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[The metabolic syndrome exists]. Critics have rightly pointed out that the syndrome's pathophysiology is uncertain, its definition hazardous, its clinical usefulness doubtful, and its public health consequences--if it is considered a disease--enormous. However, no one doubts that certain cardiovascular risk factors tend to cluster. It is this clustering (and nothing else) that defines the syndrome, which therefore does exist.

[Multiple duodenal lipomas. A x-ray computed tomographic diagnosis]. In a 65-year-old man, upper endoscopy revealed several polypoid lesions into the duodenum, for which histologic examination of the biopsy specimens showed normal mucosa. CT studies demonstrated homogeneous fat density of these nodules, and thus were diagnostic of duodenal lipomas. The diagnosis was ultimately histologically confirmed by deeper peri-endoscopic biopsies. About this case and the some previously reported ones, the authors emphasize the interest of CT examination in this small bowel tumor.

Positive H-Y antigen testing in a case of XY gonadal absence syndrome. H-Y antigen testing was positive in a case of pseudohermaphroditism due to XY gonadal absence syyndrome. In conclusion, H-Y antigen may be present even in the absence of testes. Also, the syndrome could not have originated from a defect in the H-Y antigen system.

Long-Range Contacts in Unfolding of Two-State Proteins. Predicting the unfolding rates of proteins remains complicated due to the intricacy present in the unfolding pathway of proteins and further it was observed that the experimental unfolding data were less while compared to folding kinetics. The aim of our present work is to show the variation in long-range contacts observed in various sequence separation bins belonging to all-α, all-β and mixed structural classes of 52 two-state proteins. In this work linear regression technique have been used and regression equations were developed using long-range contacts observed from various sequence separation bins. Also nine topological parameters developed from the 3-D structures of proteins are related with their experimental unfolding rates and their variation in correlation coefficient is observed before and after structural classification. The present work aims to show that long-range contacts formed between residues which are sequentially far and spatially close in the 3-D structure of proteins play a crucial role in the unfolding mechanism of proteins. Also importance of long-range contacts in various experimental and theoretical studies of protein folding along with NMR studies of the unfolded non-native states of proteins have been discussed.

Observations on the development and progression of unilateral high myopia. The purpose of this article is to document the rare observation of the development, progression, retinal changes, and results of visual rehabilitation in a young child with unilateral high myopia, as well as additional clinical observations in four very young patients with this condition. We also examine the role of factors such as amount of astigmatism, presence of strabismus, degree of anisometropia, and penalization in the development of optimal vision in these patients. A review of patients from 1997-2002 disclosed 33 individuals with a diagnosis of unilateral high myopia. Five children with adequate information on the progression of myopia and/or in whom a final visual outcome could be determined were included in this study. We excluded patients with insufficient follow-up, those who did not comply with occlusion, and those with co-existing ocular conditions such as retinopathy of prematurity. Three females and two males (four right eyes and one left) were followed for a period of 16 months to 7 years. Myopic fundus changes were present in three patients. Glasses were the preferred method of optical correction in four patients; one patient was prescribed a contact lens. Occlusion therapy was used in four of the five patients. Strabismus was present in four. Ipsilateral astigmatism of +2.00 D or more was present in three of the affected eyes. The difference in the spherical equivalent refraction between both eyes in each patient ranged from 5 to 20 diopters. In one patient, we observed the progressive development of unilateral myopia from an initial hypermetropia of +2.00 at age 2 months to myopia of -9.00 at the age of 5 years. Unilateral high myopia is probably not present at birth. Our observations support its development in the first few years of life. The results of amblyopia therapy depend on the degree of anisometropia, the co-existence of strabismus, the compliance with penalization, and the presence of retinal abnormalities.

The centenary of discovery of radium. Henri Becquerel presented the discovery of radium by Pierre and Marie Curie at the Paris Academy of Science on 26th December 1898. One century later, radium has been abandoned, mainly for radiation protection difficulties. It is, however, likely that modern techniques of brachytherapy have inherited to those designed for radium sources, and that radium has cured thousands and thousands patients all over the world for about eighty years. The history of discovery and medical use of radium is summarised.

A comparative study of self-perceived public health competencies: practice teachers and qualifying SCPHNs. There is evidence to suggest that population-focused public health nursing is more rhetoric than reality. This quantitative study compares the self-perceived public health competence of qualifying student specialist community public health nurses (SCPHNs) (n = 35) with those of the practice teachers (PTs) facilitating their practice learning (n = 31). Findings suggest that PTs felt more competent than qualifying students on leadership and management for public health, working with communities, and communication skills. However, the qualifying students self-rated higher than the PTs on principles and practice of public health, suggesting that the PTs in this study felt less competent than their qualifying students in key public health skills, such as epidemiology, population health needs assessment, research and evidence-based decision-making. It is recommended that the triennial review of PTs should address not only educational skills but knowledge and skills in contemporary public health practice, a continuing professional development framework for SCPHNs should be developed and funded, providers should assist PTs in keeping up with contemporary public health, and the role of the PT should be recognised and given appropriate support and remuneration.

Culturing cells without serum: lessons learnt using molecules of plant origin. To successfully grow cells in serum-free medium is an interesting challenge to cell biology. The use of such media for in vitro cell culture work would be a key contribution to the 3Rs concept, enabling the avoidance of the use of animals and animal products at all stages of the experiment. In addition, numerous problems related to virus infections transmitted by animal serum would be avoided, thus increasing reproducibility. Prolifix is a new reagent of plant origin. It contains a molecule (GCR 1003) that has an activity similar to that of the mitogenic molecules in serum and could be suitable to substitute serum in culture medium. Two epithelial cell lines, LLC-PK1 and Caco-2, were progressively adapted to a special culture medium containing 10% Prolifix in the absence of serum. After adaptation, cell cultures were characterised. We found that these reagents of plant origin could be promising alternatives to serum. However, more work and effort is needed to improve cell adaptation, cell attachment, growth rates as well as freezing/thawing protocols.

Do children with congenital hypothyroidism exhibit abnormal cortical morphology? Given thyroid hormone (TH)'s essential role in multiple aspects of early brain development, children with congenital hypothyroidism (CH) detected and treated early may still display subtle cognitive and behavioral impairments as well as brain abnormalities. However, effects on their cortical development are not yet known. We used an automated neuroimaging technique to determine if these children differ in cortical thickness (CT) from typically developing controls (TDC) and if the regions showing CT differences reflect severity of initial hypothyroidism and predict later neuropsychological functioning. FreeSurfer Image Analysis Suite was used on archived MRI scans from 41 CH and 42 TDC children aged 9-16 y. Vertex-based procedures were used to compare groups and perform correlations between CT and indices of disease severity and neuropsychological outcome. The CH group showed multiple regions of cortical thinning or cortical thickening within right and left hemispheres relative to TDC. CT values were significantly correlated with early T4 and thyroid-stimulating hormone (TSH) levels and current neuropsychological test indices. The developing cortex is sensitive to early TH loss in CH. Different patterns of cortical thinning or cortical thickening among brain regions may reflect timing of TH deficiency relative to timing of cortical development.

Ultrastructural study of contraction of pulmonary vascular smooth muscle cells. The pulmonary vessels of rats treated with fulvine were studied electron microscopically for morphologic signs of contraction of smooth muscle cells. Except for a number of indirect indications of vasoconstriction such as medial smooth muscle cell hypertrophy and excessive crenation of elastic laminae, conspicuous smooth muscle cell excrescences were observed and were interpreted to be a direct result of contraction. The close relationship between contraction and smooth muscle cell excrescences was confirmed by their simultaneous occurrence within 1 minute after administration of histamine to isolated perfused guinea pig lungs. The images of pulmonary vessels of rats with prolonged survival times after fulvine administration suggested a gradual increase in the size of the excrescences with a simultaneous degeneration of their cytoplasmic content, and in some cases their eventual detachment from the main cell body. The latter changes were possibly associated with the widespread vasculitis that often occurred at longer intervals after fulvine application. The smooth muscle cell excrescences in pulmonary veins were generally much more prominent than those in pulmonary arteries. This difference was probably caused by the more rigid structure of the arterial wall whcih prevented the formation of large excrescences. The mechanism of the formation of smooth muscle cell excrescences, their possible general validity as markers of vascular smooth muscle cell contraction, and the implications for the mechanism of action of fulvine are briefly discussed.

The role of CGRP and CALCA T-692C single-nucleotide polymorphism in psoriasis vulgaris. Calcitonin gene related protein (CGRP) is increased in both lesional and non-lesional psoriasis. The role of CGRP in the pathogenesis of psoriasis vulgaris is still not clear. We designed to determine the CGRP-I (or CALCA), II (or CALCB) gene expression and morbidity and CALCA T-692C single-nucleotide polymorphism (SNP). Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected, and CGRP level and CGRP-I, II mRNA expression were measured in psoriasis patients and healthy controls. The CALCA T-692C genetic polymorphism in psoriasis and control subjects was also compared. A higher expression of CGRP-I, II mRNA in PBMCs in psoriasis patients. The plasma CGRP level in psoriasis patients was also higher than that in healthy subjects. SNP analysis showed carriers of the T-692C allele were over-represented in non-drinking Patients. The plasma CGRP level was higher in alcohol-drinking patients with TT genotype than that with TC genotype. The plasma CGRP level is increased in psoriasis patients and CALCA T-692C polymorphism TT genotype is a factor for the affectability in alcohol-drinking Psoriasis vulgaris patients.

Effect of K+ channel blockers on the clinical course and histological features of experimental allergic encephalomyelitis. Beneficial clinical effects of 4-aminopyridine (4-AP) in multiple sclerosis (MS) have been reported. The use of 4-AP in MS is based upon its ability to facilitate conduction in axons blocked by demyelination. This improvement is due to blocking of potassium (K+) channels in these fibres. Because K+ channels also play an important role in immune mechanisms successful treatment with K+ channel blockers in neuroimmunological diseases may have several causes. Therefore it seems important to study effects of K+ channel blockers in animal models of autoimmune disease. We studied the effects of 4-AP and quinidine on actively induced acute experimental allergic encephalomyelitis (EAE) in Lewis rats. There was no effect on the incidence of the disease. The severity of the disease was also unchanged although the disease duration was slightly diminished in the treated groups. Immunohistological comparison between the animals of different groups showed no differences. We conclude that 4-AP and quinidine are not capable of significantly changing the clinical course of EAE.

One-year comparative study of gold sodium thiomalate and auranofin in the treatment of rheumatoid arthritis. The therapeutic benefits and toxicity profile of auranofin (AF) have been compared with that of gold sodium thiomalate (GSTM) over a one-year period in 120 patients with rheumatoid arthritis. A similar number of patients on both drugs remained in the study at one year (approximately 60%), and showed similar statistically significant improvement (p less than 0.01) in all clinical variables measured. At no time during the study was there a statistically significant difference in the clinical benefit obtained with either drug. Withdrawal from the study through lack of therapeutic benefit was twice as frequent with AF as with GSTM (11 compared to 6). Withdrawal due to a toxic reaction was twice as frequent and were potentially more serious with GSTM than with AF (15 compared to 9). We conclude that AF has a therapeutic potential similar to that of GSTM, however side effects were less prevalent and, when they did cause withdrawal of the drug, were potentially less serious.

Spatial variability of ammonium and nitrate in soils near a poultry farm. This paper assesses the distribution of ammonium (NH4+) and nitrate (NO3-) nitrogen deposition in native bushland soil adjacent to an open ventilated poultry farm. The farm is located in Thirlmere 150 km south west of Sydney, Australia. A total of 104 geographically referenced soil cores were obtained from the study area. Soil pH, electrical conductivity (EC), NH4(+) - and NO3(-)-nitrogen concentrations were analysed for variable trends at three depths, i.e. 0-30, 30-60, and 60-90 cm. Significantly higher concentrations of the two nitrogen forms and EC were observed nearer to the farm in the surface soil samples (0-30 cm). The distribution of NH4+, NO3- and EC were all correlated in surface samples throughout the study area. There was no indication of NH4+ and NO3- leaching within soil profile sampled and it appears that weeds and native vegetation had utilised the accumulated nitrogen. The level of N deposition adjacent to the poultry farm decreased downwind due to dispersion of plume and to the buffering effects from the bushland.

Antibodies to human squamous cell carcinoma. We are studying membrane antigens of human squamous cell cancer with the use of naturally occurring autologous antibodies from patients' sera, along with a set of other serologic reagents and monoclonal antibodies raised against cultured squamous cell lines. Twenty-eight squamous cell carcinoma cell lines have been established in our laboratory from tissues obtained from 23 patients. Antibody reactivity has been found against the autologous tumor cell line in 13 of 23 patients. One of these is of sufficient titer for detailed analysis. Four cell lines are available from this patient. UM-SCC-17A is derived from the primary laryngeal carcinoma, and UM-SCC-17B is derived from a lymph node metastasis removed during the same surgical procedure. Fibroblasts have been cultured from normal mucosa, and a B-lymphoblastoid line has been developed by Epstein-Barr virus transformation of the patient's peripheral blood lymphocytes. Antibody from this patient reacts with the UM-SCC-17A and -17B tumor cell lines but does not react with the normal fibroblasts (UM-NF-17).

Effect of rib cage and abdominal restriction on total respiratory resistance and reactance. In 14 healthy male subjects we studied the effects of rib cage and abdominal strapping on lung volumes, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs). Rib cage, as well as abdominal, strapping caused a significant decrease in vital capacity (respectively, -36 and -34%), total lung capacity (TLC) (-31 and -27%), functional residual capacity (FRC) (-28 and -28%), and expiratory reserve volume (-40 and -48%) and an increase in specific airway conductance (+24 and +30%) and in maximal expiratory flow at 50% of control TLC (+47 and +42%). The decrease of residual volume (RV) was significant (-12%) with rib cage strapping only. Abdominal strapping resulted in a minor overall increase in Rrs, whereas rib cage strapping produced a more marked increase at low frequencies; thus a frequency dependence of Rrs was induced. A similar pattern, but with lower absolute values, of Rrs was obtained by thoracic strapping when the subject was breathing at control FRC. Xrs was decreased, especially at low frequencies, with abdominal strapping and even more with thoracic strapping; thus the resonant frequency of the respiratory system was shifted toward higher frequencies. Partitioning Rrs and Xrs into resistance and reactance of lungs and chest wall demonstrated that the different effects of chest wall and abdominal strapping on Rrs and Xrs reflect changes mainly of chest wall mechanics.

