Purinergic system, microglia and neuropathic pain.
Extracellular nucleotides play pivotal roles in the regulation of neuronal and glial functions in the nervous system through P2X receptors (P2XRs) and P2Y receptors (P2YRs). A growing body of evidence shows that microglia express several subtypes of P2XRs and P2YRs, and that these receptors play a key role in pain signaling in the spinal cord under pathological conditions, such as following peripheral nerve injury (neuropathic pain). Following peripheral nerve injury, dorsal horn microglia become activated and show upregulated expression of purinergic receptors, and interference with the function or expression of these receptors strongly suppresses neuropathic pain. This article highlights recent advances that further increase our understanding of the mechanisms by which microglial purinergic receptors contribute to the pathogenesis of neuropathic pain.


The influence of various experimental conditions on the expression of naloxone-induced withdrawal symptoms in mice.
1. Physical dependence was induced in mice by repeated injections of increasing doses of morphine for either 4 or 7 days. 2. Withdrawal symptoms induced by naloxone (1 mg/kg, i.p.) given 3 hr postmorphine were more severe in mice treated for 7 than for 4 days. 3. In mice that developed a similar degree of dependence, various doses of naloxone (0.1-10 mg/kg) given 3 hr postmorphine produced withdrawal symptoms of different intensities. 4. Withdrawal jumping was maximal at naloxone (1 mg/kg) but declined with further increases in the dose of the antagonist. 5. "Wet dog" shakes progressively increased with increasing doses of naloxone (0.1-10 mg/kg). 6. Variation in the temporal time interval between the last dose of morphine and that of naloxone (1 mg/kg) influenced the intensity of withdrawal symptoms. 7. In male and female mice that developed a similar degree of dependence, no major differences were observed in the severity of withdrawal symptoms-induced by naloxone (1 mg/kg) given 3 hr postmorphine.


Synthetic derivatives of the natural product 13-amino 2-desoxy-4-epi-pulchellin inhibit STAT3 signaling and induce G2/M arrest and death of colon cancer cells.
2-Desoxy-4-epi-puchellin (PCL) is a sesquiterpene-lactone, which naturally occurs in many traditional Chinese medicinal plants, and has antitumor and anti-inflammatory activities. In this work, a series of 13-amino derivatives of PCL were synthesized through Michael addition reaction. Inhibition of IL-6-induced STAT3 signaling pathway and in vitro cytotoxicity of these compounds were evaluated, and their effect on the cell cycle was also studied. The methyl hydroxyethylamine derivatives showed higher potency than PCL, which could induce significant mitotic arrest via G2/M arrest in HCT116 cancer cells, indicating that these derivatives have the potential to be developed into anti-colon cancer drugs.


Ouabain-induced changes of calcium and potassium in slices of hippocampus of the rat: comparison to hypoxia and effect of R 56865.
Simple and reliable in vitro models of cerebral ischaemia are important for the identification of antiischaemic/antihypoxic compounds. Alterations of the concentrations of potassium and calcium were recorded in slices of hippocampus of the rat. The slices were subjected to hypoxia in the presence and absence of intoxication with glucose or ouabain (1 mmol/l). Normoxic slices of hippocampus showed an extracellular space of 57% and a tissue concentration of potassium of 45 mmol/kg wet wt. A cellular concentration of potassium of 92 mmol/kg was calculated. Hypoxia, in the presence of glucose, only slightly reduced tissue concentrations of potassium and did not influence concentrations of calcium. Omission of glucose during hypoxia led to tissue concentrations of potassium below 10 mmol/kg, within 10-30 min of hypoxia. Concentrations of calcium only increased from 3.3 to 3.5 mmol/kg after 30 min of hypoxia, without glucose. Intoxication with ouabain is proposed as alternative experimental model of ionic movements, associated with cerebral ischaemia/hypoxia. Tissue concentrations of potassium fell rapidly to values below 10 mmol/kg, within 5 min and concentrations of calcium rose to 5.2 mmol/kg, within 30 min of intoxication with ouabain. In quantitative terms, the model for cerebral ischaemia with intoxication with ouabain is suggested to be superior to the model based on hypoxia without glucose. To verify intoxication with ouabain as an experimental model for ischaemic/hypoxic insults, the effect of an investigational drug with antiischaemic/hypoxic properties (R 56865) was evaluated in the model. The drug R 56865 produced dose-dependent attenuation of the fall in tissue concentrations of potassium, between 3 x 10(-7) and 5 x 10(-6) mol/l.(ABSTRACT TRUNCATED AT 250 WORDS)


Hymenoptera venom allergy.
For most people, hymenoptera stings produce only a transient and bothersome local inflammatory reaction characterized by pain, redness and swelling. However, for those who are allergic to components of the venom, a re-sting may cause life-threatening, even fatal reactions. In such patients, correct diagnosis is a prerequisite for effective management (i.e., specific venom immunotherapy) and generally consists of appropriate skin testing and quantification of venom-specific immunoglobulin E antibodies. In spite of the high efficiency of properly administered venom immunotherapy, the molecular and cellular mechanisms of the desensitization process remain incompletely understood.


Mealybug transmission of Grapevine leafroll viruses: an analysis of virus-vector specificity.
To understand ecological factors mediating the spread of insect-borne plant pathogens, vector species for these pathogens need to be identified. Grapevine leafroll disease is caused by a complex of phylogenetically related closteroviruses, some of which are transmitted by insect vectors; however, the specificities of these complex virus-vector interactions are poorly understood thus far. Through biological assays and phylogenetic analyses, we studied the role of vector-pathogen specificity in the transmission of several grapevine leafroll-associated viruses (GLRaVs) by their mealybug vectors. Using plants with multiple virus infections, several virus species were screened for vector transmission by the mealybug species Planococcus ficus and Pseudococcus longispinus. We report that two GLRaVs (-4 and -9), for which no vector transmission evidence was available, are mealybug-borne. The analyses performed indicated no evidence of mealybug-GLRaV specificity; for example, different vector species transmitted GLRaV-3 and one vector species, Planococcus ficus, transmitted five GLRaVs. Based on available data, there is no compelling evidence of vector-virus specificity in the mealybug transmission of GLRaVs. However, more studies aimed at increasing the number of mealybug species tested as vectors of different GLRaVs are necessary. This is especially important given the increasing importance of grapevine leafroll disease spread by mealybugs in vineyards worldwide.


New perspectives in combined radiotherapy and chemotherapy treatment.
Strategies for developing combined modality treatment for lung cancer have, until now, depended largely on empirical approaches whereby drugs with some activity against advanced disease have been combined with radiation. Survival gains have been modest. The present article emphasizes the need for new approaches that are based on mechanisms of interaction or cooperation between radiation and drugs, such that there is a selective increase in killing of tumour cells. Potential interactions include the use of radiation and drugs to eliminate cell populations which are shown in predictive assays to have differing mechanisms of resistance to the two modalities, selective inhibition of repopulation of tumour cells during radiotherapy by using drugs or biological agents, and selective killing of cells in hypoxic or acidic regions of tumours. The feasibility and potential of such approaches should be evaluated initially in small single-arm studies where outcome in individual patients is related to biological studies of mechanism. Such treatment may need to be individualized (e.g. depending on markers of drug resistance or growth factor receptors). Ultimately, the value of such treatments will need to be evaluated (whether individualized or generic) against standard treatment in large randomized trials. Guidelines for the conduct of such trials are indicated with emphasis on quality of life, assessment of costs and benefits, and involvement of patients in clinical decision making.


Structures of mismatch replication errors observed in a DNA polymerase.
Accurate DNA replication is essential for genomic stability. One mechanism by which high-fidelity DNA polymerases maintain replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, thereby favoring subsequent mismatch excision. Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the primer terminus. Here we a present a structural characterization of all 12 possible mismatches captured at the growing primer terminus in the active site of a polymerase. Our observations suggest four mechanisms that lead to mismatch-induced stalling of the polymerase. Furthermore, we have observed the effects of extending a mismatch up to six base pairs from the primer terminus and find that long-range distortions in the DNA transmit the presence of the mismatch back to the enzyme active site, suggesting the structural basis for the short-term memory of replication errors.


Clinical device-related article surface characterization of explanted endovascular stents: evidence of in vivo corrosion.
Limited information exists regarding the in vivo stability of endovascular stents. Nine excised human vascular segments with implanted stents (n = 16) manufactured from stainless steel, nickel-titanium, tantalum, and cobalt-based alloys were analyzed. The stent/tissue components were separated using an established tissue dissolution protocol and control and explanted stents were evaluated by digital optical and electron microscopy. Metallic content in surrounding tissues was measured by mass spectroscopy. Surface alterations, consistent with corrosion mediated by electrochemical and mechanical factors, were observed in 9 of the 16 explanted stents and were absent from control stents. Tissue dissolved from around corroded stents corresponded with a higher metallic content. The effect of these changes in the microtopography of stents on their mechanical properties (fatigue strength and fracture limit) in addition to the potential for released metallic debris contributing to the biological mechanisms of in-stent restenosis supports the need for further investigations.


Variations of nickel in plasma and urine during the work period.
One of the basic problems in monitoring exposure of nickel refining workers has been the unclear correlation between plasma nickel, urine nickel, and airborne nickel during the eight-hour work period or throughout the 24-hour day. In previous studies the authors have demonstrated the value of biological sampling in an occupational health program in the nickel processing industry. Whether a single plasma or single urine sample is an adequate gauge of exposure or whether 24-hour urine specimens or a three-day average plasma level are more accurate indices remained to be determined. The purpose of this paper is to report the results of studies of diurnal variations which affect the significance of single biological samples. In addition, data gathered on the correlation of plasma and urine nickel levels with soluble and insoluble nickel compounds in the atmosphere are presented.


MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis.
The purpose of this study was to determine whether the presence of intratumoral fat in hepatocellular carcinoma (HCC) could serve as an imaging biomarker to predict a favorable prognosis. After a search of the radiology and pathology databases from January 2002 to December 2010, a cohort of patients with fat-containing HCC imaged by chemical-shift MRI techniques was matched with a cohort of patients with nonfat-containing HCC for TNM stage and type of subsequent treatment. The number and type of tumor progression, time to tumor progression (TTP), and overall survival (OS) were determined for each cohort. There were 46 patients included in each cohort. Tumor progression was more prevalent in the non-fat-containing HCC cohort (30 patients, 65.2%) compared with the fat-containing HCC cohort (16 patients, 34.7%; p = 0.001). Distant metastasis occurred more commonly in the non-fat-containing HCC cohort (10 patient, 21.7%) compared with the fat-containing HCC cohort (two patients, 4.3%; p = 0.039). The median TTP was significantly longer in the fat-containing HCC group (52 months) compared with the non-fat-containing HCC group (27 months; p = 0.037). The significantly longer TTP was primarily observed in the locoregional treatment subgroup (p = 0.028). No statistical significance in OS and subanalysis by treatment was observed (p = 0.63-0.81). Fat-containing HCC, imaged on an MRI unit, may predict a more favorable prognosis compared with nonfat-containing HCC.


Molecular characterization of two highly homologous receptor-like kinase genes, RLK902 and RKL1, in Arabidopsis thaliana.
Receptor-like kinases (RLKs) constitute a large family of signal perception molecules. We characterized two highly homologous RLK genes, RLK902 and RKL1, in Arabidopsis. RLK902 and RKL1 showed a 75% amino acid sequence identity over their entire regions. In the RLK902 pro::GUS transgenic lines, GUS activity was strong in the root tips, lateral root primordia, stipules, and floral organ abscission zones, while the RKL1 promoter activity was dominant in the stomata cells, hydathodes and trichomes of young rosette leaves, and floral organ abscission zones. Neither the rlk902 mutant line, rkl1 mutant line nor rlk902/rkl1 double-knockout mutant line showed any significant phenotypes under normal growth conditions. These results suggest that RLK902 and RKL1 might mediate the signal transduction pathway in which at least one other complementary signaling pathway to these two RLKs might exist.


Neuroimaging findings as predictors of treatment outcome of psychotherapy in anxiety disorders.
Anxiety disorders are the largest group of mental disorders and a leading cause of impairment, implicating in high costs for health systems and society. Effective pharmacological and psychological treatments are available, but a significant fraction of these patients does not respond adequately to these treatments. The objective of this study is to identify neuroimaging findings that could predict response to psychotherapy in anxiety disorders. The authors reviewed psychotherapy clinical trials with neuroimaging conducted with patients with anxiety disorders. A systematic review was performed in MEDLINE database through PubMed, the Cochrane Collaboration's Clinical Trials Register (CENTRAL), PsycINFO and Thomson Reuters's Web of Science. From the studies included in this review, 24 investigated anxiety disorder patients, and findings in the amygdala, dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC) and insula predicted response to psychotherapy in social anxiety disorder. Findings in ACC, hippocampus, insula, dlPFC, amygdala and inferior frontal gyrus (iFG) predicted response to psychotherapy in panic disorder and generalized anxiety disorder. There was great heterogeneity between the included studies regarding neuroimaging techniques and the tasks performed during functional neuroimaging. Neuroimaging studies suggest that abnormalities in hippocampus, amygdala, iFG, uncus and areas linked with emotional regulation (dlPFC and ACC), predict a good outcome to psychotherapy in anxiety disorders.


Preparation of cotton wool modified with boric acid functionalized titania for selective enrichment of glycopeptides.
An effective enrichment technique is a prerequisite to enable comprehensive analysis of protein glycosylation. In this work, a method was developed for modifying cotton wool with boric acid-functionized titania nanomaterial. The modified cotton wool was used for the preparation of solid phase extraction pipette tips for glycopeptide enrichment. Owing to the unique properties of this novel solid phase material, an enrichment protocol was proposed by using a mixed-mode of hydrophilic interaction liquid chromatography, titania affinity chromatography and boronate affinity chromatography. The performance of the tips was assessed by capturing glycopeptides from tryptic digests of horse radish peroxidase (HRP) and human immunoglobulin G. Modified cotton wool tips allowed the remove of most nonglycosylated peptides. 26 glycopeptides were detected from the HRP digest. The detection limit for glycopeptide determined by MALDI-TOF MS was below 5 fmol. The developed tips are particularly convenient tools for sample pretreatment and show a great potential in glycosylation analysis.


[Bulimia nervosa (BN)--epidemiology, etiology, clinical features, treatment, prognosis].
Bulimia nervosa is a distinctive disorder that was identified in the late 1970s. At first bulimia nervosa was closely associated with anorexia nervosa, but gradually the two disorders became partly separate. The characteristic of bulimia nervosa is the frequent occurrence of binge-eating episodes and sense of loss of control during eating episodes. Bulimia nervosa is complex disorder that are caused and then maintained by various social, psychological, and biological factors. The result of research over the 20 years have contributed significantly to cognitive-behavioural and pharmacological treatment approach for people with bulimia nervosa.


Impact of geometry on the performance of memristive nanodevices.
We examined the influence of memristor geometry on switching endurance by comparing ribbed and planar TiO(2)-based cross-point devices with 50 nm × 50 nm lateral dimensions. We observed that planar devices exhibited a factor of over four improvement in median endurance value over ribbed structures for otherwise identical structures. Our simulations indicated that the corners in the upper wires of the ribbed devices experienced higher current density and more heating during device forming and switching, and hence a shorter life time.


The synthesis of solasodine F-homo-analogues.
Solasodine derivatives continue to be attractive targets for synthetic chemists due to their interesting biological properties. Herein, we report a concise synthesis of solasodine analogues containing the seven-membered F ring from diosgenin. The key intermediate in the synthesis of 26a-homosolane derivatives was 26-cyanopseudodiosgenin. After reduction of the cyano group, the seven-membered ring was closed with MgBr2·Et2O to yield 26a-homosolanes as a mixture of 22R and 22S epimers. The acylation of the obtained mixture led to the diastereomerically pure 22S N-acylated 26a-homosolasodine derivatives. Moreover, we describe one-step protocol for stereoselective synthesis of 22R-cyanofurostane by treatment of diosgenin with TMSCN/BF3·Et2O.


The hemodynamic effect of an intravenous antispasmodic on propofol requirements during colonoscopy: A randomized clinical trial.
Hemodynamic status during induction of anesthesia may modify the amount of propofol needed to induce loss of consciousness (LOC). This study was aimed to evaluate the effect of antispasmodic-induced tachycardia on the concentration of propofol at the effect-site for inducing LOC when deep sedation was executed for colonoscopy. One hundred and sixteen adult patients were randomly assigned to receive either 20 mg of the antispasmodic Buscopan intravenously (Buscopan group; n = 58) or normal saline (control group; n = 58) for colonoscopy. After administration of Buscopan, the antispasmodic or normal saline, propofol was given by means of target-controlled infusion to induce LOC. We recorded patient characteristics, hemodynamic profiles, effect-site propofol concentration upon LOC, total propofol dosage for colonoscopy, and colonoscopy outcomes. There were no significant differences in the characteristics between the two groups. Although the patients receiving Buscopan had a higher heart rate than those of the control group (101 ± 15 beats/minute vs. 77 ± 13 beats/minute; p < 0.001), we found no significant difference between two groups in the effect-site propofol concentration for inducing LOC (3.9 ± 0.6 μg/mL vs. 3.8 ± 0.6 μg/mL; p = 0.261) nor total propofol dosage required for colonoscopy (3.2 ± 1.4 mg/kg vs. 3.1 ± 1.1 mg/kg; p = 0.698). Both groups had comparable colonoscopy outcomes, including percentage of patients completing the procedure and total procedure time. The hemodynamic responses to intravenous Buscopan neither affected the effect-site propofol concentration needed to induce LOC, nor the total propofol dosage required for colonoscopy in this study. There is no need to modify the dosage of propofol in patients subject to Buscopan premedication in colonoscopy.


Evaluation of methodologies for exposure assessment to atmospheric pollutants from a landfill site.
Epidemiological studies around landfill sites are limited by several factors, particularly a lack of accurate exposure assessment. Traditionally, exposure estimates are based on distance between place of residence and the landfill site. However, this measure of exposure ignores the effects that environmental factors may have upon exposure. A previous epidemiological study at a landfill site in the United Kingdom provided the basis for a case study to investigate exposure assessment methodologies that could support ongoing and future epidemiological work. Estimation of relative exposure to atmospheric pollutants near the site was refined using the Atmospheric Dispersion Modeling System (ADMS) 3.1. Annual average concentrations were calculated around the landfill site, which was modeled as an area source with a steady release rate over its entire active surface. Local meteorological and terrain data were used in the assessment. A geographical information system (GIS) was then used to link the results of the modeling to population and other data. Sensitivity studies were included to examine the variation of predicted exposure with several modeling assumptions and hence set other uncertainties in context. No simple relationship existed between the relative individual exposure measured by distance from the site and by dispersion modeling. A reassessment of exposure assessment in epidemiological studies around landfill sites was then undertaken with the refined estimates of exposure. This concluded that use of distance from the site as a proxy for exposure could lead to significant exposure misclassification in comparison with exposure assessment using atmospheric dispersion modeling and GIS. The study also indicated that assessment of peak exposure rates (i.e., extreme concentration levels) might be necessary in some epidemiological work. Optimum strategies for increasing the probability of observing effects in the more highly exposed population can be derived by combining the results of dispersion modeling with population data and, where feasible, knowledge of the toxicology of the substances of interest.


Vaccination coverage surveys in county health departments--Kansas, 1993-1994.
The objective of the Childhood Immunization Initiative (CII) is to protect all children in the United States by their second birthday against nine vaccine-preventable diseases. Specific objectives for 1994 were to increase coverage levels to at least 85% for the third dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP3) and the first dose of measles, mumps, and rubella vaccine (MMR1); 75% for the third doses of oral poliovirus vaccine (OPV3) and Haemophilus influenzae type b vaccine (Hib3); and 30% for the third dose of hepatitis B vaccine (HepB3) (1). To determine whether county health departments in Kansas had achieved the national vaccination objectives, in 1993 staff from the Kansas Department of Health and Environment (KDHE) began assessing vaccination coverage rates for children aged 2 years served by county health departments in that state. This report presents the results of the first vaccination coverage assessments of all 105 county health departments in Kansas during November 1993-November 1994.


