Gut-derived serotonin contributes to bone deficits in colitis.

Osteoporosis and bone fractures occur at higher frequency in patients with inflammatory bowel disease (IBD), and decreased bone mass is observed in animal models of colitis. Another consistent feature of colitis is increased serotonin (5-HT) availability in the intestinal mucosa. Since gut-derived 5-HT can decrease bone mass, via activation of 5-HT1B receptors on pre-osteoblasts, we tested the hypothesis that 5-HT contributes to bone loss in colitis. Colitis was chronically induced in mice by adding dextran sodium sulfate (DSS) to their drinking water for 21 days. At day 21, circulating 5-HT levels were elevated in DSS-inflamed mice. Micro-computed tomography of femurs showed a decrease in trabecular bone volume fraction, formation, and surface area, due largely to decreased trabecular numbers in DSS-treated mice. The colitis-induced loss of trabecular bone was significantly suppressed in mice treated with the 5-HT synthesis inhibitor, p-chloro-DL-phenylalanine (PCPA; 300 mg/kg/day IP daily), and in mice treated with the 5-HT1B receptor antagonist GR55562 (1 mg/Kg/day SC daily). The 5-HT reuptake transporter (SERT) is critical for moving 5-HT from the interstitial space into enterocytes and from serum into platelets. Mice lacking SERT exhibited significant deficits in trabecular bone mass that are similar to those observed in DSS-inflamed mice, and these deficits were not extensively worsened by DSS-induced colitis in the SERT-/- mice. Taken together, findings from both the DSS and SERT-/- mouse models support a contributing role for 5-HT as a significant factor in bone loss induced by colitis.

Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that, in addition to motor, sensory, and cognitive symptoms, also causes constipation, which is poorly understood. Here, we characterize gastrointestinal (GI) dysmotility in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS and evaluate whether autoantibodies target the enteric nervous system (ENS) and cause dysmotility. METHODS: EAE was induced in male SJL and B6 mice. GI motility was assessed in vivo and ex vivo in wild type (WT) and B cell-deficient mice. MS and EAE serum was used to survey potential targets in the ENS and changes in the ENS structure were characterized using immunohistochemistry. KEY RESULTS: EAE mice developed accelerated gastric emptying and delayed whole GI transit with reduced colonic motility. Fecal water content was reduced, and colonic migrating myoelectrical complexes (CMMC) and slow waves were less frequent. Colons from EAE mice exhibited decreased GFAP levels in glia. Sera from MS patients and from EAE mice targeted ENS neurons and glia. B-cell deficiency in EAE protected against colonic dysmotility. CONCLUSIONS & INFERENCES: Consistent with symptoms experienced in MS, we demonstrate that EAE mice widely exhibit features of GI dysmotility that persisted in the absence of extrinsic innervation, suggesting direct involvement of ENS neurocircuitry. The absence of GI dysmotility in B cell-deficient mice with EAE together with EAE and MS serum immunoreactivity against ENS targets suggests that MS could be classified among other diseases known to induce autoimmune GI dysmotility.

The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics.

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

A Rare Case of Emberger Syndrome Caused By a De Novo Mutation in the GATA2 Gene.

Emberger syndrome, or primary lymphedema with myelodysplasia, is a severe rare disease characterized by early primary lymphedema and blood anomalies including acute childhood leukemia. The syndrome is associated with heterozygous mutations in the GATA2 gene. We report on a 13-year-old boy who developed lymphedema of the right lower limb at age 6 years which was accompanied by severe panleukopenia and repeated episodes of erysipelas. The suspicion of Emberger syndrome was confirmed by detection of a new germinal line GATA2 mutation c.414_417del, p.Ser139Cysfs*78. Clinical treatment included a bone marrow transplant from the father.This case is one of a very limited number of Emberger syndrome cases documented in the literature, and genetic testing proved fundamental for definition of the condition and its association with a de novo mutation in the GATA2 which is reported here for the first time.

[Osteotomy techniques close to the knee. Effect on wedge volume and bony contact surface]. / Kniegelenknahe Osteotomietechniken. Effekt auf Keilvolumina und knöcherne Kontaktflächen.

