bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of New Maize Genes Putatively Involved in Cytokinin Metabolism and Their Expression during Osmotic Stress in Relation to Cytokinin Levels
Authors: Vyroubalová Šárka , Václavíková Kateřina , Turečková Veronika , Novák Ondřej , Šmehilová Mária , Hluska Tomáš , Ohnoutková Ludmila , Frébort Ivo , Galuszka Petr
Published: July 2009

Plant hormones, cytokinins (CKs), have been for a long time considered to be involved in plant responses to stress. However, their exact roles in processes linked to stress signalization and acclimatization to adverse environmental conditions are unknown. In this study, expression profiles of the entire gene families of CK biosynthetic and degradation genes in maize (Zea mays) during development and stress responses are described. Transcript abundance of particular genes is discussed in relation to the levels of different CK metabolites. Salt and osmotic stresses induce expression of some CK biosynthetic genes in seedlings of maize, leading to a moderate increase of active forms of CKs lasting several days during acclimatization to stress. A direct effect of CKs to mediate activation of stress responses does not seem to be possible due to the slow changes in metabolite levels. However, expression of genes involved in cytokinin signal transduction is uniformly down-regulated within 0.5 h of stress induction by an unknown mechanism. cis-Zeatin and its derivatives were found to be the most abundant CKs in young maize seedlings. We demonstrate that levels of this zeatin isomer are significantly enhanced during early stress response and that it originates independently from de novo biosynthesis in stressed tissues, possibly by elevated specific RNA degradation. By enhancing their CK levels, plants could perhaps undergo a reduction of growth rates maintained by abscisic acid accumulation in stressed tissues. A second role for cytokinin receptors in sensing turgor response is hypothesized besides their documented function in CK signaling.
Randomized clinical trial comparing 5% and 1% topical minoxidil for the treatment of androgenetic alopecia in Japanese men
Authors: TSUBOI Ryoji , ARANO Osamu , NISHIKAWA Tooru , YAMADA Hidekazu , KATSUOKA Kensei
Published: July 2009

Minoxidil is efficacious in inducing hair growth in patients with androgenetic alopecia by inducing hair follicles to undergo transition from the early to late anagen phase. Although the efficacy of 1% topical minoxidil has been confirmed in Japan, no controlled study of 5% topical minoxidil has been conducted using male Japanese subjects. The objective of this trial was to verify the superiority in clinical efficacy of 5% topical minoxidil to 1% topical minoxidil in a double‐blind controlled study with male, Japanese androgenetic alopecia patients as the subjects. The trial included 300 Japanese male patients aged 20 years or older with androgenetic alopecia who were administered either 5% topical minoxidil (n = 150) or 1% topical minoxidil (n = 150) for 24 weeks. The mean change from the baseline in non‐vellus hair/cm2, the primary efficacy variable, was 26.4 (n = 142) in the 5% topical minoxidil group and 21.2 (n = 144) in the 1% topical minoxidil group at 16 weeks, the main time point for the evaluation. The difference between the groups was significant (P = 0.020). The incidence of adverse events was 8.7% (13/150) in the 5% group and 5.3% (8/150) in the 1% group, with no significant difference between the groups (χ2‐test: P = 0.258). Our findings confirmed the superiority of 5% topical minoxidil to 1% topical minoxidil in treating Japanese men with androgenetic alopecia.
Metastatic extramammary Paget’s disease treated with paclitaxel and trastuzumab combination chemotherapy
Authors: TAKAHAGI Shunsuke , NODA Hideki , KAMEGASHIRA Akiko , MADOKORO Naoki , HORI Ikuko , SHINDO Hajime , MIHARA Shouji , HIDE Michihiro
Published: July 2009

In the treatment of metastatic breast cancer, trastuzumab, a recombinant monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is effective when tumor cells overexpress HER2 protein. Although some cases of extramammary Paget’s disease (EMPD) also express HER2 protein, no case of EMPD has been reported to be treated with trastuzumab. A 75‐year‐old man who suffered from EMPD of the scrotum and inguinal region underwent a local excision and lymph node dissection. Tumor cells invaded the dermis and lymph nodes. Although he was postoperatively treated with adjuvant chemotherapies, metastatic skin lesions appeared and spread over his left thigh, rapidly and widely. Tumor cells disseminated along lymph vessels in the dermis and overexpressed HER2 protein. We administered paclitaxel and trastuzumab according to a protocol for HER2‐positive metastatic breast cancers. The skin metastasis dramatically decreased during the regimen and a histopathological examination showed that most of HER2‐positive tumor cells diminished. Six months later, metastases were found in the central nervous system (CNS), but no other metastases were found in the skin, visceral organs or lymph nodes. Trastuzumab and paclitaxel‐combination with the assessment of central nervous system lesions should be considered as an option for the treatment of HER2‐positive EMPD.
Dental infection associated with nummular eczema as an overlooked focal infection
Authors: TANAKA Tomoko , SATOH Takahiro , YOKOZEKI Hiroo
Published: July 2009

Nummular eczema is a common skin disease, but the pathoetiology has yet to be elucidated. We report here a case of severe nummular eczema. Although the skin lesions were resistant to topical corticosteroids, the patient became responsive to treatment and no recurrence was noted after the eradication of dental infections. We have experienced 13 similar cases of nummular eczema with widely‐distributed skin lesions. The cases had moderate to severe odontogenic infections, which were detected by panorama X‐ray screening test. In 11 patients, skin lesions partially or completely improved after the dental treatment. Latent odontogenic infection may thus be an aggravating factor in treatment‐resistant nummular eczema.
Logical structures extracted from metastasis experiments
Authors: Maru Yoshiro
Published: July 2009

