Contribution of cervical cytology in the diagnostic work-up of patients with endometrial cancer.

INTRODUCTION: Abnormal cervical cytology in patients with endometrial cancer (EC) has been associated with poor outcome. The aim of this study was to evaluate whether cervical cytology could contribute to an improved preoperative identification of high-grade EC (serous, clear cell, carcinosarcoma, high-grade endometrioid EC) in final histology. METHODS: A retrospective cohort study was performed in five hospitals in the Netherlands. A total of 554 patients with EC that underwent primary surgical treatment between 2002 and 2010 were included. Primary outcome was defined as the contribution of abnormal cervical cytology in the preoperative identification of high-grade EC. As secondary outcome, recurrence-free survival (RFS) and disease-specific survival were determined based on preoperative cervical cytology, and compared to the currently established risk factors: myometrial invasion, high-grade and lymph vascular space invasion. RESULTS: Abnormal cervical cytology was present in 45.1%. For patients with preoperative inconclusive and high-grade histology, the presence of abnormal cervical cytology contributed to an improved identification of high-grade EC in final histology (odds ratio [OR] 6.40 [95% confidence interval {CI}: 1.92-21.26]; OR 2.86 [95% CI: 1.14-7.14]), respectively. Patients with abnormal cervical cytology had a significant worse 5-year median RFS. Abnormal cervical cytology was independently related to RFS (hazard ratio 1.67 [95% CI: 1.04-2.68]) and disease-specific survival (hazard ratio 3.15 [95% CI: 1.74-5.71]). CONCLUSIONS: Abnormal cytology contributes to the preoperative identification of patients with high-grade EC, and is associated with compromised outcome. Future studies are warranted to determine whether cervical cytology could be incorporated into preoperative prediction models for lymph node metastasis.

Personalization in mitigating food waste and costs in hospitalization.

BACKGROUND: Organization of food services within hospitals has been identified as a determinant of hospitalized patients' nutritional intake and associated food waste. Whereas hospital food service systems in the Netherlands traditionally consist of 3 fixed mealtimes each day, we recently implemented a new 3-channel concept that provides patients the opportunity to order extra meals or snacks in-between their 3 main mealtimes or even have dinner with their visitors in a bistro located on their ward. AIM: This study investigates the impact of transitioning from a traditional paper-based to a patient-centered, digital hospital food service system on food waste production patterns and its associated financial implications. METHODS: Plate waste (served but uneaten food) measurements were performed at baseline for all served meals during a one-week period within the traditional system and follow-up measurements were conducted annually after implementation of the new system during 3 consecutive years. Measurements were conducted at two hospital floors, each comprising four wards. Average grams of plate waste per served meal, daily meal frequency per patient and the associated production and disposal costs of the collected waste were calculated and compared between the two systems. RESULTS: A total of 4361 meals served within the traditional system were compared with 7815 meals served within the new digital system. Meal frequency increased from an average of 2.5 meals per patient per day in the old system to an average varying between 3 and 3.3 meals per patient per day in the consecutive years. Within the traditional system, average plate waste was 81 grams per served meal, whilst it ranged between 33 and 49 grams per served meal during the following years, with the 3-channel concept in place (p < 0.001, p = 0.010). Dinner demonstrated the largest reduction in plate waste at all measurement points. Following this reduction of plate waste, estimated associated costs of plate waste production and disposal decreased in a similar pattern. CONCLUSION: Transitioning from a traditional, paper based to a patient-centered and digital hospital catering system results in significantly higher daily meal frequency and less food waste per served meal.

The value of imaging of the lungs in the diagnostic workup of patients with endometrial cancer.

OBJECTIVE: Imaging of the lungs is part of the routine diagnostic workup of patients with endometrial cancer. The present study aimed to determine the incidence of lung metastases in patients with endometrial cancer and to evaluate the clinical relevance of preoperative chest imaging in this population. METHODS: A retrospective cross-sectional study was performed in four regional and one university hospital in the southeastern part of the Netherlands. A total of 784 patients with epithelial endometrial cancer diagnosed between 2002 and 2010 in five hospitals were included. Patients were followed up for at least 1 year. RESULTS: Of 784 patients, 541 (69.0%) underwent thoracic imaging and 11 showed findings suspicious for metastases perioperatively or during the 1-year follow-up period. In eight patients, the thoracic metastases were related to their endometrial cancer, resulting in an overall incidence of 1.0% (8/784, 95% CI=0.3-1.7%). These eight patients had high-risk subtypes of endometrial cancer (serous, clear cell or poorly differentiated endometrioid), and the incidence was 4.1% (8/193, 95% CI=1.9-8.3%) for these subtypes. Lung metastases were not detected in any of the patients with low-risk subtypes of endometrial cancer (n=566) at the time of diagnosis (95% CI=0-0.8%). CONCLUSIONS: The probability of detecting thoracic metastases during the diagnostic workup of patients with endometrial cancer is low. The present data suggest that thoracic imaging could be omitted from the diagnostic workup of patients with low-risk endometrial cancer.

