Chronic Fatigue Syndrome: US Central Zone

Hoffman R. · Hematology-Oncology Section, University of Illinois-Chicago College of Medicine, Chicago, IL 60607, USA. · Semin Oncol. · Pubmed #12096351 No free full text.

Abstract: Essential thrombocythemia and polycythemia vera are both chronic progressive myeloproliferative disorders of insidious onset. If the excessive production of red cells and/or platelets is controlled, patients with these disorders may have prolonged survival. However, the clinical course of these patients can be complicated by a variety of events, including thrombotic episodes, bleeding episodes, arthropathies, pruritus, weakness, weight loss, neurologic impairment, erythromelalgia, fever, abdominal pain, and the life-threatening consequences of progression to myelofibrosis and/or acute leukemia. Effective control of hematopoiesis by phlebotomy or a variety of therapeutic agents has resulted in a reduction or elimination of many of these clinical events, but has not altered the evolution to myelofibrosis or acute leukemia. Use of each of these therapeutic strategies is also associated with a range of adverse events. Monitoring overall survival or a reduction in the frequency of clinical events has previously served as a means of assessing the results of these therapeutic interventions. Quality-of-life instruments have not been applied in a systematic fashion to the evaluation of outcomes in patients with these chronic myeloproliferative disorders. Quality-of-life assessments evaluate not only the state of well-being of a patient that results from an assessment of the individual's ability to perform everyday activities, which are reflective of physical, psychological, and social well-being, but also patient satisfaction with the control of disease and/or treatment-related symptoms. Quality-of-life instruments have been used to assess the clinical course of patients suffering from a variety of disorders, ranging from cancer to renal failure to chronic fatigue syndrome. Information about quality-of-life outcomes can contribute to the evaluation of variations in dose and timing of administration of therapeutic agents. It is possible that the side effects of a particular therapy may outweigh the disease regression achieved with a particular therapy. In the future, quality-of-life instruments may prove useful in prospectively evaluating therapeutic end points in patients with essential thrombocythemia and polycythemia vera.

Miller CS. · Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, 78229-3900, USA. · Ann N Y Acad Sci. · Pubmed #12000012 No free full text.

Abstract: In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved.

Yunus MB. · Section of Rheumatology, University of Illinois College of Medicine at Peoria, 1 Illini Dr, PO Box 1649, Peoria, IL 61656, USA. · J Gend Specif Med. · Pubmed #11974674 No free full text.

Abstract: Fibromyalgia syndrome is characterized by widespread musculoskeletal pain, fatigue, poor sleep, and tenderness on palpation at multiple sites called tender points. It occurs mostly among women; only about 10% of patients are men. Two recent studies showed that women had significantly more common fatigue, morning fatigue, "hurt all over," a greater total number of symptoms, as well as a greater number of tender points. Gender differences have also been reported in other related syndromes such as tension headache, migraine, irritable bowel syndrome, chronic fatigue syndrome, and temporomandibular disorder. Although the mechanisms of gender differences in these illnesses are not fully understood, they are likely to involve an interaction between biology, psychology, and sociocultural factors.

Rodriguez T. · University of Texas Health Science Center, Houston, Texas, USA. · J Am Acad Nurse Pract. · Pubmed #11930455 No free full text.

Abstract: Fatigue, though a common complaint, presents a challenge to nurse practitioners who must evaluate its significance in the primary care setting. Fatigue is described as a multidimensional phenomenon and is classified as physiologic, acute, or chronic. A distinction is made between chronic fatigue and chronic fatigue syndrome (CFS). The use of the Piper Fatigue Scale is suggested in order to objectively quantify this symptom in clinical practice. In this article, the Habit and Lifestyle Form for the Evaluation of Fatigue is presented as a way to assist the provider in considering simple and obvious causes of fatigue that may otherwise be overlooked. Finally, an algorithm for the evaluation of fatigue is presented.

Garland EM, Robertson D. · Autonomic Dysfunction Center, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA. · Am J Med. · Pubmed #11705431 No free full text.

