Chronic Fatigue Syndrome: US Central Zone

Kumar R. · Department of Family Medicine, University of Chicago, Chicago, Illinois 60637, USA. · Drugs. · Pubmed #18729534 No free full text.

Abstract: Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.

Joyner MJ, Masuki S. · Dept. of Anesthesiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, · Clin Auton Res. · Pubmed #18704621 No free full text.

Abstract: The 2007 Streeten Lecture focused on the idea that physical deconditioning plays a key role in the symptomology and pathophysiology of POTS. Parallels were drawn between the physiological responses to orthostatic stress seen in POTS patients and the physiological responses seen in "normal" humans after prolonged periods of bedrest, deconditioning, or space flight. Additionally, the idea that endurance exercise training might ameliorate some of these symptoms was also advanced. Finally, potential parallels between POTS, chronic fatigue syndrome, and fibromyalgia were also drawn and the potential role of exercise training as a "therapeutic intervention" in all three conditions was raised. The conceptual model for the lecture was that after some "initiating event" chronic deconditioning plays a significant role in the pathophysiology of these conditions, and these physiological changes in conjunction with "somatic hypervigilence" explain many of the complaints that this diverse group of patients have. Additionally, the idea that systematic endurance exercise training might be helpful was advanced, and data supportive of this idea was reviewed. The main conclusion is that the medical community must retain their empathy for patients with unusual conditions but at the same time send a firm but empowering message about physical activity. As always, we must also ask what do the ideas about physical activity and inactivity and the conditions mentioned above not explain?

Jorgensen R. · Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · J Adv Nurs. · Pubmed #18638162 No free full text.

Abstract: AIM: This paper is a report of a concept analysis of chronic fatigue. BACKGROUND: Fatigue is a prevalent symptom encompassing both acute and chronic manifestations. It is chronic fatigue that is most problematic because of its duration and impact on life quality. The rise in prevalence of chronic conditions will result in a need to address coexistent symptoms, clarification of which is needed. Chronic fatigue is one of the most common symptoms in chronic illness. Clarification of the concept and an understanding of its use by discipline are needed. DATA SOURCES: The evolutionary method of concept analysis was used to ascertain the attributes, antecedents, consequences and surrogate terms for chronic fatigue. A review of the literature published between 1966 and 2007 was carried out to determine the contextual use of the concept of chronic fatigue among disciplines. Sources used for this analysis included CINAHL, Medline, PsychINFO and Social Work Abstracts and the search yielded 66 papers. RESULTS: The chronic fatigue experience is associated with a multitude of physical, psychological and social factors. The defining attributes of chronic fatigue are constancy, abnormality, whole-body experience, inexplicability and disabling. The antecedents of chronic fatigue are physical disease, psychopathology, female gender and a history of abuse. Consequences found include social isolation and stigmatization, physical inactivity, psychological disturbances and a reduced quality of life. CONCLUSION: Further research is needed to identify the aetiology of chronic fatigue and to address the social context of living with this disabling symptom.

Erdman KM. · Baylor College of Medicine PA Program, Houston, Texas, USA. · JAAPA. · Pubmed #18432043 No free full text.

This publication has no abstract.

Agarwal R. · Division of Nephrology, Department of Medicine, Indiana University School of Medicine, and Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA. · Am J Nephrol. · Pubmed #17804903 No free full text.

Abstract: Iron deficiency anemia is common in people with chronic kidney disease (CKD) and its importance in supporting erythropoiesis is unquestioned especially in those patients treated with erythropoietin. Clinical symptomatology such as fatigability, cold intolerance, failure to concentrate and poor effort intolerance is often attributed to anemia or uremia. That iron deficiency, per se, can cause these symptoms is poorly recognized. Clinical and animal studies that support the benefits of iron supplementation, independent of increasing hemoglobin, such as those on immune function, physical performance, thermoregulation, cognition, and restless leg syndrome and aluminum absorption is the subject of this narrative review.