An inductive argument of metastasis with a metaphor of seed and soil was made by Stephen Paget in 1889. It is commonly held that metastasis is dependent on both the organ from which the primary tumors originate, and the organs to which the tumor cells travel. The assumption is based on the statistical observation of a number of autopsy samples. Here I attempt to establish a theory on the mechanisms of metastasis with experimental evidence. I propose that dysregulation of pro‐inflammatory Toll‐like receptor 4 signaling, stimulated by its endogenous ligands, establishes pre‐metastatic soil. Once specific parameters are established, deductive judgments could be possible to predict to which organ a given tumor metastasizes. (Cancer Sci 2009)
Bone morphogenetic protein 7 induces mesenchymal‐to‐epithelial transition in melanoma cells, leading to inhibition of metastasis
Authors: Na Yi‐Rang , Seok Seung‐Hyeok , Kim Dong‐Jae , Han Ju‐Hee , Kim Tae‐Hyoun , Jung Hyun , Lee Byoung‐Hee , Park Jae‐Hak
Published: July 2009

Bone morphogenetic protein (BMP) 7 counteracts physiological epithelial‐to‐mesenchymal transition, a process that is indicative of epithelial plasticity in developmental stages. Because epithelial‐to‐mesenchymal transition and its reversed process mesenchymal‐to‐epithelial transition (MET) are also involved in cancer progression, we investigated whether BMP7 plays a role in WM‐266‐4 melanoma cell growth and metastasis. An MTT assay was conducted in WM‐266‐4 and HEK293T cell lines to show the cell growth inhibition ability of BMP7 and cisplatin. Semiquantitative RT‐PCR was used to determine MET in morphologically changed BMP7‐treated melanoma cells. MET‐induced cells expressed less a basic helix‐loop‐helix transcription factor (TWIST) in western blot analysis, and we confirm that BMP receptor (Alk2) siRNA transduction could restore TWIST protein expression via blocking of Smad 1, 5 and 8 signaling. Matrigel invasion and cell migration assays were done to investigate the BMP7‐induced metastasis inhibition ability. BMP7 treatment only slightly reduced cell growth rate, but induced apparent MET. BMP7 also reduced the invasion and migration ability. Furthermore, BMP7 reduced the resistance of WM‐266‐4 cells to cisplatin. Collectively, our findings indicate that the metastatis inhibition ability of BMP7 is involved in MET, and that BMP7 could be used as a potential metastasis inhibitor in human melanoma cells. (Cancer Sci 2009)
Angiotensin converting enzyme inhibitor induced angio‐oedema: a review of the pathophysiology and risk factors
Authors: Hoover T. , Lippmann M. , Grouzmann E. , Marceau F. , Herscu P.
Published: July 2009

Angio‐oedema (AE) is a known adverse effect of angiotensin converting enzyme inhibitor (ACE‐I) therapy. Over the past several decades, evidence of failure to diagnose this important and potentially fatal reaction is commonly found in the literature. Because this reaction is often seen first in the primary care setting, a review was undertaken to analyse and document the keys to both diagnostic criteria as well as to investigate potential risk factors for ACE‐I AE occurrence. A general review of published literature was conducted through Medline, EMBASE, and the Cochrane Database, targeting ACE‐I‐related AE pathomechanism, diagnosis, epidemiology, risk factors, and clinical decision making and treatment. The incidence and severity of AE appears to be on the rise and there is evidence of considerable delay in diagnosis contributing to significant morbidity and mortality for patients. The mechanism of AE due to ACE‐I drugs is not fully understood, but some genomic and metabolomic information has been correlated. Additional epidemiologic data and clinical treatment outcome predictors have been evaluated, creating a basis for future work on the development of clinical prediction tools to aid in risk identification and diagnostic differentiation. Accurate recognition of AE by the primary care provider is essential to limit the rising morbidity associated with ACE‐I treatment‐related AE. Research findings on the phenotypic indicators relevant to this group of patients as well as basic research into the pathomechanism of AE are available, and should be used in the construction of better risk analysis and clinical diagnostic tools for ACE‐I AE.

Cite this as: T. Hoover, M. Lippmann, E. Grouzmann, F. Marceau and P. Herscu,Clinical & Experimental Allergy, 2010 (40) 50–61.
BAFF: a local and systemic target in autoimmune diseases
Authors: Moisini I , Davidson A
Published: July 2009

BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory sites in which there is lymphoid neogenesis. BAFF antagonism has been used in several autoimmune disease models, resulting in B cell depletion, decreased activation of T cells and dendritic cells (DC) and a reduction in the overall inflammatory burden. BAFF, through its interaction with BAFF-R, is required for survival of late transitional, marginal zone and mature naive B cells, all of which are depleted by BAFF blockade. Through their interactions with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation protein), BAFF and its homologue APRIL (a proliferation-inducing ligand), support the survival of at least some subsets of plasma cells; blockade of both cytokines results in a decrease in serum levels of immunoglobulin (Ig)G. In contrast, neither BAFF nor APRIL is required for the survival or reactivation of memory B cells or B1 cells. BAFF also helps DC maturation and interleukin (IL)-6 release and is required for proper formation of a follicular dendritic cell (FDC) network within germinal centres, although not for B cell affinity maturation. The clinical efficacy of BAFF blockade in animal models of autoimmunity may be caused both by the decline in the number of inflammatory cells and by the inhibition of DC maturation within target organs. Blockade of BAFF and its homologue APRIL are being explored for human use; several Phase I and II clinical trials of BAFF inhibitors for autoimmunity have been completed and Phase III trials are in progress.
Ecosystem engineering by tubificid worms stimulates macrophyte growth in poorly oxygenated wetland sediments
Authors: Mermillod‐Blondin Florian , Lemoine Damien G.
Published: July 2009

