Assistência à saúde de pessoas com doenças colorretais no sistema público a perspectiva do usuário / Health care for people with colorectal diseases in the public system: the user's perspective

Trata-se de um estudo de desenho misto, do tipo sequencial explanatório, sendo que na etapa quantitativa descritiva e transversal, objetivou-se analisar a demanda de atendimento de assistência de pessoas com queixas colorretais em Unidades de Saúde da Família no Sistema Único de Saúde (SUS); e na etapa qualitativa exploratória, interpretar o mapa de cuidado de pessoas com adoecimento colorretal crônico no SUS (Parecer No. 210/2018 CEP/EERP-USP). Na etapa quantitativa aplicou-se um instrumento de coleta de dados, elaborado pelas pesquisadoras, com base na revisão de literatura, para caracterização sociodemográfica, clínica, terapêutica e de referência de participantes usuários da Estratégia Saúde da Família com queixas colorretais, mediante critérios de inclusão e exclusão, no período de abril a setembro de 2019. A análise estatística descritiva dos dados indicou, que do total de 107 participantes, predominou 78 (72,9%) que tinham idade acima de 60 anos, 64 (59,8%) eram do sexo feminino, 61 (57%) tinham até oito anos de estudos, 68 (63,65) com companheiro, 56 (52,3%) eram aposentados, 45 (42,1%) apresentavam renda de até um salário mínimo e 95 (88,8%) não possuíam plano de saúde privado, sendo que o encaminhamento para o nível secundário foi devido ao protocolo de rastreamento para 62 (57,9%) e 45 (42,1%) por queixa colorretal, todos haviam realizado a Pesquisa de Sangue Oculto e destes, 78% tiveram resultado positivo; todos os entrevistados haviam recebido encaminhamento para realizar a colonoscopia. Além disso, 78 (72,9%) eram sedentários; e 66 (61,7%) consumiam carne vermelha e 45 (42,1%) embutidos. A análise univariada da associação das variáveis hábitos de vida, resultado de colonoscopia, presença de alterações displásicas ou doença colorretal não foi estatisticamente significante entre consumo de carne vermelha, consumo de embutidos ou ambos com o desfecho de colonoscopia normal, displasia intestinal com potencial neoplásico e doença diverticular ou orificial. Estes resultados dimensionaram o contexto de atendimento desta clientela na Atenção Primária à Saúde (APS), auxiliando o refinamento dos critérios de seleção dos possíveis participantes da etapa qualitativa. A etapa qualitativa foi realizada, no período de junho de 2020 a julho de 2020, mediante os critérios de seleção: pessoas acima de 18 anos, de ambos os sexos, com diagnóstico colorretal crônico: Doença inflamatória intestinal ou Neoplasia colorretal em internação especialidade de Coloproctologia de um hospital universitário público, de assistência terciária/quaternária. Nesta etapa, os dados foram coletados por meio de entrevistas individuais em profundidade com 14 participantes, cuja caracterização sociodemográfica, clínica e terapêutica revelou internação para tratamento cirúrgico, com maior gravidade clínica, sendo que 13 apresentavam diagnóstico de Neoplasia colorretal. Utilizou-se questões norteadoras, diário de campo, observação não participante e participante para a obtenção dos dados, que foram interpretados com Análise Temática, fundamentado pela Epidemiologia Social. O Mapa de Cuidado construído por estes, iniciou-se com queixas e sinais/sintomas gastrointestinais, envolvendo situações de maior gravidade clínica, com sofrimento físico e psicoemocional; diagnosticados como parasitose, hemorroidas e anemia na APS, cujos tratamentos não foram resolutivos. Para esta interpretação, articulou-se as ações destes participantes às suas queixas, à condição socioeconômica, cultural e psicoemocional, assim como à capacidade de enfrentamento do adoecimento oncológico e dos tratamentos, no qual ocorreu a focalização da vida destes e de suas famílias nos acontecimentos clínicos e terapêuticos do contexto de atendimento terciário/quaternário. O acesso aos serviços do SUS ocorreu de diferentes maneiras, com utilização de estratégias que agilizaram e asseguraram a resolução do seu problema de saúde, sendo que o agir leigo foi uma produção social, no cotidiano do SUS, mediado pelos acontecimentos, pelas ações dos profissionais e de suas próprias ações ou pelo sistema de apoio social, enfatizando-se o sofrimento desta clientela na busca pela assistência à saúde. Este mapa de cuidado mostrou que o agir leigo constituiu uma regulação assistencial no SUS, tão importante quanto as outras formas, composto pelos vínculos dos pacientes com profissionais dos serviços dos níveis primário, secundário, terciário/quaternário, de suas necessidades e possibilidades, além dos pontos de acesso ao sistema. Estes resultados poderão contribuir na implementação da gestão de cuidados de pessoas com adoecimento colorretal crônico no SUS, dando voz e protagonismo àquele que busca pela assistência à saúde

