Dose-dependent effects of strontium on bone of chronic renal failure rats

BACKGROUND: We previously reported on increased bone strontium (Sr) levels in dialysis patients with osteomalacia versus those presenting other types of renal osteodystrophy. A causal role of strontium in the development of osteomalacia was established in a chronic renal failure (CRF) rat model. METHODS: In the present study we investigated whether the effect of Sr on bone was related to dosage. Four groups of CRF rats were studied: a control group (control-CFR; N=6) not receiving strontium and three groups of animals loaded orally with Sr during 18 weeks by adding the element as the SrCl2. H20 compound to the drinking water at concentrations of 0.03 g/100mL (Sr-30; N=6), 0.075 g/100mL (Sr-75; N=6), or 0.15 g/100mL (Sr-150; N=6) respectively. A fifth group consisting of seven animals with intact renal function (control-NRF), not receiving Sr served as controls for the effect of CRF on bone histology. RESULTS: As compared to the control-NRF and control-CRF groups, Sr administration resulted in a dose-dependent increase in bone and serum Sr levels. No difference in body weight and biochemical serum and urinary parameters [i.e., calcium (Ca), phosphorus (P), and creatinine] was noted between the various CRF groups. At sacrifice, intact parathyroid hormone (iPTH) levels of CRF groups were significantly (P < 0.05) higher than the values measured in the control-NRF group indicating the development of hyperparathyroidism secondary to the installation of the CRF. This is further supported by the differences in bone histomorphometry between the control-CRF and control-NRF animals, which, respectively, showed an increased amount of osteoid (mean +/- SEM 3.4 +/- 1.2% vs. 0.37 +/- 0.14%, P < 0.05) in combination with a distinct osteoblastic activity (35 +/- 11% vs. <2%, P < 0.05) and an increased bone formation rate [(BFR), 677 +/- 177 microm 2/mm2/day vs. 130 +/- 50 microm 2/mm2/day, P < 0.05]. Bone surface area and erodic perimeter did not differ between the various study groups. In the Sr-30 group, Sr loading went along with a dramatic reduction of the BFR as indicated by the total absence of double tetracyclin labels and osteoblastic activity, which in the presence of a low to normal amount of osteoid (2.7 +/- 1.9%) points to the development of the adynamic type of renal osteodystrophy. Interestingly, compared to the control-CRF group, histodynamic and histologic parameters of the Sr-75 group did not differ significantly and a substantial osteoblastic activity (7.6 +/- 4.0%) was seen also. In the Sr-150 group, the various osteoid parameters were significantly (P < 0.05) increased vs. all other groups and were accompanied by a reduced BFR and mineral apposition rate (MAR) and an increased mineralization lag time (MLT), indicating a mineralization defect and the development of osteomalacia. CONCLUSIONS: Our findings indicate that the role of Sr in the development of bone lesions in renal failure is complex and that, depending on the dose, the element may act via multiple pathways.     

P_(16)蛋白在食管鳞状细胞癌的表达及临床意义

应用免疫络化S－P法检测88例食管浸润世鳞癌P16蛋白的表达，结果P16蛋白阳性率为55．68％（49/88），其阳性颗粒位于细胞浆内；组织学Ⅰ、Ⅱ、Ⅲ级阳性率分予的85．71％（18/21）、55.13％（16/29）、39.47％（15/38）（P＜0．01）；淋巴结转移组和无转移组阳世事分别为36.36％（12／33），67．27％（37／55）（P＜0．01）;3年生存率P16蛋白阳性组和阴性组分别36％和16．67％。结果表明食管鳞癌中P16蛋白的表达可以反映肿瘤的分化程度和转移情况．提示P16蛋白的检测可作为食管鳞癌的重要预后指标之一。     

Primary care anticoagulant clinic management using computerized decision support and near patient International Normalized Ratio (INR) testing: routine data from a practice nurse-led clinic

BACKGROUND: Increasing indications for warfarin therapy has led to increased pressure on primary care to undertake therapeutic monitoring. OBJECTIVE: This study evaluates a primary care model of oral anticoagulation monitoring which utilises computerized decision support (CDSS) and near patient testing (NPT) within a practice nurse-led clinic. Whilst this has been shown to be a successful model under trial conditions, this paper reports the first data from a long-standing clinic, outside a formal study. METHOD: A prospective evaluation of therapeutic and clinical control of all patients taking warfarin within one inner city general practice. Data were collected via CDSS. RESULTS: 29 patients were seen in 208 appointments. The mean percentage of patients within therapeutic range was 72%. The costs to the practice were pound sterling 1751. The costs the practice would have incurred had these patients been seen at the hospital with the same frequency would have been pound sterling 2290. CONCLUSIONS: The use of CDSS and NPT for nurse-delivered oral anticoagulation monitoring could enable the safe transfer of the majority of patients from secondary to primary care. Funding mechanisms to support the transfer of costs will be essential for most practices, as will be the maintenance of adequate staff training and quality assurance.      

