L. M. A. Akkermans

The symptom-association probability: An improved method for symptom analysis of 24-hour esophageal pH data

BACKGROUND/AIMS All methods currently used to quantify the temporal relationships between symptoms and episodes of gastroesophageal reflux, as assessed by 24-hour pH monitoring, have major shortcomings. The aim of this study was to develop and validate a simple, all-comprising statistical method to calculate the probability that gastroesophageal reflux episodes and symptoms are associated. METHODS The 24-hour pH signal was divided into consecutive 2-minute periods. These periods and the 2-minute periods preceding the onset of symptoms were evaluated for the occurrence of reflux. Fishers Exact Test was then applied to calculate the probability (P value) that reflux and symptom episodes were unrelated. Finally, the symptom-association probability (SAP) was calculated as (1.0 - P) x 100%. The SAP values found in 184 24-hour esophageal pH tests were compared with the symptom index and the symptom sensitivity index. RESULTS Discordance between the SAP and the symptom index was found in 21 patients (11%) and discordance between the SAP and the symptom-sensitivity index in 28 (15%). False-positive and false-negative symptom index values occurred preferentially in patients with small and large numbers of symptom episodes during the test, respectively (P < 0.05). CONCLUSIONS The SAP is a single, simple, quantitative measure of the strength of the association between symptoms and reflux episodes that is devoid of the disadvantages inherent to previously used methods.

Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

SummaryGastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p<0.001), the 50% gastric emptying time for the liquid meal (p<0.05) and oesophageal emptying (p<0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p>0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r=0.58, p<0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.

Mechanisms of gastroesophageal reflux in ambulant healthy human subjects

BACKGROUND/AIMS Investigation of the motor events underlying gastroesophageal reflux has largely been confined to resting, recumbent subjects. The motor events associated with reflux during physical activity remain unknown. The aim of this study was to investigate the patterns of lower esophageal sphincter (LES) function underlying reflux in healthy subjects and the effect of exercise and physical activity on reflux mechanisms. METHODS LES pressure was recorded with a perfused sleeve sensor in 10 healthy subjects; intraluminal transducers recorded pressure in the stomach, esophagus, and pharynx, and pH was recorded 5 cm above the LES. Signals were stored in a portable data-logger. Recordings were made for 24 hours, including moderate physical activity, periods of rest and sleep, standardized meals, and standardized exercise. RESULTS Most reflux episodes (81 of 123; 66%) occurred in the 3 hours after food intake; only 2 episodes occurred during exercise. LES pressure was < or = 3 cm H2O in 79% of reflux episodes. Transient LES relaxation was the mechanism of reflux in 82% of episodes, irrespective of activity or body position, whereas swallow-related LES relaxations accounted for 13% and persistently absent LES pressure accounted for 1%. Straining occurred in only 20% of episodes. CONCLUSIONS In ambulant healthy subjects, accurate continuous recording of LES function is possible, reflux usually occurs during transient LES relaxations, and straining is not a major factor in the induction of reflux.

Safety assessment of probiotics for human use

The safety of probiotics is tied to their intended use, which includes consideration of potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are alive when administered, and unlike other food or drug ingredients, possess the potential for infectivity or in situ toxin production. Since numerous types of microbes are used as probiotics, safety is also intricately tied to the nature of the specific microbe being used. The presence of transferable antibiotic resistance genes, which comprises a theoretical risk of transfer to a less innocuous member of the gut microbial community, must also be considered. Genetic stability of the probiotic over time, deleterious metabolic activities, and the potential for pathogenicity or toxicogenicity must be assessed depending on the characteristics of the genus and species of the microbe being used. Immunological effects must be considered, especially in certain vulnerable populations, including infants with undeveloped immune function. A few reports about negative probiotic effects have surfaced, the significance of which would be better understood with more complete understanding of the mechanisms of probiotic interaction with the host and colonizing microbes. Use of readily available and low cost genomic sequencing technologies to assure the absence of genes of concern is advisable for candidate probiotic strains. The field of probiotic safety is characterized by the scarcity of studies specifically designed to assess safety on the one hand contrasted with the long history of safe use of many of these microbes in foods on the other hand.

