The chronic fatigue syndrome – an update

Background –  In this article, current scientific knowledge on the chronic fatigue syndrome (CFS) is reviewed. The US case definition of CFS (the CDC-definition) is most widespread in research and clinical practice. Estimates of prevalence vary from 0.2% to above 2%. The female–male ratio is approximately 3:1.
Clinical Features –  Severe fatigue is the dominating complaint; it is worsened from exertions and not substantially relieved by rest. In addition, the patients might have a varying combination of accompanying symptoms. Clinical evaluation should be based upon standardized guidelines, including an assessment of functional impairments.
Pathophysiology –  The pathophysiology should be interpreted within a biopsychosocial framework. Present knowledge suggests that certain genetic polymorphisms and personality traits might be regarded as predisposing factors, some infections and severe psychosocial stress constitute precipitating factors, whereas disturbances of immunity, skeletal muscle, cognitive abilities, endocrine control and cardiovascular homeostasis are possible perpetuating factors.
Treatment –  Cognitive behavioural therapy and graded exercise therapy are of proven value in randomized controlled trials. Several pharmaceutical measures have been explored and found to have no beneficial effect. Most patients might expect long-term improvement, but full recovery is rare; however, the prognosis is better among adolescents.     

Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells

We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta- mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta- treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL- 1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.     

The effect of a pre- and post-operative orthogeriatric service on cognitive function in patients with hip fracture. The protocol of the Oslo Orthogeriatrics Trial

ABSTRACT: BACKGROUND: Hip fracture mainly affect older people. It is associated with high morbidity and mortality, and in particular a high frequency of delirium. Incident delirium following hip fracture is associated with an increased risk of dementia in the following months, but it is still not firmly established whether this is an association or a causal relationship. Orthogeriatric units vary with respect to content and timing of the intervention. One main effect of orthogeriatric care may be the prevention of delirium, especially if preoperative and postoperative care are provided. Thus, the aim of Oslo Orthogeriatric Trial, is to assess whether combined preoperative and postoperative orthogeriatric care can reduce the incidence of delirium and improve cognition following hip fracture. Methods/design: Inclusion and randomisation will take place in the Emergency Department, as soon as possible after admission. All patients with proximal femur fractures are eligible, irrespective of age, pre-fracture function and accommodation, except if the fracture is caused by a high energy trauma or the patient is terminally ill. The intervention is pre-and post-operative orthogeriatric care delivered on a dedicated acute geriatric ward. The primary outcome measure is a composite endpoint combining the Clinical Dementia Rating Scale (CDR) and the 10 word memory task at four months after surgery. Secondary outcomes comprise incident delirium, length of stay, cognition, mobility, place of residence, activities of daily living and mortality, measured at 4 and 12 months after surgery. We have included 332 patients in the period 17th September 2009 to 5th January 2012. DISCUSSION: Our choice of outcome measures and our emphasis of orthogeriatric care in the preoperative as well as the postoperative phase will enable us to provide new knowledge on the impact of orthogeriatric care on cognition. Trials registration: ClinicalTrials.gov NCT01009268.     

Relations between background,process and outcome in the first semester of a new,problem-based medical curriculum

The authors investigated the relations between students' background (gender, age, study experience), learning process (learning approach, independent study time) and outcome (examination results, satisfaction) in the first semester of a new, integrated undergraduate medical curriculum, combining PBL and conventional learning methods. Data were obtained from official records and from a questionnaire answered by 113 students (response rate 92%). Variables were subjected to multivariate analyses. Significantly more males than females reported a strategic learning approach, and these students were less satisfied and more prone to fail on the exam. Time used on independent study did not predict examination results. The authors suggest that in a problem-based curriculum, the strategic males should be identified and supervised to improve the qualitative aspects of their study behaviour.     

Angiotensin‐converting enzyme inhibition increases glucose‐induced insulin secretion in response to acute restraint

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GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

• 1 The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload‐induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short‐term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload‐induced hypertrophy.
• 2 Twenty‐six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS‐GH group) or saline (AAS‐P group) for 14 days. Sham‐operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.
• 3 Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS‐P group than in the control group. However, in the AAS‐GH group, PWSV was between that in the control and AAS‐P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS‐P and AAS‐GH groups compared with control (10.34 ± 1.29, 4.44 ± 1.37 and 1.88 ± 0.88%, respectively; P < 0.05) and was higher still in the AAS‐P group compared with the AAS‐GH group.
• 4 The present study has shown that short‐term administration of GH to rats with chronic pressure overload‐induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.