PubMed Health⌕ Search

Biomedical subjects

T Lembo

Publications and source records attributed to T Lembo.

At least 19 recordsLinked to original sources
PubMed2004

Anti-hyperalgesic effect of octreotide in patients with irritable bowel syndrome.

BACKGROUND: Octreotide has been found to be beneficial in the treatment of chronic pain, although the mechanisms underlying its therapeutic effect are incompletely understood. AIMS: To assess the effect of octreotide on perceptual responses to rectal distension in irritable bowel syndrome patients and healthy controls at baseline and following the experimental induction of rectal hyperalgesia. METHODS: In study 1, rectal perception thresholds for discomfort were determined in seven irritable bowel syndrome patients and eight healthy controls on three separate days using a computer-controlled barostat. Subjects received saline, low-dose and high-dose octreotide in a random double-blind fashion. In study 2, perceptual responses to rectal distension were obtained in nine irritable bowel syndrome patients and seven controls before and after repetitive high-pressure mechanical sigmoid stimulation. RESULTS: Octreotide increased the discomfort thresholds in irritable bowel syndrome patients, but not in controls, without changing rectal compliance. Repetitive sigmoid stimulation resulted in decreased rectal discomfort thresholds in the patient group only. In irritable bowel syndrome patients, octreotide prevented the sensitizing effect of repetitive sigmoid stimulation on rectal discomfort thresholds. CONCLUSIONS: Octreotide effectively increased discomfort thresholds in irritable bowel syndrome patients, but not in controls, at baseline and during experimentally induced rectal hyperalgesia. These findings suggest that octreotide exerts primarily an anti-hyperalgesic rather than analgesic effect on visceral perception.

Adult↗
PubMed2001

Gastroenterological causes of pelvic pain.

Chronic pelvic pain is a common condition, which accounts for up to 10% of gynecological consultations and for over a third of diagnostic laparoscopies. In addition to gynecological etiologies for the pelvic pain, the physician must also consider gastroenterological, urological, and neurological disease as a possible basis for the pain. This article discusses the major gastroenterological causes of pelvic pain.

Appendicitis↗
PubMed2001

Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients. The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind, randomized, placebo-controlled study. METHODS: Female IBS patients with lack of satisfactory control of bowel urgency were randomized 2:1 to alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS Global Improvement (responder defined as patient-reported moderate or substantial improvement in IBS symptoms) and improvements in bowel function (stool frequency, consistency, and sensation of incomplete evacuation). RESULTS: A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p < 0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.

Carbolines↗
PubMed2000

Mechanical activation of dorsal root ganglion cells in vitro: comparison with capsaicin and modulation by kappa-opioids.

The aim of this study was to characterize plasma membrane pathways involved in the intracellular calcium ([Ca(2+)](i)) response of small DRG neurons to mechanical stimulation and the modulation of these pathways by kappa-opioids. [Ca(2+)](i) responses were measured by fluorescence video microscopy of Fura-2 labeled lumbosacral DRG neurons obtained from adult rats in short-term primary culture. Transient focal mechanical stimulation of the soma, or brief superfusion with 300 nM capsaicin, resulted to [Ca(2+)](i) increases which were abolished in Ca(2+)-free solution, but unaffected by lanthanum (25 microM) or tetrodotoxin (10(-6) M). 156 out of 465 neurons tested (34%) showed mechanosensitivity while 55 out of 118 neurons (47%) were capsaicin-sensitive. Ninty percent of capsaicin-sensitive neurons were mechanosensitive. Gadolinium (Gd(3+); 250 microM) and amiloride (100 microM) abolished the [Ca(2+)](i) transient in response to mechanical stimulation, but had no effect on capsaicin-induced [Ca(2+)](i) transients. The kappa-opioid agonists U50,488 and fedotozine showed a dose-dependent inhibition of mechanically stimulated [Ca(2+)](i) transients but had little effect on capsaicin-induced [Ca(2+)](i) transients. The inhibitory effect of U50,488 was abolished by the kappa-opioid antagonist nor-Binaltorphimine dihydrochloride (nor-BNI; 100 nM), and by high concentrations of naloxone (30-100 nM), but not by low concentrations of naloxone (3 nM). We conclude that mechanically induced [Ca(2+)](i) transients in small diameter DRG somas are mediated by influx of Ca(2+) through a Gd(3+)- and amiloride-sensitive plasma membrane pathway that is co-expressed with capsaicin-sensitive channels. Mechanical-, but not capsaicin-mediated, Ca(2+) transients are sensitive to kappa-opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Development of constipation in nursing home residents.

