Summary of the 2021 ICRP workshop on the future of radiological protection.

The International Commission on Radiological Protection (ICRP) has embarked on a process to review and revise the current System of Radiological Protection ('the System'). To stimulate discussion, the ICRP published two open-access articles: one on aspects of the System that might require review, and another on research that might improve the scientific foundation of the System. Building on these articles, the ICRP organized a Workshop on the Future of Radiological Protection as an opportunity to engage in the review and revision of the System. This digital workshop took place from 14 October-3 November 2021 and included 20 live-streamed and 43 on-demand presentations. Approximately 1500 individuals from 100 countries participated. Based on the subjects covered by the presentations, this summary is organized into four broad areas: the scientific basis, concepts and application of the System; and the role of the ICRP. Some of the key topics that emerged included the following: classification of radiation-induced effects; adverse outcome pathway methodologies; better understanding of the dose-response relationship; holistic and reasonable approaches to optimization of protection; radiological protection of the environment; ethical basis of the System; clarity, consistency and communication of the System; application of the System in medicine and application of the principles of justification and optimization of protection.

GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice.

BACKGROUND: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. METHODS: Ear thickness of wild-type (wt) and Sucnr1-deficient (Sucnr1-/- ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin-induced asthma and arthritis models. RESULTS: We found augmented ACD reactions in Sucnr1-/- mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1-/- mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: A deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell-dependent arthritis. On the contrary, the fact that Sucnr1-/- mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases.

Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus.

Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.

[Management of Idiopathic Frozen Shoulder - Prospective Evaluation of Mobilisation under Anaesthesia and an Additional Subacromial Cortisone Injection]. / Management der idiopathischen Schultersteife - prospektive Evaluation der reinen Narkosemobilisation und einer additiven subakromialen Kortikosteroidinjektion.

BACKGROUND: Management of primary frozen shoulder is still controversial. Many authors tend to treat patients with an arthroscopic release, if conservative therapy fails. We aimed to demonstrate the efficiency of manipulation under anaesthesia (MUA) in patients with primary frozen shoulder and to contrast the outcome of single MUA with the results of MUA with an additional subacromial injection of cortisone. MATERIAL AND METHODS: A prospective trial with a 1-year follow-up was performed. Between 2008 and 2011 30 patients with idiopathic frozen shoulder underwent MUA, 15 of them received an additional injection of triamcinolone and bupivacain. Thereafter all patients underwent a standardised physiotherapy treatment regime for three months. The patients were assessed for pain, function, range of motion and the Constant-Murley score (CMS) before MUA as well as 1, 6 and 12 months after the intervention. RESULTS: Range of motion increased significantly (p < 0.05) in all planes at every point of follow-up. Preinterventional abduction improved from 65.80° ± 13.25 to 145.40° ± 18.50, preinterventional forward flexion from 90.20° ± 18.98 to 155.60° ± 13.51 at 1 month after MUA. At this point 80 % of patients had returned to work, 66.7 % were free of pain. One year after MUA abduction was improved to 173.07° ± 6.03, forward flexion to 175.47° ± 4.03. The CMS rose significantly (p < 0.05) from 24.53 ± 9.28/100 to 73.97 ± 10.77/100 after 1 month and up to 86.30 ± 5.62/100 after 1 year. Range of motion and function as described for a healthy shoulder were recognised in every patient during 1 year. However additional subacromial injections of triamcinolone and bupivacain did not lead to a significant improvement. There were no complications reported. CONCLUSION: This study demonstrates that MUA is a safe and effective tool in the management of idiopathic frozen shoulder, if conservative therapy fails. An additional subacromial injection of cortisone however does not generate a significant improvement.

[ARDS after Incidental Aspiration of Petroleum in an Adult]. / ARDS nach akzidentieller Aspiration von Petroleum bei einem Erwachsenen.

Petroleum aspiration as a reason for lipid pneumonia is a rare complication. Mostly children are affected and mortality rates are low. In most case series, virtually every subject survived.We describe here the case of a patient who developed ARDS and pneumatoceles with a fatal outcome. Due to the undulant nature of the disease, multipe thoracic CT were performed, enabling us to describe the precise radiologic course of the disease.

Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial.

OBJECTIVE: We conducted a prospective phase II clinical trial to determine the efficacy of sorafenib in patients with advanced radio-iodine refractory differentiated thyroid cancer. In this article, the long-term results are presented. PATIENTS AND METHODS: Thirty-one patients with progressive metastatic or locally advanced radioactive iodine refractory differentiated thyroid cancer received sorafenib 400 mg orally twice daily. The study end points included response rate, progression-free survival (PFS), overall survival (OS), best response by Response Evaluation Criteria in Solid Tumors criteria 1.0, and toxicity. RESULTS: Median PFS was 18 months (95% confidence interval (95% CI): 7-29 months) and median OS was 34.5 months (95% CI: 19-50 months). Eight patients (31%) achieved a partial response and 11 patients (42%) showed stable disease after a median follow-up of 25 months (range 3.5-39 months). Toxicity mostly included hand foot syndrome, weight loss, diarrhea, and rash. CONCLUSION: Sorafenib has clinically relevant antitumor activity in patients with progressive metastatic or locally advanced radio-iodine refractory differentiated thyroid cancer. Sorafenib can nowadays be considered as the standard option in these patients.

Alternativas de propagação na produção de óleo essencial de Mentha canadensis L. no Litoral Norte Catarinense / Propagation alternatives for the production of Mentha canadensis L. essential oil at the Santa Catarina State northern coast

O gênero Mentha é cultivado mundialmente para a produção de óleo essencial, com ênfase no constituinte mentol, amplamente utilizado nas indústrias farmacêutica, cosmética, alimentícia e de higiene pessoal. Este trabalho teve como objetivo avaliar o efeito da utilização de diferentes estruturas de propagação e épocas de colheita de Mentha canadensis L. no Litoral Norte Catarinense. O delineamento experimental foi em blocos ao acaso em esquema fatorial 4x2, comparando quatro estruturas de propagação (estolões com 10, 15 e 20 cm de comprimento e estacas com 5 cm de comprimento) e duas épocas de colheita (95 dias após o plantio e 60 dias após a rebrota). Em cada colheita foi avaliado o crescimento vegetativo e produtividade de óleo essencial e de mentol. Na primeira colheita, houve maior acúmulo de massa seca de folhas, caules e total; produtividade de óleo essencial e de mentol quando o plantio foi realizado com mudas obtidas por estaquia. Na segunda colheita, no entanto, não houve diferença significativa entre os tratamentos para todas as variáveis analisadas. A primeira colheita resultou em médias superiores em relação à segunda colheita à exceção do plantio por estolão com 10 cm em todas as variáveis e estolão com 20 cm para a massa seca de caules. Os constituintes majoritários do óleo essencial foram mentol, mentona e neomentol. Os teores de mentol foram significativamente superiores na segunda colheita e de mentona na primeira colheita, sendo que o neomentol não apresentou diferença significativa em ambas as colheitas. Os resultados obtidos sugerem que a colheita antecipada da rebrota proporciona maior concentração de mentol no óleo essencial. O uso de estolões como estrutura de propagação pode ser considerada uma alternativa viável para menta, pois além de apresentar níveis similares de produção de óleo essencial e de mentol a partir da segunda colheita ao de áreas implantadas com mudas, diminui o custo de produção.

The genus Mentha is cultivated worldwide for essential oil production, with emphasis on its major constituent, menthol, which is used in the pharmaceutical, cosmetics, and food industries and for personal care. This work investigates the use of different propagation structures and harvesting times of Mentha canadensis L., in the Santa Catarina State north coast. The experimental design was in randomized blocks in a 4X2 factorial, comparing four propagation structures (stolon with 10, 15 and 20 cm and stem cuttings with 5 cm) and two harvesting times (95 days after planting and 60 days after the regrowth). In each harvesting time, the vegetative growth, essential oil and menthol productivities were evaluated. The first harvest showed greater leaf, branch and total dry mass accumulation, and essential oil and menthol productivities when stem cuttings were used. In the second harvest, no differences were observed for all evaluated variables. The first harvest resulted in higher averages than the second harvest, with exception in all variables for the use of stolon with 10 cm and in stem dry mass for stolon with 20 cm. The major constituents of the essential oil were menthol, menthone, neomenthol. The levels of menthol were significantly higher in the second harvest and of menthone in the first harvest, while neomenthol showed no significant difference. The results suggest that early harvest of the regrowth results in great menthol concentrations in the essential oil. The use of stolons as a propagation structure can be considered a viable alternative for mint, as it provides similar levels of essential oil and menthol productions after the second harvest, when compared to stem cuttings and also reduces the production cost.

