Influence of diurnal hyperosmotic loading on the metabolism and matrix gene expression of a whole-organ intervertebral disc model

It is generally agreed that the mechanical environment of intervertebral disc cells plays an important role in maintaining a balanced matrix metabolism. The precise mechanism by which the signals are transduced into the cells is poorly understood. Osmotic changes in the extracellular matrix (ECM) are thought to be involved. Current in-vitro studies on this topic are mostly short-term and show conflicting data on the reaction of disc cells subjected to osmotic changes which is partially due to the heterogenous and often substantially-reduced culture systems. The aim of the study was therefore to investigate the effects of cyclic osmotic loading for 4 weeks on metabolism and matrix gene expression in a full-organ intervertebral disc culture system. Intervertebral disc/endplate units were isolated from New Zealand White Rabbits and cultured either in iso-osmotic media (335 mosmol/kg) or were diurnally exposed for 8 hours to hyper-osmotic conditions (485 mosmol/kg). Cell viability, metabolic activity, matrix composition and matrix gene expression profile (collagen types I/II and aggrecan) were monitored using Live/Dead cell viability assay, tetrazolium reduction test (WST 8), proteoglycan and DNA quantification assays and quantitative PCR. The results show that diurnal osmotic stimulation did not have significant effects on proteoglycan content, cellularity and disc cell viability after 28 days in culture. However, hyperosmolarity caused increased cell death in the early culture phase and counteracted up-regulation of type I collagen gene expression in nucleus and annulus cells. Moreover, the initially decreased cellular dehydrogenase activity recovered with osmotic stimulation after 4 weeks and aggrecan gene down-regulation was delayed, although the latter was not significant according to our statistical criteria. In contrast, collagen type II did not respond to the osmotic changes and was down-regulated in both groups. In conclusion, diurnal hyper-osmotic stimulation of a whole-organ disc/endplate culture partially inhibits a matrix gene expression profile as encountered in degenerative disc disease and counteracts cellular metabolic hypo-activity.

Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants

BACKGROUND: A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries. OBJECTIVE: To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants. DESIGN: Sixteen preterm neonates of <34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography. RESULTS: The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO2, and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively). CONCLUSION: A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.

Immediate loading of implants with 3-unit fixed partial dentures: a 12-month clinical study

PURPOSE: The aim of the present clinical trial was to evaluate the 12-month success rate of titanium dental implants placed in the posterior mandible and immediately loaded with 3-unit fixed partial dentures. MATERIALS AND METHODS: Patients with missing mandibular premolars and molars were enrolled in this study. To be included in the study, the implants had to show good primary stability. Implant stability was measured with resonance frequency analysis using the Osstell device (Integration Diagnostics). Implants were included in the study when the stability quotient (ISQ) exceeded 62. Clinical measurements, such as width of keratinized tissue, ISQ, and radiographic assessment of peri-implant bone crest levels, were performed at baseline and at the 12-month follow-up. The comparison between the baseline and the 12-month visits was performed with the Student t test for paired data (statistically significant at a level of alpha = 0.05). RESULTS: Forty implants with a sandblasted, large grit, acid-etched (SLA) surface (Straumann) were placed in 20 patients. At 12 months, only 1 implant had been lost because of an acute infection. The remaining 39 implants were successful, resulting in a 1-year success rate of 97.5%. Neither peri-implant bone levels, measured radiographically, nor implant stability changed significantly from baseline to the 12-month follow-up (P > .05). DISCUSSION: The immediate functional loading of implants placed in this case series study resulted in a satisfactory success rate. CONCLUSION: The findings from this clinical study showed that the placement of SLA transmucosal implants in the mandibular area and their immediate loading with 3-unit fixed partial dentures may be a safe and successful procedure.

Calcium indicator loading of neurons using single-cell electroporation

Studies of subcellular Ca(2+) signaling rely on methods for labeling cells with fluorescent Ca(2+) indicator dyes. In this study, we demonstrate the use of single-cell electroporation for Ca(2+) indicator loading of individual neurons and small neuronal networks in rat neocortex in vitro and in vivo. Brief voltage pulses were delivered through glass pipettes positioned close to target cells. This approach resulted in reliable and rapid (within seconds) loading of somata and subsequent complete labeling of dendritic and axonal arborizations. By using simultaneous whole-cell recordings in brain slices, we directly addressed the effect of electroporation on neurons. Cell viability was high (about 85%) with recovery from the membrane permeabilization occurring within a minute. Electrical properties of recovered cells were indistinguishable before and after electroporation. In addition, Ca(2+) transients with normal appearance could be evoked in dendrites, spines, and axonal boutons of electroporated cells. Using negative-stains of somata, targeted single-cell electroporation was equally applicable in vivo. We conclude that electroporation is a simple approach that permits Ca(2+) indicator loading of multiple cells with low background staining within a short amount of time, which makes it especially well suited for functional imaging of subcellular Ca(2+) dynamics in small neuronal networks.

