Myalgic encephalomyelitis: International Consensus Criteria.

The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

Definitions and aetiology of myalgic encephalomyelitis: how the Canadian consensus clinical definition of myalgic encephalomyelitis works.

A perspective on the various definitions of myalgic encephalomyelitis and the process of discovering its aetiology is presented. The importance of clinical guidelines is emphasised to encourage clinicians to provide clear descriptions of their individual patients required for proper clinical activity; diagnosis, estimation of severity of effect, prognosis, treatment and rehabilitation. This individual knowledge is informed by general and (hopefully) publicly confirmed knowledge resulting from scientific research during the second-person interaction which lies at the core of the clinical encounter. Both types of knowledge are essential.

Dosimetric characteristics of a low-kV intra-operative x-ray source: implications for use in a clinical trial for treatment of low-risk breast cancer.

The dosimetric characteristics of a low-kV x-ray device for performing intra-operative irradiations, the Intrabeam (Photoelectron Corporation, Lexington, MA), are examined. Two dosimetric models are considered--an analytical model considering only the primary x-ray beam, and a Monte Carlo model utilizing the EGSnrc code and a spherical simulation geometry. Both models prove reliable for verifying measured dose distributions for the device. The Monte Carlo model is necessary for examining spectral variations and the influence of inhomogeneities. The predictions of the Monte Carlo model are utilized to examine points of consideration for a multi-center clinical trial using the Intrabeam in the intra-operative, single fraction post-resection treatment of low-risk breast cancer. Predicted differences in radiological equivalence of breast tissue and water suggest a 3-5% under-dose of breast tissue (in a 50 kV beam) when dose fall-off data in water is used. A substantial dose enhancement in bone (i.e., ribs) adjacent to the treatment site is predicted though, based on published clinical data for radiation-induced rib fracture, it is concluded that induction of radiation-induced rib fracture would not pose a significant risk. Dose-volume changes with size of the treatment area (defined by the size of the resection volume) are examined indicating large variations in dose-volume characteristics across the range of possible "target" volumes.

Dosimetry of a low-kV intra-operative X-ray source using basic analytical beam models.

The low energy (30-50 kVp) beams from an intra-operative X-ray source are modelled using a basic analytical model considering just primary beam attenuation and absorption. Spatial dosimetry at such low energies is difficult due to the rapid changes in dose-rate from the radiation source. The purpose of the model was to determine the variation with distance in water of coefficients required for beam dosimetry and to validate beam measurements performed in water of high-gradient dose distributions. The model predicts a change in mean mass-energy absorption coefficient of up to 3 % over the range of clinically-relevant distances in water. Distance-dose distributions (variation in dose with distance in water) for the X-ray source were calculated with the model and found to be in agreement with measurement (at clinically-relevant distances), to within a spatial distance comparable to the dimensions and positional accuracy of the ionization chamber used, and comparable to the expected dosimetric anisotropy of the radiation source. Measured and calculated distance-doses begin to diverge at relatively large distances from the radiation source, which is where dose-rates are so low that detector signal levels are comparable with noise.

Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat.

Although it is accepted that the intervertebral disc has a sensory component, it has not been previously shown by any specific method. Immunoreactivity of the physiologically active neuropeptide, calcitonin gene-related peptide (CGRP), was used as a specific marker of sensory nerve fibers and their endings in the intervertebral disc of the rat. In this study, positive fiber immunoreactivity was taken as an indication that those fibers were of sensory, and not sympathetic, origin. Immunoreactivity was found in the outer annulus fibrosus of all intervertebral discs studied. The CGRP-like immunoreactivity was also found in structures that resembled nerve endings. To the authors' knowledge, this is the first report presenting detailed positive evidence of sensory fibers and their endings in the lumbar intervertebral disc of any mammalian species.

Changes in partial pressure of carbon dioxide with time in carotid arterial blood in cats.