BACKGROUND: Bone geometry following osteotomy around the knee suggests that biplanar rather than uniplanar open wedge techniques simultaneously create smaller wedge volumes and larger bone surface areas. However, precise data on the bone surface area and wedge volume resulting from both open and closed wedge high tibial osteotomy (HTO) and distal femoral osteotomy (DFO) techniques remain unknown. OBJECTIVES: It was hypothesized that biplanar rather than uniplanar osteotomy techniques better reflect the ideal geometrical requirements for bone healing, representing a large cancellous bone surface combined with a small wedge volume. METHODS: Tibial and femoral artificial bones were assigned to four different groups of valgisation and varisation osteotomy consisting of open wedge and closed wedge techniques in a uniplanar and biplanar fashion. Bone surface areas of all osteotomy planes were quantified. Wedge volumes were determined using a prism-based algorithm and applying standardized wedge heights of 5 mm, 10 mm and 15 mm. RESULTS: Both femoral and tibial biplanar osteotomy techniques created larger contact areas and smaller wedge volumes compared to the uniplanar open wedge techniques. CONCLUSION: Although this idealized geometrical view of bony geometry excludes all biological factors that might influence bone healing, the current data suggest a general rule for the standard osteotomy techniques applied and all surgical modifications: reducing the amount of slow gap healing and simultaneously increasing the area of faster contact healing may be beneficial for osteotomy healing. Thus, biplanar rather than uniplanar osteotomy should be performed for osteotomy around the knee.

[Arthroscopic nerve release and decompression of ganglion cysts around the shoulder joint]. / Arthroskopische Neurolyse und Therapie periglenoidaler Ganglien am Schultergelenk.

OBJECTIVE: Arthroscopic visualisation and release of nerves around the shoulder, decompression of ganglion cysts. INDICATIONS: Arthroscopic treatment of nerve entrapment syndromes around the shoulder (suprascapular nerve, axillary nerve). Arthroscopic visualisation and release of osseous or ligamentous structures causing nerve entrapment. Arthroscopic decompression and resection of periglenoid ganglion cysts. Arthroscopic release of concomitant lesions (labrum, rotator cuff, biceps). CONTRAINDICATIONS: No clinical or neurological evidence for nerve entrapment syndrome. Lack of conditions for a complex arthroscopic procedure (technique of visualisation, instrumentation, knowledge of specific neuroanatomy). SURGICAL TECHNIQUE: Diagnostic arthroscopy, decompression/resection of ganglion cyst. Visualisation and decompression of nerve. Detection and fixation of concomitant pathologies. POSTOPERATIVE TREATMENT: Immobilisation in sling during the day after the operation. Actively assisted and active mobilisation of shoulder controlled by discomfort level. Manual lymph drainage starting on postoperative day 1. Sling and further rehabilitation according to treatment of concomitant lesions.

Possible combinations of electronic data capture and randomization systems. principles and the realization with RANDI2 and OpenClinica.

BACKGROUND: Clinical trials (CT) are in a wider sense experiments to prove and establish clinical benefit of treatments. Nowadays electronic data capture systems (EDCS) are used more often bringing a better data management and higher data quality into clinical practice. Also electronic systems for the randomization are used to assign the patients to the treatments. OBJECTIVES: If the mentioned randomization system (RS) and EDCS are used, possibly identical data are collected in both, especially by stratified randomization. This separated data storage may lead to data inconsistency and in general data samples have to be aligned. The article discusses solutions to combine RS and EDCS. In detail one approach is realized and introduced. METHODS: Different possible settings of combination of EDCS and RS are determined and the pros and cons for each solution are worked out. For the combination of two independent applications the necessary interfaces for the communication are defined. Thereby, existing standards are considered. An example realization is implemented with the help of open-source applications and state-of-the-art software development procedures. RESULTS: Three possibilities of separate usage or combination of EDCS and RS are presented and assessed: i) the complete independent usage of both systems; ii) realization of one system with both functions; and iii) two separate systems, which communicate via defined interfaces. In addition a realization of our preferred approach, the combination of both systems, is introduced using the open source tools RANDI2 and OpenClinica. CONCLUSION: The advantage of a flexible independent development of EDCS and RS is shown based on the fact that these tool are very different featured. In our opinion the combination of both systems via defined interfaces fulfills the requirements of randomization and electronic data capture and is feasible in practice. In addition, the use of such a setting can reduce the training costs and the error-prone duplicated data entry.

