Biomedical subjects

L A Houghton

Publications and source records attributed to L A Houghton.

At least 19 recordsLinked to original sources

PubMed2006

Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder, characterized by abdominal pain/discomfort, bloating and altered bowel habit. AIM: To conduct a systematic evidence-based review of pharmacological therapies currently used, or in clinical development, for the treatment of IBS in Europe. The safety and tolerability of these therapies are the subject of an accompanying review. METHODS: A literature search was completed for randomized controlled studies which included adult patients with IBS and an active or placebo control, assessed IBS symptoms, and were published in English between January 1980 and June 2005. The level of evidence for efficacy was graded according to the quality of the trial design and the study outcome. RESULTS: There is some evidence for improvement of individual IBS symptoms with antidiarrhoeals (diarrhoea), antispasmodics (abdominal pain/discomfort), bulking agents (constipation), tricyclic antidepressants (abdominal pain/discomfort) and behavioural therapy. In contrast, there is strong evidence for the improvement of global IBS symptoms with two new serotonergic agents: the 5-HT4 selective agonist tegaserod (IBS with constipation) and the 5-HT3 antagonist alosetron (IBS with diarrhoea). Further data are required for the 5-HT3 antagonist, cilansetron, and the mixed 5-HT3 antagonist/5-HT4 agonist renzapride before their utility in IBS can be appraised. CONCLUSIONS: There is limited evidence for the efficacy, safety and tolerability of therapies currently available in Europe for the treatment of IBS. Overall, there is an absence of pharmacological agents licensed specifically for the treatment of IBS subtypes, and new agents are awaited in Europe that will allow changes in clinical practice to focus on and improve global IBS symptoms.

Adult↗

PubMed2005

Towards a better understanding of abdominal bloating and distension in functional gastrointestinal disorders.

Abdominal bloating is an extremely common symptom affecting up to 96% of patients with functional gastrointestinal disorders and even 30% of the general population. To date bloating has often been viewed as being synonymous with an actual increase in abdominal girth, but recent evidence suggests that this is not necessarily the case. This review examines the relationship between the symptom of bloating and the physical sign of abdominal distension, as well as examining the epidemiology, pathophysiology and treatment options available for this debilitating aspect of the functional gastrointestinal disorders. Pathophysiological mechanisms explored include psychological factors, intestinal gas accumulation, fluid retention, food intolerance and malabsorption of sugars, weakness of abdominal musculature, and altered sensorimotor function. Treatment options are currently rather limited but include dietary changes, pharmacological approaches, probiotics and hypnotherapy.

Abdomen↗

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

Diagnostic criteria for irritable bowel syndrome: utility and applicability in clinical practice.

BACKGROUND/AIMS: Symptom-based criteria have been introduced to aid the diagnosis of irritable bowel syndrome (IBS). Although they have been widely adopted and have proved useful for research purposes by ensuring homogeneity of study populations, there is little information about their utility in routine clinical practice. It was the aim of this study to assess the applicability of the Manning, Rome I and Rome II criteria in the clinical setting and to ascertain how often hospital specialists and general practitioners (GPs) use them. METHODS: Hundred secondary-care IBS patients were assessed for their conformity to these criteria. Forty-eight hospital specialists and 68 GPs were asked about their knowledge and utilization of these criteria. RESULTS: Seventy-three percent of IBS patients met Rome II diagnostic criteria with 82 and 94% meeting Rome I and Manning, respectively. Approximately 80% of GPs had no knowledge of any of the specific criteria, and only 4% had ever used them. The majority of specialists had knowledge of the criteria, with 70% having used them. CONCLUSION: The Rome II criteria are remarkably insensitive and if rigidly applied in the clinical situation would lead to much diagnostic uncertainty. The current lack of interest in them, especially amongst GPs, is unlikely to change unless they can be considerably improved.

Diagnosis, Differential↗

PubMed2004

Inter-digestive and post-prandial antro-pyloro-duodenal motor activity in humans: effect of 5-hydroxytryptamine 1 receptor agonism.

