Phosphate diabetes in patients with chronic fatigue syndrome

Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered. We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire. Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes. In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements.     

Attention and verbal learning in patients with chronic fatigue syndrome

Former neuropsychological studies with Chronic Fatigue Syndrome (CFS) patients evaluated a broad range of cognitive functions. Several, but not all, reported subtle attentional and memory impairments suggesting possible mild cerebral involvement. In this study, a battery of attentional tests and a verbal memory task were administered to 20 CFS patients and 22 healthy controls (HC) in order to clarify the specific nature of attention and memory impairment in these patients. The results provide evidence for attentional dysfunction in patients with CFS as compared to HC. CFS patients performed more poorly on a span test measuring attentional capacity and working memory. Speeded attentional tasks with a more complex element of memory scanning and divided attention seem to be a sensitive measure of reduced attentional capacity in these patients. Focused attention, defined as the ability to attend to a single stimulus while ignoring irrelevant stimuli, appears not to be impaired. CFS patients were poorer on recall of verbal information across learning trials, and poor performance on delayed recall may be due to poor initial learning and not only to a retrieval failure.     

Edge detection in brain SPET perfusion imaging: a comparison of several methods

Four methods of brain edge detection on brain SPET perfusion (99Tcm-hexamethylpropylene amine oxime) images were compared: ellipse adaptation, simple thresholding (four threshold values), a low threshold (40%) followed by 1, 2 or 3 pixel erosion, and the Deriche 3D adaptive cut-off frequency method (four filter widths: alpha = 1, 2, 3 or 4). The SPET data of six patients were reconstructed to obtain 10 axial slices, each 10 mm thick, covering the whole brain. On the 60 axial slices, the methods were compared based on automaticity, computation time and accuracy of edge detection compared with morphological edges drawn manually on the patients' 3D co-registered magnetic resonance imaging (MRI) scans. The proportion of pixels inside the contour defined by the MRI scan but outside the SPET edge (p(i)), and the proportion of pixels inside the contour defined by the SPET image but outside the MRI contour (pe), were calculated. The thresholding methods provided interesting results, particularly the application of a low threshold value (40%), followed by a 2 pixel erosion, which required a computation time of 12 s (p(i) = 5.7 +/- 2.2%; pe = 2.7 +/- 0.9%). Because of adjustments to each slice of the ellipse axis, the processing time of this method was about 3 min (p(i) = 1.5 +/- 1.4%; pe = 11.3 +/- 3.4%). The Deriche 3D filter was time-consuming (6 min for 10 slices on a NXT workstation, SMV International). With this method, the best edge fitting was found with a filter width of 3 and 4 (p(i) = 9.6 +/- 11.1%; pe = 14.1 +/- 23.2%; alpha = 3). Three-dimensional filtering methods must be refined to reduce the computation time and to improve brain edge fitting accuracy when compared with the eroded thresholding method.     

Sociosomatics and illness in chronic fatigue syndrome

Angiogenesis is essential for tumour growth and important in tumour metastasis and prognosis. Vascular endothelial growth factor (VEGF) stimulates endothelial proliferation in vitro and angiogenesis in vivo. VEGF expression has been correlated with high vascularity in tumours, including carcinoma of the breast. This study investigated VEGF expression and vascularity of invasive lobular (n = 10) and invasive ductal carcinoma (n = 28), and pure ductal carcinoma in situ of the breast (n = 33). VEGF protein expression was studied with immunohistochemistry and VEGF mRNA with in situ hybridization. Vascular density was assessed on sections stained for von Willebrand factor. There was more expression of both VEGF protein (P = 0.006) and mRNA (P = 0.002) in invasive ductal than in invasive lobular carcinoma. VEGF protein (rs = 0.32, P = 0.047) and mRNA (rs = 0.56, P = 0.04) correlated with vascular density in invasive ductal carcinoma. In invasive lobular carcinoma, vascular density did not correlate with VEGF mRNA (rs = 0.15, P = 0.35) and was inversely related to VEGF protein (rs = -0.57, P = 0.04). There were no significant differences in vascular density between the two types of invasive carcinoma, suggesting that VEGF is important in angiogenesis in invasive ductal carcinoma, but that other angiogenic factors are important in invasive lobular carcinoma. Although VEGF protein was frequently expressed in ductal carcinoma in situ, no relationship was found between VEGF and the two patterns of angiogenesis previously described.     

