Imaging of intestinal lymphocyte homing by means of pinhole SPECT in a TNBS colitis mouse model

BACKGROUND AND AIMS: The increasing knowledge of the molecular basis of leukocyte trafficking results in the development of novel anti-inflammatory strategies for inflammatory bowel disease (IBD). For optimal evaluation of therapy efficacy, information about inflammatory activity in bowel segments or lymphocyte recirculation and kinetics in the follow-up of experimental treatment for IBD is needed. The aim of this study was to evaluate a non-invasive scintigraphic technique, able to assess lymphocyte trafficking in a trinitrobenzene sulfonic acid (TNBS) induced mouse colitis model of IBD. METHODS: TNBS sensitized and non-sensitized murine total splenocytes were labeled in vitro with 111In-oxine and injected into either control or TNBS colitis BALB/c mice. Biodistribution and specific radioactive uptake, representing transferred cells, were determined by serial dedicated animal planar scintigraphy and pinhole SPECT of the abdomen 4, 24 and 48h post injection of labeled cells. In addition, the severity of inflammation was determined by histological scoring. RESULTS: Migration of 111In labeled splenocytes to the colon increased in time and was maximal at 48h after administration. The highest specific radioactive uptake ratio in the colon after 48h was observed in mice with TNBS colitis that received TNBS sensitized lymphocytes. Histological scoring confirmed the presence of colitis in the TNBS treated groups. CONCLUSION: Homing of TNBS-sensitized lymphocytes can be assessed in vivo by means of dedicated animal pinhole SPECT. Generally, this technique enables serial measurement of specific cell trafficking with potential of in vivo evaluation of novel anti-inflammatory strategies in inflammatory bowel disease.     

Population screening for fetal trisomy 21: easy access to screening should be balanced against a uniform ultrasound protocol

OBJECTIVES: To evaluate the performance of a first-trimester fetal aneuploidy screening program, with a documented underestimation of nuchal translucency thickness measurements (NT) compared to the Fetal Medicine Foundation (FMF) reference range. METHODS: We analysed the data of Algemeen Medisch Laboratorium (AML) in Antwerp, Belgium, on combined screening with pregnancy-associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (FB-hCG) and NT. NT-multiples of the median (MoM), relative to the FMF reference range, were used for risk calculations. RESULTS: The proportion of first-trimester screening tests in the total of serum screening tests increased from 1.3% (125/9424) in 2000 to 53.1% (6577/12 377) in 2003. Only 11.4% (1514/13 267) of NT measurements were performed according to FMF criteria. The 80.8% (21/26) trisomy 21 (T21) detection rate (DR) at cut off 1:300 resulted from maternal serum screening. NT measurements did not add to this DR, but reduced the false-positive rate from 16.8% (2212/13181) to 8.6% (1130/13181). Only 23.8% (5/21) of T21 detections were by FMF trainees. CONCLUSION: Easy access to screening and maternal serum parameters accounted for the majority of T21 detections in our first-trimester combined screening program.     

Consumer-identified barriers and strategies for optimizing technology use in the workplace

Purpose.?This article explores the experiences of 26 assistive technology (AT) users having a range of physical impairments as they optimized their use of technology in the workplace.

Method.?A qualitative research design was employed using in-depth, open-ended interviews and observations of AT users in the workplace.

Results.?Participants identified many factors that limited their use of technology such as discomfort and pain, limited knowledge of the technology's features, and the complexity of the technology. The amount of time required for training, limited work time available for mastery, cost of training and limitations of the training provided, resulted in an over-reliance on trial and error and informal support networks and a sense of isolation. AT users enhanced their use of technology by addressing the ergonomics of the workstation and customizing the technology to address individual needs and strategies. Other key strategies included tailored training and learning support as well as opportunities to practice using the technology and explore its features away from work demands.

Conclusions.?This research identified structures important for effective AT use in the workplace which need to be put in place to ensure that AT users are able to master and optimize their use of technology.     

The development and decay of kindling-induced increases in paired-pulse depression in the dentate gyrus

Epileptogenic stimulation (kindling) leads to an increase in recurrent inhibition in the dentate gyrus, possibly due to an increase in benzodiazepine receptors. A second, late inhibitory component also potentiates as a result of kindling. In the present experiments, the time course of the development and decay of this kindling-induced increase in inhibition was studied. Rats were kindled by stimulation of the perforant path or by direct stimulation of the dentate gyrus. Paired-pulse stimulation was applied to the perforant path and field potential measures were taken within the dentate gyrus. These procedures allowed the monitoring of inhibitory events in chronic preparations over prolonged periods. Input/output measures of the baseline responses were also monitored during the course of, and after the completion of kindling. The increase in the early component (about 20-50+ ms) of paired-pulse depression was seen after the first kindling stimulation. The increase in the late component of depression (about 100-500+ ms) did not develop until after about 10 stimulations had been delivered. The late component then decayed more rapidly than the early component after the completion of kindling. The baseline response also showed some indication of depression, particularly in the dentate gyrus kindled group, raising the possibility that feedforward inhibition had also been potentiated.     

Micturition symptoms and urinary incontinence after non-radical hysterectomy

The effects of 554 non-radical vaginal and abdominal hysterectomies on micturition symptoms and urinary incontinence were studied. From the urological point of view, two groups of women may be distinguished prior to hysterectomy: one without urological symptoms and the second with urological complaints (present in no less than 57% of all women and differing significantly from the distribution of urological symptoms in the normal population). In the first group, frequency developed significantly more often than nocturia, dysuria, stress incontinence and nocturnal and diurnal urge incontinence. The type of hysterectomy was not related to this development, except that urgency more often followed vaginal hysterectomy. In the second group, highly significant improvement and disappearance of symptoms was observed. Age, parity, menopausal status, the presence of myomas, height, weight and body mass index had no influence.     

The human sperm acrosome reaction does not depend on arachidonic acid metabolism via the cyclooxygenase and lipoxygenase pathways.

The objective of this study was to determine whether the metabolism of arachidonic acid via the cyclooxygenase pathway, the lipoxygenase pathway, or both has a pivotal role in the human sperm acrosome reaction. To do so, the stimulatory effect of arachidonic acid and a number of its metabolites, as well as the inhibitory effect of cyclooxygenase and lipoxygenase inhibitors on the acrosome reaction, was evaluated. Arachidonic acid, prostaglandin E2, and prostacyclin (PGI2) induced the acrosome reaction when added to 3-hour preincubated (capacitated) spermatozoa. The arachidonic acid-induced acrosome reaction was dependent upon extracellular calcium. Leukotriene B4 and 15-HPETE only induced the acrosome reaction when present throughout the preincubation period, indicating that they may enhance the capacitation process rather than the acrosome reaction. Thromboxane did not affect the acrosome reaction under any of the conditions tested. Inhibitors of cyclooxygenase (indomethacin, phenylbutazone) and lipoxygenase (phenidone, nordihydroguiaretic acid) or FPL 55712 (a leukotriene antagonist) did not prevent the arachidonic acid-stimulated acrosome reaction. Furthermore, 5, 8, 11, 14-eicosatetraynoic acid (ETYA), the acetylenic analog of arachidonic acid that inhibits arachidonic acid metabolism, induced an acrosome reaction equivalent to that of arachidonic acid. These results strongly suggest that the acrosome reaction induced by exogenous arachidonic acid is not mediated via either the cyclooxygenase pathway or the lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)