Chronic Fatigue Syndrome: California

Guilleminault C, Palombini L, Poyares D, Chowdhuri S. · Stanford University Sleep Disorders Clinic, Stanford 94305, USA. · J Psychosom Res. · Pubmed #12127180 No free full text.

Abstract: OBJECTIVE: The question addressed here is: Can a discrete sleep disordered breathing (SDB) play a role in the insomnia complaint of postmenopausal chronic insomniacs? To respond to the query, two groups of individuals derived from a cohort of postmenopausal chronic insomniacs recruited mostly from the community were enlisted in a treatment protocol. These subjects were all individuals identified with normal breathing (n=68) and all those recognized with Upper Airway Resistance Syndrome (UARS) (n=62) pooled from a cohort of 349 postmenopausal insomniacs. TREATMENT PROTOCOL: The 62 UARS were allocated to either treatment of chronic insomnia by behavioral approaches or treatment of SDB. Based on ENT evaluation, health professionals in charge of patients selected either treatment with nasal CPAP or treatment of nasal turbinates. A stratification correction was performed to obtain a near equal number of both treatment modalities in each of the two subgroups. The 68 individuals with normal breathing were randomly allocated to immediate behavioral treatment of insomnia or delay treatment of insomnia. The delay treatment received a list of 10 sleep hygiene recommendations by mail. METHODOLOGY: Questionnaires, visual analog scales (VAS), Epworth Sleepiness Scale (ESS), clinical interviews, clinical evaluation with oto-laryngologic clinical assessment of a presence/absence of narrow upper airway and location of narrowing. Actigraphy and polysomnography (PSG) with pressure transducer/and nasal cannula system and esophageal manometry. DATA ANALYSES: All recording data were scored blind to patient's condition. RESULTS: Two subjects in the SBD-CPAP treated group (Group B) and two subjects in the delayed treatment group (Group D) dropped out. Total sleep time was improved compared to baseline in all groups, including the delayed treatment group. One group was significantly better (ANOVA, P=.05) with a more important delta score compared to baseline, and this was the behaviorally treated non-SDB. Sleep latency was significantly decreased in the behaviorally treated group (with or without SBD), P=.05, compared to SBD-treated and delayed treatment groups. Sleep latency was, however, improved in all groups. VAS for "quality of sleep" was higher at 6 months in all the groups when compared to "baseline" values. VAS for "daytime fatigue" showed significant differences among the four groups (ANOVA, P=.01); the overall score at the end of treatment was significantly better in the SDB-treated group than the other three groups. SBD was treated either by radio frequency on nasal turbinate or by nasal CPAP. CPAP-treated patients had a lower VAS score than nasal turbinate treatment, but the difference was only a trend. The delta improvement (6-month baseline condition) in "daytime fatigue" of each subgroup was calculated and compared within and between groups. Despite the small number of subjects, the turbinate-treated subgroup was significantly different from Groups B, C and D (ANOVA, P=.05). When a similar comparison was made with the nasal CPAP group, there was only a nonsignificant trend when compared to Groups B, C and D. CONCLUSION: Abnormal breathing during sleep significantly enhanced complaints of daytime fatigue in postmenopausal chronic insomniacs and this complaint improved with SDB treatment. This improvement is significantly better compared to SDB insomniacs treated with a behavioral regimen. Behavioral treatment, however, gave the best response in the non-SDB chronic insomnia group and improved better long sleep latency even in the SDB group. These results suggest the need to find an appropriate treatment for SBD even if mild and to recognize the role of SDB in relation to symptoms seen with chronic insomnia.

Gordon R, Michalewski HJ, Nguyen T, Gupta S, Starr A. · Department of Neurology, University of California, Irvine, Med. Surge I, Room 154, Irvine, CA 92697-4290, USA. · Int J Mol Med. · Pubmed #10534571 No free full text.

Abstract: Premovement, sensory, and cognitive brain potentials were recorded from patients with Chronic Fatigue Syndrome (CFS) in four tasks: i) target detection, ii) short-term memory, iii) self-paced movement, and iv) expectancy and reaction time (CNV). Accuracy and reaction times (RTs) were recorded for tasks i, ii, and iv. Results from CFS patients were compared to a group of healthy normals. Reaction times were slower for CFS patients in target detection and significantly slower in the short-term memory task compared to normals. In target detection, the amplitude of a premovement readiness potential beginning several hundred milliseconds prior to stimulus onset was reduced in CFS, whereas the poststimulus sensory (N100) and cognitive brain potentials (P300) did not differ in amplitude or latency. In the memory task, a negative potential related to memory load was smaller in CFS than normals. The potentials to self-paced movements and to expectancy and RT (CNV) were not different between groups. The findings in CFS of slowed RTs and reduced premovement-related potentials suggest that central motor mechanisms accompanying motor response preparation were impaired in CFS for some tasks. In contrast, measures of neural processes related to both sensory encoding (N100) and to stimulus classification (P300) were normal in CFS.

