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Biomedical subjects

I Ferber

Publications and source records attributed to I Ferber.

At least 19 recordsLinked to original sources
PubMed2006

Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo-controlled study.

We studied effects of i.v. atilmotin (BAX-ACC-1638, a novel motilin agonist, circulating t(1/2) < 10 min) on gastrointestinal transit in humans using a randomized, parallel-group, dose-response double-blind study of i.v. atilmotin, 6, 30, 60 microg or vehicle (placebo) given 2 min after standardized breakfast, lunch and dinner. The breakfast meal contained (99m)Tc-eggs and (111)In-milk. Full gastrointestinal transit was measured by scintigraphy. Primary endpoints were % gastric emptying (GE) at 30 min, GE t(1/2), colonic filling (CF) at 6 h, and geometric centre of colonic transit at 24 h. Analysis included adjustment for age, gender and body mass index, with Bonferroni correction applied for multiple comparisons. A significant treatment effect of atilmotin was detected for GE (%) at 30 min for solids and liquids (P < 0.01 for both). There were no significant effects on CF or CT and no significant adverse clinical events. Thus, atilmotin accelerates GE of solids and liquids in healthy humans. These data suggest that, at the doses tested, atilmotin should be considered for treatment of stomach motility disorders.

Adolescent↗
PubMed2006

Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo-controlled study.

Cannabinoid receptor (CBR) stimulation inhibits motility and increases food intake in rodents. Effects of CBR stimulation in human gastrointestinal (GI) tract are unclear. We compared effects of dronabinol (DRO) and placebo (PLA) on GI transit, gastric volume and satiation in humans. In a double-blind, randomized study, 30 healthy volunteers were randomly assigned to DRO 5 mg b.i.d. or PLA for three doses. We measured GI functions noninvasively: day 0, Ensure satiation test to measure maximum tolerated volume (MTV) and 30-min post-Ensure symptoms; day 1, scintigraphic transit ((111)In-egg meal) and fasting and postprandial gastric volume ((99Tcm)-SPECT); day 2, 24-h colonic transit and repeat satiation test. ancova was used to compare treatment groups with gender, age, and, for the satiation test, the baseline MTV, as covariates. A log-rank test was used to assess treatment effects on gastric emptying. Planned sample size had 80% power to detect 25-30% differences in primary end points. There was an overall retardation of gastric emptying with DRO (P = 0.018); this was more pronounced in females (P = 0.011), than in males (P = 0.184). No significant treatment differences were detected for gastric volumes, MTV, post-Ensure(R) symptoms, small bowel and colonic transit. Fasting gastric volume was greater in males receiving DRO compared with PLA (238 +/- 17 vs 185 +/- 16, P = 0.04). DRO retards gastric emptying in humans; effects are gender-related. Dronabinol also increases fasting gastric volumes in males.

Age Factors↗
PubMed2005

Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility.

We assessed reproducibility of measurements of rectal compliance and sensation in health in studies conducted at two centres. We estimated samples size necessary to show clinically meaningful changes in future studies. We performed rectal barostat tests three times (day 1, day 1 after 4 h and 14-17 days later) in 34 healthy participants. We measured compliance and pressure thresholds for first sensation, urgency, discomfort and pain using ascending method of limits and symptom ratings for gas, urgency, discomfort and pain during four phasic distensions (12, 24, 36 and 48 mmHg) in random order. Results obtained at the two centres differed minimally. Reproducibility of sensory end points varies with type of sensation, pressure level and method of distension. Pressure threshold for pain and sensory ratings for non-painful sensations at 36 and 48 mmHg distension were most reproducible in the two centres. Sample size calculations suggested that crossover design is preferable in therapeutic trials: for each dose of medication tested, a sample of 21 should be sufficient to demonstrate 30% changes in all sensory thresholds and almost all sensory ratings. We conclude that reproducibility varies with sensation type, pressure level and distension method, but in a two-centre study, differences in observed results of sensation are minimal and pressure threshold for pain and sensory ratings at 36-48 mmHg of distension are reproducible.

Adult↗
PubMed2004

Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders.

BACKGROUND: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (alpha(2)) adrenoceptors, norepinephrine transporter, and serotonin transporter protein (soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and high somatic symptom scores. METHODS: Validated bowel and somatic symptom questionnaires characterised the phenotype: 90 with IBS constipation (IBS-C), 128 IBS diarrhoea, 38 IBS alternating bowel function, and 20 chronic abdominal pain. Logistic regression analyses assessed associations of different polymorphisms for alpha(2) adrenoceptor and SLC6A4 with IBS or chronic abdominal pain phenotypes and high somatic score. RESULTS: Two distinct polymorphisms independently appeared to be associated with the phenotype IBS-C: alpha(2C) Del 322-325 (odds ratio (OR) 2.48 (95% confidence interval (CI) 0.98, 6.28); p = 0.05) and alpha(2A) -1291 (C-->G) (OR 1.66 (95% CI 0.94, 2.92); p = 0.08) relative to wild-type. Overall, the alpha(2C) Del 322-325 polymorphism (alone or combined with other polymorphisms) was also significantly associated with a high somatic symptom score (OR 2.2 (95% CI 1.06, 4.64); p = 0.03). Combinations of polymorphisms were also associated with high somatic scores. CONCLUSION: Functionally distinct alpha(2A) and alpha(2C) adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear.

