HLA-DR3 transgenic mice immunized with adenovirus encoding the thyrotropin receptor: T cell epitopes and functional analysis of the CD40 Graves' polymorphism.
The major histocompatibility (MHC) molecule HLA-DR3 is a susceptibility gene for Graves' disease (GD) in Caucasians. Mice lacking murine MHC and expressing human HLA-DR3 develop thyrotropin receptor (TSHR) antibodies and sometimes hyperthyroidism after vaccination with TSHR-DNA. MHC molecules present peptides processed from antigens to T cells. Therefore, we used DR3-transgenic mice to investigate recognition of TSHR ectodomain peptides. After immunization with TSHR A-subunit adenovirus (A-subunit-Ad) but not control-adenovirus (Control-Ad), splenocytes from DR3 mice responded to A-subunit protein in culture by producing interferon-gamma (IFN-gamma). When challenged with 29 overlapping TSHR peptides, splenocytes from A-subunit-Ad- or Control-Ad-immunized mice responded to several peptides. However, in splenocytes from A-subunit-Ad but not Control-Ad mice, a peptide containing TSHR residues 142-161 induced significantly more IFN-gamma than the same splenocytes in medium alone. Immunized DR3 mice also permitted testing the TSHR-specific function of the CD40 single nucleotide polymorphism (C vs. T) associated with GD. Of three human DR3 human Epstein-Barr virus lines (EBVL), two had C in both alleles (CC) and one was CT. However, these EBVL presented peptides poorly and there was no difference between CC vs. CT EBVL in peptide presentation to splenocytes from immunized mice. A peptide corresponding to residues 145-163 is one of seven suggested to be important in GD based on HLA-binding affinities, T-epitope algorithms, and human studies. Consequently, as in human GD, TSHR amino acids 142-161 appear to include a major T cell epitope in HLA-DR3 transgenic mice immunized with A-subunit-Ad.


Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug.
Interleukin (IL)-10 is a pleiotropic cytokine produced by both T cells and macrophages and possesses both anti-inflammatory and immunosuppressive properties. IL-10 circulates in the blood of patients with sepsis syndromes, and increased concentrations of IL-10 have been associated with an adverse clinical outcome. Experimental studies in rodents and primates have demonstrated that endogenously produced and exogenously administered IL-10 can reduce the magnitude of the inflammatory response and improve outcome, primarily in models of endotoxemic and bacteremic shock. However, endogenous IL-10 production and systemic administration can also exacerbate T-cell dysfunction, decrease T-cell apoptosis, reduce antimicrobial function, and increase mortality in other less acute bacterial models of sepsis or after thermal injury. Targeted delivery of IL-10 to individual tissues may obviate the adverse effects of systemic delivery. The potential anti-inflammatory properties of IL-10 will have to be carefully weighed against its immunosuppressive properties when considering its use in patients with acute inflammation and sepsis syndromes.


Background music and cognitive performance.
The present experiment employed standardized test batteries to assess the effects of fast-tempo music on cognitive performance among 56 male and female university students. A linguistic processing task and a spatial processing task were selected from the Criterion Task Set developed to assess verbal and nonverbal performance. Ten excerpts from Mozart's music matched for tempo were selected. Background music increased the speed of spatial processing and the accuracy of linguistic processing. The findings suggest that background music can have predictable effects on cognitive performance.


Comparison of continuous wave Doppler ultrasound of the radial artery and laser Doppler flowmetry of the fingertips with sympathetic stimulation.
Laser Doppler is widely used to evaluate sympathetic vasoconstrictor function. Continuous wave (cw)-Doppler of the radial artery may be an alternative but less expensive approach to quantify sympathetically induced resistance changes in the peripheral vascular system. In order to compare the power of both methods, this study was performed with simultaneous assessment of cw Doppler and laser Doppler flowmetry in volunteers. Twenty-five healthy subjects (median age years, range 20-27) rested in a relaxed supine position and were asked to perform a deep inspiratory gasp and a commanded cough (DIG + C). Radial artery blood flow was assessed with a standard cw Doppler device, arteriolar blood flow was assessed simultaneously employing a single point laser Doppler perfusion monitor at the fingertips. We quantified the latency between stimulus and onset of vasoconstriction, the latency to the maximum vasoconstriction and the duration of response. The decrease in flow velocities (cw Doppler) after stimulus was compared with the decrease in capillary flow (laser Doppler). While the flow profile as measured with laser Doppler remained monophasic after stimulation, cw Doppler showed biphasic flow (or absent diastolic flow) in all subjects after DIG + C. The latencies between stimulus and onset of reaction were significantly shorter when measured with laser Doppler (1.8 s vs. 2 s, p = 0.049), the latencies till the maximum extent of the reaction was reached did not differ significantly (3.2 vs. 3.3 s). The duration of the response was significantly shorter when measured by laser Doppler (12.0 vs. 14.5 s (p < 0.0001). While skin blood flow in the laser Doppler measurement decreased after stimulation from 654 flux units (FU) to 319 FU (-59%), mean flow velocities in the radial artery declined from 1.07 kHz to 0.14 kHz (-87%). This relative change was significantly different (p < 0.0001). The correlation between the decline of flux units as measured by laser Doppler and cw Doppler changes was r = 0.616 (p = 0.004). Both methods are feasible to monitor flow changes due to sympathetic stimulation. Latencies and relative quantitative changes were closely correlated.Thus, cw Doppler is a valid alternative approach to laser Doppler flowmetry in healthy volunteers.


Applications of microdialysis in studies of exercise.
Microdialysis provides a means of determining nutrient blood flow as well as continuous simultaneous determination of the interstitial concentration of nutrients and metabolites. Microdialysis also allows for local delivery of pharmacological agents to tissue without resultant systemic effects. The potential of microdialysis for exercise studies is clear, yet relatively untapped.


A Novel Electron Microscopic Characterization of Core/Shell Nanobiostimulator Against Parasitic Plants.
Nanoencapsulation has proven to be an efficient route to increase significantly the solubility and bioavailability of organic compounds. This aspect of nanotechnology is illustrated for the case of phthalimide-lactone (PL), a recently synthesized strigolactone mimic whose very limited solubility in water, as a free chemical, precludes its practical use as an agrochemical in the fight against parasitic plants. Pluronic F-127 (P127) nanoparticles functionalized with PL have been synthesized and embedded in a polymeric matrix of poly(vinyl alcohol) (PVA). Low-voltage and medium voltage imaging and spectroscopic scanning electron microscopy (S(T)EM) techniques were combined to confirm the synthesis of multicore nanoparticles that were rich in nitrogen, a finding that is due to the successful encapsulation of PL. This PL@P127/PVA nanobiostimulator formulation has an impressive solubility in water, that is, 27 times higher than that of pure phthalimide-lactone. Also critical from the functional point of view, comparative bioassays clearly showed that the intrinsic stimulatory activity of this agrochemical is fully maintained in the nanoencapsulated formulation.


Future practice plans of orthodontic residents in the United States.
The purpose of this study was to investigate the future clinical practice plans of orthodontic residents in the United States. All program chairs and directors of the 65 US orthodontic residency programs were contacted by e-mail and telephone and asked for permission to e-mail their residents and invite them to take part in an anonymous 57-item questionnaire online. A total of 335 e-mails from 37 programs were obtained, and the survey was sent in May 2007. Basic statistics including chi-square comparative analyses were performed by sex, age, and year of program. A total of 63.04% of orthodontic residents plan to use self-ligating brackets; 84.06% plan to use Invisalign (Align Technology, Santa Clara, Calif); 92.03% plan to use temporary anchorage devices, and 72.26% plan on placing them themselves; 28.26% plan to use cone-beam computerized tomography; 92.75% plan to use a digital imaging program; 45.65% plan to use indirect bonding; and 10.87% plan to use lingual orthodontics. A total of 70.07% plan to use 2-phase treatment, and 61.59% said they will use functional appliances. A total of 81.16% plan to become certified by the American Board of Orthodontics, but only 18.12% thought certification should be mandatory for licensure; 36.50% indicated that a master of science degree should be required in their program, and 77.94% believe that a 24- to 30-month program adequately prepares them for future orthodontic practice. Newer orthodontic technologies such as self-ligating brackets, temporary anchorage devices, and Invisalign as well as functional appliances are expected to grow in popularity in the United States because of projected future use by orthodontic residents. Two-phase orthodontic treatment with functional appliance mechanics will continue to be used. Most orthodontic residents will become certified by the American Board of Orthodontics but do not believe it should be necessary for licensure. Orthodontic residents in the United States believe that a 2-year program adequately prepares them for private practice.


Hypocaloric diet reduces exercise-induced alpha 2-adrenergic antilipolytic effect and alpha 2-adrenergic receptor mRNA levels in adipose tissue of obese women.
Previous investigations have shown that alpha 2-adrenoceptor (alpha 2-AR) stimulation blunts lipid mobilization during physiological activation of the sympathetic nervous system promoted by exercise in sc abdominal adipose tissue (SCAAT) in obese men. To investigate the effect of a low calorie diet (LCD) on the alpha 2-adrenergic responsiveness and on the expression of alpha 2-AR and beta 2-adrenoceptor (beta 2-AR) in SCAAT, 11 obese women (weight: 99.1 +/- 4.6 kg; body mass index: 34.3 +/- 1.1 kg/m(2)) received a 12-wk diet providing 500 kcal/d less than their usual diet. The exercise-induced alpha 2-adrenergic antilipolytic effect was investigated in SCAAT before and at the end of LCD. Changes in extracellular glycerol concentration and local blood flow were measured in SCAAT during a 45-min exercise bout (50% of heart rate reserve) using a control microdialysis probe and a probe supplemented with the alpha2-AR antagonist phentolamine. SCAAT biopsies were performed for determination of mRNA levels using RT-competitive PCR. Plasma catecholamine responses to exercise bout were not different before and at the end of LCD. Before LCD, the exercise-induced increase in extracellular glycerol concentration was potentiated by phentolamine supplementation, while this potentiating effect of the alpha-antagonist was not observed at the end of LCD. No changes were observed for beta 2-AR and hormone-sensitive lipase mRNA levels, while alpha 2-AR mRNA level was significantly decreased in adipose tissue during LCD. These findings show that alpha 2-AR-mediated antilipolytic action is reduced by a moderate hypocaloric diet and that down-regulation of alpha 2-AR mRNA levels may participate in the decrease of the alpha 2-adrenergic effect revealed by microdialysis.