This is a study of mixed design, of an explanatory sequential type, and in the quantitative descriptive and transversal stage, the objective was to analyze the demand for assistance from people with colorectal symptoms in Family Health Units in the Unified System Health (SUS); and in the qualitative exploratory stage, interpret the care map for people with chronic colorectal illness in SUS (Note Nº. 210/2018 CEP / EERP-USP). In the quantitative stage, a data collection instrument was developed by the researchers, based on the literature review, for sociodemographic, clinical, therapeutic, and reference characterization of participating users of the Family Health Strategy with colorectal symptoms, considering inclusion and exclusion criteria, from April to September 2019. The descriptive statistical analysis of the data indicated that, out of a total of 107 participants, 78 (72.9%) predominated who were over 60 years old, 64 (59.8%) were female, 61 (57%) had up to eight years of study, 68 (63.65) with a partner, 56 (52.3%) were retired, 45 (42.1%) had an income of up to one minimum wage and 95 (88.8%) did not have a private health plan, and the referral to the secondary level was due to the screening protocol for 62 (57.9%) and 45 (42.1%) due to colorectal complaints, all had carried out the Occult Blood Survey and of these, 78% had a positive result; all respondents had been referred for colonoscopy. In addition, 78 (72.9%) were sedentary; and 66 (61.7%) consumed red meat and 45 (42.1%) sausages. The univariate analysis of the association of the variables life habits, the result of colonoscopy, presence of dysplastic changes or colorectal disease was not statistically significant between consumption of red meat, consumption of sausages or both with the outcome of normal colonoscopy, intestinal dysplasia with neoplastic potential and diverticular or artificial disease. These results have dimensioned the context of care for this clientele in Primary Health Care (PHC), helping to refine the selection criteria of possible participants in the qualitative stage. The qualitative stage was carried out, from June 2020 to July 2020, using the selection criteria: people over 18 years of age, of both sexes, with chronic colorectal diagnosis: Inflammatory bowel disease or Colorectal neoplasia in Coloproctology specialty hospitalization of a public university hospital, of tertiary/quaternary assistance. In this stage, data were collected through in-depth individual interviews with 14 participants, whose sociodemographic, clinical, and therapeutic characterization revealed hospitalization for surgical treatment, with greater clinical severity, with 13 presenting a diagnosis of colorectal neoplasia. Guiding questions, field diary, non-participant and participant observation were used to obtain the data, which were interpreted with Thematic Analysis, based on Social Epidemiology. The Care Map built by them started with gastrointestinal complaints and signs/symptoms, involving situations of greater clinical severity, with physical and psycho-emotional suffering; diagnosed as parasitosis, hemorrhoids, and anemia in PHC, whose treatments were not effective. For this interpretation, the actions of these participants were linked to their complaints, to their socioeconomic, cultural, and psycho-emotional condition, as well as to their ability to cope with oncological illness and treatments, in which the lives of these and their families were focused on the events and therapeutic aspects of the tertiary/quaternary care context. Access to SUS services occurred in different ways, using strategies that streamlined and ensured the resolution of their health problem, and the lay agency as social production, in the daily routine of SUS, mediated by events, by the actions of professionals and their actions or the social support system, emphasizing the suffering of this clientele in the search for health care. This care map showed that the lay act constituted an assistance regulation in SUS, as important as the other forms, composed by the bonds of patients with professionals from the services of the primary, secondary, tertiary/quaternary levels, of their needs and possibilities, in addition to the access points to the system. These results may contribute to the implementation of the care management of people with chronic colorectal illness in SUS, giving voice and leadership to those seeking health care.

Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging.

BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.

Standardized herbal treatments on functional bowel disorders: moving from putative mechanisms of action to controlled clinical trials.

