Infrared coagulator treatment of high-grade anal dysplasia in HIV-infected individuals: an AIDS malignancy consortium pilot study.
To evaluate prospectively the safety of the infrared coagulator (IRC) as a treatment for anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals and to seek preliminary evidence for efficacy. HIV-infected patients with </=3 biopsy-proven internal anal HSILs received office-based treatment with the IRC at participating AIDS Malignancy Consortium sites. Treatments were performed during high-resolution anoscopy (HRA) under local anesthesia. Patients were reevaluated at 3 months, and persistent lesions could be retreated. Patients were evaluated every 3 months for a year with anal cytology and HRA with biopsy. Human papillomavirus (HPV) DNA was measured at baseline and at follow-up using MY09/MY11 L1 polymerase chain reaction. A total of 44 HSILs were treated from 16 men and 2 women. HPV 16 was the most common HPV type identified. There was no consistent change in HPV type or viral load in patients before and after treatment with the IRC. No procedure-related severe adverse events were reported. Twelve patients reported mild or moderate anal/rectal pain or bleeding. The IRC is a well-tolerated method of treating discrete anal canal HSILs in HIV-infected patients. A larger study to characterize its efficacy better in the management of HSILs in HIV-infected individuals is warranted.


Meningococal Septicemia with Cutaneous Vasculitis.
Two cases-had meningococcal septicemia with vasculitis of skin. Out 9 year old female developed generalised ,asymptomatic, purpuric atrophic plaques on the limbs, trunk and face on the fourth day of high fever. The second patient was 20 year old male who developed purplish plaques. Nodules, and bullae mainly on the extensor surface of the hands and feet on the tenth day, of high fever. Bullae had clear fluid and bluish-black peripheral rim.


Decomposition of aniline in supercritical water.
The decomposition of aniline in supercritical water (SCW) was studied. Experiments were performed at various temperatures, pressures, residence times, dosage of oxidant H2O2 and initial aniline concentrations to investigate their effect on the destruction efficiency. Manganous sulfate and ferrous sulfate were screened out during the experiment to study the effect of the homogenous catalysts on destruction efficiency. The effect of pH was also studied. The experiments showed that the dosage of oxidant H2O2, experimental temperature, pressure, reaction residence time and even initial concentration of the aniline in wastewater have a significant affect on the TOC removal; manganous sulfate and ferrous sulfate improve the oxidation; TOC removal improves slightly with a decrease in the initial pH value. At a system temperature 450 degrees C, pressure 28 MPa, initial pH 4.0, residence time 46 s and K value 1.1, TOC removal can reach 100%.


Immunoreactive calcitonin production by a human promyelocytic leukemia cell line HL60.
Using a sensitive radioimmunoassay, we detected human immunoreactive calcitonin in cell extracts and in cell-exposed media of the HL60 cell line derived originally from a patient with acute promyelocytic leukemia. The cell extract was chromatographed on a reverse-phase high-pressure liquid chromatography system. Radioimmunoassay of the fractions showed that the immunoreactive calcitonin was heterogeneous but had peaks corresponding to those of synthetic human calcitonin monomer and its sulphoxide. We have previously shown that levels of immunoreactive calcitonin are elevated in the plasma of the majority of patients with acute and chronic myeloid leukemias. Our studies with the HL60 cell line add further support to the concept that leukemic cells can synthesize immunoreactive calcitonin "ectopically."


Neurotoxicological effects of nicotine on the embryonic development of cerebellar cortex of chick embryo during various stages of incubation.
Long-acting nicotine is known to exert pathological effects on almost all tissues including the cerebellar cortex. The present work was designed to elucidate the effect of nicotine on the development of cerebellar cortex of chick embryo during incubation period. The fertilized eggs of hen (Gallus gallus domesticus) were injected into the air space by a single dose of long acting nicotine (1.6 mg/kg/egg) at the 4th day of incubation. The embryos were taken out of the eggs on days 8, 12 and 16 of incubation. The cerebellum of the control and treated embryos at above ages were processed for histopathological examination. The TEM were examined at 16th day of incubation. The results of the present study revealed that, exposure to long-acting nicotine markedly influence the histogenesis of cerebellar cortex of chick embryo during the incubation period. At 8th day of incubation, nicotine delayed the differentiation of the cerebellar analge; especially the external granular layer (EGL) and inner cortical layer (ICL). Furthermore, at 12th day of incubation, the cerebellar foliation was irregular and the Purkinje cells not recognized. By 16th day of incubation, the cerebellar foliations were irregular with interrupted cerebellar cortex and irregular arrangement of Purkinje cells. Immunohistochemical analysis for antibody P53 protein revealed that the cerebellar cortex in all stages of nicotine treated groups possessed a moderate to weak reaction for P53 protein however; this reaction was markedly stronger in the cerebellar cortex of control groups. Moreover, the flow cytometric analysis confirmed that the percentage of apoptosis in control group was significantly higher compared with that of nicotine treated group. At the TEM level, the cerebellar Purkinje cells of 16th day of treated groups showed multiple subcellular alterations in compared with those of the corresponding control group. Such changes represented by appearing of vacuolated mitochondria, cisternal fragmentation of RER, irregular grooves of Golgi tubules. Also, multiple cytoplasmic vacuoles and aggregation of Nissl granules were recorded around pyknotic nucleus.


Immune and clinical parameters associated with Leishmania infantum infection in the golden hamster model.
For experimental infections with viscerotropic strains of Leishmania, a suitable animal model is not yet defined. In the present work, we have reappraised the use of golden hamster (Mesocricetus auratus) as an experimental model for infection with Leishmania infantum. Groups of hamsters were challenged by the intracardial route with doses ranging from 10(3) to 10(5) infectious promastigotes and the animals were monitored for 1-year follow-up period. The outcome of the infection was assessed by clinical symptoms of leishmaniasis, parasite loads in both liver and spleen, humoral response to Leishmania antigens and antibody levels in kidneys. The humoral response was analysed using either crude antigens (by ELISA and Western blotting) or several recombinant Leishmania antigens (Hsp70, Hsp83, LiP2a, LiP2b, H2A, H3 and KMP-11). From the analysis of all these parameters, we established the existence of three groups of animals: symptomatic or susceptible, oligosymptomatic, and resistant. Given the parallelism existing between the outcomes of Leishmania-infection in hamsters, dogs and humans, we believe that our data illustrate that the hamster is an excellent experimental model to study visceral leishmaniasis and for the design of vaccine development.


The effect of intravenous administration of WEB 2086 on PAF-induced platelet aggregation in healthy Friesian calves.
The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable.


[Resistance to antiretroviral therapy].
After some time under treatment, HIV+ patients have a virologic failure rate of 50%, being development of resistance to therapy responsible for up to 80% of the virologic failure. In addition, resistance rates in naive patients is around 10% in developed countries. Inherent characteristics of HIV (replication cycle, viral subtype), of patients (therapy compliance, intra-/interindividual variability, genetic polymorphisms), and of therapy (genetic barrier to drug resistance, inhibitory ratio, drug interactions) are the factors involved in the development of resistance, and their interpretation requires to be studied. Resistance identification will be carried out using genotypical and/or phenotypical methods, and their adequacy has been validated by various expert panels on resistance. The role of the pharmacokinetic and pharmacodynamic monitoring of antiretroviral therapy is also crucial within the field of resistance, and concerns us directly as pharmacists. Finally, understanding the resistance patterns of currently available or experimental antiretroviral drug families will provide the necessary tools to prevent and/or manage their development. To know and understand the mechanisms and patterns of resistance for each antiretroviral family. To identify factors involved in the development of resistance to ART, and to interpret various resistance tests. Studies were identified using Medline, the Cochrane database of systemic reviews, abstracts from international meetings on AIDS, Conference on Retroviruses and Opportunistic Infections, international meetings on resistance to antiretrovirals, and product monographs from January 1999 to February 2004. To be eligible, studies had to describe viral genome mutations responsible for resistance or hypersusceptibility to ART in relation to precipitating factors. Papers describing resistance identification techniques were also selected. In all, 1,083 full articles and 64 abstracts and communications at international meetings were retrieved, of which 74 articles and 20 abstracts met the inclusion criteria for our review. Of the 94 reports selected, 86 discussed factors involved in the development of resistance and resistance test interpretation. The remaining 8 reports focused on resistance patterns to the various antiretroviral drug families. Every article described the enzymatic mechanisms induced by mutations responsible for resistance or hypersusceptibility to each antiretroviral family, the classification and nomenclature for each mutation, and the influence of each mutation on the success or failure of patient treatment. REVIEWER S CONCLUSIONS: Knowledge of the mechanisms and patterns of resistance to each antiretroviral family will allow us to overall understand the evolution and outcome of treatment for any given patient. Only thus shall we be able to play an integral role in the therapy of patients.


