Nontuberculous mycobacterial disease and Aspergillus-related lung disease in bronchiectasis.

The aim of the present study was to determine whether patients with bronchiectasis and nontuberculous mycobacteria (NTM) have a higher prevalence of Aspergillus-related lung disease. A series of 30 consecutive patients with bronchiectasis and NTM (cases) were compared with 61 patients with bronchiectasis and no evidence of NTM (controls). Aspergillus serology and computerised tomography of the thorax were used to identify Aspergillus-related lung diseases, including aspergilloma, allergic bronchopulmonary aspergillosis and chronic necrotising pulmonary aspergillosis. The rate of positive Aspergillus serology was higher in cases with NTM disease compared with controls (10 out of 30 versus six out of 61). The radiological features of Aspergillus-related lung disease were also more common among patients with NTM disease than controls (six out of 30 versus none out of 61). This association between NTM disease and Aspergillus-related lung disease remained significant after adjustment for confounding effects of age and lung function (adjusted odds ratio 5.1, 95% confidence interval 1.5-17.0). Patients with bronchiectasis and nontuberculous mycobacterial disease have a higher prevalence of coexisting Aspergillus-related lung disease than patients with bronchiectasis and without nontuberculous mycobacteria. Identification of Aspergillus-related lung disease is important as prognosis amongst undetected cases is invariably poor.     

Electrical therapeutic procedures in recurrent, drug refractory tachycardias. II. Electrical transvenous catheter ablation

In 6 patients with medicamentously therapy-refractory tachycardias (3 times auricular flutter/auricular fibrillation with very rapid atrioventricular conduction, once focal atrial tachycardia, once paroxysmal atrioventricular reentry tachycardia, once recurrent ventricular tachycardia on the basis of an interventricular reentry) percutaneous transvenous catheter ablations of the atrioventricular conduction region (bundle of His ablation, 5 cases) and the right Tawara branch (1 case), respectively, were performed. During a follow-up period of 2-26 months (on an average 10.5 +/- 8.0 months) a permanent total block in 4 cases could be obtained (3 times AV-block III. once complete right bundle branch block). In two other patients the total AV block receded to the AV block I. and II. respectively, within 2 and 8 days, respectively; in the first case the AV node reentry tachycardias were no more to be evoked, in the second case a tolerable ventricular frequency was the result during the auricular flutter recidivations. In all patients treated by means of catheter ablation after the intervention an impressive improvement of the clinical symptomatology developed. Due to possible complication and the dependence upon the pacemaker of the patients concerned which is to be expected the indication to the ablation should be made only after the exhaustion of all medicamentous possibilities and taking into consideration other electric therapy methods.     

Altered regulation of lipid biosynthesis in a mutant of Arabidopsis deficient in chloroplast glycerol-3-phosphate acyltransferase activity

The leaf membrane lipids of many plant species, including Arabidopsis thaliana (L.) Heynh., are synthesized by two complementary pathways that are associated with the chloroplast and the endoplasmic reticulum. By screening directly for alterations in lipid acyl-group composition, we have identified several mutants of Arabidopsis that lack the plastid pathway because of a deficiency in activity of the first enzyme in the plastid pathway of glycerolipid synthesis, acyl-ACP:sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) (where ACP is acyl carrier protein). The lesion results in an increased synthesis of lipids by the cytoplasmic pathway that largely compensates for the loss of the plastid pathway and provides nearly normal amounts of all the lipids required for chloroplast biogenesis. However, the fatty acid composition of the leaf membrane lipids of the mutants is altered because the acyltransferases associated with the two pathways normally exhibit different substrate specificities. The remarkable flexibility of the system provides an insight into the nature of the regulatory mechanisms that allocate lipids for membrane biogenesis.     

Post-1950 mortality trends and medical care: gains in life expectancy due to declines in mortality from conditions amenable to medical intervention in The Netherlands

In order to assess the impact of medical care innovations on post-1950 mortality in The Netherlands, we analysed trends in mortality from a selection of conditions suggested by Rutstein et al.'s lists of "unnecessary untimely mortality". This selection covers 11 types of innovation, and includes 35 conditions which have become amenable to medical care. Loglinear regression analysis shows that for most of these conditions mortality declined during each of two subperiods (1950-1968; 1969-1984). Mortality decline accelerated in the second subperiod for many conditions. Reductions in mortality from these conditions between 1950/54 and 1980/84 added 2.96 and 3.95 years to life expectancy at birth of Dutch males and Dutch females respectively. A priori evidence indicates that these mortality reductions are due to some extent to 'spontaneous' incidence declines. Although the exact contribution of medical care innovations to these changes in mortality thus cannot be determined, the impact of medical care on post-1950 mortality in The Netherlands could well have been substantial.     

Regional differences in mortality from conditions amenable to medical intervention in The Netherlands: a comparison of four time periods.