MPBuilder: A PyMOL Plugin for Building and Refinement of Solubilized Membrane Proteins Against Small Angle X-ray Scattering Data.

Membrane proteins (MPs) are the target of numerous structural and functional studies in biological and medical/pharmaceutical sciences. Strategies for the high-throughput structural analysis of MPs and of their perturbations driven by ligands having potential therapeutic applications are uncommon, often requiring scaled up crystallization, electron microscopy, and nuclear magnetic resonance (NMR) efforts. Small-angle X-ray scattering (SAXS) provides a rapid means to study low resolution structures and conformational changes of native MPs in solution without cumbersome sample preparations/treatment. The method requires the MPs solubilized in an appropriate medium (eg. detergents, mixed micelles and nanodiscs) and reliable and robust models are needed to describe the relevant complexes. Here we present MPBuilder, a simple and versatile tool for the generation and refinement of all-atom MP systems in the popular software PyMOL, an environment familiar to most biologists. MPBuilder provides building capability for protein-detergent, bicelle, and lipid-scaffold (saposin nanoparticles, nanodiscs) complexes and links this to the ATSAS software package modules for model refinement and validation against the SAXS data.

[Evaluation of veterinary advice given to dairy farmers]. / Beoordeling van de bedrijfsadvisering door dierenartsen op rundveebedrijven.

In this pilot study, the manner and effectiveness of advice given by four cattle practitioners was investigated during health management visits to 34 dairy farms. Farmers were asked about their satisfaction with the advice given, and an independent observer evaluated the manner in which practitioners carried out the farm visit. There were no major differences between the cattle practitioners, but there were minor differences in the way practitioners gave advice, in the duration of the herd visit, and in the subjects talked about. The farmers were positive about the manner in which advice was given and its effect. The method used in this pilot study could be used to gain insight into the manner in which veterinary advice is given by veterinary practitioners and veterinary practices, and may contribute to improving the quality of veterinary services provided.

Junctionless versus inversion-mode lateral semiconductor nanowire transistors.

This paper reports on gate-all-around silicon nanowire field-effect transistors (FETs) built in a lateral configuration, which represent the ultimate scaling limit of triple-gate finFET devices and allow a less disruptive CMOS scaling path in terms of processing and circuit layout design. We address several of their critical technological challenges, looking in particular at doping strategies. A comprehensive review of junctionless versus inversion-mode type of transistors is here presented, evaluating the impact on the devices' operation mode and on device properties such as: variability, reliability, noise, DC and analog/RF performance. We also discuss the potential for further manufacturable co-integration options.

ATSAS 2.8: a comprehensive data analysis suite for small-angle scattering from macromolecular solutions.

ATSAS is a comprehensive software suite for the analysis of small-angle scattering data from dilute solutions of biological macromolecules or nanoparticles. It contains applications for primary data processing and assessment, ab initio bead modelling, and model validation, as well as methods for the analysis of flexibility and mixtures. In addition, approaches are supported that utilize information from X-ray crystallography, nuclear magnetic resonance spectroscopy or atomistic homology modelling to construct hybrid models based on the scattering data. This article summarizes the progress made during the 2.5-2.8 ATSAS release series and highlights the latest developments. These include AMBIMETER, an assessment of the reconstruction ambiguity of experimental data; DATCLASS, a multiclass shape classification based on experimental data; SASRES, for estimating the resolution of ab initio model reconstructions; CHROMIXS, a convenient interface to analyse in-line size exclusion chromatography data; SHANUM, to evaluate the useful angular range in measured data; SREFLEX, to refine available high-resolution models using normal mode analysis; SUPALM for a rapid superposition of low- and high-resolution models; and SASPy, the ATSAS plugin for interactive modelling in PyMOL. All these features and other improvements are included in the ATSAS release 2.8, freely available for academic users from https://www.embl-hamburg.de/biosaxs/software.html.

