[Scientific assessment and regulatory approval of radiological screening examinations in Germany]. / Wissenschaftliche Bewertung und rechtliche Zulassung von radiologischen Früherkennungsuntersuchungen in Deutschland.

BACKGROUND: Radiologic imaging technologies like computed tomography (CT) have the potential to screen for various diseases. The potential benefits of screening are always associated with risks, particularly from the application of ionizing radiation. MATERIALS AND METHODS: The International Basic Safety Standards as well as the Council Directive 2013/59/Euratom have set guidelines for the application of ionizing radiation in early detection which were transposed into the German Radiation Protection Law. Accordingly, the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) approves screening examinations on a generic level, based on a scientific report provided by the German Federal Office for Radiation Protection (BfS), and defines in a federal statutory ordinance which type of screening is permissible for detecting a disease for a particular group of persons and under which conditions. RESULTS: With exception of the mammography screening programme, no radiological examination for the early detection of disease has been approved in Germany to date. However, such screenings are currently being offered in Germany. The BfS is currently conducting a scientific evaluation for lung cancer screening with low-dose CT. CONCLUSIONS: Screening examinations with radiological imaging can only be approved when studies with the highest level of evidence have demonstrated that the benefits outweigh the risks. To translate this favourable benefit-risk balance into general health care, strict requirements for the entire screening process including quality assurance must be defined.

Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial.

BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.

Inhalation of tobramycin in patients with cystic fibrosis: comparison of two methods.

Inhalant tobramycin is established in the treatment of cystic fibrosis patients. Conventional nebulizers require a large amount of the expensive compound, because only a small fraction is deposited in the targeted lung region. In contrast, techniques based on controlled inhalation allow a high and reproducible deposition of the drug in specific lung regions. In our study we compared the efficiency of two techniques based on conventional and controlled inhalation in 16 cystic fibrosis patients aged 13-39 years. Inhalations with the doses of tobramycin of 300 mg and 150 mg were performed twice daily for three days. The efficiency of the drug deposition was measured by the determination of its serum concentration 1 h after the end of the inhalation. The mean FEV1 value in our patients was 61% of predicted, range 36%-116%. There were no differences in tobramycin serum concentrations among the three study days in both methods (controlled inhalation: 0.983 +/-0.381(+/-SD) mg/l, 1.119+/-0.448 mg/l, 1.194+/-0.568 mg/l; conventional inhalation: 1.075+/-0.798 mg/l, 1.294 0.839 mg/l and 1.269+/-0.767 mg/l, on Day 1, Day 2, and Day 3, respectively). Even though the drug amount was double in the conventional technique, there was no significant difference in its overall serum concentration from the three study days (conventional inhalation: 1.210+/-0.783 mg/l, controlled inhalation: 1.092+/-0.461 mg/l). In addition, the coefficient of variation and the required inhalation time were shorter in controlled inhalation than in conventional inhalation (42% vs. 65% and 7-8 min vs. 20 min, respectively). Our data suggest that controlled inhalation can significantly reduce the amount of a drug required for therapy, the inhalation time required for drug deposition, and the variability of pulmonary dosage. It seems probable that controlled inhalation can improve the antibiotic prevention of pulmonary infection.

Functional morphology of a double-walled multiporous olfactory sensillum: the sensillum coeloconicum of Bombyx mori (Insecta, Lepidoptera).

The fine structure of coeloconic sensilla of Bombyx mori was studied in cryofixed specimens. These sensilla belong to the category of double-walled wall-pore sensilla. The pegs are approximately 10 microm long, located in pits on the dorsal side of the antennal branches, and longitudinally grooved in their distal half (grooved surface approximately 30 microm(2)). The central lumen contains the outer dendritic segments of usually five receptor cells, and is surrounded by up to 15 partially fused cuticular fingers. The peripheral lumina of these cuticular fingers are filled with material resembling wax-canal filaments. Radial spoke channels (approximately 600 per peg), each 10-20 nm wide, connect the central lumen with the longitudinal groove channels. Groove and spoke channels are assumed to mediate the transport of odorant molecules from the outer epicuticular surface layers to the sensory dendrites. Thus the double-walled wall-pore sensilla represent a bauplan essentially different from single-walled wall-pore sensilla; the reason, however, why the two types are found together throughout the insect orders remains enigmatic. Other peculiar features of the coeloconic sensilla of the silkmoth are invaginations of the outer dendritic segments and direct contacts between the receptor cell somata. The latter may be the structural correlate to electrophysiological observations indicative of peripheral interaction between the receptor neurons. All three auxiliary cells have elaborately folded apical plasma membranes studded with portasomes and associated with an abundance of mitochondria; basally they often contact tracheal branches. As compared to the auxiliary cells of the single-walled olfactory sensilla of the same species, all the mentioned features are much more prominent and hint to a higher ion pumping activity at the border to the sensillum-lymph cavities.

