Laser-guided lumbar medial branch kryorhizotomy

The authors describe a modification of the medial branch kryorhizotomy technique for the treatment of lumbar facet joint syndrome using a fluoroscopy-based laser-guided method. A total of 32 patients suffering from lumbar facet joint syndrome confirmed by positive medial nerve block underwent conventional or laser-guided kryorhizotomy. The procedural time (20.6 +/- 1.0 vs 16.3 +/- 0.9 minutes, p < 0.01), fluoroscopy time (54.1 +/- 3.5 vs 28.2 +/- 2.4 seconds, p < 0.01), radiation dose (407.5 +/- 32.0 vs 224.1 +/- 20.3 cGy/cm(2), p < 0.01), and patient discomfort during the procedure (7.1 +/- 0.4 vs 5.2 +/- 0.4 on the visual analog scale, p < 0.01) were significantly reduced in the laser-guided group. There was a tendency for a better positioning accuracy when the laser guidance method was used (3.0 +/- 0.3 vs 2.2 +/- 0.3 mm of deviation from the target points, p > 0.05). No difference in the outcome was observed between the 2 groups of patients (visual analog scale score 3.5 +/- 0.2 vs 3.3 +/- 0.3, p > 0.05). This improved minimally invasive surgical technique offers advantages to conventional fluoroscopy-based kryorhizotomy.

Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis

The aim of this study was to assess the prevalence of incomplete distal renal tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its potential impact on bone mineral density. We conducted a retrospective analysis of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs), which had originally been referred to the tertiary care stone center of the University Hospital of Berne for further metabolic evaluation. All RCSFs had been maintained on a free-choice diet while collecting two 24-h urine samples and delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age, i.e., 50 patients, without any acidification defect (non-RTA group) for comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses. The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6 ± 0.4 vs. 5.2 ± 0.1, p = 0.001; 24-h urine pH: 6.1 ± 0.2 vs. 5.3 ± 0.3, p = 0.001), 24-h urinary calcium excretion (7.70 ± 1.75 vs. 5.69 ± 1.73 mmol/d, p = 0.02), but significantly lower 24-h urinary urea excretion (323 ± 53 vs. 399 ± 114 mmol/d, p = 0.01), urinary citrate levels (2.32 ± 0.82 vs. 3.01 ± 0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the glomerular filtration rate (TmPO(4)/GFR: 0.66 ± 0.17 vs. 0.82 ± 0.21, p = 0.03) compared to non-RTA patients. No significant difference in bone mineral density (BMD) was found between idRTA and non-RTA patients for the lumbar spine (LS BMD (g/cm(2)): 1.046 ± 0.245 SD vs. 1.005 ± 0.119 SD, p = 0.42) or femoral neck (FN BMD (g/cm(2)): 0.830 ± 0.135 SD vs. 0.852 ± 0.127 SD). Thus, idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium nephrolithiasis patients. Bone mineral density, however, does not appear to be significantly affected by idRTA.

Early assessment of brain maturation by MR imaging segmentation in neonates and premature infants

PURPOSE: We evaluated the impact of premature extrauterine life on brain maturation. PATIENTS AND METHODS: Twelve neonates underwent MR imaging at 40 (39.64 +/- 0.98) weeks (full term). Fifteen premature infants underwent 2 MR imaging examinations, after birth (preterm at birth) and at 40 weeks (41.03 +/- 1.33) (preterm at term). A 3D MR imaging technique was used to measure brain volumes compared with intracranial volume: total brain volume, cortical gray matter, myelinated white matter, unmyelinated white matter, basal ganglia (BG), and CSF. RESULTS: The average absolute volume of intracranial volume (269.8 mL +/- 36.5), total brain volume (246.5 +/- 32.3), cortical gray matter (85.53 mL +/- 22.23), unmyelinated white matter (142.4 mL +/-14.98), and myelinated white matter (6.099 mL +/-1.82) for preterm at birth was significantly lower compared with that for the preterm at term: the average global volume of intracranial volume (431.7 +/- 69.98), total brain volume (391 +/- 66,1), cortical gray matter (179 mL +/- 41.54), unmyelinated white matter (185.3 mL +/- 30.8), and myelinated white matter (10.66 mL +/- 3.05). It was also lower compared with that of full-term infants: intracranial volume (427.4 mL +/- 53.84), total brain volume (394 +/- 49.22), cortical gray matter (181.4 +/- 29.27), unmyelinated white matter (183.4 +/- 27.37), and myelinated white matter (10.72 +/- 4.63). The relative volume of cortical gray matter (30.62 +/- 5.13) and of unmyelinated white matter (53.15 +/- 4.8) for preterm at birth was significantly different compared with the relative volume of cortical gray matter (41.05 +/- 5.44) and of unmyelinated white matter (43.22 +/- 5.11) for the preterm at term. Premature infants had similar brain tissue volumes at 40 weeks to full-term infants. CONCLUSION: MR segmentation techniques demonstrate that cortical neonatal maturation in moderately premature infants at term and term-born infants was similar.

