bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Dimebon in cellular model of Huntington's disease
Authors: Wu Jun , Li Qin , Bezprozvanny Ilya 
Published: October 2008

Abstract

Background
Dimebon is an antihistamine compound with a long history of clinical use in Russia. Recently, Dimebon has been proposed to be useful for treating neurodegenerative disorders. It has demonstrated efficacy in phase II Alzheimer's disease (AD) and Huntington's disease (HD) clinical trials. The mechanisms responsible for the beneficial actions of Dimebon in AD and HD remain unclear. It has been suggested that Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition.

Results
We evaluated the effects of Dimebon in experiments with primary striatal neuronal cultures (MSN) from wild type (WT) mice and YAC128 HD transgenic mice. We found that Dimebon acts as an inhibitor of NMDA receptors (IC50 = 10 μM) and voltage-gated calcium channels (IC50 = 50 μM) in WT and YAC128 MSN. We further found that application of 50 μM Dimebon stabilized glutamate-induced Ca2+ signals in YAC128 MSN and protected cultured YAC128 MSN from glutamate-induced apoptosis. Lower concentrations of Dimebon (5 μM and 10 μM) did not stabilize glutamate-induced Ca2+ signals and did not exert neuroprotective effects in experiments with YAC128 MSN. Evaluation of Dimebon against a set of biochemical targets indicated that Dimebon inhibits α-Adrenergic receptors (α1A, α1B, α1D, and α2A), Histamine H1 and H2 receptors and Serotonin 5-HT2c, 5-HT5A, 5-HT6 receptors with high affinity. Dimebon also had significant effect on a number of additional receptors.

Conclusion
Our results suggest that Ca2+ and mitochondria stabilizing effects may, in part, be responsible for beneficial clinical effects of Dimebon. However, the high concentrations of Dimebon required to achieve Ca2+ stabilizing and neuroprotective effects in our in vitro studies (50 μM) indicate that properties of Dimebon as cognitive enhancer are most likely due to potent inhibition of H1 histamine receptors. It is also possible that Dimebon acts on novel high affinity targets not present in cultured MSN preparation. Unbiased evaluation of Dimebon against a set of biochemical targets indicated that Dimebon efficiently inhibited a number of additional receptors. Potential interactions with these receptors need to be considered in interpretation of results obtained with Dimebon in clinical trials.
Permutation – based statistical tests for multiple hypotheses
Authors: Camargo Anyela , Azuaje Francisco , Wang Haiying , Zheng Huiru 
Published: October 2008

Abstract

Background
Genomics and proteomics analyses regularly involve the simultaneous test of hundreds of hypotheses, either on numerical or categorical data. To correct for the occurrence of false positives, validation tests based on multiple testing correction, such as Bonferroni and Benjamini and Hochberg, and re-sampling, such as permutation tests, are frequently used. Despite the known power of permutation-based tests, most available tools offer such tests for either t-test or ANOVA only. Less attention has been given to tests for categorical data, such as the Chi-square. This project takes a first step by developing an open-source software tool, Ptest, that addresses the need to offer public software tools incorporating these and other statistical tests with options for correcting for multiple hypotheses.

Results
This study developed a public-domain, user-friendly software whose purpose was twofold: first, to estimate test statistics for categorical and numerical data; and second, to validate the significance of the test statistics via Bonferroni, Benjamini and Hochberg, and a permutation test of numerical and categorical data. The tool allows the calculation of Chi-square test for categorical data, and ANOVA test, Bartlett's test and t-test for paired and unpaired data. Once a test statistic is calculated, Bonferroni, Benjamini and Hochberg, and a permutation tests are implemented, independently, to control for Type I errors. An evaluation of the software using different public data sets is reported, which illustrates the power of permutation tests for multiple hypotheses assessment and for controlling the rate of Type I errors.

