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Friday, August 24, 2012

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This examine was accepted by the institutional assessment board or ethics committee from each of the participating PI3K Inhibitors

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PF299804 as solitary agents, we targeted on RPMI 8226, CCRF CEM, Raji, U937, and K562 cells as a panel of agent leukemia mobile lines. The IC50 concentrations for the ongoing publicity of leukemia cells to every single drug as a solitary agent for 72 h had been calculated utilizing the Cell Cycle

assay. The table demonstrates the IC50 values of F araA and carboplatin for leukemia cells. The sensitivity of the leukemia cells to 72 h ongoing publicity to F araA ranged from the nM to lM, which is clinically achievable in sufferers blood.

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Probably the most generally reported AEs within the asenapine deal with ment group had been somnolence, dizziness, sedation, in creased excess weight, and vomiting. EPS was reported at prices of ten. 3% within the asenapine group and six. 8% within the olanzapine group. Probably the most generally reported EPS presentations within the asenapine group had been akathisia and bradykinesia.

PTHrP isoforms have differing effect on chondrogenic differentiation and hypertrophy of mesenchymal stem cells.

PTHrP isoforms have differing effect on chondrogenic differentiation and hypertrophy of mesenchymal stem cells.
Biochem Biophys Res Commun. 2012 May 18;421(4):819-24
Authors: Lee JM, Im GI
Abstract
While several isoforms of parathyroid hormone-related peptide (PTHrP) have been commercially available, the difference in their effect has not been widely studied. The purpose of this study was to determine which isoform most effectively promoted chondrogenesis and suppressed hypertrophy from mesenchymal stem cells (MSCs). MSCs isolated from fresh bone marrow were cultured in pellet in chondrogenic medium containing 5 ng/ml of transforming growth factor (TGF)-?(3). From day 14 of culture, subsets of pellets were additionally treated with one of the four PTHrP isoforms (1-34, 1-86, 7-34, and 107-139) at 100 nM. After a further 2 weeks of in vitro culture, pellets were harvested for analysis. PTHrPs 1-34 and 1-86 significantly decreased the DNA level (p<0.05) while PTHrPs 7-34 and 107-139 significantly increased DNA level (p<0.05) compared with the control treated with TGF-?(3) only. Glycosaminoglycan per DNA significantly increased when treated with PTHrPs 1-34 and 1-86 (p<0.05) while it significantly decreased with PTHrPs 7-34 and 107-139 (p<0.05). PTHrP 1-34 significantly increased the gene and protein expression of the chondrogenic marker COL2A1, and decreased those of hypertrophic markers COL10A1 and alkaline phosphatase while other isoforms showed inconsistent effects. All of PTHrP isoforms significantly suppressed the gene and protein expression of indian hedgehog (p<0.05) while all isoforms except PTHrP 107-139 significantly reduced the gene and protein expression of patched 1 (p<0.05). In conclusion, of several PTHrP isoforms, PTHrP 1-34 most significantly enhanced chondrogenesis and suppressed hypertrophy in MSCs, supporting its use for cartilage tissue engineering.

PMID: 22554518 [PubMed - indexed for MEDLINE]
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Determination of morphine, codeine, and paclitaxel in human serum and plasma by micellar electrokinetic chromatography.

Determination of morphine, codeine, and paclitaxel in human serum and plasma by micellar electrokinetic chromatography.
J Sep Sci. 2012 Aug 7;
Authors: Rodr�guez J, Contento AM, Casta�eda G, Mu�oz L, Berciano MA
Abstract
A micellar electrokinetic chromatography method is proposed for the determination of morphine, codeine, and paclitaxel at clinical relevant levels in human serum and plasma, which are employed in the treatment of patients with cancer. Optimal conditions for the separation were investigated. A background electrolyte solutions consisting of 20 mM borate buffer adjusted to pH 8.5, sodium dodecyl sulphate 60 mM and 15% methanol, hydrodynamic injection, and 25 kV as separation voltage were used. Detection wavelength was 212 nm for morphine and codeine and 200 nm for paclitaxel. Aspects such as stability of the solutions, linearity, accuracy, precision, and robust and ruggedness were examined in order to validate the proposed method. Detection limits obtained for all the studied compounds ranged between 26 and 52 ng/mL. Before micellar electrokinetic chromatography determination, the samples were purified and enriched by means of an extraction-preconcentration step with a preconditioned C(18) cartridge. This method was applied to the analysis of serum and plasma samples from different cancer patients undergoing treatment with paclitaxel or/and codeine.

PMID: 22887651 [PubMed - as supplied by publisher]
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Tuesday, August 14, 2012

Confirmation of the existence of two distinct genetic groups of infectious bursal disease virus in Australia.

Confirmation of the existence of two distinct genetic groups of infectious bursal disease virus in Australia.

