Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

Summary. In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-¹⁴C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l^-1. The subjects' ages were 64±2.7 and 66±1.1 (mean±SEM) years in the COPD and control groups, respectively. TOR was 0.73±0.06 and 0.52±0.02 mmol min^-1 (P<0.05) in the basal state, 0.33±0.04 and 0.30±0.02 at an insulin level of 50 mU I^-1 and 0.32±0.08 and 0.24±0.02 at an insulin level of 100 mU I^-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98±0.08 and 0.75±0.06 mmol 1^-1 (P<0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.     

Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities

A series of substituted indolyldihydropyridazinones and related compounds 1-18 were synthesized and evaluated for positive inotropic activity. In rats, most of these indole derivatives produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. Compound 13, 4,5-dihydro-5-methyl-6-(2-pyridin-4-yl-1H-indol-5-yl)pyrazin-3(2H) -one (BM 50.0430), was further investigated in cats. The increase in contractility in this animal model was not mediated via stimulation of beta-adrenergic receptors. After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h. However, the cardiotonic effect of 13 was at least 2-fold that of pimobendan after this period of time. The structural requirements necessary for optimal cardiotonic activity within this novel class of indole derivatives are a heterocyclic aromatic ring in position 2, a hydrogen or a methyl group in position 3, and a dihydropyridazinone ring system in position 5 of the indole.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Carbon blacks as EPR sensors for localized measurements of tissue oxygenation.

New electron paramagnetic resonance (EPR) oximetry probes were identified in the class of carbon black materials. These compounds exhibit very high oxygen sensitivity and favorable EPR characteristics for biological applications. At low pO(2), the linewidth is particularly sensitive to changes in oxygen tension (sensitivity of 750 mG/mmHg). The application of the probes for oximetry was demonstrated in vivo: the pO(2) was measured in muscle in which the blood flow was temporarily restricted as well as in tumor-bearing mice during a carbogen breathing challenge. The responsiveness to pO(2) was stable in muscle for at least 3 months. No toxicity was observed using these materials in cellular experiments and in histological studies performed 2, 7, and 28 days after implantation. In view of their EPR characteristics (high sensitivity) as well as the well-characterized production procedure that make them available on a large scale, these probes can be considered as very promising tools for future developments in EPR oximetry.     

Physical training and multiple sclerosis.

For many years, patients with multiple sclerosis (MS) were advised to avoid exercise because of the risk of increased neurological impairment. This article reviews the literature related to MS and physical exercise. Physical exercise depends on patients' physiological tolerance and response to exercise. MS patients can exhibit dysfunction of cardiovascular adjustment accompanied by respiratory involvement, which can alter aerobic capacity. These abnormalities tend to increase with the neurological impairment. Muscle weakness is the consequence of not only altered central motor drive but also disuse. Several studies have shown the benefits of physical training, with improvements in aerobic capacity, gait parameters and fatigue, and an influence on quality of life. Regular aerobic physical activity is necessary to maintain the benefit of physical training.     

Group B streptococcal endocarditis mimicking mitral valve myxoma

A patient with group B streptococcal endocarditis and large vegetations resembling mitral valve myxoma is described. Group B streptococcal endocarditis and the differential diagnosis of vegetations and cardiac tumors are briefly reviewed.     

Metastatic bone disease from occult carcinoma: a profile

Summary To assess the general profile of metastatic bone disease from occult primary carcinoma, the records of 172 patients with skeletal metastases seen between 1965 and 1985 were reviewed. In 51 patients (30%), the origin of the primary could not be identified when bone metastases were first diagnosed. This group were predominantly male with a high incidence of spinal metastases, cord compression and pathological fractures, and a significantly shorter (P<0.1) survival compared with bony metastases when the primary was known. The site of the primary was established in 33 patients (65%), mostly at autopsy. Lung carcinoma was by far the most common primary tumour in 52% of the cases, while it accounted for only 7% of those with a diagnosed primary. We believe that the onset of bony metastases from an occult source must initially raise the possibility of lung carcinoma. If the primary remains undetected, it appears justifiable to assume it to be in the lung, since the probability of a missed lung tumour being responsible for the metastases is high.

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Résumé Les auteurs ont revu les observations de 172 malades porteurs de métastases osseuses, vus entre 1965 et 1985, afin d'apprécier l'aspect général des métastases provenant d'un cancer primitif méconnu. Chez 51 malades (30%) l'origine du cancer primitif n'avait pu être découverte lors du diagnostic de métastase osseuse. Ce groupe était à prédominance masculine, comportant un nombre élevé d'atteintes vertébrales, de compressions médullaires et de fractures pathologiques, et un taux de survie significativement plus court (P<0,1) comparativement à celui des métastases d'un cancer primitif connu. La localisation du cancer primitif a été découverte dans 33 cas (65%), la plupart du temps à l'autopsie. Le cancer du poumon était le plus fréquemment en cause (52%), alors qu'il n'était responsable que de 7% des cas quand le cancer primitif était connu. Il semble que l'apparition de métastases osseuses d'origine inconnue doive faire évoquer d'emblée la possibilité d'un cancer du poumon. Si le cancer primitif ne peut être découvert il est vraisemblable qu'il siège au niveau du poumon, la probabilité d'un cancer du poumon méconnu, responsable des métastases, étant élevée.

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Presented in part at the International Symposium on Bone Metastases, Rome, Italy, June 1986