Psychomotor effects of dopamine infusion under decreased glutathione conditions.
Administration of buthionine sulfoximine (BSO) selectively inhibits glutathione (GSH) biosynthesis, thereby inducing a GSH deficiency. Because GSH plays a critical role in intracellular antioxidant defense, decreased GSH levels in the brain may result in less oxidative stress (OS) protection. Thus, the pro-oxidant effects of dopamine (DA), which rapidly oxidizes to form reactive oxygen species, may increase. In this study, the behavioral consequences of reduced OS protection were examined by administering BSO (3.2 mg in 30 microl Ringer's solution, intracerebroventricularly) every other day for 12 d to male Fischer 344 rats. In addition, DA (15 microl of 500 microM) was administered every day; when given on the same day as BSO, it was either 1 h after BSO (BSO + DA group) or 1 h before BSO (DA + BSO group). Tests of psychomotor behavior--rod walking, wire suspension, and plank walking--were performed five times during the experiment. BSO + DA administration, but not DA + BSO, impaired performance by decreasing latency to fall in the rod and plank walk tests compared to a vehicle only (Ringer's) group. Therefore, depletion of GSH with BSO, followed by DA treatment, produced deficits in psychomotor behavior. These deficits are similar to those seen in aged rats, suggesting that the oxidation of DA coupled with a reduced capacity to respond to OS may be responsible for the induction of age-related motor behavioral deficits.


Diagnostic Accuracy of Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Analysis.
Purpose To evaluate diagnostic accuracy of low-dose volume perfusion (VP) computed tomography (CT) compared with original VP CT regarding the detection of cerebral perfusion impairment after aneurysmal subarachnoid hemorrhage. Materials and Methods In this retrospective study, 85 patients (mean age, 59.6 years; 62 women) with aneurysmal subarachnoid hemorrhage and who were suspected of having cerebral vasospasm at unenhanced CT and VP CT (tube voltage, 80 kVp; tube current-time product, 180 mAs) were included, 37 of whom underwent digital subtraction angiography (DSA) within 6 hours. Low-dose VP CT data sets at tube current-time product of 72 mAs were retrospectively generated by validated realistic simulation. Perfusion maps were generated from both data sets and reviewed by two neuroradiologists for overall image quality, diagnostic confidence and presence and/or severity of perfusion impairment indicating vasospasm. An interventional neuroradiologist evaluated 16 vascular segments at DSA. Diagnostic accuracy of low-dose VP CT was calculated with original VP CT as reference standard. Agreement between findings of both data sets was assessed by using weighted Cohen κ and findings were correlated with DSA by using Spearman correlation. After quantitative volumetric analysis, lesion volumes were compared on both VP CT data sets. Results Low-dose VP CT yielded good ratings of image quality and diagnostic confidence and classified all patients correctly with high diagnostic accuracy (sensitivity, 99.0%; specificity, 99.5%) without significant differences regarding presence and/or severity of perfusion impairment between original and low-dose data sets (Z = -0.447; P = .655). Findings of both data sets correlated significantly with DSA (original, r = 0.671; low dose, r = 0.667). Lesion volume was comparable for both data sets (relative difference, 5.9% ± 5.1 [range, 0.2%-25.0%; median, 4.0%]) with strong correlation (r = 0.955). Conclusion The results suggest that radiation dose reduction to 40% of original dose levels (tube current-time product, 72 mAs) may be performed in VP CT imaging of patients with aneurysmal subarachnoid hemorrhage without compromising the diagnostic accuracy regarding detection of cerebral perfusion impairment indicating vasospasm. © RSNA, 2018 Online supplemental material is available for this article.


The spatial population dynamics of insects exploiting a patchy food resource : II. Movements between patches.
The population dynamics of ten species of phytophagous insects and seven parasitoids inhabiting the flowerheads of two herbaceous plants, Centaurea nigra and Arctium minus, were studied, and three main aspects of their ecology were examined, namely, rates of population extinction, density dependence in population changes from one generation to the next, and movements between populations. The study was based on monitoring the insect populations on more than 50 patches of each plant, scattered over 5 km2 of arable farmland and the results were used to test the relative importance of immigration and population regulation to the persistence of these populations. This paper describes the study of movements between patches of food plant. Experimentally planted new patches of plants were rapidly colonised by all species and this appeared to be unaffected by distance from a source population, up to the maximum distance of 800 m considered in the experiment. Large patches tended to be colonised more readily than small ones. Movements between plant patches were studied with the use of chemical markers (Rb, Sr, Dy and Cs) which were applied as chloride salts to individual patches, and which were translocated to the flowerheads and so to insects feeding on the seed, and to their parasitoids. Initial experiments in the laboratory showed that these elements could be readily detected by ICP (Inductively Coupled Plasma) mass spectrometry in the bodies of all species reared on potted plants sprayed with solutions containing them. Background levels of strontium were patchily high on the study area, but the other elements were naturally either absent or in very low concentrations. Four patches of each plant were marked with a different element in 1991. In 1992, samples of four species of tephritid fly and two parasitoids were collected from all patches, and analysed for the four elements. These analyses showed that individual of all species moved considerable distances, with movements of up to 2 km being commonly recorded. Estimates of rates of immigration to patches showed that movement plays an important role in the population dynamics of these insects. There was some evidence that immigration was density-dependent: it was highest when the resident populations (numbers per flowerhead) were low.


The depiction of the bilaminar zone of the temporomandibular joint by magnetic resonance imaging.
The existence of two distinct strata forming the bilaminar zone of the temporomandibular joint disc has recently been questioned. We report their successful demonstration using protondensity MR imaging. Our findings confirm earlier anatomical descriptions of the behaviour of the upper stratum during mouth opening.


Multiplex ligation-dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements.
Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation-dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD-MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ-1 genes. We then applied this technique to screen 16 EOP patients who were then cross-tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH-L1 exon 9, respectively. These results show that PD-MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ-1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP.


Kinocilia heights on utricular hair cells.
Kinocilium height is a critical determinant of any hair cell's response to head movement, but accurate measurements of kinocilia heights have been difficult to achieve. We have developed a method for measuring kinocilia heights that combines immunochemical staining with three-dimensional morphometry, and we have used this method to measure kinocilia in the utricle of a turtle, Pseudemys scripta. Our results suggest that kinocilium height varies with position on the utricular epithelium and that kinocilia in the striola are significantly shorter than kinocilia in other regions of the utricle.


Perspectives on Perspective Taking: How Children Think About the Minds of Others.
Perspective taking, or "theory of mind," involves reasoning about the mental states of others (e.g., their intentions, desires, knowledge, beliefs) and is called upon in virtually every aspect of human interaction. Our goals in writing this chapter were to provide an overview of (a) the research questions developmental psychologists ask to shed light on how children think about the inner workings of the mind, and (b) why such research is invaluable in understanding human nature and our ability to interact with, and learn from, one another. We begin with a brief review of early research in this field that culminated in the so-called litmus test for a theory of mind (i.e., false-belief tasks). Next, we describe research with infants and young children that created a puzzle for many researchers, and briefly mention an intriguing approach researchers have used to attempt to "solve" this puzzle. We then turn to research examining children's understanding of a much broader range of mental states (beyond false beliefs). We briefly discuss the value of studying individual differences by highlighting their important implications for social well-being and ways to improve perspective taking. Next, we review work illustrating the value of capitalizing on children's proclivity for selective social learning to reveal their understanding of others' mental states. We close by highlighting one line of research that we believe will be an especially fruitful avenue for future research and serves to emphasize the complex interplay between our perspective-taking abilities and other cognitive processes.


Rational electronic tuning of CBS catalyst for highly enantioselective borane reduction of trifluoroacetophenone.
α,α,α-Trifluoroacetophenone (2), which is susceptible to noncatalytic reduction by BH(3), could be reduced to chiral alcohol up to 90% ee by using electronically tuned-CBS catalyst (1) with BH(3). The enantioselectivities highly correlated with the differential orbital energies between 1-BH(3) adduct and 2, which were calculated by DFT method.


Can the sensitivity of the Alzheimer's Disease Assessment Scale be increased?
The author analyzed and compared Mini-Mental State Exam and Alzheimer's Disease Assessment Scale (ADAS) scores for 48 patients with Alzheimer's disease to determine whether improvements could be made in the ADAS. Results suggest that cognitive ability could be more accurately evaluated by shortening the number of words on the ADAS word recall task and reducing the number of trials on the word recognition task. These modifications would increase the likelihood of identifying medication effects.


Effect of prolyl endopeptidase inhibition on arginine-vasopressin and thyrotrophin-releasing hormone catabolism in the rat brain.
Compound S 17092 is a potent and selective inhibitor of prolyl endopeptidase (EC 3.4.21.26, PEP) that may be of therapeutic value for the treatment of memory impairment associated with neurodegenerative diseases. In the present study, we investigated the effects of S 17092 on the catabolism of the promnesic neuropeptides thyrotrophin-releasing hormone (TRH) and arginine-vasopressin (AVP) in the rat brain. In vitro, bacterial PEP hydrolysed both TRH and AVP, and the breakdown of the two peptides was almost completely prevented by 10(-5) M S 17092. In vivo, a single oral administration of S 17092 provoked a significant increase in TRH-like immunoreactivity (TRH-LI) in the cerebral cortex (+63% for a 10 mg/kg dose and +72% for a 30 mg/kg dose), as well as AVP-LI in the hippocampus (+54% for a 30 mg/kg dose), but did not affect TRH-LI in the amygdala nor AVP-LI in the cerebral cortex. Chronic administration of S 17092 (10 or 30 mg/kg daily) lead to a significant increase in THR-LI in the cerebral cortex (+55% and +56%, respectively), but did not modify AVP-LI in the hippocampus, nor in the cerebral cortex. These results show that the selective PEP inhibitor S 17092 increases TRH and AVP content in discrete regions of the rat brain. The present data suggest that the promnesic and antiamnesic effects of S 17092 can be accounted for, at least in part, by blockage of AVP and TRH degradation by PEP.