Development of a FPGA based fuzzy neural network system for early diagnosis of critical health condition of a patient.
The paper describes the design and training of a fuzzy neural network used for early diagnosis of a patient through an FPGA based implementation of a smart instrument. The system employs a fuzzy interface cascaded with a feed-forward neural network. In order to obtain an optimum decision regarding the future pathophysiological state of a patient, the optimal weights of the synapses between the neurons have been determined by using inverse delayed function model of neurons. The neurons that are considered in the proposed network are devoid of self connections instead of commonly used self connected neurons. The current work also find out the optimal number of neurons in the hidden layer for accurate diagnosis as against the available number of CLB in the FPGA. The system has been trained and tested with renal data of patients taken at 10 days interval of time. Applying the methodology, the chance of attainment of critical renal condition of a patient has been predicted with an accuracy of 95.2%, 30 days ahead of actually attaining the critical condition. The system has also been tested for pathophysiological state prediction of patients at multiple time steps ahead and the prediction at the next instant of time stands out to be the most accurate.


Use of immobilised biocatalysts in the processing of cheese whey.
Food processing industry operations need to comply with increasingly more stringent environmental regulations related to the disposal or utilisation of by-products and wastes. These include growing restrictions on land spraying with agro-industrial wastes, and on disposal within landfill operations, and the requirements to produce end products that are stabilised and hygienic. Much of the material generated as wastes by the dairy processing industries contains components that could be utilised as substrates and nutrients in a variety of microbial/enzymatic processes, to give rise to added-value products. A good example of a waste that has received considerable attention as a source of added-value products is cheese whey. The carbohydrate reservoir of lactose (4-5%) in whey and the presence of other essential nutrients make it a good natural medium for the growth of microorganisms and a potential substrate for bioprocessing through microbial fermentation. Immobilised cell and enzyme technology has also been applied to whey bioconversion processes to improve the economics of such processes. This review focuses upon the elaboration of a range of immobilisation techniques that have been applied to produce valuable whey-based products. A comprehensive literature survey is also provided to illustrate numerous immobilisation procedures with particular emphasis upon lactose hydrolysis, and ethanol and lactic acid production using immobilised biocatalysts.


Autotransplantation of severed limbs. A case report.
A case report of a successful autotransplantation of a forearm and hand at the distal third of the forearm is presented. The plan of repair is described and the functional result is demonstrated.


Association of target organ damage with 24-hour systolic and diastolic blood pressure levels and hypertension subtypes in untreated Chinese.
The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure <130/<80 mm Hg. Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P≤0.003) left ventricular mass index (+4.31 g/m(2)), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P≥0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (<55 years), the mutually independent effect sizes associated with 1 SD increases in 24-hour systolic/diastolic blood pressure were +3.31/-0.36 g/m(2) (P=0.009/0.79) for left ventricular mass index, +1.15/+1.14 mg/mmol (P=0.02/0.04) for the urinary albumin:creatinine ratio, and +0.54/-0.05 m/s (P<0.001/0.54) for pulse wave velocity. In older participants, these estimates were +3.58/+0.30 g/m(2) (P=0.045/0.88), +1.23/+1.05 mg/mmol (P=0.002/0.54), and +0.76/-0.49 m/s (P<0.001/<0.001), respectively. In conclusion, 24-hour systolic blood pressure and mixed hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.


Rye bran diet increases epithelial cell apoptosis and decreases epithelial cell volume in TRAMP (transgenic adenocarcinoma of the mouse prostate) tumors.
A rye bran diet has been suggested to retard prostate cancer growth and increase tumor cell apoptosis in animal models and in men with prostate cancer. Transgenic mice designed to develop prostate cancer (transgenic adenocarcinoma of the mouse prostate, TRAMP) were therefore treated with a rye bran diet. TRAMP mice were fed a rye bran (n = 13) or a control diet (n = 15) from 4 to 24 wk of age. Tumor histology, cell proliferation, and apoptosis were accessed using stereological and immunohistochemical techniques. In the dorsolateral prostate lobe in TRAMP mice, epithelial cell apoptosis was increased by 31%, and the volume fraction of epithelial cells was reduced by 20% (P < 0.05) in the rye bran-treated group compared with the control diet group. There were, however, no significant changes detected in lobe weights or tumor grade. In conclusion, a rye bran diet increases epithelial apoptosis and reduces the epithelial cell fraction in TRAMP tumors.


Relationships between sagittal alignment of the cervical spine and morphology of the spinal cord and clinical outcomes in patients with cervical spondylotic myelopathy treated with expansive laminoplasty.
A total of 103 patients with cervical spondylotic myelopathy undergoing laminoplasty were retrospectively reviewed to evaluate whether sagittal alignment of the cervical spine and morphology of the spinal cord influence surgical outcomes. Sagittal alignment of the cervical spine did not influence surgical outcomes. Neurologic recovery in patients with anterior convexity of the spinal cord was better than in those without this type of spinal cord. In patients with supplementation of decompression at C2, sagittal morphology of the spinal cord did not influence neurologic recovery. It is important to acquire anterior convexity of the spinal cord after surgery if laminoplasty is performed below C3. In patients with kyphosis, where anterior convexity of the spinal cord is not thought to be obtained postoperatively, it is possible that additional decompression of C2 improves outcome.


Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells.
Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer. Vectors containing a variety of strong promoters driving enhanced green fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency. Transduction efficiencies and transgene expression levels in MSCs were found to be higher with lentiviral vectors than with a vector based on the murine stem cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture for at least 5 months. HIV-1-based lentiviral vectors were able to transduce clonogenic mesenchymal progenitor cells, which were capable of maintaining transgene expression by their MSC progeny, over several cell divisions and during differentiation into adipocytes, indicating that terminal adipocyte cell differentiation was unaffected by lentivirus-mediated reporter gene transfer. Collectively these results suggest that lentivirus-mediated gene transfer strategies provide an efficient tool for ex vivo modification of MSCs that does not interfere with differentiation.


[Solitary malignant fibrous inguinal tumor. Case report].
Solitary fibrous tumours (SFTs) are rare neoplasias that were first reported in pleura, but can occur in different sites. Inguinal location is extremely rare. We report one case of a 74 year old man with a right inguinoscrotal mass with 50 years of evolution. After surgical extirpation, solitary fibrous tumour was diagnosed. The vast majority of solitary fibrous tumours (SFTs) have a benign course. Only a few cases have aggressive behaviour, with local recurrence and metastasis. Treatment is surgical, but we must do a long-term follow up in all cases.


Effect of application of force to self-adhesive defibrillator pads on transthoracic electrical impedance and countershock success.
To examine the effect of the application of force to self-adhesive defibrillator pads on transthoracic electrical impedance and countershock success. A prospective, randomized, controlled pilot study was carried out in an experimental animal laboratory, involving 32 mixed-breed swine weighing 36.5 to 55.7 kg each. Ventricular fibrillation (VF) was induced, and the animals were randomly allocated to 1 of 4 groups, with 8 animals per group. Animals in groups I and II remained in VF for 30 seconds; those in groups III and IV remained in VF for 5 minutes. At the end of the VF period, up to 3 countershocks were given. In groups I and III, countershocks were delivered through the self-adhesive defibrillator pads alone; in groups II and IV, they were delivered through the defibrillator pads with 25 lb of applied force. Any animal without return of spontaneous circulation after 3 countershocks was given epinephrine after 1 minute of CPR, followed by 1 additional minute of CPR and 1 additional countershock if required. The main measurements included baseline and countershock transthoracic impedance, cumulative countershock success rate, and 30-minute survival rate. Application of 25 lb of force to the defibrillator pads significantly decreased transthoracic impedance, compared with baseline values (group II, 15. 1% decrease; group IV, 16.1% decrease). The first-shock success rate was higher when force was applied during the countershock (87.5% versus 50% for groups II and I, respectively; 62.5% and 37.5% for groups IV and III, respectively). In the animals who experienced 5 minutes of VF, there were greater rates of success after the second, third, and fourth countershocks when force was applied (group IV) than when no force was applied (group III). Groups I and II (VF for 30 seconds) demonstrated 100% survival at 30 minutes. Group IV had a higher 30-minute survival rate (3/8 animals) than did group III (1/8). However, the rates of countershock success and 30-minute survival were not statistically different among the groups. Application of force to self-adhesive defibrillator pads decreases transthoracic impedance during countershock. This effect may contribute to improving the countershock success rate.


An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis.
Voltage-gated potassium channel antibody-positive limbic encephalitis (VGKC+LE) frequently improves with immunotherapy, although the optimum regimen is unknown. The effectiveness of a combination immunomodulatory regimen was tested in consecutive VGKC+LE patients. This was an open-label prospective study of nine VGKC+LE patients. All patients had plasma exchange (50 ml/kg), intravenous immunoglobulin (2 g/kg) and intravenous methylprednisolone (1 g×3), followed by maintenance oral prednisolone (1 mg/kg/day). Mycophenolate (2 g/day) was used in the first three patients. Assessments included serial clinical, cognitive, brain MRI and VGKC antibody testing. Within 1 week, seizures and hyponatraemia remitted in all affected patients. Cognitive function improved in all patients within 3 months. MRI appearances improved substantially within 9 months, with remission of inflammation in the majority of patients. All achieved immunological remission with normal VGKC antibody titres within 1-4 months. Major adverse events of therapy included one septicaemia and one thrombosis on plasma exchange and one death from sepsis after incidental bowel surgery. One patient remains in remission after 40 months of follow up, 26 months after being off all treatment. Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.


Natural killer cells: versatile roles in autoimmune and infectious diseases.
Natural killer (NK) cells are essential members of innate immunity and they rapidly respond to a variety of insults via cytokine secretion and cytolytic activity. Effector functions of NK cells form an important first line of innate immunity against viral, bacterial and parasitic infections, as well as an important bridge for the activation of adaptive immune responses. The control of NK-cell activation and killing is now understood to be a highly complex system of diverse inhibitory and activatory receptor-ligand interactions, sensing changes in MHC expression. NK cells have a functional role in innate immunity as the primary source of NK-cell-derived immunoregulatory cytokines, which have been identified in target organs of patients suffering from autoimmune diseases, and play a critical role in early defense against infectious agents. This review focuses on recent research of NK cells, summarizing their potential immunoregulatory role in modulating autoimmunity and infectious diseases.