1. Positive interactions driven by ecosystem engineers have been determined to be important community forces in stressed environments. By ameliorating habitat conditions, ecosystem engineering can create available ecological niches for other species. In poorly oxygenated sediments of freshwater wetlands, small invertebrates such as tubificid worms and chironomid larvae are known to function as active bioturbators; however, their effects on the growth and physiology of organisms which are constrained by low oxygenation of sediments have never been studied.

2. We examined whether the common bioturbator, Tubifex tubifex, significantly influences the growth and the physiological state of two plant species, Elodea canadensis and Myriophyllum spicatum, in experimental systems simulating a water–sediment interface of wetlands. We also quantified the influence of plant–animal interactions on biogeochemical processes (fluxes of oxygen and nitrogen at the water–sediment interface) and microbial compartment in sediments.

3. Tubificid worms stimulated growth of aboveground and belowground biomasses of the two plants through reduction in the anoxic stress in sediments. Myriophyllum spicatum, which was the best adapted to sedimentary anaerobic conditions, essentially increased its biomass whereas E. canadensis, less adapted to anaerobic conditions, shifted its root metabolism from anaerobic to aerobic.

4. Biogeochemical processes were not significantly influenced by plant–animal interactions: (i) oxygen flux from overlying water to sediments probably reached a threshold that could not be raised by the increased plant biomass induced by worms and (ii) nitrogen fluxes were essentially linked to bioturbation activities of worms.

5. Our study confirmed that the reduction in constraining variables by physical habitat modifications (ecosystem engineering) may play a crucial role in community and ecosystem processes. The fact that positive interactions measured between ecosystem engineers and plant species in anoxic wetland sediments were highly dependent on the ecophysiology of plant species suggests an extension of this first study to a wide range of macrophytes in order to determine the main plant functional traits driving plant–animal interactions in wetland sediments.
Pharmacokinetic study of a high‐purity factor IX concentrate (Factor IX Grifols®) with a 6‐month follow up in previously treated patients with severe haemophilia B
Authors: AZNAR J. A. , CABRERA N. , MATYSIAK M. , ZAWILSKA K. , GERCHEVA L. , ANTONOV A. , MONTAÑÉS M. , PÁEZ A. M. , LISSITCHKOV T.
Published: July 2009

Summary.  Optimal replacement treatment in haemophilia B patients requires a good understanding of the pharmacokinetics of factor IX (FIX).

The aim of this study was to compare the pharmacokinetic profile of Factor IX Grífols®, a highly purified human FIX concentrate with two specific pathogen inactivation/removal steps, to that of available FIX preparations.

The study was an open, non‐randomized trial including 25 male subjects older than 12 years of age with severe haemophilia B. Pharmacokinetic profile of the FIX preparation regularly used by the subjects was determined as control. Pharmacokinetic profile of Factor IX Grifols® was determined twice, one 7–15 days after control assessment and second after a 6 months period had elapsed.

Results showed that all products had peak plasma levels of FIX:C within 30 min. Mean recovery was 1.3 ± 0.3 IU dL−1 per IU kg−1 for Factor IX Grifols® and 1.0 ± 0.3 IU dL−1 per IU kg−1 for control products (P < 0.001). The mean terminal half‐life (t1/2) for Factor IX Grifols® was 26.7 h and 26.8 h for control product. Pharmacokinetic parameters after 6 months of treatment with Factor IX Grifols® did not statistically differ from the parameters obtained with the first infusion. There were no adverse events related to Factor IX Grifols® for the duration of the study.

In conclusion, Factor IX Grifols® has adequated pharmacokinetic properties comparable to the control plasma‐derived FIX and these parameters remain stable after 6 months of treatment. Factor IX Grifols® can be an effective and safe plasma‐derived FIX concentrate for replacement therapy in haemophilia B patients.
Bioprosthetic heart valves: modes of failure
Authors: Siddiqui Raheela Fareed , Abraham Johnathan Rajiv , Butany Jagdish
Published: July 2009

Valve replacement started in 1960, with the surgeon now having a significant variety of prosthetic heart valves from which to choose. These valves are broadly divided into mechanical heart valves (MHV) and bioprosthetic heart valves (BHV). Improvements in the performance and ease of usage of BHV without the need for anticoagulant therapy are among the desired features of BHV and hence the increasingly preferred choice over their mechanical counterparts. However, with increased use the post‐implantation complications have become more apparent, and these include: calcification, cusp tears, pannus growth, infective endocarditis, valve thrombosis and other factors specific to valve type. In this review we describe these complications in order to bring awareness among surgeons, clinicians and pathologists. Diagnosis, treatment and preventive measures, if taken in a timely manner, can help reduce their impact and further enhance the quality of life of patients with prosthetic heart valves.
Histopathological work‐up and interpretation of sentinel lymph nodes removed for vulvar squamous cell carcinoma
Authors: Regauer Sigrid
Published: July 2009

Aims:  To evaluate the work‐up of sentinel lymph nodes (SLNs) removed for vulvar pT1–pT2 squamous cell carcinoma (SCC). Inguinal lymphadenectomy yields metastases in only 30% of cases. Patients with missed inguinal disease, however, have a risk of dying from systemic disease. SLN dissections reduce morbidity, but work‐up should reliably identify metastatic disease.