Traumatic aortic rupture: twenty-year metaanalysis of mortality and risk of paraplegia.
A metaanalysis of articles concerning the surgical management of acute traumatic rupture of the descending thoracic aorta published in the English-language literature between 1972 and July 1992 was performed. The overall mortality of 1,742 patients who arrived at the hospital alive was 32.0%, one-third died before surgical repair was started. Paraplegia was noted preoperatively in 2.6% of these hospitalized patients, and paraplegia complicated the surgical repair in 9.9% of 1,492 patients who reached the operating room in a relatively stable condition. Patients then were analyzed according to the surgical intervention used. Simple aortic cross-clamping (n = 443) was associated with a hospital mortality of 16.0% and incidence of paraplegia of 19.2%, despite lower average mean cross-clamp times (32 minutes; p < 0.01 versus passive or active methods of providing distal perfusion). In a subset of 290 patients in whom individual data were available, the cumulative risk of paraplegia was shown to increase substantially if the duration of aortic cross-clamping exceeded 30 minutes, but only when distal perfusion was not augmented (p < 0.00001). "Passive" perfusion shunts (n = 424) were associated with a mortality of 12.3%, and the incidence of paraplegia decreased to 11.1% (p < 0.001). However, shunts inserted from the apex of the left ventricle had a contradictory high 26.1% incidence of paraplegia compared with shunts from the ascending aorta (8.2%; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


WITHDRAWN: Dieting to reduce body weight for controlling hypertension in adults.
As early as the 1920's, researchers noted a relationship between caloric restriction, weight loss and a decreased incidence of hypertension (Terry 1922, Preble 1923, Bauman 1928, Master 1929). In 1988 a meta-analysis of aggregate data from 12 prospective studies, including 5 randomized controlled trials (RCTs), found that on average each 1 kilogram decrease in body weight in obese hypertensive patients was associated with a 2.4 mm Hg systolic and 1.5 mm Hg diastolic decrease in blood pressure (Staessen 1988). Blood pressure reductions were not dependent upon degree of baseline obesity.This review aims to: 1) update the work of Staessen (Staessen 1988) looking specifically at randomized controlled trials, and 2) assess whether any of the trials assess effects of weight-reducing diets on clinical outcomes such as quality of life, morbidity or mortality. Evaluate whether weight-loss diets are more effective than regular diets or other antihypertensive therapies in controlling blood pressure and preventing morbidity and mortality in hypertensive adults. MEDLINE and The Cochrane Library were searched through November 1997. Trials known to experts in the field were included through June 1998. For inclusion in the review, trials were required to meet each of the following criteria: 1) randomized controlled trials with one group assigned to a weight-loss diet and the other group assigned to either normal diet or antihypertensive therapy; 2) ambulatory adults with a mean blood pressure of at least 140 mm Hg systolic and/or 90 mm Hg diastolic; 3) active intervention consisting of a calorie-restricted diet intended to produce weight loss (excluded studies simultaneously implementing multiple lifestyle interventions where the effects of weight loss could not be disaggregated); and 4) outcome measures included weight loss and blood pressure. Studies were dual abstracted by two independent reviewers using a standardized form designed specifically for this review. The primary mode of analysis was qualitative; graphs of effect sizes for individual studies were also used. Eighteen trials were found. Only one small study of inadequate power reported morbidity and mortality outcomes. None addressed quality of life or general well being issues. In general, participants assigned to weight-reduction groups lost weight compared to control groups.Six trials involving 361 participants assessed a weight-reducing diet versus a normal diet. The data suggested weight loss in the range of 4% to 8% of body weight was associated with a decrease in blood pressure in the range of 3 mm Hg systolic and diastolic. Three trials involving 363 participants assessed a weight-reducing diet versus treatment with antihypertensive medications. These suggested that a stepped-care approach with antihypertensive medications produced greater decreases in blood pressure (in the range of 6/5 mm Hg systolic/diastolic) than did a weight-loss diet. Trials that allowed adjustment of participants' antihypertensive regimens suggested that patients required less intensive antihypertensive drug therapy if they followed a weight-reducing diet. Data was insufficient to determine the relative efficacy of weight-reduction versus changes in sodium or potassium intake or exercise. Weight-reducing diets in overweight hypertensive persons can affect modest weight loss in the range of 3-9% of body weight and are probably associated with modest blood pressure decreases of roughly 3 mm Hg systolic and diastolic. Weight-reducing diets may decrease dosage requirements of persons taking antihypertensive medications.


Dual infection with human papillomavirus in a population with overt genital condylomas.
Multiple human papillomavirus (HPV) genotypes have been demonstrated in individual patients; usually, different genotypes occur in different anatomic sites. Our purpose was to evaluate the prevalence of multiple HPV types from the same anatomic site. During the course of a study evaluating topical versus ablative therapy for external genital HPV, sequential biopsies on patients with external genital warts were performed. HPV DNA content was determined by Southern hybridization. Ninety-two specimens from 63 patients (48 women, 15 men) with genital warts were evaluated. Dual infection with two HPV genotypes was documented in each of four specimens (6.3%). Sequential biopsy specimens from the same anatomic site in the same person revealed dual infection in 5 of 12 sampled patients (41%). Overall, 14% of patients had dual genitourinary HPV infection. Counseling and follow-up of long-term complications, such as transmission and the risk of subsequent genitourinary carcinoma, should be performed on all patients with HPV because of the possibility of undetected HPV DNA types in the individual patient.


Development of gonadotropes in the chicken embryonic pituitary gland.
Although a number of immunohistochemical studies have been carried out on the differentiation of chicken gonadotropes during embryogenesis, the temporal and spatial properties of appearance of gonadotropes are not clear. In this study, we studied the appearance and morphological characteristics of gonadotropes in the embryonic and adult chicken anterior pituitary glands using RT-PCR, in situ hybridization and immunohistochemistry. For this purpose, we raised specific antisera against chicken follicle-stimulating hormone beta-subunit (cFSHbeta) and chicken luteinizing hormone beta-subunit (cLHbeta) based on each putative amino acid sequence. RT-PCR analysis revealed that cFSHbeta mRNA was expressed from embryonic day 7 (E7). Chicken FSHbeta mRNA-expressing (-ex) and -immunopositive (-ip) cells started to appear in the ventral part of the caudal lobe in the anterior pituitary gland at E8. Chicken LHbeta-ip cells were also first observed there at E8, but cLH mRNA expression was confirmed from E4 by RT-PCR analysis. The distribution of these chicken gonadotropin-ex and -ip cells spread from the ventral part to dorsal part in the caudal lobe around E10 and subsequently expanded to the cephalic lobe from E12 to E20. These cells were morphologically classified into two types (round- and club-shaped cells). It was found that the density of gonadotropin-ip cells in the caudal lobe was always higher than that in the cephalic lobe throughout the period of development. To the best of our knowledge, this is the first report focusing on the differentiation of chicken gonadotropes by assessment of both protein and mRNA of chicken gonadotropin.


Association between factors predicting and assessing the airway and use of intubating laryngeal mask airway.
The Intubating Laryngeal Mask Airway FastrachTM (ILMA) has been used with success in difficult intubation cases. The purpose of this study is to evaluate the effect of mouth opening, Mallampati classification, thyromental distance and Cormack-Lehane Grade, on the ease of ILMA use. Eighty one patients ASA I-II, were assessed preoperatively for mouth opening, Mallampati classification and thyromental distance. After induction with propofol and rocuronium, the first investigator recorded Cormack-Lehane Grade by direct laryngoscopy. Subsequently an appropriate size ILMAwas inserted by the second investigator and correct placement was confirmed by adequate ventilation and normal capnogram. A maximum of three ILMA insertion attempts were allowed and the number was recorded. Then blind intubation was attempted and classified as follows, according to Intubation Difficulty Grade (IDG): IDG-1: intubation succeeded: at first attempt requiring no or minor ILMA manipulations. IDG-2: intubation succeeded at second attempt requiring major ILMA manipulations or size change. IDG-3: intubation failed after the second attempt or oesophageal intubation occurred at either attempt. In failure of the technique direct laryngoscopy was the alternative approach. Success rates in insertion of ILMA and in blind intubation were 100% and 92.6% respectively. No difference was found between Cormack-Lehane Grade I-II and II-IV or Mallampati classification and number of ILMA insertion attempts or IDG. There was also no correlation between mouth opening, or thyromental distance and number of ILMA insertion attempts or IDG. It is concluded that easiness of ILMA use is irrelevant to mouth opening, thyromental distance, Mallampati classification or Cormack-Lehane Grade.


[High frequency of thyroid abnormalities in polycystic ovary syndrome].
The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p<0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities (p<0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.


Scapegoating and the unpopular nurse.
This paper considers the theories of scapegoating and their application to nursing. It reviews the literature on scapegoating drawing particular attention to those studies which have emphasised on the instrumental uses of scapegoating in organisational contexts. The paper draws on data from a qualitative study of the identification and management of the 'problem' nurse conducted in three healthcare Trusts. It describes a number of illustrative cases in which different types of scapegoating occurred. The paper argues that scapegoating is an ethical challenge which nurses must face.