Derivation of the extended fan-beam formula.
The fan-beam tomographic reconstruction formulas that have previously appeared in the literature have been restricted to the case where the source points are situated on a circle. This paper extends the fan-beam formula to "curves of source points" other than a circle of source points (e.g., a straight line or a hexagon). In the derivation new mathematical techniques are presented. For both the straight line and the hexagon a discrete version of the "extended" formula is developed.


[Construction of rye-wheat amphidiploids with the cytoplasm of rye-secalotriticum (RRAABB, 2n = 42): meiosis characteristics in rye-triticale F1 hybrids (RRABR, 5x = 35)].
Results of cytogenetic analysis of microsporogenesis in rye-triticale F1 hybrids (RRABR, 5x = 35) are presented. Meiosis of pentaploids is described as the key stage in the synthesis of secalotriticum, lines with intergenomic substitutions of chromosomes, or alloplasmic rye and wheat lines. Properties of meiotic processes and cytological mechanisms in formation of functional gametes and plants of various genomic and chromosomal composition are discussed.


Screening anti-HIV Chinese materia medica with HIV and equine infectious anemic virus reverse transcriptase.
The inhibitory activities of human immunodeficiency virus reverse transcriptase (HIV-RT) inhibitors PFA and Suramin against HIV-RT and equine infectious anemic virus reverse transcriptase (EIAV-RT) were studied in this paper. The 50% inhibitory concentration (IC50) of HIV-RT and EIAV-RT treated by PFA and Suramin were 0.2 mumol, 9.8 mumol and 17 mumol, 19.9 mumol, respectively. More than thirty Chinese medicines, including recipes, herbs, extracts of traditional materia medica and isolated compounds were tested using HIV-RT and EIAV-RT as target enzymes. It was found that 5 crude extracts such as Rhizoma Polygoni Cuspidati, and Radix Notoginseng, 7 isolated compounds like Flavone of Ramulus Visci, Flavone of Ajuga Decumbens Thumb, and Aristolochic acid, as well as the extract of the complex prescription Xiao Chai Hu Tang have shown various inhibitory actions on these two enzymes. The activities of the two enzymes were comparable, but HIV-RT was more sensitive, suggesting that HIV-RT can be used as index for the screening of anti-aids drugs.


Synergic effect of cisplatin, Adriamycin, and cyclophosphamide combination chemotherapy and radiotherapy in non-small cell lung cancer.
61 patients with inoperable non-small cell lung cancer were treated by combination chemotherapy with cisplatin, Adriamycin and cyclophosphamide. 23 patients received radiotherapy in addition to the chemotherapy. 49 out of 55 adequately treated patients were evaluable for tumor response. Of 29 patients who received chemotherapy alone, 6 (21%) achieved partial responses. Of 20 patients who received combined chemotherapy and radiotherapy, 16 (80%) achieved complete or partial responses. The median survival time was 18 months for 22 patients treated with combined therapies.


Separation and analysis of the major forms of plasma fibronectin.
Human plasma fibronectin exists in circulation in multiple molecular forms that are distinguishable by SDS-polyacrylamide gel electrophoresis (zone I, approx. 450 kDa dimers; zone II, 190-235 kDa; Zone III, 146-175 kDa). (Chen, A.B., Amrani, D.L. and Mosesson, M.W. (1977) Biochim. Biophys. Acta 493, 310-322). We report here on investigations of plasma fibronectin that had been purified from the 'heparin-precipitable fraction' of plasma by DEAE-cellulose chromatography using buffers containing a chaotropic salt (KSCN). Zone I fibronectin and zone II fibronectin were subsequently separated by Sepharose CL-6B chromatography in the presence of 0.3 M KSCN. Electrophoresis of reduced zone I fibronectin dimers showed the presence of three types of subunits (i.e., 220 kDa, 215 kDa, 207 kDa), evidently all having the same NH2-terminal sequence. Subunits of this size were also found in reduced zone II fibronectin, as well as another polypeptide of 190 kDa, the latter amounting to under 5% of the total. Unreduced zone I fibronectin was resolved by gel electrophoresis into a doublet. The upper component amounted to approx. 90% of the total and was comprised of 220 kDa and/or 215 kDa subunits; the lower component contained 207 kDa plus a 220 kDa or 215 kDa subunit. Scanning transmission electron microscopy indicated that under physiologic conditions zone II fibronectin molecules, like those in zone I, exist as pleiomorphic, loosely folded structures (approx. 16 X 8-12 nm) that are somewhat smaller than dimeric zone I molecules (approx. 24 X 16 nm). Circular dichroic spectral analyses suggests that both types have similarly folded local domains. Affinity chromatography experiments revealed a relative decrease in the binding of zone II fibronectin to gelatin but no difference from zone I fibronectin with respect to heparin or fibrin binding.


Chitosan-assisted immunotherapy for intervention of experimental leishmaniasis via amphotericin B-loaded solid lipid nanoparticles.
Solid lipid nanoparticles (SLNs) have emerged as an excellent substitute over polymeric nanoparticles and, when incorporated with chitosan which activates the macrophage to impart an immune response, produce excellent results to fight against deleterious diseases like leishmaniasis where its parasite diminishes the immunity of the host to induce resistance. Based upon this hypothesis, chitosan-coated SLNs were developed and loaded with amphotericin B (AmB) for immunoadjuvant chemotherapy of Leishmania infection. Both uncoated and chitosan-coated AmB-loaded SLNs (AmB-SLNs) were fabricated using solvent emulsification and evaporation method. The various processes and formulation parameters involved in AmB-SLN preparation were optimized with respect to particle size and stability of the particles. In vitro hemolytic test credited the formulations to be safe when injected in the veins. The cellular uptake analysis demonstrated that the chitosan-coated AmB-SLN was more efficiently internalized into the J774A.1 cells. The in vitro antileishmanial activity revealed their high potency against Leishmania-infected cells in which chitosan-coated AmB-SLNs were distinguishedly efficacious over commercial formulations (AmBisome and Fungizone). An in vitro cytokine estimation study revealed that chitosan-coated AmB-SLNs activated the macrophages to impart a specific immune response through enhanced production of TNF-α and IL-12 with respect to normal control. Furthermore, cytotoxic studies in macrophages and acute toxicity studies in mice evidenced the better safety profile of developed formulation in comparison to marketed formulations. This study indicates that the AmB-SLNs are a safe and efficacious drug delivery system which promises strong competence in antileishmanial chemotherapy and immunotherapy.


Emerging paradigms in immunonutrition.
Nutritional immunology is the study of the relationship between food and the immune system. It evolved with the study of immune deficiencies caused by malnutrition. However, because of technological advances made over the past few decades, malnutrition is no longer the main cause of lowered immune status in otherwise healthy people/animals. Rather, life stage (neonate or old age) and natural stressors have taken over as the primary cause for immune deficiency. Unlike malnutrition, immune deficiency due to life stage or natural stress cannot be addressed by correcting underlying nutritional problems. Lowered immune status because of life stage or naturally occurring stress is characterized by reduced capacity to process and present foreign antigens to immune cells, resulting in a less efficient or altered immune response that leads to increased susceptibility to infections and an increase in autoimmunity and cancers. Beyond providing essential nutrients, diet can actively influence the immune system. Over 65% of the immune cells in the body are present in the gut, making the gut the "largest immune organ." Receptors present on the immune cells in the gut are the primary targets for immunomodulation via diet. Diet interacts with the immune system at multiple levels, starting with providing basic nutrients, then moving on to providing higher levels of key nutrients such as protein, vitamins, and minerals, and leading to a more focused modulation of the immune system. A framework outlining this interaction, along with relevant examples, will be discussed.


Cutaneous sarcoidosis in Caucasians.
One hundred eighty-eight Caucasian patients with cutaneous sarcoid lesions were studied prospectively. Twenty-five had erythema nodosum, while 163 had infiltrative cutaneous lesions. One hundred thirty-eight patients had systemic as well as cutaneous lesions, and fifty had cutaneous lesions only. All types of clinical lesions were seen among patients with cutaneous lesions only. The extent of cutaneous lesions did not correlate with the extent of systemic disease. Papular lesions were relatively uncommon and occurred as the only manifestation of the disease or were associated with hilar adenopathy and acute disease. Lupus pernio, scar infiltrates, and plaque lesions were the most common clinical lesions and were typically chronic and commonly associated with pulmonary mottling and/or fibrosis. Forty-eight of 127 had a histologically positive Kveim test. Among patients followed for more than 2 years, dinitrochlorobenzene (DNCB) sensitivity was higher among those with acute disease than among those with chronic disease. Seventy-nine patients with infiltrative cutaneous lesions were followed until the cutaneous lesions had healed. Those with lupus pernio were often left with unsightly telangiectatic scars, while the other types of lesions left either pale, slightly depressed scars or no scars at all.


Magnetic resonance imaging for abnormally invasive placenta: the added value of intravenous gadolinium injection.
To assess the added value of intravenous gadolinium injection to magnetic resonance imaging (MRI) -based diagnosis of abnormally invasive placenta (AIP) and to examine this in relation to the radiologist's experience. Retrospective study. Between March 2009 and October 2012, 31 pregnant women who had previous caesarean delivery together with a placenta praevia and suspected placenta accreta on ultrasound in the third trimester of pregnancy. All were offered MRI examination, and made aware of the limited (but so far reassuring) data regarding fetal safety of gadolinium. Twenty pregnant women agreed to undergo prenatal MRI (1.5 T), with and without gadolinium injection. Two sets of MRI examinations without and with gadolinium were reviewed independently 2 months apart by two senior and two junior radiologists; all were blinded to the outcome (known in all cases). Histopathological findings and clinical signs of AIP were considered as the defining criteria of diagnosis. accuracy of MRI with and without gadolinium was assessed. Eight of the 20 women had confirmed abnormal placental invasion. The overall performance of both sets of readers in detecting AIP increased with gadolinium-sensitivity and specificity of 75.0% (42.0-100%) and 47.9% (19.9-75.9%) increasing to 87.5% (57.1-100%) and 60.4% (33.9-86.9%), respectively (P = 0.04). The added value of gadolinium remained irrespective of radiologist's experience, although senior radiologists performed better overall (sensitivity and specificity of 87.5% and 62.5% versus 62.5% and 33.3%, respectively, increasing with injection to 93.8% and 70.8% versus 81.3% and 50%, respectively; P < 10-4 ). There was an association between gadolinium use and improvement in MRI-based diagnostic accuracy for the diagnosis of AIP, for both junior and senior radiologists. Gadolinium injection improves MRI performance of radiologists for the diagnosis of placenta accreta.


