bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spectrum of substance abuse in bipolar disorder: reasons for use, sensation seeking and substance sensitivity
Authors: Bizzarri Jacopo V , Sbrana Alfredo , Rucci Paola , Ravani Laura , Massei Guido Jacopo , Gonnelli Chiara , Spagnolli Sabrina , Doria Maria Rosa , Raimondi Federica , Endicott Jean , Dell'Osso Liliana , Cassano Giovanni Battista 
Published: April 2007

Objectives:  To examine the spectrum of alcohol and substance abuse, including reasons for use, in patients with bipolar I disorder, compared with patients with substance use disorder and healthy controls, with a specific focus on the relationship between substance use, substance sensitivity, other comorbid psychiatric symptoms and traits related to sensation seeking.Methods:  This study included 104 patients with bipolar I disorder (BPD I), of whom 57 (54.8%) met DSM‐IV criteria for lifetime alcohol or substance use disorder (BPD + SUD), 35 patients with substance use disorder (SUD) and no psychiatric disorder and 50 healthy controls. Assessments included the Structured Clinical Interview for DSM‐IV Axis I Disorders (SCID) and the Structured Clinical Interview for the Spectrum of Substance Use (SCI‐SUBS).Results:  Patients with BPD + SUD and SUD had significantly higher scores on the SCI‐SUBS domains of self‐medication, substance sensitivity and sensation seeking compared with patients with BPD and healthy controls. Reasons for substance use did not differ between patients with BPD + SUD and patients with SUD. Those most frequently cited were: improving mood; relieving tension; alleviating boredom; achieving/maintaining euphoria; and increasing energy.Conclusions:  Recourse to substances is associated with increased mood and anxiety symptoms, substance sensitivity, and sensation seeking among patients with BPD + SUD and SUD. Substance sensitivity and sensation seeking traits should be investigated in all patients with BPD as possible factors associated with a development of SUD, in order to warn patients of the specific risks related to improper use of medications and substances.
Specificity of mood stabilizer action on neuronal growth cones
Authors: Shaltiel Galit , Dalton Emma C , Belmaker Robert H , Harwood Adrian J , Agam Galila 
Published: April 2007

Objectives: Lithium, valproic acid (VPA) and carbamazepine (CBZ) are commonly used mood stabilizers, but their therapeutic mechanism is unclear. These drugs all cause the same morphological effects on postnatal rat neuronal dorsal root ganglia (DRG) growth cones via an inositol‐reversible mechanism. However, due to limitations in earlier analysis, the effects of combining drugs, drug specificity and inositol stereoisomer specificity are unknown. We devised an improved analytical method to address these issues.Methods: Dorsal root ganglia explants were cultured individually and incubated with combinations of psychotropic drugs and inositol stereoisomers. We recorded axonal growth cone morphology and calculated growth cone area per a modified method described by Williams et al. (Nature2002;417: 292–295). Statistically significant changes in area were calculated using non‐parametric statistical testing.Results: (i) Lithium and VPA showed an additive effect on growth cone spreading. (ii) Among eight additional psychotropic drugs to those previously tested, only imipramine and chlorpromazine altered DRG growth cone morphology. As this effect was not reversed bymyo‐inositol, it arises from a different mechanism to the mood stabilizers lithium, VPA and CBZ. (iii)Myo‐inositol, but notscyllo‐ orepi‐inositol, causes a significant reversal of the lithium effect on the growth cones spreading, consistent with the inositol depletion hypothesis.Conclusions: These results show that lithium, VPA and CBZ are unique in causing altered neuronal morphology viamyo‐inositol depletion.
The occurrence of cavum septi pellucidi enlargement is increased in bipolar disorder patients
Authors: Kim Minue J , Lyoo In Kyoon , Dager Stephen R , Friedman Seth D , Chey Jeanyung , Hwang Jaeuk , Lee Yu‐Jin , Dunner David L , Renshaw Perry F 
Published: April 2007

