Glucose utilisation in the lungs of septic rats

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose (¹⁸FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of ¹⁸FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. ¹⁸FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions. Received 15 February and in revised form 28 April 1999     

Prevalence of symptomatic pelvic organ prolapse in a Swedish population

Our aim was to estimate the prevalence of symptomatic pelvic organ prolapse (POP) in a Swedish urban female population. The cross-sectional study design included 8,000 randomly selected female residents in Stockholm, 30–79-year old. A postal questionnaire enquired about symptomatic POP, using a validated set of five questions, and about urinary incontinence and demographic data. Of 5,489 women providing adequate information, 454 (8.3%, 95% confidence interval 7.3–9.1%) were classified as having symptomatic POP. The prevalence rose with increasing age but leveled off after age 60. In a logistic regression model that disentangled the independent effects, parity emerged as a considerably stronger risk factor than age. There was a ten-fold gradient in prevalence odds of POP with parity, the steepest slope (four-fold) being between nulliparous and primiparous women. The prevalence of frequent stress urinary incontinence was 8.9% and that of frequent urge incontinence 5.9%. Out of the 454 women with prolapse, 37.4% had either or both types of incontinence.     

The complement-derived anaphylatoxin C5a increases microglial GLT-1 expression and glutamate uptake in a TNF-α-independent manner

Microglia can express Na⁺-dependent high-affinity glutamate transporters during pathological conditions in the CNS. The transporter expression seems to be activation dependent, and we therefore sought to identify factors that could induce it, in addition to the well-known effect of lipopolysaccharide (LPS) that is mediated by tumour necrosis factor-α (TNF-α). The complement-derived anaphylatoxins C3a and C5a are of potential interest as the complement system is activated in nearly all insults to the nervous system, and both C3a and C5a have been shown to protect against excitotoxicity. We have found that C5a, but not C3a, increased the expression of the microglial glutamate transporter GLT-1 in a dose-dependent manner without eliciting or modulating the release of TNF-α. However, the increase was not as prominent as the one induced by LPS, indicating that the microglia are in different activity states. The increase in microglial GLT-1 expression led to an increased functional uptake of glutamate without affecting the release. This suggests that C5a-stimulated microglia can be self- and neuroprotective by removing extracellular glutamate.     

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome—a randomised controlled trial

We have previously conducted a small treatment study on staphylococcus toxoid in fibromyalgia (FM) and chronic fatigue syndrome (CFS). The aim of the present study was to further assess the efficacy of the staphylococcus toxoid preparation Staphypan Berna (SB) during 6 months in FM/CFS patients. One hundred consecutively referred patients fulfilling the ACR criteria for FM and the 1994 CDC criteria for CFS were randomised to receive active drug or placebo. Treatment included weekly injections containing 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 0.9 ml, and 1.0 ml SB or coloured sterile water, followed by booster doses given 4-weekly until endpoint. Main outcome measures were the proportion of responders according to global ratings and the proportion of patients with a symptom reduction of > or =50% on a 15-item subscale derived from the comprehensive psychopathological rating scale (CPRS). The treatment was well tolerated. Intention-to-treat analysis showed 32/49 (65%) responders in the SB group compared to 9/49 (18%) in the placebo group (P<0.001). Sixteen patients (33%) in the SB group reduced their CPRS scores by at least 50% compared to five patients (10%) in the placebo group (P< 0.01). Mean change score on the CPRS (95% confidence interval) was 10.0 (6.7-13.3) in the SB group and 3.9 (1.1-6.6) in the placebo group (P<0.01). An increase in CPRS symptoms at withdrawal was noted in the SB group. In conclusion, treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS. Maintenance treatment is required to prevent relapse.     

Design paper: the DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of aerobic versus non-aerobic versus relaxation training for patients with light to moderate depression

