bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional interaction between mutations in the granulocyte colony‐stimulating factor receptor in severe congenital neutropenia
Authors: Ward Alister C. , Gits Judith , Majeed Fidel , Aprikyan Andrew A. , Lewis Rowena S. , O’Sullivan Lynda A. , Freedman Melvin , Shigdar Sarah , Touw Ivo P. , Dale David C. , Dror Yigal
Published: May 2008

Most severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony‐stimulating factor receptor (G‐CSF‐R). We have described a case with constitutive extracellular G‐CSF‐R mutation hyporesponsive to ligand. Here we report two independent acquired G‐CSF‐R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co‐expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G‐CSF‐R mutant, while constitutively‐active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G‐CSF.
Antiplatelet drugs
Authors: De Meyer Simon F. , Vanhoorelbeke Karen , Broos Katleen , Salles Isabelle I. , Deckmyn Hans
Published: May 2008

Platelets play a major role in thromboembolic diseases, and so antiplatelet therapy remains crucial in treatment and prophylaxis. Upon vascular injury, platelets rapidly adhere to the exposed subendothelial matrix, after which they become activated, resulting in the recruitment of additional platelets from the circulation to eventually form a stable arterial platelet plug. Although controlled plug formation is desired for the prevention of excessive blood loss and for promoting wound healing, several pathological conditions may result in the formation of occlusive thrombi leading to severe clinical complications, including myocardial infarction and ischaemic stroke.

Many antiplatelet approaches have been investigated, interfering with one or more of the different stages in thrombus formation. This review discusses antiplatelet agents that interfere with the three principal phases in thrombus formation: platelet adhesion, amplification of platelet activation and platelet aggregation. For each stage, novel experimental targets and clinically established antiplatelet strategies will be reviewed. Limitations and possible benefits will be discussed for each target.
Advances in the understanding of mast cell function
Authors: Heib Valeska , Becker Marc , Taube Christian , Stassen Michael
Published: May 2008

Mast cells were formerly thought to contribute mainly to, sometimes even, fatal allergic reactions through the release of biologically highly active cytokines, chemokines, lipid mediators, proteases and biogenic amines. This potential harmful response is triggered by crosslinking of cell‐bound IgE by the respective allergen. This review updates our current understanding of the emerging roles of mast cells with an emphasis on their relevance in protective host immunity. The activation of mast cells independently of Immunoglobulin E can lead to the initiation of fast inflammatory reactions, which were shown to be life‐saving in murine models of bacterial infections. Besides their critical functions in innate immunity, mast cells promote and shape the development of adaptive immune responses. Thus, mast cells are increasingly being recognized as sentinels of innate and modulators of adaptive immunity.
Effects of food‐web structure on periphyton stoichiometry in eutrophic lakes: a mesocosm study
Authors: DANGER M. , LACROIX G. , OUMAROU C. , BENEST D. , MÉRIGUET J.
Published: May 2008

1. Aquatic herbivores typically have much higher concentrations of nutrients (e.g. N and P) in their tissues than there is in the food they eat. These stoichiometric differences can cause herbivores to be limited by the elemental quality of their food, which could affect, in turn, the structure of consumer communities and even alter key ecosystem processes.

2. In streams and in the littoral zone of shallow lakes, periphyton is an important food resource for benthic animals. Studying the elemental composition of periphyton may help us to understand food‐web structure, and any reciprocal effect of this structure on periphyton stoichiometry.

3. To understand how alterations in the food‐web structure affect the elemental composition of periphyton in a eutrophic lake, we carried out a long‐term experiment (14 months) in large‐scale mesocosms (40 m3), in which we manipulated food‐web structure, and which were dominated either by planktivorous fish (Rutilus rutilus) or herbivorous invertebrates (without fish). Periphyton was sampled monthly at three depths (0.5, 1.5 and 2.5 m) to determine its biomass and elemental composition (C/N/P ratio). Food‐web structure, physical and chemical parameters were monitored throughout the experiment.

4. Fish had indirect positive effect on periphyton biomass, leading to twofold higher levels than in herbivore‐dominated mesocosms. This result was probably due to control of benthic consumers by fish, suggesting a strong top–down control on periphyton by their consumers in fishless enclosures.

5. The elemental ratios C/P and C/N were lower in deep water in both treatments, mainly mediated by light availability, in accordance with the light/nutrient ratio hypothesis. These ratios were also lower in fishless treatments, probably due to increases in inorganic nutrient availability and grazing pressure in herbivore‐dominated systems. During winter, periphyton elemental composition was similar in both treatments, and was unrelated to inorganic nutrient availability.

6. These results indicate that any alteration of food‐web structure in lakes, such as in biomanipulation experiments, is likely to modify both the biomass and elemental quality of periphyton. Resultant effects on the consumers of periphyton and macrophytes could play a key role in the success of biomanipulations and should be taken into account in further studies.
Transport of phosphatidylinositol 3‐phosphate into the vacuole via autophagic membranes in Saccharomyces cerevisiae
Authors: Obara Keisuke , Noda Takeshi , Niimi Kaori , Ohsumi Yoshinori
Published: May 2008