Methods and results:  All SLNs removed from 38 patients with pT1–pT2 SCC and clinically negative inguinal lymph nodes were submitted for frozen section analysis. When negative, SLN were formalin‐fixed, sectioned entirely at 330‐μm intervals to produce three slides per millimetre [two haematoxylin and eosin (H&E) stained slides; one slide for immunohistochemistry]. If screening of H&E‐stained sections was negative, all remaining slides were subjected to immunohistochemistry with an antibody to cytokeratin. Twenty‐five of 38 patients (66%) were pN0, 7/38 (18%) had metastases on frozen sections/H&E stains. Immunohistochemistry detected micrometastases in two patients and single tumour cells and anucleate cell structures in four patients. In 12/13 patients the SLN metastases, including all single‐cell deposits, were from lichen sclerosus (LS)‐associated SCC. Twelve of 13 patients with metastases had a pT2 SCC.

Conclusions:  Micrometastases and single tumour cell deposits in SLNs are typical of LS‐associated vulvar SCC. Single tumour cell deposits in SNLs should be regarded as ‘positive’. Identification requires serial sectioning and immunohistochemical analysis of all removed SLNs.
Immunohistochemical and molecular genetic profiling of acquired cystic disease‐associated renal cell carcinoma
Authors: Pan Chin‐Chen , Chen Yann‐Jang , Chang Liang‐Che , Chang Yen‐Hwa , Ho Donald M‐T
Published: July 2009

Aims:  Acquired cystic disease‐associated renal cell carcinoma (ACD‐associated RCC) is a unique neoplasm that specifically develops in the background of acquired cystic disease of the kidney. The aim was to analyse nine ACD‐associated RCCs from three patients to determine their immunohistochemical and molecular characteristics using immunohistochemistry, comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH).

Methods and results:  ACD‐associated RCC preferentially expressed proximal nephron phenotype (CD10+/RCC marker+/α‐methylacyl‐CoA racemase+/glutathione S‐transferase‐α+/BerEP4+/cytokeratin 7–/E‐cadherin–/high‐molecular‐weight cytokeratin−/MOC31−). CGH combined with FISH demonstrated non‐random chromosomal gains clustering on chromosomes 3 (8/9), 7 (6/9), 16 (7/9), 17 (4/9) and Y (5/9). Chromosomal losses were uncommon. The chromosomal aberrations in all multifocal tumours were not identical for the same kidney or for the same patient, indicating a ‘field effect’ that induces multiple independent clones.

Conclusions:  Although the genetic profiles of ACD‐associated RCC showed some similarity to those of papillary RCC, ACD‐associated RCC distinctly revealed frequent gains on chromosomes 3 and Y. ACD‐associated RCC is characterized not only by its particular clinical setting and histology, but also by its unique immunohistochemical and molecular genetic profiles.
Wolf survival and population trend using non‐invasive capture–recapture techniques in the Western Alps
Authors: Marucco Francesca , Pletscher Daniel H. , Boitani Luigi , Schwartz Michael K. , Pilgrim Kristy L. , Lebreton Jean‐Dominique
Published: July 2009

1. Reliable estimates of population parameters are often necessary for conservation management but these are hard to obtain for elusive, rare and wide‐ranging species such as wolvesCanis lupus.This species has naturally recolonized parts of its former habitat in Western Europe; however, an accurate and cost‐effective method to assess population trend and survival has not been implemented yet.

2. We used open‐model capture–recapture (CR) sampling with non‐invasive individual identifications derived from faecal genotyping to estimate survival and trend in abundance for wolves in the Western Alps between 1999 and 2006. Our sampling strategy reduced individual heterogeneity in recaptures, thus minimizing bias and increasing the precision of the estimates.

3. Young wolves had lower apparent annual survival rates (0·24 ± 0·06) than adult wolves (0·82 ± 0·04); survival rates were lower in the summer than in the winter for both young and adults. The wolf population in the study area increased from 21 ± 9·6 wolves in 1999 to 47 ± 11·2 wolves in late winter 2005; the population growth rate (λ = 1·04 ± 0·27) was lower than that recorded for other recolonizing wolf populations.

4. We found a positive trend in wolf abundance, regardless of the method used. However, the abundance estimate based on snow‐tracking was on average 36·2% (SD = 13·6%) lower than that from CR modelling, because young dispersing wolves are likely to have lower sign detection rates in snow‐track surveys, a problem adequately addressed by CR sampling.

5. Synthesis and applications.We successfully implemented a new method to assess large carnivore population trend and survival at large spatial scales. These are the first such estimates for wolves in Italy and in the Alps and have important management implications. Our approach can be widely applied to broader spatial and temporal scales for other elusive and wide‐ranging species in Europe and elsewhere.
Clinical spectrum of gram‐positive infections in lung transplantation
Authors: Gupta M.R. , Valentine V.G. , Walker Jr J.E. , Lombard G.A. , LaPlace S.G. , Seoane L. , Taylor D.E. , Dhillon G.S.
Published: July 2009

Purpose. Gram‐positive (GP) organisms are among the most common cause of infections in early postsurgical and immunocompromised populations. Patients recovering from lung transplantation (LT) are particularly susceptible owing to the physiologic stress imposed by surgery and induction with intense immunosuppression. Sites, types, and timing of GP infections following LT  are not well documented. This report describes the clinical spectrum of GP infections and their effects on surgical airway complications (SAC) and bronchiolitis obliterans syndrome (BOS) following LT.