In The Netherlands, as in many other countries, important geographical variation in mortality from conditions amenable to medical intervention exists. Associations with a number of simple medical care supply characteristics (general practitioner density, hospital bed density, and percentage of regional hospital beds located in university and small hospitals) are generally weak and inconsistent, both before and after controlling for possible confounding factors. We explored one of the possible reasons for this lack of consistency, which is the time dependency of the relationship between medical care supply and avoidable mortality. A comparison of associations in four time periods (1950-54, 1960-64, 1970-74 and 1980-84) shows that the percentage of variance in regional mortality levels which can be "explained" by the medical care supply variables has changed over time. Although the patterns of change differ little from what one would expect on the basis of the time of introduction of medical care innovations, the exact nature of the associations is puzzling. Apart from some expected negative associations between mortality and the presence of university hospitals, we also found a few unexpected positive associations with general practitioner density. Possible explanations for these findings are discussed, and it is concluded that further study is necessary to reveal the causes of a higher or lower mortality level for conditions considered to be amenable to medical intervention.     

The volume-activated chloride current in endothelial cells from bovine pulmonary artery is not modulated by phosphorylation

We employed the patch-clamp technique to investigate the effects of various phosphorylation pathways on activation and modulation of volume-activated Cl- currents (I _Cl,vol) in cultured endothelial cells from bovine pulmonary arteries (CPAE cells). Half-maximal activation ofI _Cl,vol occurred at a hypotonicity of 27.5 ± 1.2%. Run-down of the current upon repetitive activation was less than 15% within 60 min. Stimulation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) or by (–)-indolactam did not affectI _Cl,vol. Down regulation of PKC activity by a 24-h preincubation of the cells with 0.2 mol/l PMA, or its inhibition by loading the cells with the specific inhibitory 19–31 pseudosubstrate peptide, did not influenceI _Cl,vol. Trifluoperazine and tamoxifen fully blockedI _cCl,vol with concentrations required for half-maximal inhibition of 3.0 and 2.4 mol/1 respectively. This inhibitory effect is probably not mediated by the calmodulin-antagonistic action of these compounds, because it occurs at free intracellular [Ca²⁺] of 50 nmol/l, which are below the threshold for calmodulin activation. The tyrosine kinase inhibitor herbimycin A (1 ol/1) and genistein (100 ol/1) did not affectI _Cl,vol Exposing CPAE cells to lysophosphatidic acid (1mol/1), an activator of p42 MAPkinase and the focal adhesion kinase p125^FAK in endothelial cells, neither evoked a Cl^– current nor affectedI _Cl,vol Neither wortmannin (10 mol/1), an inhibitor of MAP kinases and of PI-3 kinase, nor rapamycin (0.1 mmol/1), which interferes with the p70S6 kinase pathway, affectedI _Cl,vol Exposure of CPAE cells to heat or Na-arsenite, both activators of a recently discovered stress-activated tyrosine phosphorylation pathway, neither activated a current nor affected the hypotonic solution-induced Cl^– current. We conclude that none of the studied phosphorylation pathways is essential for the activation of the Cl^– current induced by hypotonicity.     

Myoid hamartomas of the breast: report of 3 cases and review of the literature

Hamartomas were first described by Albrecht in 1904, who defined them as tumor-like malformations in which there was abnormal blending of the normal components of an organ. The myoid hamartoma is a rare benign lesion of the breast and has an uncertain origin, possibly in the walls of the blood vessels, muscularis mammillae of the areolae, and mainly in myoepithelium. We report 3 cases of myoid hamartomas of the breast, with the clinical, radiologic, and histopathological findings, and review the literature. The 3 lesions showed normal breast ducts and lobules, entrapped by a muscular stroma and some foci of mature adipose tissue. The muscular origin of part of the stroma was confirmed by strong reactiveness with smooth-muscle actin.     

On the effect of solvent/nonsolvent combination in the column fractionation of polymers

The effect of some solvent/nonsolvent pairs on the efficiency of the column fractionation of polystyrene was investigated. Extensive cloud point titration experiments were shown to be needed for the correct assessment of thermodynamic qualities of a solvent/nonsolvent pair used in the column fractionation of polymers. Besides the thermodynamic suitability of solvent pairs their kinetic behavior was shown to differ. Possible reasons for the observed differences were discussed.     

Reduction of glycine receptor-mediated miniature inhibitory postsynaptic currents in rat spinal lamina I neurons after peripheral inflammation

Peripheral inflammation may induce long-lasting sensitization in the central nociceptive system. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the integration and relay of pain-related information. In rats we studied whether changes in passive and active membrane properties and/or alteration of glycine receptor-mediated inhibitory control of spinal lamina I neurons may contribute to central sensitization in a model of peripheral long-lasting inflammation (complete Freund's adjuvant, hindpaw). Spontaneously occurring glycine receptor-mediated miniature inhibitory postsynaptic currents (GlyR-mediated mIPSCs) were recorded in lumbar spinal lamina I neurons. Miniature IPSC rise, decay kinetics and mean GlyR-mediated mIPSC amplitude were not affected by peripheral inflammation. The mean frequency of GlyR-mediated mIPSCs of lamina I neurons ipsilateral to the inflamed hindpaw was, however, significantly reduced by peripheral inflammation when compared with neurons from noninflamed animals. Principal passive and active membrane properties and firing patterns of spinal lamina I neurons were not changed by inflammation. These results indicate that long-lasting peripheral inflammation leads to a reduced glycinergic inhibitory control of spinal lamina I neurons by a presynaptic mechanism.