bluuebunny/crossref_metadata_2025 huggingface dataset:
A Unique Story in Neonatal Research: The Development of a Porcine Surfactant
Authors: Curstedt Tore , Halliday Henry L. , Speer Christian P.
Published: June 2015

Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf® (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983. Subsequent randomized clinical trials were planned a year later by Bengt Robertson, Tore Curstedt and Henry Halliday, and the first trial was begun in 1985. This showed that Curosurf reduced pulmonary air leaks and neonatal mortality in preterm infants with severe RDS. A second trial, coordinated by Christian Speer, demonstrated that multiple doses of Curosurf were more effective than a single dose. Subsequent trials conducted by the Collaborative European Multicenter Study Group, which included among others Guilio Bevilacqua, Janna Koppe, Ola Saugstad, Nils Svenningsen and Jean-Pierre Relier, showed that early treatment was more effective than later administration and that infants treated at birth had similar neurodevelopmental status to untreated controls at a corrected age of 2 years. Members of the Collaborative European Multicenter Study Group in Denmark and Sweden performed studies to demonstrate the benefits of a combination of surfactant treatment and early continuous positive airway pressure. Curosurf has also been compared with several synthetic and natural surfactants, and at a dose of 200 mg/kg Curosurf has been shown to be superior to either Survanta® or Curosurf used at a dose of 100 mg/kg. Recently, new-generation synthetic surfactants containing both phospholipids and proteins have been developed. After preclinical testing, CHF5633 (developed by Tore Curstedt and Jan Johansson in collaboration with Chiesi Farmaceutici) has undergone a preliminary first study in humans under the guidance of Christian Speer. If effective, this new surfactant preparation could revolutionize the treatment of preterm infants worldwide as it could be made consistently and safely in almost unlimited quantities. This story of a porcine surfactant preparation has been truly remarkable, and many thousands of preterm babies worldwide are now alive and well because of it.
Surgery for Severe Ulcerative Colitis during Pregnancy: Report of Two Cases
Authors: Uchino Motoi , Ikeuchi Hiroki , Matsuoka Hiroki , Bando Toshihiro , Hirose Kei , Hirata Akihiro , Chohno Teruhiro , Sasaki Hirofumi , Yokoyama Yoko , Nakamura Shiro , Nakamura Yuko , Takesue Yoshio
Published: June 2015

Refractory ulcerative colitis (UC) that does not respond to medical therapy often requires surgery even during pregnancy. Although surgical cases of UC during pregnancy were reported previously, the standard surgical strategy for both colitis and pregnancy was unclear. Herein, fetal and maternal safety as well as the strategy for this unusual surgical procedure during pregnancy in patients with UC are considered. A 28-year-old woman was diagnosed with left-sided moderate UC at 12 weeks of pregnancy; toxic megacolon was suspected, and surgery was required. Although the baby's gestational age was 23 weeks and 3 days, a cesarean section was performed before the colectomy. In a next case, a 28-year-old woman had a 2-year history of left-sided UC. Her colitis flared up at 11 weeks of pregnancy. Colectomy was performed because her colitis was unresponsive to conservative therapy, and the pregnancy was continued, with a transvaginal delivery at 36 weeks. In patients with UC, the need for surgery should be determined promptly based on disease severity, whether or not the patient is pregnant. The need for surgery should not be affected by pregnancy. The pregnancy should be continued for as long as possible when there are no fetal and maternal complications. Both cesarean section and colectomy should be performed independently if necessary.
The Relationship of Health Behaviors to Childhood Cognition and Brain Health
Authors: Hillman Charles H. , Khan Naiman A. , Kao Shih-Chun
Published: June 2015

Background: Physical activity and aerobic fitness have been shown to have positive implications for children's cognitive performance and brain structure and function. In addition, emerging evidence suggests that excess body mass is related to decreased cognitive performance and differential brain structure and function. Recently, several randomized controlled trials have provided causal evidence for the beneficial effects of daily physical activity on cognition and its neural underpinnings. However, the data linking excess body mass to compromised cognitive function are largely correlational since trials that manipulate body mass to determine changes in brain and cognition remain sparse. Such studies are sorely needed to provide strong evidence for the relation of childhood health behaviors to not only physical, but brain health as well. Summary: This manuscript provides a brief review of the current literature on physical activity and excess body mass on brain structure, brain function, and an aspect of cognition known as executive control, which refers to cognitive processes involved in the intentional component of environmental interaction. Generally, the findings indicate that daily physical activity or higher aerobic fitness is related to greater volume and integrity of brain structure, efficient and effective brain function, and superior executive control. Alternatively, excess body mass is related to decreased integrity of brain structure, less effective brain function, and poorer executive control. Key Messages: The findings have considerable implications for lifespan health and effective functioning, and demonstrate that childhood health behaviors have implications not only for cognitive and brain health but also for scholastic performance and educational attainment.
Increasing Water Intake of Children and Parents in the Family Setting: A Randomized, Controlled Intervention Using Installation Theory
Authors: Lahlou Saadi , Boesen-Mariani Sabine , Franks Bradley , Guelinckx Isabelle
Published: June 2015

