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Biomedical subjects

A A M Masclee

Publications and source records attributed to A A M Masclee.

15 recordsLinked to original sources

Efficacy of depot long-acting release octreotide therapy in severe dumping syndrome.

BACKGROUND: Dumping syndrome is a serious complication occurring in 10% of patients after gastric surgery. Dumping symptoms are effectively reduced by subcutaneous application of the somatostatin analogue octreotide, but side-effects limit its use. AIM: To evaluate the efficacy of depot long-acting release octreotide (Sandostatin-LAR) vs. octreotide subcutaneous on dumping symptoms, quality of life and side-effects. METHODS: Twelve patients (five females, age 58 +/- 3 years) with severe dumping symptoms, requiring daily use of octreotide subcutaneous, were included in an open study and changed from octreotide subcutaneous after a 2 weeks washout to Sandostatin-LAR 10 mg i.m., every 4 weeks for 6 months. Symptoms (diary), body weight, fat excretion, food intake and Gastrointestinal Specific Quality of Life Index were evaluated. RESULTS: Gastrointestinal Specific Quality of Life Index increased significantly (P < 0.05) during Sandostatin-LAR treatment (88 +/- 4) compared with octreotide (74 +/- 4) and washout (75 +/- 6). During Sandostatin-LAR treatment, abdominal symptom score was lower compared with octreotide and washout, but not significantly. During Sandostatin-LAR treatment, body weight increased (66 +/- 4 to 70 +/- 3 kg; P = 0.19). CONCLUSIONS: Sandostatin-LAR is at least as effective as octreotide subcutaneous in suppressing symptoms in patients with severe dumping syndrome and is more effective than octreotide subcutaneous in increasing body weight and quality of life.

Body Weight↗

Risk factors of frequent exacerbations in difficult-to-treat asthma.

Recurrent exacerbations are a major cause of morbidity and medical expenditure in patients with asthma. Various exogenous and endogenous factors are thought to influence the level of asthma control, but systematical data on the involvement of these factors in the recurrence of asthma exacerbations are scarce. In this study, 13 clinical and environmental factors potentially associated with recurrent exacerbations were investigated in 136 patients with difficult-to-treat asthma. Patients with more than three severe exacerbations (n = 39) in the previous year were compared with those with only one exacerbation per year (n = 24). A systematic diagnostic protocol was used to assess 13 potential risk factors. Factors significantly associated with frequent exacerbations included: severe nasal sinus disease (adjusted odds ratio (OR) 3.7); gastro-oesophageal reflux (OR 4.9); recurrent respiratory infections (OR 6.9); psychological dysfunctioning (OR 10.8); and obstructive sleep apnoea (OR 3.4). Severe chronic sinus disease and psychological dysfunctioning were the only independently associated factors (adjusted OR 5.5 and 11.7, respectively). All patients with frequent exacerbations exhibited at least one of these five factors, whilst 52% showed three or more factors. In conclusion, the results show that recurrent exacerbations in asthma are associated with specific co-morbid factors that are easy to detect and that are treatable. Therapeutic interventions aimed at correcting these factors are likely to reduce morbidity and medical expenditure in these patients.

Adolescent↗

Gallbladder volume as a biomarker for the motilin effect in healthy volunteers and patients with functional dyspepsia.

