Body mass index and mortality: the influence of physical activity and smoking

PURPOSE: To study the association between body mass index (BMI) and mortality, and to evaluate the effect of physical activity during leisure time and smoking on this association in a general male population. METHODS: During 1974-1978, all men aged 35-49 yr living in three Norwegian counties were invited to a cardiovascular screening, and 87.1% attended and had their weight and height measured. Men with recognized cardiovascular diseases, diabetes mellitus, or cancer at screening were excluded. The cohort (N = 22,304) was followed for an average of 16.3 yr with respect to total and cause-specific mortality. RESULTS: During follow-up, 1909 men died. We found a J-shaped association between BMI and total mortality, and the form of association was similar for death from cardiovascular diseases. Although not statistically significant, a J-shaped association was also suggested in never-smokers. Irrespective of BMI level, ex- and never-smokers had lower mortality than current smokers. Obese smoking men had a relative risk of dying of 2.01 (95% CI: 1.29-3.11) compared with obese never-smokers, and a relative risk of 4.55 (95% CI: 3.34-6.20) compared with normal weight never-smokers (BMI 22-24.9 kg x m(-2)). Within each category of physical activity during leisure time, obese men had a similar increased relative risk of death compared with normal-weight individuals. However, the U- to J-shaped association between BMI and mortality seemed to disappear by increasing level of physical activity, but this finding was not significant. CONCLUSION: This study suggests a J-shaped association between BMI and total mortality, also when stratified on smoking habits and physical activity. The suggested linear trend in the most physical active men needs to be reassessed.     

Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[11C]rolipram and positron emission tomography

Evidence of disruptions in cAMP-mediated signaling in several neuropsychiatric disorders has led to the development of R-[(11)C]rolipram for imaging phosphodiesterase-4 (PDE4) enzymes with positron emission tomography (PET). The high-affinity PDE4 inhibitor rolipram was previously reported to have an antidepressant effect in humans. PDE4 is abundant in the brain, and it hydrolyzes cAMP produced following stimulation of various neurotransmitter systems. PDE4 is regulated by intracellular cAMP levels. This paper presents the first PET study of R-[(11)C]rolipram in living human brain. Consistent with the wide distribution of PDE4, high radioactivity retention was observed in all regions representing the gray matter. Rapid metabolism was observed, and kinetic analysis demonstrated that the data fit in a two-tissue compartment model. R-[(11)C]Rolipram is thus suitable for imaging PDE4 and possibly cAMP signal transduction in the living human brain with PET.     

Functional MRI and 18F FDG-positron emission tomography for presurgical planning: comparison with electrical cortical stimulation

Summary.  Background: In patients with mass lesions near “eloquent” cortical areas different preoperative mapping techniques can be used. Two of the most widely used approaches include positron emission tomography (PET) and functional MRI (fMRI). We employed both methods in the same patients undergoing presurgical evaluation and compared the results to those obtained by direct electrical cortical stimulation (DECS).  Method: 22 patients with tumours of different aetiology near the central region were investigated. FMRI was performed using a T2^*-weighted gradient-echo BOLD sequence at 1.5 T, PET was performed after injection of 122–301 MBq ¹⁸F-Fluorodeoxyglucose (18-FDG) under rest and activation conditions. DECS was performed in all patients with recordings of muscles primarily involved in the investigated tasks.  Findings: In 19 patients all three modalities could be compared, 1 patient demonstrated discordance between fMRI and PET with DECS speaking in favour of fMRI, 6 patients had neighbouring results of PET and fMRI (between 1–2 cm distance), 12 patients had overlapping results.  Interpretation: The high incidence of neighbouring results is presumably related to fMRI specific artefacts. Advantages of fMRI are: Higher spatial and temporal resolution, more and different functional runs, shorter examination time, wider availability, longitudinal examinations, non-invasiveness and cost-effectiveness, easy registration to anatomical images. Advantages of PET are: higher signal-to-noise ratio, lesser susceptibility to artefacts (motion, draining veins), evaluation of tumour metabolism. It is our opinion that the neurosurgeon has to decide on a case-by-case basis which study suits his specific needs in the presurgical evaluation of his patient. Published online September 2, 2002 Acknowledgments  This study was supported by a grant from the German research council (Deutsche Forschungsgemeinschaft – DFG) (KR 2008 2/1). Correspondence: Timo Krings M.D., Department of Neuroradiology, University Hospital of the Technical University Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.     