'Deletion rescue' by mitotic 11q uniparental disomy in a family with recurrence of 11q deletion Jacobsen syndrome.

We describe a family with recurrent 11q23-qter deletion Jacobsen syndrome in two affected brothers, with unique mosaic deletion 'rescue' through development of uniparental disomy (UPD) in the mother and one of the brothers. Inheritance studies show that the deleted chromosome is of maternal origin in both boys, and microarray shows a break near the ASAM gene. Parental lymphocyte chromosomes were normal. However, the mother is homozygous in lymphocytes for all loci within the deleted region in her sons, and presumably has UPD for this region. In addition, she is mosaic for the 11q deletion seen in her sons at a level of 20-30% in skin fibroblasts. We hypothesize that one of her #11 chromosomes shows fragility, that breakage at 11q23 occurred with telomeric loss in some cells, but 'rescue' from the deletion occurred in most cells by the development of mitotic UPD. She apparently carries the 11q deletion in her germ line resulting in recurrence of the syndrome. The older son is mosaic for the 11q cell line (70-88%, remainder 46,XY), and segmental UPD11 'rescue' apparently also occurred in his cytogenetically normal cells. This is a novel phenomenon restoring disomy to an individual with a chromosomal deletion.

An apparatus for pulsed ESR and DNP experiments using optically excited triplet states down to liquid helium temperatures.

In standard Dynamic Nuclear Polarization (DNP) electron spins are polarized at low temperatures in a strong magnetic field and this polarization is transferred to the nuclear spins by means of a microwave field. To obtain high nuclear polarizations cryogenic equipment reaching temperatures of 1 K or below and superconducting magnets delivering several Tesla are required. This equipment strongly limits applications in nuclear and particle physics where beams of particles interact with the polarized nuclei, as well as in neutron scattering science. The problem can be solved using short-lived optically excited triplet states delivering the electron spin. The spin is polarized in the optical excitation process and both the cryogenic equipment and magnet can be simplified significantly. A versatile apparatus is described that allows to perform pulsed dynamic nuclear polarization experiments at X-band using short-lived optically excited triplet sates. The efficient (4)He flow cryostat that cools the sample to temperatures between 4 K and 300 K has an optical access with a coupling stage for a fiber transporting the light from a dedicated laser system. It is further designed to be operated on a neutron beam. A combined pulse ESR/DNP spectrometer has been developed to observe and characterize the triplet states and to perform pulse DNP experiments. The ESR probe is based on a dielectric ring resonator of 7 mm inner diameter that can accommodate cubic samples of 5mm length needed for neutron experiments. NMR measurements can be performed during DNP with a coil integrated in the cavity. With the presented apparatus a proton polarization of 0.5 has been achieved at 0.3 T.

Tiotropium Handihaler and the risk of cardio- or cerebrovascular events and mortality in patients with COPD.

BACKGROUND: Tiotropium has been associated with an increased risk of mortality and/or cardiovascular events. Recent data from RCTs suggests tiotropium Handihaler to be safe, but its safety has not yet been fully investigated under real-life circumstances. METHODS: We conducted 2 nested case-control studies in a COPD cohort from the Dutch IPCI database. In the first case-control study, cases had a cardiovascular or cerebrovascular endpoint (CCVE): stroke and transient ischemic attack (TIA), myocardial infarction, heart failure and/or ventricular arrhythmia. In the second, cases were all patients who died. Cases were matched to controls on age, sex and index date. Conditional logistic regression analysis was used to calculate adjusted odds ratios (OR(adj)) with 95% confidence intervals (CI) for tiotropium vs. long-acting beta-agonists (LABA). RESULTS: Within a cohort of 6788 COPD patients, 784 CCVE's and 1032 deaths were reported. Compared to current LABA use, use of tiotropium Handihaler was neither associated with an increased risk of a CCVE (OR(adj) 0.89, 95% 0.55-1.44) nor with an increased risk of death (OR(adj) 0.79, 95% CI 0.49-1.28). CONCLUSIONS: In real life, use of tiotropium Handihaler in COPD patients is not associated with an increased risk of a CCVE or mortality compared to LABA.

