Differential response of bone cells isolated by sequential digestion to dichloromethylenebisphonate in culture

Summary Dichloromethylenebisphosphonate (Cl₂MBP), a compound structurally related to inorganic pyrophosphate but resistant to hydrolysis of endogenous phosphatase to yield inorganic phosphate, inhibits bone resorption and soft tissue mineralizationin vivo. Previously, we have shown that bone cells isolated from rat calvaria respond profoundly to the exposure of Cl₂MBP. To determine whether the cellular effects evoked by Cl₂MBP are confined to a particular bone cell type, calvaria from 1 day postnatal rats were subjected to a sequential time-dependent enzyme digestion, yielding five bone cell populations marked by differences in PTH response, alkaline phosphatase activity and collagen, as well as hyaluronic acid synthesis. Culturing these bone cell populations with Cl₂MBP revealed that previously observed results found with mixed bone cells (inhibition of cell proliferation, diminution of hyaluronic acid synthesis, and increase in alkaline phosphatase) were limited to cell populations which, according to the isolation scheme, stem from the outer tissue layer(s) of the calvaria. Collagen synthesis, however, was found to be equally increased regardless of cell type. These present results indicate that the action of Cl₂MBP on bone may be cell specific.     

Impact of intraoperative duodenal feeding on the oxygen balance of the splanchnic region in severely burned patients

Enteral feeding causes an increase of intestinal oxygen demand depending on the amount administered. The aim of this study presented was to evaluate, whether intraoperative duodenal feeding might put patients at risk developing splanchnic O(2)-imbalance due to an intraoperatively compromised intestinal perfusion based on stress and unrecognized hypovolemia. In 18 severely burned patients, the CO(2)-gap between the arterial and gastric CO(2), as a parameter for the intestinal O(2)-balance, was measured during the first operation. All operations were performed on day 3-5 after admission and lasted for 4-5h. Half of the patients (nine patients) were fed intraoperatively, whereas in the other nine patients feeding was suspended beginning 1h prior to surgery until 6h after surgery. CO(2)-gap measurements were carried out prior to surgery, hourly during the operation and 5h postoperatively. Measurements 3 and 4h after beginning of the operation revealed significantly higher CO(2)-gap values in the fasting group. All other measurements showed no significant difference between both groups. Therefore, intraoperative enteral nutrition, at least in the early postburn phase, is not only necessary for reducing caloric deficits, but also seems to have a protective effect on gut oxygen balance.     

Cardiac transplantation complicated by acute thrombotic occlusion of the right coronary artery

We report the case of a 63-year-old male patient undergoing cardiac transplantation due to fourth time aortic valve endocarditis. The postoperative course was complicated by thrombotic occlusion of the right coronary artery (RCA) causing acute right ventricular myocardial infarction, which required extracorporeal membrane oxygenation. The RCA could be reopened by catheter-based intervention and the patient stabilized. In order to avoid further immobilization, a right ventricular assist device was implanted and an aortocoronary bypass to the RCA was performed. After that, the patient stabilized progressively, could be weaned from the assist device, and was discharged home 6 weeks after transplantation. On coronary angiography, which is routinely performed 4 to 6 weeks after transplantation, a fistula from the RCA to the right ventricle was detected which was treated conservatively. Five months after transplantation, the patient is in good clinical condition without signs of recurrent endocarditis. This case shows that intense interdisciplinary cooperation of cardiac specialists allows the successful management of very complex patients in serious clinical conditions.     

Mitral valve repair provides improved outcome over replacement in active infective endocarditis

OBJECTIVES: Mitral repair in active infective endocarditis still remains controversial. Several studies demonstrate the feasibility of mitral repair in infective endocarditis; however, superiority of repair has never been shown. The aim of the investigation was to compare valve repair and valve replacement in respect to the extent of destruction and to analyze survival, recurrent endocarditis, and reoperation (event-free survival). METHODS: Sixty-eight consecutive patients underwent surgical intervention for mitral endocarditis. Thirty-four (50%) patients had valve repair, and 34 (50%) patients had valve replacement. Leaflet destruction involving at least one mitral leaflet was present in 15 (44.1%) patients of the repair group and 11 (32.4%) patients of the replacement group. Repair of the mitral annulus with pericardium was performed in 4 (11.8%) patients in the repair group and 3 (8.8%) patients in the replacement group. Patients in both groups were similar concerning the progression of valvular destructions and comorbidities. RESULTS: Hospital mortality was 11.8% (8 patients). No significant differences were found in all baseline parameters, with the exception of a higher incidence of previous septic embolism and sepsis in the repair group. Actuarial event-free survival at 1 year was 88.2% in the repair group compared with 67.7% in the replacement group, and 5-year event-free survival was 80.4% in the repair group and 54.6% in the replacement group (P = .015). Mitral valve repair remained the superior treatment regarding event-free survival in the multivariate analysis (hazard ratio, 0.33; 95% confidence interval, 0.12-0.93; P = .02). CONCLUSIONS: Mitral valve repair offers excellent early and late results and is the preferable treatment option in the surgical therapy of native infective endocarditis.     

