[Prehospital management of acute coronary syndrome in patients on long-term direct oral anticoagulant treatment]. / Prähospitale Behandlung des akuten Koronarsyndroms unter DOAK-Dauertherapie.

BACKGROUND: Despite an increasing incidence of patients suffering from acute coronary syndrome (ACS) under simultaneous treatment with direct oral anticoagulants (DOAC), neither sufficient scientific data nor uniform guidelines for the anticoagulation treatment of these patients are currently available. OBJECTIVE: The aim of this study was to determine the current practice of preclinical treatment of ACS in patients under DOAC treatment. MATERIAL AND METHODS: An internet and paper-based survey of emergency physicians, specialists of internal medicine, anesthesiologists, emergency and intensive care physicians was performed concerning the prehospital treatment of ACS in patients under long-term DOAC treatment. RESULTS: Overall, 284 questionnaires were answered. Substantial differences in the current treatment of ACS under long-term DOAC therapy were identified. While 39% of the respondents stated that they administer a combination treatment of heparin and acetylsalicylic acid (ASA), 36% renounced the administration of heparin. If a dose reduction was performed, 71% answered that they reduce the heparin dosage. Also, in cases of ST-segment elevation myocardial infarction 48% of the physicians renounced the administration of heparin. CONCLUSION: In Germany there is currently a heterogeneous practice of emergency treatment of ACS patients under DOAC therapy with respect to the administration of heparin and ASA. Therefore, guidelines of the specialist medical societies should address the prehospital emergency anticoagulation management of ACS in patients under therapy with DOAC, which correspond to the needs of patients and emergency physicians.

Prospective Assessment of Radiation in Pediatric Urology: The Pediatric Urology Radiation Safety Evaluation Study.

PURPOSE: Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. MATERIALS AND METHODS: Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. RESULTS: A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). CONCLUSIONS: Pediatric radiation exposure is not insignificant during urological procedures. Further multi-institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives.

Tracking of radiation exposure in pediatric stone patients: The time is now.

BACKGROUND: Despite the increasing incidence of pediatric nephrolithiasis, there is little data quantifying the radiation exposure associated with treatment of this disease. In this study, pediatric patients with nephrolithiasis who were managed at a single institution were identified, and the average fluoroscopy time and estimated radiation exposure associated with their procedures were reported. METHODS: Stone procedures performed on pediatric patients between 2005 and 2012 were retrospectively identified. Procedures were classified as primary ureteroscopy (URS), stent placement prior to ureteroscopy (SURS), percutaneous nephrolithotomy (PCNL), and bilateral ureteroscopy (BLURS). Patient demographic information, stone size, stone location, number of radiographic images, and fluoroscopy times were analyzed. RESULTS: A total of 152 stone procedures were included in the final analysis (92 URS, 38 SURS, eight BLURS and 14 PCNL). Mean patient age at time of stone treatment was 15.94 ± 4.1 years. Median fluoroscopy times were 1.6 (IQR 0.8-2.4), 2.1 (IQR 1.6-3.0), 2.5 (IQR 2.0-2.9), and 11.7 (IQR 5.0-18.5) minutes for URS, SURS, BLURS and PCNL, respectively. There was a moderate correlation between stone size and fluoroscopy time (r = 0.33). When compared with ureteroscopic procedures, PCNL was associated with a significantly higher fluoroscopy time (11.7 vs 2.1 min, P < 0.001). The estimated median effective dose was 3 mSv for ureteroscopic procedures and 16.8 mSv for PCNL. In addition to radiation exposure during treatment, patients in this cohort were exposed to an average of one (IQR1-3) CT scan and three (IQR 1-8) abdominal X-rays. No new malignancies were identified during the limited follow-up period. CONCLUSIONS: Radiation exposure during treatment of pediatric stone disease is not trivial, and is significantly greater when PCNL is performed. Given the recommended maximum effective dose of 50 mSv in any one year, urologists should closely monitor the amount of fluoroscopy used, and consider the potential for radiation exposure when choosing the operative approach. Prospective studies are currently underway to elucidate precise dose measurements and localize sites of radiation exposure in children during stone treatment.