On average, children and adults in developed countries consume too little water, which can lead to negative health consequences. In a one-year longitudinal field experiment in Poland, we compared the impact of three home-based interventions on helping children and their parents/caregivers to develop sustainable increased plain water consumption habits. Fluid consumption of 334 children and their caregivers were recorded over one year using an online specific fluid dietary record. They were initially randomly allocated to one of the three following conditions: Control, Information (child and carer received information on the health benefits of water), or Placement (in addition to information, free small bottles of still water for a limited time period were delivered at home). After three months, half of the non-controls were randomly assigned to Community (child and caregiver engaged in an online community forum providing support on water consumption). All conditions significantly increased the water consumption of children (by 21.9-56.7%) and of adults (by 22-89%). Placement + Community generated the largest effects. Community enhanced the impact of Placement for children and parents, as well as the impact of Information for parents but not children. The results suggest that the family setting offers considerable scope for successful installation of interventions encouraging children and caregivers to develop healthier consumption habits, in mutually reinforcing ways. Combining information, affordances, and social influence gives the best, and most sustainable, results.
A Novel Homozygous c.800C>G Substitution in GP1BA Exon 2 in a Kuwaiti Family with Bernard-Soulier Syndrome
Authors: Shlebak Abdul , Poles Anthony , Manning Richard , Almuhareb Shaikha , De La Funte Josu , Mitchell Mike , Lucas Geoff
Published: June 2015

Background: Bernard-Soulier syndrome (BSS) is a congenital bleeding disorder characterised by thrombocytopenia, giant platelets and decreased platelet adhesion resulting from genetic alterations of the glycoprotein (GP) Ib/IX/V complex. Objectives: Three sisters with a lifelong bleeding history and a provisional diagnosis of BSS were referred for further characterisation of their bleeding diathesis. The siblings' symptoms varied in severity from skin and gum bleeding to menorrhagia associated with iron-deficiency anaemia requiring regular transfusion of red cells and platelets. The parents were consanguineous but did not demonstrate any bleeding disorder. Methods: The family were investigated using standard haematological techniques, platelet aggregometry, platelet membrane GP analysis and DNA sequencing of the genes encoding the GPIb/IX complex. Results: All 3 sisters had thrombocytopenia and giant platelets. Platelet aggregation and flow cytometry studies confirmed the lack of aggregation with ristocetin and a markedly reduced GPIb/IX surface expression. Molecular analysis demonstrated a novel homozygous c.800C>G substitution in GP1BA exon 2 leading to a serine 267 Ter stop codon in all 3 siblings. Conclusions: A novel, nonsense mutation was identified as the cause of the bleeding disorder in this family. This is the first reported BSS mutation identified in a family from Kuwait.
Contralateral Routing of Signal Hearing Aid versus Transcutaneous Bone Conduction in Single-Sided Deafness
Authors: Leterme Gaëlle , Bernardeschi Daniele , Bensemman Anissa , Coudert Cyrille , Portal Jean-Jacques , Ferrary Evelyne , Sterkers Olivier , Vicaut Eric , Frachet Bruno , Bozorg Grayeli Alexis
Published: June 2015

The aim of this study was to compare a contralateral routing of signal (CROS) hearing aid to a transcutaneous bone-anchored device in the same conditions. This prospective crossover study included 18 adult patients with a single-sided deafness (SSD). After a trial period of 60 days with CROS and 7 days with a transcutaneous bone-anchored device (Alpha 1®, Sophono, Boulder, Colo., USA) on a headband, 13 (72%) patients opted for Alpha 1, 2 patients for CROS, and 3 rejected both rehabilitation methods. Clinical tolerance, satisfaction, hearing performances (pure-tone audiometry, speech test in quiet and in noise, stereo audiometry, sound localization, and Hearing in Noise Test), and quality of life (Glasgow Benefit Inventory, Abbreviated Profile of Hearing Aid Benefit and Glasgow Hearing Aid Benefit questionnaires) were measured at 3 and 12 months after the implantation. Both devices improved equally the hearing in noise and the quality of life. Transcutaneous devices represent an effective option in SSD.
Acoustic Analysis of Madhya and Taar Saptak/Sthayi in Indian Classical Singers
Authors: Gunjawate Dhanshree R. , Aithal Venkataraja U. , Guddattu Vasudeva , Bellur Rajashekhar
Published: June 2015