Conclusion
The analytical options offered by the software can be applied to support a significant spectrum of hypothesis testing tasks in functional genomics, using both numerical and categorical data.
Bladder incarceration following anterior external fixation of a traumatic pubic symphysis diastasis treated with immediate open reduction and internal fixation
Authors: Finnan Ryan P , Herbenick Michael A , Prayson Michael J , McCarthy Mary C 
Published: October 2008

Abstract
Anterior pelvic ring disruptions are often associated with injuries to the genitourinary structures with the potential for considerable resultant morbidity. Herniation of the bladder into the symphyseal region after injury with subsequent entrapment upon reduction of the symphyseal diastasis has seldom been reported in the literature. We report such a case involving bladder herniation and subsequent entrapment after attempted closed reduction with anterior pelvic external fixation immediately treated with open reduction and internal fixation along with a review of the literature.
Seroprevalence and epidemiological correlates of Toxoplasma gondii infections among patients referred for hospital-based serological testing in Doha, Qatar
Authors: Abu-Madi Marawan A , Al-Molawi Naema , Behnke Jerzy M 
Published: October 2008

Abstract

Background
The city of Doha in Qatar has a high density of feral cats and there is a high risk of toxoplasmosis for the resident human population. No data currently exist for the prevalence of infection with Toxoplasma gondii in the city.

Methods
We analysed the serological response to Toxoplasma gondii of 1625 subjects referred for routine hospital based serological tests in Doha, Qatar. Prevalence of current/recent infection was assessed through an enzyme-linked immunosorbent assay (ELISA) for the presence of specific anti-T. gondii IgM antibodies, and previous history of infection through IgG.

Results
Overall prevalence of IgG responses was 29.8% and this did not differ between the sexes nor between the three years of the study although there was a marked age effect. Among children less than 1 year old prevalence was 22.9%, but then dropped to <4% in the 1 year old group, indicating that these antibodies were most likely acquired in utero from immune mothers. Prevalence then increased steadily to peak at 41.2% among the oldest age class (>45 years). The prevalence of IgG antibody also varied significantly with region of origin, with higher rates for subjects from Africa, followed by those from the Eastern Mediterranean or Asia and lowest rates for subjects from the Arabian Peninsula. No IgM antibodies were detected in any subjects younger than 19 years, but prevalence increased to plateau at 7 – 9% in subjects aged over 20 years, and also varied with region of origin. In this case prevalence was highest among subjects from the Arabian Peninsula and least among those from Asia. Prevalence of IgM was higher among male subjects but did not vary between the three years of the study.

Conclusion
Although these data are based on a selected subset of the population, they nevertheless provide the first evidence that toxoplasmosis is endemic in Qatar in the human population, and that both age and region of origin play a role in the epidemiology of the infection. Concerns relating to the role of high density of feral cats in sustaining the infection were highlighted.
Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy
Authors: Amstutz Ursula , Farese Simone , Aebi Stefan , Largiadèr Carlo R 
Published: October 2008

Abstract

Background
The activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme of pyrimidine catabolism, is thought to be an important determinant for the occurrence of severe toxic reactions to 5-fluorouracil (5-FU), which is one of the most commonly prescribed chemotherapeutic agents for the treatment of solid cancers. Genetic variation in the DPD gene (DPYD) has been proposed as a main factor for variation in DPD activity in the population. However, only a small proportion of severe toxicities in 5-FU based chemotherapy can be explained with such rare deleterious DPYD mutations resulting in severe enzyme deficiencies. Recently, hypermethylation of the DPYD promoter region has been proposed as an alternative mechanism for DPD deficiency and thus as a major cause of severe 5-FU toxicity.

Methods
Here, the prognostic significance of this epigenetic marker with respect to severe 5-FU toxicity was assessed in 27 cancer patients receiving 5-FU based chemotherapy, including 17 patients experiencing severe toxic side effects following drug administration, none of which were carriers of a known deleterious DPYD mutation, and ten control patients. The methylation status of the DPYD promoter region in peripheral blood mononuclear cells was evaluated by analysing for each patient between 19 and 30 different clones of a PCR-amplified 209 base pair fragment of the bisulfite-modified DPYD promoter region. The fragments were sequenced to detect bisulfite-induced, methylation-dependent sequence differences.

