[Increased signal intensities and gadolinium levels in the brain after administration of gadolinium-based MR contrast agents : Clinical observations and results from preclinical research]. / Erhöhte Signalintensitäten und Gadolinium-Werte im Gehirn nach Gabe Gadolinium-haltiger MR-Kontrastmittel : Klinische Beobachtungen und Ergebnisse aus präklinischer Forschung.

BACKGROUND: Numerous clinical MRI studies have been published that describe an association between the repeated administration of (linear) gadolinium-based contrast agents and increased signal intensity in certain brain areas. In November 2017, the European Commission suspended the use of some of these contrast agents. OBJECTIVES: The background for this decision, both regulatory and scientific, are presented and discussed. MATERIALS AND METHODS: The regulatory decisions are evaluated and the clinical and preclinical literature is discussed. RESULTS: Differences in the structure and stability of gadolinium-based contrast agent molecules explain the observed increased signal intensities in individual brain regions (e. g. dentate nucleus) after administration of multiple doses of linear contrast agents. This phenomenon was not observed after administration of multiple doses of macrocyclic contrast agents. Preclinical studies have confirmed these results. CONCLUSION: To date, no clinical symptoms have been confirmed to be associated with the increased signal intensity or gadolinium presence in the brain.

Contrast-enhanced magnetic resonance angiography (MRA): evaluation of three different contrast agents at two different doses (0.05 and 0.1 mmol/kg) in pigs at 1.5 Tesla.

OBJECTIVE: To compare the image quality of contrast-enhanced magnetic resonance angiography (CE-MRA) of the supra-aortic vessels at 0.05 mmol/kg bw and 0.1 mmol/kg bw, between gadobutrol, Gd-DTPA and Gd-BOPTA quantitatively and qualitatively a total of eight pigs were evaluated intraindividually at 1.5 T. METHODS: Each pig was examined using 0.1 mmol/kg gadobutrol, Gd-DTPA and Gd-BOPTA on day one and 0.05 mmol/kg on day two. MRA datasets for the carotid artery and the infraorbital artery were qualitatively assessed regarding overall image quality on an ordinal four-point scale (4-excellent, 1-non-diagnostic). The signal-to noise-ratio (SNR) was measured. RESULTS: The qualitative assessment of the carotid artery showed a higher median image quality for the 0.1 mmol dose than for the 0.05 mmol dose for all three compounds. No difference was found for the infraorbital artery. Mean SNR of Gd-BOPTA, Gd-DTPA, gadobutrol at 0.05 mmol/kg were 36.0 ± 13.4/37.9 ± 16.3/43.7 ± 0.4 and at 0.1 mmol/kg they were 50.1 ± 12.4/46.6 ± 6.5 / 54.6 ± 10.2. Gd-BOPTA 0.05 revealed a significantly lower SNR than all other agents at normal dose. CONCLUSIONS: Full-dose gadolinium MRA results in higher image quality and significantly higher SNR compared with the half dose. Gadobutrol and Gd-BOPTA have similar enhancement properties at full dose but at half dose, gadobutrol appears superior.

Lower Extremity Impact and Injury Responses of Male and Female PMHS to High-Rate Vertical Loading.

Whole-body PMHS (Post Mortem Human Surrogate) testing was conducted on the Accelerative Loading Fixture (ALF), which is designed to generate floor and seat loading conditions at the level, rate, location, direction, and extent seen in UBB (Underbody Blast). The overarching goal of this research effort was to examine potential differences in the lower extremity response of females and males under UBB conditions. The ALF consists of an occupant platform that is driven upward by the detonation of an explosive charge. The floor plate undergoes plastic deformation. The occupant platform supports two rigid seats for surrogates. Twenty un-embalmed PMHS were tested, including 50th-percentile males, 75th-percentile females, and 5th-percentile females. Two test series were conducted. Series A had a target floor speed of 8 m/s (2-ms time-to-peak) with a target seat speed of 5 m/s (4-ms time-to-peak). Series B had a target floor speed of 20 m/s (2-ms time-to-peak) with a target seat speed of 4 m/s (7-ms time-to-peak). Major damage occurred to the femur, tibia, fibula, talus, and calcaneus. Lower extremity damage type, incidence, and extent varied between the two sexes. Fifty-percent probability of calcaneus fracture for less than 3-ms time-to-peak is associated with a 781-g peak tibia vertical acceleration for 50th-percentile males, 650-g for 75th-percentile females, and 396-g for 5th-percentile females. Fifty-percent probability of calcaneus fracture, regardless of time-to-peak, is associated with a 368-g peak femur vertical acceleration for 50th-percentile males, 332-g for 75th-percentile females, and 218-g for 5th-percentile females. These results show differences in kinematics and damage outcome between female and male PMHS in UBB conditions. These findings will inform future decisions regarding the requirements for test capabilities that incorporate the female Warfighter. Ultimately, advancements can be made in injury assessment tools such as improved physical surrogates, injury assessment and prediction criteria, modeling and simulation capabilities, test methods, and the optimization of military ground vehicles, personal protective equipment, and injury countermeasures.

