Prevalence and associated factors of lower digestive symptoms in type 2 diabetics in Tunisia.

AIMS: To estimate the prevalence of lower digestive symptoms according to the Rome III criteria among diabetic patients of type 2, and second to identify the factors associated with the digestive symptoms among these subjects. METHODS: A cross-sectional study was carried out among recruited diabetes mellitus type 2 patients from basic health centers at Sousse and Monastir (Tunisia). Diagnosis of digestive symptoms was based on Rome III criteria. We studied the influence of socio-demographic characteristics, life style, diabetes mellitus characteristics, somatization, psychological state (HAD scale) and quality of life (SF-12 scale) on the prevalence of digestive symptoms. RESULTS: Four hundred and seventeen patients were enrolled in our study. The average age was 61.3±10.4 years with a female predominance (68.8%). The overall prevalence of digestive symptoms was 44.8%. The main digestive symptoms found were abdominal bloating (23%), diarrhea (11.7%), constipation (8.6%), irritable bowel syndrome (8.6%) and fecal incontinence (8.1%). Logistic regression showed that digestive intolerance (OR=2.28; 95%CI[2-5.31]), request care for a digestive problem (OR=2.95; 95%CI [1.49-5.83]), anti-acid treatment (OR=4.22; 95%CI [1.13-15.69]), diabetic retinopathy (OR=2.66; 95%CI [1.52-4.7]), somatization (OR=1.75; 95%CI [1.06-2.88]), and a deteriorated mental health state (OR=2.8; [1.66- 4.72]) were the independent factors associated with digestive symptoms. CONCLUSION: Digestive symptoms cause an important request for care and have a negative impact on quality of life of diabetics. Thus digestive symptoms should be systematically diagnosed in patients with type 2 diabete.

Prevalence and risk factors of functional gastrointestinal disorders in early period medical students: a pilot study in Tunisia.

Functional gastrointestinal disorders (FGIDs) are highly prevalent in medical students around the world. However, there is no specific data on FGIDs in Tunisia. The objectives of this study were to evaluate the prevalence of FGIDs in medical students according to the rome III criteria and to identify risk factors associated with these disorders. A self-administered questionnaire survey was carried out among the students from the first and the second year of medical studies. We studied the influence of socio-demographic characteristics, lifestyle, health care seeking, psychosomatic symptoms and hospital anxiety and depression scale on the prevalence of FGIDs among these students. Three hundred and forty-three students (20.3 ± 0.8years) were included in our study. The prevalence of FGIDs was 54.2%. The main FGIDs found were the unspecified functional bowel disorder (46.6%), functional constipation (11.6%), irritable bowel syndrome (7.6%) and functional dyspepsia (6.7%). In logistic regression, abnormal BMI (OR = 2.1, 95% CI= 1-4.3), living in school dormitory (OR = 3.7, 95% CI = 1.7-7.8), low water intake (OR = 2.2, 95% CI = 1.1-4.2), digestive medication use (OR = 3.4, 95% CI= 1.3-8.5), and probable or definite anxiety (OR = 2.5, 95% CI = 1.1-5.8) were the five risk factors associated with FGIDs. We demonstrate a high prevalence of FGIDs (54.2%) among our students. Risk factors for FGIDs were abnormal BMI, living in school dormitory, low water intake, digestive medication use and anxiety.

Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome.

BACKGROUND AND AIMS: Allgrove syndrome is characterized by achalasia, alacrima, and adrenal insufficiency as well as being associated with progressive neurological signs. This is an autosomal recessive disorder due to mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes a protein of 546 amino acids, ALADIN. Mutations in this genwere reported in families from North Africa and Europe. Our objective is to conduct a clinical, molecular and genetic study of 26 Tunisian patients with Allgrove syndrome. METHODS: We report 26 Tunisian patients with between two and four clinical features associated with Allgrove syndrome. Blood samples were collected and isolated DNA derived from subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR and sequencing. PCR-RFLP method was performed to identify the frequent mutations found. RESULTS: Sequencing of the AAAS gene revealed a major homozygous mutation (c.1331+1G>A) in 25 patients and R286X mutation in one patient. The presence of a major mutation in several unrelated affected individuals suggests the presence of a founder effect in Tunisia and allows for a fast and targeted molecular diagnosis. CONCLUSIONS: We created an easy and rapid molecular enzymatic protocol based on PCR-RFLP using MvaI restriction enzyme that directly targets this major mutation and can be used for prenatal diagnosis and genetic counseling for Tunisian families at risk. To the best of our knowledge, this is the first major series report of Allgrove syndrome in Tunisia.

