The EuroNet paediatric hodgkin network - modern imaging data management for real time central review in multicentre trials.

Since 2007, children and adolescents with Hodgkin lymphomas are treated in the Europe-wide EuroNet-PHL trials. A real time central review process for stratification of the patients enhances quality control and efficient therapy management. This process includes reading of all cross-sectional-images. Since reference evaluation is time critical, a fast, easy to handle and safe data transfer is important. In addition, immediate and constant access to all the data has to be guaranteed in case of queries and for regulatory reasons. To meet the mentioned requirements the EuroNet Paediatric Hodgkin Data Network (funded by the European Union - Project Number: 2007108) was established between 2008 and 2011. A respective tailored data protection plan was formulated. The aim of this article is to describe the networks' mode of operation and the advantages for multi-centre trials that include centralized image review.

[Modified Lambrinudi arthrodesis with additional posterior tibial tendon transfer in adult drop foot]. / Modifizierte Arthrodese nach Lambrinudi mit zusätzlichem Transfer der Tibialis-posterior-Sehne zur Behandlung des adulten Fallfußes.

OBJECTIVE: Treatment of adult instable drop foot by modified Lambrinudi arthrodesis (removal of a wedge between the talus and calcaneus), followed by a posterior tibial tendon transfer to the medial cuneiform in order to provide active dorsiflexion. INDICATIONS: Severe drop foot (of various etiologies) in combination with hindfoot instability. Sufficient function of the posterior tibial muscle. CONTRAINDICATIONS: Neurologic dysfunction of the posterior tibial muscle, infection of foot/hindfoot, Charcot arthropathy, and insufficient patient compliance. RELATIVE CONTRAINDICATIONS: Previous surgery of posterior tibial tendon, critical soft tissues/skin conditions, insufficient neurovascular conditions. SURGICAL TECHNIQUE: Lateral skin incision. Debridement of sinus tarsi and removal of the bifurcate ligament to expose the subtalar, calcaneocuboidal, and talonavicular joints. Resection of a bone wedge from the calcaneus and talus (25-30°) to correct the drop foot deformity. Cartilage removal from the calcaneocuboid joint. Debridement of both the talar head and the navicular to allow adequate fitting. After reduction (neutral dorsiflexion and 10° foot abduction), preliminary fixation with Kirschner wires. Final fixation with canulated screws (talonavicular, calcaneocuboidal, and subtalar joints). Medial skin incision at the navicular tuberositas to deattach the posterior tibial tendon with a bony fragment. The tendon stump is harvested 10 cm proximal to the tibiotalar joint. Small skin incision at the anterolateral aspect of the distal lower leg. The posterior tibial tendon is transferred through the interosseous membrane and reattached to the medial cuneiform with a screw. POSTOPERATIVE MANAGEMENT: Immobilization with a removable short leg cast for 2-4 days. Ambulation with full weightbearing in a cast for 8 weeks. Radiographic assessment 8 weeks postoperatively. After bony healing, mobilization in normal shoes is allowed. Intensive physiotherapy to train the dorsiflexion. RESULTS: The average correction of drop foot deformity was 18.7°. Active dorsiflexion increased significantly from 30° preoperatively to 10° postoperatively.

Haemophilic arthropathy of the ankle treated by total ankle replacement: a case series.

The standard treatment for end-stage osteoarthritis of the ankle joint in haemophilic patients has been fusion of the ankle joint. Total ankle replacement is still controversial as a treatment option. The objective of this prospective study was to evaluate the mid-term outcome in patients treated with total ankle replacement using an unconstrained three-component ankle implant. Ten haemophilic ankles in eight patients (mean age: 43.2 years, range 26.7-57.5) treated with total ankle replacement were followed up for a minimum of 2.7 years (mean: 5.6, range 2.7-7.6). The outcome was measured with clinical and radiological evaluations. There were no intra- or peri-operative complications. The AOFAS-hindfoot-score increased from 38 (range 8-57) preoperatively to 81 (range 69-95) postoperatively. All patients were satisfied with the results. Four patients became pain free; in the whole patient cohort pain level decreased from 7.1 (range 4-9) preoperatively to 0.8 (range 0-3) postoperatively. All categories of SF-36 score showed significant improvements in quality of life. In one patient, open ankle arthrolysis was performed because of painful arthrofibrosis. For patients with haemophilic osteoarthritis of the ankle joint, total ankle replacement is a valuable alternative treatment to ankle fusion.

