Effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and physical function in patients with symptomatic knee osteoarthritis: the ETRELKA randomized clinical trial.

OBJECTIVE: To determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis. METHODS: Multi-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes. RESULTS: There was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference -0.06; 95%CI -0.41 to 0.29; P = 0.74), nor throughout the trial duration (P = 0.98). Subgroup analyses did not indicate an interaction between patient/treatment characteristics and treatment effect on WOMAC pain at the end of treatment (P-interaction ≥0.22). The occurrence of adverse events was similar across groups, with 10.4% and 10.6% of patients reporting events in the TENS and placebo TENS groups, respectively (P = 0.95). No relevant differences were observed in secondary outcomes. CONCLUSIONS: TENS does not improve knee osteoarthritis pain when compared to placebo TENS. Therapists should consider other potentially more effective treatment modalities to decrease knee osteoarthritis pain and facilitate strengthening and aerobic exercise. Our findings are conclusive and further trials comparing TENS and placebo TENS in this patient population are not necessary.

Finishing performance and diet digestibility for feedlot steers fed corn distillers grains plus solubles and distillers solubles with and without oil extraction.

Three experiments evaluated the effects of corn oil removal using centrifugation in ethanol plants, on animal performance and digestion characteristics by finishing cattle fed by-products. In Exp. 1, 225 crossbred steers (300 ± 9.1 kg) were utilized in a randomized block design with a 2 × 2 + 1 factorial arrangement of treatments. Factors consisted of oil concentration [de-oiled (DO) or full fat (FF)] and by-product type [condensed distillers solubles (CDS) or modified distillers grains plus solubles (MDGS)] compared to a corn-based control. Fat concentration was 6.0% for DO CDS, 21.1% for FF CDS, 9.2% for DO MDGS, and 11.8% for FF MDGS. No oil concentration by by-product type interactions (P ≥ 0.17) were observed. There were no differences in DMI, ADG, or G:F between DO and FF CDS (P ≥ 0.29) or DO and FF MDGS (P ≥ 0.58). No differences (P ≥ 0.25) due to oil concentration were observed for carcass characteristics. Experiment 2 was a 5 × 5 Latin Square digestion trial with treatments similar to Exp. 1. Fat concentration was 8.7% or 15.4% for DO or FF CDS and 9.2% or 12.3% for DO or FF MDGS. Intake and total tract digestibility of fat were greater (P ≤ 0.02) for FF CDS compared with DO CDS. Digestible energy (megacalorie per kilogram), adjusted for intake, was greater (P = 0.02) for steers fed FF CDS compared to DO CDS. Average ruminal pH for cattle fed FF MDGS was greater than DO MDGS (P = 0.06). In Exp. 3, 336 yearling, crossbred steers (352 ± 19 kg) were utilized in a randomized block design with a 2 × 3 + 1 factorial arrangement of treatments. Factors included oil concentration (DO or FF) and inclusion [35%, 50%, and 65% wet distillers grains plus solubles (WDGS)] along with a corn-based control. The fat concentrations of DO and FF WDGS were 7.9% and 12.4%, respectively. A linear interaction (P < 0.01) was observed for DMI, which produced different slopes for DO and FF WDGS. No linear or quadratic interactions were observed for BW, ADG, or G:F (P ≥ 0.31). For the main effect of oil concentration, there were no statistical differences (P > 0.19) for final BW, ADG, or G:F. No statistical differences were observed for all carcass traits (P ≥ 0.34). Corn oil removal via centrifugation had minimal impact on finishing performance suggesting that cattle fed DO by-products will have similar performance to cattle fed FF by-products in dry-rolled and high-moisture corn diets.

Effects of grind size when alkaline treating corn residue and impact of ratio of alkaline-treated residue and distillers grains on performance of finishing cattle.