BACKGROUND: In western countries, the yearly incidence of depression is estimated to be 3-5% and the lifetime prevalence is 17%. In patient populations with chronic diseases the point prevalence may be 20%. Depression is associated with increased risk for various conditions such as osteoporoses, cardiovascular diseases, and dementia. WHO stated in 2000 that depression was the fourth leading cause of disease burden in terms of disability. In 2000 the cost of depression in the US was estimated to 83 billion dollars. A predominance of trials suggests that physical exercise has a positive effect on depressive symptoms. However, a meta-analysis from 2001 stated: "The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow-up." OBJECTIVES: The major objective for this randomized trial is to compare the effect of non-aerobic, aerobic, and relaxation training on depressive symptoms using the blindly assessed Hamilton depression scale (HAM-D(17)) as primary outcome. The secondary outcome is the effect of the intervention on working status (i.e., lost days from work, employed/unemployed) and the tertiary outcomes consist of biological responses. DESIGN: The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are recruited through general practitioners and psychiatrist and randomized to three different interventions: 1) non-aerobic, -- progressive resistance training, 2) aerobic training, -- cardio respiratory fitness, and 3) relaxation training with minimal impact on strength or cardio respiratory fitness. Training for all three groups takes place twice a week for 4 months. Evaluation of patients' symptoms takes place four and 12 months after inclusion. The trial is designed to include 45 patients in each group. Statistical analysis will be done as intention to treat (all randomized patients). Results from the DEMO trial will be reported according to the CONSORT guidelines in 2008-2009.     

The Alzheimer's disease-associated gamma-secretase complex: functional domains in the presenilin 1 protein

Alzheimer's disease is neuropathologically characterized by the presence of neurofibrillary tangles and amyloid plaques in the brain. Amyloid plaques are extracellular deposits primarily composed of the amyloid beta-peptide, which is derived from the amyloid beta-precursor protein (APP) by sequential cleavages at the beta-secretase and gamma-secretase sites. gamma-Secretase cleavage is performed by a high molecular weight protein complex containing presenilin (PS), nicastrin, Aph-1 and Pen-2. The gamma-secretase complex is an unusual transmembrane aspartyl protease that cleaves APP within the transmembrane domain. In addition to APP, a large number of other single membrane-spanning proteins have been shown to be cleaved within their transmembrane domains by the gamma-secretase complex in a process referred to as regulated intramembrane proteolysis. Here we review recent research leading to the identification and understanding of the gamma-secretase complex components with emphasis on PS, which harbors the catalytic site. In addition, we summarize our own work focused on identifying and studying domains in PS1 that are critical for mediating gamma-secretase activity. Biochemical understanding of the gamma-secretase complex is important from a basic biological and physiological point of view, and could help in the development of small molecules that modulate gamma-secretase processing in an APP-specific manner.     

Nutritional treatment of patients with severe traumatic brain injury during the first six months after injury

OBJECTIVE: This study explored current nutritional treatment policies and nutritional outcome in patients with severe traumatic brain injury. METHODS: We performed a retrospective, structured survey of the medical records of 64 patients up to 6 months after injury or until the patients were independent in nutritional administration. RESULTS: Enteral nutrition was administered to 86% of patients. Fourteen patients (22%) had a gastrostomy; after 6 months four were still in use. At 6 months, 92% of patients received all food orally and 84% had gained nutritional independence. Energy intake was equal to the calculated basal metabolic rate throughout the first month after injury and increased by 21% during the second month. Sixty-eight percent exhibited signs of malnourishment with weight losses of 10-29%. CONCLUSION: This study suggests that most patients with severe traumatic brain injury regain their nutritional independence within the first 6 months after injury, but also that most develop signs of malnutrition.     

Long-term use of cellular phones and brain tumours: increased risk associated with use for > or =10 years

Aim

To evaluate brain tumour risk among long‐term users of cellular telephones.

Methods

Two cohort studies and 16 case–control studies on this topic were identified. Data were scrutinised for use of mobile phone for ⩾10 years and ipsilateral exposure if presented.

Results

The cohort study was of limited value due to methodological shortcomings in the study. Of the 16 case–control studies, 11 gave results for ⩾10 years'' use or latency period. Most of these results were based on low numbers. An association with acoustic neuroma was found in four studies in the group with at least 10 years'' use of a mobile phone. No risk was found in one study, but the tumour size was significantly larger among users. Six studies gave results for malignant brain tumours in that latency group. All gave increased odd ratios (OR), especially for ipsilateral exposure. In a meta‐analysis, ipsilateral cell phone use for acoustic neuroma was OR = 2.4 (95% CI 1.1 to 5.3) and OR = 2.0, (1.2 to 3.4) for glioma using a tumour latency period of ⩾10 years.

Conclusions

Results from present studies on use of mobile phones for ⩾10 years give a consistent pattern of increased risk for acoustic neuroma and glioma. The risk is highest for ipsilateral exposure.