Methods and materials. Data were collected from 202 patients undergoing 208 LT procedures at a single institution between November 1990 and November 2005. Data were retrospectively analyzed according to timing, location, and causative pathogen.

Results. In the median follow‐up period of 2.7 years (range, 0–13.6 years), 137 GP infections were confirmed in 72 patients. Sites of infection included respiratory tract (42%), blood (27%), skin, wound and catheter (21%), and other (10%). GP pathogens identified were Staphylococcus species (77%), Enterococcus species (12%), Streptococcus species (6%), Pneumococcus (4%), and Eubacterium lentum (1%). The likelihood of SAC and BOS was increased in lung allograft recipients with GP pneumonia as compared with those without (hazard ratio 2.1; 95% confidence interval=1.5–3.1).

Conclusions. GP organisms were responsible for infections in 40% of lung allograft recipients and most commonly isolated from the respiratory tract and blood stream. Staphylococcal species were most frequently identified, 42% of which were methicillin‐resistant Staphylococcus aureus (MRSA). Given the strong association of respiratory tract infections with the development of SAC and BOS, empiric antimicrobial strategies after LT should include agents directed against GP organisms, especially MRSA.
Mycobacterium avium‐intracellulare‐associated acute interstitial nephritis: a rare cause of renal allograft dysfunction
Authors: Rawla M.S. , Kozak A. , Hadley S. , LeCates W.W.
Published: July 2009

Abstract: Nontuberculous mycobacterium (NTM) infections are unusual in the renal transplant population. We present a case of disseminated Mycobacterium avium‐intracellulare in a renal transplant recipient who was negative for human immunodeficiency virus infection. Our patient developed renal allograft dysfunction in the setting of disseminated disease and reduced immunosuppression. Transplant biopsy showed acute interstitial nephritis with granulomas and acid‐fast bacilli. Acute renal failure resolved completely with further reductions in immunosuppression and anti‐mycobacterial therapy. Our patient demonstrates the challenges in diagnosis and treatment of this rare infectious complication.
Long‐term prognosis of patients with endoscopically treated postoperative bile duct stricture and bile duct stricture due to chronic pancreatitis
Authors: Sakai Yuji , Tsuyuguchi Toshio , Ishihara Takeshi , Yukisawa Seigo , Sugiyama Harutoshi , Miyakawa Kaoru , Kuroda Yasuhisa , Yamaguchi Taketo , Ozawa Shinichi , Yokosuka Osamu
Published: July 2009

Aim:  To compare the outcome of endoscopic therapy for postoperative benign bile duct stricture and benign bile duct stricture due to chronic pancreatitis, including long‐term prognosis.

Methods:  The subjects were 20 patients with postoperative benign bile duct stricture and 13 patients with bile duct stricture due to chronic pancreatitis who were 2 years or more after initial therapy. The patients underwent transpapillary drainage with tube exchange every 3 to 6 months until being free from the tube. Successful therapy was defined as a stent‐free condition without hepatic disorder.

Results:  Endoscopic therapy was successful in 90% (18/20) of the patients with postoperative bile duct stricture. The stent was removed (stent free) in 100% (20/20) of the patients, but jaundice resolved in only 10% (2/20) of patients while biliary enzymes kept increasing. Restricture occurred in 5% (1/20) of the patients, but after repeat treatment the stent could be removed. In patients with bile duct stricture due to chronic pancreatitis the therapy was successful in only 7.7% (1/13) of the patients; the stent was retained in 92.3% (12/13) of the patients during a long period. Severe acute pancreatitis occurred in 3.0% (1/33) of the patients as an accidental symptom attributable to endoscopic retrograde cholangiopancreatography (ERCP); however, it remitted after conservative treatment.

Conclusion:  Our results further confirm the usefulness of endoscopic therapy for postoperative benign bile duct strictures and good long‐term prognosis of the patients.
Comparison of p.o. or i.v. proton pump inhibitors on 72‐h intragastric pH in bleeding peptic ulcer
Authors: Javid Gul , Zargar Showkat Ali , Riyaz‐u‐saif.  , Khan Bashir Ahmad , Yatoo Ghulam Nabi , Shah Altaf Hussain , Gulzar Ghulam Mohammad , Sodhi Jaswinder Singh , Khan Mushtaq Ahmad
Published: July 2009

Background and Aims:  After successful endoscopic hemostasis in bleeding peptic ulcer, addition of proton pump inhibitors reduce the rate of recurrent bleeding by maintaining intragastric pH at neutral level. The aim of the present study was to evaluate the effect of various proton pump inhibitors given through different routes on intragastric pH over 72 h after endoscopic hemostasis in bleeding peptic ulcer.

Methods:  Ninety consecutive patients who had successful endoscopic therapy of bleeding peptic ulcer underwent 72‐h continuous ambulatory intragastric pH study, were randomly assigned to receive p.o. omeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg omeprazole followed by infusion 8 mg/h for 72 h. Oral pantoprazole 80 mg bolus followed by 80 mg every 12 h for 72 h or i.v. 80 mg pantoprazole followed by infusion of 8 mg/h for 72 h. Oral rabeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg rabeprazole followed by infusion 8 mg/h for 72 h. Five patients received no treatment after successful endoscopic therapy and underwent 72‐h pH study.