Hand antiseptics: rubs versus scrubs, alcoholic solutions versus alcoholic gels.

This report describes three different investigations undertaken to demonstrate the advantage of fluid alcoholic hand disinfectants. In the first study, the skin compatibility of Sterillium, a liquid alcoholic rub-in hand disinfectant was compared with that of Hibiscrub, a water-based handwashing antiseptic. Using various parameters such as image analysis of removed squames (D-squames), skin roughness or transepidermal water loss, Hibiscrub was found to be significantly inferior to Sterillium. Hibiscrub caused skin irritation in 15 volunteers who could not complete the test. In a second study, the microbicidal efficacy of Sterillium and Hibiscrub was tested in surgical hand disinfection. The microbial reduction by Sterillium was significantly greater than that of Hibiscrub, immediately after application as well as after the surgical procedure. In a third study, certain alcoholic gels were tested according to the EN 1500 'hygienic hand disinfection'. None of the gels tested passed the EN 1500 within 30s. However, Sterillium met the EN 1500 requirement within 30s. We conclude that Sterillium is superior to Hibiscrub in terms of skin tolerance and microbicidal efficacy in surgical hand disinfection. It is also superior to alcoholic gels.

How to improve instrument disinfection by ultrasound.

Ultrasound technologies have a wide range of hospital and dental applications which include cleaning and disinfection of surgical and dental instruments. We measured the germicidal efficacy of sonication, with or without chemical disinfectants, in an ultrasonic bath delivering a frequency of 35 kHz and an intensity of 0.66 W/cm2. Cultures of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans were exposed to ultrasound and to an amine-based disinfectant in non-bactericidal concentrations. Ultrasonication for 60 min alone did not cause a significant killing of the bacteria and yeast. However, we were able to show that sonication can act as a powerful synergistic agent to increase the cidal efficacy of the disinfectant against S. aureus and P. aeruginosa. C. albicans was more resistant to the combination of ultrasound and chemical disinfection. The key role in the action of ultrasound in cleaning of instruments and perhaps in enhanced disinfection is played by cavitation phenomena. The distribution of cavitations in an ultrasonic bath is not homogenous. We found a similar synergistic effect of ultrasound and disinfectant in positions with low cavitation. The synergistic effect was not reduced inside rubber tubes. Before ultrasound can be accepted as an integral part of the cleaning and disinfection process of medical instruments, the influence of intensity and frequency of sonication and the effects of cavitation must be clarified.

Disinfectant activity against different morphological forms of Helicobacter pylori: first results.

The pathogenic bacterium Helicobacter pylori, which has infected more than one-half of the world's human population, exists in two morphological forms; the viable helical form and the disputed viable-but-not-culturable coccoid form. Infection by the helical form proceeds through the oral-oral route, while that by the coccoid form, if possible at all, is by the faecal-oral and/or the oral-oral route. The present pilot study addresses the question of disinfectant efficacy against both forms of the bacterium.

The influence of tube voltage and phantom size in computed tomography on the dose-response relationship of dicentrics in human blood samples.

The aim of this study was to investigate the dose response relationship of dicentrics in human lymphocytes after CT scans at tube voltages of 80 and 140 kV. Blood samples from a healthy donor placed in tissue equivalent abdomen phantoms of standard, pediatric and adipose sizes were exposed at dose levels up to 0.1 Gy using a 64-slice CT scanner. It was found that both the tube voltage and the phantom size significantly influenced the CT scan-induced linear dose-response relationship of dicentrics in human lymphocytes. Using the same phantom (standard abdomen), 80 kV CT x-rays were biologically more effective than 140 kV CT x-rays. However, it could also be determined that the applied phantom size had much more influence on the biological effectiveness. Obviously, the increasing slopes of the CT scan-induced dose response relationships of dicentrics in human lymphocytes obtained in a pediatric, a standard and an adipose abdomen have been induced by scattering effects of photons, which strongly increase with increasing phantom size.

The influence of x-ray contrast agents in computed tomography on the induction of dicentrics and gamma-H2AX foci in lymphocytes of human blood samples.