Ghrelin, appetite and gastric electrical stimulation.

Ghrelin is a peptide hormone produced mainly by the stomach and has widespread physiological functions including increase in appetite. The stimulation of the ghrelin system represents a potential therapeutic approach in various disorders characterized by deficient ghrelin signaling or by low appetite. This stimulation may be achieved via pharmacological targeting of the ghrelin receptor with synthetic ghrelin or ghrelin mimetics or via increased endogenous ghrelin production. Recently, it was demonstrated that gastric electrical stimulation (GES) with Enterra parameters results in increased ghrelin production in rats. Furthermore, recent data revealed putative role of ghrelin-reactive immunoglobulins in the modulation of the ghrelin signaling which can be also stimulated by GES. Here, we review the links between GES and ghrelin in existing GES experimental and clinical applications for treatment of gastroparesis, functional dyspepsia or obesity and discuss if GES can be proposed as a non-pharmacological approach to improve ghrelin secretion in several pathological conditions characterized by low appetite, such as anorexia nervosa or anorexia-cachexia syndrome.

Gastric electrical stimulation increases ghrelin production and inhibits catecholaminergic brainstem neurons in rats.

Gastric electrical stimulation (GES) is a new therapeutic option for functional dyspepsia and gastroparesis. In addition to ameliorating nausea and vomiting, GES results in improved appetite which is not always associated with accelerated gastric emptying. To explore the central and peripheral factors underlying GES-associated improvement of appetite we developed a GES model in anaesthetized Wistar rats. During laparotomy, two electrodes were implanted into the stomach and high-frequency low-energy GES (14 Hz, 5 mA) was applied. The effects of 1 h GES were compared with sham stimulation. After GES, c-Fos expression was increased in the mucosal and submucosal layers of the stimulated area (174%). In the stomach, GES increased ghrelin mRNA (178%) and doubled the number of ghrelin-positive cells, resulting in elevated plasma levels of ghrelin (2.3 ± 0.2 vs. 1.6 ± 0.2 ng/mL). In the arcuate nucleus of the hypothalamus, GES increased c-Fos (277%) and agouti-related protein (AgRP) mRNA expression (135%). GES reduced the number of c-Fos-positive cells throughout the nucleus of the solitary tract (between 93 and 75% from rostral to caudal levels) including catecholaminergic neurons (81% at caudal level). Gastric emptying, plasma glucose and heart rate variability were not affected by GES. This study shows that GES may improve appetite via stimulation of main orexigenic pathways, including ghrelin production in the stomach and AgRP in the hypothalamus, as well as by reducing the activity of catecholaminergic brainstem neurons.

Chemotherapy-induced anorexia is accompanied by activation of brain pathways signaling dehydration.