TAFI and PAI-1 levels in human sepsis

BACKGROUND: Plasminogen activator inhibitor type-1 (PAI-1) is considered to be the main inhibitor of fibrinolysis in sepsis. However, the contribution of TAFI to the inhibition of fibrinolysis in sepsis is currently unknown. METHODS: TAFI antigen and PAI-1 levels were measured in severe sepsis (n = 32) and septic shock (n = 8) patients. In addition, TAFI antigen levels had been determined in 151 controls. RESULTS: Septic patients had significantly (p < 0.0001) decreased TAFI levels (median: 78.9% [range: 32.4-172.6]) as compared to controls (108.1% [35.9-255.4]). TAFI levels were equal in septic shock and severe sepsis (68.9% [32.4-172.6] vs. 82.5% [32.7-144.9], p = 0.987) as well as in survivors and non-survivors (87.1% [32.7-172.6] vs. 65.8% [32.4-129.5], p = 0.166). PAI-1 levels were significantly (705.5 ng/ml [131-5788]) higher in septic shock as in severe sepsis patients (316.5 ng/ml [53-1311], p = 0.016) and were equal in survivors and non-survivors (342 ng/ml [53-1311] vs. 413 ng/ml [55-5788], p = 0.231). TAT/PAP ratio (R((TAT/PAP))) reflecting the dysbalance between coagulation and fibrinolysis was calculated. R((TAT/PAP)) significantly increased with fatality and was significantly dependent on PAI-1, but not on TAFI. PAI-1 levels (570.5 ng/ml [135-5788]) and R((TAT/PAP)) (1.6 [0.3-6.1]) were significantly (p = 0.008 and p = 0.047) higher in patients with overt DIC as compared to patients without overt DIC (310 ng/ml [53-1128] and 0.6 [0.1-4.3]), whereas no difference was found for TAFI levels (68.9% [32.7-133.2] vs. 86.4% [32.4-172.6], p = 0.325). CONCLUSIONS: Although inhibition in sepsis is mediated by both, PAI-1 might be involved early in the sepsis process, whereas TAFI might be responsible for ongoing fibrinolysis inhibition in later stages of sepsis.

Development of labial gingival recessions in orthodontically treated patients

INTRODUCTION Our aim was to assess the prevalence of gingival recessions in patients before, immediately after, and 2 and 5 years after orthodontic treatment. METHODS Labial gingival recessions in all teeth were scored (yes or no) by 2 raters on initial, end-of-treatment, and posttreatment (2 and 5 years) plaster models of 302 orthodontic patients (38.7% male; 61.3% female) selected from a posttreatment archive. Their mean ages were 13.6 years (SD, 3.6; range, 9.5-32.7 years) at the initial assessment, 16.2 years (SD, 3.5; range, 11.7-35.1 years) at the end of treatment, 18.6 years (SD, 3.6; range, 13.7-37.2 years) at 2 years posttreatment, and 21.6 (SD, 3.5; range, 16.6-40.2 years) at 5 years posttreatment. A recession was noted (scored "yes") if the labial cementoenamel junction was exposed. All patients had a fixed retainer bonded to either the mandibular canines only (type I) or all 6 mandibular front teeth (type II). RESULTS There was a continuous increase in gingival recessions after treatment from 7% at end of treatment to 20% at 2 years posttreatment and to 38% at 5 years posttreatment. Patients less than 16 years of age at the end of treatment were less likely to develop recessions than patients more than 16 years at the end of treatment (P = 0.013). The prevalence of recessions was not associated with sex (P = 0.462) or extraction treatment (P = 0.32). The type of fixed retainer did not influence the development of recessions in the mandibular front region (P = 0.231). CONCLUSIONS The prevalence of gingival recessions steadily increases after orthodontic treatment. The recessions are more prevalent in older than in younger patients. No variable, except for age at the end of treatment, seems to be associated with the development of gingival recessions.

Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (1998–2012): emergence of multidrug-resistant clones less susceptible to cephalosporins

Background: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. Methods: We compared the characteristics of Ng detected during 1998–2001 (n = 26) to those detected during 2009–2012 (n = 34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet (M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. Results: The following susceptibility results were obtained (period: % of non-S, MIC90 in mg/L): penicillin (1998–2001: 42.3%, 3; 2009–2012: 85.3%, 16), cefixime (1998–2001: 0%, ≤0.016; 2009–2012: 8.8%, 0.125), ceftriaxone (1998–2001: 0%, 0.004; 2009–2012: 0%, 0.047), ciprofloxacin (1998–2001: 7.7%, 0.006; 2009–2012: 73.5%, ≥32), azithromycin (1998–2001: 11.5%, 0.25; 2009–2012: 23.6%, 0.38), tetracycline (1998–2001: 65.4%, 12; 2009–2012: 88.2%, 24), spectinomycin (1998–2001: 0%, 12; 2009–2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998–2001 to 70.6% in 2009–2012. International STs and genogroups (G) emerged during 2009–2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). Conclusions: The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.

Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

We assessed the suitability of the radiolanthanide 155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods 155Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~ 1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. 155 Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules – a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) – were radiolabeled with 155 Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. Results The total yield of the two-step separation process of 155 Tb was 86%. 155 Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The 155 Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (> 95%). 155 Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of 155 Tb-DOTATATE and 155 Tb-MD, respectively. The relatively long physical half-life of 155 Tb matched in particular the biological half-lives of 155 Tb-cm09 and 155 Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions The radiolanthanide 155 Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β--emitting radiolanthanides 177Lu, 161 Tb, 166Ho, and the pseudo-radiolanthanide 90Y.

Impact of chorioamnionitis and preeclampsia on neurodevelopmental outcome in preterm infants below 32 weeks gestational age

ABSTRACT Aim: Intrauterine conditions may interfere with fetal brain development. We compared the neurodevelopmental outcome between infants <32 weeks gestational age after maternal preeclampsia or chorioamnionitis and controls. Methods: Case-control study on infants with maternal preeclampsia, chorioamnionitis and controls (each n = 33) matched for gestational age. Neurodevelopment at two years was assessed with the Bayley Scales of Infant Development II. Results: Ninety-nine infants were included with a median gestational age of 29 weeks (range 25-32). Median mental developmental index (MDI) was 96 in the control, 90 in the chorioamnionitis and 86 in the preeclampsia group. Preeclampsia infants had a lower MDI compared with the control group (univariate p = 0.021, multivariate p = 0.183) and with the chorioamnionitis group (univariate p = 0.242; multivariate p = 0.027). Median psychomotor index was 80.5 in the control, 80 in the preeclampsia and 85 in the chorioamnionitis group, and was not different between these three groups (p > 0.05). Chorioamnionitis or preeclampsia exposure was not associated with major neurodevelopmental impairments (cerebral palsy, MDI<70, PDI<70). Conclusion: The results of this preliminary study suggest that preeclampsia and chorioamnionitis play a relatively minor role among risk factors for adverse neurodevelopment outcome. Postnatal factors such as ventilation and bronchopulmonary dysplasia may have a greater impact on neurodevelopmental outcome.

A 5-year prospective multicenter study of early loaded titanium implants with a sandblasted and acid-etched surface

For dental implants to be successful, osseointegration must occur, but it is unknown how much time must pass for osseointegration to be established. Preclinical studies suggested that titanium implants with a sandblasted and acid-etched (SLA) surface were more osteoconductive and allowed more rapid osseointegration than machined or turned implant surfaces. The hypothesis of this study was that implants with an SLA surface could be loaded in half the conventional healing time of machined-surface implants and that, after loading, the implants would be successful for 5 years.