Aust Vet J. 2002 Nov;80(11):689-94

Authors: Ignjatovic J, Sapats S

Abstract
OBJECTIVE: To characterise infectious bursal disease viruses (IBDVs) prevalent at major commercial sites throughout Australia and to compare the nucleic acid sequences of local strains of IBDV with those of characterised overseas strains.
DESIGN: Samples of bursae were collected from 20 broiler farms that belonged to different poultry companies in New South Wales (NSW), Queensland (Qld), Victoria (Vic), Westem (WA) and South Australia (SA).
METHOD: Bursae were collected from broilers between 24 and 35 days of age. Bursal tissue was homogenised and tested for the presence of IBDV antigen using four monoclonal antibodies (Mabs) which detect antigenic variation in IBDV strains. The nucleotide sequences of the hypervariable region (HVR) within the VP2 gene of IBDVs was determined and the deduced amino acid sequences compared with three vaccine strains and six previously characterised Australian IBDV strains. The deduced amino acid sequences were also compared with the published amino acid sequences of overseas strains. The phylogenetic relationships between Australian strains and overseas strains were then determined.
RESULTS: IBDV was detected in birds from 14 out of 20 farms sampled. Typing with four Mabs showed that all viruses from Vic (6) and SA (10) were antigenic variants, whereas all viruses from NSW (29), Qld (4) and WA (5) were classical-like strains. Nucleotide sequencing of one sample from each of the 14 farms on which IBDV was detected confirmed results obtained with Mabs. The amino acid sequences of all Australian viruses differed from the amino acid sequences of foreign IBDV strains. Phylogenetic analysis showed that Australian IBDV viruses belonged to two distinct genetic groups. Very virulent (vv) IBDV strains belonged to a third genetic group, and overseas classical and variant strains belonged to a fourth genetic group.
CONCLUSIONS: The results confirmed previous findings that there are two groups of IBDV strains circulating in commercial broilers in Australia. The majority are classical-like strains that are antigenically and genetically similar to vaccine strains 002/73 and V877. These classical strains were prevalent in broilers in three states, NSW, Qld and WA. The second group of strains are antigenic variants that were only found in broilers in two states, Vic and SA. All Australian IBDVs characterised to date are genetically distinct and can be differentiated from all other overseas strains. This enables identification of incursion of any exotic strain into Australian poultry, be it classical, US variant or wIBDV strains.

PMID: 12465828 [PubMed - indexed for MEDLINE]

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[Re-evaluation of interval debulking surgery in advanced epithelial ovarian cancer].

[Re-evaluation of interval debulking surgery in advanced epithelial ovarian cancer].

Zhonghua Fu Chan Ke Za Zhi. 2012 May;47(5):355-60

Authors: Ma Y, Li Y, Cui H, Liang XD, Tang ZJ, Li XP, Zhao Y, Wei LH

Abstract
OBJECTIVE: Previous study showed that interval debulking surgery (IDS) may improve the survival of patients with advanced epithelial ovarian cancer (EOC). The precise significance of IDS needs to be evaluated.
METHODS: Totally 136 consecutive patients with stage IIIc or IV EOC (including primary peritoneal carcinoma and primary fallopian tube carcinoma) who completed primary debulking surgery (PDS) and platinum-based chemotherapy were enrolled from January 2000 to December 2009 in a retrospective cohort study. The study group was divided into three groups: 65 cases underwent optimal PDS (Group A), 41 cases received chemotherapy alone after suboptimal PDS (Group B), and 30 patients underwent IDS after suboptimal PDS (Group C). All patients received six to eight courses of platinum-based combination chemotherapy (paclitaxel plus carboplatin/cisplatin, cyclophosphamide plus epirubicin and cisplatin). Patients' clinical characteristics, perioperative situation and prognosis were compared.
RESULTS: Sixty-five cases (47.8%, 65/136) from 136 patients achieved optimal PDS. For Group C, 77% (23/30) patients obtained optimal debulking surgery after IDS. Intraoperative injury rates were similar between Group B and Group C (P > 0.05). Mild perioperative complications rate was also similar (P > 0.05). Median progression-free survival (PFS) of Group A was 26 months. Median overall survival (OS) of Group B and Group C were 31 months and 40 months, respectively (P = 0.254). Median PFS of Group B and Group C were 13 months and 24 months, respectively (P = 0.289). Although when it came to 20 months after PDS, patients who underwent IDS had a significantly lower progressive disease (PD) rate (Group B 33% versus Group C 61%, P = 0.046), it still showed that there was no significant difference in either OS or PFS of these two groups. Those patients in Group C who obtained no visible residual got similar PFS (27 months) comparing to Group A (26 months, P = 0.730), but OS was still shorter (P = 0.010).
CONCLUSIONS: For advanced EOC patients, IDS has little effect on improving survival. While it is safe and acceptable, also may prolong PFS in those patients who got no visible residual after IDS. The results suggest that IDS might be used as an alternative treatment for advanced EOC patients who cannot obtain optimal PDS in certain local hospitals.

PMID: 22883524 [PubMed - in process]

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Self-assembled micelles of monosialogangliosides as nanodelivery vehicles for taxanes.

Self-assembled micelles of monosialogangliosides as nanodelivery vehicles for taxanes.

