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Biomedical subjects

B D Naliboff

Publications and source records attributed to B D Naliboff.

At least 19 recordsLinked to original sources

Sex specific alterations in autonomic function among patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is associated with increased psychological symptoms, early life stressors, and alterations in visceral perception and brain responses to noxious visceral stimuli. The autonomic nervous system (ANS) is a likely mediator for these brain-gut interactions. The few studies directly examining ANS measures have been suggestive of alterations in some IBS patients, but no studies to date have examined the potentially critical variables of sex differences or response to visceral stimulation. AIMS: (1) To test differences in ANS function during rest and during a visceral stressor (rectosigmoid balloon distension) between IBS patients and healthy control subjects. (2) To examine the role of sex on the autonomic responses of IBS patients. METHODS: Baseline autonomic measures were evaluated from 130 Rome I positive IBS patients and 55 healthy control subjects. Data were also collected from a subset of 46 IBS patients and 16 healthy control subjects during a sigmoid balloon distension study. Heart rate variability measures of peak power ratio (PPR) and peak power high frequency (PPHF) were analysed to assess sympathetic balance and parasympathetic response, respectively. Peripheral sympathetic response was measured by skin conductance. RESULTS: IBS patients showed a greater skin conductance response to visceral distension than controls. IBS patients had higher PPR and lower PPHF across conditions. Male IBS patients had higher skin conductance and PPR than females and lower PPHF. CONCLUSIONS: IBS patients have altered autonomic responsiveness to a visceral stressor, with increased sympathetic and decreased parasympathetic activity. These differences are predominantly seen in males.

Adult↗

The Visceral Sensitivity Index: development and validation of a gastrointestinal symptom-specific anxiety scale.

BACKGROUND: Anxiety related to gastrointestinal sensations, symptoms or the contexts in which these may occur is thought to play a significant role in the pathophysiology as well as in the health outcomes of patients with irritable bowel syndrome. AIM: To develop a valid and reliable psychometric instrument that measures gastrointestinal symptom-specific anxiety. METHODS: External and internal expert panels as well as a patient focus group evaluated a large pool of potential item stems gathered from the psychological and gastrointestinal literature. Potential scale items were then administered to 96 patients diagnosed with irritable bowel syndrome along with a set of validating questionnaires. Final item selection was based upon rigorous empirical criteria and the psychometric properties of the final scale were examined. RESULTS: A final unidimensional 15-item scale, the Visceral Sensitivity Index, demonstrated excellent reliability as well as good content, convergent, divergent and predictive validity. CONCLUSIONS: The findings suggest that the Visceral Sensitivity Index is a reliable, valid measure of gastrointestinal symptom-specific anxiety that may be useful for clinical assessment, treatment outcome studies, and mechanistic studies of the role of symptom-related anxiety in patients with irritable bowel syndrome.

Adult↗

The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.

AIM: To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses. METHODS: Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales. RESULTS: Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron. CONCLUSIONS: In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.

Adult↗

Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity.

Neurotransmitters can accelerate HIV-1 replication in vitro, leading us to examine whether differences in autonomic nervous system (ANS) activity might promote residual HIV-1 replication in patients treated with highly active antiretroviral therapy. Patients who showed constitutively high levels of ANS activity before highly active antiretroviral therapy experienced poorer suppression of plasma viral load and poorer CD4(+) T cell recovery over 3-11 months of therapy. ANS activity was not related to demographic or behavioral characteristics that might influence pathogenesis. However, the ANS neurotransmitter norepinephrine enhanced replication of both CCR5- and CXCR4-tropic strains of HIV-1 in vitro via chemokine receptor up-regulation and enhanced viral gene expression, suggesting that neural activity may directly promote residual viral replication.

Adult↗

V. Stress and irritable bowel syndrome.

Different types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.

Animals↗

Basic pathophysiologic mechanisms in irritable bowel syndrome.

Converging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events.

Animals↗

Depression, anxiety, and the gastrointestinal system.

Functional disorders of the digestive system, such as irritable bowel syndrome, are often associated with affective disorders, such as depression, anxiety, panic, and posttraumatic stress disorder (PTSD). Some of these associations are observed not only in clinical populations, but also in population-based samples, suggesting a relationship with pathophysiologic mechanisms underlying both gastrointestinal (GI) dysfunction and certain affective disorders. Sustained and acute life-threatening stressors play an important role in the onset and modulation of GI symptoms as well as in the development of affective disorders and PTSD. A neurobiological model is proposed that attempts to explain the development of visceral hypersensitivity, the neuroendocrine and autonomic dysfunction characteristic of functional GI disorders, as well as the overlap with affective disorders.

Anxiety Disorders↗

Depression determines illness conviction and pain impact: a structural equation modeling analysis.

