L-FABP and NGAL are novel biomarkers for detection of abdominal injury and hemorrhagic shock.

INTRODUCTION: Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries. PATIENTS AND METHODS: Traumatized patients with an age ≥18 years and an abdominal injury (AISabd≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. RESULTS: All patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2-1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8-88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0-235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4-540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5-88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6-163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0-89.6],p<0.001) and "Abd" group (70.5 ng/ml [IQR=53.3-115.5], p<0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. CONCLUSION: L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same.

Rise of extremity fractures and sport accidents in children at 8-12 years and increase of admittance via the resuscitation room over a decade.

INTRODUCTION: In an emergency department, the majority of pediatric trauma patients present because of minor injuries. The aim of this study was to evaluate temporal changes in age-related injury pattern, trauma mechanism, and surgeries in pediatric patients. METHODS: This retrospective study included patients < 18 years of age following trauma from 01/2009 to 12/2018 at a level I trauma center. They were divided into two groups: group A (A: 01/2009 to 12/2013) and group B (B: 01/2014 to 12/2018). Injury mechanism, injury pattern, and surgeries were analyzed. As major injuries fractures, dislocations, and organ injuries and as minor injuries contusions and superficial wounds were defined. RESULTS: 23,582 patients were included (58% male, median age 8.2 years). There was a slight increase in patients comparing A (n = 11,557) and B (n = 12,025) with no difference concerning demographic characteristics. Significant more patients (A: 1.9%; B: 2.4%) were admitted to resuscitation room, though the number of multiple injured patients was not significantly different. In A (25.5%), major injuries occurred significantly less frequently than in B (27.0%), minor injuries occurred equally. Extremity fractures were significantly more frequent in B (21.5%) than in A (20.2%), peaking at 8-12 years. Most trauma mechanisms of both groups were constant, with a rising of sport injuries at 8-12 years. CONCLUSION: Although number of patients increases only slightly over a decade, there was a clear increase in major injuries, particularly extremity fractures, peaking at 8-12 years. At this age also sport accidents significantly increased. At least, admittance to resuscitation room rose but without an increase of multiple injured patients.

[Fractures of the lower extremities in childhood : Part 2: lower leg and ankle fractures]. / Frakturen der unteren Extremität im Kindesalter : Teil 2: Unterschenkel- und Sprunggelenksfrakturen.

The treatment of pediatric patients in trauma surgery is a special situation in every aspect. For deciding on the correct treatment of fractures of the lower leg and ankle joint, various parameters, such as residual growth rate, skeletal age and height of the patient are decisive. The differences between fractures in children and adolescents are the open epiphyseal plate and the resulting residual growth. The bones of young children have a higher healing tendency and a greater potential for correction than in adolescents. Especially in the lower leg and the ankle joint, the potential for correction is decisive for the healing of fractures and for possible development of growth disorders. The limits of tolerance concerning axial malalignments and the expected spontaneous potential for correction must play an essential role for further treatment with conservative or operative therapy. This article deals with the special features of pediatric fractures of the lower leg and ankle joint.

[Fractures of the lower extremities in childhood : Part 1: fractures of the thigh and in the proximity of the knee]. / Frakturen der unteren Extremität im Kindesalter : Teil 1: Oberschenkel- und kniegelenksnahe Frakturen.

Fractures in children are a major challenge in everyday clinical practice. The decision about the correct treatment of fractures follows the consideration of individual factors. The age of the child and the resulting residual growth play an essential role. This article aims to facilitate a structured approach with respect to examination, diagnostics and treatment in clinical practice. This first part of this series deals with fractures of the thigh and in the proximity of the knee joint in children. The peculiarity of pediatric bone lies in its growth, which results not only in a much faster healing tendency than in adults but also possesses a greater correction potential. It is therefore very important for fracture healing to include the tolerance limits for existing axis misalignment as well as the expected spontaneous correction potential and the resulting remodeling in the therapy decision. The various operative measures must be used in a targeted manner. Incongruencies of joints as well as significant length differences should be avoided.

[Pediatric finger and hand injuries : An epidemiological study]. / Finger- und Handverletzungen bei Kindern : Eine epidemiologische Studie.

