The strategic control of multiple routes in imitation of actions.
The aim of this study was to bring to the surface the strategic use of imitative processes in the context of a 2-route model: (a) direct imitation, used in reproducing new, meaningless actions, and (b) imitation based on stored semantic knowledge of familiar meaningful actions. Three experiments were carried out with healthy participants who reproduced meaningful and meaningless actions within an established time limit. The study investigated 3 factors that could potentially affect the selection of processes used for imitation: (a) the composition of the experimental list (blocked or mixed presentation), (b) the presence-absence of instructions (Experiments 1 and 2), and (c) the relative proportions of the stimuli (Experiment 3). Overall, the results suggest that each of these factors influences the selection of imitative strategies in healthy individuals with temporarily reduced capacities, as happens in the case of brain-damaged patients.


HPLC-DAD profiles and pharmacological insights of Onobrychis argyrea subsp isaurica extracts.
Onobrychis argyrea Boiss. subsp. Isaurica (Fabaceae), endemic to the eastern Mediterranean region, is a poorly studied medicinal plant. This study sets out to investigate into antioxidant and inhibitory activities of O. argyrea extracts (ethyl acetate, methanol, and water) against key enzymes linked to diabetes (α-amylase, α-glucosidase), Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase), and skin hyperpigmentation (tyrosinase). Phytochemical composition was determined by HPLC-DAD and in silico approach used to provide additional insight of the possible interaction of the identified phenolic compounds with the studied enzymes. The methanol extract showed potent inhibitory action against acetylcholinesterase (1.55 mg GALAE/g extract), tyrosinase (61.61 mg KAE/g extract), and glucosidase (20.17 mmol ACAE/g extract). The methanol extract of O. argyrea exhibited potent radical scavenging potential (126.51 mg TE/g extract for DPPH scavenging assay) and reducing capacities (311.36 and 200.70 mg TE/g extract, for CUPRAC and FRAP assays, respectively). Quercetin, apigenin, and benzoic acid were identified in significant amounts in the methanol extract of O. argyrea. Quercetin interacted with the catalytic pocket of glucosidase by establishing hydrogen bonds with Ser157, Ser241, Asp307, and π-π interactions with His280 and Tyr158. The observed inhibitory effects of O. argyrea extracts on the studied enzyme suggest that this plant could be a promising source of naturally occurring chemical compounds for the management of diabetes, Alzheimer's disease, skin hyperpigmentation disorders, as well as, oxidative stress-related complications.


Glucose-induced insulin secretion from purified beta-cells. A role for modulation of Ca2+ influx by cAMP- and protein kinase C-dependent signal transduction pathways.
The effects of activation of cAMP- and protein kinase C-dependent signal transduction pathways were investigated on intracellular Ca2+ concentration ([Ca2+]i), cAMP content and insulin secretion from beta-cells purified by fluorescence-activated cell sorting from normal rat islets. The secretion of insulin from suspensions of purified beta-cells was dependent on glucose concentration and hormonal signals, including cAMP and activators of protein kinase C. Microfluorimetric measurement of [Ca2+]i with the fluorescent Ca2+ indicator fura-2 indicated that beta-cells differed immensely in their individual responsiveness to glucose stimulation. An increase in [Ca2+]i occurred in approximately 70% of beta-cells, whereas approximately 30% of beta-cells were nonresponsive to a glucose stimulus. Elevation of cAMP levels by theophylline or glucagon transformed nonresponsive beta-cells into cells which displayed marked increases in [Ca2+]i, and beta-cells which exhibited glucose-induced changes in [Ca2+]i showed further increases in [Ca2+]i and in the amplitude of Ca2+ oscillations. Carbachol and 12-O-tetradecanoylphorbol-13-acetate, activators of protein kinase C, did not induce any alterations in intracellular cAMP levels; nonetheless, these agents increased both the number of beta-cells which exhibited glucose-induced changes in [Ca2+]i and the amplitude of oscillations. The ability of cAMP or activators of protein kinase C to increase [Ca2+]i in single beta-cells was directly correlated with the ability of beta-cell suspensions to secrete insulin in response to a glucose stimulus. These results suggest that both cAMP- and protein kinase C-dependent pathways may regulate Ca2+ entry into beta-cells, possibly via voltage-dependent Ca2+ channels. Thus, this may represent a common mechanism whereby these different signal transduction pathways potentiate glucose-induced insulin secretion from beta-cells.


The determination of the structure of Saturn's F ring by nearby moonlets.
Saturn's narrow F ring exhibits several unusual features that vary on timescales of hours to years. These include transient clumps, a central core surrounded by a multistranded structure and a regular series of longitudinal channels associated with Prometheus, one of the ring's two 'shepherding' satellites. Several smaller moonlets and clumps have been detected in the ring's immediate vicinity, and a population of embedded objects has been inferred. Here we report direct evidence of moonlets embedded in the ring's bright core, and show that most of the F ring's morphology results from the continual gravitational and collisional effects of small satellites, often combined with the perturbing effect of Prometheus. The F-ring region is perhaps the only location in the Solar System where large-scale collisional processes are occurring on an almost daily basis.


Successful removal of massive intragastric gallstones by endoscopic electrohydraulic lithotripsy and mechanical lithotripsy.
We describe a case of massive gallstones discharged into the stomach through a cholecystoduodenal fistula and the successful removal of these stones by endoscopic electrohydraulic lithotripsy (EEHL) and endoscopic mechanical lithotripsy (EML) for the prevention of gallstone ileus. A 60-yr-old woman was admitted with epigastric pain and nausea. Upper gastrointestinal tract examination demonstrated backflow of contrast medium from the duodenal bulb into the gallbladder. Endoscopic examination revealed a large fistula on the anterior wall of the duodenal bulb, and two brown stones (about 3 cm in diameter) were found in the stomach. To prevent gallstone ileus, removal of these stones was attempted. They were broken into pieces by EEHL, then crushed into smaller pieces by EML and removed orally. Chemical analysis showed the composition of the gallstones to be at least 98% cholesterol. The patient was discharged one month after removal of the gallstones and has remained asymptomatic.


Intraoperative angiography after coronary bypass grafting in a patient presenting with a single coronary artery: a case report.
Among coronary artery anomalies, single coronary artery is one of the rarest anomalies. Pulmonary origins of the coronary arteries, coronary artery fistulae, and anomalous aortic origins of the coronary arteries are the most common anomalies requiring surgical intervention. In this case, we describe the performance of bypass grafting after unsuccessful attempts at percutaneous coronary intervention in a 72-year old male patient with single coronary artery arising from the right sinus of Valsalva and with associated diffuse coronary atherosclerosis. Intraoperative angiography was performed to evaluate the revascularization of this anomalous coronary system. The patient remains symptom free 6 months after the operation.


Ischemic stricture of the small intestine associated with acute pancreatitis.
A 37-yr-old man underwent an open drainage operation for severe acute pancreatitis and received respiratory ventilation support for 4 mo because of respiratory failure based on disseminated intravascular coagulation (DIC) and septic shock. Under intensive care, he sometimes had bloody diarrhea for about 6 wk. Colonoscopic findings suggested that the bleeding had derived from the small intestine. The patient then gradually recovered from acute pancreatitis and was discharged from the hospital. Thereafter, he suffered relapses of ileus and his symptoms progressively worsened. The patient underwent a second operation about 2 yr after the onset of acute pancreatitis. At celiotomy, multiple stenoses of the distal ileum measuring about 60 cm in length were found and the segment was resected. The resected specimen demonstrated six separate circumferential strictures and shallow ulcerations. Histologically, multiple ulcerations were restricted to the mucosa and were accompanied by marked submucosal edema and fibrosis. The mucosa between the ulcers revealed chronic regenerative changes: intimal thickening of small mesenteric arteries causing luminal narrowing and organized thrombosis in small mesenteric veins. Therefore, these were considered to be a series of segmental ischemic lesions. Note that delayed ischemic stricture of the small intestine may occur as a chronic complication of acute pancreatitis.


The discovery of 4-{1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic acid (MK-2894), a potent and selective prostaglandin E2 subtype 4 receptor antagonist.
The discovery of highly potent and selective second generation EP(4) antagonist MK-2894 (34d) is discussed. This compound exhibits favorable pharmacokinetic profile in a number of preclinical species and potent anti-inflammatory activity in several animal models of pain/inflammation. It also shows favorable GI tolerability profile in rats when compared to traditional NSAID indomethacin.


Adjuvant radiotherapy to an initial bulky mass in diffuse large B-cell lymphoma: lack of survival benefit.
The role of adjuvant radiotherapy to the site of the initial bulky mass in lymphoma remains to be determined. We retrospectively analyzed clinical data for 35 consecutive patients with diffuse large B-cell lymphoma who had an initial bulky mass were treated successfully by chemotherapy reaching complete remission or complete remission unconfirmed according to International Workshop Criteria. Median age was 57 years. Median follow-up period for surviving patients after completion of chemotherapy was 45 months. Twenty patients (group A) received adjuvant radiotherapy to the bulky mass, while 15 (group B) did not. Median dose of radiation in group A was 40 Gy (range, 30-60 Gy). In group A, four relapses occurred, all from other sites; group B included three relapses from bulky and one from other sites. Overall survival (P = 0.15) and recurrence-free survival (P = 0.48) did not differ significantly between groups. Although adjuvant radiotherapy to the initial bulky site is useful for controlling local disease, no survival benefit was seen.


First tandem free-radical cyclization reaction of alkylenecyclopropanes: a novel and efficient method for the preparation of 2-(3,4-dihydronaphthalen-2-yl)malonic acid diethyl esters.
Alkylidenecyclopropanes undergo Mn(OAc)3-mediated addition with malonate, leading to dihydronaphthalene derivatives in moderate yields.