Results:  Mean 72‐h intragastric pH for p.o. omeprazole was 6.56 versus 6.93 for omeprazole infusion (P = 0.48). Mean 72‐h intragastric pH for p.o. pantoprazole was 6.34 versus 6.32 for pantoprazole infusion (P = 0.62). Mean 72‐h intragastric pH for rabeprazole p.o. was 6.11 versus 6.18 rabeprazole i.v. (P = 0.55). Mean 72‐h pH for the no proton pump inhibitor group was 2.04.

Conclusion:  There was no significant difference among various proton pump inhibitors given through different routes on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.
Delayed endoscopy as a risk factor for in‐hospital mortality in cirrhotic patients with acute variceal hemorrhage
Authors: Hsu Yao‐Chun , Chung Chen‐Shuan , Tseng Cheng‐Hao , Lin Tzu‐Ling , Liou Jyh‐Ming , Wu Ming‐Shiang , Hu Fu‐Chang , Wang Hsiu‐Po
Published: July 2009

Background and Aims:  Risk factors for mortality in acute variceal hemorrhage remain incompletely understood. Whether endoscopy timing is associated with risk of mortality has not been investigated. We aimed to investigate risk factors for in‐hospital mortality in cirrhotic patients with acute variceal hemorrhage, with emphasis on endoscopy timing.

Methods:  Three hundred and eleven (73% male and 23% female) consecutive cirrhotic patients presenting with acute variceal hemorrhage from July 2004 to July 2007 were investigated. The univariate association of endoscopy timing as the predictor for in‐hospital mortality was examined. Independent risk factors for mortality were determined by multivariate logistic regression analysis consisting of clinical, laboratory and endoscopic parameters.

Results:  Twenty‐five (8.04%) patients died within admission. By plotting the receiver operating curve of endoscopy timing for mortality, we selected 15 h as the optimal cut‐off point to define delayed endoscopy. Multivariate regression analysis revealed that independent risk factors predictive for in‐hospital mortality included delayed endoscopy performed 15 h after admission (adjusted odds ratio [aOR] = 3.67; 95% confidence interval [CI], 1.27–10.39), every point increment of model for end‐stage liver disease (MELD) score (aOR = 1.16; 95% CI, 1.07–1.25), failure of the first endoscopy (aOR = 4.36; 95% CI, 1.54–12.30) and hematemesis as the chief complaint (compared with melena, aOR = 8.66; 95% CI, 1.06–70.94).

Conclusion:  Delayed endoscopy for more than 15 h, high MELD score, failure of the first endoscopy and hematemesis are independent risk factors for in‐hospital mortality in cirrhotic patients with acute variceal hemorrhage.
Non‐invasive model predicting clinically‐significant portal hypertension in patients with advanced fibrosis
Authors: Park Seung Ha , Park Tae Eun , Kim Young Mook , Kim Sung Jung , Baik Gwang Ho , Kim Jin Bong , Kim Dong Joon
Published: July 2009

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily‐available data in predicting the presence of significant portal hypertension and esophageal varices.

Methods:  This study included a total of 61 consecutive treatment‐naive patients with advanced fibrosis (METAVIR F3, F4), established by liver biopsy. All patients underwent subsequent HVPG measurement and upper gastrointestinal endoscopy within 1 week of liver biopsy.

Results:  Seventeen patients (F3, 2/26; F4, 15/35) had clinically‐significant portal hypertension (HVPG ≥ 10 mmHg). The Risk Score for predicting significant portal hypertension was 14.2 − 7.1 × log10 (platelet [109/L]) + 4.2 × log10 (bilirubin [mg/dL]). The area under the receiver–operator curve (AUC) curve was 0.91 (95% confidence interval [CI], 0.84–0.98). The optimized cut‐off value (Risk Score = −1.0) offered a sensitivity of 88% (95% CI, 62–98%) and a specificity of 86% (95% CI, 72–94%). The AUC of the Risk Score in predicting varices was 0.82 (95% CI, 0.67–0.98). The cut‐off had a sensitivity of 82% (95% CI, 48–97%) and a specificity of 76% (95% CI, 62–86%).

Conclusion:  A predictive model that uses readily‐available laboratory results may reliably identify advanced fibrosis patients with clinically‐significant portal hypertension as well as esophageal varices. However, before accepted, the results of the current study certainly should be validated in larger prospective cohorts.
Severe acute exacerbation of chronic hepatitis B: A unique presentation of a common disease
Authors: Wong Vincent Wai‐Sun , Chan Henry Lik‐Yuen
Published: July 2009

