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Purpose: There are only limited data on drug utilization patterns in pediatric inpatients, especially on general wards. The aim of the study was to describe prescribing patterns and their associations with prescribing errors in a university children’s hospital in the German-speaking part of Switzerland. Method: This was a subanalysis of a retrospective single-center observational study. Patient characteristics and drug use of 489 patients with 2693 drug prescriptions were associated with prescribing errors. Drugs were categorized by the Anatomic Therapeutic Chemical Classification System (ATC), patients were categorized by age group according to European Medicines Agency guidelines, and prescribing errors were analyzed by type [Pharmaceutical Care Network Europe (PCNE) classification] and severity of error [adapted National Coordinating Council for Medication Error Reporting (NCC MERP) index]. Results: The most frequently prescribed ATC classes were nervous system (N) (42.6%), alimentary system (A) (15.6%), and anti-infective drugs (J) (10.7%). Eighty-two percent of patients were prescribed an analgesic. Most drugs were prescribed for oral (47%) or intravenous (32%) administration, but the rectal route was also frequent (10%). The most frequently prescribed drugs were paracetamol, metamizole, and ibuprofen. The high number of metamizole prescriptions (37% of patients were prescribed metamizole) is typical for German-speaking countries. Older pediatric patients were prescribed more drugs than younger patients. A statistically significant difference was found in the rate of potentially harmful errors across age groups and for gender; children between 2 and 11 years had a higher rate of potentially harmful errors than infants under 2 years (p= 0.029) and female patients had a higher rate of potentially harmful errors than male patients (p= 0.023). Recurring errors were encountered with certain drugs (nalbuphine, cefazolin). Conclusions: Our study provides insight into prescribing patterns on pediatric general wards in a university children’s hospital in Switzerland and highlights some areas for future research. Especially, the higher risk for prescribing errors among female pediatric patients needs further investigation.

Research provides ample evidence that positive social relations and access to knowledge are supportive for educational change. However, few studies have examined how personnel turnover and restructuring in school districts influence these processes, specifically as they relate to leaders’ access to research evidence and perception of organizational learning and culture. In this longitudinal exploratory mixed-methods case study, we examine the changes in social networks and organizational learning among school and district leaders during a 3-year district restructuring process. Our study uses social network analysis, bivariate analyses, and qualitative coding. We surveyed district and school leaders about their districts’ capacity for organizational learning, organizational culture, and social ties around research evidence. Our results suggest a decrease in the district’s capacity to diffuse ideas from research between Years 1 and 3, which may inhibit efforts for improvement. Further, the data on school and district leaders who did not leave the district indicates a decrease in the perception of organizational learning and culture in school sites, but not in the district with differences between principals and central office staff. Qualitative findings support an association between the restructuring and changes in organizational learning and social structures and provide further reasons for the changes (e.g., lack of communication, time to maintain/build relationships, and opportunities for professional development). These findings speak to the importance of leaders focusing on the social side of change during times of churn, including strengthening trust, fostering collective values and beliefs, and countering division.

Purpose: The study analyzes how equity-focused knowledge brokers, working at different levels of the US education system, understand and discuss capacity building in education systems, such as schools, districts, state and local education agencies, to answer this research question: How do equity-focused knowledge brokers support capacity building in education systems? Design/methodology/approach: Semi-structured interviews were conducted with five well-known equity-focused organizations that broker evidence-based knowledge and resources to educational systems, practitioners and policymakers. The research team members qualitatively analyzed 18 h of recordings, using their co-developed codebook based on the research questions and prior research on knowledge mobilization. Findings: Four strategies to build capacity within the educational systems were identified. Pursuing sustainable educational change, brokering organizations built capacity with context-specific strategies: (1) engaging various roles within educational systems, (2) fostering communities and partnerships, (3) supporting educators and policymakers’ agency and efficacy and (4) creating a wider culture of external support beyond the systems themselves. Originality/value: This study shows how knowledge brokers employed context-specific strategies targeting whole systems instead of individuals to ensure that the organization and individuals within had the mindsets, capability, and conditions to engage with and adapt the brokered knowledge and resources. Findings build on existing literature showing how knowledge brokers build capacity through well-known approaches, such as workshops/training, online tutorials and other online resources.