Vps34, the sole PtdIns 3‐kinase in yeast, is essential for autophagy. Here, we show that the lipid‐kinase activity of Vps34 is required for autophagy, implying an essential role of its product PtdIns(3)P. The protein‐kinase activity of Vps15, a regulatory subunit of the PtdIns 3‐kinase complex, is also required for efficient autophagy. We monitored the distribution of PtdIns(3)P in living cells using a specific indicator, the 2xFYVE domain derived from mammalian Hrs. PtdIns(3)P was abundant at endosomes and on the vacuolar membrane during logarithmic growth phase. Under starvation conditions, we observed massive transport of PtdIns(3)P into the vacuole. This accumulation was dependent on the membrane dynamics of autophagy. Notably, PtdIns(3)P was highly enriched and delivered into the vacuole as a component of autophagosome membranes but not as a cargo enclosed within them, implying direct involvement of this phosphoinositide in autophagosome formation. We also found a possible enrichment of PtdIns(3)P on the inner autophagosomal membrane compared to the outer membrane. Based on these results we discuss the function of PtdIns(3)P in autophagy.
Differentiation of mouse and human embryonic stem cells into hepatic lineages
Authors: Shiraki Nobuaki , Umeda Kahoko , Sakashita Naomi , Takeya Motohiro , Kume Kazuhiko , Kume Shoen
Published: May 2008

We recently reported a novel method to induce embryonic stem (ES) cells differentiate into an endodermal fate, especially pancreatic, using a supporting cell line. Here we describe the modified culture condition with the addition and withdrawal of secreted growth factors could induce ES cells to selectively differentiate into a hepatic fate efficiently. The signaling of BMP and FGF that have been implicated in hepatic differentiation during normal embryonic development are shown to play pivotal roles in generating hepatic cells from the definitive endoderm derived from ES cells. Moreover, the expression of AFP, Albumin or a biliary molecular marker appeared sequentially thus suggested the differentiation of ES cells recapitulated normal developmental processes of liver. The ES cell‐derived differentiated cells showed evidence of glycogen storage, secreted Albumin, exhibited drug metabolism activities and expressed a set of cytochrome or drug conjugate enzymes, drug transporters specifically expressed in mature hepatocytes. With the same procedure, human ES cells also gave rise to cells with mature hepatocytes’ characteristics. In conclusion, this novel procedure for hepatic differentiation will be useful for elucidation of molecular mechanisms of hepatic fate decision at gut regionalization, and could represent an attractive approach for a surrogate cell source for pharmaceutical studies such as toxicology.
About Stress Hormones and Resilience to Psychopathology
Authors: De Kloet E. R.
Published: May 2008

Neuroendocrinology links experience and behaviour to the action of hormones. This review focusses on the corticosteroids, released in hourly pulses and after stress, to illustrate the integration of body, brain and mind achieved by these hormones. Corticosteroids coordinate cell and organ function in concert with other mediators of the stress response over time spans from seconds to hours, days, weeks, or even permanently. The actions exerted by these stress hormones are mediated by two receptor types that control initial stress reactions and manage the later adaptive phases. How the balance between the stress and adaptive responses contributes to resilience and health is a conundrum to be resolved during the next two decades of the existence of the Journal of Neuroendocrinology.
Genetic Dissection of Glucocorticoid Receptor Function in the Mouse Brain
Authors: Erdmann G. , Berger S. , Schütz G.
Published: May 2008

In the brain, glucocorticoids exert functions in neurogenesis, synaptic plasticity and behavioural responses, as well as in the control of hypothalamic‐pituitary‐adrenal axis activity. The generation of mice harbouring germline mutations that result either in loss or in gain of glucocorticoid receptor function provided a useful tool for understanding the role of glucocorticoids in the brain in vivo. The improvement of genomic technologies additionally allowed the establishment of mouse models with function‐selective point mutations of the receptor as well as the generation of mice harbouring spatially and/or temporally restricted loss of glucocorticoid receptor, specifically within the brain. These models will provide the opportunity to better understand the mechanisms involved in glucocorticoid signalling within the nervous system.
Epigenetic Programming of Phenotypic Variations in Reproductive Strategies in the Rat Through Maternal Care
Authors: Cameron N. M. , Shahrokh D. , Del Corpo A. , Dhir S. K. , Szyf M. , Champagne F. A. , Meaney M. J.
Published: May 2008

Studies across multiple organisms reveal considerable phenotypic variation in reproductive tactics. In some species, this variation is associated with maternal effects in which variation in maternal investment results in stable individual differences in reproductive function. Recent studies with the rat suggest that maternal effects can alter the function of neuroendocrine systems associated with female sexual behaviour as well as maternal behaviour. These maternal effects appear to be mediated by epigenetic modifications at the promoter for oestrogen receptor alpha (ERα) and subsequent effects on gene expression. The tissue‐specific nature of such effects may underlie the co‐ordinated variation in multiple forms of reproductive function, resulting in distinct reproductive strategies.
Determinants of postprandial flow across the human ileocaecal junction: a combined manometric and scintigraphic study
Authors: Dinning P. G. , Szczesniak M. M. , Cook I. J.
Published: May 2008

