Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orlistat (Ro 18-0647) is an inhibitor of gastric, carboxylester and pancreatic lipase and specifically reduces the absorption of dietary fat due to the inhibition of triglyceride hydrolysis. Orlistat can be used for the treatment of obesity. Of 52 healthy obese patients entering a four-week single-blind run-in period with diet (500 kcal-reduced, containing 30% of calories in the form of fat) and placebo three times a day, 44 patients showed compliance to the diet by reducing their body weight by 0.5-4 kg from screening. These patients were randomized for a 12-week double-blind, parallel group, placebo-controlled treatment period with diet and 50 mg Orlistat or placebo three times a day. Complete data were available for 39 patients, 20 on Orlistat (3 men, 17 women; mean weight 85.5 +/- 12.1 kg; mean body mass index 30.6 +/- 3.7 kg/m2) and 19 on placebo (3 men, 16 women; mean weight 81.9 +/- 7.9 kg; mean body mass index 30.0 +/- 2.6 kg/m2. Total weight loss after randomization was 4.3 +/- 3.4 kg in the Orlistat group and 2.1 +/- 2.8 kg in the placebo group (P = 0.025, analysis of variance with repeated measurements; 95% confidence interval for the weight loss difference 0.2-4.2 kg). Gastrointestinal side effects were seen in the Orlistat group, but in most patients the symptoms were mild or transient. One patient dropped out because of faecal incontinence. No effect was seen on vitamin A levels, but vitamin E levels became lower in the Orlistat group (P < 0.05, paired t test).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipase inhibition: a novel concept in the treatment of obesity. 838 73

Non pharmacological treatments are useful in cerebral vascular diseases. An adequate diet, physical exercise and avoidance of modificable risk factors associated with lifestyle (smoking, obesity and alcohol abuse) are recommended as primary prevention against these diseases. In the early treatment, on initiation of the neurologic focalization, hyperthermia and hyperglycemia should be avoided and adequate nutrition must be achieved. The cephalic position of the patient should be adequate and physiotherapy should be initiated early. Urinary dysfunction, fecal incontinence and cutaneous complications should be prevented and appropriately controlled.
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PMID:[Non pharmacological treatments in cerebral vascular diseases]. 1061 32

To summarize the literature on immediate pelvic floor damage from childbirth and episiotomy, a MEDLINE search of English language articles published from 1983 to 2001 was performed. Vaginal delivery causes varying degrees of muscular, neuromuscular, and connective tissue damage. This damage may result in urinary and/or fecal incontinence. Routine midline episiotomy increases the risk of third- and fourth-degree perineal lacerations, which may lead to fecal incontinence. Routine use of mediolateral episiotomy does not prevent urinary incontinence (UI) or severe perineal tears. It is possible to reduce the rate of mediolateral episiotomy to as low as 20% in primiparas without increasing the risk of anal sphincter damage. Control of obesity before delivery, as well as pelvic floor exercises and regular physical exercise both before and after delivery, seem to reduce the risk of postpartum UI.
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PMID:Childbirth-induced trauma to the urethral continence mechanism: review and recommendations. 1455 Aug 36

Electrical stimulation of the gastrointestinal (GI) tract is an attractive concept. Since these organs have their own natural pacemakers, the electrical signals they generate can be altered by externally delivering electric currents by intramuscular, serosal, or intraluminal electrodes to specific sites in the GI tract. This article reviews the advances in electrical stimulation of the GI tract by describing various methods of GI electrical stimulation and their peripheral and central effects and mechanisms; updating the status of GI electrical stimulation in the clinical settings of gastroparesis, obesity, fecal incontinence, and constipation; and predicting future directions and developments of GI electrical stimulation technology and their areas of possible clinical applications.
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PMID:Gastrointestinal electrical stimulation for treatment of gastrointestinal disorders: gastroparesis, obesity, fecal incontinence, and constipation. 1795 Apr 45

