barnase in free-solution unfolds by a different pathway, our results demonstrate that mitochondria catalyze unfolding in the way that enzymes catalyze reactions, namely by changing reaction pathways. The effectiveness of this mechanism depends on the structure of the N-terminal part of the precursor protein.

Animals↗

Office or emergency department: what's the difference?

Many studies have examined why patients with nonurgent conditions seek care in emergency rooms. These studies have evaluated financial concerns, demographic variables, and proximity of the emergency room. However, none of these studies have attempted to predict which patients with nonurgent conditions will seek care at the emergency room and which will postpone medical treatment until regular office appointments can be obtained. Demographic and psychological variables help predict which patient will go to the emergency room for treatment. Since the demographics cannot be changed, health professionals must focus on problem-solving skills to lessen the burden on our already overcrowded emergency rooms.

Adaptation, Psychological↗

Gastric metaplasia and Helicobacter pylori infection.

Duodenal and antral mucosal biopsy specimens were obtained from 139 patients with dyspeptic complaints to study the prevalence and extent of gastric metaplasia in the duodenal bulb in relation to Helicobacter pylori (H pylori) infection and duodenal ulcer disease. On logistic regression, the presence and extent of gastric metaplasia was not significantly associated with H pylori infection. The prevalence of gastric metaplasia, however, was found to be higher in patients with current or past evidence of duodenal ulcer disease in comparison with subjects with functional dyspepsia (p = 0.01). A follow up study on 22 patients before and at least one year after eradication of H pylori showed that the mean extent of gastric metaplasia did not change significantly after eradication and did not differ when compared with 21 patients with persisting infection. It is concluded that the unchanged gastric acid output after eradication of H pylori is a more important factor in the development of gastric metaplasia than the H pylori related inflammatory process.

Adult↗

Brand logo recognition by children aged 3 to 6 years. Mickey Mouse and Old Joe the Camel.

OBJECTIVE: Little is known about the influence of advertising on very young children. We, therefore, measured product logo recognition by subjects aged 3 to 6 years. DESIGN: Children were instructed to match logos with one of 12 products pictured on a game board. Twenty-two logos were tested, including those representing children's products, adult products, and those for two popular cigarette brands (Camel and Marlboro). SETTING: Preschools in Augusta and Atlanta, Ga. PARTICIPANTS: A convenience sample of 229 children attending preschool. RESULTS: The children demonstrated high rates of logo recognition. When analyzed by product category, the level of recognition of cigarette logos was intermediate between children's and adult products. The recognition rates of The Disney Channel logo and Old Joe (the cartoon character promoting Camel cigarettes) were highest in their respective product categories. Recognition rates increased with age. Approximately 30% of 3-year-old children correctly matched Old Joe with a picture of a cigarette compared with 91.3% of 6-year-old children. CONCLUSION: Very young children see, understand, and remember advertising. Given the serious health consequences of smoking, the exposure of children to environmental tobacco advertising may represent an important health risk and should be studied further.

Advertising↗