Specific surface area and volume fraction of the cherry-pit model with packed pits.

This paper investigates volume fraction phi and specific surface area s for statistically homogeneous systems of partially penetrating spheres, i.e. so-called 'cherry-pit models'. In contrast to the version where the pits form an equilibrium system of hard spheres, here pits or hard spheres are considered which are packed, can be in direct contact, and form a nonequilibrium distribution. For this kind of system, new formulas for phi and s are given, which yield values in good agreement with the ones for large models constructed from hard sphere packings generated both experimentally and numerically. Surprisingly, the existing formulas for phi and s in the equilibrium cherry-pit model lead to values which deviate substantially from the values obtained here.

Mueller matrix retinal imager with optimized polarization conditions.

A new Mueller matrix polarimeter was used to image the retinas of normal subjects. Light from a linearly polarized 780 nm laser was passed through a system of variable retarders and scanned across the retina. Light returned from the eye passed through a second system of retarders and a polarizing beamsplitter to two confocal detection channels. Optimization of the polarimetric data reduction matrix was via a condition number metric. The accuracy and repeatability of polarization parameter measurements were within +/- 5%. The magnitudes and orientations of retardance and diattenuation, plus depolarization, were measured over 15 degrees of retina for 15 normal eyes.

[Cleavage lines and incisions in foot surgery]. / Die Hautspaltlinien und die Schnittführung bei Fussoperationen.

BACKGROUND: In the constantly evolving, increasingly important field of foot surgery, the question arises as to whether the incision types currently in use are adequate. Whether Langer's lines should be considered during the operative approach to the foot is examined here. The goal of the current study was to investigate the pattern of skin cleavage lines of cadaveric feet and to establish the optimal incision type for surgical approaches to the foot. MATERIALS AND METHODS: Twelve feet from older deceased subjects were examined. The samples were fixed. The cleavage lines of the individual skin regions were outlined and evaluated. To emphasize the significance of the investigative findings, the cleavage lines and the current, relevant operative approaches were compared. RESULTS: Standard current approaches often ignore skin cleavage lines, understandably resulting in cosmetically unsatisfactory scars. A chart with ideal incision types for individual operations was created. CONCLUSION: The ideal incision should run parallel to skin cleavage lines. If this is not completely possible due to operative requirements, then at least a large part of the incision should follow these lines.

Relationship between foveal birefringence and visual acuity in neovascular age-related macular degeneration.

PURPOSE: To investigate the relationship between visual acuity and foveal birefringence in patients with neovascular age-related macular degeneration. METHODS: In total, 40 patients with choroidal neovascularization underwent macular imaging with scanning laser polarimetry. Bowtie patterns, typically seen in birefringence images of the macula, were evaluated and classified into three categories: (1) regular bowtie present; (2) bowtie present, but disrupted; and (3) no bowtie present. The relation of the bowtie appearance to the best-corrected logMAR visual acuities was tested (ANOVA). RESULTS: Mean visual acuity was best for the group that had regular bowties (mean logMAR=0.34) and differed statistically significantly from the disrupted bowtie group and no bowtie group (P=0.01 and 0.0007). Ages for the three groups did not differ (P=0.31). CONCLUSIONS: Appearance of a regular bowtie indicates a substantially intact Henle fibre layer with the potential for good visual function, despite the presence of underlying pathology. Conversely, disruption or absence of a bowtie may indicate severe damage to the photoreceptors, consistent with the finding of poorer visual acuity.

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment.

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.

Blue on yellow perimetry with scanning laser ophthalmoscopy in patients with age related macular disease.