Cardiovascular and gastrointestinal safety of NSAIDs: a systematic review of meta-analyses of randomized clinical trials.

As part of the Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project, we reviewed the incidence of cardiovascular (CV) and gastrointestinal (GI) events associated with the use of this category of drugs. We collected data from published meta-analyses (MAs) of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs). The Medline, Cochrane, ISI, and SCOPUS databases were systematically searched for MAs of NSAID clinical trials that could potentially contain data on adverse incidents such as myocardial infarction (MI), cerebrovascular events (CeVs), stroke, thromboembolic events (ThEs), heart failure (HF), gastrointestinal bleeding (GIB), and perforation, ulcer, and bleeding (PUB). From 1,733 identified references, 29 MAs were selected for the review. This allowed 109 estimations of incidence rates of CV adverse events and 26 estimations of incidence rates for GI adverse events. No data were found on hemorrhagic stroke or LGIB. Coxibs were studied in more MAs than traditional NSAIDs were (21 MAs for coxibs vs. 7 for traditional NSAIDs; one meta-analysis studied both). Many NSAIDs were not considered in any of the MAs. Our systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.

[Arthroscopic coracoid transfer : Indications, technique and initial results]. / Arthroskopischer Korakoidtransfer : Indikation, Technik und erste Ergebnisse.

Recurrent anterior shoulder instability is a frequent and severe problem for patients. The Bankart operation with reconstruction of the labrum, capsule and ligament is the established treatment method, which is usually performed arthroscopically. However, the results of the Bankart operation deteriorate if there is significant bone loss at the glenoid or humerus and also when there is structural damage to the anteroinferior glenohumeral ligament and labrum. In 1954 Latarjet described the technique of coracoid transfer to the anterior glenoid. This procedure has become popular for the treatment of anterior shoulder instability especially in France and is performed in an open technique.In this paper we describe the indications, operative technique and early results of coracoid transfer in a completely arthroscopic technique.

Long-chain polyunsaturated fatty acids: selected mechanisms of action on bone.

Evidence presented over the past 20 years has shown that long-chain polyunsaturated fatty acids (LCPUFAs), especially the n-3 fatty acids such as eicospentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health. Some studies in humans indicate that LCPUFAs can increase bone formation, affect peak bone mass in adolescents and reduce bone loss as measured using bone mineral densitometry. The cellular mechanisms of action of the LCPUFAs, however, are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signalling pathways, cytokines and growth factors. LCPUFAs affect receptor activator of nuclear factor κß (RANK), a receptor found on the osteoclast, the cell causing bone resorption, which controls osteoclast formation. Lipoxygenase (LOX) generated lipid mediators (resolvins, lipoxins, protectins and docosanoids) have both anti-inflammatory and pro-resolving activities. Both resolvins and lipoxins inhibit inflammation-induced bone resorption. Arachidonic acid significantly upregulates inducible NO synthase (iNOS) mRNA expression in human osteoblast-like cells, thereby possibly enhancing osteoclastic activity. The protective effect of EPA on osteoblastogenesis could be mediated by the biphasic cross-talk between PGE(2) and NO production involving COX-2 and iNOS pathways. Other mediators of osteoblast maturation include PPARα ligands such as linoleic acid and possibly DHA in association with bone morphogenic proteins. Since DHA is a weaker ligand for PPARγ, more uncommitted mesenchymal stem cells are thought to differentiate into osteoblasts rather than adipocytes. This review addresses selected cellular mechanisms that may explain the beneficial effects of the LCPUFAs on bone.

Short-term fatty acid effects on adipocyte glucose uptake: mechanistic insights.