Two studies were conducted to optimize use of alkaline-treated corn stover and wheat straw and distillers grains as partial corn replacements. In Exp. 1, a finishing experiment used 30 pens (12 steers/pen) of calf-fed steers (initial BW = 374 ± 23.9 kg) with a 2 × 2 + 1 factorial arrangement of treatments with 6 replications per treatment. Factors were grind size, where corn stover was processed through a 2.54- or 7.62-cm screen, and chemical treatment (corn stover either fed in native, non-treated form [NT; 93.4% DM] or alkaline treated [AT; 5% CaO hydrated to 50% DM]). No interactions (P ≥ 0.38) were noted between grind size and chemical treatment. Feeding AT compared with NT improved (P ≤ 0.02) final BW, ADG, and G:F. Reducing grind size improved (P ≤ 0.01) ADG and G:F, and no interaction with chemical treatment was observed. Steers fed AT had similar DMI, ADG, G:F, and carcass characteristics compared with a 5% roughage control that contained 15 percentage units (DM basis) more corn. In Exp. 2, 60 individually fed steers (initial BW = 402 ± 61.4 kg) were randomly assigned to 10 diets. Six treatments evaluated 10, 25, or 40% dry-rolled corn (DRC), which was replaced with either a 2:1 or 3:1 ratio (DM basis) of modified distillers grains plus solubles (MDGS) and treated corn stover analyzed as a 2 × 3 factorial. An additional 3 treatments were added where a 3:1 ratio of MDGS:straw were compared with a 3:1 ratio of MDGS:stover. As DRC increased, G:F (P = 0.06) quadratically increased for 3:1 MDGS:stover diets. Increasing DRC increased (P = 0.07) G:F in treated stover diets, regardless of ratio. Increasing DRC increased (P = 0.10) ADG for 3:1 ratios for both straw and stover. Reducing grind size, feeding a maximum of 20% treated crop residue, and maintaining at least 25% corn in the diet are strategies for optimizing cattle performance when replacing dry-rolled and high-moisture corn with treated crop residues and distillers grains.

[Regulatory aspects of biosimilars. Myths and facts]. / Regulatorische Aspekte zu Biosimilars. Mythen und Fakten.

BACKGROUND: Biosimilars are currently a hot topic and there are many unsolved questions, misunderstandings and sometimes considerable uncertainty, especially among clinicians and patients. Regulatory agencies, such as the European Medicines Agency (EMA) issue guidelines for the development and approval of biosimilars, which are based on scientific principles. OBJECTIVE: This article addresses some of the frequently noted misunderstandings and misperceptions. For example, why biosimilars are (or can only be) "similar" but not "identical" compared to the original pharmaceutical product, and aspects, such as the pharmaceutical quality of biosimilars, immunogenicity and the approval process for biosimilars are highlighted.

Effects of repetitive peripheral magnetic stimulation on normal or impaired motor control. A review.

INTRODUCTION: Repetitive magnetic stimulation at the periphery (rPMS), i.e. over spinal roots, nerves or muscles, represents a new painless and noninvasive approach that can contribute to motor recovery. This method is based on the assumption that, under rPMS, neural networks involved in motor control would be regulated by the large recruitment of proprioceptive afferents, with little activation of cutaneous receptors. STUDY AIM: This literature review dealing with rPMS after-effects on motor control aimed at better understanding the outcome measures and further discussing some possible involved mechanisms. RESULTS: Our literature search resulted in 13 studies that used different types of outcomes (neurophysiological, biomechanical, clinical) to test the influence of rPMS over spinal roots or muscles in healthy individuals and in persons with stroke or spinal disorders. Dynamic changes were reported post-rPMS, such as spasticity reduction and improvements of movement dynamics. Studies also brought about some interesting insights on the cortical plasticity associated with rPMS effects, such as the activation of fronto-parietal loops that may explain the post-rPMS improvement of motor planning. CONCLUSIONS: Due to the heterogeneous and scant literature on the topic, no conclusion can be drawn to date. However, the results encourage the concurrent testing of clinical, neurophysiological and biomechanical outcomes to investigate more precisely the relevance of rPMS in neurological rehabilitation.

[Problems in microbial safety of advanced therapy medicinal products. Squaring the circle]. / Probleme der mikrobiellen Sicherheit bei neuartigen Therapien. Die Quadratur des Kreises.

Today, sterility of parenteral drugs is practically guaranteed. Well-defined procedures in the pharmaceutical industry enable effective protection against contamination by bacteria and fungi. In contrast, problems regarding microbial safety of advanced therapy medicinal products (ATMPs), especially of cell therapeutics, are at best only partially solved. The latter should be understood as a challenge for manufacturers, regulators, and physicians. Many of the manufacturing principles mentioned above are not applicable in production of cell therapeutics. Sterility of source materials cannot be guaranteed and the hitherto known procedures for sterilization are, as a rule, not feasible. Thus, the sterility of the final product cannot be guaranteed. Considering the extremely short shelf life of many cell therapeutics, sometimes only a few hours, the results from established methods for sterility testing are often available too late. Furthermore, the sterility of a test sample does not indicate sterility of the whole product. In most cases, conventional methods for pyrogen testing are not applicable for ATMPs. This paper demonstrates relevant limitations regarding microbial safety and pyrogenicity. Possibilities to overcome these problems are discussed and some novel solutions are proposed.