J Control Release. 2012 Aug 1;

Authors: Leonhard V, Alasino RV, Bianco ID, Garro AG, Heredia V, Beltramo DM

Abstract
We demonstrate herein that taxanes (paclitaxel (Ptx) and docetaxel (Dtx)) can be spontaneously loaded into ganglioside nanomicelles. The efficiency of gangliosides to solubilize taxanes was highly dependent on their self-aggregating structure. Thus, GM3 that forms unilamellar vesicles was less efficient to solubilize taxanes than gangliosides that form micelles (i.e. GM1 and GM2). Sialic acid cyclization of GM1 by acid treatment led to an important reduction in its capacity to solubilize taxanes, as also did the replacement of the fatty acid of ceramide by a dicholoracetyl group. Water solubility of paclitaxel (Ptx) is less than 1?gmL(-1) and increased up to 6.3mg.mL(-1) upon its association with GM1 micelles. The incorporation of Ptx in GM1 reached an optimum at GM1/Ptx 20/1 molar ratio when performed at room temperature. An increase in the solubilization capacity of GM1 micelles was observed upon dehydration of their polar head group by pre-treatment at 55�C. Loading of Ptx into the micelle induced a structural reorganization that led to an important protection of Ptx reducing its hydrolysis at alkaline pH. Diffusion of either GM1 or Ptx was restricted upon mixed-micelle formation indicating that they are kinetically more stable than pure ganglioside micelles. X-ray powder diffraction of lyophilized GM1 micelles with Ptx showed a change in their internal structure from a crystalline state to completely amorphous. Taxane-ganglioside mixed micelles were stable in solution for at least 4months and also upon freeze-thawing or lyophilization-solubilization cycles. Upon mixing with human blood constituents, GM1/Ptx micelles did not induce hemolysis or platelet aggregation and were spontaneously covered with human serum albumin (HSA), which could aid in the delivery of micellar content to tumors. In vitro antimitotic activity of GM1/Ptx mixed micelles was qualitatively equivalent to that of free drug in DMSO solution.

PMID: 22877735 [PubMed - as supplied by publisher]

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Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

BMJ. 2012;344:e1771

Authors: Hemmingsen B, Christensen LL, Wetterslev J, Vaag A, Gluud C, Lund SS, Almdal T

Abstract
OBJECTIVES: To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes.
DESIGN: Systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.
DATA SOURCES: The Cochrane Library, Medline, Embase, Science Citation Index Expanded, Latin American Caribbean Health Sciences Literature, and Cumulative Index to Nursing and Allied Health Literature until March 2011. We also searched abstracts presented at the American Diabetes Association and European Association for the Study of Diabetes Congresses, contacted relevant trial authors and pharmaceutical companies, hand searched reference lists of included trials, and searched the US Food and Drug Administration website.
REVIEW METHODS: Two authors independently screened titles and abstracts for randomised clinical trials comparing metformin and insulin versus insulin alone (with or without placebo) in patients with type 2 diabetes, older than 18 years, and with an intervention period of at least 12 weeks. We included trials irrespective of language, publication status, predefined outcomes, antidiabetic interventions used before randomisation, and reported outcomes.
RESULTS: We included 26 randomised trials with 2286 participants, of which 23 trials with 2117 participants could provide data. All trials had high risk of bias. Data were sparse for outcomes relevant to patients. Metformin and insulin versus insulin alone did not significantly affect all cause mortality (relative risk 1.30, 95% confidence interval 0.57 to 2.99) or cardiovascular mortality (1.70, 0.35 to 8.30). Trial sequential analyses showed that more trials were needed before reliable conclusions could be drawn regarding these outcomes. In a fixed effect model, but not in a random effects model, severe hypoglycaemia was significantly more frequent with metformin and insulin than with insulin alone (2.83, 1.17 to 6.86). In a random effects model, metformin and insulin resulted in reduced HbA(1c), weight gain, and insulin dose, compared with insulin alone; trial sequential analyses showed sufficient evidence for a HbA(1c) reduction of 0.5%, lower weight gain of 1 kg, and lower insulin dose of 5 U/day.
CONCLUSIONS: There was no evidence or even a trend towards improved all cause mortality or cardiovascular mortality with metformin and insulin, compared with insulin alone in type 2 diabetes. Data were limited by the severe lack of data reported by trials for patient relevant outcomes and by poor bias control.

PMID: 22517929 [PubMed - indexed for MEDLINE]

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The treatment of West syndrome: a Cochrane review of the literature to December 2000.

The treatment of West syndrome: a Cochrane review of the literature to December 2000.

Brain Dev. 2001 Nov;23(7):624-34

Authors: Hancock E, Osborne JP, Milner P

Abstract
BACKGROUND: West syndrome is an age dependent syndrome, which includes a peculiar type of epileptic seizure (infantile spasms), usually hypsarrhythmia and in the majority psychomotor retardation. Despite huge advances in medicine it still remains a poorly understood entity and although with newer imaging techniques we are more often able to elicit the underlying 'causes' of these spasms, still little is known about their pathophysiological basis and treatment remains problematic.
OBJECTIVES: To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of long-term psychomotor development, subsequent epilepsy, control of the spasms and side effects.
METHODS: A search of the central trials register of the Cochrane Epilepsy Group, medline database, embase database and the reference lists of all retrieved articles was undertaken. Correspondence with colleagues and drug companies and appeals at international conferences were also undertaken to try and discover unpublished data. All randomised controlled trials (RCTs) on the medical treatment of infantile spasms were included. Data was then extracted independently by the three reviewers and analysed using the RevMan software package.
MAIN RESULTS: We found ten small RCTs on the pharmacological treatment of infantile spasms. No unpublished trials were discovered. These ten studies looked at just 335 patients treated with a total of eight different pharmaceutical agents. Overall methodology of the studies was poor, partly because of ethical dilemmas such as giving placebo injections to children. No study considered the effects of treatment on long-term psychomotor development or onset of other seizure types. One small study found vigabatrin to be more efficacious in stopping infantile spasms in a group of patients with tuberous sclerosis than hydrocortisone. One underpowered study showed a trend for vigabatrin to be more efficacious than placebo in stopping infantile spasms, another two equally underpowered studies suggested adrenocorticotrophic hormone (ACTH) to be more efficacious than low-dose prednisone. It was not possible to compare reduction in the number of spasms between the different treatments because of differences in methods of analysis. Overall, only nine patients were reported to have been withdrawn from the trial treatments due to side effects and two deaths were reported.
CONCLUSIONS: There is still little evidence available on the optimum treatment for infantile spasms. Further trials with larger number of patients, and longer follow-up are required.