Immediate loading of single SLA implants: drilling vs. osteotomes for the preparation of the implant site

OBJECTIVES: To evaluate whether or not preparation of the implant site with osteotomes instead of drilling may improve peri-implant bone density and/or osseointegration, and whether or not this further improves the predictability of immediate loading of SLA implants. MATERIAL AND METHODS: The second, third, and fourth premolars were extracted in both sides of the mandible in six dogs, and after at least 3 months four SLA implants were inserted into each side of the jaw. In three animals, the implant sites were prepared by means of osteotomes, while standard stepwise drilling was used in the remaining animals. In each side of the jaw, two non-adjacent implants were restored with single crowns 4 days after installation, while the remaining two implants were left without crowns to serve as non-loaded controls. After 2, 4, or 12 weeks of loading, specimens including the implants and surrounding tissues were obtained and processed for histologic analysis of undecalcified sections. RESULTS: All implants placed with osteotomes were lost (five before delivery of the crowns and the rest during the first week after loading). None of the conventionally inserted implants, however, was lost, and histomorphometrical analysis revealed similar soft- and hard peri-implant tissue characteristics at immediately loaded and non-loaded implants at all observation times. Average bone-to-implant contact was 59-72% at immediately loaded implants vs. 60-63% at non-loaded ones. CONCLUSION: Preparation of the implant site by means of osteotomes had a deleterious effect on osseointegration, while immediate loading of single, free-standing, SLA implants following a conventional surgical protocol did not jeopardize their osseointegration.

Safety of ondansetron loading doses in children with cancer

INTRODUCTION: In highly emetogenic chemotherapy, the recommended dose of the serotonin-receptor antagonist ondansetron (5 mg/m(2) q8h) may be insufficient to prevent chemotherapy-induced nausea and vomiting. In adults, ondansetron-loading doses (OLD) of 32 mg are safe. We aimed to evaluate in children the safety of an OLD of 16 mg/m(2) (top, 24 mg) i.v., followed by two doses of 5 mg/m(2) q8h. MATERIALS AND METHODS: This retrospective single-center study included all pediatric oncology patients having received >/=1 OLD between 2002 and 2005. Adverse events (AE) definitely, probably, or possibly related to OLD were studied, excluding AE not or unlikely related to the OLD. Associations between potential predictors and at least moderate AE were analyzed by mixed logistic regression. RESULTS: Of 167 patients treated with chemotherapy, 37 (22%) received 543 OLD. The most common AE were hypotension, fatigue, injection site reaction, headache, hot flashes/flushes, and dizziness. At least mild AE were described in 139 OLD (26%), at least moderate AE in 23 (4.2%), and severe AE in 5 (0.9%; exact 95% confidence interval [CI], 0.4-2.1). Life-threatening or lethal AE were not observed (0.0%; 0.0-0.6). At least moderate AE were significantly more frequent in female patients (odds ratio [OR] 3.5; 95% CI 1.4-8.8; p = 0.010), after erroneously given second OLD (17.0; 1.9-154; p = 0.012) and higher 24 h cumulative surface corrected dose (1.26 per mg/m(2); 1.06-1.51; p = 0.009). OLD given to infants below 2 years were not associated with more frequent AE. CONCLUSIONS: Ondansetron-loading doses of 16 mg/m(2) (top, 24 mg) i.v. seem to be safe in infants, children, and adolescents.

Immediate and early non-occlusal loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: interim results from a prospective multicenter randomized-controlled study

OBJECTIVE: Immediate and early loading of dental implants can simplify treatment and increase overall patient satisfaction. The purpose of this 3-year prospective randomized-controlled multicenter study was to assess the differences in survival rates and bone level changes between immediately and early-loaded implants with a new chemically modified surface (SLActive). This investigation shows interim results obtained after 5 months. MATERIAL AND METHODS: Patients > or =18 years of age missing at least one tooth in the posterior maxilla or mandible were enrolled in the study. Following implant placement, patients received a temporary restoration either on the day of surgery (immediate loading) or 28-34 days after surgery (early loading); restorations consisted of single crowns or two to four unit fixed dental prostheses. Permanent restorations were placed 20-23 weeks following surgery. The primary efficacy variable was change in bone level (assessed by standardized radiographs) from baseline to 5 months; secondary variables included implant survival and success rates. RESULTS: A total of 266 patients were enrolled (118 males and 148 females), and a total of 383 implants were placed (197 and 186 in the immediate and early loading groups, respectively). Mean patient age was 46.3+/-12.8 years. After 5 months, implant survival rates were 98% in the immediate group and 97% in the early group. Mean bone level change from baseline was 0.81+/-0.89 mm in the immediate group and 0.56+/-0.73 mm in the early group (P<0.05). Statistical analysis revealed a significant center effect (P<0.0001) and a significant treatment x center interaction (P=0.008). CONCLUSIONS: The results suggested that Straumann implants with an SLActive can be used predictably in time-critical (early or immediate) loading treatment protocols when appropriate patient selection criteria are observed. The mean bone level changes observed from baseline to 5 months (0.56 and 0.81 mm) corresponded to physiological observations from other studies, i.e., were not clinically significant. The presence of a significant center effect and treatment x center interaction indicated that the differences in bone level changes between the two groups were center dependent.