Symptom relief in functional gastrointestinal disorders (FGID) is frequently sought with complementary and alternative medicine, and various herbal medicine compounds are popular in different parts of the world. Only a few products, however, are standardized and are backed by scientific evidence. This review mainly focuses on mechanistic and clinical data in support of the Japanese traditional compound Rikkunshi-to (RKT) and of STW-5. Their effects on gut sensori-motor function, neurohormonal network, and controlled clinical data in FGID are revised. RKT and STW-5 appear to possess some degree of gastroprokinetic, visceral analgesic properties, and seem to increase the gastric accommodation response. Controlled trials of RKT and STW-5 support at least a modest effect on symptoms of functional dyspepsia and irritable bowel syndrome, with low side effects profile. With the widespread use of herbals and the relative paucity of effective pharmacological options for FGID, rigorous studies to further elucidate pharmacological actions and clinical applications of herbal compounds are a priority.

Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses.

PURPOSE: Plecanatide, an analogue of uroguanylin, activates the guanylate cyclase C (GC-C) receptor found on the GI mucosal epithelial cells, leading to secretion of fluid, facilitating bowel movements. Plecanatide is being investigated as a potential treatment for constipating GI disorders. The aim of this investigation was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single doses of plecanatide in healthy volunteers. METHODS: A total of 72 healthy volunteers at a single site were randomized in 9 cohorts to receive oral plecanatide or placebo from 0.1 to 48.6 mg. Plasma PK samples were collected pre-dose and post-dose. PD assessments included time to first stool, stool frequency, and stool consistency using the Bristol Stool Form Scale. All adverse events were documented. RESULTS: Plecanatide was safe and well-tolerated at all dose levels. A total of 17 of 71 subjects (23.9%) reported 25 treatment-emergent adverse events (TEAEs) during the study. The number of TEAEs reported by subjects who received plecanatide or placebo was comparable (24.5 vs. 22.2%, respectively). There were no dose-related increases in TEAEs or any SAEs reported. No measurable systemic absorption of oral plecanatide was observed at any of the oral doses studied, utilizing an assay sensitive down to 1 ng/mL. CONCLUSIONS: Plecanatide, an oral GC-C agonist, acting locally within the GI tract without measurable systemic exposure, was safe and well-tolerated in single doses up to 48.6 mg. The study was not powered for statistical analyses, but trends in PD parameters supported continued clinical development.

A role for O-1602 and G protein-coupled receptor GPR55 in the control of colonic motility in mice.

OBJECTIVE: The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid (CB) receptor, whose role in the gastrointestinal (GI) tract remains unknown. Here we studied the significance of GPR55 in the regulation of GI motility. DESIGN: GPR55 mRNA and protein expression were measured by RT-PCR and immunohistochemistry. The effects of the GPR55 agonist O-1602 and a selective antagonist cannabidiol (CBD) were studied in vitro and in vivo and compared to a non-selective cannabinoid receptor agonist WIN55,212-2. CB1/2(-/-) and GPR55(-/-) mice were employed to identify the receptors involved. RESULTS: GPR55 was localized on myenteric neurons in mouse and human colon. O-1602 concentration-dependently reduced evoked contractions in muscle strips from the colon (∼60%) and weakly (∼25%) from the ileum. These effects were reversed by CBD, but not by CB1 or CB2 receptor antagonists. I.p. and i.c.v. injections of O-1602 slowed whole gut transit and colonic bead expulsion; these effects were absent in GPR55(-/-) mice. WIN55,212-2 slowed whole gut transit effects, which were counteracted in the presence of a CB1 antagonist AM251. WIN55,212-2, but not O-1602 delayed gastric emptying and small intestinal transit. Locomotion, as a marker for central sedation, was reduced following WIN55,212-2, but not O-1602 treatment. CONCLUSION: GPR55 is strongly expressed on myenteric neurons of the colon and it is selectively involved in the regulation of colonic motility. Since activation of GPR55 receptors is not associated with central sedation, the GPR55 receptor may serve as a future target for the treatment of colonic motility disorders.

A novel UPLC-MS/MS method for simultaneous quantification of rhein, emodin, berberine and baicalin in rat plasma and its application in a pharmacokinetic study.