Effect of lauric acid and coconut oil on ruminal fermentation, digestion, ammonia losses from manure, and milk fatty acid composition in lactating cows.

This experiment (replicated 3 x 3 Latin square design) was conducted to investigate the effects of lauric acid (LA) or coconut oil (CO) on ruminal fermentation, nutrient digestibility, ammonia losses from manure, and milk fatty acid (FA) composition in lactating cows. Treatments consisted of intraruminal doses of 240 g of stearic acid/d (SA; control), 240 g of LA/d, or 530 g of CO/d administered once daily, before feeding. Between periods, cows were inoculated with ruminal contents from donor cows and allowed a 7-d recovery period. Treatment did not affect dry matter intake, milk yield, or milk composition. Ruminal pH was slightly increased by CO compared with the other treatments, whereas LA and CO decreased ruminal ammonia concentration compared with SA. Both LA and CO decreased protozoal counts by 80% or more compared with SA. Methane production rate in the rumen was reduced by CO compared with LA and SA, with no differences between LA and SA. Treatments had no effect on total tract apparent dry matter, organic matter, N, and neutral detergent fiber digestibility coefficients or on cumulative (15 d) in vitro ammonia losses from manure. Compared with SA, LA and CO increased milk fat 12:0, cis-9 12:1, and trans-9 12:1 content and decreased 6:0, 8:0, 10:0, cis-9 10:1, 16:0, 18:0, cis 18:1, total 18:2, 18:3 n-3 and total polyunsaturated FA concentrations. Administration of LA and 14:0 (as CO) in the rumen were apparently transferred into milk fat with a mean efficiency of 18 and 15%, respectively. In conclusion, current data confirmed that LA and CO exhibit strong antiprotozoal activity when dosed intraruminally, an effect that is accompanied by decreases in ammonia concentration and, for CO, lowered methane production. Administration of LA and CO in the rumen also altered milk FA composition.

Effect of preslaughter feeding and ractopamine hydrochloride supplementation on growth performance, carcass characteristics, and end product quality in market dairy cows.

An experiment was conducted in market dairy cows to determine the effect of feeding time and ractopamine hydrochloride (RAC) on growth performance, carcass characteristics, and end product quality. In 3 replicates, 9 Holstein cows per replicate (n = 27; 659 +/- 25.3 kg initial BW) culled from 3 dairies were randomly assigned to 3 treatments: 1) slaughter immediately (control), 2) feed for 90 d (NoR), or 3) feed for 90 d with RAC (312 mg.cow(-1).d(-1)) for the final 32 d (RAC). On d 0, NoR and RAC cows were placed in individual pens and fed a high concentrate diet (86% concentrate, DM basis) for 90 d before slaughter. All cows were subjectively scored for BCS and locomotion score on d 0, and NoR and RAC cows were evaluated again after 90 d. Individual DMI was recorded daily throughout the trial, and BW was collected every 14 d. Age and age x treatment did not affect (P > 0.05) any of the traits evaluated in this study. When cows fed for 90 d (NoR and RAC combined) were compared with nonfed controls, fed cows had greater (P < 0.001) final BCS, BW and HCW, lower (P < 0.001) final locomotion score, and greater (P < 0.03) dressing percentage, external fat thickness, and marbling score. Fed cows also tended to have more desirable yield grade (P = 0.08), ribeye area (P = 0.11), fat color (P = 0.09), lean maturity (P = 0.06), and quality grade (P = 0.09) compared with control cows. Warner-Bratzler shear force was not affected (P = 0.23) by feeding. However, a 12-member trained sensory panel revealed that fed cow carcasses had more desirable (P < 0.04) tenderness, juiciness, and overall acceptability than control cow carcasses. Flavor intensity also tended (P = 0.10) to be more desirable for fed vs. control cows. No difference (P > 0.10) in off-flavor was detected among treatments. Finally, there was no effect (P > 0.10) of RAC on growth performance, carcass characteristics, or end product quality. In conclusion, feeding a high concentrate diet for 90 d improved important live animal, carcass, and end product characteristics related to the quality and palatability of beef from market dairy cows; however, no effect of RAC supplementation was observed.

[After the TGN1412 incident. Principles for assessment of first-in-man trials with monoclonal antibodies by the Paul Ehrlich Institute]. / Nach dem TGN1412-Zwischenfall. Prinzipien der Bewertung von First-in-Man-Studien mit monoklonalen Antikörpern durch das Paul-Ehrlich-Institut.

