Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease.

BACKGROUND: Body composition is poorly studied in inflammatory bowel disease (IBD). Sarcopenia describes a loss of muscle mass and strength. AIM: To assess the prevalence of low lean mass (LM), sarcopenia and associated morbidity in an adult IBD cohort. METHODS: Cross-sectional data were gathered on pre-menopausal 18- to 50-year-old patients with IBD. Whole-body dual-energy X-ray absorptiometry, anthropometric assessment and grip strength were performed. Low LM was defined as ≥1 s.d. below the population mean for appendicular skeletal muscle index [ASMI (kg)/height (m)²], and sarcopenia as both ASMI and grip strength ≥1 s.d. below population mean. Multivariate regression analyses were performed. RESULTS: Of 137 participants (median age 31 years, BMI 24.8 kg/m(2) ), 56% were male and 69% had Crohn's disease (CD). Low LM and sarcopenia were observed in 21% and 12% of patients, respectively, and osteopenia/osteoporosis in 38% of patients (mean lumbar spine t-score -0.3 ± s.d. 1.1). Grip strength predicted low LM and sarcopenia better than did body mass index (BMI) (OR 4.8 vs. OR 0.7 for low-LM, P < 0.05 both). Normal BMI was falsely reassuring in 72% and 76% of patients with low ASMI and sarcopenia, respectively. Low LM and sarcopenia (OR = 3.6, P = 0.03; OR = 6.3, P = 0.02; respectively), but not BMI nor fat mass, predicted osteopenia/osteoporosis. CONCLUSIONS: Low lean mass and sarcopenia are common in patients with IBD, and important to recognise as they predict osteopenia/osteoporosis. Grip strength testing should be incorporated into routine clinical practice to detect low lean mass deficits, which may go unrecognised using BMI alone.

Systematic review: body composition in adults with inflammatory bowel disease.

BACKGROUND: There is a paucity of data on body composition in patients with inflammatory bowel disease (IBD). Alterations of fat and muscle may affect bone health, muscle performance, quality of life (QoL) and overall morbidity. AIMS: To systematically review the literature on body composition in adults with IBD, and to discuss potential contributory factors and associations. METHODS: A systematic search was performed in July 2012 of OVID SP MEDLINE, OVID EMBASE and National Library of Medicine's PubMed Central Medline (Limitations: English, humans, from 1992). A total of 19 articles comparing body composition in patients with IBD with healthy age- and sex-matched control populations were included in the primary analysis. RESULTS: A total of 631 patients with Crohn's disease (CD) and 295 with ulcerative colitis (UC), mean age 37.1 (s.d. ± 9.2) years; 485 (52%) female, were reported upon. Data were heterogeneous and methodology varied. Compared with controls, a statistically significant reduction in body mass index (BMI) was reported in 37% of CD and 20% of UC patients; reduced fat-free mass in 28% CD and 13% UC patients, and reduced fat mass in 31% CD and 13% UC patients. There was no consistent association between body composition and disease activity, duration, extent or therapies. BMI did not accurately predict body composition. CONCLUSIONS: Current data, although heterogeneous, suggest that many patients with IBD are affected by aberrations in fat and lean mass, which may not be detected during routine clinical assessment. The prevalence and impact of altered body composition amongst this population warrant further investigation.

Host immune response determines visceral hyperalgesia in a rat model of post-inflammatory irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is associated with visceral hyperalgesia and frequently occurs after a transient gastrointestinal infection. Only a proportion of patients with acute gastroenteritis develop post-infectious IBS suggesting differences in host response to inflammatory stimuli. We aimed to investigate this concept by characterizing visceral sensitivity in two rat strains, following a chemically induced colitis. METHODS: Colorectal instillation of trinitrobenzenesulfonic acid (TNBS) in aqueous ethanol was used to induce a transient colitis in Lewis and F344 rats. The colitis was characterized semiquantitatively by histology, as well as by quantitative methods using (99m)Tc-leukocytes (radioactive organ assay) and plasma IL-2 and IL-6 levels. Visceromotor response to colorectal distensions was assessed after 2 h and, 5, 14, and 28 days. RESULTS: The colitis peaked on day 5 and dissipated to no visible mucosal damage on day 14. Cytokines were significantly increased in TNBS-treated rats at 2 h and on day 5. On day 14 cytokines were still significantly enhanced in Lewis but not Fisher rats. Both strains had a highly inflamed to non-inflamed tissue ratio at 3 h after TNBS instillation with increased uptake in Lewis compared to F344 rats. No (99m)Tc-tin-colloid-leukocytes were detected in colon samples on day 28. Visceromotor response was significantly elevated in both strains during the acute colitis (day 5), whereas only Lewis rats developed a post-inflammatory (day 28) visceral hyperalgesia. CONCLUSION: Genetically determined host factors account for prolonged immune activation in response to a standardized inflammatory stimulus and are linked to susceptibility for a post-inflammatory visceral hyperalgesia.

