Basma Issa

Comparative study into the robustness of compartmental modeling and model-free analysis in DCE-MRI studies

To evaluate and compare the reproducibility of the preferred phenomenological parameter IAUC60 (initial area under the time‐concentration curve [IAUC] defined over the first 60 seconds postenhancement) with the preferred modeling parameter (Ktrans), as derived using two simple models, in abdominal and cerebral data collected in typical Phase I clinical trial conditions.

Rome III Functional Constipation and Irritable Bowel Syndrome With Constipation Are Similar Disorders Within a Spectrum of Sensitization, Regulated by Serotonin

BACKGROUND & AIMS Patients with irritable bowel syndrome with constipation (IBS-C) and patients with functional constipation (FC) have similar symptoms, and these disorders overlap in their diagnostic features. Little is known about their overlap in physiology or the involvement of serotonin signaling. We investigated relationships between platelet-depleted plasma concentrations of serotonin, gastrointestinal symptoms, and motor-sensory function in patients with FC or IBS-C compared with healthy volunteers (controls). METHODS We measured platelet-depleted plasma concentrations of serotonin in fasting and fed individuals with IBS-C (n = 23; 19-50 years old), FC (n = 11; 25-46 years old), and controls (n = 23; 20-49 years old) recruited in Manchester, UK. We also quantified abdominal and bowel-related symptoms, rectal sensitivity, oro-cecal transit, and colonic (whole intestine) transit. RESULTS Patients with IBS-C or FC had similar baseline symptoms, bowel habits, oro-cecal and colonic transit, and fasting concentrations of serotonin and response to meal ingestion. Only patients with IBS-C had increased symptoms after ingestion of a meal (P < .001)-these patients tended to have lower sensory thresholds than patients with FC. Defecation frequency in the combined group of patients with IBS-C or FC correlated inversely with serotonin concentration (r = -0.4; P = .03). Serotonin concentration also correlated with pain threshold (r = 0.4; P = .02) and stool threshold (r = 0.5; P = .06), which correlated inversely with defecation frequency (r = -0.3; P = .10). CONCLUSIONS FC and IBS-C, based on Rome III criteria, are not distinct disorders, symptomatically or physiologically. Instead, they appear to lie in a spectrum of visceral sensitivity modulated by serotonin signaling. Symptom response to meal ingestion should be considered in patient classification.

Visceral hypersensitivity in endometriosis: a new target for treatment?

Objective In women presenting to gynaecological clinics with lower abdominal pain, the cause is frequently attributed to endometriosis irrespective of whether it is found to be minimal or extensive at laparoscopy. Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis. Methods Visceral sensitivity to balloon distension, symptoms and psychological status were assessed following laparoscopy in 20 women with minimal to mild endometriosis, 20 with moderate to severe endometriosis, 20 with laparoscopy negative abdominal pain and 20 asymptomatic women undergoing laparoscopic sterilisation who acted as controls, and compared with 20 women with IBS. Results Compared with controls, patients with minimal to mild and moderate to severe endometriosis had a higher prevalence of symptoms consistent with IBS (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain thresholds (39.5 mm Hg (95% CI 36.0 to 43.0) vs 28.1 mm Hg (95% CI 24.5 to 31.6), p=0.001 and 28.8 mm Hg (95% CI 24.9 to 32.6), p=0.002) not explained by differences in rectal compliance. Patients with laparoscopy negative pain had symptoms and visceral sensitivity similar to patients with IBS. Controls undergoing laparoscopy had normal sensitivity, indicating that the laparoscopic procedure was not inducing hypersensitivity. Conclusion Visceral hypersensitivity is extremely common in endometriosis and could be intensifying the pain. This finding might explain why mildly affected individuals often complain of severe symptoms out of proportion to the extent of their disease. This study has introduced a completely new concept into the understanding of pain in endometriosis and could open up new opportunities for treatment.

Abdominal Bloating and Distension: What Is the Role of the Microbiota

Most patients with irritable bowel syndrome complain of a sensation of an increase in pressure within their abdomen during the course of the day which is called bloating and, in approximately half of these individuals, this symptom is accompanied by an actual increase in abdominal girth, which is referred to as distension. The pathophysiology of these two phenomena is somewhat different and it is now recognised that a whole variety of overlapping mechanisms are involved. Some of these are potentially amenable to treatment by modification of the bacterial flora of the gut and this article reviews the evidence for this.

Abdominal distension in health and irritable bowel syndrome: The effect of bladder filling

Abdominal distension is a common feature of irritable bowel syndrome (IBS), which is difficult to treat and can have the appearance of late pregnancy. It results from an abnormality of the normal accommodation reflex which keeps abdominal girth constant despite changes in gastrointestinal volume resulting from food ingestion or gas accumulation. We speculated that bladder filling might also trigger this abnormal reflex in IBS and this study tested this hypothesis.

Endometriosis and irritable bowel syndrome: a dilemma for the gynaecologist and gastroenterologist

Chronic pelvic pain has a significant impact on health services, accounting for 20% of gynaecological referrals. The overlap between irritable bowel syndrome and endometriosis, two of the leading causes of chronic pelvic pain, should not be overlooked. Visceral sensitivity has been demonstrated in both conditions, further highlighting their similarities. Close communication between gastroenterologists and gynaecologists should help to distinguish the causative condition and improve management.

PWE-062 Can magnetic neural stimulation improve anorectal sensitivity in IBS?

