Instruct: Given a question, retrieve relevant passages that answer the question.
Query: acetaminophen
PURPOSE OF REVIEW: This review provides a comprehensive selection of the latest clinical trial results in antimigraine treatment. RECENT FINDINGS: The oral calcitonine gene-related peptide antagonist telcagepant is efficacious in acute treatment. Compared to triptans, its efficacy is almost comparable but its tolerance is superior. The same is true for the 5HT-1F agonist lasmiditan, another agent devoid of vascular effects. Triptans, as other drugs, are more efficient if taken early but nonsteroidal anti-inflammatory drugs and analgesics remain useful for acute treatment, according to several meta-analyses. Single-pulse transcranial magnetic stimulation during the aura rendered more patients pain-free (39%) than sham stimulation (22%) in one study. Topiramate could be effective for migrainous vertigo, but it did not prevent transformation to chronic migraine in patients with high attack frequency. Onabotulinumtoxin A was effective for chronic migraine and well tolerated, but the therapeutic gain over placebo was modest; the clinical profile of responders remains to be determined before widespread use. Occipital nerve stimulation was effective in intractable chronic migraine with 39% of responders compared to 6% after sham stimulation. This and other neuromodulation techniques, such as sphenopalatine ganglion stimulation, are promising treatments for medically refractory patients but large controlled trials are necessary. One study suggests that outcome of patent foramen ovale closure in migraine might depend on anatomic and functional characteristics. SUMMARY: Drugs with a better efficacy or side-effect profile than triptans may soon become available for acute treatment. The future may also look brighter for some of the very disabled chronic migraineurs thanks to novel drug and neuromodulation therapies.
The use of the artificial sweetener, aspartame, has long been contemplated and studied by various researchers, and people are concerned about its negative effects. Aspartame is composed of phenylalanine (50%), aspartic acid (40%) and methanol (10%). Phenylalanine plays an important role in neurotransmitter regulation, whereas aspartic acid is also thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor, aspartic acid. Methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. Previously, it has been reported that consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that have been encountered, and these may be accredited to changes in regional brain concentrations of catecholamines, which include norepinephrine, epinephrine and dopamine. The aim of this study was to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also in compromised learning and emotional functioning.
Intestinal permeability was estimated in healthy subjects after ingestion of aspirin (1.2+1.2 g), ibuprofen (400+400 mg) and indomethacin (75+50 mg) at midnight and an hour before starting a 51chromium labelled ethylenediaminetetraacetate absorption test. Intestinal permeability increased significantly from control levels following each drug and the effect was related to drug potency to inhibit cyclooxygenase. Intestinal permeability increased to a similar extent after oral and rectal administration of indomethacin showing that the effect is systemically mediated. Prostaglandin E2 decreased intestinal permeability significantly but failed to prevent the indomethacin induced increased intestinal permeability. These studies show that non-steroidal anti-inflammatory drugs disrupt the intestinal barrier function in man and suggest that the morphological correlates of the damage may reside at the level of the intercellular junctions.
A 24-year-old female patient presented to her community hospital with mild elevations of serum transaminase and bilirubin levels. Because of multiple sclerosis, she was treated with interferon beta-1a for 6 weeks. After exclusion of viral hepatitis due to hepatitis A-E, interferon beta-1a was withdrawn under the suspicion of drug-induced hepatitis. One week later, she was admitted again to her community hospital with severe icterus. The transaminase and bilirubin levels were highly elevated, and a beginning impairment of the liver synthesis was expressed by a reduced prothrombin time. The confinement to our department occurred with a fulminant hepatitis and the suspicion of beginning acute liver failure. There was no evidence for hepatitis due to potentially hepatotoxic viruses, alcoholic hepatitis, Budd-Chiari syndrome, hemochromatosis, and Wilson's disease. In her serum there were high titers of liver-kidney microsomal type 1 autoantibody; the serum gamma globulin levels were in the normal range. Fine-needle aspiration biopsy of the liver ruled out an autoimmune hepatitis but showed signs of drug-induced toxicity. During the interview, she admitted that for 'general immune system stimulation' she had been drinking Noni juice, a Polynesian herbal remedy made from a tropical fruit (Morinda citrifolia), during the past 4 weeks. After cessation of the Noni juice ingestion, her transaminase levels normalized quickly and were in the normal range within 1 month. Copyright 2006 S. Karger AG, Basel.
OBJECTIVE: To examine adverse effects, adverse events, and potential interactions of vitamins in light of their current prevalence of use, and to discuss whether vitamins should be considered over-the-counter drugs or natural health products/dietary supplements. DATA SOURCES: We performed a MEDLINE/PubMed search, explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine Comprehensive Database, and the database of the University of Maryland), and examined reference lists of included studies published from 1966 through October 2009. STUDY SELECTION AND DATA EXTRACTION: The studies were reviewed, with an emphasis on randomized controlled clinical trials. We included articles with the most clinically important information with regard to adverse events and interactions. DATA SYNTHESIS: Vitamins are used by over one third of the North American population. Vitamins have documented adverse effects and toxicities, and most have documented interactions with drugs. While some vitamins (biotin, pantothenic acid, riboflavin, thiamine, vitamin B(12), vitamin K) have minor and reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can cause serious adverse events. Two water-soluble vitamins, folic acid and niacin, can also have significant toxicities and adverse events. CONCLUSIONS: Our recommendation is that vitamins A, E, D, folic acid, and niacin should be categorized as over-the-counter medications. Labeling of vitamins, especially those intended for children and other vulnerable groups, should include information on possible toxicities, dosing, recommended upper intake limits, and concurrent use with other products. Vitamin A should be excluded from multivitamin supplements and food fortificants.
