bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Great Britain and Ireland perspective: current perfusion safety issues, preparing for the future
Authors: Mulholland J W 
Published: July 2005

The Great Britain and Ireland (GBI) recommendations for standards of monitoring and alarms during cardio-pulmonary bypass (CPB) came into force in January 2004. While perfusion departments in Great Britain and Ireland should now have a good baseline level of safety, it is important that department-specific safety is also considered. Patient safety is paramount, but safety within our speciality must also take into account the protection of the perfusionists’ health and the protection of their careers. These different aspects of safety are fundamentally interrelated. This paper focuses on the importance of careful assessment, implementation and documentation when a new component or technique is being introduced to the CPB circuit, even when the aim is to increase safety. Knowledge of the civil justice system and the trends in medical negligence claims are an integral part of perfusionist safety. Perfusion in Great Britain and Ireland is rightly striving for professional recognition from the Health Professions Council (HPC). As we raise the profile of perfusion, we educate more people about the importance of our role and level of responsibility within the cardiac operating team. This will increase the potential for medical negligence claims to be directed specifically at our speciality. All these issues are discussed in detail.
Assessment of ovarian failure and osteoporosis in premenopausal breast cancer survivors
Authors: McCune Jeannine S , Games Dona M , Espirito Janet L 
Published: July 2005

Premenopausal women who develop ovarian failure after receiving chemotherapy are at a higher risk of rapid bone loss. Pharmacists have successfully implemented osteoporosis screening programmes in the general population and thus, assessment of breast cancer survivors for ovarian failure and osteopenia could represent a novel focus for oncology pharmacists. Therefore, we conducted a retrospective chart review to determine the adequacy of ovarian failure and osteoporosis assessment and management in premenopausal breast cancer survivors. Methods and results. The charts of 20 women diagnosed with early stage breast cancer treated with cyclophosphamide over a 4.5-year timespan were included. Their median age was 36.7 years (range 29.8-41). The median cyclophosphamide cumulative dose was 9 g/m2 (range 2.4-14.45), with a median duration of follow-up being 4.62 years. The assessment of ovarian failure mainly occurred by documenting menstrual periods, which has been questioned as a reliable method for assessing ovarian failure. Menses stopped while or shortly after receiving chemotherapy in 11 women. Prior to and during cyclophosphamide administration, osteoporosis screening or counselling was not documented for any patient. After completion of chemotherapy administration, eight patients were counselled regarding osteoporosis and seven women were screened for osteoporosis with a dual X-ray absorptimetry (DXA) scan. Five women had DXA scans indicative of osteopenia according to World Health Organization guidelines. Conclusions. Improvements are needed in the documentation and potentially also the management of ovarian failure and osteoporosis in premenopausal breast cancer survivors receiving cyclophosphamide-based regimens. This represents a potential opportunity for pharmacists to manage long-term chemotherapy toxicity.
Alendronate for steroid-induced osteopenia in children with acute lymphoblastic leukaemia or non-Hodgkin’s lymphoma: results of a pilot study
Authors: Wiernikowski JT , Barr RD , Webber C , Guo CY , Wright M , Atkinson SA 
Published: July 2005

Background/objectives. Osteopenia is a significant morbidity in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or non-Hodgkin’s lymphoma (NHL). We conducted a pilot study to assess the impact of alendronate on whole body bone mineral content (WB-BMC), lumbar spine bone mineral density (LS-BMD), biochemical measures of bone mineral metabolism, as well as gross motor function and health-related quality of life (HRQL) in children undergoing therapy for ALL or NHL. Methods. Ten children (nine boys) between the ages of 3.6 and 14.6 years, on identical maintenance chemotherapy for ALL or NHL were treated with oral alendronate once weekly, and daily calcium supplementation, for a period of six months. Outcome measures were WB-BMC and LSBMD; biochemical measures of bone mineral metabolism including plasma osteocalcin, C-terminal telopeptide of type I collagen (CTx), serum calcium, 25-hydroxy-vitamin D (25-OHD), and parathyroid hormone (PTH); as well as assessments of motor function and HRQL. Results. A gain in Z score was observed in 7/9 evaluable patients for WB-BMC (mean increase of 0.49) and LS-BMD (0.51). Plasma osteocalcin and CTx showed a change in bone turnover favouring formation over resorption. Serum calcium and 25- OHD remained normal throughout treatment. After an initial spike, serum PTH returned to baseline values at week 4. Measures of motor function showed some improvement and there were modest gains in HRQL. Conclusions. Alendronate therapy was tolerated well. Further study in a larger sample of children with ALL or NHL is warranted, in the context of a randomized clinical trial.
Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature
Authors: Dranitsaris George , Johnston Mary , Poirier Susan , Schueller Trudi , Milliken Debbie , Green Esther , Zanke Brent 
Published: July 2005

