Digital Volume Correlation for large deformations of soft tissues: Pipeline and proof of concept for the application to breast ex vivo deformations.

Being able to reposition tumors from prone imaging to supine surgery stances is key for bypassing current invasive marking used for conservative breast surgery. This study aims to demonstrate the feasibility of using Digital Volume Correlation (DVC) to measure the deformation of a female quarter thorax between two different body positioning when subjected to gravity. A segmented multipart mesh (bones, cartilage and tissue) was constructed and a three-step FE-based DVC procedure with heterogeneous elastic regularization was implemented. With the proposed framework, the large displacement field of a hard/soft breast sample was recovered with low registration residuals and small error between the measured and manually determined deformations of phase interfaces. The present study showed the capacity of FE-based DVC to faithfully capture large deformations of hard/soft tissues.

Effect and tolerability of perampanel in patients with drug-resistant epilepsy.

OBJECTIVE: Perampanel is one of the most recently approved antiseizure medications. The aim of the present study was to assess clinical efficacy and tolerability, in combination with pharmacokinetic variability, of perampanel treatment in patients at a tertiary referral center for epilepsy. METHODS: We performed a retrospective observational study of patients given perampanel as adjunctive treatment in the period January 2013 - February 2019 at the National Center for Epilepsy at Oslo University Hospital, Norway. RESULTS: Clinical data were available for 175 mainly adult patients with drug-resistant epilepsy with mean treatment duration of 16.1 months. We found that 23% (40 patients) were responders (i.e., achieving more than 50% reduction in seizure frequency), four of whom became seizure free, 29% (51 patients) experienced a modest effect, whereas for 29% (50 patients) perampanel had no seizure-reducing effect. A paradoxical effect, with seizure aggravation, was reported in 9% (15 patients). The responder rate was significantly higher in those with slow vs. fast dosage titration. Logistic regression analysis showed better efficacy among those with generalized vs. those with focal epilepsy. Adverse effects were reported by 135 patients (77%), ranging from mild (34%), to moderate (41%) and severe (2%). In 55 patients (41%), these adverse effects resulted in discontinuation of treatment with perampanel. The most frequent adverse effects were psychiatric symptoms (34%), dizziness (31%), and sleepiness (26%). Of the 31 patients for whom serum concentration measurements were available, the mean daily perampanel dose was 6.3 mg (SD 3.0), with a mean serum concentration at steady state of 1.03 µmol/L (range: 0.15-3.59 µmol/L). There were pronounced differences between patients, as demonstrated by a 12-fold variability in the range of concentration/dose (C/D)-ratios (0.06 to 0.69 µmol/L/mg), where enzyme inducers contributed. CONCLUSION: Our results demonstrate that perampanel had a modest seizure-reducing effect in this very treatment-resistant patient group. Predictors of treatment success were generalized epilepsy and slow dosage titration. In patients without a history of psychiatric problems, clinicians could consider increasing dose of perampanel beyond 6 mg daily, taking co-medication and serum concentrations into account.

Ruthenium(II) and iridium(III) complexes featuring NHC-sulfonate chelate.

Three new complexes bearing a chelating (κ(2)C,O) NHC-SO3 ligand have been prepared. An original method for the synthesis of the imidazolium-sulfonate NHC precursor is described. The 5-membered ruthena- and irida-cycle containing complexes were fully characterized and evaluated in a series of catalytic transformations involving hydrogen auto-transfer processes.

Computation of full-field displacements in a scaffold implant using digital volume correlation and finite element analysis.

Measurements of three-dimensional displacements in a scaffold implant under uniaxial compression have been obtained by two digital volume correlation (DVC) methods, and compared with those obtained from micro-finite element models. The DVC methods were based on two approaches, a local approach which registers independent small volumes and yields discontinuous displacement fields; and a global approach where the registration is performed on the whole volume of interest, leading to continuous displacement fields. A customised mini-compression device was used to perform in situ step-wise compression of the scaffold within a micro-computed tomography (µCT) chamber, and the data were collected at steps of interest. Displacement uncertainties, ranging from 0.006 to 0.02 voxel (i.e. 0.12-0.4 µm), with a strain uncertainty between 60 and 600 µÎµ, were obtained with a spatial resolution of 32 voxels using both approaches, although the global approach has lower systematic errors. Reduced displacement and strain uncertainties may be obtained using the global approach by increasing the element size; and using the local approach by increasing the number of intermediary sub-volumes. Good agreements between the results from the DVC measurements and the FE simulations were obtained in the primary loading direction as well as in the lateral directions. This study demonstrates that volumetric strain measurements can be obtained successfully using DVC, which may be a useful tool to investigate mechanical behaviour of porous implants.

Development of a synchrotron biaxial tensile device for in situ characterization of thin films mechanical response.