Abstract  The relationships between ileocolonic motor patterns and flow have not been defined in humans. Utilizing simultaneous ileocolonic manometry and scintiscanning, we aimed to examine this relationship and test the hypotheses that ileal propagating sequences (PSs) underlie caecal filling, that caecal filling is a stimulus for proximal colonic PSs and that the ileocolonic junction (ICJ) regulates flow between the small and large bowel. In six healthy volunteers, a 5‐m‐long nasocolonic manometry catheter was positioned such that 16 recording sites, spaced at 7.5‐cm intervals, spanned the ileum and proximal colon. Subjects were positioned under a gamma camera 30 MBq of 99mTc sulphur colloid was instilled, 22.5 cm proximal to the ICJ. Isotopic images were recorded (10 s per frame) and synchronized with the manometric trace. We identified 171 ileal PSs, 47 caecal PSs and 117 discrete episodes of caecal filling. Of the 117 episodes of caecal filling, 72% were associated temporally with ileal PSs. Conversely, 87% of ileal PSs were associated with caecal filling. Of the PSs originating in the caecum, 90% were temporally associated with caecal filling. We conclude that ileal PSs are highly propulsive and are the major determinant of episodic caecal filling and that caecal filling may be a major stimulus for caecal propagating sequences.
Ultrastructural study of florid plaques in variant Creutzfeldt–Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt–Jakob disease and Gerstmann–Sträussler–Scheinker disease
Authors: Sikorska B. , Liberski P. P. , Sobów T. , Budka H. , Ironside J. W.
Published: May 2008

Background: Although the histological features of the amyloid plaques in variant Creutzfeldt–Jakob disease (vCJD) are distinct from those in other forms of prion disease [kuru, sporadic Creutzfeldt–Jakob disease (sCJD) and Gerstmann–Sträussler–Scheinker disease (GSS)], their ultrastructural features have only been described in a single case report. Aims: To study vCJD plaques systematically and compare them with plaques in kuru, sCJD, GSS and Alzheimer disease (AD). Methods: Amyloid plaques were studied by transmission electron microscopy and image analysis in five cases of vCJD, three cases of GSS, two cases of sCJD, one case of kuru and five cases of AD. Immunohistochemistry was performed on paraffin sections from one case of vCJD, two cases of GSS, one case of kuru and two cases of sCJD. Results: The florid plaques in vCJD were either compact or more diffuse; in both forms, the radiating fibrils were organized into thick ‘tongues’, in contrast to kuru plaques. Dystrophic neurites (DNs) containing lysosomal electron‐dense bodies or vesicles surrounded florid plaques. Microglial cells were found within florid plaques; occasional amyloid fibrils were identified in membrane‐bound pockets of microglial cells. In vCJD, there was significant tau immunoreactivity in DNs around florid plaques while, in sCJD, GSS and kuru, minimal tau immunoreactivity was observed around plaques. Conclusions: The ultrastructure of the florid plaques and DNs in vCJD is more reminiscent of neuritic plaques in AD than kuru or multicentric plaques. These findings may reflect differences both in the strains of the transmissible agents responsible for these disorders and in host factors.
Wheat allergen exposure and the prevalence of work‐related sensitization and allergy in bakery workers
Authors: Jacobs J. H. , Meijster T. , Meijer E. , Suarthana E. , Heederik D.
Published: May 2008

Background:  Occupational airway diseases are common among bakers. The present study describes the association between exposure to wheat allergen levels and sensitization to wheat allergens, work‐related upper and lower respiratory symptoms and asthma in bakery workers.

Methods:  As part of a Health Surveillance System for early detection of (allergic) occupational airway diseases a so‐called ‘validation study’ was performed among Dutch bakers for validation of a diagnostic model that predict the likelihood of sensitization to specific workplace allergens. The present study used serology and questionnaire results of a subgroup of 860 bakers participating in the validation study. An earlier developed job‐exposure matrix was used to predict average and cumulative personal exposure to wheat allergens.

Results:  The prevalence of wheat sensitization, work‐related respiratory symptoms and asthma increased till average wheat exposure levels of approximately 25–30 μg/m3, leveled off and decreased at higher exposure concentrations. Exposure–response curves showed a stronger pronounced bell‐shape with cumulative exposure. Associations were strongest for asthma and work‐related lower respiratory symptoms (PR∼2 and PR∼3.5–4.5 for average and cumulative exposure, respectively). Associations were only found in atopics. Wheat sensitization was an important factor in the prevalence of respiratory symptoms.

Conclusion:  In accordance with earlier studies, the present study showed a bell‐shaped exposure–response relationship especially for cumulative wheat allergen exposure with sensitization, allergic respiratory symptoms and asthma. The healthy worker effect may be the possible explanation for the bell‐shaped relationship.
Competitive speciation and costs of choosiness
Authors: KOPP M. , HERMISSON J.
Published: May 2008

We investigate how costs of choosiness affect the evolution of assortative mating in a simple model of competitive speciation. The model allows for a comprehensive analysis by analytical and numerical techniques. We obtain results for two types of costs: mating costs, which restrict the number of males a choosy female can evaluate, and viability costs, which decrease a choosy female's survival. Mating costs significantly reduce the range of parameters for which speciation is possible, but only if the number of males a female can evaluate is small (less than 10). This type of costs can be eliminated if females are allowed to mate randomly at the end of the mating period. Although, in this case, it is not possible to achieve complete reproductive isolation, our results show partial isolation with strong phenotypic clustering. Viability costs counteract selection for assortative mating. As this selection is typically weak, speciation is possible only if viability costs, too, are weak. The above restrictions are less severe if extreme phenotypes have an intrinsically higher carrying capacity.
Anatomical Features of the Carpal Flexor Retinaculum of the Horse
Authors: Probst A. , Macher R. , Hinterhofer C. , Polsterer E. , Guarda I. H. , König H. E.
Published: May 2008