[Tadalafil for erectile dysfunction associated with cardiovascular diseases]. Erectile dysfunction (ED) seriously affects the quality of men's sexual life. Recent studies have shown that ED is closely related with cardiovascular diseases, and they have many similar pathogenic mechanisms and common risk factors. A great many researches have confirmed the clinical efficacy of tadalafil in the treatment of ED associated with cardiovascular diseases. With its prolonged action of 36 hours, tadalafil can not only increase the self-confidence of ED males but also improve the quality of life of both the patients and their partners.

Interpretation of blood glutethimide, meprobamate, and methyprylon concentrations in nonfatal and fatal intoxications involving a single drug. We evaluated blood concentrations of three nonbarbiturate sedative-hypnotics in 19 nonfatal (NF) and five fatal (F) intoxications which were "pure" (i.e. which involved only one drug each): glutethimide, 4 (NF), 3 (F); meprobamate, 9 (NF), 1 (F); and methyprylon, 6 (NF), 1 (F). For each of the 24 cases, both a comprehensive toxicology panel (including blood and urine) and the clinical history established that only a single drug had been ingested. Blood drug concentrations showed statistically significant correlation with the level of consciousness for nonfatal meprobamate intoxication (p less than 0.01) and nonfatal methyprylon intoxication (p less than 0.05). Blood glutethimide concentrations did not show such correlation. Death was associated with a mean blood glutethimide concentration in excess of 4.0 mg/dL, a blood meprobamate concentration of 20.5 mg/dL, and a blood methyprylon concentration of 11.7 mg/dL. Interpretation of blood concentrations of these compounds is discussed, and physical findings and demographic data are presented.

Solid phase synthesis of diamides as potential bone resorption inhibitors. Unsymmetrical diamide libraries have been prepared by a general and versatile solid phase route, using diacid templates in combination with aromatic and aliphatic amines chosen with the help of statistical experimental design. The compounds were tested as potential inhibitors of osteoclast vacuolar ATPase.

Mucosal and systemic immunity to intestinal reovirus infection in aged mice. Systemic immunity is progressively impaired in aging, predisposing to morbidity and mortality from neoplasia and infectious disease. However, the effect of aging on mucosal immunity is controversial. To assess intestinal immunity in aging, young and aged mice were orally exposed to reovirus or cholera toxin (CT) and specific antibody and reovirus-specific cytotoxic T-cell (CTL) responses were assessed. As previously reported, aged mice immunized orally with CT mounted diminished intestinal IgA responses to CT compared to young mice. In contrast, aged mice yielded two to three-fold more reovirus-specific IgA-producing cells in the Peyers's patches (PP) compared to young mice, and higher titers of reovirus-specific IgA in fragment culture supernatants. Cytotoxicity and CTL frequencies from aged mice were not different from those of young mice. Together, these results suggest a diminished potential for systemic and intestinal immunity to orally applied protein antigens in aging, but an intact ability to respond to intestinal virus infection. Infection with a replicating virus may induce inflammatory mediators and innate immune factors that potentiate the priming of mucosal immunity; overcoming aging related deficits otherwise observed following oral immunization with non-replicating antigens, and suggests the importance of antigen replication to antigen-specific immunotherapy strategies in the elderly.

Evaluation of skull base erosion in nasopharyngeal carcinoma: comparison of plain radiography and computed tomography. Over a period of 16 months, a total of 175 patients with newly diagnosed nasopharyngeal carcinoma (NPC) were evaluated with plain radiography and computed tomography (CT) of nasopharynx and base of skull. 54 of 175 patients (30.9%) had CT evidence of skull base erosion. Plain radiography failed to demonstrate the skull base erosion in 22 of 54 patients (40.7%) and underestimated the extent of bony involvement in another 21 patients (38.9%). In 14 of 54 patients (25.9%), there was also false suspicion of bony erosion in the plain films in one or more regions of the skull base which was not substantiated by CT and subsequent clinical course. The present study shows that plain radiography lacks sensitivity and specificity in detecting skull base erosion by NPC. CT evaluation of NPC patients should include thin CT sections of base of skull for detection of subtle bone erosion, and this would allow better decision concerning the shielding of the pituitary-hypothalamic axis during radiotherapy for improvement in therapeutic ratio. For the investigation of individuals highly suspicious of harboring NPC, even when the plain radiography is negative, CT should still be performed as this may give the only clue to the presence of a small submucosally spreading NPC.

Vegetal fiber paper matrix impregnated with silica gel for benzene removal. Removing benzene from indoor space plays an important role in indoor air purification. A novel filter with vegetal fiber paper (VFP) as matrix hosting silica gel is proposed in this paper for benzene removal. In order to investigate the feasibility and performance of this idea, firstly, three pieces of VFP samples impregnated with different amounts of silica gel are fabricated and their benzene adsorption quantities are tested. The results show that three times is recommended as the optimal number for impregnating. The VFP sample impregnated with silica gel after the third impregnating exhibits commendable coating stability and good benzene adsorption performance. Additionally, at low relative pressure (Pb /Ps ≤ 0.05), the experimental data of benzene adsorption isotherms fit well with the Langmuir model with R2 greater than 0.97. Then, two actual filters made of VFP impregnated with silica gel after the third impregnating were fabricated. It is found that the pressure drop of the actual filter is only 1200 Pa/m when the air velocity is 2 m/s. Besides, the one-pass efficiency of the filter can reach to 19.44%. It is expected that the silica gel coated on the filter can be modified to improve the purification performance of the filter.

Transactivation of the human MDR1 gene by hepatitis B virus X gene product. Persistent hepatitis B virus (HBV) infection may cause hepatocellular carcinoma. Patients with hepatocellular carcinoma are characterized by nonresponsiveness to chemotherapeutic agents. While many studies have been devoted to understanding the hepatocarcinogenesis mechanism of HBV, the possible relationship between HBV and the drug sensitivity phenotype of cancer cells has rarely been addressed. The hepatitis B virus X gene encodes a transcription transactivator which has been suggested to be a potential factor in viral hepatocarcinogenesis. The role of HBV pX in mediating the drug resistance phenotype of hepatoma cell lines was examined in this study. Standard transfection and chloramphenicol acetyltransferase assay were utilized to examine the effect of HBV pX transactivator on a reporter gene under the control of the human multidrug resistance (MDR) 1 upstream regulatory elements. Selected Hep G2 clones with or without HBV pX expression were tested for their sensitivity towards various anti-cancer agents by utilization of MTT assay. The expression of HBV pX in both Hep G2 (p53+) and Hep 3B (p53-) cells resulted in transactivation of the reporter gene under control of the human MDR1 upstream regulatory elements. Northern blot analysis indicated that expression of the endogenous MDR1 gene was also elevated in Hep G2 clones with HBV pX expression. Decreased drug sensitivity towards adriamycin, vinblastine, and VP-16 was observed in Hep G2 clones with HBV pX expression. HBV pX can transactivate the MDR1 gene. Drug sensitivity was altered in Hep G2 cells with HBV pX expression.

Informatics in radiology: image exchange: IHE and the evolution of image sharing. The sharing of radiologic images has become a fundamental part of radiology services and is essential for delivering high-quality care. Film is quickly becoming obsolete as a means of transporting and sharing large volumes of imaging data. Image sharing has evolved from film to transportable media (eg, compact disks) to direct electronic exchange over the Internet. The latter two means of image sharing have associated work flow-related and technical challenges for which solutions are being developed. Integrating the Healthcare Enterprise (IHE) provides a standards-based approach to the development of robust, universally accepted solutions. Several IHE profiles have been developed to provide a framework for current image sharing efforts. The Philadelphia and New Jersey Health Information Exchanges and the Canada Health Infoway represent efforts to apply IHE technical profiles to facilitate the secure and confidential exchange of electronic images over the Internet. The research community is concomitantly developing solutions that solve image exchange issues that are specific to research (eg, the sharing of deidentified data) but that might also be encountered in the general population. The personal health record is a more recent development that may provide consumers with direct control over the process of sharing images electronically with their healthcare providers.

Increase in the capability of interleukin 2 gene-transduced renal cell carcinoma cells to induce cytotoxic lymphocytes. The immunogenicity of human cancer cells transfected with interleukin 2 (IL-2) gene, a potent vaccine candidate, has not yet been fully investigated. Human renal cell carcinoma (RCC) cells transduced with human IL-2 gene (RCC-IL-2) were investigated in vitro for the capability to induce lymphokine-activated killer (LAK) or cytotoxic T lymphocyte (CTL) activity in peripheral blood mononuclear cells (PBMC) or tumor-infiltrating lymphocyte (TIL). The RCC-IL-2 cells stimulated PBMC to demonstrate LAK activity, and also stimulated autologous TILs to proliferate and exhibit cytotoxicity relatively restricted to autologous tumor cells. In contrast, both parental RCC and RCC transduced with neomycin gene alone failed to induce these activities. These results indicate that RCC-IL-2 cells are more potent than the other RCC cells with regard to inducing cytotoxic lymphocytes against autologous tumor cells.

Adenoma of the iris pigment epithelium. The clinical, fluorescein angiographical and histopathological findings of a mucous-producing adenoma apparently arising from the iris pigment epithelium is reported, and the differential diagnosis is discussed. Benign epitheliomas of the iris pigment epithelium are exceedingly rare and are usually heavily pigmented tumors. This appears to be the second documented case of a nonpigmented benign epithelioma of the iris.

Mechanisms of selenium-mediated protection from photocarcinogenesis and cell death are not solely p53-dependent. Recent studies published in Oncogene and Proc. Natl. Acad. Sci. USA ascribe a role for selenium, acting through wild type p53, in protecting skin cells in culture from ultraviolet radiation-induced death. While selenium clearly protects cells against ultraviolet radiation-induced death, data that we present and discuss in this letter shows that wild type p53 is not required for such protection. Moreover the non-physiologically high levels of selenium used in some studies leads us to question the relevance of such effects for selenium-induced photoprotection.

Persisting remodeling and less airway wall eosinophil activation in complete remission of asthma. Individuals with asthma may outgrow symptoms despite not using treatment, whereas others reach complete remission (CoR) with absence of airway obstruction and bronchial hyperresponsiveness. It is uncertain whether this associates with remission of all inflammatory and remodeling asthma features. To compare the pathologic phenotype of individuals with asthma with CoR and clinical remission (ClinR) and those with active asthma, with and without the use of inhaled corticosteroids (ICS). We investigated 165 individuals known with active asthma, on reexamination having CoR (n = 18), ClinR (n = 44), and current asthma (CuA, n = 103, 64 with and 39 without ICS). MEASUREMENTS MAIN RESULTS: Inflammatory cells were measured in blood, induced sputum, and bronchial biopsies; histamine and ECP in sputum; and eosinophilic peroxidase (EPX) immunopositivity and remodeling (epithelial changes, E-cadherin expression, basement membrane [BM] thickening, collagen deposition) in bronchial biopsies. Median (range) blood eosinophils from CoR were significantly lower than those from CuA (0.10 [0.04-0.24] vs. 0.18 [0.02-1.16] × 10⁹/L). Bronchial EPX immunopositivity was lower in CoR than in both ClinR and CuA (67 [0.5-462] vs. 95 [8-5329] and 172 [6-5313] pixels). Other inflammatory findings were comparable. BM thickness was lowest in CuA, caused by lower BM thickness in those using ICS (CoR, 6.3 [4.7-8.4]; ClinR, 6.5 [3.8-11.7]; CuA, 5.7 [2.8-12.6]; and ICS using CuA, 5.3 [2.8-8.2] μm). CoR is still accompanied by airway abnormalities because BM thickness is similar in individuals with asthma with CoR, ClinR, and CuA without ICS. Airway eosinophilic activation best differentiates these three groups, signifying their importance in the clinical expression and severity of bronchial hyperresponsiveness in asthma.

MicroRNA-494 plays a role in fiber type-specific skeletal myogenesis in human induced pluripotent stem cells. Mitochondrial oxidative capacity in skeletal muscle is known to decrease in diabetic patients, and sarcopenia is a risk factor for diabetes, particularly in elderly people. We previously revealed that microRNA (miR)-494 inhibits mitochondrial biogenesis during myogenic differentiation in murine C2C12 cells and others reported that exercise regulates miR-494 levels in obese sedentary individuals with increased risk of type 2 diabetes. In this study, to investigate the therapeutic potential of miR-494, we first investigated the role of miR-494 during human skeletal myogenesis. Using human induced pluripotent stem (hiPS) cells stably transfected with the Tet/ON-myogenic differentiation 1(MYOD1) gene (MyoD-hiPS cells), we found that miR-494 expression transiently increased and was downregulated after myogenic induction. In miR-494 transfected MyoD-hiPS cells, the level of high oxidative fiber (type IIa) marker proteins specifically decreased, while no change in the total number of cells was observed. In contrast, the expression of both type I and type IIx markers was unaffected by miR-494 overexpression. Furthermore, miR-494 overexpression suppressed basal oxygen consumption rate concomitant with the inhibition of myotube formation and without significant effects on the mitochondrial content. These results suggest that miR-494 plays a novel role in the fiber type-specific skeletal myogenesis in MyoD-hiPS cells, distinct from murine C2C12 myogenesis.

Blood pressure, cognitive dysfunction, and dementia. With the aging of the population, the incidence and prevalence of cognitive disorders are increasing. Blood pressure plays an important role in the pathogenesis or clinical progression of stroke, vascular dementia, and Alzheimer's disease. Data from different studies reveal that the uses of antihypertensive medications decrease the risk of dementia and cognitive dysfunction. Several studies also have demonstrated a relationship between hypotension, cognitive decline, and dementia. In this review we are trying to demonstrate the relationship between blood pressure and cognitive function and also the effect of antihypertensive medications on dementia and cognitive dysfunction.

Recurrent reversible acute renal failure from amphotericin. A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.