Evaluation of the Pharmacokinetic Interaction Between the Voltage- and Use-Dependent Nav1.7 Channel Blocker Vixotrigine and Carbamazepine in Healthy Volunteers.
Vixotrigine is a voltage- and use-dependent Nav1.7 channel blocker under investigation for the treatment of peripheral neuropathic pain conditions, including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine diphosphate-glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first-line treatment for trigeminal neuralgia. We conducted a double-blind, randomized, placebo-controlled, parallel-group, single-center phase 1 study to investigate the impact of coadministering vixotrigine and carbamazepine on their respective pharmacokinetics (PK) in healthy volunteers, the safety and tolerability of combined treatment, and PK recovery of vixotrigine following carbamazepine discontinuation. Randomly assigned treatments were carbamazepine (100 mg twice a day, days 1-3 and 200 mg twice a day, days 4-21) or placebo on days 1 to 21. All volunteers received vixotrigine 150 mg 3 times a day on days 16 to 28. At prespecified times, whole-blood samples were collected for PK assessment. Statistical analyses were performed on the log-transformed PK parameters area under the concentration-time curve within a dosing interval (AUC0-tau ) and maximum observed concentration (Cmax ) for vixotrigine, carbamazepine, and metabolites. Vixotrigine AUC0-tau and Cmax were reduced by 31.6% and 26.3%, respectively, when coadministered with carbamazepine compared with placebo. Seven days after carbamazepine discontinuation, vixotrigine AUC0-tau and Cmax remained 24.5% and 21.4% lower compared with placebo. Carbamazepine AUC0-tau and Cmax were <10% lower when coadministered with vixotrigine compared on days 15 and 21. Vixotrigine/carbamazepine coadministration was well tolerated. These results suggest that vixotrigine does not have an effect on carbamazepine PK, and although carbamazepine has an effect on the exposure of vixotrigine, the effect is not considered clinically relevant.


Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.
Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.


Compression of an extracardiac fontan following classic fontan revision.
The extracardiac Fontan arose as an alternative in order to prevent the classical procedure's sequelea. Complications of the extracardiac Fontan have been described, but this case report aims to highlight the devastating and infrequent complication of external conduit compression. A 25-year-old male underwent Fontan conversion to extracardiac Fontan for atrial arrhythmias and giant right atrium. He developed postoperative respiratory distress, renal failure, and hemorrhagic pancreatitis, which prompted CT scans of his chest and abdomen that demonstrated external compression of the conduit by mediastinal hematoma. Endovascular stenting restored flow through the conduit, but the patient ultimately expired. External Fontan compression, which can be caused by numerous sources, may lead to significant organ dysfunction and can be difficult to recognize despite invasive monitoring. We report this complication and suggest ringed conduits to be considered to avoid the possibility of external compression.


General aspects of the effectiveness of anabolic agents in increasing protein production in farm animals, in particular in bull calves.
The role of farm animals as converters of feed protein into protein edible for humans has often been criticized for the lack of efficiency of this process. In a series of 192 N-balance studies with veal calves it was found, however, that these animals convert at an early age even more than 70 percent of the feed protein into body protein. The deterioration of the N-conversion, so undesirable from a point of view of food production, is found when the animals grow older. With increasing age the conversion ratio went down to approximately 40-50 percent in our studies. This could only be explained by assuming a poorer efficiency of the intermediate metabolic processes with increasing age. For an increase of the production of edible protein from the available feed sources in the world, it is obviously of great importance to maintain the favourable conversion ratio of young farm animals for the longest possible time. The object of this paper is to consider whether and to what extent a positive effect on the efficiency of the protein formation can be exerted by the application of anabolic agents using the veal calf as a model. In the category of artificial estrogens we found DES to be effective in this respect. In the category of natural hormones testosterone and progesterone did not exert anabolic effects. The implantation of 17beta-estradiol improved the conversion of feed protein into body protein to approximately the same extent as DES. A combination of estradiol with testosterone tended to be more effective than estradiol alone. The more recently isolated agents zeranol and trenbolone did not lead to significant improvements in N-retention. A combination of trenbolone with estradiol improved N-retention better than any of the other treatments. The quantitative importance of the phenomena discussed for protein production is illustrated as follows. With the most effective treatment studied, the percentage of feed protein converted into body protein was increased during an experimental period of 38 days, from 39 percent in the control group to 58 percent in the treated group. There is no doubt that a further intensification of the research in this field is recommendable in order to create and study active agents combinining a high degree of efficacy with the absence of undesirable side effects for man and animals.


[WHO Polio Eradication Programme:Status quo and implementation in Austria].
In 1988 the 41(th) World Health Assembly declared polio to be worldwide eradicated until the year 2000. Although this ambitious aim could not be reached completely, the yearly worldwide incidence was reduced by 99% and three WHO-Regions were declared polio-free (Americans, West Pacific, Europe). To maintain this status the following measures have to be carried out: polio vaccination, enterovirus surveillance, AFP-surveillance, quality control of laboratories and notification of labs keeping stocks of polio wildvirus. Especially after the Second World War Austria faced severe polio epidemics and thus general and free of charge polio vaccination for children and young adults up to 21 years was started in winter 1961/62 by the Austrian Ministry of Health (MoH). Immediately the yearly incidence dropped from 3.65/100.000 (n = 292) in 1961 to 0.1/100.000 (n = 8) in 1962. Since 1998 all mandatory national measures according the WHO polio eradication programme have been performed. Despite the worldwide success of the programme there are currently still four countries with endemic polio and since November 2006 eleven further countries have faced epidemics due to imported cases. Therefore the 60(th) World Health Assembly in 2007 again pointed to the threat of failing worldwide polio eradication. Currently the Global Polio Eradication Initiative (GPEI) works intensively with the concerned countries to fight against this development.


Identifying opinion leaders to promote behavior change.
This article reviews 10 techniques used to identify opinion leaders to promote behavior change. Opinion leaders can act as gatekeepers for interventions, help change social norms, and accelerate behavior change. Few studies document the manner in which opinion leaders are identified, recruited, and trained to promote health. The authors categorize close to 200 studies that have studied or used opinion leaders to promote behavior change into 10 different methods. They present the advantages and disadvantages of the 10 opinion leader identification methods and provide sample instruments for each. Factors that might influence programs to select one or another method are then discussed, and the article closes with a discussion of combining and comparing methods.


The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma II: longer-term outcomes from a single surgeon.
To analyze the longer-term surgical outcomes of Ahmed and Baerveldt shunt implants in the treatment of refractory glaucoma. Retrospective, nonrandomized, comparative trial. Consecutive patients who underwent glaucoma shunt implantation (70 Baerveldt, 48 Ahmed) by a single surgeon. Follow-up retrospective analysis of 118 consecutive cases of refractory glaucoma that required placement of either Ahmed or Baerveldt shunt implants for intraocular pressure (IOP) control. The longer term clinical course (survival curve analysis up to 48 months) was reviewed. The primary outcome measure was surgical success (6 mmHg < or = IOP < or = 21 mmHg without additional glaucoma surgery or devastating complication). Secondary outcome measures included mean IOP and number of medications used at the following postoperative visits: day 1, 1 week, 1 month, 3 months, 6 months, and every 6 months thereafter (up to 48 months). In unsuccessful cases, the median time to failure was determined. No significant differences in success rates were noted at 1, 2, 3, or 4 years after surgery, with 4-year success rates of 62% for the Ahmed group and 64% for the Baerveldt group (P = 0.843). Mean IOPs were comparable from 1 to 48 months (P>0.05). However, patients in the Ahmed group required more glaucoma medications at 18, 24, 30, and 36 months (P<0.05). The median times to failure were 3.2 months in the Baerveldt group, compared with 15.0 months in the Ahmed group (P = 0.009). No differences were observed in longer term survival rates and IOP profiles between Ahmed and Baerveldt shunt implants up to 48 months following surgery. Patients in the Baerveldt group were more likely to develop early postoperative hypotony-related complications and failure, whereas patients undergoing Ahmed implants were more likely to be on additional glaucoma medications (starting at 18 months postsurgery) and develop later onset failure.


Formation of the immunogenic α1,3-fucose epitope: elucidation of substrate specificity and of enzyme mechanism of core fucosyltransferase A.
Glycans of glycoproteins are often associated with IgE mediated allergic immune responses. Hymenoptera venoms, e.g., carry α1,3-fucosyl residues linked to the proximal GlcNAc of glycoproteins. This epitope, formed selectively by α1,3-fucosyltransferase (FucTA), is xenobiotic and as such highly immunogenic and it also shows cross-reactivity if present on different proteins. Production of post-translationally modified proteins in insect cells is however commonly used and, thus, resulting glycoproteins can carry this highly immunogenic epitope with potentially significant side effects on mammals. To analyze mechanism, specificity and reaction kinetics of the key enzyme, we chose FucTA from Apis mellifera (honeybee) and characterized it by saturation transfer difference (STD) NMR and surface plasmon resonance (SPR) experiments. Specifically, we show here that the donor substrate, GDP-Fucose, binds mostly via its guanine and less so via pyrophosphate and fucosyl fragments and has a K(D) = 37 μM. Affinity and kinetic studies with both the core α1,6-fucosylated and the unfucosylated octa- or heptasaccharides, respectively, as acceptor substrate revealed that honeybee FucTA prefers the latter structure with affinities of K(D) ∼ 10 mM. Establishment of progress curve analysis using an explicit solution of the integrated Michaelis-Menten equation allowed for determination of key constants of the transfer reaction of the glycosyl residue. The dominant minimum acceptor substrate is an unfucosylated heptasaccharide with K(m) = 420 μM and k(cat) = 6 min(-1). Time-resolved NMR spectra as well as STD NMR allow molecular insights into specificity, activity and interaction of the enzyme with substrates and acceptors.