A proposed mechanism(s) of transitory ischemic injury to myocardium.
The main objective of this study was to produce primary acute ischemic injury to myocardium in a live animal. In vitro, guinea pig platelets were sensitive to perturbation and aggregation by a suspension of ultrafine fibrillary collagen material isolated from the aorta of an aged burro (Equus asinus). The platelets responded to the stimulatory action of this material down to 100 to 200 ng (dry weight) added to 0.45 ml of platelet-rich plasma, as determined by aggregometric technique. Aortic fibrillary collagen material injected IV into guinea pigs (350 to 1900 microgram protein/kg of weight) produced a transitory disappearance of virtually all circulating platelets within 5 minutes. In animals in which blood samples were taken 2.5 hours after injection, 50 to 75% of the average base-line platelets in the circulation of controls returned to the circulation. In other experiments, 3 anesthetized animals were injected by jugular vein with an amount of active fibrillary collagen material (300 microgram as protein/kg of animal weight) estimated to produce reversible platelet aggregation in vivo. Two control animals were injected with the same dose of the material that had been inactivated (15 minutes at 100 C) to abolish platelet aggregation. Treated and control animals were maintained under general anesthesia for 2.5 hours. Intraventricular pressures and electrocardiographs (ECG) were monitored continuously for the first 30 minutes. The injection of the active fibrillary collagen material caused a large ventricular pressure elevation (170/10, 180/10, and 150/10 mm of Hg) in approximately 40 s. Preinfusion ventricular pressures in the 3 animals were 65/0, 85/5, and 88/0 mm of Hg, respectively. Within 60 s, there was a reduction in the absolute platelet number in the peripheral circulation. The elevation of ventricular pressure persisted for approximately 5 minutes and was followed within 30 minutes by a set of ECG events suggestive of acute myocardial ischemic injury, which included premature ventricular contractions, transient S-T segment depression concurrent with ventricular hypertension, and S-T segment elevation with reversed tall upright T-waves in association with a decrease to the preinfusion ventricular base line. Other ECG changes included prolongation of the P-R segment, missed ventricular contractions, and arrhythmia. The ECG changes seemed to be subsequent to platelet microthrombus formation in the pulmonary arterial microcirculation. By 2.5 hours after the treatment, platelets "rebounded" into the circulation in 2 surviving guinea pigs, and left ventricular pressures and ECG profiles returned to the preinfusion base lines. Guinea pigs IV infused with similar amounts of inactivated (15 minutes at 100 C) fibrillary collagen material did not show changes.


Microsporidial keratopathy in two dogs.
A microsporidial keratopathy is described in two dogs. Both dogs presented with a unilateral stromal keratopathy characterized by multifocal coalescing opacities, and the diagnosis was made on histopathologic examination of keratectomy specimens. Transmission electron microscopy (TEM) on formalin-fixed, paraffin-embedded corneal tissue was performed in one dog, and the morphologic features were consistent with Nosema species infection. Both dogs were initially diagnosed and treated by superficial keratectomy. One dog received additional antifungal medication and underwent a penetrating keratoplasty following local recurrence two years later. No other systemic lesions attributable to the microsporidial infection were identified clinically. The clinical and diagnostic pathology findings, treatment, and follow-up are discussed.


Iterative image reconstruction for limited-angle inverse helical cone-beam computed tomography.
Helical trajectory satisfying the condition of exact reconstruction, has been widely utilized in the commercial computed tomography (CT). While limited by the scanning environment in some practical applications, the conventional helical cone-beam CT imaging is hard to complete, thus, developing an imaging system suited for long-object may be valuable. Three-dimensional C-arm CT is an innovative imaging technique which has been greatly concerned. Since there is a high degree of freedom of C-arm, more flexible image acquisition trajectories for 3D imaging can be achieved. In this work, a fast iterative reconstruction algorithm based on total variation minimization is developed for a trajectory of limited-angle inverse helical cone-beam CT, which can be applied to detect long-object without slip-ring technology. The experimental results show that the developed algorithm can yield reconstructed images of low noise level and high image quality.


Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study.
Currently, all patients with vulvar cancer with a positive sentinel node undergo inguinofemoral lymphadenectomy, irrespective of the size of sentinel-node metastases. Our study aimed to assess the association between size of sentinel-node metastasis and risk of metastases in non-sentinel nodes, and risk of disease-specific survival in early stage vulvar cancer. In the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V), sentinel-node detection was done in patients with T1-T2 (<4 cm) squamous-cell vulvar cancer, followed by inguinofemoral lymphadenectomy if metastatic disease was identified in the sentinel node, either by routine examination or pathological ultrastaging. For the present study, sentinel nodes were independently reviewed by two pathologists. Metastatic disease was identified in one or more sentinel nodes in 135 (33%) of 403 patients, and 115 (85%) of these patients had inguinofemoral lymphadenectomy. The risk of non-sentinel-node metastases was higher when the sentinel node was found to be positive with routine pathology than with ultrastaging (23 of 85 groins vs three of 56 groins, p=0.001). For this study, 723 sentinel nodes in 260 patients (2.8 sentinel nodes per patient) were reviewed. The proportion of patients with non-sentinel-node metastases increased with size of sentinel-node metastasis: one of 24 patients with individual tumour cells had a non-sentinel-node metastasis; two of 19 with metastases 2 mm or smaller; two of 15 with metastases larger than 2 mm to 5 mm; and ten of 21 with metastases larger than 5 mm. Disease-specific survival for patients with sentinel-node metastases larger than 2 mm was lower than for those with sentinel-node metastases 2 mm or smaller (69.5%vs 94.4%, p=0.001). Our data show that the risk of non-sentinel-node metastases increases with size of sentinel-node metastasis. No size cutoff seems to exist below which chances of non-sentinel-node metastases are close to zero. Therefore, all patients with sentinel-node metastases should have additional groin treatment. The prognosis for patients with sentinel-node metastasis larger than 2 mm is poor, and novel treatment regimens should be explored for these patients.


Synthesis, properties, and endothelial progenitor cells labeling stability of dextranes as polymeric magnetic resonance imaging contrast agents.
Magnetic resonance imaging is one of the most important fields for cellular imaging due to its non-invasive capacity, spatial resolution, and sensibility to visualized transplanted cells. An enhanced magnetic resonance image can be achieved by using contrast agents containing paramagnetic gadolinium chelates, which have the widest clinical use. To obtain a better contrast-enhancement and reduce the concentration of Gd for payload, one strategy is to conjugate the gadolinium(III) chelate to polymeric materials that will lead into an increase in the rotational correlation time and therefore improve the relaxivity. Four series of dextran gadolinium chelates were synthesized which are of interest as potential MRI contrast agents to track bone marrow-derived endothelial progenitor cells in vivo. The dextranes with molecular weights were characterized, introduced into the endothelial progenitor cells by electroporation, and injected in aqueous solution into rats to acquire the MR images. We have shown that by selecting polymers of the appropriate molecular weight, stability into the cell after labeling, relaxivity, and retention into the body can be accomplished.


[Current therapeutic approach in non-infectious uveitis].
The aim of this paper is to summarize current therapeutic approach in non-infectious uveitis. It focuses on different immunosuppressive/immunomodulatory treatment modalities and address' its adverse effects.


Effects of peristaltic and longitudinal wave motion of the channel wall on movement of micro-organisms: application to spermatozoa transport.
A mathematical model is presented to study the motion of the spermatozoa in the cervical canal by considering the transverse waves along its tail and the transverse and longitudinal motions of the cervical wall. In an attempt to control fertility by reducing the speed of sperm, the transverse waves have been considered in the direction opposite to the motion of the spermatozoa. It has been shown that by having appropriate transverse wave motion and longitudinal velocity, the sperm may not be able to move towards the oviduct even if it could continue to have its own propelling velocity. A particular case of the motion of a thin plane sheet in a channel under peristaltic motion of its walls has also been obtained and studied.


Decreased density in membrane localized macromolecules in cells enlarged after X-irradiation or polyploidization.
Cytophotometric measurements of DNA, dry mass (total proteins) and surface localized IgM and Ia were performed on individual cells of a Burkitt lymphoma derived cell line after X-irradiation and after polyploidization. Blockage of cell division was achieved with 250 r, and an arrest in G2 was found 48 hr after irradiation. The cells unable to divide increased in volume and total protein content. Cell enlargement was also achieved by polyploidization. The amount of surface localized IgM and Ia did not keep up pace with the increase in total proteins, thus their density decreased. This was reflected in decreased sensitivity of the enlarged cells to the cytotoxic effect of specific antisera.


[Selection of the type in revision total hip replacement for failed hip arthroplasty].
To evaluate the selection of the type of prosthesis in revision hip arthroplasty. There were 33 hips in our study, male in 7 hips and female in 26 hips. The average age of the patients were 59 years. The reasons of the revision included aseptic loosing in 22 hips, infection in 8 hips (2 infection hips with discharging sinuses), and acetabular erosion in 3 hips. The operations for revision were 13 cemented and 12 cementless acetabular prosthesis with autograft in morselized form; the femoral revision were all selected in cemented prosthesis. The revision for infection hip were all cemented prosthesis of extensively porouse-coated. The average follow-up duartion was 3.9 years and 11 months. There was a radiolucency but no clinical instability accompanied in 2 hips and remaining moderate pain in 4 hips. No dislocation and fracture were seen in the series. Harris score were improved to 82.4 (68-88). The commonest reason of revision hip arthroplasty was aseptic loosing. The acetabular prosthesis in revision could select cemented or cementless components and femoral prosthesis could select extensively coated stem. The cemented components could yield good results in infection hips revision.


The clinical usefulness of prostate specific antigen: update 1994.
In conclusion, PSA is the first prostate specific serum marker of clinical usefulness in urology. It represents a valuable clinical tool that has improved our ability to detect early prostate cancer and to monitor response to therapy. While large PSA screening studies have demonstrated an appreciable increase in the detection of organ confined, potentially curable prostate cancers, no study to date has yet demonstrated that the increased detection rate will decrease the prostate cancer-specific mortality rate. Yet more importantly, no study to date has demonstrated that early diagnosis using PSA will not decrease the prostate cancer specific mortality rate and until such data exist, PSA should be used to aid in early diagnosis and treatment planning for men with prostate cancer. PSA, when combined with other variables such as Gleason score and clinical stage, improves the prediction of pathological stage for prostate cancer. The introduction of PSA velocity and age specific reference ranges should further enhance the clinical usefulness of PSA. New advances in PSA research hold great promise for further improvements in PSA, and truly make it the most important and useful tumor marker for adenocarcinoma of the prostate.