BACKGROUND/AIM: The loss of short wavelength sensitive (SWS) cone mechanism sensitivity is related to severe vision loss in patients with age related maculopathy (ARM). A case-control study of patients with ARM and age matched controls was performed, using blue on yellow static perimetry. METHODS: A bright yellow background at 594 nm isolated the responses of short wavelength cone mechanisms to 458 nm targets. A scanning laser ophthalmoscope produced stimuli and provided real time, simultaneous fundus illumination. The macula was probed with 16 Goldmann IV targets, 1-10 degrees from fixation, using a staircase method. RESULTS: 24 patients with non-exudative ARM were matched to 24 subjects with normal fundus appearance. SWS cone pathway sensitivity for macular targets was significantly reduced in the patients with ARM compared to normals--15.45 (SD 4.56) dB v 17.22 (0.28) dB, respectively (p<0.0005). There was not only a diffuse loss of sensitivity in ARM patients, but also a localised loss of sensitivity over drusen (p<0.025). Neither the mean age, 69 (8) years, nor the mean visual acuity differed between groups, logMAR 0.09 (0.10) v 0.05 (0.06) for ARM patients v normals, respectively. Patients with soft drusen had lower sensitivity than those with hard drusen (p<0.05). CONCLUSION: A loss of SWS cone pathway sensitivity occurred in most patients with early ARM, despite good visual acuity, demonstrating a loss of visual function that cannot be attributed to ageing changes. The loss of sensitivity, despite good visual acuity, included both a diffuse loss and localised losses.

Response to lysine in a wheat gluten diet in adult minipigs after short-and long-term dietary adaptation as assessed with an indicator amino acid oxidation and balance technique.

An experiment was conducted to examine the response to wheat gluten (WG)-based diets at two lysine levels in adult minipigs (23 kg BW) using the indicator AA oxidation (IAAO) approach and N balance. Twenty minipigs (n = five per group), fitted with reentrant ileoileal cannulas allowing collection of ileal effluents, were fed restrictively two WG-based diets (WG and WG + Lys; 2.7 and 6.6 g of lysine/kg, respectively) for adaptation periods of 10 and 100 d. On d 7 and 9, for pigs fed the diets for 10 d, and on d 97 and 99, for pigs fed the diets for 100 d, primed i.v. fasted/fed tracer protocols with [(13)C]bicarbonate, and [(13)C]leucine were performed. With the WG diet, [(13)C]bicarbonate recoveries (%) were lower irrespective of the adaptation period, and higher during the fed period (fasted: WG + Lys = 82.5, and WG = 69.1; fed: WG + Lys = 90.6, and WG = 85.9; P < 0.05). Leucine oxidation rate was higher with the lower lysine intake (WG = 194.6 vs. 109.5 mg/[kg BW x d]; P < 0.05). Wheat gluten feeding resulted in a negative leucine balance independent of the adaptation period (WG = -29.1, and WG + Lys = 48.2 mg/[kg BW x d]; P < 0.05). In contrast with the IAAO method, N balance did not differ between the two lysine intakes, possibly because of an underestimation of N losses. The finding of a lower (13)C bicarbonate recovery with the lower dietary lysine intake suggests that caution should be taken in using a single recovery factor for all AA oxidation studies.

Short wavelength automated perimetry in age related maculopathy.