[Value of diffusion-weighted imaging for diagnosing vertebral metastases due to prostate cancer in comparison to other primary tumors]. / Stellenwert der Diffusionsbildgebung in der Diagnostik von Wirbelkörpermetastasen des Prostatakarzinoms im Vergleich zu anderen Primärtumoren.

PURPOSE: Several publications have reported that the apparent diffusion coefficient is generally lower in metastatically affected vertebrae. Therefore, metastases are represented in diffusion-weighted images by increased signal intensity in comparison to unaffected vertebrae. However, there were indications that metastases due to prostate cancer may differ from this. Therefore, the contrast behavior of vertebral metastases due to prostate cancer or tumors with another histology are to be systematically studied using diffusion-weighted images. The present study is intended to examine whether the two groups differed and whether possible differences depended on the degree of sclerosis. MATERIALS AND METHOD: In a retrospective study the vertebral metastases of patients with prostate cancer (n = 18) were compared to those of patients with tumors of another histology (n = 20). A steady-state free precession sequence was used for the diffusion-weighted imaging. Additionally, a T1 weighted sequence before and after administration of contrast agent as well as a fat suppressed T2 weighted sequence were performed. The contrast behavior of the metastases was evaluated for all four sequences and was compared to that of the unaffected parts of the vertebra. RESULTS: In 18 patients of the tumor group, the vertebral metastases showed positive contrast in the diffusion-weighted images, and 2 had minimally negative contrast up to - 0.04. In the prostate cancer group, the contrast was positive in 9 patients and negative in 9. 6 of the metastases with negative contrast had an osteoblastic metastasization, 1 had an osteolysis, and 1 had a normal finding in the conventional X-ray image. Between the tumor group and the prostate cancer group, the medians of the contrasts were not significantly different (p = 0.054). CONCLUSION: In general, the metastatically affected vertebrae appear hyperintense in the diffusion-weighted images. This observation is only true for some vertebral metastases due to prostate cancer. The cause for this seems to be the degree of sclerosis of the metastases. Thus, it cannot be generally deduced from the hypointensity in diffusion-weighted images that a lesion is benign.

[Diagnostic image (261). A woman with vulval ulcera and uveitis]. / Diagnose in beeld (261). Een vrouw met vulvaire ulcera en uveitis.

A 49-year-old woman suffered from vulval and vaginal ulcera and from oral mucosal lesions and uveitis due to Behçet's disease.

[Comparison of time-oriented cost accounting catalogs to control a department of radiology]. / Vergleich zeitorientierter Leistungskataloge zum Controlling einer radiologischen Abteilung.

PURPOSE: Within a hospital, the radiology department has taken over the role of a cost center. Cost accounting can be applied to analyze the costs for the performance of services. By assigning the expenditures of resources to the service, the cash value can directly be distributed to the costs of equipment, material and rooms. Time-oriented catalogs of services are predefined to calculate the number of the employees for a radiology department. Using our own survey of time data, we examined whether such catalogs correctly represent the time consumed in a radiology department. Only services relevant for the turnover were compared. MATERIALS AND METHODS: For 96 primary radiological services defined by the score-oriented German fee catalog for physicians (Gebuhrenordnung fur Arzte), a ranking list was made for the annual procedures in descending frequency order. According to the Pareto principle, the 11 services with the highest frequency were chosen and the time consumed for the technical and medical services was collected over a period of 2 months. This survey was compared with the time-oriented catalogs TARMED and EBM 2000plus. RESULTS: The included 11 relevant radiological services represented 80.3 % of the annual procedures of our radiology department. When comparing the technical services between the time-oriented catalogs and our own survey, TARMED gives a better description of the time consumed in 7 of the 11 services and EMB 2000plus in 3 services. When comparing the medical services, TARMED gives a better description of the time consumed in 6 of the 11 services and EBM 2000plus in 4 services. When averaging all the radiological services, TARMED overestimates the current number of physicians necessary for primary reading by a factor of 10.0 % and EBM 2000plus by a factor of 2.6 %. CONCLUSION: As to the time spent on performing the relevant radiological services, TARMED is slightly superior to describe the radiology department of a hospital than EBM 2000plus. For calculating the number of physicians necessary for primary reading, EBM 2000plus is superior to TARMED.