Objectives:  This study was conducted to evaluate the prevalence of cavum septi pellucidi (CSP) enlargement in patients with bipolar disorder (BD) and healthy comparison subjects.Methods:  The occurrence of enlarged CSP in patients with BD (n = 41, age 35.4 ± 10.8 years) and healthy volunteers (n = 41, age 35.3 ± 10.0 years) was studied using magnetic resonance imaging. The length of the CSP was measured by counting the number of consecutive resliced coronal 0.5‐mm images in which the CSP was present. A CSP length ≥ 6 mm was a priori defined as abnormal enlargement of the CSP.Results:  Bipolar subjects exhibited a significantly higher prevalence of abnormal CSP enlargement (8 of 41 subjects, 19.5%) than healthy comparison subjects (1 of 41 subjects, 2.4%) (logistic regression analysis: Wald statistic = 5.07, df = 1, p = 0.024). The prevalence of abnormally enlarged CSP was not significantly different between drug‐naïve and drug‐exposed bipolar subjects or when comparing bipolar I and II sub‐diagnoses. Bipolar subjects with abnormal CSP enlargement had a significantly earlier onset of BD than those without (14.3 ± 3.6 versus 20.1 ± 7.4 years, respectively).Conclusions:  The current study is the first to report an increased prevalence of abnormally enlarged CSP in a well‐characterized bipolar population. Our finding that an abnormal enlargement of CSP, a neurodevelopmental abnormality, is associated with early onset of illness implicates early maturational processes as contributing to BD.
Alteration in human defensin-5 expression following gastric bypass surgery
Authors: Sundbom M , Elphick D A , Mahida Y R , Cunliffe R N , Midtvedt T , Engstrand L , Rubio C , Axelsson L Göran 
Published: April 2007

Background:Roux-en-Y gastric bypass surgery provides a novel human model to investigate small bowel mucosal innate immunity, in which there is loss of gastric acid-mediated protection against orally-acquired microorganisms.Aim:To study changes in jejunal mucosal immunoreactivity of human defensin (HD)-5, an antimicrobial peptide normally produced by Paneth cells.Methods:Mucosal samples were obtained from 18 female patients (24–54 years), from the same segment of jejunum during and after gastric bypass surgery. Samples were used for bacterial culture and immunohistochemistry using anti-HD-5 antibody. The number of immunoreactive cells per crypt and villus were determined and expressed as mean (SD).Results:No bacteria were cultured from any of the perioperative jejunal samples but colonies of bacteria normally present in the pharynx were identified during culture of all postoperative jejunal biopsy specimens (1–>100 colonies). Paneth cell numbers per crypt were unchanged after gastric bypass (4.16 (0.71) vs 4.24 (0.78)). However, following surgery, there was an increase in HD-5-positive intermediate cells per crypt (0.25 (0.41) vs 1.12 (0.66), p<0.01), HD-5 staining enterocytes per crypt (0.03 (0.09) vs 1.38 (1.10), p<0.01), HD-5 staining material in the crypt lumen (crypt lumens: 5.0% (10.9%) vs 68.1% (27.9%), p<0.01) and HD-5 immunoreactivity coating the luminal surface of villus enterocytes (villi sampled: 15.0% (31.0%) vs 67.5% (42.0%), p<0.01).Conclusions:Bacteria normally resident in the pharynx were present in the proximal jejunal mucosa following Roux-en-Y gastric bypass surgery. After gastric bypass, there was increased secretion of HD-5 and an increase in HD-5 expressing intermediate cells and enterocytes in the crypt. The increase in HD-5 expression in the jejunal mucosa following gastric bypass surgery is likely to be secondary to exposure to orally-acquired microorganisms.
Laboratory costs of a hospital-based blood transfusion service in Malawi
Authors: Lara Antonieta Medina , Kandulu James , Chisuwo Laphiod , Kashoti Andrew , Mundy Catherine , Bates Imelda 
Published: April 2007

