The natural history of low-risk non-muscle-invasive bladder cancer: a collaborative multi-centre study.

BACKGROUND: International guidelines vary in terms of their definition and recommendation for management of low-risk non-muscle-invasive bladder cancer (LRNMIBC). The ideal management for this large subset of bladder cancer patient remains unclear. OBJECTIVE: To evaluate long-term outcomes of patients with LRNMIBC. As a secondary objective, to assess for intergroup heterogeneity in disease-specific outcomes between G1 and G2LG diseases. METHODS: A multi-centre, retrospective study of patients who met the 2015 NICE definition of LRNMIBC. Timeline of diagnosis ranged from 01/01/2012 to 30/06/2016. RESULTS: A total 390 patients had available follow-up data (G1: 142, G2LG: 249). Over a median follow-up time of 36 months (IQR 25-50), 29.2% of the patients developed a recurrence. G2LG patients were statistically more likely to develop a recurrence (G1: 26.8%, G2LG: 33.7%, p < 0.05). 51.8% of recurrences occurred after 1 year of surveillance. Progression to high-grade disease occurred in 1.8% (n = 7, G1: 3, G2LG: 4) and a further 1.0% (n = 4, G1:3, G2LG: 1) of patients developed muscle-invasive bladder cancer (MIBC). CONCLUSION: The majority of recurrences occurred after 1 year of surveillance. The risk of disease progression was low; however, this was observed in a cohort of patients with regular cystoscopic follow-up. The risk may be higher if patients were pre-maturely discharged. If a 5-year surveillance programme were to be followed, 96.5% of recurrences would be captured. Lastly, there appears to be intergroup heterogeneity within LRNMIBC with G2LG patients having a statistically higher risk of recurrence compared to G1.

A comparative assessment of phenotypic and molecular diversity in Doum (Hyphaene thebaica L.).

Doum palm (Hyphaene thebaica L.) has been reported as one of the most beneficial species worldwide. Its fruits are a good source of fibers, antioxidants, B-complex vitamins, essential minerals, monosaccharides, essential oil and flavonoids. Fruit extract shows anti-inflammatory, antioxidant, antimicrobial, anticancer and pharmacological potential. However, there is a lack of investigations dealing with its genetic diversity. Therefore, a collection of twelve mature female palm landraces grown in the botanical garden of Aswan, "Egypt" were used for genetic diversity assessment based on phenotypic and molecular levels. 18 vegetal and chemical traits were evaluated. Fifteen of them showed highly significant variation among the tested landraces. Euclidian-based-dendrogram discriminated the tested landraces based on their phenotypic similarities to three main clusters showing a high level of variability. Molecular analysis using inter simple sequence repeats (ISSR) vis-à-vis start codon targeted (SCoT) polymorphism markers displayed the relationships among the tested landraces molecularly. Both markers showed a reasonable degree of polymorphism, however SCoT was more effective than the ISSR by showing a higher percentage of polymorphism, polymorphism information content, resolving power and diversity index. Cluster analysis based on molecular data showed a clear relationship among the doum landraces. However, ISSR- and SCoT-based dendrograms were slightly different, and completely unlike that based on phenotypic data. Nevertheless, phenotypic and molecular evaluations might complement each other, and by data of both an excellent overview was obtained from principle coordinate analysis. The information herein is valuable and considered as a keystone for further proximate studies on doum genetic diversity to help in improvement and breeding approaches.

Acute ICH in patients identified as being treated with either warfarin or direct-acting oral anticoagulant agents (DOACs) from a radiology perspective; a cross-sectional observational of 2359 emergency CT head studies.

AIM: To determine and compare the rates of acute intracranial haemorrhage (ICH) in emergency computed tomography (CT) head studies performed on patients treated with either warfarin or a direct-acting oral anticoagulant agent (DOAC) in a real-world acute setting from a radiology service perspective. METHOD: A retrospective automated search was undertaken via the hospital's radiology information system (RIS) for emergency CT head studies performed over a 2-year period where the clinical details indicated treatment with warfarin or a DOAC. The report of each scan was reviewed for the presence of unequivocal ICH. Duplicate and follow-up scans were excluded. Other parameters (trauma history and time of scan) were also reviewed. RESULTS: Following exclusions, 2,359 cases were eligible for analysis; 1,822 patients were treated with warfarin and 537 treated with DOACs. One hundred and nineteen CT heads, of which 104 were treated with warfarin and 15 treated with DOACs, were positive for various types of ICH. The positive rate for ICH was lower in the DOACs group than the warfarin group; 2.7% (number needed to scan: 37) versus 5.7% (number needed to scan: 17.5; p=0.0067). This is also true in a cohort of patients who had traumatic head injury; 2.14% (number needed to scan: 46.7) versus 5.80% (number needed to scan: 17.2; p=0.02). CONCLUSION: The present study has shown a lower rate of ICH in patients treated with DOACs compared to those treated with warfarin in an acute setting. A similar trend is demonstrated in a cohort of patients with a history of traumatic head injury.