The use of monoclonal antibodies has led to new therapeutic possibilities for many clinical conditions. However, their application also bears risks, as demonstrated by the acute occurrence of a cytokine storm following administration of TGN1412, an anti-CD28 superagonist, in March 2006. This article highlights the principles of the Paul-Ehrlich-Institut (PEI) for the scientific assessment of first-in-man clinical trial applications for monoclonal antibodies. These principles are implemented as a standard operating procedure in the PEI Quality Management System and are intended as a supplement specific to monoclonal antibodies to the published general guideline issued by the Committee for Medicinal Products for Human Use (CHMP). Central aspects are the identification of risk factors for monoclonal antibodies based on defined criteria, since not every novel monoclonal antibody represents a risk per se. Furthermore, a PEI expert group that supports the scientific assessment procedure has been founded.

Stimulation of neuronal receptors, neuropeptides and cytokines during experimental oil of mustard colitis.

Oil of mustard (OM), administered intracolonically, produces severe colitis in mice that is maximized within 3 days. The purpose of this study was to characterize the cytokine response, and to establish expression patterns of enteric neuronal mediators and neuronal receptors affected during active colitis. We measured the changes in the mRNA levels for neuronal receptors and mediators by real-time PCR, and cytokine and chemokine protein levels in the affected tissue. Significant increases in neuronal receptors, such as transient receptor potential A1 (TRPA1), cannabinoid type 1 receptor, neurokinin 1 receptor (NK1R) and delta-opioid receptor; prokineticin-1 receptor; and soluble mediators, such as prodynorphin, proenkephalin1, NK1, prokineticin-1 and secretory leukocyte protease inhibitor, occurred. Significant increases in cytokines, such as interleukin (IL)-1beta, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF), and in chemokines, such as macrophage chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 (MIP-1alpha) and Kupffer cell derived chemokine (KC), were detected, with no changes in T-cell-derived cytokines. Furthermore, immunodeficient C57Bl/6 RAG2(-/-) mice exhibited OM colitis of equal severity as seen in wt C57Bl/6 and CD-1 mice. The results demonstrate rapidly increased levels of mRNA for neuronal receptors and soluble mediators associated with pain and inflammation, and increases in cytokines associated with macrophage and neutrophil activation and recruitment. Collectively, the data support a neurogenic component in OM colitis coupled with a myeloid cell-related, T- and B-cell-independent inflammatory component.

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster.

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.

Potential device interaction of a dual chamber implantable cardioverter defibrillator in a patient with continuous spinal cord stimulation.

Spinal cord or thalamic deep brain stimulation with a pacemaker is becoming more important in the treatment of drug refractory pain due to peripheral vascular disease, angina pectoris and intractable tremor in patients with neurologic disorders such as Parkinson's disease. An additional indication for a cardiac pacemaker or implantable cardioverter defibrillator raises concerns about possible interactions between the implanted electrical devices. We report on a patient with existing spinal cord stimulation who survived sudden cardiac death and received a dual chamber cardioverter defibrillator capable of delivering tiered therapies in both the atrium and ventricle.

[Spontaneous hyphema caused by Ginkgo biloba extract]. / Hyphéma spontané provoqué par l'extrait de Ginkgo biloba.

We report the first case of a patient in whom Ginkgo biloba extract proved to be the unique cause of spontaneous hyphema. Extensive ophthalmological and biological investigations were undertaken in order to assess the role of Ginkgo biloba: platelet numbering, hemostasis factors, Willebrand antigen, ristocetin cofactor, platelet glycoprotein immunophenotyping, glycoprotein expression after activation by thrombin, inflammatory markers, B-scan ultrasonography, and fluorescent iridography. No putative causes of hyphema were recorded other than Gingko biloba intake. The bleeding originated from the 12-o'clock position of the iris margin. Anamnesis identified Ginkgo biloba extract ingestion from 2 weeks before the appearance of the patient's visual trouble. Ginkgo biloba intake was stopped and the hemorrhage resolved with no recurrence during the 18 months of follow-up. Ginkgo biloba is known for platelet inhibition and is extensively used in the elderly because of its beneficial effects as a vascular protector. The clinical progression of the present case strongly suggests that Ginkgo biloba may cause hemorrhage and hyphema, even in the absence of any other predisposing factor.

A model program: exercise intervention for cancer rehabilitation.