BACKGROUND AND AIMS: Cancer chemotherapy is accompanied by anorexia and mucositis. To clarify the mechanisms of chemotherapy-induced anorexia, we studied the expression of c-fos and appetite-regulating neuropeptidergic and inflammatory mediators in the hypothalamus of rats treated with methotrexate (MTX). METHODS: Sprague-Dawley rats received MTX (2.5mg/kg, subcutaneously) on three consecutive days and were compared with ad libitum- and pair-fed control rats five days after the first injection. RESULTS: MTX administration inhibited food and water intake and induced lean and fat mass losses. MTX also induced mucositis and diarrhea without changes in plasma osmolality. Pair-fed rats lost a similar amount of body weight but had no mucositis or diarrhea. Increased number of c-fos positive hypothalamic vasopressin neurosecretory neurons as well as numerous c-fos positive cells in the subfornical organ and in the organum vasculosum of the lamina terminalis were found in MTX-treated as compared to control or pair-fed rats. In both MTX and pair-fed rats, a decrease of hypothalamic proopiomelanocortin mRNA expression and low plasma levels of interleukin-1ß (IL-1ß) were found reflecting probably the energy deficit. No significant changes of IL-1ß mRNA expression and intensity of microglial staining in the hypothalamus were found in MTX-treated rats. CONCLUSION: The pattern of c-fos expression in the hypothalamus during MTX treatment is similar to that seen with systemic dehydration, which is known to cause anorexia. No evidence of inflammatory origin of anorexia was found, suggesting that chemotherapy accompanied by mucositis and diarrhea may cause anorexia associated with systemic dehydration.

Sensory transcutaneous electrical stimulation improves post-stroke dysphagic patients.

Oropharyngeal dysphagia is frequent in stroke patients and increases mortality, mainly because of pulmonary complications. We hypothesized that sensitive transcutaneous electrical stimulation applied submentally during swallowing could help rehabilitate post-stroke oropharyngeal dysphagia by improving cortical sensory motor circuits. Eleven patients were recruited for the study (5 females, 68 ± 11 years). They all suffered from recent oropharyngeal dysphagia (>eight weeks) induced by a hemispheric (n = 7) or brainstem (n = 4) stroke, with pharyngeal residue and/or laryngeal aspiration diagnosed by videofluoroscopy. Submental electrical stimulations were performed for 1 h every day for 5 days (electrical trains: 5 s every minute, 80 Hz, under motor threshold). During the electrical stimulations, the patients were asked to swallow one teaspoon of paste or liquid. Swallowing was evaluated before and after the week of stimulations using a dysphagia handicap index questionnaire, videofluoroscopy, and cortical mapping of pharyngeal muscles. The results of the questionnaire showed that oropharyngeal dysphagia symptoms had improved (p < 0.05), while the videofluoroscopy measurements showed that laryngeal aspiration (p < 0.05) and pharyngeal residue (p < 0.05) had decreased and that swallowing reaction time (p < 0.05) had improved. In addition, oropharyngeal transit time, pharyngeal transit time, laryngeal closure duration, and cortical pharyngeal muscle mapping after the task had not changed. These results indicated that sensitive submental electrical stimulations during swallowing tasks could help to rehabilitate post-stroke swallowing dysphagia by improving swallowing coordination. Plasticity of the sensory swallowing cortex is suspected.

Gastric electrical stimulation in intractable nausea and vomiting: assessment of predictive factors of favorable outcomes.

BACKGROUND: Gastric electrical stimulation (GES) represents a new therapy in patients with intractable vomiting and nausea. We aimed to determine preoperative factors associated with positive response during GES. Thirty-three consecutive patients received implants for medically refractory nausea or vomiting or both. STUDY DESIGN: Symptoms, Quality of Life (QOL), and gastric emptying (GE) were monitored before and 6 months after implantation. Compared with baseline, dyspeptic symptoms including nausea and vomiting, and QOL all improved at 6 months, yielding a significant weight gain while the GE rate remained unchanged. Twenty-four patients reported improvement; nine remained unimproved at 6 months. RESULTS: In multivariate analysis, baseline QOL and appetite alterations were predictive of improvement; previous history of gastric surgery was associated with failure. Surprisingly, patients with initial delayed GE (21 of 33) displayed similar improvement compared with patients with normal GE. Likewise, basal GE was not found to be predictive of positive outcomes, QOL, or symptoms improvement. CONCLUSIONS: Patients with severe symptoms and altered QOL at inclusion particularly benefit from GES; delay in GE is not predictive of positive outcomes. This suggests that indication for GES should be based on clinical settings rather than initial GE, and then possibly extended to patients with normal GE.

Constipation in 44 patients implanted with an artificial bowel sphincter.