An integrated study of endocrine disruptors in sediments and reproduction-related parameters in bivalve molluscs from the Biosphere's Reserve of Urdaibai (Bay of Biscay).
Urdaibai was declared a Biosphere's Reserve by UNESCO in 1984. Because we observed a high prevalence of hermaphroditism in mussels sampled in Urdaibai in March 2004, we started the present research work in order to determine the presence of endocrine disruptors (EDs) in sediments and to study possible EDs effects on mussels and oysters using gonad index and vitellogenin (VTG)-like protein levels as biomarkers. Samples were collected at five localities in April 2007 and 2008, and in October 2007. Estrogenic hormones were not detected in sediments and levels of bisphenol A and organotin compounds were very low. Alkylphenols were found at moderate levels and showed a time-dependent decrease. Phthalates were found at levels up to 8000 ng/g. High prevalence of oocyte atresia and necrosis occurred in mussels sampled in April. Retarded gametogenesis was observed in an oyster population from a shipyard. Hermaphrodites or alterations in VTG-like protein levels were not found but the high prevalence of histopathological alterations in oocytes is of concern.


Regulating managed care plans: is the telecommunications industry a possible model?
Merger mania has been a striking trend in the health and managed care fields during the last decade, promising to improve integration of services, decrease excess capacity, enhance price competition, and increase the ability of providers and insurers to handle risk-based payment. In view of these promises, our first argument in this paper is that undoubtedly strong, well-financed managed care plans and health networks will continue to utilize the merger concept to acquire additional insurers and providers, eventually gaining more control over the organization and the financing of a region's health care delivery system. Our second thesis is that the quasicompetitive, quasiregulatory authority inherent in the Telecommunications Act of 1996, somewhat similar in concept to the American Hospital Association's earlier Ameriplan (1970), might serve as an appropriate model for Congress to use in designing future managed care, health field, and federal/state governmental interrelationships.


Dissociation in adolescent girls with anorexia: relationship to comorbid psychopathology.
This study investigated the relationship between dissociation and psychological symptoms in adolescent girls with anorexia. First, the psychometric properties of the Adolescent Dissociative Experiences Scale (A-DES) were examined using data from 181 nonclinical adolescent boys and girls. Thereafter, A-DES scores and correlations with a range of psychological symptoms were compared across 20 girls with anorexia, 19 mixed clinical girls, and 86 nonclinical girls. The A-DES had a one-factor structure and good psychometric characteristics. Dissociation scores were significantly correlated with level of symptomatology for all groups. Although the group with anorexia did not have significantly higher dissociation scores than the other two groups, dissociation in the anorexic girls was related to psychopathology in a distinct way. Adolescent girls with anorexia appear to use dissociation specifically to avoid processing angry affect with an interpersonal basis, although it is also related to their use of somatization, and obsessive-compulsive features.


[Radiation therapy for lung cancer].
Radiation therapy is one of the most important modalities for the treatment of lung cancer. Current progress of radiation therapy in cooperation with the development of physics and biology is remarkable. The techniques of three-dimensional treatment planning and three-dimensional conformal radiotherapy (3D-CRT) have facilitated the use of higher radiation doses. Patients with early-stage non-small cell lung cancer (NSCLC) are candidates for curative surgical resection. However, the number of elderly patients has been increasing, and these patients often have medical contraindications that prevent curative surgery. Recently, several clinical trials on stereotactic body radiotherapy (SBRT) using the 3D-CRT technique for solitary lung tumors have been reported. The local control rate for stage I disease is more than 90%, and survival rates are promising. Now a prospective multi-institutional trial is ongoing to determine whether this modality can become a standard treatment for inoperable patients or an alternative to lobetectomy. For locally advanced NSCLC, unfortunately, recent studies have demonstrated that conventional therapies may have reached a therapeutic plateau. Now several radiation dose escalation studies utilizing conventional fractionation and 3D-CRT techniques are ongoing. The strategies of almost all of these trials are to eliminate elective nodal irradiation and deliver a higher dose of radiation to gross tumor volume while sparing normal tissues. Preliminary experience has resulted in promising survival, but should be developed to integrate into the combined treatment to completely control both local disease and other microscopically involved lesions. The combination of novel chemotherapeutic agents and molecular targeting therapies with radiation therapy is being investigated. Development of molecular imaging techniques is expected to facilitate more selective dose escalation in tumors.


Accuracy between optical and inertial motion capture systems for assessing trunk speed during preferred gait and transition periods.
Motion capture through inertial sensors is becoming popular, but its accuracy to describe kinematics during changes in walking speed is unknown. The aim of this study was to determine the accuracy of trunk speed extracted using an inertial motion system compared to a gold standard optical motion system, during steady walking and stationary periods. Eleven participants walked on pre-established paths marked on the floor. Between each lap, a 1-second stationary transition period at the initial position was included prior to the next lap. Resultant trunk speed during the walking and transition periods were extracted from an inertial (240 Hz sampling rate) and an optical system (120 Hz sampling rate) to calculate the agreement (Pearson's correlation coefficient) and relative root mean square errors between both systems. The agreement for the resultant trunk speed between the inertial system and the optical system was strong (0.67 < r ≤ 0.9) for both walking and transition periods. Moreover, relative root mean square error during the transition periods was greater in comparison to the walking periods (>40% across all paths). It was concluded that trunk speed extracted from inertial systems have fair accuracy during walking, but the accuracy was reduced in the transition periods.


A simple procedure for estimation of total body surface area and determination of a new value of Meeh's constant in rats.
Precise calculation of total body surface area (TBSA) or premarked surface areas (P-MSAs) is of great importance in many biomedical applications. The aim of the paper was to present a simple procedure of measurement of P-MSAs in small animals and to determine a more accurate Meeh's constant (k), for a commonly used weight range of laboratory rats. A series of 30 Wistar rats, weighing 195-240 g, were anaesthetized and weighted. The TBSA of each animal was measured using a clear pocket and a planimeter. The data obtained were entered into the Meeh's formula (TBSA = kW(2/3)), the most commonly used for small experimental animals, so that a k value for each animal as well as a mean k value (9.83) were obtained. The TBSA of the animals was also calculated using the aforementioned mean k value and compared with that obtained using k values reported in previous studies. According to our findings, the new mean k value, determined with the use of our procedure of surface area measurement, ensured greater accuracy in the determination of the TBSA of experimental rats of a specific weight range. We also suggest a new procedure of surface area measurement which is easy, accurate and does not require animal sacrifice.


Production of adenosine from extracellular ATP at the striatal cholinergic synapse.
The components of the ectonucleotidase pathway at the immunoaffinity-purified striatal cholinergic synapse have been studied. The ecto-ATPase (EC 3.6.1.15) had a Km of 131 microM, whereas the ecto-ADPase (EC 3.6.1.6) had a Km of 58 microM, was Ca(2+)-dependent, and was inhibited by the ATP analogue 5'-adenylylimidodiphosphate (AMPPNP). The ecto-5'-nucleotidase (EC 3.1.3.5) had a Km of 21 microM, was inhibited by AMPPNP and alpha,beta-methylene ADP, and by a specific antiserum. The Vmax values of the ATPase, ADPase, and 5'-nucleotidase enzymes present at this synapse were in a ratio of 30:14:1. Very little ecto-adenylate kinase activity was detected on these purified synapses. The intraterminal 5'-nucleotidase enzyme, which amounted to 40% of the total 5'-nucleotidase activity, was inhibited by AMPPNP, alpha,beta-methylene ADP, and the antiserum, and also had the same kinetic properties as the ectoenzyme. The time course of ATP degradation to adenosine outside the nerve terminals showed a delay, followed by a period of sustained adenosine production. The delay in adenosine production was proportional to the initial ATP concentration, was a consequence of feedforward inhibition of the ADPase and 5'-nucleotidase, and was inversely proportional to the ecto-5'-nucleotidase activity. The function and characteristics of this pathway and the central role of 5'-nucleotidase in the regulation of extraterminal adenosine concentrations are discussed.


[Temperament and attachment in alcohol addicted patients of type 1 and 2].
Our study first objective is the evaluation of the attachment to partner and affective temperamental traits in alcohol addicted patients; the second objective is the evaluation of differences between alcohol addicted patients of type 1 and 2 according to Cloninger and Sullivan. The sample is composed of 40 adult patients with a alcohol addiction diagnosis enrolled at the Alcoholic Service of the Viterbo "Villa Rosa" Nursing Home. Patients have been submitted the semistructured interviews SCID I and SCID II and the self submitted TCI-R test. Furthermore they have completed the TEMPS-A (Temperament Evaluation Memphis, Pisa, Paris and San Diego) and the ECR (Experiences in Close Relationships). The attachment profile shows that 50% of patients have an insecure type of attachment so distributed: 25.5% of patients show a preoccupied type of attachment, 17.5% appear dismissing and 7.5% fearful. As for the affective temperament we observed a major frequency of elevated scores of Hyperthymic TEMPS-A (OR = 1.68; p < 0.01) compared to controls. At last type 2 compared to type 1 is characterized by a more elevated mid scores presence at the Avoiding dimension of Scale ECR. The alcohol addicted patients sample mainly show an attachment of insecure type and, with major frequency, a hyperthymic temperament. Moreover in type 2 patients there is a prevalence of the avoiding dimension in intimate relationships.


Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients.
Proto-oncogenes (HER-2) and tumor suppressor genes (p53) are commonly deregulated in gallbladder cancer (GBC). Available literature discloses skewed data from endemic Asian countries, especially north India. This study evaluates the prognostic significance of HER-2 and p53 in GBC patients from two major hospitals. Sixty resectable tumor and control specimens were prospectively collected from December 2012 to January 2016. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and p53 protein expression. The criterion for HER-2 positivity was set at >30% tumor cells showing complete, membranous staining while p53 positivity was established at <50% tumor cells showing complete nuclear staining. Clinicopathological correlations were drawn with major clinical outcomes. It was observed that 36.67% (22/60) tumor cases and 5% (3/60) control cases showed strong HER-2 overexpression significantly correlating with sex, T-stage, nodal spread and distant metastasis (p < 0.05), while 33.3% (20/60) positivity was observed for p53 in tumor cases and 1.7% (1/60) in control cases. Multivariate analysis showed HER-2 (p = 0.04; hazard ratio: 2.36; 95% confidence interval: 1.04-5.33) and p53 (p = 0.03; hazard ratio: 5.63; 95% confidence interval: 1.21-26.26) expression to be independent prognostic factors. Our study thus suggests the plausible role of HER-2 and p53 expression in worse prognosis of GBC in a north Indian population.