PURPOSE: Constipation is a common complaint among geriatric patients and may result in significant morbidity, especially among nursing home residents. The prevalence of constipation increases with advancing age and may be a result of the aging process, but the exact cause is unknown. The aim of this study was to describe the prevalence of constipation and to determine risk factors for the development of constipation in a large population of nursing home residents. METHODS: The Minimum Data Set is an assessment instrument used in nearly all Medicare-certified and Medicaid-certified nursing facilities. Nursing home residents who were at least 65 years of age and who had assessments at baseline and at three months were included in the study (N = 21,012). Baseline risk factors were included in a multivariate logistic regression to determine their association with the development of constipation. To allow causal implications, nursing home residents with constipation at baseline were excluded. The variables examined included medications, mobility, comorbid illness, and nutrition. RESULTS: The mean age (+/- standard deviation) of nursing home residents was 83 +/- 8 years, and the population was 70 percent female and 83 percent white. At baseline, the prevalence of constipation was 12.5 percent (N = 2,627). By the three-month assessment, 7 percent (N = 1,291) of nursing home residents had developed constipation. The factors associated independently with the development of constipation were, in order of magnitude, race, decreased fluid intake, pneumonia, Parkinson's disease, and the presence of allergies. Congestive heart failure and the use of a feeding tube were two factors identified as having a protective effect. CONCLUSION: The variables associated with the development of constipation may be used to identify geriatric nursing home residents at risk and to prevent constipation and its potential complications. Further study is needed to demonstrate a causal relationship between the risk factors and the development of constipation.

Aged↗
PubMed2000

GERD progressing to diffuse esophageal spasm and then to achalasia.

The pathophysiology of achalasia is not completely understood. Several reports have suggested that esophageal motility disorders may progress from one type to another. We report a patient with symptoms and esophageal motility findings consistent with gastroesophageal reflux who subsequently developed a diffuse esophageal spasm and then achalasia. We believe this to be the first report showing such a progression in esophageal motility.

Adult↗
PubMed1999

Involvement of stretch-sensitive calcium flux in mechanical transduction in visceral afferents.

The spinal and vagal visceral innervation to the gastrointestinal tract contains mechanosensitive afferents that are activated by contraction, distension of smooth muscle or movement in the receptive field. The mechanism by which free nerve endings detect changes in smooth muscle tension is not clear. The present study investigated the effects of mechanical stimulation on dorsal root ganglion neurons in vitro. Neurons were cultured using standard techniques and used in experiments after 24-72 h. Intracellular calcium [Ca2+]i was visualized using a video microscopic technique (Attoflour) in Fura-2 loaded neurons. DRG neurons innervating the stomach or colon were identified by the presence of a retrograde tracer, dextran-conjugated Texas Red, injected into the visceral wall 14-28 days previously. Increases in [Ca2+]i were measured in response to transient (0.5 s) mechanical stimulation of the cell soma using a flame polished probe. Approximately 25% of the whole population of DRG neurons (n = 199) were mechanosensitive, showing a transient rise in [Ca2+]i. In labeled afferents (n = 12), approximately 40% of neurons were mechanosensitive. The increase in [Ca2+]i in response to mechanical stimulation was reduced (100 microM) or abolished (250 microM) by superfusion with gadolinium or by removal of extracellular calcium. Cell somata of visceral spinal afferents show a stretch-sensitive calcium flux that may be involved in sensory transduction of mechanical stimuli that lead to autonomic and sensory reflexes.

Animals↗
PubMed1999

Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome.