Background: Indapamide can cause hypokalaemia and hyponatraemia. Rhabdomyolysis associated with these electrolyte abnormalities has been reported. Objective: The aim of this study was to assess causal association between the use of indapamide and the occurrence of rhabdomyolysis using the Bradford Hill criteria. Methods: Variables in the rhabdomyolysis case reports and literature were reviewed. Bradford Hill criteria were used in the assessment of causal association. Results: Up to 11 November 2020, there were 28 unique cases in VigiBase from 13 countries reporting indapamide-associated rhabdomyolysis. In 18 of these cases, hypokalaemia (n= 14) or hyponatremia (n= 8) was a co-reported event, including four cases where both of these events were reported. Indapamide was the only suspected drug in nine of these 18 cases and positive dechallenge was mentioned in 13 of them. In addition, there were risk factors such as falls, concomitant drugs with risk of hypokalaemia, or muscle injury. In two cases, liquorice (containing glycyrrhizin) was concomitantly used with indapamide before hypokalaemia and rhabdomyolysis occurred. Thiazide diuretics, known to cause hypokalaemia, showed similar disproportionality patterns as indapamide regarding rhabdomyolysis and myopathy, while calcium channel blockers (not causing hypokalaemia), had lower disproportionality values than indapamide. Conclusions: Based on the review of case series and causality assessment using Bradford Hill criteria, indapamide may cause rhabdomyolysis due to hypokalaemia or hyponatremia. Considering the seriousness of the reported cases, health care professionals should be aware of this potential risk following indapamide intake, particularly when there are risk factors for hypokalaemia and hyponatremia such as excessive liquorice consumption. A similar risk of muscle injuries may apply to thiazide diuretics as well.

Surface-attached microbial communities constitute a vast amount of life on our planet. They contribute to all major biogeochemical cycles, provide essential services to our society and environment, and have important effects on human health and disease. They typically consist of different interacting genotypes that arrange themselves non-randomly across space (referred to hereafter as spatial self-organization). While spatial self-organization is important for the functioning, ecology, and evolution of these communities, the underlying determinants of spatial self-organization remain unclear. Here, we performed a combination of experiments, statistical modeling, and mathematical simulations with a synthetic cross-feeding microbial community consisting of two isogenic strains. We found that two different patterns of spatial self-organization emerged at the same length and time scales, thus demonstrating pattern diversification. This pattern diversification was not caused by initial environmental heterogeneity or by genetic heterogeneity within populations. Instead, it was caused by nongenetic heterogeneity within populations, and we provide evidence that the source of this nongenetic heterogeneity is local differences in the initial spatial positionings of individuals. We further demonstrate that the different patterns exhibit different community-level properties; namely, they have different expansion speeds. Together, our results demonstrate that pattern diversification can emerge in the absence of initial environmental heterogeneity or genetic heterogeneity within populations and can affect community-level properties, thus providing novel insights into the causes and consequences of microbial spatial self-organization.

Surface-attached microbial communities constitute a vast amount of life on our planet. They contribute to all major biogeochemical cycles, provide essential services to our society and environment, and have important effects on human health and disease. They typically consist of different interacting genotypes that arrange themselves non-randomly across space (referred to hereafter as spatial self-organization). While spatial self-organization is important for the functioning, ecology, and evolution of these communities, the underlying determinants of spatial self-organization remain unclear. Here, we performed a combination of experiments, statistical modeling, and mathematical simulations with a synthetic cross-feeding microbial community consisting of two isogenic strains. We found that two different patterns of spatial self-organization emerged at the same length and time scales, thus demonstrating pattern diversification. This pattern diversification was not caused by initial environmental heterogeneity or by genetic heterogeneity within populations. Instead, it was caused by nongenetic heterogeneity within populations, and we provide evidence that the source of this nongenetic heterogeneity is local differences in the initial spatial positionings of individuals. We further demonstrate that the different patterns exhibit different community-level properties; namely, they have different expansion speeds. Together, our results demonstrate that pattern diversification can emerge in the absence of initial environmental heterogeneity or genetic heterogeneity within populations and can affect community-level properties, thus providing novel insights into the causes and consequences of microbial spatial self-organization.