BACKGROUND/AIMS: Previous studies reported the predictive value of the short wavelength sensitive (SWS) cone mediated sensitivity for visual outcome in age related macular degeneration. In this study SWS sensitivity was measured by commercially available blue on yellow perimetry in patients with non-exudative age related maculopathy (ARM) and compared with the presence of morphological risk factors and the status of the fellow eye. METHODS: In a prospective cross sectional study, 126 patients (57 males, 69 females, mean age 71 (SD 6) years) with ARM (visual acuity >20/50) were tested. Central visual fields (blue on yellow) were obtained with a conventional perimeter. Fundus slides were graded by two independent observers for soft drusen and presence of focal hyperpigmentation. RESULTS: Mean sensitivity and standard deviation of all patients exhibited a significant reduction with age. Patients with soft drusen had significantly lower sensitivity than those without, whereas there were no differences in visual acuity (log MAR). Sensitivity was also reduced in those eyes with fellow eyes having a sight threatening complication of age related macular degeneration (AMD). Eyes with focal hyperpigmentation compared with those without had no loss of sensitivity, but did have a significant decrease in the central part of the field compared with the more eccentric. CONCLUSION: SWS sensitivity loss is associated with common risk factors for progression to AMD. Short wavelength automated perimetry is moderately rapid and readily available. It may serve as a tool in future ARM trials.

Blue-on-yellow perimetry with a scanning laser ophthalmoscope: small alterations in the central macula with aging.

The sensitivity of short-wavelength-sensitive (SWS) cone pathways was measured in the central fields of 74 normal subjects, aged 17-86 yr, with healthy maculas. The new fundus perimetry technique used a research scanning laser ophthalmoscope with a small entrance pupil to present blue static perimetry targets on a bright yellow background. Simultaneous infrared imaging aided target positioning and rapid assessment of potential pathology in elderly subjects. Targets were positioned peripheral to fixation, avoiding both the SWS-cone-free area and the peak macular pigment, determined in 11 subjects. Sensitivity declined 0.019 log unit per decade, while intraindividual variability across loci increased. The nasal-temporal asymmetry remained constant. Sensitivity of older subjects was relatively less for the most central targets but was unrelated to transmission through macular pigment. Retinal changes with age occur to differing extents or at differing rates and are readily detectable in the central macula.

Detecting AMD with multiply scattered light tomography.

PURPOSE: to use a novel technique, Multiply Scattered Light Tomography (MSLT), to provide a comfortable, rapid, and noninvasive method for detection and management of Age-related Macualar Degeneration. METHODS: two patient groups were studied in clinical settings with MSLT and confocal scanning laser tomography. In Poway, CA, 21 retinal patients underwent tomography, and the 17 patients with suspicion of exudation also had ICG. An Angio-Scan (Laser Diagnostic Technologies, Inc.) was used to provide simultaneous fundus reflectance and ICG imaging. In Methuen, MA, 20 retinal patients underwent tomography with fluorescein angiography for suspicion of exudation. The MSLT was based on the TopSS (Laser Diagnostic Technologies, Inc.), with a Vertical Cavity Surface Emitting Laser array at 850 mm as the illumination source. The central laser produced confocal images. The surrounding lasers produced multiply scattered light images. RESULTS: MSLT emphasized structures beneath the retina such as drusen, choroidal new vessel membranes, and pigment epithelial detachments. Exudation seen on angiography was visualized by MSLT as topographical structures with distinct borders. Superficial structures, e.g., cysts and epiretinal membranes, were visualized in 850 nm images. DISCUSSION: confocal tomography and MSLT provided a rapid, noninvasive method to detect and localize macular degeneration and pathological structures found in eyes of older patients.

Three dimensional imaging in age-related macular degeneration.

The ability of confocal scanning laser tomography to quantify the subretinal features was investigated. The slope ratios (anterior slope/posterior slope) of the axial intensity profiles were analyzed. The data fromnormal subjects showed only minimal influence of individual ocular pigmentation. In the eyes with agerelated macular degeneration, the light-tissue interactions vary according to the type of retinal features. Three-dimensional information could be obtained from the axial intensity profiles.

Long-term high protein intake does not increase oxidative stress in rats.