A 56-year-old woman with chronic fatigue syndrome

The IgG and secretory IgA (S-IgA) responses to the HIV-1 envelope (gp160 antigen) were analyzed in the colostrum (Col) and in the cervicovaginal fluid (CVF) of HIV-l-infected women. We show IgG antibodies (Abs) to the recombinant gp160 to be predominant as compared with the corresponding S-IgA isotype. The low level of the S-IgA response cannot be related to a general disturbance of the mucosal-associated Iymphoid tissue (MALT) because the level of a current Ab to a caries-associated antigen from Streptococcus sobrinus was in the normal range in these secretions. The major subclass of IgA to gp160 was of the alpha1 isotype both in Col and in CVF. However, the specific activities of S-IgA1 and S-IgA2 were different when expressed as the ratio of the anti-gp160 related to total Ig of each subclass. Indeed, the specific activity of the S-IgA2 was predominant over S-IgA1 in the Col, whereas the reciprocal results were found in CVF, showing a subcompartmentalization of these secretions. The ability of S-IgA and IgG to block one of the pathways involved in the HIV-1 penetration across mucosa, i.e., transcytosis through epithelial cells, was evaluated using a functional in vitro assay. Both S-IgA and IgG Abs impaired virus transcytosis, irrespective of the level of antigp160 specific activities. However, specific S-IgA was more efficient than IgG. These features suggest that mucosal specific S-IgA to HIV-1 could be relevant in decreasing infectivity of HIV-1 in corporal fluids.     

Prevalence of fatigue and chronic fatigue syndrome in a primary care practice

BACKGROUND: Our goals were to determine the prevalence of unusual, debilitating fatigue and the frequency with which it was associated with the chronic fatigue syndrome (CFS) or other physical or psychological illness in an outpatient clinic population. METHODS: We prospectively evaluated a cohort of 1000 consecutive patients in a primary care clinic in an urban, hospital-based general medicine practice. The study protocol included a detailed history, physical examination, and laboratory and psychiatric testing. RESULTS: Five patients who came because of CFS studies were excluded. Of the remaining 995, 323 reported fatigue, and 271 (27%) complained of at least 6 months of unusual fatigue that interfered with their daily lives. Of the 271, self-report or record review revealed a medical or psychiatric condition that could have explained the fatigue in 186 (69%). Thus, 85 (8.5%) of 995 patients had a debilitating fatigue of at least 6 months' duration, without apparent cause. Of these patients, 48 refused further evaluation, and 11 were unavailable for follow-up; 26 completed the protocol. Three of the 26 were hypothyroid, and one had a major psychiatric disorder. Of the remaining 22 patients, three met Centers for Disease Control and Prevention criteria for CFS, four met British criteria, and 10 met the Australian case definition. The point prevalences of CFS were thus 0.3% (95% confidence interval [CI], 0% to 0.6%), 0.4% (95% CI, 0% to 0.8%), and 1.0% (95% CI, 0.4% to 1.6%) using the Centers for Disease Control and Prevention, British, and Australian case definitions, respectively. These estimates were conservative, because they assumed that none of the patients who refused evaluation or were unavailable for follow-up would meet criteria for CFS. CONCLUSIONS: While chronic, debilitating fatigue is common in medical outpatients, CFS is relatively uncommon. Prevalence depends substantially on the case definition used.     

Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome

A rabbit antiserum was raised against the N-terminal fragment peptide, GEGLSS (Gly-Glu-Gly-Leu-Ser-Ser) of bovine neuropeptide AF (NPAF, A18Famide). NPAF is an octadecapeptide isolated from the bovine brain together with neuropeptide FF (NPFF). GEGLSS-like immunoreactivity was localized with immunofluorescence technique in colchicine-treated rats in neuronal cell bodies of the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei. A few neurons were also observed in the retrochiasmatic part of the SON. GEGLSS-like immunoreactivity was also localized to nerve terminals of the posterior pituitary. No GEGLSS-ir neuronal cell bodies were observed in the medial hypothalamus, in an area that contains NPFF-ir neurons. GEGLSS immunoreactivity was also seen in the fibers and terminals of nucleus of the solitary tract. We injected a retrograde tracer, fluorogold, to the posterior pituitary gland and visualized GEGLSS-ir neuronal cell bodies double-labeled with the tracer in SON, PVN, and SOR. The pituitary stalk transsection totally abolished the GEGLSS-ir structures from the posterior pituitary. Our results suggest that GEGLSS immunoreactivity in the rat brain has a more limited distribution than NPFF immunoreactivity. GEGLSS immunoreactivity was partially colocalized with arginine-vasopressin and oxytocin in neuronal cell bodies in the SON and PVN. Considering the fact that the known rat NPFF-NPAF precursor does not contain GEGLSS structure, the detected GEGLSS immunoreactivity may be derived from a previously unknown precursor.     