OBJECTIVE: Abdominal pain is thought to be a hallmark of the irritable bowel syndrome (IBS), although currently used symptom criteria do not differentiate between abdominal pain and discomfort. By focusing on viscerosensory symptoms, we sought to determine: 1) which type of symptoms are most commonly reported by IBS patients, and 2) whether patients who report pain as their most bothersome symptom differ in clinical, psychological, and physiological characteristics. METHODS: A total of 443 consecutive new patient referrals to a tertiary referral center for functional gastrointestinal disorders who met symptom criteria for IBS were given validated, psychometric, health status, and bowel symptom questionnaires containing specific questions regarding the patients' predominant viscerosensory gastrointestinal symptom. Of these patients, 155 (35%) also met criteria for functional dyspepsia. A representative subset of the total IBS patient population (n = 58) underwent evaluation of perceptual responses to controlled rectal distension before and after a noxious sigmoid conditioning stimulus. RESULTS: Viscerosensory symptoms clustered into four groups: 1) abdominal pain, 2) bloating-type discomfort, 3) sensation of incomplete rectal evacuation, and 4) extraabdominal (chest pain or pressure and nausea). A total of 66% of patients reported gas as one of their viscerosensory symptoms, whereas 60% reported abdominal pain as one of their symptoms. Only 29% rated abdominal pain as their most bothersome symptom, whereas bloating-type symptoms were listed by 60% as most bothersome. Although pain predominance did not correlate with the severity of gastrointestinal or psychological symptoms, there was a significant correlation with the development of rectal hypersensitivity in response to the sigmoid conditioning stimulus. CONCLUSIONS: In a tertiary referral population of IBS patients: 1) abdominal pain is reported by only one third of patients as their most bothersome viscerosensory symptoms; and 2) pain-predominance correlates with development of rectal hypersensitivity after a noxious sigmoid stimulus.

Abdominal Pain↗
PubMed1999

Inflammation of the gastro-oesophageal junction (carditis) in patients with symptomatic gastro-oesophageal reflux disease: a prospective study.

BACKGROUND: Recent data have suggested that cardia biopsy specimens may be more reflective of gastro-oesophageal reflux disease (GORD) than squamous biopsy specimens. AIMS: To assess the distribution, severity, and types of mucosal injury in GORD. PATIENTS: Thirty patients with symptomatic GORD with no or minimal erosions. METHODS: Biopsies were performed at the squamocolumnar junction (Z-line) and 1-2 cm below the Z-line. Injury to the columnar mucosa was scored for inflammatory cells, epithelial cell abnormalities, and for the presence of intestinal metaplasia and Helicobacter pylori. A carditis score above 2 was considered positive (maximum score = 9). RESULTS: Mean carditis scores and percentages of patients with a positive carditis score were higher in Z-line biopsy specimens containing both squamous and columnar mucosa than in those with just columnar mucosa or in specimens taken 1-2 cm below the Z-line. Carditis at the Z-line was focal in 49% of the specimens and was always present adjacent to the squamous epithelium. Goblet cells were present more frequently in the specimens immediately at the Z-line than in those 1-2 cm below the Z-line. H pylori was present in only four patients. The mean carditis scores of specimens 1-2 cm below the Z-line in these patients was significantly higher than in those patients without H pylori. CONCLUSIONS: Mucosal injury at the gastric cardia is highly localised to the region adjacent to the squamocolumnar junction in patients with GORD. Morphological studies of the cardia in GORD should focus on tissue samples that contain both squamous and columnar epithelium in order to obtain an accurate picture of the spectrum of injury.

Adult↗
PubMed1999

Approaches to the modulation of abdominal pain.

Despite their high prevalence and significant economic impact on the health care system, functional gastrointestinal disorders have evaded successful therapy. Conventional medical therapies are based on inadequate disease models, and the great majority of published treatment trials are flawed in their design, permitting no conclusions to be drawn about the true efficacy of any particular treatment. During the past several years, a new, comprehensive disease model based on alterations in brain-gut interactions has rapidly evolved. Even though the precise mechanisms and sites underlying these alterations remain incompletely understood, plausible targets for the development of effective pharmacological treatments are receptors on peripheral terminals of visceral afferent nerves (opioids and serotonin), ion channels and receptors on dorsal horn neurons within the spinal cord (opioids, glutamate, calcitonin gene-related peptide and neurokinin-1), and supraspinal targets in the brainstem within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine and acetylcholine). Regardless of the primary pathophysiology underlying functional gastrointestinal disorders (ie, central versus peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may become effective therapies in the future.