[Perioperative antibiotic prophylaxis in radical retropubic prostatectomy: a randomised pilot study of perioperative and postoperative administration]. / Antibiotikaprophylaxe bei der radikalen retropubischen Prostatektomie: Eine randomisierte Pilotstudie zur perioperativen und postoperativen Gabe.

PURPOSE: A standard protocol for perioperative antibiotic prophylaxis in radical retropubic prostatectomy has not been established until now. The present pilot study compared the perioperative single-dose of piperacillin/tazobactam to the administration of ciprofloxacin or cotrimoxazol for 5 days with regard to postoperative infections. For the first time these antibiotic regimes were described in radical retropubic prostatectomy. MATERIAL AND METHODS: The patients were divided into three groups, each consisting of 17 patients: group 1: a single-dose of piperacillin / tazobactam 4.5 g i. v., group 2: ciprofloxacin 500 mg or cotrimoxazol 960 mg i. v. / p. o. and group 3: varying administration and duration of different kinds of antibiotics as control group. The basic characteristics of the patients such as age, body-mass-index, risk factors, diseases, former surgeries and medication were similar between all three groups. Also there were no significant differences in intraoperative parameters such as operation time, blood loss and other postoperative complications. RESULTS: The piperacillin / tazobactam group showed a significantly lower body temperature on postoperative days (POD) 1-3. The laboratory values were not significantly different among the groups, except the piperacillin / tazobactam group showed a significantly lower CRP level on POD 1-3 than group 3. All antibiotic regimes could afford an efficient protection: None of the patients died and there were no cases of serious consequences such as pneumonia, urosepsis or bacteriuria. Although not statistically significant, the piperacillin / tazobactam group showed better clinical outcomes: here the length of hospitalisation was two days less than in the other groups, no cases of wound infection occurred, the antimicrobial resistance rates were lower and fewer patients were treated with antibiotics in the postoperative course. CONCLUSIONS: Comparable to similar studies with a larger number of patients our pilot study demonstrated, although statistically not significant, better clinical results overall. We therefore conclude that a single-dose of piperacillin / tazobactam appears to be an efficient antibiotic prophylaxis in radical retropubic prostatectomy and even in some clinical parameters piperacillin / tazobactam seems to be equivalent or better than the usual 5-day administration of antimicrobial prophylaxis.

Do gender, age or lifestyle factors affect responses to antimuscarinic treatment in overactive bladder patients?

AIMS: Gender, age, obesity, smoking and alcohol or caffeine intake have been shown or proposed to be risk factors for the prevalence and/or severity of the overactive bladder symptom complex (OAB) or related parameters. We have explored whether any of these factors affect the therapeutic response to a muscarinic receptor antagonist during routine clinical use. METHODS: Data were analysed from 3766 OAB patients (77.1% woman, age 62.6 +/- 12.8 years) participating in an observational, open-label postmarketing surveillance study of the safety and efficacy of darifenacin. Multiple logistic regression models were applied to explore the effect of potential OAB risk factors on the darifenacin treatment-associated improvement of OAB symptoms, patient's subjective rating of bladder problems and global efficacy and tolerability. RESULTS: Age and (less consistently) gender were statistically significantly correlated with efficacy parameters, but the extent of their impact was judged to be too small to be clinically relevant. Except for a very small effect of body mass index on urgency episode improvement, none of the lifestyle-associated factors had significant effects on the efficacy of darifenacin. Except for a very small age effect, none of the potential risk factors had significant effects on global tolerability. DISCUSSION AND CONCLUSIONS: We conclude that the efficacy and tolerability of a muscarinic receptor antagonist, such as darifenacin is largely independent of potential OAB risk factors, such as gender, age, obesity, smoking and alcohol or caffeine intake.