Objectives: We aimed to compare the acoustic parameters of voice between Madhya Saptak/Sthayi (MS) and Taar Saptak/Sthayi (TS) in trained Indian classical singers and between males and females. Participants and Method: Sixty-five adult trained Indian classical singers were instructed to produce MS and TS; the acoustic parameters were analyzed with the Multidimensional Voice Program. Descriptive statistics were used for analysis across tasks and gender. Two-way random-effects ANOVA was used to test the effect of gender and task. Results: Male participants had a restricted range of fundamental frequency (F0), especially at high pitches. The acoustic analysis showed a statistically significant difference for F0 measures, range of F0, jitter and pitch perturbation quotient between males and females during MS and TS. Conclusion: The use of TS, that is, high-pitch phonation, during the clinical evaluation of singers enables an understanding of their vocal behavior in the higher scales of singing.
The Histamine H4 Receptor Regulates Chemokine Production in Human Natural Killer Cells
Authors: Mommert Susanne , Dittrich-Breiholz Oliver , Stark Holger , Gutzmer Ralf , Werfel Thomas
Published: June 2015

Background: Natural killer (NK) cells have been detected in the lesional skin of patients with inflammatory skin diseases, where high levels of histamine are also present. Therefore, we investigated the effect of histamine, in particular via the histamine H4 receptor (H4R), on gene expression levels in human NK cells. Methods: Comprehensive microarray-based mRNA expression profiling was performed to assess the gene expression levels in human NK cells in response to H4R stimulation in an unbiased approach. The expression of selected cytokines and chemokines was quantified by real-time PCR and enzyme-linked immunosorbent assay. Results: The microarray analysis identified only few genes which were differentially regulated upon H4R stimulation. In follow-up studies, a significant upregulation of CCL3 and CCL4 at the mRNA level and in addition for CCL3 also at the protein level via the H4R was observed. Conclusion: The elevated expression levels of chemokines in response to H4R stimulation might foster the inflammation in allergic skin diseases and characterize the H4R as a promising therapeutic target.
Early Mobilization in Ischemic Stroke: A Pilot Randomized Trial of Safety and Feasibility in a Public Hospital in Brazil
Authors: Poletto Simone Rosa , Rebello Letícia Costa , Valença Maria Júlia Monteiro , Rossato Daniele , Almeida Andrea Garcia , Brondani Rosane , Chaves Márcia Lorena Fagundes , Nasi Luiz Antônio , Martins Sheila Cristina Ouriques
Published: June 2015

Background: The effect of early mobilization after acute stroke is still unclear, although some studies have suggested improvement in outcomes. We conducted a randomized, single-blind, controlled trial seeking to evaluate the feasibility, safety, and benefit of early mobilization for patients with acute ischemic stroke treated in a public teaching hospital in Southern Brazil. This report presents the feasibility and safety findings for the pilot phase of this trial. Methods: The primary outcomes were time to first mobilization, total duration of mobilization, complications during early mobilization, falls within 3 months, mortality within 3 months, and medical complications of immobility. We included adult patients with CT- or MRI-confirmed ischemic stroke within 48 h of symptom onset who were admitted from March to November 2012 to the acute vascular unit or general emergency unit of a large urban emergency department (ED) at the Hospital de Clínicas de Porto Alegre. The severity of the neurological deficit on admission was assessed by the National Institutes of Health Stroke Scale (NIHSS). The NIHSS and modified Rankin Scale (mRS, functional outcome) scores were assessed on day 14 or at discharge as well as at 3 months. Activities of daily living (ADL) were measured with the modified Barthel Index (mBI) at 3 months. Results: Thirty-seven patients (mean age 65 years, mean NIHSS score 11) were randomly allocated to an intervention group (IG) or a control group (CG). The IG received earlier (p = 0.001) and more frequent (p < 0.0001) mobilization than the CG. Of the 19 patients in the CG, only 5 (26%) underwent a physical therapy program during hospitalization. No complications (symptomatic hypotension or worsening of neurological symptoms) were observed in association with early mobilization. The rates of complications of immobility (pneumonia, pulmonary embolism, and deep vein thrombosis) and mortality were similar in the two groups. No statistically significant differences in functional independence, disability, or ADL (mBI ≥85) were observed between the groups at the 3-month follow-up. Conclusions: This pilot trial conducted at a public hospital in Brazil suggests that early mobilization after acute ischemic stroke is safe and feasible. Despite some challenges and limitations, early mobilization was successfully implemented, even in the setting of a large, complex ED, and without complications. Patients from the IG were mobilized much earlier than controls receiving the standard care provided in most Brazilian hospitals.
Potent Gastric Acid Inhibition Over 24 Hours by 4-Times Daily Dosing of Esomeprazole 20 mg
Authors: Sahara Shu , Sugimoto Mitsushige , Uotani Takahiro , Ichikawa Hitomi , Yamade Mihoko , Kagami Takuma , Hamaya Yasushi , Iwaizumi Moriya , Osawa Satoshi , Sugimoto Ken , Miyajima Hiroaki , Furuta Takahisa
Published: June 2015