BACKGROUND: Little is known about the effect of 5-hydroxytryptamine 1 (5-HT(1)) receptor agonism on the co-ordinated motor activity of the gastric antrum, pylorus and duodenum under fasting and fed conditions. AIM: To evaluate the effect of sumatriptan, a 5-HT(1) agonist, on fasting and fed antro-pyloro-duodenal motility. METHODS: In study 1, antro-pyloro-duodenal motility was recorded for two phase IIIs of the migrating motor complex and then, following either a subcutaneous injection of sumatriptan 6 mg or saline control, for at least one additional phase III in 11 healthy volunteers (21-36 years). In study 2, the post-prandial motility was recorded for 3 h after either a subcutaneous injection of sumatriptan 6 mg or saline control in 10 healthy volunteers (18-36 years). RESULTS: Sumatriptan prolonged the migrating motor complex cycle (P = 0.009) by increasing the duration of phase II (P = 0.02) but not phases I and III. Post-prandially, sumatriptan reduced the activity index (P = 0.017) by reducing the frequency of co-ordinated motor activity involving the antrum and/or the duodenum (P < 0.05). CONCLUSION: 5-HT(1) receptor agonism increases the periodicity of the migrating motor complex and reduces the occurrence of post-prandial co-ordinated motor activity involving the gastric antrum, pylorus and duodenum.

Adolescent↗

PubMed2003

Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome.

BACKGROUND: We have previously shown that hypnotherapy alters rectal sensitivity in some patients with irritable bowel syndrome. However, this previous study used incremental volume distension of a latex balloon, which might be susceptible to subject response bias and might compromise the assessment of compliance. In addition, the study group was symptomatically rather than physiologically defined. AIM: To assess the effect of hypnotherapy on rectal sensitivity in hypersensitive, hyposensitive and normally sensitive irritable bowel syndrome patients using a distension technique (barostat) that addresses these technical issues. METHODS: Twenty-three irritable bowel syndrome (Rome I) patients (aged 24-72 years) were assessed before and after 12 weeks of hypnotherapy in terms of rectal sensitivity, symptomatology, anxiety and depression. Normal values for sensitivity were established in 17 healthy volunteers (aged 20-55 years). RESULTS: Compared with controls, 10 patients were hypersensitive, seven hyposensitive and six normally sensitive before treatment. Following hypnotherapy, the mean pain sensory threshold increased in the hypersensitive group (P = 0.04) and decreased in the hyposensitive group, although the latter failed to reach statistical significance (P = 0.19). Normal sensory perception was unchanged. Sensory improvement in the hypersensitive patients tended to correlate with a reduction in abdominal pain (r = 0.714, P = 0.07). CONCLUSION: Hypnotherapy improves abnormal sensory perception in irritable bowel syndrome, leaving normal sensation unchanged.

Abdominal Pain↗

PubMed2003

Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome.

BACKGROUND: Meal ingestion is often associated with exacerbation of gastrointestinal symptoms in subjects with irritable bowel syndrome (IBS). Furthermore, recent preliminary data suggest that 5-hydroxytryptamine (5-HT) concentration in platelet poor plasma is elevated following meal ingestion in some subjects with diarrhoea predominant IBS (d-IBS) compared with healthy subjects, although it is not known whether this is related to postprandial symptomatology. AIM: To expand on previous data by evaluating a larger number of subjects but also to assess plasma 5-hydroxyindole acetic acid (5-HIAA) concentrations, 5-HT turnover, platelet 5-HT stores, and any relationship to symptomatology. METHODS: We assessed platelet depleted plasma 5-HT and 5-HIAA concentrations for two hours (60 minute intervals) under fasting conditions, and then for a further four hours (30 minute intervals) after a standard carbohydrate meal (457 kcal), together with fasting platelet 5-HT concentrations in 39 female subjects with d-IBS (aged 19-52 years; mean age 33) and 20 healthy female volunteers (aged 20-46 years, mean age 28). IBS symptomatology, in particular abdominal pain and bloating, and urgency to defecate were assessed throughout the study RESULTS: When related to fasting levels, there was no statistically significant difference in postprandial plasma 5-HT concentrations between d-IBS and healthy subjects. However, when fasting levels were not taken into consideration, d-IBS subjects exhibited higher postprandial plasma 5-HT concentrations compared with healthy subjects (p=0.040). Furthermore, d-IBS subjects who exhibited postprandial symptomatology had higher levels of postprandial plasma 5-HT, whether assessed with respect to fasting baseline levels (p=0.069) or not (p=0.047), compared with d-IBS subjects who did not report postprandial symptomatology. This appeared to be associated with a concomitant increase in plasma 5-HIAA (p=0.161) but reduction in turnover (p=0.058). Lastly, d-IBS subjects had higher platelet concentrations of 5-HT than healthy subjects (p=0.009). CONCLUSIONS: These data suggest that postprandial symptomatology may be associated with increased platelet depleted plasma 5-HT concentrations in female subjects with d-IBS. In addition, the presence of increased platelet stores of 5-HT may act as a useful marker for the diagnosis and management of d-IBS.