Ciprofloxacin-related acute severe myalgia necessitating emergency care treatment: a case report and review of the literature.

OBJECTIVE: To report a case of an uncommon and up to date unpublished peracute and overwhelming muscle pain following administration of ciprofloxacin. CASE SUMMARY: A 58-year-old male developed fulminating musculoskeletal pain associated with third-time exposure to ciprofloxacin administered for treatment of chronic otitis media. Symptoms resolved slowly after intense combined analgetic therapy and cessation of ciprofloxacin therapy. 24 h after ciprofloxacin discontinuation the symptoms had completely disappeared and no more analgetic treatment was needed. Laboratory values, especially muscle enzymes, did not reveal any pathological pattern. The patient's past medical history highlighted reproducible side effects with both systemic and local administration of ciprofloxacin including milder symptoms of the musculoskeletal system. DISCUSSION: Common side effects of fluoroquinolones include gastrointestinal, central nervous and allergic reactions, but also more uncommon reactions such as tendonitis and rhabdomyolysis. In our case, there had been no signs of rhabdomyolysis. Besides an elevated IgE level no clinical signs of a true anaphylactic reaction associated with release of mast cell mediators had been observed. A pharmacokinetic interaction between ciprofloxacin and the patient's comedication carbamazepine is unlikely to be the responsible mechanism, since fluoroquinolones inhibit cytochrome P450 isoenzyme CYP1A2 but not CYP3A4 which metabolizes carbamazepine. CONCLUSION: To our knowledge, this is the first report describing fulminating musculoskeletal pain following administration of ciprofloxacin without any signs of rhabdomyolysis. Physicians should notice that there is a variety of adverse reactions of this usually well-tolerated agent and they should be aware of unusual complaints of their patients who receive fluoroquinolone treatment.

In-vivo measurements of coronary blood flow using 16-slice multidetector spiral computed tomography (MDCT) in a porcine model.

PURPOSE: To determine whether CTCA supplemented with CT flow measurements can be used to demonstrate and semiquantitatively evaluate poststenotic coronary blood flow in a porcine model. MATERIALS AND METHODS: In 10 thoracotomized pigs, transit time flow meter probes were attached to the aorta and left anterior descending artery (LAD) for real-time blood flow volumetry. A vascular silicone occluder was deployed around the LAD proximal to the probe to create medium-grade (MGS) and high-grade stenoses (HGS). The blood flow was measured by CT without vessel occlusion and distal to the stenoses. Time-density curves were generated from CT data. The curves were evaluated by calculating and cross-plotting the variables "slope of the density increase", "peak density" and "slope of the post-peak density decrease" from the LAD and aortic CT data. RESULTS: The flow in the LAD dropped to 41 % +/- 9 % (mean +/- SD) for MGS and 12 % +/- 6 % for HGS of the baseline. Coronary time-density curves plateaued proportional to luminal narrowing. Unimpaired flow could be differentiated statistically significant from poststenotic flow adjacent to MGS and HGS (p < 0.000 and p < 0.002, respectively). Flow adjacent to MGS and HGS was successfully differentiated for "slope of the density increase" and "slope of the post-peak density decrease" (p < 0.003 and p < 0.030, respectively). CONCLUSION: CT measurements allow semiquantitative evaluation of poststenotic coronary blood flow.

Recurrent pleural effusion: who benefits from a tunneled pleural catheter?

Recurrent malignant pleural effusion (MPE) is a common concomitant phenomenon of malignant disease, which can worsen the patient's quality of life and lead to significant morbidity. Tunneled indwelling pleural catheters (TIPC) offer new modalities in patients with recurrent MPE and impaired dilatability of the lung. We report on our experience with 100 consecutive patients suffering from recurrent benign (n = 12) and malignant pleural effusion (n = 88) who were treated with TIPC. The catheter was placed during a VATS procedure or under local anesthesia in an open technique. The median residence time of the TIPC was 70 days; spontaneous pleurodesis was achieved in 29 patients. The rate of complications was low: pleura empyema (n = 4), accidental dislodgement (n = 2), malfunction of the drainage (n = 3). In conclusion, TIPC is a useful method for the palliative treatment of patients with recurrent malignant or nonmalignant pleural effusions and 3 groups of patients seem to benefit most: a) patients with the intraoperative finding of a trapped lung in diagnostic VATS procedure; b) patients after a history of repeated pleuracenteses or previously failed attempts at pleurodesis; c) patients in a reduced condition with a limited lifespan due to underlying disease.