Abstract: There is much interest in a putative relationship between Chiari I malformation and symptoms of orthostatic intolerance. It has been reported at scientific meetings that a number of patients with chronic fatigue syndrome or fibromyalgia have Chiari I malformation, or hindbrain compression in the absence of Chiari, and that they experience improvement after decompression surgery. Many of these patients have symptoms of orthostatic intolerance. A connection between Chiari I malformation and these conditions has been discussed in newspaper articles and on national television programs. Patients have also had access to much information on this topic via the Internet. Unfortunately, the Chiari I malformation and orthostatic intolerance connection is almost entirely unsupported by peer-reviewed literature. The purpose of this article is to provide an objective review of the available information.

Valentine AD, Meyers CA. · Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #11598889 links to  free full text

Abstract: Fatigue, cognitive dysfunction, and depression are very common in cancer patients. A relationship among the three entities is recognized but poorly understood. Factors that contribute to this poor understanding are the subjective nature of the symptoms, multiple potential causes, and a lack of reliable assessment tools. An understanding of fatigue in cancer patients may benefit from studies of chronic fatigue syndrome (CFS) and other nonmalignant diseases indicating that cognitive impairment varies with physical and mental fatigue, and that symptoms of depression experienced by patients with physical illnesses and primary mood disorders are qualitatively different. The multidimensional nature of fatigue suggests that interventions should be patient-specific. They could be related to lifestyle or involve the use of specific behavioral or pharmacologic therapies. As is the case with depression and cognitive disorders, targeted interventions against cancer-related fatigue will benefit from a better understanding of its potential biologic causes. Consideration of cognitive dysfunction and depression complicates the understanding of cancer-related fatigue; however, it provides opportunities to assist patients who must deal with this serious problem.

Morrison RE, Keating HJ. · Department of Medicine, Division of General Internal Medicine, University of Tennessee at Memphis, Memphis, Tennessee, USA. · Obstet Gynecol Clin North Am. · Pubmed #11430174 No free full text.

Abstract: Fatigue is a common problem in primary care that may represent a reaction to life problems or be a component of a disease state. A careful history, physical examination, and a few directed laboratory tests can usually allow the physician to differentiate between fatigue caused by depression, situational stress, or physical causes such as postviral or drug-induced fatigue, endocrine disorders, sleep disorders, infectious diseases, autoimmune disorders, or neurologic disease. Uncommonly, patients may have otherwise unexplained fatigue lasting 6 months or more that fulfills the criteria of chronic fatigue syndrome. A range of diagnostic skills coupled with a therapeutic physician-patient relationship will usually be successful in treating women with symptoms of fatigue.

Yunus MB. · College of Medicine at Peoria, University of Illinois, One Illini Drive, PO Box 1649, Peoria, IL 61656, USA. · Curr Rheumatol Rep. · Pubmed #11286669 No free full text.

Abstract: Fibromyalgia syndrome (FMS), characterized by widespread pain and tenderness on palpation (tender points), is much more common in women than in men in a proportion of 9:1. Two recent studies have shown important gender differences in various clinical characteristics of FMS. In a community and a clinic sample, women experienced significantly more common fatigue, morning fatigue, hurt all over, total number of symptoms, and irritable bowel syndrome. Women had significantly more tender points. Pain severity, global severity and physical functioning were not significantly different between the sexes, nor were psychologic factors, eg, anxiety, stress, and depression. Gender differences have also been observed in other related syndromes, eg, chronic fatigue syndrome, irritable bowel syndrome, and headaches. The mechanisms of gender differences in these illnesses are not fully understood, but are likely to involve an interaction between biology, psychology, and sociocultural factors.

Miller CS. · Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA. · Addiction. · Pubmed #11177524 No free full text.

Abstract: Drug addiction and multiple chemical intolerance (abdiction) appear to be polar opposites--the former characterized by craving and dependency, the latter by aversion. However, when the two are viewed in juxtaposition similarities emerge, revealing a common underlying dynamic, one which appears to be a new paradigm of disease. TILT, or toxicant-induced loss of tolerance, bridges the gap between addiction and abduction and has the potential to explain a variety of illnesses, including certain cases of asthma, migraine headaches and depression, as well as chronic fatigue syndrome, fibromyalgia and "Gulf War syndrome". This paper argues that both addiction and chemical intolerance involve a fundamental breakdown in innate tolerance, resulting in an amplification of various biological effects, particularly withdrawal symptoms. While addicts seek further exposures so as to avoid unpleasant withdrawal symptoms, chemically intolerant individuals shun their problem exposures, but for the same reason--to avoid unpleasant withdrawal symptoms. These observations raise critical questions: do addictive drugs and environmental pollutants initiate an identical disease process? Once this process begins, can both addictants and pollutants trigger symptoms and cravings? TILT opens a new window between the fields of addiction and environmental medicine, one that has the potential to transform neighboring realms of medicine, psychology, psychiatry and toxicology.