Chakrabarty S, Zoorob R. · Department of Family and Community Medicine, Meharry Medical College, Nashville, TN 37208, USA. · Am Fam Physician. · Pubmed #17695569 links to  free full text

Abstract: Fibromyalgia is an idiopathic, chronic, nonarticular pain syndrome with generalized tender points. It is a multisystem disease characterized by sleep disturbance, fatigue, headache, morning stiffness, paresthesias, and anxiety. Nearly 2 percent of the general population in the United States suffers from fibromyalgia, with females of middle age being at increased risk. The diagnosis is primarily based on the presence of widespread pain for a period of at least three months and the presence of 11 tender points among 18 specific anatomic sites. There are certain comorbid conditions that overlap with, and also may be confused with, fibromyalgia. Recently there has been improved recognition and understanding of fibromyalgia. Although there are no guidelines for treatment, there is evidence that a multidimensional approach with patient education, cognitive behavior therapy, exercise, physical therapy, and pharmacologic therapy can be effective.

Raj SR, Robertson D. · Autonomic Dysfunction Center, Division of Clinical Pharmacology, Departments of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2195, USA. · Am J Med Sci. · Pubmed #17630594 No free full text.

Abstract: The postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia with chronic symptoms that are associated with upright posture. These chronic symptoms (of at least 6 months' duration) include tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache, and mental clouding. Patients with POTS demonstrate an increase in heart rate of at least 30 beats/min within 5 to 30 minutes of assuming an upright posture, in the absence of orthostatic hypotension (a fall in blood pressure >20/10 mm Hg) and in the absence of other medical disorders that might cause tachycardia. POTS can be associated with a high degree of functional disability. The blood volume has been found to be low in many patients with POTS. This article will review some of the data regarding blood volume perturbations in POTS, blood volume regulation in POTS, and potential treatment approaches.

Crofford LJ. · Center for the Advancement of Women's Health, University of Kentucky, USA. · Trauma Violence Abuse. · Pubmed #17596347 No free full text.

Abstract: Syndromes characterized by pain, fatigue, mood disorder, cognitive dysfunction, and sleep disturbance have been referred to as stress-related somatic disorders by virtue of the observation that onset and exacerbation of symptoms occur with stress. These syndromes include but are not limited to fibromyalgia, chronic fatigue syndrome, temporomandibular disorder, and irritable bowel syndrome. As with most chronic illnesses, genetic susceptibility and lifetime environmental exposures play a role in creating vulnerability to disease. Cumulative lifetime stress has been associated with a number of physiologic changes in the brain and body that reflect dysregulated hormonal and autonomic activity. Exposure to the stressor of violence is likely to create a state of vulnerability for the stress-related somatic syndromes and also to contribute to symptom expression and severity. Understanding the relationship between violence, stress, and somatic syndromes will help in clarifying the consequences of violence exposure to long-term health and health-related quality of life.

Atallah E, Kantarjian H, Cortes J. · Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Clin Lymphoma Myeloma. · Pubmed #17382019 No free full text.

Abstract: Imatinib and other Abl tyrosine kinase inhibitors (TKIs), such as dasatinib and nilotinib, have significantly improved the outcome of patients with chronic myeloid leukemia. Imatinib and dasatinib are currently Food and Drug Administration (FDA) approved, and nilotinib is expected to gain FDA approval soon. In addition, several other Abl TKIs are being evaluated in various clinical trials. Imatinib has also shown efficacy in the therapy of gastrointestinal stromal tumors, Philadelphia chromosome-positive acute lymphocytic leukemia and hypereosinophilic syndrome. Because of their efficacy, more patients will receive Abl TKIs for a longer period of time. Imatinib was FDA approved after a short follow-up because of its exceptional efficacy and safety profile. The most common adverse events reported included fluid retention, fatigue, diarrhea, and muscle cramps. With longer follow-up, issues related to the long-term use of imatinib have been discussed. Our aim is to review the emerging safety issues of Abl TKIs after a longer follow-up.

Yunus MB. · Section of Rheumatology, The University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA. · Semin Arthritis Rheum. · Pubmed #17350675 No free full text.

Abstract: OBJECTIVES: To discuss fibromyalgia syndrome (FMS) and overlapping conditions, eg, irritable bowel syndrome, headaches, and chronic fatigue syndrome, within the concept of central sensitivity syndromes (CSS). METHODS: A critical overview of the literature and incorporation of the author's own views. RESULTS: The concept of CSS seems viable. It is based on mutual associations among the CSS conditions as well as the evidence for central sensitization (CS) among several CSS members. However, such evidence is weak or not available in other members at this time, requiring further studies. The biology of CSS is based on neuroendocrine aberrations, including CS, that interact with psychosocial factors to cause a number of symptoms. CONCLUSIONS: CSS is an important new concept that embraces the biopsychosocial model of disease. Further critical studies are warranted to fully test this concept. However, it seems to have important significance for new directions for research and patient care involving physician and patient education. Each patient, irrespective of diagnosis, should be treated as an individual considering both the biological and psychosocial contributions to his or her symptoms and suffering.