Use of ecological niche models to predict the distribution of invasive species: a scientometric analysis / Uso de modelos de nicho ecológico para predizer a distribuição de espécies invasoras: uma análise cienciométrica

We conducted a scientometric analysis to determine the main trends and gaps of studies on the use of ecological niche models (ENMs) to predict the distribution of invasive species. We used the database of the Thomson Institute for Scientific Information (ISI). We found 190 papers published between 1991 and 2010 in 82 journals. The number of papers was low in the 1990s, but began to increase after 2003. One-third of the papers were published by researchers from the United States of America, and consequently, the USA was also the most studied region. The majority of studies were carried out in terrestrial environments, while only a few investigated aquatic systems, probably because important aquatic predictor variables are scarce or unavailable for most regions in the world. Species-occurrence records were mainly composed of presence-only records, and almost 70% of the studies were carried out with plants and insects. Twenty-three different distribution modelling methods were used. The Genetic Algorithm for Rule-set Production (GARP) was used most often. Our scientometric analysis showed a growing interest in the use of ENMs to predict the distribution of invasive species, especially in the last decade, which is probably related to the increase in species introductions worldwide. Among some important gaps that need to be filled, the relatively small number of studies conducted in developing countries and in aquatic environments deserves careful attention.

Conduziu-se uma análise cienciométrica para determinar as principais tendências e lacunas de estudos sobre o uso de modelos de nicho ecológico (MNEs) para predizer a distribuição de espécies invasoras. Usou-se a base de dados Thomson Institute for Scientific Information (ISI). Foram encontrados 190 artigos publicados entre 1991 e 2010, em 82 periódicos. O número de trabalhos foi baixo na década de 1990, mas começou a aumentar após 2000. Um terço dos trabalhos foi publicado por pesquisadores dos Estados Unidos da América e, consequentemente, os Estados Unidos também foram a região mais estudada. A maioria dos estudos foi realizada em ambientes terrestres. Apenas alguns sistemas aquáticos foram investigados, provavelmente porque importantes variáveis preditoras aquáticas são escassas ou inexistentes na maioria das regiões do mundo. Registros de ocorrência de espécies foram compostos principalmente por registros de presença (ou seja, sem registros de ausência) e quase 70% dos estudos foram realizados com plantas e insetos. Vinte e três diferentes métodos de modelagem foram utilizados. O Algoritmo Genético para Produção de Conjunto de Regras (GARP) foi o mais utilizado. Esta análise cienciométrica mostrou um interesse crescente no uso de MNEs para prever a distribuição de espécies invasoras, especialmente na última década, estando esse aumento provavelmente relacionado ao crescimento na introdução de espécies em todo o mundo. Entre algumas lacunas importantes que precisam ser preenchidas, destaca-se o número relativamente pequeno de estudos realizados em países em desenvolvimento e em ambientes aquáticos.

Use of ecological niche models to predict the distribution of invasive species: a scientometric analysis.

We conducted a scientometric analysis to determine the main trends and gaps of studies on the use of ecological niche models (ENMs) to predict the distribution of invasive species. We used the database of the Thomson Institute for Scientific Information (ISI). We found 190 papers published between 1991 and 2010 in 82 journals. The number of papers was low in the 1990s, but began to increase after 2003. One-third of the papers were published by researchers from the United States of America, and consequently, the USA was also the most studied region. The majority of studies were carried out in terrestrial environments, while only a few investigated aquatic systems, probably because important aquatic predictor variables are scarce or unavailable for most regions in the world. Species-occurrence records were mainly composed of presence-only records, and almost 70% of the studies were carried out with plants and insects. Twenty-three different distribution modelling methods were used. The Genetic Algorithm for Rule-set Production (GARP) was used most often. Our scientometric analysis showed a growing interest in the use of ENMs to predict the distribution of invasive species, especially in the last decade, which is probably related to the increase in species introductions worldwide. Among some important gaps that need to be filled, the relatively small number of studies conducted in developing countries and in aquatic environments deserves careful attention.

Spectral reflectance and responsivity of Ge- and InGaAs-photodiodes in the near-infrared: measurement and model.