Richman JA, Jason LA, Taylor RR, Jahn SC. · Department of Psychiatry, University of Illinois, Chicago 60612, USA. · Health Care Women Int. · Pubmed #11111464 No free full text.

Abstract: We contrast Western medical views of chronic fatigue syndrome (CFS) etiology, diagnosis, and treatment with views maintained by a predominantly female CFS population. We argue that the failure of Western medicine to demonstrate a viral etiology for CFS led to a paradigmatic shift in research perspectives, which then embraced psychiatric and sociocultural explanations for CFS. As a result, CFS was delegitimized as a biomedical phenomenon within medical, academic, governmental, and public arenas. We compare alternative social constructions of CFS with issues pertaining to multiple sclerosis (MS), an illness that similarly predominates among women. Patient perspectives suggest that the history of medical attitudes toward CFS may eventually parallel the transformations that occurred in relation to MS. In particular, the discovery of biological markers for CFS may lay to rest the categorization of CFS as largely within the psychiatric realm.

Millea PJ, Holloway RL. · Department of Family and Community Medicine, Medical College of Wisconsin, Milwaukee 53226, USA. · Am Fam Physician. · Pubmed #11037075 links to  free full text

Abstract: Fibromyalgia is an extremely common chronic condition that can be challenging to manage. Although the etiology remains unclear, characteristic alterations in the pattern of sleep and changes in neuroendocrine transmitters such as serotonin, substance P, growth hormone and cortisol suggest that dysregulation of the autonomic and neuroendocrine system appears to be the basis of the syndrome. The diagnosis is clinical and is characterized by widespread pain, tender points and, commonly, comorbid conditions such as chronic fatigue, insomnia and depression. Treatment is largely empiric, although experience and small clinical studies have proved the efficacy of low-dose antidepressant therapy and exercise. Other less well-studied measures, such as acupuncture, also appear to be helpful. Management relies heavily on the physician's supportive counseling skills and willingness to try novel strategies in refractory cases.

Bradley LA, McKendree-Smith NL, Alarcón GS. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, School of Medicine, 475 Boshell Diabetes Building, 1808 7th Avenue South, Birmingham, AL 35294, USA. · Curr Rev Pain. · Pubmed #10998728 No free full text.

Abstract: Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias. However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or allodynia. We identify the abnormalities in the neuroendocrine axes that are common to FM and CFS as well as the abnormalities in central neuropeptide levels and functional brain activity that differentiate these disorders. These two sets of factors, respectively, may account for the similarities and differences in the pain experiences of persons with FM and CFS.

Kroenke K, Swindle R. · Regenstrief Institute and Department of Medicine, Indiana University School of Medicine, Indianapolis, Ind., USA. · Psychother Psychosom. · Pubmed #10867588 No free full text.

Abstract: OBJECTIVE: Few treatments for somatization have been proven effective. In the past decade, however, clinical trials of cognitive-behavioral therapy (CBT) have been promising. Our aim was to critically review and synthesize the evidence from these trials. METHODS: A search of the Medline database from 1966 through July 1999 was conducted to identify controlled trials designed to evaluate the efficacy of CBT in patients with somatization or symptom syndromes. RESULTS: A total of 31 controlled trials (29 randomized and 2 nonrandomized) were identified. Twenty-five studies targeted a specific syndrome (e.g. chronic fatigue, irritable bowel, pain) while 6 focused on more general somatization or hypochondriasis. Primary outcome assessment included physical symptoms, psychological distress and functional status in 28, 26 and 19 studies, respectively. Physical symptoms appeared the most responsive: CBT-treated patients improved more than control subjects in 71% of the studies and showed possibly greater improvement (i.e., a trend) in another 11% of the studies. A definite or possible advantage of CBT for reducing psychological distress was demonstrated in only 38 and 8% of studies, and for improving functional status in 47 and 26%. Group therapy and interventions as brief as 5 sessions proved efficacious. Benefits were sustained for up to 12 months. CONCLUSION: CBT can be an effective treatment for patients with somatization or symptom syndromes. Benefits can occur whether or not psychological distress is ameliorated. Since chronic symptoms are exceptionally common and most studies were conducted in referral populations, the optimal sequencing of CBT in treating primary care patients and the identification of those most likely to accept and respond to therapy should be further evaluated.