Rai A, Whaley-Connell A, McFarlane S, Sowers JR. · Departments of Internal Medicine, Division of Nephrology, University of Missouri-Columbia School of Medicine, Columbia, MO, USA. · Am J Nephrol. · Pubmed #17170524 No free full text.

Abstract: Hyponatremia is often associated with arginine vasopressin (AVP) dysregulation that is regulated by the hypothalamo-neurohypophyseal tract in response to changes in plasma osmolality, commonly in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Potentially lethal complications of hyponatremia most frequently involve the central nervous system and include anorexia, fatigue, lethargy, delirium, seizures, hypothermia and coma, and require prompt treatment. Chronic hyponatremia also complicates patient care and is associated with increased morbidity and mortality, particularly among patients with congestive heart failure. Conventional treatments for hyponatremia (e.g. fluid restriction, diuretic treatment, and sodium replacement) may not be effective in all patients and can lead to significant adverse events. Preclinical and clinical trial results have shown that AVP receptor antagonism is a promising approach to the treatment of hyponatremia that directly addresses the effects of increased AVP and consequent decreased aquaresis, the electrolyte-sparing excretion of free water. Agents that antagonize V(2) receptors promote aquaresis and can lead to increased serum sodium. Dual-receptor antagonism, in which both V(2) and V(1A) receptors are blocked, may provide additional benefits in patients with hyponatremia.

Panichpisal K, Angulo-Pernett F, Selhi S, Nugent KM. · Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, Texas, 79430-79410, USA. · BMC Nephrol. · Pubmed #16723030 links to  free full text

Abstract: BACKGROUND: Cisplatin is a well-known nephrotoxic antineoplastic drug. Chronic hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria is one of the rare complications associated with its use. CASE PRESENTATION: A 42-year-old woman presented with a 20 year-history of hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria after cisplatin-based chemotherapy for ovarian cancer. This patient has had chronic muscle aches and fatigue and has had episodic seizure-like activity and periodic paralysis. Only thirteen other patients with similar electrolyte abnormalities have been described in the literature. This case has the longest follow-up. CONCLUSION: Cisplatin can cause permanent nephrotoxicity, including Gitelman-like syndrome. This drug should be considered among the possible causes of chronic unexplained electrolyte disorders.

Tharakan B, Manyam BV. · Plummer Movement Disorders Center, Department of Neurology, Scott and White Clinic and the Texas A&M University System, HSC College of Medicine, Temple, Texas, USA. · Phytother Res. · Pubmed #16444659 No free full text.

Abstract: Chronic fatigue often occurs in aging and in various neurological, psychiatric and systemic diseases. The available therapies in modern medicine are limited. The exploration of potential alternative therapies from traditional medicine is reviewed, as there are several botanicals with experimental evidence of efficacy based on animal models and clinical studies.

Wood PB. · Department of Family Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71103, USA. · Int Rev Neurobiol. · Pubmed #16291022 No free full text.

This publication has no abstract.

Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C. · DePaul University, Chicago, Illinois 60614, USA. · Neuropsychol Rev. · Pubmed #15929497 No free full text.

Abstract: Chronic fatigue syndrome (CFS) is an important condition confronting patients, clinicians, and researchers. This article provides information concerning the need for appropriate diagnosis of CFS subtypes. We first review findings suggesting that CFS is best conceptualized as a separate diagnostic entity rather than as part of a unitary model of functional somatic distress. Next, research involving the case definitions of CFS is reviewed. Findings suggest that whether a broad or more conservative case definition is employed, and whether clinic or community samples are recruited, these decisions will have a major influence in the types of patients selected. Review of further findings suggests that subtyping individuals with CFS on sociodemographic, functional disability, viral, immune, neuroendocrine, neurology, autonomic, and genetic biomarkers can provide clarification for researchers and clinicians who encounter CFS' characteristically confusing heterogeneous symptom profiles. Treatment studies that incorporate subtypes might be particularly helpful in better understanding the pathophysiology of CFS. This review suggests that there is a need for greater diagnostic clarity, and this might be accomplished by subgroups that integrate multiple variables including those in cognitive, emotional, and biological domains.