Objective. A systematic review and meta-analysis was conducted to test the hypothesis that oncology health care workers are at an increased risk of cancer, reproductive complications and acute toxic events. Design. A structured literature search of Index Medicus/MEDLINE, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews and Healthstar was performed from 1966 to December 2004 for human epidemiological studies evaluating the risk of toxic events in health care workers exposed to cytotoxic drugs. Raw data and adjusted odds ratios (OR) reported in eligible studies were combined using a random effects model to calculate point estimates and 95% confidence intervals (CI) for each potential risk outcome. Main outcome measures. Adjusted OR for congenital malformations, stillbirths and spontaneous abortions among health care workers exposure to cytotoxic agents compared to a non-exposed control group. Results. The systematic review identified 14 studies evaluating the outcomes of interest, seven of which were suitable for statistical pooling. Due to lack of evidence, we were unable to estimate a pooled OR for the risk of cancer and acute toxic events. However, no significant association was detected between exposure to cytotoxic drugs and; congenital malformations (OR=1.64; 95% CI: 0.91-2.94) and stillbirths (OR=1.16; 95% CI: 0.73-1.82). In contrast, an association was identified between exposure to chemotherapy and spontaneous abortions (OR=1.46; 95% CI: 1.11-1.92). Conclusions. The results of this systematic review identified a small incremental risk for spontaneous abortions in female staff working with cytotoxic agents. Health policy decision makers should effectively communicate the magnitude of this risk to their staff and implement cost effective interventions for its reduction or elimination.
Pharmaceutical validation as a process of improving the quality of antineoplastic treatment
Authors: Fabiá Amparo Serrano , Rodrigo Elisa Cavero , Marí Asunción Albert , Cubells Daniel Almenar , Jiménez Torres N Victor 
Published: July 2005

Objective. To quantify the improvement added by standardization of pharmaceutical validation (PV) of antineoplastic treatment to the processes of prescription and preparation of the pharmacotherapeutic sequence, in terms of prevention and reduction of medication errors (ME). Design. Prospective cohort study during two years (from 2001-2002) for oncohaematologic patients (inpatients and outpatients) that compared the percentage of medication errors detected and resolved and the number of medication errors with potential clinical significance (severity value ≥4) intercepted during PV in both years. Results. During the PV processes, 202 ME were identified and resolved, which is the equivalent of 16.88 ME/1000 patient-days. In 2001 14.08 ME/1000 patient-days were detected and 19.83 ME/1000 patient-days in 2002. This means that the effectiveness of the identification method increased by 41%. The number of ME intercepted with clinical significance (severity value ≥4) increased in a statistically significant manner by 2.18 times in 2002. Conclusion. This study shows that the standardization of PV is an effective method of improving the quality of antineoplastic treatment use, by increasing the ability to intercept ME.
Pediatric Melanoma: Risk Factor and Survival Analysis of the Surveillance, Epidemiology and End Results Database
Authors: Strouse John J. , Fears Thomas R. , Tucker Margaret A. , Wayne Alan S. 
Published: July 2005

Purpose To evaluate risk factors for the development of and factors influencing survival in pediatric melanoma. Patients and Methods We evaluated 1,255 children (age < 20 years) and 2,673 young adults (age 20 to 24 years) with melanoma in the 2001 National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER) database. We estimated exposure to UV radiation based on Environmental Protection Agency (EPA) measurements. Results The incidence of pediatric melanoma increased 46% (95% CI, 40 to 52) per year of age and 2.9% (95% CI, 2.1 to 3.6) per year from 1973 to 2001. Incidence rates were lower in black patients (−95%; 95% CI, −98 to −90) compared with white patients and in male patients (−39%; 95% CI −46 to −31) compared with females. Increased ambient UV radiation was associated with elevated risk (19% per kJ; 95% CI, 9 to 30). Children with melanoma had a 5-year melanoma-specific survival of 93.6% (95% CI, 91.9 to 94.9), which improved from 1973 to 2001. The hazard ratio of death from melanoma increased with male sex; older age; advanced disease; location of the primary other than extremities or torso; earlier year of diagnosis; and previous cancer. Conclusion The incidence of melanoma in the United States is increasing rapidly in children. Risk factors for pediatric melanoma include being white, being female, increasing age, and environmental UV radiation. Survival is decreased for children and adolescents with unfavorable prognostic factors (male sex, unfavorable site, and/or second primary or regional or distant metastasis). More effective therapeutic strategies are needed for these groups.
Immunoglobulin M Monoclonal Gammopathies of Undetermined Significance and Indolent Waldenström's Macroglobulinemia Recognize the Same Determinants of Evolution Into Symptomatic Lymphoid Disorders: Proposal for a Common Prognostic Scoring System
Authors: Baldini Luca , Goldaniga Maria , Guffanti Andrea , Broglia Chiara , Cortelazzo Sergio , Rossi Andrea , Morra Enrica , Colombi Mariangela , Callea Vincenzo , Pogliani Enrico , Ilariucci Fiorella , Luminari Stefano , Morel Pierre , Merlini Giampaolo , Gobbi Paolo 
Published: July 2005