Jason LA, Melrose H, Lerman A, Burroughs V, Lewis K, King CP, Frankenberry EL. · DePaul University, Chicago, IL, USA. · AAOHN J. · Pubmed #10205371 No free full text.

Abstract: 1. The basic principles of envelope theory are explained. By not overexerting themselves, people with CFS can avoid the setbacks and relapses that commonly occur in response to overexertion while increasing their tolerance to activity. 2. By collecting time series data on fluctuations in energy levels, important clinical observations can be made in respect to a client's unique condition and experience with CFS.

Marshall GS. · Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, USA. · J Pediatr. · Pubmed #10190912 No free full text.

This publication has no abstract.

Ondo WG, Sethi KD, Kricorian G. · Baylor College of Medicine, Department of Neurology, 6550 Fannin, Houston, TX 77030, USA. · Clin Neuropharmacol. · Pubmed #17909308 No free full text.

Abstract: BACKGROUND: Selegiline orally disintegrating tablet (ODT; Zelapar) is a selective monoamine oxidase B inhibitor developed as an adjunct to levodopa (LD) for Parkinson disease. Most patients on long-term LD therapy eventually experience deterioration at the end of the LD dosing interval, with predictable "wearing off" and "on-off" fluctuations. METHODS: We conducted a 12-week, double-blind, placebo-controlled, parallel-design trial of selegiline ODT. The primary efficacy point was reduction in the percentage of average daily "off" time. Secondary measures included reductions in daily off hours and total daily off time, Clinical Global Impressions-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I). Patients on LD received selegiline ODT (1.25 mg/d for 6 weeks, then 2.5 mg/d for 6 weeks) or placebo. Safety and tolerability were measured. RESULTS: The intent-to-treat population included 98 patients receiving selegiline ODT and 50 patients receiving placebo. Combined efficacy results for weeks 10 and 12 revealed an 11.6% reduction in percentage of daily off time for selegiline ODT versus a 9.8% reduction for placebo (NS). PGI-I detected a statistically significant difference between treatment groups in favor of selegiline ODT (P = 0.02), whereas CGI-I detected a strong trend toward improvement (P = 0.06). Selegiline ODT was safe and well tolerated. CONCLUSIONS: This study showed no significant difference in improvement in percentage of off time with selegiline ODT versus placebo. Some clinical impressions (e.g., PGI-I, CGI-I) improved. This result contrasts with an identically designed study that showed a significant improvement in off time with selegiline ODT. A combined analysis of both studies suggested overall efficacy.

Jabbour E, Kantarjian H, Cortes J, Thomas D, Garcia-Manero G, Ferrajoli A, Faderl S, Richie MA, Beran M, Giles F, Verstovsek S. · Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #17849460 links to  free full text

Abstract: BACKGROUND: Interferon-alpha (IFN-alpha) has shown significant activity in the treatment of BCR-ABL-negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-IFN-alpha-2b is a pegylated IFN-alpha-2b with a significant advantage over nonpegylated form in that it is administered once a week. METHODS: Thirty-eight patients with BCR-ABL-negative MPDs were treated with PEG-IFN-alpha-2b, given subcutaneously weekly, at the starting dose of 3 microg/kg/wk for the first 14 patients and then 2 microg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy. RESULTS: Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR-ABL-negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3-4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months. CONCLUSIONS: PEG-IFN-alpha-2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR-ABL-negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG-IFN-alpha-2b therapy are similar to those obtained with conventional IFN-alpha, thus limiting the duration of therapy.

