Impaired bolus clearance in asymptomatic older adults during high-resolution impedance manometry.

BACKGROUND: Dysphagia becomes more common in old age. We performed high-resolution impedance manometry (HRIM) in asymptomatic healthy adults (including an older cohort >80 years) to assess HRIM findings in relation to bolus clearance. METHODS: Esophageal HRIM was performed in a sitting posture in 45 healthy volunteers (n = 30 young control, mean age 37 ± 11 years and n = 15 older subjects aged 85 ± 4 years) using a 3.2-mm solid-state catheter (Solar GI system; MMS, Enschede, The Netherlands) with 25 pressure (1-cm spacing) and 12 impedance segments (2-cm intervals). Five swallows each of 5- and 10-mL liquid and viscous bolus were performed and analyzed using esophageal pressure topography metrics and Chicago classification criteria as well as pressure-flow parameters. Bolus transit was determined using standard impedance criteria. A p-value <0.05 was considered significant. KEY RESULTS: Impaired bolus clearance occurred more frequently in asymptomatic older subjects compared with young controls (YC) during liquid (40 vs 18%, χ2  = 4.935; p < 0.05) and viscous (60 vs 17%; χ2  = 39.08; p < 0.001) swallowing. Longer peristaltic breaks (p < 0.05) and more rapid peristalsis (L: p < 0.004, V: p = 0.003) occurred in the older cohort, with reduced impedance-based clearance for both bolus consistencies (L: p < 0.05, V: p < 0.001). Decreased peristaltic vigor (distal contractile integral <450 mmHg/s/cm) was associated with reduced liquid clearance in both age groups (p < 0.001) and of viscous swallows in the older group (p < 0.001). Impedance ratio, a marker of bolus retention, was increased in older subjects during liquid (p = 0.002) and viscous (p < 0.001) swallowing. CONCLUSIONS & INFERENCES: Impaired liquid and viscous bolus clearance, esophageal pressure topography, and pressure-flow changes were seen in asymptomatic older subjects.

Rising incidence of hepatitis B-related hepatocellular carcinoma in South Australia: 1996-2010.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is likely to be an important driver of increasing hepatocellular carcinoma (HCC) incidence in Australia. However, there is paucity of Australian data on HBV-related HCC incidence or outcomes. AIMS: To determine the incidence rates and survival trends of HBV-related HCC in South Australia (SA) over 15 years. METHODS: A population-based cohort study was performed in HBV patients notified to the SA Communicable Disease Control Branch between 1996 and 2010. The dataset was probabilistically linked with the SA Cancer Registry and death registry. Incidence rate trends and survival were determined for three 5-year time periods (1996-2000, 2001-2006 and 2006-2010). RESULTS: Forty-seven of 3881 notifications with HBV were linked to a HCC record (median (interquartile range) age at diagnosis: 58.9 (13.4) years, 83% males, 8.5% born in Australia, 62% diagnosed between 51-69 years). The overall crude HCC incidence was 111.3/100 000 person-years with an age-standardised HCC incidence of 189.1/100 000 person-years, the rate for men was higher than for women: 241.7 versus 88.6/100 000 person-years. The age-standardised HCC incidence increased over time with an annual percentage increase of 20.8% (95% CI: 10.06-32.54, P = 0.001). Median survival following HCC diagnosis was 12.5 months (95% CI: 3.6-21.4), with a trend towards longer survival during the 2006-2010 time period (21.8 months) compared to the previous two time periods (9.2 and 10.2 months, P = 0.056). CONCLUSION: Both crude and age-standardised incidences of HBV-related HCC increased between 1996 and 2010 in SA. There was a trend to longer survival in the latter time-period.

Maximum upper esophageal sphincter (UES) admittance: a non-specific marker of UES dysfunction.

BACKGROUND: Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. METHODS: Sixty-six healthy subjects (n = 50 controls 20-80 years; n = 16 elderly >80 years), 11 patients with CPB (51-83 years) and 16 with MND (58-91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. KEY RESULTS: In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. CONCLUSIONS & INFERENCES: The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction.

Swallowing dysfunction in healthy older people using pharyngeal pressure-flow analysis.