Analysis of FGF function in normal and no tail zebrafish embryos reveals separate mechanisms for formation of the trunk and the tail.
To analyse the roles of FGF activity and brachyury during gastrulation we have directly compared the consequences of inhibition of FGF-receptor signalling with the phenotype of the zebrafish brachyury mutant, no tail (ntl). We show that expression of ntl is regulated by FGF and that inhibition of FGF receptor-signalling leads to complete loss of the trunk and tail. Since the ntl mutant lacks the tail and notochord but has an otherwise normal trunk, this demonstrates that trunk development is dependent upon an unidentified gene, or set of genes, referred to as no trunk (ntk) which is regulated by FGF. We propose a model to explain the FGF-dependent regulation of ntl and ntk that accounts for the above phenotypes. Consistent with this model, over-expression of eFGF led to suppression of anterior fates and development of trunk and tail derivatives only. In addition, widespread activation of convergence and extension movements resulted in the formation of multiple axis-like structures. Expression of eve1 and cad1 was also regulated by FGF activity, suggesting that during gastrulation FGF activity is normally restricted to the germ ring where these genes, and ntl, are expressed. Taken together these data suggest that the germ ring acts as a posteriorising centre during AP patterning, mediated by FGF activity in this tissue.


Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids.
Dendritic cells (DC) are the most potent antigen-presenting cells (APC) and stimulators of T cells. Dendritic cells are also likely to be essential for the initiation of allergic immune responses in the lung. However, there are not many data on the presence of dendritic cells in the airways of patients with atopic asthma and on the effects of corticosteroid-treatment on such dendritic cells. We investigated the distribution of dendritic cells in the bronchial epithelium and mucosa of 16 non-smoking atopic asthmatic patients and eight healthy control subjects using detailed immunohistochemistry (CD1a, HLA-DR, L25 as markers for dendritic cells). Eleven asthmatics were treated for 2.5 years with bronchodilators only and five with bronchodilators and inhaled beclomethasone dipropionate (BDP), 800 micrograms daily. The patients were randomly sampled from a double-blind multicentre study. There were higher numbers of CD1a+ DC (P = 0.003), L25+ DC (P = 0.002) and HLA-DR expression (P = 0.042) in the bronchial mucosa of asthmatic patients compared with healthy controls. After 2.5 years of treatment, we found a significant increase in flow expiratory volume in 1 second (FEV1) (P = 0.009) and a significant decrease in hyperresponsiveness (PC20 histamine) (P = 0.013) in the corticosteroid group (n = 5) compared with the bronchodilator group (n = 11). This clinical improvement in the corticosteroid-treated group was accompanied by significantly lower numbers of CD1a+ DC (P = 0.008), and HLA-DR expression (P = 0.028) in the bronchial mucosa than in the bronchodilator-treated group. Our data suggest that dendritic cells are involved in asthmatic inflammation and that corticosteroids may downregulate the number of dendritic.


Mechanistic roles of leptin in osteogenic stimulation in thoracic ligament flavum cells.
Obesity is a risk factor for thoracic ossification of ligament flavum (TOLF) that is characterized by ectopic bone formation in the spinal ligaments. Hyperleptinemia is a common feature of obese people, and leptin, an adipocyte-derived cytokine with proliferative and osteogenic effects in several cell types, is believed to be an important factor in the pathogenesis of TOLF. However, how leptin might stimulate cell osteogenic differentiation in TOLF is not totally understood. We reported here that leptin-induced osteogenic effect in TOLF cells is associated with activation of signaling molecules STAT3, JNK, and ERK1/2 but not p38. Blocking STAT3 phosphorylation with a selective inhibitor, AG490, significantly abolished leptin-induced osteogenic differentiation of TOLF cells, whereas blocking ERK1/2 and JNK phosphorylation with their selective inhibitors PD98059 and SP600125, respectively, had only marginal effects. In addition, we showed that STAT3 interacted with Runt-related transcription factor 2 (Runx2) in the nucleus, and STAT3, Runx2, and steroid receptor coactivator steroid receptor coactivator-1 were components of the transcription complex recruited on Runx2 target gene promoters in response to leptin treatment. Our experiments identified STAT3, Runx2, and steroid receptor coactivator-1 as critical molecules in mediating leptin-stimulated cell osteogenesis in TOLF.


Does the nasogastric tube has a role in elective colo-rectal surgery?
Routine use of nasogastric tubes (NGT) after abdominal operations is intended to hasten the return of bowel function, diminish the risk of anastomotic leakage and prevent pulmonary complications. The aim of our study was to prospectively assess the tolerability and the safety of the non use of NGT after elective colorectal open operations. Between March 2009 and December 2010, 110 consecutive patients underwent colo-rectal elective open surgery for neoplasm without nasogastric decompression. We analyzed the incidence of nausea and vomiting, the pulmonary complications, the return of bowel function the deep wound breakdown (fascial dehiscence) and the anastomotic leakage. Only 15 patients (13,6%) reported nausea without vomiting immediately after surgery and 9 cases of vomiting were observed (8%), requiring the insertion of the NGT (nasogastric tube) in 5 (4,5%). A total of 105 patients (96,3%) were NGT free. No deep wound dehiscence was observed and only one real pneumonia occurred. Anastomotic dehiscence occurred in 4 patients (3,6%) and a second surgical procedure was needed in three cases. The return of bowel function, except in the last four patients, occurred in 3,8 days average (range 2-7 days). We confirm the uselessness of the NGT in the framework of fast track program adopted in elective open colo-rectal surgery.


Greater efficacy of episodic than continuous growth hormone-releasing hormone (GHRH) administration in promoting slow-wave sleep (SWS).
It has been suggested that growth hormone (GH)-releasing hormone (GHRH) stimulates the surge in GH and enhances slow-wave sleep (SWS), two phenomena that characterize the beginning of nocturnal sleep. However, in human studies the effects of systemic GHRH administration on sleep were not consistent. This may reflect the differential influence of administration procedures being episodic in one of the above studies, but either a continuous infusion or a single bolus in the others. The present study in healthy volunteers compared changes in nocturnal sleep following 200 micrograms GHRH administered iv either episodically (4 boluses of 50 micrograms each at 2200, 2300, 2400, and 0100 h) or as a continuous infusion (57 micrograms/h between 2130 and 0100 h). Time spent in stage 4 of SWS on nights of episodic GHRH administration significantly exceeded that on nights of continuous GHRH administration (P < 0.01). Compared with a placebo condition, episodic administration of GHRH enhanced SWS (P < 0.01) and rapid eye movement (REM) sleep (P < 0.05) and diminished time spent in wakefulness and sleep stage 1 (P < 0.05). Effects of continuous GHRH infusion on sleep generally remained insignificant compared with placebo. Plasma GH concentrations were enhanced during both conditions of GHRH administration (P < 0.01), with the increase following episodic administration slightly exceeding that during continuous infusion (P < 0.05). The results support a greater physiological efficacy of episodic GHRH stimulation in promoting sleep.


[Pneumomyelography with regard to cerebrospinal fluid replacement].
Spinal arachnoidal space was investigated with cerebrospinal fluid drained and replaced with air. Some adequate parameters of the CSF replacement with gases were calculated according to rules derived from 140 pneumomyelographic investigations in patients with lumbar osteochondrosis: baseline CSF pressure, its withdrawal time and total volume. These parameters reflect the volume of arachnoidal space and its conductivity. Due account of these data allowed to determine the beginning of gas insufflation and its total amount.


History of treated periodontitis may signal a greater likelihood of implant problems.
SYSTEMATIC REVIEW CONCLUSION: Limited evidence exists to support the premise that subjects with a history of treated periodontitis are more likely to experience implant loss or other implant-related complications than are subjects without a history of periodontitis. CRITICAL SUMMARY ASSESSMENT: The authors' extensive review of the current literature yielded limited evidence supporting decreased implant longevity and increased implant-related complications in subjects treated for periodontitis. EVIDENCE QUALITY RATING: Limited.


[Hyperglycemia, hyperinsulinism, atherosclerosis].
The paper deals with a group of 117 patients with clearly defined clinical signs of atherosclerosis following myocardial infarction appearing in middle age, analyzes relationship between indicators of saccharide metabolism and cardiovascular morbidity within a ten-year period, and discusses its potential cause. Fasting levels taken at 120 minutes after the administration of glucose and the sum of the fasting level and three stimulated levels of blood sugar, or insulin (IRI), were compared with 54 controls as well as within the group of patients. Compared with the control group, the patients had glycemia levels elevated. In the group of patient with ischaemic heart disease (glycemia levels especially the sum but also glycemias at 120 min.) were elevated in persons with signs of ischaemic disease of lower extremities, with hypertension, in cases with increased serum triacylglyceroles, with increased energy intake (including fasting levels). The sum of insulin kept increasing in cases with familial disposition to atherosclerosis, with clinical progression of atherosclerosis over a period of 5 years (non-fatal reinfarctions). This had a highly significant correlation with linoleic acid in total serum lipids suggesting correlation with cardiovascular morbidity. This finding stresses the necessity of a comprehensive view of deviations in sacharide metabolism, especially as regards the relationship between elevated glycemia and cardiovascular morbidity, and between insulin and mortality-causing factors.


Adsorptive removal of methylene blue from colored effluents on fuller's earth.
The adsorption behavior of methylene blue (MB) on four fuller's earth (FE) samples of varying compositions was investigated using a spectrophotometric technique to obtain information on the color removal. The distribution coefficient (K(D)) increased with an increase in the initial concentration (C(0)) of the dye, attained a maximum value, and decreased again at higher initial concentrations. Dye solutions became colorless for a C(0) value corresponding to maximum K(D). A progressively increased flocculation behavior in the clay suspensions was observed and the maximum value of K(D) corresponds to optimum flocculation of the clay. The K(D) values were found to decrease exponentially after of the solution again became colored while the amount adsorbed increased with an increase in the initial concentration of MB. Only adsorption data obtained for this region could be defined by adsorption isotherm equations. The shifts of the C(0) values corresponding to K(D)(max) toward higher concentrations were correlated with the composition of FE samples by using XRF, XRD patterns, and SEM images. The influence of temperature on MB adsorption was also studied and thermodynamic parameters were calculated.


Nurse writers internet and World Wide Web sites.
Nurse writers can use the Internet to find vast amounts of current information on topics for professional articles. The following excerpts are based on concepts in the Second Edition of the authors' book, How to Write and Publish Articles in Nursing, published by Springer Publishing Company. The Second Edition will is now available.