Surface proteins and antigens of adult Schistosoma mansoni tegumental membranes detached onto poly-lysine coated beads.
Poly-lysine coated beads attached readily onto Schistosoma mansoni. On detachment, the beads removed membranes from the surface of the tegument. Analysis of the proteins of the detached membranes showed that three major proteins of 94, 73 and 62 kDa were present in contrast to a more complex range of proteins present in the phosphate-buffered saline released membranes. The membranes attached to beads were radio-iodinated and the antigens examined in immunoprecipitates by sodium dodecyl sulphate-polyacrylamide gel electrophoresis using various antisera. In addition to the well-established 32 and 20 kDa antigens of the tegument, other major antigens of 200, 25 and 11-12 kDa were iodinated in the membranes attached to the beads. The results suggest that the major antigens studied in the tegument may not correspond to the major proteins identified. The present approach shows promise for deducing the topography of the surface antigens and proteins of schistosomes.


Compliance and findings in a Swedish population screened for colorectal cancer with sigmoidoscopy.
The aim of this study was to evaluate the patterns of compliance and the frequency of adenomas and neoplasms in a Swedish population. In 1996, 2000 men and women born in 1935 or 1936 were selected at random from the population registers of Uppsala and Malmö/Lund. All subjects were invited by mail to participate. In a randomised study design, subjects were either called up by a nurse to schedule the appointment for sigmoidoscopy or instructed to call themselves. At sigmoidoscopy subjects with a cancer, an adenoma (neoplastic polyp) or more than three hyperplastic polyps were scheduled for a complete colonoscopy. Thirty-nine percent (770/1988) of all the invited subjects had a sigmoidoscopy. The participation differed between the two centres, 47% at the Uppsala centre and 30% at the Malmö/Lund centre (P<0.01). There was no statistically significant difference between the two different invitation groups. In all, 98 subjects (13%) were planned for colonoscopy. Thirty-one (35%) of the subjects having a colonoscopy were women and 57 (65%) were men. Fifty-five true adenomas were found in 46 subjects. All together, six subjects had proximal adenomas. Five adenocarcinomas were diagnosed, all within the reach of the sigmoidoscope. The compliance was lower and the adenomas were fewer than expected. To increase compliance it is necessary with rigorously controlled invitation routines.


Enzymatic purification and structure characterization of glucuronoxylan from water extract of Cassia obtusifolia seeds.
Enzymatic hydrolysis was proposed for the first time to purify the sub-fraction of water-extracted cassia polysaccharide (CP-40), and a homogeneous polysaccharide CP-40-M was obtained with relatively high yield. The structural features of CP-40-M were characterized using size-exclusion chromatography equipped with multiple detectors (SEC-MALLS), high-performance anion-exchange chromatography (HPAEC), methylation and gas chromatography-mass (GC-MS), as well as nuclear magnetic resonance (NMR) spectra. The weight-average molecular weight for CP-40-M was determined to be 0.29×105Da, and the molar ratio of xylose to glucuronic acid was 4.62. The structure of CP-40-M was elucidated to be glucuronoxylan, with glucopyranosyluronic acid group terminally attached to O-2 of the →4)-β-Xylp-(1→ backbone. It was the first time to obtain this type of xylan from the water extract of Cassia obtusifolia seeds. The structure elucidation of CP-40-M was meaningful for better understanding the natural characteristics of cassia polysaccharide and important for their potential use in food industry and folk medicine.


Effect of sinus rhythm restoration after electrical cardioversion on apelin and brain natriuretic Peptide prohormone levels in patients with persistent atrial fibrillation.
Because humoral alterations have been implicated in the generation and perpetuation of atrial fibrillation (AF), we aimed to elucidate possible abnormalities in atrial endocrine function in the setting of lone AF. Levels of plasma apelin and amino terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) were measured in 40 patients with persistent AF, before and 1 month after electrical cardioversion, and in 15 controls in sinus rhythm (SR). All patients were successfully cardioverted to SR, although in 9 of them AF recurred. Baseline apelin levels were lower and NT-pro-BNP levels higher in patients with AF compared to controls (380 +/- 186 vs 700 +/- 151 pg/ml, p <0.001, and 615 +/- 611 vs 50 +/- 28 pg/ml, p <0.001, respectively). Maintenance of SR resulted in an increase of apelin and a decrease of NT-pro-BNP levels during the postcardioversion follow-up period compared to baseline (497 +/- 170 vs 368 +/- 178 pg/ml, p <0.001, and 206 +/- 106 vs 398 +/- 269 pg/ml, p <0.001 respectively). Patients who developed AF recurrence by the end of the follow-up period had similar values of apelin and NT-pro-BNP on final and initial evaluations (444 +/- 142 vs 422 +/- 217 pg/ml, p = 0.62, and 1,328 +/- 714 vs 1,362 +/- 862 pg/ml, p = 0.74, respectively). Stepwise logistic regression analysis showed that left atrial diameter (b =-0.49, p = 0.05), and baseline NT-pro-BNP (b = 0.006, p = 0.022), but not apelin, were independent predictors for AF recurrence. In conclusion, this study suggests that endocrine heart function, as judged from apelin and NT-pro-BNP levels, is reversibly modified in the setting of lone AF. This could influence systemic hemodynamics and pharmacologic measures designed to treat this arrhythmia.


Influence of carbohydrate and supplemental fat source on the metabolizable energy of the diet.
An experiment involving 60 Single Comb White Leghorn laying hens was conducted to measure the influence of the carbohydrate source and supplemental fat on nitrogen-corrected metabolizable energy(MEn) of the diet. Twelve diets with the same calculated metabolizable energy (ME) and protein levels were arranged in a 2 X 6 factorial composed of two different yellow grease to soy oil ratios (6%:0% and 4%:2% of the diet) and 6 corn starch to sucrose ratios (from 49%:0% to 0%:49%). The diets were assayed for MEn content by using the total feces collection method. There was a positive linear relationship between sucrose level and MEn of the diet. When sucrose replaced corn starch, the MEn of the diets increased more than expectd, and these increments were statistically significant (P < .01). The diets containing a mixture of yellow grease and soy oil had significantly higher MEn values than those in which supplemental fat was supplied exclusively as yellow grease (P < .05). A comparison of the "calculated" regression equation describing the expected dietary ME with changing sucrose and soy oil levels, Y = 3110 + 1.03 (% sucrose) + 9 (% soy oil), and the regression equation determined experimentally, Y = 3177 + 3.25 (% sucrose) + 18 (% soy oil), illustrates the relatively large increases in dietary ME caused by sucrose and soy oil. These effects of sucrose and soy oil were independent. These data support the concept that the addition of a relatively unsaturated fat (soy oil) to a saturated fat (yellow grease) enhances dietary MEn. Also, the data indicate that the presence of supplemental fat in the diet increases the utilization of energy from sucrose. Thus, the "extra-caloric" effect of fats on MEn may be the culmination of a favorable interaction between supplemental fats and fats inherent in other diet components, and a beneficial influence of supplemental fats on energy utilization from certain nonlipid dietary constituents.


Use of combination therapy in asthma: are they prescribed according to guidelines.
Combination therapy should be prescribed to patients with moderate to severe asthma after daily long-term treatment with inhaled inhaled corticosteroids (ICS) has been tried without obtaining adequate control and it is not indicated to be used as first line treatment in asthma. To describe the use of combination therapy for the treatment of asthma and to evaluate to which extent it is prescribed as recommended. A cohort of 14559 new users of a combination therapy identified between January 1, 2000 and September 30, 2003 was selected from beneficiaries of the Régie de l'assurance maladie du Québec. We evaluated whether the combination therapy was prescribed according to the Canadian Asthma Guidelines. A logistic regression analysis was also performed to identify patient's and physician's characteristics associated with the adherence to the recommendations of the Canadian Asthma Guidelines for the prescription of a combination therapy. Only 40% of users of combination therapy filled a prescription of ICS in the year preceding the initiation of the therapy and this proportion decreased by 21.8% from 2000 to 2003. Patients who received their first combination therapy in an emergency department were less likely to have used ICS previously, but patients treated by a respiratory physician and patients with co-morbidities, markers of asthma severity and markers of uncontrolled asthma were more likely to have used ICS previously. Combination therapy has not been used according to the Canadian Asthma Guidelines in a large proportion of patients.


Biallelic somatic inactivation of the NF1 gene through chromosomal translocations in a sporadic neurofibroma.
Neurofibroma is a benign tumor originating from Schwann cells in peripheral nerve sheaths and may occur as a sporadic tumor or as part of the dominantly inherited tumor syndrome NF1. NF1 is caused by constitutional mutations in the NF1 gene, located in chromosome band 17q11. Whereas the involvement of the NF1 gene in neurofibroma development in NF1 patients has been fairly well characterized, the significance of inactivation of this gene in sporadic neurofibromas remains less well investigated. Inactivation of both copies of NF1 has been described in a few neurofibromas from NF1 patients, and LOH at the same locus has been reported in additional cases. In the present study, we report the cytogenetic and molecular cytogenetic findings in a sporadic neurofibroma that at G-banding analysis showed a translocation between one chromosome 2 and the long arms of both copies of chromosome 17. FISH analysis using a set of 3 BAC clones covering the entire coding region of NF1 revealed the complete loss of one allele and the deletion of the 5' portion of the second allele as a result of 2 translocation events. To the best of our knowledge, this represents the first demonstration of a somatic biallelic inactivation of the NF1 gene in neurofibroma, providing further evidence for the importance of NF1 inactivation also in sporadic neurofibromas.


