bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two novel germline KRAS mutations: expanding the molecular and clinical phenotype
Authors: Stark Z , Gillessen‐Kaesbach G , Ryan MM , Cirstea IC , Gremer L , Ahmadian MR , Savarirayan R , Zenker M 
Published: July 2011

Stark Z, Gillessen‐Kaesbach G, Ryan MM, Cirstea IC, Gremer L, Ahmadian MR, Savarirayan R, Zenker M. Two novel germline KRAS mutations: expanding the molecular and clinical phenotype.Noonan and Cardio‐facio‐cutaneous (CFC) syndromes are characterized by typical dysmorphic features, cardiac defects, short stature, variable ectodermal anomalies, and intellectual disability. Both belong to the Ras/mitogen‐activated protein kinase pathway group of disorders and clinical features overlap other related conditions, notably LEOPARD and Costello syndromes. KRAS mutations account for about 2% of reported Noonan and <5% of reported CFC cases. The mutation spectrum includes recurrent missense changes clustering in particular domains of the KRAS protein and conferring gain‐of‐function. We report three patients from two unrelated families with novel missense KRAS mutations, p.K147E and p.Y71H. Both mutations affect a residue which is highly conserved in KRAS and other RAS isoforms. One of the families includes a mother and son pair who represent the first report of a vertically transmitted KRAS mutation. In addition, the mother and son pair had peripheral neuropathy, complicated by Charcot arthropathy in the mother. An unusual phenotypic effect of the specific KRAS mutation or a coincidence of two independent disorders may be considered. KRAS mutation‐associated phenotypes appear to be subject to considerable clinical heterogeneity. All three cases highlight the challenges of clinical assessment in KRAS mutation‐positive patients, and the utility of molecular testing as an adjunct to diagnosis.
The use of recombinant human activated protein C (drotrecogin alpha) in solid organ transplant recipients: case series and review of the literature
Authors: Funk D.J. , Palma Vargas J. , Tuttle‐Newhall J. , Moretti E.W. 
Published: July 2011

D.J. Funk, J. Palma Vargas, J. Tuttle‐Newhall, E.W. Moretti. The use of recombinant human activated protein C (drotrecogin alpha) in solid organ transplant recipients: case series and review of the literature. Transpl Infect Dis 2011: 13: 592–597. All rights reserved
Abstract: Septic shock occurs frequently in solid organ transplant (SOT) recipients. Standard therapy includes fluid resuscitation, the administration of antimicrobials, and source control of the infection. Adjunctive therapy with recombinant human activated protein C (rhaPC), also called drotrecogin alpha, is another treatment that is used in patients but has not been studied in SOT patients. Concerns regarding the use of this drug in this patient population include the risk of bleeding and the potential to adversely affect graft survival. Here we report the largest case series of SOT recipients with septic shock who received rhaPC. This was a retrospective chart review that looked at the impact of this drug in the SOT population. In this single‐center study, we identified 17 patients with a SOT and septic shock who received rhaPC. Six of the patients underwent kidney transplants, 5 received lung transplants, 4 received cadaveric liver transplants, and 2 received combined kidney/pancreas transplants. The average APACHE II score was 26.6 ± 5.5; all patients were undergoing mechanical ventilation and receiving vasopressors at the time of rhaPC administration. Overall mortality in the group was 23.5% (4/17) at 28 days post infusion. All of the deaths were due to complications of septic shock. Allograft survival was present in 13/17 (76.5%) of the patients at 28 days. Bleeding occurred in 17.6% of patients (3/17). The use of rhaPC appears to be associated with a favorable effect on mortality, with the potential for increased risk of bleeding. Clinicians must balance this risk with the potential benefit of this drug until further research can be conducted.
Antifungal susceptibility of Candida albicans in biofilms
Authors: Tobudic Selma , Kratzer Christina , Lassnigg Andrea , Presterl Elisabeth 
Published: July 2011