PURPOSE: Constipation with or without obstructed defecation (OD) is frequent in patients with artificial bowel sphincter (ABS). The aims of this study were (1) to evaluate the functional outcome of ABS based on postoperative constipation and (2) to assess pre-implantation data to predict post-implantation constipation. MATERIALS AND METHODS: Thirteen men and 31 women were followed up. Both fecal incontinence and constipation with and without OD were assessed after implantation. Pre-implantation characteristics were compared in patients with and without postoperative constipation. RESULTS: After implantation, nine patients (20.4%) had constipation without OD, 16 patients (36.4%) had OD, and 19 patients (43.2%) had neither of these. Incontinence was significantly more frequent in patients with postoperative constipation with or without OD. In these patients, an increase in preoperative constipation, anismus, and ultraslow waves was noted. CONCLUSION: Constipation with and without OD is frequent after implantation and interfere with the functional outcome of ABS.

Sacral nerve stimulation in fecal incontinence: are there factors associated with success?

PURPOSE: Sacral nerve stimulation has been used successfully in treating fecal incontinence. This study was designed to evaluate the proportion of patients with unsuccessful implantation despite positive test stimulation and to examine and compare factors associated with the success of the transitory and permanent sacral nerve stimulation. METHODS: A total of 61 patients (55 females; median age, 56 (range, 33-77) years) with refractory fecal incontinence underwent temporary stimulation. A 50 percent or greater improvement in the number of episodes of fecal incontinence or urgency was required to proceed to permanent implantation and was the criteria of success of permanent sacral nerve stimulation at the last follow-up visit in implanted patients. The factors compared between the success and the failure groups during temporary and permanent stimulation were patients' age and gender, diagnosis and characteristics of fecal incontinence, previous surgery, quality of life scores, anorectal manometry, endoanal ultrasound, and electrophysiologic tests performed before stimulation. RESULTS: Temporary stimulation was successful in 35 patients (57.4 percent). A permanent neurostimulation device was implanted in 33 patients. Age was the only factor related to success of the temporary stimulation (P=0.03). After permanent implantation, 31 percent of patients did not attain screening phase results for the number of episodes of fecal incontinence or urgency. A neurologic disorder was more frequently the origin of fecal incontinence in the success group compared with others (P=0.03). The left bulbocavernosus reflex was more frequently delayed in the success group than in the others (P=0.03), and a prolonged or absent bulbocavernosus reflex was more frequent in the success group than in the failure group (P=0.03). CONCLUSIONS: Patients with fecal incontinence from neurologic origins could be good candidates for sacral nerve stimulation.

Anal incontinence: the role of medical management.

BACKGROUND AND AIMS: Consensus recommendations suggest that patients with anal incontinence (AI) should be managed by medical treatment when indicated. Our aims were to prospectively evaluate from two different populations of patients: (1) the proportion of incontinent patients referred to a specialized center who were candidates for first line medical treatment (study 1); (2) the results of medical treatment in incontinent patients (study 2). METHODS: In study 1, standardized management of AI based on an algorithmic decision tree was applied to 287 incontinent patients (209 women, ranging from 16 to 84 years old). In study 2, 36 other incontinent patients with transit disorders (28 women, ranging from 29 to 86 years old) seen consecutively, were treated by a medical treatment of their transit disorders. The result of the medical treatment was objectively and subjectively evaluated after 2 months. RESULTS: Study 1: medical treatment was indicated in 126 of 287 patients (43.9%) (62 for diarrhea and 64 for constipation) while biofeedback was indicated in 52 patients (18.1%) and surgery specific for AI in 99 patients (34.5%). Eighty percent of the patients who were proposed conservative medical treatment were referred by their gastroenterologist or their general practitioner. Study 2: the continence score decreased from a median of 12 to 6.5 (P<0.001). 61% of patients regarded themselves as cured or improved after medical treatment. CONCLUSION: Conservative treatment can be proposed as a first line treatment in more than 50% of patients with anal incontinence referred to a specialized center. Medical treatment for anal incontinence associated with transit disorders improves continence.