Genome scans for the contemporary response to selection in quantitative traits.
Genome scans have been an important approach for discovering historical signatures of selection in both model and nonmodel species. An exciting new experimental design for genome scans is to measure the change in allele frequency before and after contemporary selection within a generation, from a single population. The most widely-used methods, however, have two major limitations: they are based on testing one locus at a time, and they only have power to uncover loci that have evolved under relatively strong selection. On the other hand, complex quantitative traits are common in nature and are caused by several loci of small effect. Selection on a quantitative trait at the phenotypic level is predicted to be accompanied by subtle allele frequency changes in many loci that covary (a polygenic soft sweep), rather than a large, single-effect allele (a selective sweep). In this issue of Molecular Ecology, Bourret et al. (2014) measure the contemporary response to natural selection across the genome in multiple cohorts of Atlantic salmon during their first year at sea. They introduce a multilocus framework based on groups of markers that covary in their genotypic distribution. While the traditional, single-locus approach did not find evidence for repeated patterns of selection, the multivariate approach found that a group of covarying SNPs was selected for in different cohorts at one site. Their multilocus framework has potential to be a more fruitful approach for uncovering the genomic basis of adaptation in quantitative traits, although caution should be applied as the framework has yet to be validated with simulated data.


Metabolic responses to intraduodenal glucose loading in insulin-infused diabetic dogs.
The hormonal and metabolic responses to an intraduodenal glucose load (0.5 g/kg) were first determined in eight normal dogs before diabetes (alloxan/streptozotocin) was induced and then comparison made of the responses to the glucose load when normal plasma glucose profiles were recreated by preprogrammed infusion of insulin via the portal or peripheral circulations. Basal intraportal and peripheral insulin infusions at 0.021 +/- 0.001 and 0.022 +/- 0.000 U . kg-1 . h-1, respectively, for 16 h to fasting diabetic dogs normalized peripheral plasma levels of glucose (5.5 +/- 0.3 and 5.6 +/- 0.6 mmol/liter, respectively), immunoreactive insulin (IRI) (11.5 +/- 1.2 and 16.4 +/- 1.6 microU/ml), glucagon (65 +/- 7 and 62 +/- 5 pg/ml), lactate (0.63 +/- 0.04 and 0.54 +/- 0.03 mmol/liter), and alanine (0.236 +/- 0.037 and 0.191 +/- 0.008 mmol/liter). However, peripheral but not intraportal infusion of insulin depressed levels of glycerol, nonesterified fatty acids (NEFA), and 3-hydroxybutyrate (0.074 +/- 0.006 vs. 0.109 +/- 0.013, P less than 0.01; 0.67 +/- 0.04 vs. 0.84 +/- 0.09, P less than 0.05; and 0.018 +/- 0.004 vs. 0.059 +/- 0.015 mmol/liter, P less than 0.01, respectively). With the preprogrammed insulin infusions used to normalize plasma glucose profiles to the intraduodenal glucose load, all hormonal and metabolic responses were normalized during intraportal infusion (IRI, 72.5 +/- 4.2 microU/ml; glucagon, 66 +/- 10 pg/ml; lactate, 1.06 +/- 0.10 mmol/liter; alanine, 0.251 +/- 0.042 mmol/liter; glycerol, 0.043 +/- 0.013 mmol/liter; NEFA, 0.24 +/- 0.03 mmol/liter; and 3-hydroxybutyrate, 0.012 +/- 0.007 mmol/liter) but marked hyperinsulinemia (103.2 +/- 6.1 microU/ml) and depressed glycerol, NEFA, and 3-hydroxybutyrate responses at 2 h (0.056 +/- 0.005, 0.52 +/- 0.10, and 0.019 +/- 0.010 mmol/liter, respectively) resulted during peripheral infusion. Therefore, only the portal route of insulin infusion achieved complete metabolic normalization during glucose loading in diabetic dogs.


Quantitative kinetics of glucose appearance and disposal following a 13C-labelled starch-rich meal: comparison of male and female subjects.
In the UK, starch contributes up to 25 % of energy intake in adults (). The present study investigated the acute response to a starchy meal on whole-body glucose metabolism and assessed insulin sensitivity in men compared with women. Low insulin sensitivity has been postulated to pre-dispose individuals to a cluster of associated abnormalities known to increase the risk of CHD. Metabolic responses to a 13C-labelled meal were determined in conjunction with a primed continuous infusion of d-[6,6-2H]glucose in groups of healthy age- and BMI-matched men and women. Peripheral plasma glucose disposal (Gd) was computed using non-steady state kinetics in a single compartment model, simultaneously with determination of whole-body net glucose oxidation by indirect calorimetry. Insulin sensitivity was derived using cumulative Gd as the dependent variable, and time and the integrated insulin concentration as independent variables. The female group had the higher fractional rate of glucose appearance in plasma from starch (P=0.019) immediately after ingestion. Females also had a higher rate of plasma Gd and a significantly higher insulin-dependent Gd (6.8 v. 5.6 microg glucose/(min.kg) per pmol insulin, P<0.05) compared with the males. A smaller absolute pool of endogenous glucose in females allowed the rate of exogenous 13CO2 production to be significantly higher in the females (P=0.007) corresponding also to a significantly higher (P<0.05) carbohydrate oxidation rate obtained by indirect calorimetry. The present study suggests that during the ingestion of a starchy meal, females exhibit higher glucose flux and greater whole-body insulin sensitivity than males.


Effects of intravenous endothelin on hemodynamics and cardiac contractility in conscious Milan normotensive rats.
The effects of endothelin-1 (ET-1) on hemodynamics and cardiac contractility were compared with the responses to angiotensin I (AI) and phenylephrine (PE) in Milan normotensive rats. Intravenous (i.v.) injection of ET-1 (0.8 nmol/kg) initially decreased mean blood pressure (MBP), total peripheral resistance (TPR), and dP/dt (-28 +/- 2, -34.8 +/- 3.7, and -9.4 +/- 1.3%, p less than 0.01, respectively), and increased heart rate (HR), cardiac output (CO), and the velocity of myocardial anterior wall shortening (dL/dt) (11.8 +/- 2.1, 10.4 +/- 2.9, and 28.3 +/- 8.3% p less than 0.05, respectively). These effects were followed by a sustained increase in MBP and TPR and a decrease in CO. As compared with AI (0.25 nmol/kg) and PE (35 nmol/kg), which produced a similar degree of increase in TPR, the reduction in CO induced by ET-1 was more prominent (-25 +/- 2 by ET-1 vs. -14 +/- 2 by AI and -14 +/- 3% by PE, p less than 0.05, respectively). Moreover, ET-1 induced a significant decrease in dP/dt, shortening fraction (SF), and dL/dt (-6.1 +/- 1.6, -35.0 +/- 3.8, and -38.6 +/- 5.5%, p less than 0.01, respectively), whereas these indexes of left ventricle performance were not affected by either AI or PE. Furthermore, the reduction in SF induced by ET-1 was mainly due to the decrease in myocardial diastolic segment length, suggesting reduction in diastolic filling volume.(ABSTRACT TRUNCATED AT 250 WORDS)


Aortic valve replacement with freehand autologous pericardium.
Fifty-one patients with a mean age of 31.2 years underwent aortic valve replacement with glutaraldehyde-treated autologous pericardium. Pure aortic regurgitation was present in 28 (54.9%), stenosis in 9, and mixed disease in 14. Simultaneous mitral valve repair was done in 17 patients and replacement in 1. There were no hospital and two late deaths. Three patients required reoperation because of failure of the pericardial valve as a result of infective endocarditis in two (5 and 31 months after operation) and commissural tear at 8 months in another. One patient underwent reoperation at 24 months because of failure of the mitral valve repair. The pericardial aortic valve, which had 2+ regurgitation since the first operation, was also replaced. Macroscopic and microscopic examination findings in the excised pericardium were excellent. No thromboembolic events have been detected and no patient received anticoagulation therapy except one after mitral valve reoperation and replacement with a mechanical valve. The actuarial survival was 84.53% +/- 12.29% at 60 months, freedom from failure of the aortic reconstruction 83.83% +/- 8.59%, and freedom from any event 72.59% +/- 12.79%. Doppler echocardiographic study at most recent follow-up showed a mean gradient of 12.56 +/- 8.10 mm Hg and mean regurgitation on a scale from 0 to 4+ of 0.80 +/- 0.66. Although the maximum follow-up is only 5 years, the results obtained so far encourage us to continue replacing the aortic valve with stentless autologous pericardium.


Rapid translocation and insertion of the epithelial Na+ channel in response to RhoA signaling.
Activity of the epithelial Na+ channel (ENaC) is limiting for Na+ absorption across many epithelia. Consequently, ENaC is a central effector impacting systemic blood volume and pressure. Two members of the Ras superfamily of small GTPases, K-Ras and RhoA, activate ENaC. K-Ras activates ENaC via a signaling pathway involving phosphatidylinositol 3-kinase and production of phosphatidylinositol 3,4,5-trisphosphate with the phospholipid directly interacting with the channel to increase open probability. How RhoA increases ENaC activity is less clear. Here we report that RhoA and K-Ras activate ENaC through independent signaling pathways and final mechanisms of action. Activation of RhoA signaling rapidly increases the membrane levels of ENaC likely by promoting channel insertion. This process dramatically increases functional ENaC current, resulting in tight spatial-temporal control of these channels. RhoA signals to ENaC via a transduction pathway, including the downstream effectors Rho kinase and phosphatidylinositol-4-phosphate 5-kinase. Phosphatidylinositol 4,5-biphosphate produced by activated phosphatidylinositol 4-phosphate 5-kinase may play a role in targeting vesicles containing ENaC to the plasma membrane.


Gay and lesbian parents.
An anonymous survey of 23 gay and lesbian parents and 16 heterosexual single parents was conducted in order to see whether the parents' homosexuality created special problems or benefits or both, for their children. Both sets of parents reported relatively few serious problems and generally positive relationships with their children, with only a minority encouraging sex-typed toys, activities, and playmates. Heterosexual parents made a greater effort to provide an opposite-sex role model for their children, but no other differences in their parenting behaviors were found. Gay and lesbian parents saw a number of benefits and relatively few problems for their children as a result of their homosexuality, with lesbians perceiving greater benefits than gay men. Conversely, the gay males reported greater satisfaction with their first child, fewer disagreements with their partners over discipline, and a greater tendency to encourage play with sex-typed toys than did the lesbians. The findings suggest that being homosexual is clearly compatible with effective parenting and is not a major issue in parents' relationships with their children.