[How can the mentally ill achieve sustained employment? Supported employment versus pre-vocational training]. People with severe mental disorders are often without work, although work may have a positive effect on their health. The paper presents some results in this field from the German S3 guidelines on psychosocial therapies. In terms of evidence-based medicine supported employment (SE - first place then train) has proven to be most effective. Nevertheless, SE is still rare in Germany. Pre-vocational training, however, follows the concept first train then place and is offered in rehabilitation of the mentally ill (RPK) centres in Germany. There is some evidence that the programs are beneficial for users. The UN Convention for the Rights of Persons with Disabilities outlines an obligation for work on an equal basis with others and for vocational training. So far, the German mental health system only partly meets these requirements.

Detection of noroviruses in foods: a study on virus extraction procedures in foods implicated in outbreaks of human gastroenteritis. Disease outbreaks in which foods are epidemiologically implicated as the common source are frequently reported. Noroviruses and enteric hepatitis A viruses are among the most prevalent causative agents of foodborne diseases. However, the detection of these viruses in foods other than shellfish is often time-consuming and unsuccessful. In this study, three virus concentration methods were compared: polyethylene glycol (PEG) plus NaCl, ultracentrifugation, and ultrafiltration. Two RNA extraction methods, TRIzol and RNeasy Mini Kit (Qiagen), were compared for detection of viruses in whipped cream and lettuce (as representatives of the dairy and vegetable-fruit food groups, respectively). A seeding experiment with canine calicivirus was conducted to determine the efficiency of each virus extraction procedure. The PEG-NaCl-TRIzol method was most efficient for the detection of viruses in whipped cream and the ultracentrifugation-RNeasy-Mini Kit procedure was best for detection on lettuce. Based on the seeding experiments, food items implicated in norovirus-associated gastroenteritis outbreaks were subjected to the optimal procedure for a specific composition and matrix. No noroviruses were detected in the implicated food items, possibly because the concentration of virus on the food item was too low or because of the presence of inhibitory factors. For each food group, a specific procedure is optimal. Inhibitory factors should be controlled in these procedures because they influence virus detection in food.

Cholinergic innervation of the retrosplenial cortex via the fornix pathway as determined by high affinity choline uptake, choline acetyltransferase activity, and muscarinic receptor binding in the rat. The cholinergic projections from basal forebrain nuclei to the retrosplenial cortex (RSC) have previously been studied using a variety of histological approaches. Studies using acetylcholinesterase (AChE) histochemistry and choline acetyltransferase (ChAT) immunocytochemistry have demonstrated that this projection travels via the cingulum on route to the RSC. Preliminary studies from our laboratory, however, have shown that the fornix may also be involved in this projection. The present study uses the combination of pathway lesions, and the analysis of cholinergic neurochemical markers in the RSC to determine the role of the fornix in the cholinergic projection to the RSC. High affinity choline uptake (HACU) and ChAT activity were measured in the RSC of control rats, animals with cingulate lesions, and animals with fornix plus cingulate lesions. Fornix plus cingulate lesions resulted in significant deceases in HACU and ChAT activity in comparison to cingulate lesions alone. Muscarinic receptor binding was also evaluated in combination with the various lesions, and a significant increase in retrosplenial receptor binding was noted following fornix lesions. Together, these results support the concept of a fornix-mediated cholinergic pathway to the RSC.

Lymphocyte function in experimental African trypanosomiasis. VII. Loss of antigen-nonspecific suppressor-T-cell activity. The extent of immunosuppression occurring in mice infected with the pathogenic African trypanosomes was studied. Spleen cells from Trypanosoma rhodesiense-infected C57BL/6J mice were tested for antigen-nonspecific suppressor-T-cell (Ts) activity after concanavalin A (Con A) treatment in vitro. After exposure to Con A, control and infected mouse spleen cells were added to responder spleen cell cultures stimulated with sheep erythrocytes (SRBC). Assays for the resultant plaque-forming cell responses to SRBC revealed that antigen-nonspecific Ts activity was lost during the first week of infection. Changes in infected mouse T-cell subpopulations, including a terminal loss of Lyt 2.2+ cells, accompanied but did not precede the demonstrable loss of Ts function. Splenic suppressor macrophages which arise during infections with T. rhodesiense also did not seem to be associated with the loss of antigen-nonspecific Ts activity. It is concluded that the generalized immunosuppression associated with experimental African trypanosomiasis extends to the mitogen-induced Ts population.

Diagnostic and therapeutic problems with an unusual congenital cystic hygroma of the orbit. A case of an extensive congenital cystic hygroma in an unusual situation in the orbit is presented. The lesion occurred as an ulcerative, rapidly--growing and repeatedly--bleeding tumour with destruction of the left orbit, parts of the middle face, the nose and the base of skull. Despite X-ray investigation, computed tomography, nuclear magnetic resonance imaging and angiography it was impossible to give a reliable diagnosis. Because of the rapid growth of the tumour and its uncertain nature a radical resection with exenteration of the orbit, resection of the zygoma, the soft tissues of the cheek and parts of the nose and skull base was performed. One year after the resection there was no sign of recurrence.

A comparative genome analysis of the RpoS sigmulon shows a high diversity of responses and origins. The stationary-phase response mediated by the RpoS sigma factor (σ(S), σ³⁸) has been widely studied as a general mechanism of activation of highly diverse genes that maintain cell viability. In bacteria, genes for diverse functions have been associated with this response, showing that bacteria use a large number of functions to contend with adverse conditions in their environment. However, little is known about how the genes have been functionally recruited in diverse organisms. In this work, we address the analysis of genes regulated by σ(S), based on a comparative genomic-scale analysis considering four versatile bacterial species that represent different lifestyles and taxonomic groups, Escherichia coli K-12, Geobacter sulfurreducens, Borrelia burgdorferi and Bacillus subtilis, as well as the extent of conservation in bacterial genomes, as a means of assessing the evolution of this sigmulon across all organisms completely sequenced. The analysis presented here shows that genes associated with the σ(S) response have been recruited from diverse regulons to achieve a global response. In addition, and based on the distribution of orthologues, we show a group of genes that is highly conserved among all organisms, mainly associated with glycerol metabolism, as well as diverse functional genes recruited in a lineage-specific manner.

Image analysis of proliferating cells in tumors of the human nervous system: an immunohistological study with the monoclonal antibody Ki-67. Obtaining growth fractions from immunohistological preparations by the commonly used cell count calculation method is time consuming. For the first time, we investigated and compared the detection of proliferating cells in immunohistologically labeled tissue from tumors of the nervous system using the monoclonal antibody Ki-67 by a new computerized image analysis system and by cell count calculation. The two methods showed a high correlation (correlation index, 0.98) in 37 gliomas (2 pilocytic astrocytomas, 10 Grade II astrocytomas, 5 Grade III astrocytomas, 20 Grade IV astrocytomas and glioblastoma multiforme) and a heterogenous group of 10 additional tumors of the nervous system, including oligodendroglioma, pineoblastoma, primary central nervous system lymphoma, and neurofibroma. Advantages of and indications for image analysis are as follows: 1) time-saving evaluation of immunohistological preparations enables their use in neuro-oncological routine diagnostics and examination of larger cell populations, thus leading to more precisely reproducible results, especially in heterogenous tumors; 2) image analysis, calculating the area of cell nuclei rather than their number, avoids difficulties with fragmented or overlapping nuclei; 3) analysis of different antibodies (for example, Ki-67 and anti-proliferating cell nuclear antigen) may be performed with the same program; 4) investigation of a larger patient group may lead, in combination with the histopathological diagnosis and clinical parameters, to better adapted therapeutic concepts.

Reduction of faecal worm egg count, worm numbers and worm fecundity in sheep selected for worm resistance following artificial infection with Teladorsagia circumcincta and Trichostrongylus colubriformis. We examined the changes to populations of Trichostrongylus colubriformis and Teledorsagia circumcincta in mature sheep selected for reduced faecal worm egg count (WEC). Worm resistant (n=19) and control (n=10) genotype sheep were penned and dosed with a total of 10,000 T. colubriformis and 10,000 T. circumcincta per week for 18-weeks. Sheep genotypes were from lines previously bred over 15 years for either low WEC (resistant) or non-selected (control). Weekly WEC and the proportion of larvae from each species in faecal culture were measured during weeks 3-17. Egg hatchability was assessed on a pooled faecal sample from worm resistant or control genotype sheep at weeks 7, 9, 10, 13, 14 and 17. At week 18 the number of adult and immature worms (early and late 4th, and 5th stage), and indicators of worm fecundity (female worm length and number of eggs in utero) were assessed at necropsy. Results show that resistant sheep had reduced mean WEC to only 18% of the control (P<0.05) and increased the proportion of T. circumcincta larvae in faecal culture during weeks 8-17 (P<0.10). Egg hatch assays indicated a slight reduction in the viability of eggs from worm resistant genotypes at weeks 14 (P<0.05) and 17 (P<0.10). At necropsy, resistant animals had 93% fewer adult T. colubriformis, 44% fewer adult T. circumcincta and had reduced indicators of fecundity in T. circumcincta by up to 40% (P<0.05). We observed no change in the number T. circumcincta worms but an 11% increase in the proportion of early 4th stage T. circumcincta larvae in resistant animals (P<0.05). There were different temporal patterns in WEC and different prediction equations for WEC from necropsy traits for the two sheep genotypes (P<0.05). Thus, our results suggest a changed host-parasite relationship in sheep selected for low WEC. We conclude that lower WEC is achieved through reduced number of adult worms for both species and reduced fecundity for T. circumcincta. These results support the hypotheses that worm resistant sheep with a strong immune function can regulate T. colubriformis by rejecting adult worms but that T. circumcincta is regulated through a combination of suppressed development and reduced female fecundity.

Multifactorial determination of hypertensive nephroangiosclerosis. Essential hypertension causes renal injury. Hypertensive nephroangiosclerosis (HN) or hypertensive nephropathy are terms most commonly used to describe this renal pathology. Although specific histological lesions occurring in affected kidneys are well known, pathogenesis of hypertension-related renal scarring is not completely understood. Evidence exists to support the theory that other factors such as aging, black race or smoking, beside blood pressure, contribute to the development and progression of HN. Metabolic disturbances, cocaine and nonsteroidal anti-inflammatory drug abuse, ochratoxin A exposure, dietary salt intake, heavy metal toxicity, hantavirus infection and perinatal programming are also considered risk factors. Renal susceptibility genes may determine whether hypertension-induced progressive renal damage occurs and how severe it is. Determination of all risk factors may identify patients at high risk of renal failure and help tailor an appropriate management. In the present paper, the knowledge available on this clinically important objective is discussed.

Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory. Aging is characterized by a progressive cognitive decline that leads to memory impairment. Because the cyclic nucleotide cascade is essential for the integrity of synaptic function and memory, and it is down-regulated during aging and in neurodegenerative disorders, we investigated whether an increase in cGMP levels might rescue age-related synaptic and memory deficits in mice. We demonstrated that acute perfusion with the phosphodiesterase-5 inhibitor sildenafil (50 nM) ameliorated long-term potentiation in hippocampal slices from 26-30-month-old mice. Moreover, chronic intraperitoneal injection of sildenafil (3mg/kg for 3 weeks) improved age-related spatial learning and reference memory as tested by the Morris Water Maze, and recognition memory as tested by the Object Recognition Test. Finally, sildenafil restored central cAMP responsive element-binding protein (CREB) phosphorylation, which is crucial for synaptic plasticity and memory. Our data suggest that inhibition of phosphodiesterase-5 may be beneficial to treat age-related cognitive dysfunction in a physiological mouse model of aging.

Circumstances leading to injurious falls in older men and women in the Netherlands. Fall-induced injuries in persons aged 65 years and older are a major public health problem. Data regarding circumstances leading to specific injuries, such as traumatic brain injury (TBI) and hip fractures in older adults are scarce. To investigate the activity distributions leading to indoor and outdoor falls requiring an emergency department (ED) visit, and those resulting in TBIs and hip fractures. 5880 older adults who visited the ED due to a fall. Data is descriptive and stratified by age and gender. Two-thirds of all falls occurred indoors. However, there were higher proportions of outdoor falls at ages 65-79 years (48%). Walking up or down stairs (51%) and housekeeping (17%) were the most common indoor activities leading to a TBIs. Walking (42%) and sitting or standing (16%) was the most common indoor activities leading to a hip fracture. The most common outdoor activities were walking (61% for TBIs and 57% for hip fractures) and cycling (10% for TBIs and 24% for hip fractures). In the present study we found that the indoor activities distribution leading to TBIs and hip fractures differed. Notably, about half of the traumatic brain injuries and hip fractures in men and women aged 65-79 years occurred outdoors. This study provides new insights into patterns leading to injurious falls by age, gender and injury type, and may guide the targeting of falls prevention at specific activities and risk groups, including highly functional older men and women.

Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group. Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition. Patients with active duodenal ulcer were randomized either to omeprazole, 20 mg twice daily until healing, followed by omeprazole, 20 mg/ day for 1 year, or to eradication therapy (metronidazole, amoxicillin, and omeprazole for 2 weeks) followed by placebo for 1 year. All patients were followed up passively for an additional year. Clinical controls were performed every 2 months the 1st year (maintenance phase) and every 6 months during the passive follow-up phase. The study was multicentric and double-blind. The primary end-point was discontinuation of treatment, irrespective of reason. Two hundred and seventy-six patients were randomized (139 in the eradication treatment group). In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal. In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer, compared with 51 patients initially randomized to long-term omeprazole. There were no differences in reflux symptoms or in the development of reflux oesophagitis. Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers. One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period. Eradication therapy does not increase the risk of reflux in ulcer patients.

Molecular signaling operated by a diet-compatible mixture of oxysterols in up-regulating CD36 receptor in CD68 positive cells. Oxidation of dietary cholesterol during food storage and processing, and/or that of endogenous cholesterol in the presence of increased steady-state levels of reactive oxygen species, leads to the production of derivatives, termed oxysterols. Among the biochemical effects exerted by an oxysterol mixture, it has recently been observed that marked up-regulation of CD36 scavenger receptor on macrophage cells plays a primary role in foam cell formation. This article reports evidence of a significant co-localization of CD36 receptor with cells of the macrophage lineage, i.e. CD68 positive cells, LDL apoprotein B100 and lipids in human advanced atherosclerotic lesions. In addition, it provides a comprehensive analysis of the molecular signaling operated by a nutritionally relevant mixture of oxysterols in overexpressing CD36 receptor in cells of the macrophage lineage. The involvement of a G protein, Src, phospholipase C cascade and peroxisome proliferator-activated receptor gamma in oxysterol-mediated signaling was demonstrated by using selective inhibitors, while the central role of the downstream protein kinase Cdelta and extracellular signal-regulated kinase pathways in oxysterol-induced enhancement of CD36 was conclusively proved by means of small interfering RNA (siRNA) technology.