Severe acute exacerbation is a unique presentation of chronic hepatitis B characterized by very high alanine aminotransferase level accompanied by jaundice and hepatic decompensation. The underlying pathogenesis is likely related to excessive immune clearance, which may be related to the genotype of hepatitis B virus. The mortality is very high once hepatic encephalopathy develops, but some patients can recover to almost normal liver function in contrast to patients with end‐stage liver cirrhosis. This condition should be differentiated from acute hepatitis B and other causes of acute hepatitis must be excluded. Conventional prognostic systems may not be applicable to severe acute exacerbation of chronic hepatitis B. In general, patients who have thrombocytopenia, hyperbilirubinemia and coagulopathy have a higher risk of mortality regardless of the serum alanine aminotransferase levels. There is no evidence that lamivudine treatment can reduce the short‐term mortality of severe acute exacerbation. However, patients with severe acute exacerbation tend to have a higher rate of maintained virological response, higher rate of hepatitis B e antigen seroconversion and low rate of drug resistance on extended lamivudine treatment as compared to other chronic hepatitis B patients. Virological relapse and severe hepatitis reactivation is common after treatment cessation and therefore long‐term antiviral treatment is recommended. Liver transplantation, particularly living donor liver transplantation, should be considered for patients who develop hepatic failure secondary to severe acute exacerbation.
Rescue strategies against non‐steroidal anti‐inflammatory drug‐induced gastroduodenal damage
Authors: Lim Yun Jeong , Lee Jeong Sang , Ku Yang Suh , Hahm Ki‐Baik
Published: July 2009

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti‐inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of “coxibs” (selective cyclooxygenase‐2 [COX‐2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID‐induced gastroduodenal damage beyond COX‐2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID‐associated gastroduodenal damage will be described.
A case of renal mucinous tubular and spindle cell carcinoma
Authors: Kato Manabu , Soga Norihito , Arima Kiminobu , Sugimura Yoshiki
Published: July 2009

A 33‐year‐old man was hospitalized for treatment of a left renal tumor. The radiological findings were consistent with those of a left renal cell carcinoma (RCC). Subsequently, a radical nephrectomy was carried out. Macroscopic examination showed that a well‐demarcated tumor measuring 2.9 × 2.6 × 2.5 cm was present in the middle portion of the resected kidney. The cut surface of the tumor was grayish‐white in color. Pathological examination of the resected specimen showed a mucinous tubular and spindle cell carcinoma of the kidney (MTSCC‐K). MTSCC‐K is a low‐grade renal epithelial neoplasm that has recently been recognized as a specific entity in the World Health Organization 2004 classification of RCC. To our knowledge, 17 cases of MTSCC‐K in Japan have been reported by Japanese investigators. To avoid administration of excessive adjuvant treatment to patients, pathologists and urologists should consider this newly recognized low‐grade malignancy when diagnosing renal tumors.
Ketamine‐associated bladder dysfunction
Authors: Tsai Tsung‐Hsun , Cha Tai‐Lung , Lin Chang‐Min , Tsao Chih‐Wei , Tang Shou‐Hung , Chuang Feng‐Pin , Wu Sheng‐Tang , Sun Guang‐Huan , Yu Dah‐Shyong , Chang Sun‐Yran
Published: July 2009

Objective:  To assess the impact of ketamine abuse on genitourinary tract dysfunction.

Methods:  Eleven patients with urinary tract symptoms and a history of ketamine abuse in recent years were studied. Urinalysis, urine culture, renal function tests, abdominal sonography and urodynamic studies were done. Bladder biopsies were carried out in selected cases.

Results:  The most common complaints were lower urinary tract symptoms, including dysuria, frequency, urgency and gross hematuria. Urinalyses showed nonbacterial pyuria and were negative for tuberculosis. All biopsy specimens showed infiltrations of granulocytes (mostly eosinophils) and mast cells within the bladder tissue. Medications produced only slight clinical improvements. Intravesical instillation of hyaluronan solution was performed for some patients and a significant improvement of lower urinary tract symptoms was observed.

Conclusions:  Although the dosage and duration of ketamine abuse causing severe side‐effects are still unclear, some patients develop irreversible histological changes in the urinary tract. Therefore, clinicians should be aware of the negative effects of ketamine abuse on genitourinary tract function.
Chronic pain following a Lichtenstein inguinal hernia repair: a clinical and legal dilemma
Authors: Paily Abhilash , Thornton Michelle
Published: July 2009

Background:  Chronic pain following a Lichtenstein inguinal hernia is frequent and raises major concerns regarding informed consent recall

Objective:  To assess the frequency of chronic pain and associated factors following inguinal hernia repair in a district general hospital. To assess patient recall of the consent process as it pertains to chronic pain.

Methods:  A random sample (170/293 patients) of those who underwent a Lichtenstein inguinal hernia repair between 2002 and 2004 were retrospectively assessed for the frequency, intensity and other co‐factors of chronic pain. They were also questioned about their recollection of the consent process and information given regarding chronic pain.

Results:  50 percent of patients reported chronic pain at a median follow‐up of 62 months with 30% reporting a significant impact on daily activities. Younger age, the absence of a lump at presentation, pre‐operative pain and elective repair were the only factors significantly shown to increase the likelihood of post‐operative pain. Patients with post‐operative pain were significantly more likely to report that they had not been informed of the possibility of chronic pain pre‐operatively or at the time of consent. Twenty percent of these patients stated that they would not have undergone the operation if they had been informed of the possibility of chronic pain.

Conclusion:  Chronic pain is frequent and debilitating. Documentation of chronic pain as a possible outcome at the time of consent should be mandatory as patient recall is poor.
The harassment and stalking of plastic surgeons by their patients in Australasia
Authors: Allnutt Stephen , Samuels Anthony , Taylor Gregory
Published: July 2009

Medical professionals come into direct contact with the public. The relationships are often personal. The aim of the survey is to examine the prevalence of harassment of plastic surgeons by their patients.

Survey questionnaires were mailed to all plastic surgeons listed in the 1999 Australasian Society of Aesthetic Plastic Surgery List of Members. A very wide definition of harassment was then provided and information in regard to the nature of the harassment was obtained.