Smoking habits of emergency department patients: an opportunity for disease prevention.
To determine smoking habits, levels of addiction, readiness to quit, and access to primary care among ED patients. A questionnaire was administered prospectively to all noncritical adult patients who presented to one university hospital ED during 23 randomly selected four-hour time blocks; 336 (89%) of 376 eligible patients responded. Self-reported smoking was validated by carbon monoxide breath testing in a pilot sample of 49 patients. The study patients were mostly young (mean age = 35 +/- 15 years), female (59%), white (62%), and high school-educated (73%). Of the 336 ED patients, 41% were current smokers (95% CI = 0.36-0.46); 42% of these were "moderately" to "very highly" dependent on nicotine (Fagerstrom Test for Nicotine Dependence > 4). Of those who smoked, 68% stated they wanted to quit, and 49% wanted to quit within the month. Fifty-six percent of all those who smoked stated that they had never been told to quit smoking by any physician. Thirty-five percent of the ED sample (118 patients) relied upon EDs for most or all of their routine, primary health care; 55% (95% CI = 0.46-0.64) of these patients were current smokers. The prevalence rates of smoking and nicotine addiction among ED patients are high. Almost half of ED smokers are ready to quit, but most state they have never been told by a physician to do so. Finally, a large proportion of ED smokers receive their primary care in EDs. Therefore, the ED may be an underused setting for smoking cessation intervention.


Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi.
Although Th1-type responses tend to be associated with resistance to Trypanosoma cruzi infection, mixed Th1 and Th2 cytokine responses are generally observed in both resistant and susceptible mice. To help clarify the role of type 1 and type 2 cytokine responses in immunity to T. cruzi, mice with induced deficiencies in the Stat4 or Stat6 genes were infected with T. cruzi. As expected, Stat4-/- mice deficient in type 1 cytokine responses were highly susceptible to infection, exhibiting increased parasitemia levels relative to wild-type mice and 100% mortality. In contrast, parasitemia levels and survival in Stat6-deficient mice were not different from wild type. The type 1 and type 2 cytokine bias of Stat6- and Stat4-deficient mice, respectively, was confirmed by in situ immunocytochemical analysis of cytokine-producing cells in the tissues of infected mice and by subclass analysis of anti-T. cruzi serum Abs. Notably, both Stat4- and Stat6-deficient mice produced substantial amounts of anti-T. cruzi Abs. Tissues from chronically infected Stat6-deficient mice had little to no evidence of inflammation in the heart and skeletal muscle in contrast to wild-type mice, which exhibited substantial inflammation. In situ PCR analysis of these tissues provided evidence of the persistence of T. cruzi in wild-type mice, but no evidence of parasite persistence in Stat6-deficient mice. These data suggest that type 1 T cells are required for the development of immune control to T. cruzi, but that type 2 T cells contribute to parasite persistence and increased severity of disease.


Correlation of clinical, MRI and Tc-99m HMPAO SPECT findings in neuro-Behçet's disease.
Behçet's disease (BD) is a systemic disorder of unknown cause. In our study, we investigated the utility of Tc-99m HMPAO SPECT and MRI in patients with neuro-Beh,cet's disease (n-BD). Twelve patients (two females, ten males; mean age 33 +/- 9.6 yr; age range 18-45 yr) with n-BD, fulfilling the criteria of the International Study Group for BD, were included in the study. MRI was performed according to a standard protocol with 1 or 1.5 T imagers. Brain SPECT data were obtained using a single head gamma camera after 555 MBq Tc-99m HMPAO injections. Following image reconstruction, regional cerebral perfusion was evaluated both visually and semi quantitatively. Neurological examination showed parenchymal brain involvement in 6 of 12 patients (50%). All 6 patients had white matter lesions on MRI, while only 5 of them showed perfusion defects on brain SPECT. Out of 6 patients (50%) without clinical signs of parenchymal brain involvement, 1 patient showed a pathological brain SPECT and 3 patients showed pathological MRI findings. Semiquantitative analysis of brain regions on SPECT study showed statistically significant hypoperfusion of biparietal regions. This study investigates the correlation between clinical, MRI and SPECT findings and it shows discrepancy between these findings in some cases. Brain SPECT may act as a complementary modality to increase the detection rate of affected regions in patients with n-BD.


Glutathione-sensitive PEGylated curcumin prodrug nanomicelles: Preparation, characterization, cellular uptake and bioavailability evaluation.
The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.


Heterogeneity in patellofemoral cartilage adaptation to anterior cruciate ligament transection; chondrocyte shape and deformation with compression.
The purpose of this study was to determine if the opposing cartilages of the feline patellofemoral joint adapted differently to short-term anterior cruciate ligament transection (ACL-T) and if the magnitude of chondrocyte deformation upon tissue loading was altered under ACL-T conditions compared to contralateral controls. In situ static compression of physiological magnitude was applied to the feline patellofemoral cartilage 16 weeks post-ACL-T and cartilage and chondrocyte deformation were evaluated by histomorphometry. Six adult cats were euthanized 16 weeks after unilateral ACL-T. A peak surface pressure of 9 MPa was applied to the fully intact patella and femoral groove cartilages. After in situ fixation under compression, sections from the centre of the indent and from an adjacent unloaded area of the cartilages were analysed. Chondrocyte shape, size, clustering and volumetric fraction were quantified. Experimental patellar articular cartilage was thicker, contained larger chondrocytes that were more frequently arranged in clusters and had, on average, a larger chondrocyte volumetric fraction compared to contralateral controls. In contrast, the experimental femoral groove cartilage demonstrated little adaptation to ACL-T. The patellar articular cartilage adapts to short-term ACL-T to a greater extent than femoral groove cartilage. We speculate that differences in the histological parameters of control tissues, such as cartilage thickness and the magnitude and depth distribution of chondrocyte shape, size and volumetric fraction may contribute to predisposing patellar cartilage, and not femoral groove cartilage, to adaptation after ACL-T.


The liquidlike ordering of lipid A-diphosphate colloidal crystals: the influence of Ca2+, Mg2+, Na+, and K+ on the ordering of colloidal suspensions of lipid A-diphosphate in aqueous solutions.
A comprehensive study was performed on electrostatically stabilized aqueous dispersion of lipid A-diphosphate in the presence of bound Ca2+, Mg2+, K+, and Na+ ions at low ionic strength (0.10-10.0-mM NaCl, 25 degrees C) over a range of volume fraction of 1.0 x 10(-4)< or =phi< or =4.95 x 10(-4). These suspensions were characterized by light scattering (LS), quasielastic light scattering, small-angle x-ray scattering, transmission electron microscopy, scanning electron microscopy, conductivity measurements, and acid-base titrations. LS and electron microscopy yielded similar values for particle sizes, particle size distributions, and polydispersity. The measured static structure factor, S(Q), of lipid A-diphosphate was seen to be heavily dependent on the nature and concentration of the counterions, e.g., Ca2+ at 5.0 nM, Mg2+ at 15.0 microM, and K+ at 100.0 microM (25 degrees C). The magnitude and position of the S(Q) peaks depend not only on the divalent ion concentration (Ca2+ and Mg2+) but also on the order of addition of the counterions to the lipid A-diphosphate suspension in the presence of 0.1-microM NaCl. Significant changes in the rms radii of gyration (R2G) 1/2 of the lipid A-diphosphate particles were observed in the presence of Ca2+ (24.8+/-0.8 nm), Mg2+ (28.5+/-0.7 nm), and K+ (25.2+/-0.6 nm), whereas the Na+ salt (29.1+/-0.8 nm) has a value similar to the one found for the de-ionized lipid A-diphosphate suspensions (29.2+/-0.8 nm). Effective particle charges were determined by fits of the integral equation calculations of the polydisperse static structure factor, S(Q), to the light-scattering data and they were found to be in the range of Z*=700-750 for the lipid A-diphosphate salts under investigation. The light-scattering data indicated that only a small fraction of the ionizable surface sites (phosphate) of the lipid A-diphosphate was partly dissociated (approximately 30%). It was also discovered that a given amount of Ca2+ (1.0-5.0 nM) or K+ (100 microM) influenced the structure much more than Na+ (0.1-10.0-mM NaCl) or Mg2+ (50 microM). By comparing the heights and positions of the structure factor peaks S(Q) for lipid A-diphosphate-Na+ and lipid A-diphosphate-Ca2+, it was concluded that the structure factor does not depend simply on ionic strength but more importantly on the internal structural arrangements of the lipid A-diphosphate assembly in the presence of the bound cations. The liquidlike interactions revealed a considerable degree of ordering in solution accounting for the primary S(Q) peak and also the secondary minimum at large particle separation. The ordering of lipid A-diphosphate-Ca2+ colloidal crystals in suspension showed six to seven discrete diffraction peaks and revealed a face-centered-cubic (fcc) lattice type (a=56.3 nm) at a volume fraction of 3.2 x 10(-4)< or =phi< or =3.9 x 10(-4). The K+ salt also exhibited a fcc lattice (a=55.92 nm) at the same volume fractions, but reveals a different peak intensity distribution, as seen for the lipid A-diphosphate-Ca2+ salt. However, the Mg2+ and the Na+ salts of lipid A-diphosphate showed body-centered-cubic (bcc) lattices with a=45.50 nm and a=41.50 nm, respectively (3.2 x 10(-4)< or =phi< or =3.9 x 10(-4)), displaying the same intensity distribution with the exception of the (220) diffraction peaks, which differ in intensity for both salts of lipid A-diphosphate.


Genetic education and counseling.
This special issue of Patient Education and Counseling on genetic education and counseling provides an overview of studies and findings in this field. It features a mixture of papers dealing with five different topics related to several psychosocial aspects of genetic education and counseling. Attention is paid to new issues in counseling for hereditary cancer and Huntington Disease. Articles are presented on information recall of counseled individuals, the use and impact of genetic services on counselees (acceptance of testing; knowledge of inherited cancer susceptibility; risks of genetically testing children). Also topics are addressed with respect to the counselor (neutral attitude; understandable language; information recall; satisfaction with the services provided by the genetic counselor). Furthermore, recommendations are discussed for screening practices for women with a family history of breast cancer, and in addition, the effectiveness of genetic counseling is addressed. In conclusion several suggestions for future research are given.