OBJECTIVE: The present study sought to derive an algorithm using factor analysis and structural equation modeling (SEM) to describe headache and orofacial pain patients using measures of behavioral and psychological functioning. This investigation further examined whether the underlying factor structure differed in 3 presumed distinct diagnostic categories: myofascial, neuropathic, and neurovascular pain. DESIGN: The Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Multidimensional Pain Inventory (MPI), Beck Depression Inventory-II (BDI-II), and visual analog scale for functional limitation (VAS-FL) were administered to the subjects. A split group design was used. Exploratory factor analysis (EFA) was used to describe distinct factor domains in the first group. Confirmatory factor analysis (CFA) using SEM tested this structure in the second group and described causal relationships between the revealed (latent) factors. Analysis of variance (ANOVA) was used to test for differences in demographic variables and diagnostic group factor structure. SETTING: The Pain Center is a comprehensive, multidisciplinary pain medicine program at Cedars-Sinai Medical Center, Los Angeles, California. SUBJECTS: Three hundred and ninety (N = 390) subjects were assigned to 1 of 3 diagnostic categories: myofascial pain syndrome, neuropathic pain, or neurovascular pain. RESULTS: EFA revealed a 3-factor solution. The factors were labeled Depression, Illness Conviction, and Pain Impact, reflecting the content of their respective variables with highest loadings. CFA using SEM validated the 3-factor solution, and further revealed that Depression was a critical causal factor determining Illness Conviction and Pain Impact. No causal relationship was observed between Illness Conviction and Pain Impact. ANOVA found no differences in demographics. No difference in factor structure emerged for the 3 diagnostic categories. CONCLUSIONS: Analysis derived a 3-factor solution. The factors were Pain Impact, Illness Conviction, and Depression. SEM revealed the critical causal pathway showing that Depression determined Illness Conviction and Pain Impact. We conclude that the main target for pain treatment is depression. No differences in factor structure were found for the 3 diagnostic categories of myofascial, neuropathic, or neurovascular pain. This suggests that psychological processes are similar in chronic headache and orofacial pain patients despite their presumed distinct underlying pathophysiological mechanisms. SME is a powerful methodology to construct causal models that has been underutilized in the pain literature.

Journal Article↗

Gender differences in regional brain response to visceral pressure in IBS patients.

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.

Adult↗

Measurement of symptoms in irritable bowel syndrome clinical trials.

Irritable bowel syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. A variety of approaches to symptom assessment are used in IBS, although there is little literature directly comparing or validating them. Determining the presence or absence of specific symptoms is the primary focus of diagnostic evaluation and categorization. In contrast, outcome assessment usually entails assessment of symptom severity. Symptom severity scales can themselves vary on a wide range of factors, including specificity (pain, discomfort, gastrointestinal problem), scaling properties (numerical, analogue, or descriptor), range (usual, highest, lowest), time frame (now, past week), response category (intensity, unpleasantness, change, relief), and use of modifying variables (frequency, impact, location). The measurement properties of similar symptom scales have been investigated more extensively in the context of somatic pain, and these studies will be reviewed in suggesting some guidelines for IBS symptom assessment in clinical trials.

Colonic Diseases, Functional↗

Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus.

Since rabbit prostate extract strongly stimulated intestinal zinc absorption and improved the diabetic condition of streptozotocin-induced diabetic rats, we examined the effects of 200 mg bovine prostate powder supplemented with 20 mg zinc (Pro-Z) on the clinical manifestations of older male patients with type II diabetes. Twenty-two male patients who received Pro-Z capsules two to four times per day for 3 months showed reduced mean fasting blood glucose levels from 202 to 169 mg/dL, hemoglobin A1C-(HbA1C) concentrations from 12.2% to 9.5%, and mean values for the 3-hour area response above the fasting glucose concentration (TAFGC) from 141 to 102 mg glucose/dL/h. In eighteen patients who received placebo, mean values for fasting blood glucose decreased from 167 to 165 mg/dL and HbA1C from 10.4% to 10.2%, and for TAFGC increased from 121 to 126 mg glucose/dL/h. No detrimental changes occurred in the liver and kidney function of patients receiving either Pro-Z or placebo. However, blood cholesterol and low-density lipoprotein in patients receiving Pro-Z decreased slightly, whereas values in the placebo group tended to increase. The mean fasting plasma insulin decreased 15.5 to 13.8 microU/mL in subjects given Pro-Z, while the zinc concentration increased from 1.21 to 1.39 microg/mL. In contrast, the mean value for plasma insulin in the placebo group changed from 14.4 to 15.4 microU/mL (worsened), and for zinc, from 1.24 to 1.30 microg/ml. Interestingly, fasting urinary glucose concentrations in subjects given Pro-Z decreased from 1,249 to 378 mg/dL, whereas in those given placebo the values changed from 877 to 778 mg/dL. Since plasma zinc concentrations in both the placebo and the Pro-Z group were normal, these results suggest that biochemical constituents in the prostate including zinc may be involved in controlling glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

Aged↗

Psychosocial moderators of quality of life in irritable bowel syndrome.