Increase in tracheal pressure during jet ventilation. Gas injection systems used in several techniques of ventilation cause increases in airway pressure and physiological changes which are frequently overlooked. The momentum flux theory describes such phenomena most appropriately. We have defined and measured the characteristics of such increases in airway pressure, using a lateral tracheal injection system which has been described previously. In such a system, wall friction is a major source of loss in jet momentum flux, in contrast with the changes in axis-symmetrical systems. This process results in a potentially beneficial increase in airway pressure and in greater mixing, which might be clinically useful.

Walking meditation promotes ankle proprioception and balance performance among elderly women. Age-related change of proprioception affects body balance among the elderly. Walking meditation (WM)-a mindfulness practice-involves focusing on leg movements while walking slowly, possibly improving brain processes for perception and balance adjustments. This study investigates the WM's effects on ankle proprioception and balance among the elderly. Fifty-eight women aged 69.25 ± 6.06 were randomized into control (n = 29) and WM (n = 29) groups. The WM group engaged in 8 weeks of WM practice (30 min/day, 3 days/week). The absolute angular error of the ankle reposition test (AAE) was measured by an electrogoniometer. The balance performance was evaluated using the Berg Balance Scale (BBS), Functional Reach Test (FRT), and Timed Up and Go test (TUG). Data were analyzed using two-way ANOVA and Bonferroni post hoc test and BBS with nonparametric statistics. At baseline, the WM group's AAE, BBS, FRT, and TUG were 4.2 ± 1.6°, 51.3 ± 4.1 points, 21.7 ± 5.7 cm, and 11.1 ± 2.5 s, respectively, whereas those of the control group were 3.6 ± 2.0°, 51.0 ± 5.0 points, 21.6 ± 5.2 cm, and 10.2 ± 3.1 s, respectively. Post-training, WM group showed significant decrease in AAE (2.4 ± 0.9°) and displayed improvements in BBS, FRT, and TUG (55.4 ± 0.9 points, 29.1 ± 5.8 cm, and 8.1 ± 1.1 s, respectively) (p < 0.01). Conversely, the control group presented no change in AAE, significant decreases in BBS and FRT, and slower TUG (p < 0.01). No difference was found between WM and control groups at the baseline. However, post-training, WM group demonstrated significant improvements in AAE, BBS, FRT, and TUG as compared to the control group (p < 0.001). WM practice improved the balance and ankle reposition sense among the elderly. It can be used as an alternative form of training to promote balance and ankle proprioception. The results supported that balance performance worsens among the elders who do not engage in physical training.

[Methods of assessing postoperative pain in children]. A study of the evaluation of postoperative pain in 210 children using physiological, reference and observation methods. A comparison with other methods leads to the conclusion that observation is the best choice and that some children do not need analgesics during the postoperative period.

Rapid Novel Facile Biosynthesized Silver Nanoparticles From Bacterial Release Induce Biogenicity and Concentration Dependent In Vivo Cytotoxicity With Embryonic Zebrafish-A Mechanistic Insight. In this study, rapid one step facile synthesis of silver nanoparticles (AgNPs) was done using culture supernatant of two Gram positive (B. thuringiensis and S. aureus) and Gram negative (E. coli and Salmonella typhimurium [STAgNP]) bacterial strains and were termed as "Bacillus thuringiensis," "Staphylococcus aureus," "Escherichia coli," and "STAgNP," respectively. Synthesized AgNPs were well characterized with the help of different standard techniques like FESEM, DLS, UV-Vis spectroscopy, and Fourier transform infrared. Mechanism of AgNPs synthesis was elucidated using in silico approach. In vivo cytotoxicity of synthesized AgNPs was assessed in embryonic Zebrafish model with the help of uptake, oxidative stress, and apoptosis induction experimental assays, and the mechanism was investigated through in silico approach at the molecular level. The result showed successful biosynthesis of 20-40 nm sized AgNPs stable with zeta potential of - 45 to - 35 mV having standard silver nanoparticles SPR peaks due to the interaction of reduced silver particles with amino acid residues of bapA proteins of the bacterial supernatant. In vivo cytotoxicity with embryonic Zebrafish was found to be dependent on biogenicity and concentration of biosynthesized AgNPs as consequence of oxidative stress induction and apoptosis due to the influential regulation of sod1 and tp53 genes clarified by pathway analysis with reference to experimental and computational results. The study suggested that cytotoxicity of biologically synthesized silver nanoparticles from bacteria depends on strain specificity with significant difference in use of Gram positive and Gram negative bacterial strains.

Activation of protein kinase C inhibits cellular production of the amyloid beta-protein. The 39-43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels in Alzheimer's disease (AD), is released by cultured human cells during normal metabolism. Here we show that agents which activate protein kinase C or otherwise enhance protein phosphorylation caused a substantial decrease in A beta production in vitro. Protein kinase C activation also markedly decreased A beta release from cells that express mutant forms of the beta-amyloid precursor protein genetically linked to familial AD. Inhibition of A beta secretion could also be effected by direct stimulation of m1 muscarinic acetylcholine receptors with carbachol. These results demonstrate that activation of the protein kinase C signal transduction pathways down-regulates the generation of the amyloidogenic A beta peptide. Pharmacologic agents that activate this system, including a variety of first messengers, could potentially slow the development or growth of some A beta plaques during the early stages of AD.

Environmental temperature has an influence on timing of the first ovulation of seasonal estrus in the mare. A 10-yr retrospective analysis of the time of onset of seasonal ovulation derived from the records of a Thoroughbred horse stud at latitude 35 degrees S revealed a significant variation between years. The onset of seasonal ovulation was closely related to both the maximum (correlation coefficient r=0.56; P=0.09) and minimum (r=-0.67; P<0.01) environmental temperatures. The trend of the temperature rise and the levels attained in the weeks immediately prior to ovulation were similar for both the environmental maximum and minimum temperatures in all years of the study. Environmental temperature may therefore play an important adjuvant zeitgeber for the timing of the first ovulation of estrus in the mare.

Correlation of Alzheimer-like tau hyperphosphorylation and fMRI bold intensity. To explore the correlation between cerebral functional alterations revealed by functional magnetic resonance imaging (fMRI) and Alzheimer disease- (AD)-like tau hyperphosphorylation, we injected bilaterally 2 microl each of 20 mM isoproterenol (IP), a PKA activator, or of saline as a vehicle control into the hippocampus of rats. FMRI was employed to measure the intensity of BOLD signal, one of the cerebral functional markers reflecting the changes of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), in hippocampus and cortex 24 h after the operation. Immunohistochemical staining of hippocampus and cortex was carried out using phosphorylation-dependent tau antibodies. The results showed (1) that BOLD intensity in hippocampus and cortex of IP-injected rats was obviously lower than that of sham-operated group, indicating a decrease in CMRO2 and CBF of the particular brain regions in IP-treated rats; (2) that tau was hyperphosphorylated at Ser-262/Ser-356 (12e8), Ser-396/Ser-404 (PHF-1) sites in CA1 CA2 CA3 CA4 and dentate gyrus regions of hippocampal formation and cortex area in IP group, but not in sham rats; (3) that a negative correlation between tau hyperphosphorylation and BOLD intensity in hippocampus and cortex area of IP rats was observed. The data suggested that hippocampal and cortical tau hyperphosphorylation was intimately related to BOLD intensity of the same areas. To our knowledge, this is the first report exploring the relationship between fMRI BOLD signal and AD-like tau hyperphosphorylation.

Pharmacokinetics of tazobactam M1 metabolite after administration of piperacillin/tazobactam in subjects with renal impairment. Tazobactam is a new derivative of penicillinic acid sulfone, which functions as an irreversible inhibitor of many beta-lactamases. The disposition of tazobactam M1 metabolite after intravenous (i.v.) infusion of 3 g of piperacillin/0.375 g of tazobactam was evaluated in 26 subjects with various degrees of renal impairment. Participants in the study were 18 subjects with creatinine clearances (ClCR) ranging from 7.4-41.8 mL/min, 4 subjects maintained on continuous ambulatory peritoneal dialysis (CAPD), and 4 subjects undergoing chronic hemodialysis (HD). The pharmacokinetic parameters of piperacillin and tazobactam were evaluated and were similar to previous reports. Tazobactam M1 metabolite maximum plasma concentration increased as renal function declined. The terminal elimination half-life and area under the plasma concentration-time curve of the tazobactam M1 metabolite increased as renal function declined. The mean rate of recovery of the tazobactam M1 metabolite in hemodialysate during a 3- to 4.2-hour HD session 1 hour after the i.v. infusion of piperacillin/tazobactam was 25.3%. However, when HD was performed at 36-48 hours after the i.v. infusion, 57.6% of the tazobactam dose was recovered as M1 metabolite, suggesting further conversion of tazobactam to M1 metabolite. Peritoneal dialysis removed 15.8% (n = 2) of the tazobactam dose as the M1 metabolite. Using a dose of 3 g of piperacillin/0.375 g of tazobactam, the predicted maximum steady-state plasma concentrations of the tazobactam M1 metabolite are 14.6 micrograms/mL, 34.8 micrograms/mL, and 48.8 micrograms/mL for subjects with ClCR 20-40 mL/min (every 6 hour dosing), ClCR < 20 mL/min (every 8 hour dosing), and on CAPD (every 12 hour dosing), respectively.

Oxygen delivery and utilization in dogs with a sublethal dose of cobalt chloride. Four groups of eight dogs each were anesthetized with pentobarbital, paralyzed with succinylcholine, and ventilated at constant rate. Control measurements were made for 30 min, then 15 mg/kg of cobaltous chloride was given slowly intravenously to one group. A second group was also given 1 mg/kg per h propranolol (beta-block); a third group was given NaHCO3 to correct pH changes after CoCl2; and a fourth group had both beta-block and NaHCO3. Vo2 was measured every 10 min for 4 h and blood was taken frequently for lactate, pyruvate, and blood gas measurements. Cobalt transiently decreased Vo2 in all groups but significantly more in those with beta-block (groups 2 and 4). Cardiac output and mean arterial pressure were also decreased in all groups but to similar extent. Recovery of Vo2 was complete, usually within 60 min with little evidence of deficit repayment. Total O2 transport (Q X Cao2) appeared to limit Vo2 below 12 ml/kg times min. Above that value, histotoxic effects of CoCl2 reduced Vo2 approximately 20%. Excess lactate (XL) in arterial blood was linearly correlated with measured O2 deficit during the acute reaction of CoCl2, in all but group 3, similar to results previously obtained in hypoxic hypoxia.

Lactic acidosis in medical ICU - the role of diabetes mellitus and metformin. To evaluate the significance of diabetes mellitus and metformin in patients admitted to medical ICU with lactic acidosis. All the patients admitted to medical ICU with serum lactic acid exceeding 5 mmol/L and pH<7.35 were enrolled into analysis. The impact of diabetes mellitus and metformin treatment on ICU presence of lactic acidosis and its mortality was evaluated. The metabolic parameters were compared with respect to the presence of diabetes mellitus and metformin application. Lactic acidosis was detected in 69 (4%) out of 1,755 admitted patients, 44 were nondiabetic and 25 had diabetes mellitus, 11 of them treated with metformin. No significant impact of diabetes mellitus or metformin application on presence of lactic acidosis and its mortality was detected. In nondiabetic subjects mortality was associated with eGFR and the presence of acute renal failure while in diabetic patients with sepsis. Acute renal failure was detected in 9 out of 11 patients on metformin. Three patients died due to sepsis, however only 1 out of 6 due to another cause if renal replacement therapy was started soon after admission. The acidosis was more expressed in diabetic subjects mainly in patients taking metformin. It might be attributed to the more pronounced acute renal failure in diabetic patients. The presence of diabetes mellitus and metformin application is not associated with the presence of lactic acidosis in medical ICU and its mortality. The prognosis of acute renal failure of patients on metformin is good if the subjects with sepsis are excluded.

Underdiagnosis of acute rheumatic fever in primary care settings in a developing country. To determine the incidence rate, characterize the clinical features and assess the diagnostic evaluation of children presenting with features of acute rheumatic fever (ARF) at two clinics in a region of Fiji where rheumatic heart disease is known to be endemic. We reviewed 5 years (2003-2008) of primary care records from 15 841 patients aged 4-20 years using a pre-determined case definition for ARF; and we reviewed detailed clinical data from 944 cases with features of possible ARF. The crude incidence of first episodes of definite ARF in this setting among patients aged 4-20 years was 24.9 per 100 000 person-years. Joint involvement suggestive of a potential first presentation of ARF but not sufficient for a definite retrospective diagnosis was documented in a further 94 records. There were another 514 cases of joint involvement less suggestive of ARF and 316 cases of unexplained fever with no evidence of localized infection. Patients presenting with potential features of ARF seldom had a diagnostic evaluation sufficient to exclude its diagnosis. The incidence of ARF at these clinics is nearly twice that reported in a local hospital-based study, but it is likely to under-represent the actual number of cases presenting to primary care. There is a need for better surveillance for ARF and to develop simple and practical approaches to diagnosing ARF in primary care in low-resource settings.

Non-invasive prenatal diagnosis: public and patient perceptions. The possibility of the application of reliable non-invasive prenatal diagnosis to clinical practice, and its likely availability as a tool for routine antenatal screening, is an important and exciting development that will be of interest to women and couples - especially where there is a known risk arising from family history, or some other source, of having a baby with a serious, disabling or life-limiting condition. Managing the introduction of this new technology will require attention to the understanding and perceptions of women, couples and the wider society, as well as to the clinical, scientific, technical and logistic issues that will inevitably arise.