The spectral reflectance and responsivity of Ge- and InGaAs-photodiodes at (nearly) normal and oblique incidence (45 degrees) were investigated. The derived data allow a calculation of the photodiodes responsivities for any incident angle. The measurements were carried out with s- and p-polarized radiation in the wavelength range from 1260 to 1640 nm. The spectral reflectance of the photodiodes was modeled by using the matrix approach developed for thin-film optical assemblies. The comparison between the calculated and measured reflectance shows a difference of less than 2% for the Ge-photodiode. For the InGaAs-photodiode, the differences between measured and calculated reflectance are larger, i.e., up to 6% for wavelengths between 1380 and 1580 nm. Despite the larger differences between calculated and measured spectral reflectances for the InGaAs-photodiode, the difference between calculated and measured spectral responsivity is even smaller for the InGaAs-photodiode than for the Ge-photodiode, i.e., < or =1.2% for the InGaAs-photodiode compared to < or =2.2% for the Ge-photodiode. This is because the difference in responsivity is strongly correlated to the absolute spectral reflectance level, which is much lower for the InGaAs-photodiode. This observation also shows the importance of having small reflectances, i.e., appropriate antireflection coatings for the photodiodes. The relative standard uncertainty associated with the modeled spectral responsivity is about 2.2% for the Ge-photodiode and about 1.2% for the InGaAs-photodiode for any incident angle over the whole spectral range measured. The data obtained for the photodiodes allow the calculation of the spectral responsivity of Ge- and InGaAs-trap detectors and the comparison with experimental results.

Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism.

Cryptorchidism is a common anomaly of male sexual differentiation. Two phases of testicular descent are recognized, transabdominal and inguinoscrotal. With evidence that androgens and Müllerian inhibitory hormone were not completely responsible for testicular descent, the existence of a third testicular hormone mediating testicular descent was postulated. Insulin-like 3 (INSL3) [also known as relaxin-like factor (RLF) and Leydig insulin-like protein (LEY I-L)] is a member of the insulin/relaxin hormone superfamily that is highly expressed in Leydig cells. The phenotype of transgenic mice with targeted deletion of the Insl3 gene was bilateral cryptorchidism with morphological evidence of abnormal gubernacular development. With this implicit evidence that Insl3 mediates testicular descent in mice, we performed mutation detection analysis of the coding regions of the 2 exon INSL3 gene in genomic DNA samples obtained from 145 formerly cryptorchid patients and 36 adult male controls. Single-strand conformational polymorphism analysis was used for the mutation detection studies. Two mutations, R49X and P69L, and several polymorphisms were identified. Both mutations were located in the connecting peptide region of the protein. The frequency of INSL3/RLF gene mutations as a cause of cryptorchidism is low, because only 2 of 145 (1.4%) formerly cryptorchid patients were found to have mutations.

Work of breathing during spontaneous ventilation in anesthetized children: a comparative study among the face mask, laryngeal mask airway and endotracheal tube.

Work of breathing (WOB) increases during general anesthesia in adults, but such information has been limited in pediatric patients. We studied WOB in 24 healthy children (mean age 2+/-1.9 yrs), during elective urogenital surgery under 1 minimum alveolar anesthetic concentration halothane-nitrous oxide anesthesia with a caudal block while breathing spontaneously. WOB was measured with an esophageal balloon, miniature flowmeter, and a computerized (Bicore) system. In each patient, WOB was computed under four conditions: a mask without oral airway (-AW), a mask with oral airway (+AW), a laryngeal mask airway (LMA), and an endotracheal tube (ETT). With each apparatus WOB was studied both with continuous positive airway pressure (CPAP) (5-6 cm H(2)O) and without CPAP (or zero end-expiratory pressure [ZEEP]). Under ZEEP, WOB (g x cm/kg) among the four apparatus were (mean +/- SEM): mask (-AW) (64 +/-19.2) > mask (+AW) (44+/-17.2), LMA (42+/-15.6) > ETT (25.4+/- 12.4) (P<0.05). WOB with CPAP significantly (P<0.05) decreased from WOB with ZEEP in three groups (mask [-AW], mask [+AW], and LMA), but not in the ETT group. Tidal volume (both ZEEP and CPAP) and end-tidal PCO(2) (with CPAP only) were significantly (P<0.05) decreased only in the ETT group, whereas no significant difference was found in respiratory rate or minute volume among the four airway apparatus groups, either with or without CPAP. The reduction in WOB, when breathing through ETT was primarily attributable to decreases in tidal volume and volume work. The finding that WOB decreases with CPAP in all groups except for the ETT group suggests that the decrease is a result of improved patency of the upper airway rather than of increases in functional residual capacity and lung compliance.