PMID: 11701267 [PubMed - indexed for MEDLINE]

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Monday, August 13, 2012

Neutral Loss Fragmentation Pattern Based Screening for Arginine-Rich Natural Products in Xenorhabdus and Photorhabdus.

Neutral Loss Fragmentation Pattern Based Screening for Arginine-Rich Natural Products in Xenorhabdus and Photorhabdus.

Anal Chem. 2012 Aug 6;

Authors: Fuchs SW, Sachs CC, Kegler C, Nollmann FI, Karas M, Bode HB

Abstract
Although sharing a certain degree of structural uniformity, natural product classes exhibit variable functionalities such as different amino acid or acyl residues. During collision induced dissociation, some natural products exhibit a conserved fragmentation pattern close to the precursor ion. The observed fragments result from a shared set of neutral losses, creating a unique fragmentation pattern, which can be used as a fingerprint for members of these natural product classes. The culture supernatants of 69 strains of the entomopathogenic bacteria Photorhabdus and Xenorhabdus were analyzed by MALDI-MS(2), and a database comprising MS(2) data from each strain was established. This database was scanned for concordant fragmentation patterns of different compounds using a customized software, focusing on relative mass differences of the fragment ions to their precursor ion. A novel group of related natural products comprising 25 different arginine-rich peptides from 16 different strains was identified due to its characteristic neutral loss fragmentation pattern, and the structures of eight compounds were elucidated. Two biosynthesis gene clusters encoding nonribosomal peptide synthetases were identified, emphasizing the possibility to identify a group of structurally and biosynthetically related natural products based on their neutral loss fragmentation pattern.

PMID: 22873683 [PubMed - as supplied by publisher]

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Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

Eur Respir J. 1996 Nov;9(11):2263-72

Authors: Hoekx JC, Hedlin G, Pedersen W, Sorva R, Hollingworth K, Efthimiou J

Abstract
The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF). In addition, pulmonary function tests were performed at each clinic visit and a self-administered patient-centred questionnaire was completed by one parent of each patient at the start and end of study treatment. Mean morning PEF increased following treatment both with FP and BUD, but was significantly higher following treatment with FP during Weeks 1-4 (p=0.015) and Weeks 1-8 (p=0.019). Similar results were found for mean evening PEF and percentage predicted morning and evening PEF. Children receiving FP experienced significantly less disruption in their physical activities (i.e. sports, games) because of their asthma compared to children treated with BUD (p=0.03). Mean cortisol levels increased in both groups, but the increase was significantly higher in the FP group at 4 weeks (p=0.022). Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change. Fluticasone propionate at a dosage of 400 microg x day(-1) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1) from the Turbuhaler. Both treatments were well-tolerated, with a similar safety profile.

PMID: 8947070 [PubMed - indexed for MEDLINE]

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Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

J Clin Oncol. 1995 Sep;13(9):2457-63

Authors: Bennett CL, Smith TJ, George SL, Hillner BE, Fleishman S, Niell HB

Abstract
PURPOSE: Both economic and clinical data on new agents are important to policy-makers who approve pharmaceuticals for widespread use. Randomized clinical trials have been used to evaluate both clinical results and total medical costs associated with new agents. With new expensive pharmaceutical agents, early assessments of economic benefit have taken on greater importance to physicians and patients. Who should provide financial support to these integrated economic and clinical analyses in clinical trials? Here we describe issues that hinder funding of economic analyses and propose potential support mechanisms.
RESULTS: The Cancer and Leukemia Group B (CALGB), a large, national cooperative group of academic and community hospitals in the United States, designed a non-small-cell lung cancer (NSCLC) treatment trial to compare two widely used supportive care regimens that varied 20-fold in cost. One important objective of this trial was to compare the cost-effectiveness of the two regimens. While funding for the clinical trial was supported by grants from the National Cancer Institute and the pharmaceutical companies involved in the trial, no specific funding agency was willing and/or able to provide financial support for the economic analyses. After 2 years of planning, the clinical trial was retracted when the funding for the economic analyses could not be secured. The prisoner's dilemma, individual reluctance to support a common social good, explains the lack of funding.
CONCLUSION: Economic theory predicts difficulties in evaluating cost-effectiveness of new pharmaceuticals and reluctance to support economic analyses of clinical trials. Economic analyses will require new sources of funds that will not take scarce resources from clinical trials groups. Options for funding include a new federal agency, coordinated work by existing agencies, or academic centers for economic analysis.