Potential effectiveness of Community Health Strategy to promote exclusive breastfeeding in urban poor settings in Nairobi, Kenya: a quasi-experimental study.
Early nutrition is critical for later health and sustainable development. We determined potential effectiveness of the Kenyan Community Health Strategy in promoting exclusive breastfeeding (EBF) in urban poor settings in Nairobi, Kenya. We used a quasi-experimental study design, based on three studies [Pre-intervention (2007-2011; n=5824), Intervention (2012-2015; n=1110) and Comparison (2012-2014; n=487)], which followed mother-child pairs longitudinally to establish EBF rates from 0 to 6 months. The Maternal, Infant and Young Child Nutrition (MIYCN) study was a cluster randomized trial; the control arm (MIYCN-Control) received standard care involving community health workers (CHWs) visits for counselling on antenatal and postnatal care. The intervention arm (MIYCN-Intervention) received standard care and regular MIYCN counselling by trained CHWs. Both groups received MIYCN information materials. We tested differences in EBF rates from 0 to 6 months among four study groups (Pre-intervention, MIYCN-Intervention, MIYCN-Control and Comparison) using a χ(2) test and logistic regression. At 6 months, the prevalence of EBF was 2% in the Pre-intervention group compared with 55% in the MIYCN-Intervention group, 55% in the MIYCN-Control group and 3% in the Comparison group (P<0.05). After adjusting for baseline characteristics, the odds ratio for EBF from birth to 6 months was 66.9 (95% CI 45.4-96.4), 84.3 (95% CI 40.7-174.6) and 3.9 (95% CI 1.8-8.4) for the MIYCN-Intervention, MIYCN-Control and Comparison group, respectively, compared with the Pre-intervention group. There is potential effectiveness of the Kenya national Community Health Strategy in promoting EBF in urban poor settings where health care access is limited.


Dupilumab: human monoclonal antibody against IL-4Rα for moderate to severe atopic dermatitis.
Atopic dermatitis (AD) is one of the most common skin disorders with a prevalence of about 20% in children and affecting adults in significant numbers. Moderate to severe AD significantly impairs a patient's quality of life with severe pruritus as a major issue that impairs sleep and contributes to major psychological disturbances. Detailed studies of its pathogenesis have revealed that immune mechanisms are involved including activation of T helper type 2 cells (Th2). Dupilumab is a fully human Ig4 monoclonal antibody directed against the interleukin-4 receptor subunit α (IL-4Rα) of IL-4 and IL-13 receptors. In clinical studies it has been demonstrated to significantly reduce the molecular signature in the skin of patients with AD and to significantly reduce the clinical manifestations of moderate to severe AD. It also very importantly significantly reduces the pruritus of moderate to severe AD thus improving the patients' quality of life. Dupilumab is administered by subcutaneous injection every other week. It was approved by the FDA in March 2017 for the treatment of moderate to severe AD.


Potentiometric sensors enabling fast screening of the benign prostatic hyperplasia drug alfuzosin in pharmaceuticals, urine and serum.
The construction and characterization of potentiometric membrane electrodes are described for the quantification of alfuzosin, a drug used in a mono- and combined therapy of benign prostatic hyperplasia (BPH). The membranes of these electrodes consist of alfuzosin hydrochloride-tetraphenyl borate, (Az-TPB), chlorophenyl borate (Az-ClPB), and phosphotungstate (Az(3)-PT) ion associations as molecular recognition reagent dispersed in PVC matrix with dioctylpthalate as plasticizer. The performance characteristics of these electrodes, which were evaluated according to IUPAC recommendations, revealed a fast, stable and liner response for alfuzosin over the concentration ranges of 8.3 x 10(-6) to 1.0 x 10(-2) M, 3.8 x 10(-6) to 1.0 x 10(-2) M, 7.5 x 10(-7) to 1.0 x 10(-2) M AzCl with cationic slopes of 57.0, 56.0 and 58.5 mV/decade, respectively. The solubility product of the ion-pair and the formation constant of the precipitation reaction leading to the ion-pair formation were determined conductometrically. The electrodes, fully characterized in terms of composition, life span and usable pH range, were applied to the potentiometric determination of alfuzosin hydrochloride ion in different pharmaceutical preparations and biological fluids without any interference from excipients or diluents commonly used in drug formulations. The potentiometric method was also used in the determination of alfuzosin hydrochloride in pharmaceutical preparations in four batches with different expiration dates. Validation of the method showed suitability of the proposed electrodes for use in the quality control assessment of alfuzosin hydrochloride. This potentiometric method offers the advantages of high-throughput determination, simplicity, accuracy, automation feasibility, and applicability to turbid and colored sample solutions.


[Larynx transplant: a therapeutic option for the 21st century? Literature review].
The time and space devoted recently in the mass media to the transplantation of non-vital organs, such as the hands or the face, have raised questions in our patients regarding the possibility of transplanting the larynx, an essential organ for communication. The main barriers to larynx transplantation are tissue viability of the transplanted organ, immunological tolerance and functional restoration. This review of the literature aims to update the compendium of knowledge about this procedure and to explore the prospects of larynx transplantation as a viable therapeutic option.


Assessment of hypoxia and perfusion in human brain tumors using PET with 18F-fluoromisonidazole and 15O-H2O.
Hypoxia predicts poor treatment response of malignant tumors. We used PET with (18)F-fluoromisonidazole ((18)F-FMISO) and (15)O-H(2)O to measure in vivo hypoxia and perfusion in patients with brain tumors. Eleven patients with various brain tumors were investigated. We performed dynamic (18)F-FMISO PET, including arterial blood sampling and the determination of (18)F-FMISO stability in plasma with high-performance liquid chromatography (HPLC). The (18)F-FMISO kinetics in normal brain and tumor were assessed quantitatively using standard 2- and 3-compartment models. Tumor perfusion ((15)O-H(2)O) was measured immediately before (18)F-FMISO PET in 10 of the 11 patients. PET images acquired 150-170 min after injection revealed increased (18)F-FMISO tumor uptake in all glioblastomas. This increased uptake was reflected by (18)F-FMISO distribution volumes >1, compared with (18)F-FMISO distribution volumes <1 in normal brain. The (18)F-FMISO uptake rate K(1) was also higher in all glioblastomas than in normal brain. In meningioma, which lacks the blood-brain barrier (BBB), a higher K(1) was observed than in glioblastoma, whereas the (18)F-FMISO distribution volume in meningioma was <1. Pixel-by-pixel image analysis generally showed a positive correlation between (18)F-FMISO tumor uptake at 0-5 min after injection and perfusion ((15)O-H(2)O) with r values between 0.42 and 0.86, whereas late (18)F-FMISO images (150-170 min after injection) were (with a single exception) independent of perfusion. Spatial comparison of (18)F-FMISO with (15)O-H(2)O PET images in glioblastomas showed hypoxia both in hypo- and hyperperfused tumor areas. HPLC analysis showed that most of the (18)F-FMISO in plasma was still intact 90 min after injection, accounting for 92%-96% of plasma radioactivity. Our data suggest that late (18)F-FMISO PET images provide a spatial description of hypoxia in brain tumors that is independent of BBB disruption and tumor perfusion. The distribution volume is an appropriate measure to quantify (18)F-FMISO uptake. The perfusion-hypoxia patterns described in glioblastoma suggest that hypoxia in these tumors may develop irrespective of the magnitude of perfusion.


Attitudes and support needs of Black Caribbean, south Asian and White British carers of people with dementia in the UK.
Family carers are the most important source of dementia care, especially among ethnic minority populations, who are less likely to access health or social services. The evidence base on the carer experience in these communities is profoundly limited. To explore the caregiving attitudes, experiences and needs of family carers of people with dementia from the three largest ethnic groups in the UK. A qualitative study, using a grounded theory approach. Indepth individual interviews were conducted with 32 carers of people with dementia (10 Black Caribbean, 10 south Asian, 12 White British). Carers were identified as holding a 'traditional' or 'non-traditional' caregiver ideology, according to whether they conceptualised caregiving as natural, expected and virtuous. This informed feelings of fulfilment, strain, carers' fears and attitudes towards formal services. The majority of the south Asian, half of the Black Caribbean and a minority of the White British participants were found to possess a traditional ideology. The findings suggest that specific cultural attitudes towards the caregiving role have important implications for how carers can best be supported.


Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cells.
In Hodgkin's lymphoma, F-18-fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy-D-glucose or the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients.


Solid phase assay of urine cystine supersaturation in the presence of cystine binding drugs.
We report a new kind of assay system for urine cystine supersaturation that is accurate in the presence of cystine binding thiol drugs. We measured the molar ratio of cystine dissolved per mole of drug. Measured amounts of cystine crystals were incubated in buffer or urine for 48 hours with stirring. The solid phase remaining was pelleted by centrifugation, extracted into a high pH buffer and measured. D-penicillamine, tiopronin and captopril were added to determine their effect on solid phase dissolution. Total cystine calculated from urine and solid measurements closely matched the amounts of cystine weighed in, meaning that the assay system successfully recovered the total cystine from the 2 phases. Each drug dissolved solid cystine in a specific and fixed proportion to its molar concentration in the range of 0.2 to 0.4 mM. dissolution per mM. of drug. Solution measurements were not a reliable gauge to the actual amounts of cystine dissolved. Changes in solid phase cystine accurately reflect buffer or urine supersaturation when thiol drugs are present. The solid phase assay is a technically straightforward and reliable way of assessing cystine movement into and out of urine that avoids complexity of measurement and distortions of assay systems by drugs. This assay enables one to assess the level of drug effect and the need for a change in dosing.


What information survives saccades in the real world?
Recent change detection research demonstrates impressively that we do not retain and fuse the pictorial content of successive fixations. This raises two distinct issues: (1) when and how is point-by-point information lost or replaced? and (2) might more abstract information be extracted and retained from fixations? In this chapter I explore both of these issues. I consider the evidence for a very short-term richly detailed visual representation of the current target of fixation that survives the saccade but is overwritten by the content of each new fixation shortly after it begins. The possibility of abstract representations of the visual surroundings is then discussed. Under conditions of competitive, parallel processing, as are present in real life situations, multiple types of information are extracted and retained from complex natural scenes. Time courses for extraction vary between different types of information. The inclusion of eye movement data reveals a crucial role for fixations in information extraction. The data suggest that information assimilation into the representations tested here is dominated by the fovea and is integrated and accumulated from multiple foveations. From these studies we are able to construct a rudimentary framework, in which representational faithfulness and richness depend upon fixation history of that part of the visual scene, thus producing an efficient and potentially task-specific representation.