Purpose To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. Patients and Methods We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. Results After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). Conclusion MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.
Treatment of Refractory Hodgkin's Lymphoma Patients With an Iodine-131–Labeled Murine Anti-CD30 Monoclonal Antibody
Authors: Schnell Roland , Dietlein Markus , Staak Jan Oliver , Borchmann Peter , Schomaecker Klaus , Fischer Thomas , Eschner Wolfgang , Hansen Hinrich , Morschhauser Franck , Schicha Harald , Diehl Volker , Raubitschek Andrew , Engert Andreas 
Published: July 2005

PurposeHodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 (131I).Patients and MethodsThe biodistribution of131I–Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq131I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4.ResultsWe treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses.ConclusionTreatment with131I–Ki-4 is effective but can be associated with severe hematotoxicity.
Estrogen Mediates Phosphorylation of Histone H3 in Ovarian Follicle and Mammary Epithelial Tumor Cells via the Mitotic Kinase, Aurora B
Authors: Ruiz-Cortés Z. Tatiana , Kimmins Sarah , Monaco Lucia , Burns Kathleen H. , Sassone-Corsi Paolo , Murphy Bruce D. 
Published: July 2005

AbstractCells of the ovarian follicle undergo extensive proliferation and differentiation from the time that the follicle escapes from the primordial state to its acquisition of ovulatory capacity. We examined the dynamic modification of the phosphorylation state of the histone H3 N-terminal tail in granulosa cells during follicular development. In rodent follicles, the granulosa cell H3 phosphorylation on Ser10 peaks during proestrus. This epigenetic mark is induced by both FSH and 17β-estradiol (E2), acting independently. E2-induced H3 phosphorylation fails to occur in mice with inactivated α-isoform of the nuclear estrogen receptor. E2 induction of histone phosphorylation is attenuated by cell cycle inhibition. Further, E2 induces the activity of the mitotic kinase, Aurora B, in a mammary tumor cell model where mitosis is estrogen receptor-α dependent. These results provide evidence for mitotic regulation in follicle development by estrogen and demonstrate a previously undiscovered mechanism for induction of cell proliferation in ovarian and mammary gland cells.
Amino-Truncated β-Amyloid42 Peptides in Cerebrospinal Fluid and Prediction of Progression of Mild Cognitive Impairment
Authors: Vanderstichele Hugo , De Meyer Geert , Andreasen Niels , Kostanjevecki Vesna , Wallin Anders , Olsson Annika , Blennow Kaj , Vanmechelen Eugeen 
Published: July 2005

AbstractBackground: Early identification of patients with mild cognitive impairment (MCI) progressing to Alzheimer disease (MCI-AD) by use of biomarkers in cerebrospinal fluid (CSF) is an essential step toward improving clinical diagnosis and drug development. We evaluated whether different β-amyloid42 (Aβ42) peptides can add further information to the combined use of tau and Aβ1–42 for predicting risk of progression of MCI to AD.Methods: We used xMAP® technology to simultaneously quantify different Aβ42 peptides modified at the amino terminus, tau, and phosphorylated tau (P-tau181P) in CSF. Aβ42 peptide concentrations were measured by use of immunoreactivity toward Aβ monoclonal antibodies [3D6 (Aβ42-3D6), WO2 (Aβ42-WO2), 6E10 (Aβ42-6E10), and 4G8 (Aβ42-4G8)]. The discriminant ability of the markers was evaluated by ROC curve analysis.Results: The areas under the curves for the separation of MCI-AD from nonprogressing MCI (MCI-N) were significantly higher when we used Aβ42-3D6/Aβ42-WO2, Aβ42-3D6/Aβ42-6E10, or Aβ42-3D6/Aβ42-4G8 compared with Aβ42-3D6. In addition, differentiation of MCI-N from MCI-AD was improved by quantification of full-length Aβ1–42 (Aβ42-3D6) compared with Aβ42-WO2, Aβ42-6E10, or Aβ42-4G8. Several Aβ42 peptides truncated at the amino terminus (Aβ11–42 and Aβ8–42) were identified in CSF by surface-enhanced laser desorption/ionization time-of-flight technology.Conclusion: The CSF markers tau, Aβ42 forms, and P-tau181P, when used as adjuncts to clinical diagnosis, have the potential to help identify AD pathology and could be a valuable asset for early AD diagnosis.
Optimized Real-Time Quantitative PCR Measurement of Male Fetal DNA in Maternal Plasma
Authors: Zimmermann Bernhard , El-Sheikhah Ahmad , Nicolaides Kypros , Holzgreve Wolfgang , Hahn Sinuhe 
Published: July 2005