Analgesic and anti-inflammatory activities of the aqueous stem and leaf extract of Asystasia gangetica (Linn) T. Anderson.
Asystasia gangetica (Linn) T. Anderson [family Acanthaceae] is used commonly in the sub-tropics and tropics for the management of inflammatory and algesic conditions. The study was done to evaluate the analgesic and inflammatory activity of the aqueous stem and leaf extract of Asystasia gangetica. The analgesic effect of the aqueous stem and leaf extract of Asystasia gangetica (25, 50, 100 and 200 mg/kg) was evaluated in rats and mice using the acetic acid induced writhing, cold water tail flick and hot plate models. Its anti-inflammatory effect was evaluated using carrageenan induced rat paw oedema and xylene induced mouse ear oedema models. The aqueous stem and leaf extract of Asystasia gangetica (25-200 mg/kg) significantly (p < 0.05) reduced the number of writhes in the acetic acid induced writhing test. At 100 mg/kg, it produced an increase in pain threshold comparable to that produced by morphine (10 mg/kg) in the tail flick test and peak analgesia at 200 mg/kg in the hot plate test. The extract (25-200 mg/kg) also produced significant (p < 0.05) inhibition of oedema comparable to indomethacin (10 mg/kg) in the carrageenan induced paw oedema model. The extract (200 mg/kg) produced a significant inhibitory effect (p < 0.05) comparable to that produced by 1 mg/kg dexamethasone in the xylene induced mouse ear oedema model. Preliminary phytochemical screening showed that the extract contains alkaloids, tannins, cardiac glycosides and flavonoids. It did not produce mortality or any visible sign of lethality 24 hours after single oral administration of 10 g/kg. The results show that the aqueous stem and feaf extract of Asystasia gangetica possesses analgesic and antiinflammatory activities.


Nocturnal rotational behavior in rats: further neurochemical support for a two-population model.
The relationship between circling behavior and the concentrations of dopamine (DA), serotonin, and their metabolites in corpus striatum was investigated in rats. We have previously reported evidence indicating that in both sexes there are two kinds, or populations, of rats: those with their turning biases directed away from (Contra greater than Ipsi rats), and those with their turning biases directed towards (Ipsi greater than Contra rats), the side containing the striatum with the greater dopaminergic innervation. In the present experiment rats were classified according to whether the contralateral or ipsilateral striatum contained the greater dopamine concentration. Whereas the ipsilateral striata were found to contain the same concentrations of dopamine, the contralateral sides were found to differ significantly; and the difference between the contralateral and ipsilateral dopamine concentrations was significantly correlated with the contralateral, but not the ipsilateral, dopamine concentration. These results are identical to those we previously reported using the Vmax for dopamine uptake in vitro as the measure for striatal dopaminergic innervation. As an initial attempt to determine what neurochemical mechanisms might underlie the differences between the "Contra greater than Ipsi" and "Ipsi greater than Contra" rats, it was found that dopamine turnover, as measured by the ratios of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid to DA, was higher in the striata of the latter group than in the former group. The present results are discussed in terms of their support for the two-population model, and in relation to previous work on behavioral and neurochemical asymmetry in rats.


[Transcutaneous electric muscle stimulation--a "new" possibility for the prevention of thrombosis?].
Adhesive electrodes for transcutaneous electrical stimulation of the calf were applied on the skin of 11 patients with ruptures of the fibular ligaments (treated surgically or conservatively with cast) during the period of immobilisation (four weeks). Muscle stimulations were performed several times a day over a period of at least 15 minutes with a small rechargable muscle stimulation apparatus. Duplex sonography revealed that a significant rise of the venous flow velocity could be achieved with an 8.5-fold increase of the venous flow velocity as measured over the popliteal vein. Transcutaneous muscle stimulation might move to be a "new" efficient method for the prophylaxis of deep vein thrombosis.


Pathology of Listeria infection in murine severe combined immunodeficiency. A study by immunohistochemistry and electron microscopy.
Mice bearing the scid mutation lack functional T and B lymphocytes and partially resist infection with the intracellular pathogen Listeria monocytogenes. In this study, we describe the histopathologic features of the infection in scid mice. Infected scid showed hyperplasia of mononuclear cells in lymphoid organs without any evidence of granulomas nor of lymphoid cell development. Mononuclear phagocytes in various tissues of infected scid mice had markedly enhanced expression of class II histocompatibility molecules (or Ia molecules). Furthermore, Ia expression was also found in endothelial and epithelial cells of many organs in the later stages of infection. These results confirm that scid mice have a mechanism for activation of Ia antigen expression, which is independent of lymphocyte function.


Protective effects of panaxadiol saponins on cardiac functions in burned rats.
To study the effects of panaxadiol saponins (PDS) on burn rat heart functions and try to find its mechanisms. A 35% skin-full-thickness burn was produced by using napalm in Wistar rats. PDS 30 mg kg-1 was injected i.p. to rats immediately after burn and repeated 2 h before examination. Using the isolated perfused working heart and biochemistry methods, heart rate (HR), cardiac output (CO), coronary flow (CF), left ventricular pressure (LVP), aortic pressure (AP), +/- dp/dtmax, and content of malondialdehyde (MDA), activity of superoxide dismutase (SOD) in ventricular myocardium homogenate were examined 8 h after burn. After burn, HR, CO, CF, LVP, AP, +dp/dtmax, -dp/dtmax, and SOD activity decreased from 206 bpm, 92 mL min-1 g-1, 26 mL min-1 g-1, 7 kPa, 5.9 kPa, 149 kPa s-1, 73 kPa s-1, 2.9 NU/mg protein to 162 bpm, 72 mL min-1 g-1, 14 mL min-1 g-1, 4 kPa, 2.2 kPa, 77 kPa s-1, 44 kPa s-1, 1.7 NU/mg protein, respectively, and MDA content raised from 0.77 nmol/mg protein to 1.35 nmol/mg protein (P all < 0.05). But in PDS-treated group, above decreased or increased dates restored to 202 bpm, 91 mL min-1 g-1, 25 mL min-1 g-1, 6 kPa, 4.1 kPa, 112 kPa s-1, 62 kPa s-1, 2.8 NU/mg protein, 0.91 nmol/mg protein, respectively (P all < 0.05 vs burn). PDS exerts definite protective effects on the cardiac functions after burn injury possibly through its enhancement of SOD activity and the reduction of both the levels of free radicals and lipid peroxides (LPO) of the myocardium.


Intrapulmonary cystic lymphangioma: report of a case.
We describe herein the case of a 52-year-old man found to have a solitary pulmonary lymphangioma. Computed tomography (CT) scan demonstrated a nodule with homogeneous density and a well-defined border in the lower lobe of the right lung. T2-Weighted magnetic resonance imaging (MRI) revealed a nodule with homogeneously high signal intensity. The tumor was removed by partial resection, and pathologic examination confirmed a diagnosis of primary lymphangioma of the lung.


Rectovaginal fistula.
Despite the prevalence and severe implications of rectovaginal fistula, there is no universally accepted evidence-based approach to surgical management. This article offers a disease-based review of traditional management strategies and highlights the variety of technical approaches that are currently effective for the eradication of this socially disabling condition.


[The role of myelin oligodendrocyte glycoprotein antibodies for detection of demyelinating optic neuritis].
The incidence of neuromyelitis optica spectrum disorders (NMOSD) in the Asian population is much higher than in Europe and North America. Optic neuritis is the first sign of NMOSD for some people. Identification of aquaporin 4 antibody is a milestone in the research of NMOSD and has been included in the diagnosis standard of NMOSD, but about 20% to 30% of NMOSD patients is aquaporin 4 antibody-negative. With the cell-based assays, oligodendrocyte glycoprotein antibodies in demyelinating diseases of the central nervous system have aroused the attention of researchers. This article reviews the research history of oligodendrocyte glycoprotein antibodies in optic neuritis. (Chin J Ophthalmol, 2017, 53: 874-877).


Factors affecting rapid growth of unruptured cerebral aneurysms during the acute stage of subarachnoid hemorrhage.
Several unruptured cerebral aneurysms have been reported to grow and rupture. To determine which factors affect the growth of these aneurysms during the acute stage of subarachnoid hemorrhage (SAH), a retrospective review was performed. Between January 2000 and January 2003, 130 patients with angiographically proven ruptured cerebral aneurysms were treated at our institution. Of these patients, 32 also had simultaneous unruptured aneurysms, and the total number of the unruptured aneurysms was 40, including two neck remnants which had remained since the past clipping. Seventeen patients had 17 unruptured aneurysms and two neck remnants. The unruptured aneurysms were not treated during the acute stage of SAH but had received a complete short term follow-up. The rapid growth of one unruptured aneurysm and two neck remnants was confirmed by a second angiogram performed on average 40 days after the first angiogram. Several candidate factors responsible for the growth of aneurysm were selected, and the results of a statistical analysis indicate that a systolic blood pressure above 200 mmHg during the acute stage of SAH and vasospasm, confirmed by transcranial Doppler ultrasound (TCD) or neurological examination, and neck remnants, are risk factors that affect the growth. Short term follow-up angiography is thus important for patients with untreated unruptured cerebral aneurysms after the acute stage of SAH.


High volume local anesthesia as a postoperative factor of pain and swelling in dental implants.
To determine whether the administration of high-volume local anesthesia can influence postoperative pain and swelling, and the degree of patient satisfaction, following dental implant placement. One hundred patients (45 women and 55 men) between 19 and 80 years old were divided into two groups: group A (n = 50, with placement of an implant using an atraumatic approach in each patient, with sub-periosteal injection of a volume of Ultracain(®) ≤0.9 mL [half a carpule]) and group B (n = 50, involving the same surgical procedure but infiltrating a local anesthetic volume of ≥7.2 mL [four carpules]). Visual analog scales were used in all patients to rate intraoperative pain and postoperative pain and swelling. After the first week, the patients completed a questionnaire evaluating satisfaction with treatment. The intraoperative pain scores were similar in both groups (p = 0.363), while the postoperative pain and swelling scores were significantly lower in group A at all time points. Patient rated satisfaction with the surgical treatment was higher in group A. Excess injected volume of local anesthetic in dental implant surgery has a negative impact upon both postoperative pain and swelling, and on patient rated satisfaction.