Clostridium difficile and One Health.
For over four decades, Clostridium difficile has been a significant enteric pathogen of humans. It is associated with the use of antimicrobials that generally disrupt the microbiota of the gastrointestinal tract. Previously, it was thought that C. difficile was primarily a hospital-acquired infection; however, with the emergence of community-associated cases, and whole-genome sequencing suggesting the majority of the hospital C. difficile infection (CDI) cases are genetically distinct from one another, there is compelling evidence that sources/reservoirs of C. difficile outside hospitals play a significant role in the transmission of CDI. To review the 'One Health' aspects of CDI, focusing on how community sources/reservoirs might be acting as a conduit in the transfer of C. difficile between animals and humans. The importance of a One Health approach in managing CDI is discussed. A literature search was performed on PubMed and Web of Science for relevant papers published from 1 January 2000 to 10 July 2019. We present evidence that demonstrates transmission of C. difficile in hospitals from asymptomatic carriers to symptomatic CDI patients. The source of colonization is most probably community reservoirs, such as foods and the environment, where toxigenic C. difficile strains have frequently been isolated. With high-resolution genomic sequencing, the transmission of C. difficile between animals and humans can be demonstrated, despite a clear epidemiological link often being absent. The ways in which C. difficile from animals and humans can disseminate through foods and the environment are discussed, and an interconnected transmission pathway for C. difficile involving food animals, humans and the environment is presented. Clostridium difficile is a well-established pathogen of both humans and animals that contaminates foods and the environment. To manage CDI, a One Health approach with the collaboration of clinicians, veterinarians, environmentalists and policy-makers is paramount.


Surgical control of obstetric hemorrhage: hypogastric artery ligation or hysterectomy?
Sixty-four patients with severe postpartum hemorrhage (PPH) required surgical intervention during the years 1983 to 1987. Bilateral hypogastric artery ligation (HAL) was the initial surgical approach in 45% (29/64) and hysterectomy in 55% (35/64). HAL successfully controlled hemorrhage in 65% (19/29), and failed in 35% (10/29) where hysterectomy was required as a life saving procedure. Failure of HAL was more evident in atonic PPH than in other situations. Complications were more following hysterectomy; six (6/45) patients required re-exploration for intraperitoneal hemorrhage and two (2/45) patients died following hysterectomy. HAL was found to be a relatively easy, safe and successful procedure to be attempted as an initial surgical approach for all severe PPH, specially where uterine conservation was desired.


Comparison of the nasal release of IL-4, IL-10, IL-17, CCL13/MCP-4, and CCL26/eotaxin-3 in allergic rhinitis during season and after allergen challenge.
Allergic rhinitis is an inflammatory disease characterized by local overproduction of type 2 cytokines and tissue eosinophilia. Recent research suggests the involvement of additional cytokines such as IL-17, chemokine (C-C motif) ligand (CCL) 26/eotaxin-3, and CCL13/monocyte chemoattractant protein-4 (MCP-4) in its pathophysiology. Furthermore, bronchial epithelial cells treated with IL-17 and type 2 cytokines distinctively up-regulated eotaxin-3 gene expression. In this study we investigated the kinetics of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in seasonal allergic rhinitis volunteers after nasal allergen challenge (NAC) and their release during natural pollen exposure. The nasal lavages of 15 symptomatic allergic and 14 nonallergic subjects were collected during the pollination season. Additionally, six allergic subjects underwent a single unilateral nasal allergen and control challenge out of season, and nasal secretions were collected. Levels of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in nasal lavages and secretions were measured using an electrochemiluminescent assay. After NAC, allergic subjects had a significant immediate response of nasal symptoms as well as a significant increase at 5 hours of IL-4, IL-10, and IL-17 and at 2, 5, and 24 hours significantly raising levels of eotaxin-3. IL-17 and eotaxin-3 concentrations at 5 hours were correlated (r = 0.94; p = 0.005). During natural pollen exposure, barely detectable levels of IL-17 in allergic subjects were also correlated with eotaxin-3 (r = 0.62; p = 0.01). Eotaxin-3 and MCP-4 levels were significantly elevated 9- or 3.7-fold, respectively, and IL-10 and, unexpectedly, IL-4 were significantly lower in allergic subjects compared with nonallergic subjects. Nasal IL-17, MCP-4, and, possibly, eotaxin-3 may aggravate and IL-10 may alleviate nasal mucosal allergy.


Anti-CD3/anti-CD28 bead stimulation overcomes CD3 unresponsiveness in patients with head and neck squamous cell carcinoma.
To test whether T-cell CD3 responses are altered in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC) and whether anti-CD3/anti-CD28 (alphaCD3/alphaCD28) bead stimulation could reverse CD3 unresponsiveness. Anti-CD3 (alphaCD3) monoclonal antibody immobilized on tissue culture plastic was used to stimulate lymph node mononuclear cells (LNMCs) and peripheral blood mononuclear cells (PBMCs) from patients with advanced-stage HNSCC. Proliferation, T-cell phenotype, and cytokines were measured during 8-day in vitro stimulation. Immune-enhancing properties of alphaCD3/ alphaCD28 beads were also tested on LNMCs and PBMCs. Cytotoxicity of bead-activated T cells (ATCs) was measured against autologous and allogeneic HNSCC. Six patients were nonresponders to alphaCD3 stimulation defined by tritium (3H) incorporation of less than 3500 cpm, whereas 11 patients were responders with 3H incorporation of 3500 cpm or more. Responders produced higher levels of interleukin (IL)-12 and interferon gamma (IFN-gamma) after alphaCD3 stimulation than nonresponders. No phenotypic or clinical differences were identified between groups. Stimulation with alphaCD3/alphaCD28 beads enhanced IFN-gamma and IL-2 produced by both groups. Bead ATCs were generated from PBMCs of patient 11 in the responder group and lysed (+/- SD) 100% +/-1% of autologous tumor and 49% +/-1% of allogeneic tumor. Bead ATCs from LNMCs of this patient lysed 58%+/-1% of autologous tumor and 63%+/-1% of allogeneic tumor. A subpopulation of patients with HNSCC who are nonresponders to alphaCD3 stimulation has been identified, showing reduced proliferation and IL-12 and IFN-gamma secretion. Nonresponders stimulated with alphaCD3/alphaCD28 beads reversed immune unresponsiveness and induced a type 1 cytokine response. Bead-generated ATCs from patient 11 in the responder group lysed autologous and allogeneic HNSCC in vitro, suggesting a possible effective immunotherapeutic modality in the treatment of HNSCC.


Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix.
Several studies have shown that pretreatment oxygenation status of cervical tumors measured with a polarographic oxygen electrode could be a predictive factor for radiation response and survival. The purpose of this study was to evaluate the impact of intratumoral pO2 levels and hypoxic fractions on local control and disease free survival employing a standardized measuring procedure under routine conditions. Between April 1994 and December 1997 pO2 measurements were performed prior to radiotherapy with an Eppendorf histograph in 51 evaluable patients with primary cervical carcinoma. All patients were treated with curative intent by combined external beam therapy (median total dose 49.6 Gy) and 3-6 applications of high dose rate- (7 Gy/fr. at point 'A') or pulse dose rate brachytherapy (20-25 h pulses, 1 Gy/pulse at point 'A'). Oxygenation data are given as median pO2 of pooled readings and percentage of readings below 5 mm Hg (HF 5). Median pO2 values ranged from 0 to 60 mm Hg (median 10). HF5 ranged from 0 to 95% (median 22%). Median follow-up was 26 months (range 9-54 months). Actuarial overall and disease-free survival rates (OS/DFS) at 3 years were 53%/50%. Comparing patients with median pO2 < or = 10 mm Hg (n = 26) to patients with higher median pO2 levels (n = 25) calculated DFS was 34 and 69%, respectively (P < 0.02). Corresponding data for local control were 47 and 84% (P = 0.053). Comparing patients with HF5 below and above the median calculated DFS was 36 and 66%, respectively (P < 0.02). Patients who had median pO2 < 10 mm Hg and HF5 > 20% had the worst prognosis (3-year DFS: 28%). Besides oxygenation status, stage and initial hemoglobin concentration were statistically significant for treatment outcome. This study confirms earlier data that the presence of hypoxia is associated with poor local control and survival in patients with carcinoma of the uterine cervix. Polarographic pO2 measurements are feasible under routine conditions and can be regarded as a reproducible predictive assay.


The role of the serine protease active site in the mode of action of epidermolytic toxin of Staphylococcus aureus.
The sequences of the epidermolytic toxins and V8 serine proteinase share about 25% identity, including the catalytic triad at the proteinase active centre. Here we have altered the putative ETA active-site serine-195 to glycine by site-directed mutagenesis. No epidermolytic activity was detected when up to 100-fold greater amounts of the homogeneous mutant ETA were injected subcutaneously into neonatal mice showing that serine-195 is required for toxicogenesis.


Insulin-like growth factors (IGFs) and IGF-binding proteins in the developing rhesus monkey.
Rhesus monkeys follow a developmental pattern of serum insulin-like growth factor-I (IGF-I) levels similar to that found in humans. In these monkeys, serum IGF-I levels peak during puberty (2.5-4.5 yr of age in males). We have examined the developmental pattern of IGF-binding protein-1 (IGFBP-1), -2, and -3 in serum by Western ligand blotting, the levels of IGFBP-3, IGF-I, and IGF-II in serum by RIA, and the IGFBP mRNA levels of IGFBP-1, -2, and -3 in the livers of rhesus monkeys from fetal life through adulthood by Northern analysis. The pattern of the serum levels of the IGFBPs reflected the liver mRNA levels of the IGFBPs. The IGFBP-1 and IGFBP-2 liver mRNA and serum levels were highest in the fetus and first year of life and were very low after 4 yr of age. Conversely, the IGFBP-3 liver mRNA and serum levels were relatively low early in life and peaked during puberty. The serum levels of IGF-I and IGF-II were strongly correlated with the level of IGFBP-3. We conclude that the developmental pattern of IGFBPs in the rhesus monkey is similar to that in the human, and that serum IGFBP levels are probably regulated by the rate of IGFBP mRNA synthesis.