Andrology--development and future. Critical remarks after 45 years of medical practice.
The development of andrology from its beginning to the present time is discussed from a historical point of view. Since andrology is a clinical discipline, only well-trained physicians are allowed to investigate and treat patients. The term 'andrology', which was first introduced in the USA more than 100 years ago, was independently reborn in Germany and thereafter used in other European countries. Since then, an increasing number of physicians all over the world have applied the term 'andrology' for their professional work. Many local societies and groups of andrologists were established. In 1969, Andrologia was founded as the first international journal of andrology in Germany. In the meantime, further andrological journals have been established. Concerning the future development of andrology, the following should be considered: (i) the organizational structure of andrology must include the basic training of physicians working in this field; (ii) the necessity of andrology as a medical specialty with regard to modern technologies of assisted reproduction etc., must be emphasized; (iii) internationally accepted recommendations for the training of andrologists with special reference to both clinical andrology and laboratory techniques should be established; (iv) andrology should be established as a separate specialty.


Reverse Monte Carlo modelling of neutron powder diffraction data.
A new reverse Monte Carlo (RMC) method for modelling both lattice and magnetic disorder in powder crystalline materials by direct calculation of the structure factor has been developed. The method, the program and the basic theory are described in some detail. Initial results from modelling the lattice and magnetic structure of MnO around the Néel temperature are also presented.


Enhancement of brain p0(2) during cardiopulmonary bypass using a hyperosmolar oxygen carrying solution.
During the past decade a new syndrome has been recognized: cerebral hypoxia secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory. The incidence of the syndrome appears to be no less that 30% in patients over 65 years of age undergoing cardiac surgery. There are several factors contributing to hypoxia produced by cardiopulmonary bypass. One of these factors is crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying capacity and (2) devoid of protein and its colloid osmotic pressure. This shortcoming of cardiopulmonary crystalloid solutions is partially responsible for two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and diminishes interstitial fluid accumulation. This blood substitute consists of perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus hyperosmolar ingredients other than saccharides. The advantage of a perfluorochemical is its ability to access small channels and to be centrifuged off the patient post-operatively with a cell saver. The advantage of saccharides is that they can be metabolized by the patient for energy, and they produce a moderate diuresis coming off bypass.


Molecular detection of Anaplasma platys in dogs using polymerase chain reaction and reverse line blot hybridization.
Several polymerase chain reactions (PCRs) and a reverse line blot hybridization (RLB) method were used to identify Anaplasma platys in dogs held in a kennel in Italy. Whereas PCR techniques confirmed the presence of A. platys, the RLB method not only correlated the results obtained by PCR but also ruled out the presence of other species such as Ehrlichia canis or E. chaffeensis. There was no correlation between infection status and age or breed of the dogs. Polymerase chain reaction performed on the Rhipicephalus sanguineus ticks collected from those dogs showed that they were also infected with A. platys. Sequences obtained from some samples and compared with those within the GenBank also confirmed the presence of A. platys.


TB and human rights.
Health is defined as a state of complete physical, mental and social well-being and is fundamental to human rights. TB affects nearly all aspects of health-physical, mental and social. The poor are vulnerable to TB and TB continues to be a stigma in large sections of society. TB is curable and an effective strategy ie, DOTS is now available. DOTS is perhaps the answer for protecting human rights of TB patients. The five components of DOTS are: Political commitment, diagnosis by sputum microscopy, directly observed therapy, uninterrupted supply of drugs and accountability. TB needs to be designated by a full acknowledgment.


Speckle mechanism in holographic optical imaging.
Speckle imaging was investigated by using dynamic holography and photorefractive AlGaAs/GaAs multiple quantum wells in a holographic optical imaging system. We showed that the speckle contrast depends on holographic fringes and the photorefractive effect. We further demonstrated that a moving grating technique can be used to suppress the random speckle.


Oligomerization of 3'-amino-3'deoxyguanosine-5'phosphorimidazolidate on a d(CpCpCpCpC) template.
3'-Amino-3'-deoxyguanosine-5'-phosphorimidazolidate (ImpGNH2) oligomerizes more rapidly and regiospecifically than related nucleotide derivatives on a d(CpCpCpCpC) template. The greater nucleophilicity of the amino group leads to efficient oligomerization even when the structure of the double-helical complex formed by the template and the substrate is not optimal for reaction. The use of amine-containing analogues should permit us to develop models of potentially prebiotic polymerization reactions that cannot be studied easily using natural nucleotides.


Predictors of health-related quality of life in community-dwelling stroke survivors: a cohort study.
Impaired health-related quality of life (HRQoL) post stroke is common, though prevalence estimates vary considerably. Few longitudinal studies explore post-stroke patterns of HRQoL and factors contributing to their change over time. Accurately identifying HRQoL after stroke is essential to understanding the extent of stroke effects. This study aimed to assess change in levels of, and identify independent predictors of, HRQoL over the first 12-months post-stroke. Design. A prospective cohort study. Community-dwelling stroke survivors in metropolitan Newcastle, New South Wales (NSW), Australia. Consecutively recruited stroke patients (n = 134) participated in face-to-face interviews at baseline, 3, 6, 9 and 12 months. HRQoL (measured using the Assessment Quality-of-life).Independent measures. Physical and psycho-social functioning, including depression and anxiety (measured via Hospital Anxiety and Depression Scale), disability (Modified Rankin Scale), social support (Multi-dimensional Scale Perceived Social Support) and community participation (Adelaide Activities Profile). A linear mixed model was used to establish the predictors of, change in HRQoL over time. On multivariable analysis, HRQOL did not change significantly with time post-stroke. Higher HRQoL scores were independently associated with higher baseline HRQoL (P = 0.03), younger age (P = 0.006), lower disability (P = 0.003), greater community participation (P ≤ 0.001) and no history of depression (P = 0.03). These results contribute to an understanding of HRQoL in the first year post-stroke. Community participation and stroke-related disability are potentially modifiable risk factors affecting post-stroke HRQoL. Interventions aimed at addressing participation and disability post-stroke should be developed and tested.


Sequential healing at implants installed immediately into extraction sockets. An experimental study in dogs.
To compare the sequential healing at implants installed in a healed alveolar bony ridge or immediately after tooth extraction without functional load. In the mandible of 12 dogs, the mesial roots of the first molars were endodontically treated, the tooth hemisected, and the distal roots extracted. After 3 months, the mesial roots of the fourth premolars were endodontically treated, the tooth hemisected, and the distal roots extracted in one side of the mandible. Implants were placed immediately into extraction sockets (IPIES) of the fourth premolar and in the healed sites in the molar regions. Healing abutments were placed, and the flaps were sutured to allow a non-submerged healing. The time of surgery and of sacrifices were planned in such a way to obtain biopsies representing the healing after 1 and 2 weeks and 1 and 3 months, respectively. Ground sections were prepared for histological evaluation of tissues components on the implant surface and the coronal termination level of osseointegration (M-B). New bone apposition on the implant surface was slightly higher at the healed compared to the IPIES sites, being 7.4% and 4.1% after 1 week, and 67.3% and 65.3% after 3 months, respectively. Old bone was progressively resorbed, from 27.0% and 21.9% after 1 week, to 2.5% and 2.0% after 3 months, at healed and IPIES sites, respectively. M-B was 1.4 mm and 2.6 mm after 1 week, 1.2 mm and 1.2 mm after 3 months, at healed and IPIES sites, respectively. Similar patterns of sequential osseointegration were found at implants installed in healed alveolar bone or in alveolar sockets immediately after tooth extraction. The coronal termination level of osseointegration, that was different after 1 week, was found similar at the 3-month observation.


Midline diastema and its aetiology--a review.
Maxillary midline diastema is a common aesthetic complaint of patients. Treating the midline diastema is a matter of concern for practitioners, as many different aetiologies are reported to be associated with it. The appearance of midline diastema as part of the normal dental development makes it difficult for practitioners to decide whether to intervene or not at an early stage. The aim of this article is to review the possible aetiology and management options which will help the clinician to diagnose, intercept and to take effective action to correct the midline diastema. The available data shows that an early intervention is desirable in cases with large diastemas. Treatment modality, timing and retention protocol depends on the aetiology of the diastema. Therefore, priority needs to be given to diagnosing the aetiology before making any treatment decisions. Clinical Relevance: This article aims to determine and evaluate the aetiology and possible treatment options of midline diastema.


Sigh rate and respiratory variability during mental load and sustained attention.
Spontaneous breathing consists of substantial correlated variability: Parameters characterizing a breath are correlated with parameters characterizing previous and future breaths. On the basis of dynamic system theory, negative emotion states are predicted to reduce correlated variability whereas sustained attention is expected to reduce total respiratory variability. Both are predicted to evoke sighing. To test this, respiratory variability and sighing were assessed during a baseline, stressful mental arithmetic task, nonstressful sustained attention task, and recovery in between tasks. For respiration rate (excluding sighs), reduced total variability was found during the attention task, whereas correlated variation was reduced during mental load. Sigh rate increased during mental load and during recovery from the attention task. It is concluded that mental load and task-related attention show specific patterns in respiratory variability and sigh rate.


Surgical transgastric debridement of walled off pancreatic necrosis: an option for patients with necrotizing pancreatitis.
Transgastric debridement of walled off pancreatic necrosis (WOPN) is a surgical treatment option for patients requiring pancreatic debridement for necrotizing pancreatitis. The reported experience with surgical transgastric pancreatic debridement is limited, however, the lower incidence of postoperative pancreatic fistulae with this procedure compared to other options warrants further evaluation of this technique. Retrospective chart review. Twenty-two patients underwent transgastric debridement with a cystogastrostomy for clinically symptomatic WOPN from January 1, 2005 to July 31, 2013. Eight cases were performed laparoscopically and 14 were performed by an open approach. The mean patient age was 50.9 (50.9 ± 14.5) and the median American Society of Anesthesiologist score was 3. The most common etiology for pancreatitis was gallstones and the median time from attack of pancreatitis to definitive surgical management was 60 days (range 22-300 days). Median operative time was 182 min (range 85-327 min) with 100 cc (range 20-500 cc) of blood loss. In seven patients the necrosis was infected and in 15 patients the necrosis was sterile as determined by the intraoperative culture of the necrotic material. The overall significant morbidity (Clavien type 3 or greater) was 13.6 % and the mortality was 0 %. The incidence of postoperative pancreatic fistula was 0 %. 20 patients (90 %) were symptom free during a median follow-up of 12 months. In selected patients with clinically symptomatic WOPN, surgical transgastric pancreatic debridement appears to be a safe procedure with a low morbidity and mortality. The low incidence of postoperative pancreatic fistulae warrants further evaluation.


