A Comparison of Cranial Cavity Extraction Tools for Non-contrast Enhanced CT Scans in Acute Stroke Patients.

Cranial cavity extraction is often the first step in quantitative neuroimaging analyses. However, few automated, validated extraction tools have been developed for non-contrast enhanced CT scans (NECT). The purpose of this study was to compare and contrast freely available tools in an unseen dataset of real-world clinical NECT head scans in order to assess the performance and generalisability of these tools. This study included data from a demographically representative sample of 428 patients who had completed NECT scans following hospitalisation for stroke. In a subset of the scans (n = 20), the intracranial spaces were segmented using automated tools and compared to the gold standard of manual delineation to calculate accuracy, precision, recall, and dice similarity coefficient (DSC) values. Further, three readers independently performed regional visual comparisons of the quality of the results in a larger dataset (n = 428). Three tools were found; one of these had unreliable performance so subsequent evaluation was discontinued. The remaining tools included one that was adapted from the FMRIB software library (fBET) and a convolutional neural network- based tool (rBET). Quantitative comparison showed comparable accuracy, precision, recall and DSC values (fBET: 0.984 ± 0.002; rBET: 0.984 ± 0.003; p = 0.99) between the tools; however, intracranial volume was overestimated. Visual comparisons identified characteristic regional differences in the resulting cranial cavity segmentations. Overall fBET had highest visual quality ratings and was preferred by the readers in the majority of subject results (84%). However, both tools produced high quality extractions of the intracranial space and our findings should improve confidence in these automated CT tools. Pre- and post-processing techniques may further improve these results.

The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra.

Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra-affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation, where basal and basal and/or apical expression patterns were observed. The physiological expression of SR-B1 in metestrous endometrial surface epithelia might be related to the implantation process and embryo development, as SR-B1 was also identified in the epithelial cells of the canine placental chambers. The increased levels of SR-B1 in pyometra-affected uteri indicate a potential role for this scavenger receptor in endometrial bacterial adhesion.

Sports in LCHAD Deficiency: Maximal Incremental and Endurance Exercise Tests in a 13-Year-Old Patient with Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency (LCHADD) and Heptanoate Treatment.

Exercise and subsequent catabolism is a potential trigger for creatine kinase (CK) concentration increase (rhabdomyolysis) in patients with LCHADD, therefore we evaluated the clinical and biochemical stability under physical exertion conditions at the age of 13 years in a currently 14-year-old LCHADD patient treated with heptanoate.LCHADD was diagnosed during first decompensation at age 20 months. In the following 2 years, the patient had several episodes of rhabdomyolysis. Heptanoate 0.5-1 g/kg/day was started at 4 years, with no further CK elevations since. He is clinically stable, has retinopathy without vision impairment or polyneuropathy. Maximal incremental and endurance exercise tests were performed to evaluate both clinical and metabolic stability during and after exertion.Physical fitness was adequate for age (maximum blood lactate 7.0 mmol/L, appropriate lactate performance curve, maximum heart rate of 196 bpm, maximum power 139 Watt = 2.68 Watt/kg body weight). There were no signs of clinical (muscle pain, dark urine) or metabolic derangement (stable CK, acyl carnitine profiles, blood gas analyses) - neither after maximal incremental nor endurance exertion.This case illustrates that both under maximal incremental and endurance exertion, clinical and biochemical parameters remained stable in this currently 14-year-old LCHADD patient receiving heptanoate treatment.

Imaging of acute stroke prior to treatment: current practice and evolving techniques.

Standard imaging in acute stroke is undertaken with the aim of diagnosing the underlying cause and excluding stroke mimics. In the presence of ischaemic stroke, imaging is also needed to assess patient suitability for treatment with intravenous thrombolysis. Non-contrast CT is predominantly used, but MRI can also exclude any contraindications to thrombolysis treatment. Advanced stroke imaging such as CT and MR angiography and perfusion imaging are increasingly used in an acute setting. In this review, we discuss the evidence for the application of these advanced techniques in the imaging of acute stroke.

Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers.

Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema. A total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance). Emphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV(1)), FEV(1)/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George's Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution. Distribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.

Prognostic implications of a biphasic waveform for APTT analysis in a district general hospital.

Activated partial thromboplastin time analysis creates waveforms of light transmittance against time. An abnormal biphasic waveform has been linked to morbidity and mortality. This study aims to quantify this link for patients in a district general hospital and determine the prognostic implications of the biphasic waveform. Data were collected over a 5-month period and analysed retrospectively to ascertain rates of infection, disseminated intravascular coagulation (DIC) and death. This was followed by a one month prospective study to assess prognostic implications. Rates of infection, DIC and death were high in this study population. The biphasic waveform often pre-empts these outcomes and is shown to be useful in predicting a poor prognosis.

The role of radiotherapy in treating small early invasive breast cancer.

AIM: The aim of the study was to identify if radiotherapy can be safely avoided in a selected subgroup of largely screening detected small invasive breast cancer. METHODS: One hundred and eighty-eight patients with node negative invasive early breast cancer < or =1cm (< or =T1b) treated in our centre between 1990 and 2004 were retrospectively followed for local, regional and distant recurrences. Treatment involved adequate local excision by breast conserving surgery (BCS). Axillary staging was performed by a four node axillary sampling until 2000, following which sentinel lymph node sampling was employed. All sections were assessed histologically by haematoxylin and eosin stained sections. The inked margins were reported as being involved, close and clear. Radiotherapy (RT) was employed only if the resected margins were inadequate, and in those with involved axillary nodes who refused further completion axillary clearance. RESULTS: Ninety-four patients (Group A) had BCS alone and 79 patients (Group B) had both BCS and RT. There was no ipsilateral breast tumour recurrence (IBTR) in 88 patients in Group A, corresponding to an actuarial freedom from IBTR of 96%, 91% and 88.1% at 5 years, 8 years and 9 years. In Group B, there was no IBTR in 75 patients corresponding to an actuarial freedom from IBTR of 97%, 94.9% and 90.6% at 5 years, 8 years and 10 years. CONCLUSION: Our experience over 14 years has shown that it is possible to safely avoid radiotherapy in a selected subgroup of small invasive breast cancer.

A Au82Si18 liquid metal field-ion emitter for the production of Si ions: fundamental properties and mechanisms.

Focused silicon beams are useful for direct write applications, e.g., lithography on silicon without the undesirable effect of substrate contamination. However, since pure silicon is not amenable to liquid metal ion source (LMIS) manufacture, a suitable alloy containing silicon has to be produced. This paper covers almost all fundamental aspects of a Au82Si18 eutectic, including the most detailed beam mass spectra reported to date of a AuSi source. A finding worthy of note in this investigation, manifested in the behaviour of the ion extraction voltage with temperature, is the abnormal behaviour of the surface tension coefficient of the alloy with temperature. An important deduction from this work, however, concerns the mechanisms responsible for the creation of doubly charged ions: reasons of self-consistency indicate that while Si2+ is directly field evaporated, Au2+ must form by the post-ionization of Au+. Finally, two different mechanisms seem to co-exist, as far as the production of cluster ions is concerned. While for cluster ions containing only a few atoms some sort of surface field-ionization mechanism might be responsible for their creation, for larger clusters, a droplet break-up mechanism, possibly by ion capture, seems very likely.

Cicloral versus neoral: a bioequivalence study in healthy volunteers on the influence of a fat-rich meal on the bioavailability of cicloral.