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by partially blocking the hydrolysis of dietary triglycerides. A recent meta-analysis evaluated 22 studies lasting for at least 12 months, in obese patients with a mean body mass index of 36.7 kg/m2, where orlistat was associated with hypocaloric diet or behavioral interventions: the net average weight loss was 2.89 kg (confidence interval 2.27-3.51 kg). Considering the principal studies, attrition rate ranged from 33 to 57%. Orlistat significantly decreases waist circumference, blood pressure, total and LDL cholesterol, but has no effect on HDL and triglycerides. This drug significantly reduced the incidence of diabetes only in subjects with impaired glucose tolerance. The major adverse effects with orlistat are mainly gastrointestinal (fatty and oily stool, fecal urgency, oily spotting, fecal incontinence) and attenuate over time. Orlistat should be avoided in patients with chronic malabsorption and cholestasis. Rimonabant is a selective antagonist of cannabinoid type 1 receptor. This drug, by inhibiting the overactivation of the endocannabinoid system, produces anorectic stimuli at the central nervous level, but also has effects on the peripheral systems involved in metabolism control, such as liver, adipose tissue, skeletal muscles, endocrine pancreas, and gastrointestinal apparatus, influencing many processes partially unknown. An ample experimental program named RIO (Rimonabant In Obesity) involved about 6600 obese or overweight patients to identify the effects of rimonabant in weight loss and associated cardiometabolic abnormalities, over and beyond a caloric restriction of 600 kcal in the treatment and placebo arms. In the four double-blind RIO trials published (Rio-North America, RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant 20 mg significantly (p <0.001) reduced weight by 6.3-6.9 kg in the non-diabetic groups vs placebo (-1.5-1.8 kg), whereas in the diabetic subjects enrolled in RIO-Diabetes, weight loss was 5.3 vs 1.4 kg in the placebo group. Attrition rate at 1 year ranged between 40 and 50%, similar to the studies with sibutramine or orlistat. Similarly to weight loss, also waist circumference was significantly reduced by rimonabant. As for cardiometabolic parameters, rimonabant induced a significant increase in HDL cholesterol and a significant decrease in triglycerides. Even if no significant LDL reduction was achieved, the RIO-Lipids study showed a significant decrease in small dense LDL particles, more atherogenic, in rimonabant-treated subjects. Non-diabetic treated patients improved basal insulin and indirect indexes of insulin resistance, while in the RIO-Diabetes study, the only one including diabetics, glycated hemoglobin improved by 0.7% in the active treatment arm vs placebo. The effects on HDL cholesterol and glycated hemoglobin seem in a large percentage unrelated to weight loss. These effects have been confirmed by another trial, named SERENADE, evaluating the treatment in naive diabetic patients. Rimonabant is not recommended in patients with a history of depressive disorders or suicidal ideation and with uncontrolled psychiatric illness, and is contraindicated in patients with ongoing major depression or ongoing antidepressive treatment. In conclusion, despite an enormous advancement in basic research to understand the pathogenetic mechanisms at the base of obesity, the pharmacological research did not reach the therapeutic opportunities available for other chronic conditions, like hypertension and dyslipidemia. However, the few molecules available for clinical practice (sibutramine, orlistat, rimonabant) have shown, when properly used, to contribute to reduce body weight and undoubtedly improve cardiometabolic risk factors. With this preamble, according to current guidelines and pharmacoeconomic studies, patients who might benefit from antiobesity treatment are those with a body mass index > or =30 or 27-29.9 kg/m2 with major obesity-related comorbidities such as hypertension, diabetes, dyslipidemia, obstructive sleep apnea, and metabolic syndrome.
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PMID:[Pharmacological therapy of obesity]. 1877 55

Fecal incontinence is a common problem in women, which often enforces life changes owing to embarrassment and social stigma. It is frequently not reported or diagnosed. Age, obstetric trauma, pelvic surgery, chronic diarrhea, obesity and other medical conditions, such as diabetes and stroke, increase the risk of fecal incontinence. Preventive strategies include avoiding diarrheal triggers, discouraging the routine use of episiotomies, early recognition and management of obstetric injuries and possibly pelvic floor muscle exercises after childbirth. Treatment options are available and should be discussed with the patient. These, in order of progression, are education and medications for diarrhea or constipation, supportive care, biofeedback training and surgery.
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PMID:Fecal incontinence in women: causes and treatment. 1907 90