Toward a method of selecting among computational models of cognition.
The question of how one should decide among competing explanations of data is at the heart of the scientific enterprise. Computational models of cognition are increasingly being advanced as explanations of behavior. The success of this line of inquiry depends on the development of robust methods to guide the evaluation and selection of these models. This article introduces a method of selecting among mathematical models of cognition known as minimum description length, which provides an intuitive and theoretically well-grounded understanding of why one model should be chosen. A central but elusive concept in model selection, complexity, can also be derived with the method. The adequacy of the method is demonstrated in 3 areas of cognitive modeling: psychophysics, information integration, and categorization.


Assessment of side branch predilation before a provisional T-stent strategy for bifurcation lesions. A randomized trial.
A simple approach is the predominant strategy for the percutaneous coronary intervention of bifurcation lesions. Performing side branch (SB) predilation in this context is currently a matter of controversy. In this study, we assess the efficacy of SB predilatation before a provisional T-stent strategy for bifurcation lesions. Between February 2009 and November 2012, 372 patients with true bifurcation lesions were randomized to either predilation of the SB (n = 187) or no predilatation (n = 185) before main branch (MB) stent implantation and a subsequent SB provisional stent strategy. There were no significant differences between the patient groups regarding the baseline characteristics. After MB stent implantation, the TIMI flow of the SB was higher in the patients with SB predilation: TIMI flow 0 to 1; 2 (1%) versus 18 (10%), P < .001; and TIMI flow III; 179 (96%) versus 152 (82%), P < .001. Side branch stenting rates were 4% versus 3%, P = not significant. In addition, 60 patients (32%) from the SB predilation group presented SB residual stenosis by visual inspection <50%, and TIMI flow ≥III did not require any additional treatment. The failure rate of SB rewiring, the time of rewiring, the number of wires used, and the incidence of major events were similar in both groups of patients. Predilation of the SB resulted in improved TIMI flow after MB stenting and less indication to subsequently treat the SB. If rewiring of the SB is required, predilation did not hinder this maneuver.


Obtaining snapshots of genetic variation using hemiclonal analysis.
Hemiclones are naturally occurring or artificially produced individuals that share a single specific genetic haplotype. Natural hemiclones are produced via hybridization between two closely related species, whereas hemiclonal analysis in Drosophila is carried out in the laboratory via crosses with artificially created 'clone-generator' females with a specific genetic make-up. Hemiclonal analysis in Drosophila has been applied successfully to date to obtain measures of standing genetic variation for numerous traits. Here, we review the current hemiclonal literature and suggest future directions for hemiclonal research, including its application in molecular and genomic studies, and the adaptation of natural hemiclonal systems to carry out Drosophila-type studies of standing genetic variation.


Vaginal assessment and expedited amniotomy in oral misoprostol labor induction in nulliparas: a randomized trial.
Labor is induced in 20-30% of maternities, with an increasing trend of use. Labor induction with oral misoprostol is associated with reduced risk of cesarean deliveries and has a safety and effectiveness profile comparable to those of mechanical methods such as Foley catheter use. Labor induction in nulliparous women continues to be challenging, with the process often quite protracted. The eventual cesarean delivery rate is high, particularly when the cervix is unfavorable and ripening is required. Vaginal examination can cause discomfort and emotional distress particularly to nulliparous women, and plausibly can affect patient satisfaction with the induction and birth process. The aim of this study was to evaluate regular (4-hourly prior to each oral misoprostol dose with amniotomy when feasible) compared with restricted (only if indicated) vaginal assessments during labor induction with oral misoprostol in term nulliparous women MATERIALS AND METHODS: We performed a randomized trial between November 2016 and September 2017 in a university hospital in Malaysia. Our oral misoprostol labor induction regimen comprised 50 μg of misoprostol administered 4 hourly for up to 3 doses in the first 24 hours. Participants assigned to regular assessment had vaginal examinations before each 4-hourly misoprostol dose with a view to amniotomy as soon as it was feasible. Participants in the restricted arm had vaginal examinations only if indicated. Primary outcomes were patient satisfaction with the birth process (using an 11-point visual numerical rating scale), induction to vaginal delivery interval, and vaginal delivery rate at 24 hours. Data from 204 participants (101 regular, 103 restricted) were analyzed. The patient satisfaction score with the birth process was as follows (median [interquartile range]): 7 [6-9] vs 8 [6-10], P = .15. The interval of induction to vaginal delivery (mean ± standard deviation) was 24.3 ± 12.8 vs 31.1 ± 15.0 hours (P = .013). The vaginal delivery rate at 24 hours was 27.7% vs 20.4%; (relative risk [RR], 1.4; 95% confidence interval [CI], 0.8-2.3; P = .14) for the regular vs restricted arms, respectively. The cesarean delivery rate was 50% vs 43% (RR, 1.1; 95% CI, 0.9-1.5; P = .36). When assessed after delivery, participants' fidelity to their assigned vaginal examination schedule in a future labor induction was 45% vs 88% (RR, 0.5; 95% CI, 0.4-0.7; P < .001), and they would recommend their assigned schedule to a friend (47% vs 87%; RR, 0.6; 95% CI, 0.5-0.7; P < .001) in the regular compared with the restricted arms, respectively. Despite a shorter induction to vaginal delivery interval with regular vaginal examination and a similar vaginal delivery rate at 24 hours and birth process satisfaction score, women expressed a higher preference for the restricted examination schedule and were more likely to recommend such a schedule to a friend.


Enhancement of Cellulase and Xylanase Production Using pH-Shift and Dissolved Oxygen Control Strategy with Streptomyces griseorubens JSD-1.
In this study, the production of cellulase and xylanase by Streptomyces griseorubens JSD-1 was improved by integrating the pH-shift and dissolved oxygen (DO)-constant control strategies. The pH-shift control strategy was carried out by analyzing the specific cell growth rate (μ) and specific enzyme formation rate (Q p) of S. griseorubens JSD-1. The pH was controlled at 8.0 during the first 48 h to maintain high cell growth, which then shifted to 7.5 after 48 h to improve the production of cellulase and xylanase. Using this method, the maximum activities of cellulase, xylanase, and filter paper enzyme (FPase) increased by 47.9, 29.5, and 113.6 %, respectively, compared to that obtained without pH control. On the basis of pH-shift control, the influence of DO concentrations on biomass and enzyme production was further investigated. The maximum production of cellulase, xylanase, and FPase reached 114.38 ± 0.96 U mL(-1), 330.57 ± 2.54 U mL(-1), and 40.11 ± 0.38 U mL(-1), which were about 1.6-fold, 0.6-fold, and 3.2-fold higher than that of neutral pH without DO control conditions. These results supplied a functional approach for improving cellulase and xylanase production.


Transfection of lipoma cells with papilloma bovine virus subgenomic fragment.
Lipoma cells with consistent chromosomal aberration have been transfected with plasmids carrying papilloma bovine virus subgenomic fragment (PBV 69). The successful transformation of the cells was ascerted on the changed growth pattern of the cells in liquid medium, colony formation in soft agar and modified cell appearance in electron microscopy; transfection with PBV 69 has not been, however, sufficient to immortalize lipoma cells.


Household food insecurity is associated with higher child undernutrition in Bangladesh, Ethiopia, and Vietnam, but the effect is not mediated by child dietary diversity.
Household food insecurity (HFI) is a recognized underlying determinant of child undernutrition, but evidence of associations between HFI and child undernutrition is mixed. The purpose of this study was to investigate if HFI is associated with undernutrition in children aged 6-59.9 mo in Bangladesh (n = 2356), Ethiopia (n = 3422), and Vietnam (n = 3075) and if child dietary diversity (DD) mediated this effect. We used baseline survey data from the Alive & Thrive project. Logistic regression, adjusting for potential confounding factors, was used to determine the magnitude and significance of the association of HFI with stunting, underweight, and wasting. The mediating effect of child DD was tested by using a Sobel-Goodman mediation test. The prevalences of HFI were 66%, 40%, and 32% in Ethiopia, Vietnam, and Bangladesh, respectively. The prevalences of stunting, underweight, and wasting were higher in Bangladesh (47.1%, 43.7%, and 19.1%, respectively) and Ethiopia (50.7%, 27.5%, and 5.9%, respectively) than in Vietnam (20.7%, 15.8%, and 5%, respectively). In the adjusted models, the odds of being stunted or underweight were significantly higher for children in severely food-insecure households in Bangladesh (stunting OR: 1.36; 95% CI: 1.05, 1.76; underweight OR: 1.28; 95% CI: 0.99, 1.65) and Ethiopia (stunting OR: 1.48; 95% CI: 1.09, 2.00; underweight OR: 1.68; 95% CI: 1.22, 2.30) and in moderately food-insecure households in Vietnam (stunting OR: 1.39; 95% CI: 1.16, 1.65; underweight OR: 1.69; 95% CI: 1.28, 2.23). HFI was significantly associated with wasting in Bangladesh where close to 1 in 5 children demonstrated wasting. Child DD did not mediate the relation between HFI and undernutrition in any of the countries. Further research is recommended to investigate potential mediators in this pathway.


