[Individual aspects in eldery patients with fragility fractures]. / Individuelle Besonderheiten bei hochbetagten Patienten mit Fragilitätsfrakturen.

BACKGROUND: Due to our ageing population, the number of elderly patients who are treated in the emergency department due to low-energy trauma (e.g., tripping) continues to rise. These minor accidents often result in fragility fractures classically located in the proximal humerus, distal radius, spine, pelvis, and near the hip joint. Pre-existing conditions, polypharmacy, and general frailty increase the risk of fragility fractures in this patient population. METHODS: Geriatric trauma fractures and especially insufficiency fractures of the posterior pelvic ring are often difficult to diagnose by plain X­ray. Therefore, in geriatric trauma patients, cross-sectional imaging, e.g., computed tomography (CT), dual-energy CT (DECT), or magnetic resonance imaging (MRI), should be considered early for reliable evaluation of a suspected fracture. This also allows for the identification of older fractures. Particularly in cognitively impaired elderly patients, difficult examination conditions or an unclear fall event, cross-sectional imaging is often indicated. However, this may also involve risks, e.g., use of contrast medium in patients with impaired renal function, so that each case must be considered individually. Furthermore, the diagnosis and treatment of osteoporosis, which is an underlying disease that leads to fragility fractures, is of particular importance. In the diagnostic workup, measurement of bone density using dual energy X­ray absorptiometry (DXA) is the standard method according to guidelines. In specific situations, high-resolution peripheral quantitative CT (HR-pQCT) may also be used. CONCLUSION: Due to the special challenges of correctly detecting fragility fractures and being able to quickly initiate adequate therapy, good cooperation between radiologists and trauma surgeons is necessary.

Correction: Role of growth arrest-specific gene 6-mer axis in multiple myeloma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Differential diagnoses of osteoporosis]. / Differenzialdiagnosen der Osteoporose.

The differential diagnoses of osteoporosis in geriatric and trauma patients are very important as they may induce different therapies. On average approximately 20% of women and 50% of men have secondary causes of osteoporosis. The foundation of the diagnostics is a basic osteological laboratory investigation with which the most important secondary causes can be identified. From a geriatric and traumatological point of view vitamin D deficiency with secondary hyperparathyroidism, primary hyperparathyroidism, male hypogonadism, multiple myeloma and monoclonal gammopathy of unclear significance (MGUS) are of particular importance.

Microplastic in a macro filter feeder: Humpback whale Megaptera novaeangliae.

Marine filter feeders are exposed to microplastic because of their selection of small particles as food source. Baleen whales feed by filtering small particles from large water volumes. Macroplastic was found in baleen whales before. This study is the first to show the presence of microplastic in intestines of a baleen whale (Megaptera novaeangliae). Contents of its gastrointestinal tract were sieved, dissolved in 10% potassium hydroxide and washed. From the remaining dried material, potential synthetic polymer particles were selected based on density and appearance, and analysed by Fourier transform infrared (FTIR) spectroscopy. Several polymer types (polyethylene, polypropylene, polyvinylchloride, polyethylene terephthalate, nylon) were found, in varying particle shapes: sheets, fragments and threads with a size of 1mm to 17cm. This diversity in polymer types and particle shapes, can be interpreted as a representation of the varying characteristics of marine plastic and the unselective way of ingestion by M. novaeangliae.

Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma.

Multiple myeloma is a mostly incurable malignancy characterized by the expansion of a malignant plasma cell (PC) clone in the human bone marrow (BM). Myeloma cells closely interact with the BM stroma, which secretes soluble factors that foster myeloma progression and therapy resistance. Growth arrest-specific gene 6 (Gas6) is produced by BM-derived stroma cells and can promote malignancy. However, the role of Gas6 and its receptors Axl, Tyro3 and Mer (TAM receptors) in myeloma is unknown. We therefore investigated their expression in myeloma cell lines and in the BM of myeloma patients and healthy donors. Gas6 showed increased expression in sorted BMPCs of myeloma patients compared with healthy controls. The fraction of Mer(+) BMPCs was increased in myeloma patients in comparison with healthy controls whereas Axl and Tyro3 were not expressed by BMPCs in the majority of patients. Downregulation of Gas6 and Mer inhibited the proliferation of different myeloma cell lines, whereas knocking down Axl or Tyro3 had no effect. Inhibition of the Gas6 receptor Mer or therapeutic targeting of Gas6 by warfarin reduced myeloma burden and improved survival in a systemic model of myeloma. Thus, the Gas6-Mer axis represents a novel candidate for therapeutic intervention in this incurable malignancy.

[Osteogenic differentiation of human bone marrow stromal cells (hBMSC) by cyclic longitudinal mechanical strain and dexamethasone]. / Osteogene Differenzierung von humanen stromalen Zellen aus dem Knochenmark (hBMSC) unter dem Einfluss von zyklischem mechanischem Dehnungsstress und Dexamethason.