AIM: To investigate a motilin effect on gallbladder volume in healthy volunteers and patients with functional dyspepsia. METHODS: Forty-three healthy volunteers and 10 patients with functional dyspepsia received motilin (4 pmol.min/kg) or placebo in four separate double-blind, randomized, placebo-controlled, cross-over studies. The gallbladder volume was measured by ultrasonography. Analysis of variance of the combined data of these studies was performed to investigate a motilin effect on gallbladder volume and potential differences between patients and healthy volunteers. RESULTS: The baseline gallbladder volume was similar for placebo and motilin treatment, as well as for patients and healthy volunteers. Motilin, compared with placebo, significantly decreased the gallbladder volume in healthy volunteers (P = 0.003) and patients (P < 0.0001). A linear concentration-response relationship was observed. The decrease in gallbladder volume by motilin was greater in patients (P = 0.03). The motilin effect was consistent between studies. CONCLUSION: The interdigestive gallbladder volume is a non-invasive end-point for motilin activity, displaying a consistent response across studies, a clear response to motilin and a clear concentration-response relationship. However, it is less suitable as a biomarker for future pharmacological studies on motilin agonists or antagonists as the effect is probably indirect, and a relatively large study population of 27 subjects is required to demonstrate a 15% decrease in gallbladder volume. Further investigation is required to confirm altered gallbladder motility as a feature of functional dyspepsia.

Adolescent↗

Chronic pancreatitis: relation between function and morphology.

BACKGROUND: In our department, we routinely use a combined exocrine-endocrine function test to evaluate the pancreatic function in chronic pancreatitis i.e. urinary para amino benzoic acid (PABA) recovery and pancreatic polypeptide secretion in response to a meal and glucose tolerance test. AIM: To study the relationship between changes in morphology and exocrine/endocrine function in patients with chronic pancreatitis. PATIENTS AND METHODS: In 103 patients with chronic pancreatitis seen by our department for evaluation of pancreatic function between 1989 and 1999, we retrospectively analysed the correlation between morphology (Cambridge-score) and function. Furthermore the differences in presentation, function and morphology between patients with alcohol-induced chronic pancreatitis and idiopathic chronic pancreatitis were evaluated. RESULTS: Significant correlation were found for both PABA recovery and pancreatic polypeptide secretion with morphologic score, respectively r = -0.205 (P = 0.037) and r = -0.209 (P = 0.031), but not with endocrine function. The correlation between morphology and PABA recovery or pancreatic polypeptide secretion was observed in the subgroup with alcohol-induced chronic pancreatitis but not in those with idiopathic chronic pancreatitis. Pain is a prominent symptom of chronic pancreatitis. Pain was more frequent and more severe in patients suffering from chronic pancreatitis caused by alcohol or idiopathy. CONCLUSIONS: Morphology and exocrine function correlate in patients with alcohol-induced chronic pancreatitis but not in patients with chronic pancreatitis. When compared to patients with chronic pancreatitis of idiopathic origin, patients with alcoholic origin show differences in presentation and morphology but not in function.

4-Aminobenzoic Acid↗

Comparison of two techniques for lower oesophageal sphincter manometry: sleeve and sphinctometer.

We have compared the sphinctometer with the water-perfused sleeve (gold standard) for measurement of lower oesophageal sphincter (LOS) characteristics by simultaneous recording. LOS pressure and transient LOS relaxations (TLOSR) measured by sleeve and sphinctometer in 11 healthy volunteers showed identical patterns. However, output of the sphinctometer was significantly (P < 0.01) lower than output of the sleeve. A total of 249 TLOSR were recorded. Of these, 176 TLOSR were identified by both sleeve and sphinctometer, 50 TLOSR were identified by sleeve alone and 23 TLOSR by sphinctometer alone. Due to the lower pressure output of the sphinctometer, 29 LOS relaxations did not reach criteria to qualify as TLOSRs. When TLOSR criteria were adjusted for sphinctometer pressure measurements, the number of TLOSRs identified by both sleeve and sphinctometer increased from 176 to 205. In conclusion, in healthy volunteers the sphinctometer registers TLOSR with results comparable with sleeve recording. However at low LOS pressures, the number of TLOSR is underscored by the sphinctometer.

Adult↗

Size of the pancreatic head as a prognostic factor for the outcome of Beger's procedure for painful chronic pancreatitis.