Container-based sanitation (CBS) within a comprehensive service system value chain offers a low-cost sanitation option with potential for revenue generation but may increase microbial health risks to sanitation service workers. This study assessed occupational exposure to rotavirus and Shigellaspp. during CBS urine collection and subsequent struvite fertilizer production in eThekwini, South Africa. Primary data included high resolution sequences of hand-object contacts from annotated video and measurement of fecal contamination from urine and surfaces likely to be contacted. A stochastic model incorporated chronological surface contacts, pathogen concentrations in urine, and literature data on transfer efficiencies of pathogens to model pathogen concentrations on hands and risk of infection from hand-to-mouth contacts. The probability of infection was highest from exposure to rotavirus during urine collection (∼10–1) and struvite production (∼10–2), though risks from Shigellaspp. during urine collection (∼10–3) and struvite production (∼10–4) were non-negligible. Notably, risk of infection was higher during urine collection than during struvite production due to contact with contaminated urine transport containers. In the scale-up of CBS, disinfection of urine transport containers is expected to reduce pathogen transmission. Exposure data from this study can be used to evaluate the effectiveness of measures to protect sanitation service workers.

Medical anthropology is a social science that uses qualitative methods to better understand how people in different parts of the world perceive and experience illness. This field of study emphasizes research approaches that humanize and add richness to our understanding of cancer in complex settings.

Zusammenfassung.Die neusten Erkenntnisse zu der Pathogenese des Zervixkarzinoms führten zu Anpassungen in der zytologischen und histologischen Nomenklatur seiner Vorstufen. Die aktuelle, 2014 eingeführte histologische WHO-Terminologie unterscheidet, analog zum zytologischen Bethesda-System, zwischen zwei histologischen Stufen der HPV-bedingten Veränderungen: LSIL und HSIL, die mit unterschiedlichen Risiken der Progredienz zum invasiven Karzinom einhergehen und klinisch entsprechend unterschiedlich gehandhabt werden sollen. Die immunhistochemische Detektion des p16-Proteins als Surrogat der neoplastischen Transformation der HPV-infizierten Zellen hilft, die rein mikroskopische Diagnose zu objektivieren und zu sichern, und ist ein wichtiges Hilfsmittel in der Histopathologie. Die Verfügbarkeit der HPV-Impfung und die HPV-Detektion werden in den kommenden Jahren die Abläufe in der Frühentdeckung und die Epidemiologie der Zervixkarzinom-Vorstufen beeinflussen.

Durich Chiampell's (c. 1510 - c. 1581) »Raetiae alpestris topographica descriptio « deals with the geography of the Republic of the Three Leagues - today the region of Graubünden - in a manner influenced to such a high degree by rhetorical principles that it is rather a mise-en-scene constructed to transmit a certain view of his subject rather than objective knowledge. The article shows this in the chosen examples relating to geography and history. The criticism he faced by his orderers in Zurich were refuted by Chiampell with arguments drawn from contemporary historiography. [ABSTRACT FROM AUTHOR]

To assess adverse drug reaction reports of "abnormal sleep related events" associated with varenicline, a partial agonist to the α4β2 subtype of nicotinic acetylcholine receptors on neurones, indicated for smoking cessation.

An immunocompetent 9-year-old boy with disseminated catscratch disease involving spleen, cervical and abdominal lymph nodes, skull, and one clavicle is reported. Antibodies toRochalimaea quintanaandR. henselaewere detected, at increasing, then decreasing concentration. DNA extracted from the biopsied skull lesion was amplified by polymerase chain reaction and hybridized with species-specific oligonucleotides proving the presence ofR. henselaein affected tissue. Our findings suggest thatR. henseleaplays a pathogenic role in cat-scratch disease.

Ameloblastic fibro-odontoma (AFO) is a rare benign tumor which contributes to 1–3% of all odontogenic tumors. AFO is mainly localized in the posterior region of the mandible and typical patients are children who present to their dentists due to non-erupting teeth. We describe an unusual example of a large AFO located in the upper right maxilla and maxillary sinus of a 3-year-old girl. The aims of this case report are to strengthen the knowledge of and to stimulate the discussion about AFO and to point out, that a conservative surgical procedure with regular follow up is highly recommended.

Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep-infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.

Mutations of the tumor-suppressor gene ARID1Aresult in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1Amutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep-infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.