Background: When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition. Methods: In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens. Results: Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384). Conclusion: Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.
Burden of Epilepsy in Colombia
Authors: Méndez-Ayala Alejandro , Nariño Daniel , Rosselli Diego
Published: June 2015

Background: Epilepsy lays an important burden on healthcare systems and society in general. Disability adjusted life years (DALYs) have been developed to compare the burden of this disease both between conditions and between geographical boundaries. With improving data on disease incidence and prevalence in Colombia, we can refine our DALYs-based estimates. Methods: Using different strategies, including the official healthcare provision database and death certificates, as well as extrapolation from published neuroepidemiologic studies, we estimated the incidence and prevalence by age groups, disease duration and attributable mortality. With this information we calculated DALYs for the year 2012. Results: Overall, it was found that epilepsy was responsible for 0.88% of all deaths in Colombia. A total of 5.25 DALYs per 1,000 person-years are lost due to epilepsy in Colombia, 75% of which (3.91 DALYs) are due to premature mortality, with a higher burden in men (6.12 DALYs) than in women (4.41 DALYs). Conclusions: We reported new estimations on epilepsy incidence and prevalence by age groups in Colombia and conclude that DALYs lost due to epilepsy in Colombia are almost double the previous figure, mostly because of the underestimation of attributable mortality. With this figure, epilepsy ranks 12th instead of 19th in the list of the most important causes of DALYs lost.
Obinutuzumab (GA101) for the Treatment of Chronic Lymphocytic Leukemia and Other B-Cell Non-Hodgkin's Lymphomas: A Glycoengineered Type II CD20 Antibody
Authors: Goede Valentin , Klein Christian , Stilgenbauer Stephan
Published: June 2015

Obinutuzumab (GA101) is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. Preclinical data demonstrated more efficient B-cell depletion in whole blood and superior antitumor activity in xenograft models of obinutuzumab as compared to the type I CD20 antibody rituximab. In previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities, obinutuzumab plus chlorambucil increased response rates and prolonged progression-free survival compared with rituximab plus chlorambucil. Obinutuzumab had an acceptable and manageable safety profile, with infusion-related reactions during the first infusion as the most common adverse event. Further phase I/II clinical trials have also shown promising activity in other CD20-positive B-cell non-Hodgkin's lymphomas (NHL). Therefore, several clinical studies are planned or ongoing to investigate obinutuzumab with different combination partners in both untreated and relapsed/refractory patients with different B-cell NHL entities, which in addition to CLL include diffuse large B-cell lymphoma and follicular lymphoma.
Retinal Angiomatous Proliferation in an Eye with Cuticular Drusen
Authors: Sato Atsuko , Senda Nami , Fukui Emi , Ohta Kouichi
Published: June 2015

Purpose: To report the presence of retinal angiomatous proliferation (RAP) in an eye with cuticular drusen detected by fluorescein and indocyanine green angiography by confocal scanning laser ophthalmoscopy and by spectral-domain optical coherence tomography (SD-OCT). Methods: Case report of a 65-year-old Japanese woman with cuticular drusen. Results: At her first ophthalmic examination, her visual acuity was 20/20 in both eyes. An ophthalmoscopy showed many small subretinal pigment epithelial deposits in both eyes. These deposits had a ‘saw-tooth pattern' in the SD-OCT images. During the follow-up examination, retinal hemorrhages were observed, and fluorescein angiography showed a ‘stars-in-the-sky' appearance and intraretinal neovascularization. The patient was diagnosed with cuticular drusen associated with RAP. Conclusion: We suggest that the cuticular drusen were associated with RAP, so periodic follow-up examinations are needed for patients with cuticular drusen for the early detection and treatment of RAP.
New Onset, Aggravation and Recurrence of Crohn's Disease upon Treatment with Three Different Tumor Necrosis Factor Inhibitors
Authors: Zeitz Jonas , Enderlin Susann , Biedermann Luc , Turina Matthias , Leibl Sebastian , Prakash Meher , Rogler Gerhard , Misselwitz Benjamin
Published: June 2015