Effects of symmetric and asymmetric fetal growth on pregnancy outcomes.
To assess the prevalence of head circumference to abdomen circumference (HC/AC) asymmetry among small for gestational age (SGA) fetuses, and to determine the likelihood of adverse outcomes among asymmetric and symmetric SGA infants compared with their appropriate for gestational age (AGA) counterparts. In a retrospective cohort study, we analyzed consecutive live-born singletons of women who had antepartum sonography within 4 weeks of delivery and delivered between January 1, 1989 and September 30, 1996. A gestational age-specific HC/AC nomogram was derived from our sonographic database of 33,740 nonanomalous live-born singletons. Asymmetric HC/AC was defined as greater than or equal to the 95th percentile for gestational age. Among 1364 SGA infants, 20% had asymmetric HC/AC and 80% were symmetric. Asymmetric SGA infants were more likely to have major anomalies than symmetric SGA infants or AGA infants (14% versus 4% versus 3%, respectively; P <.001). After exclusion of anomalous infants, pregnancy-induced hypertension at or before 32 weeks' gestation and cesarean delivery for nonreassuring fetal heart rate were more common in the asymmetric SGA than the AGA group (7% versus 1% and 15% versus 3%, respectively; both P <.001). A neonatal outcome composite, including one or more of respiratory distress, intraventricular hemorrhage, sepsis, or neonatal death, was more frequent among asymmetric SGA than AGA infants (14% versus 5%, P =.001). Symmetric SGA infants were not at increased risk of morbidity compared with AGA infants. The minority of SGA fetuses with HC/AC asymmetry are at increased risk for intrapartum and neonatal complications.


Identification of the crystallographic sites of Eu(2+) in Ca9NaMg(PO4)7: structure and luminescence properties study.
The substituted activator ions Eu(2+) in the β-Ca3(PO4)2-type structure, Ca9NaMg(PO4)7 compound, have been studied as emission centers, as well as structural probes. The crystal structure and crystallographic sites of Eu(2+) in Ca9NaMg(PO4)7 have been identified by Rietveld refinements, electron paramagnetic resonance (EPR) spectroscopy analysis and combined photoluminescence spectral analysis, respectively. Ca9NaMg(PO4)7:Eu(2+) phosphor exhibits a broad emission band in the visible light region with three distinguished peaks centered at 415, 458, and 615 nm, which are ascribed to different Eu(2+) emission centers occupied in three different Ca crystallographic sites. The concentration quenching behavior, variation in lifetimes and the temperature dependent luminescence properties have been investigated as a function of different emission centers, 415, 458, and 625 nm for Ca9NaMg(PO4)7:Eu(2+) phosphor. Accordingly, the relationship among three different Eu(2+) luminescence centers originating from three different Ca(2+) crystallographic sites has been found and verified.


The amino acid transporter, SLC1A3, is plasma membrane-localised in adipocytes and its activity is insensitive to insulin.
The hormone insulin coordinates the catabolism of nutrients by protein phosphorylation. Phosphoproteomic analysis identified insulin-responsive phosphorylation of the Glu/Asp transporter SLC1A3/EAAT1 in adipocytes. The role of SLC1A3 in adipocytes is not well-understood. We show that SLC1A3 is localised to the plasma membrane and the major regulator of acidic amino acid uptake in adipocytes. However, its localisation and activity were unaffected by insulin or mutation of the insulin-regulated phosphosite. The latter was also observed using a heterologous expression system in Xenopus laevis oocytes. Thus, SLC1A3 maintains a constant import of acidic amino acids independently of nutritional status in adipocytes.


Lung function and precipitating antibodies in low exposed wood trimmers in Sweden.
Wood trimmers are exposed to molds that periodically grow on timber that may induce alveolitis and obstructive lung disease. We have evaluated respiratory symptoms, bronchial reactivity, and lung function in 28 wood trimmers at a Swedish sawmill and in 19 unexposed office workers. Eleven (sero-positive) of the wood trimmers had precipitating antibodies in peripheral blood against one or several molds. The exposure to dust (median 0.26 mg/m3), viable mold spores (median 2950 cfu/m3), viable bacteria (median 370 cfu/m3), airborne endotoxins (range 0.0015-0.0025 microgram/m3), and terpenes (range 0.4-23 mg/m3) was lower than levels that earlier have been reported to affect lung function. The wood trimmers reported an increased prevalence of cough and breathlessness. They also showed signs of a mild obstructive impairment with a tendency to increase bronchial sensitivity to metacholine and decreased FEV1 after 2 days free from exposure. FEV1 decreased more during the working week in the sero-positive workers than among the sero-negative workers, and for the whole group the decrease in FEV1 and MEF25 was correlated to the degree of mold exposure.


Preexercise energy drink consumption does not improve endurance cycling performance but increases lactate, monocyte, and interleukin-6 response.
The purpose of this study was to investigate the influence of an energy drink (ED) on cycling performance and immune-related variables. Eleven trained male cyclists (33.4 ± 8.9 years; 81 ± 7.6 kg; maximal VO2, 52 ± 3.4 ml·kg(-1)·min(-1)) consumed 500 ml of (a) ED (2.0 g taurine, 1.2 g glucuronolactone, 160 mg caffeine, 56 g carbohydrate [CHO], and B vitamins), (b) cola matched for caffeine and CHO (CC), or (c) flavored placebo (PL: sparking water and flavoring) 50 minutes before racing in a randomized, crossover design. Performance was measured as time to complete (TTC) a 25-mile simulated road race. Blood was collected at baseline, 30 minutes after drink consumption, during exercise at miles 5 (M5), 15 (M15), and immediately (POEX) and 30 minutes (30minPO) after exercise. TTC was not different (p > 0.05) among trials (ED, 68.6 ± 2.7; CC, 68.9 ± 3.8; PL, 69.6 ± 3.8 minutes). Consumption of CC and ED elicited a mild hypoglycemia elicited a mild hypoglycemia during cycling. POEX interleukin-6 (IL-6) was greatest after ED, whereas CC IL-6 was greater than PL (10.2 ± 1.6, 6.7 ± 0.6, and 4.8 ± 0.7 pg·ml(-1), respectively; p < 0.001). Cycling increased leukocyte number in all conditions with ED leukocyte number greater than that of PL at M15 (9.8 ± 0.6, 8.5 ± 0.3 × 10(6) cells·mL(-1)). Energy drink induced an earlier recruitment of monocytes to the blood stream than CC. Mean fat oxidation was greater in PL compared with CC (0.43 ± 0.06 and 0.28 ± 0.04 g·min(-1); p = 0.033) but did not differ between ED (0.32 ± 0.06) and PL. Lactate was higher in ED compared with CC and PL at M5 and M15 (p = 0.003), but there was no significant influence of either ED or CC on performance. Carbohydrate and caffeine consumption before endurance cycling significantly increased the IL-6 release and leukocytosis, and the additional ingredients in ED seem to have further augmented these responses.


Retinal projection to the formatio reticularis tegmenti mesencephali in the Old World monkeys.
We studied the retinal projections of Old World monkeys using the anterograde transport of tritiated amino acid and wheat germ agglutinin conjugated to horseradish peroxidase. In addition to well-known retinal connections, these methods revealed that a small number of labeled retinofugal fibers might terminate in a small area of the contralateral formatio reticularis tegmenti mesencephali between the red nucleus and the substantia nigra. In the autoradiographic cases, a few labeled retinal terminals were also found in the same area on the ipsilateral side. In order to reach their terminal field, these labeled fibers appeared to leave the accessory optic tract in the vicinity of the dorsal border of the lateral terminal nucleus and run medially through the substantia nigra.


Geographic variation in the management and outcome of patients with AIDS-related Pneumocystis carinii pneumonia.
Pneumocystis carinii pneumonia (PCP) is one of the most common reasons for the hospitalization of AIDS patients; however, geographic differences in PCP management have not been evaluated previously. Therefore, we abstracted data on socioeconomic characteristics, prior HIV care, severity of illness, timeliness and intensity of in-hospital care, duration of hospitalization, and survival from 1547 randomly selected medical records of patients hospitalized with AIDS-related PCP between 1987 and 1990 at 82 hospitals in Chicago, Los Angeles, Miami, New York City, and Raleigh-Durham, North Carolina. Multivariate regression models were used to assess factors associated with longer hospital stays and increased inpatient mortality. Our results showed that in-hospital mortality ranged from 15% to 27%, bronchoscopy rates from 53% to 70%, and mean length of stay from 14 days to 23 days. Geographic variations in mortality were accounted for by differences in severity of illness at admission, insurance status, and in-hospital patient management. However, significant regional variations in hospital length of stay persisted, even after adjusting for patient demographics, severity of illness, and use of diagnostic and therapeutic care resources.


Reaction times to painless and painful CO2 and argon laser stimulation.
The introduction of lasers in pain research has made it possible to activate the nociceptive system without activating mechanosensitive afferents. In the present study the reaction times to painless and painful laser stimuli were studied to investigate if the reaction time to experimental pain is reproduceable. CO2 and argon lasers were used for stimulation, and the influence of stimulus (intensity and duration) and skin parameters (temperature, thickness, and reflectance) on reaction time were investigated. When these parameters were controlled the reaction times to painful CO2 and argon laser stimulation were within the same range (350-450 ms), and the intra-individual variability minimal (6.9%). The reaction time was used to estimate peripheral conduction velocity (10 m.s-1) for the activated fibre population when distinct pain was perceived. Determination of reaction times to non-painful and painful stimuli may be suitable ways to assess the functioning of thermal and nociceptive pathways.