[Corneal transparency: anatomical basis and evaluation methods].
Being just a relatively small part of the fibrous tunic of the eyeball, the cornea is, nevertheless, unique in terms of the variety of its functions. Because the cornea differs significantly from other protective frames in its structure, it provides the possibility of light transmission and strong refraction that largely contributes to the total refraction of the eye. The development of ophthalmology is impossible without improving methods of adequate anatomical and functional assessment of the eye not only as a whole, but also as a collection of interacting structures.In this regard, examination methods of the cornea have undergone significant advances in recent years. So far, the level of corneal transparency has been judged by biomicroscopy findings or indirect characteristics (thickness, structure, etc.). Confocal microscopy of the cornea and wave-based examinations involving one of the available laser interferometers (OCT or HRT) are also used. However, the data obtained with these methods resembles that of layer-specific reflectometry, i.e. the magnitude of directed reflection of the light beam from corneal corpuscles, which does not completely agree with the classical idea of transparency.


Bright light during nighttime: effects on the circadian regulation of alertness and performance.
The present studies evaluated to what extent duration (all-night or 4-hour exposures) and timing of nocturnal bright light (BL) (beginning or end of the night) modulate effects on vigilance. The results showed that all-night BL exposure is able to alleviate the nocturnal decrements in alertness and performance. However, under certain circumstances, this continuous BL exposure may induce adverse effects on mood and finally reveal to be counterproductive. Shorter BL exposure (4 h) during nighttime helps improve mood and performance, although the effects of short BL pulses were less efficacious than all-night BL exposure. The latter part of the night appears the best time for using the alerting effect of BL. The immediate alerting effect of BL seems to be mediated by a global activation of the central nervous system.


Tissue and blood protozoa including toxoplasmosis, Chagas disease, leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in solid organ transplant recipients- Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of tissue and blood protozoal infections in the pre- and post-transplant period. Significant new developments in the field have made it necessary to divide the previous single guideline published in 2013 into two sections, with the intestinal parasites separated from this guideline devoted to tissue and blood protozoa. The current update reflects the increased focus on donor screening and risk-based recipient monitoring for parasitic infections. Increased donor testing has led to new recommendations for recipient management of Toxoplasma gondii and Trypanosoma cruzi. Molecular diagnostics have impacted the field, with access to rapid diagnostic testing for malaria and polymerase chain reaction testing for Leishmania. Changes in Babesia treatment regimens in the immunocompromised host are outlined. The risk of donor transmission of free-living amebae infection is reviewed. Changing immigration patterns and the expansion of transplant medicine in developing countries has contributed to the recognition of parasitic infections as an important threat to transplant outcomes. Medications such as benznidazole and miltefosine are now available to US prescribers as access to treatment of tissue and blood protozoa is increasingly prioritized.


Micromachining with a 50 W, 50 muJ, subpicosecond fiber laser system.
A 50 W sub-picosecond fiber chirped pulse amplification system generating 50 muJ pulses at a repetition rate of 1 MHz is demonstrated. As required for precision high speed micro-machining, this system has a practical system configuration enabled by the fiber stretcher and 1780 l/mm dielectric diffraction grating compressor and is capable of ablation rates >0.17 mm3/s metal, ceramic, and glass.


Stretch-induced growth-promoting activities stimulate fetal rat lung epithelial cell proliferation.
There is increasing evidence to suggest that fetal lung growth requires normal fetal breathing movements. To study this process in vitro, the effect of mechanical stretch on proliferation of fetal rat lung cells maintained in organotypic cultures was examined. In previous studies it has been demonstrated that DNA synthesis and cell division are stimulated by stretch. To determine whether stretched cells release soluble growth factors into their culture medium, conditioned media (CMs) were collected after static culture or culture while stretched. At a 10% dilution (v/v), CM from stretched cells (S-CM) increased [3H]thymidine incorporation into DNA of mixed fetal rat lung cells by 60%, compared to CM from nonstretched cells (C-CM) (p < .01). S-CM increased [3H]thymidine incorporation of fetal lung epithelial cells by 3 to 4-fold (p < .01) and increased cell number by 11.9% (p < .05), but had no effect on fetal lung fibroblast growth. Addition of either PDGF-BB (20 ng/mL), IGF-I (25 ng/mL), or EGF (50 ng/mL) to C-CM, did not mimic the effect of S-CM on epithelial cell DNA synthesis. The stimulatory activity of S-CM on epithelial cell proliferation was heat-, acid- and trypsin-sensitive. It is concluded that organotypic fetal lung cell cultures respond to stretch by elaborating growth-promoting factors which stimulate fetal rat lung epithelial cell, but not fibroblast, proliferation.


Is migration to Canada associated with unhealthy weight gain? Overweight and obesity among Canada's immigrants.
This paper aims to address a gap in our understanding of immigrant health issues by examining the determinants of excess weight--an important indicator of current and future health. The paper combines data drawn from recent large health surveys to identify how the weight of recent immigrants compares with that of native-born people, and how the likelihood of becoming overweight or obese changes with additional years in Canada. We find evidence that on average, immigrants are substantially less likely to be obese or overweight upon arrival in Canada. These measures converge slowly to native-born levels, but there is marked variation by the ethnicity of the immigrant. Since changes in weight will reflect choices with respect to diet and activity, the extent to which overweight and obesity rates change with years in Canada may reflect the extent to which immigrants interact with or are influenced by members of their ethnic group who reside in the same area. We find evidence that ethnic group social network effects exert a quantitatively important influence on the incidence of being overweight and obese for members of most ethnic minorities, tempering the process of adjustment to Canadian lifestyle norms that may be driving excess weight gain with additional years in Canada.


Off-axis partial coherence interferometry in myopes and emmetropes.
This study describes the axial and peripheral dimensions of myopic and emmetropic eyes in a wide range of retinal locations using a non-contact optical biometer (Zeiss IOLMaster) based upon the principle of partial coherence interferometry. Understanding the optical properties of the peripheral eye may provide insight into myopia development and the possible effects on off-axis visual performance. Fifty-two myopes (spherical equivalent between -2.00 and -9.62 D) and 27 emmetropes (spherical equivalent between -0.50 and +0.50 D) with astigmatism less than 0.75 D, participated in this study. Axial length and peripheral cornea to retina lengths were measured using partial coherence interferometry at the fovea and up to ± 30° eccentricity along the horizontal and vertical meridian in 10° steps. Relative cornea to retina length was calculated by subtracting the axial length from that obtained at each peripheral location. Our results showed significant differences between refractive groups for both horizontal (p < 0.001) and vertical (p < 0.001) meridians, illustrating that the retinal shape profile is significantly different between myopes and emmetropes. Myopic eyes exhibited a greater rate of change in cornea to retina lengths with increasing eccentricity than emmetropic eyes, with the temporal portion of the retina exhibiting the steepest shift. In addition, significant nasal-temporal asymmetry was observed, which was more pronounced in myopic eyes. Axial and peripheral cornea to retina dimension measurements, using partial coherence interferometry, suggest that myopic eyes tend toward an ellipsoid shape compared to the spherical emmetropic eyes.


The early history of keratoconus prior to Nottingham's landmark 1854 treatise on conical cornea: a review.
In an era of scientific method, precision of nomenclature and an electronically accessible publication record, the early history of keratoconus still remains, in parts, as complex and perplexing as the disease itself. Historically, the disease has been somewhat confusingly referred to by several different terms, including hyperkeratosis, ochlodes, conical formed cornea, cornea conica, cornée conique, sugar loaf cornea, prolapses corneae, procidentia corneae, staphyloma transparent de la cornée, staphyloma pellucidum, staphyloma corneae totale conicum pellucidum, staphyloma diaphanum, keratconus and keratoconus. In his major 1854 treatise on conical cornea, John Nottingham is widely cited as the first author to succinctly define keratoconus and its associations; however, for 150 years prior to this landmark publication, others had been slowly deciphering elements of keratoconus and distilling their knowledge in a series of publications obscured by the passage of years. Uncritical re-writing of core information and references without their full verification has also led to confusion in the published literature in the 150 years since Nottingham's comprehensive description of keratoconus. In the light of the preceding limitations in the established literature, the authors conducted an historical survey, based on the analysis of original sources, to more fully establish the chronology of early descriptions of keratoconus prior to 1854, with particular focus on the works of Duddell, Taylor, Mauchart, Scarpa, Wardrop, Lyall, MacKenzie, Lawrence, Schmidt, von Ammon and Pickford. This review attempts to place the observations of these practitioners and others both in the context of contemporary ophthalmic practice and historical precedent.


Pharmacologic patient management in pediatric dentistry: an update.
This paper reviews the issue of sedation in pediatric dentistry in the light of recent controversies and rapidly increasing legal, professional and governmental regulations. Consideration is given to "Guidelines for safe administration of pharmacologic agents in dental practice". The various avenues of drug administration are reviewed with specific comment on recent approaches. Many of the older pharmacologic agents used for pediatric sedation are falling into disfavor. Chloral hydrate, in particular, would seem to be heading toward its demise. The benzodiazepines appear to have a very promising future as sedative agents. When administered and monitored appropriately, they have a wide margin of safety. Consideration is given to research and development into agents that reverse the action of sedative drugs. It is emphasized that contemporary electronic monitoring equipment in no way diminishes the necessity for sound and expert clinical judgment, supplemented by such simple devices as the precordial stethoscope and observation and communication in the form of simple commands.