Ponalrestat: a potent and specific inhibitor of aldose reductase. Many of the complications of diabetes appear to be closely linked to increased conversion of tissue glucose to sorbitol which is catalysed by aldose reductase (aldehyde reductase 2, ALR2). Inhibition of ALR2 could, therefore, lead to a reduction in the development of diabetic complications. Ponalrestat ["Statil" (a trademark, the property of Imperical Chemical Industries PLC), "Prodiax" (a trademark, the property of Merck, Sharp and Dohme), ICI 128436, MK538] inhibits ALR2 from a number of sources. Until now, the mechanism of this inhibition has not been fully elucidated. In this paper, we present a detailed mechanism for inhibition of bovine lens ALR2 by ponalrestat. Treatment of humans with some ALR2 inhibitors leads to side-effects, some of which may result from interactions with other enzymes. Aldehyde reductase (ALR1) is probably the most closely related enzyme to ALR2. Inhibition of ALR1 from bovine kidney was, therefore, investigated in order to assess the specificity of ponalrestat. The values of Ki and Kies (apparent dissociation constants for inhibitor from enzyme-inhibitor and enzyme-inhibitor-substrate complexes, respectively) for the interactions of ponalrestat with ALR1 and ALR2 has been calculated by non-linear fitting of kinetic data. These values indicate that ponalrestat does not compete with binding of glucose of NADPH to ALR2, nor with binding of glucuronate or NADPH to ALR1. Lack of competition and the structural dissimilarity of substrates and inhibitor make it unlikely that ponalrestat will utilize substrate binding sites on other enzymes, and so produce undesirable side-effects via such a mechanism. Ponalrestat is a potent inhibitor (Ki = Kies = 7.7 nM) of ALR2 and follows a pure noncompetitive mechanism with respect to glucose. Efficacy, therefore, will not be decreased by development of hyperglycaemia. The compound is a mixed noncompetitive inhibitor of ALR1 when glucuronate is varied. The values of Ki and Kies are 60 microM and 3 microM, respectively, so that inhibition tends towards uncompetitive. The selectivity of ponalrestat in favour of ALR2, therefore, lies in the range 390 to 7,800-fold, being higher at lower concentrations of glucuronate. The high selectivity of ponalrestat in favour of ALR2 rather than ALR1 suggests that the compound is unlikely to inhibit other enzymes which have less homology with ALR2.

Improved solid-phase extraction procedure for the isolation and in-sorbent pentafluorobenzyl alkylation of polyfunctional mercaptans. Optimized procedure and analytical applications. A fast method for the determination of aroma-powerful polyfunctional thiols at ng L(-1) level has been developed. Mercaptans are selectively retained in a 50mg solid-phase extraction cartridge and derivatization takes place in the same cartridge at room temperature (25 degrees C) in 20 min by adding small amounts of pentafluorobenzyl bromide (PFBBr) and a strong alkali: 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The corresponding derivatives are further eluted and determined by gas chromatography-negative ion mass spectrometry (GC-NCI-MS). Isolation, derivatization, clean-up, elution and calibration conditions were examined. Carrying the reaction in the cartridge makes it possible to use water and non-polar reagents simultaneously, to avoid large volumes of toxic solvent, and to eliminate the excess of reagent. This was last accomplished by the reaction with mercaptoglycerol and further rinsing with a hydromethanolic solution. The method makes it possible to simultaneously determine 2-methyl-3-furanthiol (MF), 2-furfurylthiol (2-furanmethanethiol) (FFT), 4-mercapto-4-methyl-2-pentanone (MP) (as its methoxime), 3-mercaptohexylacetate (MHA) and 3-mercaptohexanol (MH). Absolute limits of detection were 0.2 (MF), 0.1 (FFT), 0.1 (MP), 0.3 (MHA) and 2 (MH) ng L(-1). Repeatability (1%<RSD<20%) and linearity (0.978<R(2)<0.999) were satisfactory. Problems with matrix effects were solved by the use of deuterated analogues for MP, MHA and MH and by avoiding the oxidation of analytes and standards via addition of cysteine and EDTA. The different aspects of the method optimization are discussed.

Post dural puncture headache following combined spinal epidural or epidural anaesthesia in obstetric patients. A retrospective review of obstetric anaesthesia charts was performed for all parturients receiving regional anaesthesia over a 22-month period. The incidence of headache, post dural puncture headache (PDPH) and various other complications of regional anaesthesia that had been prospectively assessed were noted, as was the anaesthetic technique used (epidural or combined spinal epidural (CSE)). PDPH was rare (0.44%) and occurred with similar frequency in those managed with either epidural or CSE anaesthesia or analgesia. The pencil-point spinal needle gauge (27 or 29) did not influence the incidence of PDPH. Following a CSE technique, the epidural catheter more reliably produced effective analgesia/anaesthesia as compared with a standard epidural technique (1.49% versus 3.18% incidence of replaced catheters respectively). We conclude, based on the results of this retrospective review, that CSE is acceptable with respect to the occurrence of PDPH and that it is possible it is advantageous in relation to the correct placement of the epidural catheter

Dissociation kinetics of open-chain and macrocyclic gadolinium(III)-aminopolycarboxylate complexes related to magnetic resonance imaging: catalytic effect of endogenous ligands. The kinetics of the metal exchange reactions between open-chain Gd(DTPA)(2-) and Gd(DTPA-BMA), macrocyclic Gd(DOTA)(-) and Gd(HP-DO3A) complexes, and Cu(2+) ions were investigated in the presence of endogenous citrate, phosphate, carbonate and histidinate ligands in the pH range 6-8 in NaCl (0.15 M) at 25 °C. The rates of the exchange reactions of Gd(DTPA)(2-) and Gd(DTPA-BMA) are independent of the Cu(2+) concentration in the presence of citrate and the reactions occur via the dissociation of Gd(3+) complexes catalyzed by the citrate ions. The HCO(3)(-)/CO(3)(2-) and H(2)PO(4)(-) ions also catalyze the dissociation of complexes. The rates of the dissociation of Gd(DTPA-BMA), catalyzed by the endogenous ligands, are about two orders of magnitude higher than those of the Gd(DTPA)(2-). In fact near to physiological conditions the bicarbonate and carbonate ions show the largest catalytic effect, that significantly increase the dissociation rate of Gd(DTPA-BMA) and make the higher pH values (when the carbonate ion concentration is higher) a risk-factor for the dissociation of complexes in body fluids. The exchange reactions of Gd(DOTA)(-) and Gd(HP-DO3A) with Cu(2+) occur through the proton assisted dissociation of complexes in the pH range 3.5-5 and the endogenous ligands do not affect the dissociation rates of complexes. More insights into the interaction scheme between Gd(DTPA-BMA) and Gd(DTPA)(2-) and endogenous ligands have been obtained by acquiring the (13)C NMR spectra of the corresponding diamagnetic Y(III)-complexes, indicating the increase of the rates of the intramolecular rearrangements in the presence of carbonate and citrate ions. The herein reported results may have implications in the understanding of the etiology of nephrogenic systemic fibrosis, a rare disease that has been associated to the administration of Gd-containing agents to patients with impaired renal function.

Phylogeny of five fungus-like protoctistan Phytophthora species, inferred from the internal transcribed spacers of ribosomal DNA. Ribosomal DNA variation was used to study evolutionary relationships among five fungal-like protoctistan Phytophthora species. On the basis of morphological and ecological characteristics, four of these species--P. palmivora, P. megakarya, P. capsici, and P. citrophthora--were once thought to be related. Variation within a species was extensively studied in a fifth, outgroup species--P. cinnamomi--known, on the basis of ecological, isozyme, and mitochondrial DNA studies, to be variable. Internal transcribed spacer regions (ITS I, between the 18S and 5.8S rDNAs; and ITS II, between the 5.8S and 25S rDNAs) from 27 isolates of these five species were analyzed by polymerase chain reaction amplification and direct sequencing. Intraspecific variability was undetected or low. Interspecific nucleotide difference was 0.3%-14.6%, and comparisons of variable regions permitted the evaluation of phylogenetic relationships among species. Both neighbor-joining and parsimony analysis of ITS variability support a close relationship between cacao isolates of P. capsici and P. citrophthora and a common lineage for P. palmivora and P. megakarya. Large distance values were estimated between P. cinnamomi and the other species. Inferred relationships based on ITS variability were compared with those based on other characters. The catalog of sequences provides the information necessary to design taxon-specific probes potentially useful in taxonomic, ecological, and population-level studies.

Cancer risk assessment for 1,3-butadiene: dose-response modeling from an epidemiological perspective. The dose-response assessment of the association between 1,3-butadiene (BD) and leukemia mortality among workers in the North American synthetic rubber industry is explored. Analyses are based on the most recent University of Alabama at Birmingham epidemiological study and exposure estimation. The U.S. EPA Science Advisory Board recommendations of using the most recent data and giving consideration to peak exposures to BD have been followed. If cumulative BD ppm-years is to be used as the predictor of the leukemia rate ratio, then the performance of that predictor is statistically significantly improved if the slope in the predictor is estimated with age and the cumulative number of BD peaks (where a BD peak is any exposure, regardless of duration, to a BD concentration above 100 ppm) added as categorical covariates. After age and the cumulative number of BD peaks are incorporated as categorical covariates in the Poisson regression model, the estimated concentration (EC(001)) corresponding to an excess risk of 0.001 as a result of continuous environmental exposure is 11.2 ppm; however, the estimated slope for BD cumulative ppm-years in the linear rate ratio for leukemia used to derive this EC(001) is not statistically significantly different from zero. Sensitivity analyses using alternative models indicate either essentially no risk or estimated EC(001) values of 9 and 77 ppm. Analyses suggesting the absence of a statistically significant low-dose risk versus cumulative BD ppm-years are presented. Sensitivity analyses of other malignant neoplasms of lymphatic and hematopoietic tissue (specifically, lymphoid and myeloid neoplasms) resulted in conclusions about the dose-response modeling methodology that were supportive of the methodology used for leukemia.

The novel use of wooden spoons for control of massive intra-abdominal hemorrhage. Massive intra-abdominal hemorrhage represents a challenging operative emergency. Temporary control of the aorta and inferior vena cava (IVC) using intra-luminal balloon occlusion, preemptive trans-thoracic clamping or infra-diaphragmatic clamping has been achieved with variable success. We report the use of wooden spoons with convex arches cut from their bases as a cheap and effective alternative. They can be used to compress the aorta or IVC against the vertebrae, giving vascular control while leaving good surgical access. This equipment requires minimal financial investment and only basic woodworking skills.

Strong male/male competition allows for nonchoosy females: high levels of polygynandry in a territorial frog with paternal care. Our knowledge about genetic mating systems and the underlying causes for and consequences of variation in reproductive success has substantially improved in recent years. When linked to longitudinal population studies, cross-generational pedigrees across wild populations can help answer a wide suite of questions in ecology and evolutionary biology. We used microsatellite markers and exhaustive sampling of two successive adult generations to obtain population-wide estimates of individual reproductive output of males and females in a natural population of the Neotropical frog Allobates femoralis (Aromobatidae), a pan-Amazonian species that features prolonged iteroparous breeding, male territoriality and male parental care. Parentage analysis revealed a polygynandrous mating system in which high proportions of males (35.5%) and females (56.0%) produced progeny that survived until adulthood. Despite contrasting reproductive strategies, successfully reproducing males and females had similar numbers of mating partners that sired the adult progeny (both sexes: median 2; range 1-6); the numbers of their offspring that reached adulthood were also similar (both sexes: median 2; range 1-8). Measures of reproductive skew indicate selection on males only for their opportunity to breed. Reproductive success was significantly higher in territorial than in nonterritorial males, but unrelated to territory size in males or to body size in both sexes. We hypothesize that female polyandry in this species has evolved because of enhanced offspring survival when paternal care is allocated to multiple partners.

Protein turnover and physical fitness in man. The whole-body flux and protein-synthesis rates were determined in two groups of adult males aged 20-30 years who were matched for height and weight. [15N]Glycine was used as a tracer. Flux and synthesis rates were calculated from the urinary ammonia 15N excretion enrichment. Group I consisted of international competition level oarsmen, while Group II engaged in no exercise program. Measurement of the urinary nitrogen excretion rate showed that the oarsmen excreted more than twice as much nitrogen as the control group (P less than 0.05). flux and synthesis were 21.3 +/- 3.2 gN/9 hr and 188.7 +/- 59.9 g protein/day for the oarsmen and 16.4 +/- 2.1 g N/9 hr and 201.7 +/- 33.0 g protein/day for the controls. Data are +/- 1 SD for the eight oarsmen and eight controls. The flux values were different at the P less than 0.05 level. We concluded that (i) an exercise program does not lead to an increase in the basal protein turnover rate in adequately nourished individuals.

Molecular hydrogen consumption in the human body during the inhalation of hydrogen gas. Inhaling or ingesting hydrogen (H2) gas improves oxidative stress-induced damage in animal models and humans. We previously reported that H2 was consumed throughout the human body after the ingestion of H2-rich water and that the H2 consumption rate ([Formula: see text]) was 1.0 μmol/min/m(2) body surface area. To confirm this result, we evaluated [Formula: see text]during the inhalation of low levels of H2 gas. After measuring the baseline levels of exhaled H2 during room air breathing via a one-way valve and a mouthpiece, the subject breathed low levels (160 ppm) of H2 gas mixed with purified artificial air. The H2 levels of their inspired and expired breath were measured by gas chromatography using a semiconductor sensor. [Formula: see text] was calculated using a ventilation equation derived from the inspired and expired concentrations of O2/CO2/H2, and the expired minute ventilation volume, which was measured with a respiromonitor. As a result, [Formula: see text] was found to be approximately 0.7 μmol/min/m(2)BSA, which was compatible with the findings we obtained using H2-rich water. [Formula: see text] varied markedly when pretreatment fasting to reduce colonic fermentation was not employed, i.e., when the subject's baseline breath hydrogen level was 10 ppm or greater. Our H2 inhalation method might be useful for the noninvasive monitoring of hydroxyl radical production in the human body.