The biopsychosocial model and chronic fatigue syndrome

Comments on the article of L. A. Jason et al (see record 199705605-007) on the diagnosing of chronic fatigue syndrome (CFS) and its comorbidity with psychiatric disorders. The present author points out that one of the most consistent research findings is the inconsistency and failure to replicate reports of pathophysiology in CFS. However, it is suggested, it is unlikely that either psychiatric disorder alone or physiological factors alone will sufficiently explain CFS. It is argued that ultimately, a biopsychosocial model should prove the most constructive way of conceptualizing this illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with the chronic fatigue syndrome (neurasthenia)

The authors report a case of biliary colic secondary to gallstones formed during a course of therapy with Ceftriaxone. Three weeks after cessation of therapy the gallstones dissolved.     

Can dual-headed 18F-FDG SPET imaging reliably supersede PET in clinical oncology? A comparative study in lung and gastrointestinal tract cancer

In this study, we prospectively compared the sensitivity of PET and planar SPET (collimated gamma camera) 18F-FDG imaging in patients with lung and gastrointestinal tract cancer and analysed their respective impact on patient management. Twenty-eight patients with lung cancer and 14 with gastro-intestinal tract tumours were scanned on the same day with a PET and a collimated planar SPET gamma camera. The planar SPET procedure consisted of whole-body planar views and a tomographic acquisition centred over the torso or the abdomen, with the total imaging time within the same range as the whole-body PET procedure. The staging of lung cancer patients was accurate in 86% with PET and 64% with planar SPET. Planar SPET would have led to inappropriate therapeutic decisions in 8 of 28 patients, mainly due to undetected distant metastases. In patients with suspected gastrointestinal tract cancer, planar SPET identified 7 of 15 (47%) proven tumour sites, whereas PET identified 14 of 15 (93%). Our results suggest that collimated planar SPET cameras are not a substitute for dedicated PET scanners. The sensitivity for the detection of tumours is unacceptably low and can impair patient management. The use of multiple tomographic acquisitions could improve the sensitivity but would require a longer scanning time.     

Physical activity before and after exercise in women with chronic fatigue syndrome

Placenta growth factor (PlGF) is a homodimeric glycoprotein, 46-50 kDa in size, belonging to the vascular endothelial growth factor (VEGF) sub-family. It exists as two isoforms, PlGF-1 and -2, the latter having a heparin-binding domain. Like VEGF, it is a potent angiogenic factor; however, PlGF homodimers interact with the VEGF receptor Flt-1 (fms-like tyrosine kinase), but not with the kinase domain-containing region (KDR). Since PlGF is made by the human placenta and extravillous trophoblast (EV-T) cells of the human placenta express Flt-1 in situ, these cells may be responsive to PlGF. Therefore, this study examined whether first trimester EVT cells propagated in vitro expressed the mRNA or the protein of Flt-1 and PlGF, and whether exogenous PlGF-1 had any effect on EVT cell proliferation, migration or invasiveness. Immunocytochemical and RT-PCR analyses revealed that both normal and SV40 Tag-immortalized EVT cells expressed the protein and mRNA for Flt-1, but not for PlGF-1 or -2. Exogenous PlGF-1 stimulated proliferation (measured by 3H-thymidine uptake) of normal EVT cells in a concentration-dependent manner, but only in the presence of excess heparan sulphate proteoglycans (HSPGs). These results raise two possibilities: that exogenous PlGF-1 (in spite of having a low affinity for heparin) was sequestered away from its receptor because of binding to heparan sulphate proteoglycans on the EVT cell surface or the ECM, or that HSPGs could modify the interaction between Flt-1 and PlGF. PlGF-1, in the presence or absence of HSPGs, however, had no effect on EVT migration or invasiveness, when measured with a transwell invasion (in the presence of Matrigel) or migration (in the absence of Matrigel) assay. These findings place PlGF amongst a large group of growth factors that promote EVT cell proliferation without influencing their migratory or invasive behaviours, and suggest that PlGF-Flt-1 interactions may be regulated by HSPGs in situ.     