BACKGROUND: Duodenum-preserving resection of the head of the pancreas (DPRHP) according to Beger has been developed as an alternative to pylorus-preserving resection of the pancreatic head for painful chronic pancreatitis. METHODS: Between 1988 and 2000, 36 consecutive DPRHPs were performed. The group was divided into patients with (group 1; n = 23) and without (group 2; n = 13) significant enlargement of the pancreatic head. Pain was the indication for surgery in all patients. RESULTS: Complications occurred in 12 patients, necessitating reoperation in 11. Initial overall results were favourable; significant improvement or complete relief of pain was reported in 27 of 35 patients. Long-term results were obtained in 27 of 30 patients; the overall success rate was 16 of 27, 13 of 16 patients with distinct enlargement of the pancreatic head and 3 of the 11 with minimal or no enlargement (P = 0.018). CONCLUSION: DPRHP can be performed with good early results. This effect is sustained in patients with distinct localized disease of the pancreatic head. In those without, the long-term results are disappointing.

Adult↗

Gallbladder motility in inflammatory bowel diseases.

In patients with Crohn's disease, the prevalence of gallstones is increased, especially in patients with ileal disease or after ileal resection. Recent studies point to alterations in enterohepatic bilirubin cycling, resulting in increased biliary bilirubin levels leading to pigment rather than cholesterol gallstones. Gallbladder (hypo)motility is another important factor in the pathogenesis of gallstones leading to bile stasis, crystallisation and stone formation. Postprandial gallbladder emptying is not markedly reduced in patients with Crohn's disease but lower fasting gallbladder volumes have been observed in patients with colonic disease or after ileocaecal resection. Prolonged and repeated bowel rest before and after intestinal surgery has been recognised as a significant risk factor for gallstone formation in patients with Crohn's disease.

Cholecystokinin↗

The effect of motilin on the rectum in healthy volunteers.

AIMS: The role of motilin in the regulation of upper gastrointestinal (GI) motility is well defined. However, little is known about the effects on the distal GI tract. To investigate the effect of exogenous motilin on rectal function, barostat measurements in the rectum were performed and lower abdominal symptoms were scored. METHODS: Eight fasted, healthy volunteers were infused intravenously with synthetic motilin or placebo over 90 min in a double-blind, randomized, cross-over design. Rectum volume was measured with a barostat device during constant pressure and during isobaric distensions. Lower abdominal symptoms were scored by visual analogue scales. Plasma motilin concentrations were measured by radioimmunoassay. RESULTS: Baseline rectum volumes were similar between treatments: 185 +/- 62 mL (motilin) and 136 +/- 41 mL (placebo). During the constant pressure procedure, motilin increased rectum volume [area under the effect curve (AUEC)] by 6%[95% confidence interval (CI) -3, 16] of baseline, compared with placebo. During isobaric distensions motilin increased rectum volume (AUEC) by 43 mL (95% CI 0.4, 85; P < 0.05) and compliance by 10 mL mmHg-1 (95% CI 0.3, 20; P < 0.05) relative to placebo. Motilin did not induce changes in the sensation of rectal feelings. CONCLUSION: Exogenous motilin increased rectal compliance in healthy volunteers, without affecting rectal sensations.

Adult↗

Function of the proximal stomach after partial versus complete laparoscopic fundoplication.

OBJECTIVES: After antireflux surgery, more than 30% of patients develop dyspeptic symptoms such as fullness and early satiety. We have previously shown that these symptoms are related to fundoplication-induced changes in proximal gastric motor and sensory function, especially impaired postprandial relaxation. We hypothesize that impaired fundus relaxation may be more pronounced after complete versus partial fundoplication. METHODS: Fasting and postprandial proximal gastric motor and sensory function were measured with an electronic barostat in patients after laparoscopic partial (n = 14) and complete (n = 14) fundoplication, in gastroesophageal reflux disease (GERD) patients (n = 12), and in healthy control subjects (n = 15). Gastric emptying and vagus nerve function tests were performed in all patients. RESULTS: Minimal distending pressure (MDP) and proximal gastric compliance were not significantly different among patients after antireflux surgery, GERD patients, and healthy controls. Maximal postprandial fundus relaxation was significantly (p < 0.01) reduced in patients after partial (267 +/- 32 ml) and complete (294 +/- 34 ml) fundoplication compared with GERD patients (448 +/- 30 ml) and healthy controls (409 +/- 25 ml). Sensations of fullness were not significantly different between patients with partial and complete fundoplication. There was a significant positive correlation between the postoperative duration and the degree of postprandial fundus relaxation (r = 0.67; p < 0.001). CONCLUSIONS: Both after complete and after partial fundoplication, proximal gastric motor function is affected, with impaired postprandial relaxation and increased sensation of fullness. These alterations are not related to the type of fundoplication but correlate significantly with the duration of the postoperative period.