Benca RM, Ancoli-Israel S, Moldofsky H. · University of Wisconsin, Madison, USA. · J Clin Psychiatry. · Pubmed #15153065 No free full text.

Abstract: Patients with insomnia who also have chronic pain or depression or who are elderly represent segments of the population that are particularly difficult to treat. These populations tend to be at higher risk for experiencing difficulty sleeping and are more likely to experience chronic insomnia, sleep maintenance problems, and/or nonrestorative sleep. Worsening insomnia may exacerbate other somatic and psychological symptoms and vice versa. Conversely, there is evidence that appropriate recognition and management of the sleep complaint may alleviate other symptoms related to the associated condition and help interrupt this vicious cycle.

Shaver JL. · University of Illinois at Chicago, College of Nursing, M/C 802, 845 South Damen Avenue, Chicago, IL 60612-7350, USA. · Nurs Clin North Am. · Pubmed #15062736 No free full text.

Abstract: Many more women than men experience the chronically fatiguing condition of fibromyalgia syndrome (FMS), a growing diagnosis in the United States. Estimates are that upwards of 2% to 6% of adults have been diagnosed with FMS, and at high societal costs. In this article, common manifestations are described to guide assessment and various lines of research are explored as a basis for under-standing contributing factors and potential treatments for FMS and other chronic disorders, such as chronic fatigue syndrome (CFS), irritable bowel syndrome (IBS), and temporomandibular disorders (TMD), and the effectiveness of current treatment options.

Anyanwu E, Campbell AW, Jones J, Ehiri JE, Akpan AI. · Neurosciences Research, Cahers Inc., Conroe, TX, USA. · ScientificWorldJournal. · Pubmed #14625399 No free full text.

Abstract: Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.

Brokering KL, Qaqish RB. · Division of Pharmacy Practice, Saint Louis College of Pharmacy, St. Louis, Missouri 63110, USA. · Pharmacotherapy. · Pubmed #14620393 No free full text.

Abstract: Anemia is the most frequently encountered hematologic complication in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome. The prevalence estimates vary widely with the severity of HIV disease. Data suggest that treatment with highly active antiretroviral therapy may have a positive impact on reducing the prevalence of anemia of chronic disease in patients infected with HIV. Anemia consistently has been shown to be a predictor of decreased survival, and treatment plays an important role in improving patients' survival and quality of life (e.g., fatigue and dementia). Addressing potential underlying reversible causes and treating the chronic anemia are important strategies in the management of anemia. Erythropoietin therapy should be considered a first-line treatment, and blood transfusions should be limited to situations requiring immediate correction of hemoglobin levels.

Madariaga MG, Rezai K, Trenholme GM, Weinstein RA. · Division of Infectious Disease, Cook County Hospital, Chicago and the Section of Infectious Diseases, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA. · Lancet Infect Dis. · Pubmed #14592601 No free full text.

Abstract: Coxiella burnetii, which causes Q fever, is a highly infectious agent that is widespread among livestock around the world. Although the culture process for coxiella is laborious, large amounts of infectious material can be produced. If used as an aerosolised biological weapon, coxiella may not cause high mortality, but could provoke acute disabling disease. In its late course, Q fever can be complicated by fatal (eg, endocarditis) or debilitating (eg, chronic fatigue syndrome) disorders. The diagnosis of Q fever might be delayed because of non-specific and protean presentations. Effective antibiotic treatment is available for the acute form of disease but not for the chronic complications. Vaccination and chemoprophylaxis in selected individuals may be used in the event of bioterrorism.

Hanley NR, Van de Kar LD. · Department of Pharmacology, Center for Serotonin Disorders Research, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA. · Vitam Horm. · Pubmed #12852256 No free full text.

Abstract: Serotonin (5-hydroxytryptamine, 5-HT)-containing neurons in the midbrain directly innervate corticotropin-releasing hormone (CRH)-containing cells located in paraventricular nucleus of the hypothalamus. Serotonergic inputs into the paraventricular nucleus mediate the release of CRH, leading to the release of adrenocorticotropin, which triggers glucocorticoid secretion from the adrenal cortex. 5-HT1A and 5-HT2A receptors are the main receptors mediating the serotonergic stimulation of the hypothalamic-pituitary-adrenal axis. In turn, both CRH and glucocorticoids have multiple and complex effects on the serotonergic neurons. Therefore, these two systems are interwoven and communicate closely. The intimate relationship between serotonin and the hypothalamic-pituitary-adrenal axis is of great importance in normal physiology such as circadian rhythm and stress, as well as pathophysiological disorders such as depression, anxiety, eating disorders, and chronic fatigue.