Altered hippocampal plasticity by prenatal kynurenine administration, kynurenine-3-monoxygenase (KMO) deletion or galantamine.

Glutamate receptors sensitive to N-methyl-D-aspartate (NMDA) are involved in embryonic brain development but their activity may be modulated by the kynurenine pathway of tryptophan metabolism which includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at these receptors. Our previous work has shown that prenatal inhibition of the pathway produces abnormalities of brain development. In the present study kynurenine and probenecid (both 100mg/kg, doses known to increase kynurenic acid levels in the brain) were administered to female Wistar rats on embryonic days E14, E16 and E18 of gestation and the litter was allowed to develop to post-natal day P60. Western blotting revealed no changes in hippocampal expression of several proteins previously found to be altered by inhibition of the kynurenine pathway including the NMDA receptor subunits GluN1, GluN2A and GluN2B, as well as doublecortin, Proliferating Cell Nuclear Antigen (PCNA), sonic hedgehog and unco-ordinated (unc)-5H1 and 5H3. Mice lacking the enzyme kynurenine-3-monoxygenase (KMO) also showed no changes in hippocampal expression of several of these proteins or the 70-kDa and 100-kDa variants of Disrupted in Schizophrenia-1 (DISC1). Electrical excitability of pyramidal neurons in the CA1 region of hippocampal slices was unchanged, as was paired-pulse facilitation and inhibition. Long-term potentiation was decreased in the kynurenine-treated rats and in the KMO(-/-) mice, but galantamine reversed this effect in the presence of nicotinic receptor antagonists, consistent with evidence that it can potentiate glutamate at NMDA receptors. It is concluded that interference with the kynurenine pathway in utero can have lasting effects on brain function of the offspring, implying that the kynurenine pathway is involved in the regulation of early brain development.

Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway.

During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog.

Information extraction from FN plots of tungsten microemitters.

Tungsten based microemitter tips have been prepared both clean and coated with dielectric materials. For clean tungsten tips, apex radii have been varied ranging from 25 to 500 nm. These tips were manufactured by electrochemical etching a 0.1 mm diameter high purity (99.95%) tungsten wire at the meniscus of two molar NaOH solution. Composite micro-emitters considered here are consisting of a tungsten core coated with different dielectric materials-such as magnesium oxide (MgO), sodium hydroxide (NaOH), tetracyanoethylene (TCNE), and zinc oxide (ZnO). It is worthwhile noting here, that the rather unconventional NaOH coating has shown several interesting properties. Various properties of these emitters were measured including current-voltage (IV) characteristics and the physical shape of the tips. A conventional field emission microscope (FEM) with a tip (cathode)-screen (anode) separation standardized at 10 mm was used to electrically characterize the electron emitters. The system was evacuated down to a base pressure of ∼10(-8) mbar when baked at up to ∼180 °C overnight. This allowed measurements of typical field electron emission (FE) characteristics, namely the IV characteristics and the emission images on a conductive phosphorus screen (the anode). Mechanical characterization has been performed through a FEI scanning electron microscope (SEM). Within this work, the mentioned experimental results are connected to the theory for analyzing Fowler-Nordheim (FN) plots. We compared and evaluated the data extracted from clean tungsten tips of different radii and determined deviations between the results of different extraction methods applied. In particular, we derived the apex radii of several clean and coated tungsten tips by both SEM imaging and analyzing FN plots. The aim of this analysis is to support the ongoing discussion on recently developed improvements of the theory for analyzing FN plots related to metal field electron emitters, which in particular introduces a new form of intercept correction factors. The results derived demonstrate the applicability of the applied method on needle shaped - i.e. non planar - emitters as well as its limits.

Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats.

Probiotic bacteria and phytosterols are natural hypocholesterolemic agents with potential cardiovascular benefits. Accordingly, the present study was conducted to evaluate the effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats. Mixed probiotics treatment consisted of 8 probiotic strains: 2 strains of each of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus reuteri. The rats were fed for 8 wk with the given treatments in addition to a high-fat-high-cholesterol basal diet to induce hypercholesterolemia. Results showed that supplementation significantly reduced serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol, and triglycerides compared with the controls. The symbiotic treatment was more effective in lowering LDL-C, whereas mixed probiotics treatment more effectively lowered serum total cholesterol and LDL-C than the phytosterol-containing treatment. The phytosterol-containing treatments induced the increased activity of thyroid glands, as evident by elevated levels of serum total thyroxine, total triiodothyronine, and free triiodothyronine. In conclusion, the lipid profile can effectively be reduced to lower the incidence of cardiovascular disease using combinations of Lactobacillus-based probiotics and phytosterols in functional foods.

Noninvasive determination of hemoglobin and hematocrit using a temperature-controlled localized reflectance tissue photometer.

We performed visible/near-infrared optical measurements on the forearm of human subjects. We conducted four studies: one study using a commercial diffuse reflectance spectrometer, and three studies using a breadboard temperature-controlled localized reflectance tissue photometer. Calibration relationships were established between skin reflectance signal and either the reference blood hemoglobin (Hb) concentration or the hematocrit values (Hct). Prediction results were expressed as the prediction correlation coefficient (r(p)) and the standard error for cross-validation prediction (CV-SEP). Using diffuse reflectance measurement, r(p) = 0. 8, CV-SEP = 0.9 g/dL for Hb and r(p) = 0.7, CV-SEP = 3.3% for Hct (n = 40). In a localized reflectance study involving calculating the absorption and scattering coefficients and including effect of change of skin temperature in the calibration model, the best prediction results were r(p) = 0.9, CV-SEP = 0.8 g/dL for Hb and r(p) = 0.8, CV-SEP = 3% for Hct (n = 26). In a second localized reflectance study on a population having diverse skin colors at 34 degrees C, the optimal model led to r(p) = 0.8, CV-SEP = 0.9 g/dL for Hb and r(p) = 0.9, CV-SEP = 2.1% for Hct (n = 28) using the localized reflectance values without deducing the absorption and scattering coefficients. Improvement in the correlation was more noticeable for Hct than for the case of Hb. The photometer was used to screen prospective blood donors with low Hb concentration. It was possible to predict anemic subjects in the limited prospective blood donor population.

Spectroscopic and clinical aspects of noninvasive glucose measurements.

Frequent determination of glucose concentrations in diabetic patients is an important tool for diabetes management. This requires repetitive lancing and finger bleeding. Use of noninvasive (NI) detection techniques offers several advantages, such as the absence of pain and exposure to sharp objects and biohazard materials, the potential for increased frequency of testing, and hence, tighter control of the glucose concentrations, and the potential for a closed-loop system including a monitor and an insulin pump. These potential advantages have led to considerable interest in the commercialization of NI glucose monitoring devices. Review of the scientific, patent, and commercial literature indicates that the spectroscopic basis for NI determination of glucose is not yet well established, and attempts at commercialization may be several steps ahead of our understanding the origin and characteristics of an in vivo glucose-specific or glucose-related signal. Several technologies have potential for leading to viable measuring devices, but most of the data are based on in vitro experimentation. Because of the technical complexity of in vivo glucose measurements, this review aims at discussing the gap between the established need and current technology limitations.

Double oocyte aspiration may be a solution for empty follicle syndrome: case report.

OBJECTIVE: To assess the possibility of salvaging the cycle in a case of empty follicle syndrome by scheduling a second retrieval. SETTING: Miami IVF/Intracytoplasmic Sperm Injection Center, Alexandria, Egypt. It is a private center. PATIENT(S): A 24-year-old female with a 6-year history of primary infertility. Intracytoplasmic sperm injection was performed because of her partner's obstructive azoospermia. No oocytes could be retrieved despite normal ultrasonic and hormonal responses and the presence of 25 mature follicles. INTERVENTION(S): Serum hCG on the day of the first retrieval. A second dose of hCG was given after the first retrieval, and a second retrieval was scheduled 24 hours later. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, fertilization and cleavage rates, and pregnancy outcome. RESULT(S): Serum beta-hCG level on the day of the first retrieval was 300 IU/mL. Eleven oocytes were retrieved, (7 were metaphase II, 3 fertilized, and 2 cleaved) and two embryos were transferred. No pregnancy resulted. CONCLUSION(S): In a variant of empty follicle syndrome, the cycle could be salvaged by giving another dose of hCG and scheduling another retrieval 24 hours later.