Adult↗

PubMed2002

A device for 24 hour ambulatory monitoring of abdominal girth using inductive plethysmography.

Inductive plethysmography (IP) sensors and oscillator modules were assessed for their potential use in the ambulatory monitoring of abdominal girth in subjects with irritable bowel syndrome (IBS) in order to objectively quantify their bloating symptoms. A dedicated microprocessordata logger was designed to record over 24 h the frequency output of IP oscillators connected to a belt around the subject's lower abdomen. Posture was also recorded via tilt switches (standing, sitting and lying). The system was separately calibrated by placing the belts around a variable rectangular phantom and measuring the frequency of oscillation. A theoretical geometric model was devised to convert measured frequency into circumference and account for changes caused by variations in shape. Using the calibration factors, it was found that the circumference of a circular phantom could be measured accurately (mean difference 1.27 cm and SD 0.25 cm). The system has been tested over 24 h with 20 volunteers. Movement introduced variations in measured girth larger than those found during periods of non-movement during sleep. We conclude that IP promises to be a useful and quantitative tool suitable for ambulatory monitoring of abdominal girth, a hitherto relatively unexplored symptom of IBS.

Abdomen↗

PubMed2002

The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers.

BACKGROUND: We have previously shown that the menstrual cycle has no effect on rectal sensitivity of normal healthy women, despite them having looser stools at the time of menses. Patients with irritable bowel syndrome (IBS) often report significant exacerbation of their IBS symptoms with menses, raising the possibility that IBS patients may respond differently to the menstrual cycle. AIM AND METHODS: Rectal responses to balloon distension during days 1-4 (menses), 8-10 (follicular phase), 18-20 (luteal phase), and 24-28 (premenstrual phase) of the menstrual cycle were assessed in 29 female IBS patients (aged 21-44 years), diagnosed by the Rome I criteria. During the course of the study patients completed symptom diaries to assess abdominal pain and bloating (visual analogue scale), and frequency and consistency of bowel habits. In addition, levels of anxiety and depression were assessed using the hospital anxiety and depression questionnaire. RESULTS: Menses was associated with a worsening of abdominal pain and bloating compared with most other phases of the menstrual cycle (p<0.05). Bowel habits also became more frequent (p<0.05) and patients tended to have a lower general well being. Rectal sensitivity increased at menses compared with all other phases of the cycle (p<0.05). There was no associated change in rectal compliance, wall tension, or motility index. Neither was there any difference in resting anal pressure or the distension volumes required to relax the internal anal sphincter during the menstrual cycle. CONCLUSION: These data (1) confirm that IBS symptomatology is exacerbated at menses and (2) show for the first time that in contrast with healthy women, rectal sensitivity changes with the menstrual cycle. These cyclical changes in sensitivity suggest that women with IBS respond differently to fluctuations in their sex hormonal environment or its consequences compared with healthy females.

Adult↗

PubMed2002

Visceral sensation and emotion: a study using hypnosis.

BACKGROUND AND OBJECTIVES: We have previously shown that hypnosis can be used to study the effect of different emotions on the motility of the gastrointestinal tract. These studies demonstrated that both anger and excitement increased colonic motility while happiness led to a reduction. The purpose of this study was to investigate the effect of hypnotically induced emotion on the visceral sensitivity of the gut. METHODS: Sensory responses to balloon distension of the rectum and compliance were assessed in 20 patients with irritable bowel syndrome (IBS) (aged 17-64 years; 17 female) diagnosed by the Rome I criteria. Patients were studied on four separate occasions in random order either awake (control) or in hypnosis, during which anger, happiness, or relaxation (neutral emotion) were induced. RESULTS: Hypnotic relaxation increased the distension volume required to induce discomfort (p=0.05) while anger reduced this threshold compared with relaxation (p<0.05), happiness (p<0.01), and awake conditions (p<0.001). Happiness did not further alter sensitivity from that observed during relaxation. There were no associated changes in rectal compliance or wall tension. CONCLUSIONS: Further to our previous observations on motility, this study shows that emotion can also affect an IBS patient's perception of rectal distension and demonstrates the critical role of the mind in modulating gastrointestinal physiology. These results emphasise how awareness of the emotional state of the patient is important when either measuring visceral sensitivity or treating IBS.