BACKGROUND: Dahuang Huanglian Xiexin Decoction (DHXD) is a classical formula in traditional Chinese medicines. In this study, a novel UPLC-MS/MS method was developed for the simultaneous quantification of rhein, emodin, berberine and baicalin, the major bioactive compounds of DHXD in rat plasma. RESULTS: The method possessed high sensitivity and ultrashort analysis time (7 min). Linearity, accuracy, precision and extraction recovery of four analytes were all satisfactory. The method was then successfully applied in a pharmacokinetic study of four bioactive components after a single oral administration of DHXD extract to rats. CONCLUSION: The method was applicable for simultaneous bioanalysis of rhein, emodin, berberine and baicalin.

Novel diagnostics and therapy of colonic motor disorders.

Colonic motor abnormalities are implicated in several gastrointestinal disorders including constipation, irritable bowel syndrome and functional diarrhoea. Defining the colonic abnormalities is difficult and several novel techniques including, high-resolution fibre optic manometry, wireless motility capsules, ultrasound and magnetic resonance imaging have emerged to help in the diagnosis of these conditions. Coupled with the developing techniques are the novel treatments that look to restore normal colonic motility. These treatments include pharmacological agents (pharmabiotics, serotonin agonist, secretagogues) and medical devices (sacral nerve stimulation, transcutaneous electrical stimulation and biofeedback). This review summarizes the novel techniques used to record and define colonic motor abnormalities and the current status of the emerging treatments used to treat them.

New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders.

IMPORTANCE OF THE FIELD: Gastrointestinal (GI) dysmotility is an important mechanism in functional GI disorders (FGIDs) including constipation, irritable bowel syndrome, functional dyspepsia, and gastroparesis. 5-hydroxytryptamine(4) (5-HT(4)) receptors are targets for the treatment of GI motility disorders. However, older 5-HT(4) receptor agonists had limited clinical success because they were associated with changes in the function of the cardiac HERG potassium channel. AREAS COVERED IN THIS REVIEW: We conducted a PubMed search using the following key words alone or in combination: 5-HT(4), safety, toxicity, pharmacokinetics, pharmacodynamics, clinical trial, cardiac, hERG, arrhythmia, potassium current, elderly, prucalopride, ATI-7505, and velusetrag (TD-5108), to review mechanisms of action, clinical efficacy, safety and tolerability of three new-generation 5-HT(4) receptor agonists. WHAT THE READER WILL GAIN: Prucalopride, ATI-7505, and velusetrag (TD-5108) are highly selective, high-affinity 5-HT(4) receptor agonists that are devoid of action on other receptors within their therapeutic range. Their efficacy has been demonstrated in pharmacodynamic studies which demonstrate acceleration of colonic transit and, to a variable degree, in clinical trials that significantly relieve chronic constipation. Currently available evidence shows that the new 5-HT(4) receptor agonists have safe cardiac profiles. TAKE HOME MESSAGE: New-generation 5-HT(4) receptor agonists and future drugs targeting organ-specific splice variants are promising approaches to treat GI dysmotility, particularly colonic diseases.

Functional constipation in children: a systematic review on prognosis and predictive factors.

BACKGROUND AND AIM: Knowledge regarding prognosis and factors influencing the clinical course of functional constipation in children is important to enable general practitioners and paediatricians to give accurate patient information, to compare treatment strategies, and identify children with high risk for unfavourable outcome. The objective of the study was to investigate and summarize the quantity and quality of evidence on prognosis of childhood constipation with and without treatment and its predictive factors. METHODS: An extensive literature search in MEDLINE and Embase was performed to identify prospective follow-up studies evaluating the prognosis or prognostic determinants of functional constipation. Methodological quality was assessed using a standardised list. Results on prognosis of constipation were statistically pooled, and the influence of prognostic factors was summarised in a best evidence synthesis. RESULTS: The search strategy resulted in a total of 2882 abstracts. Only 14 publications met our inclusion criteria, of which 21% scored high methodological quality. Included studies showed large heterogeneity in study populations and outcome measures. Without regard to these differences, 49.3% +/- 11.8% of all of the children followed for 6 to 12 months were found to recover and taken off laxatives. The percentage of children who were free from complaints, regardless of laxative use, after 6 to 12 months was 60.6% +/- 19.2%. There is substantial evidence that defecation frequency and a positive family history are not associated with recovery from constipation. CONCLUSIONS: The few studies published on prognosis of childhood functional constipation and predictive factors showed large heterogeneity and poor methodological quality. Overall, 60.6% of children are found to be free from symptoms after 6 to 12 months. Recovery rate showed no relation with defecation frequency or positive family history. Based on the present literature, we are unable to identify a group of children with high risk for poor prognosis.