[Ornithine carbamoyltransferase deficiency. A clinical case].
Disorders of urea cycle account for up to 60% of severe neonatal hyperamoniemias. The base of this cycle disorders results in a deficit of its enzymes. Deficiency of the enzyme ornithine transcarbamylase is the most frequently detected. The prognosis depends on the degree of enzyme deficiency, age, early diagnosis and initiation of treatment. We report the case of a teenager who was treated with prednisone because of a peripheral facial palsy. He showed a progressive worsening and died a few days later. The high levels of ammonia made suspect a congenital disorder of urea cycle. The postmortem genetic study confirmed it. We studied the family and advised carriers. We reflect about the importance of the neonatal screening programs and their applicability for detection of inborn errors of metabolism.


Overdose of booster tetanus toxoid given in error: a clinical study.
16 reserve soldiers received an overdose of tetanus toxoid vaccine (5 ml instead of 0.5 ml) in error. We assessed the incidence and severity of adverse reactions and determined tetanus antibody titer immediately and after 5 days, 1 month and 1 year, and compared it with the titers in a control group of 20 soldiers. The incidence and severity of reactions was significantly higher in the overdose group. The mean tetanus antibody titer rose to similar levels in both groups after 1 month (153.75 +/- 82.5 IU/ml and 62.02 +/- 42.15 IU/ml respectively) but decreased sharply after 1 year in the overdose group.


Expression of heat-shock protein Hsp25 in mouse Purkinje cells during development reveals novel features of cerebellar compartmentation.
The small heat shock protein Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal stripes of Purkinje cells confined to the caudal central zone ( approximately lobules VI and VII), the nodular zone ( approximately ventral lobule IX and lobule X), and the paraflocculi/flocculi. During development several distinct phases in Hsp25 expression can be distinguished. Hsp25-immunopositive Purkinje cells are first seen at birth, when four clusters are visible in the vermis of lobules IV/V, and scattered Hsp25-immunoreactive Purkinje cells are seen in lobule VIII. By postnatal day 2/3, six narrow parasagittal stripes of Hsp25-immunopositive Purkinje cells are seen in the vermis of the anterior lobe. In the posterior lobules, most Purkinje cells in the vermis of lobules VIII and IX express Hsp25. This initial limited expression is followed by a phase of widespread expression (postnatal days 6-9) in which Hsp25 immunoreactivity is detected in virtually all Purkinje cells. This global cerebellar expression of Hsp25 then gradually disappears, first in the anterior zone and the hemispheres and subsequently in the posterior zone, to leave the restricted adult expression pattern. Western blotting analysis and immunoprecipitation with anti-Hsp25 suggest that all immunocytochemistry can be attributed the expression of Hsp25. Furthermore, visual deprivation had no effect on the development of Hsp25 expression in Purkinje cells, suggesting that visuomotor input is not responsible for the establishment of constitutive Hsp25 expression in the cerebellar cortex.


Searching for evidence about health education and health behavior interventions.
Evidence is fundamental to science, but finding the right evidence in health education and health behavior (HEHB) is often a challenge. The authors discuss some of the controversies about the types of evidence that should be considered acceptable in HEHB, the tension between the use of qualitative versus quantitative data, the need for measures of important but neglected constructs, and interpretation of data from experimental and nonexperimental research. This article discusses some of the challenges to the use of evidence and describes a number of strategies and some forces encouraging the use of evidence-based interventions. Finally, the authors suggest ways to improve the practice and dissemination of evidence-based HEHB. Ultimately, if evidence-based interventions are not disseminated, the interventions will not achieve their potential. The goal should be to develop more effective interventions and disseminate them to improve the public's health.


Clinical features and treatment outcomes of six patients with disseminated intravascular coagulation resulting from acute promyelocytic leukemia and treated with recombinant human soluble thrombomodulin at a single institution.
Acute promyelocytic leukemia (APL) is characterized by the proliferation of blasts with distinct morphology and promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) transcripts. Although the treatment outcome is dramatically improved by all-trans retinoic acid (ATRA), life-threatening bleeding from enhanced fibrinolytic-type disseminated intravascular coagulation (DIC) remains a serious clinical problem, and a standard treatment has not been established. However, recent reports indicate that recombinant human soluble thrombomodulin (rTM) is effective against DIC. To elucidate the clinical characteristics and outcomes of DIC resulting from APL, we retrospectively analyzed 10 patients with DIC resulting from APL at our institution over a six year period. Of the 10 patients, four were treated with serine protease inhibitors (SPI) and six were treated with rTM. The diagnosis of DIC was based on the diagnostic criteria of the Japanese Ministry of Health and Welfare. In addition to treating APL with ATRA, rTM was administered for six consecutive days. The DIC was resolved within seven days after initiating treatment in 25.0% (1/4) of the patients in the SPI group and 66.6% (4/6) of the patients in the rTM group. Although the rTM group consisted of patients with life-threatening bleeding who required RCC transfusion, a prompt resolution rate and reduced DIC score without progression of bleeding was achieved in this group. All patients were alive after the 28-day observation period. Based on the present findings, rTM administration may be an effective, safe, and feasible therapeutic modality, producing a rapid resolution without progression of hemorrahage.


Identification of in vivo liver metabolites of delta 1-tetra-hydrocannabinol, cannabidiol, and cannabinol produced by the guninea-pig.
The metabolites of delta 1-tetrahydroannabinol (delta 1-THC), cannabidiol (CBD), and cannabinol (CBN) produced in vivo by the guinea-pig have been studed by combined gas-liquid chromatography-mass spectrometry, 45 metabolites of delta 1-THC were identified of which 12 have not been reported before. Several other metabolites were detected but not identified. The major metabolic routes involved allylic and aliphatic hydroxylations, oxidations to ketones and acids, oxidative degradation of the side-chain presumably by the beta-oxidation pathway, and formation of glucuronide conjugates. Di- and tri-substituted metabolites were abundant. The metabolism differed considerably from that observed in mouse and rat in that 1''- and 6 beta-hydroxylation and oxidation degradation of the side-chain were major metabolic pathways. 1''-Hydroxy-delta 1-THC was found as a pair of diasteroisomers. Similar metabolic pathways were observed with CBD; twenty metabolites were identified of which two were new. Only 6 metabolites of CBN were identified. These mainly mono-substituted in the same positions as were observed with delta 1-THC and CBD.


For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality.
Despite early diagnosis and treatment, almost 20% of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic, clinical, and histopathologic factors. The aim of this multicenter international study was to find which of the factors age, gender, stage, grade, lymphocytic host response, perineural invasion, worst pattern of invasion, or depth of invasion has the strongest prognostic power in early-stage OTSCC. Patient data of 479 patients with early-stage (cT1-2N0) OTSCC in Finland, Brazil, and the USA were retrieved and analyzed using Cox proportional hazards regression models. Our results indicate that depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest pathological predictors for locoregional recurrence, with a hazard ratio (HR) for 4 mm DOI of 1.67 (95% confidence interval (CI) 1.07-2.60) and HR for WPOI of 1.46 (95% CI 0.95-2.25). In addition, mortality from early OTSCC was also predicted by DOI (HR 2.44, 95% CI 1.34-4.47) and by WPOI (HR 2.34, 95% CI 1.26-4.32). We suggest that clinically early-stage oral tongue carcinomas 4 mm or deeper, or with a growth pattern of small cell islands or satellites, should be considered as high-risk tumors which require multimodality treatment.


A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR beta ser 57- asp 57).
The single DR beta chain gene of the DRw8 haplotype has been suggested to carry both the DRw8 and the DRw52 epitopes. Cellular typing has shown that the DRw8 haplotype can be split into three subtypes, Dw8.1, Dw8.2, and Dw8.3, presumably due to a polymorphism in the DRw8 beta chain. Furthermore, Dw8.1 and Dw8.2 cells present influenza virus antigen to different T-cell clones. In the present study, DRw8/Dw8.2 beta chain cDNA was cloned and characterized. A comparison of this sequence with a partial DRw8/Dw8.1 beta chain gene suggested that the DRw8 split is due to a single amino acid replacement of ser57-asp57 caused by three nucleotide substitutions in the same codon. In most DR haplotypes, two expressed DR beta chain genes exist. Comparing the nucleotide sequence of the single beta gene in the DRw8 haplotype to those of other DR beta genes revealed that the DRw8 beta gene sequence is most closely related to the DRB1 genes of the DR3, 5, and w6 haplotypes. However, the comparisons also showed that it was not possible from sequence similarities to divide the DR beta genes into two or more distinct allelic series.


Urethral replacement with vascularized tunica vaginalis: defining the optimal form of use.
Residual urethral defects after failed hypospadias surgery present difficulties in reconstruction. In these situations, repair using vascularized tissue flaps remains ideal, yet challenging. In order to offer more surgical alternatives in these cases, the use of vascularized tunica vaginalis flaps as urethral replacements has recently been established in an animal model. We undertook the following studies to further define the role of tunica vaginalis in urethral reconstruction. A vascularized flap of tunica vaginalis was used to replace an experimentally created 25-30 mm. gap in the anterior urethra of 26 rabbits, either as an onlay or tube flap. A control group consisting of 7 animals underwent only a segmental anterior urethral resection and primary re-anastomosis. Satisfactory urethral healing occurred in all control animals that survived the procedure. All 8 animals which had tunica vaginalis tube flap reconstruction underwent contracture of the neourethra probably secondary to the presence of striated cremasteric muscle elements brought with the tunica during mobilization. All 16 animals available for long term study in the onlay flap group had excellent flap viability and 100% urethral patency rates. The mesothelial lining of the tunica was seen to be replaced by a stratified epithelial lining similar to the urothelial lining of the native urethra. The tunica vaginalis is a viable alternative to other tissues presently used for urethral replacement and can be used successfully as a vascularized onlay flap.