BACKGROUND: Age-related loss of swallowing efficiency may occur for multiple reasons. Objective assessment of individual dysfunctions is difficult and may not clearly differentiate these from normal. Pharyngeal pressure-flow analysis is a novel technique that allows quantification of swallow dysfunction predisposing to aspiration risk based on a swallow risk index (SRI). In this study, we examined the effect of ageing on swallow function. METHODS: Studies were performed in 68 healthy subjects aged 20-91 years (mean 59 years; 29 male), asymptomatic for oropharyngeal disease. Swallowing of liquid and viscous boluses was recorded with a pressure-impedance catheter. Indices of swallow function including the SRI, postswallow residues, upper esophageal sphincter opening and bolus transit time were derived using purpose designed software. KEY RESULTS: Swallow function worsened with increasing age with a significant decline after 80 years. Higher SRI correlated with increasing age (r = 0.257, p < 0.05 for liquids and r = 0.361, p < 0.005 viscous bolus). Subjects over 80 years were overrepresented amongst those with an SRI considered diagnostically relevant (SRI > 15). In addition, upper esophageal sphincter opening was reduced and postswallow residues increased in older subjects. CONCLUSIONS & INFERENCES: Pharyngeal pressure-flow analysis reveals multiple functional abnormalities in older individuals. The higher SRI levels seen in asymptomatic elders possibly reflect a loss of functional reserve with ageing. Automated impedance manometry analysis of swallow function may allow the risk of developing disordered swallowing to be quantified numerically.

Pharmacological interventions for geriatric cachexia: a narrative review of the literature.

OBJECTIVE: The objective of this review was to investigate the range of pharmacological interventions that have been studied for treatment of geriatric cachexia, and to evaluate their effect on selected clinical outcomes in this population. METHODS: Databases including Medline and Cochrane Central Register of Controlled Trials were searched up to March 2010 with search terms including "cache*", "intervention", "megestrol acetate" and "cytokine inhibitors". Studies investigating subjects with mean age <60y or disease-related cachexia were excluded. Outcomes assessed were weight or BMI, body composition, appetite and laboratory parameters indicative of cachexia. RESULTS: Fifteen publications met the selection criteria, reporting on ten studies. Seven studies investigated use of megestrol acetate (MA): two randomised controlled trials, one case control study, two pre-test/post-test studies and two retrospective chart reviews. Weight/BMI was common amongst outcomes and these studies showed an improvement in weight compared with baseline. MA studies which investigated body composition, appetite and/or laboratory parameters provided some evidence for improvement in these outcomes. Three randomised controlled trials investigated the use of other interventions: ghrelin, growth hormone and vitamin supplementations. All demonstrated a significant increase in lean body mass. The only other outcome of interest in these three trials was weight in one study with a significant increase demonstrated. CONCLUSION: Little investigation has been conducted in this population and the diagnosis of cachexia is problematic however these trials provide preliminary evidence for beneficial outcomes in older adults likely to have cachexia. Further high quality adequately powered prospective studies are necessary to provide effective treatment for geriatric cachexia.

Gastric emptying of a liquid nutrient meal in the critically ill: relationship between scintigraphic and carbon breath test measurement.

OBJECTIVE: It is assumed that delayed gastric emptying (GE) occurs frequently in critical illness; however, the prevalence of slow GE has not previously been assessed using scintigraphy. Furthermore, breath tests could potentially provide a convenient method of quantifying GE, but have not been validated in this setting. The aims of this study were to (i) determine the prevalence of delayed GE in unselected, critically ill patients and (ii) evaluate the relationships between GE as measured by scintigraphy and carbon breath test. DESIGN: Prospective observational study. SETTING: Mixed medical/surgical intensive care unit. PATIENTS: 25 unselected, mechanically ventilated patients (age 66 years (49-72); and 14 healthy subjects (age 62 years (19-84)). INTERVENTIONS: GE was measured using scintigraphy and (14)C-breath test. A test meal of 100 ml Ensure (standard liquid feed) labelled with (14)C octanoic acid and (99m)Technetium sulphur colloid was placed in the stomach via a nasogastric tube. MAIN OUTCOME MEASURES: Gastric 'meal' retention (scintigraphy) at 60, 120, 180 and 240 min, breath test t(50) (BTt(50)), and GE coefficient were determined. RESULTS: Of the 24 patients with scintigraphic data, GE was delayed at 120 min in 12 (50%). Breath tests correlated well with scintigraphy in both patients and healthy subjects (% retention at 120 min vs BTt(50); r(2)=0.57 healthy; r(2)=0.56 patients; p≤0.002 for both). CONCLUSIONS: GE of liquid nutrient is delayed in approximately 50% of critically ill patients. Breath tests correlate well with scintigraphy and are a valid method of GE measurement in this group.