Results
No evidence of DPYD promoter methylation was observed in any of the investigated patient samples, whereas in a control experiment, as little as 10% methylated genomic DNA could be detected.

Conclusion
Our results indicate that DYPD promoter hypermethylation is not of major importance as a prognostic factor for severe toxicity in 5-FU based chemotherapy.
PTTG: an important target gene for ovarian cancer therapy
Authors: Panguluri Siva Kumar , Yeakel Casey , Kakar Sham S 
Published: October 2008

Abstract
Pituitary tumor transforming gene (PTTG), also known as securin is an important gene involved in many biological functions including inhibition of sister chromatid separation, DNA repair, organ development, and expression and secretion of angiogenic and metastatic factors. Proliferating cancer cells and most tumors express high levels of PTTG. Overexpression of PTTG in vitro induces cellular transformation and development of tumors in nude mice. The PTTG expression levels have been correlated with tumor progression, invasion, and metastasis. Recent studies show that down regulation of PTTG in tumor cell lines and tumors in vivo results in suppression of tumor growth, suggesting its important role in tumorigenesis. In this review, we focus on PTTG structure, sub-cellular distribution, cellular functions, and role in tumor progression with suggestions on possible exploration of this gene for cancer therapy.
The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability
Authors: Waeschle Reiner M , Moerer Onnen , Hilgers Reinhard , Herrmann Peter , Neumann Peter , Quintel Michael 
Published: October 2008

Abstract
Introduction
The purpose of this study was to assess the relation between glycaemic control and the severity of sepsis in a cohort of patients treated with intensive insulin therapy (IIT).

Methods
In a prospective, observational study, all patients in the intensive care unit (ICU) (n = 191) with sepsis, severe sepsis or septic shock were treated with IIT (target blood glucose (BG) level 80 to 140 mg/dl instead of strict normoglycaemia). BG values were analysed by calculating mean values, rate of BG values within different ranges, rate of patients experiencing BG values within different levels and standard deviation (SD) of BG values as an index of glycaemic variability.

Results
The number of patients with hypoglycaemia and hyperglycaemia was highly dependent on the severity of sepsis (critical hypoglycaemia ≤ 40 mg/dl: sepsis: 2.1%, severe sepsis: 6.0%, septic shock: 11.5%, p = 0.1497; hyperglycaemia: >140 mg/dl: sepsis: 76.6%, severe sepsis: 88.0%, septic shock: 100%, p = 0.0006; >179 mg/dl: sepsis: 55.3%, severe sepsis: 73.5%, septic shock: 88.5%, p = 0.0005; >240 mg/dl: sepsis: 17.0%, severe sepsis: 48.2%, septic shock: 45.9%, p = 0.0011). Multivariate analyses showed a significant association of SD levels with critical hypoglycaemia especially for patients in septic shock (p = 0.0197). In addition, SD levels above 20 mg/dl were associated with a significantly higher mortality rate relative to those with SD levels below 20 mg/dl (24% versus 2.5%, p = 0.0195).

Conclusions
Patients with severe sepsis and septic shock who were given IIT had a high risk of hypoglycaemia and hyperglycaemia. Among these patients even with a higher target BG level, IIT mandates an increased awareness of the occurrence of critical hypoglycaemia, which is related to the severity of the septic episode.
Does Age Really Matter? Recall of Information Presented to Newly Referred Patients With Cancer
Authors: Jansen Jesse , Butow Phyllis N. , van Weert Julia C.M. , van Dulmen Sandra , Devine Rhonda J. , Heeren Thea J. , Bensing Jozien M. , Tattersall Martin H.N. 
Published: October 2008

