bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated array-CGH optimized for archival formalin-fixed, paraffin-embedded tumor material
Authors: Joosse Simon A , van Beers Erik H , Nederlof Petra M 
Published: March 2007

Abstract

Background
Array Comparative Genomic Hybridization (aCGH) is a rapidly evolving technology that still lacks complete standardization. Yet, it is of great importance to obtain robust and reproducible data to enable meaningful multiple hybridization comparisons. Special difficulties arise when aCGH is performed on archival formalin-fixed, paraffin-embedded (FFPE) tissue due to its variable DNA quality. Recently, we have developed an effective DNA quality test that predicts suitability of archival samples for BAC aCGH.

Methods
In this report, we first used DNA from a cancer cell-line (SKBR3) to optimize the aCGH protocol for automated hybridization, and subsequently optimized and validated the procedure for FFPE breast cancer samples. We aimed for highest throughput, accuracy, and reproducibility applicable to FFPE samples, which can also be important in future diagnostic use.

Results
Our protocol of automated array-CGH on archival FFPE ULS-labeled DNA showed very similar results compared with published data and our previous manual hybridization method.

Conclusion
This report combines automated aCGH on unamplified archival FFPE DNA using non-enzymatic ULS labeling, and describes an optimized protocol for this combination resulting in improved quality and reproducibility.
Is abdominal wall contraction important for normal voiding in the female rat?
Authors: Smith Phillip P , Smith Christopher P , Boone Timothy B , Somogyi George T 
Published: March 2007

Abstract

Background
Normal voiding behavior in urethane-anesthetized rats includes contraction of the abdominal wall striated muscle, similar to the visceromotor response (VMR) to noxious bladder distension. Normal rat voiding requires pulsatile release of urine from a pressurized bladder. The abdominal wall contraction accompanying urine flow may provide a necessary pressure increment for normal efficient pulsatile voiding. This study aimed to evaluate the occurrence and necessity of the voiding-associated abdominal wall activity in urethane-anesthetized female rats

Methods
A free-voiding model was designed to allow assessment of abdominal wall activity during voiding resulting from physiologic bladder filling, in the absence of bladder or urethral instrumentation. Physiologic diuresis was promoted by rapid intravascular hydration. Intercontraction interval (ICI), voided volumes and EMG activity of the rectus abdominis were quantified. The contribution of abdominal wall contraction to voiding was eliminated in a second group of rats by injecting botulinum-A (BTX, 5 U) into each rectus abdominis to induce local paralysis. Uroflow parameters were compared between intact free-voiding and BTX-prepared animals.

Results
Abdominal wall response is present in free voiding. BTX preparation eliminated the voiding-associated EMG activity. Average per-void volume decreased from 1.8 ml to 1.1 ml (p < 0.05), and reduced average flow from 0.17 ml/sec to 0.11 ml/sec (p < 0.05). Intercontraction interval (ICI) was not changed by BTX pretreatment.

Conclusion
The voiding-associated abdominal wall response is a necessary component of normal voiding in urethane anesthetized female rats. As the proximal urethra may be the origin of the afferent signaling which results in the abdominal wall response, the importance of the bladder pressure increment due to this response may be in maintaining a normal duration intermittent pulsatile high frequency oscillatory (IPHFO)/flow phase and thus efficient voiding. We propose the term Voiding-associated Abdominal Response (VAR) for the physiologic voiding-associated EMG/abdominal wall response, to distinguish it from the visceromotor response (VMR) to noxious bladder distension.
Structure and characterization of a novel chicken biotin-binding protein A (BBP-A)
Authors: Hytönen Vesa P , Määttä Juha AE , Niskanen Einari A , Huuskonen Juhani , Helttunen Kaisa J , Halling Katrin K , Nordlund Henri R , Rissanen Kari , Johnson Mark S , Salminen Tiina A , Kulomaa Markku S , Laitinen Olli H , Airenne Tomi T 
Published: March 2007

Abstract

Background
The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin.

Results
Here, we expand the repertoire of known macromolecular biotin binders by reporting a novel biotin-binding protein A (BBP-A) from chicken. The BBP-A recombinant protein was expressed using two different expression systems and purified with affinity chromatography, biochemically characterized and two X-ray structures were solved – in complex with D-biotin (BTN) and in complex with D-biotin D-sulfoxide (BSO). The BBP-A protein binds free biotin with high, "streptavidin-like" affinity (Kd ~ 10-13 M), which is about 50 times lower than that of chicken avidin. Surprisingly, the affinity of BBP-A for BSO is even higher than the affinity for BTN. Furthermore, the solved structures of the BBP-A – BTN and BBP-A – BSO complexes, which share the fold with the members of the avidin and lipocalin protein families, are extremely similar to each other.