Determination of predictors and risk factors in patients with multiple emergency surgical traumas.
In the rescue and management of patients with multiple traumas, identifying and eliminating risk factors can guarantee a promising outcome. This was a prospective randomized cohort study in trauma patients in the Department of Surgery, Jundishapour University of Medical Sciences, covering 17 months. Based on the cause of mortality, complications and discharge, the patients were divided into groups as non-survivor and complicated and non-complicated groups. The results were compared for the risk factor extraction. From 125 studied patients, 27 died, 19 cases were complicated and 79 injured patients were successfully treated and discharged. Three extracted classifications as main (real), moderate and predictive risk factors were determined. Referral delay, delay in diagnosis and treatment, decreased blood pressure on arrival, multiple intra-abdominal visceral injuries, and severe acidosis were identified as the main risk factors. Age, multiple surgery and pitfalls, intensive care unit admittance, electrolyte imbalance, and mismanagement during transfer were identified as moderate risk factors. Low hemoglobin, hypoxemia, observation in multiple services, and distance of more than 100 kilometers were identified as predictive factors. Elimination of the main risk factors is a substantial issue to decrease inevitable mortalities. Thus, attempt to shorten the lethal chain of the risk factors can lengthen a patient's life and improve the prognosis.


Prolactin and growth hormone release and calcium influx are stimulated by galanin within a 'window' range of concentrations in pituitary GH3 B6 cells.
Galanin is widely distributed throughout the rat neural and endocrine system with the highest concentration in the anterior pituitary. The effects of galanin were investigated in rat tumor pituitary cells (GH3/B6). A single stimulation with galanin caused prolactin (PRL) and growth hormone (GH) release within a narrow range of concentrations (10(-11)-10(-9) M). However, secretory responses were not consistently observed upon subsequent galanin stimulation. Galanin triggered a rise in cytosolic Ca2+ (burst in [Ca2+]i transients) with a similar responsiveness. By contrast, no change in PRL mRNA was detectable in response to the peptide. These data suggest that galanin which binds to high-affinity receptors in anterior pituitary cells can exert subtle modulations of pituitary cell functions.


Changes in muscle fiber conduction velocity indicate recruitment of distinct motor unit populations.
To obtain more insight into the changes in mean muscle fiber conduction velocity (MFCV) during sustained isometric exercise at relatively low contraction levels, we performed an in-depth study of the human tibialis anterior muscle by using multichannel surface electromyogram. The results show an increase in MFCV after an initial decrease of MFCV at 30 or 40% maximum voluntary contraction in all of the five subjects studied. With a peak velocity analysis, we calculated the distribution of conduction velocities of action potentials in the bipolar electromyogram signal. It shows two populations of peak velocities occurring simultaneously halfway through the exercise. The MFCV pattern implies the recruitment of two different populations of motor units. Because of the lowering of MFCV of the first activated population of motor units, the newly recruited second population of motor units becomes visible. It is most likely that the MFCV pattern can be ascribed to the fatiguing of already recruited predominantly type I motor units, followed by the recruitment of fresh, predominantly type II, motor units.


Implications of surgery in very elderly patients.
As the number of people more than 75 years of age increase, the demands on ambulatory day surgery, operating room, and PACU nurses will increase. Nurses recognize the changes that this "graying" patient population will force on hospitals' surgical units. There is a paucity of studies on the educational needs of operating room nursing staffs responsible for the care of elderly patients. How can these needs best be met? What additional staffing is needed to cope with the increasing numbers of older patients who do not move or respond as quickly as younger patients? Research is needed in every step of the nursing process and its application to the care of very elderly patients undergoing surgery. This frail and unstable population does not easily lend itself to empirical research design; however, findings on the impact of nursing procedures, such as prevention of postoperative joint pain and hypothermia, can increase patient safety and comfort.


Physical activity history and end-of-life hospital and long-term care.
Little is known about the early predictors of need for care in late life. The purpose of this study was to investigate whether physical activity from midlife onward was associated with hospital and long-term care in the last year of life. We studied a decedent population of 846 persons aged 66-98 years at death, who, on average 5.8 years prior to death, had participated in an interview about their current and earlier physical activity. Data on the use of care in the last year of life are register-based data and complete. Men needed on average 96 days (SD 7.0) and women 138 days (SD 6.2) of inpatient care in the last year of life. Among men, the risk for all-cause hospital care in the last year of life was higher for those who had been sedentary since midlife (adjusted incidence rate ratio [IRR] 1.98, 95% confidence interval [CI] 1.14-3.42) compared with those who had been consistently physically active, whereas use of long-term care did not correlate with physical activity history. Among women, the risk for long-term care was higher for those who had been sedentary (IRR 2.03, 95% CI 1.28-3.21) or only occasionally physically active (IRR 1.60, 95% CI 1.06-2.43), than for those who had been consistently active from midlife onward, whereas use of hospital care did not correlate with physical activity history. People who had been physically active since midlife needed less end-of-life inpatient care but patterns differed between men and women.


Electroporation-induced damage in mammalian cell DNA.
Electroporation induced damage in the DNA of HL60 cells has been investigated by alkaline elution techniques. DNA damage is minimised by reducing the total charge applied (i.e., voltage x capacitance). Reduction of either of these electrical parameters, however, compromises the induced permeability of the cells to small molecules. The data presented concerning the effects of voltage and capacitance on DNA damage and the permeability of cells can be used to specify optimum conditions for electroporation in which DNA damage is minimised. The duration for which the current is applied can be seen to have a significant effect on the level of DNA damage. A modest temperature rise may occur when an electric charge is passed through electroporation buffer, but this event alone does not induce DNA damage in cells. The effect of voltage upon the permeability of HL60 cells to fluorescent-labelled molecules of varying molecular weight is reported.


[Sialendoscopy for obstructive disorders of the salivary glands].
Obstructive disorders of the salivary glands usually manifest as a swelling which is associated with meals ('mealtime syndrome') as well as inflammation of the gland. Obstruction of the salivary ducts of the parotid and submandibular glands is usually caused by a salivary stone, mucous plug or by a stenosis. Until recently, the options for diagnosis and treating these conditions were limited. Ultimately, the decision to remove the salivary gland was often made. Sialendoscopy is a recently developed semi-rigid optical technique that can be used to detect and usually treat obstructions in the salivary ductal system. This new, minimally invasive technique has resulted in the reduction of morbidity related to salivary gland obstruction. In many patients, surgical removal of the salivary gland can be avoided by using this technique.


Monomeric phospholamban overexpression in transgenic mouse hearts.
Phospholamban, a prominent modulator of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity and basal contractility in the mammalian heart, has been proposed to form pentamers in native SR membranes. However, the monomeric form of phospholamban, which is associated with mutating Cys41 to Phe41, was shown to be as effective as pentameric phospholamban in inhibiting Ca2+ transport in expression systems. To determine whether this monomeric form of phospholamban is also functional in vivo, we generated transgenic mice with cardiac-specific overexpression of the mutant (Cys41-->Phe41) phospholamban. Quantitative immunoblotting indicated a 2-fold increase in the cardiac phospholamban protein levels compared with wild-type controls, with approximately equal to 50% of phospholamban migrating as monomers and approximately 50% as pentamers upon SDS-PAGE. The mutant-phospholamban transgenic hearts were analyzed in parallel with transgenic hearts overexpressing (2-fold) wild-type phospholamban, which migrated as pentamers upon SDS-PAGE. SR Ca(2+)-uptake assays revealed that the EC50 values for Ca2+ were as follows: 0.32 +/- 0.01 mumol/L in hearts overexpressing monomeric phospholamban, 0.49 +/- 0.05 mumol/L in hearts overexpressing wild-type phospholamban, and 0.26 +/- 0.01 mumol/L in wild-type control mouse hearts. Analysis of cardiomyocyte mechanics and Ca2+ kinetics indicated that the inhibitory effects of mutant-phospholamban overexpression (mt) were less pronounced than those of wild-type phospholamban overexpression (ov) as assessed by depression of the following: (1) shortening fraction (25% mt versus 45% ov), (2) rates of shortening (27% mt versus 48% ov), (3) rates of relengthening (25% mt versus 50% ov) (4) amplitude of the Ca2+ signal (21% mt versus 40% ov), and (5) time for decay of the Ca2+ signal (25% mt versus 106% ov) compared with control (100%) myocytes. The differences in basal cardiac, myocyte mechanics and Ca2+ transients among the animal groups overexpressing monomeric or wild-type phospholamban and wild-type control mice were abolished upon isoproterenol stimulation. These findings suggest that pentameric assembly of phospholamban is important for mediating its optimal regulatory effects on myocardial contractility in vivo.


Validation of uranium determination in urine by ICP-MS.
A rapid procedure--dilution of urine+ICP-MS measurement--for the determination of uranium in urine was validated. Large ranges of concentration and isotopic composition were studied on urine samples excreted by occupationally exposed workers. The results were consistent with those obtained by fluorimetry and by alpha spectrometry after a purification procedure, two currently used techniques. However, the proposed procedure is limited for determination of the minor isotope 234U. Thus for worker monitoring, the conversion of 234U mass concentration into activity concentration can lead to an erroneous value of the effective dose, in particular for a contamination at very low level with highly enriched uranium. A solution to avoid this hazard is to perform a chemical purification prior to ICP-MS measurement to lower uncertainty and detection limit for 234U.


Upper gastrointestinal bleeding revealing the stomach metastases of renal cell carcinoma.
Renal cell carcinoma (RCC) constitutes 3% of all adult malignancies and often presents insidiously. Consequently, 25-30% of patients have metastases at the time of diagnosis. Gastrointestinal (GI) bleeding from RCC metastases is an uncommon and underrecognized manifestation of this disease. We hereby report a rare case of RCC with stomach metastasis which heralded the primary manifestation of the disease. This case highlights the importance of maintaining vigilance for unusual causes during endoscopy in cases of upper GI hemorrhage.


Intraurethral honey application for urethral injury: an experimental study.
To evaluate the effect of honey applied intraurethrally after urethral injury on histopathological healing. A total of Wistar male rats were used. The rats were divided into four groups: control (Group 1), sham (Group 2), 1 week honey applied group (Group 3) and 3 weeks honey applied group (Group 4). The urethral damage was caused with a 29 G needle. In sham group, only intraurethral saline solution was given, and 10% of honey was applied to rats in Groups 3 and 4 intraurethrally. After killing, penile tissues were investigated under a light microscopy. The irregularities of urethral epithelium and connective tissue were observed in Group 1. Also narrowing of lumen was present in control group rats except one rat in which no inflammation and total healing were observed. Hyperemia-bleeding was found in whole rats. In Group 2, there were irregularities in urethral epithelium and connective tissue. Total healing was observed in one rat. In Group 3, while regularity in urethral epithelium was present in six rats, inflammation and fibrosis was absent in rats. In Group 4, inflammation and fibrous tissue accumulation were not observed in rats. Intraurethral honey, applied after urethral injury, prevents inflammation, accelerates urethral healing and provides perfect healing.


