BioMed Central - Most viewed articles

Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

2008-04-22

Background: Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results: We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent) were toxic for both central nervous system (CNS) progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions: Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group

2004-05-24

IntroductionThere is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. Methods: We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. Results: We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at http://www.ADQI.net) Conclusion: Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology.

Nutritional therapies for mental disorders

Shaheen E Lakhan and Karen F Vieira — 2008-01-21

According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD).Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.

Food Advertising and Marketing Directed at Children and Adolescents in the US

Mary Story and Simone French — 2004-02-10

In recent years, the food and beverage industry in the US has viewed children and adolescents as a major market force. As a result, children and adolescents are now the target of intense and specialized food marketing and advertising efforts. Food marketers are interested in youth as consumers because of their spending power, their purchasing influence, and as future adult consumers. Multiple techniques and channels are used to reach youth, beginning when they are toddlers, to foster brand-building and influence food product purchase behavior. These food marketing channels include television advertising, in-school marketing, product placements, kids clubs, the Internet, toys and products with brand logos, and youth-targeted promotions, such as cross-selling and tie-ins. Foods marketed to children are predominantly high in sugar and fat, and as such are inconsistent with national dietary recommendations. The purpose of this article is to examine the food advertising and marketing channels used to target children and adolescents in the US, the impact of food advertising on eating behavior, and current regulation and policies.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal

2008-04-08

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.

Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration

Edward L Tobinick and Hyman Gross — 2008-01-09

Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligomers. The efficacy of etanercept, a biologic antagonist of TNF-alpha, delivered by perispinal administration, for treatment of Alzheimer's disease over a period of six months has been previously reported in a pilot study. This report details rapid cognitive improvement, beginning within minutes, using this same anti-TNF treatment modality, in a patient with late-onset Alzheimer's disease. Rapid cognitive improvement following perispinal etanercept may be related to amelioration of the effects of excess TNF-alpha on synaptic mechanisms in Alzheimer's disease and provides a promising area for additional investigation and therapeutic intervention.

Respiratory effects of different recruitment maneuvers in acute respiratory distress syndrome

2008-04-16

IntroductionAlveolar derecruitment may occur during low tidal volume ventilation and may be prevented by recruitment maneuvers (RMs). The aim of this study was to compare two RMs in acute respiratory distress syndrome (ARDS) patients. Methods: Nineteen patients with ARDS and protective ventilation were included in a randomized crossover study. Both RMs were applied in each patient, beginning with either continuous positive airway pressure (CPAP) with 40 cm H2O for 40 seconds or extended sigh (eSigh) consisting of a positive end-expiratory pressure maintained at 10 cm H2O above the lower inflection point of the pressure-volume curve for 15 minutes. Recruited volume, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), and hemodynamic parameters were recorded before (baseline) and 5 and 60 minutes after RM. All patients had a lung computed tomography (CT) scan before study inclusion. Results: Before RM, PaO2/FiO2 was 151 ± 61 mm Hg. Both RMs increased oxygenation, but the increase in PaO2/FiO2 was significantly higher with eSigh than CPAP at 5 minutes (73% ± 25% versus 44% ± 28%; P < 0.001) and 60 minutes (68% ± 23% versus 35% ± 22%; P < 0.001). Only eSigh significantly increased recruited volume at 5 and 60 minutes (21% ± 22% and 21% ± 25%; P = 0.0003 and P = 0.001, respectively). The only difference between responders and non-responders was CT lung morphology. Eleven patients were considered as recruiters with eSigh (10 with diffuse loss of aeration) and 6 with CPAP (5 with diffuse loss of aeration). During CPAP, 2 patients needed interruption of RM due to a drop in systolic arterial pressure. Conclusion: Both RMs effectively increase oxygenation, but CPAP failed to increase recruited volume. When the lung is recruited with an eSigh adapted for each patient, alveolar recruitment and oxygenation are superior to those observed with CPAP.

Childhood obesity, prevalence and prevention

Mahshid Dehghan, Noori Akhtar-Danesh and Anwar T Merchant — 2005-09-02

Childhood obesity has reached epidemic levels in developed countries. Twenty five percent of children in the US are overweight and 11% are obese. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Consequently, both over-consumption of calories and reduced physical activity are involved in childhood obesity.Almost all researchers agree that prevention could be the key strategy for controlling the current epidemic of obesity. Prevention may include primary prevention of overweight or obesity, secondary prevention or prevention of weight regains following weight loss, and avoidance of more weight increase in obese persons unable to lose weight. Until now, most approaches have focused on changing the behaviour of individuals in diet and exercise. It seems, however, that these strategies have had little impact on the growing increase of the obesity epidemic. While about 50% of the adults are overweight and obese in many countries, it is difficult to reduce excessive weight once it becomes established. Children should therefore be considered the priority population for intervention strategies. Prevention may be achieved through a variety of interventions targeting built environment, physical activity, and diet. Some of these potential strategies for intervention in children can be implemented by targeting preschool institutions, schools or after-school care services as natural setting for influencing the diet and physical activity. All in all, there is an urgent need to initiate prevention and treatment of obesity in children.

Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health–AARP Diet and Health Study

2008-04-30

IntroductionBy inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal. Methods: We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health–AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). We estimated relative risks of breast cancer for NSAID exposures using multivariate Cox proportional hazards regression models. The state cancer registry and mortality index linkage identified 4,501 primary incident breast cancers through 31 December 2003, including 1,439 estrogen receptor (ER)-positive cancers and 280 ER-negative cancers. Results: Proportional hazards models revealed no statistically significant association between overall NSAIDs and total breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type. Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin (relative risk = 0.93, 95% confidence interval = 0.85 to 1.01) or nonaspirin NSAIDS (relative risk = 0.96, 95% confidence interval = 0.87 to 1.05), risk of ER-positive breast cancer was significantly reduced with daily aspirin use (relative risk = 0.84, 95% confidence interval = 0.71 to 0.98) – a relationship not observed for nonaspirin NSAIDS. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer. Conclusion: Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype.

How chemotherapy damages the central nervous system

Christina A Meyers — 2008-04-22

Chemotherapy adversely affects cognitive function both acutely and chronically, but little is known about the underlying mechanisms. A new study shows that short-term chemotherapy causes not only acute injury to progenitor cells, but also delayed damage to myelin.