Enhanced Ca²+ influx through cardiac L-type Ca²+ channels maintains the systolic Ca²+ transient in early cardiac atrophy induced by mechanical unloading.

Cardiac atrophy as a consequence of mechanical unloading develops following exposure to microgravity or prolonged bed rest. It also plays a central role in the reverse remodelling induced by left ventricular unloading in patients with heart failure. Surprisingly, the intracellular Ca(2+) transients which are pivotal to electromechanical coupling and to cardiac plasticity were repeatedly found to remain unaffected in early cardiac atrophy. To elucidate the mechanisms underlying the preservation of the Ca(2+) transients, we investigated Ca(2+) cycling in cardiomyocytes from mechanically unloaded (heterotopic abdominal heart transplantation) and control (orthotopic) hearts in syngeneic Lewis rats. Following 2 weeks of unloading, sarcoplasmic reticulum (SR) Ca(2+) content was reduced by ~55 %. Atrophic cardiac myocytes also showed a much lower frequency of spontaneous diastolic Ca(2+) sparks and a diminished systolic Ca(2+) release, even though the expression of ryanodine receptors was increased by ~30 %. In contrast, current clamp recordings revealed prolonged action potentials in endocardial as well as epicardial myocytes which were associated with a two to fourfold higher sarcolemmal Ca(2+) influx under action potential clamp. In addition, Cav1.2 subunits which form the pore of L-type Ca(2+) channels (LTCC) were upregulated in atrophic myocardium. These data suggest that in early cardiac atrophy induced by mechanical unloading, an augmented sarcolemmal Ca(2+) influx through LTCC fully compensates for a reduced systolic SR Ca(2+) release to preserve the Ca(2+) transient. This interplay involves an electrophysiological remodelling as well as changes in the expression of cardiac ion channels.

Fluxgate magnetorelaxometry: a new approach to study the release properties of hydrogel cylinders and microspheres.

Hydrogels are under investigation as long term delivery systems for biomacromolecules as active pharmaceutical ingredients. The release behavior of hydrogels can be tailored during the fabrication process. This study investigates the applicability of fluxgate magnetorelaxometry (MRX) as a tool to characterize the release properties of such long term drug delivery depots. MRX is based on the use of superparamagnetic core-shell nanoparticles as model substances. The feasibility of using superparamagnetic nanoparticles to study the degradation of and the associated release from hydrogel cylinders and hydrogel microspheres was a major point of interest. Gels prepared from two types of photo crosslinkable polymers based on modified hydroxyethylstarch, specifically hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA) and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA), were analyzed. MRX analysis of the incorporated nanoparticles allowed to evaluate the influence of different crosslinking conditions during hydrogel production as well as to follow the increase in nanoparticle mobility as a result of hydrogel degradation during release studies. Conventional release studies with fluorescent markers (half-change method) were performed for comparison. MRX with superparamagnetic nanoparticles as model substances is a promising method to analyze pharmaceutically relevant processes such as the degradation of hydrogel drug carrier systems. In contrast to conventional release experiments MRX allows measurements in closed vials (reducing loss of sample and sampling errors), in opaque media and at low magnetic nanoparticle concentrations. Magnetic markers possess a better long-term stability than fluorescent ones and are thus also promising for the use in in vivo studies.

Preserving oxygenation during walking in severe chronic obstructive pulmonary disease: noninvasive ventilation versus oxygen therapy.

BACKGROUND: Physical activity is known to cause significant deoxygenation in patients with severe chronic obstructive pulmonary disease (COPD). Although noninvasive positive pressure ventilation (NPPV) has been shown to improve oxygenation and physical activity in these patients, no practical approach for the application of NPPV during walking has yet been established. OBJECTIVE: To elucidate the most effective approach to preserving oxygenation during walking in patients with severe COPD receiving long-term NPPV. METHODS: Three 12-min walking tests were performed in a randomized cross-over design on 3 consecutive days, comparing the usual and double dosages of oxygen versus NPPV plus the usual dosage of oxygen. The ventilator and oxygen tank were placed in a backpack. RESULTS: Eleven patients (FEV(1) 26 +/- 9% predicted) completed the study, while 8 patients refused to walk with NPPV, due to the weight of the ventilatory device (7.3 kg with NPPV vs. 3.1 kg without). PaO(2) changes during walking differed [p = 0.01, repeated-measures (RM)-ANOVA], whereas dyspnea was unchanged. The difference in PaO(2) change was 14.0 +/- 16.6 mm Hg (unadjusted p = 0.0036, critical level = 0.017, RM-ANOVA) in favor of NPPV compared to the usual dosage of oxygen. Changes in FEV(1), tidal volume and inspiratory impedance were in favor of NPPV-aided exercise (all p < 0.05, RM-ANOVA). Walking distance was reduced under NPPV (555 +/- 227 m) compared to the usual (619 +/- 210 m) and double (622 +/- 215 m) dosages of oxygen (p = 0.024, RM-ANOVA). CONCLUSIONS: NPPV plus supplemental oxygen, but not oxygen alone, preserves oxygenation during walking in patients with severe COPD. However, dyspnea and walking distance were not improved due to the burden of carrying the heavy ventilatory equipment in a backpack.