Stahl SM. · Department of Psychiatry, University of California, San Diego, CA, USA. · Hum Psychopharmacol. · Pubmed #19479906 No free full text.

Abstract: Fibromyalgia is a syndrome of widespread chronic pain associated with sleep disorders, depressed mood, cognitive impairment and fatigue. Its etiology and pharmacopathology are poorly understood but it is thought to result from a dysfunction of central pain processing mechanisms leading to generalised pain sensitisation. Pain perception is the result of a bidirectional process of ascending and descending pathways. Nociceptive input from peripheral afferent neurons is sent via the dorsal horn of the spinal cord to the higher brain centres involved in pain perception. Some descending inhibitory projections to the spinal cord attenuate the nociceptive effects. Numerous neurotransmitters including serotonin, dopamine, noradrenaline and substance P are involved in these processes. In other neuronal pathways in the brain, the same neurotransmitters are involved in mood control, sleep regulation and cognitive function providing a neurochemical substrate for the wide range of symptoms seen in fibromyalgia. Attenuation of neuronal hyperactivity through ligands acting at the alpha2-delta subunits of voltage-dependent calcium channels and increased inhibitory activity of the descending pathways by inhibition of serotonin and noradrenaline reuptake are two mechanisms that are currently exploited by new medication for the treatment of fibromyalgia.

Presson AP, Sobel EM, Papp JC, Suarez CJ, Whistler T, Rajeevan MS, Vernon SD, Horvath S. · Biostatistics, University of California, Los Angeles, CA, USA. · BMC Syst Biol. · Pubmed #18986552 links to  free full text

Abstract: BACKGROUND: Systems biologic approaches such as Weighted Gene Co-expression Network Analysis (WGCNA) can effectively integrate gene expression and trait data to identify pathways and candidate biomarkers. Here we show that the additional inclusion of genetic marker data allows one to characterize network relationships as causal or reactive in a chronic fatigue syndrome (CFS) data set. RESULTS: We combine WGCNA with genetic marker data to identify a disease-related pathway and its causal drivers, an analysis which we refer to as "Integrated WGCNA" or IWGCNA. Specifically, we present the following IWGCNA approach: 1) construct a co-expression network, 2) identify trait-related modules within the network, 3) use a trait-related genetic marker to prioritize genes within the module, 4) apply an integrated gene screening strategy to identify candidate genes and 5) carry out causality testing to verify and/or prioritize results. By applying this strategy to a CFS data set consisting of microarray, SNP and clinical trait data, we identify a module of 299 highly correlated genes that is associated with CFS severity. Our integrated gene screening strategy results in 20 candidate genes. We show that our approach yields biologically interesting genes that function in the same pathway and are causal drivers for their parent module. We use a separate data set to replicate findings and use Ingenuity Pathways Analysis software to functionally annotate the candidate gene pathways. CONCLUSION: We show how WGCNA can be combined with genetic marker data to identify disease-related pathways and the causal drivers within them. The systems genetics approach described here can easily be used to generate testable genetic hypotheses in other complex disease studies.

Turk Charles S, Gatz M, Kato K, Pedersen NL. · Department of Psychology, University of California, Irvine, CA 92697-7085, USA. · Health Psychol. · Pubmed #18624602 No free full text.

Abstract: OBJECTIVE: Neuroticism, a personality trait related to distress and emotional stability, is often correlated with physical symptoms and disease presence. Theorists have posited that chronic emotional instability creates physiological changes detrimental to health, yet most findings are based on cross-sectional analyses. The objective of the current study was to examine neuroticism assessed in 1973 and the likelihood of reporting physical conditions 25 years later. DESIGN: Participants included 21676 adult twins (n = 8143 intact twin pairs) ranging from 15 to 47 years old in 1973 who were assessed again between 1998 and 2002. MAIN OUTCOME MEASURES: Thirteen physical conditions, including chronic fatigue syndrome, ulcers, and coronary heart disease, were selected based on their prior theoretical and empirical links to personality traits. RESULTS: Results indicate that the likelihood of having a physical condition is related to higher levels of prior neuroticism, with some associations attenuated when controlling for familial similarity. CONCLUSION: Familial influences are most pronounced for conditions most related to systemic pain, suggesting genetic pathways between neuroticism and these pain experiences.