AIM: The aim of the study was to investigate the effects of dexamethasone and cyclic mechanical strain on human bone marrow stromal cells (hBMSCs) in osteogenic differentiation by determing levels of mRNA of collagen I, II, III, tenascin C and Cbfa1. METHOD: hBMSCs from seven donors (32.5 +/- 6.2 years old) were cultivated with (D +) or without (D -) dexamethasone. After the second passage 2.2 x 10 (5) cells were seeded on flexible silicon dishes. A cyclic mechanical strain with an elongation of 2 % (D + 2; D - 2) or 8 % (D + 8; D - 8) was applied for three days with a stimulation time of three times for two hours each day. Cells were harvested on day 1, day 1 after stress (day 4) and day 4 after stress (day 7). mRNA expression of collagen I, II, III, tenascin C and Cbfa1 was investigated by RT-PCR. RESULTS: Cbfa1 mRNA levels were significantly different on different days (p < 0.05), and for strain on day 1: 8 %: 0.0291 +/- 0.0338 versus 0 %: 0.00 528 +/- 0.0127, p = 0.017; day 8: 8 %: 0.0411 +/- 0.116, 0 %: 0.00 103 +/- 0.00 217, p = 0.009. All other observed paramaters showed tendencies without significant differences. CONCLUSION: In the short-term over seven days, cyclic stretching is a stronger differentiation factor than dexamethasone.

Influence of perfusion and cyclic compression on proliferation and differentiation of bone marrow stromal cells in 3-dimensional culture.

Until now, there has been no in vitro model that duplicates the environment of bone marrow. The purpose of this study was to analyze proliferation and differentiation of human bone marrow stromal cells (hBMSC) under the influence of continuous perfusion and cyclic mechanical loading. hBMSC of seven individuals were harvested, grown in vitro, and combined. 10(6) hBMSC were seeded on a bovine spongiosa disc and incubated in a bioreactor system. Cell culture was continued using three different conditions: Continuous perfusion (group A), 10% cyclic compression at 0.5Hz (group B) and static controls (group C). After 24h, 1, 2, and 3 weeks, we determined cell proliferation (MTS-assay) and osteogenic differentiation (osteocalcin ELISA, Runx2 mRNA). Tenascin-C mRNA was quantified to exclude fibroblastic differentiation. In groups A and B, proliferation was enhanced after 2 weeks (48.6+/-19.6x10(3) (A) and 44.6+/-14.3 x 10(3) cells (B)) and after 3 weeks (46.6+/-15.1 x 10(3) (A) and 44.8+/-10.2 x 10(3) cells (B)) compared with controls (26.3+/-10.8 x 10(3) (2 weeks) and 17.1+/-6.5 x 10(3) cells (3 weeks), p<0.03). Runx2 mRNA was upregulated in both stimulated groups after 1, 2, and 3 weeks compared to control (group A, 1 week: 5.2+/-0.7-fold; p<0.01, 2 weeks: 4.4+/-1.9-fold; p<0.01, 3 weeks: 3.8+/-1.7-fold; p=0.013; group B, 1 week: 3.6+/-1.1-fold, p<0.01, 2 weeks: 4.2+/-2.2-fold, p<0.01; 3 weeks: 5.3+/-2.7-fold, p<0.01). hBMSC stimulated by cyclic compression expressed the highest amount of osteocalcin at all time points (1 week: 294.5+/-88.4 mg/g protein, 2 weeks: 294.4+/-73.3mg/g protein, 3 weeks: 293.1+/-83.6 mg/g protein, p0.03). The main stimulus for cell proliferation in a 3-dimensional culture of hBMSC is continuous perfusion whereas mechanical stimulation fosters osteogenic commitment of hBMSC. This study thereby contributes to the understanding of physical stimuli that influence hBMSC in a 3-dimensional cell culture system.

Femoral avulsion fracture of the posterior cruciate ligament in association with a rupture of the popliteal artery in a 9-year-old boy: a case report.

Ruptures of the posterior cruciate ligament (PCL) and especially proximal bony avulsion fractures in children are very rare. This in combination with a rupture of the popliteal artery is extremely rare. Thus, an exact incidence is not available from the literature. Overall, these injuries are severe and often lead to chronic knee instability. We report a case of a 9-year-old boy who suffered a traumatic displacement of the left knee with a rupture of the popliteal artery. Prior to transfer to our department, he was treated by a saphenous vein bypass graft and by a transfixation of the knee using two oblique percutaneous pins. We performed magnetic resonance imaging (MRI) scan of the knee which revealed a femoral avulsion fracture of the PCL. Other ligaments and menisci were intact. A transosseous femoral fixation using non-absorbable stitches was carried out. A 1-year follow-up after surgery demonstrates intact peripheral perfusion and sensation, straight axes of both legs and a physiological gait. Minimal differences of the length and circumference of both legs could be measured. The posterior laxity (Lachman-test) was about 5/8 mm (right/left knee) and 2/5 mm (right/left knee) in 90 degrees flexion. The range of motion (extension/flexion) was 5/0/140 degrees -/5/100 degrees (right-left knee). Intact cruciate ligaments were confirmed by MRI. Minimal experience exists in treatment of combined injuries to the PCL and the popliteal artery in children.