Tumor necrosis factor (TNF) is a major cytokine in the pathogenesis of inflammatory bowel disease (IBD), and TNF inhibition is a cornerstone of contemporary IBD therapy. However, paradoxical induction of IBD has recently been reported upon treatment of rheumatologic disorders with TNF inhibitors. In previous cases, induction of IBD was associated with one single drug and IBD was successfully managed by switching TNF inhibitors. We report the case of a patient with juvenile rheumatoid arthritis under long-term treatment with etanercept. After switching TNF inhibition to adalimumab, symptoms of Crohn's disease (CD) occurred and the diagnosis of CD was established by endoscopy. Further treatment with adalimumab and subsequently infliximab aggravated the abdominal symptoms, necessitating ileocecal resection, after which symptoms resolved for several months. Etanercept treatment due to recurrent rheumatologic symptoms was followed by recurrent CD symptoms and findings, which resolved upon discontinuation of etanercept. This case suggests that induction, aggravation and recurrence of IBD can be rare class effects of TNF inhibition.
Conjunctival Intraepithelial Neoplasia with Mucoepidermoid Differentiation: A Case Report of a Subtle Lesion
Authors: Joag Madhura G. , Gupta Anita , Galor Anat , Dubovy Sander R. , Bermudez-Magner Jose Antonio , Wang Jianhua , Karp Carol L.
Published: June 2015

Objective: To describe the clinical presentation, diagnostic imaging, and treatment options of conjunctival intraepithelial neoplasia (CIN) with mucoepidermoid differentiation, an in situ stage of mucoepidermoid carcinoma of the conjunctiva (MCC). Results: We report the case of an 86-year-old man presenting with a subtle limbal lesion that had only mild erythema and elevation. Based on a few atypical clinical features and an abnormal ultrahigh-resolution optical coherence tomography (UHR OCT), an incisional biopsy was performed revealing CIN with mucoepidermoid differentiation. Treatment involved aggressive surgical excision. No evidence of recurrence was noted in the 5 years of follow-up. Conclusion: MCC is an aggressive tumor that has a tendency to be invasive and recur after treatment. Therefore, early diagnosis and treatment is critical. CIN with mucoepidermoid differentiation may represent the earliest stage of MCC. It can present subtly, with a clinical resemblance to benign and less aggressive ocular surface lesions. Imaging with UHR OCT may be helpful to detect early neoplasia. A high level of suspicion must be maintained when evaluating potential ocular surface tumors.
Phonetic and Visual Cues to Questionhood in French Conversation
Authors: Torreira Francisco , Valtersson Emma
Published: June 2015

We investigate the extent to which French polar questions and continuation statements, two types of utterances with similar morphosyntactic and intonational forms but different pragmatic functions, can be distinguished in conversational data based on phonetic and visual bodily information. We show that the two utterance types can be distinguished well over chance level by automatic classification models including several phonetic and visual cues. We also show that a considerable amount of relevant phonetic and visual information is present before the last portion of the utterances, potentially assisting early speech act recognition by addressees. These findings indicate that bottom-up phonetic and visual cues may play an important role during the production and recognition of speech acts alongside top-down contextual information.
Human Papillomavirus 16 Variants May Be Identified by E6 Gene Analysis
Authors: Fontecha Nerea , Basaras Miren , Arrese Elixabete , Hernáez Silvia , Andía Daniel , Cisterna Ramon
Published: June 2015

Aims: The aims of the study were (1) to characterize the genetic variability of human papillomavirus (HPV) genotype 16 in the E6 region when this genotype is present in multiple infection samples, (2) to assess the prevalence of variants in our region and (3) to analyze the relationship between variants, patients' ages and pathology. Methods: The Clinical Microbiology and Infection Control Department analyzed samples which were positive for genotype 16 and other genotypes from 2007 to 2013. Variants were assigned to European, Euro-German, Asian, Asian-American or African lineage by sequence analysis. The relationship among variants, age and different types of lesion was studied. Results: In HPV-16 sequence analysis, the European variant was detected in 85.10% of samples, the Asian-American in 7.80%, the African in 4.25% and the Euro-German in 2.83% of specimens. Sequence genetic variability showed 16 nucleotide substitutions. Moreover, non-European variants were mainly found in old women and in isolates from high-grade squamous intraepithelial lesions since European variants were mainly detected in negative cytologies. Conclusion: Multiple infections may take effect on nucleotide substitution and the appearance of recombinant samples. Single gene analysis makes it impossible to detect recombination which has a great influence on drug response and vaccine strategies. Thus, E6 gene analysis would be enough to identify HPV-16 intratypic variants but not to confirm the results.
A Modified Dummy Plaque for the Accurate Placement of Ruthenium-106 Plaques in Brachytherapy of Intraocular Tumours
Authors: Krohn Jørgen
Published: June 2015