Is esophageal dysphagia in the extreme elderly (>or=80 years) different to dysphagia younger adults? A clinical motility service audit.

Dysphagia in elderly patients has major effects on nutrition and quality of life. Although aging itself is associated with changes in esophageal motility, the impact of this on symptoms such as dysphagia is unclear. Data in the extreme elderly are also limited. Symptoms and manometric diagnoses from 23 consecutive older patients (older dysphagia [OD]) >or=80 reporting esophageal dysphagia (12 female, mean age 83 (range 80-93) were compared with those from 23 gender matched younger patients (young dysphagia [YD]) also with dysphagia (mean age 35, range [17-46]). More older patients reported dysphagia as their primary symptom (OD 22/23 vs YD 14/23, P = 0.005). Overall, dysphagia was most common for solids only (OD 16/23 vs YD 15/23) and rare for liquids only (OD 1/23 vs YD 3/23). Dysphagia for both liquids and solids was more frequent in older patients (OD 6/23 vs YD 1/23, P < 0.05). Fewer older patients reported heartburn (OD 3/23 vs YD 14/23, P = 0.001). Manometric diagnoses were generally similar between OD and YD patients with the most common diagnoses being 'nonspecific esophageal motility disorder' (nine each) and 'ineffective peristalsis' (OD = 6, YD = 7). There was a trend for diagnoses related to lower esophageal sphincter failure to be more frequent in younger subjects (OD 1 vs YD 7, P = 0.053). Despite differences in symptom patterns, broad manometric diagnoses in the extreme elderly with dysphagia are similar to younger dysphagia patients. Further studies are required to determine whether this relates to insensitivity in recording or reporting of esophageal manometry (or perceptual differences associated with aging).

Gastric emptying and the organization of antro-duodenal pressures in the critically ill.

The motor dysfunctions underlying delayed gastric emptying (GE) in critical illness are poorly defined. Our aim was to characterize the relationship between antro-duodenal (AD) motility and GE in critically ill patients. AD pressures were recorded in 15 mechanically ventilated patients and 10 healthy volunteers for 2 h (i) during fasting, (ii) following an intragastric nutrient bolus with concurrent assessment of GE using the (13)C-octanoate breath test and (iii) during duodenal nutrient infusion. Propagated waves were characterized by length and direction of migration. Critical illness was associated with: (i) slower GE (GEC: 3.47 +/- 0.1 vs 2.99 +/- 0.2; P = 0.046), (ii) fewer antegrade (duodenal: 44%vs 83%, AD: 16%vs 83%; P < 0.001) and more retrograde (duodenal: 46%vs 12%, AD: 38%vs 4%; P < 0.001) waves, (iii) shorter wave propagation (duodenal: 4.7 +/- 0.3 vs 6.0 +/- 0.4 cm; AD: 7.7 +/- 0.6 vs 10.9 +/- 0.9 cm; P = 0.004) and (iv) a close correlation between GE with the percentage of propagated phase 3 waves that were antegrade (r = 0.914, P = 0.03) and retrograde (r = -0.95, P = 0.014). In critical illness, the organization of AD pressure waves is abnormal and associated with slow GE.

Functional association between proximal and distal gastric motility during fasting and duodenal nutrient stimulation in humans.

A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.

Gastric feed intolerance is not increased in critically ill patients with type II diabetes mellitus.