Thyroid function and circulating antithyroid antibodies in myasthenia gravis.

Evaluation of thyroid function in 104 patients with myasthenia gravis by T3, T4, TBG, and TSH radioimmunoassays and the TRH-stimulation test in 47 patients disclosed thyrotoxicosis in 5.7%, preclinical hyperthyroidism probably due to autonomously functioning thyroid tissue in about 10% of patients stimulated with TRH, hypothyroidism in 1.9%, and preclinical hypothyroidism in 3.4%. Eighty-four percent were euthyroid. Antithyroid antibody activity was detected by hemagglutination tests. Twelve patients had antithyroglobulin antibodies (Tab), and 28 had antimicrosomal antibodies (Mab). Among the euthyroid myasthenic patients, 7 were Tab-positive and 20 were Mab-positive. Euthyroid antibody-positive patients had a significantly higher TSH response in the TRH stimulation test and may be at high risk for hypothyroidism.

Uptake kinetics of technetium-99m-methoxyisobutylisonitrile and thallium-201 in adult rat heart endothelial and fibroblast-like cells in comparison to myocytes.

Endothelial and fibroblast-like cells comprise 5%-10% of total cardiac cell volume and are more resistant to hypoxia than cardiomyocytes. However, their role in the uptake of radiotracers used for myocardial perfusion imaging has largely been ignored. Net uptake of 201TI and 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi) by cultured rat heart endothelial and fibroblast-like cells and quiescent myocytes was examined. Over a 30-min period, endothelial cells continuously accumulated 99mTc-sestamibi. Initial 201TI accumulation paralleled that of 99mTc-sestamibi; however, after 7 min 201TI accumulation plateaued whereas there was continued slow accumulation of 99mTc-sestamibi. Net uptake of the two radiotracers by fibroblast-like cells was similar to that of 201TI by endothelial cells. In the quiescent myocytes, there was an initial accumulation of both tracers with 201TI net uptake quickly reaching a plateau, whereas 99mTc-sestamibi accumulation continued throughout the 30-min period reaching a level 15-fold greater than that for 201TI. Myocyte uptake of 99mTc-sestamibi was approximately eight times greater than by the endothelial cells when expressed either as activity per mg protein or activity per cell volume. Although significant uptake differences exist among the three cell types, the fact that there is uptake by endothelial and fibroblast-like cells should be considered during image interpretation, particularly in situations in which the hypoxia resistant endothelial and fibroblast-like cells might be the remaining healthiest cell types.

Multiparameter flow cytometry in the diagnosis of a gynaecologic double tumor: a case report.

PURPOSE: An uncommon clinical presentation of metastatic tumor will often lead to additional diagnostic examinations. The patient of the present study was known to have endometrial cancer which was thought to be limited to the endometrium. Three months postoperatively, she developed ascites due to spread of the tumor, which is rarely seen in low-stage endometrial cancer. METHOD: Multiparameter flow cytometry using both cell phenotype information and DNA ploidy was performed. RESULTS: Retrospectively, the patient was diagnosed as having a DNA-diploid epithelial tumor of the endometrium as well as a DNA-aneuploid epithelial tumor in the left fallopian tube. It was shown that 3 months after primary surgery she developed ascites caused by metastatic tumor from the primary fallopian tube cancer. CONCLUSION: The complete diagnosis was made using multiparameter flow cytometry which, at present, is not routinely applied in gynecologic pathology.

Contrast-enhanced magnetic resonance angiography of mammary artery grafts after minimally invasive coronary bypass surgery.

BACKGROUND: The aim of the study was to investigate the application of the contrast-enhanced magnetic resonance angiography (CE-MRA) for the visualization of left internal mammary artery (LIMA) bypass. METHODS: A total of 30 patients with LIMA bypass (22 men, 8 women, 35 to 77 years) received a CE-MRA 4 to 20 days after surgery. The non-ECG-triggered CE-MRA was performed during expiration using a body array coil at a 1.5 Tesla scanner (Magnetom-Vision). A three-dimensional gradient-echo sequence with slice interpolation technique was applied. For the three-dimensional visualization, single coronal slices were postprocessed with maximal intensity projection. Of 30 patients 22 agreed to a comparative coronary angiography. RESULTS: Five bypasses were identified up to the end-to-side anastomosis. A total of 80% of the bypass course was detectable in 13 patients and 60% in 11 patients. In two LIMA bypasses only 30% of the proximal part could be viewed; one was found by conventional coronary angiography to be occluded. The other conventional coronary angiography showed the LIMA bypass to be patent. CONCLUSIONS: The complete course of the LIMA bypass to the left anterior descending coronary artery can be visualized by the MRA technique. The most reliable imaging of the distal anastomosis can be realized by reducing the negative influence of the beating heart.