BACKGROUND: The hand is the second most frequently injured region of the body in children. The aim of this study was to evaluate age-related injury patterns, trauma mechanisms, as well as the need for surgery in pediatric patients with injuries to the hand. PATIENTS AND METHODS: This was a retrospective study analyzing the data between January 2008 and December 2014 at Frankfurt University Hospital. All patients were younger than 18 years old. All patients suffering trauma to the hand or the fingers were included. The injury mechanism, injury pattern as well as need for surgery were analyzed according to different age groups (0-3 years, 4-7 years, 8-12 years and 13-17 years). Major injuries were defined as fractures, dislocations, amputations and injuries of the tendons or nerves. Minor injuries included contusions and superficial wounds. RESULTS: Overall, 2823 emergency pediatric patients with an injury to the hand or fingers were included (61.5% male, median age 10.3 years). Of the injuries 60.4% were located on the fingers and 39.6% on the hand. Major injuries were found in 703 patients (24.9%) and minor injuries in 2120 patients (75.1%). Of those patients with a major injury, 74.8% suffered a fracture, 9.4% an injury of nerves and tendons and 7.0% an amputation. The most common trauma mechanism for major injuries was sports (24.2%), followed by crushing (17.9%) and falls (14.7%). Overall, 436 patients (15.5%) were surgically treated of which 9.4% were operated on in the operation room and 6.1% in the emergency room. CONCLUSION: Almost 75% of all children who presented to the emergency department following trauma to the fingers or the hand revealed minor injuries; however, 25% suffered a relevant, major injury. Overall, 15.5% had to be surgically treated. The most frequently found major injuries were fractures of the hand and the fingers.

What injuries should we expect in the emergency room?

INTRODUCTION: Beside serious and potentially fatal injuries, the majority of pediatric trauma patients present with minor injuries to emergency departments. The aim of this study was to evaluate age-related injury pattern, trauma mechanism as well as the need for surgery in pediatric patients. PATIENTS AND METHODS: Retrospective Study from 01/2008 to 12/2012 at a level I trauma center. All patients <18years of age following trauma were included. Injury mechanism, injury pattern as well as need for surgery were analyzed according to different age groups (0-3 years, 4-7 years, 8-12 years and 13-17 years). Major injuries were defined as fractures, dislocations and visceral organ injuries. Minor injuries included contusions and superficial wounds. RESULTS: Overall, 15300 patients were included (59% male, median age 8 years). A total of 303 patients (2%) were admitted to the resuscitation room and of these, 69 (0.5% of all patients) were multiply injured (median Injury Severity Score (ISS) 20 pts). Major injuries were found in 3953 patients (26%). Minor injuries were documented in 11347 patients (74%). Of those patients with a major injury, 76% (2991 patients) suffered a fracture, 3% (132 patients) a dislocation and 3% (131 patients) an injury of nerves, tendons or ligaments. The majority of fractures were located in the upper extremity (73%) (elbow fractures 16%; radius fractures 16%; finger fractures 14%). Patients with minor injuries presented with head injuries (34%), finger injuries (10%) and injuries of the upper ankle (9%). The most common trauma mechanisms included impact (41%), followed by falls from standing height (24%), sport injuries (15%) and traffic accidents (9%). Overall, 1558 patients (10%) were operated. Of these, 61% had a major and 39% a minor injury. CONCLUSION: Almost 75% of all children, who presented to the emergency department following trauma revealed minor injuries. However, 25% suffered a relevant, major injury and 0.5% suffered a multiple trauma with a median ISS of 20. Overall, 10% had to be operated. The most frequently found major injuries were extremity fractures, with elbow fractures as the most common fracture.

I-FABP is a Novel Marker for the Detection of Intestinal Injury in Severely Injured Trauma Patients.