OBJECTIVE: To examine the occurrence of feed intolerance in critically ill patients with previously diagnosed type II diabetes mellitus (DM) who received prolonged gastric feeding. DESIGN AND SETTING: Retrospective study in a level 3 mixed ICU. PATIENTS: All mechanically ventilated, enterally fed patients (n = 649), with (n = 118) and without type II DM (n = 531) admitted between January 2003 and July 2005. INTERVENTIONS: Patients with at least 72 h of gastric feeding were identified by review of case notes and ICU charts. The proportion that developed feed intolerance was determined. All patient received insulin therapy. RESULTS: The proportion of patients requiring gastric feeding for at least 72 h was similar between patients with and without DM (42%, 50/118, vs. 42%, 222/531). Data from patients with DM were also compared with a group of 50 patients matched for age, sex and APACHE II score, selected from the total non-diabetic group. The occurrence of feed intolerance (DM 52% vs. matched non-DM 50% vs. unselected non-diabetic 58%) and the time taken to develop feed intolerance (DM 62.6 +/- 43.8 h vs. matched non-DM 45.3 +/- 54.6 vs. unselected non-diabetic 50.6 +/- 59.5) were similar amongst the three groups. Feed intolerance was associated with a greater use of morphine/midazolam and vasopressor support, a lower feeding rate and a longer ICU length of stay. CONCLUSIONS: In critically ill patients who require prolonged enteral nutrition, a prior history of DM type II does not appear to be a further risk factor for feed intolerance.

Stimulation of small intestinal burst activity in the postprandial state differentially affects lipid and glucose absorption in healthy adult humans.

Small intestinal motor activity is important for the optimal digestion and absorption of nutrients. These motor responses to feeding are frequently abnormal during critical illness, with the persistence of migrating bursts of contractions during enteral feeding. Whether this disturbance influences nutrient absorption is not known. In this study, the effects of small intestinal burst activity on lipid and glucose absorption were evaluated in 10 healthy human adults (6 males, 4 females, 19-47 yr). Upper gastrointestinal manometry was recorded for 6 h during and shortly after a 20-min intravenous infusion of either erythromycin (1 mg/kg), to stimulate burst activity, or saline (0.9%) in a double-blind randomized fashion. Simultaneously with the start of the intravenous infusion, 60 ml liquid feed mixed with 200 microl 13C-triolein and 2 g 3-O-methylglucose (3-OMG) was infused intraduodenally for 30 min. Absorption of lipid and glucose was assessed using the [13C]triolein breath test and plasma concentrations of 3-OMG, respectively. Infusion of erythromycin was followed by a more rapid onset of burst activity following commencement of the duodenal infusion compared with saline (30 +/- 6.1 vs. 58 +/- 10.7 min; P < 0.05). Erythromycin was associated with a slower recovery of 13CO2 (P < 0.01). A positive correlation existed between the time to onset of burst activity and 13CO2 recovery (P < 0.001). Erythromycin had no effect on 3-OMG absorption. In conclusion, stimulation of small intestinal burst activity reduces the rate of lipid absorption but not glucose absorption in healthy human adults.

Effects of acute hyperglycaemia on anorectal motor and sensory function in diabetes mellitus.

AIMS: To determine the effects of acute hyperglycaemia on anorectal motor and sensory function in patients with diabetes mellitus. METHODS: In eight patients with Type 1, and 10 patients with Type 2 diabetes anorectal motility and sensation were evaluated on separate days while the blood glucose concentration was stabilized at either 5 mmol/l or 12 mmol/l using a glucose clamp technique. Eight healthy subjects were studied under euglycaemic conditions. Anorectal motor and sensory function was evaluated using a sleeve/sidehole catheter, incorporating a barostat bag. RESULTS: In diabetic subjects hyperglycaemia was associated with reductions in maximal (P<0.05) and plateau (P<0.05) anal squeeze pressures and the rectal pressure/volume relationship (compliance) during barostat distension (P<0.01). Hyperglycaemia had no effect on the perception of rectal distension. Apart from a reduction in rectal compliance (P<0.01) and a trend (P=0.06) for an increased number of spontaneous anal sphincter relaxations, there were no differences between the patients studied during euglycaemia when compared with healthy subjects. CONCLUSIONS: In patients with diabetes, acute hyperglycaemia inhibits external anal sphincter function and decreases rectal compliance, potentially increasing the risk of faecal incontinence.

Antropyloroduodenal, cholecystokinin and feeding responses to pulsatile and non-pulsatile intraduodenal lipid infusion.