SummaryCandida albicans are the most common fungi associated with biofilm‐related infections. Biofilms are defined as microbial communities encased in a matrix of extracellular polymeric substances. The most important feature of biofilm growth is the high resistance to antimicrobial agents that can be up to 1000‐fold greater than that of planktonic cells. This review discusses the factors affecting antifungal resistance as well as activity of mono‐ and combination therapy of different antifungal classes and antifungal activity in vitro and in vivo against C. albicans biofilms.
Early on‐treatment predictions of clinical outcomes using alpha‐fetoprotein and des‐gamma‐carboxy prothrombin responses in patients with advanced hepatocellular carcinoma
Authors: Lee Myoung Ha , Kim Seung Up , Kim Do Young , Ahn Sang Hoon , Choi Eun Hee , Lee Kwang Hun , Lee Do Yun , Seong Jinsil , Han Kwang‐Hyub , Chon Chae Yoon , Park Jun Yong 
Published: July 2011

AbstractBackground and Aim:  The clinical utility of alpha‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) as a predictor of treatment outcome in patients with advanced hepatocellular carcinoma (HCC) receiving hepatic artery infusional chemotherapy (HAIC) or concurrent chemoradiation therapy (CCRT) has been poorly defined.Methods:  Between January 2003 and December 2007, we enrolled 127 treatment‐naïve patients who received HAIC (n = 60) or CCRT (n = 67) as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 20% from the baseline level.Results:  AFP responders showed significantly better overall survival (OS) than non‐responders among patients with HAIC (median 17.3 vs 6.4 months, P < 0.001) and with CCRT (median 17.6 vs 8.7 months, P = 0.014). DCP responders in the CCRT group also showed significantly better progression‐free survival (PFS) than non‐responders (median 9.2 vs 3.1 months, P < 0.001). Multivariate Cox regression analyses showed that AFP response was independently predictive of OS in both groups (P = 0.009 in HAIC and P = 0.008 in CCRT) whereas DCP only predicted PFS in patients with CCRT (P = 0.015).Conclusions:  Early on‐treatment AFP response was predictive of OS in treatment‐naïve patients with advanced HCC receiving HAIC and CCRT as an initial treatment modality. Furthermore, DCP response was useful for predicting PFS in patients with CCRT.
Hepatocellular carcinoma with duodenal invasion and metastasis
Authors: Liang Ja‐Der , Chen Chien‐Hung , Hsu Shih‐Jer , Sheu Jin‐Chuan , Yang Pei‐Ming , Lee Hsuan‐Shu , Lee Cha‐Ze , Huang Guan‐Tarn 
Published: July 2011

AbstractBackground and Aim:  Hepatocellular carcinoma (HCC) is the leading cause of cancer‐related deaths in Taiwan. HCC with duodenal involvement are rare and are associated with a poor prognosis. The purpose of this retrospective study was to collect clinical information and data regarding survival following various treatments.Methods:  Between 1996 and 2009, 21 cases (17 men) were diagnosed with HCC and duodenal invasion and metastases by diagnostic imaging, endoscopy with biopsy, or surgically collected specimens sent to pathology. The clinical course was analyzed from the patients' medical records.Results:  Gastrointestinal bleeding was reported in 18/21 patients. Diagnostic imaging showed that the majority of cases involved direct tumor invasion (predominantly from the right liver lobe) and six cases from metastasis. Tumor mass and ulcerations were the most common features noted on endoscopy. In addition to the component therapy and medication treatment, panendoscopic hemostasis, surgery, transcatheter arterial embolization, and radiotherapy were performed for the management of duodenal involvement and gastrointestinal bleeding. Survival duration after duodenal involvement ranged from 0.2 to 57.8 months (mean 10.5 months).Conclusions:  Gastrointestinal bleeding in advanced HCC should raise suspicions of duodenal involvement. HCC can involve the duodenum by direct invasion (from either the left or right liver lobes) or metastasis. The prognosis for HCC patients with duodenal involvement is poor, but is improved by supportive care and application of various treatment modalities.
Laparoscopic splenectomy with interferon therapy in 100 hepatitis‐C‐virus‐cirrhotic patients with hypersplenism and thrombocytopenia
Authors: Akahoshi Tomohiko , Tomikawa Morimasa , Kawanaka Hirofumi , Furusyo Norihiro , Kinjo Nao , Tsutsumi Norifumi , Nagao Yoshihiro , Hayashi Jun , Hashizume Makoto , Maehara Yoshihiko 
Published: July 2011