Ratner Y, Gibel A, Yorkov V, Ritsner MS. · Acute Department, Sha'ar Menashe Mental Health Center, Mobile Post Hefer 38814, Hadera, Israel. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #17669574 No free full text.

Abstract: OBJECTIVE: This is a first report from a long-term study aimed to evaluate efficacy, safety, tolerability, cognitive functioning, and quality of life outcomes during ziprasidone treatment of chronic schizophrenia patients in the "real-world". METHOD: Seventy clinically unstable schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40-160 mg/day), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI-S) scale, the Global Assessment of Functioning Scale (GAF) scores, treatment-emergent adverse events, body weight, and drug attitude. RESULTS: Thirty-two patients fully completed the study protocol. A discontinuation of treatment for any cause occurred in 54.3% of patients; the mean time until discontinuation was 4.4 +/- 2.7 months. A discontinuation due to lack of clinical efficacy was more predominantly linked to patient perception (25.7%) than to physicians' conclusions alone (8.6%), adverse events (11.4%), and other reasons (8.6%). After controlling daily dose of ziprasidone, concomitant medications and sex, ANCOVA revealed improvement in PANSS factors, and global functioning among patients who had completed the study. Improvement in PANSS and GAF dimensions was evident at a 6-month visit, and it continued until the endpoint. When a cutoff of 20% improvement of PANSS total scores was used, the response rate among completers was 43.8%. Most common side effects were: fatigue, sleep disturbances, and headache. Ziprasidone did not appear to be linked to weight gain. CONCLUSION: This study suggests that ziprasidone may be beneficial for long-term treatment of schizophrenia patients in terms of severity of symptoms, and general functioning. Ziprasidone is well tolerated during the long-term treatment of chronic schizophrenia patients undergoing usual care.

Teitelbaum JE, Johnson C, St Cyr J. · Fibromyalgia and Fatigue Centers, Dallas, TX, USA. · J Altern Complement Med. · Pubmed #17109576 No free full text.

Abstract: OBJECTIVES: Fibromyalgia (FMS) and chronic fatigue syndrome (CFS) are debilitating syndromes that are often associated with impaired cellular energy metabolism. As D-ribose has been shown to increase cellular energy synthesis in heart and skeletal muscle, this open-label uncontrolled pilot study was done to evaluate if D-ribose could improve symptoms in fibromyalgia and/or chronic fatigue syndrome patients. DESIGN: Forty-one (41) patients with a diagnosis of FMS and/or CFS were given D-ribose, a naturally occurring pentose carbohydrate, at a dose of 5 g t.i.d. for a total of 280 g. All patients completed questionnaires containing discrete visual analog scales and a global assessment pre- and post-D-ribose administration. RESULTS: D-ribose, which was well-tolerated, resulted in a significant improvement in all five visual analog scale (VAS) categories: energy; sleep; mental clarity; pain intensity; and well-being, as well as an improvement in patients' global assessment. Approximately 66% of patients experienced significant improvement while on D-ribose, with an average increase in energy on the VAS of 45% and an average improvement in overall well-being of 30% (p < 0.0001). CONCLUSIONS: D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome.

Yee KW, Zeng Z, Konopleva M, Verstovsek S, Ravandi F, Ferrajoli A, Thomas D, Wierda W, Apostolidou E, Albitar M, O'Brien S, Andreeff M, Giles FJ. · Authors' Affiliations: Departments of Leukemia and Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, Texas. · Clin Cancer Res. · Pubmed #16951235 links to  free full text