Propofol attenuation of renal ischemia/reperfusion injury involves heme oxygenase-1.
To examine the protective effect of propofol in renal ischemia/reperfusion (I/R) injury and the role of heme oxygenase-1 (HO-1) in this process. Sprague-Dawley rats were randomly divided into 3 groups: (i) sham-operated group; (ii) I/R group; and (iii) propofol group. Bilateral renal warm ischemia for 45 min was performed. After 2, 6, and 24 h reperfusion, blood samples and kidneys were collected for assessment of renal injury, and HO-1 expressions were analyzed by immunohistochemical analysis, RT-PCR and Western blotting. Blood urea nitrogen and serum creatinine levels in the propofol group were significantly lower than that in the I/R group at 24 h after reperfusion. The mean histological score by Palleros standard showed that propofol significantly attenuated renal I/R injury after 6 h reperfusion. Propofol increased HO-1 mRNA and protein levels 2 h after reperfusion, whereas HO-1 expressions were present at exceedingly low levels in the I/R group and the sham-operated group at same time point. Propofol also markedly increased HO-1 mRNA and protein levels than I/R at 6 and 24 h after reperfusion. These results suggest that propofol mitigates renal I/R injury in rats. This protection may be partly through the induction of the HO-1 expression.


The incidence and mechanism of hypotension following thrombolytic therapy for acute myocardial infarction with streptokinase-containing agents--lack of relationship to pretreatment streptokinase resistance.
The incidence, amplitude, mechanism and relationship to prior exposure to streptococcal antigen of blood pressure changes to streptokinase-containing thrombolytic agents were investigated in 125 patients treated with either 1.5 x 10(6) IU streptokinase over 60 min or 30 U anistreplase over 5 min, within 6 h of onset of acute myocardial infarction. Twenty-one of 52 patients with anterior and 34 of 73 with inferior myocardial infarction had a hypotensive response. There were no significant differences in the incidence, duration or amplitude of hypotension between the two treatment groups. The maximum mean fall in systolic blood pressure was 16.9 mmHg (95% confidence limits, CL 12.2 to 24.5 mmHg), and the maximum mean fall in diastolic blood pressure was 13.7 mmHg (CL 10.3 to 17.1 mmHg), starting 4 min after start of therapy and resolving within 34 min. Blood pressure changes were well tolerated. Hypotension was not related to pretreatment streptokinase resistance titre, or anti-SK IgG concentration, to changes in plasma fibrinogen, B-beta 15-42 peptide, D-dimer--as indices of thrombin activation and fibrin (-ogen) breakdown--to plasma viscosity. The blood pressure changes following treatment with streptokinase-containing thrombolytic agents in acute myocardial infarction are frequent but well tolerated. The mechanism of hypotension remains unclear, but is not related to prior exposure to streptococcal antigen.


[Radiation exposure in diagnostic nuclear medicine: risk comparisons on the basis of effective doses].
The hypothetical risk of medical radiation exposure is often extrapolated to large population groups using arbitrary assumptions. To assess risk and benefit of diagnostic nuclear medicine and roentgenology, estimation of individual loss of life expectancy should be preferred. Employing ICRP 60 figures, diagnostic medical radiation exposure yields effective doses which commonly lie below or within the range of annual exposure from natural radiation (1-6 mSv). On an average, the individual medical exposure in Germany is estimated to be between 1 and 2 mSv which--extrapolated to total lifespan--leads to a hypothetical loss of life expectancy of 20-40 days. In the light of the rapid increase of life expectancy due to progresses in medical diagnostics and treatment after the introduction of X-rays, this figure is negligibly small.


The use of a rectus abdominis myocutaneous flap to reconstruct a groin defect.
An inferiorly based rectus abdominis myocutaneous skin flap was used carrying a large transversely aligned superior abdominal skin paddle to close successfully an infected and seriously compromised wound in the contralateral groin. The versatility of the rectus abdominis myocutaneous muscle unit, with its dual blood supply, is indicated yet again.


The role of ultrasound in the management of retinopathy of prematurity.
The authors reviewed the ultrasonic appearance of 54 eyes (27 patients) with advanced retinopathy of prematurity (ROP) and compared the various retinal configurations with the findings at surgery. They found that ultrasound is a sensitive indicator of retinal configuration (type and degree of retinal detachment [RD]), as well as showing the existence of subretinal or choroidal hemorrhage often present in these severely affected eyes. Ultrasound is a useful modality to evaluate, document, and follow the progression of RD in ROP.


Clinically Relevant In Vitro Testing of Orally Inhaled Products-Bridging the Gap Between the Lab and the Patient.
Current pharmacopeial methods for in vitro orally inhaled product (OIP) performance testing were developed primarily to support requirements for drug product registration and quality control. In addition, separate clinical studies are undertaken in order to quantify safety and efficacy in the hands of the patient. However, both laboratory and clinical studies are time-consuming and expensive and generally do not investigate either the effects of misuse or the severity of the respiratory disease being treated. The following modifications to laboratory evaluation methodologies can be incorporated without difficulty to provide a better linkage from in vitro testing to clinical reality: (1) examine all types of OIP with patient-representative breathing profiles which represent normal inhaler operation in accordance with the instructions for use (IFU); (2) evaluate OIP misuse, prioritizing the importance of such testing on the basis of (a) probability of occurrence and (b) consequential impact in terms of drug delivery in accordance with the label claim; and (3) use age-appropriate patient-simulated face and upper airway models for the evaluation of OIPs with a facemask. Although it is not necessarily foreseen that these suggestions would form part of future routine quality control testing of inhalers, they should provide a closer approximation to the clinical setting and therefore be useful in the preparation for in vivo studies and in improving guidance for correct use.


Serum uric acid as an independent predictor of mortality in high-risk patients with obstructive coronary artery disease: a prospective observational cohort study from the ET-CHD registry, 1997-2003.
Serum uric acid (SUA) has been observed to be highly associated with the development of cardiovascular disease for more than 50 years. Several studies have reported elevated SUA as an independent predictor of mortality in patients with coronary artery disease (CAD) after adjustment for classic risk factors but some studies did not find similar results. Between January 1997 and December 2003, a prospective cohort study was performed in 1054 patients with angiographically defined CAD, and their classic risk factors and SUA levels were determined at enrollment. The study cohort was followed for an average of 3.2 years, with a median of 3.1 years. The main outcome measure was death from cardiac disease and any cause. Of all study patients, 789 (74.9%) were men and 265 (25.1%) were women. The mean age of the male and female patients was 64.8 and 66.9 years, respectively. The mean SUA level of all patients was 410.4 μmol/L. There were grading effects of SUA quartiles on cardiac and all-cause mortality in univariate and multivariate Cox regression analyses. After adjustment, the multivariate analyses revealed that patients in the highest SUA quartile (>487 μmol/L) had 2.08 (95% CI=1.19-3.62, p=0.01) fold increased risk of cardiac death, and 1.68 (95% CI=1.10-2.57, p=0.017) fold increase risk of overall mortality compared with the lowest quartile (<315 μmol/L). SUA may be a significant predictor of cardiac and overall mortality, independent of classic risk factors in high-risk patients with obstructive CAD.


Intranasal airway/pack: description of a new device.
We have designed and developed a new intranasal pack which has been found to be most effective in controlling anterior and posterior epistaxis. Its ease of introduction and patient tolerance make it ideal for treating posterior epistaxis on an outpatient basis, and as packing for septal, sinus, or rhinoplastic surgery. The unique features of a breathing cannula and total intranasal tamponade distinguish this device from all preceding ones.


[Therapy of diaphyseal fractures of the leg in a district hospital].
During the period between 1987 and 1991 at the surgical department of the Trebíc hospital 136 casualties with closed diaphyseal fractures were treated. All patients were older than 18 years and monotraumas were involved. The patients were treated by immobilization by a classical high plaster bandage, functional plaster as recommended by Sarmient, extension treatment, miniosteosynthesis, osteosynthesis using a splint, intramedullary fixation as described by Küntscher and Simon-Enders-Weidner, or possibly by a combination of the mentioned methods. The author divides fractures of the leg into stable and unstable fractures and fracture with so-called urgently indicated osteosynthesis. The mean period of treatment with high plaster bandage was 31.7 weeks, functional plaster according to Sarmient 20.2 weeks, miniosteosynthesis with plaster fixation 25.5 weeks. When splints were used, the mean period of treatment was 30.5 weeks, in osteosynthesis according to Enders 20.6 weeks. The best results in stable fractures were achieved by functional plaster according to Sarmient, in unstable fractures and those with indicated osteosynthesis by using intramedullary fixation as described by Enders.


Reduced skin hyperemia during tap water iontophoresis after intake of acetylsalicylic acid.
Skin microcirculation and skin temperature of 10 healthy subjects (6 men and 4 women, 20-44 yr of age) without any vascular diseases were registered when a thermoindifferent tap water iontophoresis was applied. The aim of this controlled study was to evaluate the development of skin hyperemia after the intake of 500 mg of acetylsalicylic acid (ASA). The measurement was conducted by laser-Doppler flowmetry on the proximal forearm. The skin temperature was measured before and after the treatment by an infrared thermometer. In all persons there was an intense erythema on the side of the cathode and only a modest one on the side of the anode. Without ASA preliminary treatment, the cutaneous flow showed an increase of 106% at the anodal side and that of 834% at the cathodal side (P < 0.001). After ending tap water iontophoresis, the skin temperature increased more on the cathode side than on the anode side (P < 0.001). After the intake of 500 mg ASA, the increase of the flow was 78% at the anode and 88% at the cathode. The comparison of the skin microcirculation did not show any differences at the anodal side when acetylsalicylic acid was taken before, but a strong suppression of the galvanic erythema at the cathodal side was observed after the intake of ASA. There is a direct influence of acetylsalicylic acid on the induction of the neurogenic inflammation caused by a galvanic erythema. The intensity of the induced erythema correlates with the analgesic effects of constant current treatment. An attenuation of the electrotherapeutic analgesia is possible.