Reversal effect of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone on multi-drug resistance in resistant human hepatocellular carcinoma cell line BEL-7402/5-FU.
Multi drug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a chalcone, isolated from the buds of Cleistocalyx operculatus, has been shown to have antitumor effects on human carcinoma SMMC-7721 cells in vitro and in vivo. In this paper, we studied the reversal effect and the mechanism of DMC on human hepatocellular carcinoma drug-resistant cells BEL-7402/5-FU in vitro. Administration of DMC reversed the multi-drug resistance of human hepatocellular carcinoma BEL-7402/5-FU cells significantly. DMC enhanced the sensitivity of BEL-7402/5-FU cells to 5-fluorouracil (5-FU) and doxorubicin (DOX). Staining with Hoechst 33258 and flow cytometric analysis showed that DMC has apoptosis-inducing effect on BEL-7402/5-FU cells. It could also increase the concentration of 5-FU in the resistant multi-drug-resistant cells. We also observed that over-expression of the multi-drug resistance-associated protein (MRP1) and of the glutathione S-transferase π (GST-π) contributed to MDR in BEL-7402/5-FU cells. The mRNA expressions of MRP1 and GST-π and the protein expression of MRP1 were decreased by DMC. These data demonstrated that DMC could effectively reverse MDR in BEL-7402/5-FU cells.


Free-choice responding for ethanol versus water in alcohol preferring (P) and unselected Wistar rats is differentially modified by naloxone, bromocriptine, and methysergide.
The role of opioids, dopamine and serotonin in ethanol (EtOH) reward and preference was investigated in non-deprived, Alcohol-Preferring (P), and genetically heterogenous Wistar rats. Operant responding for ethanol was initiated using sweet-solution substitution procedures. The rats were then trained in 30-min daily sessions to respond for ethanol (10% v/v) versus water under a two-lever, free-choice contingency. All testing was conducted in the absence of water and food deprivation or addition of sweeteners to the ethanol drinking solution. Rats of both strains developed stable preferences in responding for ethanol over water and consumed ethanol at quantities sufficient to produce pharmacologically relevant mean blood alcohol concentrations (P-Rats: 98 +/- 19.6 mg%; unselected Wistars: 41.7 +/- 8.5 mg%). In P-rats, systemic naloxone (NAL; 0.125, 0.25 and 0.5 mg/kg) pretreatments resulted in a dose-dependent suppression in responding for both ethanol and water, but did not alter ethanol preference (expressed as percent ethanol of total intake). In contrast, bromocriptine (BRO; 1.0, 2.0 and 4.0 mg/kg) produced a significant, dose-dependent shift in preference from ethanol toward water by inhibiting responding for ethanol while enhancing water consumption. In unselected Wistar rats, NAL and BRO treatments produced changes in ethanol preference patterns similar to those observed in P-rats. However, compared to P-rats, these changes were smaller and not consistently dose dependent. No changes in ethanol preference and water or ethanol intake were observed with methysergide (MET; 2.5, 5.0, 10.0 mg/kg) in either strain of rat. Together, the results suggest a possible involvement of dopaminergic mechanisms in the reinforcing properties of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)


Severe febrile respiratory illnesses as a cause of mass critical care.
Febrile respiratory illnesses with respiratory failure are one of the most common reasons for admission to the intensive care unit. Most causes of febrile respiratory illness are bacterial and viral agents of community-acquired pneumonia. However, a small number of rare and highly contagious agents can initially present as febrile respiratory illnesses, which can lead to an epidemic that can greatly impact the health care system. This impact includes sustained mass critical care, with potential scarcity of critical resources (eg, positive-pressure ventilators), spread of disease to health care workers, sustained spread within the community, and extensive morbidity and mortality. The main agents of febrile respiratory illness that would lead to an epidemic include influenza, the coronavirus that causes severe acute respiratory syndrome, smallpox, viral hemorrhagic fever, plague, tularemia, and anthrax. Recognition of these agents occurs largely based on epidemiological clues, and management consists of antibiotics, antivirals, supportive care, and positive-pressure ventilation. Acute respiratory failure and acute respiratory distress syndrome occur with these agents, so a lung-protective (low tidal volume) ventilation strategy is indicated. Additional respiratory care measures, such as nebulized medications, bronchoscopy, humidified oxygen, and airway suctioning, potentiate aerosolization of the virus or bacteria and increase the risk of transmission to health care workers and patients. Thus, appropriate personal protective equipment, including an N95 mask or powered air-purifying respirator, is indicated. A basic understanding of the epidemiology, clinical findings, diagnosis, and treatment of these agents will provide a foundation for early isolation, evaluation, infection control, and public health involvement and response in cases of a febrile respiratory illness that causes respiratory failure.


Exploring the 3D geometry of the diffusion kurtosis tensor--impact on the development of robust tractography procedures and novel biomarkers.
Diffusion kurtosis imaging (DKI) is a diffusion-weighted technique which overcomes limitations of the commonly used diffusion tensor imaging approach. This technique models non-Gaussian behaviour of water diffusion by the diffusion kurtosis tensor (KT), which can be used to provide indices of tissue heterogeneity and a better characterisation of the spatial architecture of tissue microstructure. In this study, the geometry of the KT is elucidated using synthetic data generated from multi-compartmental models, where diffusion heterogeneity between intra- and extra-cellular media is taken into account, as well as the sensitivity of the results to each model parameter and to synthetic noise. Furthermore, based on the assumption that the maxima of the KT are distributed perpendicularly to the direction of well-aligned fibres, a novel algorithm for estimating fibre direction directly from the KT is proposed and compared to the fibre directions extracted from DKI-based orientation distribution function (ODF) estimates previously proposed in the literature. Synthetic data results showed that, for fibres crossing at high intersection angles, direction estimates extracted directly from the KT have smaller errors than the DKI-based ODF estimation approaches (DKI-ODF). Nevertheless, the proposed method showed smaller angular resolution and lower stability to changes of the simulation parameters. On real data, tractography performed on these KT fibre estimates suggests a higher sensitivity than the DKI-based ODF in resolving lateral corpus callosum fibres reaching the pre-central cortex when diffusion acquisition is performed with five b-values. Using faster acquisition schemes, KT-based tractography did not show improved performance over the DKI-ODF procedures. Nevertheless, it is shown that direct KT fibre estimates are more adequate for computing a generalised version of radial kurtosis maps.


Prevalence and distribution of Helicobacter pylori cagA and vacA genotypes in the Moroccan population with gastric disease.
Helicobacter pylori infection is the etiologic agent of various gastric pathologies. The severity of disease outcome has been attributed to some H. pylori genotypes, which varies geographically. In Morocco, there are no data regarding the pattern of H. pylori genotypes; therefore, this is the first prospective study conducted in our country to investigate the genotype profiles (vacA and cagA) of H. pylori in patients with gastric pain. Endoscopic biopsies were obtained in patients attending the gastroenterology department of the Hospital University Hassan II of Fez for gastric pain and were directly used for H. pylori detection and genotyping by polymerase chain reaction (PCR). The SPSS software program was used to study the genotype correlation to different clinical outcomes. A total of 429 patients were included in this study, with an infection rate of 69.9%. cagA was detected in 42.3% of cases. However, vacA genotyping reveal a large predominance of s2m2. Infection with multiple strains was detected in 10.8% of cases and incomplete vacA was observed in 31.5%. In Morocco, vacA s1m1 was significantly associated to peptic ulcer diseases, while s2m2 was associated to gastritis. Moroccan H. pylori vacA genotype profiles differ from the Latin American, European, and South African profiles, with more similarities to the North African profile. Because of the small number of cases with gastric cancer, no correlations with H. pylori have been studied, so, further studies will be required in order to highlight the effects of those genes on this disease.


Morphological changes induced by class III chitin synthase gene silencing could enhance penicillin production of Penicillium chrysogenum.
Chitin synthases catalyze the formation of β-(1,4)-glycosidic bonds between N-acetylglucosamine residues to form the unbranched polysaccharide chitin, which is the major component of cell walls in most filamentous fungi. Several studies have shown that chitin synthases are structurally and functionally divergent and play crucial roles in the growth and morphogenesis of the genus Aspergillus although little research on this topic has been done in Penicillium chrysogenum. We used BLAST to find the genes encoding chitin synthases in P. chrysogenum related to chitin synthase genes in Aspergillus nidulans. Three homologous sequences coding for a class III chitin synthase CHS4 and two hypothetical proteins in P. chrysogenum were found. The gene which product showed the highest identity and encoded the class III chitin synthase CHS4 was studied in detail. To investigate the role of CHS4 in P. chrysogenum morphogenesis, we developed an RNA interference system to silence the class III chitin synthase gene chs4. After transformation, mutants exhibited a slow growth rate and shorter and more branched hyphae, which were distinct from those of the original strain. The results also showed that the conidiation efficiency of all transformants was reduced sharply and indicated that chs4 is essential in conidia development. The morphologies of all transformants and the original strain in penicillin production were investigated by light microscopy, which showed that changes in chs4 expression led to a completely different morphology during fermentation and eventually caused distinct penicillin yields, especially in the transformants PcRNAi1-17 and PcRNAi2-1 where penicillin production rose by 27 % and 41 %, respectively.


A simple surgical treatment for bovine digital dermatitis-associated white line lesions and sole ulcers.
Non-healing white line disease (nhWLD) and sole ulcers (nhSU) are seen increasingly in herds endemically affected with bovine digital dermatitis (BDD). In 35 cows with 42 nhWLD or nhSU lesions, the healing process was monitored for up to 28 or 38 days following extensive debridement of loose horn and infected corium under regional anaesthesia, and topical application of tetracycline spray with bandaging. By 28 days, 27/42 (64%) nhWLD and nhSU were completely covered by a new horn layer and this increased to 30/42 (71%) that had healed by 38 days. Lesion sizes on day 0 correlated with clinical healing within the study period. In view of this satisfying therapeutic result, the terms nhWLD and nhSU are proposed for BDD-associated white line disease (BDD-WLD) and BDD-associated sole ulcers (BDD-SU), respectively.