Adult↗

Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.

BACKGROUND AND AIM: The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients. PATIENTS AND METHODS: Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial. RESULTS: HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p</=0.05) but no effects on cholesterol saturation index were seen with either treatment. CONCLUSIONS: We suggest that impaired gall bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall stone disease in HTG patients. Triglyceride lowering therapy by both fish oil and bezafibrate improve gall bladder dysmotility without adversely affecting biliary cholesterol saturation.

Analysis of Variance↗

Exogenous motilin affects postprandial proximal gastric motor function and visceral sensation.

Our aim was to investigate the effect of motilin on postprandial proximal gastric motor and sensory function in healthy volunteers. Ten fasted, healthy volunteers were infused intravenously with synthetic motilin or placebo over 90 min. A liquid meal (200 ml) was ingested within 2 min at the start of the infusion. Proximal gastric volume was measured with a barostat device. Abdominal symptoms were scored by visual analog scales. Plasma motilin concentrations were measured using RIA. Endogenous motilin levels were not affected by meal ingestion. After meal intake, gastric relaxation was similar for motilin and placebo. After postprandial relaxation, motilin resulted in a faster return of gastric volume to baseline (P = 0.007). Motilin significantly increased postprandial feelings of nausea (P = 0.03) and tended to increase abdominal pain and abdominal tension. In conclusion, after normal postprandial gastric relaxation, motilin accelerated the return of gastric volume to baseline. In addition, motilin increased postprandial feelings of nausea.

Abdominal Pain↗

Dose-related effects of motilin on proximal gastrointestinal motility.

AIM: To assess non-invasively the dose-response relations for the effects of exogenous motilin on antrum contraction frequency, gall-bladder volume and gastric myoelectrical activity. METHODS: In a double-blind, randomized, placebo-controlled, five-way crossover study, 10 fasted healthy volunteers were infused intravenously with synthetic human motilin (0.5, 1, 2 and 4 pmol x min/kg) or placebo for 60 min. Gall-bladder volume and antrum contractions were assessed by ultrasonography and gastric myoelectrical activity by electrogastrography. Motilin concentrations were measured using a radioimmunoassay. RESULTS: Baseline plasma motilin levels (60 pmol/L) were similar for all treatments. Motilin levels increased upon the start of infusion and rapidly returned to baseline after cessation of the infusion. At motilin doses of 2 and 4 pmol.min/kg, the antrum contraction frequency was significantly augmented, with maximum differences of two contractions per 2-min interval compared to placebo, while no changes in gastric myoelectrical activity were observed. Changes in gall-bladder volume were not significantly different for any of the motilin doses compared to placebo. CONCLUSIONS: Motilin increased antrum contraction frequency, whereas no effect on gastric myoelectrical activity was observed. Antrum contraction frequency appears to be a useful biomarker for motilin efficacy, and motilin doses of 2 and 4 pmol x min/kg were equally effective.

