Hand-assisted laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma.

OBJECTIVE: We report our experience with hand-assisted laparoscopic nephroureterectomy (HALN) for upper urinary tract transitional cell carcinoma and compare our results with a contemporary series of open nephroureterectomy (ON) performed at our institution. METHODS: Between August 1996 and May 2003, 90 patients underwent nephroureterectomy for upper-tract transitional cell carcinoma (TCC). Thirty-eight patients underwent HALN, while 52 had an ON. End-points of comparison included operative time, estimated blood loss (EBL), intraoperative and postoperative complications, length of hospital stay, pathologic grade and stage of tumor, and tumor recurrence. RESULTS: The mean patient age was 72.3 and 70.6 years in the ON and HALN groups, respectively. Mean operative duration was 243 minutes (ON) and 244 minutes (HALN), with an EBL of 478mL in the open group versus 191 mL in the hand-assisted group (P<0.001). No intraoperative complications occurred, but postoperative complications occurred in 4% and 11% of the ON and HALN groups, respectively (P=0.21). The mean hospital duration was 7.1 days (ON) versus 4.6 days (HALN) (P<0.01). No difference existed in the pathologic grade or stage distribution of urothelial tumors between the 2 groups. The mean follow-up was 51.0 months in the ON group and 31.7 months in the HALN group. Recurrence of urothelial carcinoma occurred in 50% of patients who underwent ON and 40% treated by HALN (P=0.38) at a median interval of 9.1 and 7.7 months, respectively, after surgery. CONCLUSION: Hand-assisted laparoscopic nephroureterectomy is an effective modality for the treatment of upper urinary tract urothelial carcinoma. Patients benefited from less intraoperative blood loss and a shorter hospitalization with an equivalent intermediate-term oncologic outcome compared with that of the open approach.     

The use of oral sedatives in dental care

Oral administration of tranquillizing and anxiety-suppressing drugs has long been the commonest method of achieving light sedation. The benzodiazepines are the drugs of first choice. Benzodiazepines given orally may be indicated to avoid 'treatment stress', alleviate mild anxiety before dental treatment, and facilitate sleep on the night before the treatment. Furthermore, they could be used for the dental treatment of medically poor risk patients, particularly those with cardiovascular disease. The drug can be given either in a fractionated dose or a single dose. The recommended doses for diazepam vary from 0.1–0.8 mg/kg body weight, depending on age, with higher doses in children and lower doses in elderly patients. Few side effects are reported.     

The program for phenotyping of genetically modified animals at AstraZeneca

Genetically modified mice offer a wide range of possibilities in preclinical drug discovery, e.g. for use in target identification, target validation and disease model generation. However, genomic modification and alteration in gene expression may cause unpredicted phenotypic alterations in the organism other than the intended ones. The aim of this study was to determine the importance of establishing the phenotype of transgenic and knockout mice models for use in pharmaceutical research.

A total number of 51 mouse models (transgenic and knockout) produced at AstraZeneca during a 4 year period were subjected to a thorough phenotyping package covering clinical as well as morphological aspects. Phenotype abnormalities were recorded in 36 (70.6%) of the mouse models. The majority of findings were considered to be minor in magnitude. Histopathological changes related to the genotype of the animals were observed in 33% of the mouse models, underlining the importance of pathology in the phenotyping program.     

Neutralization assay using a modified vaccinia virus Ankara vector expressing the green fluorescent protein is a high-throughput method to monitor the humoral immune response against vaccinia virus

Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.     

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

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CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin

Background  

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX₃CL1 (fractalkine) in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX₃CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX₃CL1 and CX₃CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis (EAE).     

Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

Background  

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.     

Optimizing Online Suicide Prevention: A Search Engine-Based Tailored Approach

Search engines are increasingly used to seek suicide-related information online, which can serve both harmful and helpful purposes. Google acknowledges this fact and presents a suicide-prevention result for particular search terms. Unfortunately, the result is only presented to a limited number of visitors. Hence, Google is missing the opportunity to provide help to vulnerable people. We propose a two-step approach to a tailored optimization: First, research will identify the risk factors. Second, search engines will reweight algorithms according to the risk factors. In this study, we show that the query share of the search term “poisoning” on Google shows substantial peaks corresponding to peaks in actual suicidal behavior. Accordingly, thresholds for showing the suicide-prevention result should be set to the lowest levels during the spring, on Sundays and Mondays, on New Year’s Day, and on Saturdays following Thanksgiving. Search engines can help to save lives globally by utilizing a more tailored approach to suicide prevention.