Analysis of the sequence of a dicot-infecting mastrevirus (family Geminiviridae) originating from Syria.
Chickpea stunt disease (CSD) across southern Asia, the Middle East and North Africa is caused by a number of viruses that include single-stranded DNA viruses of the genus Mastrevirus (family Geminiviridae). Despite the importance of CSD in reducing chickpea and lentil production, until recently little was known of the nature of the pathogens causing the disease. Sequence characterisation of virus isolates from Sudan and Pakistan showed the viruses concerned to potentially be new mastrevirus species related to Bean yellow dwarf virus (BeYDV), a virus known to occur in both southern Africa and southern Asia. Here we have determined the complete nucleotide sequence of a mastrevirus associated with CSD in Syria. This virus represents a proposed new species, closely related to the recently characterised Chickpea chlorotic dwarf Sudan virus and Chickpea chlorotic dwarf Pakistan virus but with the highest sequence identity to BeYDV, for which we propose the name Chickpea chlorotic dwarf Syria virus. In addition the biological integrity of the clone was confirmed by infection of Nicotiana benthamiana plants using Agrobacterium-mediated inoculation.


[Acute intestinal obstruction caused by congenital intestinal abnormalities].
By means of two examples--one in pregnancy, the other one after an abdominal hysterectomy--we report on a rare cause of an acute mechanical ileus. In both cases an incomplete intestinal turn with distinct mobility of the colon caused a volvulus. It is pointed to the importance of an early diagnosis inspite of aggravating circumstances in late pregnancy, parturition and postoperatively after gynecologic operations. Effective operative treatment is based on careful exploration of the abdomen in order not to overlook rare causes of an ileus, among those also fetal developmental disturbances of the intestine and other abdominal viscera. Only by operative removing of the causes of an ileus in cooperation with surgeons--and that in good time--the results in gynecology can be improved especially during pregnancy but also postoperatively.


Pulse radiolysis studies of some aza analogues of nucleic acid components.
The technique of pulse radiolysis has been utilized to study the reactions of some aza analogues of nucleic acid components with hydrated electrons and OH radicals. The absorption spectra of the transient free radical adducts which result from these reactions and their decay kinetics were determined. The 5-aza analogues gave similar results to those of pyrimidine bases. The 6-aza analogues also showed similar kinetics, however, transient spectra were different. The presence of the sugar moiety in these aza analogues changed the rate law of the OH adduct transient decay from second order to first order kinetics. This finding may have implications for the understanding of the radiation chemistry of DNA.


Tilt adaptation as a feedback control process.
Adaptation to optical tilt was analyzed with time-varying input signals in the form of step, ramp, and triangular wave-form functions. Step-function transients appeared to stabilize at about 15 min, suggesting a time constant of 4-5 min. Gain decreased with input rate beyond about 1.4 degrees min-1 and with input amplitude. In all instances gain was considerably less than one. The frequency of the triangular waves was relatively faithfully reflected in the output, but the wave form was distorted by the uneven influence of clockwise over counter-clockwise inputs. A control system with output proportional to error and an exponential delay was proposed as a model of tilt adaptation. The relationship to adaptation of the vestibulo-ocular response also is discussed.


A review on directional information in neural signals for brain-machine interfaces.
Brain-machine interfaces (BMIs) can be characterized by the technique used to measure brain activity and by the way different brain signals are translated into commands that control an effector. We give an overview of different approaches and focus on a particular BMI approach: the movement of an artificial effector (e.g. arm prosthesis to the right) by those motor cortical signals that control the equivalent movement of a corresponding body part (e.g. arm movement to the right). This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single-units. Here, we review recent findings showing that analog neuronal population signals, ranging from intracortical local field potentials over epicortical ECoG to non-invasive EEG and MEG, can also be used to decode movement direction and continuous movement trajectories. Therefore, these signals might provide additional or alternative control for this BMI approach, with possible advantages due to reduced invasiveness.


Proposal of a low-cost protocol for colorimetric semi-quantification of secretory phospholipase by Candida albicans grown in planktonic and biofilm phases.
Biofilms are aggregates of microorganisms living in multilayered structures inside polymeric matrices onto surfaces. These biofilms may subvert the physiological properties of adjacent tissues causing morphofunctional failure. Many studies have shown that the expression of virulence attributes is maximized when microbes form such communities. This study evaluated the differential phospholipasic activity of Candida albicans SC5314 grown in planktonic phase and in biofilm. We propose two distinct protocols for the colorimetric evaluation of phosphatidylcholine hydrolysis in neutral and acidic conditions. The results showed that both protocols are suitable for the proposed intention and that 72 h-old planktonic cultures of C. albicans SC5314 secrete higher quantities of neutral (6.42-fold) and acidic (3.85-fold) phospholipases than biofilms.


Mohs micrographic surgery for fungal soft tissue infections.
Invasive fungal infections of the integument are relatively rare. In the immunocompromised patient, however, they may show an extremely aggressive biological behavior despite high dosed topical or systemic antifungal therapy. As the fungal tissue invasion usually reaches well beyond the area of clinical necrosis or other visible changes, standard surgical excision often proves to be inadequate, resulting in the need for repeated relatively wide excisions with the resulting substantial loss of initially healthy tissues. To present the use of Mohs surgery as a safe and effective treatment modality for invasive fungal infections in a patient with a zygomycetes infection of his scalp. The micrographic excision of the highly aggressive fungal infection, the acute postoperative course, and the delayed reconstruction with a split-thickness skin graft were all well tolerated without complications. Mohs micrographic excision deserves serious consideration in the treatment of aggressive localized fungal infections.


Prevalence of soft tissue calcifications in the maxillofacial region detected by cone beam CT.
To determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) scans with different fields of view (FOV) and to assess its relation with the clinical relevance of the CBCT findings. One thousand CBCT scans were grouped according to FOV's size and region scanned (MX-FOV, maxilla; MD-FOV, mandible; and MM-FOV, maxilla/mandible) and evaluated for the presence of soft tissue calcifications. Laterality and length of the elongated styloid processes (ESP) were also assessed. Eight hundred and eighty-two soft tissue calcifications were detected in 626 (62.6%) patients. MM-FOV presented the highest prevalence (76.8%), followed by MD-FOV (60.6%) and MX-FOV (57.2%). ESP and tonsillolith were the most frequent calcifications. Calcifications requiring treatment or not and those in need of follow-up accounted for 6.9%, 92.7%, and 0.3% of cases, respectively. There was no association between calcifications and subjects' gender or age (p > .05). Most cases of ESP occurred bilaterally and were longer in males (p < .05). There is a high prevalence of soft tissue calcifications in CBCT, and ESP and tonsilloliths are the most common types in all evaluated FOVs. While most cases do not require treatment, we emphasize the importance of detailed CBCT assessment for its diagnosis.


Phase-controlling phononic crystals: realization of acoustic Boolean logic gates.
A phononic crystal (PC) consisting of a square array of cylindrical polyvinylchloride inclusions in air is used to construct a variety of acoustic logic gates. In a certain range of operating frequencies, the PC band structure shows square-like equi-frequency contours centered off the gamma point. This attribute allows for the realization of non-collinear wave and group velocity vectors in the PC wave vector space. This feature can be utilized to control with great precision, the relative phase between propagating acoustic waves in the PC. By altering the incidence angle of the impinging acoustic beams or varying the PC thickness, interferences occur between acoustic wave pairs. It is recognized that information can be encoded with this mechanism (e.g., wave amplitudes/interference patterns) and accordingly to construct a series of logic gates emulating Boolean functions. The NAND, XOR, and NOT gates are demonstrated with finite-difference time-domain simulations of acoustic waves impinging upon the PC.


Increased ambulatory pulse pressure is a strong risk factor for coronary endothelial vasomotor dysfunction.
This study was aimed to determine the relationship between pulse pressure (PP) and coronary vasomotor dysfunction, a predictor of coronary events. Pulse pressure is a strong risk factor for coronary artery disease (CAD). However, the mechanisms by which an increase in PP affects the pathogenesis of CAD are unclear. Ambulatory blood pressure (BP) monitoring for 24 h was performed in 103 consecutive patients with normal coronary angiograms (51 hypertensive and 52 normotensive; age 42 to 70 years). The relationship between changes in coronary arterial diameter and blood flow during an intracoronary infusion of acetylcholine (ACh) (5, 10, 50 microg/min), and BP parameters, and other traditional risk factors was evaluated using univariate and multivariate linear regression analyses. With multivariate analyses, the 24-h PP showed an inverse correlation with the epicardial coronary dilator response to ACh independently of other covariates including age, smoking, and 24-h systolic BP in normotensive as well as hypertensive patients. Furthermore, multivariate analysis showed that the 24-h PP was inversely and independently correlated with the increase in coronary blood flow in response to ACh. The dilator response of epicardial coronary arteries to nitrate was not significantly correlated with 24-h PP. Increased 24-h PP is independently associated with endothelial vasomotor dysfunction in conduit and resistance coronary arteries irrespective of the presence of hypertension. Increased ambulatory PP may have an intimate relation to coronary endothelial vasomotor dysfunction.


Additive Manufacturing of Functionally Graded Ceramic Materials by Stereolithography.
An additive manufacturing technology is applied to obtain functionally graded ceramic parts. This technology, based on digital light processing/stereolithography, is developed within the scope of the CerAMfacturing European research project. A three-dimensional (3-D) hemi-maxillary bone-like structure is 3-D printed using custom aluminum oxide polymeric mixtures. The powders and mixtures are fully analyzed in terms of rheological behavior in order to ensure proper material handling during the printing process. The possibility to print functionally graded materials using the Admaflex technology is explained in this document. Field-emission scanning electron microscopy (FESEM) show that the sintered aluminum oxide ceramic part has a porosity lower than 1% and no remainder of the original layered structure is found after analysis.