The role of interdigestive small bowel motility in the regulation of gut microflora, bacterial overgrowth, and bacterial translocation in rats.

OBJECTIVE To clarify the role of the migrating motor complex (MMC) in the regulation of small intestinal microflora and bacterial translocation. SUMMARY BACKGROUND DATA The intestinal microflora may serve as a source of infectious microorganisms. Failure of regulatory mechanisms of the intestinal flora could therefore play an important role in the pathogenesis of gut-derived infections. METHODS Rats were fitted with small intestinal myoelectrodes. MMCs were measured on a control day and 3 consecutive days during continuous administration of morphine or placebo. Mesenteric lymph nodes, liver, spleen, peripheral blood, duodenum, and ileum samples were cultured quantitatively. RESULTS The mean MMC cycle length in placebo-treated animals was 15.1+/-0.5 minutes. MMCs were completely disrupted after morphine treatment. Total bacterial growth in the duodenum was 7.27+/-0.34 10log colony-forming units (CFU)/g with placebo and 8.28+/-0.27 CFU/g with morphine. In placebo-treated animals, the mean MMC cycle length the day before culturing correlated with total bacterial growth in the duodenum. Translocation incidences to the mesenteric lymph nodes, liver, spleen, and blood were 0/8, 1/8, 0/8, and 0/8 with placebo and 7/8, 6/8, 5/8, and 0/8 with morphine. The overall translocation incidence was 1/8 in placebo-treated animals and 8/8 in morphine-treated animals. CONCLUSIONS The MMC is an important mechanism controlling bacterial growth in the upper small bowel. Its disruption with morphine promotes duodenal bacterial overgrowth and bacterial translocation.

Responses to gastric distension in functional dyspepsia

Background—Studies have shown that an altered visceral perception threshold plays a role in the pathogenesis of upper gastrointestinal tract symptoms in dyspeptic patients. However, it is not clear whether the compliance and adaptive relaxation of the proximal stomach contribute to the symptoms. Aims—To investigate whether abnormal relaxation or adaptation of the proximal stomach during the interdigestive state and the postprandial phase could explain the symptoms of functional dyspepsia. Subjects—Twelve volunteers and 12 patients with dysmotility-like functional dyspepsia were included in the study. Methods—An electronic barostat was used to investigate adaptation to distension of the proximal stomach and accommodation in response to a liquid meal. Dyspeptic symptoms during distension and accommodation were assessed. Results—When the subjects were in the fasting state, the pressure-volume curve showed slightly higher compliance in the dyspeptic patients (p<0.05). Patients not only had a higher score for nausea, bloating, and pain but also the increase in nausea and pain scores with intragastric pressure was higher than in volunteers (p<0.05). The increase in intragastric bag volume in response to a meal was significantly lower in patients (p<0.05). Both bloating and pain significantly increased in the patients (p<0.05), but not in the healthy volunteers. Conclusions—Patients with functional dyspepsia show slightly higher compliance to mechanical distension. Their visceral perception of mechanical stress is enhanced. In contrast with the balloon distension, relaxation after a meal was less. Therefore the postprandial symptoms cannot be explained fully by greater global tension in the stomach wall, as assessed by the barostat technique. Visceral hypersensitivity plays a major role in the pathogenesis of the symptoms.

Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract

This review describes the current state of knowledge on the hazards of exercise and the potential benefits of physical activity on the gastrointestinal tract. In particular, acute strenuous exercise may provoke gastrointestinal symptoms such as heartburn or diarrhoea. A substantial part (20–50%) of endurance athletes are hampered by these symptoms which may deter them from participation in training and competitive events. Nevertheless, these acute symptoms are transient and do not hamper the athletes health in the long term. The only exception is repeated gastrointestinal bleeding during training and competition, which in the long term may occasionally lead to iron deficiency and anaemia. In contrast, repetitive exercise periods at a relatively low intensity may have protective effects on the gastrointestinal tract. There is strong evidence that physical activity reduces the risk of colon cancer by up to 50%. Less convincing evidence exists for cholelithiasis and constipation. Physical activity may reduce the risk of diverticulosis, gastrointestinal haemorrhage, and inflammatory bowel disease although this cannot be substantiated firmly. Up to now, underlying mechanisms are poorly understood although decreased gastrointestinal blood flow, neuro-immuno-endocrine alterations, increased gastrointestinal motility, and mechanical bouncing during exercise are postulated. Future research on exercise associated digestive processes should give more insight into the relationship between physical activity and the function of the gastrointestinal tract.