Adolescent↗

PubMed2001

Ambulatory abdominal inductance plethysmography: towards objective assessment of abdominal distension in irritable bowel syndrome.

BACKGROUND: Abdominal distension is one of the cardinal features of irritable bowel syndrome (IBS) with patients often ranking it as more intrusive than their pain or bowel dysfunction. If this symptom could be quantified accurately and reliably it would provide, for the first time, an objective way of assessing this disorder. Using the principle of inductance plethysmography we have developed a microprocessor based system capable of recording even minimal changes in girth over 24 hours and we describe its validation and establish normal ranges. METHODS: Twenty four hour recordings were made in 20 healthy female volunteers (aged 23-58 years) to assess changes in abdominal girth with respect to time, posture, meals, and sleep. Normal daily activity was encouraged and meals were standardised. The feeling of abdominal distension was also assessed using a visual analogue scale. FINDINGS: Measurement of abdominal girth using abdominal inductance plethysmography (AIP) at a static point in time showed a close relationship with that measured using a tape measure (rho=0.8910, p<0.001). Furthermore, girth was significantly greater both in the sitting and standing postures compared with lying (p<0.01). Measurement over a 24 hour period showed that girth was significantly greater at the end compared with the beginning of the day, and ingestion of a standard meal also increased its value (p<0.05). Sleep was associated with a reduction in girth (p<0.05). CONCLUSIONS: AIP promises to add an objective dimension to the assessment of IBS which could prove invaluable in clinical trials. Furthermore, it should aid research into the pathogenesis of this symptom for which no satisfactory explanation has yet emerged.

Abdomen↗

PubMed2000

Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers.

BACKGROUND: Alosetron is a potent and selective 5-HT3 receptor antagonist, which has been shown to be beneficial in the treatment of female patients with non-constipated irritable bowel syndrome. AIMS: To investigate the effect of alosetron on whole gut, small bowel and colonic transit in patients with irritable bowel syndrome (Study 1) and healthy volunteers (Study 2). SUBJECTS: Thirteen patients with irritable bowel syndrome and 12 healthy volunteers. METHODS: Both studies were randomized, double-blind, placebo-controlled with a two-way crossover design, in which each subject received alosetron (2 mg b.d. administered orally) or placebo for 8 days. Mean whole gut transit was determined from the excretion of radio-opaque markers; small bowel transit was determined from rise in breath hydrogen after a meal; and colonic transit and segmental transit were evaluated from abdominal X-ray. In addition, colonic transit was calculated by subtracting small bowel transit time from whole gut transit time. RESULTS: Alosetron increased colonic transit time by prolonging left colonic transit in both patients with irritable bowel syndrome and controls. This resulted in a tendency for the whole gut transit to be delayed in irritable bowel syndrome patients (P=0.128), which was confirmed in controls (P=0.047). CONCLUSION: Alosetron delays colonic transit by prolonging left colonic transit. These results add to the body of evidence suggesting that alosetron should have a therapeutic role in patients with non-constipated irritable bowel syndrome.

Adult↗

PubMed2000

Do male sex hormones protect from irritable bowel syndrome?

OBJECTIVE: Irritable bowel syndrome (IBS) is more common in women and it is frequently assumed that being female may predispose to the development of this disorder. Alternatively, being male could offer some degree of protection and if so, this might be mediated by testosterone. The aim of this study was to assess whether male patients with IBS have lower levels of testosterone and related gonadotrophins than their unaffected counterparts and if this relates to rectal sensitivity. METHODS: Fifty secondary care, male outpatients with IBS (aged 19-71 yr) were compared with 25 controls (aged 22-67 yr). Each subject had serum testosterone, free testosterone, sex hormone-binding globulin, follicle stimulating hormone, and luteinizing hormone (LH) measured, together with rectal sensitivity to balloon distension. Anxiety and depression were also assessed. RESULTS: The only difference in the hormone levels between patients and controls that reached statistical significance was the lower value for LH in the IBS patients (p = 0.014). Although patients were more anxious and depressed than the controls (p < 0.001), this could not solely account for the reduced level of LH, as adjusting for these (analysis of variance) still tended to show that LH values were lower in men with rather than without IBS [F(1,70) = 2.74; p = 0.10]. Men with IBS were more sensitive to balloon distension of the rectum, with the distension volumes required for "urgency" (p < 0.001) and "discomfort" (p = 0.001) significantly lower than controls. Paradoxically, the patient's sensory thresholds negatively correlated with levels of testosterone (p < 0.05) and free testosterone (p < 0.002), and positively with levels of sex hormone-binding globulin (p < 0.05). Finally, there was a tendency for IBS symptomatology to be inversely related to testosterone levels (p = 0.15). CONCLUSIONS: These results support the need for further exploration of the role of male sex hormones in the pathophysiology of IBS.

