A simulation of food-web interactions leading to rainbow smelt Osmerus mordax dominance in Sparkling Lake, Wisconsin.
A process-based simulation model was used to examine the nature and intensity of food-web interactions that allow Osmerus mordax to dominate invaded lakes. The model simulates food-web interactions among linked populations of O. mordax, Coregonus artedi and Sander vitreus. Simulations indicated that O. mordax dominate where: (1) adult O. mordax prey on young-of-the-year (YOY) C. artedi, (2) YOY O. mordax negatively affect YOY S. vitreus through competition and (3) adult S. vitreus experience moderate fishing mortality. Osmerus mordax dominated simulations across a broad range of variable values that regulated competition and predation, and displayed threshold responses to increasing angler harvest. Consequently, angler harvest should be carefully managed in lakes susceptible to O. mordax invasions because the alternative could lead to fishery collapse.


An arts-based intervention at a nursing home to improve medical students' attitudes toward persons with dementia.
Emerging data suggest that students' attitudes toward older patients may be positively affected by geriatric experiences that are not clinically based, but no known interventions have used creative arts to integrate humanistic experiences into medical student geriatric education. This 2012 study evaluated whether participating in TimeSlips, a creative group-based storytelling program involving persons with dementia, improved medical students' attitudes toward such patients. The authors administered the Dementia Attitudes Scale (DAS) to 22 fourth-year medical students to evaluate the mean change in their self-reported attitudes toward persons with dementia. The authors used paired t tests or Wilcoxon signed-rank tests to analyze pre- and post-program scores on the individual items of the DAS, on the subdomains of "comfort" and "knowledge," and on the overall scale. They used Cronbach alpha to evaluate the internal consistency and reliability of the "comfort" and "knowledge" subdomains and of the overall scale. Medical students' attitudes, as measured by the significantly higher scores on 12 of the 20 items, on each of the two subdomains, and on the overall scale, showed improvement after the TimeSlips sessions. The DAS showed acceptable to good internal consistency on both subdomains and on the overall scale both pre and post session; however, the internal consistency analysis is preliminary because of small sample size. The authors' findings provide preliminary evidence that participation in a creative storytelling program at a nursing home improves medical students' attitudes toward persons with dementia and adds to evidence supporting the reliability of the DAS.


Individualized medicine using intestinal responses to CFTR potentiators and correctors.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators that target the mutant CFTR protein are being introduced for treatment of cystic fibrosis. Stratification of subjects based on their CFTR genotype has been proven essential to demonstrate clinical efficacy of these novel treatments. Despite this stratification, considerable heterogeneity between subjects receiving CFTR modulators is still observed which remains largely uncharacterized. The CFTR genotype, and additional genetic and environmental factors that impact either tissue-specific CFTR protein characteristics or the pharmacokinetic properties of treatments will likely determine the individual response to therapy. The development of intestinal biomarkers for CFTR modulators may help to better quantitate individual responses to treatment, with potential to optimize treatments for subjects with limited responses, and the selection of responsive subjects that currently do not receive treatments. Here, recent advances concerning the use of intestinal biomarkers for CFTR modulator treatments are reviewed, with a focus on biomarkers of CFTR function in ex vivo rectal biopsies and in vitro cultured primary intestinal organoids. Their potential value is considered in the context of the current unmet needs for better treatments for the majority of subjects with CF, and individual biomarkers that enable the prediction of long term therapeutic responses to CFTR modulators. Pediatr Pulmonol. 2016;51:S23-S34. © 2016 Wiley Periodicals, Inc.


Induction of c-fos Gene Expression by Urokinase-Type Plasminogen Activator in Human Ovarian Cancer Cells.
The ability to fractionate nucleic acids and to determine which of them has sequences complementary to an array of DNA or RNA molecules is one of the most powerful tools of molecular biology. The Southern blot, named for its inventor, is a method for transferring size-fractionated DNA from a gel matrix to a solid support followed by hybridization to a labeled probe (1. The identical process for RNA became known as) the Northern blot i2 1i The identical process for RNA became known as the Northern blot (2). Both are, then, often key elements in establishing the identity of nucleic acids of interest. Northern blot analysis was used by us as a tool in order to answer the question whether or not the nuclear transcripitional apparatus of human ovarian cancer cells might be activated in response to the urokinase.


Serum tetraiodothyroacetate (T4A) levels in normal healthy euthyroid individuals determined by gas chromatography-mass fragmentography (GC-MF).
A gas chromatography-mass fragmentography (GC-MF) assay for T4A in human serum is described. The assay involves a multistage extraction, followed by conversion of T4A to its dimethyl derivative prior to GC-MF. Using this assay, the concentration of T4A in 37 normal euthyroid subjects was, mean +/- S.D., 114.5 +/- 26.4 pmol/l, which is considerably lower than previous reports. Thyroxine binding prealbumin (TBPA) did not appear to be a major determinant of T4A concentration.


Altered corticogenesis and neuronal morphology in irradiation-induced cortical dysplasia: a Golgi-Cox study.
Cortical dysplasia has a strong clinical association with epilepsy and mental retardation, but the relationship between alterations in cortical structure and function in dysplasia-related disorders is poorly understood. The cerebral cortex of irradiated rats, an experimental model of cortical dysplasia, was studied using cresyl violet-stained sections and the Golgi-Cox method. The irradiated cortex is characterized by reductions in size, volume, and number of neurons and fibers reflecting the original lethal injury to neuronal precursors. Consequently, only neurons that survived this injury were able to continue their, albeit altered, development. The result is an altered corticogenesis characterized by neuronal, fiber circuitry, and microvascular alterations. Abnormal aggregates (nodules) of excitatory pyramidal neurons with altered dendritic profiles and functional territories are found between 200 and 400 microm from the pial surface. Their horizontal dendritic profiles and functional territories contrast with the vertical (columnar) dendritic profiles and functional territories of normal pyramidal neurons. This horizontal concentration of spiny dendrites and, hence, of excitatory synaptic contacts suggests a response to the presence of an abnormal horizontal plexus of afferent fibers terminals. Stellate neurons, some morphologically compatible with inhibitory basket cells, are also essential components of these nodules. Some neuronal nodules are characterized by a rich plexus of anastomotic capillaries that contrasts with the sparser vasculature of surrounding gray matter tissue. The presence of well-vascularized aggregates of altered pyramidal and inhibitory neurons suggests a high level of metabolic activity. Well-vascularized deep heterotopias are also found. We propose that the functional activity of well-vascularized neuronal nodules and heterotopias could play a role in the abnormal cortical function in this model.


[Cystic degeneration of autonomous adenomas (author's transl)].
Follow-up examinations in four patients with autonomous adenomas showed cystic degeneration in the autonomous adenomas 20 to 45 months after the first examination, confirmed by fine needle biopsy. Clinical improvement occurred three times with scintigraphic compensation, decompensation occurred once without clinical deterioration. In particular cases a therapeutic policy of wait and see is justified in patients with autonomous adenomas because they may remain clinically inconspicuous for a long time; on the other hand there is a possibility of a cystic degeneration.


Factors controlling sediment and nutrient fluxes in a small microtidal salt marsh within the Venice Lagoon.
Coastal salt marshes are among the Earth's most productive ecosystems and provide a number of ecosystem services. Water quality regulation by storing, transforming and releasing nutrients, organic matter and suspended sediment is recognized as one of the most important functions of salt marshes. The self-purification capacity of intertidal ecosystems contributes to mitigating nutrient inputs, acting as a buffer zone between watersheds and coastal waters, especially in relation to climate change and the increasing frequency of impulsive extreme events. Understanding sediment and nutrient fluxes and assessing the mechanisms that control them are valuable for the preservation and future restoration of salt marshes and for enhancing their effectiveness in providing water quality regulation services. To investigate the main driving factors in microtidal environments, changes in suspended sediment and nutrient concentrations were measured during several tidal cycles in a small microtidal reconstructed salt marsh in the Venice Lagoon, which was selected as the experimental site. The tidal amplitude, nutrients and total suspended solid concentrations were measured during 6 tidal cycles between September 2011 and October 2013. The water discharge was derived by forcing the hydrodynamic MIKE-DHI numerical model with the measured tidal levels. Fluxes were assessed by coupling field data with the calculated discharges. The salt marsh filtering function was related to the inflow matter concentrations and tidal amplitude. When high suspended solid and nutrient concentrations enter the salt marsh, accumulation processes prevail on release. In contrast, in the case of low concentrations and high tidal excursion, the salt marsh functions as a nutrient and sediment source. During all campaigns, the nitrogen removal function was more effective within the intertidal vegetated areas. Sediment release was the dominant process in the outermost creek, whereas sedimentation prevailed in the inner area of the salt marsh because of the attenuation of hydrodynamic forcing during tide propagation.


Extra-nasopharyngeal extension of juvenile angiofibroma.
Nasopharyngeal angiofibroma (NPA) is a highly vascular, infiltrative tumour that occurs exclusively in the nasopharynx of young males. It is of special interest on account of its serious complications, and the difficulties that are encountered at the time of treatment. Various surgical approaches have been mentioned for both naso- and extra-nasopharyngeal angiofibromas. But a massive extra-NPA involving the naso-spheno-oro-palato-maxillary-infratemporal region, orbit and cheek is difficult to treat adequately with any of the approaches so far described in the literature. In these cases, a more radical approach (constituting embolization and subsequent clamping or ligation of the external carotid artery followed by total maxillectomy) may be needed. These procedures will not only give a dry operative field but also adequate exposure to the different parts of the extension of the tumour, thereby facilitating complete removal without any risk of recurrence.