Recent studies of the minute morphology of the skin by optical coherence tomography showed that the sweat ducts in human skin become helically shaped tubes in the Epidermis and are filled with an aqueous solution. When considered as entities embedded in a dielectric media, they resemble helical antennas. The spectral response obtained by our computer simulations coincides with the analytical prediction of antenna theory and support this hypothesis, if a fast enough current mechanism exists in the duct. In particular the strongest spectral response of the simulation was noted around the predicted frequencies (240 GHz and 380 GHz) for the respective normal and axial modes of the helical structure. Furthermore, circular dichroism of the reflected electromagnetic field is a characteristic property of such helical antennas and it was shown that it is indeed a characteristic of the simulation model. Fast proton hopping is posited as the current mechanism. Consequently experimental evidence is presented that the spectral response of the skin in the sub-Terahertz region is governed by the level of activity of the perspiration system. This in turn is moderated by the Sympathetic Nerve Response and is demonstrated by the correlation to physiological stress as manifested by the pulse rate and the systolic blood pressure. These physical relaxations are tonic in nature (lasting more than a minute). Could the phasic characteristic of emotional excitation also be evident in the reflection coefficient? By applying techniques borrowed from psychiatric science we hope to answer this point in our paper.

AbstractThe low strain-rate behavior of the human myometrium under compression was determined. To this end, uniaxial, unconstrained compression experiments were conducted on a total of 25 samples from three excised human uteri at strain rates between 0.001 s-1and 0.008 s-1. A three-dimensional finite element model of each sample was created and used together with an optimization algorithm to find material parameters in an inverse estimation process. Friction and shape irregularities of samples were incorporated in the models. The uterine specimens in compression were modeled as viscoelastic, non-linear, nearly incompressible and isotropic continua. Simulations of uniaxial, frictionless compressions of an idealized cuboid were used to compare the resulting material parameters among each other. The intra- and inter-subject variability in stiffness of specimens was found to be large and to cover such a wide range that the effect of anisotropy which is of minor influence under compressive deformations in the first place could be neglected. Material parameters for a viscoelastic model based on a decoupled, reduced quadratic strain-energy function were presented for the uterine samples representing a median stiffness.

Background: Glucose measurement from different skin areas might be influenced by changes in skin texture due to several environmental confounders. Our study was performed to investigate the effect of changes in ambient temperature on skin thickness and microvascular skin blood flow in subjects with and without diabetes at the lower forearm.Methods: Thirteen subjects with diabetes and seven without diabetes participated in the study. The investigations were performed in a temperature- and humidity-controlled climatic chamber (EMPA, St. Gallen, Switzerland). Starting at 25°C, the environmental temperature was changed in 4°C steps every 40 min. Skin thickness was measured by an ultrasonic reflection technique, and microcirculation was measured by laser Doppler fluxmetry at the lower forearm. Study participants underwent the entire procedure on up to four separate study trials.Results: Our study revealed a significantly reduced skin thickness (P < 0.05) and microvascular blood flow (P < 0.05) in patients with diabetes mellitus compared with controls without diabetes during the entire investigation. During declining ambient temperature a significant reduction in skin thickness (with diabetes, –0.09 ± 0.13 mm; without diabetes, –0.06 ± 0.11 mm; P < 0.05) and microvascular blood flow (with diabetes, –41 ± 49 arbitrary units; without diabetes, –46 ± 51 arbitrary units; P < 0.05) could be observed in both groups without significant differences between the two.Conclusions: Although skin thickness and microvascular skin blood flow at the lower forearm were found to be reduced in patients with diabetes compared with controls without diabetes, both groups revealed comparable dynamics in skin thickness and microvascular blood flow during changes in environmental temperature.

The global muscle and collagen fiber orientation in the human uterus has been analyzed hitherto by various standard microscopic techniques. However, no widely accepted model of the fiber architecture of the myometrium could be acquired. The purpose of the present study was to investigate the uterus by magnetic resonance (MR) diffusion tensor imaging (DTI) in a 3D macroscopic approach. Ex vivo MR DTI measurements were performed on five uteri from nonpregnant patients. The main diffusion directions reflecting the orientation of directional structures in the examined tissues were determined from diffusion-weighted spin-echo measurements. A fiber tracking algorithm was used to extrapolate the fiber architecture. The method was validated against histological slides and indirectly through the analysis of leiomyomas, which exhibit less anisotropy than normal myometrium. Significant anisotropy was found in most regions of all examined nonpregnant human uteri. But only two systems of fibers were found running circularly along the intramural part of the uterine tubes. They merged caudally and built a close fitting envelope of circular layers around the uterine cavity. On the cervix, circular fibers were observed in the outer part as well as mostly longitudinal fibers in the inner part. These results confirm the existence of directional structures in the complex fiber architecture of the human uterus. They also indicate that MR DTI is a beneficial and complementary tool to standard microscopic techniques to determine the intrinsic fiber architecture in human organs. © 2005 Wiley-Liss, Inc.