The bioavailability of cyclosporine a (CyA) was assessed in 2 cross-over studies with 12 healthy male volunteers each. Study A compared the bioavailability of Cicloral (test) with the microemulsion Neoral (reference) in the fasting state. Study B examined the influence of a fat-rich meal composed according to the Food and Drug Administration (FDA) recommendations on the bioavailability of Cicloral. Each volunteer received a single dose of 200 mg CyA in each period. Whole blood CyA concentrations were determined using HPLC up to 48 hours after drug administration. The pharmacokinetic parameters were determined using standard noncompartmental methods. The mean bioavailability of Cicloral compared with Neoral amounted to 83% (AUC) and 78% (Cmax), respectively. When administered after a fat-rich meal, the bioavailability of Cicloral was 121% (AUC) and 132% (Cmax) compared with fasting administration. Time to Cmax was 1.3 to 1.4 hours for both medications and modes of administration. Bioequivalence could not be proven either between Cicloral and Neoral, or between Cicloral fasting versus after a fat-rich meal. We conclude that the lower bioavailability and the influence of food on the bioavailability of Cicloral must be taken into account when switching from Neoral to the generic formulation.

Organization of the musculature of schistosome cercariae.

Phalloidin-fluorescein isothiocyanate staining of filamentous actin was used to identify muscle systems within the cercariae of Schistosoma mansoni. Examination of labeled cercariae by confocal scanning laser microscopy revealed distinct organizational levels of myofiber arrangements within the body wall, anterior cone, acetabulum, and esophagus. The body wall throughout showed a typical latticelike arrangement of outer circular and inner longitudinal myofibers, with an additional innermost layer of diagonal fibers in the anterior portion of the body. Circular and longitudinal fibers were also evident in the anterior organ and esophagus and, to some extent, the ventral acetabulum. Most striking was the striation of the cercarial tail musculature.

Microscopical evaluation of neural connectivity between paired stages of Eudiplozoon nipponicum (Monogenea: Diplozoidae).

Diplozoidae monogeneans am fish-gill ectoparasites comprising 2 individuals fused in so-called permanent copula. This unique situation occurs when 2 larvae (diporpee) make contact on the host gin, such that their union triggers maturation into an individual adult worm. The present study examined paired stages of Eudiplozoon nipponioun microscopicaily to ascertain whether somatic fusion involves neural connectivity between these 2 heterogenic larvae. Neuronal pathways were demonstrated in whole-mount preparations of the worm, using indirect immunocytochemical techniques interfaced with confocal scanning laser microscopy for peptidergic and serotoninergic innervations and enzyme cytochemical methodology and light microscopy for cholinergic component. Elements of the central nervous systems of paired worms are connected by commissures in the region of fusion so that the 2 systems are in structural continuity. Interindividual connections were mast apparent between corresponding ventral nerve cords. All 3 classes of neuronal mediators were identified throughout both central and peripheral connections of the 2 nervous systems. The anatomical complexity and apparent plasticity of the diplozoon nervous system suggest that it has a pivotal role not only in motility, feeding, and reproductive behavious but also in the events of larval pairing and somatic fusion.

The relationship between birth weight and maternal glycated haemoglobin (HbA1c) concentration in pregnancies complicated by Type 1 diabetes.

AIM: To examine the relationships between maternal HbA1c concentration at different time points and birth weight in pregnancies complicated by pre-existing Type 1 diabetes. METHODS: A comprehensive audit dataset was collected prospectively on all deliveries in Scotland to women with pre-existing Type 1 diabetes occurring between 1 April 1998 and 31 March 1999. Data items included HbA1c concentrations prior to conception and in each of the three trimesters of pregnancy, and birth weight. Relationships between standardized birth weight and HbA1c concentrations at each of the four time points were examined using correlation analysis. RESULTS: Standardized birth weight (Z scores) could be calculated for 203 of 208 singleton liveborn infants. HbA1c concentrations, standardized to correct for assay differences among hospitals, at different time points were available for between 134 (pre-pregnancy) and 192 (third trimester) cases. Standardized birth weight, relative to a reference population, showed a unimodal distribution, shifted to the right (mean, +1.57 sd). There was a significant negative correlation between pre-pregnancy HbA1c and birth weight (Spearman's R, -0.208; P = 0.016). There were no statistically significant correlations for other time points. CONCLUSIONS: Standardized birth weight scores of the infants of diabetic mothers are higher than those of a reference population. There is no simple relationship between maternal glycaemic status and birth weight, but there appears to be a paradoxical inverse relationship between pre-pregnancy glycaemic control and standardized birth weight.