The role of an effective isotropic tissue modulus in the elastic properties of cancellous bone.
Conceptually, the elastic characteristics of cancellous bone could be predicted directly from the trabecular morphology--or architecture--and by the elastic properties of the tissue itself. Although hardly any experimental evidence exists, it is often implicitly assumed that tissue anisotropy has a negligible effect on the apparent elastic properties of cancellous bone. The question addressed in this paper is whether this is actually true. If it is, then micromechanical finite element analysis (micro-FEA) models, representing trabecular architecture, using an 'effective isotropic tissue modulus' should be able to predict apparent elastic properties of cancellous bone. To test this, accurate multi-axial compressive mechanical tests of 29 whale bone specimens were simulated with specimen-specific micro-FEA computer models built from true three-dimensional reconstructions. By scaling the micro-FEA predictions by a constant tissue modulus, 92% of the variation of Young's moduli determined experimentally could be explained. The correlation even increased to 95% when the micro-FEA moduli were scaled to the isotropic tissue moduli of individual specimens. Excellent agreement was also found in the elastic symmetry axes and anisotropy ratios. The prediction of Poisson's ratios was somewhat less precise at 85% correlation. The results support the hypothesis; for practical purposes, the concept of an 'effective isotropic tissue modulus' concept is a viable one. They also suggest that the value of such a modulus for individual cases might be inferred from the average tissue density, hence the degree of mineralization. Future studies must clarify how specific the tissue modulus should be for different types of bone if adequate predictions of elastic behavior are to be made in this way.


Late flexor pollicis longus tendon rupture due to retained glass fragments.
A retained glass fragment caused a flexor pollicis longus tendon rupture 23 years after the patient's initial injury. A review of the literature shows that although previous cases of delayed damage from retained objects have been reported, this is the first report of a tendon injury that was preceded by such a long asymptomatic period. The lesion was treated with a flexor digitorum superficialis tendon transfer from the ring finger with excellent functional results.


Ultraviolet-C-induced apoptosis protected by 635-nm laser irradiation in human gingival fibroblasts.
The purpose of this study was to examine the protection afforded by 635-nm irradiation against ultraviolet (UV)-C-induced apoptosis in primary human gingival fibroblasts (hGFs). UV irradiation is known to cause photoaging and cellular apoptosis of skin cells and is considered to be one of the leading causes of skin carcinogenesis. To induce apoptosis, UV-C (100 mJ/cm2) was used to irradiate hGFs. To protect them from apoptosis, pretreatment with 635-nm irradiation was performed for 1 h immediately after cell plating 36 or 48 h before UV-C irradiation. The light source used for irradiation was a continuous-wave 635-nm LED laser emitting at 1 mW/cm2. Experimental samples were selected 24 h after UV-C irradiation. To measure the numbers of apoptotic cells, MTT assay and flow cytometric analyses were performed. For histomorphologic findings, Diff-Quick staining was carried out. Also, the activities and mRNA expression of caspase-3, caspase-8, and caspase-9 were measured. In the present study, the number of apoptotic cells declined in the cells that were pretreated with 635-nm light irradiation in a time-dependent manner. In addition, the activities and mRNA expression of caspase-3, caspase-8, and caspase-9 were significantly recovered by pretreatment with 635-nm irradiation. These results suggest that 635-nm visible light irradiation may be used as a protective tool to prevent UV-C-induced apoptosis.


Nonalcoholic Fatty Liver Disease Among Individuals with HIV Mono-infection: A Growing Concern?
Liver disease is a leading cause of non-AIDS-related death in the HIV population since the introduction of highly active antiretroviral treatment (HAART). Recent studies suggest that patients with HIV are at high risk for nonalcoholic fatty liver disease (NAFLD) and progressive liver fibrosis. Evidence for the prevalence, risk factors, and diagnostic methodologies of NAFLD in patients with HIV mono-infection is summarized here. Although limited, published studies suggest that the prevalence of NAFLD is higher (30-50%) and progresses at an increased rate in patients with HIV compared to the general population. Identifying those at risk for significant liver fibrosis is critical, preferably with non-invasive screening tests. While there is a paucity of evidence in this population, transient elastography (TE) appears to provide a sensitive, non-invasive screening modality. Identifying NAFLD early will allow for dietary and lifestyle interventions, as well as future drug therapies to decrease the risk of progressive liver fibrosis and cirrhosis in the high-risk HIV population. Clinicians should be aware of this risk and consider using TE for NAFLD diagnosis and surveillance.


Runt syndrome induced in the rat by polyinosinic-polycytidylic acid.
Polyinosinic with polycytidylic acid (poly l with poly C), a double-stranded synthetic RNA, produced in newborn rats a runt syndrome characterized by mortality and retarded growth rates of the total body, thymus, and kidneys. In contrast, it induced a hyperplasia in the epidermis and in the spleen. Within 10 days of treatment, the epidermis became 2 or 3 times thicker and the spleen mass was increased by 50%. The epidermal hyperplasia involved all layers, but hair follicles were excluded. Splenic hyperplasia did not result from accelerated erythropoiesis. Double-stranded RNA was required; single-stranded homopolymers were ineffective. Theophylline, a phosphodiesterase inhibitor, did not potentiate the effects. The uptake of iododeoxyuridine-125 was not enhanced in the hyperplastic epidermis or spleen. Thus we concluded that poly l with poly C can retard the growth of some organs in newborn rats, but that it causes epidermis and spleen to accumulate cells. The cytokinetic mechanisms involved in these contrasting effects were not clear.


Identification and partial characterization of factor Va heavy chain kinase from human platelets.
Factor Va, the essential cofactor for prothrombinase, is phosphorylated on the acidic COOH terminus of the heavy chain of the cofactor, at Ser692, by a platelet membrane-associated casein kinase II (CKII). Consistent with this observation, phosphorylation of the factor Va heavy chain by the platelet kinase was inhibited by heparin. The membrane-associated platelet CKII kinase was partially purified using heparin-agarose, phosphocellulose, and ion exchange chromatography. CKII antigen was monitored using a polyclonal antibody to the alpha-subunit, and kinase activity in the various fractions was confirmed using human factor Va as a substrate. Immunoblotting experiments using polyclonal antibodies raised against synthetic peptides mimicking a portion of the deduced amino acid sequence of the alpha-, alpha'-, and beta-subunits of human CKII demonstrated the coexistence of both alpha- and alpha'-subunits in platelets and suggested that the platelet CKII kinase may exist in part as an alpha alpha'beta2 complex. It is also possible that there are two distinct populations of CKII in platelets, one that is alphaalpha/betabeta and one that is alpha'alpha'/betabeta. In the presence of the purified platelet-derived CKII, human factor Va incorporates between 0.8 and 1.3 mol of phosphate/mol of factor Va depending on the concentration of the beta-subunit in the kinase preparation. A peptide mimicking the sequence 687-705 of the human factor V molecule incorporates radioactivity in the presence of purified CKII and inhibits factor Va heavy chain phosphorylation by the platelet CKII. In contrast, a peptide with an alanine instead of a serine at position 692 neither incorporates phosphate nor inhibits factor Va phosphorylation by the platelet CKII. Human factor Va is inactivated by activated protein C following three cleavages of the heavy chain at Arg506, Arg306, and Arg679. Cleavage at Arg506 is necessary for efficient exposure of the inactivating cleavage site at Arg306. The phosphorylated cofactor has increased susceptibility to inactivation by activated protein C, since phosphorylated factor Va was found to be inactivated approximately 3-fold faster than its native counterpart. Acceleration of the inactivation process of the phosphorylated cofactor occurs because of acceleration of the rate of cleavage at Arg506. These data suggest a critical role for factor Va phosphorylation on the surface of platelets in regulating cofactor activity.


Gonadotrophin responses to oestrogen provocation in women with minimal endometriosis.
The gonadotrophin responses to the negative and positive feedback effects of orally administered ethinyl oestradiol in 12 women with minimal endometriosis were compared with those in six normal women of proven fertility. Basal concentrations of LH, FSH and oestradiol did not differ between the two groups. LH and FSH concentration declined within 12-24 h of starting treatment and there was no difference between minimum values, which occurred in both groups after 12-48 h. In five women with minimal endometriosis, LH concentrations subsequently increased above basal values to maximum values indistinguishable in magnitude and timing from those in the control group. An exaggerated LH response to oestrogen positive feedback occurred in one subject. In the remaining six women LH concentrations increased above levels which could be attributed to episodic variation in basal LH secretion but maximum LH values were below control limits. There was no relationship between previously documented progesterone secretion nor LH concentrations during the early luteal phase of the cycle and the LH response to oestrogen positive feedback. These data suggest that minor abnormalities of hypothalamopituitary function may contribute to infertility associated with minimal endometriosis.


FEM-based evaluation of deformable image registration for radiation therapy.
This paper presents a new concept to automatically detect the neighborhood in an image where deformable registration is mis-performing. Specifically, the displacement vector field (DVF) from a deformable image registration is substituted into a finite-element-based elastic framework to calculate unbalanced energy in each element. The value of the derived energy indicates the quality of the DVF in its neighborhood. The new voxel-based evaluation approach is compared with three other validation criteria: landmark measurement, a finite element approach and visual comparison, for deformable registrations performed with the optical-flow-based 'demons' algorithm as well as thin-plate spline interpolation. This analysis was performed on three pairs of prostate CT images. The results of the analysis show that the four criteria give mutually comparable quantitative assessments on the six registration instances. As an objective concept, the unbalanced energy presents no requirement on boundary constraints in its calculation, different from traditional mechanical modeling. This method is automatic, and at voxel level suitable to evaluate deformable registration in a clinical setting.


Case Report in Clinical Pediatric Dentistry: How to Review, Organize and Prepare a Manuscript.
A case report is a useful type of publication to describe information on unusual clinical diseases or syndromes, new management techniques, potential risk factors/oral disease associations, and uncommon side effects or responses to traditional dental treatments. In the practice of Dentistry and Medicine, the publication of case reports has the purpose of sharing new clinical experiences and knowledge with interested colleagues. Case reports in the field of Evidence-Based Pediatric Dentistry convey unique contributions to the clinical practice and help improve the process of clinical decision making in the form of a brief written communication. Additionally, case reports are potential resources of new hypotheses for more complex methodological designs in clinical research studies and are one of the best ways to get started in scholarly writing. The purposes of the present report were to comment on the role, relevance, and main limitations of case reports in Clinical Pediatric Dentistry, to describe the reasons for writing a case report and some recommendations for critically reviewing a published case report, and finally, to provide the fundamentals of preparing a case report, and finally, to provide the fundamentals of preparing a case report manuscript in a structured manner.