AbstractBackground: Circulating fetal DNA (cfDNA) in maternal plasma has been measured to investigate its possible relationship with pregnancy-related disorders, including fetal trisomy 21 and preeclampsia. The circulating concentrations of single-copy fetal genes, however, are close to the detection limits of PCR methods.Methods: We optimized a protocol for the real-time quantitative PCR amplification of the multicopy sequence DYS14 on the Y-chromosome. This was compared with an established real-time PCR assay for the single-copy SRY gene.Results: By probit regression analysis, the measurements of male DNA by the DYS14 assay had a 10-fold lower detection limit (0.4 genome equivalents) than did measurements of SRY. For plasma samples from women in the first trimester of pregnancy, imprecision (CV) was 2%–22% when amplifying DYS14 compared with 26%–140% for SRY.Conclusions: The low copy numbers of fetal DNA in plasma of women in the first trimester of pregnancy cannot be measured precisely when targeting single-copy sequences. Better results are obtained by amplifying a sequence that is present in multiple copies per male genome.
Direct Molecular Haplotyping of the IVS-8 Poly(TG) and PolyT Repeat Tracts in the Cystic Fibrosis Gene by Melting Curve Analysis of Hybridization Probes
Authors: Millson Alison , Pont-Kingdon Genevieve , Page Sam , Lyon Elaine 
Published: July 2005

AbstractBackground: Molecular haplotyping is a developing technology with great potential for use in clinical diagnostics. We describe a haplotyping method that uses PCR combined with hybridization probes.Methods: We designed a LightCycler assay that uses fluorescence resonance energy transfer hybridization probes to haplotype the poly(TG) and polyT (TG-T) tract in the IVS-8 region of the CFTR gene. The reporter probe was designed as a perfect match to the TG12-5T allele.Results: Analysis of 132 samples revealed 9 unique derivative melting temperatures (Tms); the lowest was 42.4 °C and the highest was 63.6 °C. The lowest Tms were in the TGn-9T group, the intermediate Tms in the TGn-7T group, and the highest Tms in the TGn-5T group. Haplotype frequencies were highest (39%) for TG11-7T and lowest (0.4%) for TG13-5T.Conclusions: Different combinations of polymorphisms under the reporter hybridization probe had unique and characteristic Tms. This property enables genotyping as well as determination of the phase of multiple variants under the probe, a principle we demonstrated by haplotyping the TG-T repeat tract in the IVS-8 region of the CFTR gene.
Routine Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry Assay for Simultaneous Measurement of the 25-Hydroxy Metabolites of Vitamins D2 and D3
Authors: Maunsell Zoë , Wright Dennis J , Rainbow Sandra J 
Published: July 2005

Abstract
Background: Measurement of 25-hydroxyvitamin D2 and D3 (25-OH D2 and D3) is essential for investigating vitamin D deficiency. Competitive binding techniques are unable to distinguish between the 2 metabolites and suffer from interference from other hydroxy metabolites of vitamin D.
Methods: We used isotope-dilution liquid chromatography–tandem mass spectrometry (ID-LC-MS/MS) for routine determination of 25-OH D2 and D3 with a stable-isotope–labeled internal standard (IS). Serum samples (100 μL) were denatured with methanol–propanol containing IS, vortex-mixed, extracted into hexane, and dried under nitrogen. The reconstituted extract was chromatographed on a BDS C8 HPLC column, and the metabolites and IS were detected by electrospray ionization MS/MS in multiple-reaction monitoring mode.
Results: 25-OH D2 and D3 and the IS nearly coeluted, whereas 1α-hydroxyvitamin D3 was separated; total run time was 8 min. The interassay CVs for 25-OH D2 were 9.5% and 8.4% at 52 and 76 nmol/L, respectively, and for 25-OH D3 were 5.1% and 5.6% at 55 and 87 nmol/L, respectively. The detection limit of the present method was &lt;4 nmol/L for both metabolites. Method comparison with a commercial RIA measuring total 25-hydroxyvitamin D showed good correlation: y = 0.97x − 2.7 nmol/L (r = 0.91). The analytical system can assay 100 samples in 12.5 h.
Conclusions: This simple robust interference-free LC-MS/MS assay is suitable for routine measurement of the 25-hydroxy metabolites of vitamins D2 and D3 in human serum. The assay has been in use for 9 months and has been used to assay more than 6000 routine samples.