Ethanol production from steam-explosion pretreated wheat straw.
Bioconversion of cereal straw to bioethanol is becoming an attractive alternative to conventional fuel ethanol production from grains. In this work, the best operational conditions for steam-explosion pretreatment of wheat straw for ethanol production by a simultaneous saccharification and fermentation process were studied, using diluted acid [H2SO4 0.9% (w/w)] and water as preimpregnation agents. Acid- or water-impregnated biomass was steam-exploded at different temperatures (160-200 degrees C) and residence times (5, 10, and 20 min). Composition of solid and filtrate obtained after pretreatment, enzymatic digestibility and ethanol production of pretreated wheat straw at different experimental conditions was analyzed. The best pretreatment conditions to obtain high conversion yield to ethanol (approx 80% of theoretical) of cellulose-rich residue after steam-explosion were 190 degrees C and 10 min or 200 degrees C and 5 min, in acid-impregnated straw. However, 180 degrees C for 10 min in acid-impregnated biomass provided the highest ethanol yield referred to raw material (140 L/t wheat straw), and sugars recovery yield in the filtrate (300 g/kg wheat straw).


Dynamics of field-induced ordering in magnetic colloids studied by new time-resolved small-angle neutron-scattering techniques.
The reversal of magnetic moments of nanoparticles in concentrated Co ferrofluids was monitored in an oscillating magnetic field by new time-resolved stroboscopic small-angle neutron-scattering techniques. Time resolution in the micros range was achieved by using a pulsed beam technique, TISANE, while in continuous mode resolution was limited by the wavelength spread to about 1 ms. The frequency dependence of anisotropic scattering patterns has been modeled using Langevin dynamics. The dynamics follows a two step mechanism: field-induced ordering is governed by fast Brownian rotation of nanoparticles with a characteristic time of about 160 micros. Magnetic relaxation of locally ordered domains of about 100 nm in size takes place within a few seconds by Brownian rotation or by Néel type rotation of magnetic moments.


Consent for the Pelvic Examination Under Anesthesia by Medical Students: Recommendations by the Association of Professors of Gynecology and Obstetrics.
The pelvic examination is a critical tool for the diagnosis of women's health conditions and remains an important skill necessary for students to master before becoming physicians. Recently, concerns regarding student involvement in pelvic examinations-specifically those performed while a woman is under anesthesia-have been raised in the scientific, professional, and lay literature. These concerns have led to calls to limit or halt the performance of pelvic examinations by students while a woman is under anesthesia. Although ensuring adequate informed consent for teaching pelvic examinations is a priority, we must not lose sight of the critical pedagogical value of teaching pelvic examination in familiarizing students with the female anatomy and instilling a physician workforce with confidence in pelvic examination skills. A compromise that addresses all of these values is possible. In this commentary, we review the educational and legal aspects of the pelvic examination under anesthesia, then provide strategies that individuals and institutions can consider to optimize processes regarding consent for pelvic examination under anesthesia.


Nicotine gum treatment before smoking cessation: a randomized trial.
New ways of improving the efficacy of nicotine therapy need to be explored. We tested whether starting nicotine polacrilex gum treatment 4 weeks before the quit date improved smoking abstinence rates compared with starting treatment on the quit date. An open randomized trial of 314 daily smokers (mean, 23.7 cigarettes/d) enrolled through the Internet and by physicians in Switzerland from November 2005 to January 2007. In the precessation treatment group, participants received nicotine polacrilex gum (4 mg, unflavored) by mail for 4 weeks before and 8 weeks after their target quit date, and they were instructed to decrease their cigarette consumption by half before quitting. In the usual care group, participants received the same nicotine gum for 8 weeks after their quit date and were instructed to quit abruptly. Instructions were limited to a booklet sent by mail and access to a smoking cessation Web site. Results are expressed as self-reported abstinence rates at the end of treatment and as biochemically verified smoking abstinence (cotinine plus carbon monoxide) after 12 months. Eight weeks after the target quit date, self-reported 4-week abstinence rates were 41.6% in the precessation treatment group and 44.4% in the usual care group (P = .61). One year after the target quit date, biochemically verified 4-week smoking abstinence rates were 20.8% in the precessation treatment group and 19.4% in the usual care group (P = .76). Starting nicotine gum treatment 4 weeks before the target quit date was no more effective than starting treatment on the quit date.


[Escherichia coli mastitis in cattle. III. Antibacterial therapy].
This review paper is concerned with antibacterial therapy of mastitis caused by Escherichia coli. The choice of an antibacterial agent is discussed, and nine criteria are referred to, on which this choice should be based. In the second part possible forms of antibacterial treatment are discussed. Literature on parenteral and local treatment of mastitis due to E. coli is scarcely available. The evaluation of antibacterial drugs is mainly based on MIC values and pharmacokinetic studies in normal animals. Unfortunately, results of clinical trials are hardly available. Today combinations of trimethoprim/sulphonamide apparently are the best available choice for the parenteral treatment of mastitis caused by E. coli. Infusion of polymyxins or gentamycin is discussed as a method of intramammary therapy.


Effects of coinfection with HIV and hepatitis C virus on the nervous system.
We evaluated a cohort of persons with late-stage HIV infection currently enrolled in a longitudinal tracking study to determine whether coinfection with hepatitis C virus (HCV) is associated with a greater prevalence and/or severity of HIV-associated cognitive-motor complex and distal predominantly sensory peripheral polyneuropathy compared with persons with HIV infection alone. Of 159 subjects, 31 tested positive for HCV, and this group was compared with 31 randomly selected subjects with HIV infection alone. All subjects underwent a structured neurological examination and a formal neuropsychological testing battery. Blood and cerebrospinal fluid samples were analyzed for cryoglobulins and glutamine levels, respectively. HIV/HCV-coinfected subjects showed a greater, statistically significant cognitive-motor impairment compared with those not coinfected. Despite the well-recognized neurological manifestations of both HIV infections and more recently hepatitis C, it is still uncertain whether the effects of HIV and HCV augment one another or are partially additive in their deleterious effects on the nervous system.


Sedatives, tranquilizers, and stimulants.
Drugs of relevance to equine practice that modify the central nervous system (CNS) can be broadly classified as depressants or stimulants. The pharmacologic mechanisms of action, uses, and side effects of selected CNS depressant and stimulant drugs in horses are reviewed. Knowledge of the way these CNS-modifying drugs may affect performance is limited.


Excessive light sensitivity in Papio papio: its variation with age, sex, and geographic origin.
Excessive sensitivity (levels 3 and 4) in a population of 1,122 Papio papio was related with age, sex, and geographical origin. (1) Age. There was no clinical response to intermittent light stimulation under the age of 5 months. These was no difference between animals 6 months to 2 years (J1) and those aged 2 to 4 years (J2). Adult females were less often light sensitive (levels 3 and 4 = 32.9%) than immature females (52.4%). Adult males could usually not be tested, but were probably less often sensitive than immature males. (2) Sex. Immature females (J1 + J2) were more often light sensitive (52.4%) than immature males (38.1%). (3) Geographical origin. No animals from East Senegal (Sansande Region) were very light sensitive. Animals from Casamance were more often light sensitive (56.2%) than those from the Niokolo-Koba National Park (N.K.N.P.) (20%). Of two samples taken at one spot between these two regions, one group resembled the population from Casamance and the second resembled that from the N.K.N.P. This observation raises several questions about the respective roles of genetic, ecological, and ethological factors.


Role of endoluminal techniques in treatment of gastro-esophageal reflux disease.
This chapter addresses emergent endoluminal technologies available currently for treatment of gastroesophageal reflux disease (GERD). To date, the mainstay of GERD therapy has been achieved with either open or laparoscopic fundoplication, or life-long medical treatment. Endoluminal treatment modalities attempt to augment the gastroesophageal junction (GEJ) function by various techniques. We searched the PubMed database from 1980 to 2005 for studies on endoscopic GERD techniques. Product investigators were contacted for data presented mainly in Abstract form. Endoluminal management of GERD includes using radiofrequency energy, injection of biocompatible polymers, and endoluminal sutures to alter the GEJ and reduce reflux. With currently earned and further growing experience, endoscopic treatment of GERD has future promise; however, more experience and perhaps further refinement in techniques and technology must occur before widespread clinical application can be encouraged.


Safety of probiotics: translocation and infection.
The long history of safety has contributed to the acceptance of probiotics as a safe food adjunct. Consequently, many probiotic products and their applications have been granted GRAS (generally regarded as safe) status. However, this classification has been frequently generalized for all probiotic strains regardless of their application. Cases of probiotics from the genera Lactobacillus, Leuconostoc, Pediococcus, Enterococcus, and Bifidobacterium have been isolated from infection sites, leading to the postulation that these probiotics can translocate. Probiotic translocation is difficult to induce in healthy humans, and even if it does occur, detrimental effects are rare. Despite this, various reports have documented health-damaging effects of probiotic translocation in immunocompromised patients. Due to probiotics' high degree of safety and their morphological confusion with other pathogenic bacteria, they are often overlooked as contaminants and are least suspected as pathogens. However, the antibiotic resistance of some strains has increased the complexity of their eradication. Probiotic translocation and infection deserve further investigation and should become a facet of safety assessment so the negative effects of probiotics do not outweigh the benefits.


A sex-related difference in the hypertrophic versus hyperplastic response of vascular smooth muscle cells to repeated passaging in culture.
Activation of growth of vascular smooth muscle cells (VSMC) in adults participates in pathogenesis of dysplastic diseases of the vascular system. In this study, we examined the impact of gender of rat donors on the degree of hyperplastic and hypertrophic responses of VSMC in cultures subjected to repeated passaging. The cells were derived from the outgrowth zone of explants of the thoracic aorta and were studied up to passage 45. Under these conditions, the cells undergo repeated growth stimulation by the serum growth factors mimicking some pathological situations in vivo. At lower passages (5-7), the cells from both sex donors did not differ significantly in their doubling time, maximum population density, protein content and ploidy. At higher passages (40-45), we found that the hyperplastic response, monitored by doubling time and BrdU-revealed DNA synthesis, was more intense in VSMC of male origin. In contrast, female-derived cells reacted by more prominent hypertrophic changes. The latter included a relatively higher increase in the volume and protein content of cells. As indicated by the DNA content histograms and chromosome numbers, these cells also showed a higher degree of passage-dependent polyploidization. In addition, the female-derived VSMC were found to be more effective in adhesion to the growth support evidenced by wider spreading and higher resistance of these cells to trypsin-mediated detachment as well as higher expression of some integrin and cytoskeletal molecules. These features could partly account for the slower proliferation and polyploidization of these cells. The results suggest that rat VSMC populations of male and female origin contain cells which are intrinsically different with respect to their capability of reacting to growth stimuli. The lower responsiveness of female-derived cells to growth stimuli may contribute to less frequent formation of hyperplastic vascular lesions in female organisms.