Purpose: To present a new technique to ensure the correct positioning of ruthenium plaques in episcleral brachytherapy. Materials and Methods: An acrylic dummy plaque is made opaque by sanding both sides with sandpaper, and its edge is covered by a black marking tape. This modified plaque is temporarily sutured to the sclera overlying the choroidal tumour site. The tip of an endoillumination probe is placed at the anterior edge of the plaque, yielding a strong light scattering within the opaque acrylic material. Due to the light-absorbing tape around the plaque border, the scattered light is confined within the plaque, and its perimeter can be observed by indirect ophthalmoscopy as a circle of transilluminated light surrounding the tumour. When the correct position has been found, the dummy plaque is replaced by a ruthenium-106 plaque. Results: The technique was successfully applied in 5 patients with posterior choroidal melanoma. Compared to standard focal transillumination, its main advantage is that the position of the entire plaque and tumour can be observed simultaneously in one field without any movement or manipulation of the light probe or plaque. Conclusion: The described transillumination technique and modified dummy plaque facilitate the correct positioning of ruthenium plaques in brachytherapy of choroidal melanoma.
Severe, Persistent and Fatal Delirium in Psychogeriatric Patients Admitted to a Psychiatric Hospital
Authors: Jans Ingrid S. , Oudewortel Letty , Brandt Paulien M. , van Gool Willem A.
Published: June 2015

Background/Aims: Although delirium is generally regarded as a transient syndrome, persistence of delirium in patients with cognitive impairment - even with fatal outcome - has been reported as well. This study aims to describe the clinical features and neuropathological correlates of this type of delirium. Methods: Inclusion criteria for this case series were: (1) severe persistent delirium until death, (2) history of cognitive decline and (3) consent for brain autopsy. Medical records were examined in combination with collected clinical data and neuropathological findings. Result: In 15 patients, all living at home before admission, episodes with delirium lasted for 4.2 months on average. No distinct medical causes of persistent delirium could be identified. Pathological diagnoses included Alzheimer's disease and dementia with Lewy bodies as well as single cases of Creutzfeldt-Jakob disease and progressive supranuclear palsy. Conclusion: Severe, persistent and fatal delirium in patients with cognitive impairment can occur relatively early in the disease trajectory and is associated with diverse neuropathologies.
Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy
Authors: Musa Faisal , Baidas Said
Published: June 2015

We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse.
Lung Cancer Presenting as a Soft-Tissue Metastasis
Authors: Baldeo Candice , Ali Robert , Seeram Vandana , House Jeff
Published: June 2015

Soft-tissue metastasis refers to the growth of cancer cells, originating from internal cancer, in soft tissues. In most cases, soft-tissue metastases develop after initial diagnosis of the primary internal malignancy and late in the course of the disease. In very rare cases, they may occur at the same time or before the primary cancer has been detected. In our cases, the soft-tissue metastases and the primary lung cancer were diagnosed at the same time.
Frequency of TERT Promoter Mutations in Prostate Cancer
Authors: Stoehr Robert , Taubert Helge , Zinnall Ulrike , Giedl Johannes , Gaisa Nadine T. , Burger Maximilian , Ruemmele Petra , Hurst Carolyn D. , Knowles Margaret A. , Wullich Bernd , Hartmann Arndt
Published: June 2015

Objective: Recently, recurrent mutations within the core promoter of the human telomerase reverse transcriptase (TERT) gene generating consensus binding sites for ETS transcription factor family members were described in melanomas and other malignancies (e.g. bladder cancer, hepatocellular carcinoma). These mutations were discussed as early drivers for malignant transformation. In prostate cancer (PrCa) TERT expression has been associated with a poor prognosis and higher risk for disease recurrence. The underlying mechanisms for high TERT expression in PrCa have still not been clarified. To date, data on TERT promoter mutation analysis in PrCa are sparse. Therefore, we performed sequence analysis of the core promoter region of the TERT gene in an unselected cohort of prostate tumors. Methods: Sections from 167 formalin-fixed, paraffin-embedded and cryopreserved prostate tumors were microdissected and used for DNA isolation. The mutation hotspot region within the TERT core promoter (-260 to +60) was analyzed by direct Sanger sequencing or SNaPshot analysis. Results: All cases were analyzed successfully. Mutations within the core promoter of the TERT gene were not detected in any of the cases with all tumors exhibiting a wild-type sequence. Conclusion:TERT core promoter mutations reported from several other malignancies were not detected in our unselected cohort of PrCa. These data indicate that alterations within the core promoter of the TERT gene do not play an important role in prostate carcinogenesis.
Being Born Small for Gestational Age Influences Amplitude-Integrated Electroencephalography and Later Outcome in Preterm Infants
Authors: Schwindt Eva , Thaller Cornelia , Czaba-Hnizdo Christine , Giordano Vito , Olischar Monika , Waldhoer Thomas , Fuiko Renate , Berger Angelika , Weninger Manfred , Klebermass-Schrehof Katrin
Published: June 2015