Bronchial thermoplasty: a novel technique in the treatment of severe asthma.
New therapies are needed for patients with severe persistent asthma who cannot achieve control with current therapy of inhaled corticosteroids and long-acting beta(2)-agonists. Bronchial thermoplasty is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction in airway smooth muscle mass. We review the method of performing bronchial thermoplasty with the Alair System, how to appropriately select and manage patients undergoing bronchial thermoplasty, and the clinical experience to date with this treatment. Randomized, controlled clinical trials with bronchial thermoplasty in subjects with severe asthma have resulted in improvements in overall asthma control as demonstrated by significant improvement in quality of life, asthma symptoms, severe exacerbations requiring corticosteroids, days lost from work/school/other daily activities due to asthma, and healthcare utilization.


[Evaluation of mouse brain-derived, inactivated Japanese encephalitis vaccine].
Japanese encephalitis (JE) is a serious encephalitis caused by JE virus. Approximately 20% of JE patients die and 50% patients recover with neuro-psychiatric sequelae. In Japan, the number of JE patients was over 1000 per year in 1960s; however, the number decreased dramatically and has been less than 10 since 1990. Ministry of Health, Labour and Welfare suspended the strong recommendation for vaccination with the mouse brain-derived JE vaccine, because of cases who developed acute disseminated encephalomyelitis (ADEM) after vaccination with JE vaccine. However, it has not been fully confirmed on scientific bases that ADEM was caused by mouse brain-derived JE vaccine. Tissue culture derived-JE vaccine is under development. It is expected that this new vaccine will come to the market soon and that the recommendation of universal vaccination with JE vaccine will be implemented at the earliest occasion.


Analysis of differentially co-expressed genes based on microarray data of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide. Although great progress in diagnosis and management of HCC have been made, the exact molecular mechanisms remain poorly understood. The study aims to identify potential biomarkers for HCC progression, mainly at transcription level. In this study, chip data GSE 29721 was utilized, which contains 10 HCC samples and 10 normal adjacent tissue samples. Differentially expressed genes (DEGs) between two sample types were selected by t-test method. Following, the differentially co-expressed genes (DCGs) and differentially co-expressed Links (DCLs) were identified by DCGL package in R with the threshold of q < 0.25. Afterwards, pathway enrichment analysis of the DCGs was carried out by DAVID. Then, DCLs were mapped to TRANSFAC database to reveal associations between relevant transcriptional factors (TFs) and their target genes. Quantitative real-time RT-PCR was performed for TFs or genes of interest. As a result, a total of 388 DCGs and 35,771 DCLs were obtained. The predominant pathways enriched by these genes were Cytokine-cytokine receptor interaction, ECM-receptor interaction and TGF-β signaling pathway. Three TF-target interactions, LEF1-NCAM1, EGR1-FN1 and FOS-MT2A were predicted. Compared with control, expressions of the TF genes EGR1, FOS and ETS2 were all up-regulated in the HCC cell line, HepG2; while LEF1 was down-regulated. Except NCAM1, all the target genes were up-regulated in HepG2. Our findings suggest these TFs and genes might play important roles in the pathogenesis of HCC and may be used as therapeutic targets for HCC management.


Development and evaluation of sustained-release ibuprofen-wax microspheres. II. In vitro dissolution studies.
A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.


Pathways regulating the removal of nitrogen in planted and unplanted subsurface flow constructed wetlands.
Single-stage constructed wetlands (CWs) are characterized by a low potential for N removal. Understanding the pathways regulating N cycling as well as their dependence on environmental variables might improve the potential of CWs for N removal and results in more accurate simulation tools. In this study we employed qPCR targeting marker functional genes (amoA, nirK, nirS, clade I and II nosZ) or microorganisms (anammox) regulating key pathways of N cycling to unravel their relative importance. Furthermore, the influence of plant species on treatment performance was studied. Our findings indicated nitrification-denitrification as the principal route of N removal in CWs, while anammox did not have a strong contribution. Evidence was also arisen that ammonia oxidizing archaea (AOA) contributed on NH3 oxidation. Overall, plant species had a weak effect on the abundance of N functional genes (amoA of AOA), but it strongly affected the performance of CWs in terms of N removal in the following order: unplanted < Phragmites communis < Typha latifolia. These findings suggest that plant species stimulate N removal by upregulating the rates that the responsible biochemical pathways operate, probably by increasing O2 supply. In addition, our study revealed differences in indicators linked to N2O emissions. The abundance of clade II nosZ genes remained low across the season scaling down a strong contribution in the reduction of the emitted N2O. The increasing ratios of nosZ/Σnir and nirS/nirK with the progress of season indicate a shift in the composition of denitrifiers towards strains with a lower genetic potential for N2O release. Similar trends were observed among the treatments but the mechanisms differed. The planted treatments stimulated an increase in the ΣnosZ/Σnir ratio, while the unplanted an increase in the nirS/nirK ratio.


Influence of ketone bodies on oxidative stress parameters in brain of developing rats in vitro.
Pro-oxidant and antioxidant properties have been found for acetoacetate (AcAc) and beta-hydroxybutyrate (BHB) in peripheral tissues. In the present study we investigated the role of AcAc and BHB at concentrations found in diabetic patients during ketoacidotic crises and in individuals affected by succinyl CoA: 3-oxoacid CoA transferase and acetoacetyl-CoA thiolase deficiencies, disorders clinically characterized by neurological symptoms, on a large number of oxidative stress parameters in fresh cerebral cortex of developing rats. Lipid peroxidation (chemiluminescence and thiobarbituric acid-reactive substances levels), protein oxidative damage (carbonyl formation and sulfhydryl oxidation), 2',7'-dichlorofluorescin diacetate oxidation and the non-enzymatic (total antioxidant reactivity and glutathione levels) and enzymatic (glutathione peroxidase, superoxide dismutase and catalase activities) antioxidant defenses were not changed by doses of BHB and AcAc as high as 25 mM in cortical supernatants under basal conditions. Furthermore, BHB did not affect the increased thiobarbituric acid-reactive substances levels provoked by 3-hydroxy-3-methylglutaric and 3-methylglutaconic acids and by a hydroxyl-induced generation system. Finally, BHB and AcAc were not able to oxidize sulfhydryl groups from a commercial GSH solution. Therefore, under basal conditions or under situations with high production of free radicals, AcAc and BHB were not able to reduce or increase the oxidative stress parameters in the brain. Taken together, our present results do not support the hypothesis that BHB and AcAc act as potent direct or indirect pro-oxidants or antioxidants in the CNS.


Sublingual immunotherapy: current concepts for the U.S. practitioner.
Estimates of the prevalence of allergic rhinitis in the United States range from 20% to 40%. Allergen-specific immunotherapy (SIT) is typically recommended for patients with allergic rhinitis who fail medical treatment, desire an alternative to pharmacotherapy, or would like to pursue therapy that can potentially change the natural history of the disease. Sublingual immunotherapy (SLIT) involves dosing the allergen under the tongue of the sensitized individual in controlled amounts, frequently, over a period of several years, in order to increase immunologic tolerance and diminish symptoms to that allergen. The U.S. Food and Drug Administration (FDA) approved the use of SLIT tablets in 2014, whereas the use of aqueous SLIT by U.S. practitioners is considered an "off-label" use. This study is a review of published English language scientific literature, focusing on systematic reviews and randomized controlled trials of SLIT for inhalant allergic rhinitis. SLIT is a safe and effective immune modulating treatment that decreases symptoms and medication use for allergic rhinitis. Further study is needed to determine the relative effectiveness of SLIT compared to subcutaneous immunotherapy, the role of multiple-allergen vs single-allergen SLIT, the use of SLIT in special populations (pregnancy, patients taking beta-blockers), and optimal dosing of U.S. products. SLIT is safe and effective, and offers a convenient alternative to injection immunotherapy for appropriate patients with allergic rhinitis.


Phylogeography and historical demography of the Italian treefrog, Hyla intermedia, reveals multiple refugia, population expansions and secondary contacts within peninsular Italy.
We investigated the geographical patterns of genetic diversity in the Italian treefrog through sequence analysis of a mitochondrial cytochrome b gene fragment. Three main mitochondrial lineages were identified, distributed in northern, central and southern Italy, respectively. Their divergence appears indicative of a split time largely predating Late Pleistocene climatic oscillations, and syntopy between them was only observed in the geographically intermediate populations. The historical demographic reconstructions suggest that in both northern and central Italy, an expansion occurred during the last major glacial phase, when a vast widening of the lowland habitats followed the glaciation-induced fall of the sea level. Instead, in southern Italy an expansion event likely followed the end of the last glaciation, although the inference of expansion appears less reliable for the southern clade than for the others. Within this geographical area, a sharp phylogeographic discontinuity separated peninsular from Sicilian populations, and the overall pattern of diversity suggests that the latter derived from a recent colonization of the island, probably through a Late Pleistocene land bridge. Phylogenetic, phylogeographic and historical demographic analyses thus concur in delineating a scenario of multiple refugia, with four groups of populations which survived the last glacial-interglacial cycles in at least three distinct refugia arranged along peninsular Italy, and have recently come into contact following range expansions. Therefore, these results support the hypothesis that a plethora of microevolutionary processes, rather than the prolonged stability of populations, were mainly responsible for shaping the patterns of diversity within this major biodiversity hotspot.


A practice-based approach to group identification in nonverbal learning disorders.
Evidence-based practice, the rigorous conduct of clinical analysis and intervention, includes practice-based evidence. Here, practice data were the source of three "clinical portraits" used for exploratory analysis of an array of cognitive and social problems in 30 children whose neurobehavioral profiles fulfilled psychometric criteria for a nonverbal learning disability (NLD). Qualitative analysis of the children's academic and adjustment difficulties revealed patterns of dissociable deficits. These findings argue for at least three groups within the NLD construct. Identifying such subgroups is of practical importance: More precise characterization of neuropsychological competencies leads to improved interventions and better outcomes.