The contribution of the pulsatile nature of gastric emptying to small intestinal feedback mechanisms modulating antropyloroduodenal motility and appetite is unknown. On separate days, eight healthy male volunteers (18-34 years) received randomized, single-blind, intraduodenal (ID) infusions of 10% Intralipid (2 kcal min(-1)), either continuously [CID], or in a pulsatile manner [PID] (5 s on/15 s off) and 0.9% saline (control) administered continuously, each at a rate of 1.8 mL min(-1) for 3 h. During each infusion, subjective ratings of appetite were assessed and antropyloroduodenal pressures recorded with a 16-lumen manometric assembly incorporating a pyloric sleeve sensor. Plasma cholecystokinin was measured from blood collected at regular intervals throughout the infusion. At the end of each infusion the manometric assembly was removed, subjects were offered a buffet meal and the energy and macronutrient content of the meal was measured. Both ID lipid infusions stimulated isolated pyloric pressure waves (IPPWs) (P < 0.001) and basal pyloric pressure (P < 0.01) and suppressed antral (P < 0.05) and duodenal (P < 0.05) pressure waves when compared to controls; there was no difference in the effects of CID and PID lipid on antropyloroduodenal pressures. Infusions of lipid significantly increased plasma CCK concentrations (P < 0.05) compared with saline, but concentrations were not different between the two modes of lipid delivery (P > 0.05, CID vs. PID). Both intraduodenal lipid infusions decreased hunger (P < 0.05), increased fullness (P < 0.05) and reduced energy intake (P < 0.05) when compared with controls; again there was no difference between CID and PID lipid. We conclude that at the infusion rate of similar 2 kcal min(-1), the acute effects of intraduodenal lipid on antropyloroduodenal pressures, plasma CCK concentration and appetite are not modified by a pulsatile mode of lipid delivery into the duodenum.

Effect of a lacto-ovo vegetarian diet on fasting small intestinal motility.

BACKGROUND: Changes in diet can alter gastric and small intestinal (SI) motility. The effects of a vegetarian diet on fasting SI motility are unknown. METHODS: Manometric studies were performed in 9 lacto-ovo vegetarians (7 women) and 9 omnivores (7 women) of similar age and body mass index. On each study day, manometry was used to assess SI motility for 5 h, or 3 complete cycles of the interdigestive motor complex (IDMC). Lacto-ovo vegetarians were studied once: omnivores were studied twice, on their usual diet, and after consuming a 14-day lacto-ovo vegetarian diet. Diet diaries were kept for 5 days prior to each manometric study. Data were analysed for dietary composition and for cycle length and duration of each phase (I, II and III) of the IDMC. RESULTS: Dietary intake did not differ between chronic vegetarians and chronic omnivores apart from a trend to higher fibre intake (29 +/- 3 versus 20 +/- 3 g/day; P = 0.058). Omnivores eating a vegetarian diet showed a trend to decreased alcohol consumption (P = 0.068), but did not increase their fibre intake (20 +/- 3 versus 21 +/- 3 g/day). Neither cycle length nor duration of each IDMC phase differed between chronic vegetarians and chronic omnivores. After 14 days of a vegetarian diet, omnivores had a reduction in cycle length (128 +/- 19 versus 86 +/- 12 min; P = 0.02), with a non-significant reduction of Phase II (99 +/- 20 versus 50 +/- 8 min: P = 0.066). CONCLUSIONS: A chronic vegetarian diet has no major effect on fasting SI motility; but acute dietary change may alter the cycle length and component phases of the IDMC.

Erythromycin improves gastric emptying in critically ill patients intolerant of nasogastric feeding.