This study aims to elucidate the topographical anatomy of the carpal flexor retinaculum or palmar anular carpal ligament (PACL) in the horse. Ten specimen of the carpus of five healthy horses were studied by dissection in layers. Slices of 5 mm in thickness facilitated observation of the soft tissues. The superficial layer of the PACL subdivides into five compartments: one for the palmar nerve and the arterial and venous branches, one for only the radial artery, one for the radial vein, and one for the tendon of the radial carpal flexor muscle, and finally for the deep layer that supports all tendinous structures located palmar to the carpus, as well as the median artery and palmar medial nerve. The sections of the segmented PACL that are affected by carpal canal syndrome may vary with the aetiology of the space‐occupying process. Precise anatomical knowledge of the structures may help in understanding the pathological processes and determining the most appropriate therapy.
Cost analysis of chronic obstructive pulmonary disease in a tertiary care setting in Taiwan
Authors: CHIANG Chi‐Huei
Published: May 2008

Background and objective:  The prevalence of COPD in the Western Pacific is increasing. The present study determined the total direct health‐care costs for the management of COPD patients with differing degrees of disease severity. The study also aimed to find the key cost drivers in the management of COPD.

Methods:  COPD patients were recruited from a tertiary care hospital during April 2002 and March 2003. One‐year costs were identified by applying cost data to medical information obtained by review of medical records. Costs included those for medications, oxygen therapy, laboratory and diagnostic tests, clinic visits, emergency room visits and hospital stays.

Results:  There were 160 patients recruited. Patients were categorized by COPD severity: moderate A COPD (50 ≤ FEV1% < 80; n = 54), moderate B COPD (30 ≤ FEV1% < 50; n = 54) and severe COPD (FEV1% < 30; n = 52). Patients with moderate A, moderate B and severe COPD had an average of 0.82, 2.6 and 3.5 exacerbations per year, respectively. Average numbers of emergency room visits were 0.41 ± 0.94, 1.20 ± 1.39 and 1.73 ± 2.44 per year in moderate A, moderate B and severe COPD patients, respectively. The mean total direct costs were New Taiwan dollars 288 825, 149 031 and 38 203 for severe COPD, moderate B COPD and moderate A COPD, respectively. The total annual cost was correlated with the disease severity. Hospitalization contributed the major portion of cost and also correlated with disease severity.

Conclusions:  There is a correlation between the cost of COPD and disease severity with hospitalization owing to disease exacerbation being a major contributor to cost. The keys to reducing health‐care costs lie with reducing the frequency of exacerbations and the disease severity.
Patient satisfaction with sedation for flexible bronchoscopy
Authors: HIROSE Takashi , OKUDA Kentaro , ISHIDA Hiroo , SUGIYAMA Tomohide , KUSUMOTO Sojiro , NAKASHIMA Masanao , YAMAOKA Toshimitsu , ADACHI Mitsuru
Published: May 2008

Background and objective:  Patient satisfaction with health care has increasingly been recognized as an important health outcome, but few studies have examined patient satisfaction with flexible bronchoscopy (FB). The purpose of this study was to assess patient satisfaction with FB conducted under conscious sedation and to identify the aspects of the procedure related to patient satisfaction.

Methods:  Patients' willingness to return for repeat FB was measured on a 5‐point scale. Patients were asked whether they were bothered by the anaesthetic spray, scope insertion, shortness of breath, coughing, pharyngeal pain, chest pain or swallowing pain. Patients were asked to assess the quality of the physician, the institution and nursing, and their satisfaction with the privacy, waiting time and information provided about the procedure.

Results:  Of 161 consecutive eligible patients who underwent FB, 129 (80.1%) completed the questionnaire. Of the 129 patients, 65.8% reported that they would return for a repeat FB (12.4% would definitely return and 53.4% would probably return). Male gender, shorter examination time, excellent physician quality and not being bothered by coughing, pharyngeal pain or swallowing pain were related to greater patient satisfaction. The results of multiple logistic regression analysis showed that male gender was related to greater patient satisfaction.

Conclusions:  Bronchoscopists should try to recognize the factors that influence patient satisfaction and adjust their management accordingly.
Trends in asthma prevalence and severity in Omani schoolchildren: Comparison between ISAAC phases I and III
Authors: AL‐RAWAS Omar A. , AL‐RIYAMI Bazdawi M. , AL‐MANIRI Abdullah A. , AL‐RIYAMI Asya A.
Published: May 2008

Background and objective:  This study evaluated changes in the prevalence of asthma symptoms and asthma severity in Omani school children over time.

Methods:  Two cross‐sectional surveys, in 1995 and 2001, were conducted as part of the International Study of Asthma and Allergies in Children on Omani schoolchildren in two different age groups (6–7 and 13–14 years).

Results:  There were 7067 children surveyed in 1995 (3893 in the younger and 3174 in the older group) and 7879 in 2001 (4126 in the younger and 3753 in the older group). Over the 6 years there was a significant increase in the prevalence of current wheeze ‘any wheeze during the past 12 months’ (from 7.1% to 8.4%; P = 0.035) in the younger group with no significant change in asthma diagnosis (10.5% vs 10.6%) or any other asthma symptoms. In the older group, all asthma symptoms remained unchanged except speech‐limiting wheeze which declined from 4.0% to 2.8% (P = 0.007). In both surveys, more than 60% of current wheezers reported severe asthma symptoms, while only 60% of these reported a diagnosis of asthma.