The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD50) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.
In 2011, the protease inhibitors boceprevir and telaprevir were approved in the United States and European Union for the treatment of hepatitis C infection. While remarkably effective, the newly approved therapies are also accompanied by additional side effects and considerable costs. Understanding the balance between costs and effectiveness is critical to making decisions about the optimal use of these new agents, especially for health care systems constrained by rising costs. Our goal for this review is to facilitate an understanding of the importance of cost-effectiveness analyses in guiding policy decisions about the use of newly approved drugs as well as future therapies for hepatitis C.
We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.
BACKGROUND: Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen. OBJECTIVE: To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use. METHODS: Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized. RESULTS: Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose-response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users. CONCLUSIONS: Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful.
Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.
CONTEXT: Lead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs). OBJECTIVES: To determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards. DESIGN AND SETTING: Systematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003. MAIN OUTCOME MEASURES: Concentrations (microg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers' dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards. RESULTS: A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 microg/g; range, 5-37,000), mercury (n = 6; median concentration, 20,225 microg/g; range, 28-104,000), and/or arsenic (n = 6; median concentration, 430 microg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards. CONCLUSIONS: One of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.
Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.
Artemisia dracunculus L. (tarragon) has a long history of use as a spice and remedy. Two well-described "cultivars" (Russian and French) are used widely and differ in ploidy level, morphology, and chemistry. Key biologically active secondary metabolites are essential oils (0.15-3.1%), coumarins (>1%), flavonoids, and phenolcarbonic acids. In vivo studies mainly in rodents, particularly from Russian sources, highlight potential anti-inflammatory, hepatoprotective, and antihyperglycemic effects. Despite concerns about the toxic effects of two of its main constituents, estragole (up to 82%) and methyleugenol (up to 39%), no acute toxicity or mutagenic activity has been reported at doses relevant for human consumption. Water extracts of A. dracunculus contain very low amounts of estragole and methyleugenol and, therefore, are considered to pose a very limited risk. Overall, a stronger focus on clinical studies and precise taxonomic and phytochemical definition of the source material will be essential for future research efforts.
Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome (IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore, Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort.
BACKGROUND/AIMS: Herbal agents are popular and perceived as safe because they are supposedly 'natural'. We report 10 cases of toxic hepatitis implicating Herbalife products. METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Sinusoidal obstruction syndrome was observed in one case. Three patients without liver biopsy presented with hepatocellular (2) or mixed (1) liver injury. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.
Context Antidepressant medications represent the best established treatment for Major Depressive Disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources Pubmed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of FDA approved antidepressants in the treatment of Major or Minor Depressive Disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, included a medication vs placebo comparison for at least 6 weeks, did not exclude patients on the basis of a placebo washout period, and utilized the Hamilton Rating Scale for Depression. Data from six studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with Hamilton scores below 23, Cohen’s d-type effect sizes for the difference between medication and placebo were estimated to be < .20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline Hamilton severity and crossed the NICE threshold for a clinically significant difference at a baseline score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.
Migraine treatment has evolved from the realms of the supernatural into the scientific arena, but it seems still controversial whether migraine is primarily a vascular or a neurological dysfunction. Irrespective of this controversy, the levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter, seem to decrease during migraine (with associated carotid vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation. The last decade has witnessed the advent of sumatriptan and second generation triptans (e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs, now known as 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the second-generation triptans have a higher oral bioavailability and longer plasma half-life. In line with the vascular and neurogenic theories of migraine, all triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and presynaptic inhibition of the trigeminovascular inflammatory responses implicated in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D (PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system without producing vasoconstriction. Nevertheless, PNU-142633 proved to be ineffective in the acute treatment of migraine, whilst LY344864 did show some efficacy when used in doses which interact with 5-HT1B receptors. Finally, although the triptans are effective antimigraine agents producing selective cranial vasoconstriction, efforts are being made to develop other effective antimigraine alternatives acting via the direct blockade of vasodilator mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors, inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully lead to fewer side-effects.
Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity.
OBJECTIVE: To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references. REVIEW METHODS: Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. RESULTS: Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. DISCUSSION: Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. CONCLUSION: A number of herbal medicines show promise in the management of mild-to-moderate depression.