Conclusion
BBP-A is an avidin-like protein having a β-barrel fold and high affinity towards BTN. However, BBP-A differs from the other known members of the avidin protein family in thermal stability and immunological properties. BBP-A also has a unique ligand-binding property, the ability to bind BTN and BSO at comparable affinities. BBP-A may have use as a novel material in, e.g. modern bio(nano)technological applications.
Hedgehog pathway activity in the LADY prostate tumor model
Authors: Gipp Jerry , Gu Guangyu , Crylen Curtis , Kasper Susan , Bushman Wade 
Published: March 2007

Abstract

Background
Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined.

Results
We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc) was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin.

Conclusion
Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.
The impact of radiotherapy in the treatment of desmoid tumours. An international survey of 110 patients. A study of the Rare Cancer Network
Authors: Baumert Brigitta G , Spahr Martin O , Hochstetter Arthur Von , Beauvois Sylvie , Landmann Christine , Fridrich Katrin , Villà Salvador , Kirschner Michael J , Storme Guy , Thum Peter , Streuli Hans K , Lombriser Norbert , Maurer Robert , Ries Gerhard , Bleher Ernst-Arnold , Willi Alfred , Allemann Juerg , Buehler Ulrich , Blessing Hugo , Luetolf Urs M , Davis J Bernard , Seifert Burkhardt , Infanger Manfred 
Published: March 2007

Abstract
Purpose
A multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours.

Patients and methods
One hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed.

Results
The combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis.

Conclusion
Postoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients.
Single Serum Activin A Testing to Predict Ectopic Pregnancy
Authors: Florio Pasquale , Severi Filiberto Maria , Bocchi Caterina , Luisi Stefano , Mazzini Massimo , Danero Secondo , Torricelli Michela , Petraglia Felice 
Published: March 2007

Abstract
Context: Ectopic pregnancy (EP) is an important cause of maternal deaths in early pregnancy because most fatal cases result from delayed diagnosis and inappropriate investigation.
Objective: We evaluated whether the measurement of activin A may be useful in the diagnosis of EP in women with unknown pregnancy location.
Design: The study was designed as an open observational study.
Setting: The study was set in a tertiary referral center for obstetric care.
Patients: Patients were women with unknown pregnancy location (n = 536) who had complaints of bleeding, pain, or cramping.
Interventions: Interventions included clinical examination; transvaginal ultrasound scan; human chorionic gonadotropin (hCG), progesterone, and activin A measurements; laparoscopy; uterine curettage; and histological examination.
Main Outcome Measures: Main outcome measures were pregnancy outcomes and evaluation of sensitivity, specificity, and predictive values of hCG, progesterone, and activin A as diagnostic tests for the detection of EP.
Results: Pregnancy outcomes included 155 (28.9%) viable intrauterine pregnancies (IUP), 305 (56.9%) first-trimester spontaneous abortion (SAB), and 76 (14.2%) EP. SAB had the lowest (P &lt; 0.0001) hCG and progesterone concentrations, significantly lower than EP (P &lt; 0.001) and IUP (P &lt; 0.001). In EP, levels were significantly (P &lt; 0.001) lower than in IUP. On the contrary, activin A levels were lowest (P &lt; 0.0001) in EP, significantly lower than in SAB (P &lt; 0.001) and IUP (P &lt; 0.001). IUP had significantly (P &lt; 0.001) lower activin A levels than SAB. When evaluated by the receiver operating curve analysis, activin A at the cutoff of 0.37 ng/ml combined a sensitivity and a specificity of 100 and 99.6%, respectively, for prediction of EP. When activin A concentrations were below the cutoff, the positive predictive value for EP was 97.43%, and 0% for concentrations higher than 0.37 ng/ml.
Conclusions: Activin A measurement may identify patients at risk of EP with a high sensibility and specificity.
Germline Mutation in the Aryl Hydrocarbon Receptor Interacting Protein Gene in Familial Somatotropinoma
Authors: Toledo Rodrigo A. , Lourenço Delmar M. , Liberman Bernardo , Cunha-Neto Malebranche B. C. , Cavalcanti Maria G. , Moyses Cinthia B. , Toledo Sergio P. A. , Dahia Patricia L. M. 
Published: March 2007