Purpose To examine age- and age-related differences in recall of information provided during oncology consultations. Patients and Methods Two hundred sixty patients with cancer diagnosed with heterogeneous cancers, seeing a medical or radiation oncologist for the first time, participated in the study. Patients completed questionnaires assessing information needs and anxiety. Recall of information provided was measured using a structured telephone interview in which patients were prompted to remember details physicians gave about diagnosis, prognosis, and treatment. Recall was checked against the actual communication in audio-recordings of the consultations. Results Recall decreased significantly with age, but only when total amount of information presented was taken into account. This indicates that if more information is discussed, older patients have more trouble remembering the information than younger ones. In addition, recall was selectively influenced by prognosis. First, patients with a poorer prognosis recalled less. Next, the more information was provided about prognosis, the less information patients recalled, regardless of their actual prognosis. Conclusion Recall is not simply a function of patient age. Age only predicts recall when controlling for amount of information presented. Both prognosis and information about prognosis are better predictors of recall than age. These results provide important insights into intervention strategies to improve information recall in patients with cancer.
Clinical Outcome and Predictors of Survival in Late Relapse of Germ Cell Tumor
Authors: Sharp David S. , Carver Brett S. , Eggener Scott E. , Kondagunta G. Varuni , Motzer Robert J. , Bosl George J. , Sheinfeld Joel 
Published: October 2008

Purpose Late relapse (LR) of germ cell tumor (GCT) is a well recognized entity associated with poor survival. We report on our experience with LR and determine predictors of survival. Patients and Methods From 1990 to 2004, 75 patients were managed for LR of GCT at our institution. Clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method, and a Cox proportional hazards model was used to assess potential predictors of outcome. Results The median time to LR was 6.9 years (range, 2.1 to 37.7 years). Overall, 56 patients (75%) had LR in the retroperitoneum, including 25 (93%) of 27 patients initially managed without retroperitoneal lymph node dissection. The 5-year cancer-specific survival (CSS) was 60% (95% CI, 46% to 71%). Patients who underwent complete surgical resection at time of LR (n = 45) had a 5-year CSS of 79% versus 36% for patients without complete resection (n = 30; P < .0001). The 5-year CSS for chemotherapy-naive patients was significantly greater than patients with a prior history of chemotherapy as part of their initial management (5-year CSS, 93% v 49%, respectively). In multivariable analysis of pretreatment parameters available at the time of LR, the presence of symptoms (hazard ratio [HR] = 4.9) and multifocal disease (HR = 3.0) were associated with an inferior CSS. Conclusion The data suggest that meticulous control of the retroperitoneum is critical to prevent LR in the retroperitoneum. In multivariable analysis, patients with a symptomatic presentation and those with multifocal disease have a significantly decreased survival. Survival is greatly improved if complete surgical excision of disease is attained.
Chemotherapy As an Alternative to Radiotherapy in the Treatment of Stage IIA and IIB Testicular Seminoma: A Spanish Germ Cell Cancer Group Study
Authors: Garcia-del-Muro Xavier , Maroto Pablo , Gumà Josep , Sastre Javier , López Brea Marta , Arranz José A. , Lainez Nuria , de Prado Diego Soto , Aparicio Jorge , Piulats José M. , Pérez Xavier , Germá-Lluch Josep R. 
Published: October 2008

Purpose To assess the long-term efficacy and toxicity of front-line cisplatin-based chemotherapy in patients with stage IIA or IIB testicular seminoma. Patients and Methods Untreated patients with pure seminoma of the testis after orchiectomy, with clinical stage IIA or IIB, were considered eligible for this prospective observational study. Chemotherapy consisted of either four cycles of cisplatin and etoposide or three cycles of cisplatin, etoposide, and bleomycin. Results Between April 1994 and March 2003, 72 patients were entered onto the study at 26 participating centers. Eighteen patients had stage IIA disease, and 54 patients had stage IIB disease. Eighty-three percent of patients achieved complete response, and 17% achieved partial response with residual mass. After a median follow-up time of 71.5 months, six patients with stage IIB disease experienced relapse, and one of these patients died as a result of seminoma. Three patients experienced non–seminoma-related deaths (two died from a further esophageal carcinoma, and one died from an upper digestive hemorrhage). The estimated 5-year progression-free survival rates for patients with stage IIA or IIB disease were 100% and 87% (95% CI, 77.5% to 97%), respectively. Five-year progression-free and overall survival rates for the whole group were 90% (95% CI, 82% to 98%) and 95% (95% CI, 89% to 100%), respectively. Severe granulocytopenia and thrombocytopenia were observed in eight and two patients, respectively. Mild to moderate emesis, stomatitis, and diarrhea were the most common nonhematologic effects. Conclusion Chemotherapy is a highly effective and well-tolerated treatment for patients with stage IIA or IIB seminoma and represents an available alternative that could avoid some of the serious late effects associated with radiotherapy. Further studies focusing on long-term toxicities of different treatment modalities are needed.
Pathologic Response to Preoperative Chemotherapy: A New Outcome End Point After Resection of Hepatic Colorectal Metastases
Authors: Blazer Dan G. , Kishi Yoji , Maru Dipen M. , Kopetz Scott , Chun Yun Shin , Overman Michael J. , Fogelman David , Eng Cathy , Chang David Z. , Wang Huamin , Zorzi Daria , Ribero Dario , Ellis Lee M. , Glover Katrina Y. , Wolff Robert A. , Curley Steven A. , Abdalla Eddie K. , Vauthey Jean-Nicolas 
Published: October 2008