Background: The impact of growth restriction on perinatal morbidity is well known, but electroencephalographic (EEG) data on its influence are still scarce. Objectives: We aimed to analyze the influence of being born small for gestational age (SGA; defined as a birth weight <10th percentile) on the amplitude-integrated EEG (aEEG) score in the first 2 weeks of life in preterm infants born before 30 weeks of gestation, and its impact on later outcome. Methods: aEEG data obtained within the first 2 weeks of life on preterm infants born SGA and before 30 weeks of gestational age (GA) were analyzed retrospectively using a combined score [including background activity, occurrence of sleep-wake cycles (SWC) and suspected seizure activity]. Neurodevelopmental outcome was evaluated at 24 months by means of the Bayley Scales of Infant Development II and a standardized neurological examination. Results: One hundred and thirty-six patients were included (47 SGA and 89 controls). Infants with SGA had abnormal aEEG scores significantly more often (57 vs. 24%, p = 0.002) than infants born appropriate for gestational age (AGA). They also displayed SWC less frequently (65 vs. 96%, p = 0.001), were more likely to develop seizure activity (15 vs. 4%, p = 0.013) and had a normal neurodevelopmental outcome at the age of 2 years less frequently (36.2 vs. 59.6%, p = 0.02). Conclusion: Preterm infants born SGA and before 30 weeks of GA had less optimal scores on early aEEG and a poorer neurodevelopmental outcome at 24 months than the AGA controls.
Serum Oxytocin, Posttraumatic Coping and C-Reactive Protein in Motor Vehicle Accident Survivors by Gender
Authors: Nishi Daisuke , Hashimoto Kenji , Noguchi Hiroko , Kim Yoshiharu , Matsuoka Yutaka
Published: June 2015

Background: Previous studies indicate that oxytocin (OT) might play a major role in the prevention of posttraumatic stress disorder (PTSD) and that the effects of OT might differ by gender. This exploratory study aimed to clarify the relationships between the OT level and physical and psychosocial factors by gender in accident survivors. Methods: Two hundred and thirty-five accident survivors offered blood samples at baseline, 155 of whom participated in follow-up assessments 1 month later. Spearman's correlation coefficients were calculated between the serum OT levels and physical and psychosocial factors assessed at baseline by gender. Univariate and multivariate regression analyses were then used to examine the relationships between the serum OT levels and psychological variables by gender. Results: In men, the OT levels were negatively associated with C-reactive protein at baseline and did not predict any psychological variables at the 1-month follow-up. On the other hand, in women, the OT levels were positively associated with cooperativeness at baseline and predicted seeking social support, positive reappraisal, accepting responsibility and planful problem solving at the 1-month follow-up. The OT levels were not associated with PTSD, depression, and anxiety symptoms. Conclusions: The findings suggest that the role of OT in posttraumatic coping and inflammation differs by gender in accident survivors. Gender differences in the effects and mechanism of OT might be a key consideration when developing interventions using OT.
Prolonged Survival in a Case of Chemotherapy-Sensitive Gastric Cancer That Produced Alpha-Fetoprotein and Protein Induced by Vitamin K Antagonist-II
Authors: Ogasawara Naotaka , Takahashi Emiko , Matsumoto Tomoko , Amaike Manami , Nohara Mako , Nagao Kazuhiro , Ebi Masahide , Funaki Yasushi , Sasaki Makoto , Kasugai Kunio
Published: June 2015

The number of reported cases of alpha-fetoprotein (AFP)-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II) are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT) revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD) revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy.
A Case of Acute Bilateral Irvine-Gass Syndrome following Uncomplicated Phacoemulsification, Demonstrated with Optical Coherence Tomography
Authors: Shields Melissa K. , Adler Paul A. , Fuzzard Dujon R.W. , Chalasani Rajeeve , Teong Joanne M.Y.
Published: June 2015