Adolescent↗

Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) consists of various subtypes. It is not known whether these subtypes share a common pathophysiology. Evaluation of motor and sensory function of the rectum using a barostat may help to explore a common pathophysiological background or differences in pathophysiology in subtypes of IBS. We have evaluated compliance, tone and sensitivity of the rectum, in both fasting state and postprandially, using a computerized barostat in 15 patients with diarrhoea-predominant IBS (IBS-D), 14 patients with constipation-predominant IBS (IBS-C) and compared the results with those obtained in 12 healthy controls. Rectal compliance as calculated over the steep part of the pressure-volume curve (17-23 mmHg) was decreased in both IBS groups (IBS-D 8.0 +/- 1.4 mL mmHg-1; IBS-C 5.6 +/- 1.1 mL mmHg-1) compared with controls (24.7 +/- 3.5 mL mmHg-1). The perception of urge was increased only in IBS-D patients, whereas pain perception was significantly increased in both IBS groups. Spontaneous adaptive relaxation was decreased in IBS-D patients. Postprandially, rectal volume decreased significantly in the controls and in IBS-D patients, but not in IBS-C patients. In conclusion, both rectal motor and sensory characteristics are different between IBS-D and IBS-C patients. Therefore, testing of rectal visceroperception, adaptive relaxation and the rectal response to a meal may help distinguish groups of patients with different subtypes of irritable bowel syndrome.

Adult↗

The effect of equicaloric medium-chain and long-chain triglycerides on pancreas enzyme secretion.

It has been shown previously that medium chain triglycerides (MCT) do not affect gallbladder emptying and cholecystokinin (CCK) release. The effect of MCT on exocrine pancreas secretion in humans is unknown. We have compared the effect of enteral administration of MCT versus long chain triglycerides (LCT) on exocrine pancreatic secretion. Eight healthy subjects (three female, five male; mean age 22 +/- 1.9 years) participated in two experiments, performed in random order. Duodenal contents, obtained by aspiration, were used to calculated the output of pancreatic enzymes and bilirubin. An equicaloric amount of either MCT or LCT (2 kcal min-1) oil was continuously administered in the proximal jejunum for 2 h. Gallbladder volume was measured by ultrasonography and blood samples were drawn for determination of CCK. The experiments consisted of 1 h basal secretion, 2 h of continuous oil administration and 1 h poststimulation. During the LCT feeding the pancreatic enzyme secretion, bilirubin output, gallbladder emptying and CCK release increased significantly (P < 0.05) over basal levels. MCT had no effect on pancreatic enzyme secretion nor gallbladder emptying or CCK release. We conclude that enteral administration of MCT in the proximal jejunum does not stimulate exocrine pancreatic secretion nor gallbladder contraction or CCK release, in contrast to an equicaloric amount of LCT.

Adolescent↗

Provocation of transient lower esophageal sphincter relaxations during continuous gastric distension.

BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) are triggered by gastric distension. The aim of the study was to investigate TLESRs during controlled prolonged gastric distensions using the barostat technique. METHODS: Twelve healthy volunteers (4 M, 8 F, age range 19-42 years) were studied under fasting conditions with combined esophageal manometry (Dentsleeve) and gastric barostat. Randomized isobaric distensions at 0 (control), 10, 12 and 14 mmHg were performed each period for 30 min with 30-min recovery periods in between. RESULTS: The frequency of TLESR was significantly (P < 0.05) higher during all distension periods compared to control periods (4.0 +/- 0.4 TLESR/30 min versus 2.6 +/- 0.4 TLESR/30 min). The frequency of TLESR in the first 15-min period of distension was significantly (P < 0.001) higher compared to the second 15-min period pointing to adaptation (2.7 +/- 0.3 TLESR/15 min versus 1.3 +/- 0.2 TLESR/15 min, respectively). The frequency of TLESR correlated significantly with intragastric pressure (r = 0.47; P < 0.01) and wall tension (r = 0.48; P < 0.01), but not with intragastric volume. TLESR characteristics such as duration were not related to pressure or wall tension. CONCLUSIONS: Acute gastric distension increases the frequency of TLESR but adaptation occurs rapidly. The frequency of TLESR during distension is related to pressure and wall tension rather than to intragastric volume.

Adult↗