BACKGROUND: Intestinal injury is a rare injury in multiply traumatized patients, and its diagnosis remains difficult. Delayed diagnosis of an intestinal injury increases the risk of sepsis, multiple organ failure and mortality. The intestinal fatty acid-binding protein (I-FABP) is solely expressed in the intestine and is released extracellulary after tissue damage. This study evaluates the validity of I-FABP as an early biomarker to detect an abdominal injury and particularly an injury to the intestine. PATIENTS AND METHODS: Patients with an Abbreviated Injury Scale (AIS) score for abdominal body region (AIS abdomen) ≥3 were included in this study from 07/2006 to 12/2014. Of those, ten patients retrospectively had an intestinal injury (int. injury). According to the Injury Severity Score and the AIS abdomen, corresponding patients with an abdominal injury but without an intestinal injury (no int. injury) were included for matched-pair analysis. Twenty healthy volunteers served as controls. Plasma I-FABP levels were measured at admission to the emergency room and up to 10 days daily (d1-d10). RESULTS: Median I-FABP levels were significantly higher in the "int. injury" group compared to the "no int. injury" group [2101.0 pg/ml (IQR = 1248.1-4117.8) vs. 351.4 pg/ml (IQR = 287.6-963.3), p < 0.05]. Furthermore, I-FABP levels of both groups were significantly higher compared to the control group [Ctrl: 127.2 pg/ml (IQR = 57.4-310.6), p < 0.05]. The time course of I-FABP levels showed a peak on the day of admission and a decline to the control levels in the further post-traumatic course. The development of complications such as single- or multi-organ failure, sepsis, acute respiratory distress syndrome, pneumonia and mortality was higher in the "int. injury" group; however, this difference was not statistically significant. CONCLUSION: This study confirmed our previous observation that I-FABP might be used as a suitable early biomarker for the detection of abdominal injuries in general. In addition and more specific, I-FABP may be a useful and promising parameter in the diagnosis of intestinal injuries.

Effects of positive blood alcohol concentration on outcome and systemic interleukin-6 in major trauma patients.

BACKGROUND: The influence of alcohol on the outcome after major trauma remains controversial. In several recent studies, alcohol has been associated with neuroprotective effects in head injuries, while others reported negative or no effects on survival and/or the in-hospital stay in major trauma patients (TP). The purpose of this study was to examine the relationship of alcohol with injury characteristics and outcome as well as to analyze possible anti-inflammatory properties in major TP. PATIENTS/METHODS: 184 severely injured TP with an Injury Severity Score (ISS) ≥16 were successively enrolled. All patients had measured blood alcohol concentration (BAC). Patients were grouped according to their positive BAC (>0.5‰, BAC) vs. <0.5‰ alcohol (no BAC) upon arrival at the emergency department (ED). Injury characteristics, physiologic parameters and outcome with respect to organ or multiple organ failure (MOF), SIRS, sepsis, pneumonia, ARDS or mortality were assessed. Systemic levels of interleukin (IL)-6 at ED were determined. RESULTS: Forty-nine TP had positive BAC without chronic alcohol abuse history and 135 patients had BAC levels below 0.5‰. Overall injury severity and age were comparable in both groups. No BAC TP received significantly higher numbers of packed red blood cells and fresh frozen plasma (transfused within the initial 24h or in total) compared to BAC TP. Organ failure, MOF, SIRS, sepsis, pneumonia, ARDS and the in-hospital mortality were not different between both groups. Trauma patients with positive BAC had significantly decreased leukocyte numbers and systemic IL-6 levels compared to no BAC group. There was a significant positive correlation between leukocyte counts and IL-6 as well as BAC and leukocytes. BAC levels did not correlate with IL-6. CONCLUSIONS: Positive BAC is associated with reduced leukocyte numbers and lowered systemic IL-6 levels at admittance indicating immune-suppressive effects of alcohol in major trauma patients.

[Thoracic and lumbar spinal injuries in children and adolescents]. / Brust- und Lendenwirbelsäulenverletzungen im Kindes- und Jugendalter.