Conclusion:  The prevalence of both asthma and severe asthma remains high among Omani children. There is significant ‘under‐diagnosis’ and/or ‘under‐treatment’ of asthmatic children which requires urgent evaluation and intervention.
Peripheral blood picture following mild head trauma in children
Authors: Alioglu Bulent , Ozyurek Emel , Avci Zekai , Atalay Basar , Caner Hakan , Ozbek Namik
Published: May 2008

Background: The aim of the present study was to investigate changes in peripheral white blood cell, and differential counts following mild head trauma in a pediatric population.

Methods: Fifty‐one patients (mean age, 79 ± 62 months) with mild head trauma (Glasgow Coma Scale [GCS] score 15) who were admitted to the emergency department, were studied. Two blood specimens were collected from each patient, one on arrival and one after 24 h at the emergency department. Complete blood count was performed using a hemocytometer and the absolute cell counts for each sample were calculated after examination of peripheral smear.

Results: No patient developed any complication during the hospital stay or after discharge. Significant differences were found for white blood cell, neutrophil, and immature cell counts just after and 24 h after trauma (P = 0.047, 0.039 and 0.009, respectively).

Conclusions: Mild head trauma may cause an increase in white blood cell, neutrophil and band counts in children just after trauma. In a child with a mild head trauma, who is asymptomatic, with GCS score of 15 and absence of risk factors, and without clinical deterioration, complete blood cell count may be omitted from laboratory workup. But a prospective randomized study comparing mild head trauma patients with good and bad clinical outcome is needed to draw a definite conclusion.
Hemorrhage due to tracheoarterial fistula with severe motor and intellectual disability
Authors: Hamano Kimiko , Kumada Satoko , Hayashi Masaharu , Uchiyama Akira , Kurihara Eiji , Tamagawa Kimiko , Enomoto Syoko , Chou Hiroyuki
Published: May 2008

Background: Tracheoarterial fistula (TAF) is an unusual but highly lethal complication of tracheostomy, and successful surgical intervention for TAF has been reported. Few investigations are available for TAF in severe motor and intellectual disability (SMID). The aim of the present paper was to analyzed TAF in SMID to clarify which clinical variables might predict the occurrence of TAF, and adequate management for lifesaving.

Methods: Medical records at Metropolitan Fuchu Medical Center were retrospectively investigated for SMID between 1970 and 2000, and 10 TAF patients verified on operation or autopsy were identified. Details were reviewed including clinical status, emergency treatment at the occurrence of TAF, and operation and/or autopsy recordings.

Results: Four of 10 patients underwent successful operation and survived, while the other six died from hemorrhagic shock. Eight patients had tracheoinnominate artery fistula, the others had tracheocarotid artery fistula. Characteristic features as SMID such as etiology of brain disease, muscle tonus and convulsion were no apparent relevance to occurrence of TAF. All patients suffered from endotracheal granuloma extending to the arterial walls. Seven of 10 patients had re‐bleeding after stabilization of the first massive hemorrhage, especially fiber bronchoscopy to confirm the diagnosis of TAF precipitated to fatal re‐bleeding. One patient underwent interruption of the artery at relapse of TAF, the other three underwent suturing and had good outcome.

Conclusions: There were no apparent predictors of TAF in SMID. Tracheal granuloma was recognized and consequent on formation of TAF, so control of granuloma may prevent TAF. Fiber bronchoscopy for suspected TAF is not recommended because it precipitates fatal bleeding.
Barriers to vaccination among Japanese medical students: Focus group interviews
Authors: Okamoto Shigeru , Slingsby Brian Taylor , Nakayama Takeo , Nakamura Kanae , Fukuda Risa , Gomi‐Yano Harumi , Ohno Hiroshi , Matsumura Tadashi
Published: May 2008

Background: To date, medical schools and clinical training hospitals in Japan that require students to show immunity for measles, mumps, rubella, varicella (chickenpox), and hepatitis B prior to the commencement of residency are limited.

Methods: This qualitative study used focus group interviews to elucidate why medical students do not undergo vaccination. A total of three groups were identified and interviewed: group A (two men, three women), group B (two men, two women), group C (three men, two women). All recorded interviews were transcribed verbatim and analyzed according to the constant comparative method with a series of codes and categories.

Results: Findings elucidated that vaccination for medical students is not mandatory in Japan. Analysis found that the factors that influence willingness to be vaccinated can be divided into three dimensions (individual level, university/regional hospital level, governmental level) and two primary categories (cost of vaccination, awareness of vaccination) consisting of 10 codes. These factors did not exist in isolation, but have mutually overlapping areas.

Conclusions: Vaccination against vaccine‐preventable diseases is essential to a hospital’s infectious‐disease countermeasures and cannot continue to be overlooked by physicians (at the individual level), by universities and residency programs (at the community level) nor by the government (at the national level).
mRNA expression of T‐helper 1, T‐helper 2 cytokines in autoimmune hepatitis in childhood
Authors: Kawashima Hisashi , Kato Naoki , Ioi Hiroaki , Nishimata Shigeo , Watanabe Chiako , Kashiwagi Yasuyo , Takekuma Kouji , Hoshika Akinori , Szenborn Leszek , Bergman Kacprzak
Published: May 2008

Background: In the pathology of autoimmune hepatitis the immunity mechanism of T‐helper 1 (Th1) and Th2 cells was recently evaluated. The purpose of the present study was to measure the mRNA levels in peripheral mononuclear cells and serum cytokines obtained from children with autoimmune hepatitis for a better understanding of the mechanism.