On the temperature dependence of the electric characteristics and mass spectra of liquid metal alloy ion sources.

This paper reports on an extensive study of the characteristics of AuGeSi and CoNd liquid metal alloy ion sources (Focused Ion Beams From Liquid Metal Ion Sources, Research Studies Press, Taunton, Somerset, UK, 1991). Such characteristics include current-voltage curves and ion beam mass spectra. A careful investigation has been undertaken where the emitter temperature is the main variable experimental parameter. Theoretical models, or theoretical attempts in certain cases, tend to support the experimental results. The experimental results, in conjunction with existing theories, suggest that simply for reasons of self-consistency two mechanisms must be operative for the production of doubly-charged ions from the AuGeSi source: direct field-evaporation and post-ionisation.

Is radiotherapy needed after breast conservation for small invasive breast cancers?

AIMS: The purpose of this study was to determine the rate of local recurrence in patients with small invasive breast cancers (<1 cm) who had been treated with breast-conserving surgery either with (group 1) or without (group 2) adjuvant radiotherapy. METHODS: This is a retrospective study of 110 patients with an invasive breast cancer less than 1 cm in size, treated in our centre by breast-conserving surgery. Parameters examined included age at and mode of presentation, histopathological features, adjuvant therapy, length of follow-up and outcome in terms of local recurrence rate and death. RESULTS: In group 1 there were 59 women of median age 57 (38-80) years. The median tumour size was 9 (1-10) mm and median follow-up was 74 (15-110) months. There were no local recurrences. In group 2 the median age at presentation was 59 (48-81) years. The median tumour size was 7 (2-10) mm and median follow-up was 47 (14-93) months. There were three non-breast-cancer related deaths and three local recurrences (6%). CONCLUSIONS: A local recurrence rate of 6% at almost 4 years median follow-up suggests that it may be possible to avoid adjuvant radiotherapy in a subgroup of largely screen-detected, node-negative patients with invasive tumours less than 1 cm, in whom adequate local excision is performed. Further follow-up is required to substantiate this.

Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers.

OBJECTIVE: To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinetics of lovastatin. METHODS: In an open, randomized, crossover study, 12 healthy volunteers received 80 mg lovastatin orally either alone or concomitantly with 300 mg roxithromycin after 5-day pretreatment with roxithromycin 300 mg daily. Plasma concentrations of lovastatin (lactone and acid) were determined using high-performance liquid chromatography, and the pharmacokinetic parameters were estimated. RESULTS: The mean (+/- SD) pharmacokinetic parameters of lovastatin lactone with and without roxithromycin were maximum concentration (Cmax) 8.49+/-6.80/16.3+/-9.4 ng ml(-1), time to Cmax (tmax) 1.8+/-0.4/1.7+/-0.6 h, terminal plasma half-life (t1/2) 4.3+/-2.0/3.7+/-2.5 h, area under the plasma concentration-time curve from zero to infinity (AUC0-infinity) 53+/-60/85+/-67 ng ml(-1) h. The respective parameters of lovastatin acid were Cmax 24.6+/-13.4/17.8+/-11.0 ng ml(-1), tmax 3.7+/-1.1/4.1+/-0.7 h, t1/2 3.2+/-2.5/4.3+/-2.8 h, AUC0-infinity 149+/-123/105+/-58 ng ml(-1) h. Mean bioavailability of lovastatin lactone was lower and that of lovastatin acid was higher with concomitant treatment. However, the differences were significant only with respect to lovastatin lactone (AUC and Cmax) and Cmax of lovastatin acid. CONCLUSION: Roxithromycin does not influence the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin seems to be necessary during co-administration.

Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers.