1. A rapidly responding CO2 sensor and cuvette were placed in the carotid artery of anaesthetized cats and changes of PCO2 in post-pulmonary capillary blood were recorded when flow through the cuvette was suddenly stopped. 2. Under control conditions when the cats breathed spontaneously or were ventilated artificially, stop-flow caused Pa, CO2 to decay by 2--5 mmHg reaching a new equilibrium in 10--15 sec. The amount by which CO2 decayed was reduced by the inhalation of high O2. The decay was enhanced by hypoxia, the inhalation or infusion of CO2. It was reversed by the administration of acetazolamide: now with stop-flow, Pa, CO2 rose by 8--15 mmHg. 3. the mechanism of this decay is uncertain. We propose that it is due to the transfer of CO2 from plasma to red cells in post-capillary blood in response to the reduction of [H+]i as H+ binds to Hb following the oxylabile release of CO2 from Hb.

Preservation of the hypoxic pulmonary vasoconstrictor mechanism during methoxyflurane anaesthesia in the dog.

The effect of methoxyflurane on the hypoxic pulmonary vasoconstrictor response in the dog lung was assessed by measuring the redistribution of pulmonary blood flow in response to two levels of unilateral alveolar hypoxia. Methoxyflurane 0.5% had no significant effect on the redistribution of blood flow resulting from the unilateral administration of oxygen 7% or nitrogen and there were no significant differences in PaO2 between the measurements made during unilateral hypoxia with methoxyflurane and those made during unilateral hypoxia in the control periods.

Effect of orciprenaline on hypoxic pulmonary vasoconstriction in dogs.

The effect of orciprenaline on hypoxic pulmonary vasoconstriction and arterial oxygen tension (PaO2) was studied in 8 dogs by measuring the redistribution of blood flow in response to unilateral alveolar hypoxia. The distribution of blood flow was recorded continuously by measuring the radioactivity of the mixed expired gas from each lung during the continuous intravenous infusion of xenon-133. The hypoxic vasoconstrictor response was significantly depressed by an infusion of 1.0 micrograms/kg/min of orciprenaline but not by a dose of 0.1 micrograms/kg/min. PaO2 during unilateral hypoxia was significantly lower during the infusion of the high dose of orciprenaline than it was in the control periods before or after the infusion. A bolus dose of 0.5 mg significantly increased blood flow to a lung with established hypoxic vasoconstriction and also caused a significant reduction in PaO2. Since these effects were produced in the absence of airway pressure or pulmonary vascular pressure changes, it is concluded that orciprenaline may depress the hypoxic pulmonary vasoconstrictor response in dogs.

A comparison of the cardiorespiratory effects of continuous positive airway pressure breathing and continuous positive pressure ventilation in dogs.

Five patterns of ventilation have been compared in dogs: (1) spontaneous ventilation at ambient pressure (SV); (2) intermittent positive pressure ventilation (IPPV); (3) spontaneous ventilation at 0.98 kPa positive airway pressure, delivered from a non-rebreathing circuit incorporating a 5-litre reservoir bag and fresh-gas flow of twice the minute volume (CPAP (bag)); (4) spontaneous ventilation at 0.98 kPa positive airway pressure, with the reservoir bag replaced by a weighted bellows (CPAP (bellows)) and (5) IPPV with 0.98 kPa positive end-expiratory pressure (CPPV). CPAP significantly decreased the rate of respiration compared with SV. CPAP (bellows) resulted in a significant increase in tidal volume. Mean oesophageal pressure, right atrial pressure, pulmonary wedge pressure and pulmonary artery pressure increased during IPPV, CPAP (bag), CPAP (bellows), and CPPV compared with SV. There were no significant changes in mean systemic arterial pressure, cardiac output, PaO2, PaCO2, CaO2, (CaO2-CVO2), PAO2-PAO2) or pulmonary venous admixture. Under the conditions of this study oxygen transport was not altered by positive airway pressure ventilation.