Overstay and Readmission in Ear, Nose, and Throat Day Surgery-Factors Affecting Postanesthesia Course.
Many procedures in ear, nose, and throat (ENT) day surgery are carried out under local anesthesia in Finland, whereas many other countries use general anesthesia. We investigated overstay and readmission rates in local and general anesthesia at Helsinki University Hospital. We conducted a retrospective study on ENT (n = 1011) day surgery patients within a 3-month period using the hospital's surgery database to collect data pertaining to anesthesia, overstays, readmissions, and contacts within 30 days of surgery. We examined the effect of American Society of Anesthesiologists (ASA) class, age, sex, type of procedure, and anesthesia type on overstay, contact, and readmission rates. A multivariable logistic regression model included ASA class, age, sex, type of procedure, and anesthesia (local vs general). Sex, age, and type of procedure had an effect on the outcomes of overstay, readmission, or contact. With general anesthesia, 3.2% (n = 23) had an overstay or readmission compared to 1.4% (n = 4) after local anesthesia. This was mainly explained by the number of study outcomes in tonsillar surgery that was performed only in general anesthesia. Day surgery could be done safely using local anesthesia, as the number of study outcomes was no greater than in general anesthesia. Sex, type of procedure, and age affected the rate of study outcomes, but ASA class and anesthesia form did not. Our overstay, contact, and readmission rates are on the same level, or lower, than in international studies.


Epidemiology of nephropathia epidemica in Sweden.
A comprehensive study of nephropathia epidemica (NE), caused by Puumala virus, was conducted in Sweden. Human sera from residents of various regions of Sweden were examined for antibody to Puumala virus, and the incidence of NE was determined. Small mammals were captured at locations throughout Sweden and were examined for antibody to Puumala virus and for antigen. The human serosurvey found the highest prevalence rates and the highest incidence rates in northern Sweden. The bank vole was found to be the most-abundant rodent, as well as the species most frequently positive for antibody. Antibody-positive voles were restricted to the northern two-thirds of the country, an area corresponding to that where most human disease was noted. These results suggest that the bank vole is the principal host of Puumala virus in Sweden and clearly establish the region near 64 degrees N as highly endemic for NE in humans.


Active and passive smoking and the risk of stomach cancer, by subsite, in Canada.
This study assessed the influence of active and passive smoking on the risk of stomach cancer by subsite. Mailed questionnaires were used to obtain information on 1171 newly diagnosed histologically confirmed stomach cancer cases and 2207 population controls between 1994 and 1997 in eight Canadian provinces. Data were collected on socio-economic status, lifestyle and passive smoking status. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived by logistic regression. Compared with those who had never smoked, there was strongly increased risk for ex- and current smokers among subjects with cardial stomach cancer. For men with cardial cancer, the adjusted ORs were 1.9 (95% CI 1.2-3.0) and 2.6 (95% CI 1.6-4.3) for ex-smokers and current smokers, respectively, with a similar pattern among women. Among men, the adjusted ORs were lower for subsites of stomach cancer other than cardia. These findings suggest that active and passive smoking may play an important role in the development of cardial stomach cancer.


Nanosized Drug Delivery Systems for Direct Nose to Brain Targeting: A Review.
Drug targeting to brain has always been problematic due to Blood-Brain Barrier (BBB), which, does not allow most of the drugs to pass through it as they are hydrophilic and macromolecular drugs. So, in order to bypass the BBB, alternative modes of administration were searched and nasal to brain delivery route was tried by many workers. Such studies yielded patented nano-formulations with the ability to cross blood brain barrier. Nanoparticles being smaller in size and large surface area help in increasing the rate of drug permeation to the brain. In this review work, emphasis has been laid on discussion on various works done in the field of nasal delivery of drugs to brain over the last decade. The works that are discussed in this paper show better drug targeting of brain when given through nasal route as nanoparticles. Experiments performed in animal models have clearly exhibited that nano-sized formulations are able to facilitate the delivery of drugs to brain through nose in comparison to tantamount drug solutions. However, it is not yet confirmed whether the drug is freed from the formulation in the nasal cavity and then absorbed or the nanoparticles themselves are absorbed and then the drug is released in the CNS. Furthermore, the toxicity studies were not carried out extensively in suitably designed model, which should be considered before going for further studies and application.


[Therapy for HAM/TSP and AIDS].
(1) We evaluated efficacy of several treatments for HTLV-I-associated myelopathy (HAM) on the basis of our study on 254 HAM patients and of literature review. Improvement of motor disability more than fair response was obtained as follows: 82% in prednisolone, 69% in interferon-alpha, 92% in fosfomycin, 82% in high-dose vitamin C, 72% in blood purification therapy, 70% in heparin, 59% in salazosulfapyridine, 56% in thyrotropin-releasing hormone, 55% in erythromycin, 50% in mizoribine. (2) In the absence of clear guideline, the efficacy of zidovudine in the AIDS dementia complex has been demonstrated. There are also efficacy of amytriptylinein controlling HIV headache, corticosteroid in mononeuritis multiple and inflammatory myositis, hydrocortisone in autonomic neuropathy and plasmapheresis in distal sensory neuropathy respectively. Otherwise, it is emphasized that ddI, ddC and d4T have peripheral neuropathy as major, dose related side effect.


Effect of erythrocytes on brain water content and haem oxygenase-1 expression in rats with traumatic intracerebral haemorrhage.
Studies have demonstrated that brain oedema formation following spontaneous intracerebral haemorrhage is associated with substances derived from blood clots or blood components. However, these studies did not completely reveal the role of blood components in brain oedema formation following traumatic intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in brain oedema development by studying the effect of erythrocytes on brain water content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH. A total of 120 Sprague-Dawley rats were randomly divided into four experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs (PRBC). Following TBI, which was established by applying a free-falling device, WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the greatest. However, BWC in the LRBC group at 1 day was markedly higher than that at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC group was the highest at 1 day, and the highest at 3 days in the WB and PRBC groups; there was no significant difference at 5 days. Positive expression of HO-1 in the WB, PRBC and LRBC groups coincided with changes in BWC. Our results indicate that erythrocytes play an important role in delayed brain oedema formation (3 days post-injury) following TICH, but have no significant influence on brain oedema at early stages (1 day post-injury), and that the mechanisms of delayed brain oedema involve RBC breakdown products.


[Arthroscopic management of articular cartilage defect.]
The chondral changes of the carpus are frequent, often after trauma but also being able to be secondary with degenerative disease. The wrist arthroscopy generally makes it possible to make the diagnosis of these lesions, before they are visible by the usual paraclinic examinations. It will make it possible to withdraw foreign body, cartilage or osseous fragments free in the articulation at the origin of pains. It will also allow the abrasion of small size area of chondral change. Lastly, it will be an essential tool for a secondary conventional treatment. The installation of partial implants in necrosis of proximal pole by arthroscopy is a recent technique very well adapted.


Seasonality and bipolar disorder: a systematic review, from admission rates to seasonality of symptoms.
Bipolar disorder (BD) is a severe mental disorder affecting 1-4% of the population worldwide. It is characterized by periods of (hypo)manic and depressive episodes. Seasonal patterns (SP) may be observed in admission rates, mood relapses and symptom fluctuations. We conducted a systematic review of seasonality in BD, classifying studies based on seasonal admission rates to seasonality of symptoms assessments. Fifty-one papers were identified of which 32 addressed hospitalization rates by season, 6 addressed categorical diagnoses, and 13 explored symptom dimensions. Seasonal peaks for different BD mood episodes are observed worldwide and widely replicated. Manic episodes peak during spring/summer and, to a lesser extent, in autumn, depressive episodes peak in early winter and, to a lesser extent, summer, and mixed episodes peak in early spring or mid/late summer. There was a high frequency of SP for manic episodes (15%) and depressive episodes (25%), the latter being associated with a more complex clinical profile (BD II subtype, comorbid eating disorders, more relapses and rapid cycling). Finally, there was evidence for greater seasonal fluctuations in mood and behavior in individuals with BD than in those with unipolar depression or 'healthy' controls. Sample size, gender distribution, methodological quality and sophistication of the analytical approaches employed varied considerably. There is evidence of seasonality in BD, with emerging evidence that climatic conditions may trigger BD symptoms or episodes. A better understanding of the underlying mechanisms would facilitate the development of personalized chronobiological therapeutic and preventive strategies.


Production, biological activity, and structure of recombinant basic fibroblast growth factor and an analog with cysteine replaced by serine.
We have chemically synthesized the gene encoding bovine basic fibroblast growth factor (bFGF) and cloned it into a plasmid vector. This gene was then used as a template for site-directed mutagenesis to produce the human bFGF gene and a gene coding for an analog in which serine residues were substituted for the cysteine residues at positions 70 and 88. All three constructs were cloned and expressed in Escherichia coli and the proteins purified. The recombinant human and bovine bFGFs exhibited the potent mitogenic activity toward both fibroblasts and endothelial cells, which characterizes natural bFGF. The serine-70,88 analog and natural sequence bovine and human forms were equally active in all assays. Sulfhydryl titration of the purified recombinant bovine bFGF in 4.8 M guanidine hydrochloride indicated the presence of approximately two free sulfhydryl groups. This was consistent with the sequence analysis of peptides derived from trypsin digestion, which suggests that cysteines 70 and 88 exist in free sulfhydryl form while cysteines 26 and 93 form a disulfide bond. Circular dichroism shows that the protein has little ordered structure but is folded into a rigid tertiary configuration. Carboxymethylation of the free sulfhydryl groups resulted in no change in the mitogenic activity or conformation. These results are consistent with previous suggestions that, for tissue-derived bFGF, at least 2 of the 4 cysteines in the molecule are not involved in a disulfide bond.


