Effects of ileocolonic delivered vitamin B2, B3 and C (ColoVit) or the Groningen anti-inflammatory diet on disease course and microbiome of patients with Crohn's disease (VITA-GrAID study): a protocol for a randomised and partially blinded trial.

BACKGROUND: Diet plays a pivotal role in the onset and progression of Crohn's disease (CD). Nutritional interventions revealed effects on intestinal inflammation and gut microbial composition. However, data from well-designed and controlled dietary trials are lacking. Therefore, evidence-based dietary recommendations are still unavailable to patients and physicians. Here, we aim to investigate the effects of an evidence-based anti-inflammatory diet, and an ileocolonic-targeted capsule containing vitamin B2, B3 and C (ColoVit) on patients with CD and their healthy household members. METHODS AND ANALYSIS: In this multicentre, randomised, placebo-controlled, partially blinded nutritional intervention trial, we aim to recruit 255 CD patients with Harvey-Bradshaw Index <8 and a faecal calprotectin (FCal) cut-off of ≥100 µg/g at baseline. Participants will be randomised into two experimental intervention groups and one placebo group. In the experimental groups, participants will either adhere to the Groningen anti-inflammatory diet (GrAID) or ingest an ileocolonic-delivered oral vitamin B2/B3/C capsule (ColoVit). The study consists of a 12-week controlled interventional phase, which proceeds to a 9-month observational follow-up phase in which patients allocated to the GrAID group will be requested to continue the intervention on their own accord. Household members of participating patients will be asked to participate in the trial as healthy subjects and are allocated to the same group as their peer. The primary study outcome for patients is the change in FCal level from baseline. The primary outcome for household members is the change in gut microbial composition, which is set as secondary outcome for patients. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board of the Stichting Beoordeling Ethiek Biomedisch Onderzoek in Assen, the Netherlands. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04913467.

Extremity exposure in nuclear medicine: preliminary results of a European study.

The Work Package 4 of the ORAMED project, a collaborative project (2008-11) supported by the European Commission within its seventh Framework Programme, is concerned with the optimisation of the extremity dosimetry of medical staff in nuclear medicine. To evaluate the extremity doses and dose distributions across the hands of medical staff working in nuclear medicine departments, an extensive measurement programme has been started in 32 nuclear medicine departments in Europe. This was done using a standard protocol recording all relevant information for radiation exposure, i.e. radiation protection devices and tools. This study shows the preliminary results obtained for this measurement campaign. For diagnostic purposes, the two most-used radionuclides were considered: (99m)Tc and (18)F. For therapeutic treatments, Zevalin(®) and DOTATOC (both labelled with (90)Y) were chosen. Large variations of doses were observed across the hands depending on different parameters. Furthermore, this study highlights the importance of the positioning of the extremity dosemeter for a correct estimate of the maximum skin doses.

Beta radiation exposure of staff during and after therapies with 90Y-labelled substances.

Radioimmunotherapies (RITs) and peptide receptor radiotherapies (PRRTs) with (90)Y-labelled compounds offer promising prospects for tumor treatment in nuclear medicine. However, when preparing and performing these therapies, which require manipulations of high activities of (90)Y (>1 GBq), technicians and physicians may receive high exposures, mainly to the skin of the hands. Even non-occupationally exposed persons, such as caregivers and family members, receive external exposures in the initial period after therapy, arising from the (90)Y in the patient. The local skin doses of the individual staff members, measured during RITs and PRRTs with thermoluminescence detectors fixed with tapes to the fingers, vary considerably. The exposure of staff can exceed the annual permissible dose limit of 500 mSv if radiation protection standards are low. Thus, adequate safety measures are needed. Measurements of the dose rate around patients, made using survey meters with sufficient response to beta particles, indicate that the exposure of caregivers and family members is considerably higher than previously assumed, and was dominated by primary beta radiation instead of bremsstrahlung. Nevertheless, under normal circumstances, the annual dose limits for the public (effective dose: 1 mSv, skin dose: 50 mSv) will be complied with.

Beta radiation exposure of medical staff and implications for extremity dose monitoring.

Sealed and unsealed beta radiation sources come into use to a greater extent in radiation therapy, e.g. for treating inflammatory joint diseases by radiosynoviorthesis (RSO), by injecting 90Y, 186Re or 169Er-solutions. Sealed 90Sr/90Y and 32P-sources or 188Re-liquid-filled balloon catheter are applied in vascular brachytherapy. Recently, 90Y-labelled antibodies are being successfully used in radioimmunotherapy (RIT) of malign lymphoma. Such practices require handling of high activities at small distances to the skin. Thus, the medical staff may be exposed to high beta doses. Investigations of the extremity exposure were performed at several workplaces, in particular during RSO treatments. The local skin dose (LSD), Hp(0,07), was measured with thin-layer TLD (LiF:Mg,P,Cu) fixed to the fingers (TLD-tapes). The findings indicate that the exposure of the staff can exceed the annual dose limit of 500 mSv when working at low protection standard. Routine monitoring of the extremity exposures with ring dosemeters appropriate to beta radiation and provided by the approved German dosimetry services was found to be needed. But even monitoring with these official 'beta-dosemeters' does mostly not give suitable results to demonstrate compliance with the dose limit. A study was conducted at RSO-workplaces in order reveal a correlation between doses measured with ring dosemeters and the maximum LSD obtained from the TLD-tapes. The results are discussed and conclusions for routine monitoring are drawn.

[Radiation exposure in (90)Y-Zevalin therapy: results of a prospective multicentre trial]. / Strahlenexposition bei der (90)Y-Zevalin-Therapie: Ergebnisse einer prospektiven multizentrischen Studie.