Recent advances in cancer detection and treatment have resulted in an increase in the survival rate of individuals diagnosed with cancer. The increased survival rate brings new challenges for increasing the quality of life for cancer survivors. Debilitating side effects can result from the cancer itself and the cancer treatment. The negative effects lead to decreased functional (work) capacity, increased fatigue, and debilitating muscular weakness. There have been very positive benefits seen from the use of individualized prescriptive exercise intervention in alleviating these cancer treatment related symptoms. The role of exercise intervention as a complementary therapy is just emerging. Studies have shown that exercise decreases the amount of fatigue, improves functional capacity, increases immune function, and leads to improved quality of life. The effects of cancer and cancer treatments require that an exercise intervention program be well based in sound scientific principles. The exercise intervention needs to be carefully structured and controlled. All patients should be assessed and reassessed to evaluate progress. A cancer exercise specialist should closely monitor the exercise regime. Exercise should involve a whole-body approach that emphasizes all areas of fitness. Exercise therapy for cancer patients is a new and exciting area that will continue to grow as medical professionals realize the necessity for post-cancer treatment intervention to improve quality of life.

Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals.

The mechanism of formation of 4-hydroxy-2E-nonenal (4-HNE) has been a matter of debate since it was discovered as a major cytotoxic product of lipid peroxidation in 1980. Recent evidence points to 4-hydroperoxy-2E-nonenal (4-HPNE) as the immediate precursor of 4-HNE (Lee, S. H., and Blair, I. A. (2000) Chem. Res. Toxicol. 13, 698-702; Noordermeer, M. A., Feussner, I., Kolbe, A., Veldink, G. A., and Vliegenthart, J. F. G. (2000) Biochem. Biophys. Res. Commun. 277, 112-116), and a pathway via 9-hydroperoxylinoleic acid and 3Z-nonenal is recognized in plant extracts. Using the 9- and 13-hydroperoxides of linoleic acid as starting material, we find that two distinct mechanisms lead to the formation of 4-H(P)NE and the corresponding 4-hydro(pero)xyalkenal that retains the original carboxyl group (9-hydroperoxy-12-oxo-10E-dodecenoic acid). Chiral analysis revealed that 4-HPNE formed from 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13S-HPODE) retains >90% S configuration, whereas it is nearly racemic from 9S-hydroperoxy-10E,12Z-octadecadienoic acid (9S-HPODE). 9-Hydroperoxy-12-oxo-10E-dodecenoic acid is >90% S when derived from 9S-HPODE and almost racemic from 13S-HPODE. Through analysis of intermediates and products, we provide evidence that (i) allylic hydrogen abstraction at C-8 of 13S-HPODE leads to a 10,13-dihydroperoxide that undergoes cleavage between C-9 and C-10 to give 4S-HPNE, whereas direct Hock cleavage of the 13S-HPODE gives 12-oxo-9Z-dodecenoic acid, which oxygenates to racemic 9-hydroperoxy-12-oxo-10E-dodecenoic acid; by contrast, (ii) 9S-HPODE cleaves directly to 3Z-nonenal as a precursor of racemic 4-HPNE, whereas allylic hydrogen abstraction at C-14 and oxygenation to a 9,12-dihydroperoxide leads to chiral 9S-hydroperoxy-12-oxo-10E-dodecenoic acid. Our results distinguish two major pathways to the formation of 4-HNE that should apply also to other fatty acid hydroperoxides. Slight ( approximately 10%) differences in the observed chiralities from those predicted in the above mechanisms suggest the existence of additional routes to the 4-hydroxyalkenals.

Improvement of myocardial blood flow to ischemic regions by angiotensin-converting enzyme inhibition with quinaprilat IV: a study using [15O] water dobutamine stress positron emission tomography.