Costs associated with diffuse large B-cell lymphoma patient treatment in a Canadian integrated cancer care center.
The objective of this study was to provide a detailed comparative microcosting analysis for two cancer treatment pathways to contribute evidence for resource allocation and operational decision-making in a Canadian cancer care context. We estimated direct medical costs (in 2004 CAN$) of the entire pathway of care for diffuse large B-cell lymphoma (DLBCL) patients in a large Canadian cancer treatment center. Patient samples were defined as those who received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; n = 85) or CHOP (i.e., without rituximab; n = 86) as first-line treatment. All subsequent treatments including palliative care for these patient samples were assessed. Hospitalization costs and unit costs of medical resources were collected from integrated medical organizations. Individual patient resource consumption was assessed via medical chart review. For first-line treatment, drug cost was the largest contributor to total cost, followed by hospitalization cost. Rituximab was the largest contributor to mean cost differences between R-CHOP and CHOP treatments. For treatments subsequent to first-line treatment, no significant cost differences were found. Hospitalization and transplantation costs were the two largest constituents of total costs subsequent to first-line treatment, followed by drug cost. Patients with advanced stage disease cost significantly more than patients with limited stage disease. This is the first detailed microcosting study that has employed consistent local data to estimate total medical costs for DLBCL patients in Canada. This information is useful for resource allocation planning and operational decisions, because it provides more substantive, relevant evidence as compared to aggregated, literature or extrapolated information.


The peculiarities and paradoxes of Plasmodium heme metabolism.
For over a century, heme metabolism has been recognized to play a central role during intraerythrocytic infection by Plasmodium parasites, the causative agent of malaria. Parasites liberate vast quantities of potentially cytotoxic heme as a by-product of hemoglobin catabolism within the digestive vacuole, where heme is predominantly sequestered as inert crystalline hemozoin. Plasmodium spp. also utilize heme as a metabolic cofactor. Despite access to abundant host-derived heme, parasites paradoxically maintain a biosynthetic pathway. This pathway has been assumed to produce the heme incorporated into mitochondrial cytochromes that support electron transport. In this review, we assess our current understanding of the love-hate relationship between Plasmodium parasites and heme, we discuss recent studies that clarify several long-standing riddles about heme production and utilization by parasites, and we consider remaining challenges and opportunities for understanding and targeting heme metabolism within parasites.


Enhancing Fenton oxidation of TNT and RDX through pretreatment with zero-valent iron.
The effect of reductive treatment with elemental iron on the rate and extent of TOC removal by Fenton oxidation was studied for the explosives 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) using a completely stirred tank reactor (CSTR). The results support the hypothesis that TNT and RDX are reduced with elemental iron to products that are oxidized more rapidly and completely by Fenton's reagent. Iron pretreatment enhanced the extent of total organic carbon (TOC) removal by approximately 20% and 60% for TNT and RDX, respectively. Complete TOC removal was achieved for TNT and RDX solutions with iron pretreatment under optimal conditions. On the other hand, without iron pretreatment, complete TOC removal of TNT and RDX solutions was not achieved even with much higher H(2)O(2) and Fe(2+) concentrations. Nitrogen was recovered as NH(4)(+) and NO(3)(-) when Fe(0)-treated TNT and RDX solutions were subjected to Fenton oxidation. The bench-scale iron treatment-Fenton oxidation integrated system showed more than 95% TOC removal for TNT and RDX solutions under optimal conditions. These results suggest that the reduction products of TNT and RDX are more rapidly and completely degraded by Fenton oxidation and that a sequential iron treatment-Fenton oxidation process may be a viable technology for pink water treatment.


Guidelines for creating effective slides and overhead transparencies used for teaching.
Slides, 35-mm transparencies, and overhead transparencies are popular teaching tools. This article outlines basic design principles and ways of producing transparencies so that the audience--whether student or professional--will benefit the most from this teaching device.


Vascular permeability during the early and late phases of ocular anaphylaxis.
The role of enhanced vascular permeability in a model of ocular anaphylaxis was investigated during both early- and late-phase reactions (EPR and LPR). Vascular permeability was assessed by measuring the extravascular retention of 125I-bovine serum albumin (125I-BSA) in ocular tissues. Ten groups of guinea pigs (n = 5-12 per group) were injected with dinitrophenylated (DNP) bovine gamma globulin emulsified in Freund's adjuvants and challenged after a 4-week interval by topical application of di-DNP-lysine to one eye and phosphate-buffered saline to the other eye. Thereafter, the eyes were examined and the animals were killed at different intervals after topical challenge. They were injected intravenously with 125I-BSA 0.5 hr before death. Retained radioactivity was measured separately in four tissues. The EPR (period between 0.5-1.5 hr after challenge) was characterized by enhanced retention of radioactivity in lids, conjunctiva, and orbital content. There was no significant retention of extravascular radioactivity in the globe and lacrimal gland. Thereafter (period between 2-3.5 hr after challenge), retained radioactivity was significantly diminished. The subsequent period, between 4.5-6.5 hr (LPR), was characterized by a smaller, although significant, increment of radioactivity retained in lids and conjunctiva but not in the other tissues examined. These findings indicate that enhanced microvascular permeability occurs during two phases in actively immunized guinea pigs challenged topically with di-DNP-lysine and that these phases correspond to the clinical signs that constitute the EPR and LPR of ocular anaphylaxis.


Novel 12N-substituted matrinanes as potential anti-coxsackievirus agents.
A series of novel 12N-substituted matrinane derivatives were synthesized and evaluated for their activities against coxsackievirus type B3 (CVB3) taking compound 1 as the lead. SAR analysis indicated that the introduction of a suitable heteroaromatic ring on the 12N-atom might be beneficial for the activity. Among them, compound 8a exhibited the highest potency against all CVB serotypes as well as CVA16 with IC50 values ranging from 2.02μM to 7.41μM, indicating a broad-spectrum anti-coxsackieviruse effect. Furthermore, compound 8a demonstrated a good safety profile in vivo. Thus, we consider 12N-substituted matrinanes to be a promising family of anti-coxsackievirus agents, and compound 8a to be a promising drug candidate in the treatment of various diseases related to coxsackievirus infection.


Characteristics of Asian mosquito saliva allergens for specific diagnoses and effective therapies.
An allergic reaction to mosquitoes can result in severe or abnormal local or systemic reactions such as anaphylaxis, angioedema, and general urticarial or wheezing. In this review we aim to provide information on mosquito saliva allergens that can support the production of highly specific recombinant saliva allergens. In particular, candidate allergens of mosquitoes that are well suited to the ecology of mosquitoes that occur mainly in East Asia will be identified and introduced. By doing so, we will improve the diagnosis and treatment of patients with severe sensitivity to mosquito allergy by predicting the characteristics of East Asian mosquito allergy, presenting the future direction of production of recombinant allergens, and understanding the difference between East and West.


Clinical Profile and Outcome of Children with Congenital Obstructive Uropathy.
To study the etiology and clinical profile of congenital obstructive uropathy in children, renal status and growth at diagnosis and at follow-up and to determine the predictors for development of chronic kidney disease (CKD). An observational (retrospective-prospective) study was conducted at a tertiary care hospital in South India from September 2014 through September 2016. Sixty children diagnosed to have congenital obstructive uropathy with a minimum follow-up period of 5 y were included and followed up prospectively for 2 more years during the study period. The data of the children at admission and follow-up was obtained from the medical records and analyzed. Congenital uretero-pelvic junction obstruction followed by Posterior urethral valve were the most common etiologies identified. Male preponderance (88.3%) was observed with poor urinary stream being the most common presentation (36.6%). Forty percent of the population had elevated creatinine. Fifteen percent were hypertensive and 25% had growth failure at diagnosis. However, there was a reduction in the number of children with poor estimated glomerular filtration rate (eGFR), hypertension and growth faltering during follow-up. Among the risk factors, hypertension at diagnosis [O.R-12.8 (2.21-74.22) and p value <0.05] and frequent urinary tract infection (UTI) [O.R-14.06 (2.32-85.42) and p value <0.05] were the most important factors for CKD progression. Children with low eGFR (< 60 ml/min/1.73m2) had more height faltering and hypertension at follow-up (p value <0.05). Hypertension and frequent UTI were observed to be strongly associated with progression of CKD. Estimated GFR was found to be significantly associated with faltering of height and hypertension. Preserving the renal function prevents growth faltering and development of hypertension at follow-up thereby ensuring a better quality of life.


Successful surgical treatment of primary aorto-duodenal fistula associated with inflammatory abdominal aortic aneurysm: A case report.
We report a rare case of a 50-year-old woman with intermittent gastrointestinal (GI) bleeding and diagnosed as having primary aortoenteric fistula (PAEF) with inflammatory abdominal aortic aneurysm (IAAA). She was transferred to our institution with suspected PAEF as assessed by duodenoscopy and CT scan. As the patient was in shock due to massive GI-bleeding two days after admission, we performed an emergency laparotomy. The fistula was closed and the aneurysm replaced by a Woven Dacron Graft with an inter-positioning omental flap. A high index of suspicion is the most important diagnostic aid to prevent overlooking this often fatal disease.


Combined activities of Gurken and decapentaplegic specify dorsal chorion structures of the Drosophila egg.
During Drosophila oogenesis Gurken, associated with the oocyte nucleus, activates the Drosophila EGF receptor in the follicular epithelium. Gurken first specifies posterior follicle cells, which in turn signal back to the oocyte to induce the migration of the oocyte nucleus from a posterior to an anterior-dorsal position. Here, Gurken signals again to specify dorsal follicle cells, which give rise to dorsal chorion structures including the dorsal appendages. If Gurken signaling is delayed and starts after stage 6 of oogenesis the nucleus remains at the posterior pole of the oocyte. Eggs develop with a posterior ring of dorsal appendage material that is produced by main-body follicle cells expressing the gene Broad-Complex. They encircle terminal follicle cells expressing variable amounts of the TGFbeta homologue, decapentaplegic. By ectopically expressing decapentaplegic and clonal analysis with Mothers against dpp we show that Decapentaplegic signaling is required for Broad-Complex expression. Thus, the specification and positioning of dorsal appendages along the anterior-posterior axis depends on the intersection of both Gurken and Decapentaplegic signaling. This intersection also induces rhomboid expression and thereby initiates the positive feedback loop of EGF receptor activation, which positions the dorsal appendages along the dorsal-ventral egg axis.