The maximum dietary protein intake that does not cause adverse effects in a healthy population is uncertain. We tested whether a high protein intake enhances oxidative stress. Adult rats were adapted to different casein-based diets containing either an adequate (13.8%; AP), medium (25.7%; MP), or high (51.3%; HP) level of crude protein; a fourth group received a HP diet but no RRR-alpha-tocopherol acetate (HP-toc). After 15 wk of feeding, plasma protein carbonyl concentration, liver lipid peroxide levels [thiobarbituric acid-reacting substances (TBARS)], reduced glutathione (GSH) status and leucine kinetics ([1-(13)C]leucine) were measured. Higher concentrations of protein carbonyls and TBARS were found in rats fed the AP and the HP-toc diets compared with those fed the MP and HP diets (P: < 0.05). GSH concentrations in plasma did not differ but total blood GSH concentrations were significantly (P: < 0.05) lower in rats fed the HP-toc diet compared with those fed the AP, MP and HP diets. Liver GSH concentrations were significantly (P: < 0.01) lower in rats fed the AP diet compared with the other groups. Rates of postabsorptive leucine oxidation (LeuOX) and flux (Q(Leu)) were positively correlated with the dietary protein level (for AP, MP, and HP, respectively: LeuOX, 74.9 +/- 28.5, 109 +/- 35.2, 142.3 +/- 38.4 micromol/(kg. h); Q(Leu), 425 +/- 102, 483 +/- 82, 505 +/- 80 micromol/(kg. h). Only HP-toc resulted in a significantly greater protein breakdown (PB(Leu)) and Q(Leu). No difference was seen in nonoxidative leucine disposal. Long-term intake of high protein diets did not increase variables of oxidative stress, in contrast to our initial hypothesis. An unexpected finding was that adequate protein feeding (AP) may in fact induce oxidative stress.

Urinary alpha-tocopherol metabolites in alpha-tocopherol transfer protein-deficient patients.

Patients with alpha-tocopherol transfer protein (alpha-TTP) defects experience neurological symptoms characteristic of vitamin E deficiency and depend on continuous high alpha-tocopherol supplements. We investigated the excretion of 2,5,7, 8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC), a urinary metabolite of alpha-tocopherol, as a putative marker for the alpha-tocopherol status of alpha-TTP-deficient patients and control subjects. In three patients vitamin E supplementation was stopped for short periods of time, during which plasma alpha-tocopherol concentrations and urinary alpha-CEHC excretion were measured. In the patients, plasma alpha-tocopherol decreased below normal (<5 micromol/l) but alpha-CEHC excretion remained above the range of unsupplemented control subjects (0.118-0.306 mg/day, n = 6). In healthy subjects, however, alpha-CEHC excretion was increased only after surpassing a plasma alpha-tocopherol threshold of 30-40 micromol/l. Such a threshold did not exist in patients. The general mechanism of alpha-tocopherol degradation did not appear to differ between patients and control subjects. The presumed mechanism of omega- and subsequent beta-oxidation was supported by the detection of alpha- CPHC, an alpha -CEHC homolog with a side chain longer by 3 carbon atoms, both in supplemented patients and in control subjects.

Infrared scanning laser tomography of macular cysts.

OBJECTIVE: To perform three-dimensional, noninvasive, quantitative analysis of cystoid macular edema and macular cysts using infrared scanning laser tomography and to correlate findings with visual acuity (VA) as a basis for interventional studies. DESIGN: Cross-sectional, nonrandomized study. PARTICIPANTS: Seventeen patients (29-86 years of age) with macular cysts associated with a broad spectrum of diseases. INTERVENTION: Confocal infrared imaging with scanning laser tomography with the TopSS (790 nm) (Laser Diagnostic Technologies, San Diego, CA) with digitized images was used to perform three-dimensional, quantitative analysis of cysts in the central 5 degrees of the macula. MAIN OUTCOME MEASURES: Measurements of macular cyst number, area, volume, depth, slope, height of the surrounding macular elevation, and correlation with VA. RESULTS: Scanning laser tomography detected macular cysts in all patients. The number per patient ranged from 1 through 15. Cysts were accompanied by surrounding macular elevation in 16 patients (mean macular height, 216 microm). The area covered by cysts in the central 5 degrees was 0.087 to 0.969 mm2, and volume was 0.007 to 0.549 mm3. Visual acuity was significantly poorer in patients with greater cyst area (P = 0.0007), cyst volume (P = 0.0009), macular thickening (P = 0.0002), and cyst depth (P = 0.0013). Cyst number, average slope, and maximum slope, however, did not correlate significantly with VA. Grouping of macular cysts according to macular height and average cyst depth revealed that cysts in a more thickened retina were significantly deeper, had steeper slopes, and corresponded to worse VA. Macular height and average cyst depth were highly associated with each other, suggesting that in eyes with surrounding macular edema, cysts were deeper and may reflect more widespread tissue destruction. Individual confocal tomographic images provided additional information. Neither ophthalmoscopy nor fluorescein angiography delineated features such as retinal folds that suggested vitreous traction or changes in deeper layers that suggested occult choroidal new vessels. CONCLUSIONS: Infrared scanning laser tomography is a rapid and noninvasive imaging method that provides quantitative analysis of macular cysts in addition to qualitative information not seen clinically. Because poor VA is related to severe involvement of the central retina, scanning laser tomography could provide an objective outcome measure for interventional studies.