Traveling front solutions to directed diffusion-limited aggregation, digital search trees, and the Lempel-Ziv data compression algorithm.
We use the traveling front approach to derive exact asymptotic results for the statistics of the number of particles in a class of directed diffusion-limited aggregation models on a Cayley tree. We point out that some aspects of these models are closely connected to two different problems in computer science, namely, the digital search tree problem in data structures and the Lempel-Ziv algorithm for data compression. The statistics of the number of particles studied here is related to the statistics of height in digital search trees which, in turn, is related to the statistics of the length of the longest word formed by the Lempel-Ziv algorithm. Implications of our results to these computer science problems are pointed out.


Suppression of liver allograft rejection by administration of 15-deoxyspergualin. Comparison of administration via the hepatic artery, portal vein, or systemic circulation.
In this experiment, the effect of the administration route-the hepatic artery, portal vein, or systemic circulation-of the immunosuppressive drug 15-deoxyspergualin (DSG) on the suppression of liver allograft rejection is investigated. A 3-day injection of DSG at a dose of 0.32-1.28 mg/kg per day into the systemic circulation of a rat that had received a liver transplant was not effective in prolonging liver graft survival (14.3 +/- 2.9 days vs. 14.1 +/- 2.5 days for controls). However, the administration of DSG into the portal vein following liver transplantation markedly prolonged survival for up to 24.9 +/- 10.0 days. Survival times were prolonged even more when the DSG was administered via the hepatic artery for 3 successive days after liver grafting (30.9 +/- 9.6 days). The concentration of DSG in the blood following the one-shot injection of DSG was highest when DSG was administered via the hepatic artery, intermediate when injected into the portal vein, and lowest when injected into the systemic vein. In conclusion, DSG can inhibit liver graft rejection more effectively via the hepatic arterial route than via the portal vein or systemic circulation.


Splitting and tuning characteristics of the point defect modes in two-dimensional phononic crystals.
Point defect modes of acoustic wave in two-dimensional square arrays of square water rods in a mercury host were studied. The defects are created by three kinds of geometry, namely, square defect, circular defect, and rectangular defect, respectively. The results show that for both square defect and circular defect, the defect modes are only related to the defect filling fraction F(d), but not with the geometry of defects (square or circular), as well as the orientations of the square defect. For the rectangular defect, the defect modes could be tuned by changing the ratio of edge width of the defect, moreover, the double degenerate one will split into two nondegenerate modes when the ratio of edge widths Lx / L(y) >9.0. Meanwhile the corresponding pressure distributions also will be changed.


A novel electrochemiluminescence sensor based on Ru(bpy)₃²⁺/N-doped carbon nanodots system for the detection of bisphenol A.
A novel Ru(bpy)3(2+)-based electrochemiluminescence (ECL) sensing platform, using N-doped carbon nanodots (N-C dots) as co-reactant, was established for the sensitive and selective detection of bisphenol A (BPA). N-C dots not only could enhance the ECL signal, but also significantly improved the reproducibility and stability of Ru(bpy)3(2+) ECL system. The developed ECL sensing system was sensitive to detect BPA based on its efficient quenching effect on Ru(bpy)3(2+)/N-C dots. The N-C dots-enhanced ECL mechanism and BPA-quenched ECL mechanism were investigated. Under the optimum conditions, the inhibited ECL intensity was in good linear relationship versus the concentration of BPA in the range of 0.03-1.0 μM with the detection limit of 10 nM. The relative standard deviation (RSD) for 25 successive measurements with one sensor was 1.1% and for eight different sensors was 2.5%, respectively. The fabricated sensing platform was successfully applied for the detection of BPA in baby bottle and nipple, and relatively satisfactory recoveries were obtained.


Direct Oral Anticoagulants (DOACs): Current Status Among Distinct Patient Subgroups.
The landscape of anticoagulant therapy for atrial fibrillation and deep-vein thrombosis has evolved considerably in the last decade with the advent of Novel or Direct-Acting Oral Antiocoagulants (DOACs). The initial phase III randomized controlled trials established the individual DOACs as viable alternatives to warfarin for thromboprophylaxis but generalizations to the larger population were limited by the small number of protocol subjects with renal insufficiency, congestive heart failure, advanced age and other comorbidities. All the DOACs have some degree of renal excretion and while safe and effective in patients with mild to moderate renal insufficiency, dose adjustment is necessary based on creatinine clearance. Subsequent data registries and real-world experience with DOACs have continued to refine their role in these particular patient subgroups. Off-label use with both under- and overdosing is not uncommon in renal failure and carries increased risk. Their increasing use among the elderly, in patients with heart failure, hepatic and renal insufficiency and among the Asian population has been shown to be relatively safe and effective compared to warfarin. Gaps in our current understanding of this new class of anticoagulants will continue to narrow as additional data becomes available through ongoing registries and real-world experience. [Full article available at http://rimed.org/rimedicaljournal-2017-05.asp].


The effect of delayed versus early loading on nitric oxide metabolism around dental implants: an 18-month comparative follow-up study.
Nitrite is a stable end-product of nitric oxide oxidation. The aim of the present study was to quantitatively analyze peri-implant sulcular fluid (PISF) nitrite levels in a longitudinal study design to evaluate the potential changes in nitric oxide metabolism in relation to the clinical status of the peri-implant site and the loading style of the dental implants. A total of 34 implants, either early loaded (EL) or delayed loaded (DL), in 17 patients were followed up for a period of 18 months. Clinical parameters were recorded, PISF samples were obtained, and PISF nitrite levels were spectrophotometrically determined. Clinical measurements and nitrite analysis were repeated at 1, 3, 6, 9, 12, and 18 months. Despite the gradual decrease in clinical parameters, fluctuations in PISF total nitrite levels were observed during follow-up. The pattern of nitric oxide metabolism, as reflected by PISF nitrite levels, also demonstrated differences between EL and DL implants that diminished toward the end of the experimental period. Although the presence of clinical and subclinical gingival inflammation contributes to the PISF total nitrite levels, nitric oxide metabolism is also associated with healing and bone remodeling, and the pattern of loading seemed to have an impact on nitric oxide production at dental implant sites. Nitric oxide production at dental implant sites seems to be tightly regulated to enable the maintenance of peri-implant bone.


The effect of anti-rheumatic drugs on factors from porcine synovium inducing chondrocyte mediated cartilage degradation.
A selection of NSAID's and diphosphonates were studied in a tissue culture model of cartilage degradation utilising porcine synovium and bovine nasal cartilage. All the NSAID's significantly reduced cartilage degradation when incorporated into the synovial culture medium. Lesser reductions were recorded when preformed chondrocyte stimulating factors were used and NSAID's added at the cartilage assay stage. These findings suggested that the principle site of action of NSAID's is upon the production of chondrocyte stimulating factors. None of the NSAID's tested affected inherent cartilage degradation. Diphosphonates had the opposite effects, they increased inherent cartilage degradation but had no effect on chondrocyte mediated cartilage degradation. The relationship of these results to previous known effects of NSAID's and diphosphonates upon cartilage is discussed. In addition, correlations between chondrocyte stimulating factors, catabolin and interleukin 1 are made.


[The relaxation principle in generalized convulsion (author's transl)].
According to the relaxation principle (Selbach) a phase of vagotropic preponderance is preceding to a generalized convulsion and is immediately overcome during convulsion by an increased sympathicus tonus. Conditions of generalized convulsions recently observed by animal experiments, such as high exspiratory neuronal activity and apnea a short time before the fit, and during the fit an increase of inspiratory and reticular neuronal activity as also an increased activity of the renal sympathicus, are thus attached to this two-phase-reaction.


The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children.
The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks.


Readmissions after major urologic cancer surgery.
We examine the incidence and predictors of readmission after major urologic cancer surgery using a national, prospective-maintained database specifically developed to assess quality of surgical care. Patients undergoing major urologic cancer surgery (radical prostatectomy [RP], radical nephrectomy [RNx], partial nephrectomy [PNx]), radical cystectomy [RC]) in 2011 were identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) using Current Procedural Terminology (CPT) codes. Those readmitted within 30 days after surgery were identified. Multivariable logistic regression models examined the association between patient characteristics and the odds of readmission. Overall, we identified 5356 RP, 1301 RNx, 918 PNx and 623 RC patients, of which 206 (3.8%), 533 (6.8%), 348 (6.3%) and 129 (20.7%) were readmitted within 30 days respectively. Independent predictors of readmission for RP included age (Odds Ratio [OR]: 1.02, p = 0.02), American Society of Anesthesiology (ASA) score 3-5 (versus 1-2, OR: 1.35, p = 0.04), smoking status (OR: 1.53, p = 0.04), and the occurrence of wound complications (OR: 9.31, p < 0.001), thromboembolic (OR: 14.7, p < 0.001), and renal failure (OR: 1.62, p = 0.01) complications during the index hospitalization. For RC patients, the only predictor of readmission was age (OR: 0.98, p = 0.04). Predictors of readmission for RNx included higher ASA score (OR: 1.77, p = 0.03), and the presence of any complications during the index hospitalization (OR: 2.21, p = 0.03). Several patient characteristics have a significant impact on the risk of 30 day readmission after major urologic cancer surgery. Our data suggests that improving prevention and management of complications during the index hospitalization may lead to a substantial decrease in readmission rates.


Acupuncture Sample Injection for Microchip Capillary Electrophoresis and Electrokinetic Chromatography.
A simple nanoliter-scale injection technique was developed for polydimethylsiloxane (PDMS) microfluidic devices to form the well-defined sample plugs in microfluidic channels. Sample injection was achieved by performing acupuncture on a channel with a needle and applying external pressure to a syringe. This technique allowed us to achieve reproducible injection of a 3-nL segment into a microchannel for PDMS microchip-based capillary electrophoresis (CE). Capillary zone electrophoresis (CZE) and capillary electrochromatography (CEC) with bead packing were successfully performed by applying a single potential in the most simplified straight channel. The advantages of this acupuncture injection over the electrokinetic injection in microchip CE include capability of minimizing sample loss and voltage control hardware, capability of serial injections of different sample solutions into a same microchannel, capability of injecting sample plugs into any position of a microchannel, independence on sample solutions during the loading step, and ease in making microchips due to the straight channel, etc.