Methods: Twenty‐five patients with autoimmune hepatitis and seven controls were enrolled. mRNA levels in peripheral mononuclear cells and serum cytokines were measured using real‐time polymerase chain reaction and immunoassay.

Results: Serum interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) were rarely detected. In contrast the IFN‐γ/β‐actin mRNA levels were high.

Conclusion: Autoimmune hepatitis is a Th1‐predominant state, therefore immune modulation therapies that target the control of Th1 cytokines should be used.
Changes in the presence of urine Helicobacter pylori antibody in Japanese children in three different age groups
Authors: Naito Yukiko , Shimizu Toshiaki , Haruna Hidenori , Fujii Tohru , Kudo Takahiro , Shoji Hiromichi , Suzuki Ken
Published: May 2008

Background: The rates of acquisition and spontaneous eradication of Helicobacter pylori infection in children has yet to be established. To determine these rates in children living in an urban region of Japan, the levels of urine H. pylori antibodies in children of three different age groups were measured.

Methods: A urine‐based enzyme‐linked immunosorbent assay (ELISA) was used to detect H. pylori antibodies twice within a 12 month interval over 2 years in 452 healthy children living in Tokyo. The subjects were divided into three groups: ages 4, 7, and 10 years.

Results: The prevalence of H. pylori infection was not different among the groups, being between 4.0% and 6.7%. The rate of turn to positivity for H. pylori infection was 1.5% per year and the rate of turn to negativity was 1.1%, but in the 10 year age group the rates were markedly lower than in the younger children.

Conclusion: The prevalence of H. pylori infection in Tokyo was 4.0–6.7% and was not different among 4, 7, and 10 year age groups.
Clinical predictors of respiratory syncytial virus infection in children
Authors: Durani Yamini , Friedman Marla J. , Attia Magdy W.
Published: May 2008

Aim: The aim of this study was to develop a clinical prediction model that identifies respiratory syncytial virus (RSV) infection in infants and young children.

Methods: Children ≤ 36 months of age with respiratory illness, who were suspected of having RSV infection, were enrolled in this prospective cohort study during the study period between January and February 2002. RSV testing was performed on all patients.

Results: Of the 197 patients enrolled in the study, 126 (64%) were positive for RSV and 71 (36%) patients were either negative for RSV or had a positive culture for viruses other than RSV. The mean age of patients was 5 months and 57% were male. Backwards stepwise logistic regression analysis identified cough (p = 0.000), wheezing (p = 0.002), and retractions (p = 0.008) as independent variables predictive of RSV infection. The prediction model had a sensitivity of 80% (95% CI, 71–87%), specificity of 68% (95% CI, 54–79%), positive predictive value 82% (95% CI, 74–89%), negative predictive value 66% (95% CI, 52–77), positive likelihood ratio 2.5 (95% CI, 1.8–3.7) and post‐test probability of 82%.

Conclusion: The combination of cough, wheezing and retractions predicts RSV infection in infants and young children.
Clinical significance of reduced systemic Windkessel size in severe ventricular septal defect patients
Authors: Kamisaka Keiko , Awa Shoichi , Akagi Michio , Watanabe Naoyuki , Kato Kaoru , Waragai Tadashi
Published: May 2008

Background: Large‐shunt ventricular septal defect (VSD) infants manifest varied serious symptoms resulting from peripheral arterial constriction to compensate for increased pulmonary blood flow (Qp) and concomitantly decreased systemic blood flow (Qs). The aim of the present paper was therefore to estimate the whole arterial space proximal to arterioles as the systemic Windkessel size (WS) in these infants and compare it with aortic volume (AV) estimated angiographically.

Method: Subjects were divided into three groups. Group 1a consisted of the so‐called balanced‐pressure VSD infants; group 1b consisted of those with normal or moderately increased pulmonary artery pressure (PAP) and highly augmented Qp; and group 2 consisted of those with a history of mucocutaneous lymph node syndrome as controls for Qp and pulmonary artery pressure. WS was computed from the Windkessel model, while the AV was calculated from the angiogram. Maximal systolic (WSs), mean (WSm), and minimum diastolic (WSd) WS were defined, computed, and compared.

Result: All WS were significantly smaller in group 1a; those of group 1b were between group 1a and group 2, with Qs‐dependent reduction of WS throughout all these three groups. WSs, WSm, and WSd had negative correlations with right ventricular systolic pressure/left ventricular systolic pressure in group 1a and group 1b. WSm, or the time averaged size, proved to be larger than the corresponding AV in all patients. The ratio of WSm/AV was significantly reduced in group 1a compared to group 1b and group 2, indicating that systemic arterial Windkessel space in severe VSD infants is significantly small, especially so in terms of space distal to aortic valve and proximal to arterioles.

Conclusion: In severe VSD infants the whole systemic arterial space proximal to arterioles (WS) is reduced in size according to severity.
CURRENT TECHNIQUES AND DEVICES FOR SAFE AND CONVENIENT ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) AND KOREAN EXPERIENCE OF ESD
Authors: Seol Sang‐Yong
Published: May 2008

Conventional endoscopic mucosal resection (EMR) technique has limitations in its capacity of achieving en bloc resection and, for lesions greater than 20 mm, removal in a piecemeal resection is often required. This leads to uncertainty as to whether or not the lesion has been completely removed and to an increase in local recurrence. To overcome this limitation, a new technique using specifically designed cutting devices, termed endoscopic submucosal dissection (ESD) has been developed. The present article discuss the current indication, new diagnostic, cutting and hemostatic devices and long‐term outcomes of EMR and ESD in early gastric cancer in Korea.
EVALUATION OF COLONOSCOPIC FINDINGS IN PATIENTS WITH DIARRHEAGENIC ESCHERICHIA COLI‐INDUCED HEMORRHAGIC COLITIS
Authors: Shigeno Takashi , Akamatsu Taiji , Fujimori Kazuya , Nakatsuji Yoshiyuki , Nakamura Yoshiyuki
Published: May 2008

Background:  We evaluated the clinical significance of colonoscopic findings in the acute infectious phase of diarrheagenic Escherichia coli (E. coli)‐induced hemorrhagic colitis.

