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.

Predictors of eating disorder scores in children ages 6 through 14: a longitudinal study.

The objective of this study was to identify variables that predict higher eating disorder scores in non-clinical boys and girls ages 6 through 14. Two hundred sixteen children participated and were tested annually for 3 years. A TV-video procedure was used to measure the accuracy of body size judgments. Variables examined included demographic, familial, sociocultural, social, esteem, and clinical variables. Predictors of higher eating disorder scores for both sexes included height and weight, children's perceptions of parental concerns about their body size, low body esteem, and depression. For girls only, a larger perceived body size and smaller idealized body size were also predictors. Teasing was a predictor for boys only. An analysis of longitudinal changes suggests that low body esteem becomes a significant factor around age 9, depression emerges as a predictor at age 10, and body size judgments in perceived and ideal sizes at ages 11 and 12. Changes over 2 years in individuals' weight and height, teasing, body dissatisfaction, and eating disorder scores were also found to predict higher eating disorder scores.

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.

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.

Body-size estimations in children six through fourteen: a longitudinal study.

Estimates of perceived and ideal body size were collected in 216 boys and girls ages 6 through 14 years. Video methodology was used to adjust the width of a life-size frontal image of the children. Longitudinal data were collected annually for three years, beginning at ages 6, 9, and 12. Three psychological methods were used, including the method of adjustment, staircase method, and adaptive probit estimation technique which permitted separate measures of the children's point of subjective equality and just noticeable difference values. The point of subjective equality is the body size which is subjectively equal to the child's perception of self. The just noticeable difference is the amount of change in body size necessary to detect the difference 50% of the time. Acceptable size boundaries were also measured, using the method of adjustment. Over-all, children were accurate in estimating their body width, with average overestimation of less than 2%. Overestimation decreased within each age group during the three years of the study. There were no differences between ages or sexes. Both point of subjective equality and just noticeable difference values decreased significantly during the three years of the study. The latter values significantly decreased as children became older. Body dissatisfaction (the discrepancy between perceived and ideal size) remained low for boys in all age groups. Girls' body dissatisfaction significantly increased across ages, beginning at age 9. Test-retest consistency of both perceived and ideal size judgments at intervals of one and two years were low. Acceptable boundaries in body width were similar between sexes and across age cohorts.

Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions.

Only two virus-neutralizing peptide microantibodies (MicroAbs) have been described and little is known about their mode of action. This report concerns a 17 amino acid cyclized MicroAb, derived from the third complementarity-determining region of the heavy chain of MAb F58 (IgG1), that recognizes the same minimum epitope in the V3 loop of the gp120 envelope protein of human immunodeficiency virus type 1 (HIV-1) as the MAb. The MicroAb was able to bind to and neutralize free virus particles. It was up to 5-fold more efficient in mass terms than F58 IgG and its neutralization rate on a molar basis was only 32-fold lower. The mechanism of neutralization of the MicroAb was also investigated. A high level of neutralization (99%) occurred without any significant decrease in attachment of virus to target C8166 cells. Neutralized virus attached to CD4, the HIV-1 primary receptor. Fusion of virions to cells was partially inhibited by the MicroAb, whereas F58 IgG has been shown to inhibit fusion significantly. Thus, neutralization by the MicroAb appears to be mediated, at least in part, by inhibition of fusion. Control peptides, in which the tyrosine at position 5 or 6 was deleted or changed to phenylalanine, showed no antiviral activity, attesting to the specificity of interaction of the MicroAb with the virion. It therefore appears that the MicroAb acts like an immunoglobulin. The data also show that the MicroAb/MAb F58 epitope on the V3 loop is not involved in attachment of virus to CD4 but is required for subsequent events in early infection.

Development and validation of two new scales for assessment of body-image.

This study reports the development and validation of two new and improved tools for assessment of body-image. Two schematic contour scales were created using a frontal view photograph of an adult male and female with height and weight of the median American. A 2-figure analogue scale was created by distorting this drawing by +/- 30%. A 13-card scale was created by generating 13 drawings distorted between +/- 30% by increments of 5%. Evidence is presented for the reliability and validity of both scales. The advantages of these new scales over existing figural and silhouette scales are discussed.

Rapid analysis of epitope-paratope interactions between HIV-1 and a 17-amino-acid neutralizing microantibody by electrospray ionization mass spectrometry.