Caro XJ, Winter EF, Dumas AJ. · Division of Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Rheumatology (Oxford). · Pubmed #18208823 No free full text.

Abstract: OBJECTIVES: The aetiopathogenesis of the fibromyalgia syndrome (FMS) remains unknown. Recent reports, however, suggest that a subgroup of FMS subjects has an immune-mediated disease. Therefore, our primary objective was to study FMS subjects for evidence of an immune-mediated demyelinating polyneuropathy. Our secondary objective was to determine the effects of treating these FMS subjects with the immune modulator, intravenous immunoglobulin (IVIg). METHODS: Fifty-eight FMS subjects, 26 rheumatic non-FMS subjects and 52 non-rheumatic non-FMS subjects were studied. Subjective measures of paraesthesias, weakness, stocking hypaesthesia, pain, fatigue and stiffness were made. Objective measures of tenderness, proximal muscle strength and electrodiagnostic (EDX) evidence of polyneuropathy and demyelination were also made. Eleven other FMS subjects underwent sural nerve biopsy. RESULTS: Paraesthesias, subjective weakness and stocking hypaesthesia were more common in FMS than in rheumatic non-FMS (P < or = 0.0001). Proximal muscle strength was less in FMS than in rheumatic non-FMS (P < or = 0.0001). EDX demonstrated a distal demyelinating polyneuropathy, suggestive of chronic inflammatory demyelinating polyneuropathy (CIDP), in 33% of FMS subjects. No rheumatic non-FMS subject had polyneuropathy (P = 0.005), or demyelination (P = 0.05). Fifteen FMS/CIDP subjects were subsequently treated with IVIg (400 mg/kg each day for 5 days). Pain (P = 0.01), tenderness (P = 0.001) and strength (P = 0.04) improved significantly. Fatigue and stiffness trended towards improvement. CONCLUSIONS: A significant subset of FMS subjects have clinical and EDX findings suggestive of CIDP. IVIg treatment shows promise in treating this subset. These observations have implications for better understanding and treating some FMS patients.

Higashimoto T, Baldwin EE, Gold JI, Boles RG. · Division of Medical Genetics and the Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, California, USA. · Arch Dis Child. · Pubmed #18192313 No free full text.

Abstract: OBJECTIVE: Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy (RSD), is an idiopathic condition characterised by localised, abnormally intense and prolonged pain, allodynia and autonomic nervous system changes (ie, swelling, skin colour and temperature changes and altered perspiration) that usually appear following a "noxious" trigger such as trauma or surgery. The objective of this report is to demonstrate that children with CRPS-I can have additional dysautonomic conditions secondary to an underlying maternally inherited mitochondrial disease, an association not previously published. METHODS: Medical records of about 500 patients seen by one paediatric metabolic geneticist were reviewed to identify children meeting established CRPS diagnostic criteria. RESULTS: CRPS-I was present in eight children in seven families, each of which also had additional functional/dysautonomic conditions, the most common (> or = 4 cases per condition) being gastrointestinal dysmotility, migraine, cyclic vomiting and chronic fatigue. All seven probands studied met Nijmegen (2002) diagnostic criteria for definite mitochondrial disease on the basis of the clinical signs and symptoms and biochemical analyses. Six of the seven families met our pedigree-based criteria for probable maternal inheritance. CONCLUSION: In one tertiary-care paediatric genetics practice, children meeting the CRPS-I diagnostic criteria frequently had additional autonomic-related conditions secondary to maternally inherited mitochondrial disease, suggesting that mitochondrial DNA sequence variants can predispose children towards the development of CRPS-I and other dysautonomias. CRPS-I should be considered in patients with mitochondrial disease who complain of idiopathic pain. Maternally inherited mitochondrial disease may not be a rare cause of CRPS-I, especially in children who present with other manifestations of dysautonomia.

Koppel A, Lim S, Osby M, Garratty G, Goldfinger D. · Department of Medicine, Division of Hematology-Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Transfusion. · Pubmed #17880618 No free full text.