Abstract: PURPOSE: Everolimus (RAD001, Novartis), an oral derivative of rapamycin, inhibits the mammalian target of rapamycin (mTOR), which regulates many aspects of cell growth and division. A phase I/II study was done to determine safety and efficacy of everolimus in patients with relapsed or refractory hematologic malignancies. EXPERIMENTAL DESIGN: Two dose levels (5 and 10 mg orally once daily continuously) were evaluated in the phase I portion of this study to determine the maximum tolerated dose of everolimus to be used in the phase II study. RESULTS: Twenty-seven patients (9 acute myelogenous leukemia, 5 myelodysplastic syndrome, 6 B-chronic lymphocytic leukemia, 4 mantle cell lymphoma, 1 myelofibrosis, 1 natural killer cell/T-cell leukemia, and 1 T-cell prolymphocytic leukemia) received everolimus. No dose-limiting toxicities were observed. Grade 3 potentially drug-related toxicities included hyperglycemia (22%), hypophosphatemia (7%), fatigue (7%), anorexia (4%), and diarrhea (4%). One patient developed a cutaneous leukocytoclastic vasculitis requiring a skin graft. One patient with refractory anemia with excess blasts achieved a major platelet response of over 3-month duration. A second patient with refractory anemia with excess blasts showed a minor platelet response of 25-day duration. Phosphorylation of downstream targets of mTOR, eukaryotic initiation factor 4E-binding protein 1, and/or, p70 S6 kinase, was inhibited in six of nine patient samples, including those from the patient with a major platelet response. CONCLUSIONS: Everolimus is well tolerated at a daily dose of 10 mg daily and may have activity in patients with myelodysplastic syndrome. Studies of everolimus in combination with therapeutic agents directed against other components of the phosphatidylinositol 3-kinase/Akt/mTOR pathway are warranted.

Lundell K, Qazi S, Eddy L, Uckun FM. · Parker Hughes Institute and Parker Hughes Clinics, St. Paul, MN 55113, USA. · Arzneimittelforschung. · Pubmed #16889122 No free full text.

Abstract: A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody responses to EBV.

O'Shaughnessy JA, Pluenneke R, Sternberg J, Khandelwal P, Ilegbodu D, Asmar L. · US Oncology, Dallas, TX 75246, USA. joyce.o' · Clin Breast Cancer. · Pubmed #16595033 No free full text.

Abstract: PURPOSE: A phase II study evaluated weekly docetaxel/gemcitabine as first-line chemotherapy for locally recurrent or metastatic breast cancer in a multicenter community oncology practice setting. PATIENTS AND METHODS: Eligible patients who had not received chemotherapy for metastatic disease received docetaxel 30 mg/m2 followed by gemcitabine 800 mg/m2, each administered weekly for 3 weeks (days 1, 8, and 15), followed by a 1-week rest period (28-day cycle). Patients also received oral dexamethasone to reduce the incidence/severity of fluid retention and hypersensitivity reactions. Of the 46 enrolled patients, 45 were treated as part of the intent-to-treat (ITT) population and were evaluable for safety. RESULTS: There were 3 complete responses and 12 partial responses among the 39 evaluable patients, for an objective response rate (ORR) of 39% (95% confidence interval [CI], 24%-54%). The ORR in the ITT population was 33% (95% CI, 18%-48%). Median time to response was 3.4 months, with a median response duration of 6.7 months. Median survival was 15.8 months, and median time to progression was 5.8 months. The most common grade 3/4 hematologic toxicity was neutropenia (13.3%); there was a low incidence of other grade 3/4 hematologic toxicities. Grade 3 fatigue (15.6%) was the most common grade 3/4 nonhematologic toxicity, and grade 2 alopecia occurred in 47% of patients. One patient who had been receiving chronic corticosteroid therapy died from treatment-related neutropenia and acute respiratory distress syndrome. CONCLUSION: These phase II results suggest that weekly docetaxel/gemcitabine is moderately active and well tolerated as first-line therapy for locally recurrent or metastatic breast cancer. No clear advantage for combined weekly docetaxel/gemcitabine was observed compared with published results on the efficacy of docetaxel and gemcitabine given as single agents.

O'Brien SM, Cunningham CC, Golenkov AK, Turkina AG, Novick SC, Rai KR. · M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77030-7305, USA. · J Clin Oncol. · Pubmed #16186597 No free full text.