Predictors of sustained response to therapy resumption after treatment interruption in HIV-infected patients failing antiretroviral therapy.
In order to evaluate whether a sustained virologic response to therapy resumption after treatment interruption can be achieved in the setting of virologic failure, we reviewed retrospectively the data relating to 56 human immunodeficiency virus (HIV)-infected subjects selected from 3,145 patient charts. At the time of treatment interruption (study entry), the median (interquartile range) CD4+ counts and HIV-RNA levels were respectively 247 (127-502) x 10(6) cells/L and 4.24 (3.68-5.02) log(10) copies/ml, and the patients had been exposed to eight (5-9) antiretroviral drugs. After treatment interruption, the patients received at least three drugs depending on their treatment history. Forty-eight weeks after the resumption of therapy, 19 of the 56 patients (34%) had HIV-RNA levels of <400 copies/ml and, in comparison with study entry, the difference in the median increase in CD4+ counts between the virologic responders and non-responders (83 vs. 8.5 x 10(6) cells/L) was statistically significant (P = 0.02). Multivariate analysis showed that higher peak HIV-RNA levels before treatment interruption were independently predictive of virologic failure, whereas a longer treatment interruption period independently correlated with a virologic response. Four patients with CD4+ counts of <200 x 10(6) cells/L at study entry developed HIV-related clinical events. A sustained virologic response to therapy resumption after treatment interruption can be achieved in the setting of virologic failure. An evaluation of clinical history may help to identify the patients who are more likely to respond.


Glutaredoxin is essential for maintenance of brain mitochondrial complex I: studies with MPTP.
Mitochondrial complex I dysfunction is implicated in the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Identification of factors involved in maintenance and restoration of complex I function could potentially help to develop prophylactic and therapeutic strategies for treatment of this class of disorders. Down-regulation of glutaredoxin (thioltransferase, a thiol disulfide oxido-reductase) using antisense oligonucleotides results in the loss of mitochondrial complex I activity in mouse brain. 1-Methyl-4-phenyl-1,2,3,6,tetrahydro-pyridine (MPTP), the neurotoxin that causes Parkinson's disease-like symptoms in primates and dopaminergic cell loss in mice, acts through the inhibition of complex I. Regeneration of complex I activity in the striatum occurs concurrently with increase in glutaredoxin activity, 4 h after the neurotoxic insult, and is mediated through activation of activating protein-1. Down-regulation of glutaredoxin using anti-sense oligonucleotides prevents recovery of complex I in the striatum after MPTP treatment, providing support for the critical role for glutaredoxin in recovery of mitochondrial function in brain. Maintenance and restoration of protein thiol homeostasis by glutaredoxin may be important factors in preventing complex I dysfunction.


Counterion-induced translational isomerism in a bistable [2]rotaxane.
Translational isomerization can be induced by changing the anions associated with a bistable rotaxane in which the tetracationic cyclophane (blue box), cyclobis(paraquat-p-phenylene), encircles a dumbbell component containing bispyrrolotetrathiafulvalene (green) and a dioxynaphthalene (red) recognition sites. The rotaxane was isolated as both its hexafluorophosphate and tris(tetrachlorobenzenediolato)phosphate(v) (TRISPHAT(-)) salts. Photophysical measurements and NMR spectroscopy carried out in acetone (CD(3)COCD(3)) and acetonitrile (CD(3)CN) solutions reveal that the much larger TRISPHAT(-) anion favors predominantly the encirclement of the green site by the blue box.


Intraoperative detection of inferior vena caval tumor thrombus extending from metastatic lymph node of renal cell carcinoma using ultrasonography.
A 67-year-old man consulted our department with gross hematuria. Computed tomography (CT) revealed a huge renal tumor with a paracaval metastatic lymph node (mLN). Right total nephrectomy was planned for the renal tumor diagnosed as renal cell carcinoma preoperatively. Just before the resection of the renal vein and artery, intraoperative ultrasonography revealed an inferior vena caval tumor thrombus (IVCTT) extending from the mLN. Ultrasonography clearly and dynamically demonstrated a rhythmic flapping movement of the IVCTT with blood flow in the inferior vena cava. Following right radical nephrectomy, IVCTT resection with the vessel wall was performed to reduce the risk of pulmonary tumor thrombus. Histopathological diagnosis of the renal tumor was clear cell renal cell carcinoma, and the resected IVCTT was confirmed histopathologically as tumor involvement from the mLN of the renal cell carcinoma. Intraoperative ultrasonography can detect IVCTT extending from the mLN, whereas CT cannot.


Nonsteroidal anti-inflammatory drugs attenuate proliferation of colonic carcinoma cells by blocking epidermal growth factor-induced Ca++ mobilization.
Numerous studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal carcinogenesis. We have previously reported that NSAIDs, in human colonic carcinoma cells (Caco-2), attenuate epidermal growth factor (EGF)-induced cellular proliferation through a process independent of their inhibitory effects on prostaglandin synthesis. Furthermore, separate studies have also suggested that NSAIDs inhibit EGF-induced store-operated Ca++ influx. Thus we developed the hypothesis that NSAIDs may limit the activity of EGF by altering intracellular Ca++ ([Ca++]i) mobilization. Serum-deprived Caco-2 cells were employed for all experimentation. [Ca++]i was measured with Fluo-3 and extracellular Ca++ influx was monitored by quenching Fluo-3 fluorescence with Mn++. Proliferation was quantitated with two assays: cellular nucleic acid and total protein content. Caco-2 cells exposed to EGF demonstrated an initial increase in [Ca++]i which was blocked by neomycin, an inhibitor of IPsubscript 3 generation, and the phospholipase C inhibitor U73122 but not U73343 (inactive control). This was followed by sustained extracellular Ca++ influx, which was attenuated with calcium-free buffer (-Ca++), the store- operated Ca++ channel blocker lanthanum, indomethacin, ibuprofen, and aspirin. In subsequent studies, cells were treated with either serum-free media or EGF +/- the aforementioned inhibitors, and again serum starved. Cells exposed to EGF +/- the inactive phospholipase C inhibitor U73343 demonstrated a significant increase in nucleic acid and protein. However, proliferation induced by EGF was not observed when [Ca++]i elevation was prevented by blocking either internal Ca++ store release via phospholipase C/IPsubscript 3 or sustained Ca++ influx through store-operated Ca++ channels. Sustained [Ca++]i elevation, as induced by EGF, appears to be required for mitogenesis. These data support our premise that one mechanism whereby NSAIDs may attenuate colonic neoplasia is by blocking EGF-induced Ca++ mobilization.


Anterior pituitary functions in patients with uremia tested by stimulation with four combined hypothalamic releasing hormones.
Seven cases with uremia (6 men, 1 woman, mean age = 55.6 +/- 2.2 years) were studied with four combined hypothalamic releasing hormones (corticotropin-releasing hormone, CRH; luteinizing hormone-releasing hormone, LHRH; thyrotropin-releasing hormone, TRH; and growth hormone-releasing hormone, GHRH) for assessment of anterior pituitary functions. The mean basal levels of corticotropin (ACTH, 22.4 +/- 5.2 pg/ml), thyrotropin (TSH, 2.4 +/- 0.6 microU/ml), and follicle stimulating hormone (FSH, 26.0 +/- 3.4 mIU/ml) in uremic patients were not significantly different from those (34.0 +/- 3.5 pg/ml, 2.0 +/- 0.4 microU/ml, and 23.2 +/- 6.4 mIU/ml) of controls (5 men, 1 woman, mean age = 54 +/- 2.5 years), but the ACTH and TSH responses to the releasing hormones were significantly lower than those of the controls. The mean basal levels of luteinizing hormone (LH, 70.7 +/- 16.3 mIU/ml), cortisol (9.8 +/- 1.2 micrograms/dl) and prolactin (109.3 +/- 23.2 ng/ml) in uremic patients were significantly higher than those of normals (27.3 +/- 6.6 mIU/ml, 6.5 +/- 0.7 micrograms/dl and 15.7 +/- 3.4 ng/ml), while suppressed LH, cortisol and prolactin responses to the releasing hormones were observed in the uremic group. The mean basal growth hormone (GH) level in uremic patients (3.1 +/- 0.4 ng/ml) was not significantly different from that (2.8 +/- 0.7 ng/ml) of normals, but the GH response to the releasing hormones was significantly higher than that of controls. These results show pituitary dysfunction, such as blunted ACTH, TSH, LH and prolactin response, exists in uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of intima media thickness of the common and internal carotid arteries with inflammatory markers in familial Mediterranean fever as possible predictors for atherosclerosis.
The aim of the present study was to determine whether intima-media thickness (IMT) of the common (CCA) and internal carotid arteries (ICA) was increased due to chronic inflammation occurring in familial Mediterranean fever (FMF) patients compared to healthy controls. Erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), serum amyloid A protein (SAA), lipid profile and homocysteine levels were examined in 70 FMF patients [median age 14 years (range 4-24)] in an attack free period and in 50 healthy controls [median age 14 years (range 4-18)]. All the patients were homozygous or compound heterozygous for MEFV mutations. IMT of both CCA and ICA was evaluated with a high resolution B-mode ultrasonography. ESR, CRP, fibrinogen and SAA levels were significantly higher in FMF patients as compared to healthy controls (P < 0.05). Intima media thickness of the common carotid artery was found to be significantly higher in FMF patients when compared to those in healthy controls [0.37 mm (0.26-0.61) vs. 0.28 mm (0.21-0.35), P < 0.001]. The median ICA-IMT was significantly increased in the patients when compared to those in the controls [0.25 mm (0.18-0.44) vs. 0.22 mm (0.10-0.26), P < 0.001]. A positive correlation between CCA-IMT and SAA levels (r = 0.24, P = 0.04) was found while ICA-IMT positively correlated with ESR (r = 0.31, P = 0.008) and fibrinogen levels (r = 0.30, P = 0.012). Intima media thickness, an early predictor of atherosclerosis, may be associated with subclinical inflammation in children with FMF. Further studies will enlighten whether these patients will be predisposed more to coronary artery disease.