Background:Despite policies advocating centralised transfusion services based on voluntary donors, the hospital-based replacement donor system is widespread in sub-Saharan Africa.Aims:To evaluate the cost of all laboratory resources needed to provide a unit of safe blood in rural Malawi using the family replacement donor systemMethods:Full economic costs of all laboratory tests used to screen potential donors and to perform cross-matching were documented in a prospective, observational study in Ntcheu district hospital laboratory.Results:1729 potential donors were screened and 11 008 tests were performed to ensure that 1104 units of safe blood were available for transfusion. The annual cost of all transfusion-related tests (in 2005 US$) was $17 976, equivalent to $16.28 per unit of transfusion-ready blood. Transfusion-related tests used 53% of the laboratory’s total annual expenditure of $33 608.Conclusions:This is the first study to provide prospective economic costs of all laboratory tests associated with the family replacement donor system in a district hospital in Africa. Results show that despite potential economies of scale, a unit of blood from the centralised system costs about three times as much as one from the hospital-based “replacement” system. Factors affecting these relative costs are complex but are in part due to the cost of donor recruitment in centralised systems. In the replacement system the cost of donor recruitment is entirely borne by families of patients needing a blood transfusion.
Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy
Authors: Hofmann M , Stoss O , Gaiser T , Kneitz H , Heinmöller P , Gutjahr T , Kaufmann M , Henkel T , Rüschoff J 
Published: April 2007

Aims:To investigate the correlation between centrally assessed human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) results and response to treatment of patients with metastatic breast cancer enrolled in a first-line, phase II, open-label, 3-weekly trastuzumab (Herceptin) monotherapy trial (WO16229).Methods:Samples from participants in the WO16229 trial were collected and tumour HER2 status determined by IHC and FISH. HER2 test results were interpreted according to manufacturers’ test kit protocols. Responders were defined as patients showing either partial or complete responses.Results:Response data were available for 103/105 patients; centrally confirmed HER2 status was available for 95 patients. Intra-laboratory concordance for central IHC and FISH results was 93%. Complete responses were seen in two patients; their samples were IHC 3+ and FISH positive. Partial responses were seen in 17 patients; all were IHC 3+ and 14 were FISH positive. IHC and FISH showed 100% and 84.2% sensitivity, respectively, in determining response to trastuzumab. Polysomy was observed in 27% of patients; six responded to trastuzumab treatment. All six responders showed HER2 overexpression (IHC 3+) and HER2 gene amplification; two were FISH negative due to chromosome 17 polysomy.Conclusions:HER2 determination by IHC and FISH correlates with clinical response data in the WO16229 trial with high concordance of IHC and FISH results. Polysomy is the major cause of response in FISH-negative cases; polysomic cases should be retested by strictly standardised IHC.
Cancer Immunologists and Cancer Biologists: Why We Didn't Talk Then but Need to Now
Authors: Prendergast George C. , Jaffee Elizabeth M. 
Published: April 2007

Abstract
What is cancer? Cancer is a disease initiated by a series of cumulative genetic and epigenetic changes that occur in a normal cell. However, in addition to the malignant cell itself, cancer is a disease of microenvironment and immunity. Although genetic and epigenetic alterations drive cellular transformation, genomic plasticity, and evolution, it has become increasingly apparent that multiple signals delivered within the tumor microenvironment by modifier genes, stromal and endothelial cells, and immune cells are critical factors in determining the progression versus dormancy or destruction of an initiated lesion and also whether metastasis may occur. With regard to the important roles of immune cells in cancer, a chasm exists between immunologists and biologists: although sharing a common disease interest, there is little history for workers to draw on based on shared perspectives or understanding. How did this disconnect arise? Here, we look at how these workers became separated in the past and address why it has now become critical to spur greater cross-fertilization. In particular, we highlight three ideas that we believe are important for discussion and debate. The first idea is that therapeutic strategies that fail to harness the immune system will always be defeated by tumor resistance, due to the large “genomic space” that genetically plastic tumor cells can readily access to evolve resistance mechanisms. Because all therapies drive tumor progression by imposing a selection for resistant cells, harnessing the adaptivity of the immune system will be indispensable to ultimately stanching the deadly adaptability of the tumor cell. The second idea is that using molecular targeted agents to reverse tumoral immune suppression may offer a powerful method to leverage the efficacy of most if not all therapeutic agents. We suggest that the mechanisms that support evolution of a “smoldering” inflammatory environment in cancer overlap with those that support evolution of tumoral immune escape. If true, relieving immune suppression will switch the inflammatory state from supportive to destructive for the tumor. The third idea is that by ablating immunosuppression mechanisms, cytotoxic chemotherapy might synergize with, rather than antagonize, active immunotherapy. Provocative preclinical studies in this area prompt clinical attention. We believe that increased efforts to intermingle the perspectives and work of cancer immunologists with cancer biologists and pharmacologists will be needed to realize the National Cancer Institute's goal of managing cancer in the clinic by 2015. [Cancer Res 2007;67(8):3500–4]
S100A6 Is Increased in a Stepwise Manner during Pancreatic Carcinogenesis: Clinical Value of Expression Analysis in 98 Pancreatic Juice Samples
Authors: Ohuchida Kenoki , Mizumoto Kazuhiro , Yu Jun , Yamaguchi Hiroshi , Konomi Hiroyuki , Nagai Eishi , Yamaguchi Koji , Tsuneyoshi Masazumi , Tanaka Masao 
Published: April 2007