Long-term Study of Large Ceramic Implants (Porous Hydroxyapatite) in Dog Femora

Blocks of porous ceramic hydroxyapatite (dimensions, 2.5 X 1.25 X 0.5 cm; sintering temperature, 1300 degrees; macroporosity, 56%; average pore size 0.18 mm2) were implanted into surgically created defects in dog femora. The implants were retrieved up to 3.5 years after implantation. The implants were 3.5 years after implantation. The implants were firmly attached to the bone. Histologic evaluation suggests that optimal contact between bone and implant should be provided to accelerate bone ingrowth. Bone growth in the pores reached a maximum level after 35 weeks, at which time about one-third of the pore space was filled with bone. When measuring the relative surface areas of bone and ceramic on histologic slides, no change in ceramic mass could be detected, indicating that hydroxyapatite ceramics are not affected by biodegradation processes. The implants effectively provided a scaffold for bone growth bridging a larger bone defect.

Symptom perception in gastroesophageal reflux disease is dependent on spatiotemporal reflux characteristics

BACKGROUND/AIMS The mechanisms responsible for the development of symptoms in gastroesophageal reflux disease (GERD) are poorly understood. The aims of this study were to identify differences in spatiotemporal reflux characteristics (proximal extent and duration of reflux episodes, ascending velocity of the refluxate) between symptomatic and asymptomatic reflux episodes and to assess the influence of different pH sensor positions on the yield of symptom analysis. METHODS Esophageal pH was measured for 24 hours at 3, 6, 9, 12, and 15 cm above the lower esophageal sphincter (LES) in 18 symptomatic patients with GERD, and spatiotemporal reflux characteristics were assessed for symptomatic and asymptomatic reflux episodes. Additionally, the symptom-association probability (SAP) was calculated for each esophageal level. RESULTS The median episode duration (at 3 cm above the LES) was longer and the proximal extent was higher in symptomatic than in asymptomatic reflux episodes (P = 0.006 and P = 0.01). The ascending velocity of the refluxate was not significantly different. The SAP decreased significantly (P < 0.05) from distal to proximal, but no significant differences were found between distal and proximal esophageal levels for the proportion of patients with positive (> 95%) SAP values. CONCLUSIONS The perception of reflux symptoms depends on the duration of acid-exposure episodes and on the proximal extent of the refluxate. Small changes in pH-sensor position do not significantly influence the yield of symptom analysis.

Hyperglycemia induces abnormalities of gastric myoelectrical activity in patients with type I diabetes mellitus.

BACKGROUND/AIMS Blood glucose concentration has been shown to be an important factor in gastric motility. However, the effect of hyperglycemia on gastric myoelectrical activity has not yet been studied in patients with diabetes. METHODS Surface electrogastrography was performed in eight patients with type I diabetes mellitus under normoglycemic and hyperglycemic conditions (glucose clamp technique) and in eight normoglycemic control subjects. RESULTS In the early postprandial state, the frequency of the normal pacemaker rhythm tended to be higher during hyperglycemia than during normoglycemia (3.10 +/- 0.27 vs. 2.92 +/- 0.19 cycle/min; P = 0.061). The frequency decrease that occurs immediately after a meal was found less frequently during hyperglycemia (in 25% vs. 75% of the patients; P = 0.046). Higher harmonics of the 3-cycle/min component, indicating an electrogastrographic waveform change, were found less often during hyperglycemia (in 13% vs. 63% of the patients; P = 0.039). Dysrhythmias (in particular, tachygastrias) were more prevalent during hyperglycemia (40.6% vs. 6.5% of the time; P = 0.028). No differences were found between normoglycemic patients and control subjects. CONCLUSIONS This study has shown that hyperglycemia is an important factor in the generation of gastric myoelectrical disturbances and tachygastrias in particular.