Screening urine samples by leukocyte esterase test and ligase chain reaction for chlamydial infections among asymptomatic men.

Urine samples from 358 asymptomatic males were screened for urethral inflammation by the leukocyte esterase (LE) test and for Chlamydia trachomatis by the ligase chain reaction (LCR). LE and LCR positivity rates were 7.5% (27 of 358 samples) and 2.8% (10 of 358 samples), respectively. Eight of the 10 LCR-positive samples were detected by the LE screening test. The urine LE prescreening test in combination with the LCR assay may be a reasonable approach for genitourinary chlamydial disease control.

Hydrocele in filarial and non filarial patients. Histopathological, histochemical and ultrastructural studies.

Twenty biopsied material of the testicular tissue were obtained from patients with unilateral hydrocele (eight due to lymphatic filariasis and twelve of idiopathic causes). Twenty biopsies lymphatic were also obtained from the normal unaffected testes and were used as control. The data obtained from histopathological, histochemical and ultrastructural studies revealed alternation in the testicular tissue with hydrocele than in the normal control testis. In the filarial hydrocele 37.5% of the cases showed thickening of the basement membrane and fibrosis with arrest of the spermatogenesis at the level of secondary spermatocytes. In addition, 12.5% showed thickening with interstitial fibrosis. Microfilariae were seen in hydrocele fluid of 3/8 cases (37.5%). In the idiopathic hydrocele 50% of the testicular tissue showed marked collagen deposits and testicular atrophy with fibrosis and thickening of basement membrane. The second 50% of cases showed variable degree of maturation arrests. Explanation for these variations in the pathological and anatomical pictures in both types of hydrocele is suggested. In the filariasis hydrocele it is due to the inflammatory response that may subside and recurrent. In the idiopathic hydrocele, it is due to the irreversible hypoxia caused by the continuous mechanical pressure due to huge amount of hydrocele fluid resulting in irreversible degenerative process with marked fibrosis.

Histo- and immuno-pathological and electron microscopy studies of the splenic red pulps of schistosomiasis mansoni patients.

The histo- and immuno-pathological and electron microscopy (EM.) of the splenic red pulps studies were carried out for schistosomiasis mansoni patients and normal controls. The main pathological processes were interstitial haemorrhages, congestion, proliferation and hyperplasia of the red pulps of the schistosomiasis mansoni patients. The IgG showed marked reaction, moderate with IgA and mild with IgM. The E.M. showed an increase in the size of the different types of the reticular cells particularly those of the nuclear membrane with type II, nuclear degeneration, deposition of fibrin threads, marked fibrosis and phagocytosis and formation of pores at the sinusoidal basement membrane. It was concluded that these pathological processes and the alteration in the immunoregulatory system of the spleen of schistosomiasis mansoni patients reflect the role played and perpetrated in the development of splenomegaly.

Abbott prism: a multichannel heterogeneous chemiluminescence immunoassay analyzer.

We describe a multichannel heterogeneous immunoassay analyzer in which a sample is split between disposable reaction trays in a group of linear tracks. The system's pipettor uses noninvasive sensing of the sample volume and disposable pipet tips. Each assay track has (a) a conveyor belt for moving reaction trays to predetermined functional stations, (b) temperature-controlled tunnels, (c) noncontact transfer of the reaction mixture between incubation and detection wells, and (d) single-photon counting to detect a chemiluminescence (CL) signal from the captured immunochemical product. A novel disposable reaction tray, with separate reaction and detection wells and self-contained fluid removal, is used in conjunction with the transfer device on the track to produce a carryover-free system. The linear immunoassay track has nine predetermined positions for performing individual assay steps. Assay step sequence and timing is selected by changing the location of the assay modules between these predetermined positions. The assay methodology, a combination of microparticle capture and direct detection of a CL signal on a porous matrix, offers excellent sensitivity, specificity, and ease of automation. Immunoassay configurations have been tested for hepatitis B surface antigen and for antibodies to hepatitis B core antigen, hepatitis C virus, human immunodeficiency virus I and II, and human T-cell leukemia virus I and II.