Early loading of sandblasted and acid-etched implants: a randomized-controlled double-blind split-mouth study. Five-year results

OBJECTIVES: The aim of the present split-mouth study is to assess the peri-implant conditions around early-loaded sandblasted and acid-etched (SLA) implants, 5 years after abutment connection and to compare, in the same patients, the results obtained with a standard protocol using identical implants with a TPS surface. MATERIAL AND METHODS: Surgical procedure was performed by the same operator and was identical at test (SLA) and control (TPS) sites, in 32 healthy patients. Abutment connection was carried out at 35 N cm 6 weeks postsurgery for test sites and 12 weeks for the controls. Patients were seen regularly, for control and professional cleaning. At 60 months, clinical measures and radiographic bone changes were recorded by the same operator, blind to the type of surface of the implant, on 27 patients, as five patients were lost to follow-up. RESULTS: A total number of 106 implants were examined. No implant was lost. No significant differences were found with respect to the presence of plaque [modified plaque index (mPI) 0.27+/-0.56 vs. 0.32+/-0.54], bleeding on probing (29% vs. 32%), mean pocket depth (3.2+/-1 vs. 3.2+/-1 mm) or mean marginal bone loss (0.32+/-1.04 vs. 0.44+/-1.12 mm) between test and control. Four implants that presented 'spinning' at the time of abutment connection presented no significant differences from the rest of the test sites. CONCLUSION: The results of this prospective study confirm that SLA implants, under defined conditions, are suitable for early loading at 6 weeks in both the mandible and the maxilla. Limited implant spinning, occasionally found at abutment connection, produces no detrimental effect on the clinical outcome when properly handled.

Minimally invasive strabismus surgery for horizontal rectus muscle reoperations

AIMS: To study if minimally invasive strabismus surgery (MISS) is suitable for rectus muscle reoperations. METHODS: The study presents a series of consecutive patients operated on by the same surgeon at Kantonsspital St Gallen, Switzerland with a novel MISS rectus muscle reoperation technique. Surgery is done by applying two small radial cuts along the muscle insertion. Through the tunnel obtained after muscle separation from surrounding tissue, a recession, advancement or plication is performed. RESULTS: In 62 eyes of 51 patients (age 35.4 (SD 16.3) years) a total of 86 horizontal rectus muscles were reoperated. On the average, the patients had 2.1 strabismus surgeries previously. Preoperative logMAR visual acuity was 0.38 (0.82) compared with 0.37 (0.83) at 6 months (p>0.1). On the first postoperative day, in the primary gaze position conjunctival and lid swelling and redness was hardly visible in 11 eyes, discrete in 15 eyes, moderate in 11 eyes and severe in 15 eyes. One corneal dellen and one corneal erosion occurred, which both quickly resolved. The preoperative deviation at distance for esodeviations (n = 15) of 12.5 (8.5) degrees decreased to 2.6 (7.8) degrees at 6 months (p<0.001). For near, a decrease from 12.0 (10.1) degrees to 2.9 (1.6) degrees was observed (p<0.001). The preoperative deviation at distance for exodeviations (n = 35) of -16.4 (8.5) degrees decreased to -7.9 (6.5) degrees at 6 months (p<0.005). For near, a decrease from -16.5 (11.4) degrees to -2.9 (1.5) degrees was observed (p<0.005). Within the first 6 months, only one patient had a reoperation. At month 6, in four patients a reoperation was planned or suggested by us because of unsatisfactory alignment. No patient experienced persistent diplopia or necessitated a reoperation because of double vision. Stereovision improved at month 6 compared with preoperatively (p<0.01). CONCLUSIONS: The study demonstrates that a small-cut, minimal dissection technique allows to perform rectus muscle reoperations. The MISS technique seems to reduce conjunctival and lid swelling in the direct postoperative period.