Introduction Visceral pain is a major clinical problem being a primary feature of irritable bowel syndrome (IBS). Treatments for this condition are limited, but there is increasing evidence that neural stimulation may be able to alter pain thresholds in the somatic literature. By contrast, little is known about the role of neurostimulation applied to visceral pain and its ability to alter sensitivity. The aim of this study was to ascertain whether repetitive magnetic stimulation (MS) applied to the lumbosacrum and motor cortex can alter anorectal sensitivity in IBS patients. Methods Participants: 10 IBS patients (9 females, age range 22 and 54 years). All IBS patients fulfilled Rome III criteria for IBS. Anorectal electrical sensory measurements were performed via a stimulating catheter positioned in the rectum, 10 cm from the anal verge andan anal plug. Sensory and pain thresholds in the rectum and anal sphincter were determined using trains of electrical stimuli, repeated three times. Anorectal sensory and pain thresholds were performed at baseline before intervention and then immediately, 30 and 60 min after each intervention. Interventions comprised 3 neurostimulation paradigms delivered in random order over separate days: repetitive 1 Hz lumbosacral magnetic stimulation (rLSMS), repetitive 10 Hz cortical transcranial magnetic stimulation (rTMS) and sham in the form of tilted coil. Results Data (mean±SEM) were analysed by two way ANOVA (see Abstract PWE-062 tables 1 and 2) showed a significant increase in sensory (ST) and pain (PT) thresholds immediately, at 30 and 60 min in the rectum following both 1 Hz rLSMS (ST (p=0.015, 0.048 and 0.022, respectively), PT (p=0.014, 0.004 and 0.012, respectively)) and 10 Hz rTMS (ST (p=0.046, 0.041 and 0.017, respectively), PT (p=0.005, 0.02 and 0.007, respectively)). In addition, only 10 Hz rTMS increased anal sphincter pain thresholds immediately, at 30 and 60 min after the intervention (PT (p=0.032, 0.004 and 0.001, respectively)). Sham stimulation had no effect on any of the anorectal sensory parameters.Abstract PWE-062 Table 1 Rectal Baseline 0 min 30 min 60 min rLSMS 1 Hz  ST 22.6±2.8 27.1±3.4* 28.8±3.5* 29.6±3.6*  P 45.9±6.4 53.8±6.5* 53.8±7** 56.9±8.2* rTMS 10 Hz  ST 24.4±2.7 27.9±3* 29.1±3.8* 29.3±3.6*  P 44.1±5.5 53±8.7** 54.6±8.9* 57.1±9** Sham  ST 21.3±3 23.3±3 24.1±3.3 23.2±2.8  P 38.7±3.4 38.6±3.2 39.8±3.6 40.4±3.5 *p<0.05, **p<0.01.Abstract PWE-062 Table 2 Anal Baseline 0 min 30 min 60 min rLSMS 1 Hz  ST 6.3±0.7 7.3±1.2 7.1±1.1 6.7±1  P 24.3±5.2 23.6±5.1 25.2±4.9 25.6±4.7 rTMS 10 Hz  ST 5.3±0.6 5.5±0.7 5.4±0.8 6±0.7  P 23.3±5.3 25.9±6* 27±5.4** 29.4±6** Sham  ST 5.8±0.7 5.8±0.6 6.4±0.7 6.1±0.6  P 22±3.3 22.3±3.1 24±3.7 23.7±3.8 *p<0.05, **p<0.01. Conclusion The application of repetitive magnetic stimulation to lumbosacral area and motor cortex is able to modulate human visceral sensitivity in IBS patients and holds promise as a future therapeutic intervention. Competing interests None declared.

757 Evidence for Alteration in Anorectal Sensation to Non-Invasive Repetitive Lumbosacral and Cortical Magnetic Stimulation in Patients With IBS

Background: Visceral pain is a major clinical problem being a primary feature of irritable bowel syndrome (IBS). Treatments for this condition are limited, but there is increasing evidence that neural stimulation may be able to alter pain thresholds in the somatic literature. By contrast, little is known about the role of neurostimulation applied to visceral pain and its ability to alter sensitivity. The aim of this study was to ascertain whether repetitive magnetic stimulation (MS) applied to the lumbosacrum and motor cortex can alter anorectal sensitivity in IBS patients. Methods: Participants: 10 IBS patients (9 females, age range 22 and 54 years). All IBS patients fulfilled Rome III criteria for IBS. Anorectal electrical sensory measurements were performed via a stimulating catheter positioned in the rectum, 10 cm from the anal verge and an anal plug. Sensory and pain thresholds in the rectum and anal sphincter were determined using trains of electrical stimuli, repeated three times. Anorectal sensory and pain thresholds were performed at baseline before intervention and then immediately, 30 and 60 min after each intervention. Interventions comprised 3 neurostimulation paradigms delivered in random order over separate days: repetitive 1 Hz lumbosacral magnetic stimulation (rLSMS), repetitive 10 Hz cortical transcranial magnetic stimulation (rTMS) and sham in the form of tilted coil. Results: Data (mean�SEM) were analysed by two way ANOVA (see Tables 1 and 2) showed a significant increase in sensory (ST) and pain (PT) thresholds immediately, at 30 and 60 min in the rectum following both 1 Hz rLSMS (ST (p=0.015, 0.048 and 0.022, respectively), PT (p=0.014, 0.004 and 0.012, respectively)) and 10 Hz rTMS (ST (p=0.046, 0.041 and 0.017, respectively), PT (p=0.005, 0.02 and 0.007, respectively)). In addition, only 10 Hz rTMS increased anal sphincter pain thresholds immediately, at 30 and 60 min after the intervention (PT (p=0.032, 0.004 and 0.001, respectively)). Sham stimulation had no effect on any of the anorectal sensory parameters. Conclusion: The application of repetitive magnetic stimulation to lumbosacral area and motor cortex is able to modulate human visceral sensitivity in IBS patients and holds promise as a future therapeutic intervention.