Adult↗

PubMed1999

Altered oesophageal motility following the administration of the 5-HT1 agonist, sumatriptan.

BACKGROUND: The 5-HT1 agonist sumatriptan, used in the treatment of migraine, can cause chest pain. AIM: To investigate the effect of a therapeutic dose of sumatriptan (6 mg s.c.) on oesophageal motility. METHODS: In 16 normal healthy subjects aged 19-32 years (9 males), the manometric response of the lower oesophageal sphincter (sleeve sensor), oesophageal body (four sites), stomach and pharynx (to register swallows) to 5 mL water swallows was assessed before and after a subcutaneous injection of either sumatriptan (6 mg) or saline control. Symptoms and ECGs were also monitored. RESULTS: Sumatriptan 6 mg s.c. altered oesophageal motility in all subjects. This was reflected by a significant increase in the amplitude of oesophageal body contractions (change from pre- to 1 h post-injection: sumatriptan 9.9 (2.8, 17.1) mmHg vs. placebo -0.8 (-4.2, 2.6) mmHg, difference 10.8 (4.4, 17.1) mmHg; P=0.003) and a transient increase in lower oesophageal sphincter pressure (change from pre- to 5 min post-injection: sumatriptan 10.9 (5.2, 16.6) mmHg vs. placebo 5.1 (1.8, 8.4) mmHg, difference 5.8 (-0.7, 12.3) mmHg; P=0.08). Sumatriptan had no effect on the velocity of propagation of oesophageal contractions (change from pre- to 1 h post-injection: sumatriptan -0.1 (-0.3, 0.1) cm/s vs. placebo -0.1 (-0.3, 0.0) cm/s, difference 0.1 (-0.1, 0.2) cm/s; P = 0.40). One subject experienced chest symptoms following sumatriptan and, although motility was altered, this did not reach pathological levels. No ECG abnormalities were observed. CONCLUSION: Sumatriptan (6 mg s.c.) significantly alters oesophageal motor function without affecting the ECG. It is therefore possible that sumatriptan-induced chest symptoms may have an oesophageal origin. The evaluation of similar therapeutic agents for migraine on oesophageal function may be justified.

Adult↗

PubMed1999

5-HT4 receptor antagonism in irritable bowel syndrome: effect of SB-207266-A on rectal sensitivity and small bowel transit.

BACKGROUND: Pre-clinical studies indicate that the 5-hydroxytryptamine (5-HT)4 receptor may be involved in the pathophysiology of irritable bowel syndrome and that antagonism of this receptor may be an effective therapeutic strategy. AIM: To investigate the effects of SB-207266-A, a selective 5-HT4 receptor antagonist on rectal sensitivity and small bowel transit in patients with irritable bowel syndrome. METHODS: Eighteen patients with diarrhoea-predominant irritable bowel syndrome and a history of increased rectal sensitivity were randomized to receive either SB-207266-A (20 mg) or placebo for 10 days. Following a washout period, patients were then crossed over to receive the alternative therapy for 10 days. Rectal sensitivity and orocaecal transit time were assessed on day 10 of each treatment period. In addition, patients were asked whether they had experienced any changes in their symptoms. RESULTS: Fifteen patients completed the study. SB-207266-A significantly increased orocaecal transit time towards normal (placebo: 5.3 h (4.0-7.2 h), mean (IQR) vs. SB-207266-A: 6.5 h (4.8-8.0 h); P=0.027) and tended to decrease rectal sensitivity (volume to discomfort 89 mL (60-150 mL), geometric mean (IQR) vs. 107 mL (75-150 mL); P=0.134). Eleven out of 15 patients reported symptomatic improvements with SB-207266-A but none with placebo. SB-207266-A was well tolerated. CONCLUSION: Our results support a role for the 5-HT4 receptor in the pathophysiology of irritable bowel syndrome and suggest that the selective 5-HT4 antagonist, SB-207266-A, is worthy of further evaluation in this disorder.

Adult↗

PubMed1999

Sensory dysfunction and the irritable bowel syndrome.