Methods:  According to the strain of cultured pathogen, 38 patients with diarrheagenic E. coli‐induced hemorrhagic colitis were divided into an enterohemorrhagic E. coli (EHEC) group consisting of 20 patients and a non‐EHEC group consisting of 18 patients. The inflammatory findings were classified into five grades primarily according to the severity of the edema, and attendant on the degree of erythema. The inflammatory grade was determined for each part of the colon, rectum, and terminal ileum.

Results:  In the EHEC group, colonoscopy manifested characteristic findings of an inflammatory gradient in most patients. Additionally, in approximately half of the patients, longitudinal ulcers were observed in part of the transverse colon and/or the descending colon. In the non‐EHEC group, inflammatory findings were milder than those of EHEC‐induced colitis, and were restricted to the left‐side colon in most patients. In five of 18 patients, colonoscopic findings closely resembled those of transient ischemic colitis. In two of 18 patients, geographic ulcerations were seen in the left‐side colon. In 11 of 18 patients, only mild inflammations were observed in restricted segments of the colon.

Conclusions:  In the EHEC group, colonoscopy manifested characteristic findings not seen in other colonic diseases, and which are useful in predicting the probability of EHEC as the causative pathogen in patients with hemorrhagic colitis. In the non‐EHEC group, colonoscopic findings did not demonstrate the common inflammatory findings seen in the EHEC group.
SMALL SPHINCTEROTOMY COMBINED WITH ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION IN PATIENTS WITH BILLROTH II GASTRECTOMY
Authors: Minami Atsushi
Published: May 2008

Background:  The difficulty in orienting a duodenoscope or sphincterotome in Billroth II gastrectomy patients with an afferent loop is well known to experienced biliary endoscopists. In patients who have large biliary stones, stone retrieval is technically difficult, particularly when a mechanical lithotriptor is required. To address this issue a new technique was developed to gain greater access to the common bile duct.

Methods:  This new technique, small endoscopic sphincterotomy combined with endoscopic papillary large balloon dilation (SES + EPLD), was carried out in eight cases with Billroth II reconstruction. First, endoscopic sphincterotomy (ES) with a small incision was performed with a capped forward‐viewing endoscope. Then, endoscopic papillary dilation was performed with a large balloon to slowly match the size of the bile duct. Stones were then retrieved from the biliary duct with a balloon and a basket.

Results:  Stone retrieval was successful in all cases. Dilating the papillary orifice with a large balloon made it possible to remove large stones smoothly without crushing them. After dilation with the large balloon, there were some instances of oozing, but no perforations near the papilla.

Conclusions:  SES + EPLD was effective for the retrieval of large biliary stones without the use of mechanical lithotripsy for B‐II reconstruction cases. This new method, incorporating a slow dilation of the papilla up to a large diameter, could provide a larger opening than a large ES. This method of stone retrieval is easy to perform and may be able to play a role in the treatment of large and multiple bile duct stones with B‐II gastrectomy.
THERAPEUTIC OPTION FOR CHILDREN WITH ESOPHAGEAL CAUSTIC STENOSIS
Authors: Ortolan Erika Paiva , Bustamante Thais França , Takegawa Bonifácio Katsunori , Mendonça Fernanda Alves , Rodrigues Antonio Marcos , Mendes ÉLson Felix
Published: May 2008

Caustic ingestion is a leading cause of esophageal stenosis in children. Herein we report four cases using mitomycin C (MMC), a drug that inhibits cell division, protein synthesis and fibroblast proliferation and has been used as an adjuvant therapy for caustic esophageal stenosis that is recalcitrant to conventional dilation techniques. A retrospective chart review was performed on four pediatric patients with severe, recurrent esophageal stricture after caustic ingestion. The patients had required six to 20 esophageal dilations over a 4–16‐month period before MMC application. MMC was applied after an endoscopic dilation on saturated pledgets at a dose of 0.1 mg/mL for 2 min in the area where the strictures had been lyzed. From the four children treated with MMC, two have been asymptomatic for 16 and 20 months and two still require esophageal dilation, however, at longer intervals. All patients have shown satisfactory weight gain with food intake exclusively per oral. Although further studies are required, there is strong evidence that MMC is a safe and effective adjuvant therapy in the treatment of esophageal caustic stenosis.
RISK FACTORS IN SURGICAL MANAGEMENT OF THORACIC EMPYEMA IN ELDERLY PATIENTS
Authors: Hsieh Ming‐Ju , Liu Yun‐Hen , Chao Yin‐Kai , Lu Ming‐Shian , Liu Hui‐Ping , Wu Yi‐Cheng , Lu Hung‐I , Chu Yen
Published: May 2008

Background:  Although elderly patients with thoracic disease were considered to be poor candidates for thoracotomy before, recent advances in preoperative and postoperative care as well as surgical techniques have improved outcomes of thoracotomies in this patient group. The aim of this study was to investigate surgical risk factors and results in elderly patients (aged ≥70 years) with thoracic empyema.

