Instruct: Given a question, retrieve passages that answer the question.
Query: anesthesia
This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than "S" (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.
Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to "rest." We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.
The U.S. Food and Drug Administration (FDA) should reevaluate its position on aspartame as being safe under all conditions. Animal bioassay results predict human cancer risks, and a recent animal study confirms that there is a potential aspartame risk to humans. Aspartame is produced and packaged in China for domestic use and global distribution. Japan, France, and the United States are also major producers. No study of long-term adverse occupational health effects on aspartame workers have been conducted. The FDA should consider sponsoring a prospective epidemiologic study of aspartame workers.
2- and 4-methylimidazoles are present as contaminants in caramel colorings manufactured with ammonia catalysts. Both contaminants have been shown to induce cancer in animals and may be present in caramel colorings in amounts that exceed federal guidelines. California requires warning notices on products that could lead to consumption of more than 30 micrograms per day. The US Food and Drug Administration should bar the use of excessively contaminated caramel coloring in food.
We conducted an investigation of the levels of the neurotoxin 2-amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour. Analysis of 30 flour samples processed from the endosperm of Cycas circinalis seeds collected on Guam indicated that more than 87% of the total BMAA content was removed during processing. Furthermore, in 1/2 the samples almost all (greater than 99%) of the total BMAA was removed. We found no significant regional differences in the BMAA content of flour prepared from cycad seeds collected from several villages on Guam. Testing of different samples prepared by the same Chamorro woman over 2 years suggests that the washing procedure probably varies in thoroughness from preparation to preparation but is routinely efficient in removing at least 85% of the total BMAA from all batches. Analysis of a flour sample that had undergone only 24 hours of soaking indicated that this single wash removed 90% of the total BMAA. We conclude that processed cycad flour as prepared by the Chamorros of Guam and Rota contains extremely low levels of BMAA, which are in the order of only 0.005% by weight (mean values for all samples). Thus, even when cycad flour is a dietary staple and eaten regularly, it seems unlikely that these low levels could cause the delayed and widespread neurofibrillary degeneration of nerve cells observed in amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam (ALS-PD).
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.
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.
In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.
Apple cider vinegar products are advertised in the popular press and over the Internet for treatment of a variety of conditions. After an adverse event was reported to the authors, eight apple cider vinegar tablet products were tested for pH, component acid content, and microbial growth. Considerable variability was found between the brands in tablet size, pH, component acid content, and label claims. Doubt remains as to whether apple cider vinegar was in fact an ingredient in the evaluated products. The inconsistency and inaccuracy in labeling, recommended dosages, and unsubstantiated health claims make it easy to question the quality of the products.
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.
The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.
OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve pathways in primary and secondary dysmenorrhea. Data sources. The Cochrane Menstrual Disorders and Subfertility Group Trials Register (9 June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to Nov. 2003), EMBASE (1980 to Nov. 2003), CINAHL (1982 to Oct. 2003), MetaRegister of Controlled Trials, the citation lists of review articles and included trials, and contact with the corresponding author of each included trial. REVIEW METHODS: The inclusion criteria were randomized controlled trials of uterosacral nerve ablation or presacral neurectomy (both open and laparoscopic procedures) for the treatment of dysmenorrhea. The main outcome measures were pain relief and adverse effects. Two reviewers extracted data on characteristics of the study quality and the population, intervention, and outcome independently. RESULTS: Nine randomized controlled trials were included in the systematic review. There were two trials with open presacral neurectomy; all other trials used laparoscopic techniques. For the treatment of primary dysmenorrhea, laparoscopic uterosacral nerve ablation at 12 months was better when compared to a control or no treatment (OR 6.12; 95% CI 1.78-21.03). The comparison of laparoscopic uterosacral nerve ablation with presacral neurectomy for primary dysmenorrhea showed that at 12 months follow-up, presacral neurectomy was more effective (OR 0.10; 95% CI 0.03-0.32). In secondary dysmenorrhea, along with laparoscopic surgical treatment of endometriosis, the addition of laparoscopic uterosacral nerve ablation did not improve the pain relief (OR 0.77; 95% CI 0.43-1.39), while presacral neurectomy did (OR 3.14; 95% CI 1.59-6.21). Adverse events were more common for presacral neurectomy than procedures without presacral neurectomy (OR 14.6; 95% CI 5-42.5). CONCLUSION: The evidence for nerve interruption in the management of dysmenorrhea is limited. Methodologically sound and sufficiently powered randomized controlled trials are needed.
The anti-genotoxic effect of Ocimum sanctum L. extract was studied against the genotoxic effect induced by a synthetic progestin cyproterone acetate, on human lymphocytes using chromosomal aberrations, mitotic index, sister chromatid exchanges and replication index as a parameters. About 30 microM of cyproterone acetate was treated with O. sanctum L. infusion, at dosages of 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) g/ml of culture medium. A clear dose-dependent decrease in the genotoxic damage of cyproterone acetate was observed, suggesting a possible modulating role of the plant infusion. The results of the present study suggest that the plant infusion per se does not have genotoxic potential, but can modulate the genotoxicity of cyproterone acetate on human lymphocytes in vitro.