Dysfunction of the sensory system of the gut is now generally believed to be important in the pathophysiology of irritable bowel syndrome (IBS). This disturbance may well account for some of the symptoms of the disorder, such as abdominal pain, by virtue of the fact that intra-lumenal events (e.g. contractions) may be 'sensed' more easily. It can be assessed in the laboratory by a variety of techniques, but usually involves measuring the patient's response to distension of any site of the gut, most commonly the rectum. Hypersensitivity is the most frequent finding, but hyposensitivity can also occur--hypersensitivity does not appear to be specific to any particular pattern of bowel habit, but hyposensitivity does tend to be generally only seen in patients with constipation, especially those with the 'no urge' type. Although there is some evidence to support hypersensitivity being related to enhanced vigilance in some patients, other data suggest that there may be a true alteration in sensory processing. The mechanisms underlying this sensory dysfunction remain to be elucidated, but could involve changes in either the enteric, spinal and/or central nervous systems. Finally, factors such as gender, stress, emotion and infection can all influence the sensitivity of the gut and may therefore play a role in IBS.

Colonic Diseases, Functional↗

PubMed1998

Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females.

OBJECTIVE: The study was designed to determine the impact of currently available oral contraceptive agents (OCAs), smoking, and alcohol on biochemical indexes of folate and vitamin B-12 in adolescent females. DESIGN: Subjects completed a 3-day weighed food record along with a detailed lifestyle questionnaire that included questions on OCA, cigarette, and alcohol use. After subjects had fasted overnight, blood samples were collected and analyzed for levels of serum and red blood cell (RBC) folate and serum B-12 and homocysteine. SUBJECTS/SETTINGS: Two hundred twenty-nine adolescent females (aged 14 to 20 years) were recruited from southern Ontario, Canada, by advertisements in newspapers, high schools, universities, shopping malls, adolescent drop-in centers, and community groups. STATISTICAL ANALYSES PERFORMED: Multiple regression models were used to determine the effect of lifestyle factors and covariates (e.g., dietary folate intake, supplemental folate intake, and age) on biochemical indexes. RESULTS: OCA use, alcohol use, and smoking were not significantly associated with lower serum or RBC folate levels, after controlling for folate intake. Serum homocysteine levels were not associated with smoking or OCA use; however, we estimated a 13% higher concentration among alcohol users than nonusers. Smoking and alcohol use were not associated with serum B-12 levels, but OCA use was associated with an estimated 33% lower serum B-12 level than nonuse. APPLICATIONS: Our findings provide no evidence to suggest that currently available OCAs have a negative impact on the folate status of adolescent females; thus, dietary advice designed to specifically encourage an increase in folate intake among adolescents who use OCAs is not supported. In contrast, serum B-12 levels were lower among OCA users than nonusers, which suggests that an interaction between OCA and some vitamins may persist. The suboptimal biochemical folate indexes of smokers may have more to do with the dietary quality of smokers than previously appreciated. Thus, efforts to improve dietary folate intakes of adolescents who smoke may be an important strategy for improving the folate status of young women.

Adolescent↗

PubMed1997

Zamifenacin (UK-76, 654) a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome.

BACKGROUND: Zamifenacin is a new potent gut M3 selective muscarinic antagonist developed for possible use in irritable bowel syndrome. METHODS: In this multicentre, double-blind, parallel group, placebo-controlled study, the effect of a single dose of zamifenacin 10 mg or 40 mg on both fasting (30 min) and fed (60 min) colonic motor activity was assessed in 36 patients with irritable bowel syndrome (aged 25-68 years; 19 male). Colonic motility was recorded using a five-channel solid-state catheter introduced by colonoscopy to a depth of 35 cm in an unprepared colon. RESULTS: Zamifenacin 40 mg profoundly reduced colonic motility, particularly after the meal (P < 0.05). This was reflected by a significant reduction in the mean amplitude of contractions, number of contractions, percentage duration of contractions, activity index and the motility index (P < 0.05). A smaller reduction in all the motility parameters was obtained with 10 mg zamifenacin, but these changes were not statistically significant. Three patients each on placebo and zamifenacin reported side-effects, but these were mild and transient. CONCLUSION: A single 40 mg dose of zamifenacin significantly reduces colonic motility in irritable bowel syndrome patients without significant antimuscarinic effects. The results of this study confirm that the concept of developing selective antimuscarinic agents may be a promising approach to the treatment of irritable bowel syndrome. Not only would such compounds benefit from not having the usual side-effects of anticholinergics but they might also offer much more in the way of dose flexibility.

Adult↗