PMID: 7545222 [PubMed - indexed for MEDLINE]

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Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

J Clin Oncol. 1995 Sep;13(9):2457-63

Authors: Bennett CL, Smith TJ, George SL, Hillner BE, Fleishman S, Niell HB

PMID: 7545222 [PubMed - indexed for MEDLINE]

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Sunday, August 12, 2012

Comparison of the efficacy and safety of Consupren solution and Sandimmun Neoral solution, 50 ml in stable heart transplant patients.

Comparison of the efficacy and safety of Consupren solution and Sandimmun Neoral solution, 50 ml in stable heart transplant patients.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2002 Dec;146(2):87-90
Authors: Toman J, Spinarov� L, Krejc� J, Hude P, Kopecn� E, Kamar�d V
Abstract
Cyclosporine A (CyA) is a standard component of immunosuppressive regimen after heart transplantation in most centres. The widespread clinical use of cyclosporine-based immunosuppressive regimens since 1983 has led to significant improvements in the survival of cardiac allograft recipients due to decreased mortality from infections and rejections. (1-3) CyA has been shown to be safe and effective. Owing to its success when used after the heart transplantation the number of patients has also risen. This caused growing financial demands on health insurance companies in the Czech Republic where the immunosuppressive drugs are fully reimbursed. A prospective randomized study in 11 stable heart transplant patients was performed to compare the efficacy and safety of Consupren (IVAX-CR) a Sandimmun Neoral (Novartis) solution based immunosuppressive regimen. The results suggest that Consupren solution can be used as an alternative treatment to Sandimmun Neoral in CyA based regimen.

PMID: 12572904 [PubMed - indexed for MEDLINE]
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S-Nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer.

S-Nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer.

Mol Cancer Res. 2012 Aug 9;

Authors: Switzer CH, Glynn SA, Cheng RY, Ridnour LA, Green JE, Ambs S, Wink DA

Abstract
Increased inducible nitric oxide synthase (NOS2) expression in breast tumors is associated with decreased survival of estrogen receptor-negative (ER-) breast cancer patients. We recently communicated the preliminary observation that nitric oxide (NO) signaling results in EGFR tyrosine phosphorylation. To further define the role of NO in the pathogenesis of ER- breast cancer, we examined the mechanism of NO-induced EGFR activation in human ER- breast cancer. NO was found to activate EGFR and Src by a mechanism that includes S-nitrosylation. NO, at physiologically relevant concentrations, induced an EGFR/Src-mediated activation of oncogenic signal transduction pathways (including c-Myc, Akt and ?-catenin) and the loss of PP2A tumor suppressor activity. Additionally, NO signaling increased cellular EMT, expression and activity of COX-2 and chemoresistance to adriamycin and paclitaxel. When connected into a network, these concerted events link NO to the development of a stem cell-like phenotype, resulting in the upregulation of CD44 and STAT3 phosphorylation. Our observations are also consistent with the finding that NOS2 is associated with a basal-like transcription pattern in human breast tumors. These results indicate that the inhibition of NOS2 activity or NO signaling networks may have beneficial effects in treating basal-like breast cancer patients.

PMID: 22878588 [PubMed - as supplied by publisher]

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[Short-acting insulin analogs--critical assessment of meta-analyses].

[Short-acting insulin analogs--critical assessment of meta-analyses].

Dtsch Med Wochenschr. 2006 Dec;131 Suppl 8:S274-9

Authors: Kunt T

Abstract
Short-acting insulin analogs have for nearly ten years been prescribed for type 1 and 2 diabetes mellitus. There is extensive scientific and practical evidence of their being better than normal insulin. For this reason these insulins have been recommended in the guidelines of most leading specialist societies. In everyday practice they are an important component of the therapeutic portfolio which can produce an improvement in insulin treatment, especially of selective cases. On the other hand, there is growing economic pressure, especially in Germany, affecting their use. However, it must be critically asserted that those meta-analyses on insulin analogs, which have been commissioned by insurance companies or governmental organisations, do not do justice to their advantage. Current meta-analyses of short-acting insulin analogs exclude decisive advantages of insulin analogs from their analyses and compare highly heterogeneous groups. They do not distinguish between differing incidences of hypoglycemia associated with different HbA1c values as well as between conventional and intensive treatment. Furthermore positive data and positive major studies are excluded, while approval studies or trials with completely different aims are cited. Short study duration is also often neglected. As a result, the International Diabetes Federation (IDF) has rejected the Cochrane Review for 2005 for methodological reasons. Also, no recommendations can be derived from the recommendations of of the Institut f�r Qualit�tssicherung und Wirtschaftlichkeit in der Medizin (IQWiG: Institute for Quality Assurance and Cost Effectiveness in Medicine). After critical assessment of meta-analyses the IDF concluded in its guidelines that insulin analogs should generally be used.

PMID: 17139586 [PubMed - indexed for MEDLINE]

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S-Nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer.

S-Nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer.

Mol Cancer Res. 2012 Aug 9;

Authors: Switzer CH, Glynn SA, Cheng RY, Ridnour LA, Green JE, Ambs S, Wink DA

PMID: 22878588 [PubMed - as supplied by publisher]

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Saturday, August 11, 2012

Neutral Loss Fragmentation Pattern Based Screening for Arginine-Rich Natural Products in Xenorhabdus and Photorhabdus.