AbstractContext: Acromegaly is usually sporadic, but familial cases occur in association with several familial pituitary tumor syndromes. Recently mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were associated with familial pituitary adenoma predisposition.Objective: The objective of the study was to investigate the status of AIP in a pituitary tumor predisposition family.Settings: The study was conducted at a nonprofit academic center and medical centers.Patients: Eighteen members of a Brazilian family with acromegaly were studied.Results: A novel germline mutation in the AIP gene, Y268X, predicted to generate a protein lacking two conserved domains, was identified in four members of this family: two siblings with early-onset acromegaly; a third, 41-yr-old sibling with a microadenoma but no clinical features of disease, and his 3-yr-old son. No changes were found in 14 unaffected at-risk relatives or 92 healthy controls.Conclusions: We confirm the role of the AIP gene in familial acromegaly. This finding increases the spectrum of molecular defects that can give rise to pituitary adenoma susceptibility. Establishment of genotype-phenotype correlations in AIP mutant tumors will determine whether AIP screening can be used as a tool for clinical surveillance and genetic counseling of families with pituitary tumor predisposition. The underlying basis for the phenotypic variation within AIP-mutant families and the mechanism of AIP-mediated tumorigenesis remain to be defined.
Cost-Justification of a Clinical Pharmacist-Managed Anticoagulation Clinic
Authors: Gray David R. , Garabedian-Ruffalo Susan M. , Chretien Steven D. 
Published: March 2007

A cost-benefit evaluation of a clinical pharmacistmanaged anticoagulation clinic (AC) was performed. Outpatient and hospital records were examined for 26 patients in the treatment group with an AC clinic and 26 patients in the control group. Therapeutic prothrombin times were maintained within the treatment group to a significantly greater extent than within the control group (p < 0.001). The AC was successful in preventing hospitalizations resulting from hemorrhage or thromboembolism (p < 0.01). The abnormal prothrombin times on admission in the control group correlated with hemorrhagic and thromboembolic admissions (p < 0.05, p < 0.005, respectively). Patients were hospitalized 3.22 days and .048 days per patient-treatment-year in the control and treatment groups, respectively. The net savings in reduced hospitalization costs per year in the treatment group was $211776. The benefit:cost ratio (B:C) was 6.55, suggesting the program is socially valuable. This clinical pharmacist-managed AC was effective in maintaining therapeutic prothrombin times, and reducing the incidence of hospitalizations resulting from anticoagulation complications, and can be cost-justified based on a cost-benefit analysis.
Universal versus Selective Iron Supplementation for Infants and the Risk of Unintentional Poisoning in Young Children: A Comparative Study of Two Populations
Authors: Finkelstein Yaron , Wahl Michael S , Bentur Yedidia , Schechter Tal , Garty Ben Zion , Erickson Timothy B , Chodick Gabby , Cahana Alfred , Mounstephen Bill J , Koren Gideon , Aks Steven E 
Published: March 2007

Background: Iron continues to be a common cause of poisoning in young children, in part due to its widespread use and easy accessibility. Objective: To determine differences in the epidemiology and outcome of unintentional iron ingestion by young children in populations practicing selective (eg, US) versus universal (eg, Israel) iron supplementation to infants. Methods: All cases of unintentional iron ingestion in children younger than 7 years in a one year period were identified through the poison control center databases of 2 sites (Illinois and Israel). Parameters compared include patient sex and age; type, form, and dose of iron preparation; circumstances and clinical manifestations; management; and outcome. Results: A total of 602 children were identified: 459 in Illinois and 143 in Israel. The majority of Illinois children ingested multivitamin preparations (94%), whereas Israeli children ingested single-ingredient iron preparations (78%) (p < 0.001). Iron doses ingested were higher in Israel (median 14.5 vs 6.6 mg/kg; p < 0.001) but remained within the nontoxic range for most children. No deaths or severe poisonings were reported, and 93% of children in both groups were asymptomatic. The majority of ingestions in both locations were due to unintentional self-ingestion. However, parental miscalculation occurred more frequently in Israel (16%) than in Illinois (1%). Conclusions: Universal iron supplementation to infants was not associated with a negative impact on the outcome of pediatric unintentional ingestions. Low-dose exposures were safely managed by on-site observation.
Opioid-Related Adverse Drug Events in Surgical Hospitalizations: Impact on Costs and Length of Stay
Authors: Oderda Gary M , Said Qayyim , Evans R Scott , Stoddard Gregory J , Lloyd Jim , Jackson Kenneth , Rublee Dale , Samore Matthew H 
Published: March 2007