Assessment of gastric cancer survival: using an artificial hierarchical neural network.
This study is designed to assess the application of neural networks in comparison to the Kaplan-Meier and Cox proportional hazards model in the survival analysis. Three hundred thirty gastric cancer patients admitted to and surgically treated were assessed and their post-surgical survival was determined. The observed baseline survival was determined with the three methods of Kaplan-Meier product limit estimator, Cox and the neural network and results were compared. Then the binary independent variables were entered into the model. Data were randomly divided into two groups of 165 each to test the models and assess the reproducibility. The Chi-square test and the multiple logistic model were used to ensure the groups were similar and the data was divided randomly. To compare subgroups, we used the log-rank test. In the next step, the probability of survival in different periods was computed based on the training group data using the Cox proportional hazards and a neural network and estimating Cox coefficient values and neural network weights (with 3 nodes in hidden layer). Results were used for predictions in the test group data and these predictions were compared using the Kaplan-Meier product limit estimator as the gold standard. Friedman and Kruskal-Wallis tests were used for comparisons as well. All statistical analyses were performed using SPSS version 11.5, Matlab version 7.2, Statistica version 6.0 and S_PLUS 2000. The significance level was considered 5% (alpha = 0.05). The three methods used showed no significance difference in base survival probabilities. Overall, there was no significant difference among the survival probabilities or the trend of changes in survival probabilities calculated with the three methods, but the 4 year (48th month) and 4.5 year (54th month) survival rates were significantly different with Cox compared to standard and estimated probabilities in the neural network (p < 0.05). Kaplan-Meier and Cox showed almost similar results for the baseline survival probabilities, but results with the neural network were different: higher probabilities up to the 4th year, then comparable with the other two methods. Estimates from Cox proportional hazards and the neural network with three nodes in hidden layer were compared with the estimate from the Kaplan-Meier estimator as the gold standard. Neither comparison showed statistically significant differences. The standard error ratio of the two estimate groups by Cox and the neural network to Kaplan-Meier were no significant differences, it indicated that the neural network was more accurate. Although we do not suggest neural network methods to estimate the baseline survival probability, it seems these models is more accurately estimated as compared with the Cox proportional hazards, especially with today's advanced computer sciences that allow complex calculations. These methods are preferable because they lack the limitations of conventional models and obviate the need for unnecessary assumptions including those related to the proportionality of hazards and linearity.


Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6.
Somites, segmented mesodermal units of the vertebrate embryo, are the precursors of adult skeletal muscle, bone and cartilage. During embryogenesis, somite progenitor cells ingress through the primitive streak, move laterally to a paraxial position (alongside the body axis) and segment into epithelial somites. Little is known about how this paraxial mesoderm tissue is specified. We have previously described a mouse T-box gene, Tbx6, which codes for a putative DNA-binding protein. The embryonic pattern of expression of Tbx6 in somite precursor cells suggests that this gene may be involved in the specification of paraxial mesoderm. We now report the creation of a mutation in Tbx6 that profoundly affects the differentiation of paraxial mesoderm. Irregular somites form in the neck region of mutant embryos, whereas more posterior paraxial tissue does not form somites but instead differentiates along a neural pathway, forming neural-tube-like structures that flank the axial neural tube. These paraxial tubes show dorsal/ventral patterning that is characteristic of the neural tube, and have differentiated motor neurons. These results indicate that Tbx6 is needed for cells to choose between a mesodermal and a neuronal differentiation pathway during gastrulation; Tbx6 is essential for the specification of posterior paraxial mesoderm, and in its absence cells destined to form posterior somites differentiate along a neuronal pathway.


Anti-obesity compounds in green leaves of Eucommia ulmoides.
The anti-hypertensive effect of Eucommia leaves has been confirmed clinically, and the study of their anti-obesity properties has advanced. However, the compounds involved in their anti-obesity effect have not been fully elucidated. In this Letter, we examined the anti-obesity effect of Eucommia green leaf extract (EGLE) divided into five fractions with high porous polystyrene gel and of the compounds isolated, geniposidic acid, asperuloside and chlorogenic acid, respectively. A metabolic syndrome-like clinical model in mice was generated by feeding a 40% high-fat diet to examine the anti-obesity effects of chronic administration of test substance. After 4 weeks, body weight, white adipose tissue weight, plasma triglyceride levels and total cholesterol levels in the model mice were significantly inhibited by the 30% MeOH fraction (containing much higher levels of asperuloside than the other fractions), and these effects were similar to those of EGLE. Chronic administration of isolated asperuloside in Eucommia leaves suppressed increases in model mouse body weight, white adipose tissue weight, plasma triglyceride levels and free fatty acids levels. These results suggest that asperuloside in Eucommia leaves has important anti-obesity effects.


Stimulatory effects of brain natriuretic peptide on cyclic GMP accumulation and tyrosine hydroxylase activity in cultured bovine adrenal medullary cells.
We studied the effect of brain natriuretic peptide (BNP) on the accumulation of cyclic GMP and the phosphorylation and activity of tyrosine hydroxylase, compared with that of atrial natriuretic peptide (ANP), in cultured bovine adrenal medullary cells. 1. BNP as well as ANP increased cellular cyclic GMP accumulation in a concentration-dependent manner (10-1000 nmol/l). BNP (1 mumol/l) and ANP (1 mumol/l) produced a 60-fold and 30-fold increase in cyclic GMP accumulation, respectively. 2. The stimulatory effects of BNP and ANP on cyclic GMP accumulation were observed even when Ca2+ or Na+ was removed from the incubation medium. 3. 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, inhibited the stimulatory effect of BNP on cyclic GMP accumulation in a concentration-dependent manner (1-100 nmol/l). Furthermore, the BNP-induced accumulation of cyclic GMP was attenuated by forskolin (1 mumol/l), an activator of adenylate cyclase. 4. BNP (1 mumol/l) and ANP (1 mumol/l) caused a significant increase in phosphorylation and activity of tyrosine hydroxylase in the cells. 5. In digitonin-permeabilized cells, cyclic GMP (1-100 mumol/l) activated tyrosine hydroxylase in the presence of ATP and Mg2+. These results suggest that BNP stimulates the accumulation of cyclic GMP in a manner similar to that of ANP. The increased accumulation of cyclic GMP by these peptides may be negatively modulated by protein kinase C and cyclic AMP and may cause the phosphorylation and activation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.


An appraisal of the tuberculosis programme in India using an ethics framework.
This is a review of the manner in which the Revised National Tuberculosis Control Programme (RNTCP) is being implemented, with a focus on the attention being paid to ethical principles and the incorporation of these into the programme. The article elucidates how ethical principles can be applied to protect the rights of the potential beneficiaries of the RNTCP. The authors consider the RNTCP in the light of a framework that is usually applied in research to evaluate ethical principles in public health practice. The three key principles of the framework are: respect for persons, beneficence and justice. The authors propose that this framework be used to make an ethical evaluation of other pu health programmes at several levels, since this could bring far-reaching benefits to society.


Cerclage wiring and intramedullary nailing, a helpful and safe option specially in proximal fractures. A multicentric study.
Antegrade intramedullary nailing is an alternative for humeral shaft fracture treatment. This surgical technique can be especially demanding in some fracture patterns, leading to problems like malunion and non-union. The purpose of our study is to demonstrate that the use of a nail with cerclage wires could be a safe procedure that facilitate reduction, specially in fractures with abduction of the proximal fragment. Fifty-six patients were included, from January 2007 to March 2016. In this cohort forty-two patients were females and eighteen males; mean age was sixty-seven (32-89). The fractures were reduced using a cerclage wire through a small lateral or anterior approach, then, antegrade intramedullary nailing was performed. Fracture healing was established by clinical and radiographic evaluation. Shoulder function was assessed using the Constant Score. Fifty-three patients healed (94.6%) adequately. Two patients developed a non-union (3.5%). One patient developed an infection (1.8%). Transient radial nerve palsy was observed in two patients (3.5%). The mean Constant Score at the end of the study was 70 points (range from 34 to 98 points). Surgical treatment of humeral shaft fractures with cerclage wire and intramedullary nailing is a safe technique to improve fracture reduction. The use of cerclage wires leads to better bone contact while minimizing malunions. The rate of non-union in our study is lower than the rate reported in the literature for humeral shaft fractures treated by intramedullary nailing alone.


Purification and characterization of the precursor tRNA 3'-end processing nuclease from Aspergillus nidulans.
The precursor-tRNA 3'-end processing nuclease activity was purified homogeneously about 15,300 fold from the heat-treated fraction. The precursor-tRNA 3'-end processing nuclease was a single polypeptide of 160,000 Da. This nuclease generates a mature 3'-end of nuclear tRNA(Asp) of Aspergillus nidulans by the endonuclease activity and prefers the 5'-end processed tRNA(Asp) rather than primary precursor-tRNA(Asp) as a substrate. However, this enzyme did not process both primary mitochondrial precursor-tRNA(His) and 5'-end processed mitochondrial precursor-tRNA(His) of A. nidulans.