The aim of this study was to investigate and quantify two biomarkers for radiation exposure (dicentrics and gamma-H2AX foci) in human lymphocytes after CT scans in the presence of an iodinated contrast agent. Blood samples from a healthy donor were exposed to CT scans in the absence or presence of iotrolan 300 at iodine concentrations of 5 or 50 mg ml(-1) blood. The samples were exposed to 0.025, 0.05, 0.1 and 1 Gy in a tissue equivalent body phantom. Chromosome aberration scoring and automated microscopic analysis of gamma-H2AX foci were performed in parts of the same samples. The theoretical physical dose enhancement factor (DEF) was calculated on the basis of the mass energy-absorption coefficients of iodine and blood and the photon energy spectrum of the CT tube. No significant differences in the yields of dicentrics and gamma-H2AX foci were observed in the absence or presence of 5 mg iodine ml(-1) blood up to 0.1 Gy, whereas at 1 Gy the yields were elevated for both biomarkers. At an iodine concentration of 50 mg ml(-1) serving as a positive control, a biological DEF of 9.5 +/- 1.4 and 2.3 +/- 0.5 was determined for dicentrics and gamma-H2AX foci, respectively. A physical DEF of 1.56 and 6.30 was calculated for 5 and 50 mg iodine ml(-1), respectively. Thus, it can be concluded that in the diagnostic dose range (radiation and contrast dose), no relevant biological dose-enhancing effect could be detected, whereas a clear biological dose-enhancing effect could be found for a contrast dose well outside the diagnostic CT range for the complete radiation dose range with both methods.

The involvement of pro-inflammatory cytokines in nephrogenic systemic fibrosis - a mechanistic hypothesis based on preclinical results from a rat model treated with gadodiamide.

The evidence for the potential involvement of gadolinium-based contrast agents (GBCAs) in the pathomechanism of nephrogenic systemic fibrosis (NSF), a rare but serious disease occurring in patients with severe or end-stage renal failure, has grown due to recent epidemiological and preclinical research. Nevertheless there is still uncertainty with regard to the prevailing patho-physiological processes that may lead to NSF. To examine the potential mechanism of the fibrotic skin changes we applied a recently published rat model of NSF for investigations into serum markers for inflammation. For this purpose male Wistar rats were treated either once, three, or eight times with a daily intravenous injection of 2.5 mmol/kg gadodiamide, the drug substance of the magnetic resonance imaging (MRI) agent Omniscan. Clinical observations, hematology, clinical pathology, histopathology including electron microscopy and gadolinium (Gd) determination in serum, skin, femur and liver tissue, and a multiplexed analysis of 70 protein serum markers were performed. Gd was detectable in the skin, femur, and liver of the gadodiamide-treated rats 6h after the first administration. Macroscopic skin changes, appearing as reddening and early scab formation, were observed in one animal after the third daily administration and affected all animals after 8 daily administrations. Microscopy revealed dermal infiltrations after three administrations, progressing towards inflammatory lesions, ulcerations and crusts. Among the investigated serum marker panel 13 cytokines were significantly (p<0.01) elevated 6 h after the first injection, and eight stayed elevated over all time points: the monocyte chemotactic proteins MCP-1 and MCP-3, the macrophage inflammatory proteins MIP-1beta and MIP-2, the tumor necrosis factor TNF-alpha, the extracellular matrix regulator tissue inhibitor of metalloproteinase type 1 (TIMP-1), the vascular epithelial growth factor (VEGF) and osteopontin. The latter cytokine is of particular interest, since this matrix cellular glycoprotein is involved in the regulation of dystrophic calcification but also plays a role as a chemoattractant for dendritic cells, macrophages and T-lymphocytes, which in turn activate inflammatory pathways. Reflecting the physiological role of osteopontin, we hypothesize that Gd release from the GBCA-complex leads to the formation of insoluble Gd-deposits subsequently eliciting a physiological response similar to that seen during dystrophic calcification, i.e. an up-regulation of osteopontin and chemoattractant cytokines. Concomitant increase in vascular permeability caused by MIP-1, TNF-alpha and VEGF may lead to extravasation of chelated Gd or Gd-deposits. The inherent persistence of the Gd-deposits may subsequently result in an overactivation of pro-inflammatory pathways progressing towards overt skin effects.

Contrast media: future aspects.

In spite of the dramatic development in CT, there was no major breakthrough in the iodinated contrast media development. New agents based on hybrid between MRI and CT compounds may be a new innovative alternative. This new approach may also open new indications such as radiotherapy.

[Social medicine aspects in expert assessment according to the new long-term care legislation]. / Sozialmedizinische Aspekte bei der Begutachtung nach dem Betreuungsgesetz.