Phase II evaluation of gallium nitrate by continuous infusion in breast cancer. We evaluated the role of gallium nitrate infusion in the treatment of metastatic breast cancer. Gallium nitrate was administered at 300 mg/m2/day for 7 days every 3 weeks by continuous infusion concomitantly with oral calcium supplement of 500 mg twice daily and oral hydration. Fifteen patients with refractory metastatic breast cancer received such treatment for a total of 30 courses. Median age was 51, and median performance status (Zubrod scale) was 1. These patients had minimal prior chemotherapy (median 1 regimen). All patients were evaluable for toxicity and 14 for response. Nine patients had one to two metastatic sites, five patients had three to four sites. No major objective response was seen, but one patient had a minor response (10 weeks), and another showed no change in disease (16 weeks). Diverse low-grade toxicities were observed, including nausea and vomiting in 11 patients, anorexia in 11, diarrhea in eight, stomatitis in five, dysgeusia in six, musculoskeletal pain in five, skin rash in seven, partially reversible tinnitus and/or mild hearing loss in four and sensory neuropathy in two. A consistent drop in hemoglobin (median of 3.2 g/dL per patient) necessitated blood transfusion in seven patients. There was no granulocytopenia or thrombocytopenia; however, significant lymphopenia was noted. Reversible, moderate nephrotoxicity occurred in two patients. The hypocalcemic effect was consistent, with a median drop in serum calcium of 1.25 mg/dL per course. There was no hepatic toxicity. While no single toxicity was severe, overall toxicity adversely influenced treatment tolerance. Gallium nitrate by continuous infusion, as given in this study, has no activity in metastatic breast cancer.

Temperature variation on root surface with three root-end cavity preparation techniques. Thermal changes can occur on the external root surface when root-end cavity preparation is performed, which may damage periodontal ligament cells and alveolar bone. The purpose of this study was to evaluate the temperature changes during preparation of the root-end cavities at 1 and 3 mm to the sectioned apical root surfaces when either tungsten carbide round bur, diamond round bur or ultrasonic diamond tip was used. Root-end resection was performed at 90 degrees to the long axis of the root, 3 mm from the apex. Specimens were randomly divided into three groups of 12 teeth each for three different root-end cavity preparation techniques to be used, i.e. tungsten carbide bur, diamond bur and ultrasonic diamond retro tip.Thermocouples were used to measure temperature changes at 1 mm (T1) and 3 mm (T2) to the cutting plane during the preparations. For T1, the lowest and the highest mean temperature increases of 3.53 degrees C and 4.34 degrees C were recorded for the carbide and diamond burs, respectively. For T2, the lowest and the highest mean temperature increases of 2.62 degrees C and 4.39 degrees C where recorded for the carbide and diamond burs, respectively. The mean temperatures with the ultrasonic tip were 3.68 and 3.04 degrees C at T1 and T2 region, respectively. For root-end preparation, the ultrasonic preparation technique took the shortest preparation time (10.25 sec) and the diamond bur took the longest time (28.17 sec). Ultrasonic retro tips and burs caused temperature to rise from 2.62 degrees to 4.39 degrees C, and these rises were within safety levels.

Dialectal differences in hemispheric specialization for Japanese lexical pitch accent. Language experience can alter perceptual abilities and the neural specialization for phonological contrasts. Here we investigated whether dialectal differences in the lexical use of pitch information lead to differences in functional lateralization for pitch processing. We measured cortical hemodynamic responses to pitch pattern changes in native speakers of Standard (Tokyo) Japanese, which has a lexical pitch accent system, and native speakers of 'accentless' dialects, which do not have any lexical tonal phenomena. While the Standard Japanese speakers showed left-dominant responses in temporal regions to pitch pattern changes within words, the accentless dialects speakers did not show such left-dominance. Pitch pattern changes within harmonic-complex tones also elicited different brain activation patterns between the two groups. These results indicate that the neural processing of pitch information differs depending on the listener's native dialect, and that listeners' linguistic experiences may further affect the processing of pitch changes even for non-linguistic sounds.

Wilms tumor in horseshoe kidneys: radiologic diagnosis. Two cases of nephroblastoma occurring in a horseshoe kidney are reported, and 32 cases from the literature are reviewed. The radiologic signs of horseshoe kidney may be difficult to evaluate with excretory urography when the mass is large. Rotational abnormalities of the opposite kidney that is not involved by tumor should suggest the possibility of an associated horseshoe kidney. Real-time ultrasonography and computed tomography are helpful in identifying the isthmus of the horseshoe kidney. Aortography confirms the presence of the horseshoe kidney and demonstrates the arterial supply to the isthmus and the tumor. Radionuclide scans demonstrate the isthmus when the tumor arises from an upper pole, but may not be diagnostic if the tumor arises from the isthmus.

Elevated lead exposure in American woodcock (Scolopax minor) in Eastern Canada. We investigated the degree and incidence of elevated lead (Pb) accumulation in the American woodcock (Scolopax minor) in eastern Canada by measuring the concentration of Pb in undamaged wing bones of 1,588 birds from Ontario, Quebec, Nova Scotia, and New Brunswick. Overall median bone-Pb concentrations were 21 microgram/g (DW) for adults and 11 microgram/g for young of the year. A high proportion of birds had elevated Pb concentrations, compared with other wild bird species. Fifty-two percent of adults and 29% of young of the year had bone concentrations exceeding 20 microgram/g. Pb concentration varied significantly with age, gender, and geographical region (p </= 0.0001). Mean Pb concentrations were lower for young of the year than for adults and lower for males than for females in both age groups. Atlantic Canada (New Brunswick and Nova Scotia) tended to have the highest frequency of individuals with elevated Pb accumulation. Potential sources of Pb exposure in woodcock include ingestion of spent lead shot from hunting, ingestion of Pb-contaminated soil, and/or ingestion of Pb-contaminated earthworms.

An improved method for thick film preparation using saponin as a lysing agent. Thick film examination for malaria is often hampered by the presence of cellular debris obscuring parasites. This is a major problem for diagnostic laboratories that do not have a high exposure to material identification. Films that are relatively free of cellular debris, allowing easier identification of parasites are an obvious advantage. Saponin has been used by researchers to liberate malarial parasites for harvesting from infected erythrocytes. It has also been used for thick film preparations for diagnosis, but has not gained widespread acceptance, possibly due to the persistence of cellular debris inherent in the technique. In the present study the saponin method for thick film examination has been modified by the inclusion of a centrifugation step to remove cellular debris. Thick films were run in parallel with films made using the standard Fields stain technique and the original saponin. Results indicate that the modified saponin technique provides superior preparations free of cellular debris.

Mechanisms of burn injury secondary to airbag deployment. The efficacy of airbags as a vital, supplemental restraining device has been proven by their role in diminishing the rate of fatalities and severity of injury in motor vehicle crashes. Unfortunately, as with any developing technology, deployment of the airbag itself has caused some new problems. Most airbag-related injuries are minor and, surprisingly, more than 5% are burns typically involving the upper extremity or head and neck. These are a result of the high temperature of the gases released during inflation or of direct contact with the corrosive alkaline plume created as a combustion by-product. Fortunately, these are superficial burns that usually require only expectant treatment, but a high degree of suspicion in these circumstances is needed to make the proper diagnosis.

Craniocerebral gunshot wound in a baby chimpanzee--an uncommon experience of neurosurgical treatment conducted in the Guinean forest. An orphan female chimpanzee was wounded by a left craniocerebral gunshot complicated with a right hemiparesis. Local treatment and long-term antibiotherapy failed to lead to healing. A neurosurgical procedure was planned and achieved. She fully recovered, and 2 years after the procedure, there is no evidence of infection.

Clinicopathologic evaluation of malignancy adjacent to dental implants. The aim of this study was to describe a new case series of peri-implant malignancy, review the literature, and discuss the implications of malignancies resembling peri-implantitis. This study was a retrospective analysis of cases from 2000 to 2016. Seven patients (two males and five females), aged 44 to 89 years, were included, representing 1.5% of oral malignancy cases. Five cases were squamous carcinoma, one of basal cell carcinoma, and one of carcinoma of metastatic origin. Six cases presented with nonulcerated overgrowth, with bone loss in three and massive osteolysis in one. Misinterpretation as peri-implantitis delayed diagnosis in six cases. Risk factors included previous oral malignancy (2), potentially malignant conditions (2), and smoking (1). Of the 47 cases in the English language literature, 85% were squamous cell carcinoma and 8.5% had distant metastasis. Most cases had one or more risk factors. Peri-implant malignancy may represent up to 1.5% of oral malignancy cases. Clinical features imitating peri-implantitis may delay diagnosis. Lesions failing to respond to treatment, especially in patients with pre-existing risk factors, should significantly increase suspicion. Histopathology is crucial for diagnosis.

Cell-type specific occurrence of apoptosis in taste buds of the rat circumvallate papilla. The present study employed immunohistochemistry for single-stranded DNA (ssDNA) to detect apoptotic cells in taste buds of the rat circumvallate papilla. Double-labeling of ssDNA and markers for each cell type - phospholipase C beta2 (PLCbeta2) and alpha-gustducin for type II cells, neural cell adhesion molecule (NCAM) for type III cells, and Jacalin for type IV cells - was also performed to reveal which types of cells die by apoptosis. We detected approximately 16.8% and 14.0% of ssDNA-immunoreactive nuclei among PLCbeta2-immunoreactive and alpha-gustducinimmunoreactive cells, respectively, but rarely found ssDNA-immunoreactive cells among NCAM-immunoreactive or Jacalin-labeled cells, indicating that type II cells die by apoptosis. We also applied double labeling of ssDNA and human blood group antigen H (AbH) - which mostly labels type I cells as well as other cell types - and found that approximately 78% of ssDNA-immunoreactive cells were labeled with AbH, indicating that apoptosis also occurs in type I cells. The present results revealed that apoptosis occurs in both type I cells (dark cells) and type II cells (light cells), suggesting that there are two major cell lineages (dark cell and light cell lineages) for the differentiation of taste bud cells. In summury, type IV cells differentiate into dark and light cells and type III cells differentiate to type II cells within the light cell line.

Quality of life of living kidney donors in Brazil: an evaluation by the short form-36 and the WHOQOL-bref questionnaires. There are few studies that evaluate donors' quality of life (QOL) following renal transplant in developing countries. This study was conducted to evaluate post-donation QOL of Brazilian living kidney donors using SF-36 and WHOQOL-bref questionnaires. Demographic, socioeconomic and the QOL data were analyzed utilizing SF-36 and WHOQOL-bref questionnaires of 69 living kidney donors and compared with 68 non-donor subjects from the same community. The donors and controls were similar as for gender and ethnicity, predominating the female. There was no difference in the educational level or socioeconomic class between the groups, the lower income being more prevalent. The evaluation of the donors' QOL was not significantly different from that of the control group. In some domains of the SF-36 and of the WHOQOL-bref questionnaires, donors scored higher than controls. Even the evaluation of the QOL of donors whose recipients had suffered loss of the graft or death following renal transplantation, showed in a general manner a similar QOL to the controls. Living kidney donors in a mainly low-income segment of the Brazilian population present a post-donation quality of life equal or superior to that of the non-donor population with the same socioeconomic profile. The two generic instruments used to evaluate the quality of life presented similar results.

In vitro analysis of the properties of Beiqishen tea. Chinese Beiqishen tea was studied in an in vitro test system. Phytochemical screening, trace element analysis, and the analysis of antioxidant properties were carried out. Characteristic constituents were determined by chromatographic (capillary gas chromatography and GCQ Ion Trap mass spectrometry) and spectrometric (ultraviolet and UV-VIS) methods. Element concentrations were determined by inductively coupled plasma optical emission spectrometry. Antioxidant capacity was studied by spectrophotometric and luminometric techniques using a Berthold Lumat 9501 luminometer. Hydrogen-donating activity, reducing power, and total scavenger capacity were measured. Total polyphenol content was 20.77 +/- 0.52 g/100 g of drug; total flavonoid content was 0.485 +/- 0.036 g/100 g of drug; and tannin content was 9.063 +/- 0.782 g/100 g of drug. Caffeine content was 1.08 mg/100 g of drug. Essential oils were identified by gas chromatography: (+)-limonene (21%), p-cymene (1.7%), estragol (3.2%), beta-ocimene (1.4%), and thymol (2.6%). Metallic ion analysis showed significantly high concentrations of Al, As, Ba, Cr, Cu, Fe, Mn, Ni, and Ti in the drug. Antioxidant and scavenger properties were identified as a function of concentration. The tea infusion contained some non-desirable trace elements and caffeine in addition to polyphenols and tannins in high concentrations. Therefore, the consumption of this tea may involve risks.

[Idiopathic bilateral paralysis of the diaphragm]. The case of a 38-year old Caucasian man with acute irreversible idiopathic bilateral paralysis of the diaphragm is presented. The relevant diagnostic procedures are discussed. Paralysis of diaphragm during fluoroscopy in the supine position, observation of paradoxical movement of the anterior abdominal wall and upright position during sleep are the major characteristics of this condition. Elevation of both hemidiaphragms on thoracic X-ray during maximal inspiration, lack of phrenic nerve conduction, gradually increasing dyspnoea without ongoing infection or simultaneous vaccination and decreased functional status may further confirm the diagnosis.

[Effect of nocodazole on endocytosis of epidermal growth factor receptor]. During endocytosis EGF-receptor complexes are transported from early peripheral endosomes to late juxtranuclear-located endosomes to be then degraded in lysosomes. It is suggested that such a spatial organization of endosomal compartments is maintained by microtubule system and is necessary for lysosomal degradation of endocytosed cargo. In the present work, a study was made of the influence of Nocodazole, a microtubule depolymerizing agent, on endocytosis of fluid phase marker HRP and EGF entering the cell via receptor-mediated endocytosis. By subcellular fractionation in Percoll gradient it was shown that Nocodazole did not affect HRP internalization but stimulated its accumulation in a fraction sedimented together with late endosomes, thus preventing HRP delivery to lysosomes. On the contrary, Nocodazole exerted no influence on dynamics of compartmentalization and lysosomal degradation of EGF-receptor complexes. Moreover, no alterations were found in the functioning of a so well-known EGF-stimulated signal transduction pathway as MAP-kinase cascade. At the same time microtubule depolymerization dramatically changed the morphology of endosomal compartments abolishing juxtranuclear localization of late endosomes. Our data suggest that translocation of EGF-receptor complexes is not necessary for their normal lysosomal processing. Rab7, traditionally considered as a marker of late endosomes, has been found to demonstrate in Nocodazole-treated cells, in contrast to the control, a low extent of co-localization with endosomal structures. It could be supposed that the role of Rab7 is not so much to mediate early-to-late endosome transition as to maintain spatial organization of endosomal apparatus by mediating endosome-cytoskeleton interactions.