Abstract: BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) attributed to a biphasic hemolysin known as the Donath-Landsteiner (DL) antibody. It is most commonly encountered as an acute transient AIHA after a viral infection in children; the disease resolves after cessation of the infection. The rarest form of PCH is a chronic form in adults that is not (nowadays) associated with infection and is not responsive to conventional therapies. Rituximab has been found to be effective therapy in other forms of AIHA, such as cold agglutinin syndrome, that are refractory to conventional therapies. We describe a case of PCH refractory to steroids that responded to rituximab therapy on two separate occasions. CASE REPORT: A 64-year-old woman with fatigue was found to be profoundly anemic with laboratory findings consistent with AIHA. She was admitted for the workup and management of her disease after she failed to respond to a course of oral steroids. Laboratory evaluation demonstrated a positive DL test suggesting PCH. She was given a course of rituximab that resulted in normalization of her hemoglobin concentration. She presented 9 months later with recurrent hemolysis. She was given another course of rituximab that again resulted in termination of hemolysis. The patient remained in remission since her last dose of rituximab 19 months previously. CONCLUSION: To our knowledge, this is the first report of an adult case of refractory PCH successfully treated with rituximab.

Chia JK, Chia AY. · EV Med Research, Lomita, California 90717, USA. · J Clin Pathol. · Pubmed #17872383 No free full text.

Abstract: BACKGROUND AND AIMS: The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was evaluated. METHODS: 165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for EV. RESULTS: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (p< or =0.001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2-8 years later showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin-embedded biopsy samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses. CONCLUSION: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.

Cecchini M, LoPresti V. · Foundation for Advancements in Science and Education, 4801 Wilshire Boulevard, Suite 215, Los Angeles, CA 90010, USA. <> · Med Hypotheses. · Pubmed #17045758 No free full text.

Abstract: For decades, scientists have investigated the environmental and human health effects of synthetic chemicals. A growing body of research has illuminated the spectrum of consequences deriving from our reliance these substances and their proliferation in air, water, soil and the food chain. Of particular concern is the fact that residues of many man-made chemicals are now detectible in virtually every person. A key to a chemical's tendency to persist in tissues once it has entered the body is its lipophilicity. Substances that are poorly soluble in water and quite soluble in fat have relatively free access, via lipid-rich cellular membranes, to the cells of all organs including the ability to cross the blood-brain and placental barriers. Substantial data exist demonstrating that in addition to pollutants, drugs and their metabolites dispose to tissues high in fat content, including brain and adipose. While their characteristic lipophilicity permits drugs and medications to reach target tissues, thereby producing therapeutic effects in the present, current perceptions of risk may be ignoring the possibility that adipose accumulations of illicit drugs and pharmaceuticals may lead to future patterns of ill health similar to those associated with exposure to other categories of xenobiotic chemicals. Empirical data are beginning to characterize the myriad regulatory functions of adipose hormones, including roles in cravings, cognitive function, energy level, and inflammation as well as changes in adipose hormone levels associated with drug use. Included in this data are the observation that a rehabilitative treatment intervention introduced by L. Ron Hubbard in 1978 to aid in the broad elimination of chemicals from body stores improves symptoms common to both chemical exposure and drug addiction. The regimen, which includes exercise, sauna bathing, and vitamin and mineral supplementation, is utilized by nearly 70 drug rehabilitation and medical practices in over 20 countries. At present, much more is unknown than is known regarding long-term drug retention and effects. This subject deserves careful evaluation given its potential implications for health and chronic illnesses of poorly defined etiology (such as chronic fatigue syndrome), as well as drug abuse prevention, drug rehabilitation, forensic and legal areas.

Guilleminault C, Poyares D, Rosa A, Kirisoglu C, Almeida T, Lopes MC. · Stanford University Sleep Disorders Clinic, 401 Quarry road, suite 3301, Stanford, CA 94305, USA. · Sleep Med. · Pubmed #16934523 No free full text.

Abstract: BACKGROUND AND PURPOSE: To investigate the complaint of unrefreshing sleep with study of sleep electroencephalogram (EEG) in patients with chronic fatigue. PATIENTS AND METHODS: Fourteen successively seen patients (mean age: 41.1 9.8) who complained of chronic fatigue but denied sleepiness and agreed to participate were compared to 14 controls (33.6+/-10.2 years) who were monitored during sleep recorded in parallel. After performing conventional sleep scoring we applied Fast Fourier Transformation (FFT) for the delta 1, delta 2, theta, alpha, sigma 1, sigma 2, beta EEG frequency bands. The presence of non-rapid eye movement (NREM) sleep instability was studied with calculation of cyclic alternating pattern (CAP) rate. Two-way analysis of variance (ANOVA) was performed to analyze FFT results and Mann-Whitney U-test to compare CAP rate in both groups of subjects. RESULTS: Slow wave sleep (SWS) percentage and sleep efficiency were lower, but there was a significant increase in delta 1 (slow delta) relative power in the chronic fatigue group when compared to normals (P<0.01). All the other frequency bands were proportionally and significantly decreased compared to controls. CAP rate was also significantly greater in subjects with chronic fatigue than in normals (P=0.04). An increase in respiratory effort and nasal flow limitation were noted with chronic fatigue. CONCLUSIONS: The complaints of chronic fatigue and unrefreshing sleep were associated with an abnormal CAP rate, with increase in slow delta power spectrum, affirming the presence of an abnormal sleep progression and NREM sleep instability. These specific patterns were related to subtle, undiagnosed sleep-disordered breathing.