Enhancement of 9-beta-d-arabinofuranosyladenine cytotoxicity to mouse leukemia L1210 in vitro by 2'-deoxycoformycin.
2'-Deoxycoformycin (2'-dCF), a potent inhibitor of adenosine deaminase, was tested in combination with 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosyladenine 5'-formate for cytotoxic activity against mouse leukemia L1210 in culture. 2'-dCF, which alone had no activity, significantly enhanced cytostatic and cytotoxic activities of ara-A and its more soluble derivative, 9-beta-D-arabinofuranosyladenine 5'-formate; the latter 2 agents, when tested at equimolar concentrations, were equivalent in their effects on proliferation and viability. The therapeutic response of mice bearing the in vitro line of L1210 cells (L1210/C2) to combination therapy with 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate was comparable to that reported elsewhere for therapy of mice bearing the parent in vivo line. Continuous exposure of cultured L1210 cells to ara-A and 2'-dCF induced a prolonged period of unbalanced growth, characterized by inhibition of proliferation and DNA synthesis while RNA and protein synthesis continued; exposure periods in excess of a single population doubling were required to achieve significant cell kill. Potentiation of ara-A activity against the relatively insensitive mouse leukemia L1210 was attributed to increased stability of ara-A resulting from 2'-dCF inhibition of adenosine deaminase.


Alteration of thymic cell subsets by cocaine administration and murine retrovirus infection in protein undernourished mice.
Retrovirus infection, cocaine administration, and nutritional deficiencies are known to individually produce impairment of the immune system. Therefore, we developed a murine model to study the effect of daily cocaine administration, protein malnutrition, and retrovirus infection causing murine AIDS on the lymphoid cell populations of the thymus. C57BL/6 female mice fed a diet containing 4% protein were studied following chronic cocaine administration and LP-BM5 murine leukemia virus (MuLV) infection. Cocaine administration reduced body and thymus weight. Cocaine partially prevented thymus enlargement due to lymphoid cell proliferation induced by murine retrovirus infection. Cocaine treatment affected dramatically the thymus of protein-malnourished mice where the absolute number of Thy 1.2+, CD4+ and CD8+ cells represented only 10% of the control values. Daily saline injection also induced a significant decrease in the number of Thy 1.2+, CD4+ and CD8+ cells per thymus. These results suggest that the thymus glands of mice fed a low protein diet were susceptible to stress. Retrovirus infection provoked a decrease in the percentage and absolute number of Thy 1.2+, CD4+ and CD8+ cells in the thymus. This effect was potentiated by cocaine treatment. Therefore, cocaine was able to potentiate the impairment of the immune system caused by MuLV infection. We consider that cocaine could alter the immune system by altering the expression of T cell differentiation markers after direct interaction with thymocytes or through the neuroendocrine-thymus axis. Moreover, this effect was more dramatic and severe during protein malnutrition.


The Ullevål acute ward follow-up study: a personal 7-year follow-up of patients with functional psychosis admitted to the acute ward of a catchment area.
Eighty-eight patients were admitted to the acute ward of a catchment area suffering from the following functional psychoses: schizophrenia (S; n = 41), affective disorder (AD; n = 22), other disorders (OD; n = 25). Follow-up data were obtained for 97%. Ten patients were dead at follow-up, 8 due to suicide. Sixty-five were personally interviewed. While nearly all the patients had only brief periods of rehospitalization, most had used neuroleptics during the follow-up period. Compared to other samples, functioning at follow-up was fairly good for the AD and OD patients, but rather poor for the S patients.


Stochastic model of metastases formation.
A mathematical model is developed to describe the dynamics of the hematogenous metastatic process to the lung from a solid tumor growing in a peripheral body site. The accumulation of tumor cell clumps of various sizes in the pulmonary circulation and the formation of metastatic foci are described by a non-homogeneous, two-dimensional Markov process. An analytical solution is found for the special case of metastases produced by the intravenous injection of tumor cell clumps. The system is decoupled experimentally to determine the time-varying entrance rate of tumor cell clumps into the circulation from a growing fibrosarcoma and the number of metastatic foci produced by the intravenous injection of tumor clumps. Model validation is based on comparisons of model simulations with data for the development of metastatic foci and the probability of cure following tumor excision. The model is used to simulate hypothetical therapy to prevent tumor metastases.


Gd-AAZTA-MADEC, an improved blood pool agent for DCE-MRI studies on mice on 1 T scanners.
A novel MRI blood-pool contrast agent (Gd-AAZTA-MADEC) has been compared with established blood pool agents for tumor contrast enhanced images and angiography. Synthesis, relaxometric properties, albumin binding affinity and pharmacokinetic profiles are reported. For in vivo studies, angiographic images and tumor contrast enhanced images were acquired on mice with benchtop 1T-MRI scanners and compared with MS-325, B22956/1 and B25716/1. The design of this contrast agent involved the elongation of the spacer between the targeting deoxycholic acid moiety and the Gd-AAZTA imaging reporting unit that drastically changed either the binding affinity to albumin (KA(HSA) = 8.3 × 10(5) M(-1)) and the hydration state of the Gd ion (q = 2) in comparison to the recently reported B25716/1. The very markedly high binding affinity towards mouse and human serum albumins resulted in peculiar pharmacokinetics and relaxometric properties. The NMRD profiles clearly indicated that maximum efficiency is attainable at magnetic field strength of 1 T. In vivo studies showed high enhancement of the vasculature and a prolonged accumulation inside tumor. The herein reported pre-clinical imaging studies show that a great benefit arises from the combination of a benchtop MRI scanner operating at 1 T and the albumin-binding Gd-AAZTA-MADEC complex, for pursuing enhanced angiography and improved characterization of tumor vascular microenvironment.


Sleep apnea syndrome: symptomatology, associated features, and neurocognitive correlates.
This article reviews the essential features, types, prevalence, pathophysiology, and neuropsychological correlates associated with the sleep apnea syndrome. Persons who experience the intermittent hypoxia and fragmented sleep characteristic of the sleep apnea syndrome tend to exhibit moderate symptoms of diffuse cognitive dysfunction as well as multiple emotional and psychosocial sequela. It is concluded that more research is required in order to elucidate the relationship between the hypoxic parameters and neurocognitive deficits seen in the sleep apnea syndrome, and that neuropsychological assessment might represent a means whereby the effectiveness of various treatments for sleep apnea may be evaluated.


Absolute or relative stability in plate fixation for simple humeral shaft fractures.
Minimal invasive plating (MIPO) techniques for humeral shaft fractures appear to have fewer complications and higher union rates compared to open reduction and internal fixation (ORIF). It is questionable if this also applies to simple humeral shaft fractures, as simple fractures are generally treated with absolute stability which cannot be obtained with MIPO. This raises the question whether biology or biomechanics is more important in fracture healing. This study was developed to investigate the biomechanical part of this equation. The aim of the study was to compare relative stability to absolute stability in simple humeral shaft fractures with regard to fracture healing METHODS: This was a retrospective study of all patients treated with plate fixation for AO/OTA type A1-B3 humeral shaft fractures. Patients were categorized into two groups: absolute stability and relative stability. Both groups were compared with regard to time to radiological union and full weight bearing RESULTS: Thirty patients were included in the relative-stability-group with either an AO/OTA type A (n = 18) or type B (n = 12) humeral shaft fracture and a mean age of 55 (SD 21) years. A total of 46 patients were included in the absolute-stability-group: 27 patients had a type A and 19 type B fracture. The mean age in this group was 45 (SD 19) years. Median follow-up was 12 months (IQR 8-13). Minimally invasive approach was used in 15 (50%) patients in the relative stability group. Time to radiological union was significantly shorter in the absolute-stability-group with a median of 14 (IQR 12-22) versus 25 (IQR17-36) weeks and HR 2.60 (CI 1.54-4.41)(p < 0.001). This difference remained significant after correction for type of approach (adjusted HR 3.53 CI 1.72-7.21) (p 0.001). There was no significant difference in time to full weight bearing. The addition of lag screws in the absolute stability group did not influence time to radiological healing or full weight bearing. Absolute stability for simple humeral shaft fractures leads to a significantly shorter time to radiological union compared to relative stability. The addition of lag screws to gain interfragmentary compression does not reduce fracture healing time.


Prostaglandins and renal function in acute extracellular volume expansion.
Mechanisms determining the natriuresis in ECV-expansion are not yet completely understood. The present study was therefore undertaken to investigate if prostaglandins (PG) are involved in the natriuresis of acute ECV-expansion and by which mechanisms PG may affect renal Na-absorption. In non-expanded rats the PG synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 37 Sprague-Dawley rats ECV-expansion with isotonic saline corresponding to an increase in b.wt. of 10% was induced. Twenty-one animals received an oral dose of 10 mg/kg b.wt. of INDO prior to ECV-expansion. Sixteen animals served as ECV-expanded controls (C). GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg b.wt.) did not significantly differ in both groups. However, total renal plasma flow (RPF) (INDO: 22.9 +/- 1.8; C: 30.1 +/- 2.7 ml/min/kg b.wt.), urinary flow rate (INDO: 1.11 +/- 0.20; C: 1.93 +/- 0.21 ml/min/kg b.wt.) and urinary excretion of sodium (INDO: 141 +/- 26; C: 267 +/- 46 muEq/min/kg b.wt.) and potassium (INDO: 13.0 +/- 0.9; C: 19.8 +/- 1.7 muEq/min/kg b.wt.) markedly decreased in animals pretreated with INDO. The results indicate that PG are involved in the natriuresis of acute ECV-expansion and suggest, that PG may inhibit the intrinsic capacity for Na-absorption in more proximal parts of the nephron possibly via intrarenal physical factors.