Polyethylene glycol-conjugated superoxide dismutase improves recovery of postischemic hypercapnic cerebral blood flow in piglets. We tested the hypothesis that administering polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the time of reperfusion would alter recovery of cerebral blood flow (CBF; microspheres) response to alteration in arterial PCO2 in pentobarbital-anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after ischemia (10 min aortic cross clamp). To determine the effect of preischemic versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a randomized, blinded fashion before ischemia and just before reperfusion. Cerebral oxygen consumption and somatosensory evoked potentials were measured during reperfusion as an assessment of brain function. During reperfusion, no group demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not different from preischemic values with either preischemic or postischemic PEG-SOD treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not attributable to improved postischemic cerebral oxygen consumption. Somatosensory evoked potential amplitude was decreased similarly during reperfusion (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct stimulation of neutrophil oxygenation activity by serum from patients with systemic lupus erythematosus: a relationship to disease activity. Sera from patients with systemic lupus erythematosus (SLE) directly stimulate polymorphonuclear leukocyte (PMNL) oxygenation activity as measured by luminol dependent chemiluminescence (CL). The stimulatory capacity of a serum, expressed as percent PMNL chemiluminescence (%CL), was calculated by dividing the integral CL response to the serum by the integral CL response to a standard stimulus, opsonified zymosan. Testing was performed on 50 sera obtained serially from 8 SLE patients and on 14 sera from 11 controls. Sera from SLE patients in remission and controls were nonstimulatory with mean %CL +/- SE values of 3.1 +/- 0.7 and 3.5 +/- 0.9, respectively. Sera obtained from the SLE patients during active disease yielded a mean %CL value of 26.6 +/- 9.0. The stimulatory capacity of SLE serum was concentration dependent and enhanced by adding normal serum complement. The CL response correlated with serological measures of SLE activity such as antibodies to double stranded DNA (p less than .0001) and Clq binding immune complexes (p less than .001). Thus, during active SLE, PMNL may become metabolically activated by exposure to serum containing immune complexes and possibly other factors. PMNL activation may contribute to the development of vasculitis, leukopenia, and susceptibility to infection. Our CL approach allows sensitive in vitro assessment of the phlogistic properties of serum to monitor SLE disease activity.

The transient receptor potential cation channel subfamily V members 1 and 2, P2X purinoceptor 3 and calcitonin gene-related peptide in sensory neurons of the rat trigeminal ganglion, innervating the periosteum, masseter muscle and facial skin. Distribution of the transient receptor potential cation channel subfamily V members 1 (TRPV1) and 2 (TRPV2), and P2X purinoceptor 3 (P2 × 3) was investigated in rat trigeminal ganglion neurons innervating the periosteum, masseter muscle and facial skin. Double immunofluorescence method for TRPV1 and TRPV2 ion channels or ATP receptor P2 × 3 with calcitonin gene-related peptide (CGRP) was performed on trigeminal ganglion neurons retrogradely labeled from the mandibular periosteum, masseter muscle, or facial skin in 15 male Wistar rats. The cell size of periosteum neurons (mean ± S.D. = 810.7 ± 36.1 μ m2) was smaller than that of masseter muscle neurons (927.0 ± 75.6 μ m2), and larger than that of facial skin neurons (661.3 ± 82.2 μ m2). Periosteum neurons contained TRPV1- (26.7%), TRPV2- (47.1%) and P2 × 3-immunoreactivity (50.1%). Expression of TRPV2-immunoreactivity was more abundant among periosteum neurons than among facial skin neurons (16.1%). Regarding to TRPV1 and P2 × 3 expression, however, there was no significant difference between periosteum neurons and, masseter muscle and facial skin neurons. TRPV1- immunoreactive trigeminal ganglion neurons which innervated the periosteum, masseter muscle and facial skin mostly had small and medium-sized cell bodies, whereas TRPV2- and P2 × 3-immunoreactive trigeminal ganglion neurons innervating those tissues were of various cell body sizes. Approximately 20% of periosteum (19.2%), masseter muscle (19.2%) and facial skin (21.5%) neurons contained both TRPV1- and CGRP-immunoreactivity. Some periosteum neurons also co-expressed CGRP-immunoreactivity with TRPV2- (10.9%) or P2 × 3- immunoreactivity (11.1%). Distributions of perivascular and free nerve fibers containing CGRP and either TRPV1, TRPV2, or P2 × 3 were occasionally very similar in the mandibular periosteum. The present study indicated that trigeminal ganglion nociceptors innervating the periosteum as well as those innervating the masseter muscle and facial skin have vanilloid, acidic, thermal, mechanical and ATP sensors. In some periosteum neurons, CGRP may act as inflammatory mediator through activation of TRPV1, TRPV2 and P2 × 3.

Reference values of right atrial longitudinal strain imaging by two-dimensional speckle tracking. The role of speckle tracking in the assessment of right atrial (RA) deformation dynamics has not been established yet. The reference ranges of RA longitudinal strain indices were measured by speckle tracking in a population of normal subjects. In 84 healthy individuals, peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and time to peak longitudinal strain (TPLS) were measured using a six-segment model for the RA. Strain rate (SR) was also measured starting from the QRS-wave onset, peak positive (x-wave), first peak negative (y-wave), and second negative peak (z-wave). The time from the QRS onset was measured to each wave peak. Adequate tracking quality was achieved in 64% of segments analyzed. Inter- and intraobserver variability coefficients of measurements ranged between 6% and 11%. Global PALS was 49 ± 13%, global TPLS was 363 ± 59 msec, x-wave was 2.12 ± 0.58 sec(-1) , y-wave was -1.91 ± 0.63 sec(-1) , and z-wave was -2.18 ± 0.78 sec(-1) . Speckle tracking is a feasible technique for the assessment of longitudinal myocardial RA deformation. Reference ranges of strain indices were reported.

Hemorrhagic shock prevents lung microvascular permeability and hypoxemia associated with complement activation in the awake sheep. The effect of hemorrhagic hypotension on pulmonary dysfunction induced by complement activation was studied in 43 awake sheep, divided into six groups: Group I (n = 6), pulmonary vascular pressure was increased by inflation of a left atrial balloon; group II (n = 9), the complement system was activated by infusion of zymosan activated plasma (ZAP); group III (n = 5), hemorrhagic shock of 50 torr was induced for 3 hr; group IV (n = 10), hemorrhagic shock was induced as in group III, and after 2 hr of shock, ZAP was infused; group V (n = 8), 5 mg/kg of indomethacin was administered before ZAP infusion; group VI (n = 5), pretreatment with indomethacin as in group V, hemorrhagic shock and ZAP as in group IV. ZAP infusion in group II led to a fall in WBC to 2,600/ml (P less than 0.001), and a rise in mean pulmonary artery pressure to 41.1 torr (P less than 0.001) and in pulmonary shunting (QS/QT) to 29.4% (P less than 0.001). Arterial oxygen tension (PaO2) fell to 62.0 torr (P less than 0.001), pulmonary lymph flow (QL) rose to 14.0 ml/hr (P less than 0.01), and lymph protein clearance (L/P.QL) to 8.9 ml/hr (P less than 0.01). Plasma thromboxane B2 (TxB2) increased to 2.43 ng/ml (P less than 0.025) and pulmonary lymph TxB2 to 3.02 ng/ml (P less than 0.005). Hemorrhagic shock was followed by a rise in PaO2 to 97.5 torr (P less than 0.01), a fall in QS/QT to 7.9% (P less than 0.005), QL to 5.0 ml/hr (P less than 0.05), and L/P QL to 2.9 ml/hr (P less than 0.05). During hemorrhage, plasma TxB2 rose to 2.18 ng/ml (P less than 0.005) and lymph TxB2 to 2.32 ng/ml (P less than 0.001). Infusion of ZAP during hemorrhagic shock was followed by a fall in WBC to 2,300/microliter (P less than 0.001); but QS/QT, PaO2, QL, and L/P.QL remained unchanged. After indomethacin and ZAP, WBC fell to 3,210/microliter (P less than 0.001), Ppa rose to 27.0 torr (P less than 0.05), QL rose to 8.3 ml/hr (P less than 0.05), and L/P.QL rose to 5.2 ml/hr (P less than 0.05). PaO2 fell to 75.0 torr (P less than 0.05) and QS/QT increased to 17.1% (P less than 0.005). The protective effect of hemorrhagic shock on ZAP-induced pulmonary dysfunction was not reversed by indomethacin. It is concluded that hemorrhagic shock prevents hypoxemia and increased pulmonary permeability induced by activation of the complement system by ZAP.

Reduced skin threshold to irritation in the presence of allergic contact dermatitis in the guinea pig. The skin is more susceptible to irritation when an active eczematous process is present. This reduced threshold to irritation occurs in skin distant from the site of the eczematous skin. Data is presented to demonstrate the appearance of irritant dermatitis to lower concentrations of sodium lauryl sulfate during the presence of an allergic contact dermatitis in the guinea pig.

Clinical Effect of Sex-Specific Cutoff Values of High-Sensitivity Cardiac Troponin T in Suspected Myocardial Infarction. It is currently unknown whether the uniform (universal clinical practice for more than 2 decades) or 2 sex-specific cutoff levels are preferable when using high-sensitivity cardiac troponin T (hs-cTnT) levels in the diagnosis of acute myocardial infarction (AMI). To improve the management of suspected AMI in women by exploring sex-specific vs uniform cutoff levels for hs-cTnT. In an ongoing prospective, diagnostic, multicenter study conducted at 9 emergency departments, the present study evaluated patients enrolled from April 21, 2006, through June 5, 2013. The participants included 2734 adults presenting with suspected AMI. Duration of follow-up was 2 years, and data analysis occurred from June 5 to December 21, 2015. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including measurements of serial hs-cTnT blood concentrations twice: once using the uniform 99th percentile cutoff value level of 14 ng/L and once using sex-specific 99th percentile levels of hs-cTnT (women, 9 ng/L; men, 15.5 ng/L). Diagnostic reclassification in women and men using sex-specific vs the uniform cutoff level in the diagnosis of AMI. Of the 2734 participants, 876 women (32%) and 1858 men (68%) were included. Median (interquartile range) age was 68 (55-77) and 59 (48-71) years, respectively. With the use of the uniform cutoff value, 127 women (14.5%) and 345 men (18.6%) received a final diagnosis of AMI. Among these, at emergency department presentation, levels of hs-cTnT were already above the uniform cutoff value in 427 patients (sensitivity, 91.3% [95% CI, 85%-95.6%] in women vs 90.7% [95% CI, 87.1%-93.5% in men]; specificity, 79.2% [95% CI, 76.1%-82.1%] in women vs 78.5% [95% CI, 76.4%-80.6%] in men). After readjudication using sex-specific 99th percentile levels, diagnostic reclassification regarding AMI occurred in only 3 patients: 0.11% (95% CI, 0.02-0.32) of all patients and 0.6% (95% CI, 0.13-1.85) of patients with AMI. The diagnosis in 2 women was upgraded from unstable angina to AMI, and the diagnosis in 1 man was downgraded from AMI to unstable angina. These diagnostic results were confirmed when using 2 alternative pairs of uniform and sex-specific cutoff values. The uniform 99th percentile should remain the standard of care when using hs-cTnT levels for the diagnosis of AMI.

Public awareness on integration of leprosy services at primary health centres in Uttar Pradesh, India. Leprosy services were integrated into the general health a decade ago but it seems that a majority of public are still ignorant of this development. Hence, a study was done in Uttar Pradesh, India to determine the awareness about integration and its relationships to various socio-demographic factors. A multistage representative random sample of 3000 persons was chosen in Faizabad district, selecting a sample of 3 villages each situated within 1 km, 1-3 km and beyond 3 km of a PHC. A systematic random sample of 10% of households was chosen from selected villages and an adult male and an adult female from each household interviewed by a qualified investigator. Data were computerized and cross- tabulated against distance from the PHC, sex, age, education and occupational status. Only 45.7% in Uttar Pradesh are aware of the availability of leprosy treatment facilities at PHC but most knew that MDT was free. A smaller proportion was also aware of other facilities such as ulcer dressing and treatment of complications. Family members and health workers and PHC were the main source of information. It is concluded that massive efforts are urgently needed to educate the rural public on integration.

Are heterozygous carriers for hereditary fructose intolerance predisposed to metabolic disturbances when exposed to fructose? High fructose intake causes hepatic insulin resistance and increases postprandial blood glucose, lactate, triglyceride, and uric acid concentrations. Uric acid may contribute to insulin resistance and dyslipidemia in the general population. In patients with hereditary fructose intolerance, fructose consumption is associated with acute hypoglycemia, renal tubular acidosis, and hyperuricemia. We investigated whether asymptomatic carriers for hereditary fructose intolerance (HFI) would have a higher sensitivity to adverse effects of fructose than would the general population. Eight subjects heterozygous for HFI (hHFI; 4 men, 4 women) and 8 control subjects received a low-fructose diet for 7 d and on the eighth day ingested a test meal, calculated to provide 25% of the basal energy requirement, containing 13C-labeled fructose (0.35 g/kg), glucose (0.35 g/kg), protein (0.21 g/kg), and lipid (0.22 g/kg). Glucose rate of appearance (GRa, calculated with [6,6-2H2]glucose), fructose, net carbohydrate, and lipid oxidation, and plasma triglyceride, uric acid, and lactate concentrations were monitored over 6 h postprandially. Postprandial GRa, fructose, net carbohydrate, and lipid oxidation, and plasma lactate and triglyceride concentrations were not significantly different between the 2 groups. Postprandial plasma uric acid increased by 7.2% compared with fasting values in hHFI subjects (P < 0.01), but not in control subjects (-1.1%, ns). Heterozygous carriers of hereditary fructose intolerance had no significant alteration of postprandial fructose metabolism compared with control subjects. They did, however, show a postprandial increase in plasma uric acid concentration that was not observed in control subjects in responses to ingestion of a modest amount of fructose. This trial was registered at the US Clinical Trials Registry as NCT02979106.