Ezetimibe-associated adverse effects: what the clinician needs to know.
Ezetimibe is a relatively new lipid lowering agent, which is indicated for the treatment of primary hypercholesterolaemia, either as monotherapy or in combination with other hypolipidaemic drugs. The objective of the present article was to review the side effects attributed to ezetimibe administration and discuss their possible underlying mechanisms. Moreover, we aimed to comment on the possible drug interactions of ezetimibe and present current guidelines regarding its safe use. Relevant articles were identified through a PubMed search (up to June 2007). Compelling evidence from the majority of the data reviewed here showed that adverse effects associated with ezetimibe use are few and mild without having been associated with serious clinical outcomes. In most studies ezetimibe has not been associated with increased rates of myopathy or rhabdomyolysis, whether used alone or in combination with statins, although there have been some case reports of myopathy attributed to this agent. Moreover, ezetimibe has been associated with mild elevations of liver transaminases, mainly in combination with a statin. Other side effects are extremely rare. It should be noted, however, there are no long-term safety data or outcome studies for ezetimibe yet. Ezetimibe is a safe alternative option for hyperlipidaemic patients intolerant to other lipid lowering drugs as well as a beneficial supplementary agent for patients who do not reach the recommended serum cholesterol level with their current hypolipidaemic treatment. However, as is the case with all new medications, physicians should be alert to recognise adverse effects associated with ezetimibe and report them to regulatory authorities.


Genetic data on three complex STRs (ACTBP2, D21S11 and HUMFIBRA/FGA) in the Galician population (NW Spain).
The allele frequency distributions of three complex STRs, ACTBP2 (SE33), D21S11 and HUMFIBRA/ FGA in the population of Galicia were investigated. Analysis was carried out under denaturing conditions and fluorescent detection in the ALF DNA sequencer and typing was made by comparison with sequenced allelic ladders. No significant deviations from Hardy-Weinberg equilibrium were observed. No significant differences were found between our data and other Caucasian population data. ACTBP2 seems to be one of the most informative and polymorphic STRs.


[Cerebrospinal fluid phospholipids and cerebrosides in several demyelinating diseases].
The author reports of the achieved results in a quantitative study of general lipids, phospholipids and cerebrosides in the CSF of 37 patients with demyelinating diseases, of 11 patients with vascular brain pathology and 7 with Van Bogart's panencephalitis. The control group consisted of 14 patients without focal lesions of the nervous system, with normal CSF indices. In demyelinating diseases there was a significant increase in the content of kephalines and cerebrosides. In Van Bogart's panencephalitis there was a much higher increase of kephalines, general lipids and phospholipids. In vascular brain disorders there was a moderate increase of all lipids. The possible pathochemical mechanisms of the depicted changes in the content of the lipids in the CSF are discussed.


Two cases of inverse Bell's phenomenon following levator resection: a contemplation of the mechanism.
The authors observed the unusual complication of inverse Bell's phenomenon of two cases following repeated and extensive levator resection surgery for a blepharoptosis and suggest the possible mechanism of the phenomenon. Case report. The first case was a 22-year-old woman who was diagnosed with a congenital ptosis with good levator function and she underwent levator resection and several reoperations because of asymmetry of lid height. Inverse Bell's phenomenon and resultant exposure keratitis were found in both eyes following the final surgery and they resolved in 1 month. The second case was a 19-year-old man with a right residual congenital ptosis. After a maximal levator resection was performed, he had a satisfactory lid height. Inverse Bell's phenomenon of right eye developed and reverted to normal after 2 weeks. The injury of oculomotor nerves in superior rectus during the repeated and excessive operation would alter a trigemino-oculomotor projection but it is unlikely because the phenomenon resolved without any treatment. Severe edema and hyperemia of the superior fornix following the operation may aggravate the relationship between eyelid and superior rectus movements. The simultaneous resolution of eyelid edema and inverse Bell's phenomenon supports our hypothesis that the latter may be determined by the edema of the soft tissue secondary to the surgical manipulations rather than the aberrant connections of the nervous system. When the inverse Bell's phenomenon develops postoperatively, copious use of lubricant and close follow-up of corneal complication is required until it resolves.


Effects of N-methylation and amidination of cyclic β-amino acids on enantioselectivity and retention characteristics using Cinchona alkaloid- and sulfonic acid-based chiral zwitterionic stationary phases.
In the present work the effects of N-methylation and N-amidination of ampholytic cyclic β-amino acids on their retention and enantioseparation characteristics on Cinchona alkaloid- and sulfonic acid-based zwitterionic chiral selectors, namely Chiralpak ZWIX(+)™ and ZWIX(-)™ columns are described. In a polar-ionic mobile phase, a double ion-pairing interaction mechanism takes place between the charged sites of the chiral analytes (the selectands) and the chiral selector moieties. As a support to correlate the chromatographic results with the structural details of the analytes, pKa values and van der Waals volumes of the substituted amino groups were calculated. In order to ensure better understanding of the mechanistic details of the chromatographic system the composition of the bulk solvent, the role of acid base additives, the concentration of the counter-ions, temperature and the structures of the ampholytic analytes have been investigated. Applying N-Fmoc protection, the ampholytic character of the analytes diminished, leading to a marked loss of retention. In the temperature range studied (5-40 °C) thermodynamic parameters, such as the difference in the standard enthalpy change Δ(ΔH°), entropy Δ(ΔS) and Gibbs energy Δ(ΔG°) were calculated from linear van't Hoff plots derived from the ln α vs. 1/T curves. The values of the thermodynamic parameters depended on the structures of the chiral selectors applied and the analytes studied.


Comparison of macular thickness and inflammatory cytokine levels after microincision versus small incision coaxial cataract surgery.
To compare the macular thickness and volume change, and inflammatory cytokine levels after cataract surgery performed using two different sizes of incision (microincision versus small incision). In this randomized, comparative clinical trial, 84 eyes with nuclear density from Grade 3-4 were randomly divided into two groups (microincision, 2.2 mm; and small incision, 2.75 mm). Forty-two patients underwent phacoemulsification with microincision coaxial cataract surgery and 42 patients underwent phacoemulsification with small incision coaxial cataract surgery. Clinical measurements included preoperative, 1-week, 1-month and 2-month postoperative best corrected visual acuity, central corneal thickness (CCT) and endothelial cell count. ELISA and RT-PCR were performed for IL-1β, IL-6, VEGF and PGE2 preoperatively and at 1 week postoperatively. The percentage increase in CCT in the microincision group was significantly higher than that in the small incision group at 1 week after cataract surgery (p = 0.01). The increase in macular thickness in the microincision group was significantly higher than that in small incision group at 1 month after cataract operation (p = 0.04). Also, IL-1β, IL-6, VEGF and PGE2 concentrations and their expression ratio in the microincision group were significantly higher than those in the small incision group at 1 week after cataract surgery compared to the preoperative period (p < 0.05). Phacoemulsification with microincision coaxial cataract surgery may increase the macular thickness compared to phacoemulsification with small incision coaxial cataract surgery. Blood-aqueous barrier breakdown may occur more frequently after microincision cataract surgery than after small incision cataract surgery.


Generation of an optimized polyvalent monocyte-derived dendritic cell vaccine by transfecting defined RNAs after rather than before maturation.
Transfection with RNA is an attractive method of Ag delivery to dendritic cells (DCs), but has not yet been standardized. We describe in this study the methods to efficiently generate an optimized mature monocyte-derived DC vaccine at clinical scale based on the electroporation of several RNAs either into immature DC followed by maturation or, alternatively, directly into mature DCs, which has not been possible so far with such high efficiency. Electroporation of DCs resulted in high yield, high transfection efficiency (>90%), and high migration capacity. Intracellular staining allowed the study of the expression kinetics of Ags encoded by the transfected RNAs (MelanA, MAGE-3, and survivin) and a validation of the vaccine (>/=90% transfection efficiency). Expression of all three Ags peaked 3-4 h after electroporation in DC transfected either before or after maturation, but decreased differently. The DC vaccine can also be cryopreserved and nevertheless retains its viability, stimulatory capacity as well as migratory activity. In addition, we uncover that DC transfected after rather than before maturation appear to be preferable vaccines not only from a production point of view but also because they appear to be immunologically superior for CTL induction in sharp contrast to common belief. DCs transfected after maturation not only more effectively generate and present the Mage-3.A1 and MelanA.A2.1 epitopes to T cell clones, but they even are superior in priming to the standard proteasome-dependent MelanA.A2.1 wild-type prototype tumor epitope, both in terms of T cell expansion and effector function on a per cell basis.


[Standardization of the thromboplastin time determination].
The results of our studies prove that today it is possible for manufacturers of thromboplastin preparations to follow the international recommendations for standardization of methods for prothrombin time determination. This is valid not only for the PT reagents for coagulometric techniques but also for those for photometric techniques. New manufacturing processes allow to produce sensitive thromboplastins which can be calibrated according to the recommendations of international standardization committees. Calibrated thromboplastins enable introduction of a common scale (INR) for the control of the intensity of the oral anticoagulation. The INR system improves the comparability of the therapeutical ranges recommended from different organizations and from manufacturers of thromboplastin, so that the continuity of the oral anticoagulant therapy of patients even in different countries will be decisively improved.