Neutral Loss Fragmentation Pattern Based Screening for Arginine-Rich Natural Products in Xenorhabdus and Photorhabdus.

Anal Chem. 2012 Aug 6;

Authors: Fuchs SW, Sachs CC, Kegler C, Nollmann FI, Karas M, Bode HB

PMID: 22873683 [PubMed - as supplied by publisher]

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natural products research; +117 new citations

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Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.

Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.

Sci Transl Med. 2012 Apr 18;4(130):130ra47

Authors: Sun N, Yazawa M, Liu J, Han L, Sanchez-Freire V, Abilez OJ, Navarrete EG, Hu S, Wang L, Lee A, Pavlovic A, Lin S, Chen R, Hajjar RJ, Snyder MP, Dolmetsch RE, Butte MJ, Ashley EA, Longaker MT, Robbins RC, Wu JC

Abstract
Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric ?-actinin. When stimulated with a ?-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric ?-actinin distribution. Treatment with ?-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening.

PMID: 22517884 [PubMed - indexed for MEDLINE]

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Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.

Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.

Sci Transl Med. 2012 Apr 18;4(130):130ra47

PMID: 22517884 [PubMed - indexed for MEDLINE]

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Meta-analysis of everolimus-eluting stent as compared to sirolimus-eluting stent in patients undergoing percutaneous coronary interventions: an update.

Meta-analysis of everolimus-eluting stent as compared to sirolimus-eluting stent in patients undergoing percutaneous coronary interventions: an update.

Int J Cardiol. 2011 Jul 1;150(1):101-3

Authors: Chen H, Liu K

PMID: 21497406 [PubMed - indexed for MEDLINE]

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Friday, August 10, 2012

Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model.

Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model.

Nanoscale. 2012 Aug 9;

Authors: Lei N, Gong C, Qian Z, Luo F, Wang C, Wang H, Wei Y

Abstract
Many drug delivery systems (DDSs) have been investigated for local targeting of malignant disease with the intention of increasing anti-tumor activity and minimizing systemic toxicity. An injectable thermosensitive hydrogel was applied to prevent locoregional recurrence of 4T1 breast cancer in a mouse model. The presented hydrogel, which is based on poly(ethyleneglycol)-poly(?-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), flows freely at normal temperature, forms a gel within seconds in situ at body temperature, and eventually releases the drug in a consistent and sustained fashion as it gradually biodegrades. Locoregional recurrence after primary tumor removal was significantly inhibited in mice treated with the paclitaxel (PTX)-loaded PECE hydrogel subcutaneously (9.1%) administered, compared with the blank hydrogel (80.0%), systemic (77.8%) and locally (75.0%) administered PTX, and the control group (100%) (P < 0.01). In addition, tensile strength measurements of the surgical incisions showed that the PECE hydrogel accelerates wound healing at postoperative day 7 (P < 0.05), and days 4 and 14 (P > 0.05), in agreement with histopathological examinations. This novel DDSs represents a promising approach for local adjuvant therapy in malignant disease.

PMID: 22875402 [PubMed - as supplied by publisher]

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antigen peptide; +46 new citations

46 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

antigen peptide

These pubmed results were generated on 2012/08/10

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[Short-acting insulin analogs--critical assessment of meta-analyses].

[Short-acting insulin analogs--critical assessment of meta-analyses].

Dtsch Med Wochenschr. 2006 Dec;131 Suppl 8:S274-9

Authors: Kunt T

PMID: 17139586 [PubMed - indexed for MEDLINE]

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Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

Eur Respir J. 1996 Nov;9(11):2263-72

Authors: Hoekx JC, Hedlin G, Pedersen W, Sorva R, Hollingworth K, Efthimiou J

PMID: 8947070 [PubMed - indexed for MEDLINE]

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CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin.

CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin.

Clin Genet. 2012 Mar;81(3):234-9

Authors: Pauli S, von Velsen N, Burfeind P, Steckel M, M�nz J, Buchholz A, Borozdin W, Kohlhase J

Abstract
CHARGE (coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies and deafness) syndrome is a congenital malformation syndrome caused by mutations in the CHD7 gene in approximately 2/3 of cases. In the vast majority of cases, CHARGE syndrome is sporadic. There are only a few reports of parent-to-child transmission and somatic or gonadal mosaicism. To determine the parental origin of CHD7 mutations in sporadic CHARGE syndrome, we screened 30 families for informative exonic or intronic polymorphisms located near the detected CHD7 mutation. An informative polymorphism could be identified in 13 out of 30 families. Linkage analysis was performed between the CHD7 mutation and the polymorphism in the child. In 12 out of 13 families, the mutation affected the paternal allele (92.3%). In our cohort, the mean paternal age at birth was 32.92 years. Comparing the age of fathers of an affected CHARGE patient with the paternal age of the German population in general, we could not observe any paternal age effect. Taken together, we show in this study that de novo CHD7 mutations occur predominantly in the male germ line.

PMID: 21554267 [PubMed - indexed for MEDLINE]

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Thursday, August 9, 2012

antigen peptide; +47 new citations

47 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

antigen peptide

These pubmed results were generated on 2012/08/09

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Chemical genomics in plant biology.

Chemical genomics in plant biology.