The modulation of insulin sensitivity in visceral fat tissue could be important in the treatment of Type 2 diabetes mellitus. Selected fatty acids may impact on insulin-stimulated and basal glucose uptake in adipocytes, thus isolated rat epididymal adipocytes were exposed to 100 microM oleic, arachidonic, eicosapentaenoic, docosahexaenoic or stearic acids and insulin (15 nM) or vehicle for 30 min. Glucose uptake was quantified by measuring uptake of 3H-deoxyglucose/mg adipocyte protein/min. Where appropriate, inhibitors were included to elucidate the mechanisms involved. In this model, insulin stimulated glucose uptake with 62+/-7%. All fatty acids tested, except for stearic acid, depressed insulin-stimulated glucose uptake by an average of 33+/-4.2%. On the other hand, all fatty acids tested except stearic and arachidonic acids, stimulated basal glucose uptake with an average of 34+/-8.1%. Inhibitor studies showed the involvement of prostaglandins, lipoxins, protein kinase C and tyrosine kinase in these processes.

Duration of antihypertensive drug use and risk of dementia: A prospective cohort study.

BACKGROUND: The evidence from prospective observational research for a protective effect of antihypertensive drug use on the risk of dementia is far from uniform. Duration of follow-up was limited and relied mainly on baseline drug exposure data without information on duration of use. We investigated the association between the duration of antihypertensive use and risk of dementia. METHODS: We followed 6,249 participants (mean 68.4 years, 60% women) of a prospective, population-based cohort from baseline (1990-1993) until 2005 for incident dementia. Continuous data on filled prescriptions came from pharmacy records. Total cumulative duration of antihypertensive use was expressed in years. We subtracted a latent 4-year period before the date of dementia diagnosis in the quantification of exposure duration to avoid potential bias in antihypertensive prescription due to prodromal changes in blood pressure or cognition. With Cox regression models, we calculated crude and adjusted hazard ratios (HRs) of all dementia and Alzheimer disease (AD) with antihypertensive use vs never used. RESULTS: Compared to never used, antihypertensive use was associated with a reduced risk of all dementia (adjusted HR per year of use 0.95; 95% confidence interval [CI] 0.91-0.99). We observed an 8% (95% CI -15% to -1%) risk reduction per year of use for persons < or =75 years, whereas for persons >75 years this was 4% (95% CI -11% to 4%). Equivalent estimates were observed for AD. No apparent differences were observed among different types of antihypertensive drugs. CONCLUSIONS: Antihypertensive drug use was associated with 8% risk reduction of dementia per year of use for persons < or =75 years.

High-repetition-rate optical parametric chirped-pulse amplifier producing 1-microJ, sub-100-fs pulses in the mid-infrared.

We present a high-repetition-rate, femtosecond optical parametric chirped pulse amplifier (OPCPA). Its seed signal is obtained by difference frequency generation from the two-branch output of a commercially available Er:fiber laser amplifier. The optical parametric amplifier is pumped by a commercially available diode-pumped solid-state laser. In a two-stage amplification setup we have achieved a gain of 100'000, resulting in approximately 1 microJ femtosecond mid-infrared pulses in the wavelength range between 3 and 4 microm and an amplification bandwidth of >300 nm at a repetition rate of 100 kHz. The pulses have been compressed to 92 fs by a 4-prism compressor.

Challenges in the evolution of the medical informatics program at heidelberg/heilbronn (Germany).

OBJECTIVE: Health and medical informatics (HMI) is an evolving discipline. Therefore, evolving educational programs in HMI have to take a variety of requirements into account. The aim of this paper is to analyze these requirements and to compare them with the medical informatics program Heidelberg/Heilbronn, Germany. METHODS: Systematic analysis of the IMIA recommendations on educating HMI, the Bologna declaration, current technological and health care developments and the results of graduates surveys. RESULTS: The latest revision of the Heidelberg/Heilbronn medical informatics program not only takes current developments into account but also realizes the IMIA recommendations, the Bologna declaration and graduates' data and feedback obtained in structured surveys. The topics bioinformatics, IT security and telemedicine were strengthened, taking major research and application trends into account. The program has been transformed into a consecutive bachelor/master program. It qualifies its graduates to work in the field of medical informatics as well as in informatics. CONCLUSIONS: Medical informatics is a very broad field. Programs have to make concessions to scope: It is not possible to provide profound knowledge and skills in computer science and also teach a variety of application areas like bioinformatics, public health informatics and clinical informatics in depth within one medical informatics program. Many graduate programs in various nations concentrate on providing HMI skills to health care professionals.

Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study.