Depression of neuronal firing rates in somatosensory and posterior parietal cortex during object acquisition in a prehension task.
Prehension is an object-oriented behavior consisting of four components: reach, grasp, manipulation, and release. To determine how such actions are represented in primary somatosensory (S-I) and posterior parietal cortex (PPC), we used digital video to synchronize spike trains of neurons recorded in Brodmann's areas 3b, 1, 2, 5, and 7 with the hand kinematics as monkeys performed a prehension task. Statistical analyses indicated that one-third of task-modulated neurons showed significantly depressed firing rates during object acquisition and/or manipulation. This population was dominated by neurons innervated by deep receptors that sensed extension movements of the fingers, or by tactile receptors in hairy skin sensing stretch. Grasp-inhibited responses were the most common type. Tonic firing rates of these cells dropped significantly during approach as the hand was preshaped for grasping, or at contact when grasp was initiated, and persisted until hand motion ceased or as the grip relaxed. Maximum suppression of firing occurred at grasp completion. Their lack of specificity for particular hand behaviors formed the inhibitory counterpart of broadly tuned cells that fired prolonged bursts during grasp and manipulatory stages of prehension. The remainder of the task-inhibited population showed biphasic responses. Firing rates were significantly depressed during grasping and manipulation when the hand interacted directly with the object, but were enhanced prior to contact, when the hand was preshaped (approach-tuned), or upon relaxation of grasp and release of the object from the hand (loweror relax-tuned). Grasp-inhibited responses occurred primarily in S-I, whereas biphasic inhibitory activity was recorded mainly in PPC. Suppression of activity within these populations may thereby increase the saliency of excitatory responses to acquisition and manipulation of objects. Reduction of firing during prehension might also signal the flexed postures used to retain objects in the hand, rather than a generalized gating of sensory information. The similarity of responses to active and passive extension movements suggests that the inhibitory responses may provide important postural and motor information about the hand kinematics when performing skilled tasks.


Sewers and scapegoats: spatial metaphors of smallpox in nineteenth century San Francisco.
Medical geography is slowly including more social and cultural theory in its analysis of health issues. Yet there is still room for theoretical growth in the discipline, in areas such as historical inquiry, metaphoric landscapes of disease, and the role of disease and its interpretations in the production of place. With the example of four smallpox epidemics in nineteenth century San Francisco, application of these concepts is illustrated. Each successive epidemic in San Francisco brought stronger association of the disease with Chinatown, until an almost complete metonymy of place and disease had occurred by the last decades of the century. The articulation of biased medical theory onto a landscape of xenophobia engendered this metaphorical transformation of Chinatown into a pustule of contagion threatening to infect the rest of the urban body. A less metaphoric mapping of smallpox focused on the sewer. According to 19th-century miasmatic theories of epidemiology, sewers were the most dangerous urban topographical feature. In an increasingly class-stratified city, they undercut attempts of the upper classes to escape disease by carrying smallpox-causing miasmas across class and ethnic boundaries. A reinvigorated sanitation movement was the result. Both reactions to smallpox epidemics had significant influence in shaping San Francisco's landscape, real and symbolic.


Visual search training in subjects with severe to profound low vision.
Effects of practicing on feature search tasks (a 2 degrees square target amid 1 degrees square distracters) for 5 days were compared between 45 visually impaired (VI) subjects with severe to profound low vision and 23 age-matched normal controls (NV). Search accuracy and speed improved in both groups. VI subjects had larger training gains than NV subjects, but their proportional gains were similar to that of NV subjects. There were no significant differences in training effect at different set sizes in both groups. Search performance on a 40 degrees field improved more than that on a 10 degrees or 20 degrees field in VI subjects, but not in NV subjects. No significant change was found between day 5 and 1-month follow-up. The fact that feature search training is equally efficient in VI and NV subjects encourages development of general purpose perceptual training protocols for low vision rehabilitation.


Ontogeny of amicable social behavior in the mouse: gender differences and ongoing isolation outcomes.
The behavioral repertoire of male and female outbred CD-1 mice was characterized during development (postnatal Days 23-47). To assess the effects of the rearing condition, half of the subjects were individually housed (IC) at weaning (Day 21), while the remaining mice were housed in pairs (PC) of same-sex siblings. The occurrence of 22 behavioral items was scored during nine social encounters, 3 days apart, between pairs of unfamiliar same-sex and same-condition animals. Individually housed mice were much more involved than paired subjects in solitary play and social interactions (affiliative, investigative, and soliciting behaviors), while less interested in nonsocial behaviors (exploration, and escape-oriented or maintenance activities). An over-days increment for elements of social behavior was evident, with a peak of affiliative behavior at 23-32 days of age. For gender differences, in contrast with rat data, a marked female primacy in both social and playful behaviors was found. Overall, these findings clearly indicate that the behavioral repertoire of developing mice during paired encounters is strongly affected by both the sex of the subjects and the housing condition they are experiencing.


Rise in plasma leptin levels after stimulation of hypothalamic cholinoceptive neurons by neostigmine in rats.
To investigate the role of hypothalamic cholinergic neurons in the regulation of plasma leptin levels, we injected neostigmine, a cholinesterase inhibitor, or vehicle alone into the third cerebral ventricle in free moving male Wistar rats and then measured plasma leptin levels. The administration of neostigmine (5 x 10(-9) or 5 x 10(-8) mol) increased plasma leptin levels 3-6 h after stimulation in a dose-dependent manner, while intravenous injection of neostigmine (5 x 10(-8) mol) had no effect. Atropine (5 x 10(-8) mol) concomitantly injected with neostigmine (5 x 10(-8) mol) prevented neostigmine-induced increase in plasma leptin. The expression of leptin messenger ribonucleic acid (mRNA) in epididymal white adipose tissue was significantly increased at 4 and 6 h after neostigmine injection compared with that before the injection. Plasma levels of corticosterone were significantly increased at 30 min after stimulation with neostigmine and this increase was sustained for 6 h after stimulation. Furthermore, bilateral adrenalectomized rats showed no increase in plasma leptin levels after stimulation. In conclusion, stimulation of hypothalamic cholinoceptive neurons increased plasma leptin levels in rats by increasing leptin production in adipocytes. This increase may be due to an increase in glucocorticoids from the adrenal glands. These results suggest that plasma leptin levels can be regulated by hypothalamic cholinoceptive neurons.


[Long-term results of multimodality treatment in patients with primary liver cancer].
This paper report the long-term results of multimodality treatment in 2388 patients with pathologically proven primary liver cancer (PLC) over the last three decades. The 5-and 10-year survival after resection of PLC was 39.3% and 29.2% respectively for the whole series (n = 1650), and 61.9% and 45.4% respectively for patients with small PLC (< or = 5 cm, n = 569). The 5-year survival after cryosurgery was 37.9% for the whole series (n = 191), and 53.1% for patients with small PLC (n = 56). The 5-year survival of 71 patients receiving sequential resection after cytoreduction therapy was 66.0%. The 5-year survival after re-resection for recurrence tumor (n = 147) was 34.5%. 214 patients survived more than 5 years; of these 113 patients (52.8%) were small PLC, and 57 patients survived more than 10 rears. It is concluded that early detection and resection of small PLC is the leading approach to get long-term survivors, cytoreduction and sequential resection might be an important approach to improving the prognosis of patients with unresectable PLC, re-resection for subclinical recurrance and metastasis after an initial curative resection was also important to prolong survival further.


Toward a post-Charter health promotion.
The past 25 years have seen enormous shifts in the environmental, political, economic and social landscapes that condition people's abilities to be healthy. Climate change is now a reality. China, India, Brazil and other 'developing' countries are emerging as new axes of political and economic power. Global capitalism has become increasingly predatory and crisis ridden, a result of unregulated and irresponsible greed of unimaginable scale. The elite response has been the increased erosion of the health and other social protection policies of redistribution that characterized the first-world run-up to the Ottawa Charter. These new realities challenge health promoters in ways unforeseen a quarter century ago. It is imperative that local determinants of health, to which health promoters give their attention, be traced to broader, even global levels of determinants. Support for groups acting at these levels should become a fundamental practice tenet. So, too, should advocacy for the social state, in which progressive taxation and hefty social investment blunt the health inequalities created by unfettered markets. As environmental and economic insecurities and inequalities increase in many of the world's countries, so does the risk of xenophobia and conflict. The roots of racism are complex; but weeding them out becomes another health promotion practice of the new millennium. There are some hopeful signs of health promoting political change, much of it emanating now from countries in the global South; but the threat of a return to health behaviourism in the face of the new global pandemic of chronic disease is real and must be confronted.


Aspergillus nidulans nuclear proteins bind to a CCAAT element and the adjacent upstream sequence in the promoter region of the starch-inducible Taka-amylase A gene.
Aspergillus nidulans was used as an intermediate host to investigate the regulation of the Taka-amylase A (TAA) gene from Aspergillus oryzae. The induction of Taa by starch was confirmed to be regulated at the transcriptional level by analyzing the transcripts specific for Taa synthesized in vitro in nuclei from starch- and glucose-grown cells. A 55 bp DNA fragment containing a consensus CCAAT sequence from the promoter region of the Taa gene was shown to confer starch inducibility on the gene. A nuclear extract from starch-grown cells was assayed for proteins which bind to the promoter region of the Taa gene. A protein designated AnCP1 bound to the CCAAT sequence. A nuclear extract from glucose-grown cells contained two DNA-binding proteins designated AnCP2 and AnNP1. AnCP2 bound to the same CCAAT sequence as AnCP1, while AnNP1 bound to the 25 bp region just upstream of the AnCP2 binding site. Occupancy of the two binding sites appeared to be mutually exclusive, which is suggestive of a negative regulatory mechanism for gene expression.


A dose-surviving fraction curve for mouse colonic mucosa.
A dose-surviving fraction curve representing the response of the mouse colonic mucosa to single doses of 137Cs gamma radiation was obtained from the results of a multifraction in vivo colony assay. Construction of the curve required an estimate of the average number of clonogens initially present per colonic crypt. The estimated clonogen count (88) was determined by a statistical method based on the use of doses per fraction common to different fractionation protocols. Parameters for the LQ and TC models of cell survival were obtained by weighted least-squares fits to the data. A comparison of the survival characteristics of cells from the mouse colonic and jejunal crypts suggested that the epithelium of the colon is less radiosensitive than that of the jejunum.