Background: Opioid analgesics remain a mainstay in the treatment of pain associated with surgical procedures. Such use is associated with adverse drug events (ADEs). Objective: To investigate the impact of opioid-related ADEs on total hospital costs and length of stay (LOS) in adult surgical patients. Methods: This was a retrospective matched cohort study using data from computerized medical records. ADE cases were prospectively detected using computerized surveillance and verified by pharmacists. Surgical patients treated at LDS Hospital in Salt Lake City from January 1, 1998, to December 31, 2003, were included. The primary outcomes were costs and hospital LOS associated with opioid-related ADEs and the relationship of opioid dose to ADE events. Results: Patients experiencing opioid-related ADEs had significantly increased median total hospital costs (7.4% increase; 95% CI 3.83 to 10.96; p < 0.001) and increased median LOS (10.3% increase; 95% CI 6.5 to 14.2; p < 0.001) compared with matched non-ADE contrals. The increased costs attributable to ADEs, by surgery type, were general surgery ($676.51; 95% CI 351.50 to 1001.50), orthopedics ($861.50; 95% CI 448.20 to 1274.80), and obstetrics/gynecology ($540.90; 95% CI 281.40 to 800.40). Similarly, increased LOS attributable to ADEs, by surgery type, were general surgery (0.64 days; 95% CI 0.40 to 0.88), orthopedics (0.52 days; 95% CI 0.33 to 0.71), and obstetrics/gynecology (0.53 days; 95% CI 0.33 to 0.72). Higher doses of opioids were associated with increased risk of experiencing ADEs (OR 1.3; 95% CI 1.07 to 1.60; p = 0.01). Conclusions: Opioid-related ADEs following surgery were associated with significantly increased LOS and hospitalization costs. These ADEs occurred more frequently in patients receiving higher doses of opioids.
CD4+ Cell Count Decline Despite HIV Suppression: A Probable Didanosine–Valganciclovir Interaction
Authors: Tseng Alice L , Salit Irving E 
Published: March 2007

Objective: To describe a case of significant CD4+ cell decline despite complete viral suppression in an HIV-positive patient receiving didanosine and valganciclovir. Case Summary: A 68-year-old woman diagnosed with HIV and cytomegalovirus (CMV) enteritis (CD4+ cell count 22 cells/mm3, viral load 88 898 [4.95 log] copies/mL) was treated with valganciclovir and began lamivudine, didanosine, and lopinavir/ritonavir. Three months later, her viral load was less than 50 copies/mL and CD4+ cell count was 317 cells/mm3. Over the next 9 months, her viral load remained suppressed, but the CD4+ cell count declined to 83 cells/mm3 and she experienced ongoing symptoms of didanosine toxicity. Didanosine was replaced with abacavir, leading to a complete CD4+ cell recovery and resolution of symptoms. Discussion: Paradoxical declines in CD4+ cell counts have been reported in HIV-infected patients virally suppressed on tenofovir/didanosine regimens, presumably via inhibition of purine nucleoside phosphorylase (PNP) by tenofovir and enhancement of didanosine toxicity. Ganciclovir and its prodrug valganciclovir also inhibit PNP and increase didanosine concentrations; thus, a similar immunological effect with this combination is possible. This hypothesis is consistent with observations from a historic multicenter CMV retinitis study, where a negative CD4+ cell response was observed in patients receiving ganciclovir, while those treated with foscarnet experienced a C04+ cell increase and a mortality advantage. Of the subjects who received any type of nucleoside therapy during this study, didanosine use was proportionally higher in the ganciclovir arm versus the foscarnet arm. According to the Naranjo probability scale, our patient experienced a probable adverse reaction associated with the combination of didanosine and valganciclovir. Conclusions: Patients receiving didanosine-containing highly active antiretroviral therapy and ganciclovir or valganciclovir for treatment of CMV infection should be monitored for didanosine toxicity and unexpected CD4+ cell loss or failure of CD4+ cell recovery. Reduction of didanosine dosage or substitution with an alternative antiretroviral may be necessary.
Gynecomastia Associated with Fenofibrate
Authors: Gardette Virginie , Vezzosi Delphine , Maiza Jean-Christophe , Montastruc Jean-Louis , Olivier Pascale 
Published: March 2007

Objective: To report a case of probable fenofibrate-induced gynecomastia. Case Summary: A 56-year-old white hypercholesterolemic man was treated with fenofibrate 160 mg/day for 1 year. During the course of treatment, he developed gynecomastia on the left side, which resolved after the drug was stopped and replaced with alpha tocopherol acetate. Sixteen months after fenofibrate discontinuation, the patient was rechallenged and subsequently developed gynecomastia symptoms on the right side. The usual etiologies of gynecomastia were excluded by careful assessment of the patient's medical history, physical examination, and results of diagnostic tests such as chest X-ray, mammography, scrotal ultrasonography, routine blood chemistry, and extensive hormonal panel. Gynecomastia again resolved after discontinuation of fenofibrate. Discussion: In this case, the resolution of gynecomastia on discontinuation of fenofibrate and recurrence after rechallenge highly suggest the role of fenofibrate. Use of the Naranjo probability scale registered causality as probable. Case reports of gynecomastia caused by different drugs have been previously published, but, to our knowledge, this is the first report linking gynecomastia to the use of fenofibrate. The pathogenesis of this adverse drug reaction remains unclear. Conclusions: Although fenofibrate-induced gynecomastia appears to be uncommon, patients receiving this medication should be monitored for this adverse drug reaction.