An open randomized comparative study of oral itraconazole pulse and terbinafine pulse in the treatment of onychomycosis. Onychomycosis is a recalcitrant disease of the nails caused by dermatophytes, yeasts, and molds. To compare the clinical efficacy of oral itraconazole pulse therapy and oral terbinafine pulse therapy in onychomycosis. A randomized single-blind clinical comparative study was undertaken on 120 patients of onychomycosis during the period March 1999-February 2002. Sixty patients were randomly assigned to receive oral itraconazole 100 mg, two capsules twice daily for seven days a month and the other group of sixty patients received oral terbinafine 250 mg, one tablet twice daily for seven days every month. Four such monthly pulses were administered for each drug. The patients were evaluated at 4-weekly intervals till sixteen weeks and then at 24, 36 and 48 weeks. We observed a clinical cure rate of 82% and mycological cure rate of 90% in the group of patients treated with itraconazole while the group with terbinafine showed clinical and mycological cure rates of 79% and 87% respectively. This difference was not statistically significant. Both oral itraconazole and terbinafine are effective in the treatment of onychomycosis when administered in the pulse dosage form. Terbinafine is more cost effective while itraconazole has a broader spectrum of antimycotic activity.

Extraction and nutritional/hormonal regulation of tissue insulin-like growth factor 1 activity. Studies of insulin-like growth factor 1 (IGF-1) mRNA translation products suggest synthesis as a high Mr precursor, larger than circulating forms. To search for a precursor, we characterized IGF-1 immunoreactivity and IGF bioactivity in extracts from the liver and other body tissues. Sequential extraction with neutral followed by acid buffer was superior to extraction with acid/ethanol or acid alone in yield of immunoreactivity and specific activity. Extracts of normal rat liver exhibited both immuno- and bioactivity parallel to that of recombinant IGF-1 and serum IGFs over a 25-fold concentration range. Based on immunoreactivity, the liver of a 134-g rat appears to contain 1.2 micrograms of IGF-1 equivalents, 50% of the 2.45 micrograms in the circulation. Diaphragm, spleen, and kidney contained no significant IGF bioactivity and 8, 17, and 32% of the IGF-1 immunoreactivity of normal liver, respectively. Although serum IGFs were found at 7.5 kDa after size exclusion chromatography at pH 3, hepatic extracts contained a predominant peak of immuno- and bioactivity of apparent molecular mass of 30-35 kDa; both sizes were present in liver perfusates. Both immunoaffinity chromatography followed by Western blotting and IGF-binding protein affinity chromatography followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two predominant species, at 18-19 and 12 kDa. The 18-19-kDa species is consistent with the apparent size of the glycosylated propeptide encoded by IGF-1A mRNA, while the 12-kDa species may be nonglycosylated propeptide. Extract activity was pituitary-dependent; the livers of hypophysectomized rats contained 15.4 and 48.8% of normal immuno- and bioactivity, respectively. During fasting and refeeding of rats, fluctuations in hepatic extract IGF-1 immunoreactivity generally paralleled changes in serum IGF-1 (r = 0.93, p less than 0.001). These studies demonstrate that the liver contains a pituitary- and nutrition-dependent, high Mr form of IGF-1 with immunological and biological properties similar to circulating IGF-1. Processing of this 18-19-kDa molecule through a 12-kDa intermediate may contribute IGF-1 to the circulation.

The value of intramural vascular invasion in colorectal cancer - a systematic review and meta-analysis. Extramural venous invasion (EMVI) is a well-known prognostic factor in colorectal cancer (CRC). Vascular invasion within the bowel wall, intramural vascular invasion (IMVI), has received less attention and its incidence and prognostic importance in CRC is not completely known. A systematic literature search was performed focusing on the impact of IMVI in CRC. Data were analysed using Review Manager version 5.3 on incidence and clinical endpoints local recurrence, 5-year cancer-specific survival (CSS) and 5-year overall survival (OS). Meta-analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). Of the initial 1199 papers identified by our search strategy, 20 were included in this meta-analysis. Of the 8078 included patients, 1008 patients had IMVI (12.5%). Studies that re-examined histological slides showed a higher incidence of IMVI compared to studies extracting IMVI from pathology reports (17.6 versus 7.7%, P < 0.001). Detection of IMVI increased significantly with the use of additional staining (22.9 versus 12.3%, P < 0.001). IMVI was associated with a decreased CSS HR: 1.6, 95% CI 1.2-2.2 in multivariate analysis). A borderline significant effect was observed for IMVI on local recurrence (RR: 1.5, 95% CI: 0.98-2.3) and OS (RR: 1.2, 95% CI: 1.0-1.4). In conclusion, despite the limited number of studies, there is a clear association with outcome in the presence of IMVI. This warrants more attention to this under-reported prognostic factor.

Nateglinide improves postprandial hyperglycemia and insulin secretion in renal transplant recipients. Postprandial hyperglycemia (PPHG) frequently occurs among renal transplant recipients (RTR). Reduced early insulin response (EIR) after a meal leads to impaired suppression of endogenous glucose production and subsequently PPHG, which is a risk factor for cardiovascular disease. Nateglinide is a rapid acting insulin secretagogue inducing an EIR after a meal. Our main objective was to investigate the safety and effect of nateglinide treatment on postprandial plasma glucose excursions and insulin secretion in RTR with PPHG. A total of 14 Caucasian RTR with new-onset diabetes mellitus (NODM; n = 6) or impaired glucose tolerance (IGT; n = 8) were included. The insulin response and glucose excursions were measured for 240 min after a standardized liquid meal at baseline and after two-wk treatment with nateglinide. Treatment with nateglinide was followed by a significant decrease in mean two-h plasma glucose from 10.5 mmol/L (3.1) to 7.6 mmol/L (2.1; p < 0.001) and a decline in total postprandial area under the curve (AUC) of glucose concentration (p < 0.001). Both estimated EIR and the late insulin response increased significantly (p = 0.008 and p = 0.003, respectively). No serious adverse event was observed during the study period. Treating RTR with nateglinide for two-wk significantly improved PPHG, increased the insulin response following a standardized meal and was well tolerated.

Chronic pelvic pain. Chronic pelvic pain is a common and significant disorder of women. It is estimated to have a prevalence of 3.8% in women. Often the etiology of chronic pelvic pain is not clear, as there are many disorders of the reproductive tract, gastrointestinal system, urological organs, musculoskeletal system, and psychoneurological system that may be associated with chronic pelvic pain. The history and physical examination are crucial in evaluating a woman with chronic pelvic pain and must address all of the possible systems potentially involved in chronic pelvic pain, not just the reproductive system. Laboratory and imaging studies should be selectively utilized, as should laparoscopy. Conscious laparoscopic pain mapping has been proposed as a way to improve information derived from laparoscopic evaluations. Treatment of chronic pelvic pain may consist of two approaches. One is to treat chronic pain itself as a diagnosis, and the other is to treat diseases or disorders that might be a cause of or a contributor to chronic pelvic pain. These two approaches are not mutually exclusive, and in many patients effective therapy is best achieved by using both approaches. Treatment of chronic pain as well as treatment of four of the more common disorders associated with chronic pelvic pain (endometriosis, adhesions, irritable bowel syndrome, and interstitial cystitis) are discussed in this review.

Two novel p38 MAPKs identified from Epinephelus coioides and their expression pattern in response to Cryptocaryon irritans infection. P38 mitogen-activated protein kinases (MAPKs) are one of the most important central regulatory proteins response to extra environmental stresses. In this study, two novel p38 MAPKs, Ec-P38γ and Ec-P38δ, were identified from Epinephelus coioides, an economically important cultured fish in China and Southeast Asian counties. Both of Ec-p38γ and Ec-p38δ sequences contain a serine/threonine protein kinase (S_TKc) domain and a highly conserved Thr-Gly-Tyr (TGY) motif. Analysis of phylogenetic relationships illustrated that p38 amino acid sequences were conserved between different species indicating that the functions may be similar. The four subtypes of p38 (α, β, γ, and δ) mRNA can be detected in all thirteen tissues examined, but the expression level is different in these tissues. The expression patterns of the four Ec-p38 subtypes in E. coioides were also detected response to Cryptocaryon irritans infection, one of the most important protozoan pathogens of marine fish. The expression of four p38 subtypes was up-regulated in the tissues examined, with the highest expressions of Ec-p38α (5.2 times) and Ec-p38δ (4.2 times) occurring in the skin, while Ec-p38β (24.8 times) and γ (16.6 times) occurred in the spleen. There was no significantly correlation between the expression of Ec-p38γ/Ec-p38δ and the expression of nuclear factor kappaB (NF-kB). The results indicated the sequences and the characters of Ec-p38γ and Ec-p38δ were conserved, the p38 subtypes showed tissue-specific expression patterns in healthy grouper, and their expressions were significantly up-regulated post C. irritans infection, suggesting these p38 MAPKs may play important roles in these tissues during pathogen-caused inflammation.

Antigenic cross-reactivity among the venoms from several species of Brazilian scorpions. The venoms of seven species of scorpions living in different regions of Brazil were analysed with regard to their lethality, antigenic cross-reactivity and ability to induce antibody production. In mice, the tested scorpion venoms can be grouped as: (a) highly toxic: Tityus stigmurus Thorell (LD50 = 0.773 mg/kg), Tityus bahiensis (Perty) (LD50 = 1.062 mg/kg), Tityus serrulatus Lutz and Mello (LD50 = 1.160 mg/kg), and Tityus costatus (Karsch) (LD50 = 1.590 mg/kg); (b) moderately toxic: Tityus cambridgei Pocock (LD50 = 12.136 mg/kg); and (c) practically nontoxic: Rhopalurus agamemnon (Koch) (LD50 = 36.363 mg/kg), and Brotheas amazonicus Lourenço (LD50 = 90.909 mg/kg). On electrophoresis the venoms showed many protein bands displayed along the chromatogram, most of them cross-reacting in immunoelectrophoresis and immunoblotting using horse anti-T. serrulatus, anti-T. bahiensis or anti-T. serrulatus+T. bahiensis sera as probes. The antibodies present in these antivenoms combine with venom components as measured in vitro by the ELISA assay, and neutralize their lethal effects in vivo. These results indicate that horse anti-venoms against a mixture of T. serrulatus and T. bahiensis venoms or only against T. serrulatus venom yield an antibody population able to neutralize the toxic effects found in all venoms studied.

Intermittent high-dose melphalan/prednisone vs continuous low-dose melphalan treatment in multiple myeloma. Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.

High frequency activity overriding cortico-cortical evoked potentials reflects altered excitability in the human epileptic focus. We aimed to clarify that high frequency activity (HFA) of cortico-cortical evoked potentials (CCEPs), elicited by single pulse electrical stimulation (SPES), reflects cortical excitability. We recruited 16 patients with refractory partial epilepsy who had chronic subdural electrode implantation for presurgical evaluation. A repetitive SPES was given to (1) the seizure onset zone (SOZ) and (2) the control cortices (non-seizure onset zone: nSOZ). CCEPs were recorded from the neighboring cortices within SOZ and nSOZ. We applied short-time Fourier transform to obtain the induced responses for the timing of early (<50ms after SPES) and late CCEP components and analyzed the logarithmic power change for ripple (<200Hz) and fast ripple (>200Hz) bands. Twenty-one clear CCEPs were recorded for both the SOZ and nSOZ. The HFA power of early CCEPs in SOZ significantly increased compared to that in nSOZ in both frequency bands, particularly in mesial temporal lobe epilepsy (MTLE). Similar to the features of spontaneous pathological HFOs, the power of stimulus-induced HFAs in SOZ were greater than that outside SOZ, particularly in MTLE. HFA overriding CCEPs can be a surrogate marker of cortical excitability in epileptic focus.

Synaptic glutamate receptor clustering in mice lacking the SH3 and GK domains of SAP97. Postsynaptic targeting of the Drosophila tumour suppressor discs-large (Dlg) critically depends on its SH3 and GK domains. Here, we asked whether these domains are also involved in subcellular targeting of the mammalian Dlg homolog SAP97 and its interacting partners in CNS cortical neurons by analysing a recently described mouse mutant lacking the SH3 and GK domains of SAP97. Both wildtype and truncated SAP97 were predominantly expressed in perinuclear regions, in a pattern suggesting association with the endoplasmic reticulum. Weaker immunoreactivity was found in neurites colocalizing with both dendritic and axonal markers. As SAP97 has been implicated in the early intracellular processing of the glutamate receptor GluR1, we studied biochemical maturation and subcellular localization of GluR1 in the mutants. Both the glycosylation pattern and synaptic clustering of GluR1 were indistinguishable from wildtype mice. Synaptic clustering of the guanylate kinase domain interacting protein GKAP was also intact. Our data demonstrate that truncation of the SH3 and GK domains of SAP97 in mice does neither change its subcellular distribution nor does it disrupt synaptic structure or protein clustering, as opposed to severe missorting of the respective mutant Dlg protein in Drosophila.

Granulomatosis with CNS involvement: a neuroimaging clinicopathologic correlation. To present a rare case of a rheumatologic disorder with a central nervous system manifestation. A 48-year-old female with history of nasal and auricular pain and inflammation developed bilateral intermittent scleritis that was refractory to several immunosuppressive medications. She later presented with headaches and right upper extremity parasthesias. Brain magnetic resonance imaging (MRI) was obtained and she was referred to a neurosurgeon. Neurological examination did not reveal any focal deficits. Laboratory analysis demonstrated an elevated erythrocyte sedimentation rate (ESR). Brain MRI with and without gadolinium contrast revealed an extra-axial, enhancing, left frontoparietal convexity lesion. The patient was taken to the operating room for biopsy and resection of the mass. Final pathology demonstrated dural granulomatosis with vasculitis, most consistent with intracranial Wegener's granulomatosis. The patient was discharged to follow-up with her rheumatologist for further medical management. Enhancing, intracranial dural lesions are associated with a variety of disease entities. Wegener's granulomatosis is one such entity and should be considered in the correct context.