Adenylyl cyclase in the heart: an enzymocytochemical and immunocytochemical approach.
This review provides a discussion of the localization of adenylyl cyclase (AC) in normal mammalian heart tissue employing enzymocytochemistry (detection of the catalytic activity of AC by a metal precipitation technique) and immunocytochemistry (immunolabeling of the enzyme protein with antibodies against AC subtypes). By the metal precipitation technique, AC activity was localized in adult guinea pig cardiomyocytes along the sarcolemma and the T-tubule membranes. This reaction can be enhanced by hormones and guanylyl imidodiphosphate, fluoride, and forskolin. With this technique, no precipitates were detected at the sarcoplasmic reticulum. However, under ischemic conditions, AC activity was also found in the junctional sarcoplasmic reticulum of rat cardiomyocytes. Immunocytochemistry revealed AC in the plasma membrane of rat cardiomyocytes. Detection of AC in the perinuclear space of cardiomyocytes might reflect initiation of synthesis and processing of the enzyme protein. Colocalization of AC with cytoskeleton fibers of non-cardiomyocytes emerging in the cell culture of neonatal rat cardiocytes imply a direct cytoskeletal-AC interaction. Finally, it can be stated that the immunolabeling pattern of AC in cryosections of adult and new-born rat hearts reveals a good correspondence with the localization of AC activity in cardiomyocytes demonstrated by enzymocytochemistry.


[Management of irregular shaped airway foreign body in children].
To explore proper operative methods for removal of irregular shaped foreign bodies in children. Forty-eight emergency cases of irregular shaped airway foreign bodies (plastic ball-pen cap, mini-toys, whistle, pin, thumbtack, milk tooth, pen, steel ball, stone of apricot, chicken bone and screw nail) from Jan. 1998 to Nov. 2000 have been reviewed, especially the operative procedure for removing foreign bodies. The youngest patient was 9-month old and eldest 14 year-old. The average age was 8.3 year-old. The male female ratio was 2.4 storz tracheoscope (Made in German) was applied. Forty-six of the 48 foreign bodies were removed through tracheoscope. The foreign bodies slipped off at the level of the glottis in 3 cases, they were then removed from the opposite bronchus (respiratory difficult syndrome developed in these cases); a thumbtack was removed by tracheotomy; one stone of apricot was removed through. An accurate pre-operative diagnosis is most important in operative management of cases of irregular shaped foreign bodies. General anesthesia, is usually. If the foreign body is too big to pass through the glottis, removing by tracheotomy should be considered.


The role of RB in cell cycle control.
The retinoblastoma protein is an inhibitor of cell cycle progression from the G1 to the S phase of the cell cycle. It acts through its ability to interact with cellular target molecules such as E2F transcription factors. The function of pRB is negatively regulated by a cell-cycle dependent phosphorylation catalyzed by cyclin-dependent kinases in the late G1 cell cycle phase. Recent evidence indicates that this pRB inactivation is a key molecular event leading to the S-phase commitment at the G1 restriction point in the cell cycle. Deregulated inactivation of pRB in G1 phase may be a universal mechanism underlying cellular transformation.


[Treatment of paraungual HPV73-positive Bowen disease with imiquimod cream].
Bowen disease - a squamous cell carcinoma in situ - is associated with oncogenic human papilloma viruses (HPV). The association is best established for genital Bowen disease but also holds for extragenital lesions. The immunomodulatory substance imiquimod is used for the treatment of HPV-induced skin disorders. In the case of paraungual Bowen disease, established treatment options as excision, cryosurgery, radiotherapy or laser treatment might cause persistent nail damage. We successfully treated HPV73-positive Bowen disease in this location with topical imiquimod.


Neurotoxicity and oxidative damage of beta amyloid 1-42 versus beta amyloid 1-40 in the mouse cerebral cortex.
Senile plaques (SP), a neuropathological hallmark of Alzheimer's disease (AD), are characterized by extracellular accumulations of beta amyloid (A beta). SP predominantly contain A beta 42 with a small amount of associated A beta 40. We determined the neurotoxic properties of A beta 42 as compared to A beta 40 by injections into the frontal cortex of three month old C57BL/6 mice. A beta 42 was associated with a significantly larger area of glial fibrillary acidic protein (GFAP) immunoreactivity and a greater density of reactive astrocytes than A beta 40. Immunohistochemical staining for markers of oxidative damage against 3-nitrotyrosine (3-NT) and 8-hydroxydeoxyguanosine (8-OHDG) were significantly more intense around the A beta 42 injection compared to the A beta 40 injection sites. These findings are consistent with previous in vitro studies and suggest that A beta 42 is more neurotoxic and may generate more free radical damage than A beta 40.


A versatile organocatalyst for the asymmetric conjugate addition of nitroalkanes to enones.
5-Pyrrolidin-2-yltetrazole performs as an improved catalyst for the asymmetric addition of a range of nitroalkanes to cyclic and acyclic enones, with good to excellent enantioselectivity.


Association Between Changes in Thyroid Hormones and Incident Type 2 Diabetes: A Seven-Year Longitudinal Study.
Thyroid hormones are important regulators of glucose homeostasis. However, the association between thyroid hormones within the reference range and type 2 diabetes mellitus (T2DM) remains unclear. The aim of this study was to clarify the incidence of T2DM according to the baseline levels and changes of thyrotropin (TSH) and thyroid hormones (free thyroxine and triiodothyronine) in euthyroid subjects. Among the participants who consecutively underwent thyroid function tests between 2006 and 2012 through a yearly health checkup program, 6235 euthyroid subjects (3619 men and 2616 women) without T2DM were enrolled in the study. The change in each hormone was calculated by subtracting the baseline value from the level at the end of follow-up or one year before the diagnosis of diabetes. During 25,692 person-years of follow-up, there were 229 new cases of T2DM. After full adjustment for potential confounders including HbA1c and fasting glucose in Cox proportional hazards models, the individuals in the highest tertile of TSH change (2.5-4.2 μIU/mL) had a greater risk of incident T2DM (hazard ratio [HR] = 1.44 [confidence interval (CI) 1.04-1.98], p = 0.027) in comparison with individuals in the lowest tertile (-4.1 to -0.5 μIU/mL). Simultaneously, the highest tertile of triiodothyronine change (16.3-104.7 ng/dL) and free thyroxine change (0.2-1.6 ng/dL) conferred protective effects against diabetes (HR = 0.60 [CI 0.43-0.85], p = 0.002, and HR = 0.34 [CI 0.24-0.48], p < 0.001, respectively) compared with those in the lowest tertile (-76.5 to -1.8 ng/dL and -0.6 to 0.0 ng/dL, respectively). These associations remained significant when each of the hormones was analyzed as a continuous variable. However, baseline levels or tertiles of TSH and thyroid hormones were not associated with the risk of diabetes. Individual changes in TSH and thyroid hormones, even within the normal reference range, were an additional risk factor of incident T2DM.


Morphometric Analysis of the Neurocranium in an Adult South African Cadaveric Sample.
Craniometric studies of South Africans yield high accuracies of sex and ancestry classification, but most assess only inter-group variation of Black and White individuals, excluding the highly heterogeneous Colored group, which constitute a significant proportion of the population. This study applied a geometric morphometric approach to the neurocrania of 774 Black, Colored, and White individuals to assess sex and ancestry estimation accuracy based on the detected morphological variation. Accuracies of 70% and 83% were achieved for sex and ancestry, respectively, with ancestry-related variation contributing the largest proportion of overall observed variation. Even when comparing the closely related Black and Colored groups, relatively high accuracies were obtained. It is thus recommended that a similar approach be used to develop a contemporary three-dimensional database, which can be used to objectively, reliably, and accurately classify unknown remains in the South African forensic context.


Risks and benefits of sun exposure: implications for public health practice based on the Australian experience.
Over recent years, evidence has been accumulating that vitamin D has a positive impact on our overall health. This may have an impact on the future of our public health advice related to skin cancer prevention. This paper explores, from a public health perspective based on Australian experience, how skin cancer prevention messages should be managed in light of new information about vitamin D and, in particular, the times when sun protection advice should be provided and how the vitamin D message can be complementary to the sun protection message.


Salivary gland scintigraphy using technetium-99m-pertechnetate after autotransplantation of the submandibular salivary gland in the correction of dry eye.
The aim of the study was to determine whether salivary gland scintigraphy using technetium-99m pertechnetate is suitable for checking the vitality and function after autotransplantation of the submandibular salivary gland in patients with dry eye syndrome. To this end, 56 scintigraphic studies in 20 patients have so far been performed. In addition, these scans were evaluated by a region of interest (ROI) technique in order to examine tracer uptake in the early and late stages after surgery. We have been able to prove that in this special respect, too, the salivary gland scintigraphy is suitable for assessing reliably the vitality and function of the transplanted gland. The secretion into the eye and thus the patency of the efferent duct can also be displayed. This proved to be particularly valuable in those cases in which at first no secretion could be seen in the clinical examination. In patients with uncertain excretory function, we were able to distinguish between non-vitality and lack of patency of the secretory duct. Using ROI evaluation, no significant decrease in the salivary function has been detected in long-term follow-up, now extending to 1 year after surgery.


Provision of alcohol hand rub at the hospital bedside: a case study.
A pilot study was performed on a 28-bed acute hospital ward, promoting hand disinfection by providing Sterillium alcohol hand rub at the bedside. Bottles of Sterillium with pump dispensers were attached to the end of each patient's bed, next to the observation charts. Posters promoting the use of the product were prominently displayed and several ward staff attended a presentation on the effectiveness of Sterillium. Although this was a small study, Alert Organism rates during the three-month trial indicated a reduction in methicillin-resistant Staphylococcus aureus (MRSA) incidence and an increased Clostridium difficile incidence. Several other factors that may have influenced the study outcomes will be discussed. There were no health and safety problems during the trial, but other issues were identified which have implications for introducing the bedside rub on a hospital wide basis, including the type of holder used, logistical arrangements and the staff and patient information requirements. The strategies adopted to address these issues will be discussed.