Useful but not used: pediatric critical care physician views on bedside ultrasound.
The purpose of this study was to assess the learning needs of pediatric critical care (PCC) physicians in bedside ultrasound (BUS) use. This was a survey-based study conducted at an academic center with a PCC fellowship program. We surveyed PCC fellows and faculty to elicit their views on BUS and asked them about the frequency of use, their perception of the clinical utility, and their level of confidence in performing different BUS applications. There was no statistical difference in the self-reported use of BUS applications in the faculty and fellows, except for cardiac arrest, which 66.7% of the faculty used but none of the fellows did (P < 0.05). There were no statistically significant differences between perceived usefulness and confidence in the performance of BUS applications between the fellows and faculty. The largest gaps between perceived usefulness and confidence in performing BUS applications were for left ventricle ejection fraction (Δ = 2.72), inferior vena cava collapse (Δ = 2.67), pulmonary edema (Δ = 2.22), and pneumothorax (Δ = 2.11). Pediatric critical care providers report limited confidence in several applications that they perceive as useful and are therefore likely motivated to learn BUS applications. Concentrating curricula on those applications with the greatest differences between usefulness and confidence and building on the confidence of those applications the PCC providers are already using will serve to expand availability and increase use of this high-impact technology.


[Medical treatment of patients with colorectal cancer in Denmark].
In this review, the standard medical treatment of patients with colorectal cancer in Denmark is outlined in a pragmatic way. Three typical patient scenarios are described: the post-operative adjuvant setting, the patient with curable metastasis and the patient in palliative treatment. The biomedical knowledge about the disease and treatment options should always be combined with a patient-centered approach in order to individualise the treatment according to the patient's values. Furthermore, suggestions for the timing of rehabilitation, palliative care and advance care planning are given.


Triple-label hybridization assay for type-1 diabetes-related HLA alleles.
We describe a method for the detection of two type 1 (insulin-dependent) diabetes susceptibility (*0201, *0302) alleles and two protective (*0301, *0602/0603) alleles of the HLA-DQB1 gene on the human major histocompatibility complex (MHC). The test is based on DNA amplification with PCR followed by simultaneous, allele-specific triple-label hybridization performed in microtitration wells. In the hybridization, very short allele-specific oligonucleotides labeled with europium (Eu), terbium (Tb) or samarium (Sm) are used. The labeled probes could be detected using time-resolved fluorometry with sensitivities of 1 x 10(7), 3 x 10(8) and 3 x 10(8) molecules, respectively. Cross-reactions were not found among samples containing 14 common DQB1 alleles. To test the utility of the developed assay, 100 DNA and 14 dried blood spot samples with known DQB1 alleles were analyzed. A 100% agreement with the reference method was reached. Thus, this triple-label hybridization assay proved to be suitable even for detection of a large number of samples.


Brain perfusion imaging of a craniopharyngioma by transcranial duplex sonography.
The aim of this study was to test a new ultrasound software tool to assess pathological perfusion in a brain tumor patient. Tissue harmonic imaging (THI) enables an improved depiction of brain morphology, employing nonlinear parenchyma and ultrasound contrast agent (UCA) backscatter information. With specialized software, morphological information can be separated from perfusion information. Both can be superimposed at a preferred mixing ratio in a single image. Using THI and a perfluoropropane-based UCA, a pathologic perfusion pattern described by abnormal perfused areas in the tumor region could be demonstrated. After superimposing morphologic and perfusion information, subtle structural tumor inhomogeneities were depicted. Craniopharyngioma structure and perfusion defect were confirmed by T2-weighted and perfusion-weighted magnetic resonance imaging. Transcranial duplex sonography in combination with contrast specific imaging methods might be helpful to visualize perfusion defects without loss of morphological information.


Immediate versus delayed angioplasty in infarct-related arteries with TIMI III flow and ST segment recovery: a matched comparison in acute myocardial infarction patients.
Early management of patients with patent infarct-related artery (IRA) and optimal ST resolution in ST elevation myocardial infarction (STEMI) has never been assessed. We compared immediate vs delayed PCI in these patients. Matched comparison of immediate vs delayed (24 h) PCI in STEMI patients presenting with patent IRA, thrombus-containing lesion and ST resolution >or=70%. Patients were matched for duration of symptoms, intervention type, angiographic data, diabetes. Patients in immediate PCI group received standard therapy in the cathlab. Patients in delayed PCI group received dual antiplatelet therapy, antithrombins, and GPIIb-IIIa inhibitors until PCI. Primary endpoint was procedural success. Secondary endpoints were enzyme release and in-hospital adverse events. Seventy-eight patients were included: 39 per group. Average age 62 years, 75% males. There was a significantly higher procedural success rate in the delayed PCI group (95% success, Vs. 77% in the immediate group, P = 0.008). Initial thrombus burden score did not differ between immediate and delayed PCI groups, but improved significantly in the delayed group between baseline angiography and time of PCI (P = 0.039). There was no difference in major adverse events or bleeding complications between groups. Peak CK levels were significantly higher in the immediate versus delayed PCI group (P = 0.02), although there was no difference between groups in peak CK-MB, peak troponin, or peak CK-MB ratio. Our data suggest that in STEMI patients with patent IRA, optimal ST-segment resolution, and thrombus-containing lesion, deferred PCI when patients are given dual antiplatelet therapy, antithrombin agents, and GPIIb-IIIa inhibitors results in a higher procedural success rate, without an increased risk of MACE.


Autoimmune thrombocytopenia: serological behavior of platelet antibodies.
The study of the specificity of platelet autoantibodies has made it possible to expand our knowledge about the immune characterization of idiopathic thrombocytopenic purpura. We report on a study of eluates obtained from 10 patients' platelets with autoimmune thrombocytopenia. They were tested with platelets obtained from healthy donors (Zw a + and Zw a-) and with type I Glanzmann platelets. Our results, as those reported by van Leeuwen et al. in 1982, suggest that the autoantibodies recognize one or more antigenic markers probably carried by glycoproteins IIb and IIIa.


Intercostal artery aneurysmosis.
True intercostal artery aneurysms have been reported to occur in conjunction with neurofibromatosis, coarctation of the aorta, and Kawasaki disease. However, there has not been a previous report of a patient with intercostal artery aneurysmosis and no known or diagnosed associated condition. We describe the first such patient and review the literature.


Dietary glycemic load and hepatocellular carcinoma with or without chronic hepatitis infection.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for hepatocellular carcinoma (HCC). The association of diabetes mellitus with HCC suggests that dietary glycemic load (GL) may influence HCC risk. We have examined the association between dietary GL and HCC. We conducted a hospital-based case-control study in Italy in 1999-2002, including 185 HCC cases and 412 controls who answered a validated food frequency questionnaire and provided blood samples. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed using unconditional multiple logistic regression. We observed a positive association between GL and HCC overall, with an OR of 3.02 (95% CI 1.49-6.12) for the highest quintile of GL compared with the lowest and a significant trend. The OR among HCC cases with evidence of chronic infection with HBV and/or HCV was 3.25 (95% CI 1.46-7.22), while the OR among those with no evidence of infection was 2.45 (95% CI 0.69-8.64), with no significant trend. The association was not explained by the presence of cirrhosis or diabetes. High dietary GL is associated with increased risk for HCC. The positive association was most pronounced among HCC cases with HBV and/or HCV markers.


NADPH dehydrogenase-mediated respiratory electron transport in thylakoid membranes of the cyanobacterium Synechocystis sp. PCC 6803 is inactive in the light.
Non-photochemical redox changes of the plastoquinone pools in darkness were investigated in the cyanobacterium Synechocystis sp. PCC 6803 by monitoring changes in Chl fluorescence yield during light-to-dark transitions. The inhibitors rotenone and mercury with or without 1 mM succinate fully suppressed the post-illumination increase in Chl fluorescence in both NADPH dehydrogenase-defective (M55) and deltaCtaI cells. The latter cells lack subunit I of cytochrome aa3-type cytochrome c oxidase. These results strongly suggest that NADPH dehydrogenase plays the major role in electron donation in the non-photo-chemical reduction of plastoquinone. The rising phase of post-illumination Chl fluorescence in both wild type pretreated with KCN, and deltaCtaI cells, was significantly slowed by low light illumination. We detected comparable photochemical levels of both photosystem (PS) II and PSI during steady state illumination in wild type and deltaCtaI cells. From these results, we suggest that respiratory electron flow involved in the non-photochemical redox change of plastoquinone is not likely to occur in the light.


The effects of lanthanum chloride administration in newborn chicks on glutamate uptake and release by brain synaptosomes.
Acute i.p. administration of lanthanum chloride to newborn chicks at a single dose of 250 mg/kg body weight causes inhibition of the high affinity uptake of [14C]glutamate by isolated brain synaptosomes. There is also a marked decrease in the release of preloaded [14C]glutamate from brain synaptosomes in the presence of externally available Ca2+ (1.2 mM) or a high K+ concentration (71 mM). The inhibition of glutamate release has been discussed in relation to depletion of Ca2+ binding to the synaptosomal membrane under lanthanum intoxication.


The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter.
Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with high risk for developing breast and ovarian cancers. Several studies link BRCA1 to transcriptional regulation, DNA repair, apoptosis and growth/tumor suppression. BRCA1 associates with p53 and stimulates transcription in both p53 dependent and p53-independent manners. BRCA1 splice variants BRCA1a (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. Here we show that BRCA1a and BRCA1b proteins stimulate p53-dependent transcription from the p21WAF1/CIP1 promoter. In addition, the C-terminal second BRCA1 (BRCT) domain is sufficient for p53 mediated transactivation of the p21 promoter. Previous studies emphasized the importance of the BRCT domain, which shows homology with p53 binding protein (53BP1), in transcriptional activation, growth inhibition and tumor suppression. Our findings demonstrate an additional function for this domain in protein-protein interaction and co-activation of p53. We also found that BRCA1a and BRCA1b proteins interact with p53 in vitro and in vivo. The p53 interaction domain of BRCA1a/1b maps, in vitro, to the second BRCT domain (aa 1760-1863). The BRCT domain binds to the central domain of p53 which is required for sequence specific DNA binding. These results demonstrate for the first time the presence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. This BRCT domain also binds in vitro to CBP. These results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300 associated HAT/FAT activity for acetylation of p53 to specific promoters resulting in transcriptional activation.