Neonatal Ostomies

Two methods of neonatal ostomy care, nonappliance and appliance, are discussed. Skin problems associated with stoma care, such as excoriation, fungal infections, and allergic reactions, are reviewed and a number of suggestions are made for the proper care of stomas in the newborn.     

Assessment of Forces in Intradermal Injection Devices: Hydrodynamic <Emphasis Type="BoldItalic">Versus</Emphasis> Human Factors

Purpose

The force that has to be exerted on the plunger for administering a given amount of fluid in a given time, has an important influence on comfort for the subject and usability for the administrator in intradermal drug delivery. The purpose of this study is to model those forces that are subject-independent, by linking needle and syringe geometry to the force required for ejecting a given fluid at a given ejection rate.

Material and Methods

We extend the well-known Hagen-Poiseuille formula to predict pressure drop induced by a fluid passing through a cylindrical body. The model investigates the relation between the pressure drop in needles and the theoretic Hagen-Poiseuille prediction and is validated in fifteen needles from 26G up to 33G suited for intradermal drug delivery. We also provide a method to assess forces exerted by operators in real world conditions.

Results

The model is highly linear in each individual needle with R-square values ranging from 75% up to 99.9%. Ten out of fifteen needles exhibit R-square values above 99%. A proof-of-concept for force assessment is provided by logging forces in operators in real life conditions.

Conclusions

The force assessment method and the model can be used to pinpoint needle geometry for intradermal injection devices, tuning comfort for subjects and usability for operators.

     

Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220- expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.     

Tc-99m-PEG-Liposomes for the evaluation of colitis in Crohn's disease

In the present study, the potential role of 99mTc-PEG-liposome to determine the extent and severity of active disease of Crohn's colitis was investigated. Patients suspected of having an exacerbation of Crohn's disease underwent a 99mTc-PEG-liposome scan (740 MBq, imaging at 4 and 24 h p.i.). A barium enema or endoscopy was performed as the standard verification procedure. Disease activity indices (Clinical Disease Activity Index and Van Hees Activity Index) were calculated. In seven patients positive images of colon segments affected by Crohn's colitis were obtained using 99mTc-PEG-liposomes. Only a moderate relation between 99mTc-liposome scan grading and verification procedures was found (Spearman rank r = 0.22). In accordance with previous studies, no significant correlation was found between the clinical disease activity indices and the verification procedures. This study was prematurely terminated because of unacceptable side-effects in 3 out of 9 patients, which occured almost immediately after starting the infusion. The complaints consisted of dyspnea and facial erythema. The symptoms were self-limiting when the infusion was stopped. In conclusion, the extent of Crohn's colitis can be established non-invasively with 99mTc-PEG-liposome scintigraphy. However, in view of the encountered side-effects, the PEG-liposomal preparation may have to be modified.     

Cost‐effectiveness of deep brain stimulation in patients with Parkinson's disease

In addition to medical treatment, deep brain stimulation has become an alternative therapeutic option in advanced Parkinson's disease. High initial costs of surgery have to be weighted against long‐term gains in health‐related quality of life. The objective of this study was to assess the cost‐effectiveness of deep brain stimulation compared with long‐term medical treatment. We performed a cost‐utility analysis using a lifetime Markov model for Parkinson's disease. Health utilities were evaluated using the EQ‐5D generic health status measure. Data on effectiveness and adverse events were obtained from clinical studies, published reports, or meta‐analyses. Costs were assessed from the German health care provider perspective. Both were discounted at 3% per year. Key assumptions affecting costs and health status were investigated using one‐way and two‐way sensitivity analyses. The lifetime incremental cost‐utility ratio for deep brain stimulation was €6700 per quality‐adjusted life year (QALY) and €9800 and €2500 per United Parkinson's Disease Rating Scale part II (motor experiences of daily living) and part III (motor examination) score point gained, respectively. Deep brain stimulation costs were mainly driven by the cost of surgery and of battery exchange. Health status was improved and motor complications were reduced by DBS. Sensitivity analysis revealed that battery life time was the most influential parameter, with the incremental cost‐utility ratio ranging from €20,000 per QALY to deep brain stimulation dominating medical treatment. Deep brain stimulation can be considered cost‐effective, offering a value‐for‐money profile comparable to other well accepted health care technologies. Our data support adopting and reimbursing deep brain stimulation within the German health care system. © 2013 Movement Disorder Society