Spinal injuries are generally very rare in childhood. Fractures of the thoracic and lumbar spine occur mainly in older children and adolescents. Exact knowledge of the anatomy is essential for accurate diagnosis in still incomplete ossification. With increasing age the classification can be performed by using the AO classification over the age of 8 years. Neurological symptoms in the thoracic and lumbar spine occur mainly in adolescence. Conventional radiography is the standard diagnostic tool for thoracic and lumbar spinal injuries. With the appearance of abnormal neurological deficits magnetic resonance imaging (MRI) diagnostics should also be performed and for operative cases computed tomography (CT) scans are mandatory. The most common fractures of the thoracic and lumbar spine are compression fractures (type A) which can generally be treated conservatively due to the stable situation but unstable fractures of the thoracic and lumbar spine (types B and C) are stabilized dorsally (internal fixation). Ventral stabilization with vertebral body replacement is occasionally necessary in adolescents. Spinal injuries in children have a good overall prognosis.

Biological dosimetry after radiosynoviorthesis with rhenium-186 sulphide and erbium-169 citrate.

UNLABELLED: Radiosynoviorthesis (RSO) with the nuclides rhenium-186 sulphide (186Re) and erbium-169 citrate (169Er) is an established concept for the treatment of persistent synovitis of medium and small sized joints. THE AIM of the present studies was to investigate the biological radiation effect based on analysing chromosome aberrations. PATIENTS, METHODS: Immediately before and 17 to 19 days (186Re) or 45 to 50 (169Er) days after RSO with 186Re or 169Er colloid and subsequent immobilisation of the treated joint, blood samples of a total of 23 patients were collected. The yield of dicentric chromosomes in lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, for 186Re the activity leakage was measured three days after RSO by whole-body scintigraphy. RESULTS: No statistically significant increase in the number of dicentric chromosomes (40 and 88 before and 59 and 105 after treatment with 186Re and 169Er, respectively) in a total of 47017 cells analysed from 46 blood samples could be found as a result of RSO. For 186Re an activity leakage of 3.9%±7% with a maximum of 23.4% corresponding to an effective dose of 2.8±4.5 mSv , respectively 13.8 mSv, was determined. Also in the case of the maximum leakage no significant increase of dicentric chromosomes were detected. CONCLUSIONS: No significant biological radiation effect can be detected after RSO with 186Re and 169Er, also in cases of high leakage. Therefore, RSO can be classified as a save therapeutic procedure without a relevant radiation risk.

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.

"Number needed to read"--how to facilitate clinical trials in MR-angiography.

PURPOSE: To evaluate the effect of the number of readers on the statistical results in peripheral MRA. MATERIALS AND METHODS: 40 patients with peripheral arterial occlusive disease were included as a sample dataset in this study, randomly separated into two matched groups with n = 20 patients (group 1--gadobutrol, group 2--gadoterate meglumine) who underwent a continuous table movement MRA of the peripheral vessels at 3 T. Image quality (IQ) of 17 vessel segments was evaluated by 5 independent readers. The effect of the number of readers on significance and statistical power was statistically analyzed. RESULTS: Image quality in group 1 (gadobutrol) ranks significantly higher compared to group 2 (gadoterade meglumine) with a diagnostic IQ in 97% vs. 78% (p < 0.0001). For the diagnostic/non-diagnostic IQ assessment significance was reached with one reader 1/5 times (20%), with two readers in 4/10 (40%), with three readers in 6/10 (60%), with four readers in 4/5 (80%), with five readers in 1/1 (100%). Power considerations showed considerable gain when increasing the number of readers. CONCLUSION: Increasing the number of readers in a diagnostic MRA-study can be used to achieve a higher power or to decrease the number of subjects included with maintained statistical validity.

Dependence of renal blood flow on renal artery stenosis measured using CT angiography.

PURPOSE: The present study investigates the suitability of computed tomography angiography (CTA) depicting the degree of renal artery stenosis for estimating renal blood flow (RBF) in a kidney. MATERIALS AND METHODS: We investigated renal artery stenosis assessment by CTA in eight adult female hybrid pigs with an ultrasound probe implanted at the renal vein for RBF measurement. An inflatable metal-free cuff was placed around the renal artery to control the RBF. The RBF was then reduced in four steps. For each reduced RBF value and baseline RBF, CTA with a reconstructed slice thickness of 0.625 mm was performed in the arterial phase following injection of 80 ml of nonionic intravenous contrast medium. The radius of the stenotic and non-stenotic renal artery segment was measured in the reconstructed images. RESULTS: A significant linear correlation (p < 0.0001) was found between the relative apparent stenosis (calculated as the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment) and RBF. The linear regression yielded a slope of 0.57 and a y-axis of 24.1 %. A significant linear correlation (p < 0.0001) was also found between the relative true stenosis (the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment at baseline) and the RBF. The linear regression yielded a slope of 0.67 and a y-axis of 13.8 %. CONCLUSION: The results show that the relative stenosis apparent on CTA differs from the true degree of renal artery stenosis. Nevertheless, the degree of renal artery stenosis determined by CTA provides a reliable estimate of the resulting RBF reduction.