We have developed on the DIFFABS-SOLEIL beamline a biaxial tensile machine working in the synchrotron environment for in situ diffraction characterization of thin polycrystalline films mechanical response. The machine has been designed to test compliant substrates coated by the studied films under controlled, applied strain field. Technological challenges comprise the sample design including fixation of the substrate ends, the related generation of a uniform strain field in the studied (central) volume, and the operations from the beamline pilot. Preliminary tests on 150 nm thick W films deposited onto polyimide cruciform substrates are presented. The obtained results for applied strains using x-ray diffraction and digital image correlation methods clearly show the full potentialities of this new setup.

Imprint cytology of core needle biopsy specimens of breast lesions. A rapid approach to detecting malignancies, with comparison of cytologic and histopathologic analyses of 173 cases.

OBJECTIVE: To investigate whether imprint cytology of core needle biopsy (CNB) specimens from breast lesions is a useful method of rapidly obtaining additional diagnostic information and potentially can be used to reduce the number of biopsies needed. STUDY DESIGN: Cytologic analysis was performed on 173 breast lesions and compared with their histopathologic diagnoses (143 malignant and 30 benign). For imprint cytology, one CNB specimen was rolled between two slides and stained with Diff-Quik and Papanicolaou stain. RESULTS: The diagnostic overall accuracy of Diff-Quik stain (Papanicolaou stain) was 95.4% (95.9%), with a sensitivity of 96.5% (97.2%), specificity of 90% (90%), positive predictive value of 97.8% (97.8%) and negative predictive value of 84.3% (87.0%). There was no statistically significant difference between the stains. Histopathologic analysis had an overall accuracy of 97.7%, with a sensitivity of 97.2%, specificity and positive predictive value of 100% and a negative predictive value of 88.2%. CONCLUSION: Imprint cytology of CNBs is a sensitive method of detecting malignancies in breast tumors. Diff-Quik is a rapid and reliable approach that can reduce the number of biopsies. Inadequate and suspicious cases should be evaluated based on complementary diagnostic procedures for breast lesions.

Ductal orientated sonography improves the diagnosis of pathological nipple discharge of the female breast compared with galactography.

In case of abnormal nipple discharge of the female breast galactography is a recognized radiological procedure to identify and to localize intraductal growths or other ductal abnormalities. However, it harbours several methodological problems. In ductal orientated sonography the availability of high frequency linear transducers enables us now to visualize the mammary ducts in detail. The aim of this study was to compare both methods with respect to the detection of the cause of pathological nipple discharge. Thirty-five patients were first examined by ductal orientated sonography with a 13 MHz linear transducer. The results of sonography were recorded in detail before galactography was performed. Ductal abnormalities were found by sonography in 26 patients and by galactography in 19 patients. In 24 cases both methods revealed concurring results. Among those, 17 cases showed pathological findings and seven cases had normal ducts. In nine patients sonography revealed pathological results whereas galactography was completely normal. In only two cases sonography failed to show ductal abnormalities which were detected by galactography. Our study underlines that ductal orientated sonography is a promising method of diagnosis in abnormal nipple discharge, which may be recommended to be performed routinely before galactography.

Establishment of new epithelial carcinoma cell lines by blocking monolayer formation.

Human endometrial carcinoma cell lines were established by using a new cell culture technique. The malignant endometrial tumors were grossly disaggregated by mechanical means and cultivated in suspension culture. Adhesion to the bottom of the culture flasks was prevented by first coating the flasks with a thin agarose layer. Four cell lines were derived from 17 samples by this new technique. The cell lines obtained in this way were fully characterized, including karyotyping, intermediate filament staining and transplantation to nude mice. This new technique of initial suspension culture may also be applicable to other human tumors that are equally difficult to cultivate in vitro.

[Therapy of chronic myeloid leukemia with interferon-alpha. A decade of experiences]. / Therapie der chronischen myeloischen Leukämie mit Interferon alpha. Erfahrungen aus einem Jahrzehnt.

PATIENTS AND RESULTS: One hundred and fifty-nine patients with chronic myelogenous leukemia have been treated in six studies during 10 years at Hannover Medical School University Center. The prognosis of 111 patients without pretreatment has been improved compared to conventional therapy with a median survival of 5.7 years. Cytogenetic remissions have been induced in all studies followed for a longer time. The most pronounced improvement of prognosis has been observed in these patients. CONCLUSIONS: Several conclusions can be drawn on the basis of the results on the different treatment concepts: 1. Patients with pretreatment have an unfavourable response to interferon. 2. There is a likely effect of the dose of Interferon alpha on the frequency of cytogenetic remissions. 3. The combination of Interferon alpha and interferon gamma has been toxic and ineffective in a pilot study. 4. The combination of interferon and cytosine arabinoside has a positive impact on the frequency of cytogenetic remissions. A continuous parallel application of both drugs seems to be most effective in this respect. An ongoing trial has been initiated to compare a fixed combination of Interferon alpha and cytosine arabinoside and with hydroxyurea respectively. Additionally the feasibility of autologous peripheral blood stem cell transplantation will be studied in patients with insufficient response to the interferon treatment.

[Complete remission in acute promyelocytic leukemia. The advantages of all-trans-retinoic acid compared to conventional chemotherapy]. / Komplette Remission bei akuter Promyelozytenleukämie. Vorteile von all-trans-Retinsäure im Vergleich mit konventioneller Chemotherapie.