Reaction tray and noncontact transfer method for heterogeneous chemiluminescence immunoassays.

We describe a reaction tray for a heterogeneous chemiluminescence (CL) immunoassay having the following features: separate sample incubation and signal detection wells; a design that allows for noncontact transfer of the reaction mixture from incubation wells to detection wells; surface features to mate with a detector and create a light-tight seal for CL detection; and self-contained means for liquid removal. The reaction mixture is transferred by injecting a wash solution from a group of nozzles into the incubation well. Quantitative transfer of microparticles (transfer efficiencies greater than 95% and CV less than 5%) is achieved by injecting two 300-microL pulses of transfer solution at a rate of 2.1 m/s. The performance of the tray and method of transfer is tested by determining the precision of CL signal for a sample containing a concentration of anti-hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (HBsAg) close to the cutoff value for the assay.

Detection apparatus for multiple heterogeneous chemiluminescence immunoassay configurations.

We describe an apparatus for measuring signals emanated from two heterogeneous chemiluminescence immunoassay (CLIA) configurations: antibody-coated polystyrene beads, in reaction tray wells, and microparticles captured by a porous matrix. An optics and fluidics design which allows the use of a common detection head for these two different assay configurations is described. The detection head moves along three Cartesian coordinates to create a localized light-tight compartment around each individual disposable reaction vessel. Reproducibility of the light seal, trigger solution delivery, and mixing is achieved for acridinium-labeled CLIA. The coated polystyrene beads configuration is tested using beta HCG, CEA, and TSH assays. The microparticle-capture configuration is tested using beta HCG and HBsAg assays. The microparticle capture CLIA has shorter incubation times and the potential for ease of automation.

A chemiluminescent, microparticle-membrane capture immunoassay for the detection of antibody to hepatitis B core antigen.

A chemiluminescent, microparticle-membrane capture immunoassay (CLIA/MMC) for the detection of antibody to hepatitis B core antigen (anti-HBc) is described. The assay utilizes recombinant hepatitis B core antigen coupled to carboxylated latex microparticles. Human polyclonal IgG anti-HBc labelled with acridinium competes with antibody in the sample for a limited number of binding sites on the solid phase. After a 40 min incubation at 40 degrees C, the reaction mixture is transferred to a glass fiber capture membrane and washed. A chemiluminescent signal is produced by addition of alkaline peroxide and is quantitated on a semi-automated reader as described. The CLIA/MMC assay was compared with standard EIA and RIA procedures (Corzyme and Corab, respectively, Abbott Laboratories, North Chicago, IL). Assay sensitivities were RIA greater than CLIA/MMC greater than EIA. A population of 200 normal blood donors showed nearly identical distributions with the CLIA/MMC and RIA (mean = 11% inhibition, SD = 13% for both), compared with the EIA (mean = 13% inhibition, SD = 15%). With a selected plasma population (n = 307), the CLIA/MMC immunoassay showed an excellent correlation (r = 0.94) with both the EIA and RIA procedures. Association of anti-HBc reactivity near assay cutoffs with antibody to hepatitis B surface antigen suggested relative specificity in the order RIA greater than CLIA/MMC greater than EIA. The CLIA/MMC procedure, which can be readily automated, provides a non-istopic alternative to current EIA testing with performance more nearly equivalent to RIA.

Automated in-line ratio-correcting filter fluorometer.

We have developed a novel optical arrangement for the Abbott VP bichromatic analyzer, converting it into a fluorometer upon insertion of a specially designed filter carriage. Fluorescence intensity is measured by using straight-through excitation geometry and is corrected for fluctuations in light-source intensity by using the attenuated transmitted beam through the solution as a reference. The modification allows switching from the absorbance to fluorescence mode without an auxiliary light source or a major hardware change. The detection limit for an experimental prototype was estimated as 192 pmol of fluorescein per liter. In an application to a fluorescence immunoassay for theophylline in patients' sera, the data (y) correlated well with results by an enzyme immunoassay procedure (EMIT), giving a correlation equation of y = 1.849 + 0.988x (r = 0.969). A fluorometric standard curve for glucose and some performance data are also presented.