Boles RG, Powers AL, Adams K. · Division of Medical Genetics, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA. · J Child Neurol. · Pubmed #16901417 No free full text.

Abstract: Cyclic vomiting syndrome, which is characterized by severe discrete episodes of nausea, vomiting, and lethargy, is a fairly common, disabling, predominately childhood condition. Approximately 25% of cases have coexisting neuromuscular disease manifestations (cyclic vomiting syndrome plus). To determine whether patients with cyclic vomiting syndrome and neuromuscular disease represent a distinct subentity within cyclic vomiting syndrome, a clinical interview was conducted regarding 80 randomly ascertained sufferers of cyclic vomiting syndrome from a disease association database. Cyclic vomiting syndrome plus and "cyclic vomiting syndrome minus," herein defined as the presence of at least two and zero neuromuscular disease manifestations, were present in 23 and 44 subjects, respectively. Neuromuscular disease manifestations, including cognitive disorders, skeletal myopathy, cranial nerve dysfunction, and seizure disorders, were found to statistically cluster together among the same subjects. In addition, subjects with cyclic vomiting syndrome with neuromuscular disease had an earlier age at onset for vomiting episodes and a three- to eightfold statistically increased prevalence for certain dysautonomia-related (migraine, chronic fatigue, neurovascular dystrophy) and constitutional (growth retardation and birth defects) disorders. However, subjects with cyclic vomiting syndrome with and without neuromuscular disease were equally likely to have a sibling affected with neuromuscular disease manifestations. We conclude that cyclic vomiting syndrome plus, although likely not genetically distinct from cyclic vomiting syndrome minus, represents a distinct phenotypic entity that predicts an earlier onset of disease and increased comorbidity with a distinct list of medical conditions, possibly owing to a higher degree of mitochondrial dysfunction.

Flanagan JM, Rhodes M, Wilson M, Beutler E. · Department of Molecular and Experimental Medicine, The Scripps Research Institute, MEM-215, 10550 Torrey Pines, La Jolla, CA, USA. · Br J Haematol. · Pubmed #16740138 No free full text.

Abstract: Phosphoglycerate kinase (PGK) deficiency is a rare X-linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system. In a white American family, two sons presented with haemolytic anaemia, seizures, and developmental delay. The diagnosis of PGK deficiency was made based on the remarkably low (<5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A --> T) PGK1 gene mutation. This mutation results in an Asp164Val amino acid substitution, which has previously been designated PGK-Amiens and PGK-New York. The two new patients have the full clinical syndrome of PGK deficiency including haemolytic anaemia, developmental delay and seizures, and in the proband, hemiplegic migraines, retinal dystrophy and muscle fatigue. The PGK-Amiens/New York mutation had previously been found in a French patient and also in a large Chinese-Australian kindred, indicating that either the c. 91A --> T mutation is a recurrent mutation or that there is shared ancestry between the patients that have been identified so far with the mutation. Haplotype analysis of the c. 91A --> T mutation indicated that this was a recurrent mutation.

Hunsaker DH, Riffenburgh RH. · Department of Otolaryngology, Naval Medical Center San Diego, San Diego, California 92109, USA. · Otolaryngol Head Neck Surg. · Pubmed #16647530 No free full text.

Abstract: OBJECTIVE: To analyze the impact of snoring, independent of obstructive sleep apnea syndrome on patients referred for home sleep studies and to report a new technology for the reporting of snoring, using sophisticated sound collection and noise-canceling technology. STUDY DESIGN AND SETTING: A retrospective statistical review of consecutive anonymous data compiled from questionnaires and digital data of snoring loudness and duration measured at the upper lip during unattended home sleep studies in 4,860 patients referred for snoring and sleep-disturbed breathing. RESULTS: A strong relationship exists between a history of snoring and complaints of daytime sleepiness (80%), obesity (73%), and chronic fatigue (78%) (all yield P<0.001). By contrast, only 42% to 48% of patients without these symptoms complain of snoring. In 3 multiple-regression analyses, the percent of time snoring, average loudness, and peak loudness are all significantly predicted by the apnea hypopnea index (all P<0.003), body mass index (all P<0.001), and age (P=0.014). Daytime sleepiness was strongly predicted by percent time snoring (P=0.014), weakly by average loudness (P=0.046), and not at all by peak loudness (P=0.303). CONCLUSION: By using a pair of microphones placed at the upper lip, one that samples breath sounds and the other ambient sound and artifact noise, the NovaSOM QSG measures snoring while canceling ambient noise. The clinical impact of snoring on the patient as well as the bed partner, independent of obstructive sleep apnea syndrome, is an unrecognized factor in sleep-disturbed breathing. SIGNIFICANCE: Measurable criteria to define snoring are suggested. Snoring loudness is not measured in most laboratory Polysomnograms. EBM rating: B-3b.