OBJECTIVES: This study was designed to analyze the effects of acute angiotensin-converting enzyme (ACE) inhibition on myocardial blood flow (MBF) in control and ischemic regions. BACKGROUND: Although animal studies indicate an improvement of MBF to ischemic regions after ACE inhibition, this effect has not been conclusively demonstrated in patients with coronary artery disease. METHODS: Myocardial blood flow was analyzed in ischemic and nonischemic regions of 10 symptomatic patients with coronary artery disease using repetitive [15O] water positron emission tomography at rest and during maximal dobutamine stress before and after ACE inhibition with quinaprilat 10 mg i.v. To exclude the possibility that repetitive ischemia may cause an increase in MBF, eight patients underwent the same protocol without quinaprilat (placebo patients). RESULTS: Rate pressure product in control and quinaprilat patients was comparable. In placebo patients, repetitive dobutamine stress did not change MBF to ischemic regions (1.41 +/- 0.17 during the first stress vs. 1.39 +/- 0.19 ml/min/g during the second stress, p = 0.93). In contrast, MBF in ischemic regions increased significantly after acute ACE inhibition with quinaprilat during repetitive dobutamine stress (1.10 +/- 0.13 vs. 1.69 +/- 0.17 ml/min/g, p < 0.015). Dobutamine coronary reserve in ischemic regions remained unchanged in placebo patients (1.07 +/- 0.11 vs. 1.10 +/- 0.16, p = 0.92), but increased significantly after quinaprilat (0.97 +/- 0.10 vs. 1.44 +/- 0.14, p < 0.002). Total coronary resistance decreased after ACE inhibition (123 +/- 19 vs. 71 +/- 10 mm Hg x min x g/ml, p < 0.02). CONCLUSIONS: Angiotensin-converting enzyme inhibition by quinaprilat significantly improves MBF to ischemic regions in patients with coronary artery disease.

Enhancement of radiosensitivity of rat rhabdomyosarcoma R1H with normobaric carbogen and hyperbaric oxygen (HBO) using conventionally fractionated irradiation.

Hypoxic clonogenic cells are an important contributory factor in tumour radioresistance. The objective of the present study was to evaluate whether hyperbaric oxygen enhances tumour radiosensitivity, using a conventionally fractionated irradiation schedule, and whether the radiosensitizing potential is different from carbogen. Experiments were performed using the rhabdomyosarcoma R1H model transplanted subcutaneously in the flank of WAG/Rij rats. A total of 30 X-ray fractions of 2 Gy were given either in air, normobaric carbogen or high pressure oxygen (HPO) (240 kPa, 2.37 atm) without anaesthesia. The time taken to achieve complete remission was 38.7 +/- 3.6 days, 36.7 +/- 2.7 days and 32.4 +/- 4.1 days for air, normobaric carbogen and HBO, respectively. The differences between air and HBO (p = 0.002) and carbogen and HBO (p = 0.015) were significant. Use of carbogen and HBO produced the same local control probability at 150 days and this was significantly higher than local control under ambient conditions (p < 0.0001). It was concluded that the time to achieve complete remission of the rat rhabdomyosarcoma R1H can be shortened by HBO. Furthermore, both HBO and carbogen give higher local control probabilities than treatment under ambient conditions when used with a conventionally fractionated radiation schedule.

ESHO quality assurance guidelines for regional hyperthermia.

The Technical Committee and the Clinical Committee of the ESHO evaluated the experience of the institutes which are active in clinical regional hyperthermia using radiative equipment. Based on this evaluation, QA guidelines have been formulated. The focus of these guidelines lies on what must be done not on how it should be done. Subjects covered are: treatment planning, treatment, treatment documentation, requirements and characterization of equipment, safety aspects, hyperthermia staff requirements and instrumentation for quality assurance.

The measurement of fringing fields in a radio-frequency hyperthermia array with emphasis on bolus size.

The limited aperture size through which the em-field of the applicator is emanated and the constraining of this em-field near the bolus' edge is related to the appearance of superficial 'hot spot' phenomena in radiative hyperthermia. Regarding systems based on the concept of the annular phased array two questions arise: (1) what is the relative strength of the radial component present in the incident field of the radiators, and (2) in what way are fringing fields related to the bolus size? To address both of the above questions, the spatial distribution of the em-field emanated through the aperture of an applicator of the Amsterdam four waveguide-array system has been investigated for a long bolus and a short bolus. The em vector field emanated by the applicator has been characterized in two perpendicular planes, i.e. the aperture midplane and the sagittal midplane. It should be noted that this distribution depends on the propagation conditions throughout the coupling bolus, the phantom and other volumes attached, such as other applicators. Therefore two sets of propagation conditions have been measured: (1) the minimum number of parameters determining the propagation of the em-field namely one single waveguide, one bolus and a homogeneous phantom, and (2) the propagation conditions as for the clinical setting. It is stressed that the study concerns one specific radiative hyperthermia system, namely the AMC four-waveguide array, but that, based on the similarities discussed above, results may be extrapolated towards other radiative hyperthermia systems. According to the current study, bolus prolongation might lead to a clear clinical improvement, which is due to a decrease of the fringing field amplitude compared to the field amplitude in the centre of the aperture midplane. Bolus prolongation will lead to an extended heating area, the field lines being more aligned to the patient's main axis.