Clinical significance of serum and CSF findings in the Guillain-Barré syndrome and related disorders.

Clinical data and the serum and cerebrospinal fluid (CSF) findings of 71 patients with Guillain-Barré syndrome (GBS), 7 with Fisher syndrome and 24 with chronic inflammatory polyradiculoneuropathy (CIP), were analysed. Isoelectric focusing of serum and CSF together with different formulae and diagrams were applied to study blood-CSF barrier (BCB) function and possible intrathecal IgG synthesis. The CSF total protein concentration and its IgG percentage depended mainly on the degree of BCB damage, which correlated with the clinical course. Our investigations suggest that oligoclonal IgG of CSF from these patients comes essentially from serum. In the group of GBS patients, oligoclonal IgG was transitory and correlated significantly with the development of BCB damage, cranial neuritis and severity of the disease. CIP patients showed a stable IgG pattern, which varied slightly after immunosuppressive therapy.

Treatment of Lyme borreliosis. Randomized comparison of doxycycline and penicillin G.

Seventy-five patients with neurological symptoms of Lyme borreliosis were randomly assigned to intravenous treatment with either penicillin G or doxycycline. After 12 months the treatments were equally effective regarding the clinical picture and laboratory findings. No patient was considered to be a treatment failure. However, one-third of the patients showed delayed recovery, particularly after a longer primary disease duration. A slow recovery, lasting years, was typical of subacute or chronic borreliosis.

Splenectomy in myasthenia gravis: a therapeutic concept?

The case histories are presented of five patients with long-diagnosed myasthenia gravis (up to 15 years) who underwent splenectomy. A precondition for the decision to operate was muscle weakness that could not be controlled with standard therapy (e.g. anticholinesterase drugs, immunosuppressive measures). After splenectomy, a considerable improvement took place in three cases; in one case there was moderate improvement, and in another, no improvement. The alleviation of myasthenia gravis may be attributable to the reduction of either the number of immunocompetent lymphocytes in an important storage organ or of the total bulk of the immune system in an immune disease with raised auto-antibody production. The acetylcholine receptor antibody titre was not affected by the operation in a consistent way. After splenectomy, immunosuppressive medication was tolerated better with respect to its haematological side-effects.

Histopathological findings in the central and peripheral nervous systems in neuroborreliosis. A report of three cases.

Very little is known about tissue changes and pathophysiological mechanisms in Garin-Boujadoux-Bannwarth syndrome. We report histopathological findings in the central and peripheral nervous systems of three typical cases. In the acute stage of the disease mononuclear perivascular infiltrations with mainly T-helper cells were the prominent finding, whereas after treatment there was no vessel involvement. The fibre changes in the peripheral nervous system consisted of axonal degeneration. No Borrelia burgdorferi-specific antigen could be detected by immunohistochemical methods. Thus vasculitis might be one of the primary pathophysiological mechanisms for the involvement of the nervous system.

Transient muscular weakness in severe recessive myotonia congenita. Improvement of isometric muscle force by drugs relieving myotomic stiffness.

The maximum force of voluntary muscle contraction was registered under isometric conditions in nine patients with recessive myotonia congenita. The recordings were made on the upper arm. Five patients with severe myotonia had a transient weakness after muscle rest. Electromyographic registrations with wire electrodes showed that the myotonic muscle fiber discharges disappeared during the transient weakness. Medication improving myotonic stiffness also improved the weakness. The cause of transient weakness seems to be similar to that of myotonic stiffness. It is known that an increasing depolarization of the myotonic muscle fiber membrane leads to the myotonic discharges and myotonic stiffness. In severe myotonia the progressing depolarization could cause a loss of excitability of the muscle fiber membrane and thereby a transient paresis of a more or less large number of muscle fibers.

Serum myoglobin in primary and secondary skeletal muscle disorders.

Serum myoglobin was measured by a sensitive radioimmunoassay in healthy controls and patients with primary and secondary skeletal muscle disorders. The results indicate that serum myoglobin is a useful parameter in the assessment of muscle damage.