AbstractBackground and Aim:  We intended to determine whether laparoscopic splenectomy (Lap‐Sp) contributes to treatment with interferon therapy in hepatitis C virus (HCV)‐cirrhotic patients with thrombocytopenia caused by hypersplenism.Methods:  From December 2004 to August 2008, 100 cirrhotic patients (54 men and 46 women) underwent Lap‐Sp for a clinical application of interferon therapy. All the patients were Child–Pugh class A or B with thrombocytopenia (average platelet count, 56 × 103/mm3). The HCV genotype was type 1 in 80 patients and type 2 in 20 patients.Results:  Pure laparoscopic or hand‐assisted laparoscopy was performed in 78 and 22 patients, respectively, without mortality. Conversion to open surgery was not required in any of the patients. The platelet counts improved (mean platelet count 172 × 103/mm3 1 month after surgery) and interferon (IFN) therapy was started in 97 patients. In this study period, 36 patients obtained a sustained virologic response. Eight patients discontinued IFN therapy because of depression, neutropenia or other reasons.Conclusions:  Lap‐Sp permits most patients with HCV cirrhosis and hypersplenism to receive sufficient IFN therapy. Therefore, Lap‐Sp can become a strong supportive surgery for cirrhotic patients who require antiviral therapy.
DA6034 promotes gastric epithelial cell migration and wound‐healing through the mTOR pathway
Authors: Kim Young Woo , Lee Woo Hyung , Choi Seul Min , Seo Yoon Young , Ahn Byoung Ok , Kim Soon Hoe , Kim Sang Geon 
Published: July 2011

AbstractBackground and Aim: 7‐Carboxymethyloxy‐3′,4′,5‐trimethoxy flavone (DA6034), a synthetic derivative of eupatilin, has a protective effect on gastric mucosa against various ulcerogens, and is currently in the phase III clinical trial in the treatment of peptic ulcer disease. Cell migration and/or growth plays a role in the repair process of gastric ulcer, so this study investigated the effect of DA6034 on the movement and proliferation of gastric epithelial cells and its associated signaling pathway.Methods: The migration of AGS or SNU484 human gastric epithelial cells was shown by scratch‐induced wound healing and transwell assays, and the proliferation of the cells was assessed by FACS and proliferation assays.Results: Treatment of DA6034 promoted the migration of gastric epithelial cells in a concentration‐dependent manner. DA6034 treatment facilitated the phosphorylation of mTOR that led to an increase in the activity of S6K1, indicating its ability to activate mTOR and S6K1. Rapamycin aborted the wound‐healing effect of DA6034, which supported the role of mTOR activation in the wound‐healing process. In addition, DA6034 treatment increased PI3K‐dependent Akt phosphorylation, which was necessary for the enhancement of cell migration. DA6034, however, did not stimulate the proliferation of gastric epithelial cells, being consistent with no activation of ERK1/2 by the agent.Conclusions: DA6034 has the ability to heal scratch wounds, which may result from an increase in gastric epithelial cell migration as mediated by PI3K‐Akt‐dependent activation of mTOR and S6K1. Our finding may be of help in understanding the molecular basis of the anti‐ulcer effect of DA6034.
Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance
Authors: Chung Jun‐Won , Lee Gin Hyug , Jeong Jin‐Yong , Lee Sun Mi , Jung Ji Hoon , Choi Kee Don , Song Ho June , Jung Hwoon‐Yong , Kim Jin‐Ho 
Published: July 2011

AbstractBackground and Aim:  New regimens, including those with new fluoroquinolones, have been developed to overcome the antibiotic resistance of Helicobacter pylori. We aimed to assess the antibiotic resistance rates, as well as the molecular mechanisms of fluoroquinolone resistance, of the clinical isolates obtained in Korea.Methods:  The minimal inhibitory concentration (MIC) values of ciprofloxacin, amoxicillin, clarithromycin, metronidazole and tetracycline were determined by the agar dilution method for 185 treatment‐naïve Helicobacter pylori isolates. The resistant strains were evaluated for the presence of point mutations in the quinolone resistance‐determining region (QRDR) of the gyrA and gyrB genes by direct nucleotide sequencing.Results:  Twenty‐nine (29/185, 15.7%) of the strains were found to be resistant to ciprofloxacin. The resistance rates to amoxicillin, clarithromycin, metronidazole and tetracycline were 2.2% (four of 185), 10.8% (20 of 185), 30.3% (56 of 185) and 0.5% (one of 185), respectively. The most common mutations in the H. pylori gyrA gene were found at codons corresponding to Asp87 (16/29, 55.2%) and Asn91 (10/29, 34.5%).Conclusions:  Primary H. pylori resistance to ciprofloxacin occurred at a high frequency. The fluoroquinolone resistance is most likely mediated through amino acid point mutation in the gyrA gene at Asn87 and Asp91.
Increasing the duration of dual amoxicillin plus omeprazole Helicobacter pylori eradication to 6 weeks: A pilot study
Authors: Attumi Taraq A , Graham David Y 
Published: July 2011