OBJECTIVE: To evaluate the effect of intravenous erythromycin on gastric emptying and the success of enteral feeding in mechanically ventilated, critically ill patients with large volume gastric aspirates. DESIGN: Prospective, double-blind, randomized, and placebo-controlled trial. SETTING: General intensive care unit in a university hospital. PATIENTS: Twenty critically ill, mechanically ventilated patients intolerant of nasogastric feeding (indicated by a residual gastric volume of > or =250 mL during feed administration at > or =40 mL/hr). INTERVENTIONS: After a gastric aspirate of > or =250 mL, which was discarded, the enteral feeding was continued at the previous rate for 3 hrs. Intravenous erythromycin (200 mg) or placebo was then administered over 20 mins. The residual gastric contents were again aspirated and the volume was recorded 1 hr after the infusion began. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was calculated as volume of feed infused into the stomach over 4 hrs minus the residual volume aspirated. Mean gastric emptying was 139+/-37 (+/-SEM) mL after erythromycin and -2+/-46 mL after placebo (p = .027). Nasogastric feeding was successful in nine of ten patients treated with erythromycin and five of ten who received placebo 1 hr after infusion (chi-square p = .05). CONCLUSION: In critically ill patients who have large volumes of gastric aspirates indicating a failure to tolerate nasogastric feeding, a single small dose of intravenous erythromycin allows continuation of feed in the short term.

Validation of a novel luminal flow velocimeter with video fluoroscopy and manometry in the human esophagus.

There is currently no ideal method for concurrently assessing intraluminal pressures and flows in humans with high temporal resolution. We have developed and assessed the performance of a novel fiber-optic laser-Doppler velocimeter, mounted in a multichannel manometric assembly. Velocimeter recordings were compared with concurrent fluoroscopy and manometry following 50 barium swallows in healthy subjects. During these swallows, the velocimeter sensor was situated in either the proximal (24 swallows) or the distal (26 swallows) esophagus. It signaled intraluminal flow following 46 of 50 swallows. A greater mean number of deflections were recorded in the distal compared with the proximal esophagus (4. 3 vs. 2.4, P = 0.001). The maximal flow velocity recorded did not differ between the proximal and distal esophagus (76.7 vs. 73.8 mm/s). No velocimeter signals commenced after fluoroscopic lumen occlusion. The velocimeter signals were closely temporally related to fluoroscopic barium flow. Upward catheter movement on swallowing sometimes appeared to cause a velocimeter signal. Manometrically "normal" swallows were no different from "abnormal" swallows in the number and velocity of deflections recorded by the velocimeter. This novel instrument measures intraluminal flow velocity and pressures concurrently, thus enabling direct study of pressure-flow relationships. Flow patterns differed between the proximal and distal esophagus.

Hyperglycemia affects cardiovascular autonomic nerve function in normal subjects.

OBJECTIVE: To evaluate the effect of acute hyperglycemia on autonomic nerve function in normal subjects. RESEARCH DESIGN AND METHODS: Six healthy volunteers ages 19-32 years underwent paired studies during euglycemia (blood glucose 5.1 +/- 0.04 mmol/l) and hyperglycemia (blood glucose 15.7 +/- 0.48 mmol/l) induced by intravenous infusion of glucose and maintained for 150 min. The order of the two studies was randomized. In each experiment, supine heart rate, heart rate variation with respiration, ratio of the maximum to minimum R-R interval after standing ("30:15" ratio), systolic blood pressure response to standing, and diastolic blood pressure response to sustained handgrip were measured. Data were analyzed using repeated measures analysis of variance. RESULTS: The supine heart rate was greater (P = 0.04) and the "30:15" ratio less (P = 0.03) during hyperglycemia than during euglycemia. Hyperglycemia had no significant effect on any of the other cardiovascular reflex tests. CONCLUSIONS: These observations indicate that acute hyperglycemia affects autonomic nerve function in healthy humans.

Gastroparesis: diagnosis and management.

Gastroparesis occurs frequently and may be associated with gastrointestinal symptoms, impaired oral drug absorption and, in diabetic patients, poor blood glucose control. Although current knowledge of the mechanisms responsible for delayed gastric emptying is limited, it is clear that gastroparesis arises from a spectrum of motor dysfunctions. There is a poor correlation between symptoms and delay in gastric emptying, and objective measurement is therefore required for the diagnosis of gastroparesis. Scintigraphic measurement of gastric emptying is at present the only clinically applicable method, although other techniques, particularly radioisotopic breath tests and ultrasound, show considerable promise. Therapy with the prokinetic drugs, cisapride, domperidone, metoclopramide, and erythromycin, forms the mainstay of treatment. Although there have been few formal comparisons, cisapride is considered to be the drug of first choice. Current knowledge of the etiology, pathophysiology, investigation, and treatment of gastroparesis is discussed in this review.