The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.
A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.
The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or, less commonly, surgical; in many cases there is no clear diagnosis and therapy is considered inadequate. New developments, such as genetic and biological approaches, may allow better diagnosis and treatments in the future.
Is it ever right to prescribe placebos to patients in clinical practice? The General Medical Council is ambivalent about the issue; the American Medical Association asserts that placebos can be administered only if the patient is (somehow) 'informed'. The potential problem with placebos is that they may involve deception: indeed, if this is the case, an ethical tension arises over the patient's autonomy and the physician's requirement to be open and honest, and the notion that medical care should be the primary concern. This paper examines the case of depression as an entry point for understanding the complexities of the prescription of placebos. Recent important meta-analyses of antidepressants claim that they are not significantly more effective in a clinical setting than placebos. Given that antidepressants have numerous adverse side effects and are hugely expensive, this provocative research has serious potential ethical and practical implications for patients and medical providers. Should placebos be prescribed in place of antidepressants? The case of depression highlights another important issue which medical ethical codes have hitherto overlooked: well-being is not synonymous with being realistic about oneself, one's circumstances and the future. While severely depressed individuals are unduly pessimistic about themselves and the world around them, treatment of depressed individuals can be deemed successful when patients have successfully attained those positive illusions that are indicative of psychological health. This is exactly what successful psychological treatments of depression seem to achieve. It is therefore possible that there may be a limited unavoidable role for deception in medicine.
The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.
The opiate alkaloids present in poppy seed intended for use in food recently have raised major concerns. An efficient method for routine analysis of morphine and codeine using liquid chromatography in combination with tandem mass spectrometry on a triple quadrupole instrument (LC/MS/MS) was therefore developed. The optimal sample preparation was found to be cold extraction of 10 g of unground poppy seed with 30 mL of methanol containing 0.1% acetic acid for 60 min shaken at 250 rpm. The fate of morphine during food processing was also studied. All experiments led to a significant reduction of morphine and codeine. For poppy cake only 16-50% of the morphine was recovered, and in poppy buns at the highest temperature (220 degrees C) only 3% of the original morphine content was found. Ground poppy seed showed significantly lower recoveries than untreated seed. Morphine elimination during food processing has to be taken into account in the current discussion about its maximum limits in poppy seed.
Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a matter of concern worldwide, in particular in the USA. For the analysis of emergence and spread, clear definitions based on epidemiological origin are needed for discrimination between CA-MRSA, healthcare-associated community MRSA, and healthcare-associated MRSA (HA-MRSA). Although its role in pathogenesis is currently under debate, the capability for Panton-Valentine leukocidin formation is associated with the majority of CA-MRSA isolates from North America and from Europe. Most CA-MRSA isolates are attributed to clonal lineages different from HA-MRSA; there are, however, clonal lineages from which both HA-MRSA and CA-MRSA have been reported (e.g. ST1, ST5, ST8, and ST22); CA-MRSA ST8 (USA300), which is most frequent in the USA, has meanwhile been reported from Europe. CA-MRSA ST80 is widely disseminated in Europe; because of its pronounced oxacillin heteroresistance phenotype, cefoxitin-based assays are advisable for reliable detection. So far, CA-MRSA infections seem to be much less frequent in Europe than in the USA, where patients with particular predispositions and low social status are at especial risk.
Sponge samples were taken from the carcases, meat, personnel and surfaces involved in stunning, slaughter and dressing/boning activities at three abattoirs, and from retail beef products. The samples were examined for the presence of central nervous system (CNS)-specific proteins (syntaxin 1B and/or glial fibrillary acidic protein (GFAP), as indicators of contamination with CNS tissue. Syntaxin 1B and GFAP were detected in many of the sponge samples taken along the slaughter line and in the chill rooms of all three abattoirs; GFAP was also detected in one sample of longissimus muscle (striploin) taken in the boning hall of one of the abattoirs but not in the other two abattoirs or in retail meats.
BACKGROUND: On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. OBJECTIVES: To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. METHODS: Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. RESULTS: Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. CONCLUSION: This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.
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 red sap obtained by slashing the bark of Croton urucurana Baill. (Euphorbiaceae), also known as dragon's blood, was screened for a possible antidiarrhoeal activity on castor oil-induced diarrhoea in rats, cholera toxin-induced intestinal secretion in mice and on small intestinal transit in mice. Dragon's blood at an oral dose of 600 mg/kg caused in marked inhibition of the diarrhoeal response following castor oil administration as well as the intestinal fluid accumulation promoted by cholera toxin. At a similar dose the red sap significantly inhibited the small intestinal transit which was, however, found to be independent of the opioid mechanism. These results suggest a potential usefulness of the red sap from Croton urucurana Baill. in the control of secretory diarrhoea associated pathologies. Copyright 2001 John Wiley & Sons, Ltd.