Adolescent↗
PubMed2003

Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health.

AIM: To evaluate the effect of single administrations of asimadoline, a kappa-opioid agonist, on satiation volume, postprandial symptoms and gastric volumes. METHODS: Healthy subjects received oral placebo, or 0.5 or 1.5 mg asimadoline in a randomized, double-blind fashion 1 h prior to testing. We assessed effects on the volume of Ensure to achieve full satiation and postprandial symptoms 30 min after meal, and on gastric volume (fasting and postprandial) measured by 99mTc-single photon emission tomography (SPECT) imaging. RESULTS: Thirteen healthy subjects were studied in each treatment arm. Compared to placebo, asimadoline 0.5 mg decreased postprandial fullness (P = 0.027) without affecting the volume ingested at full satiation (P = 0.6). Asimadoline 1.5 mg decreased satiation during meal, allowing increased satiation volumes (P = 0.008) and tended to decrease postprandial fullness (P = 0.067), despite higher volumes ingested. There was a significant treatment-gender interaction in the effect of asimadoline on gastric volumes (P < 0.05). Asimadoline 0.5 mg (not 1.5 mg) increased fasting (P = 0.047) and postprandial (P = 0.009) gastric volumes in females but decreased fasting volumes in males (P = 0.008). The effect of asimadoline on gastric volume did not explain the effect observed on satiation volume (P = 0.371) or postprandial fullness (P = 0.399). CONCLUSION: A single oral administration of asimadoline decreases satiation and postprandial fullness in humans independently of its effects on gastric volume.

Acetamides↗
PubMed2002

A nutrient drink test to assess maximum tolerated volume and postprandial symptoms: effects of gender, body mass index and age in health.

To assess the effects of age, gender and body mass index on the maximum tolerated volume of a nutrient drink and postprandial symptoms in health. Healthy adolescents (15 M, 15 F, aged 13-17 years) and adults (15 M, 25 F, aged 19-51 years) ingested Ensure (1 kcal mL-1) at a rate of 30 mL min-1. The maximum tolerated volume was recorded. Thirty minutes later, bloating, fullness, nausea and pain were rated using visual analogue scales. The Mann-Whitney test was used for comparisons between groups using body mass index and maximum tolerated volume as covariates. Age-related differences in maximum tolerated volume were noted between adolescents and adults, and were observed in both genders. Adults had higher scores for bloating and pain, and lower scores for fullness. Gender-related differences in maximum tolerated volume were noted in the group as a whole, and separately for adolescents and adults. Females had higher scores for nausea and pain. Gender and age-related differences in the maximum tolerated volume of a nutrient drink and postprandial symptoms should be considered in future studies of upper gastrointestinal symptoms in disease. Body mass index does not appear to influence maximum tolerated volume beyond its association with age and gender.

Adolescent↗
PubMed2000

Effects of a serotonin 5-HT(4) receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans.

BACKGROUND: Serotonin 5-HT(4) receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT(4) receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT(4) agonists are used as prokinetic agents, the physiological role of 5-HT(4) receptors in the human gut is unknown. AIMS: Our aim was to characterise the role of 5-HT(4) receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT(4) receptor antagonist. METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 10-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. RESULTS: Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. CONCLUSION: 5-HT(4) receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.

Adolescent↗
PubMed1996

Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein.

Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.

Amino Acid Sequence↗
PubMed1994

Levels of peripheral T cell tolerance induced by different doses of tolerogen.

Antigen-specific immunosuppression requires an understanding of the parameters that control peripheral T cell tolerance. A liver-specific inducible promoter was used to drive the expression of the major histocompatibility complex antigen Kb in transgenic mice. Minute amounts of Kb, expressed exclusively on hepatocytes, induced tolerance by partial down-regulation of the T cell receptor (TCR) on the self-reactive CD8+ cells. Contact of these tolerant T cells with high concentrations of Kb after induction led to complete down-regulation of TCR. Thus, tolerant T cells are susceptible to further tolerogenic signals and reach different levels of tolerance depending on antigen dose.

Animals↗
PubMed1993

Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor.