Abstract: PURPOSE: To determine the maximum-tolerated dose (MTD), efficacy, safety, and pharmacokinetics of oblimersen sodium in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Eligible patients had relapsed or refractory CLL after treatment with fludarabine. Oblimersen was administered at doses ranging from 3 to 7 mg/kg/d as a 5-day continuous intravenous infusion in cycle 1 and as a 7-day continuous intravenous infusion in subsequent cycles every 3 weeks in stable or responding patients. RESULTS: Forty patients were enrolled and treated (14 patients in phase I and 26 patients in phase II). Dose-limiting reactions in phase I included hypotension and fever, and the MTD for phase II dosing was established at 3 mg/kg/d. Two (8%) of 26 assessable patients achieved a partial response. Other evidence of antitumor activity included > or = 50% reduction in splenomegaly (seven of 17 patients; 41%), complete disappearance of hepatomegaly (two of seven patients; 29%), > or = 50% reduction of lymphadenopathy (seven of 22 patients; 32%), and > or = 50% reduction in circulating lymphocyte counts (11 of 22 patients; 50%). Adverse events included transient hypotension, fever, fatigue, night sweats, diarrhea, nausea, vomiting, hypokalemia, and cough. Plasma concentrations of oblimersen (parent drug) and its major metabolites were variable. Renal clearance represented only a small portion of total parent drug clearance. CONCLUSION: Dosing with oblimersen sodium in patients with CLL is limited by development of a cytokine release syndrome that is characterized by fever, hypotension, and back pain. Oblimersen sodium has modest single-agent activity in heavily pretreated patients with advanced CLL, and further evaluation of its activity in combination with cytotoxic drugs is warranted.

Bruera E, Moyano JR, Sala R, Rico MA, Bosnjak S, Bertolino M, Willey J, Strasser F, Palmer JL. · Department of Palliative Care & Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, USA. · J Pain Symptom Manage. · Pubmed #15471656 No free full text.

Abstract: Chronic nausea occurs in most patients with advanced cancer. This study was done to assess the antiemetic effects of dexamethasone in patients with chronic nausea refractory to metoclopramide. Secondary outcomes included appetite, fatigue, and pain. Fifty-one patients who had nausea (> or = 3/10 on a 0-10 scale) for > or = 2 weeks despite 48 hours of oral metoclopramide therapy (40-60 mg/day) were enrolled. Patients received 20 mg/day dexamethasone (DM) orally (n = 25) or placebo (n = 26) for severe nausea in addition to metoclopramide (60 mg/day orally). At baseline the mean nausea intensity ratings in the DM and placebo groups were 8.0 and 7.4. At Day 8 they were 2.1 and 2.0, respectively. At Day 3 and Day 8, the mean difference in nausea intensity for the DM and placebo groups was 4.5 and 2.9 (P = 0.16) and 5.9 and 5.7 (P = 0.85), respectively. Improvement in appetite and fatigue were observed on Day 3 and Day 8 in both groups as compared with the baseline. Pain, vomiting, well-being, and quality of life remained unchanged in both groups at both times. We conclude that DM was not superior to placebo in the management of chronic nausea in our patients with advanced cancer.

Hartz AJ, Bentler S, Noyes R, Hoehns J, Logemann C, Sinift S, Butani Y, Wang W, Brake K, Ernst M, Kautzman H. · University of Iowa, College of Medicine, Department of Family Medicine, Iowa City 52242-1097, USA. · Psychol Med. · Pubmed #14971626 No free full text.

Abstract: BACKGROUND: Chronic fatigue greatly affects quality of life and is a common reason for consulting a physician. Since conventional therapy is often of limited help, fatigued patients may use herbal treatments. This randomized controlled trial evaluated the effectiveness of Siberian ginseng. METHOD: Subjects were recruited from advertisements in Iowa (82%) and members of chronic fatigue syndrome support groups (18%). Potential subjects were required to have substantial fatigue > or = 6 months with no identifiable cause. The mean change in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2 months. Comparisons were for all subjects and for subjects with characteristics previously identified in the literature as important for categorizing chronic fatigue. RESULTS: Ninety-six subjects were randomized to treatment groups, and 76 provided information at 2 months of follow-up. Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample. Fatigue severity and duration had a statistically significant interaction with response to Siberian ginseng at the P < 0.05 level. Treatment was effective at 2 months for 45 subjects with less severe fatigue (P = 0.04 unadjusted for multiple comparisons) and for 41 subjects with fatigue for > or = 5 years (P = 0.09 unadjusted for multiple comparisons). CONCLUSION: Overall efficacy was not demonstrated. However, the findings of possible efficacy for patients with moderate fatigue suggests that further research may be of value.