UNLABELLED: AIM of this study was the assessment of the radiation exposure from preparation and application of (90)Y-Zevalin, the measurement of the dose rate at the patient, the exposure of family members as well as the determination of the activity concentration in urine of patients. METHODS: Overall data from 31 therapeutic administrations carried out in four institutions were evaluated. During preparation and application of (90)Y-Zevalin the finger exposures of radiochemists, technicians, and physicians were measured. The dose rate of the patient was measured immediately after radioimmunotherapy. In patients treated in a nuclear medicine therapy unit, urine was collected over a two day period and the corresponding activity was determined. Family members of outpatients were asked to wear a dosimeter over a seven day period. RESULTS: During the preparation we found a maximum skin dose of 6 mSv at the average, and during application of 3 mSv, respectively. After administration of (90)Y the dose rate was 0.4 +/- 0.1 microSv/h at 2 m distance. Urine measurements yielded a cumulated 24 h excretion of 3.9 +/- 1.4% and 4.4 +/- 1.4% within 48 h, respectively, that is equivalent to 43 +/- 18 and 50 +/- 20 MBq of (90)Y, respectively. Family members received a radiation exposure of 40 +/- 14 microSv over seven days. CONCLUSION: During preparation and application of (90)Y-Zevalin appropriate radiation shielding is necessary. For family members as well as nursing staff no additional special radiation protection measures beyond those being common for other nuclear medicine procedures are necessary.

[Beta-radiation exposure at the finger tips during the radionuclide synovectomy]. / Beta-Ortsdosimetrie der Fingerkuppen bei der Radiosynoviorthese.

AIM: The radiation synovectomy is a widespread therapeutic option in rheumatoid arthritis. However, data for the beta-radiation exposure are rare. The aim of this study was to determine the personal dose equivalent H(P) (0.07) of the skin of the hands. METHODS: Thermo-luminescence detectors (TLDs) were attached at all fingertips of the therapist, the radiochemist and the nurse. In summary, the measurement of beta-exposure occurred in 155 joints at 6 days with different radio-nuclides ((169)Er, (186)Re, (90)Y). RESULTS: The greatest beta exposure were show at the forefinger (L-Ff) and thumb (L-Th) of the left hand, with which the therapist (right hander) fixed the injection needle. In 52 treated finger-joints (1204 MBq (169)Er), 29 treated large joints (2405 MBq (186)Re) and 15 treated knees (3100 MBq (90)Y) we found a cumulative beta exposure over all radionuclides of 190 mSv at L-Ff and 48 mSv at L-Th. The specific beta exposure for the individual radio-nuclides showed beta exposures of 0.56 mu Sv/MBq for (169)Er and 1.52 mu Sv/MBq for (186)Re-186 at the L-Ff. With using a manipulator the beta-exposure ((90)Y) could reduced from 22,09 to 0.42 mu Sv/MBq at the L-Ff. The greatest beta exposures for the radiochemist was 119 mSv at the L-Ff for all radionuclides. CONCLUSION: In usual techniques of radiation synovectomy the (90)Y produced the greatest part of radiation exposure. Especially at the L-Ff it might exceed the German limit for the official dosimetry service at the skin ( section sign 55 Strl-SchV). Using a holding forceps we can keep the legal rules and can reduce considerably the beta exposure.

Genomic difference analysis by two-dimensional DNA fingerprinting reveals typical changes in human low-grade gliomas.

Cytogenetic and molecular analyses such as allelotyping studies have revealed several genetic changes typical for human glial neoplasms. However, most studies to date have involved malignant gliomas and thus are likely to reflect late events of tumor progression. To elucidate the initial events of glial tumor growth, we performed a genome-wide search for genetic alterations in the DNA of 43 low-grade gliomas as compared to the constitutional DNA of the patients' peripheral blood leucocytes using the two-dimensional (2D) DNA fingerprint approach. Reliable results were obtained for 28 blood/tumor sample pairs (13 astrocytomas, 9 pilocytic astrocytomas, 1 oligodendroglioma, 3 oligoastrocytomas, and 2 ependymomas). DNA was digested with the restriction enzyme HaeIII and the resulting fragments were separated on 2D gels according to size and sequence in the first and second dimensions, respectively. Patterns of hundreds of spots were generated by hybridization with four different mini- and microsatellite core probes. A total of 655 to 1,122 spots could be visualized per sample. Comparison of blood and tumor spot patterns revealed two to 11 reproducible changes per patient. Most of the differences were spot losses (77.1%), while the others appeared to be gains or amplifications. Exactly the same changes were found in tumor recurrences which lacked histological signs of progression. When comparing different patients, many of the affected spots tended to cluster in particular areas of the gel as revealed by computer-aided comparison of all spot patterns. Eleven different spot clusters were identified which may correspond to several major deletion targets. This study provides the basis for the future molecular cloning of the candidate tumor suppressor genes affected by the common spot losses and will allow new insights into the genetic mechanisms of glial tumorigenesis.

Monitoring genomic alterations with a panel of oligonucleotide probes specific for various simple repeat motifs.

Germline and somatic instability of the human genome was studied, using synthetic oligonucleotides specific for simple repeat motifs. The following probes were used: (GTG)5, (GACA)4, (GATA)4, (CT)8, (TTAGGG)3, (GT)8, (GAA)6 and (GGAT)4. Each of them is unique with respect to the target regions recognized in the genome. Thus compilation of the various fingerprint data provides a complex map of the genome (and its deviations). While the fingerprints of differentiated somatic tissues never showed any alterations, in tumor tissues (namely gliomas) many changes could be detected. Most of the latter reflect secondary karyological aberrations. In nearly one third of the gliomas, drastically amplified and apparently monomorphic DNA fragments were identified. This marker should make it possible to deal with causal pathogenetic mechanisms as well as novel diagnostic strategies.