Single agent vinorelbine in the treatment of unresectable lung metastases from colorectal cancer.
Vinorelbine (VNR; 5'-nor-anydro-vinblastine) is a new semisynthetic vinca alkaloid which has demonstrated significant clinical activity against non-small cell lung cancer, bronchial adenocarcinoma, breast cancer, and head/neck squamous cell carcinoma. Moreover, vinorelbine has been widely employed in combination with cisplatinum with or without 5-fluorouracil for the treatment of lung cancer and head/neck carcinomas. Sixteen consecutive patients with lung metastases from colorectal adenocarcinomas were treated with vinorelbine tartrate (Navelbine R) given at the dose of 25 mg/m(2) i.v. bolus every week for eight consecutive times employing metoclopramide as an antiemetic tool. All patients had previous surgery, two had adjuvant chemo-immunotherapy with i.v. 5-fluorouracil and oral levamisole, 5 patients had adjuvant radiotherapy, and 1 patient had chemotherapy with levofolinic acid and 5-fluorouracil for advanced disease. Sites of disease included lung in all cases, liver metastases in 3 patients and nodal tumoral deposits in 2 cases. All patients entered in the study had lung disease as predominant site of disease and showed multiple metastases. One patient was not evaluable for response, toxicity and survival because he was lost to follow-up before completion of therapy. No major objective response was seen. Four patients had stable disease which lasted a mean of 5.2 months, and the remaining 11 patients showed progressive disease. Mean survival was 6.7+ months (range 4.0-12.0+ months). The treatment was quite well tolerated by most patients, granulocytopenia being the most frequent side-effect. Nausea/vomiting was very mild with grade 1 episodes in 5 patients (33%). Grade 1 leukopenia was seen in 5 patients (33%), grade 2 leukopenia in 3 patients (20%), and grade 3 in 2 cases (13%). Grade 1 thrombocytopenia was recorded in 3 cases (20%). No significant neurotoxicity was observed, except mild constipation in 4 cases (26%). The activity of VNR on a weekly schedule against lung metastases from large bowel adenocarcinoma is very low, however it should be noted that the treatment was well tolerated by most patients.


Expanding the clinical and genetic spectra of NKX6-2-related disorder.
Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6-2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole-exome or whole-genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6-2 in 3 and 2 unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and they show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in 2 families each) represent an addition to the phenotype, while developmental regression (observed in 3 families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype-phenotype correlation.


A comparison of fracture strength of yttrium-oxide- partially-stabilized zirconia ceramic crowns with varying core thickness, shapes and veneer ceramics.
The fracture strengths of stylized all-ceramic crowns manufactured using an yttrium-oxide-partially-stabilized (Y-TZP) zirconia ceramic core (Denzir) veneered with lithium disilicate glass-ceramics (IPS Empress 2 or IPS Eris) were evaluated. The Denzir cores were manufactured in two ways: either with different thickness in different parts of the restoration, called an 'adapted Denzir core'; or with a uniform core thickness of 0.5 mm. IPS Empress 2 all-ceramic crowns served as reference. There was no significant difference between the crowns with an 'adapted Denzir core' veneered with the two brands of glass-ceramics. No significant difference was seen between the crowns with a 0.5 mm Denzir core veneered with the two brands of glass-ceramics. The crowns with an 'adapted Denzir core' exhibited significantly higher values than those with a 0.5 mm Denzir core and than the IPS Empress 2 crowns used as reference. No significant differences were seen among the IPS Empress 2 crowns used as reference and the crowns with a 0.5 mm Denzir core. The mode of failure varied among the Empress 2 crowns and the crowns with a core of a Y-TZP zirconia ceramic. Long-term studies are necessary to assess the clinical performance of this restorative system.


Demographic and clinical features of Behcet's disease in Azerbaijan.
Behcet's disease (BD) is a multisystem inflammatory disease characterized by recurrent aphthous ulcers, genital ulcers and uveitis. Demographic and clinical features of BD are different in various countries. Due to these ethnic discrepancies, we decided to consider the clinical picture of BD in the Azeri population of Iran and compare it with other ethnic groups. This cross-sectional cohort study was carried out at the Connective Tissue Diseases Research Center of Tabriz University of Medical Sciences, Tabriz, Iran from 2006 to 2013. We considered the demographic and clinical findings in 166 patients with BD. Disease activity was measured by the Iranian Behcet's Disease Dynamic Activity Measure (IBDDAM) and Total Inflammatory Activity Index (TIAI). The male-to-female ratio was 1.7 : 1.0; the age of disease onset was 25.8 ± 8.9 years. Recurrent oral aphthous ulcers were the initial manifestations of BD in 83.1% of patients. Panophthalmitis and panuveitis were the most common ophthalmic manifestations of disease. Blindness occurred in 7.1% of patients. This study showed no difference between the two genders in mean age of disease onset and clinical manifestations. However, IBDDAM in men was higher than women. Retinal vasculitis in men was more common than women. BD in the Azeri population of Iran starts in the third decade and has a male predominance. The activity of the disease and retinal vasculitis in men is more predominant than women in Azerbaijan.


[Networking, Coordination and Responsibilities based on Health Regionsplus: New Health Political Approaches and Developments in Bavaria].
For many health and health-care problems in the population, there is a need for professional management and coordination instruments as well as a competent local network. The new "Health Regionsplus" in Bavaria offer such a structure. This new concept is presented in the following article. The "Health Regionsplus" aim to improve the population's health, the health-related quality of life, equity in health, as well as to further develop the local health care. The Bavarian State Ministry of Health and Care will support up to 24 regions with a funding of up to 50 000 Euro yearly per "Health Regionplus" until the end of 2019. The structure of "Health Regionsplus" implies the establishment of a coordinating agency that works as a "motor", a health forum on the strategic level and relevant working groups. "Health Regionsplus" involve all relevant stakeholders of the regional health system and are chaired by the district administrator or mayor. They work primarily in the fields of health care and prevention/health promotion but can also pursue other region-specific fields. The Bavarian Health and Food Safety Authority supports and evaluates the "Health Regionsplus". There is also a coordinating office which organises the exchange of information and experience among the "Health Regionsplus". Although such a comprehensive regional approach does not change the statutory decision-making structures and responsibilities it does offer the communities an instrument to involve local needs in their decision-making processes.


[Surgical method and combination chemotherapy in treating stage-III and IV ovarian cancer].
The results of treatment of 50 patients with ovarian cancer (serous carcinoma) are reported. At the first step all the patients were treated surgically. Following the operation the combined chemotherapy was employed with three schedules: 1. 5-fluoruracil-cyclophosphane--26 patients; 2. 5-fluoruracil-cyclophosphane-methotrexate-hexamethyl melamine--16 patients; 3. fluorofur-cyclophosphane-methotrexate-hexamethyl melamine--8 patients. An analysis of the results of the treatment in ovarian cancer patients has demonstrated that a positive therapeutic effect may be gained using each of the schedules of the polychemotherapy employed, of special importance being such factors as the degree of tumor proliferation, radicality of surgical intervention and the magnitude of toxic reactions of antitumor drugs.


Social environment determines the long-term effects of social defeat.
A single social defeat by a dominant conspecific induces long-term changes in several physiological and behavioral parameters in rats. These changes may represent an increased vulnerability to subsequent stress and stress-related pathology. Environmental factors, in particular possibilities for social interactions, could modulate these effects. Therefore, we assessed the influence of social environment on susceptibility for the long-term effects of social defeat. Socially housed males of an unselected strain of wild-type rats were equipped with radio-telemetry transmitters that recorded heart rate, temperature and activity. They were individually subjected to defeat and subsequently either housed alone or returned to their group. Behavioral and physiological responses to various novelty stressors were determined during a three-week period after the social defeat. Furthermore, changes in baseline behavior and physiology following defeat were studied in the rat's homecage. The results show a complex interaction between defeat and housing conditions. Depending on the parameters measured, effects were caused by both isolation alone, defeat alone or a combination of both defeat and isolation. Individual housing alone caused a characteristic hyperactive response to novelty stress. Though defeat did not affect behavioral responses, it amplified the physiological response to novelty and social housing did not attenuate this effect. However, social housing did reduce the effects of defeat on heart rate, temperature and activity in the home cage and completely prevented defeat-induced weight loss. Together these results indicate that social housing may indeed positively affect the animal's capacity to cope with stressors.


An artificial grasping evaluation system for the paralysed hand.
Neuromuscular electrical stimulation (NMES) has been used in upper limb rehabilitation towards restoring motor hand function. Quantitative evaluation of the artificially generated movement is necessary to achieve proper muscle activation. Custom-made gloves instrumented with force and position transducers were used to evaluate artificial quadriplegic grasping for a drinking activity. In spite of different sensor position, stimulation parameter dependence and lack of repeatability, grasp patterns achieved with the application of NMES follow the same patterns previously obtained with normal subjects, regarding force distribution among fingers and the shape of force curves. Larger forces were exerted by the thumb (average ranged from 2.8 to 4.5 N) following by index or long finger (average ranged from 1.8 to 3 N). The forces exerted ranged within the same interval as those previously measured and were sufficient to grasp an object of 10 N. Finger position achieved by interphalangeal joint status indicated the opening size of the hand throughout the range of movement. The instrumented gloves offer an alternative force and position feedback system for use in cylindrical grasp evaluation. The gloves can be used in a closed-loop control system, allowing on-line adjustment or in a clinical application to evaluate the results of a rehabilitation programme.


Determination of degree of substitution of formyl groups in polyaldehyde dextran by the hydroxylamine hydrochloride method.
Colorimetric or potentiometric titration of the aldehyde residues in polyaldehyde dextran by the hydroxylamine hydrochloride/sodium hydroxide method has been found to be a convenient and accurate method to determine formyl content. Nitrogen combustion analyses on the isolated oximes confirmed the titrametric results.