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.

Colonic transit studies with 99mTc-rhenium sulfide colloid in live rats. A preliminary study.

Abnormal colonic motility is associated with clinical relevant conditions such as irritable bowel syndrome or constipation. Accurate assessment of colonic transit in an animal model would be useful in studying these conditions and screen potential drug candidates. The aim of this study was to assess if scintigraphic analyses could reliably evaluate total and segmental colonic transit as a measure of colonic motility of a non-absorbable radiotracer in rats. Normal Lewis rats (250-300 g) were given oral technetium-99m-rhenium sulfide colloid (15-20 MBq; 0.5 mL; n=4) followed by a rinse with water for injection (1.0 mL). Rats were fed and hydrated ad libitum. After 30 min, each rat was contained inside an 'imaging' tube then placed on a g-camera collimator. Whole body 5 min static images were acquired every 30 min up to 9 h, and then finally at 25 hours. Region of interest analyses were applied to the caecum/proximal colon, sigmoidal loop and distal colon/rectum. The tracer entered into the colon at approximately 4 hours, and the rats remained static to permit 'live' imaging. At 4 hours the % whole body activity was: 51% caecum/proximal colon, 39% sigmoidal loop, 6% distal colon/rectum; at 8 hours, 30% caecum/proximal colon, 13% sigmoidal loop, 7% distal colon/rectum. In the whole colon there was < or =1% of total activity present at 25 hours, and the half clearance time was determined as 4.0 hours. These results suggest this is a reliable technique of measuring regional colonic transit as a measure of colonic motility in normal rats. This methodology might be well suited to screen potential motility effects of drug candidates.

Effects of protein on glycemic and incretin responses and gastric emptying after oral glucose in healthy subjects.

BACKGROUND: Dietary interventions represent a promising therapeutic strategy to optimize postprandial glycemia. The addition of protein to oral glucose has been reported to improve the glycemic profile. OBJECTIVE: The aim of the current study was to evaluate the mechanisms by which protein supplementation lowers the blood glucose response to oral glucose. DESIGN: Nine healthy men were studied on 3 d each in a random order. Subjects consumed 300-mL drinks containing either 50 g glucose (Glucose), 30 g gelatin (Protein), or 50 g glucose with 30 g gelatin (Glucose + Protein) in water labeled with 150 mg [(13)C]acetate. Blood and breath samples were subsequently collected for 3 h to measure blood glucose and plasma insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations and gastric half-emptying time, which was calculated from (13)CO(2) excretion. RESULTS: The blood glucose response was less after Glucose + Protein than after Glucose (P < 0.005); GIP was lower (P < 0.005), and there were no significant differences in plasma insulin or GLP-1. Protein alone stimulated insulin, GLP-1, and GIP (P < 0.05 for each) without elevating blood glucose. The gastric half-emptying time was greater after Glucose + Protein than after Glucose (P < 0.05) and tended to be greater for Glucose than for Protein (P = 0.06). CONCLUSIONS: In healthy humans, the addition of protein to oral glucose lowers postprandial blood glucose concentrations acutely, predominantly by slowing gastric emptying, although protein also stimulates incretin hormones and non-glucose-dependent insulin release.

Anorectal dysfunction increases with time following radiation therapy for carcinoma of the prostate.