Indian J Biochem Biophys. 2012 Jun;49(3):143-54

Authors: Sadhukhan A, Sahoo L, Panda SK

Abstract
Chemical genomics is a newly emerged and rapidly progressing field in biology, where small chemical molecules bind specifically and reversibly to protein(s) to modulate their function(s), leading to the delineation and subsequent unravelling of biological processes. This approach overcomes problems like lethality and redundancy of classical genetics. Armed with the powerful techniques of combinatorial synthesis, high-throughput screening and target discovery chemical genomics expands its scope to diverse areas in biology. The well-established genetic system of Arabidopsis model allows chemical genomics to enter into the realm of plant biology exploring signaling pathways of growth regulators, endomembrane signaling cascades, plant defense mechanisms and many more events.

PMID: 22803329 [PubMed - indexed for MEDLINE]

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The treatment of West syndrome: a Cochrane review of the literature to December 2000.

The treatment of West syndrome: a Cochrane review of the literature to December 2000.

Brain Dev. 2001 Nov;23(7):624-34

Authors: Hancock E, Osborne JP, Milner P

PMID: 11701267 [PubMed - indexed for MEDLINE]

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Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.

J Clin Oncol. 1995 Sep;13(9):2457-63

Authors: Bennett CL, Smith TJ, George SL, Hillner BE, Fleishman S, Niell HB

PMID: 7545222 [PubMed - indexed for MEDLINE]

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Twelve-month results of a Paclitaxel Releasing Balloon in Patients Presenting with In-stent Restenosis First-in-Man (PEPPER) trial.

Twelve-month results of a Paclitaxel Releasing Balloon in Patients Presenting with In-stent Restenosis First-in-Man (PEPPER) trial.

Cardiovasc Revasc Med. 2012 Aug 3;

Authors: Hehrlein C, Dietz U, Kubica J, J�rgensen E, Hoffmann E, Naber C, Lesiak M, Schneider H, Wiemer M, T�lg R, Richardt G

Abstract
BACKGROUND: Coronary in-stent restenosis (ISR) continues to be a therapeutic challenge especially after drug eluting stent (DES) implantation. We studied patients with ISR to investigate safety and efficacy of a novel drug coated balloon (DCB) incorporating paclitaxel into a microcrystalline structure by applying the inert excipient butyryltri-n-hexyl citrate (BTHC) in a prospective First-in-Man trial. METHODS AND MATERIALS: Eighty-one patients were enrolled at 9 European sites, thereof 43 (53.1%) presenting with bare metal stent (BMS)-ISR and 38 (46.9%) with DES-ISR. The primary study endpoint was in-stent late lumen loss (LLL) independently assessed by a quantitative coronary angiography laboratory at 6 months. A secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, non-fatal myocardial infarction, clinically driven target vessel revascularization after 6 and 12 months. RESULTS: At 6 months, overall LLL was 0.07�0.31 mm showing differences in BMS-ISR and DES-ISR treatment (-0.05�0.28 mm vs. 0.19�0.29 mm, respectively, P=.001). Overall MACE rates at 6 and 12 months were 6.5% and 11.8%. At the 12-month follow-up, one myocardial infarction, and no cardiac death nor stent thrombosis had occurred. CONCLUSION: Application of a novel paclitaxel coated balloon using BTHC as an excipient in patients with ISR is safe and results in very low LLL, revascularization- and MACE-rates at follow-up. (ClinicalTrials.gov:NCT00961181).

PMID: 22867706 [PubMed - as supplied by publisher]

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Wednesday, August 8, 2012

Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers.

Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers.

J Control Release. 2012 Apr 10;159(1):14-26

Authors: Wolinsky JB, Colson YL, Grinstaff MW

Abstract
Polymer-based drug delivery depots have been investigated over the last several decades as a means to improve upon the lack of tumor targeting and severe systemic morbidities associated with intravenous chemotherapy treatments. These localized therapies exist in a variety of form factors designed to facilitate the delivery of drug directly to the site of disease in a controlled manner, sparing off-target tissue toxicities. Many of these depots are biodegradable and designed to maintain therapeutic concentrations of drug at the tumor site for a prolonged period of time. Thus a single implantation procedure is required, sometimes coincident with tumor excision surgery, and thereby biodegrading following complete release of the loaded active agent. Even though localized polymer depot delivery systems have been investigated, a surprisingly small subset of these technologies has demonstrated potentially curative preclinical results for cancer applications, and fewer have progressed toward commercialization. The aims of this article are to review the most well-studied and efficacious local polymer delivery systems from the last two decades, to examine the rationale for utilizing drug-eluting polymer implants in cancer patients, and to identify the patient cohorts that could most benefit from localized therapy. Finally, a discussion of the physiological barriers to localized therapy (i.e. drug penetration, transport), technical hurdles, and future outlook of the field is presented.

PMID: 22154931 [PubMed - indexed for MEDLINE]

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Role of melatonin in the oxidative damage prevention at different times of hepatic regeneration.

Role of melatonin in the oxidative damage prevention at different times of hepatic regeneration.

Cell Biochem Funct. 2012 Aug 2;

Authors: Gonz�lez MA, Contini MD, Millen N, Mahieu ST

Abstract
The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na(+) /K(+) ATPase activities in whole plasma membrane were determined. PH decreased the Na(+) /K(+) ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na(+) /K(+) ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier. Copyright � 2012 John Wiley & Sons, Ltd.