Weight loss is a recognized alarm symptom for organic gastrointestinal (GI) disease, yet the association between obesity and specific GI symptoms remains poorly described. A meta-analysis was conducted to determine which GI symptoms predominate among obese individuals. A search of the literature using the databases MEDLINE, EMBASE PubMed and Current Contents (1950 - November 2011) was conducted. All studies assessing GI symptoms and increasing body mass index (BMI)/obesity were included. English and non-English articles were searched. A random effect model of the studies was undertaken. Overall, significant associations between GI symptoms and increasing BMI were found for upper abdominal pain (odds ratio [OR] = 2.65, 95% confidence interval [CI]: 1.23-5.72), gastroesophageal reflux (OR = 1.89, 95% CI: 1.70-2.09), diarrhoea (OR = 1.45, 95% CI: 1.26-1.64), chest pain/heartburn (OR = 1.74, 95% CI: 1.49-2.04), vomiting (OR = 1.76, 95% CI: 1.28-2.41), retching (OR = 1.33, 95% CI: 1.01-1.74) and incomplete evacuation (OR = 1.32, 95% CI: 1.03-1.71). However, no significant associations were found for all abdominal pain, lower abdominal pain, bloating, constipation/hard stools, fecal incontinence, nausea and anal blockage. Several key GI symptoms are associated with increasing BMI and obesity. In addition, there were a number of other GI symptoms that had no relationship with obesity. A greater knowledge of the GI symptoms associated with obesity along with the physiology will be important in the clinical management of these patients.
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PMID:Gastrointestinal symptoms and obesity: a meta-analysis. 2218 20

Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the 'ears-of the lynx'-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 3-4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span.
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PMID:Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients. 2344 22

Fecal incontinence (FI) is a devastating disorder that is more prevalent than previously realized. FI is the involuntary loss of stool. Many factors contribute to the pathophysiology of FI, including advanced age, bowel irregularity, parity, and obesity. A detailed history and focused rectal examination are important to making the diagnosis and determining contributing causes. Although multiple diagnostic studies are available to assess the cause of FI, specific guidelines that delineate when testing should be done do not exist. Clinicians must weigh the risk, benefit, and burden of testing against the need for empiric treatment. All types of FI are initially managed in the same way, which includes lifestyle modification to reduce bowel derangements, improved access to toileting, and initiation of a bulking regimen to improve stool consistency. If initial conservative management fails, pharmaco-logic agents, biofeedback, or surgery may be indicated.
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PMID:Office-based management of fecal incontinence. 2393 51

In August 2013, the National Institutes of Health sponsored a conference to address major gaps in our understanding of the epidemiology, pathophysiology, and management of fecal incontinence (FI) and to identify topics for future clinical research. This article is the first of a two-part summary of those proceedings. FI is a common symptom, with a prevalence that ranges from 7 to 15% in community-dwelling men and women, but it is often underreported, as providers seldom screen for FI and patients do not volunteer the symptom, even though the symptoms can have a devastating impact on the quality of life. Rough estimates suggest that FI is associated with a substantial economic burden, particularly in patients who require surgical therapy. Bowel disturbances, particularly diarrhea, the symptom of rectal urgency, and burden of chronic illness are the strongest independent risk factors for FI in the community. Smoking, obesity, and inappropriate cholecystectomy are emerging, potentially modifiable risk factors. Other risk factors for FI include advanced age, female gender, disease burden (comorbidity count, diabetes), anal sphincter trauma (obstetrical injury, prior surgery), and decreased physical activity. Neurological disorders, inflammatory bowel disease, and pelvic floor anatomical disturbances (rectal prolapse) are also associated with FI. The pathophysiological mechanisms responsible for FI include diarrhea, anal and pelvic floor weakness, reduced rectal compliance, and reduced or increased rectal sensation; many patients have multifaceted anorectal dysfunctions. The type (urge, passive or combined), etiology (anorectal disturbance, bowel symptoms, or both), and severity of FI provide the basis for classifying FI; these domains can be integrated to comprehensively characterize the symptom. Several validated scales for classifying symptom severity and its impact on the quality of life are available. Symptom severity scales should incorporate the frequency, volume, consistency, and nature (urge or passive) of stool leakage. Despite the basic understanding of FI, there are still major knowledge gaps in disease epidemiology and pathogenesis, necessitating future clinical research in FI.
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PMID:Epidemiology, pathophysiology, and classification of fecal incontinence: state of the science summary for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) workshop. 2553 2


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