[Typifying rumors in university students' everyday conversation].
The purpose of this study was to typify rumor talk in university students' everyday conversation. This study investigated the structure of rumor in conversation from the viewpoint of content attributes and functions. Study 1 found two types of rumor talk, "humor type" and "anxiety type", based on seven content attributes (humor, anxiety, certainty, importance, reliability, sharing of topic, and easiness of interpretation) and four functions (entertainment, spicing up, avoiding silence, and information supplement). "Humor type" was high humor and low certainty, and had an entertainment function. "Anxiety type" was low humor and high anxiety, and had an information supplement function. Study 2, which typified rumor talk based on three content attributes (humor, anxiety, and certainty), found a "daily type" and a "sensation-seeking type" in addition to the two types of study 1. "Daily type" was high certainty, and had an information supplement function. "Sensation-seeking type" was high humor, high anxiety, and low certainty.


Effect of External Magnetic Fields on Biological Effectiveness of Proton Beams.
The purpose is to verify experimentally whether application of magnetic fields longitudinal and perpendicular to a proton beam alters the biological effectiveness of the radiation. Proton beams with linear energy transfer of 1.1 and 3.3 keV/μm irradiated human cancer and normal cells under a longitudinal (perpendicular) magnetic field of BL (BP) = 0, 0.3, or 0.6 T. Cell survival curves were constructed to evaluate the effects of the magnetic fields on the biological effectiveness. The ratio of dose that would result in a survival fraction of 10% without the magnetic field Dwo to the dose with the magnetic field Dw, R10 = Dwo/Dw, was determined for each cell line and magnetic field. For cancer cells exposed to the 1.1- (3.3-) keV/μm proton beams, R10s were increased to 1.10 ± 0.07 (1.11 ± 0.07) and 1.11 ± 0.07 (1.12 ± 0.07) by the longitudinal magnetic fields of BL = 0.3 and 0.6 T, respectively. For normal cells, R10s were increased to 1.13 ± 0.06 (1.17 ± 0.06) and 1.17 ± 0.06 (1.30 ± 0.06) by the BLs. In contrast, R10s were not changed significantly from 1 by the perpendicular magnetic fields of BP = 0.3 and 0.6 T for both cancer and normal cells exposed to 1.1- and 3.3-keV/μm proton beams. The biological effectiveness of proton beams was significantly enhanced by longitudinal magnetic fields of BL = 0.3 and 0.6 T, whereas the biological effectiveness was not altered by perpendicular magnetic fields of the same strengths. This enhancement effect should be taken into account in magnetic resonance imaging guided proton therapy with a longitudinal magnetic field.


Effect of delta-THC on ethanol withdrawal in mice.
Delta-THC (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when delta-THC was administered chronically during the exposure to ethanol.


17α-Ethinylestradiol (EE2) treatment of wild roach (Rutilus rutilus) during early life development disrupts expression of genes directly involved in the feedback cycle of estrogen.
Fish are more sensitive to introduced disturbances from synthetic endocrine disrupting compounds during early life phases compared with mature stages. 17α-Ethinylestradiol (EE2), which is the active compound in human oral contraceptives and hormone replacement therapies, is today ever present in the effluents from sewage treatment plants. EE2 targets and interacts with the endogenous biological systems of exposed vertebrates resulting in to large extents unknown short- and long-term effects. We investigated how EE2 exposure affects expression profiles of a large number of target genes during early life of roach (Rutilus rutilus). We exposed fertilized roach eggs collected from a lake in Southern Sweden to EE2 for 12weeks together with 1+-year-old roach in aquaria. We measured the gene expression of the estrogen receptor (esr)1/2a/2b, androgen receptor (ar), vitellogenin, cytochrome P450 (cyp)19a1a/1b in fertilized eggs; newly hatched larvae; 12-week-old fry; and juvenile wild roach (1+-year-old). Results shows that an EE2 concentration as low as 0.5ng/L significantly affects gene expression during early development. Gene expression responses vary both among life stages and molecular receptors. We also show that the gene profile of the estrogen feedback cycle to a large extent depends on the relationship between the three esr genes and the two cyp19a1 genes, which are all up-regulated with age. Results indicate that a disruption of the natural activity of the dominant esr gene could lead to detrimental biological effects if EE2 exposure occurs during development, even if this exposure occurred for only a short period.


[Direct human DNA damage by unfavorable environmental and climatic factors].
To study the impact of simulated climatic conditions of the 2010 summer in Moscow on the telomere repeats of chromosomes in human blood cells. The climatic conditions of July-August 2010 in Moscow were simulated at the Medical Technical Complex, Institute of Biomedical Problems, Russian Academy of Sciences. The relative length of the telomeric repeats of blood cell chromosomes from 6 apparently healthy volunteers was measured by quantitative real-time polymerase chain reaction. These conditions were ascertained to lead to a statistically significant decline in the length of telomere repeats in the terminal portions of chromosomes by 15%. Environmental changes and abnormal temperature rises may result in oxidative stress accompanied by telomere shortening, which can be, in turn, a factor of premature aging.


Remission of essential hypertension after renal transplantation.
Six patients in whom "essential hypertension" led to nephrosclerosis and kidney failure received kidney transplants from normotensive donors. After an average follow-up of 4.5 years, all were normotensive and had evidence of reversal of hypertensive damage to the heart and retinal vessels. These six patients, all of whom were black, and six control subjects matched for age, sex, and race were admitted to the General Clinical Research Center for 11 days for observation of their blood pressure and their responses to salt deprivation and salt loading. Mean arterial pressure (+/- S.E.M.) among the patients who had previously had essential hypertension was similar to that of the normal controls (92 +/- 1.9 vs. 94 +/- 3.9; P not significant), and both groups had similar responses to salt deprivation and salt loading. Thus, essential hypertension in human beings is shown to be similar to the hypertension seen in spontaneously hypertensive rats in that both can be corrected by transplantation of a kidney from a normotensive donor. This observation supports the concept of the primary of the kidney in causing essential hypertension.


Human motion intention based scaled teleoperation for orientation assistance in preshaping for grasping.
In this paper, we present an algorithm that provides human motion intention based assistance to users teleoperating a remote gripper for preshaping over an object in order to grasp it. Human motion data from the remote arm is used to train a Hidden Markov Model (HMM) offline. During the execution of a grasping task, the motion data is processed in real time through the HMM to determine the intended preshape configuration of the user. Based on the intention, the motion of the remote arm is scaled up in those orientation directions that lead to the desired configuration, thus providing the necessary assistance to the user to preshape for grasping. Tests on healthy human subjects validated the hypothesis that the users are able to preshape quicker and with much ease. Average time savings of 36% were obtained.


The efficacy of sequential therapy using pazufloxacin followed by oral fluoroquinolones for treatment of pyelonephritis.
The efficacy of sequential therapy of pazufloxacin (PZFX), which is a parenteral fluoroquinolone, followed by oral fluoroquinolones [tosufloxacin tosilate (TFLX) or levofloxacin (LVFX)] for treatment of pyelonephritis, was evaluated. Patients with pyelonephritis who had fever (≥37.5 °C), pyuria (≥10 white blood cells/high-power field), and bacteriuria (≥10(4) colony-forming units/ml) were eligible for this study. PZFX (500 mg) was given intravenously twice a day for at least 3 days. If the patients were clinically improved, TFLX (150 mg) or LVFX (100 mg) was then administered orally three times a day for at least 5 days. Patients underwent clinical and microbiological evaluation at 5-9 days after final drug administration. Clinical and microbiological efficacy could be assessed in 21 of 25 cases enrolled. Both clinical and microbiological efficacy rates were 81.0 % (17/21 cases). In the effective cases, the mean administration time was 4.2 days for PZFX and 6.0 days for oral fluoroquinolones. The mean time to defervescence was 3.4 days for the effective cases. In the four treatment failure cases, three quinolone-resistant Escherichia coli and a quinolone-resistant Enterococcus faecalis were isolated. This sequential therapy seemed to be clinically effective in the treatment of pyelonephritis; however, the prevalence of quinolone-resistant E. coli should be taken into account.


Equestrian injuries in New Zealand, 1993-2001: knowledge and experience.
The aims of this study were to investigate the extent of equestrian injuries in New Zealand and provide a range of prevention interventions. An examination of New Zealand Health Information Service (NZHIS) morbidity data for 1993 to 2001 and mortality data for 1993 to 1999 was undertaken. Recent studies on equestrian injuries were evaluated. NZHIS data indicated that as a result of horse-related injuries 5613 people were hospitalised between 1993 and 2001 and there were 16 fatalities between 1993 and 1999. Horse-related injuries were most prevalent in young females aged 10 to 19 years. Among Maori (the indigenous people of New Zealand), men predominated in horse-related injury numbers. Overall, half of equestrian injuries occurred in those under the age of 19 years. The major injury site was the arm. High equestrian-injury rates were recorded in rural regions. The findings indicate that age and regionally specific practical injury prevention strategies, health promotion messages and educational programmes are required. In particular, clear rules and regulations on protective and safety clothing are likely to enhance safety. Education in horse behaviour is required to facilitate safer environments on and around horses. A code of practice for horse riding and trekking establishments could decrease the risk of injury to those who hire horses.


Factors associated with maternal-child separation among HIV-infected mothers.
The goal of this study was to determine the period prevalence of mother-child separation (i. e., living apart from mother) and factors associated with separation between women infected with HIV type 1 and their children (17 years old or younger). A retrospective cohort study was conducted, based on routinely collected data by the Family Advocacy, Care and Education Services (FACES) of Children's Hospital (New Orleans, Louisiana) on children (n 586) of 231 HIV-infected mothers followed from July 1, 2001 to March 20, 2003. The 3-month period prevalence of separation from mother ranged between 12.7% and 21.2% over the course of follow-up. At baseline, 14% of children were separated from their mothers. Over the course of follow-up, older children (6 to 17 years), those with mothers who used illegal drugs and/or alcohol and who suffered from mental health problem(s), those whose mothers did not live at a permanent residence, and children with mothers who had a CD4 cell count below 200 cells per microliter were more likely to be separated from their mother. No significant differences in substance use, mental health, CD4 count, or other sociodemographics were identified between women lost to follow-up and those who remained in care. Substance use and mental health problems played a role in maternal-child separation among the HIV-positive women in this sample, even after clinical status and socioeconomic factors were taken into account. Providing additional resources for substance use and mental health treatment may help to prevent or reduce maternal-child separation among similar populations.