Abstract
There are few reports describing the diagnostic significance of S100A6 expression in clinical samples obtained from patients with pancreatic disease. In the present study, we measured S100A6 expression in pancreatic tissues and juice to evaluate its involvement in pancreatic carcinogenesis. We did quantitative real-time reverse transcription-PCR to measure mRNA expression in microdissected cells and pancreatic juice samples. Microdissected invasive ductal carcinoma and intraductal papillary mucinous neoplasm (IPMN) cells expressed significantly higher levels of S100A6 than did microdissected pancreatitis-affected epithelial and normal cells (all comparison; P &lt; 0.008). Median levels of S100A6 in invasive ductal carcinoma were higher than those in IPMN, and those in pancreatitis-affected epithelial cells tended to be higher than those in normal cells, although these differences were not statistically significant. In analyses of pancreatic juice, IPMN and pancreatic cancer samples expressed significantly higher levels of S100A6 than did chronic pancreatitis samples (both; P &lt; 0.017), but levels in pancreatic cancer and IPMN samples did not differ form each other. Receiver operating characteristic (ROC) curve analysis revealed that measurement of S100A6 was useful for discriminating cancer (area under the ROC curve, 0.864) or IPMN (area under the ROC curve, 0.749) from chronic pancreatitis. The present data suggest that expression of S100A6 is increased in a stepwise manner during pancreatic carcinogenesis and may be a biomarker for evaluating malignant potential. Measurement of S100A6 in pancreatic juice may be useful to detect early pancreatic cancer or identify individuals with high-risk lesions that may progress to pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(4):649–54)
Extracellular Activity of Cyclic AMP–Dependent Protein Kinase as a Biomarker for Human Cancer Detection: Distribution Characteristics in a Normal Population and Cancer Patients
Authors: Wang Hui , Li Mao , Lin Wenyao , Wang Wenquan , Zhang Zhuo , Rayburn Elizabeth R. , Lu Jian , Chen Deng , Yue Xinsen , Shen Fuming , Jiang Feng , He Jie , Wei Wu , Zeng Xiaofei , Zhang Ruiwen 
Published: April 2007

Abstract
The overexpression of cyclic AMP (cAMP)–dependent protein kinase (PKA) has been reported in patients with cancer, and PKA inhibitors have been tested in clinical trials as a novel cancer therapy. The present study was designed to characterize the population distribution of extracellular activity of cAMP-dependent protein kinase (ECPKA) and its potential value as a biomarker for cancer detection and monitoring of cancer therapy. The population distribution of ECPKA activity was determined in serum samples from a Chinese population consisting of a total of 603 subjects (374 normal healthy volunteers and 229 cancer patients). The serum ECPKA was determined by a validated sensitive radioassay, and its diagnostic values (including positive and negative predictive values) were analyzed. The majority of normal subjects (&gt;70%) have undetectable or very low levels of serum ECPKA. In contrast, the majority of cancer patients (&gt;85%) have high levels of ECPKA. The mean ECPKA activity in the sera of cancer patients was 10.98 units/mL, 5-fold higher than that of the healthy controls (2.15 units/mL; P &lt; 0.001). In both normal subjects and cancer patients, gender and age had no significant influence on the serum ECPKA. Among factors considered, logistic analysis revealed that the disease (cancer) is the only factor contributing to the elevation of ECPKA activity in cancer patients. In conclusion, ECPKA may function as a cancer marker for various human cancers and can be used in cancer detection and for monitoring response to therapy with other screening or diagnostic techniques. (Cancer Epidemiol Biomarkers Prev 2007;16(4):789–95)
Dietary Fiber and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study
Authors: Wakai Kenji , Date Chigusa , Fukui Mitsuru , Tamakoshi Koji , Watanabe Yoshiyuki , Hayakawa Norihiko , Kojima Masayo , Kawado Miyuki , Suzuki Koji , Hashimoto Shuji , Tokudome Shinkan , Ozasa Kotaro , Suzuki Sadao , Toyoshima Hideaki , Ito Yoshinori , Tamakoshi Akiko ,   for the JACC Study Group
Published: April 2007

