Molecular and functional expression of voltage-operated calcium channels during osteogenic differentiation of human mesenchymal stem cells.

We used the patch-clamp technique and RT-PCR to study the molecular and functional expression of VOCCs in undifferentiated hMSCs and in cells undergoing osteogenic differentiation. L-type Ca2+ channel blocker nifedipine did not influence alkaline phosphatase activity, calcium, and phosphate accumulation of hMSCs during osteogenic differentiation. This study suggests that osteogenic differentiation of hMSCs does not require L-type Ca2+ channel function. INTRODUCTION: During osteogenic differentiation, mesenchymal stem cells from human bone marrow (hMSCs) must adopt the calcium handling of terminally differentiated osteoblasts. There is evidence that voltage-operated calcium channels (VOCCs), including L-type calcium channels, are involved in regulation of osteoblast function. We therefore studied whether VOCCs play a critical role during osteogenic differentiation of hMSCs. MATERIALS AND METHODS: Osteogenic differentiation was induced in hMSCs cultured in maintenance medium (MM) by addition of ascorbate, beta-glycerophosphate, and dexamethasone (ODM) and was assessed by measuring alkaline phosphatase activity, expression of osteopontin, osteoprotegerin, RANKL, and mineralization. Expression of Ca2+ channel alpha1 subunits was shown by semiquantitative or single cell RT-PCR. Voltage-activated calcium currents of hMSCs were measured with the whole cell voltage-clamp technique. RESULTS: mRNA for the pore-forming alpha1C and alpha1G subunits of the L-type and T-type Ca2+ channels, respectively, was found in comparable amounts in cells cultured in MM or ODM. The limitation of L-type Ca2+ currents to a subpopulation of hMSCs was confirmed by single cell RT-PCR, where mRNA for the alpha1C subunits was detectable in only 50% of the cells cultured in MM. Dihydropyridine-sensitive L-type Ca2+ currents were found in 13% of cells cultured in MM and in 12% of the cells cultured in ODM. Under MM and ODM culture conditions, the cells positive for L-type Ca2+ currents were significantly larger than cells without Ca2+ currents as deduced from membrane capacitance; thus, current densities were comparable. Addition of the L-type Ca2+ channel blocker nifedipine to the culture media did not influence alkaline phosphatase activity and the extent of mineralization. CONCLUSION: These results suggest that, in the majority of hMSCs, Ca2+ entry through the plasma membrane is mediated by some channels other than VOCCs, and blockade of the L-type Ca2+ channels does not affect early osteogenic differentiation of hMSCs.     

Operative Behandlung traumatischer Frakturen der Brust- und Lendenwirbelsäule

The Spine Study Group (AG WS) of the German Trauma Association (DGU) presents its second prospective Internet-based multicenter study (MCS II) for the treatment of thoracic and lumbar spinal injuries. This second part of the study report focuses on the surgical treatment, course of treatment, and radiological findings in a study population of 865 patients. A total of 158 (18,3%) thoracic, 595 (68,8%) thoracolumbar, and 112 (12,9%) lumbar spine injuries were treated. Of these, 733 patients received operative treatment (OP group). Fifty-two patients were treated non-operatively and 69 patients were treated with kyphoplasty/vertebroplasty without additional instrumentation (Plasty group). In the OP group, 380 (51.8%) patients were instrumented from a posterior (dorsal) position, 34 (4.6%) from an anterior (ventral) position, and 319 (43.5%) cases with a combined posteroanterior procedure. Angular stable internal spine fixator systems were used in 86–97% of the cases for posterior and/or combined posteroanterior procedures. For anterior procedures, angular stable plate systems were used in a majority of cases (51.1%) for the instrumentation of mainly one or two segment lesions (72.7%). In 188 cases (53,3%), vertebral body replacement implants (cages) were used and were mainly implanted via endoscopic approaches (67,4%) to the thoracic spine and/or the thoracolumbar junction. The average operating time was 152 min in posterior-, 208 min in anterior-, and 298 min in combined postero-anterior procedures (p<0,001). The average blood loss was highest in combined operations, measuring 959 ml vs. 650 ml in posterior vs. 534 ml in anterior operations (p<0,001). Computer-assisted intraoperative navigation systems were used in 95 cases. At the time of hospital admission, 58,7% of the patients had spinal canal narrowing of an average of 36% (5–95%) at the level of their injury. The average spinal canal narrowing in patients with a complete spinal cord injury (Frankel/ASIA A) was calculated to be 70%, vs. 50% in patients with incomplete neurologic deficits (Frankel/ASIA B–D), and 20% in patients without neurologic deficits (Frankel/ASIS E; p<0,001). The average procedure in the plasty treatment subgroup was 50 min (18–145 min) to address one (n=59) or two (n=10) injured vertebral bodies. In patients with nonoperative treatment mainly three-point-corsets (n=36) were administered for a duration of 6–12 weeks. During their hospital stay 93 of 195 (44,7%) patients with initial neurologic deficits improved at least one Frankel/ASIA grade until the day of discharge. Two patients (0,2%) showed a neurologic deterioration. The highest rate of complete spinal cord injury (n=36, 23%) was associated with thoracic spine injuries. Nine (1%) patients died during the initial course of treatment. A total of 105 (14,3%) cases with intraoperative (n=56) and/or postoperative complications (n=69) were registered. The most common intraoperative complication was bleeding (n=35, 4,8%). A higher relative frequency of intraoperative complications was noticed in combined (n=34, 10,7%) vs. isolated posterior (n=22, 5,9%; p=0,021) procedures. The most common postoperative complication was associated with wound healing problems in 14 (1,9%) patients. Except in the non-operative treatment subgroup, a correction of the posttraumatic measured radiological deformity was achieved to a different extent within every treatment subgroup. There were no statistically significant differences between the postoperative radiological results of the treatment subgroups (dorsal vs. combination), taking into consideration the influence of relevant parameters such as different fracture types, patient age, and the amount of posttraumatic deformity (p=0,34, ANOVA).     