Irritable bowel syndrome.

INTRODUCTION: The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT(3) receptor antagonists (alosetron and ramosetron); 5HT(4) receptor agonists (tegaserod); antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]); antispasmodics (including peppermint oil); cognitive behavioural therapy (CBT); hypnotherapy; soluble and insoluble fibre supplementation; and loperamide.

Alterations in the intestinal microbiota and functional bowel symptoms.

Functional gastrointestinal disorders (FGIDs) are highly prevalent in Western countries yet no single mechanism or etiological agent that initiates IBS has been identified. Current research has implicated the intestinal microbiota with FGIDs. This article reviews the available literature/data regarding the intestinal microbiota and FGIDS. The possible relationships between the intestinal microbiota and the intestinal function and functional bowel symptoms are discussed.

The effects of regular consumption of short-chain fructo-oligosaccharides on digestive comfort of subjects with minor functional bowel disorders.

A comparative, randomised, double-blind trial was performed in the medical departments of five hospitals to study the effects of regular consumption of short-chain fructo-oligosaccharides (sc-FOS) on the digestive comfort of subjects with minor functional bowel disorders (FBD). In step 1, 2235 subjects were questioned to assess the incidence and intensity of digestive disorders. In step 2, 105 of these patients diagnosed with minor FBD were randomised into two groups to receive either 5 g sc-FOS or 5 g placebo (sucrose and maltodextrins) per d over a 6-week period. The incidence and intensity of digestive disorders were assessed at the end of the treatment period (day 43) using the step 1 questionnaires. A quality-of-life questionnaire was also completed at the start and end of the treatment period to assess potential effects on well-being and social performance. In step 1, 44 % of the subjects questioned presented FBD, of whom 57.1 % suffered from minor FBD. In step 2, on day 43, the intensity of digestive disorders decreased by 43.6 % in the sc-FOS group v. a 13.8 % increase in the placebo group (P = 0.026). Symptoms were experienced less frequently by 75.0 % of subjects in the sc-FOS group, while 53.8 % of controls experienced no change (P = 0.064). Using the functional digestive disorders quality of life questionnaire, the discomfort item scores increased in the sc-FOS group (P = 0.031). However, expressed as change in quality of life (improvement, worsening or unchanged), daily activities were significantly improved in the sc-FOS group (P = 0.022). Regular consumption of sc-FOS may improve digestive comfort in a working population not undergoing medical treatment.

Serotonin and neuroprotection in functional bowel disorders.

The 5-HT(4) partial agonist tegaserod is effective in the treatment of chronic constipation and constipation predominant irritable bowel syndrome. 5-HT(4) receptors are located on presynaptic terminals in the enteric nervous system. Stimulation of 5-HT(4) receptors enhances the release of acetylcholine and calcitonin gene related peptide from stimulated nerve terminals. This action strengthens neurotransmission in prokinetic pathways, enhancing gastrointestinal motility. The knockout of 5-HT(4) receptors in mice not only slows gastrointestinal activity but also, after 1 month of age, increases the age-related loss of enteric neurons and decreases the size of neurons that survive. 5-HT(4) receptor agonists, tegaserod and RS67506, increase numbers of enteric neurons developing from precursor cells and/or surviving in culture; they also increase neurite outgrowth and decrease apoptosis. The 5-HT(4) receptor antagonist, GR113808, blocks all of these effects, which are thus specific and 5-HT(4)-mediated. 5-HT(4) receptor agonists, therefore, are neuroprotective and neurotrophic for enteric neurons. Because the age-related decline in numbers of enteric neurons may contribute to the dysmotilities of the elderly, the possibility that the neuroprotective actions of 5-HT agonists can be utilized to prevent the occurrence or worsening of these conditions should be investigated.

Mechanisms of serotonergic agents for treatment of gastrointestinal motility and functional bowel disorders.