Abdominal Pain↗
PubMed1998

Brain-gut interactions: implications for newer therapy.

Despite their high prevalence and significant economic impact on the healthcare system, functional GI disorders have evaded successful therapy. Conventional medical therapies are based on inadequate disease models, and the great majority of published treatment trials are flawed in their design, thus not permitting to draw any conclusions about true efficacy of any particular treatment. The past several years have seen the rapid evolution of a new, comprehensive disease model, based on alterations in brain-gut interactions. Even though the precise mechanisms and sites underlying these alterations remain incompletely understood, plausible targets for the development of effective pharmacologic treatment are receptors on peripheral terminals of visceral afferent nerves (opioids, serotonin), ion channels and receptors on dorsal horn neurons within the spinal cord (opioids, glutamate, CGRP, NK-1) and supraspinal targets in the brainstem, within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine, acetylcholine). Regardless of the primary pathophysiology underlying functional GI disorders (i.e. central vs. peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may be effective.

Brain↗
PubMed1998

The effects of preoperative irradiation on peripheral nerve regeneration.

The purpose of this study was to evaluate the effects of preoperative external cobalt60 beam irradiation on nerve regeneration. Ninety 250-g male Sprague-Dawley rats were studied. Peripheral nerve regeneration was measured by walking track analysis and histomorphology of the proximal, grafted, and distal nerve segments. Ninety animals were randomly assigned to one of five treatment groups, receiving a total fractionated dose of 30, 50, 70, and 90 Gy. Each animal received a 15-mm interposition nerve graft into the right posterior tibial nerve 6 weeks following completion of radiation therapy. The left leg served as a control. The remaining 10 animals received a nerve isograft subjected to a single dose of 30 Gy prior to placement (group 5). Walking track analysis was performed monthly through 8 months. At the conclusion of 120 and 240 days, sections of the proximal, grafted, and distal nerve were harvested, stained, and examined histomorphologically. Evaluation of the print length index demonstrated no statistical difference between our previously established nonirradiated controls, the irradiated groups, and the irradiated isograft group (group 5). The total number of axons per square millimeter was significantly decreased in the distal segment of all irradiated groups when compared with the controls. No statistical difference in number of axons per square millimeter was noted in the irradiated isograft group. Furthermore, no statistical difference was noted in the nerve fiber density between the control group, the preoperative irradiated groups, or the irradiated isograft group (group 5). Despite the reduction in myelinated regenerating fibers, no reduction in function was observed as measured by walking track analysis. Thus, immediate reconstruction of peripheral nerve defects in the face of preoperative irradiation may not be contraindicated.

Animals↗
PubMed1998

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↗
PubMed1997

Prolonged nausea and vomiting after high dose chemotherapy and autologous peripheral stem cell transplantation in the treatment of high risk breast carcinoma.

BACKGROUND: Nausea and vomiting immediately after chemotherapy is a well recognized complication of cancer drug treatment; it is usually short-lived and controllable by modem antiemetics. The authors report a high incidence of prolonged nausea and vomiting after high dose chemotherapy with autologous peripheral stem cell transplantation (PSCT) in the treatment of high risk breast carcinoma patients. METHODS: Patients with high risk breast carcinoma were conditioned with high dose carmustine, cisplatin, and cyclophosphamide followed by autologous PSCT. In Part I of the study, patients who received PSCT at UCLA Medical Center were identified if they were either readmitted with dehydration secondary to nausea and vomiting or referred to a gastroenterology specialist for the treatment of intractable nausea and vomiting. In Part II of the study, the authors examined a series of 38 women treated at UCLA Medical Center in 1993 for high risk breast carcinoma to determine the incidence of prolonged postchemotherapy nausea and vomiting (PPNV) after PSCT. These women were followed at 2-week intervals with a quality of life evaluation that included questions about nausea and vomiting. RESULTS: In Part I of the study, the authors identified 9 women with more than 1 month of significant nausea and vomiting after PSCT without evidence of obstruction or mucositis. Hospitalization was frequently required for hydration. Gastroparesis was found in all four patients who underwent gastric emptying studies. The nausea and vomiting responded to the promotility drug cisapride and high dose corticosteroids. In Part II of the study, the authors found that PPNV was frequent; 24% of patients had significant nausea and 18% had significant vomiting 6 weeks after PSCT, despite treatment with standard antiemetics. CONCLUSIONS: PPNV is a frequent complication of high dose chemotherapy with the aforementioned regimen. It may be due to gastroparesis and represents a form of gastrointestinal toxicity to chemotherapy not previously reported.