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.

Radiosynoviorthesis of medium-sized joints with rhenium-186-sulphide colloid: a review of the literature.

Hypertrophy and inflammation of the synovium with various underlying pathologies - such as rheumatoid arthritis, osteoarthritis, haemophilia and spondyloarthropathy - can be treated successfully by radiosynoviorthesis (RSO). For medium-sized joints (shoulder, elbow, wrist, hip and ankle), the radionuclide of choice is rhenium-186. We review the evidence for the efficacy of this local, relatively non-invasive therapy and evaluate its benefits and risks. We conclude good evidence of rhenium-186 RSO in rheumatoid arthritis and haemophilic arthropathy. In the remaining pathologies, up to now, the therapeutic efficacy has not been confirmed by today's most stringent criteria for clinical studies. The available data support rhenium-186 RSO as a suitable second-line treatment for patients in whom other therapies (including locally injected corticoids) have failed, as long as proper attention is paid to correct administration - including post-treatment immobilization and the co-administration of corticoids.

Therapeutic status of radiosynoviorthesis of the knee with yttrium [90Y] colloid in rheumatoid arthritis and related indications.

Radiosynoviorthesis (RSO) with an yttrium-90 colloid offers a local and minimally invasive therapy for treating inflammatory hypertrophy of the synovial membrane of the knee that has arisen from numerous kinds of disorder: these include rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthropathy, villonodular synovitis and others. There is substantial evidence that this treatment is efficacious and that, in view of the benefits that it offers, its tolerability and safety are very good. Administration should be restricted to patients in whom other therapies (including locally injected corticoids) have failed, and proper attention must be paid to correct administration, including post-treatment immobilization and the co-administration of corticoids, to minimize the risk of leakage and of efflux through the puncture channel.

Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis.

UNLABELLED: Radiosynoviorthesis (RSO) with the ss-particle-emitting nuclide yttrium-90 is an established concept for the treatment of persistent synovitis of the knee joint. The AIM of this study was to investigate the biological radiation effect on the basis of a characteristic radiation parameter. PATIENTS, METHODS: After RSO procedures with yttrium-90 citrate colloid and subsequent immobilisation of the knee, blood specimens of 10 patients were collected immediately before RSO and 11 to 13 days after the intervention. The yield of dicentric chromosomes in the lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, activity leakage was measured by wholebody bremsstrahlung-scintigraphy. RESULTS: No statistically significant increase in the number of dicentric chromosomes (26 before treatment and 34 after treatment) in 20 192 cells analyzed from the 20 blood samples could be found as a result of RSO. However, the analysis of at least 1000 cells per blood sample demonstrates a tendency for a biological radiation effect in the blood of patients on the basis of this characteristic radiation parameter. Two of the 10 RSO patients had undergone a second RSO using yttrium-90 citrate, whereby one patient displayed activity transport out of the knee joint, amounting to 6 MBq. Only for him a radiation effect (about 130 mGy per single RSO) could be calculated by biological dosimetry. CONCLUSION: Since in general, based on the analysis of dicentric chromosomes in at least 1000 lymphocytes per individual, detection limits for groups of persons after long-term exposures to low-LET radiation of 50-100 mGy are possible, we assume that RSO with yttrium-90 should be associated with a low whole-body radiation exposure.

The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

[Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction]. / Mobilisation von Stammzellen durch den Granulozyten-Kolonie stimulierenden Faktor zur Regeneration myokardialen Gewebes nach Herzinfarkt.

BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells (BMC) may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. METHODS AND RESULTS: 48 h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to 9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. CONCLUSION: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.