Irritable Bowel Syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. Similarly the impact of IBS on Quality of Life (QOL) measures can range from very small to disabling. In a very simple model one might expect a change in symptom intensity or frequency to be reflected in a similar change in QOL. However, a variety of other factors may alter this straightforward and unidirectional relationship between symptomatic treatment and QOL improvement. This paper presents several classes of these potential moderator variables in QOL outcome in IBS, as well as specific models of symptom, moderator, QOL relationships that can be investigated in future research. An illustrative example of a regression approach to analysis of psychosocial moderator variables indicates both psychosocial measures, and symptom severity, independently contribute to the prediction of QOL in IBS.

Age Factors↗

Audio and visual stimulation reduces patient discomfort during screening flexible sigmoidoscopy.

OBJECTIVE: Despite current recommendations calling for regular screening flexible sigmoidoscopies over the age of 50, only a small percentage of the population have regular examinations. Improving patient tolerance of flexible sigmoidoscopies could therefore increase patient compliance with these recommended guidelines. The aim of this study was to determine whether audio and visual stimulation reduces discomfort during flexible sigmoidoscopy and whether the effects of the stimulation are secondary to distraction. METHODS: A total of 37 patients undergoing routine screening flexible sigmoidoscopy were randomized to receive no intervention, audio stimulation alone, or audio and visual stimulation. Patient discomfort ratings and affect states were measured prior to and immediately following flexible sigmoidoscopy using a visual analogue scale and the Stress Symptom Ratings (SSR) ratings. RESULTS: Patients receiving audio and visual intervention had lower abdominal discomfort ratings (7.1 +/- 1.4) than patients receiving audio stimulation (9.5 +/- 1.3) or no intervention (10.8 +/- 1.6) (p < 0.05). Patients receiving audio and visual intervention also had higher arousal (7.3 +/- 0.4) and attention (9.2 +/- 0.2) ratings than patients receiving no intervention (6.1 +/- 0.4 and 6.2 +/- 0.7, respectively) (p < 0.05). Anxiety and anger ratings, on the other hand, were significantly lower in patients receiving audio and visual intervention (2.5 +/- 0.4, 1.4 +/- 0.3, respectively) than patients receiving no intervention (4.4 +/- 0.6, 3.6 +/- 0.7). CONCLUSION: Audio and visual stimulation reduces abdominal discomfort associated with flexible sigmoidoscopy. This effect appears to be due to distraction.

Abdominal Pain↗

Hospitalization and mortality of diabetes in older adults. A 3-year prospective study.

OBJECTIVE: In light of increased fatality from acute events and the increased frequency of chronic complications, life expectancy might well be shortened in older patients with diabetes. The current studies investigated factors affecting the likelihood of dying or being hospitalized in older patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 135 older patients with diabetes were followed for 3 years after predictive factors were evaluated and compared with a cohort of patients without diabetes. RESULTS: Mortality was only 3,250 per 100,000 patient-years, similar to that for patients without diabetes, but the frequency of hospitalizations was more than twice as high in patients with diabetes. Five factors predicted hospitalization and death. Of these, the geriatric depression score was the best predictor of these poor outcomes. CONCLUSIONS: Older patients with diabetes were hospitalized more often than those without diabetes, but mortality was similar. Dysphoria is a major predictor of poor outcomes in older patients with diabetes.

Aged↗

Effects of relaxation training on glucose tolerance and diabetic control in type II diabetes.

The present study examined the effects of progressive relaxation training and EMG biofeedback on acute glucose disposal in diabetic subjects, as measured by glucose tolerance and three other measures of diabetic metabolic control. Twenty subjects with non-insulin-using Type II diabetes took part in progressive relaxation training and EMG biofeedback in a pre-post treatment versus wait-list experimental design. Treatment effects were assessed on glucose tolerance along with three measures of diabetic control: fasting blood glucose, two-hour postprandial blood glucose, and fructosamine. Stress reduction and relaxation was assessed with two physiological measures and two subjective questionnaires. The training program produced significant reductions in stress, as measured by State Anxiety, and significant changes in physiological measures of muscle activity and skin conductance compared to the control condition. However, no changes were found in glucose tolerance (while practicing relaxation) nor in any of the three measures of general diabetic metabolic control. The major implication of this study is that relaxation training does not appear to directly improve diabetic control in mildly stressed non-insulin-using Type II diabetic patients.

Diabetes Mellitus, Type 2↗