Do fluoroquinolones commonly cause arthropathy in children?
The objective of this paper was to review the relation between fluoroquinolone (FQ) use and arthropathy in children. The biomedical literature from January 1980 to February 2007 was searched using PubMed. Key search terms included fluoroquinolones, arthropathy, tendinopathy and children. Literature was included if it was a clinical trial or meta-analysis examining the use of 1 or more FQs in a pediatric human population and if it had a primary outcome measure of reported incidence of arthropathy or tendinopathy. Articles were excluded if the primary outcome measure was efficacy of an FQ in a particular pediatric disease state, and evaluated safety was a secondary end point. Data was reviewed from 4 large retrospective studies. Three of the 4 studies failed to find a significant link between musculoskeletal injury and FQ treatment. One study reported a correlation between use of pefloxacin and arthropathy, but the authors' conclusions supported the use of FQs in select pediatric cases. Arthropathy that occurs as a result of FQ use in children has not been adequately supported by published data from safety trials in human children. Concerns about arthropathy with FQs should not preclude their use by emergency physicians when appropriate and necessary in pediatric patients.


Core skills in motivational interviewing.
Motivational interviewing (MI) is a client-centered, albeit directive, method for enhancing intrinsic motivation and strengthening commitment for change through exploring and resolving ambivalence. This article presents the core principles of MI and describes its underlying spirit, which consists of attitudes of collaboration, evocation, and respect for client autonomy. Key process markers indicating the use of MI, including ambivalence, resistance, and change talk, are described. A case example is used to illustrate the application of MI-specific core skills (i.e., rolling with resistance, expanding change talk, and developing discrepancy) in response to each of these process markers, and the theoretical basis for the demonstrated interventions is discussed.


Delivery of genes to the eye using lentiviral vectors.
The primary aim of gene transfer into the retinal cells has been to investigate the developmental mechanisms of the retinal cells or to reverse retinal diseases. Retroviruses have been used to investigate the differentiation of retinal cells, to study the embryonic retina in vivo or explant organ culture, and to trace the fate of the cells that were dividing at the time of gene transfer. Using adenovirus, Bennett et al. showed the possibility of using gene therapy to correct degenerative diseases of the central nervous system (CNS) (6). However, owing to the short duration of the gene expression, adenovirus is not suitable for correcting chronic diseases. Currently, lentivirus (7-9) and adenoassociated virus vectors (10-14) are being used for studying and correcting gene therapy of retinal degenerative diseases. Using an HIV vector carrying the green fluorescent protein (GFP) gene expressed from the cytomegalovirus (CMV) promoter, we showed that efficient and long-lasting gene expression could be obtained in the retina (7,8). Moreover, gene expression was restricted to the photoreceptor cells and was more efficient with the rhodopsin promoter. Similar results were reported using adeno-associated virus (AAV) vector. Using a lentivirus vector carrying the phosphodiesterase beta subunit (PDEbeta) gene, the mutation of which causes retinal degeneration called retinitis pigmentosa in rd mice, photoreceptor cells were rescued from degeneration in rd mice for at least 6 mo by PDEbeta transduction using HIV-based lentivirus vector (9).


[Clinical investigation of the positioning accuracy of acute pulpitis pain].
This study aims to investigate the positioning accuracy of acute pulpitis pain and its possible factors. The clinical symptoms and physical signs of 3 432 cases of acute pulpitis were recorded and analyzed by using questionnaire forms, which included age, gender, tooth position, infection origin, pain history, time of acute attack, duration and nature of pain, pain frequency, referred pain areas, percussion examination, temperature pulp test, pulp bleeding, and positioning accuracy. Univariate analysis and multivariate stepwise regression analysis were used for data processing. Pain location was accurately identified by 39.1% of the patients with acute pulpitis. Referred pain could reduce the positioning accuracy of pain (P < 0.05), whereas infection originating from the periodontium could raise it (P < 0.05). Other factors might not be directly related to positioning accuracy (P > 0.05). Some cases of acute pulpitis pain can be located accurately. Referred pain and periodontium infection origin are related to the positioning accuracy of acute pulpitis pain. The exact cause of this correlation needs further study.


Coronary flow reserve predicts cardiopulmonary fitness in patients with coronary artery disease independently of systolic and diastolic function.
Despite revascularization and optimal medical treatment, patients with coronary artery disease (CAD) have reduced exercise capacity. In the absence of coronary artery stenosis, coronary flow reserve (CFR) is a measure of coronary microvascular function, and a marker of future poor outcome in CAD patients. The aim of this study was to examine the relationship among CFR, systolic and diastolic function, peripheral vascular function, and cardiopulmonary fitness in CAD patients. Forty patients with median left ventricular ejection fraction (LVEF) 49 (interquartile 46-55) with documented CAD without significant left anterior descending artery (LAD) stenosis underwent cardiorespiratory exercise test with measurement of VO2 peak, digital measurement of endothelial function and arterial stiffness, and an echocardiography with measurement of LVEF using the biplane Simpson model, mitral early (E) and late (A) inflow velocities, and tissue Doppler diastolic (e') and systolic (s') velocities. Peak coronary flow velocity (CFV) was measured in the LAD using pulse-wave Doppler. CFR was calculated as the ratio between peak CFV at rest and during vasodilator stress. Median CFR was 2.22 (1.90-2.62) and VO2 peak was 21.8 (17.6-25.5). VO2 peak correlated significantly with CFR (r = 0.57, P < 0.001), E/e' (r = -0.35, P = 0.04), and s' (r = 0.41, P = 0.01) and with LVEF (r = 0.35, P = 0.03). CFR remained independently associated with VO2 peak after adjustment for systolic and diastolic function. Coronary flow reserve measured noninvasively predicts cardiopulmonary fitness independently of resting systolic and diastolic function in CAD patients, indicating that cardiac output during maximal exercise is dependent on the ability of the coronary circulation to adapt to the higher metabolic demands of the myocardium.


Apoptotic proteins and markers of differentiation in childhood pineal parenchymal tumors: relationships and prognostic value.
Pineal parenchymal tumors (PPTs) in children and adolescents are uncommon and more data on their biological activity and behavior are still needed. The aim of our study was to estimate the expression and prognostic value of some proteins regulating apoptosis and cell cycle as well as being markers of cellular differentiation in PPTs. Tumor specimens obtained from 27 patients who underwent surgical treatment for PPTs were evaluated in immuno-histochemical analysis. The expression of Bcl-2, Bax, p53, NSE (neuron specific enolase), GFAP (glial fibrillary acidic protein), beta-III tubulin and nestin were studied. Co-localization of two chosen antibodies (e.g. Bcl-2/Bax, BCl-2/NSE, p53/NSE, etc.) was also made with a scanning confocal microscope. Histopathological examination revealed: 15 pineocytomas, 1 intermediately differentiated PPT and 11 pineoblastomas. For further analysis two groups were created: Group I: patients with pineocytoma or intermediately differentiated PPTs (16 cases) Group II: patients with pineoblastoma (11 cases). A statistically significant positive correlation between patients' survival time and tubulin and NSE expression was found. Bcl-2, p53 and nestin correlated negatively with survival time.


Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency.
Adenosine deaminase deficiency is a disorder of purine metabolism manifesting severe combined immunodeficiency (ADA-SCID) and systemic abnormalities. Increased levels of the substrate deoxyadenosine triphosphate (dATP) lead to immunodeficiency and are associated in a murine model with pulmonary insufficiency. We compared a cohort of patients with ADA-SCID and X-linked SCID and found that despite similar radiological and respiratory findings, positive microbiology is significantly less frequent in ADA-SCID patients (p < 0.0005), suggesting a metabolic pathogenesis for the lung disease. Clinicians should be aware of this possibility and correct metabolic abnormalities either through enzyme replacement or haematopoietic stem cell transplant, in addition to treating infectious complications.


Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.
Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.


[Massive oxalosis of the kidney in association with anesthesia using methoxyflurane].
A 20-year old foreigner suffering from progressive renal insufficiency had a massive renal oxalosis. According to case history and clinical analysis oxalosis proved to occur in relation to methoxyflurane general anaesthesia.


Coagulation Profile at Diagnosis in Patients with Acute Lymphoblastic Leukemia.
To evaluate the coagulation parameters at the time of diagnosis in pediatric acute lymphoblastic leukemia (ALL) patients. A total of 65 newly diagnosed ALL patients upto 18 y of age along with 30 age and sex matched controls were included in the study. Coagulation tests including Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (FBG) assay, D-dimer (D-DI) assay, Coagulation inhibitor levels and tests for fibrinolysis were performed. At baseline, APTT of the patients was significantly prolonged (p 0.033), but PT and fibrinogen were comparable in the two groups. Protein C (PC) and Protein S (PS) were both significantly reduced in the cases, while antithrombin was comparable to control values (p < 0.001, p < 0.001 & p = 0.828 respectively). Tissue plasminogen activator levels (tPA) were significantly lower in the cases (p < 0.001) but Plasminogen activator inhibitor type 1 (PAI-1) values were comparable. D-DI levels were significantly high (p < 0.001). The onset of leukemia is associated with hemostatic derangement favouring hypercoagulability. The coagulopathy is due to thrombin activation (as evidenced by raised d-dimer). The decreased fibrinolysis (due to reduced tPA and raised PAI-1) and low levels of PC and PS contribute to the hypercoagulable state at the time of diagnosis.