Abstract

Primary synovial sarcoma outside its classical presentation in para-articular soft tissue of young patients is rare but regularly reported. One of the rarest primary locations is the lung. We describe a 73-year-old female patient who presented with a solitary malignant bone tumor 8 years after the resection of a lung neoplasm. The bone tumor was classified as an osteosarcoma and the lung tumor as an atypical carcinoid tumor at their first respective diagnostic work-ups. The resection of the affected humerus with allograft and endoprosthesis implantation followed. Reevaluation of the tumor samples at the time of the local recurrence of the bone tumor 6 years following the initial symptoms of the bone tumor lead to the reclassification of both specimens as synovial sarcomas. Both neoplasms contained the SYT-SSX1 type of the diagnostic translocation t(X;18) as detected by the reverse-transcription polymerase chain reaction analysis. The patient died 14 years after the resection of the primary synovial sarcoma of the lung and 6 years following the occurrence of the bone metastasis. This prolonged clinical course is uncommon for the SYT-SSX1 translocation, which, in other locations, is usually associated with an unfavorable prognosis.

Im vorliegenden Artikel wird der Medikamentenverschreibungsprozess von der Erhebung der Anamnese bis hin zur Einnahme bzw. Verabreichung des Medikamentes Schritt für Schritt besprochen. Mit praktischen Beispielen soll dabei auf häufige Fehler eingegangen werden, die sowohl im ambulanten wie auch im stationären Bereich zu Komplikationen führen können.

We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

Impedance spectroscopy allows for the assessment of changes in the permittivity and conductivity of erythrocyte cell membranes, induced by blood glucose variations. This study was performed to evaluate the potential influence of motion-induced microvascular blood flow variations from different forearm postures on the PENDRA® (Pendragon Medical AG, Zürich, Switzerland) signal. Fifteen volunteers without diabetes were included (seven female, eight male, mean ± SD age 33.3 ± 9.9 years, body mass index 24.8 ± 3.0 kg/m2). PENDRA devices were fixed at both upper extremities with different fixation techniques (bracelet and adhesive tape). Standardized position changes of the upper extremities were performed to induce variations in cutaneous microcirculation, which were assessed by laser-Doppler-fluxmetry with different probe temperatures on the forearm. Changes in microcirculation were seen in some of the different motion procedures: supine to hanging, 61.1 ± 29.9 arbitrary units (AU) to 46.2 ± 24.8 AU at 37°C and 15.9 ± 13.0 AU to 13.4 ± 10.1 at skin temperature (P < 0.01 for both probes); supine to upright, 80.5 ± 55.4 AU to 74.9 ± 43.8 AU (not significant) at 37°C and 18.7 ± 16.8 AU to 20.9 ± 16.1 AU at skin temperature (P < 0.01). An initially observed subtle influence of microcirculation variations on the impedance signal was minimized when the device was fixed by both bracelet and tape. Other influencing factors (such as temperature, local anatomy, etc.) are addressed in the complex calibration procedure. Well-educated patients might be the best candidates for first using the device for continuous glucose monitoring. They may especially benefit from the trend indication and the hypoglycemia/hyperglycemia threshold and alarm functions.

The radial artery (RA) is increasingly used as coronary artery bypass graft. In rare cases, however, it is macroscopically atherosclerotic at time of harvest. We examined how the regulation of vascular tone is altered under such circumstances. Macroscopically evident atherosclerotic lesions were observed in 3 of 429 RA (0.7) isolated within 2 years. Histology revealed severe plaque formation; however, von Willebrand Factor staining showed a morphologically intact endothelium (n 3). Endothelium-dependent relaxations to acetylcholine (10−5M) were reduced in atherosclerotic RA (32 ± 6; n 3) as compared with control (78 ± 4; n 10; P0.0001). Receptor-independent contractions to KCl (100 mM) were reduced in atherosclerotic RA (33.19 ± 5.06 mN; n 3) as compared with control (108.02 ± 15.76 mN; n 9; P< 0.05). Similarly, contractions to thrombin (1 U/ml) were reduced in atherosclerotic RA (3.02 ± 1.58 mN; n 3) as compared with control (10.97 ± 5.12 mN; n 8). Likewise, receptor-mediated contractions to norepinephrine were reduced in atherosclerotic RA (27.64 ± 12.48 mN; n 3) as compared with control (82.74 ± 11.36 mN; n 9; P< 0.05). Atherosclerosis is rare in RA of patients with coronary artery disease, but it does occur. Atherosclerotic RA exhibits a dysfunction of both endothelium and vascular smooth muscle. This dysfunction may favor thrombus formation and accelerated atherogenesis. Therefore, atherosclerotic RA should not be used for coronary artery bypass grafting.