In all of seven patients (six men, one woman; mean age 43 [24-55] years) with newly diagnosed acute promyelocytic leukaemia, treated between 1989 and 1993, complete remission was achieved. In three of these patients, treated between 1989 and 1991, remission was induced with conventional chemotherapy (cytarabine and anthracycline), after this in four patients with all-trans retinoic acid (tretinoin). The seventh patient who had a very rapid increase in leucocytes during tretinoin administration, was as a precaution also given conventional chemotherapy. All seven patients received consolidating chemotherapy with an intensive treatment cycle. Retrospective analysis indicated that induction with tretinoin had marked advantages: quicker regression of the clotting abnormalities (mean of 9 vs 25 days), shorter period of leukopenia (mean of 3.5 vs 30 days), shorter time until complete remission (mean of 38 vs 48 days). There were no specific side effects ascribable to tretinoin. Toxicity after chemotherapy corresponded to WHO grades 2-4. The results indicate that tretinoin markedly reduces the two main risks in the treatment of acute promyelocytic leukaemia: bleeding and infection.

Cytogenetic peculiarities in chronic myelogenous leukemia.

Cytogenetic investigations were performed in 185 patients with chronic myelogenous leukemia (CML) at all stages of the disease; 166 patients were Ph positive-159 (95.8%) of these showing the standard Ph translocation, and 7 (4.2%) variant translocations-17 patients were Ph negative. In 2 patients the cytogenetic analysis was unsuccessful. Additional aberrations were found in 40 (24.1%) of the Ph-positive patients. Nine (52.9%) of the Ph-negative patients showed chromosome anomalies. Besides the well known nonrandom abnormalities (-7, +8, i(17q), +19, +Ph) we found a high frequency of clones with rare or not yet described structural rearrangements--in 14 cases (34.2%) of the Ph-positive patients and in 2 cases (20%) of the Ph-negative patients with other chromosome abnormalities. The clinical significance of these findings is discussed.

[True XX/XY hermaphrotide, HY antigen positive, without detectable testicular tissue. Observation from birth to the age of ten years (author's transl)]. / Echter XX/XY hermaphrodit mit positivem H-Y-Antigen ohne aufgefundenes Testisgewebe. Beobachtung von Geburt bis zum 10. Lebensjahr.

A rare modification of true Hermaphroditism is demonstrated in a ten-year-old child we have observed since birth. The cytogenetic analysis revealed a XX/XY-mosaicism. Two kinds of origin are discussed: 1. an ovum with two nuclei was fertilized by two different sperm cells, 2. two heterosexual zygotes fused. -- We could not find tissue of the testes but confirmed the diagnosis of a hermaphroditism by the detection of the HY-antigen and by typical endocrinological findings. Two different cell populations found in erythrocytes and by GPT-isoenzymes indicated a chimerism. By knowledge of these findings, we could help the child to undergo a positive psychological and social development.

[Transvesical sonography of the seminal vesicles (author's transl)]. / Zur transvesicalen Sonografie der Samenblasen.

There are several techniques for the examination of the seminal vesicles. Beside vesiculography and CAT scan diagnostic ultrasound seems to provide additional help. The ultrasonic procedure and results are described. Two operable cases of prostatic carcinoma are reported.

Regeneration of the renal calyces after calycectomy: an experimental study.

On 14 rabbits, 21 kidneys were subjected to a calycectomy or the tip of the papilla was cut off by caudal nephrotomy. During an observation period of 2, 4, 6, 8 and 10 days, and further after 3 and 6 weeks the macroscopic and microscopic investigations led to the following results clearly answering the question put at the beginning of the inquiry: (1) even if parts of the renal calyces are removed, a complete regeneration of the renal pelvic mucosa takes place in the damaged area; (2) regeneration of the mucosa begins in neighbouring renal pelvic epithelium and the epithelium of the collecting tubes; (3) regeneration starts on the 4th day and is essentially ended by the 3rd week; this regeneration extends over the whole of the injured area; after the 6th week the process is finished and no inflammatory changes are to be found in the damaged area, and (4) in the process of healing no fibrous tissue is formed at the occlusion of the lamina cribrosa in the area of the papilla; there is no demonstrable necrosis of the renal parenchyma where the mucosa was removed. Hydronephrosis in this area is evident, beginning on the 3rd or 4th day and is to be regarded as the result of inflammatory process or of the operation itself. It is partly in evidence after 6 weeks but is clearly in a regressive stage. Morphologically a functional loss of the affected area of renal tissue cannot be demonstrated. The four questions made and answered by this animal experiment allow the following conclusion: calycectomy can be successfully undertaken. Regeneration of the mucosa is almost finished after 3 weeks and finally completed after 6 weeks. Considerable cicatrisation in the area of the mucous membrane injury or of its nephrons is morphologically unimportant. Calycectomy should be preferred to polar resection as there is a smaller parenchymal loss.