Increased immune response in the acute phase of systemic lupus erythematosus and psoriatic arthritis caused by serum factors.

In the acute phase of systemic lupus erythematosus the serum contains factors, with molecular weights ranging from 780,000 daltons to 1.5 million daltons, which induce blast transformation of autologous lymphocytes. In addition to the high-molecular weight components, low-molecular weight factors (75,000 and 160,000 daltons) which also induce an increase in lymphocytic transformation have also been demonstrated. In contrast to the high-molecular weight components the low-molecular factors stimulate the transformation of autologous and homologous lymphocytes. During transformation, lysis of autologous target fibroblasts occurs. The low-molecular weight mitogenic components remain stable after 30 min at 56 degrees C. The significance of such mediators for the pathogenesis of systemic lupus erythematosus is discussed.     

Age-dependent changes in the regulation mechanisms for intracellular calcium ions in ganglion cells of the mouse retina

The purpose of this study was to investigate the role of intracellular calcium buffering in retinal ganglion cells. We performed a quantitative analysis of calcium homeostasis in ganglion cells of early postnatal and adult mice by simultaneous patch-clamp recordings in sliced tissue and microfluorometric calcium measurements with Fura-2. Endogenous calcium homeostasis was quantified by using the 'added buffer' approach which uses amplitudes and decay time constants of calcium transients to give a standard for intracellular calcium buffering. The recovery phase of depolarization-induced calcium transients was well approximated by a mono-exponential function with a decay time constant that showed a linear dependence on dye concentration. Endogenous calcium binding ratios were found to be 575 (n = 18 cells) in early postnatal and 121 (n = 18 cells) in adult retinal ganglion cells. With respect to ganglion cell degeneration at early postnatal stages, our measurements suggest that neuroprotection of a majority of developing ganglion cells partially results from a specialized calcium homeostasis based on high buffering capacities. Furthermore, the dramatic decrease of the intracellular calcium buffering capacity during ganglion cell development may enhance their vulnerability to neurodegeneration.     

Antiretroviral therapy with tenofovir is associated with mild renal dysfunction

A cross-sectional study was conducted to compare patients treated with tenofovir with patients never treated with tenofovir. Patients on tenofovir showed a lower mean glomerular filtration rate estimated by creatinine clearance or cystatin C clearance compared with control patients. In total, 24 patients on tenofovir versus five control patients had proteinuria greater than 130 mg/day. In the majority of patients on tenofovir proteinuria was of tubular origin.     

High Ep-CAM Expression is Associated with Poor Prognosis in Node-positive Breast Cancer

Previous studies in small series of patients with invasive breast cancer suggested a prognostic value of Ep-CAM overexpression in primary tumor tissue. To corroborate these findings, we performed a retrospective analysis of Ep-CAM expression using a tissue microarray containing tissue specimens from a large patient set. Ep-CAM expression was evaluated by immunohistochemistry in breast cancer tissue from 1715 patients with documented raw survival data. High level Ep-CAM expression (overexpression) was found in 41.7% of tumor samples, low level expression was found in 48.0% and no expression in 10.3% of tumor samples. Ep-CAM expression predicted poor overall survival in this patient cohort (p < 0.0001). Overall survival decreased significantly with increasing Ep-CAM expression. However, in this patient sample Ep-CAM expression was not an independent prognostic marker by multivariate analysis. Subgroup analysis revealed that Ep-CAM expression was a prognostic marker in node-positive (p < 0.0001) but not in node-negative (p = 0.58) breast cancer patients. Intriguingly, Ep-CAM expression was predictive for a dismal prognosis in patients receiving adjuvant cytotoxic (p = 0.03) or hormonal therapy (p < 0.0001) but not in untreated patients (p = 0.41). In summary, this study provides strong evidence that expression of Ep-CAM is a powerful marker of poor prognosis in node-positive invasive breast carcinoma and a potential predictive marker of sensitivity to adjuvant hormonal and/or cytotoxic treatment modalities.     

Effect of subthalamic deep brain stimulation on the function of the urinary bladder

Detrusor hyperreflexia is a relevant clinical symptom for patients suffering from Parkinson's disease. In a series of 16 patients, we demonstrated that subthalamic deep brain stimulation has a significant and urodynamically recordable effect leading to a normalization of pathologically increased bladder sensibility.