[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture].
In this article authors focused to influence the physiologic IOP values after application of the aminoacid 10% L-lysine.2HCl.2H2O in 0.5% Timoptol eye drops mixture in experiments. 0.5% Timoptol, followed by 10% L-lysine.2HCl.2H2O and mixture of 10% L-lysine.2HCl.2H2O with 0.5% Timoptol was instilled weekly into the left conjunctival sac of 5 adult rabbits (females of the New Zealand White species). The IOP and pupilar diameter were measured in 5, 15, 30, 60, 120, 180 and 240 min. after instillation. The right eye was used as control. In experiments authors observed that: a) the aminoacid 10% L-lysine.2HCl.2H2O is without influence on the physiologic value of the IOP; b) 0.5% Timoptol compared with control eye nonsignificantly decreased the rabbit IOP; c) after instillation of 10% L-lysine.2HCl.2H2O and 0.5% Timoptol mixture the IOP showed decrease of the physiologic IOP in two periods. The initial non-significant period of the IOP decrease was measured after application up to the 60th min. The identical values were also in the control eye. However, the major decrease of the IOP compared with control eye was observed during the second period starting from 60th min. up to the end of experiments (to the 4th hour) after instillation of this mixture. The mean value of this significant decrease was 3.3 torrs of the physiologic IOP value showing regular and linear effectivity in the experimental eye. In the control eye the second period was without decrease of the IOP. The results demonstrate that the Timolol alone decreased the physiologic IOP no significantly, the aminoacid L-lysine.2HCl.2H2O is without influence on the physiologic value of the IOP. In experiments we confirmed that in a mixture of aminoacid L-lysine.2HCl.2H2O with antiglaucomatic 0.5% Timoptol a new substance was created, a new "bio-antiglaucomatic", responsible for more significant decrease of the physiologic IOP.


[Cerebral blood flow and event-related potential in patients with cerebral infarction].
Cerebral blood flow (CBF) and P 300, a long-latency positive component of the scalp-recorded event-related potential (ERP) associated with cognitive processing were investigated in patients with cerebral infarction to elucidate the relationship between CBF and cognitive function. Twenty-five patients with cerebral infarction with a mean age of 66.8 years were studied. ERP was recorded during auditory discrimination tasks. The latency of the P 300 from Pz region was recorded. The regional CBF was measured by the 133Xe inhalation method. The F1 (cortical gray matter flow) values were calculated using the Obrist's method. The mean F1 values in patients with cerebral infarction were significantly lower compared to the values obtained for the 15 control subjects (mean age, 68.4 years) (p less than 0.01). Patients with cerebral infarction showed significant prolongation of the P 300 latency compared to the 20 control subjects (mean age, 64.4 years) (p less than 0.02). There was a significant correlation between the P 300 latency and the mean F1 values in patients with cerebral infarction (p less than 0.01). Present results suggest that the cognitive impairment with respect to ERP may be related to the reduction of cortical blood flow in patients with cerebral infarction.


[Pathogenesis and clinical aspects of primary liver cell carcinomas].
The hepatocellular carcinoma is the most frequent primary liver cell carcinoma. On account of its geographical distribution with preferential occurrence in China, SE Asia and South Africa, exogenic causes are thought to be mainly responsible for its aetiopathogenesis. Besides mycotoxins, the hepatitis B virus infection (HBV) is particularly important. Integration of HBV-DNS into the hepatic cell DNS is considered to be an initiatory step in hepatocarcinogenesis. Clinically the tumour usually becomes manifest by upper abdominal complaints. Curative treatment can be promising only with very small tumours which can be detected most safely via ultrasound examination and alpha-1-fetoprotein determination.


Sexual activity and sexual satisfaction in Korean men with spinal cord injury.
A cross-sectional survey. The aim of this study was to identify and assess the sexual activity and perceived sexual satisfaction of Korean males with spinal cord injury (SCI) and to identify factors influencing sexuality and satisfaction. Community residents with SCI. A total of 139 male participants with SCI in Korea were eligible for inclusion in this study. All participants completed a face-to-face interview regarding sexuality and satisfaction, as well as structured questionnaires including items on socioeconomic factors, medical conditions and rehabilitation services. A total of 90 participants (65%) were engaged in sexual activity. A period of 21-25 years since SCI (compared with the initial 5 years since SCI) and an experience of direct sexual rehabilitation education were positively associated with sexual activity. Among 90 sexually active males with SCI, 8 (8.9%) and 56 (62.2%) were sexually satisfied and unsatisfied, respectively. Lower levels of education were strongly correlated with sexual dissatisfaction. Korean males with SCI showed low levels of satisfaction regarding sexual activities. Results showed that socioeconomic factors (e.g., state of employment and direct person-to-person sexual counseling services) had a greater impact on sexual activity than the degree of physical impairment. Notably, the educational background was the most influential factor on sexual satisfaction.


Scheduled appointments and patient-staff compliance.
Studies of medication compliance have focused primarily on patient resistance to treatment, medication side effects, or the complexity of the medication regimen. This study of patient visits in a large psychiatric clinic found that, because of failure to schedule appointments or to notify receptionists of rescheduled appointments, physician noncompliance was as important as patient failure.


Art Therapy Exhibitions: Exploitation or Advocacy?
Promoting awareness of human trafficking by sharing trauma survivors' art and summaries of their life stories suggests ethical complexities that have been typically neglected by bioethicists. Although these survivors voluntarily share the objects they created during art therapy sessions, they are still at risk of harm, including further exploitation, due to their vulnerability, high rates of victim sensitivity, and the mental health consequences of their traumatic experiences. While some argue that the benefits of sublimation and art therapy for human trafficking survivors make sharing their art worth the risk, anti-trafficking organizations and supporters of such art exhibitions have responsibilities to be trauma informed.


Excretion characteristics of tetrabromobisphenol-A in Wistar rats following mouth and nose inhalation exposure.
Tetrabromobisphenol-A (TBBPA), a brominated flame retardant with the largest production volume worldwide, is employed as a reactive and additive flame retardant, and also as an intermediate in the production of other retardants. The constant release of TBBPA into the environment has attracted increasing attention to its potent health effects. To date, the vast majority of health-related research on TBBPA has focused on oral exposure. This study aims to explore the excretion characteristics of TBBPA in living organisms following inhalation exposure. An inhalation exposure system was established in which the experimental animal model was exposed to inhalable particles (diameter < 10 μm) of TBBPA. The TBBPA aerosol doses used were 12.9, 54.6, 121.6, and 455.0 mg/m3 according to tuning system parameters. Following 14 d (2 h/d) of repeated inhalational exposure, the primary route of elimination was in feces for all exposed groups, and the values showed a significant positive linear relationship with exposure dose. In contrast, the elimination amount in urine was less than 0.4% of the inhaled dose. Trace levels of TBBPA (less than 0.1% of the inhaled dose) were also detected in serum, with amounts varying from 0 to 844 ng (per rat) among all groups.


Incidence of abnormalities in laboratory tests found in surveillance of adults over 40 years of age.
National health check-up systems have been used for 5 years in Japan for adults who are over 40 years of age. As part of a national project, Osaka prefecture is also conducting a program for health check-up testing and cancer screening for this age group. This surveillance revealed that incidence of obesity, hypertension, cholesterolemia, albuminuria, or abnormal ECG was high. Analysis of surveillance results should contribute to understanding the present status and recent trends in diseases in the aged. With continuation of this surveillance for a number of years, trends in life-style related diseases in Japan should be detectable.


[Prevalence and factors associated with clinical counselling on drug use among internal specialists residents of Andalusia (Spain)].
To determine the frequency of offering clinical counseling against the consumption of alcohol, tobacco and illegal drugs by internal specialist residents (EIR) of Andalusia, and the factors related to such advice. Multicenter cross-sectional study by self-administered questionnaire sent by mail. EIR of Andalusia. The questionnaire collected the frequency of counseling against the use of alcohol, tobacco and illegal drugs (dependent variable). age/gender, specialty, drug consumption and Fagerström test. Out of a total of 4245 participants, 66% responded, 29% did not respond, and 5% poorly completed questionnaires. The mean age was 29.1(±SD 5.1) years, 69% female, 89% Spanish nationality, 84% in medical training (73% hospital, 27% family medicine). The frequency of counseling against tobacco (85%) and alcohol (82%) is higher than illegal drugs (56%, p<.001, χ(2) test). Counseling against alcohol consumption is related to family medicine (OR=2.8; 95% CI [1.4-4.6]) and nursing (OR=2.5 [1.7-4.4]), and the age of first alcohol consumption (OR=1.07 [1.03-1.1]). Counseling against smoking is related to family medicine (OR=12.9;[7.6-21.9]) and nursing (OR=8.4;[4.3-16.5]), personal consumption of tobacco (OR=1.5 [1.2-2.0]), and wine (OR=1.1 [1.04-1.3]), and age of first alcohol consumption (OR=1.06 [1.01-1.1]). Counseling against illegal drugs is related to the age of first alcohol consumption (OR=1.09 [1.05-1.1]) and smoking (OR=.58 [.4-.7]). There is a high frequency of counseling against consumption of tobacco and alcohol by EIR, although remarkably smaller for illegal drugs. The influencing factors are both formative elements of their own specialty such as personal consumption of alcohol and tobacco, which should be considered for improvement of this preventive activity.


Benign prostatic hyperplasia in older men.
Urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) may adversely affect quality of life in many older men. Evaluation of patients with BPH should be focused on excluding complicating factors such as urinary tract infection, renal dysfunction, and malignancy. Watchful waiting is an appropriate option for men in whom such complicating conditions have been excluded. For those men who elect to be treated, therapy using alpha blockers (terazosin, doxazosin) or 5-alpha reductase inhibitors (finasteride) should be offered initially. Surgical treatment is generally reserved for patients who do not have a sufficient response to medical therapy and those with absolute indications for intervention, such as complete retention, recurrent infection or hematuria, renal insufficiency, and bladder stones.


Gene structure and tissue expression of human selenoprotein W, SEPW1, and identification of a retroprocessed pseudogene, SEPW1P.
We have determined that the human SEPW1 (selenoprotein W) gene maps to chromosome 19q13.3, spans approximately 6.3 kb and comprises six exons, in contrast to the previously published five exons. The gene lacks canonical TATA and CAAT boxes, but has numerous Sp1 consensus binding sites upstream of multiple transcription start sites. SEPW1 is expressed in all of the 22 tissues assayed, and shows highest expression in skeletal muscle and heart. Additionally, we have also identified a retroprocessed SEPW1 pseudogene, SEPW1P, which maps to chromosome 1p34-35.