Most of the body's serotonin is released in the gut where it plays an important role in the control of gastrointestinal (GI) motility, sensitivity and muscle tone by activating different receptor subtypes. This review focuses on the known effects of selective serotonin reuptake inhibitor and serotonin receptor agonists and antagonists on the sensorimotor function of the GI tract and describes the therapeutic potential of these actions for GI motility and functional bowel disorders.

The serotonin reuptake inhibitor citalopram does not affect colonic sensitivity or compliance in rats.

Altered serotonin signaling has been implicated in the pathophysiology of irritable bowel syndrome (IBS). Selective serotonin reuptake inhibitors (SSRI) improve IBS symptoms, although the mechanism of action remains unclear. We assessed the effects of the SSRI, citalopram, on colonic sensitivity and compliance in rats after acute and repeated administration. Colorectal distension was performed in conscious rats. Pressure-volume relationships during colorectal distension (2-20 mmHg), fitted using a power exponential model [Vol=V(max)xexp[-(kappaxRelP)(beta)], were used as a measure of colonic compliance. The visceral pain-related visceromotor response during colorectal distension (10-80 mmHg) was used to assess visceral sensitivity. Pressure-volume curves and visceromotor responses were assessed after acute citalopram (3 or 10 mg/kg, ip) or vehicle and after repeated treatment (7 and 14 days; 3 or 10 mg/kg/day). In vehicle-treated animals, pressure-volume curves were similar over time. Citalopram (acute or repeated treatment) did not affect neither the pressure-volume curves nor the visceromotor response to colorectal distension. Thus, citalopram, after acute or repeated administration, had no significant effects on colon compliance or visceral pain during colorectal distension in rats. These results agree with recent observations in humans suggesting that the therapeutic actions of citalopram in IBS are independent of any effects on colonic sensorimotor function.

Effects of nociceptin/orphanin FQ on rats with cathartic colon.

AIM: To demonstrate the change and effect of nociceptin/orphanin FQ in the colon of rats with cathartic colon. METHODS: The cathartic colon model was established by feeding rats rhubarb for 3 mo, the changes of colonic electromyography were investigated by both suspension muscle strips test and serosal recordings of colonic myoelectrical activity. Immunohistochemical staining (S-P methods) and image analysis were used to determine the changes of nociceptin/orphanin FQ in the proximal colon and distal colon of rats with cathartic colon. RESULTS: Suspension muscle strips test in vitro showed OFQ (10(-9)-10(-6) mol/L) concentration dependently caused an immediate tonic contraction in the isolated colon. But the increase of tension in cathartic colon was less than control groups (P < 0.01). Intravenous administration of OFQ (1 microg/kg) caused phasic contractions in the proximal colon, while the amplitude of phasic contractions caused by OFQ in cathartic colon was much lower than that in the control groups (2.58 +/- 0.41 vs 4.16 +/- 0.53, t = -2.6, P = 0.012). OFQ was highly expressed in the myenteric plexus of the rat colon but not in the muscle cells. The immunoreactivity of OFQ in the proximal colon in cathartic colon rats decreased significantly compared with the control group (P = 0.001). CONCLUSION: Colonic smooth muscle of cathartic colon showed low sensitivity to the stimulation of OFQ, suggesting that it might be caused by the abnormal distribution of OFQ or the abnormalities of receptors, leading to the disorganization of dynamic and incoordinated contractions.

[Treatment of a tetraplegic patient with chronic constipation with the Tibetan remedy Padma Lax--a case report]. / Behandlung der chronischen Obstipation eines tetraplegischen Patienten mit dem tibetischen Arzneimittel Padma Lax -- ein Fallbericht.

BACKGROUND: In spinal cord injuries disturbed defecation, constipation and their concomitant disorders are frequent clinical symptoms. They may severely impair the quality of life of the affected patients. The presented case study and two more case reports, summarized in table form, outline therapeutic difficulties and therapy options in the treatment of constipation in paraplegic patients. CASE REPORT: A 69-year-old male patient with tetraplegia below C4 suffered from disturbed defecation, constipation with recurrent co-prostasis and pronounced meteorism which impeded breathing. Padma Lax was applied for several months, and constipation and the concomitant meteorism were noticeably reduced. CONCLUSION: The herbal preparation based on a formula from Tibetan Medicine may offer new therapeutic options in the care and treatment of patients with severe constipation. This report could also give first indications for controlled clinical studies in tetraplegic patients.