[Laparoscopically assisted formation of end stage and loop ileostomies and colostomies]. / Laparoskopisch assistiertes Anlegen von endständigen und doppelläufigen Ileostomien und Kolostomien.

Especially in obese or severely ill patients, forming of an ileostomy or colostomy can be very difficult and laparotomy itself can lead to many complications. The intraabdominal part of this operations can easily be performed laparoscopically. The method is quick and simple and many complications can be avoided.

[Is a minimally-invasive treatment concept in the late stage of pleural empyema successful?]. / Ist ein minimal-invasives Behandlungskonzept in späten Stadien des Pleuraempyems erfolgreich?

INTRODUCTION: Thoracoscopic treatment of pleural empyema is still a controversial method, especially in the chronic stage of the disease. The issue is raised whether the thoracoscopic approach to the empyema-possibly combined with a small additional thoracotomy in advanced stages-is successful and of low risk. PATIENTS AND METHODS: Between January 1993 and May 1995 we treated 13 patients in advanced stages of pleural empyema. The patients were all seriously ill and had severe underlying disease. The procedures were performed under general anesthesia involving intubation with a double-lumen endotracheal tube. The steps of our standard operative procedure are outlined. RESULTS: In 5 patients with a pleural empyema in stage III thoracoscopy was facilitated by a small additional thoracotomy. A complete resolution of the disease was obtained in 12 cases and a secondary intervention was necessary in 1 patient. There was no peri- or postoperative mortality, and apart from a prolonged drainage of the pleural cavity in 3 patients no morbidity was registered. In the long-term follow up, 3 patients had died. There was no correlation between the deaths and the intervention or the empyema disease. DISCUSSION: We discuss the advantages of a limited additional thoracotomy in case of intraoperative difficulties encountered with late stages of empyema. This treatment can still be considered minimally invasive. All patients tolerated the procedure well, and the overall results were favourable in 92% of our collective. However, thoracoscopic treatment should preferably take place at an earlier stage. CONCLUSION: We recommend the thoracoscopic approach-possibly combined with a limited thoracotomy-as primary treatment in late stages of pleural empyema.

[Signet ring cell carcinoma of Vater's papilla: a very rare malignancy]. / Siegelringzellkarzinom der Papilla Vateri: ein sehr seltenes Malignom.

We describe a rare variant of carcinoma of the ampulla of Vater. A 70-year-old man with several illnesses and a newly appeared jaundice was investigated and a signet-ring cell carcinoma of the ampulla of Vater diagnosed. We performed a local transduodenal excision. One year after operation the patient is asymptomatic. This is the second case report in the literature.

Effects of platelet-activating factor on intracellular Ca2+ concentration and contractility in isolated cardiomyocytes.

We investigated the effects of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) on intracellular Ca2+ concentration ([Ca2+]i) and cell length in isolated and field-stimulated rat cardiomyocytes. [Ca2+]i and cell length of field-stimulated cells were determined simultaneously by confocal laser scan microscopy by using the fluorescent Ca2+ dye Fluo-3. PAF (10(-12)-10(-8) M) inhibited systolic [Ca2+]i increase in a time- and concentration-dependent manner. Maximal effects were observed after an incubation time of 6-8 min, resulting in a 17% (10(-12) M), 41% (10(-10) M), and 52% (10(-8) M PAF) inhibition of systolic [Ca2+]i increase. A time- and concentration-dependent decrease in simultaneously measured cell shortening also was demonstrated. Cell shortening was inhibited by 10% (10(-12) M), 32% (10(-10) M), and 50% (10(-8) M) after an incubation time of 8 min. The effects of PAF could be antagonized by the PAF-receptor antagonist WEB 2170. These data demonstrate that PAF receptor-dependently induces a negative inotropic effect, which is correlated with a decrease in systolic [Ca2+]i and is most likely not due to a decrease in myofilament sensitivity.