Failed back surgery syndrome.
Failed back surgery syndrome (FBSS) is a chronic pain condition that has considerable impact on the patient and health care system. Despite advances in surgical technology, the rates of failed back surgery have not declined. The factors contributing to the development of this entity may occur in the preoperative, intraoperative, and postoperative periods. Due to the severe pain and disability this syndrome may cause, more radical treatments have been utilized. Recent trials have been published that evaluate the efficacy and cost-effectiveness of therapeutic modalities such as spinal cord stimulation for the management of patients with failed back surgery. This article will describe the epidemiology and etiology of FBSS. The importance of prevention will be emphasized. In those patients with established FBSS, a guide to interdisciplinary evaluation and management will be outlined. Special attention will focus on recent trials that have studied the efficacy of more invasive procedures such as spinal cord stimulation. Finally, a suggested management pathway is presented. FBSS is a challenging clinical entity with significant impact on the individual and society. To better prevent and manage this condition, knowledge of the factors contributing to its development is necessary. While research on FBSS has increased in recent years, perhaps the best strategy to reduce incidence and morbidity is to focus on prevention. Patients diagnosed with FBSS should be managed in an interdisciplinary environment. More radical treatments for FBSS have now been extensively studied providing clinicians with much needed evidence on their efficacy. Incorporating these results into our current knowledge provides a basis on which to construct an evidence-based guide on how best to manage patients who suffer from FBSS.


Closed intramedullary femoral shortening.
Twelve cases of adult anisomelia were treated with closed intramedullary femoral shortening. Follow-up was conducted at regular intervals until the osteotomy healed. This study reviewed hospital and office records, preoperative and postoperative roentgenograms, and telephone interviews of all patients. An average femoral shortening of 3.7 cm was attained; significant complications such as deep infection or nonunion did not occur. These results suggest that closed intramedullary shortening of the femur produces excellent results in cases of adult anisomelia.


An attempt to modulate the microporous diffusion of a model polypeptide by altering its secondary structure.
The purpose of the present study was to determine whether intentional alteration of the secondary structure of a model polypeptide, conantokin-G, influenced the rate and extent of aqueous pore diffusion across a synthetic microporous membrane. Use of a microporous synthetic membrane allowed for analysis of polypeptide transport without the confounding variables of protein binding, acid- and/or enzyme-mediated degradation, endocytotic uptake, and enzymatic inactivation associated with a biological membrane. Conantokin-G was intentionally changed from its native random coil structure to the alpha-helix structure using calcium, and both structures were verified using circular dichroism. The alpha-helix structure of conantokin-G was retained even after additional free calcium was removed by equilibrium dialysis. Over the concentration range of 1.25 to 20 mM, there was a linear relationship between the solution calcium concentration and the percent of the alpha-helix conformer present. The apparent permeability, the apparent aqueous diffusion coefficient with and without inclusion of the Renkin function, and the hydrodynamic radii estimated by diffusion and a computer-software program were calculated for the random coil and alpha-helix structures of conantokin-G. Calcium-mediated conversion of conantokin-G to its alpha-helix structure did not significantly (p >.05) change its apparent permeability across a microporous membrane. It is suggested that perhaps complete conversion to the alpha-helix structure of only a fraction of the conantokin-G molecules (only 0.45 or 45% of the molecules can be converted to the alpha-helix structure at Ca(2+) concentrations >or= 20 mM) may have limited the extent of transport of the alpha-helix conformer.


The resection of non-hepatic intraabdominal recurrence of gastric cancer.
Surgical resection of hepatic or pulmonary metastases from gastrointestinal cancer has been recognized as a curative modality in some patients. However, the role and outcome of the surgical management of a non-hepatic intraabdominal recurrence of gastrointestinal cancer have not been clearly delineated. We treated 5 patients for non-hepatic intraabdominal recurrence of gastric carcinoma surgically. All the resected specimens were microscopically identified as recurrent gastric cancer. Three of 5 patients received postoperative chemotherapy. The clinicopathological findings were analyzed according to the general rules for gastric cancer study. The lymph nodes were dissected for lymph node metastases. Surgical resection of the tumors combined with total gastrectomy, esophagectomy, or colectomy was performed for the local and peritoneal recurrences. All of the recurrent tumors were macroscopically resected with curative states. One patient died of sepsis 54 days after surgery. Three patients died of recurrent gastric cancer: 2 within 1 year of surgery and 1 after 3 years. One patient still survives disease free 3 years and 6 months after the 2nd operation. Surgical resection for non-hepatic intraabdominal recurrence of gastric cancer is the treatment of choice for selected patients. Surgical resection followed by adjuvant chemotherapy may improve the outcome of these patients.


The effectiveness of person-centred planning for people with intellectual disabilities: A systematic review.
To evaluate the effectiveness of Person-Centred Planning (PCP) on outcomes for individuals with intellectual disabilities (ID) across the age range. The electronic databases PsycInfo, Embase, CINHAL, PubMed, Web of Science, Scopus and Medline were searched for studies evaluating the impact of PCP on people with ID, published between 1990 and 2014; these were supplemented by manual searches of reference lists. Studies were considered irrespective of methodology, sample size and publication source, if outcomes reflected the impact of PCP on individuals with ID. Seven quantitative, five qualitative and four mixed methods studies were included in the review. The overall quality of the evidence was low but suggestive that PCP may have a positive, yet moderate, impact on some outcomes for individuals with ID, particularly community-participation, participation in activities and daily choice-making. For other outcomes such as employment the findings were inconsistent. The evidence supporting the effectiveness of PCP is limited and does not demonstrate that PCP can achieve radical transformations in the lives of people with ID. Clearer descriptions of PCP and its components are needed. Small-scale successful demonstrations of effectiveness exist, but its clinical, cost-effectiveness and wider implementation must be investigated in large scale studies.


Primary inguinal hernia: The open repair today pros and cons.
Open anterior repair for inguinal hernia offers several distinct advantages over endoscopic repair, especially when real-world effectiveness is taken into account. The learning curve for endoscopic techniques is long, whereas the Lichtenstein and other open tension-free techniques are easier to teach and replicate at all levels. The outcomes of Lichtenstein repairs for primary inguinal hernia as performed by non-experts and supervised residents are comparable to those of experts. Moreover, open tension-free repair does not require expensive instruments or dedicated equipment, other than the prosthetic mesh. As such, it is feasible in any operating room anywhere in the world with limited costs. In our opinion, the most important advantage offered by open tension-free repair is that it can be performed under local anesthesia. Nevertheless, local anesthesia has some disadvantages: it requires training, excellent knowledge of the anatomy and the necessary technique, patience, and gentle handling of the tissues. Open inguinal hernia repair is a procedure that every surgeon should know and be able to perform because it is necessary to treat two conditions, groin hernia recurrence after a posterior approach (both laparoscopic and open) and pubic inguinal pain syndrome.


The perceptual enhancement of tones by frequency shifts.
In a chord of pure tones with a flat spectral profile, one tone can be perceptually enhanced relative to the other tones by the previous presentation of a slightly different chord. "Intensity enhancement" (IE) is obtained when the component tones of the two chords have the same frequencies, but in the first chord the target of enhancement is attenuated relative to the other tones. "Frequency enhancement" (FE) is obtained when both chords have a flat spectral profile, but the target of enhancement shifts in frequency from the first to the second chord. We report here an experiment in which IE and FE were measured using a task requiring the listener to indicate whether or not the second chord included a tone identical to a subsequent probe tone. The results showed that a global attenuation of the first chord relative to the second chord disrupted IE more than FE. This suggests that the mechanisms of IE and FE are not the same. In accordance with this suggestion, computations of the auditory excitation patterns produced by the chords indicate that the mechanism of IE is not sufficient to explain FE for small frequency shifts.


Regulatory gene expression patterns reveal transverse and longitudinal subdivisions of the embryonic zebrafish forebrain.
To shed light on the organization of the rostral embryonic brain of a lower vertebrate, we have directly compared the expression patterns of dlx, fgf, hh, hlx, otx, pax, POU, winged helix and wnt gene family members in the fore- and midbrain of the zebrafish. We show that the analyzed genes are expressed in distinct transverse and longitudinal domains and share expression boundaries at stereotypic positions within the fore- and midbrain. Some of these shared expression boundaries coincide with morphological landmarks like the pathways of primary axon tracts. We identified a series of eight transverse diencephalic domains suggestive of neuromeric subdivisions within the rostral brain. In addition, we identified four molecularly distinct longitudinal subdivisions and provide evidence for a strong bending of the longitudinal rostral brain axis at the cephalic flexure. Our data suggest a strong conservation of early forebrain organization between lower and higher vertebrates.


Roxithromycin 150 mg b.i.d. versus amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for the treatment of lower respiratory tract infections in general practice.
Two hundred and forty-two patients over 16 years of age with community-acquired lower respiratory tract infection (LRTI), matched for age and sex, were randomised to receive either roxithromycin 150 mg b.i.d. or amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for 7 days, with a further 7 days if insufficient response was seen. Clinical efficacy at 7 days was 69% for roxithromycin and 56% for amoxycillin/clavulanic acid (p = 0.05) and at study end it was 91% for both antibiotics. There were fewer second treatment courses in the roxithromycin group (26% vs. 38%, p = 0.04) and a shorter treatment duration (8.29 days vs. 9.34 days, p > 0.05). Twelve patients (9.8%) treated with roxithromycin and 19 (17.1%) treated with amoxycillin/clavulanic acid had adverse effects possibly, or probably, related to the antibiotic. Roxithromycin appears to be a more appropriate choice than amoxycillin/clavulanic acid for the treatment of LRTI in the community given its more appropriate in vitro spectrum, efficacy against most common and atypical pathogens, greater cost-effectiveness, more convenient dosage regimen (b.i.d.), and superior tolerability profile.


Evaluation of Conner's continuous performance test in hemodialysis patients.
Memory and cognitive abnormalities such as decreased attention span, impulsiveness, and slow reaction are common among chronic hemodialysis patients. We studied the changes these parameters in 38 hemodialysis patients before and after hemodialysis sessions via Conner's continuous performance test. Mean age of the study patients was 38.0 +/- 12.6 years. There was no significant difference before and after hemodialysis in the number of the successfully recognized matches, the number of the miss fires, and the mean of reaction time of matches. In addition, there was no significant effect of the duration of hemodialysis therapy on the number of successfully recognized matches, the number of missed matches, and the mean reaction time of matches. Educational level of patients did not significantly impact on the number of successfully recognized matches and the mean of reaction time of matches. However, this impact was significant on the number of miss fires during hemodialysis. (P = 0.04). We conclude from our results that hemodialysis did not significantly impact on the cognitive function. However, this hypothesis must be confirmed by other cognitive function tests on larger hemodialysis population.