Absence of microdeletions in the Y chromosome in patients with a history of cryptorchidism and azoospermia or oligospermia.

OBJECTIVE: To determine if cryptorchidism is associated with microdeletions of interval 6 of the Y chromosome, we evaluated this locus in men with a history of cryptorchidism with and without azoospermia or oligospermia and in a control group. DESIGN: Clinical study. SETTING: Academic research environment. PATIENT(S): Men in whom surgical treatment of cryptorchidism had been performed in childhood and healthy control male subjects. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genotyping of interval 6 of the Y chromosome. RESULT(S): Analysis of semen obtained from men treated for cryptorchidism in childhood showed azoospermia or oligospermia in 14 of 38 (37%) men. No microdeletions were identified with polymerase chain reaction amplification of 17 distinct sequence tagged sites located on the long arm of the Y chromosome and the sex determining region on Y (SRY) gene. CONCLUSION(S): Microdeletions of interval 6 of the Y chromosome were not detected in either the formerly cryptorchid or in the healthy subjects. Although we cannot exclude the possibility of point mutations, we conclude that cryptorchidism or cryptorchidism associated with azoospermia or oligospermia is not due to microdeletions involving interval 6 of the Y chromosome.

Embryonal adenoma of the kidney associated with polycythemia and von Willebrand disease.

PURPOSE: We studied the significance, identification and management of acquired von Willebrand disease and polycythemia associated with benign renal tumors in children. MATERIALS AND METHODS: Two patients who presented with polycythemia and a renal mass were also found to have acquired von Willebrand disease. One patient was treated with radical nephrectomy and 1 was treated with partial nephrectomy. The patients have been followed for 19 and 10 months, respectively. RESULTS: Excision of the renal mass resulted in prompt resolution of polycythemia and von Willebrand disease in each patient. Perioperatively 1-deamino-(8-D-arginine)-vasopressin was given to control bleeding. Each patient had benign embryonal adenoma of the kidney. CONCLUSIONS: Polycythemia and von Willebrand disease may be associated with benign kidney neoplasms. Children and adolescents with a renal mass may benefit from preoperative screening for coagulopathy.

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases.

Spontaneous vesicle formation at lipid bilayer membranes.

Unilamellar vesicles are observed to form spontaneously at planar lipid bilayers agitated by exothermic chemical reactions. The membrane-binding reaction between biotin and streptavidin, two strong transmembrane neutralization reactions, and a weak neutralization reaction involving an "antacid" buffer, all lead to spontaneous vesicle formation. This formation is most dramatic when a viscosity differential exists between the two phases bounding the membrane, in which case vesicles appear exclusively in the more viscous phase. A hydrodynamic analysis explains the phenomenon in terms of a membrane flow driven by liberated reaction energy, leading to vesicle formation. These results suggest that energy liberated by intra- and extracellular chemical reactions near or at cell and internal organelle membranes can play an important role in vesicle formation, membrane agitation, or enhanced transmembrane mass transfer.

Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis.

CD3+ peripheral blood T lymphocytes were evaluated for expression of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and potent angiogenic factor. VEGF mRNA expression was confirmed in CD3+ cells and Jurkat cells, a human T-cell line, by reverse transcription-PCR and in CD4+ and CD8+ T cell subtypes by Northern blot hybridization. Steady-state levels of VEGF mRNA were inducible in CD3+ T cells by hypoxia, a known inducer of VEGF mRNA accumulation. Secreted VEGF was detected in CD4+ and CD8+ T cell- and Jurkat cell-conditioned medium, indicating that T lymphocytes are capable of exporting bioactive concentrations of VEGF into the extracellular space. Human prostate and bladder cancers (prostatic adenocarcinoma and transitional cell carcinomas) were evaluated for VEGF mRNA expression by in situ hybridization. Tumor-infiltrating lymphocytes (TIL), identifiable immunocytochemically as T cells, along with tumor cells in these cancers, expressed VEGF mRNA. TIL in bladder cancers could be labeled with a specific anti-VEGF mAb, indicating that TIL are likely to be able to secrete VEGF protein in situ at bioactive concentrations. The finding that peripheral T cells and TIL in human tumors synthesize a factor known to be a specific mediator of neovascularization suggests a role for T lymphocytes as cellular effectors of angiogenesis.