In vitro resistance of articular chondrocytes to 5-Aminolevulinic acid based photodynamic therapy

OBJECTIVE: 5-Aminolevulinic acid based photodynamic therapy (5-ALA-PDT) has revealed promising results in the treatment of inflammatory joint diseases due to the sensitivity of inflamed synovial tissue. For 5-ALA-PDT to be safe and beneficial for intra-articular applications, resistance of chondrocytes is essential to prevent cartilage damage. As no data yet exist, the aim of the present study was to assess in vitro the response of the chondrocytes to 5-ALA-PDT and to compare with osteoblasts and synovial tissue derived cells. METHODS: Bovine articular chondrocytes, osteoblasts, and synovial cells were subjected to 5-ALA-PDT in cell culture. The PpIX accumulation and the function of the cells were assessed for up to 12 days. RESULTS: Bovine chondrocytes showed lower PpIX fluorescence upon incubation with 5-ALA (0.0-2.0 mM) for 4 hours as compared to osteoblasts and synovial cells suggesting a low PpIX accumulation. After incubation with 0.5 mM 5-ALA and application of light at a dose of 20 J/cm2, chondrocytes were functionally not affected (collagen type II and aggrecan mRNA, glycosaminoglycan synthesis) whereas a decrease in the proportion of viable cells was observed in osteoblasts and synovial cells (2+/-2% and 14+/-8%, respectively; chondrocytes 91+/-13%). Chondrocytes showed a 58% reduction of 5-ALA uptake using [3H]5-ALA as compared to osteoblasts and a lower mitochondrial content as assessed by the activity of the mitochondrial marker enzyme citrate synthase (9.2+/- 3.6 mU/mg protein) than osteoblasts (32.6+/-10.5 mU/mg) and synovial cells (60.0+/-10.8 mU/mg). The reduced uptake of 5-ALA and/or the low mitochondrial content, an adaptation to their in vivo environment and the site of PpIX synthesis, presumably explains the lower PpIX content in chondrocytes and their resistance against 5-ALA-PDT. CONCLUSION: 5-ALA-PDT might represent a treatment strategy in inflammatory joint diseases without endangering the cartilage function. However, further in vitro and in vivo experiments are required to confirm this data in the authentic environment of chondrocytes, the articular cartilage.

Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98)

Daily administration of 2-chlorodeoxyadenosine (Cladribine, CDA) is a standard treatment for hairy cell leukemia, but may cause severe neutropenia and neutropenic fever. This trial compared toxicity and efficacy of weekly versus daily CDA administration. One hundred patients were randomized to receive standard (CDA 0.14 mg/kg/day day 1-5 [Arm A]) or experimental treatment (CDA 0.14 mg/kg/day once weekly for 5 weeks [Arm B]). The primary endpoint was average leukocyte count within 6 weeks from randomization. Secondary endpoints included response rates, other acute hematotoxicity, acute infection rate, hospital admission, remission duration, event-free, and overall survival. There was no significant difference in average leukocyte count. Response rate (complete + partial remission) at week 10 was 78% (95% confidence interval (CI) 64-88%) in Arm A and 68% (95% CI 54-80%) in Arm B (p = 0.13). Best response rates during follow-up were identical (86%) in both arms. No significant difference was found in the rate of grade 3+4 leukocytopenia (94%vs. 84%), grade 3+4 neutropenia (90%vs. 80%), acute infection (44%vs. 40%), hospitalization (38%vs. 34%), and erythrocyte support (22%vs. 30%) within 10 weeks. Overall, these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily.

Comparing the validity and output of the GT1M and GT3X accelerometer in 5- to 9-year-old children

The purpose of this study was to compare the validity and output of the biaxial ActiGraph GT1M and the triaxial GT3X (ActiGraph, LLC, Pensacola, FL, USA)accelerometer in 5- to 9-year-old children. Thirty-two children wore the two monitors while their energy expenditure was measured with indirect calorimetry. They performed four locomotor and four play activities in an exercise laboratory and were further measured during 12 minutes of a sports lesson. Validity evidence in relation to indirect calorimetry was examined with linear regression equations applied to the laboratory data. During the sports lessons predicted energy expenditure according to the regression equations was compared to measured energy expenditure with the Wilcoxon-signed rank test and the Spearman correlation. To compare the output, agreement between counts of the two monitors during the laboratory activities was assessed with Bland-Altman plots. The evidence of validity was similar for both monitors. Agreement between the output of the two monitors was good for vertical counts (mean bias = −14 ± 22 counts) but not for horizontal counts (−17 ± 32 counts). The current results indicate that the two accelerometer models are able to estimate energy expenditure of a range of physical activities equally well in young children. However, they show output differences for movement in the horizontal direction.