Abstract
To examine the association of dietary fiber with the risk of colorectal cancer in a population with a high incidence of cancer and a low fiber intake, we analyzed the data from the Japan Collaborative Cohort Study. From 1988 to 1990, 43,115 men and women aged 40 to 79 years completed a questionnaire on dietary and other factors. Intake of dietary fiber was estimated using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 443 colorectal cancer cases were recorded. In all participants, we found a decreasing trend in risk of colorectal cancer with increasing intake of total dietary fiber; the multivariate-adjusted RRs across quartiles were 1.00, 0.96 [95% confidence interval (95% CI), 0.72-1.27], 0.72 (0.53-0.99), and 0.73 (0.51-1.03; Ptrend = 0.028). This trend was exclusively detected for colon cancer: the corresponding RRs were 1.00, 0.90 (95% CI, 0.64-1.26), 0.56 (0.38-0.83), and 0.58 (0.38-0.88; Ptrend = 0.002). The decrease in RRs with increasing intake of dietary fiber was larger in men than in women. No material differences appeared in the strength of associations with the risk between water-soluble and insoluble dietary fiber. For food sources of fiber, bean fiber intake was somewhat inversely correlated with colorectal cancer risk. This prospective study supported potential protective effects of dietary fiber against colorectal cancer, mainly against colon cancer. The role of dietary fiber in the prevention of colorectal cancer seems to remain inconsistent, and further investigations in various populations are warranted. (Cancer Epidemiol Biomarkers Prev 2007;16(4):668–75)
Health Care Utilization by Adult Long-term Survivors of Hematopoietic Cell Transplant: Report from the Bone Marrow Transplant Survivor Study
Authors: Shankar Sadhna M. , Carter Andrea , Sun Can-Lan , Francisco Liton , Baker K. Scott , Gurney James G. , Weisdorf Daniel G. , Forman Stephen J. , Robison Leslie L. , Grant Marcia , Bhatia Smita 
Published: April 2007

AbstractThe high intensity of therapy and prolonged immune suppression after hematopoietic cell transplantation (HCT) increase the risk of long-term complications and health care needs among survivors. The aim of this study was to evaluate the current status of health care utilization by long-term HCT survivors and to identify factors associated with lack of utilization. A total of 845 individuals who had undergone HCT between 1974 and 1998 at age 21 years or older and survived 2 or more years after HCT participated in the study. Health care utilization was assessed through a mailed questionnaire in three domains: general contact with health care system, general physical examination, and cancer/HCT–related visit. The median age at HCT was 38.2 years, and the median length of follow-up was 6.4 years. Overall, 98% of allogeneic and 94% of autologous HCT survivors reported medical contact 11+ years after HCT. Cancer/HCT–related visits decreased with increasing time from HCT (allogeneic HCT, 98-57%; autologous HCT, 94-63%). The prevalence of general physical examination increased with time (allogeneic HCT, 56-74%; autologous HCT, 72-81%). Primary care physicians provide health care for an increasing number of adult long-term survivors of HCT, emphasizing the need for increased awareness of the long-term follow-up needs of the HCT survivors by the health care providers. (Cancer Epidemiol Biomarkers Prev 2007;16(4):834–9)