Through binding to cholecystokinin (CCK) A receptors, CCK is an important physiologic regulator of both gallbladder contraction and pancreatic enzyme secretion. In this work, we have used a combination of hybridization screening of a cDNA library and polymerase chain reaction to clone a 2.1 kb cDNA which encodes the human gallbladder CCKA receptor. Nucleotide sequence analysis revealed an open reading frame encoding a 428 amino acid protein, with seven putative transmembrane domains and a high degree of homology with the rat CCKA receptor. COS cells transfected with this cDNA clone bound CCK-8 and L-364,718 with high affinities appropriate for the CCKA receptor, and exhibited a transient increase in intracellular calcium in response to CCK. This should provide an important resource for the analysis of the role of this receptor in human physiology and pathophysiology.

Amino Acid Sequence↗
PubMed1989

Prosthetic rehabilitation of elderly bilateral amputees.

A retrospective evaluation of vascular amputees, all over 55 years of age, found that 18 underwent bilateral lower limb amputation. The ages of patients ranged from 55 to 83 years, mean age at the time of second amputation was 65.9 years, 13 men and 5 women. Out of the 18 patients, 12 underwent bilateral below knee amputation (BK-BK), 3 below knee and above knee (BK-AK), and 3 bilateral above knee (AK-AK). Six patients (50%) of the 12 with BK-BK were fitted with prostheses. They therefore became users of two prostheses and have achieved a high functional level of rehabilitation despite a high mean age of 67.8 years. Five of these patients had been successful prosthetic users after the first leg amputation. The sixth patient underwent double BK amputation almost at the same time. He was fitted and rehabilitated with two prostheses simultaneously. Patients with BK-AK and AK-AK amputations had not been fitted with two prostheses. Deciding about prosthetic prescription and type of rehabilitation of elderly bilateral amputees is very difficult. Age alone is not a factor in success or failure of prosthetic rehabilitation. The type of rehabilitation for these patients is related mainly to the level of amputation, associated diseases and successful prosthetic use after the first leg amputation. Careful evaluation by a multidisciplinary team is the key for the right treatment decision and successful rehabilitation of this group of patients.

Activities of Daily Living↗
PubMed1985

Lower limb pain in thalassemia.

A group of 67 homozygous beta thalassemic patients was investigated for disturbances related to their lower limbs. Thirty-six patients presented a variety of complaints. Four distinct types of pain were found. Ischemic crampy muscle pain in 12 patients. Postural pulsating pain after activity or prolonged standing was described by 18 patients. High intraosseous pressure was found in a significant number of these patients. Post transfusion hemosiderosis producing synovitis was diagnosed in 2 patients. Four additional patients presented acute self-limiting episodes of pain. This pain was probably due to microfractures. Some patients presented a combination of various pain patterns.

Adolescent↗
PubMed1983

The effect of physical activity on the intraocular pressure of glaucomatous patients.

Chronic simple glaucoma patients who performed physical activity had headache and nausea, symptoms that simulated a sudden rise in intraocular pressure. Twelve patients, who were diagnosed as suffering from simple open angle glaucoma, performed multiple bicycle ergometry. The intraocular pressure was measured during the ergometry and was compared to intraocular pressure measurements at rest. A statistically significant decrease was found in intraocular pressure during the ergometry performance. It was concluded that there is no ocular restriction for simple open angle glaucoma patients in performing physical activity.

Adult↗
PubMed1983

Evaluation of the phrenic nerve in patients with neuromuscular disorders.

Twenty-six patients suffering from neuromuscular disorders underwent electrodiagnostic studies of the phrenic nerve as well as lung function and fluoroscopic evaluations. Fourteen (53.8%) out of the 26, manifested uni- or bilateral phrenic nerve involvement. Of these, only 5 (35.7%) showed a correlation between clinical complaints of shortness of breath and the pathological findings in the electrodiagnostic studies of the phrenic nerve and in the lung function and fluoroscopic evaluations. Another 5 (35.7%) patients had normal lung function and fluoroscopic evaluations, in spite of complaints of shortness of breath and pathological phrenic nerve conduction findings. It is recommended, therefore, that electrodiagnostic evaluation of both phrenic nerves be part of the evaluation of patients with neuromuscular disorders.

Adolescent↗
PubMed1983

Electrically elicited blink reflex in children.

Blink reflex was studied in 12 neurologically intact infants and children aged 2 weeks to 3 years. A coaxial needle electrode inserted in the outer lower quadrant of the orbicularis oculi muscle was used for recording. Responses were elicited by a 50-100V current delivered through a stimulating electrode placed on the supraorbital groove. Absence of contralateral R2 response was a consistent finding. Ipsilateral R2 responses were elicited in 50% of the cases. R1 response was present in all instances and showed latency values similar to adults. The amplitudes of both R1 and R2 were lower than reported in adult population. The blink reflex may be an indication of the degree of myelination of the brain stem, facial and trigeminal pathways in children.

Age Factors↗