AbstractBackground and Aim:  Helicobacter pylori infections have become increasingly difficult to treat as antimicrobial resistance has increased. The aim of this study was to test the hypothesis that a 6‐week dual regimen of amoxicillin 1 gm and omeprazole 20 gm therapy b.i.d. would cure at least 90% of treatment‐naïve H. pylori infections.Methods:  This was an open‐label prospective pilot study in which treatment‐naïve subjects with active H. pylori infection (positive by two tests) received dual amoxicillin 1 g and omeprazole 20 mg, b.i.d. daily for 6 weeks. Success was accessed by urea breath test 4–6 weeks later. A tentatively effective therapy was defined as a per‐protocol treatment success of 90% or greater; treatment success of 80% or less was prespecified as unacceptable.Results:  Sixteen patients were included in the study (14 men, two women) with an average age of 49 years. At 16 patients, the prespecified stopping rule of six treatment failures was achieved (i.e. the 95% confidence interval excluded achieving the required 90% success rate even if 50 patients were entered). As per protocol, enrollment was stopped. Per‐protocol and intention‐to‐treat treatment success were both 62.5% (95% confidence interval, 35–84%). Compliance was greater than 99%. Five patients (31%) reported side‐effects, all of which were mild and none interrupted therapy.Conclusion:  Despite the theory and pre‐existing data from Japan, in the USA, prolonging the duration of dual amoxicillin‐PPI therapy did not improve treatment outcome in 90% or more of our patients.
Understanding the recruitment and retention of overseas nurses: realist case study research in National Health Service Hospitals in the UK
Authors: O’Brien Terri , Ackroyd Stephen 
Published: July 2011

O’BRIEN T and ACKROYD S. Nursing Inquiry 2012; 19: 39–50 Understanding the recruitment and retention of overseas nurses: realist case study research in National Health Service Hospitals in the UKThis paper illustrates one of the possible applications of critical realist ideas to the analysis of health services, in the use of comparative case study research design, to elucidate the causal social processes underlying events. In the research reported here, a comparative research design was used as a basis for improving our understanding of the processes involved in the assimilation of overseas nurses (OSN) into the salient long‐term workforce of the National Health Service (NHS) hospitals in the UK. The work brought to light the salient experiences of overseas nurses during their initial work in the NHS hospitals, and these were used as a basis for developing an account of the general mechanisms typically underlying the recruitment and assimilation at work. The authors conclude that successful assimilation is often hindered by the presence of occupational closure mechanisms, by which home nurses effectively excluded recruits from participation and promotion; these mechanisms, which articulate with everyday racism, threaten successful assimilation for obvious reasons. If the treatment recruits receive does not lead to withdrawal, it is because they typically have very strong economic motives to continue despite unfavourable and sometimes inhumane treatment. Thus, the research offered substantial reasons why recruitment policies should be reviewed by policy‐makers.
Understanding health decisions using critical realism: home‐dialysis decision‐making during chronic kidney disease
Authors: Harwood Lori , Clark Alexander M 
Published: July 2011