Methods:  Seventy‐one elderly patients with empyema thoracis were enrolled and evaluated from July 2000 to April 2003. The following characteristics and clinical data were analysed: age, sex, aetiology of empyema, comorbid diseases, preoperative conditions, postoperative days of intubation, length of hospital stay after surgery, complications and mortality.

Results:  Surgical intervention, including total pneumonolysis and evacuation of the pleura empyema cavity, was carried out in all patients. Possible influent risk factors on the outcome were analysed. The sample group included 54 men and 17 women with an average age of 76.8 years. The causes of empyema included parapneumonic effusion (n = 43), lung abscess (n = 8), necrotizing pneumonitis (n = 8), malignancy (n = 5), cirrhosis (n = 2), oesophageal perforation (n = 2), post‐traumatic empyema (n = 2) and post‐thoracotomy complication (n = 1). The 30‐day mortality rate was 11.3% and the in‐hospital mortality rate was 18.3% (13 of 71). Mean follow up was 9.4 months and mean duration of postoperative hospitalization was 35.8 days. Analysis of risk factors showed that patients with necrotizing pneumonitis or abscess had the highest mortality rate (10 of 18, 62.6%). The second highest risk factor was preoperative intubation or ventilator‐dependency (8 of 18, 44.4%).

Conclusion:  This study presents the clinical features and outcomes of 71 elderly patients with empyema thoracis who underwent surgical treatment. The 30‐day surgical mortality rate was 11.3%. Significant risk factors in elderly patients with empyema thoracis were necrotizing pneumonitis, abscess and preoperative intubation/ventilation. This study also suggested that surgical treatment of empyema thoracic in elderly patients is recommended after failed conservative treatment because of the acceptably postoperative complication and mortality rate.
PELVIC DRAINAGE FOR ANTERIOR RESECTION REVISITED: USE OF DRAINS IN ANASTOMOTIC LEAKS
Authors: Tsujinaka Shingo , Kawamura Yutaka J. , Konishi Fumio , Maeda Takafumi , Mizokami Ken
Published: May 2008

Background:  Although routine pelvic drainage in colorectal surgery has not been justified in randomized controlled trials, nevertheless, many surgical institutes routinely use pelvic drains after anterior resection. Some reports have focused mainly on the effect of a pelvic drain on anastomotic complications. The purpose of this study was to assess the effectiveness of pelvic drainage in the management of anastomotic leak following anterior resection.

Methods:  One hundred and ninety‐six patients who underwent elective anterior resection for rectal cancer between April 2001 and June 2006 were included. Surgery was carried out with total or tumour‐specific mesorectal excision depending on the anastomotic level. Pelvic drainage was established in all patients using a silastic drain in a closed, gravitational method.

Results:  Anastomotic leaks occurred in 21 (10.7%) patients. Changes in drain content suggesting an anastomotic leak were observed in 15 (71.4%) patients, 11 of whom remained asymptomatic. Anastomotic leaks were resolved by conservative treatment with the existing drain in 10 (47.6%) patients and the other 11 (52.4%) required further surgical interventions. In patients who developed anastomotic leaks, the pelvic drain was kept in place for a median duration of 52 days (range 32–169 days). Complications related to the drain included stitch abscess in five patients, herniation of the omentum in two and bowel perforation due to the drain in one patient.

Conclusion:  Pelvic drainage may act as an early detector of anastomotic leaks and reduce the need for reoperation in selected patients undergoing rectal cancer surgery.
COLORECTAL CANCER IN THE ELDERLY. IS THERE A ROLE FOR SAFE AND CURATIVE SURGERY?
Authors: Basili Giancarlo , Lorenzetti Luca , Biondi Graziano , Preziuso Enrico , Angrisano Claudio , Carnesecchi Paolo , Roberto Eugenia , Goletti Orlando
Published: May 2008

Background:  Recent reports place colorectal cancer (CRC) as the third most common cancer for both sexes. Elderly patients are often viewed as high‐risk surgical candidates with high rates of emergency presentations and perioperative mortality. The aim of our study was to examine the characteristics and perioperative morbidity and mortality rates of elderly patients presented to CRC surgery.

Methods:  We retrospectively studied 248 patients who underwent surgery for CRC at our institution between July 2003 and December 2005. Risk factors included sex, age, cancer localization, Dukes’ and TNM classification, blood transfusion, preoperative Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity score and mode of presentation. Primary outcome was perioperative death.

Results:  The study consisted of 143 men and 105 women. One hundred and thirty‐four (54%) patients were more than 75 years of age. In the two older groups, cancer was more common in the proximal colon than in the youngest age group (P = 0.001). Of the 25 resections carried out as emergency, 20 were in those who were more than 75 years of age (P < 0.001). In elective procedure, perioperative mortality scores were 3.1% in those who were more than 75 years of age versus 0% in those less than 75 years, meanwhile in emergency, rates of 24 versus 0% (P = not significant) were registered. In Cox multivariate regression analysis, age and mode of presentation reached statistical significance.

Conclusion:  Old age itself is not an independent negative prognostic factor for CRC surgery. Although emergency operations were associated with poor outcome, most patients survived and left the hospital. This study suggests that, whenever possible, curative intent should be applied in patients with CRC, irrespective of the age.