Value of comprehensive renal ultrasound in children with acute urinary tract infection for assessment of renal involvement: comparison with DMSA scintigraphy and final diagnosis

The aim of this study was to evaluate the value of comprehensive renal ultrasound (US), i.e., combining greyscale US and amplitude-coded color Doppler sonography (aCDS), for assessment of urinary tract infection (UTI) in infants and children, compared to (1) ^99mTc DMSA scintigraphy and (2) final diagnosis. Two hundred eighty-seven children with UTI underwent renal comprehensive US and DMSA scintigraphy. The results were compared with regard to their reliability to diagnose renal involvement, using (1) DMSA scintigraphy and (2) final diagnosis as the gold standard. Sixty-seven children clinically had renal involvement. Sensitivity increased from 84.1% using only aCDS to 92.1% for the combined US approach, using DMSA scintigraphy as the reference standard. When correlated with the final diagnosis, sensitivity for DMSA scintigraphy was 92.5%; sensitivity for comprehensive US was 94.0%. Our data demonstrate an increasing sensitivity using the combination of renal greyscale US supplemented by aCDS for differentiation of upper from lower UTI. Sensitivity for DMSA and comprehensive US was similar for both methods compared to the final diagnosis. Comprehensive US should gain a more important role in the imaging algorithm of children with acute UTI, thereby reducing the radiation burden.     

Innovative Power of Health Care Organisations Affects IT Adoption: A bi-National Health IT Benchmark Comparing Austria and Germany

Multinational health IT benchmarks foster cross-country learning and have been employed at various levels, e.g. OECD and Nordic countries. A bi-national benchmark study conducted in 2007 revealed a significantly higher adoption of health IT in Austria compared to Germany, two countries with comparable healthcare systems. We now investigated whether these differences still persisted. We further studied whether these differences were associated with hospital intrinsic factors, i.e. the innovative power of the organisation and hospital demographics. We thus performed a survey to measure the “perceived IT availability” and the “innovative power of the hospital” of 464 German and 70 Austrian hospitals. The survey was based on a questionnaire with 52 items and was given to the directors of nursing in 2013/2014. Our findings confirmed a significantly greater IT availability in Austria than in Germany. This was visible in the aggregated IT adoption composite score “IT function” as well as in the IT adoption for the individual functions “nursing documentation” (OR?=?5.98), “intensive care unit (ICU) documentation” (OR?=?2.49), “medication administration documentation” (OR?=?2.48), “electronic archive” (OR?=?2.27) and “medication” (OR?=?2.16). “Innovative power” was the strongest factor to explain the variance of the composite score “IT function”. It was effective in hospitals of both countries but significantly more effective in Austria than in Germany. “Hospital size” and “hospital system affiliation” were also significantly associated with the composite score “IT function”, but they did not differ between the countries. These findings can be partly associated with the national characteristics. Indicators point to a more favourable financial situation in Austrian hospitals; we thus argue that Austrian hospitals may possess a larger degree of financial freedom to be innovative and to act accordingly. This study is the first to empirically demonstrate the effect of “innovative power” in hospitals on health IT adoption in a bi-national health IT benchmark. We recommend directly including the financial situation into future regression models. On a political level, measures to stimulate the “innovative power” of hospitals should be considered to increase the digitalisation of healthcare.     

Neuroendocrine tumor of the pancreas and bilateral adrenal pheochromocytomas. A rare manifestation of von Hippel-Lindau disease in childhood

Background

A 12-year-old girl presenting with intermittent epigastric pains and diarrhea was referred to our clinic. Diagnostic workup revealed nonfunctional bilateral adrenal pheochromocytomas as well as a neuroendocrine tumor of the pancreatic head. This is the first report on the combination of a neuroendocrine pancreatic tumor with adrenal pheochromocytoma in a pediatric patient with von Hippel-Lindau (VHL) disease.

Methods

von Hippel-Lindau disease was confirmed by molecular genetic analysis of peripheral blood lymphocytes, which revealed the mutation VHL c. 695 G > A. The family history showed also VHL disease in the mother who carried the same mutation.

Results and Conclusion

Open laparotomy, organ-sparing enucleation of pheochromocytoma, and pylorus-preserving resection of the pancreatic head tumor were successfully performed. After an uneventful postoperative course, the child fully recovered. She was free of further manifestations of VHL disease 30 months after surgery.     

Auxiliary liver transplantation in acute liver failure in the rat – an illustrated description of a new surgical approach

INTRODUCTION: To investigate auxiliary liver transplantation successfully in rats suffering from acute liver failure, we developed a new surgical approach. METHODS: A 70% hepatectomized liver graft was implanted into the right upper quadrant of the abdomen. The donor portal vein was anastomosed with the recipient's right renal artery using the splint technique. The donor infrahepatic vena cava was attached onto the recipient vena cava end to side. The bile duct was implanted into the duodenum.     

Aromatase inhibitors as solely treatment in postmenopausal breast cancer patients

Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high-end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52-102 years). All patients suffered from breast cancer. The mean follow-up interval was 40 months (range 5-92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.