Progress in therapeutic or prophylactic immune intervention in HIV-1 infections may only come about with a detailed understanding at the molecular/atomic level of how antibodies neutralize (inactivate) virus infectivity. Currently information on the molecular aspects of antibody-virus interaction comes predominantly from X-ray crystallography, a process that is dependent on the production of suitable crystals. NMR can also be valuable but is complex and time consuming, while mass spectrometry has been limited to matrix-assisted laser-desorption ionization (MALDI) analysis of peptides eluted from the cognate antibody. Here, we have used electrospray ionization mass spectrometry (ESI-MS) to detect directly the interactions of a novel 17-amino-acid microantibody (MicroAb) that has HIV-1-inhibitory activity, and peptides representing the V3 regions of primary HIV-1 strains isolated from Brazil (clade B) and Africa (clade A). The MicroAb is based on the third complementarity-determining region of the heavy chain (CDR-H3) of a murine monoclonal IGGI (F58) specific for the V3 loop of the gp120 envelope glycoprotein of HIV-1. ESI-MS proved to be rapid (taking < 3 h for the entire analysis), sensitive (analytes at 2 mmol/ml), and accurate (RMM estimation to 0.01-0.1%). With it, we showed that the MicroAb forms complexes with the V3 peptides, implying that its antiviral activity is mediated by binding directly to the virus particle. In addition, through controlled protease digestion of the V3 peptides, we concluded that the CDR-H3 MicroAb bound to RKXXXIGPGR, a region similar to the epitope of the whole IgG as determined by ELISA. We believe that the approach exemplified here will be applicable generally to the identification of groups involved in receptor-ligand interactions.

Methodological concerns when using silhouettes to measure body image.

This paper discusses methodological concerns of using silhouette figures to measure body images. These include concerns related to scale coarseness (limiting response options to one of a finite number of drawings), restriction of range, method of presentation, and scale of measurement. Recommendations are made to address these limitations, and an alternative silhouette scale using continuous scale measurements is proposed.

Environmental influences on fatty acid composition of membranes from autoimmune MRL lpr/lpr mice.

We analyzed fatty acid make up of cells and organs from autoimmune and immunologically normal mice to determine whether intrinsic differences in composition might be associated with an inflammatory phenotype. Macrophages (MO) isolated from 4-6-week-old MRL lpr/lpr mice were cultured with phorbol ester (PMA), fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2) and medium control to determine whether these cell signals might induce membrane fatty acid changes. Individual phospholipid analysis showed 8.4- and 5.1-fold increases in phosphatidylcholine arachidonate (20:4) mole % over baseline values following culture with FGF-1 and FGF-2, respectively. Unfractionated analysis on kidney and liver extracts from 4-6 week MRL lpr/lpr, 16-20 week lpr and 12-20 week MRL +/-/+/- mice demonstrated no significant intrastrain fatty acid differences. Higher levels of 20:4 in 4-6 week lpr mice were noted compared to 16-20 week lpr or +/+ mice in kidney, and liver samples (P < 0.05). It is possible that membrane changes precipitated by microenvironmental cytokine concentrations may contribute to the expression of autoimmune disease in this model.

Does the menstrual cycle affect anorectal physiology?

It has been shown that during the luteal phase of the menstrual cycle women excrete hard stools and have delayed transit, while at the time of menses, stools are looser and more frequent. The relationship between the menstrual cycle and anorectal physiology, and whether the timing of manometry testing should be standardized within the menstrual cycle has not been previously investigated. In this study, the anorectal responses to balloon distension during days 1-4 (menses), 8-10 (follicular phase), 18-20 (luteal phase) and 24-28 (premenstrual) of the menstrual cycle in 20 healthy female volunteers (ages 18-39 years) was measured. Stools were significantly looser during menses [2.32 (2.1-2.5); mean (95% CI)] compared with the luteal phase [1.98 (1.8-2.2): F(3,30) = 3.1; P < 0.04). However, there were no changes in rectal sensitivity, distension-induced rectal motility, rectal compliance, or the volumes required to induce the initial and sustained internal aral sphincter relaxations. In conclusion, although stools become looser at the time of menses, anorectal responses to balloon distension are unaltered. This suggests that the changes in bowel habit associated with the menstrual cycle are unrelated to changes in anorectal physiology. Furthermore, routine manometric testing can be performed at any time during the menstrual cycle without fear of conflicting results.

Composition of peritoneal macrophage membranes in autoimmune MRL lpr/lpr mice.

Adult MRL lpr/lpr mice display phenotypic features that are consistent with both rheumatoid arthritis and systemic lupus erythematosus. Previous studies have reported that peritoneal macrophages harvested from this model have an increased propensity for both spontaneous and elicited release of prostaglandins and leukotrienes relative to immunologically normal control mice. To investigate whether one aspect of the differences in secretory potential between autoimmune and normal mice was at the level of increased substrate availability, gas chromatographic analysis of peritoneal macrophage membranes from autoimmune MRL lpr/lpr, young lpr, wild type +/+, and immunologically normal mice was done. The results demonstrate enrichment of arachidonate in adult lpr macrophage membranes in all major phospholipid classes relative to young lpr, +/+ and immunologically normal C3H/HeN mice. Similarly, there was an increased mole % of arachidonic acid in lpr mice relative to controls. Elevated membrane arachidonate may contribute to the increased propensity of autoimmune strains to participate in the inflammatory process.