Jason LA, Helgerson J, Torres-Harding SR, Carrico AW, Taylor RR. · Center for Community Research, DePaul University, 990 W. Fullerton Ave., Chicago, IL 60614, USA. · Eval Health Prof. · Pubmed #12629919 No free full text.

Abstract: Chronic fatigue syndrome (CFS) is an illness that involves severe, prolonged exhaustion as well as neurologic, immunologic, and endocrine system pathology. Because the pathogenesis of CFS has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis. The current investigation examined differences between CFS as defined by Fukuda and colleagues and a set of criteria that has been stipulated for myalgic encephalomyelitis (ME). Dependent measures included psychiatric comorbidity, symptom frequency, symptom severity, and functional impairment. The ME and Fukuda et al. (1994) CFS criteria were compared with a group having chronic fatigue due to psychiatric reasons. Significant differences occurred primarily with neurologic, neuropsychiatric, fatigue/weakness, and rheumatological symptoms. These findings suggest that it might be inappropriate to synthesize results from studies of this illness that use different definitions to select study populations.

Nash J, Cheng JS, Meyer GA, Remler BF. · Medical College of Wisconsin, Milwaukee, Wis., USA. · WMJ. · Pubmed #12557611 No free full text.

Abstract: Chiari Type I malformation (Chiari I) is a congenital hindbrain anomaly characterized by downward displacement of the cerebellar tonsils through the foramen magnum. This can lead to compression of cerebellar components, the lower brainstem, and the upper cervical spinal cord. In turn, a variety of neurological deficits and permanent nervous system damage may evolve. This review article discusses the etiology, diagnosis, and treatment of patients with Chiari I malformation. Its protean manifestations cause significant overlap with multiple sclerosis, chronic fatigue syndrome, and numerous other conditions. Accordingly, the diagnosis of Chiari I is difficult to establish by clinical evaluation alone. Demonstration of the characteristic hindbrain abnormalities, however, is easily accomplished with magnetic resonance imaging. Neuroimaging should therefore be considered in patients with cerebellar, brainstem, and cervical cord dysfunction. Surgical treatment is indicated in symptomatic patients with radiographic evidence of hindbrain abnormalities. Posterior fossa decompression has also been performed in patients with fibromyalgia and chronic fatigue syndrome based solely on overlapping symptoms with Chiari I. This practice remains controversial. Appraisal of surgical outcome requires postoperative neuroimaging and long-term patient follow-up to assess the permanency of improvement. Preliminary study results of the impact of surgical technique on patient outcome are reported. Ongoing research is devoted to a better understanding of the pathophysiology of Chiari I malformation and the development of more effective medical and surgical treatments.

Katz BZ. · Department of Pediatrics, Northwestern University Feinberg, School of Medicine, Chicago, IL, USA. · Pediatr Ann. · Pubmed #12455482 No free full text.

This publication has no abstract.

Cortes JE, Kurzrock R, Kantarjian HM. · Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX 77030, USA. · Semin Hematol. · Pubmed #12214290 No free full text.

Abstract: The farnesyltransferase inhibitors (FTIs) have been shown in early clinical trials to elicit antitumor actions in a broad range of solid and hematologic malignancies. The mechanism of FTI action involves blockade of farnesyltransferase, an enzyme implicated in multiple cell-signaling pathways involved in proliferation, angiogenesis, or decreased apoptosis. Of the four main classes of FTIs, two orally bioavailable FTIs have advanced farthest in clinical development. ZARNESTRA (formerly R115777, Ortho Biotech Oncology, Raritan, NJ) and Sarasar (formerly SCH66336, Schering-Plough, Kenilworth, NJ) have demonstrated biologic and clinical activity in a range of solid tumors, and Zarnestra phase I trials have documented clinical responses in approximately 30% of patients with high-risk leukemias or myelodysplastic syndrome (MDS). The main across-class toxicities associated with the use of FTIs are myelosuppression and fatigue. Certain toxicities, such as the QTc abnormalities associated with L-778,123, do not appear to be class related. As results of phase II trials with FTIs in acute and chronic myeloid leukemias and in MDS become available, clinicians will learn more about the potential role of this class of targeted anticancer drugs-and possibly about the clinical distinctions among members of this class.