Characterisation and identification of bacteria using SERS.
Within microbiology Raman spectroscopy is considered as a very important whole-organism fingerprinting technique, which is used to characterise, discriminate and identify microorganisms and assess how they respond to abiotic or biotic stress. Enhancing the sensitivity of Raman spectroscopy is very beneficial for the rapid analysis of bacteria (and indeed biological systems in general), where the ultimate goal is to achieve this without the need for lengthy cell culture. Bypassing this step would provide significant benefits in many areas such as medical, environmental and industrial microbiology, microbial systems biology, biological warfare countermeasures and bioprocess monitoring. In this tutorial review we will report on the advances made in bacterial studies, a relatively new and exciting application area for SERS.


Excess Weight in Spain: Current Situation, Projections for 2030, and Estimated Direct Extra Cost for the Spanish Health System.
Excess weight promotes the development of several chronic diseases and decreases quality of life. Its prevalence is increasing globally. Our aim was to estimate the trend in excess weight between 1987 and 2014 in Spanish adults, calculate cases of excess weight and its direct extra costs in 2006 and 2016, and project its trend to 2030. We selected 47 articles in a systematic literature search to determine the progression of the prevalence of overweight, nonmorbid obesity, and morbid obesity and average body mass index between 1987 and 2014. We projected the expected number of cases in 2006, 2016, and 2030 and the associated direct extra medical costs. Between 1987 and 2014, the prevalence of overweight, obesity, and morbid obesity increased by 0.28%/y (P=.004), 0.50%/y (P <.001) and 0.030%/y (P=.006) in men, and by 0.10%/y (P=.123), 0.25%/y (P=.078), and 0.042%/y (P=.251) in women. The mean body mass index increased by 0.10 kg/m2/y in men (P <.001) and 0.26 kg/m2/y in women (significantly only between 1987 and 2002, P <.001). We estimated 23 500 000 patients with excess weight in 2016, generating 1.95 billion €/y in direct extra medical costs. If the current trend continues, between 2016 and 2030, there will be 3 100 000 new cases of excess weight, leading to 3.0 billion €/y of direct extra medical costs in 2030. Excess weight in Spanish adults has risen since the creation of population registries, generating direct extra medical costs that represent 2% of the 2016 health budget. If this trend continues, we expect 16% more cases in 2030 and 58% more direct extra medical costs.


Reiter's syndrome associated with HLA-B51.
A 22-year-old Japanese man developed polyarthritis with fever and urethritis. He was diagnosed as Reiter's syndrome since he was found to have uveitis and persistent aseptic pyuria. Although, he was negative for HLA-B27 or any other HLA-B27 cross-reactive MHC class I antigens, he was positive for HLA-B51. The laboratory examination showed significant elevation of serum IgG and IgA anti-Chlamydia antibodies. He was successfully treated with a combination of doxycycline, naproxen, salazosulfapyridine and methotrexate with a decrease in IgG and IgA anti-Chlamydia antibodies. Previous studies provided evidence that HLA-B51 itself might be involved in the development of Behcet's disease, which shares common features with Reiter's syndrome, such as uveitis, skin lesions, and polyarthritis. It is therefore suggested that combination of Chlamydia infection and HLA-B51 might play a role in the pathogenesis of Reiter's syndrome in our patient.


Impedimetric detection of influenza A (H1N1) DNA sequence using carbon nanotubes platform and gold nanoparticles amplification.
In this work we report the use of an impedimetric genosensor for the model detection of H1N1 swine flu correlated DNA sequence. An oligonucleotide DNA probe, complementary to the target H1N1 virus sequence, was immobilized onto the electrode surface by covalent binding. Two different protocols, i.e. direct hybridization with the DNA target and a sandwich scheme, were employed and compared. In both cases the resulting hybrid was biotin-labelled to allow the additional conjugation with streptavidin gold nanoparticles (strept-AuNPs). The latter were used with the aim of enhancing the impedimetric signal, thus improving the sensitivity of the technique. The best limit of detection, obtained with the sandwich scheme after signal amplification step was 7.5 fmol (corresponding to 577 pmol L(-1)). Furthermore, a gold enhancement treatment was performed in order to compare the presence and distribution of gold nanoparticles onto the electrode surface. As an alternative way of visualization, streptavidin conjugate quantum dots (strept-QD) were employed to obtain fluorescence images of the DNA-biotin-strept-QD electrode surface. Finally, a comparison between impedance and microscopy was performed in terms of viability and feasibility of the techniques.


The effects of heparin and cortisone on an experimental model of pannus.
The effects of heparin and cortisone were investigated in a model of experimental pannus-mediated cartilage degradation. Rat femoral head cartilages were implanted bilaterally (sc.) into female mice either non-wrapped or wrapped in cotton. Animals were treated with tap water (p.o.), heparin 1000 Units (p.o.), cortisone 2 mg/kg (s.c) and heparin-cortisone combined. After 14 days, the implants were removed and analysed for exudate volume, granulation-tissue dry weight and cartilage glycosamino-glycan (GAG) content. In the heparin-treated animals there was a significant (p less than 0.001) increase in the granulation-tissue dry weight, whilst combined treatment significantly (p less than 0.001) reduced both exudate volume and cartilage degradation. It is possible that the effects on angiogenesis may indicate novel treatment for the growth of pannus and cartilage breakdown.


Identification of mouse itih-4 encoding a glycoprotein with two EF-hand motifs from early embryonic liver.
An essential feature of cell differentiation is the specificity of signal transduction events from extracellular cues, which are considered to be conferred by scaffold, anchoring and adaptor proteins. Our aim was to identify important scaffolding proteins required for liver development. Utilizing subtraction hybridization of embryonic liver cDNA libraries, here we report the full length cDNA sequence for mouse itih-4 (Inter-alpha-trypsin inhibitor H4). Itih-4 encodes a 942 amino acid protein containing two EF-hand (helix-loop-helix) motifs with an unique short loop, with a potential calcium-binding function. Itih-4 is expressed as a strong 3.1-kb transcript in liver, to a lesser extent in lung and heart tissue. RT-PCR demonstrates itih-4 mRNAs abundantly in liver, less in heart and brain, during mid-embryonic gestation. These results suggest that itih-4 is a potential regulator for extracellular matrix proteins and plays a role during early embryonic liver development.


Relationship between persistence of Helicobacter pylori and dysplasia, intestinal metaplasia, atrophy, inflammation, and cell proliferation following partial gastrectomy.
Helicobacter pylori and partial gastric resection are risk factors for gastric cancer. Our aims were to investigate the presence of H. pylori in postgastrectomy patients and to correlate that with alterations in mucosal architecture and cell proliferation. One hundred fifty-one endoscopic biopsies from 22 patients, (15-47 years of age, mean 29.2 years) following partial gastrectomy with Billroth II reconstruction for peptic ulcer disease, were examined for the presence of H. pylori using Giemsa staining. Sections were scored for grade of hyperplasia, intestinal metaplasia, dysplasia, inflammation, and atrophy. Immunohistochemistry for proliferative cell nuclear antigen (PCNA) was used to characterize cell proliferation. H. pylori was observed in 17/22 (77.3%) of patients or in 57/151 (37.7%) of biopsies. Metaplasia was seen in 18/22, chronic atrophic gastritis in 20/22, and cystic glandular dilation in 21/22 patients. The highest type of metaplasia in each patient was: four Type I, five Type IIA and nine Type IIB. Dysplasia was present in 16 biopsies from nine patients. H. pylori was more prevalent in intestinal metaplasia type I (44.8% of biopsies), than in type IIA (32.7%) or type IIB (25%). No H. pylori was detected in regions showing dysplasia or cystic glandular dilation. H. pylori colonization was associated with degree of inflammation (P = 0.00001) and cell proliferation (P = 0.0001). In conclusion, H. pylori is commonly seen many years after gastrectomy, it is associated with an increased epithelial cell proliferation, and it is not present in areas of histologic markers of premalignancy (type IIB metaplasia and dysplasia).


Elevated urinary phenol levels not related to benzene exposure.
Two common over-the-counter medications may elevate urinary phenol to levels exceeding 75 mg/liter (ppm). This study presents data indicating that it is invalid to correct urinary phenol levels to specific gravity of 1.024. Animal studies indicate that having elevated urinary phenol levels secondary to phenyl salicylate ingestion are not harmful.


Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs.
Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished antiproliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.


Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials.
To conduct a meta-analysis of the rates of serious infection and malignancy in patients with early rheumatoid arthritis (RA) who have started anti-tumor necrosis factor (anti-TNF) therapy and had not received treatment with disease-modifying antirheumatic drugs (DMARDs) or methotrexate (MTX). A systematic literature search was conducted through the summer of 2009. All studies included were randomized, double-blind, placebo-controlled trials involving patients with early RA who were started on anti-TNF therapy without prior DMARD/MTX use. Six trials met the inclusion criteria for the meta-analysis, comprising a total of 2,183 patients receiving biologic therapy and 1,236 patients receiving MTX. The data extracted were from published trials. A pooled odds ratio (OR) (determined using Mantel-Haenszel methods, with a continuity correction designed for sparse data) was calculated for serious infections (requiring hospitalization) and malignancies, comparing anti-TNF therapy to MTX control. The pooled OR for serious infections was 1.28 (95% confidence interval [95% CI] 0.82-2.00) and that for malignancies was 1.08 (95% CI 0.50-2.32). There was no significant difference in either the rate of serious infections or the rate of malignancies between the anti-TNF therapy group and the control group. Whereas other meta-analyses have shown an increased risk of serious infection and malignancy in patients receiving anti-TNF therapy, the results of the present meta-analysis show that there is not an increased risk when the patients have early disease and have not previously been treated with DMARDs and/or MTX.