According to the new German 'Betreuungsgesetz' (BtG) legislation concerning care for the mentally and or physically disabled, instituting a "case of care" requires an expert opinion on the patient's mental and physical impairments as well as on the question as to what degree the patient lacks the ability to manage his or her own affairs. The respect for the personal autonomy has to be weighed against the need to take action for the patient's benefit. The concept of 'neglect' ('Verwahrlosung') plays an important role in judging a patient's situation. Criteria for the use of this term are derived from a study carried out by the author, and lead to a questionnaire designed for preparatory investigations. As to the question of who should act as an expert in BtG cases, the author argues that the public health offices qualify best for this task.

Kallmann's syndrome and chemosensory evoked potentials.

Kallmann's syndrome is generally assessed by history and subjective tests of olfactory function. In this study three patients suffering from Kallmann's syndrome were investigated with more objective techniques, including the recording of chemosensory evoked potentials (CSEPs). After testing olfactory function by means of a simple odor identification test, anosmia was confirmed in only one patient, since the other two patients were able to distinguish between several odorants. However, investigations in which CSEPs were employed indicated that all three patients had complete loss of their olfaction as well as hypersensitivity of the trigeminal nerve. These findings prove the usefulness of CSEPs in clinical investigations of the sense of smell.

[Intraoperative temperature measurements at the acrylic bone/cement interface in total hip endoprosthetic (TEP) implantations (author's transl)]. / Intraoperative Temperaturmessungen an der Zementknochengrenze bei TEP-Implantation.

Temperature measurements are reported effected by aid of thermocouples enclosed in tubules in TEP-implantations of the hip. Two techniques were employed: the first using as acrylic bone cement Palacos or Sulfix-6 without concomitant cooling, the second Palacos after precooling of the femur with crushed ice/water mixtures. The first method yielded, at the acrylic bone cement/bone interface, temperatures above the coagulation point of the protein (56 degrees C). The novel technique of implantation is described, i.e. the cooling of the bone with ice-water prior to the cement implantation. This technique provides a means of restricting the average temperature at the aforesaid interface to 45 degrees C.

[Homozygous C7 defect in a German family]. / Homozygoter C7-Defekt in einer deutschen Familie.

An 11 year old boy with recurrent meningitis/sepsis (once without positive bacterial culture, once with demonstration of Neisseria meningitidis in blood) was evaluated for suspected immunodeficiency. Absent activity of both the classical and alternative pathway of complement suggested a defect of the membrane attack complex. Immunochemical and functional analyses together with family studies revealed a homozygous defect of the seventh component of complement in the boy. This is the first description of C7 deficiency in a German family.

[Enzymatic determination of glucose and saccharose in selected dietetic foods]. / Zur enzymatischen Bestimmung von Glucose und Saccharose in ausgewählten diätetischen Lebensmitteln.

The need to enlarge the offer of dietetic foods requires more sensitive methods for the determination of certain food constituents. Thus, the exact estimation of glucose and saccharose in foods for diabetics is of particular importance. The enzymatic determination of the two sugars is suited for these purposes. The enzymatic method used by the authors is described. On the basis of results from their own investigations, the authors compare the values yielded by the enzymatic method with those obtained by means of the Luff-Schoorl procedure. The differences observed were more or less great from one food to another.

Familial deficiency of the seventh component of complement associated with recurrent meningococcal infections.

We describe an 11-year-old girl suffering from recurrent meningitis with a complete absence of the seventh component of complement (C7). Diagnosis was established by haemolytic titration and western blotting. The patient's serum lacked the 85 kDa C7 chain. Haemolytic activity of serum was reconstituted with either pooled normal human serum or with purified C7. The relatives (parents and one sister) had half-normal levels of both immunochemically and functionally determined C7, indicating a heterozygous state for C7 deficiency.

[Histamine poisoning following consumption of fried fish]. / Histaminvergiftungen nach Bratfischverzehr.

Cases of food poisoning after consumption of fried fish in marinades are often caused by increased content of histamine. From 1973 to 1988 28 outbreaks in groups of persons with symptoms of histamine poisoning were analysed in the district of Dresden (GDR). The content of histamine most commonly exceeded the tolerance limit of 300 mg/kg fried fish.

[Recurrent meningitis in a familial defect of the beta-subunit of the 8th complement component]. / Rezidivierende Meningitiden bei familiärem Defekt der beta-Untereinheit der achten Komplementkomponente.

Bacterial meningitides occurred in two members of a Yugoslavian family. In one case meningitis remained a singular event, Neisseria meningitidis being identified in the CSF. The second patient developed five episodes of recurrent purulent meningitis associated with petechiae and in one instance also with arthritis of the left knee but no causative germ was found. In both patients the Western blot technique revealed a defect of the beta-subunit of the eighth component of complement that was completely eliminated by purified C8. This proved that the C8 defect was isolated and that no other component was deficient.