[Polypharmacy, compliance and non-prescription medication in patients with cardiovascular disease in Germany]. / Multimedikation, Compliance und Zusatzmedikation bei Patienten mit kardiovaskulären Erkrankungen.

BACKGROUND AND OBJECTIVE: The expenses of health insurances are continuously raising. With implementation of evidence-based medicine resulting in polypharmacy, compliance is decreasing and patients as well as physicians are facing unintentional drug interactions. Furthermore the arbitrary use of additional drugs apart from prescribed medication has to be considered. The objective of this study was to analyse polypharmacy, compliance and utilisation patterns for non-prescription medications (OTC) in patients with cardiovascular diseases. METHODS: 100 patients with cardiovascular diseases (45 women, 55 men, 58 - 87 years) were interviewed using a questionnaire. The compliance was determined by the Morisky-Score. RESULTS: 78 % of the patients received more than four pills every day (median 8.34). Most common products were beta-blockers (89 %), ACE-Inhibitors/Sartans (69 %) and aspirin (65 %). Only 52 % of the patients knew the indications of their medication. Although 83 % of the patients claimed to be absolutely compliant concerning their medication, the Morisky-Score revealed a high compliance only in 52 %. The compliance decreased significantly if the number of prescribed medication increased to more than four pills a day. 48 % of the patients took regularly non-prescription products, 35 % more than three additional products daily. Most commonly multivitamins, minerals, herbals and non-steroidal anti-inflammatory drugs were used. This non-prescription medication did not affect the compliance of the patients. CONCLUSIONS: Polypharmacy with more than four pills daily leads to a lower compliance and can therefore influence the implementation of guideline-medicine. Non-prescription medication is widely used and should be considered because of their potential side-effects and drug interactions.

Designing an acupuncture study to meet evidence-based medical criteria: methodological considerations for logistic design and development of treatment interventions arising from the German randomized controlled acupuncture trial on chronic shoulder pain (GRASP).

The results from studies on potential treatment effects of acupuncture are often limited due to serious difficulties in methodology. Randomized controlled trials on acupuncture should test a widely accepted treatment strategy of verum and sham acupuncture. However, in clinical practice various patterns of acupuncture techniques are employed, and up to now no generally accepted guidelines on how to perform a reliable verum or sham treatment have been established. Another limitation is that in most studies the study populations are too small to obtain reliable data and to detect subtle differences between the unspecific needling of sham acupuncture and specific needling of verum acupuncture with sufficient statistical power. Moreover, only a multicenter trial in an outpatient setting would guarantee a naturalistic environment in which acupuncture is used in clinical practice. In the present report we discuss such methodological aspects in detail and summarize some practical considerations for planning an acupuncture trial that fulfills evidence-based medical criteria. The largest German study on the treatment effects of acupuncture in patients with chronic shoulder pain (recruited patients n = 452), might serve as an example for such a well-designed study. Before we could conduct our study, clear definitions and protocols for the verum and sham acupuncture treatments as well as adequate endpoints had to be developed. For this we used a combination of a comprehensive study of the literature and structured interviews with experienced physicians followed by an expert panel. A total of 41 physicians had to be trained to achieve a homogeneously high quality of acupuncture treatment. The latter represents a prerequisite for reproducibility, constituting a critical component of rigorous efficacy trials in scientific acupuncture research.

Element distribution in mycorrhizal and nonmycorrhizal roots of the halophyte Aster tripolium determined by proton induced X-ray emission.