Phenotypic and cytogenetic characterization of human bladder urothelia expanded in vitro.

A simple method for the harvest of bladder cell types from surgical specimens was used to generate strains of normal human urothelial cells that could be reproducibly cultivated, passaged and extensively expanded in serum-free medium. Immunostaining of the bladder epithelial cells with broadly reacting anti-cytokeratin antibodies and with an anti-cytokeratin antibody specific to cytokeratin 7, a transitional cell marker, indicated that they expressed a stable epithelial phenotype with serial passage. Low levels of immunostaining for E-cadherin and low levels of E-cadherin messenger ribonucleic acid, as determined by Northern blot analysis, and strongly positive immunostaining with an anti-vimentin antibody indicated collectively that the uroepithelial cells express a nonbarrier-forming phenotype under these culture conditions. However, when the urothelial cells were implanted subcutaneously into athymic mice on biodegradable synthetic polymers, they formed multilayered structures, suggesting that they retain the capability to differentiate in a living host. The urothelial cells proliferated in an epidermal growth factor independent manner and expressed high levels of transforming growth factor-alpha and amphiregulin messanger ribonucleic acids, suggesting the possibility of autocrine regulation of growth by epidermal growth factor-like factors. Cytogenetic analysis indicated that urothelial cells cultured for 6 passages possessed a normal chromosomal complement. These results demonstrate that primary cultures of autologous human bladder epithelial cells can be extensively expanded in vitro and, consequently, might be used in cell transplantation strategies for genitourinary reconstruction.

The "innocent" cough or sneeze: a harbinger of serious latex allergy in children during bladder stimulation and urodynamic testing.

Latex hypersensitivity is a well documented phenomenon most commonly reported in children with spina bifida during surgical and other procedures involving exposure to latex. IgE-mediated immediate hypersensitivity to the protein or polypeptide components of latex may be severe and manifest as generalized anaphylaxis or cardiovascular collapse. Of 17 children with spina bifida undergoing transurethral electrical bladder stimulation we identified 5 with latex allergy 3 to 9 years old. All 5 patients were noted to manifest sneezing or a cough several minutes before the development of a generalized hypersensitivity reaction, which in several patients progressed to bronchospasm. Subsequent investigations have shown that the inciting agent was the rectal pressure balloon made from a latex finger cot. Recognition of the earliest manifestations of latex hypersensitivity is an important clinical tool in the prevention of severe allergic reactions.

Pediatric renal transplantation under FK-506 immunosuppression.

Renal transplantation (11 cadaveric and 1 living-related donor) was performed in 12 pediatric recipients (mean age 10.8 years) under FK-506 immunosuppression in combination with prednisone therapy. At a mean followup of 6.1 months, patient and graft survival rates were 100% and 92%, respectively. The only graft loss was due to the recurrent hemolytic uremic syndrome 4 days after transplantation. In the functioning grafts the mean serum creatinine is 1.59 +/- 1.27 mg./dl. and the mean blood urea nitrogen is 36.3 +/- 24.6 mg./dl. Three patients take no prednisone, 5 are receiving 0.15 to 0.25 mg./kg. per day and 3 are taking 0.35 to 0.5 mg./kg. per day. There was a total of 8 rejection episodes in 5 patients. All rejection episodes were successfully reversed. Complications of transplantation included an episode of seizures in 1 patient, cytomegalovirus infection in 1 and steroid-induced diabetes mellitus in 1. Since pediatric transplant recipients are a group in whom the reduction or elimination of steroids is highly desirable, FK-506 immunosuppression may be particularly suited for use in this population.

Multiple renal neoplasms: a case of 3 histologically dissimilar primary tumors.

A 69-year-old woman who presented with bilateral renal masses and gross hematuria was found to have 3 different primary renal neoplasms. She first underwent left partial nephrectomy for an oncocytoma and subsequently right radical nephroureterectomy for transitional cell carcinoma of the pelvis. An incidental angiomyolipoma was found in the specimen. Deoxyribonucleic acid image analysis of all 3 tumors is presented.