Imaging of intrathoracic metastases of nonseminomatous germ cell tumors

Radiologic imaging is crucial in the evaluation of intrathoracic metastatic nonseminomatous germ cell tumors. Helical CT is the workhorse of radiologic staging and is sensitive in the detection of parenchymal nodules and mediastinal lymphadenopathy. CT may also demonstrate other less common sites of metastatic disease. Although, currently, no radiologic procedure is effective in distinguishing viable tumor or teratoma from residual fibrosis and necrosis, cross-sectional imaging remains essential in the presurgical evaluation of potential metastatic disease. FDG PET and CT-guided needle biopsy may be useful in select, high-risk patients.     

Lumboradiculopathy due to epidural varices: two case reports and a review of the literature

Lumbar radicular pain caused by epidural varices is rare. Its incidence is evaluated at 4.5% of operations for disc herniation. We report 2 cases which were only diagnosed during surgery for a herniated disk as is usually observed in the literature. The mechanism behind radicular pain is not fully understood. It may be compression by the varix itself but it may also be secondary to diffculty in venous return. Several anatomical types are described: thrombosed varix (type 1), non thrombosed varix (type 2), localized hematoma (type 3). Our 2 cases corresponded to type 2. The diagnosis can established by MRI at the pre-operative stage. The images vary according to the anatomical type and the age of the lesions. Treatment is by surgery.     

The use of digital photographs for surgical and rehabilitation records. Methods and results

Digital pictures are performed on patients in the pre and postoperative periods, and sometimes during surgery. Seven thousand fourty eight records have been recorded. This method is useful for a multidisciplinary responsibility, particularly for the hand therapist and the splint follow-up. It is also good for patient information, for Workman's compensation doctors and for experts. The pitfall is that one have to manage the records on a strict day by day base.     

Use of bacille Calmette-Guérin in superficial bladder cancer

Intravesical bacille Calmette-Guérin (BCG) has been used by urologists for several years after its first reported use as a cancer therapy in the 1930s. Morales in 1976 described the usage of BCG as a once weekly intravesical instillation for six weeks; this is a treatment regimen that still exists today. Its success as a treatment depends on it being used appropriately. It is employed: (1) to treat carcinoma in situ or occasionally residual papillary tumours; (2) to reduce the number and frequency of recurrent high grade superficial tumours; and (3) to prevent disease progression (although this remains a controversial point, on which there is no consensus view). Unfortunately, the more widespread use of BCG is often limited due its high side effect profile. Present research is directed towards reducing its side effect profile, improving its efficacy, and understanding its exact mechanism of action, which is not fully understood.     

Epidermal growth factor-mediated activation of the map kinase cascade results in altered expression and function of ABCG2 (BCRP).

Epidermal growth factor (EGF) is a multifunctional growth factor known to play a major role in proliferation and differentiation processes. EGF-induced differentiation is a prerequisite for function of various cell types, among them cytotrophoblasts, a functionally important cellular fraction in human placenta. Stimulation of cytotrophoblasts with EGF results in formation of a multinuclear syncytium representing the feto-maternal interface, which protects the fetus against exogenous substances. It is well established that part of this protection system is based on ATP-binding cassette (ABC) transporters such as ABCG2 (breast cancer resistance protein, BCRP). However, little is known about regulation of transport proteins in the framework of EGF-mediated cellular differentiation. In the present work we show a significant increase of ABCG2 expression by EGF in cytotrophoblasts, BeWo, and MCF-7 cells on both mRNA and protein levels. This increase resulted in decreased sensitivity to the ABCG2 substrates mitoxantrone and topotecan. In each cell type, EGF increases expression of ABCG2 by activation of mitogen-activated protein kinase cascade via phosphorylation of extracellular regulated kinase (ERK)1/2 and c-jun NH-terminal kinase/stress-activated protein kinase (JNK/SAPK). Consequently, the increase of ABCG2 by EGF was abolished by pretreatment of cells with the tyrosine kinase inhibitor 4-(3-chloroanillino)-6,7-dimethoxyquinazoline (AG1478) or the mitogen-activated protein kinase kinase inhibitor 2'-amino-3'methoxyflavone (PD 98059), thereby reestablishing sensitivity toward mitoxantrone. Moreover, analysis of ABCG2 expression during placental development revealed a significant increase in preterm versus term placenta. Taken together, our data show regulation of ABCG2 expression by EGF. In view of EGF signal transduction as a target for drugs (e.g., gefitinib), which are in turn substrates and/or inhibitors of ABCG2, this regulation has therapeutic consequences.