Prognostic value of NT-proBNP at rest and peak exercise in patients with impaired left ventricular function.
We aimed to identify whether N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) at peak exercise can provide incremental clinical information over resting levels. A total of 90 patients with systolic heart failure were prospectively studied. Levels of plasma NT-proBNP were assessed at rest and at peak exercise during a cardiopulmonary exercise test. Patients were followed-up for 30 ± 10 months. Levels of NT-proBNP at baseline and peak exercise were significantly correlated with left ventricular ejection fraction ([LVEF] r = -.629, P < .001 and r = -.630, P < .001, respectively) and peak oxygen uptake ([Vo (2)] r = -.752, P < .001 and r = -.740, P < .001, respectively). Levels of plasma NT-proBNP at peak exercise demonstrated similar predictive ability for the detection of patients with low peak Vo (2) and LVEF <28%. Levels of plasma NT-proBNP can detect low-functional class patients and patients who may be the candidates for heart transplantation with high sensitivity and specificity. At baseline and peak exercise, NT-proBNP demonstrates similar prognostic and predictive ability.


Cytosine arabinoside induces programmed endothelial cell death through the caspase-3 pathway.
The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However, effects on nonmalignant cells have not been elucidated and may be important to understanding treatment-related toxicity. The purpose of this study was to examine the effect of ARA-C on nondividing vascular endothelial cells. The objectives were to determine the effects of ARA-C on cell viability and to ascertain whether ARA-C caused apoptosis in cultured vascular endothelial cells and hydrocortisone blunted caspase-3-induced apoptosis. Endothelial cells were cultured until confluent and mitotically quiescent then exposed to ARA-C (10(-7)to 10(-3) M) for 1 to 4 days. Some experiments involved cotreatment with hydrocortisone (10(-11),10(-10),10(-4), and 10(-3) M). Light microscopy and the colorimetric MTS assay were used to measure viability. Fluorescent annexin-V and DNA fragmentation assays were used to measure apoptosis, and a fluorescence-based enzymatic assay was used to measure caspase-3 activity, which is one pathway involved in the apoptosis cascade. Two-way ANOVA or the appropriate nonparametric test was used to determine statistical significance in studies of viability and apoptosis. Oneway ANOVA was used to determine statistical significance for caspase-3 activity. Viability was decreased with higher concentrations of ARA-C and increased days of treatment. The percentage of apoptotic cells increased with higher concentrations of ARA-C and increased days of treatment. ARA-C-treated samples showed DNA fragmentation, indicative of apoptosis. Caspase-3 activity increased after ARA-C addition; hydrocortisone blunted this increase. ARA-C caused apoptosis in nondividing endothelial cells in culture. Hydrocortisone may protect against ARA-C-induced apoptosis by reducing caspase-3 activity.


Whats new in genodermatoses?
Recent genetic analysis of the genodermatoses, in particular the palmoplantar keratodermas, has identified the important role of proteins involved in the regulation and formation of epidermal cell junctions. There are four major types of junction, of which three have been demonstrated to be important in skin, and in which component proteins such as desmoplakin and connexins are mutated in epidermal disease. These are the gap junctions, desmosomes and adherens junctions. These junctions are responsible for cell-cell adhesion and communication, key properties to maintain the normal cellular phenotype and tissue architecture.


Use of T(2)-weighted susceptibility contrast MRI for mapping the blood volume in the glioma-bearing rat brain.
The aim of this work was to evaluate the potential of T(2)-weighted, steady-state susceptibility-enhanced contrast magnetic resonance imaging (MRI), to characterize brain tumor heterogeneity and tumor vascularization. In vivo T(2)-weighted MRI experiments were carried out on normal rats (n = 11) and rats bearing C6 glioma (n = 17), before and after the injection of a remanent superparamagnetic contrast agent. The DeltaR(2) variations of the transverse relaxation rate due to the injection of the contrast agent were used to generate relative cerebral blood volume (CBV) maps. Contrast enhancement of the tumor was shown to reflect tissue vascularization rather than leakage of the blood-brain barrier. The quantitative results clearly show the heterogeneity of tumor vascularization and reveal a high vessel density in the peripheral area (CBV(per) approximately 17.2 +/- 2.3 sec(-1)) and a low vessel density in the central area of the tumor (CBV(cen) approximately 2.5 +/- 0.5 sec(-1)). Magn Reson Med 42:754-761, 1999.


Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis.
Trimethylamine (TMA) is a short-chain tertiary aliphatic amine that is derived from the diet either directly from the consumption of foods high in TMA or by the intake of food high in precursors to TMA, such as trimethylamine-N-oxide (TMNO), choline and L-carnitine. The clinical significance of TMA may be related to its potential to contribute to neurological toxicity and 'uraemic breath' in patients with end-stage renal disease (ESRD). Concentrations of TMA and TMNO in plasma from 10 healthy adults (not on haemodialysis) and 10 adults with ESRD undergoing haemodialysis (pre- and post-dialysis) were determined by gas chromatography-mass spectrometry. The concentrations of TMA and TMNO in pre-dialysis plasma (1.39+/-0.483 and 99.9+/-31.9 microM, respectively) were significantly (P<0.05) higher than the corresponding levels in healthy subjects (0.418+/-0.124 and 37.8+/-20.4 microM, respectively). However, there were no significant differences between post-dialysis and healthy subject plasma concentrations. In the ESRD patients, there was a significant (P<0.05) reduction in plasma TMA (from 1.39+/-0.483 to 0.484+/-0.164 microM) and TMNO (from 99.9+/-31.9 to 41.3+/-18.8 microM) during a single haemodialysis session. TMA and TMNO accumulate between haemodialysis sessions in ESRD patients, but are efficiently removed during a single haemodialysis session.


[Reactive perforating collagenosis].
Reactive perforating collagenosis (RPC) belongs to the group of perforating dermatoses, which comprises elastosis perforans serpiginosa, RPC, perforating folliculitis and Kyrle's disease. RPC was initially described as a distinctive form of transepithelial elimination of altered collagen related to superficial trauma. Two types are distinguished: a hereditary type (MIM 216700), which is rare and begins during early childhood, and a second type, called acquired RPC, which is more frequent, appears in adults and is associated with other diseases, diabetes mellitus, renal insufficiency, solid tumors, lymphomas and AIDS. We report the case of a young man whose illness began during infancy, militating in favor of a diagnosis of a hereditary form of RPC. The description of similar lesions in the patient's brother confirmed our diagnosis. A 26-year-old man, the child of consanguinous parents, presented crusted papular lesions on his hands. The cutaneous lesions, located on the external side of the limbs, had been present since childhood, with flares during winter. Histologic analysis showed a cup-shaped depression in the epidermis containing keratinous material with extruded degenerated collagen towards the cutaneous surface. Treatment with topic retinoids did not result in any real resolution of the disease. The patient reported the presence of similar lesions in his brother, which was consistent with our diagnosis. The pathogenesis of hereditary RPC is still unknown, even if superficial trauma is suspected as the cause of RPC. In contrast, in diabetes, acquired RPC pathogenesis has recently been related to advanced glycation end-products of collagen.


[Serum lipoproteins in the generalized form of type III glycogenosis].
Distinct accumulation of glycogen, anomalous in structure, and absence of amylo-1,6-glucosidase activity were observed in studies of material obtained by biopsy from liver and muscle tissues of a patient with generalized form of glycogenosis type III. Anamalous glycogen (limitdextrin) was also found in erythrocytes. Concentration of lipoproteins, especially of low density lipoproteins 12.20 S and 0-12 S, was increased in blood serum. Spectrum of lipoproteins acquired a tendency to normalization simultaneously with clinical improvement after intravenous administration of glucose and treatment with cholesterolamine per os.


The repeatability and reproducibility of gingival thickness measurement with an ultrasonic device.
Successful periodontal and implant surgery as well as orthodontic treatment often depends on gingival and mucosal thickness. So far there has been no generally accepted protocol of measuring the thickness of gingiva by non-invasive methods. The aim of the study was to evaluate the repeatability and reproducibility (%R&R) of the 20 MHz A-Scan ultrasonic device in measuring gingival thickness (GT) in the mucogingival complex. A 2-stage study utilizing non-invasive ultrasonic methods was conducted. In the 1st stage, 3 operators got calibrated by measuring previously established GT in porcine cadaver jaws. In the 2nd stage, 1 periodontally healthy subject was recruited in the study. Three operators performed the measurements of GT in maxillary left central and lateral incisors and canines, using the 20 MHz A-Scan ultrasonic device with a probe of 1.7 mm in diameter. The thickness was measured in 4 standardized points located in the free gingiva (FGT), supracrestal gingiva (SGT), crestal gingiva (CGT) and the mucosa (MGT). The analysis of variance (ANOVA) method was used to quantify %R&R. The repeatability and reproducibility of the measurements was 8.4%. Interobserver reproducibility varied from 0.8% to 13.4%. The average intraobserver coefficient of variation (CV) was 6.6% (1.9-13.6%). The median of the reproducibility of all measurements was 8.1 %. Nevertheless, the median of CV was variable to the observer, i.e. 5.4%, 6.5%, 6.4%. The obtained results in %R&R prove the good recognition of methodology as well as the usefulness of the device. Non-invasive ultrasonic biometer GT measurements are crucial in periodontology as well as in other fields of dentistry.


Choosing to practice in rural dietetics: what factors influence that decision?
The present study aimed to identify those factors that influence the decision of a dietitian to consider working in a rural area. A qualitative design using focus groups was chosen for this study to allow for in-depth data to be obtained. University of Newcastle, Callaghan Campus. Twenty-three students/new graduates from the Bachelor of Health Science (Nutrition and Dietetics) degree at the University of Newcastle. Not applicable, this project was an exploratory study. A number of factors that influence the decision of dietetic students and newly graduated dietitians to consider working in a rural area were identified. These fell into the following main thematic areas: job prospects; rural lifestyle; comfort zones; support networks; promotion opportunities/professional development; type of work/work role; rural needs; and time frame. The present study found that choosing a location to work (whether it be a rural one or not) is a complex process and involves a number of interacting factors. Also those factors that may influence one dietitian to choose a career in a rural area may also be the factors that influence another dietitian not to choose a career in a rural area.