The salt aster (Aster tripolium L.) colonized by the arbuscular mycorrhizal fungus Glomus intraradices Sy167 and noncolonized control plants were grown in a greenhouse for nine months with regular fertilization by Hoagland nutrient solution supplemented with 2% NaCl. Mycorrhizal roots showed a high degree of mycorrhizal colonization of 60-70% and formed approximately 25% more dry weight and much less aerenchyma than the nonmycorrhizal controls. Cryosectioning essentially preserved the root cell structures and apparently did not cause significant ion movements within the roots during cuttings. The experimental conditions, however, did not allow to discriminate between fungal and plant structures within the roots. Quantification of proton-induced X-ray emission (PIXE) data revealed that in control roots, Na(+) was mainly concentrated in the outer epidermal and exodermal cells, whereas the Cl(-) concentration was about the same in all cells of the roots. Cross sections of roots colonized by the mycorrhizal fungus did not show this Na(+) gradient in the concentration from outside to inside but contained a much higher percentage of NaCl among the elements determined than the controls. PIXE images are also presented for the four other elements K, P, S, and Ca. Both in colonized and control roots, the concentration of potassium was high, probably for maintaining homoeostasis under salt stress. This is seemingly the first attempt to localize both Na(+) and Cl(-) in a plant tissue by a biophysical method and also demonstrates the usefulness of PIXE analysis for such kind of investigation.

[Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebo controlled multicenter study after 12 months]. / Brennnesseltrockenextrakt (Bazoton-uno) in der Langzeittherapie des benignen Prostatasyndroms (BPS). Ergebnisse einer randomisierten, doppelblinden, placebokontrollierten Multicenterstudie über 12 Monate.

Phytotherapy of BPS has a long tradition in Germany; nevertheless, data referring to single phytotherapeutic agents are rare. We therefore performed a randomized, double-blind, placebo-controlled multicenter study for 1 year with Bazoton uno (459 mg dry extract of stinging nettle roots) with 246 patients. The IPSS decreased on average from 18.7+/-0.3 to 13.0+/-0.5 with a statistically significant difference compared to placebo (18.5+/-0.3 to 13.8+/-0.5; p=0.0233). The median Q(max) increased by 3.0+/-0.4 ml/s in comparison to 2.9+/-0.4 ml/s (placebo), thus not statistically significantly different, as well as the median volume of residual urine, which changed from 35.5+/-3.4 ml before therapy to 20.0+/-2.8 ml and from 40.0+/-4.0 ml to 21.0+/-2.9 ml under placebo application. The number of adverse events (29/38) as well as urinary infections etc. (3/10 events) was smaller under Bazoton uno therapy compared to placebo. Treatment with Bazoton uno can therefore be considered a safe therapeutic option for BPS, especially for reducing irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects of the stinging nettle extract. A strong increase of Q(max) or reduction of residual urine are not to be expected.

Cellulosic building insulation versus mineral wool, fiberglass or perlite: installer's exposure by inhalation of fibers, dust, endotoxin and fire-retardant additives.

A task-specific exposure matrix was designed for workers installing building insulation materials. A priori, a matrix element was defined by type of task (installer or helper), type of work area (attic spaces or wall cavities) and type of insulation material (slabs from mineral wool, fiberglass or flax; loose-fill cellulosic material or perlite). In the laboratory a mock-up (full scale) of a one-family house was used for simulated installation of insulation materials (four replicates per matrix element). Personal exposure to dust and fibers was measured. The dust was analyzed for content of endotoxin and some trace elements (boron and aluminum) from fire-retardant or mold-resistant additives. Fibers were characterized as WHO fibers or non-WHO fibers. In support of the exposure matrix, the dustiness of all the materials was measured in a rotating drum tester. For installers in attic spaces, risk of exposure was low for inhalation of dust and WHO fibers from slab materials of mineral wool or fiberglass. Slab materials from flax may cause high risk of exposure to endotoxin. The risk of exposure by inhalation of dust from loose-fill materials was high for installers in attic spaces and for some of the materials risk of exposure was high for boron and aluminum. Exposure by inhalation of cellulosic WHO fibers was high but little is known about the health effects and a risk assessment is not possible. For the insulation of walls, the risk of installers' exposure by inhalation of dust and fibers was low for the slab materials, while a high risk was observed for loose-fill materials. The exposure to WHO fibers was positively correlated to the dust exposure. A dust level of 6.1 mg/m3 was shown to be useful as a proxy for screening exposure to WHO fibers in excess of 10(6) fibers/m3. In the rotating drum, slabs of insulation material from mineral wool or fiberglass were tested as not dusty. Cellulosic loose-fill materials were tested as very dusty, and perlite proved to be extremely dusty.

Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.

BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Isoforms of alpha1E voltage-gated calcium channels in rat cerebellar granule cells--detection of major calcium channel alpha1-transcripts by reverse transcription-polymerase chain reaction.

In primary cultures of rat cerebellar granule cells, transcripts of voltage-gated Ca2+ channels have been amplified by reverse transcription-polymerase chain reaction and identified by sequencing of subcloned polymerase chain reaction products. In these neurons cultured for six to eight days in vitro, fragments of the three major transcripts alpha1C, alpha1A, and alpha1E are detected using degenerated oligonucleotide primer pairs under highly stringent conditions. Whole-cell Ca2+ current recordings from six to eight days in vitro granule cells show that most of the current is due to L-type (25%), P-type (33%) and R-type (30%) Ca2+ channels. These data support the correlation between alpha1A and P-type Ca2+ channels (G1) and between alpha1E and R-type channels (G2 and G3). By including specific primer pairs for alpha1E the complimentary DNA fragments of indicative regions of alpha1E isoforms are amplified corresponding to the three most variable regions of alpha1E, the 5'-end, the II/III-loop, and the central part of the 3'-end. Although the complementary DNA fragments of the 5'-end of rat alpha1E yield a uniform reverse transcription-polymerase chain reaction product, its structure is unusual in the sense that it is longer than in the cloned rat alpha1E complementary DNA. It corresponds to the alpha1E isoform reported for mouse and human brain and is also expressed in cerebellum and cerebrum of rat brain as the major or maybe even the only variant of alpha1E. While fragments of a new rat alpha1E isoform are amplified from the 5'-end, three known fragments of the II/III-loop and two known isoforms homologue to the 3'-coding region are detected, which in the last case are discriminated by a 129 base pair insertion. The shift of the alpha1E expression from a pattern seen in cerebellum (alpha1Ee) to a pattern identified in other regions of the brain (alpha1E-3) is discussed. These data show that: (i) alpha1E is expressed in rat brain as a structural homologue to the mouse and human alpha1E; and (ii) rat cerebellar granule cells in primary culture express a set of alpha1E isoforms, containing two different sized carboxy termini. Since no new transcripts of high-voltage-activated Ca2+ channels genes are identified using degenerate oligonucleotide primer pairs, the two isoforms differentiated by the 129 base pair insertion might correspond to the two R-type channels, G2 and G3, characterized in these neurons. Functional studies including recombinant cells with the different proposed isoforms should provide more evidence for this conclusion.

Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family.

Low voltage-activated Ca2+ channels play important roles in pacing neuronal firing and producing network oscillations, such as those that occur during sleep and epilepsy. Here we describe the cloning and expression of the third member of the T-type family, alpha1I or CavT.3, from rat brain. Northern analysis indicated that it is predominantly expressed in brain. Expression of the cloned channel in either Xenopus oocytes or stably transfected human embryonic kidney-293 cells revealed novel gating properties. We compared these electrophysiological properties to those of the cloned T-type channels alpha1G and alpha1H and to the high voltage-activated channels formed by alpha1Ebeta3. The alpha1I channels opened after small depolarizations of the membrane similar to alpha1G and alpha1H but at more depolarized potentials. The kinetics of activation and inactivation were dramatically slower, which allows the channel to act as a Ca2+ injector. In oocytes, the kinetics were even slower, suggesting that components of the expression system modulate its gating properties. Steady-state inactivation occurred at higher potentials than any of the other T channels, endowing the channel with a substantial window current. The alpha1I channel could still be classified as T-type by virtue of its criss-crossing kinetics, its slow deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+ solutions. Based on its brain distribution and novel gating properties, we suggest that alpha1I plays important roles in determining the electroresponsiveness of neurons, and hence, may be a novel drug target.