Young readers' use of phonological information: phonological awareness, memory, and comprehension.
In this study, we explored the relationship between beginning readers' phonological awareness and other aspects of phonological processing, specifically as manifested in short-term memory and comprehension tasks. The theoretical questions underlying the study were (a) what roles phonological processes play in children's beginning reading, from word identification through sentence comprehension, and (b) whether those roles are sufficiently related that potential difficulties at one level directly affect processing at other levels. Phonologically induced effects were observed for word-list memory and for sentence judgments for both novice readers (at the end of kindergarten) and relatively more experienced readers (end of Grades 1 and 2). For both age groups, correlational analyses revealed relationships among phonological awareness, phonological processing in list memory, and word reading. However, phonological processing in sentence comprehension was not related to other types of phonological processing. These results indicate that although phonology plays a role during comprehension, phonological processing may not be as limiting a factor in comprehension as in word reading.


Reconstruction of total maxillectomy defects with preservation of the orbital contents.
Reconstruction after total maxillectomy with preservation of the orbital contents is technically more challenging than when the maxillectomy is combined with orbital exenteration. Reconstruction of such defects should (1) provide support to the orbital contents, (2) obliterate any communication between the orbit and nasopharynx, (3) reconstruct the palatal surface, and (4) achieve facial symmetry and a good aesthetic result. We report our experience in performing reconstructive surgery on 14 patients who had a total maxillectomy and preservation of the orbital contents using nonvascularized bone grafts for reconstruction of the orbital floor and maxilla, in conjunction with a soft-tissue free flap or pedicled muscle flap. The orbital floor was reconstructed using split ribs in six cases (42.9 percent), split calvaria in six cases (42.9 percent), and iliac crest graft in two cases (14.3 percent). A myocutaneous rectus abdominis free flap was used for soft-tissue reconstruction and resurfacing of the palatal mucosa in twelve patients (85.7 percent), and a temporalis muscle transposition was used in two elderly patients (14.3 percent). One patient died 2 days after surgery. Mean follow-up and aesthetic and functional results were assessed in the remaining 13 patients a minimum of 6 months postoperatively. In 9 of these 13 patients (69.2 percent), postoperative radiotherapy was administered. No reexplorations or free flap failures were observed. One rectus flap developed partial necrosis of the skin island intraorally without affecting the final result. All patients had adequate functional vision. One patient had a mild vertical dystopia; there were no cases of enophthalmos. Ectropion was the most common undesirable result and was present in 10 of 13 cases (76.9 percent). It was graded as mild in four cases (40.0 percent), moderate in four cases (40.0 percent), and severe in the remaining two cases (20.0 percent). Speech was considered normal in six cases (46.2 percent), near normal in six cases (46.2 percent), and intelligible in one case (7.7 percent). Chewing function was considered good (soft to unrestricted diet) in all cases except for one patient who was only able to eat a pureed diet. Aesthetic results after immediate reconstruction were considered good in nine cases (69.2 percent) and fair in four cases (30.8 percent). Primary reconstruction of total maxillectomy defects with orbital content preservation remains a complex problem without a perfect solution. The combination of nonvascularized bone grafts for orbital/maxillary reconstruction with a soft-tissue free flap is a safe, reliable, and effective method of maximizing postoperative functional and aesthetic results.


Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma.
Mitotane is a widely used drug in the therapy of adrenocortical carcinoma (ACC). It is important to set up preclinical protocols to study the possible synergistic effects of its association with new drugs for ACC therapy. We assessed the efficacy of different routes of administration of mitotane (i.p. and oral) in inhibiting growth of H295R ACC cell xenografts in an adjuvant setting. Both formulations of mitotane could inhibit H295R xenografts growth only at short times after carcinoma cells inoculation, even though plasma mitotane levels approached or fell within the therapeutic range in humans. Our results show that mitotane adjuvant therapy is inadequate to antagonize long-term growth of H295R cancer cells xenografts and that care should then be taken in the design of preclinical protocols to evaluate the performance of new drugs in association with mitotane.


Correction to: Cost‑effectiveness analysis of stand‑alone or combined non‑invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study.
In the Published article, the value in the abstract has been published incorrectly. The correct abstract section is as follows.


Urolithiasis associated with indinavir in a patient with spinal cord injury.
To report a case of indinavir-induced urolithiasis, and the greater risk of this occurrence in individuals with spinal cord injury (SCI) who require fluid restriction for an intermittent catheterization program (ICP). Case report. A 38-year-old man with a T4 ASIA A SCI (according to the American Spinal Injury Association classification scale) and human immunodeficiency virus (HIV) infection was using an ICP and taking indinavir (a protease inhibitor) as part of his antiviral regimen. Cystoscopy was performed to rule out recurrent urethral condylomata. He was found to have a bladder stone measuring 0.5 cm x 0.5 cm x 0.3 cm, which, on analysis, was composed of indinavir (100% exterior, 90% interior). The bladder stone was removed under direct visualization. The plain abdominal radiograph did not reveal any stones. Indinavir is a frequently used drug for the treatment of HIV that has the potential to induce urinary lithiasis. This is particularly problematic for individuals with SCI who are on fluid restriction and an ICP. Therefore, cystoscopy and monitoring for indinavir-induced urolithiasis should be undertaken in individuals with SCI who are taking indinavir. Considerations include switching to a different protease inhibitor or choosing an entirely new HIV drug cocktail with less potential for urolithiasis.


Scrotal sparganosis: with an emphasis on ultrasonographic findings.
Scrotal sparganosis is a rare parasitic infestation in which humans serve as the second intermediate host for a tapeworm of the genus Spirometra. We present one case of a 44-year-old man with an emphasis on the ultrasound (US) findings. The patient had a palpable scrotal subcutaneous nodule and a history of eating raw snakes 7 years prior. On US, we noted a well-defined, long, tubular, serpiginous lesion that had three different echoic layers, i.e., a peripheral low echoic rim, an intermediate high echoic line, and an inner slightly low echoic content that had a tram-tract appearance.


Positive surgical margins after nephron-sparing surgery for renal cell carcinoma: incidence, clinical impact, and management.
Nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) offers comparable oncologic results but a lower risk of chronic kidney disease when compared with radical nephrectomy; however it can result in positive surgical margins (PSMs) and consequently to a possible risk of oncologic failure. The aim of this review is to evaluate the incidence of PSMs after nephron-sparing surgery, to assess their clinical and oncologic impact, and to provide an overview of the possible therapeutic management. We performed a nonsystematic review of the literature in the MEDLINE database using the following keywords: partial nephrectomy, nephron-sparing surgery, and positive margin. We reviewed articles published only in English from January 2002 to May 2012. The overall incidence of PSMs after NSS ranges from 0% to 7%, with no significant differences in open, laparoscopic, and robot-assisted techniques. Smaller tumor size could result in a higher risk of PSMs. Even if there is not a clear agreement in the clinical evidence, local recurrence seems to be more likely in patients with PSMs, especially in those with high-grade tumors. Development of metastases and cancer-specific survival, as seen in midterm follow-up studies, seems to be comparable to those in patients with negative surgical margins. Considering the globally low risk of local recurrence, development of metastasis, or cancer-specific mortality, careful surveillance could be the best management option for most patients with PSMs after NSS.


Reactivation of herpes simplex virus is associated with production of a low molecular weight factor that inhibits lymphokine activity in vitro.
Peripheral blood mononuclear cells obtained during recrudescent Herpes simplex virus (HSV) infection and stimulated with UV-inactivated viral antigen (UV-HSV) for 24 hr produced a low molecular weight (dialyzable) factor that inhibited lymphokine activity. This factor prevented the expression of leukocyte inhibitory factor (LIF) activity, but not its production. It was not made in UV-HSV-stimulated cultures grown in presence of 2 X 10(-6) M indomethacin nor in cultures of peripheral blood mononuclear cells obtained during convalescence or quiescence (greater than 4 days from onset of clinical symptoms) or from seropositive controls without a history of recurrent HSV disease. Dialyzable inhibitory factor production required OKM1+, OKT8+, and OKIa+ cells as determined by complement-mediated lysis with monoclonal antibody. Dialyzable inhibitory factor activity was associated with a trypsin-sensitive 8.2 K fraction as determined by Sephadex chromatography followed by sodium dodecyl sulfate-acrylamide gel electrophoresis.


The Informant AD8 Can Discriminate Patients with Dementia From Healthy Control Participants in an Asian Older Cohort.
The informant-AD8 (i-AD8) was found to be reliable in detecting cognitive impairment and dementia in tertiary and primary health care settings. We evaluated the discriminability of the i-AD8, as compared to other brief cognitive measures, and its combination with the 5-minute Montreal Cognitive Assessment (MoCA) and Mini-Cog in detecting very mild dementia in an Asian older cohort. The Epidemiology of Dementia in Singapore (EDIS) study recruited participants from a population-based eye disease study who were of Chinese, Malay, and Indian ethnicities. Participants aged ≥60 years were clinically assessed and diagnosed using the Clinical Dementia Rating (CDR) scale. Of the 761 participants recruited, 526 (69.1%) had no dementia (CDR = 0), 193 (25.4%) had very mild dementia (CDR = 0.5), and 42 (5.5%) had dementia (CDR ≥ 1). Participants were administered the Mini-Mental State Examination, MoCA, Mini-Cog, and a local neuropsychological battery. Their informants were interviewed using the i-AD8. Receiver operating characteristic analyses were conducted to establish the optimal cut-off points, and all discriminatory indices were calculated. The i-AD8 was good and equivalent to other cognitive tools in detecting dementia [area under the curve (AUC) = 0.89, sensitivity = 0.76, and specificity = 0.94] but only fair in detecting very mild dementia (AUC = 0.69, sensitivity = 0.62, and specificity = 0.73). Combination of the i-AD8 with 5-minute MoCA or Mini-Cog in compensatory or in conjunction showed minimal improvement to the clinical utility for dementia or very mild dementia. All scales yielded a high rate of false positives (positive predictive value < 0.70). The i-AD8 has good discriminatory power in detecting dementia (CDR ≥ 1) and is brief enough to be applied as an effective screening tool in the community. However, the i-AD8 and other cognitive tools lacked classification accuracy in detecting very mild dementia (CDR = 0.5).