Purpose: To report a case of acute bilateral Irvine-Gass syndrome. Methods: This is an observational case report. Results: An 82-year-old man with no significant ocular history developed postsurgical pseudophakic cystoid macular edema (CME; Irvine-Gass syndrome) on consecutive phacoemulsification cataract surgeries. His initial first-eye (left) CME developed 25 days after surgery and was managed with topical preparations of dexamethasone 0.1% and ketorolac 0.4%, in addition to a routine post-cataract surgery drop regime. His left CME resolved completely on optical coherence tomography (OCT) by day 100, and he subsequently (after extensive discussion of CME risks) underwent cataract surgery on his right eye. He was commenced prophylactically on dexamethasone, ketorolac and oral indomethacin 25 mg t.d.s. immediately after surgery; however, he later developed CME (OD) on day 32 postoperatively. Within 6 months, he achieved complete resolution of his CME in both eyes. His clinical course was documented with serial OCT studies. Conclusion: Irvine-Gass syndrome remains an important differential diagnosis in the evaluation of blurred vision after cataract surgery, despite decreasing incidence. Those who experience CME following their first cataract operation should be counseled about the risks of developing the condition in the contralateral eye, despite prophylactic measures.
Sequence of Molecular Events during the Maturation of the Developing Mouse Prefrontal Cortex
Authors: Ueda Shuhei , Niwa Minae , Hioki Hiroyuki , Sohn Jaerin , Kaneko Takeshi , Sawa Akira , Sakurai Takeshi
Published: June 2015

Recent progress in psychiatric research has accumulated many mouse models relevant to developmental neuropsychiatric disorders using numerous genetic and environmental manipulations. Since the prefrontal cortex (PFC) is essential for cognitive functions whose impairments are central symptoms associated with the disorders in humans, it has become crucial to clarify altered developmental processes of PFC circuits in these mice. To that end, we aimed to understand a sequence of molecular events during normal mouse PFC development. Expression profiles for representative genes covering diverse biological processes showed that while there were little changes in genes for neuroreceptors and synaptic molecules during the postnatal period, there were dramatic increases in the expression of myelin-related genes and the parvalbumin gene, peaking at postnatal day (P)21 and P35, respectively. The timing of the peaks is different from that observed in the striatum. Furthermore, the evaluation of the circuitry maturation by measuring extracellular glutamate in the PFC revealed that sensitivity to an NMDA antagonist did not become an adult-like pattern till P56, suggesting that some of the maturation processes continue till P56. The trajectory of molecular events in PFC maturation described here should help us to characterize how the processes are affected in disease model mice, an important first step for translational research.
14,15-Epoxyeicosatrienoic Acid Suppresses Cigarette Smoke Extract-Induced Apoptosis in Lung Epithelial Cells by Inhibiting Endoplasmic Reticulum Stress
Authors: Yu Ganggang , Zeng Xiangjun , Wang Hongxia , Hou Qi , Tan Chunting , Xu Qiufen , Wang Haoyan
Published: June 2015

Background/Aims: Epoxyeicosatrienoic acids (EETs), a type of lipid mediators produced by cytochrome P450 epoxygenases, exert anti-inflammatory, angiogenic, anti-oxidative and anti-apoptotic effects. However, the role of EETs in cigarette smoke-induced lung injury and the underlying mechanisms are not fully known. The aim of this study was to explore the effects of CYP2J2-EETs on cigarette smoke extracts (CSE)-induced apoptosis in human bronchial epithelial cell line (Beas-2B) and the possible mechanisms involved. Methods: Cytochrome P450 epoxygenase 2J2 (CYP2J2) and its metabolites EETs were assessed by western blotting or LC-MS-MS. Cell viability and apoptosis were determined by MTT assay and AnnexinV-PI staining. Reactive oxygen species (ROS) were assessed by measuring H2DCFDA. Caspase-3, HO-1, MAPK and endoplasmic reticulum (ER) stress-related markers GRP78, p-elF2a, and CHOP were evaluated by western blotting. Results: CSE suppressed expression of both CYP2J2 and EET by Beas-2B cells. CSE also induced apoptosis, the generation of ROS and the ER stress in Beas-2B cells. These changes were abolished by pretreatment with exogenous 14,15-EET while pretreatment with 14,15-EEZE, a selective EET antagonist, abolished the protective effects of 14,15-EET. In addition, EETs increased the expression of antioxidant enzyme HO-1. Furthermore, 14,15-EET reduced CSE-induced activation of p38 and JNK. Conclusion: The data suggest that CYP2J2-derived EETs protect against CSE-induced lung injury possibly through attenuating ER stress.
Ginsenoside Rh2 Inhibits Cancer Stem-Like Cells in Skin Squamous Cell Carcinoma
Authors: Liu Shunli , Chen Mingrui , Li Pengcheng , Wu Yujia , Chang Chunjuan , Qiu Yabin , Cao Ling , Liu Zhen , Jia Chiyu
Published: June 2015

Background/Aims: Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined. Methods: Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and β-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and β-catenin were used to inhibit autophagy and β-catenin signaling pathway, respectively, as loss-of-function experiments. Results: We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced β-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on β-catenin and cell viability, while increasing β-catenin abolished the effects of GRh2 on autophagy and cell viability. Conclusion: Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and β-catenin signaling.