Vinjamury SP, Singh BB. · Southern California University of Health Sciences, Whittier, USA. · Altern Ther Health Med. · Pubmed #16189951 No free full text.

This publication has no abstract.

Zipser RD, Farid M, Baisch D, Patel B, Patel D. · Harbor-UCLA Medical Center, Torrance, USA. · J Gen Intern Med. · Pubmed #16050861 links to  free full text

Abstract: BACKGROUND: Celiac disease is a common disorder (up to 0.7%); however, it is uncommonly diagnosed in the United States. OBJECTIVE: We sought to determine physician awareness of celiac disease. DESIGN: Surveys completed by 2,440 (47%) of 5,191 patients in a support group were analyzed for frequency of diagnosis by physician specialties. Questionnaires were then sent to primary care physicians (PCPs) (n=132) in a southern California county to assess knowledge of celiac disease. RESULTS: In patient surveys, only 11% were diagnosed by PCPs (internists and family physicians) versus 65% by gastroenterologists. Physician surveys (70% response) showed that only 35% of PCPs had ever diagnosed celiac disease. Almost all physicians (95%) knew of wheat intolerance, but few (32%) knew that onset of symptoms in adulthood is common. Physicians were well aware (90%) of diarrhea as a symptom, but fewer knew of common symptoms of irritable bowel syndrome (71%), chronic abdominal pain (67%), fatigue (54%), depression and irritability (24%) or of associations with diabetes (13%), anemia (45%) or osteoporosis (45%), or of diagnosis by endomysial antibody tests (44%). CONCLUSIONS: Lack of physician awareness of adult onset of symptoms, associated disorders, and use of serology testing may contribute to the underdiagnosis of celiac disease.

Wheatland R. · The Endocrine Research Project, 574 Sims Road, Santa Cruz, CA 95060, USA. · Med Hypotheses. · Pubmed #15885924 No free full text.

Abstract: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a commonly recognized feature of many pathological conditions. Abnormal adrenal responses to experimental manipulation have been well documented in patients suffering from chronic fatigue syndrome, anorexia nervosa and major depression. Yet no defect of any single organ, gland or brain region has been identified as a cause of these abnormalities. The disruption of the HPA axis that occurs in these conditions can be understood if an interfering factor is present in these patients. Evidence indicates that this interfering factor is adrenocorticotropin hormone (ACTH) autoantibodies. Chronic high levels of ACTH autoantibodies will significantly disrupt the HPA axis and force the body to compensate for an impaired cortisol response. The resulting effect of chronic ACTH autoantibody interference is the manifestation of adrenocortical insufficient symptoms and psychological disturbances. Some symptoms of chronic fatigue syndrome, anorexia nervosa and major depression, such as anxiety, are the adverse effects of mechanisms compensating for less effective ACTH due to autoantibodies. Furthermore, these patients engage in extraordinary behaviors, such as self-injury, to increase their cortisol levels. When this compensation is inadequate, symptoms of adrenocortical insufficiency appear. Corticosteroid supplements have been demonstrated to be an effective treatment for chronic fatigue syndrome, anorexia nervosa and major depression. It allows the patients to have the corticosteroids they require for daily functioning and daily stressors. This therapy will relieve the patients of their symptoms of adrenocortical insufficiency and permit their cortisol-stimulating mechanisms to operate at levels that will not cause pathological problems.

Snell CR, Vanness JM, Strayer DR, Stevens SR. · University of the Pacific, Department of Sport Sciences, Stockton, CA 95211-0197, USA. · In Vivo. · Pubmed #15796202 No free full text.

Abstract: Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p < 0.01), with no gender effect or interaction. Follow-up analyses identified VO2(peak) as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity.