Diabetic polyneuropathy is associated with respiratory muscle impairment in type 2 diabetes.

AIMS/HYPOTHESIS: Diabetes has a major negative effect on intensive care unit outcome. This has been partly attributed to impaired respiratory neuromuscular function. However, data on respiratory neuromuscular involvement in diabetes are lacking. This study therefore aimed to assess respiratory neuromuscular function related to diabetic polyneuropathy in patients with type 2 diabetes. METHODS: Respiratory neuromuscular function was assessed by the use of volitional tests and twitch mouth (TwPmo) and twitch transdiaphragmatic (TwPdi) pressures during non-volitional bilateral anterior magnetic phrenic nerve stimulation in 21 male type 2 diabetic patients without pulmonary disease and in 23 healthy, well-matched controls (forced expiratory volume in 1 s 103 +/- 11 vs 103 +/- 12% predicted; p = 0.9). RESULTS: Both volitionally assessed maximal inspiratory and expiratory mouth pressures, and sniff nasal and transdiaphragmatic pressures were comparable between diabetic patients and controls (p > 0.1 for all). TwPmo was reduced in diabetic patients compared with controls (1.3 +/- 0.5 vs 1.0 +/- 0.4 kPa; p = 0.04), while TwPdi was comparable (1.7 +/- 0.5 vs 1.6 +/- 0.7 kPa; p = 0.6). Following subgroup analysis, patients with no or mild polyneuropathy (n = 10) as assessed by neurological disability scoring had normal respiratory neuromuscular function, whereas patients with moderate or severe polyneuropathy (n = 11) presented with markedly impaired respiratory neuromuscular function as indicated by TwPmo (1.3 +/- 0.4 vs 0.8 +/- 0.3 kPa; p = 0.01) and TwPdi (1.9 +/- 0.6 vs 1.1 +/- 0.4 kPa; p < 0.01). CONCLUSIONS/INTERPRETATION: With regard to volitional tests, diabetes does not affect respiratory neuromuscular function. In contrast, the application of non-volitional phrenic nerve stimulation provides strong evidence that diabetic polyneuropathy, as simply assessed by neurological disability scoring, is associated with substantially impaired respiratory neuromuscular function in type 2 diabetic patients.

[Hygiene in radiology]. / Hygiene in der Radiologie.

A survey is given of the hygienic management in radiological departments with special regard to the handling of injections and infusions. It includes prevention of bacterial as well as viral infections. In radiological departments disinfection of x-ray tables is necessary only in exceptional cases. A special proposal for disinfection is added. A safe method of sterilisation of flexible catheters is included, which proved to prevent bacterial infection.

[Cecal pole tuberculosis--an often forgotten differential diagnosis? Observations before and following tuberculostatic therapy]. / Zökalpoltuberkulose--eine oft vergessene Differentialdiagnose? Beobachtungen vor und nach tuberkulostatischer Therapie.

If the barium enema reveals stenosing changes of the terminal ileum and caecum, tuberculosis must be considered in differential diagnosis, even if pulmonary evidence of the illness is lacking. Since, however, radiographically no exclusive typical changes for the tuberculosis of the terminal ileum and caecum can be seen, the diagnosis must be checked histologically and bacteriologically. Under drug therapy an obvious decrease of the inflammation of the mucosa of the colon could be seen.

[Differential diagnosis of changes in density and structure of the foot bones]. / Differentialdiagnose der Dichte- und Strukturveränderungen des Fussskelets.

Skeletal disorders of the foot can be assessed radiologically by changes in bone density, structure and/or form. The knowledge of specific morphological criteria is a precondition for differential diagnosis. Our classification of skeletal disorders of the foot is based on the specific signs that can be observed in systemic and local diseases affecting the pedal bones.