Adult↗
PubMed1997

Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Only a fraction of patients with irritable bowel syndrome (IBS) show hypersensitivity to rectal distention. The current study sought to determine if repetitive high-pressure stimulation of sigmoid mechanoreceptors modulates perception of rectal pain and discomfort. METHODS: In 14 patients with IBS and 11 healthy controls, perception thresholds for discomfort and pain during rectal sensory tracking and verbal descriptor ratings of the perceived intensity of a rectal tonic stimulus were obtained before and after repetitive high-pressure mechanical sigmoid stimulation. Gastrointestinal and psychological symptoms were assessed by questionnaires. RESULTS: Despite heterogeneity in baseline rectal sensitivity in patients with IBS, after sigmoid stimulation, 100% of patients, regardless of baseline sensitivity, developed rectal hyperalgesia manifested by at least two of the following three criteria: lowered thresholds for pain and discomfort and increased viscerosomatic referral and lower abdominal discomfort outlasting the experimental stimulation. This pattern of responses was not observed in any of the healthy controls. CONCLUSIONS: In patients with IBS, repetitive stimulation of sigmoid splanchnic afferents results in the development of central sensitization manifested as hyperalgesia and increased viscerosomatic referral during rectal distention and as spontaneous rectosigmoid hyperalgesia in the absence of applied stimuli. Repetitive sigmoid contractions may induce rectosigmoid hyperalgesia in patients with IBS.

Adult↗
PubMed1997

Sigmoid afferent mechanisms in patients with irritable bowel syndrome.

Up to 60% of patients with IBS have lowered perception thresholds in the rectum to balloon distension. The current study sought to test the hypothesis that IBS patients with normal perception thresholds in the rectum show hypersensitivity of afferent pathways in the sigmoid colon. Eleven healthy normal subjects and eight IBS patients with normal rectal perception thresholds underwent a balloon distension protocol in the sigmoid and rectum. Discomfort thresholds, receptive relaxation, compliance, and referral patterns were measured. Although IBS patients had significantly lower discomfort thresholds in the sigmoid when measured as volume, pressure, and wall tension, thresholds were similar to normals. Receptive relaxation and dynamic compliance were significantly decreased in IBS patients in the sigmoid. Referral patterns were similar during sigmoid distention in IBS patients in comparison to normals. Despite normal perception thresholds in rectum and sigmoid, IBS patients show evidence for alterations in rectosigmoid afferent mechanisms. In the sigmoid, this is seen in the form of reduced reflex relaxation and compliance and in the rectum in the form of altered viscerosomatic referral.

Adult↗
PubMed1996

Effects of the corticotropin-releasing factor (CRF) on rectal afferent nerves in humans.

Corticotropin-releasing factor (CRF) released in the gastrointestinal mucosa from immune cells or enterochromaffin cells may play a role in the modulation of rectal afferent function. In the current study we evaluated the effects of peripherally administered CRF on afferent mechanisms in the human rectum. We used rectal balloon distention in seven healthy volunteers to evaluate the effect of CRF (1 microgram/kg) on visceral afferents originating in the rectum which are involved in the following functions: thresholds and intensity of conscious perception, receptive relaxation, reflex inhibition of internal anal sphincter and a viscerosomatic reflex. Rectal mechanoreceptors were stimulated either by distending the rectum using a volume ramp (40 and 400 mL/min), or by intermittent phasic distention. CRF decreased the thresholds and increased the intensity for the sensation of discomfort in response to both ramp and phasic distention. During slow ramp distention, CRF also lowered the stool threshold. CRF increased rectal compliance during slow ramp distention without affecting the rate of receptive relaxation or the inflection point of the compliance curve. CRF had no effect on viscerosomatic referral patterns, or on the rectoanal inhibitory reflex. These findings are consistent with a dual effect of CRF on afferent pathways mediating perception of aversive rectal sensations, and on rectal smooth muscle.

Adult↗