Ohayon MM. · Stanford Sleep Epidemiology Research Center, Stanford University School of Medicine, Stanford, Calif., USA. · Arch Intern Med. · Pubmed #15642872 links to  free full text

Abstract: BACKGROUND: Nonrestorative sleep (NRS) has been little studied in the general population, even though this symptom has an important role in several medical conditions such as heart disease, fibromyalgia, and chronic fatigue syndrome, as well as various sleep disorders. METHODS: A total of 25,580 individuals (age range, 15-100 years) from the noninstitutionalized general population representative of 7 European countries (France, the United Kingdom, Germany, Italy, Portugal, Spain, and Finland) were interviewed by telephone using the Sleep-EVAL system. Nonrestorative sleep was analyzed in relationship to sociodemographic determinants, environmental factors, life habits, health, sleep-wake schedule, and psychological factors. RESULTS: The prevalence of NRS was 10.8% (95% confidence interval, 10.4%-11.2%) in the sample, was higher in women than in men (12.5% vs 9.0%; P<.001), and decreased with age. The United Kingdom (16.1%) and Germany (15.5%) had the highest prevalence of NRS and Spain (2.4%), the lowest. In multivariate analyses, several factors were positively associated with NRS. The most important were younger age, dissatisfaction with sleep, difficulty getting started in the morning, stressful life, presence of anxiety, bipolar or a depressive disorder, and having a physical disease. When compared with subjects who have difficulty initiating or maintaining sleep (without NRS), subjects with NRS reported more frequently a variety of daytime impairment (irritability, physical, and mental fatigue) and consulted a physician twice as frequently for their sleeping difficulties than did other subjects with insomnia. CONCLUSIONS: Nonrestorative sleep is a frequent symptom in the general population, but its prevalence largely varies between countries. It is often associated with mental disorders and characteristics of sleep deprivation (such as extra sleep time on weekends). Nonrestorative sleep affected more frequently the active classes of the population and caused greater daytime impairment than difficulty initiating or maintaining sleep.

Martinez S, Guilleminault C. · Stanford University Sleep Disorders Clinic, Stanford, California 94305, USA. · Dev Med Child Neurol. · Pubmed #15540638 No free full text.

Abstract: This study's aims were to determine: (1) prevalence of periodic leg movements (PLMs) in walking prepubertal children consulting a sleep clinic for any sleep disorder; (2) associations between PLMs and other sleep and medical disorders; and (3) the response of other sleep disorders to treatment with the dopamine agonist pramipexol. Clinical evaluation and polysomnography were carried out for a period of 12 months on 252 consecutively seen, prepubertal children with sleep disorders (156 males, 96 females; aged 15mo to 11y, mean 7y 1mo, SD3y 10mo). Sleep disorders unrelated to PLMs were treated, and six children received pramipexol for PLMs. Follow-up included clinical evaluation and polysomnography. Twenty-three per cent of children were diagnosed with PLMs on the basis of polysomnography. The presence of PLMs had usually been unrecognized clinically. The only clinical symptom that could be related to periodic limb movement disorder was a report of leg pains at morning awakening. Only two of 58 children had PLMs without other clinical or polysomnographic findings. Comorbidity seen with PLMs included neuropsychiatric syndromes (n=20), isolated sleep disordered breathing (SDB; n=29), and several other comorbid conditions (n=7). Seven of 11 children seen with attention-deficit-hyperactivity disorder also had PLMs. Surgery for SDB was associated with subsequent cessation of PLMs in 15 of 29 children. Five out of six children with PLMs who received pramipexol were able to tolerate the drug and experienced a complete disappearance of their PLMs. Presence of chronic fatigue, sleepiness, disrupted nocturnal sleep, and difficulties in falling asleep should lead to a systematic search for PLMs that is independent of associated syndromes. Isolated treatment of SDB might help eliminate some, but not all, PLMs.

Naliboff BD, Mayer M, Fass R, Fitzgerald LZ, Chang L, Bolus R, Mayer EA. · Center for Neurovisceral Sciences & Women's Health, Department of Medicine, UCLA, Los Angeles, CA, USA. · Psychosom Med. · Pubmed #15184707 links to  free full text

Abstract: OBJECTIVE: Psychosocial stressors have been associated with exacerbations of symptoms in functional and inflammatory disorders of the gastrointestinal tract. The present longitudinal study tests the general hypothesis that life stressors can exacerbate symptoms in patients with chronic heartburn. METHODS: Sixty subjects with current heartburn symptoms were recruited by community advertisement and assessed for presence of stressful life events retrospectively over the preceding 6 months and prospectively for 4 months. Symptom severity by daily diary, quality of life, and psychological symptoms of anxiety, depression, and vital exhaustion were also measured. RESULTS: The presence of a severe, sustained life stress during the previous 6 months significantly predicted increased heartburn symptoms during the following 4 months. In addition, symptoms showed a strong, independent correlation with vital exhaustion. Affective and subjective stress ratings were not strongly related to heartburn severity; however, anxiety showed the strongest relationship to impaired quality of life and depression to heartburn medication use. CONCLUSIONS: As with other chronic conditions such as irritable bowel syndrome (IBS), heartburn severity appears to be most responsive to major life events and not an accumulation of more minor stressors or fluctuations in mood. In addition, vital exhaustion, which may in part result from sustained stress, may represent the psychophysiological symptom complex most closely associated with heartburn exacerbation. Potential mechanisms for these results include increased level and frequency of esophageal acid exposure, inhibition of gastric emptying of acid, or stress-induced hypersensitivity.