Oncofoetal fibronectin--a tumour-specific marker in detecting minimal residual disease in differentiated thyroid carcinoma.

Supposedly, thyrocyte-specific transcripts such as thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) were proposed to be useful for the diagnosis of circulating tumour cells in patients suffering from differentiated thyroid carcinoma (DTC). However, several research groups reported blood-borne Tg transcripts in healthy individuals. This study determines in particular the origin of Tg mRNA in nucleated blood cells and analyses whether other tumour-associated sequences are absent in leukocytes, but widely expressed in DTC. Therefore, expression analyses for Tg, TSH-R, cytokeratin 19 (CK 19), human telomerase reverse transcriptase (hTERT) and oncofoetal fibronectin (onfFN) were carried out using cDNAs derived from (1) leukocyte fractions, (2) 18 follicular thyroid carcinomas (FTCs) and 48 papillary thyroid carcinomas (PTCs), and (3) leukocytes of two thyrocyte-depleted individuals treated for C-cell carcinoma of the thyroid. Expression of onfFN was additionally analysed by semiquantitative RT-PCR and by quantitative fluorescence-based real-time PCR. Tg and TSH-R expression was demonstrated not only in both athyroid individuals, but in all leukocyte subgroups tested, while hTERT was absent in resting CD4+ cells and only weakly expressed in the CD8+ group. CK 19 was notable in each leukocyte population except for resting CD14(+), as well as for activated and resting CD19+ cells. All blood cell fractions proved negative for onfFN mRNA, whereas its presence in thyroid carcinoma was 78/98% (FTC/PTC). Threshold cycle values were calculated at: porphobilinogen deaminase (PBGD) = 25.95+/-0.73 (FTC)/24.55+/-5.43 (PTC) (P = 0.2878); onfFN = 25.48+/-3.15 (FTC)/21.44+/-3.44 (PTC) (*P = 0.0001). Finally, onfFN transcripts were detected in blood samples of six out of nine patients with known DTC metastases, demonstrating a reliable assay functionality. We propose that real-time RT-PCR of onfFN mRNA is superior to other markers in monitoring minimal residual disease in DTC with regard to both assay sensitivity and specificity.

Effects of TCDD-estradiol interactions in three strains of mice.

Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estradiol were studied in three strains of mice: CD-1 and C57B/6 (TCDD sensitive) and DBA/2 (TCDD resistant at lower doses). Immature females were injected with 0-200 ng/kg/day estradiol for 2 weeks, s.c. On days 7, 9, 11, and 13, mice received 10 micrograms TCDD/kg by gavage. Relative uterine weight increased in mice of all three strains treated with estradiol alone. Uterine imbibition was suppressed by TCDD treatment, although this effect was antagonized in a saturable manner by coadministration of estradiol. TCDD induced aryl hydrocarbon hydroxylase (AHH) in liver microsomes of treated mice independent of estradiol dose and strain of mice (the dose of TCDD used was high enough to cause AHH induction in the resistant DBA/2 mice). Treatment of CD-1 mice, but not other strains, with TCDD and estradiol resulted in a decrease in the electrophoretic band of hepatic microsomal proteins comigrating with cytochrome P-450a and epoxide hydrase.

Interactive effects of estradiol and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic cytochrome P-450 and mouse uterus.

Weanling C57B/6 female mice treated with 6 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 3 times a week for one month (total dose 72 micrograms/kg) were observed to have greatly reduced relative uterine weights and histopathological changes in the uterus. Weanling CD-1 female mice were then treated with estradiol (E2) subcutaneously daily for 2 weeks. Half the mice also received 10 micrograms/kg TCDD in corn oil: acetone (9:1) by gavage 4 times during the second week. Control mice received either no E2 or no TCDD. Mice were killed on day 15 and autopsied. Relative uterine weights increased with increasing E2 doses; however, TCDD decreased this effect of E2 markedly. Liver microsomes from these animals showed that cytochrome P1-450 and P3-450 and, aryl hydrocarbon hydroxylase (AHH) induction by TCDD were independent of E2 dosage. Epoxide hydrolase was induced in TCDD treated animals. Gels showed an E2 dose dependent decrease in a protein migrating near epoxide hydrolase and 'P-450a' in animals receiving both E2 and TCDD. These results suggest that: E2 may act at the TCDD receptor; the TCDD receptor may be related to the estrogen receptor; the anti-estrogenic effects of TCDD are possibly independent of the Ah locus and AHH induction, and in TCDD-treated mice a protein migrating near epoxide hydrolase and 'P-450a' may be controlled by estrogen levels.