Hemodynamic effects of colloid concentration in experimental hemorrhage: a comparison of Ringer's acetate, 3% dextran-60, and 6% dextran-70.
Hemodynamic effects of iso-oncotic 3% dextran-60, 6% dextran-70, and Ringer's acetate were compared in 28 male pigs (25 to 30 kg) subjected to experimental trauma and hemorrhage. The animals were kept anesthetized with 75% N2O/25% O2, 0.8% halothane. Hemodynamic and respiratory conditions were allowed to stabilize for one hour preoperatively (baseline data). After surgical trauma (arthroplasty), three 0.5 L of arterial blood samples were withdrawn and replaced with autologous red cells mixed with one liter of 3% dextran-60 in one group 1 (n = 9), one liter of 6% dextran-70 in group 2 (n = 10), and 3 L of Ringer's acetate in group 3 (n = 9). Pulmonary capillary wedge pressure (WP) was kept at baseline level for a further 10 h with infusion of the respective fluid; for this purpose, groups 1 through 3 needed additional infusions of 0.8 +/- 0.3, 0.5 +/- 0.4, and 5.3 +/- 3 (SD) L, respectively. Group 1 showed the highest jejunal capillary blood flow at 10 h and the lowest intragroup variations in hemodynamic and respiratory data. Group 2 had the highest pulmonary arterial pressures and group 3 had the lowest colloid oncotic and arterial BP and left ventricular volume indices. In group 3, the Hct and serum albumin indicated insufficient plasma volume replacement. This group had a significantly larger (p less than .05) amount of tissue water in skin, skeletal muscle, and jejunum than the other groups; no significant difference in lung or heart muscle water was found between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Adrenal ganglioneuromas in children with multiple endocrine neoplasia type 2: a report of two cases.
Pheochromocytomas of the adrenal gland are a common component of the multiple endocrine neoplasia type 2 (MEN2) syndromes. However, pure adrenal ganglioneuromas, an extremely rare pediatric tumor of neural crest origin composed of mature ganglion cells, have never been reported in association with MEN2 in humans. MEN2A is comprised of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. MEN2B is characterized by MTC, pheochromocytoma, neural abnormalities of the gastrointestinal tract, and mucosal neuromas. We report two pediatric patients, one with MEN2A and one with MEN2B, who developed isolated adrenal ganglioneuromas without evidence of pheochromocytomas. MEN2A and MEN2B are caused by activating mutations in the RET proto-oncogene, which encodes a tyrosine kinase receptor essential for signal transduction in neural crest-derived tissues, including the peripheral and enteric nervous systems, C cells of the thyroid gland, and chromaffin cells of the adrenal gland. Both pheochromocytomas and ganglioneuromas originate from neural crest cells. Interestingly, two mouse models of MEN2B exhibit adrenal ganglioneuroma formation. One mouse model develops only ganglioneuromas (but not pheochromocytomas) and expresses only one of the oncogenic RET isoforms. The other mouse model, created by site-directed mutagenesis to simulate the most common human mutation, develops both ganglioneuromas and pheochromocytomas. Given our two cases, our current understanding of the mouse models, and the common origins of all these tumor cell types, we recommend including ganglioneuromas as a rare, but not unexpected, component of the MEN2 syndromes.


[Spontaneous gas gangrene in a diabetic patient with Clostridium septicum].
Atraumatic infections due to Clostridium septicum are known to be associated with immunosuppression or even malignancy. In this case report, we present a patient with severe Clostridium septicum infection related to advanced colon cancer that had not previously been diagnosed. The case demonstrates the strong association between Clostridium septicum infections and malignancy, particularly in the presence of other predisposing diseases such as diabetes mellitus. It strongly suggests excluding malignant neoplasms, especially of the gastrointestinal tract, when severe Clostridium septicum infections occur. Moreover, if patients with known colorectal or other malignancy develop septicaemia or spontaneous gas gangrene, clinicians should be aware of Clostridium septicum as one of the main causative agents, as early diagnosis and aggressive treatment are important to improve prognosis.


(De)coupling of our eyes and our mind's eye: A dynamic process perspective on attentional bias.
We aimed to illuminate the theorized, yet empirically elusive, connection between covert and overt attentional processes subserving attentional biases (AB). We found that covert and overt attentional processes were each expressed dynamically, fluctuating from moment-to-moment between phases of (over)engagement and phases of avoidance of threat stimuli. The key features of the temporal dynamics of covert and overt attentional processes were significantly correlated. Moreover, the real-time, dynamic expressions of overt and covert attentional processes were significantly coupled from trial-to-trial; and voluntary inhibition of overt attention decoupled their connection in time. In contrast to this dynamic process perspective on AB, when quantified through the decades-old paradigm conceptualizing AB as a static trait-like phenomenon, covert and overt attentional processes demonstrated (seemingly) no association and poor psychometrics. We discuss the implications of the findings for better understanding the nature of AB, its measurement, bio-psycho-behavioral correlates, and clinical modification. (PsycINFO Database Record


Biogenesis of COPI-coated transport vesicles.
Biosynthetic protein transport and sorting along the secretory pathway represents the last step in biosynthesis of a variety of proteins. Proteins destined for delivery to the cell surface are inserted cotranslationally into the endoplasmic reticulum (ER) and, after their correct folding, are transported out of the ER towards their final destinations. The successive compartments of the secretory pathway are connected by vesicular shuttles that mediate delivery of cargo. The formation of these carrier vesicles depends on the recruitment of cytosolic coat proteins that are thought to act as a mechanical device to shape a flattened donor membrane into a spherical vesicle. A general molecular machinery that mediates targeting and fusion of carrier vesicles has also been identified. This review is focused on COPI-coated vesicles that operate in protein transport within the early secretory pathway. Rather than representing a general overview of the role of COPI-coated vesicles, this mini-review will discuss mechanisms specifically related to the biogenesis of COPI-coated vesicles: (i) a possible role of phospholipase D in the formation of COPI-coated vesicles, (ii) a functional role of a novel family of transmembrane proteins, the p24 family, in the initiation of COPI assembly, and (iii) the direction COPI-coated vesicles may take within the early secretory pathway.


Fetal echocardiography for planning perinatal and delivery room care of neonates with congenital heart disease.
Fetal echocardiography facilitates the prenatal diagnosis of infants with congenital heart disease (CHD) and through sequential examinations, allows assessment of fetal hemodynamics and cardiovascular status from the time of diagnosis to delivery. Fetal cardiologists have created diagnostic protocols aimed at risk stratifying severity and potential postnatal compromise in fetuses with CHD, and identifying those who may require special intervention at birth or within the first days of life. In this article, we review fetal cardiovascular physiology, the progression of CHD in utero and fetal echocardiographic findings used for risk stratification of newborns with CHD, as well as some of the basic principles of planning for the neonatal resuscitation and initial transitional care of these complex newborns.


Varenicline for smoking cessation.
Varenicline (pronounced va-re-nik-leen) (Champix - Pfizer), a nicotinic receptor partial agonist, is the first medicine of this type licensed for smoking cessation in adults. Launched in the UK in December 2006, the drug accounted for 14% of all prescription items and 22% of total expenditure, for smoking cessation products dispensed in the community in 2007. Marketing materials claim that it has a "unique dual action", a "significantly higher quit rate" than bupropion, and a "favourable safety and tolerability profile". Here we discuss the evidence for varenicline and consider its role in smoking cessation.


The evolution of ontogenetic allometric trajectories in mammalian domestication.
Morphological divergence of domesticated as compared to wild forms must result from changes in the ontogenetic process. Species-specific tests for heterochrony have rejected a single explanation of domestic forms representing juveniles of their wild relatives. Ontogenetic allometric trajectories for 12 pairs of wild and domestic mammals were examined using skull growth data for 1070 specimens, including representatives from all lineages in which domestication has occurred. A suite of tests were performed to quantify allometric disparity in wild and domestic forms and assess the extent and patterning of modification to allometric trajectories. Domestication has modified postnatal ontogenetic allometric trajectories in mammals, and has generated disparity, achieved through lengthening of trajectory slopes and alteration to slope angles. Allometric disparity was similar for domestic forms compared to their wild relatives, whereas the magnitude of dispersion along allometric vectors differed between precocial mammals and altricial mammals, underscoring the importance of life history and shared evolutionary history in patterns of ontogenetic variation. The results verify the importance of scaling in the morphological changes associated with domestication. The response to domestication for all measured trajectory parameters was variable across species, suggesting multiple pathways of change.


High frequency of G/C transversion on p53 gene alterations in breast cancers from Taiwan.
p53 gene mutation is a very frequent event in many human cancers and is associated with a poor clinical outcome in breast cancer patients. Analysis of p53 gene mutations can also provide clues to the etiology of tumor formation. The present study was conducted to investigate the p53 mutations in patients with breast cancer from Taiwan. Tumor samples from 119 patients undergoing mastectomy for breast cancer were evaluated. The mutational status of the p53 gene (exons 5-8) was screened by polymerase chain reaction-single strand conformation polymorphism analysis followed by direct sequencing. Of all 119 cases of breast carcinoma, 26 mutations of the p53 gene were found in 22 cases (18.5%). Among these mutations, 78% (20/26) were point mutations with the majority of those being missense mutations (75%, 15 of 20 mutations) and the other 22% (6/26) were frameshift mutations. No significant correlation between p53 mutations and clinicopathological features was found, including HER2 status. Moreover, our results disclosed distinct mutation spectra in excess transversions to transitions (15/21, 71.4% vs. 6/21, 28.6%) with GC to CG dominant (6/15, 40%). Mutation hot spots we identified at codons 167, 185, 186, 210, 265 and 295 have rarely been documented in the literature. These findings showed that p53 gene mutation might contribute to the pathogenesis of breast carcinoma. Furthermore, the different mutation spectrum with high transversions in G:C to C:G may imply that the exogenous mutagens outweigh the endogenous processes in breast cancer in patients in Taiwan.


Real-time numerical simulation of Doppler ultrasound in the presence of nonaxial flow.
Numerical simulations of Doppler ultrasound (DUS) relying on computational fluid dynamics (CFD) models of nonaxial flow have traditionally employed detailed (but computationally intensive) models of the DUS physics, or have sacrificed much of the physics in the interest of computational or conceptual simplicity. In this paper, we present a compromise between these extremes, with the objective of simulating the essential characteristics of DUS spectrograms in a real-time manner. Specifically, a precomputed pulsatile CFD velocity field is interrogated at some number, N, of discrete points distributed spatially within a sample volume of prescribed geometry and power distribution and temporally within a prescribed sampling window. Intrinsic spectral broadening is accounted for by convolving each of the point velocities with a semiempirical broadening function. Real-time performance is facilitated through the use of an efficient algorithm for interpolating the unstructured CFD data. A spherical sample volume with Gaussian power distribution, N = 1000 sampling points, and quadratic broadening function are shown to be adequate for simulating, at frame rates of 86 Hz on a 1.5 GHz desktop workstation, realistic-looking spectrograms at representative locations within a stenosed carotid bifurcation model. Via qualitative comparisons with matched in vitro data, these simulated spectrograms are shown to mimic the distinctive spectral envelopes, broadening and power characteristics associated with common carotid, stenotic jet and poststenotic recirculating flows. We conclude that the complex interaction between Doppler ultrasound and complicated clinically relevant blood flow dynamics can be simulated in real time via this relatively straightforward semiempirical approach.