Postoperative nausea and vomiting (PONV) continues to be one of the most common complaints following surgery, occurring in more than 30% of surgeries, or as high as 70% to 80% in certain high-risk populations without prophylaxis. The 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists continue to be the mainstay of antiemetic therapy, but newer approaches, such as neurokinin-1 antagonists, a longer-acting serotonin receptor antagonist, multimodal management, and novel techniques for managing high-risk patients are gaining prominence. The related problem of postdischarge nausea and vomiting (PDNV) has received increasing attention from health care providers. The issues of PONV and PDNV are especially significant in the context of ambulatory surgeries, which comprise more than 60% of the combined 56.4 million ambulatory and inpatient surgery visits in the United States. Because of the relatively brief period that ambulatory patients spend in health care facilities, it is particularly important to prevent and treat PONV and PDNV swiftly and effectively. Copyright (c) 2010. Published by Elsevier Inc.
Objective To determine the effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane controlled trials register up to April 2008. Review methods Randomised controlled trials comparing fibre, antispasmodics, and peppermint oil with placebo or no treatment in adults with irritable bowel syndrome were eligible for inclusion. The minimum duration of therapy considered was one week, and studies had to report either a global assessment of cure or improvement in symptoms, or cure of or improvement in abdominal pain, after treatment. A random effects model was used to pool data on symptoms, and the effect of therapy compared with placebo or no treatment was reported as the relative risk (95% confidence interval) of symptoms persisting. Results 12 studies compared fibre with placebo or no treatment in 591 patients (relative risk of persistent symptoms 0.87, 95% confidence interval 0.76 to 1.00). This effect was limited to ispaghula (0.78, 0.63 to 0.96). Twenty two trials compared antispasmodics with placebo in 1778 patients (0.68, 0.57 to 0.81). Various antispasmodics were studied, but otilonium (four trials, 435 patients, relative risk of persistent symptoms 0.55, 0.31 to 0.97) and hyoscine (three trials, 426 patients, 0.63, 0.51 to 0.78) showed consistent evidence of efficacy. Four trials compared peppermint oil with placebo in 392 patients (0.43, 0.32 to 0.59). Conclusion Fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome.
BACKGROUND/AIMS: Nutritional supplements are frequently considered to be harmless but indiscriminate use of unlabelled ingredients may lead to significant adverse reactions. METHODS: In 2004, identification of four index cases of acute hepatitis associated with Herbalife intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife products were investigated. RESULTS: Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation. One patient developed sub-fulminant and two fulminant episodes of hepatic failure. Hepatitis resolved in eleven patients, while one patient succumbed to complications following liver transplantation. Three patients resumed consumption of Herbalife products following normalization of liver enzymes, resulting in a second bout of hepatitis. CONCLUSIONS: An association between intake of Herbalife products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife products for possible hepatotoxicity. Until then, caution should be exercised by consumers, especially among individuals suffering from underlying liver disease.
2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.
The acute and subacute toxicity of five biogenic amines-tyramine, spermidine, spermine, putrescine and cadaverine-were examined in Wistar rats. Tyramine and cadaverine had a low acute oral toxicity of more than 2000 mg/kg body weight. Putrescine had an acute oral toxicity of 2000 mg/kg body weight and spermidine and spermine each of 600 mg/kg body weight. All amines investigated caused a dose-related decrease in blood pressure after intravenous administration, except for tyramine, where an increase was found. In 6-wk studies the biogenic amines were administered in the diet to groups of 10 male and 10 female rats. Tyramine and cadaverine were given at levels of 0, 200, 2000 or 10,000 ppm, spermine and putrescine at levels of 0, 200, 2000 or 5000 ppm and spermidine at levels of 0, 20, 200 or 500/1000 ppm in the first study and at levels of 0 or 10,000 ppm in a second study. Spermine was the most toxic. The high dose level showed a great number of changes, such as emaciation, aggressiveness, convulsions and paralysis of the hind legs. Growth, food intake and water intake were considerably decreased. Slight anaemia (males) and changes in plasma clinical chemistry occurred. The relative weights of the thyroid, adrenals, spleen and heart were increased and that of the liver decreased. Impaired kidney function, together with renal histopathological changes and changes in plasma electrolytes and urea, occurred with spermine. Histopathological examinations also revealed decreased glycogen content in the liver, reduction of spermatogenesis, severe depletion of splenic white pulp, acute involution of the thymus and moderate myocardial degeneration in the heart. Myocardial degeneration was also seen in one mid-dose male. Adverse effects were also observed in the top dose groups of all other amines. Decreased body weights associated with diminished food intake were generally seen. Slight increases in packed cell volume, haemoglobin concentration and thrombocytes occurred with cadaverine. With spermidine, decreased plasma creatinine, calcium and inorganic phosphate were observed and decreased potassium levels with cadaverine. The no-observed-adverse-effect level was 2000 ppm (180 mg/kg body weight/day) for tyramine, cadaverine and putrescine, 1000 ppm (83 mg/kg body weight/day) for spermidine and 200 ppm (19 mg/kg body weight/day) for spermine.
BACKGROUND: Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. SUMMARY: Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual μ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966. © 2014 S. Karger AG, Basel.