BACKGROUND: Cross-sectional reports suggest that statin users are less likely to have Alzheimer disease (AD). Prospective studies have provided inconsistent evidence. Moreover, it is unclear whether the association differs for lipophilic statins, those that could more easily pass the blood-brain barrier and hydrophilic statins. OBJECTIVES: To prospectively evaluate whether use of statins is associated with the risk of AD, and to determine whether associations differ for lipophilic and hydrophilic statins. METHOD: 6992 participants of the prospective, population-based Rotterdam Study were followed, from baseline (1990-1993) until January 2005 for incident AD. Data on all filled prescriptions came from pharmacy records. For each date on which each event occurred, cholesterol-lowering drug use for the person who experienced the event and all remaining persons in the cohort was categorised as "any" or "never" use. A distinction was made between statin, lipophilic and hydrophilic statins, and non-statin cholesterol-lowering drugs. Data were analysed with the Cox regression analysis, adjusting for sex, age and potential confounders. RESULTS: During follow-up (mean 9 years), 582 persons developed AD. Compared with never use of cholesterol-lowering drugs, statin use was associated with a decreased risk of AD (HR 0.57; 95% CI 0.37 to 0.90), but non-statin cholesterol-lowering drug use was not (HR 1.05; 95% CI 0.45 to 2.44). HRs were equal for lipophilic (HR 0.54; 95% CI 0.32 to 0.89) and hydrophilic statins (HR 0.54; 95% CI 0.26 to 1.11). CONCLUSION: In the general population, the use of statins, but not of non-statin cholesterol-lowering drugs, was associated with a lower risk of AD compared with never use of cholesterol-lowering drugs. The protective effect was independent of the lipophilicity of statins.

Controlled aggregation of superparamagnetic iron oxide nanoparticles for the development of molecular magnetic resonance imaging probes.

A method for synthesizing superparamagnetic iron oxide (SPIO) multi-nanoparticle aggregates as molecular magnetic resonance imaging (MRI) contrast agents is described. The approach utilizes organic acid/base interactions in the colloid to induce highly controllable nanoparticle aggregation. Monodisperse aggregates with diameters as large as 100 nm are synthesized by manipulating the interfacial surface chemistry of the SPIO nanoparticles in tetrahydrofuran solvent. Subsequent phospholipid micelle encapsulation yields micellar multi-SPIO (mmSPIO) aggregates with enhanced T(2) relaxivity (368.0 s(-1) mmol(-1) Fe) as compared to micellar single particle SPIO (302.0 s(-1) mmol(-1) Fe). mmSPIO conjugated to anti-CA125 monoclonal antibodies were incubated with ovarian carcinoma cell lines to demonstrate targeted in vitro molecular MRI, resulting in a 66% shortening in T(2) time for CA125 positive NIH:OVCAR-3 cells and a less than 3% change in T(2) time for CA125 negative SK-OV-3 cells. The controllable aggregation of mmSPIO shows potential for the development of molecular MRI contrast agents with optimal sizes for specific diagnostic imaging applications.

Tibial wedge osteotomy for osteochondral transplantation in talar lesions.

Between 1999 and 2002, 16 patients with osteochondral lesions on the central and posterior talar dome underwent osteochondral autografting. A new approach with temporary removal and replacement of a tibial bone block from the anterior tibial plafond was adopted. Inclusion criteria were joint stability, an age between 18 and 50 years, and osteochondral lesions stages 3 and 4 according to the radiological classification of Loomer, for which previous arthroscopic treatment was not successful. All patients underwent clinical and MRI evaluation after 12, 35 and 59 months. The AOFAS Ankle Hindfoot score improved significantly between the preoperative period and 1 year (p < 0.001), between 1 and 3 years (p < 0.001), but not between 3 and 5 years postoperative (p = 0.37). The score was independent from patients gender (p = 0.44) and age. The Spearman coefficient of correlation between clinical outcome and defect size was - 0.79 (p = 0.01), indicating that patients with small lesions had the best results. Control radiographs and MRIs showed no reduced joint space and good integration of the tibial bone block without incongruency. Osteochondral grafting with temporary removal of a tibial bone block is a successful technique with good midterm results in osteochondral talar lesions for which arthroscopic excision, curettage and drilling has failed.