OBJECTIVES: To characterize the prevalence and pathophysiology of anorectal dysfunction up to 2 yr following radiation therapy (RT) for localized carcinoma of the prostate. METHODS: Thirty-eight patients, median age 68 (range 60-82) yr with localized prostate carcinoma randomly assigned to one of two radiation dose schedules, underwent evaluation of the following variables of anorectal function before RT, as well as 4-6 wk and 1 and 2 yr after its completion: (1) symptoms, (2) anorectal motility, (3) anorectal sensory function, and (4) anal sphincteric morphology. RESULTS: There was a persistent increase in anorectal symptoms after RT. At 2 yr, bowel frequency, urgency, and fecal incontinence were increased in 50%, 47%, and 26% of patients, respectively. After RT, there were progressive reductions of (1) basal anal pressures, (2) anal pressures in response to squeeze and increased intra-abdominal pressure, (3) rectal compliance, and (4) rectal volumes associated with sensory perception and the desire to defecate. The thickness of the external anal sphincter increased with time after RT. No difference was observed between the patients in the two radiation dose schedules. CONCLUSIONS: Anorectal dysfunction following RT for prostate carcinoma is an underestimated cause of morbidity, which progresses with time. The prevalence and pathophysiology of anorectal dysfunction is similar after treatment with two commonly used radiation dose schedules.

99mTc-alafosfalin: an antibiotic peptide infection imaging agent.

The radiolabeled antibiotic peptide (99m)Tc-alafosfalin was assessed as an infection imaging agent in a rat model by comparison with (99m)Tc-DTPA and (99m)Tc-leukocytes. (99m)Tc-alafosfalin was prepared via an instant cold kit and (99m)Tc-leukocytes were prepared using (99m)Tc-stannous fluoride colloid in an ex vivo labeling procedure of whole blood. In separate experiments, the three radiotracers were administered to rats infected with staphylococcus aureus. Quantitative biodistribution studies were performed as well as scintigraphic images and histopathology. (99m)Tc-alafosfalin is a stable product, obtained in high radiochemical purity (>95%). This agent was mainly renally excreted, with low liver, spleen and bone uptake, and resulted in a mean ratio of infected/non-infected thighs of 4.3/1.0 at 4 hr post radiotracer injection. (99m)Tc-DTPA gave a corresponding ratio of 1.9/1.0 and (99m)Tc-leukocytes gave 20.0/1.0 at the same time point. An in vitro assay found the level of (99m)Tc-alafosfalin binding to staphylococcus aureas higher than (99m)Tc-DTPA (10% versus 1% respectively). (99m)Tc-alafosfalin accumulates at sites of infection in a rat model better than the perfusion molecule (99m)Tc-DTPA, yet less than (99m)Tc-leukocytes. The distribution characteristics of this (99m)Tc-antibiotic peptide would be an advantage in imaging abdominal and soft tissue infection.

Liquid gastric emptying in the pig: effect of concentration of inhaled isoflurane.

UNLABELLED: An animal model of gastric emptying may have use in the study of gastric physiology and pharmacoscintigraphy. The pig has anatomy and physiology similar to that of humans. Our aim was to develop a model of gastric emptying in the pig. It was not possible to perform this study in conscious pigs; therefore, an anesthetic model was developed. METHODS: Fifteen studies were performed on 4 pigs (age, 2-6 mo; weight, 20-100 kg). After acclimatization and training, pigs were fasted overnight before the study. Pigs were anesthetized using inhaled isoflurane without the use of injected premedication agents. An orogastric tube was inserted for the administration of a liquid meal, which consisted of (99m)Tc-diethylenetriaminepentaacetic acid either in water (nonnutrient) or with dextrose (nutrient meal). The pig was laterally positioned to enable right lateral dynamic acquisition to be performed. Anesthesia was maintained at 2% +/- 0.5% isoflurane in 4 studies and 0.8% +/- 0.5% in 11 studies (4 nutrient, 7 nonnutrient). RESULTS: With 2% +/- 0.5% isoflurane, there was delayed gastric emptying with a mean 50% emptying time (+/-SEM) of 141 +/- 14 min. With 0.8% +/- 0.5% isoflurane, the liquid meal emptied in an exponential manner similar to that of humans, with mean 50% emptying times (+/-SEM) of 30 +/- 7 min (nutrient) and 31 +/- 4 min (nonnutrient). CONCLUSION: The results indicate that high-dose anesthesia inhibits gastric emptying, but with low-dose anesthesia a useful pig model of liquid gastric emptying can be developed.

Comparison of 99mTc-alafosfalin and 67Ga-citrate in a mouse model of bacterial infection.