Assessment of pharmaceutical care needs in an ambulatory setting.
The authors assessed the perceived pharmaceutical care needs of ambulatory pharmacy patients based on their demographic characteristics and desired service mix. A questionnaire was given to repeat ambulatory pharmacy patients for 30 consecutive weekdays during April and May 1992 to assess patient satisfaction with current and future services. A total of 152 surveys were completed by patients while waiting for prescriptions to be filled. Overall, responses were favorable considering the existing level of services provided by pharmacists. More than 70% of all respondents were in favor of talking with a pharmacist about their prescriptions, receiving easy to understand advice on potential problems, and having their prescriptions thoroughly explained. Current dispensing services were also viewed as highly satisfactory by a majority of respondents. However, some patients apparently need more information regarding convenience services. Such information helps establish a profile of ambulatory patients so that an optimal service mix can be provided.


Cost effectiveness, quality-adjusted life-years and supportive care. Recombinant human erythropoietin as a treatment of cancer-associated anaemia.
To measure the cost effectiveness of a supportive care intervention when the no-treatment option is unrealistic in an analysis of recombinant human erythropoietin (epoetin) treatment for anaemic patients with cancer undergoing chemotherapy. Further, to assess whether quality-adjusted life-years (QALYs) can provide the basis for an appropriate measure of the value of supportive care interventions. A modelling study drawing cost and effectiveness assumptions from a literature review and from 3 US clinical trials involving more than 4500 patients with cancer who were treated with chemotherapy, radiotherapy, epoetin and blood transfusions as needed under standard care for patients with cancer. When compared with transfusions, epoetin is cost effective under varying assumptions, whether effectiveness is measured by haemoglobin level or quality of life. Specifically, under a base-case scenario, the effectiveness resulting from $US1 spent on standard care can be achieved with only $US0.81 of epoetin care. Due in part to the health-state dependence of the significance patients attach to incremental changes in their responses on the linear analogue scale, cost per QALY results are ambiguous in this supportive care context. Under a broad range of plausible assumptions, epoetin can be used cost effectively in the treatment of anaemic patients with cancer. Further, QALYs have limited applicability here because, as a short term supportive treatment, epoetin enhances the quality but not the length of life. Future research would benefit from the establishment of consistent values for quality-of-life changes across patients and health status, and the extension of the QALY framework to supportive care.


In vitro comparative assessment of beta-lactamase inhibitors and their penicillin combinations against selected enterobacteria.
A comparative in vitro assessment of the inhibitory activity of clavulanate, sulbactam and tazobactam against the most frequent beta-lactamases found in enterobacteria isolated in Greek hospitals, has been performed. Tazobactam and clavulanate were potent inhibitors of TEM-1, SHV-1, SHV-2 and SHV-5 while sulbactam was less effective. In addition, tazobactam exerted a moderate inhibitory activity against AmpC-type beta-lactamases. In contrast with clavulanate, tazobactam could not cause significant induction of chromosomal cephalosporinases. Potentiation of the activity of penicillins (amoxycillin, ampicillin, ticarcillin and piperacillin), when combined with the inhibitors, has also been evaluated using a sample of recently isolated enterobacteria with beta-lactamase-mediated resistance. The results showed that the most effective among the commercially available combinations, is piperacillin/tazobactam followed by ticarcillin/clavulanate.


[Child abuse--relevance for dental care].
Injuries due to maltreatment of children focus on the head and neck region, neglect often results in an early destruction of the dentition. Children suffering maltreatment or neglect are regularly seen as emergency cases and the dentist is probably the only one able to early diagnose the type of injury and protect the child by reporting the case. This implication stresses the importance of knowledge of the general dental practitioner on this topic.


Mobile phones in residential treatment: implications for practice.
A nonprofit primary care, substance abuse and mental health treatment provider that operates nine separate residential treatment facilities in both northern and southern California began allowing clients to keep their mobile phones while in treatment. From the advent of mobile phone technology and its widespread adoption through early 2013, the organization prohibited clients from having phones while in treatment. Calls to and from clients needed to be made and received at the house phone. After years of enforcing the policy with diminished success as phones became cheaper, smaller, and more prevalent, agency leadership decided to experiment with allowing the clients to keep their phones while in treatment. Elopement data as they relate to the policy are examined along with data from staff interviews about its implementation and impact. Results show that elopements resulting from being caught with a mobile phone were eliminated and some clients were able to be returned to treatment using the devices. All seven (100%) of the interviewees were supportive of the new policy and thought it should be continued. The impact of the policy on clinical disruptions, lost/stolen property liability, and confidentiality issues are discussed.


A prospective randomised non-blinded comparison of conventional and Dorgan's crossed pins for paediatric supracondylar humeral fractures.
Closed reduction and percutaneous pinning are the preferred treatment of displaced supracondylar humeral fractures in children. The purpose of this study is to evaluate the non-standard Dorgan's method and compare its results with those of the standard percutaneous cross pinning method in treatment of unstable or irreducible Gartland type II and III supracondylar humeral fractures in children. This was a prospective evaluation of 138 consecutive patients with Gartland type II or III extension supracondylar humeral fractures referred to University Children's Hospital during a four-year period. The patients were randomized into two groups: the first group, comprised of 71 patients, was treated with standard pin configuration and the second group, comprised of 67 patients, underwent Dorgan's method. The study included 88 boys and 50 girls aged 1.5-11.4 years (mean 6.5±2). At initial presentation 8.7% (n-12) fractures were classified as Gartland type IIa, 25.4% (n-35) as Gartland type IIb and 65.9% (n-91) as Gartland type III. Flynn's criteria were used to evaluate the results. An excellent clinical outcome was reported in about 90% of patients (n-90) treated with standard pin configuration and 89.5% (n-60) of patients treated with Dorgan's method. There were no statistically significant differences in outcomes between the groups in terms of their gender, age, fracture types, function and cosmetics. Neurological lesions were observed in 9.9% of patients (n=7) who were treated using the standard configuration Kirschner pins, while in those treated by Dorgan's method neurological complications were not observed. However, the procedure time was longer (mean 36.54±5.65min) and radiation exposure significantly higher (mean 10.19±2.70 exposures) in the group that was treated using Dorgan's method, compared to the conventional method (mean 28.66±3.76min and 7.54±1.63 exposures). Two laterally inserted crossed pins provide adequate stability with good functional and cosmetic outcome for most unstable paediatric supracondylar humeral fractures with no risk of iatrogenic ulnar nerve injury.


Expression Level of Circulating Cell Free miR-155 Gene in Serum of Patients with Diabetic Nephropathy.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Several factors are known to contribute to the development and progression of diabetic nephropathy. Different microRNAs have been shown to contribute in the pathogenesis of DN. This study, aimed to evaluate the expression level of circulating miR-155 in patients with diabetic nephropathy. In this case-control study, 83 diabetic patients and normal subjects were evaluated in four groups of normal healthy subjects without diabetes and nephropathy, diabetes without nephropathy, diabetes with microalbuminuria, and diabetes with macroalbuminuria. After RNA extraction from serum and cDNA synthesis, the expression of circulating miR-155 was evaluated by quantitative polymerase chain reaction (qPCR). Expression level of cell-free miR-155 was significantly lower in diabetics compared to the normal healthy controls (p < 0.05). However, no significant difference was found in miR-155 expression level between different diabetes groups with different conditions of kidney function. Furthermore, we detected a significant negative correlation between cell-free miR-155 expression and GFR only in patients with microalbuminuria (r = -0.70, p = 0.001). It seems that miR-155 can discriminate diabetic and nondiabetic status, but is not an appropriate biomarker for tracking of macroalbuminuria.


Macrophage activation by immunostimulatory DNA.
Macrophage/dendritic cells and B cells remain the only cell types where direct responses to CpG DNA are well established. The role of macrophages in vivo in DNA clearance and the potent cytokine induction in macrophages and dendritic cells places them in the central role in the in vivo response to foreign DNA. Although responses to DNA are unlikely to evolve and be retained if they are not significant in the immune response to infection, the relative contributions of DNA and other stimulators of the innate immune recognition of foreign organisms is difficult to assess. Although CpG DNA and LPS have similar actions, significant differences are emerging that make the use of DNA as a therapeutic immunostimulatory molecule feasible. The macrophage response to DNA generates cytokines favouring the development of Th1-type immunity, and active oligonucleotides now show promise as Th1-promoting adjuvants and as allergy treatments.


Evaluation of anti-inflammatory activity of Cissampelos pareira root in rats.
In the present study, 50% ethanolic extract of Cissampelos pareira roots (CPE) in acute, subacute and chronic models of inflammation was assessed in rats. Per os (p.o.) administration of CPE (200, 400 mg/kg) exhibited significant anti-inflammatory activity. In acute inflammation as produced by carrageenin 59.55% and 64.04%, by histamine 15.38% and 30.77%, by 5-hydroxytryptamine 17.78% and 31.11% and by prostaglandin E(2)-induced hind paw edema 19.23% and 30.77% protection was observed. While in subacute anti-inflammatory models using formaldehyde-induced hind paw edema (after 1.5 h) 38.36% and 47.95% and in chronic anti-inflammatory model using cotton pellet granuloma 15.02% and 19.19% protection from inflammation was observed. CPE did not show any sign of toxicity and mortality up to a dose level of 1000 mg/kg, p.o. in rats. Both acute as well as chronic administration of CPE (100, 200 and 400 mg/kg, p.o.) did not produce any gastric lesion in rats. These data indicate that CPE possesses significant anti-inflammatory activity without ulcerogenic activity suggesting its potential as an anti-inflammatory agent for use in the treatment of various inflammatory diseases.