Macular development in the premature infant.
To classify the ophthalmoscopic appearance of the developing macula, I performed retinal examinations on 129 premature neonates. In normal infants, the classification ranged from 34 weeks of gestational age when pigment was first evident in the macula, through the development of the annular ring reflex of the macula and foveolar reflex, to a mature (adult-appearing) macula at 42 weeks. This sequence allowed the observer to estimate the gestational age of the older premature neonate from the appearance of the macular area. Babies who had, or subsequently developed, retinopathy of prematurity showed a statistically significant two-week delay in macular development in the later stages. This may be the first evidence of a direct macular insult in retinopathy of prematurity.


gamma-Aminobutyric acid-induced elevation of intracellular calcium concentration in pituitary cells of neonatal rats.
Gamma-aminobutyric acid (GABA) increased intracellular calcium concentration ([Ca2+]i) of newborn rat pituitary cells in suspension measured by the FURA-2 method. The effect of GABA was dose dependent in the range of 0.1-10 microM. This effect diminished with postnatal age as measured at days 2, 14 and 21, and in adult animals. The GABA stimulation was mimicked by muscimol; in contrast, baclofen (up to 100 microM) was ineffective. Picrotoxin, a GABAA antagonist interacting with GABA-activated chloride ionophores, caused a dose-dependent inhibition of the [Ca2+]i elevating effect of 100 microM GABA or muscimol. These observations indicate the involvement of GABAA type receptors. The GABA or muscimol effect on [Ca2+]i was antagonized by nifedipine (10 microM) or verapamil (50 microM), and completely abolished in the presence of 4 mM EGTA (low-calcium medium). The findings indicate the presence of depolarizing GABAA receptors on neonatal rat pituitary cells. It seems very likely that the mechanism by which GABA receptor occupation results in elevated [Ca2+]i is a membrane depolarization by increased Cl- conductance followed by calcium influx through L-type voltage-dependent calcium channels.


Between-object and within-object saccade programming in a visual search task.
The role of the perceptual organization of the visual display on eye movement control was examined in two experiments using a task where a two-saccade sequence was directed toward either a single elongated object or three separate shorter objects. In the first experiment, we examined the consequences for the second saccade of a small displacement of the whole display during the first saccade. We found that between-object saccades compensated for the displacement to aim for a target position on the new object whereas within-object saccades did not show compensation but were coded as a fixed motor vector applied irrespective of wherever the preceding saccade landed. In the second experiment, we extended the paradigm to examine saccades performed in different directions. The results suggest that the within-object and between-object saccade distinction is an essential feature of saccadic planning.


Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice.
Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.


[Differential diagnosis of osteomalacia and other forms of renal osteodystrophy in terminal renal failure by dynamic scintigraphy with diphosphonate].
During osteomalacia in patients with terminal renal failure, the coefficient of diphosphonate elimination from the blood bed (K1) was less than 0.1 min-1, which was determined by the rise of the concentration of uremic toxins, inhibiting interaction of the radiopharmaceutical with the bone, in the patients' tissues. Dynamic scintigraphy permits one to study the pharmacokinetics of diphosphonate in every patient and thus can be used for differential diagnosis between osteomalacia and other forms of renal osteodystrophy.


Variability of oxygen affinity of blood: human subjects native to high altitude.
Whole blood O2 equilibrium curves (OEC) were measured in 46 Peruvians native to high altitude (4,540 m) and in 25 sea-level controls. A method was employed that records the entire OEC from 0 to 150 Torr with constant pH and PCO2. The data were analyzed by fitting the Adair equation describing the successive oxygenation of hemoglobin. At pH 7.4 the PO2 at which hemoglobin is half-saturated with O2 (P50) was significantly higher in the high-altitude population (31.2 +/- 1.9 Torr) than in controls (29.2 +/- 1.8 Torr, P less than 0.001). The acid-base status of the high-altitude subjects, however, was that of compensated respiratory alkalosis (plasma pH 7.439 +/- 0.065), and when the P50's were corrected to the subjects' plasma pH the values (30.1 +/- 2.2 Torr) could no longer be distinguished from the controls. We conclude that, on the average, increased P50 resulting from increased red cell 2,3-diphosphyoglycerate concentration at high altitude is offset by compensated respiratory alkalosis with the net result that the position of the OEC more closely approaches that of sea-level humans than has hitherto been thought. Considerable variation exists in P50, both at sea level and high altitude. This variation might have important consequences for acclimatization and survival under adverse environmental conditions.


The radiography of foreign bodies in the eye as carried out at the Birmingham and Midland Eye Hospital.
An account is given of the following procedures at the Birmingham and Midland Eye Hospital; (a) to show if a foreign body is present in the area of the eye; (b) to demonstrate its possible presence within the globe of the eye; (c) to localise its exact position within the globe, using the limbal ring technique.


Laryngeal mask airway vs face mask and Guedel airway during pediatric myringotomy.
To compare perioperative conditions when a face mask and Guedel oral airway (FM-OA) or a laryngeal mask airway (LMA) are used to maintain airway patency during bilateral myringotomy with insertion of tympanostomy tubes (BMT). Randomized controlled trial in children's hospital tertiary-care operating rooms. Fifty healthy children undergoing BMT procedures during halothane--nitrous oxide (N2O) anesthesia. During BMT we managed the airway by inserting a Guedel oral airway or an LMA. We recorded the time taken to insert the airway device along with oxygen saturation during the operation and time from the end of surgery to eye opening, response to commands, and home readiness. In addition the surgeon assessed perioperative conditions on a 10-point scale (1, poor, through 10, excellent). Although insertion of the LMA took longer than the Guedel oral airway (mean +/- SD, 9 +/- 2 seconds vs 6 +/- 2 seconds; P < .05), no differences were noted in the actual operating, anesthesia, or recovery times. However, the frequency of hypoxemic episodes was decreased (8% vs 36%, P < .05) and the lowest recorded oxygen saturations were higher (mean +/- SD, 95% +/- 7% vs 88% +/- 12%; P < .05) in the LMA group than in the FM-OA group. Surgeons rated perioperative conditions better when the LMA was used (median score, 9 vs 8; P < .05). The LMA is an excellent alternative to the FM-OA technique for airway maintenance in children undergoing BMT procedures during halothane--N2O anesthesia.


Prognostic value of preoperative 18F-FDG PET/CT in papillary thyroid cancer patients with a high metastatic lymph node ratio: a multicenter retrospective cohort study.
Metastatic lymph node ratio (MLNR) is a known significant predictor of disease-free survival in differentiated thyroid cancer. The authors investigated the ability of preoperative fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT to predict recurrence after surgery with radioactive iodine therapy considering MLNR. A total of 274 patients who underwent preoperative PET/CT and surgery with radioactive iodine therapy were enrolled. The tumor-to-liver uptake ratio on PET/CT was calculated by dividing the maximum standardized uptake value of a primary lesion by the mean standardized uptake value of the normal liver. High F-FDG uptake was defined as tumor-to-liver uptake ratio more than the median cutoff value (2.1). MLNR was calculated by dividing the number of metastatic lymph nodes (LNs) by the number of cervical LNs removed. A high MLNR was also defined as one more than a threshold value (0.4), identified by plotting Kaplan-Meier survival curves and comparing them using the log-rank test. The prognostic significances of clinicopathologic variables were analyzed. Fifteen (5.5%) patients developed recurrence in the thyroid bed or in cervical LNs. Cox regression analysis showed that a high MLNR was significantly associated with a worse disease-free survival (odds ratio 6.95; 95% confidence interval: 2.36-20.47; P<0.001). A subgroup analysis of 70 patients with a high MLNR showed that only high F-FDG uptake was significantly associated with a worse disease-free survival (odds ratio 5.77; 95% confidence interval: 1.22-27.16; P=0.027). High F-FDG uptake of primary lesion on preoperative PET/CT has selective prognostic value according to the extent of metastatic LNs (MLNR>0.4).


Sympathetic control of motility, fluid transport, and transmural potential difference in the rabbit ileum.
Both intestinal motility and intestinal fluid and electrolyte transport are influenced by the sympathetic nervous system. The aim of this study is to examine the relationship between the sympathetically induced inhibition of spontaneous contractile activity and epithelial function, monitoring simultaneously motility, fluid transport, and transmural potential difference (PD) in the rabbit ileum. Experiments were performed in vitro to eliminate any possible indirect effects on intestinal function caused by alterations in intestinal blood flow. Perivascular nerve stimulation induced an inhibition of spontaneous motility, a fall in transmural PD (toward more lumen positive), and an enhanced fluid absorption. The sympathetically induced inhibition of motility was abolished by the beta-adrenoceptor antagonist, propranolol, whereas the subsequent administration of phentolamine, the alpha-adrenoceptor antagonist, was required to abolish the fall in transmural PD. Thus the sympathetic nervous system is capable of simultaneously influencing intestinal motility and fluid and electrolyte function. However, separate but parallel neural mechanisms control the smooth muscle and epithelial responses; the inhibition of motility is beta-mediated, while alpha-receptors alter fluid and electrolyte transport.


Adolescent precursors of intensity of marijuana and other illicit drug use among adult initiators.
This study examined (a) adolescent psychosocial risk factors for frequency (intensity) of marijuana use and for other illicit drug use among those who started using these drugs in early adulthood (adult initiators) and (b) the protective role of parent-adolescent relations in reducing or preventing drug use when adolescents enter early adulthood. The study's participants were male and female youth from a longitudinal prospective study. The participants' mean ages were 17 and 22 years at late adolescence and early adulthood, respectively. Independent measures assessed personality, parental, peer, and self-drug-use factors during late adolescence; dependent measures assessed frequency of marijuana use and other illicit drug use during early adulthood for initiators of the respective drug categories. The authors found that intensity of marijuana use was directly associated with the personality, parental, and self-drug-use domains and indirectly associated with the peer domain. Intensity of other illicit drug use was directly associated with personality and self-drug use. Analyses also revealed that some parent-adolescent relations factors buffered the effects of risk factors for both marijuana and other illicit drug-use intensity, whereas others enhanced the effects of protective factors against other illicit drug-use intensity. The results indicate that there are both commonalities and differences in precursors of marijuana and other illicit drug-use intensity among initiators of these drugs during early adulthood.