BACKGROUND: The antibiotic-peptide (99m)Tc-alafosfalin was assessed as an infection imaging agent in Staphylococcus aureas infected mice by comparison with (99m)Ga-citrate, and also examined for influence of septic status on tracer biodistribution by comparison with normal mice. MATERIAL AND METHODS: Intramuscular doses of S. aureus were administered into the right thigh muscle of mice and the infection was allowed to develop for 20 hours. In separate experiments, (99m)Tc-alafosfalin and (67)Ga-citrate were subsequently administered and allowed to localise. Quantitative organ distribution studies were performed in conjunction with scintigraphic images at 1 and 4 hours post injection. An additional biodistribution with (99m)Tc-alafosfalin in normal mice was also performed. RESULTS: (99m)Tc-alafosfalin was predominantly renal excreted, with low liver, intestine and bone uptake. There was no difference in the uptake of these organs when infected mice were compared with normal mice. (99m)Tc-alafosfalin activity in the intestine at 1 and 4 hours was substantially less than (67)Ga-citrate. For (99m)Tc-alafosfalin, infected/non-infected thigh ratios of 2.8/1.0 and 3.6/1.0 were determined at 1 and 4 hours post injection respectively. (67)Ga-citrate gave ratios of 1.6/1.0 and 3.7/1.0 at the corresponding time points. CONCLUSIONS: (99m)Tc-alafosfalin uptake was more rapid than (67)Ga-citrate, yet diffuse at the infectious sites in mice. The small and juvenile mouse model resulted in uptake of the phosphonic acid tracer by active bone growth areas which may be a disadvantage. This (99m)Tc-antibiotic peptide has potential as an infection imaging agent, and will be investigated further in another rodent infection model in the future.

Use of Technegas as a radiopharmaceutical for the measurement of gastric emptying.

Many radiopharmaceuticals and test meals that are used to measure gastric emptying are less than optimal. A vegetable-based solid meal, such as rice, labelled with a radiopharmaceutical that also has the capacity to measure gastric emptying of liquids, is likely to be ideal. The role of Technegas as a radioisotopic marker to measure gastric emptying of rice and liquids was evaluated. Technegas-labelled rice was incubated in 0.9% saline, 1 M HCl and simulated gastric fluid (3.2 g/l pepsinogen, pH 2-3) to assess stability of the label. In eight healthy volunteers gastric emptying of two meals - 200 g rice (370 kcal) and 75 g dextrose dissolved in 300 ml water (300 kcal), both labelled with 20 MBq of Technegas - was measured scintigraphically. Over 4 h, the average label stability was 93.7%+/-0.5% in 0.9% saline, 91.0%+/-0.4% in 1 M HCl and 93.6%+/-0.7% in simulated gastric juice. The lag phase was longer for rice than dextrose (25+/-7 min vs 4+/-2 min; P<0.05), but there was no difference in the post-lag emptying rate (2.1+/-0.3 kcal/min vs 1.7+/-0.2 kcal/min; P=0.2) between the two meals. We conclude that Technegas is a suitable radiopharmaceutical for measurement of gastric emptying of rice and nutrient-containing liquids.

Relation between postprandial satiation and antral area in normal subjects.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P < 0.001) and hunger decreased (P < 0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r > 0.56, P < 0.05), the increase in antral area (r > 0.59, P < 0.05), and the scintigraphic content of the distal stomach (r > 0.57, P < 0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

The pharmacokinetics of ketoconazole after chronic administration in adults.

We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1-6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.

Changes in plasma catecholamine levels during hemodialysis.

The plasma concentrations of dopamine (DA), adrenaline (AD) and noradrenaline (NA) were measured during 29 routine hemodialysis (HD) treatments on 13 patients to determine whether any changes occurred in the concentrations of these substances during HD. All of the 13 patients studied demonstrated a fall in mean arterial pressure (MAP) when HD was commenced. Decreased concentrations of all three catecholamines were also demonstrated after the first hour of dialysis. Plasma AD rose after two hours, but NA and DA were still significantly lower than pre-dialysis values at the end of HD. Study of 12 further patients during the first hour of HD confirmed that the NA level had fallen significantly by the fifteenth minute of HD, while the DA and AD levels took somewhat longer to fall. Both NA and DA were present in the dialysate in substantial amounts. Although the fall in MAP which accompanies HD is probably multifactorial, the loss of plasma catecholamines during HD may possibly contribute to the hemodynamic changes.

Sea water. A novel self-medication for orthostatic hypotension.

We report the case of a patient who ingested sea water to combat disabling postural hypotension secondary to autonomic failure. While drinking approximately 900 mL of brine each day he had no symptoms and felt well. Serum biochemical analysis showed a very significant hyperchloraemia. Persistent diarrhoea eventually forced the patient to discontinue this most unorthodox form of treatment.