This was a descriptive survey of plastic surgeons’ experiences of harassment by patients in Australia and New Zealand. More than half of the plastic surgeons in Australia and New Zealand who responded to the questionnaire reported having been a victim of harassment at some point of their careers. One quarter had been harassed in the previous year. Over 20% of cases met the legal criteria for stalking. These estimates are in excess of those reported in the other studies of the general community. Harassment persisted in the majority of cases for at least a month and in a third of cases for up to 5 years.

The recognition of psychiatric disorder, particularly personality dysfunction, prior to embarking on surgery may limit the likelihood of harassment by difficult patients. Formal teaching may be helpful to surgical registrars and consultants. Expert intervention could assist in reducing clinician anxiety.
Estimating the risk of rare complications: is the ‘rule of three’ good enough?
Authors: Ludbrook John , Lew Michael J.
Published: July 2009

The clinical problem:  If a surgeon has performed a particular operation on n consecutive patients without major complications, what is the long‐term risk of major complications after performing many more such operations? Examples of such operations are endoscopic cholecystectomy, nephrectomy and sympathectomy.

The statistical problem and solutions:  This general problem has exercised the minds of theoretical statisticians for more than 80 years. They agree only that the long‐term risk is best expressed as the upper bound of a 95% confidence interval. We consider many proposed solutions, from those that involve complex statistical theory to the empirical ‘rule of three’, popular among clinicians, in which the percentage risk is given by the formula 100 × (3/n).

Our conclusions:  The ‘rule of three’ grossly underestimates the future risks and can be applied only when the initial complication rate is zero (that is, 0/n). If the initial complication rate is greater than zero, then no simple ‘rule’ suffices. We give the results of applying the more popular statistical models, including their coverage. The ‘exact’ Clopper–Pearson interval has wider coverage across all proportions than its nominal 95%, and is, thus, too conservative. The Wilson score confidence interval gives about 95% coverage on average overall population proportions, except very small ones, so we prefer it to the Clopper–Pearson method. Unlike all the other intervals, Bayesian intervals with uniform priors yield exactly 95% coverage at any observed proportion. Thus, we strongly recommend Bayesian intervals and provide free software for executing them.
Moral responsibility to attain thorough pediatric drug labeling
Authors: WAISEL DAVID B.
Published: July 2009

Many drugs used in children have not been labeled for pediatric use. While this was the standard for many years, recent regulations and incentives have improved the depth and breadth of pediatric drug labeling. Nonetheless, common pediatric drugs have not been adequately labeled, particularly generic and orphaned drugs and drugs that were approved for one age group but never tested in other age groups. Anesthesiologists have a moral responsibility to encourage government, pharmaceutical companies, and researchers to study drugs in children.
Comparison of the Cobalt Glidescope® video laryngoscope with conventional laryngoscopy in simulated normal and difficult infant airways*
Authors: WHITE MICHELLE , WEALE NICOLA , NOLAN JUDITH , SALE STEVEN , BAYLEY GUY
Published: July 2009

Aim:  To evaluate the new pediatric Glidescope® (Cobalt GVL® Stat) by assessing the time taken to tracheal intubation under normal and difficult intubation conditions. We hypothesized that the Glidescope® would perform as well as conventional laryngoscopy.

Background:  A new pediatric Glidescope® became available in October 2008. It combines a disposable, sterile laryngoscope blade and a reusable video baton. It is narrower and longer than the previous version and is available in a greater range of sizes more appropriate to pediatric use.

Methods:  We performed a randomized study of 32 pediatric anesthetists and intensivists to compare the Cobalt GVL® Stat with the Miller laryngoscope under simulated normal and difficult airway conditions in a pediatric manikin.

Results:  We found no difference in time taken to tracheal intubation using the Glidescope® or Miller laryngoscope under normal (29.3 vs 26.2 s, P = 0.36) or difficult (45.8 and 44.4 s, P = 0.84) conditions. Subjective evaluation of devices for field of view (excellent: 59% vs 53%) and ease of use (excellent: 69% vs 63%) was similar for the Miller laryngoscope and Glidescope®, respectively. However, only 34% of participants said that they would definitely use the Glidescope® in an emergency compared with 66% who would be willing to use the Miller laryngoscope.

Conclusions:  The new Glidescope® performs as well as the Miller laryngoscope under simulated normal and difficult airway conditions.
High Carbohydrate‐High Fibre Diets in Poorly Controlled Diabetes
Authors: Lousley S. E. , Jones D. B. , Slaughter P. , Carter R. D. , Jelfs R. , Mann J. I.
Published: July 2009

Fifteen non‐insulin‐dependent diabetic patients with persistently elevated blood glucoses despite high doses of oral hypoglycaemic agents, were randomly allocated to a high carbohydrate‐high fibre diet (HC) or a reinforced low carbohydrate diet (LC). After six weeks the diets were reversed for a similar period. Immediately preceding the study and at the end of each dietary period 24‐h biochemical profiles were performed. In the 11 patients who completed the study, fasting and preprandial glucose, percentage glycosylated haemoglobin, VLDL cholesterol and mean 24‐h triglycerides were significantly lower on HC than on LC or during the initial profile on their usual diet. There was no significant difference in any of the measurements on LC compared with the usual diet. Previous studies of high carbohydrate‐high fibre diets in diabetes have been carried out in relatively well‐controlled patients. These data show that poorly controlled non‐insulin‐dependent patients have an even more striking response.