The effect of low-dose dexmedetomidine on hemodynamics and anesthetic requirement during bis-spectral index-guided total intravenous anesthesia.
The purpose of this study was to evaluate the effects of low-dose dexmedetomidine on hemodynamics and anesthetic requirements during propofol and remifentanil anesthesia for laparoscopic cholecystectomy. Thirty adult patients were randomly allocated to receive dexmedetomidine infusion of 0.3 μg/kg/h (dexmedetomidine group, n = 15) or comparable volumes of saline infusion (control group, n = 15). Target controlled infusion of propofol and remifentanil was used for anesthetic induction and maintenance, and adjusted in order to maintain a bispectral index of 40-55 and hemodynamic stability. We measured hemodynamics and recorded total and mean infused dosages of propofol and remifentanil. For anesthesia induction and maintenance, mean infused doses of propofol (121 ± 27 vs. 144 ± 29 μg/kg/min, P = 0.04) and remifentanil (118 ± 27 vs. 150 ± 36 ng/kg/min, P = 0.01) were lower in the dexmedetomidine group than in the control group, respectively. The dexmedetomidine group required 16 % less propofol and 23 % less remifentanil. During anesthetic induction and maintenance, the dexmedetomidine group required fewer total doses of propofol (9.6 ± 2.3 vs. 12.4 ± 3.3 mg/kg, P = 0.01) and remifentanil (9.6 ± 3.4 vs. 12.7 ± 2.6 μg/kg, P = 0.01). The change in mean arterial pressure over time differed between the groups (P < 0.05). Significantly lower mean arterial pressure was observed in the dexmedetomidine group than in the control group at immediately and 5 min after pneumoperitoneum. The time to extubation after completion of drug administration did not differ between the groups (P = 0.25). This study demonstrated that a low-dose dexmedetomidine infusion of 0.3 μg/kg/h reduced propofol and remifentanil requirements as well as hemodynamic change by pneumoperitoneum without delayed recovery during propofol-remifentanil anesthesia for laparoscopic cholecystectomy.


Quantitative assessment of the probability of bluetongue virus transmission by bovine semen and effectiveness of preventive measures.
Given that bluetongue (BT) may potentially be transmitted by semen, that the disease has significantly expanded in recent years, and that millions of doses of cattle semen are annually traded throughout the world, the transmission of bluetongue virus (BTV) by semen could have severe consequences in the cattle industry. The hypothesis that infected bulls could excrete BTV in their semen led to restrictions on international trade of ruminant semen and the establishment of measures to prevent BTV transmission by semen. However, neither the risk of BTV transmission by semen nor the effectiveness of these measures was estimated quantitatively. The objective of the study was to assess, in case of introduction of BTV into a bovine semen collection centre (SCC), both the risk of BTV transmission by bovine semen and the risk reduction achieved by some of the preventive measures, by means of a stochastic risk assessment model. The model was applied to different scenarios, depending on for example the type of diagnostic test and the interval between the controls (testing) of donor bulls, or the rate of BTV spread within the SCC. Enzyme-linked immunosorbant assay (ELISA) controls of donor bulls every 60 days seemed to be an ineffective method for reducing the risk of BTV transmission in contrast to polymerase chain reaction (PCR) tests every 28 days. An increase in the rate of spread within the SCC resulted in a reduced risk of BTV transmission by semen. The storage of semen for 30 days prior to dispatch seemed to be an efficient way of reducing the risk of transmission by semen. The sensitivity analysis identified the probability of BTV shedding in semen as a crucial parameter in the probability of BTV transmission by semen. However, there is a great degree of uncertainty associated with this parameter, with significant differences depending on the BTV serotype.


Some challenges with statistical inference in adaptive designs.
Adaptive designs have generated a great deal of attention to clinical trial communities. The literature contains many statistical methods to deal with added statistical uncertainties concerning the adaptations. Increasingly encountered in regulatory applications are adaptive statistical information designs that allow modification of sample size or related statistical information and adaptive selection designs that allow selection of doses or patient populations during the course of a clinical trial. For adaptive statistical information designs, a few statistical testing methods are mathematically equivalent, as a number of articles have stipulated, but arguably there are large differences in their practical ramifications. We pinpoint some undesirable features of these methods in this work. For adaptive selection designs, the selection based on biomarker data for testing the correlated clinical endpoints may increase statistical uncertainty in terms of type I error probability, and most importantly the increased statistical uncertainty may be impossible to assess.


Prenatal determination of human platelet antigen type 4 by DNA amplification of amniotic fluid cells.
To predict a fetus at risk for neonatal alloimmune thrombocytopenia (NATP) caused by human platelet antigen (HPA)-4 incompatibility, we applied a sequence-specific polymerase chain reaction (PCR-SSP). We were able to determine the HPA-4 genotype of three infants at risk using amniotic fluid cells without the need for fetal blood sampling. The HPA-4 genotypes of amniotic fluid cells determined in this way were completely concordant with the genotype and phenotype of infants' venous blood samples obtained after delivery. Therefore, this technique is also convenient to a fetus at risk in the antenatal management of NATP induced by HPA-4 incompatibility.


Heat-shock protein 40, a novel predictor of thermotolerance in murine cells.
We have investigated the relationship between the synthesis of hsp-40, recently identified as a mammalian homologue of DnaJ protein, as well as hsp-70 and the development of thermotolerance in cells of the mouse squamous cell carcinoma line SCCVII. Thermotolerance as determined by clonogenic survival was induced not only by prior heating at 44 degrees C for 30 min but also by prior treatment with 100 microM sodium arsenite for 1 h and 5 micrograms/ml prostaglandin J2 for 4 h. These treatments concomitantly induced both hsp-70 (p72, inducible form) and hsp-40. The extent of thermotolerance correlated well with the relative amount of hsp-70 and hsp-40. These results suggest that hsp-40 is a good predictor of thermotolerance in addition to hsp-70.


Does transrectal ultrasound guided eight-core prostate biopsy improve cancer detection rates in patients with prostate-specific antigen levels of 4.1-10 ng/mL?
To investigate retrospectively whether the eight-core biopsy method improves the prostate cancer detection rate when compared with the standard sextant biopsy method in patients with prostate specific antigen (PSA) levels of 4.1-10 ng/mL. Of 437 patients whose PSA levels ranged from 4.1 to 10 ng/mL, 237 underwent a transrectal ultrasound guided sextant biopsy (sextant group), and 200 underwent an eight-core biopsy (eight-core group). Eight core samples were obtained from each of the far lateral regions in addition to the standard sextant biopsy cores. None of the patients had a previous history of prostate biopsy. Of the 237 patients in the sextant group, prostate cancer was detected in 47 patients (19.8%) and in 50 of the 200 patients in the eight- core group (25.0%). The rates of detection in the two methods were not statistically significant. However, in patients whose PSA density was less than 0.1 ng/mL per cc, the cancer detection rates in the sextant group and the eight-core group were 4.5% and 18.8%, respectively (P = 0.046). The morbidity and complications of the eight-core biopsy method were not notable. Only in patients with PSA levels of 4.1-10 ng/mL and density of less than 0.1 ng/mL per cc was the eight-core biopsy method an improvement on the sextant biopsy method in terms of prostate cancer detection rate. Accordingly, a number of cores greater than eight will be required to improve the cancer detection rates in patients with PSA levels of 4.1-10 ng/mL and PSA densities of more than 0.1 ng/mL per cc.


Bosentan: new indication. Scleroderma and finger ulcers: no tangible efficacy.
No tangible clinical efficacy, but potentially severe adverse effects and a high potential for drug-drug interactions.


[Stylocarotid syndrome: a case report].
The American otolaryngologist Eagle was the first to describe styloid syndrome in 1937 and the syndrome was named after him (Eagle's syndrome). The original description of two separate syndromes is connected with his name: classical syndrome, which almost constantly occurs after tonsillectomy and carotid artery syndrome, which occurs without tonsillectomy and also in cases when stylohyoid complex compresses the carotid segments and perivascular sympathetic fibers. In the following years, two more syndromes were defined: stylohyoid and pseudostylohyoid, which according to their manifestations, correspond to the genuine classical form. A 40-year-old male is presented, with a history of 3-year duration of pains in the upper part of the left side of the neck, in the left eye and its surroundings. Pain occurrences were not regular. Throbbing pains were most often provoked by sudden head movements and neck compression. He was healthy until the onset of these problems. The findings of all examinations were normal. The applied prophylactic therapy, typical for cluster headache, was without any effect. On 64-MSCT (multislice computed tomography), the neck arteries did not show any intraluminal pathology. The styloid processes were of normal length. On the left side, the styloid process tip pressed the internal carotid artery disturbing its longitudinal axis. In our presentation, the defined lengths of the styloid processes were normal. The medial angulation of the left styloid process was more expressed reaching 63.5 degrees (the right side angulation was normal). Persistent and throbbing pain in the region of the left eye with backward projection suggested compression on the internal carotid artery. Pains were most frequently provoked by head turning and neck compression. 64-MSCT diagnostics enabled us to determine the characteristics of styloid processes and their relation to the internal carotid artery. Improvement was achieved by administration of antiepileptic (gabapentin) and antidepressant (amitriptyline) drugs.


Moderators of ethnic differences in vasoconstrictive reactivity in youth.
Three hundred and forty-one children (170 males and 171 females: 155 whites and 186 blacks) with a mean age of 11.2 years completed laboratory stressors of forehead cold and a video game. Impedance cardiography was used to assess total peripheral resistance indexed by body surface area (TPRI) at rest and during the stressors. Black youths exhibited greater TPRI and mean arterial pressure (MAP) reactivity to both stressors. It was hypothesized that anthropometric, demographic, lifestyle, and psychosocial variables might partially account for ethnicity differences in vasoconstrictive reactivity. Black youths' higher resting MAP and TPRI and greater MAP and TPRI reactivity to forehead cold were accounted for by anthropometric characteristics, physical activity, sedentary behavior (i.e., TV viewing) and family cohesion. The ethnic differences in TPRI and MAP video game reactivity were not accounted for by the various parameters.


Ultrasonically guided fine-needle alcohol injection as an adjunct to medical treatment in secondary hyperparathyroidism.
In 12 uraemic patients with symptomatic secondary hyperparathyroidism, 13 parathyroid hyperplasias, detected by sonography and confirmed by fine-needle aspiration biopsy, were treated by ultrasonically-guided percutaneous injection of absolute ethanol, in order to reduce the gland mass. Only in the larger glands were significant volume reductions recorded, whereas in the smaller ones evident structural changes were observed. In most cases with single lesions, a reduced incidence of vitamin D hypercalcaemia and a permanent improvement in bone alkaline phosphatase and PTH were documented. This technique can be usefully employed either as an alternative to surgery in selected cases, or as support to medical therapy in single lesions.