Electron microscopic immunocytological profiles in chronic fatigue syndrome

Fluoxetine is a 5-hydroxytryptamine (5-HT, serotonin)-selective reuptake inhibitor (SSRI) and is one of the main drugs used for the treatment of depression. Because it takes 2 to 3 weeks of treatment before clinical efficacy is manifest, the acute actions of fluoxetine cannot account for the clinical actions of the drug. The chronic effects of fluoxetine have not been completely delineated. The experiments detailed here investigate the chronic effects of fluoxetine on 5-HT and gamma-aminobutyric acid (GABA) receptor-mediated actions using intracellular recording techniques in hippocampal brain slices. Rats were treated with fluoxetine for 3 weeks via osmotic minipumps implanted s.c. Fluoxetine and norfluoxetine plasma levels were determined. The hippocampal pyramidal cell characteristics and the 5-HT1A and GABA(B) receptor-mediated hyperpolarization were measured in the CA1 and the CA3 subfields. The 5-HT4 receptor-mediated decrease in the slow afterhyperpolarization amplitude was also recorded in area CA1. The time constant, magnitude of the change in resistance during 300-ms hyperpolarizing current pulses and half-decay time of the sAHP were altered by chronic fluoxetine treatment in area CA1 pyramidal cells. No changes were seen in any of the active or passive membrane properties of the CA3 hippocampal pyramidal cells. Fluoxetine treatment increased the potency of 5-HT for the 5-HT1A receptor-mediated hyperpolarization in area CA1, but not area CA3, and decreased the potency of baclofen for the GABA(B) receptor-mediated hyperpolarization in area CA1, but not area CA3. The characteristics of the concentration-response curve for the 5-HT-mediated decrease in sAHP amplitude in area CA1 were not altered by fluoxetine treatment. Chronic fluoxetine selectively and differentially altered the cell characteristics and the 5-HT1A and GABA(B) receptor-mediated responses in area CA1 of the hippocampus, which forms the final common output of the hippocampus.     

Diurnal variation of adrenocortical activity in chronic fatigue syndrome

The nutcracker esophagus, a primary motor disorder, is frequently associated with noncardiac chest pain. However, there are no data on whether its diagnosis, as in other esophageal motility disorders, is delayed. Since the disorder is frequently heralded by alarming symptoms such as chest pain and dysphagia, diagnosis should be made as soon as possible. In this study we assessed the diagnostic delay, if any, in patients with the nutcracker esophagus. Moreover, we were interested in whether the abnormalities described in the distal esophagus could also involve the entire viscus. Fifty-four subjects (age range 23-78 yr) with the nutcracker esophagus were assessed for clinical and manometric variables as an overall group and after dividing them into subgroups according to their symptoms. The manometric variables were compared with those obtained in 61 controls (age range 21-67 yr). Overall, a diagnosis of nutcracker esophagus was made after an average period of 36 +/- 6 months, and surprisingly, this was not different in the various subgroups complaining of either chest pain, dysphagia, or both. Analysis of manometric variables showed that the mean amplitude of contractions was significantly higher in the patients' group at all esophageal body levels, even in the proximal portions. Again, there were no significant differences among the subgroups of nutcracker esophagus with respect to the symptoms. Notwithstanding the presence of alarming symptoms, such as chest pain and dysphagia, the nutcracker esophagus is diagnosed on average after 3 years from the onset of symptoms. Manometric assessment seems to confirm that this entity may indeed represent a primary esophageal motor disorder. The major dysfunction is due to an abnormal increase of contraction amplitude of the entire esophageal body.     

Psychosocial correlates of chronic fatigue syndrome in adolescent girls

Behavior problems and family functioning were investigated in a sample of 10 adolescent girls with chronic fatigue syndrome (CFS), 10 matched healthy adolescent girls, and 10 adolescents with childhood cancer in remission. Based on the adolescent girls' reports, the CFS group had significantly higher scores than the cancer and healthy comparison adolescent girls on somatic complaints and also significantly higher scores than the cancer controls on internalizing symptoms and depression. Parent reports resulted in significantly higher scores in the CFS group than the adolescent girls from the healthy comparison groups on internalizing scores and somatic complaints. There were no significant differences on any family variables.