A rapid method for the extraction and determination of vitamin E metabolites in human urine.

A method for the direct extraction and routine analysis of the vitamin E metabolites gamma- and alpha-carboxyethyl hydroxychroman (gamma- and alpha-CEHC) from human urine has been developed. A relatively small sample volume (5 ml) can be used and, after enzymatic hydrolysis of the conjugated forms and acidification, the metabolites are extracted with diethyl ether. Recovery of alpha- and gamma-CEHC was compared to that of trolox, used as an internal standard, added to 24-h urine collections from vitamin E-unsupplemented volunteers. Various solvent conditions were initially tested; acidification and ether extraction gave the highest recovery. It was found that after addition and extraction from urine, trolox, alpha- and gamma-CEHC are recovered to a similar extent, hence trolox is viable as an internal standard. The samples were analyzed by both GC and HPLC with electrochemical detection (ECD). HPLC-ECD was found to give higher selectivity and higher sensitivity compared to GC or HPLC with UV detection at 290 nm. The HPLC-ECD detection limit was 10 fmol, linearity (r(2) > 0.98) was achieved in the range of 40 to 200 fmol, which was found to be optimal for 24-h urines from unsupplemented subjects. Inter-sample variability was typically 2-5%. This greater sensitivity and selectivity means that vitamin E metabolites can be analyzed even in unsupplemented subjects. It is also possible to measure unconjugated forms of the metabolites. Typically these were found to represent approximately 10% of the total alpha- and gamma-CEHC. This method can be used routinely for the determination of vitamin E metabolites in urine. The new extraction and detection methods described are relatively quick, less laborious, and more cost-effective than previously available methods.

Scanning laser reflectometry of retinal and subretinal tissues.

Measurements of the human ocular fundus that make use of the light returning through the pupil are called reflectometry. Early reflectometry studies were limited by poor light return from the retina and strong reflections from the anterior surface of the eye. Artifacts produced misleading results in diseases like age-related macular degeneration. Novel laser sources, scanning, confocal optics, and digital imaging provide improved sampling of the signal from the tissues of interest: photoreceptors and retinal pigment epithelial cells. A wider range of wavelengths is now compared, including the near infrared. Reflectometry now provides functional mapping, even in severe pathology.

Multiply scattered light tomography and confocal imaging: detecting neovascularization in age-related macular degeneration.

A novel technique, Multiply Scattered Light Tomography (MSLT), and confocal Infrared Imaging are used to provide diagnostic information using a comfortable, rapid, and noninvasive method. We investigated these techniques in detecting neovascularization in age-related macular degeneration. The MSLT used a Vertical Cavity Surface Emitting Laser (VCSEL) at 850 nm, while the confocal imaging technique used either the VCSEL or a 790 nm laser diode. Both were implemented into the topographical scanning system (TopSS, Laser Diagnostic Technologies, Inc.) Confocal imaging with both lasers provided different information about neovascularization as a function of focal plane, and different also from MSLT.