AIMS: To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously. METHODS: Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. RESULTS: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity) 32.9 ng ml(-1) h. After intravenous administration initial plasma concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 l and CL 1800 ml min(-1). An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. CONCLUSIONS: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.

Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer.

PURPOSE: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. METHODS AND MATERIALS: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2-3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m(2), vincristine 2 mg and methotrexate 60 mg/m(2) at 10-day intervals (MOPq10). RESULTS: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. CONCLUSION: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.

Immunomicroscopical observations on the nervous system of adult Eudiplozoon nipponicum (Monogenea: Diplozoidae).

Neuronal pathways have been examined in adult Eudiplozoon nipponicum (Monogenea: Diplozoidae), using cytochemistry interfaced with confocal scanning laser microscopy, in an attempt to ascertain the status of the nervous system. Peptidergic and serotoninergic innervation was demonstrated by indirect immunocytochemistry and cholinergic components by enzyme cytochemical methodology; post-embedding electron microscopical immunogold labelling revealed neuropeptide immunoreactivity at the subcellular level. All three classes of neuronal mediators were identified throughout both central and peripheral elements of a well-differentiated orthogonal nervous system. There was considerable overlap in the staining patterns for cholinergic and peptidergic components, while dual immunostaining revealed serotonin immunoreactivity to be largely confined to a separate set of neurons. The subcellular distribution of immunoreactivity to the flatworm neuropeptide, GYIRFamide, confirmed neuropeptide localisation in dense-cored vesicles in the majority of the axons and terminal varicosities of both central and peripheral nervous systems. Results reveal an extensive and chemically diverse nervous system and suggest that pairing of individuals involves fusion of central nerve elements; it is likely also that there is continuity between the peripheral nervous systems of the two partner worms.

Determination of opipramol in human plasma by high-performance liquid chromatography with photometric detection using a cyanopropyl column.

A high-performance liquid chromatographic method is described for the determination of opipramol in human plasma. Opipramol was extracted into tert.-butylmethyl ether, separated on a cyanopropyl silica column and detected at 254 nm. Imipramine was used as internal standard. The limit of quantitation was 250 pg/ml using 1.5 ml plasma. Precision was better than 9%, inaccuracy less than 8%. The assay is more sensitive than previously published methods, and it has been applied to the analysis of plasma samples from a pharmacokinetic study.

A confocal microscopical study of the musculature of adult Schistosoma mansoni.

Using the filamentous actin marker, FITC-conjugated phalloidin, the major muscle systems of adult male and female schistosomes have been examined. The body wall musculature comprises an outer sheath of circular fibres, within which there is a compact layer of short, spindle-shaped longitudinal fibres and a lattice-like arrangement of inner diagonal fibres. Within the oral sucker and acetabulum 3 fibre types, circular, radial and longitudinal can be distinguished. The wall of the oesophagus is lined by a grid-like array of circular and longitudinal fibres, whereas the walls of the intestinal caeca contain only comparably broad circular fibres. Within the female reproductive system, only circular fibres are present in the oviduct, vitelline duct and uterus. In contrast, the wall of the ootype displays closely arranged circular and longitudinal muscle fibres. Antisera to previously identified myoactive compounds (serotonin [5-hydroxytryptamine, 5-HT], neuropeptide F [Moniezia expansa] and GYIRFamide [Bdelloura candida, Dugesia tigrina]) were used as neuronal markers in a preliminary study of the spatial inter-relationships of specific nerve fibres and various muscle systems. Serotoninergic fibres innervate both suckers and also constitute a subtegumental nerve net. In males they provide innervation to the dorso-ventral muscle fibres of the gynaecophoric canal, and in females they innervate the circular and longitudinal muscle fibres of the ootype. Neuropeptide F and the FMRFamide-related peptide, GYIRFamide are both localized within nerve plexuses associated with the dorso-ventral fibres of the gynaecophoric canal, and are evident in the innervation of the ventral and oral sucker.