Vojdani A, Thrasher JD. · Section of Neuroimmunology, Immunosciences Lab Inc., 8693 Wilshire Boulevard, Suite 200, Beverly Hills, CA 90211, USA. · Environ Health Perspect. · Pubmed #15175170 links to  free full text

Abstract: We examined 100 symptomatic Gulf War veterans (patients) and 100 controls for immunologic assays. The veterans and controls were compared for the percentage of T cells (CD3); B cells (CD19); helper:suppressor (CD4:CD8) ratio; natural killer (NK) cell activity; mitogenic response to phytohemagglutin (PHA) and pokeweed mitogen (PWM); level of immune complexes; myelin basic protein (MBP) and striated and smooth muscle autoantibodies; and antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 (HSV-1), HSV-2, human herpes Type 6 (HHV-6), and Varicella zoster virus (VZV). The percentage of T cells in patients versus controls was not significantly different, whereas a significantly higher proportion of patients had elevated T cells compared with controls. The percentage of B cells was significantly elevated in the patients versus the controls. The NK cell (NK) activity was significantly decreased in the patients (24.8 +/- 16.5 lytic units) versus the controls (37.3 +/- 26.4 lytic units). The percentage of patients with lower than normal response to PHA and PWM was significantly different from controls. Immune complexes were significantly increased in the patients (53.1 +/- 18.6, mean +/- SD) versus controls (34.6 +/- 14.3). Autoantibody titers directed against MBP and striated or smooth muscle were significantly greater in patients versus controls. Finally, the patients had significantly greater titers of antibodies to the viruses compared with the controls (p < 0.001). These immune alterations were detected 2-8 years after participation in the Gulf War. The immune alterations are consistent with exposure to different environmental factors. We conclude that Gulf War syndrome is a multifaceted illness with immune function alterations that may be induced by various factors and are probably associated with chronic fatigue syndrome.

Lim BR, Tan SY, Zheng YP, Lin KM, Park BC, Turk AA. · Fuller Theological Seminary, Graduate School of Psychology, Pasadena, California, USA. · Transcult Psychiatry. · Pubmed #14649853 No free full text.

Abstract: Chronic fatigue syndrome (CFS) is a relatively new condition of unknown etiology. Research suggests that psychosocial factors such as perceived social support, life stress, and acculturation may significantly influence individuals who are prone to CFS. For 57 Chinese American individuals initially diagnosed with CFS, those who recovered after one year reported lower levels of life stress than those who did not recover. Effects of changes in perceived social support also appeared to be mediated by life stress.

Zavestoski S, Brown P, McCormick S, Mayer B, D'Ottavi M, Lucove JC. · Department of Sociology, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117-1080, USA. · Soc Sci Med. · Pubmed #14572929 No free full text.

Abstract: We examine Gulf War illnesses--which include the fatigue, joint pain, dermatitis, headaches, memory loss, blurred vision, diarrhea, and other symptoms reported by Gulf War veterans--in relation to other medically unexplained physical symptoms such as multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia. Our intent is to examine the diagnosis negotiations involved in these mysterious diseases, by showing the different forms of legitimacy involved in such interactions. Factors involved in diagnostic legitimacy are: diagnostic legitimacy in the medical community, lay acceptance of the diagnosis, uncertainty in looking for causes, and social mobilization. We conclude by noting that research may not be able to find any cause for these diseases/conditions; hence, it may be necessary to embrace medical uncertainty, and also to accept patient experience in order to facilitate diagnosis, treatment, and recovery process. Such a change can alter patients' expectations and taken-for-granted assumptions about medicine, and perhaps in turn reduce the frequency with which dissatisfied individuals form illness groups that mobilize to challenge what they see as an unresponsive medical system.

Nicolson GL, Gan R, Haier J. · The Institute for Molecular Medicine, Huntington Beach, California 92649, USA. · APMIS. · Pubmed #12887507 No free full text.

Abstract: Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans. Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive). Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant. Severity and incidence of patients' signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.