The distinction between two primary carcinomas on the one hand and a metastatic disease on the other hand in patients suffering from synchronous endometrioid carcinomas of the uterus and ovary is difficult. Exclusive histopathologic analysis appears to be insufficient and sometimes misleading. The tumor suppressor PTEN was found to be important in early neoplastic transformation in endometrioid carcinomas of the uterus. In this study, we screened synchronous endometrioid carcinomas of the uterus and ovary of 10 patients for loss of heterozygosity using seven different microsatellite markers at 10q23.3 and for mutations in the entire coding region of PTEN. Point mutations or microdeletions/insertions were found in six patients. Allelic loss at 10q23.3 was detected in eight patients. Based on conventional histology, a metastatic disease was diagnosed in seven patients and a concomitant uterine and ovarian carcinoma in three patients. After molecular analysis, the histopathologic diagnosis of three patients had to be revised. Histopathology represents the standard method to process tumor specimens from these patients. Nevertheless, mutation screen for PTEN and LOH analysis at 10q23.3 provide helpful genetic tools to establish a correct final diagnosis, which is important in view of prognosis and therapeutic implications.

During myelin formation, membrane‐associated proteins have to be sorted and transported in specified membrane regions such as compact and non‐compact myelin membranes. One protein that may be involved in such a process is the Myelin and Lymphocyte protein MAL (VIP17/ MVP17). MAL was identified as a novel myelin membrane component expressed by oligodendrocytes and Schwann cells. Since MAL has been shown to be important in the apical sorting machinery of polarized cells, we have started to investigate the possible functional role of MAL in sorting myelin membrane‐associated molecules. In this study, we have generated cDNA constructs with green fluorescent protein (GFP) either at the N‐ or C‐terminus of MAL. Transfection experiments showed that GFP‐MAL expression resembles that of normal MAL, whereas the MAL‐GFP fusion construct was not properly transported within the cell. Furthermore, we could demonstrate that GFP‐MAL is enriched in detergent insoluble glycolipid‐enriched microdomains as already seen for untagged MAL. As a prerequisite for the generation of transgenic mice expressing GFP‐MAL under the control of its own regulatory elements, we have generated a cDNA construct with an 8‐kb MAL promotor fragment fused to GFP‐MAL. Transfection experiments of the Oli‐neuoligodendrocyte cell line showed that GFP‐MAL was expressed, but only in cells, which were stimulated for differentiation with cAMP. In summary, the results confirm that the fusion protein GFP‐MAL is incorporated into detergent‐insoluble complexes and the 8‐kb MAL promotor fragment is sufficient to be activated in oligodendrocytes. Microsc. Res. Tech. 52:645–655, 2001. © 2001 Wiley‐Liss, Inc.

Detailed knowledge of chromosomal aberrations in a specific tumor may facilitate the development of individually tailored chemotherapy, hormone or gene therapy. Unfortunately, karyotype analysis requires living cells and is complicated by the low number of good metaphase spreads obtained. Comparative genomic hybridization (CGH), however, is capable of detecting and mapping genome-wide amplifications and deletions using an equimolar mixture of normal and tumor cell DNA. We show here that even the few cells from a fine needle aspirate of a tumor are sufficient for a direct CGH assay, independent of DNA amplification. Ten primary breast cancers were analyzed by CGH. A fresh frozen fine needle aspirate and a formalin-fixed and paraffin-embedded section were used for each tumor. Metaphases from each CGH reaction were imaged, and a sum ratio profile was determined for every chromosome. The ratio profiles of DNA isolated from the 2 material sources were then compared. Fine needle aspirates and the paraffin-embedded material of a single tumor yielded the same fluorescence ratio profiles, albeit with slightly different confidence intervals. Different tumors showed a variety of aberrations. The most frequently observed changes were 1q+, 8q+, 14q–, 16p+, 16q–, 17p–, 17q+, 19q+, 20q+, 21q– and 22q–. The ability of CGH to assess chromosomal changes in breast cancer from fine needle aspirates could facilitate genetic evaluation of tumors prior to surgery. Int. J. Cancer 88:607–613, 2000. © 2000 Wiley-Liss, Inc.