[Retropharyngeal hydatid cyst].
We report the case of a 37 year old male from rural area who presented as an emergency with symptoms compatible with the existence of a retropharyngeal tumoration. By the clinic it suggested an abscess but the CT scan as compatible with a carcinoma. On complementary examinations it appeared in a chest X ray an image which strongly suggested the possibility of a hydatidic cyst of the lung. Specific serologic reactions supported this and post-surgical pathological study lately confirmed the diagnosis. We believe of interest reporting this case because of it's unusual localization and difficulty in diagnosis.


Effects of the playing surface on plantar pressures during the first serve in tennis.
This study aimed at examining the influence of different playing surfaces on in-shoe loading patterns in each foot (back and front) separately during the first serve in tennis. Ten competitive tennis players completed randomly five first (ie, flat) serves on two different playing surfaces: clay vs GreenSet. Maximum and mean force, peak and mean pressure, mean area, contact area and relative load were recorded by Pedar insoles divided into 9 areas for analysis. Mean pressure was significantly lower (123 ± 30 vs 98 ± 26 kPa; -18.5%; P < .05) on clay than on GreenSet when examining the entire back foot. GreenSet induced higher mean pressures under the medial forefoot, lateral forefoot and hallux of the back foot (+9.9%, +3.5% and +15.9%, respectively; both P < .01) in conjunction with a trend toward higher maximal forces in the back hallux (+15.1%, P = .08). Peak pressures recorded under the central and lateral forefoot (+21.8% and +25.1%; P < .05) of the front foot but also the mean area values measured on the back medial and lateral midfoot were higher (P < .05) on clay. No significant interaction between foot region and playing surface on relative load was found. It is suggested that in-shoe loading parameters characterizing the first serve in tennis are adjusted according to the ground type surface. A lesser asymmetry in peak (P < .01) and mean (P < .001) pressures between the two feet was found on clay, suggesting a greater need for stability on this surface.


Imaging findings in patients with ventral dural defects and herniation of neural tissue.
The aim of this paper is to describe clinical and imaging findings in three patients with ventral dural defects and herniation of the spinal cord or cauda equina. The literature is reviewed and the clinical, radiological and operative findings are compared. Three patients with ventral dural defects of different etiologies are presented. One patient gave a longstanding history of ankylosing spondylitis, the second patient presents 37 years after spinal trauma, and the third patient presents with spontaneous spinal cord herniation. All patients had typically slowly progressive neurological symptoms with multiple hospitalizations until diagnosis was made. Characteristic findings in postmyelographic CT included a ventral or ventrolateral displacement with deformation of the spinal cord or the cauda equina. Sagittal MRI showed this abrupt and localized anterior deviation of the spinal cord or the cauda equina to the posterior portions of a vertebral body with or without a bony vertebral defect optimally. Additionally, due to the ventral displacement of the spinal cord, the dorsal subarachnoid space was relatively enlarged without evidence of an arachnoid cyst, in all patients. Magnetic resonance imaging and postmyelographic CT can diagnose ventral dural defects with spinal cord herniation or nerve root entrapment. Dural defects must be considered in the presence of neurological symptoms in cases of longstanding ankylosing spondylitis, late sequelae of fractures of vertebral bodies, and without history of spinal trauma or surgery.


Beneficial auditory and cognitive effects of auditory brainstem implantation in children.
This preliminary study demonstrates the development of hearing ability and shows that there is a significant improvement in some cognitive parameters related to selective visual/spatial attention and to fluid or multisensory reasoning, in children fitted with auditory brainstem implantation (ABI). The improvement in cognitive paramenters is due to several factors, among which there is certainly, as demonstrated in the literature on a cochlear implants (CIs), the activation of the auditory sensory canal, which was previously absent. The findings of the present study indicate that children with cochlear or cochlear nerve abnormalities with associated cognitive deficits should not be excluded from ABI implantation. The indications for ABI have been extended over the last 10 years to adults with non-tumoral (NT) cochlear or cochlear nerve abnormalities that cannot benefit from CI. We demonstrated that the ABI with surface electrodes may provide sufficient stimulation of the central auditory system in adults for open set speech recognition. These favourable results motivated us to extend ABI indications to children with profound hearing loss who were not candidates for a CI. This study investigated the performances of young deaf children undergoing ABI, in terms of their auditory perceptual development and their non-verbal cognitive abilities. In our department from 2000 to 2006, 24 children aged 14 months to 16 years received an ABI for different tumour and non-tumour diseases. Two children had NF2 tumours. Eighteen children had bilateral cochlear nerve aplasia. In this group, nine children had associated cochlear malformations, two had unilateral facial nerve agenesia and two had combined microtia, aural atresia and middle ear malformations. Four of these children had previously been fitted elsewhere with a CI with no auditory results. One child had bilateral incomplete cochlear partition (type II); one child, who had previously been fitted unsuccessfully elsewhere with a CI, had auditory neuropathy; one child showed total cochlear ossification bilaterally due to meningitis; and one child had profound hearing loss with cochlear fractures after a head injury. Twelve of these children had multiple associated psychomotor handicaps. The retrosigmoid approach was used in all children. Intraoperative electrical auditory brainstem responses (EABRs) and postoperative EABRs and electrical middle latency responses (EMLRs) were performed. Perceptual auditory abilities were evaluated with the Evaluation of Auditory Responses to Speech (EARS) battery - the Listening Progress Profile (LIP), the Meaningful Auditory Integration Scale (MAIS), the Meaningful Use of Speech Scale (MUSS) - and the Category of Auditory Performance (CAP). Cognitive evaluation was performed on seven children using the Leiter International Performance Scale - Revised (LIPS-R) test with the following subtests: Figure ground, Form completion, Sequential order and Repeated pattern. No postoperative complications were observed. All children consistently used their devices for >75% of waking hours and had environmental sound awareness and utterance of words and simple sentences. Their CAP scores ranged from 1 to 7 (average =4); with MAIS they scored 2-97.5% (average =38%); MUSS scores ranged from 5 to 100% (average =49%) and LIP scores from 5 to 100% (average =45%). Owing to associated disabilities, 12 children were given other therapies (e.g. physical therapy and counselling) in addition to speech and aural rehabilitation therapy. Scores for two of the four subtests of LIPS-R in this study increased significantly during the first year of auditory brainstem implant use in all seven children selected for cognitive evaluation.


[Endoscopic transpterygoid intervention for lesions of lateral recess of sphenoid sinus in 4 cases(with literature review) ].
Objective: To investigate the anatomy and application of endoscopic transpterygoid intervention in lesions of lateral recess of sphenoid sinus(LRSS). Method: Four hospitalized patients with lesions of LRSS were studied. The clinical presentations included spontaneous cerebrospinal fuild(CSF) leakage in 2 cases, meningoencephaolece complicated CSF leakage in 1 case and chronic invasive fungal sphenoid sinusitis invading the base of the middle fossa in 1 case. Endoscopic transpterygoid intervention and repairment of skull base defects were performed under general anesthesia. Result: he operations were successfu1 in all patients. One patient suffered from postoperative palatal hypesthesia and all the symptoms mentioned above relieved gradually 6 months after operation. No recurrence was found during the follow-up ranging from 6 to 45 months(mean follow-up period,22.75 months).Conclusion: Endoscopic transpterygoid intervention in lesions of LRSS is a minimally invasive and safe surgical approach.


Intracapsular metaphyseal osteoid osteoma of the femoral neck.
The authors discuss the 20 cases of intracapsular metaphyseal osteoid osteoma of the neck of the femur found among the total 186 cases of osteoid osteoma on the files of the Tumour Centre of the Rizzoli Orthopaedic Institute. They assess the diagnostic methods that can be used to determine the precise position of the "nidus" with reference to the surgical route to be used. The operation must expose the osteoid osteoma directly by opening the joint.


A standardized method for assigning gestational age: a tool for measuring gestational age based newborn intensive care outcomes.
We developed a computer-generated algorithm for standardizing the assignment of a best gestational age. Our database collected information on maternal last menstrual period (LMP), prenatal ultrasonography, obstetrical estimated date of confinement (EDC), use of assisted reproductive technology (ART), and newborn assessment based on the Ballard examination. The algorithm for determining best gestational age was developed based on the literature on the accuracy of prenatal and neonatal dating. We examined the performance of the algorithm using patients admitted to our neonatal intensive care unit (NICU) with a best gestational age <or= 32 completed weeks. Based on agreement of the obstetric EDC with either the first-trimester ultrasonography or LMP and first- and second-trimester ultrasonography, 64.4% of patients were classified as having certain dating. The Ballard assessment played a role in assigning a best gestational age in 11.3% of patients. We demonstrated differences in outcomes based on dating certainty within subpopulations in our NICU. An objective standardized methodology for assigning gestational age is a useful tool for comparing gestational age-based outcome measures between institutions.


Leukocyte CD18 receptors may be a better target than ICAM-1 ligands for reducing histologic evidence of cellular and vascular rejection in the rabbit.
Building evidence suggests that blocking the ICAM-1/CD18 interaction may affect the course of graft rejection. Treatment with monoclonal antibody (mAb) to CD18 was compared to antibody to ICAM-1 in a rabbit heterotopic heart transplant model to determine whether blocking the leukocyte receptor for ICAM-1, CD18, was more effective than antibody targeting of the ligand for ICAM-1. Following transplantation, 28 recipient rabbits were randomized to receive either placebo, mAb to CD18, or mAb to ICAM-1 for 7 days until sacrifice. The cellular rejection grade and percentage of arteries with vascular rejection were significantly lower in animals treated with anti-CD18 than with anti-ICAM-1. As assessed by histology, antibody treatment was more effective in reducing both cellular and vascular rejection when directed at the leukocyte receptor CD18 than the ICAM-1 ligand. These findings suggest that other ICAM ligands may play an active role in the immune response and that CD18 may be important for migration of lymphocytes through myocardium.