Acute normovolemic hemodilution is safe in neurosurgery.
To determine the safety of acute normovolemic hemodilution (ANH) for patients undergoing neurosurgical procedures. A group of 100 patients undergoing neurosurgical procedures was assigned prospectively to receive ANH. A group of 47 patients who underwent craniotomy for aneurysm clipping and standard anesthetic management was used as a control. Procedures conducted under ANH were performed without significant variations in physiologic parameters. Compared with controls, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the two groups. Although the ANH group showed a difference in prothrombin levels before and after hemodilution procedures, the levels were still considered within physiologic parameters. Platelet counts and partial thromboplastin time (PTT) levels indicated no significant variations in either group. During the ANH procedure, a considerable reduction of brain oxygen extraction was observed in individuals with worse preoperative neurologic status (P < 0.05), indicating potential benefit. Among patients with cerebral aneurysm, patients with good initial clinical grades had better clinical results as indicated by Glasgow Outcome Scale scores (P < 0.02). ANH is a safe procedure for patients undergoing neurosurgical procedures. Further studies are necessary to confirm the improvement in brain oxygen extraction and the clinical impact. Nonetheless, patients undergoing aneurysm clipping with good clinical grades seem to profit from ANH.


The difference in autofluorescence features of lipofuscin between brain and adrenal.
Lipofuscin is the autofluorescent material, which accumulates with aging in the cells of various tissues. However, its autofluorescence characteristics are different among tissues. In the present study, the autofluorescence features of lipofuscin in the brain and adrenal were compared. In 18-21-month-old rats, the brain lipofuscin was granular and its autofluorescence was bright whitish-yellow to bright orange. On the contrary, the adrenal lipofuscin was not demarkated as granules, and its autofluorescence was subdued orange. The emission maximum of the bright whitish-yellow brain lipofuscin was 540 nm to 570 nm and that of the adrenal lipofuscin was 640 nm to 660 nm, when excited at 330 nm to 380 nm. When the spectra were drawn after correcting the wavelength-dependent bias of microspectrofluorometer, the autofluorescence spectra were consistent with microscopically observable tint. To conclude, the present results showed that the autofluorescence features of the bright whitish-yellow brain lipofuscin and the adrenal lipofuscin were quite different.


[Stable shifts in systemic arterial pressure in a controlled experiment with feedback].
On the bases of experiments with bio-control feed-back connection (automatically triggering electro-cutaneous, stimulation), a model evolved permitting to achieve stable directed changes in the levels of the systemic arterial pressure (AP) in curarized rabbits and cats. Two variants of reactions are possible: 1) gradual formation of a new raised or lowered level of AP with its pronounced retention after the end of learning, and 2) reaction of following type with directed rise in AP, which is observed only during learning. It is found that the stable shifts of the AP level are accompanied by changes in the periodicity of the third order AP waves, the heart rate showing no significant changes. It is assumed that the changes in the characteristics of the third order waves reflect the rearrangement of the mechanisms providing for homeostasis.


A new index approach to measure lost benefits from progression to blindness.
An index approach for measuring the reduction in daily activities of patients suffering from an eye disease associated with progressive visual loss is proposed. The approach is illustrated using data collected from patients with cataract. The approach uses recently developed methods based on index theory together with measurements of daily activities. In a simulation based on observations of visual acuity and daily activities in patients with cataract, indexes of changes in benefits were estimated for varying levels of visual acuity. Results show the development of loss in benefits resulting from a progressive deterioration in visual acuity. The results indicate a 40% loss in benefits at low levels of visual acuity, equivalent to a potential increase in benefits of 75% for these individuals following successful treatment. The proposed index approach may prove useful for measuring reductions in daily activities resulting from the progressive loss of vision in eye disease. The approach has successfully measured the reduction in daily activities in patients with cataract and may be applicable in patients with other eye diseases, including age-related macular degeneration and open-angle glaucoma.


[Clinical trials of netilmicin against respiratory tract infection].
Netilmicin, a new semisynthetic aminoglycoside antibiotic recently developed by Shering Co., was injected to 5 patients with respiratory tract infection (2 cases of diffuse panbronchiolitis, 2 cases of bronchiectasis and 1 case of bronchial asthma with infection). A daily dose of netilmicin was 200 mg by intramuscular injection and duration of netilmicin therapy was for 7 to 14 days. Clinical response to netilmicin therapy of respiratory tract infection was good in 3 cases, fair in 1 case and poor in 1 case. No subjective and objective findings considered as the side effect was observed and laboratory examinations showed no abnormality. It may be concluded from the above clinical results that netilmicin may be effective for respiratory tract infections and further study may prove its efficacy.


The malleability of linguistic representations poses a challenge to the priming-based experimental approach.
Recent findings show that experience with a syntactic structure has long-term consequences for how that structure will be processed in the future, which suggests that linguistic representations are not static entities that can be probed reliably without alteration. Thus, leveraging the effect of previous exposure to a syntactic structure appears to be an inappropriate method for studying invariant properties of language.


Anesthetic and convulsant barbiturates alter gamma-aminobutyric acid-stimulated chloride flux across brain membranes.
gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, increases membrane chloride conductance. Previously, the authors reported that GABA increases 36Cl- uptake by membrane vesicles (microsacs) prepared from mouse brain. In the present study, we examined the actions of barbiturates on basal and GABA-stimulated chloride influx by brain vesicles. The anesthetic barbiturates pentobarbital, phenobarbital, mephobarbital, amobarbital, hexobarbital and R-(-)-1-methyl-5-phenyl-5-propyl barbiturate enhanced GABA-dependent chloride flux. Barbiturate enhancement of GABA action was seen at concentrations that are subanesthetic in vivo (e.g., 10 microM pentobarbital was effective). Pentobarbital was about 10 times more potent than pentobarbital, suggesting that chloride flux is related to the sedative rather than anticonvulsant actions of barbiturates. Pentobarbital (1 mM) prevented the antagonism of GABA-stimulated 36Cl- produced by picrotoxinin. The barbiturates generally produced no change in GABA-independent flux, although large concentrations of pentobarbital or hexobarbital produced a slight enhancement of chloride flux in the absence of GABA. The convulsant barbiturate S-(+)-1-methyl-5-phenyl-5-propyl barbiturate inhibited GABA-stimulated chloride flux, an action opposite to that of its anesthetic enantiomer. These experiments provide evidence for a functional coupling among GABA and barbiturate receptors and the chloride ionophore and suggest that the GABA-activated chloride channel is a site of action for intoxicant-anesthetic and convulsant barbiturates.


[Airway remodeling in asthma].
Asthma is a chronic inflammatory disease of the airways. Structural alteration of the airways and lung parenchyma, "remodeling", is a recognized feature of chronic asthma and a cause of irreversible airway obstruction. Airway and lung remodeling in asthma involves subepithelial fibrosis, but also alterations of bronchial epithelium, airway smooth muscle cells, myofibroblasts, extracellular matrix, mucous glands, blood vessels and nerves. Defining of morphological changes and correlating them with clinical features of the disease has been a major focus of research over the past decade. The results of these studies are often contradictory and there is still little understanding of the mechanisms underlying lung remodeling in asthma.


Use of rotational angiography in assessing relationship of the airway to vasculature during cardiac catheterization.
We are the first to describe the use of three-dimensional rotational angiography (3DRA) in creating multiplanar reconstruction (MPR) and volume rendering, in the catheterization suite, of airways at risk for compression by adjacent cardiac structures. 3DRA has emerged as a promising tool for improved visualization of cardiac and vascular structures in congenital heart disease. This is a retrospective review of all available cases at our institution in which MPR from 3DRA was used to assess airways in relation to surrounding cardiovascular structures. Eight cases were reviewed from January 1, 2011 to November 30, 2013. Seven children had complex biventricular anatomy, including repaired truncus arteriosus, repaired absent pulmonary valve, repaired double outlet right ventricle, and vascular rings. One child had double inlet left ventricle and had undergone a hybrid procedure (stenting of the patent ductus arteriosus and banding of bilateral pulmonary arteries) before the Glenn procedure. Six of these cases involved distortion or stenosis of the pulmonary conduit or branch pulmonary arteries. In all cases, the trachea and the main bronchi were clearly visualized using MPR. Management was affected by the visualization of the airways during the catheterization procedure in seven of eight cases. Four cases had intraprocedural bronchoscopy that confirmed airway findings seen by MPR. In one case, computed tomography confirmed left bronchial compression seen by MPR. 3DRA can visualize airway anatomy and its relationship to the vasculature accurately. This has significant implications for preinterventional planning, intraprocedural management, as well as postprocedural recovery.


Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages.
In this study the combined use of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for diagnoses of chronically excessive alcohol abuse is investigated at 174 hair samples from driving ability examination, workplace testing and child custody cases for family courts and evaluated with respect to the basics of interpretation. Using the cut-off values of 0.50 ng/mg for FAEE and 25 pg/mg for EtG, both markers were in agreement in 75% of the cases with 103 negative and 28 positive results and there were 30 cases with FAEE positive and EtG negative and 13 cases with FAEE negative and EtG positive. As the theoretical basis of interpretation, the pharmacokinetics of FAEE and EtG is reviewed for all steps between drinking of ethanol to incorporation in hair with particular attention to relationships between alcohol dose and concentrations in hair. It is shown that the concentrations of both markers are essentially determined by the area under the ethanol concentration in blood vs. time curve AUC(EtOH), despite large inter-individual variations. It is demonstrated by calculation of AUC(EtOH) on monthly basis for moderate, risky and heavy drinking that AUC(EtOH) increases very strongly in the range between 60 and 120 g ethanol per day. This specific feature which is caused by the zero-order elimination of ethanol is a favorable prerequisite for a high discrimination power of the hair testing for alcohol abuse. From the consideration of the different profiles of FAEE and EtG along the hair and in agreement with the literature survey, a standardized hair segment 0-3 cm is proposed with cut-off values of 0.5 ng/mg for FAEE and 30 pg/mg for EtG. This improves also the agreement between FAEE and EtG results in the cases of the present study. A scheme for combined interpretation of FAEE and EtG is proposed which uses the levels of abstinence and the double of the cut-off values as criteria in addition to the cut-off's. Considering the large variations in the relationship between ethanol dose and FAEE and EtG concentrations in hair, the combined use of both parameters strongly increases the accuracy of the diagnosis by mutual confirmation and identification of false positive or false negative results due to biological variations or analytical errors.