Purpose The primary goal of this study was to evaluate whether pathologic response to chemotherapy predicts patient survival after preoperative chemotherapy and resection of colorectal liver metastases (CLM). The secondary goal of the study was to identify the clinical predictors of pathologic response. Patients and Methods A retrospective review was performed of 305 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by resection of CLM. Pathologic response was systematically evaluated and reported as the mean of the percentage of cancer cells remaining within each tumor. Univariate and multivariate analyses were performed to identify the predictors of pathologic response and survival. Results Cumulative 5-year overall survival rates by pathologic response status were as follows: 75% complete response (no residual cancer cells), 56% major response (1% to 49% residual cancer cells), and 33% minor response (≥ 50% residual cancer cells; complete v major response, P = .037; major v minor response, P = .028). Multivariate analysis revealed that only surgical margin status (P = .050; hazard ratio [HR], 1.77) and pathologic response (major response: P = .034; HR, 4.80; minor response: P = .007; HR, 6.93) were independent predictors of survival. Multivariate analysis of the predictors of pathologic response revealed that carcinoembryonic antigen level ≤ 5 ng/mL, tumor size ≤ 3 cm, and chemotherapy with fluoropyrimidine plus oxaliplatin and bevacizumab were independent predictors of pathologic response. Conclusion Pathologic response predicts survival after preoperative chemotherapy and resection of CLM. Degree of pathologic response represents a new outcome end point for prognosis after resection of CLM.
Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry
Authors: Carling R S , Hogg S L , Wood T C , Calvin J 
Published: October 2008

BackgroundCreatine plays an important role in the storage and transmission of phosphate-bound energy. The cerebral creatine deficiency syndromes (CCDS) comprise three inherited defects in creatine biosynthesis and transport. They are characterized by mental retardation, speech and language delay and epilepsy. All three disorders cause low-creatine signal on brain magnetic resonance spectroscopy (MRS); however, MRS may not be readily available and even when it is, biochemical tests are required to determine the underlying disorder.MethodsAnalysis was performed by liquid chromatography-tandem mass spectrometry in positive ionization mode. Samples were analysed underivatized using a rapid ‘dilute and shoot’ approach. Chromatographic separation of the three compounds was achieved. Stable isotope internal standards were used for quantification.ResultsCreatine, creatinine and guanidinoacetate were measured with a 2.5 minute run time. For guanidinoacetate, the standard curve was linear to at least 5000 μmol/L and for creatine and creatinine it was linear to at least 25 mmol/L. The lower limit of quantitation was 0.4 μmol/L for creatine and guanidinoacetate and 0.8 μmol/L for creatinine. Recoveries ranged from 86% to 106% for the three analytes. Intra- and inter-assay variation for each analyte was <10% in both urine and plasma.ConclusionA tandem mass spectrometric method has been developed and validated for the underivatized determination of guanidinoacetate, creatine and creatinine in human urine and plasma. Minimal sample preparation coupled with a rapid run time make the method applicable to the routine screening of patients with suspected CCDS.