HARWOOD L and CLARK AM. Nursing Inquiry 2012; 19: 29–38 Understanding health decisions using critical realism: home‐dialysis decision‐making during chronic kidney diseaseThis paper examines home‐dialysis decision making in people with Chronic Kidney Disease (CKD) from the perspective of critical realism. CKD programmes focus on patient education for self‐management to delay the progression of kidney disease and the preparation and support for renal replacement therapy e.g.) dialysis and transplantation. Home‐dialysis has clear health, societal and economic benefits yet service usage is low despite efforts to realign resources and educate individuals. Current research on the determinants of modality selection is superficial and insufficient to capture the complexities embedded in the process of dialysis modality selection. Predictors of home‐dialysis selection and the effect of chronic kidney disease educational programmes provide a limited explanation of this experience. A re‐conceptualization of the problem is required in order to fully understand this process. The epistemology and ontology of critical realism guides our knowledge and methodology particularly suited for examination of these complexities. This approach examines the deeper mechanisms and wider determinants associated with modality decision making, specifically who chooses home dialysis and under what circumstances. Until more is known regarding dialysis modality decision making service usage of home dialysis will remain low as interventions will be based on inadequate epistemology.
Prevalence of potentially reversible conditions in dementia and mild cognitive impairment in a geriatric clinic
Authors: Muangpaisan Weerasak , Petcharat Chonachan , Srinonprasert Varalak 
Published: July 2011

Aim:  To examine the prevalence of potentially reversible conditions in dementia and mild cognitive impairment (MCI) patients in a geriatric clinic.Methods:  We retrospectively reviewed the medical records of patients who attended the outpatient geriatric clinic at Siriraj Hospital, Bangkok between January 2005 and December 2010. We collected the data regarding potentially reversible conditions of cognitive impairment.Results:  There were 233 patients newly diagnosed with dementia and 60 patients diagnosed with MCI. We found potentially reversible causes of dementia in 17 patients (7.3%). The causes were hypothyroidism (2.6%), B12 deficiency (1.7%), normal pressure hydrocephalus (NPH) (0.9%), depression (0.9%), folate deficiency (0.4%), reactive Venereal Disease Research Laboratory (VDRL; 0.4%) and chronic subdural hematoma (CSH; 0.4%). The patients with NPH and CSH were clinically suspicious for having such conditions before the investigations, while patients with low B12 level, low folate level, hypothyroidism and VDRL+ were not. In the MCI group, we found potentially reversible causes in two patients (3.3%), these were B12 deficiency (1.7%) and hypothyroidism (1.7%). Clinical improvement after treatment of the potentially reversible conditions was seen in four patients (one NPH, one subdural hematoma and two with depression) in dementia group (1.7%) and none in the MCI group. All were partially reversed.Conclusion:  Routine investigations might be more warranted for metabolic conditions (B12 level and hypothyroidism) as clinical presentations are not suggestive of the conditions. However, reversibility of dementia might not occur in these cases. Neuroimaging should be performed selectively as clinically indicated. Truly reversible conditions are rare and occur in surgical and depressive patients. Geriatr Gerontol Int 2012; 12: 59–64.
Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acids
Authors: Nakamura Akira , Hara Kenta , Yamamoto Kazuhiro , Yasuda Hisafumi , Moriyama Hiroaki , Hirai Midori , Nagata Masao , Yokono Koichi 
Published: July 2011

Aim:  Oral intake of nutrients is often compromised in elderly, multimorbid patients, but parenteral nutrition causes intestinal atrophy and impairs intestinal function. To uncover the molecular mechanisms by which amino acids are involved in intestinal atrophy and recovery, we studied whether the rapamycin‐sensitive mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway is involved in this process.Methods:  C57BL/6N mice were fed a glucose solution alone, glucose solution with amino acids or normal chow diet for various lengths of time. Intestinal sections were prepared from these mice and the villus height and villus density were quantified. As a readout for the mTORC1 pathway, the phosphorylation of the ribosomal S6 protein (S6) was analyzed by immunostaining and immunoblotting. To confirm the role of the mTORC1 pathway, the inhibitory effect of a specific mTOR inhibitor, rapamycin, was examined.Results:  Inducing fasting in mice fed only glucose caused time‐dependent intestinal mucosal atrophy, whereas supplementation with amino acids protected the intestinal mucosa from atrophy. Phosphorylation of S6 decreased in the intestinal mucosa of mice fed only glucose, whereas supplementation with amino acids increased S6 phosphorylation. Importantly, intraperitoneal injection of rapamycin attenuated the protective effect of amino acids on the intestinal mucosa in a pattern consistent with the decrease of S6 phosphorylation.Conclusions:  These results indicate that the mTORC1 pathway plays a crucial role in the in vivo maintenance of the intestinal mucosa by the oral intake of amino acids. Geriatr Gerontol Int 2012; 12: 131–139.