PMID: 22865586 [PubMed - as supplied by publisher]

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Functional characterization and substrate specificity of a novel gene encoding zinc finger-like protein, ZfLp, in Xenopus laevis oocytes.

Functional characterization and substrate specificity of a novel gene encoding zinc finger-like protein, ZfLp, in Xenopus laevis oocytes.

J Toxicol Sci. 2012;37(4):699-709

Authors: Kobayashi Y, Umemoto T, Takeshita Y, Kohyama N, Ohbayashi M, Sanada Y, Yamamoto T

Abstract
In the present study, we isolated and determined the pharmacological characteristics of a novel gene encoding the zinc finger-like protein (ZfLp). The isolated cDNA consisted of 1,581 base pairs that encoded a 526-amino acid protein. The amino acid sequence of ZfLp is 96% identical to that of zinc finger protein 415 isoform 5 (ZNF415-5). Reverse-transcription (RT)-polymerase chain reaction (PCR) analysis revealed that the ZfLp mRNA is expressed in the breast, lung, stomach, small intestine colon and ovary, but not in the liver. When expressed in Xenopus laevis oocytes, ZfLp mediated the high affinity transport of [3H]paclitaxel (taxol) in a sodium-independent manner (K<inf>m</inf> = 336.7 � 190.0 nM). The uptake of [3H]paclitaxel (taxol) by ZfLp was trans-stimulated by glutarate and glutathione (GSH). A cis-inhibition experiment revealed that ZfLp-mediated transport of [3H]paclitaxel (taxol) is inhibited by several organic solutes specifically clotrimazole. Using several clotrimazole derivatives, we found that N-benzylimidazole would be a minimum unit for producing the inhibition of ZfLp-mediated drug uptake. Our results may provide insights into the novel role of soluble protein, such as ZNF, in the human body. Our results, therefore, would be expected to facilitate research on the novel role of ZNFs and on the discovery of novel drugs for targeting ZNF-related proteins such as ZfLp.

PMID: 22863851 [PubMed - in process]

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Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

J Dermatol Sci. 2010 Aug;59(2):123-8

Authors: Muizzuddin N, Hellemans L, Van Overloop L, Corstjens H, Declercq L, Maes D

Abstract
BACKGROUND: Differences in structural and functional skin characteristics have been linked with ethnical background. But racial differences in skin have not been thoroughly investigated by objective methods and the data are often contradictory.
OBJECTIVES: This study was undertaken to compare skin barrier-related parameters of the stratum corneum on African American, Caucasian and East Asian skin by objective measurements.
METHODS: Baseline values of trans epidermal water loss were collected on the face. Consecutive stratum corneum D-squame tape strippings were collected on the panelist's ventral forearm and face to evaluate skin barrier strength and cohesion. Stratum corneum ceramides, maturation, measured as the transglutaminase-mediated cross-linking of stratum corneum proteins, and stratum corneum trypsin like enzyme activity were measured on the D-squame tape strippings.
RESULTS: East Asian and to some extent Caucasian skin was characterized by low maturation and relatively weak skin barrier. African American skin was characterized by low ceramide levels and high protein cohesion in the uppermost layers of the stratum corneum. These data can be interpreted in terms of the high prevalence of xerosis in black skin and increased skin sensitivity in East Asian skin.
CONCLUSION: These results demonstrate that skin properties at the level of the stratum corneum vary considerably among these ethnic groups. This contributes to an improved understanding of physiological differences between these study populations.

PMID: 20654785 [PubMed - indexed for MEDLINE]

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Tuesday, August 7, 2012

Kinesin heavy chain function in Drosophila glial cells controls neuronal activity.

Kinesin heavy chain function in Drosophila glial cells controls neuronal activity.

J Neurosci. 2012 May 30;32(22):7466-76

Authors: Schmidt I, Thomas S, Kain P, Risse B, Naffin E, Kl�mbt C

Abstract
Kinesin heavy chain (Khc) is crucially required for axonal transport and khc mutants show axonal swellings and paralysis. Here, we demonstrate that in Drosophila khc is equally important in glial cells. Glial-specific downregulation of khc by RNA interference suppresses neuronal excitability and results in spastic flies. The specificity of the phenotype was verified by interspecies rescue experiments and further mutant analyses. Khc is mostly required in the subperineurial glia forming the blood-brain barrier. Following glial-specific knockdown, peripheral nerves are swollen with maldistributed mitochondria. To better understand khc function, we determined Khc-dependent Rab proteins in glia and present evidence that Neurexin IV, a well known blood-brain barrier constituent, is one of the relevant cargo proteins. Our work shows that the role of Khc for neuronal excitability must be considered in the light of its necessity for directed transport in glia.

PMID: 22649226 [PubMed - indexed for MEDLINE]

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Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

Eur Respir J. 1996 Nov;9(11):2263-72

Authors: Hoekx JC, Hedlin G, Pedersen W, Sorva R, Hollingworth K, Efthimiou J

PMID: 8947070 [PubMed - indexed for MEDLINE]

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Regulation of Biosynthesis of Syringolin A, a Pseudomonas syringae Virulence Factor Targeting the Host Proteasome.

Regulation of Biosynthesis of Syringolin A, a Pseudomonas syringae Virulence Factor Targeting the Host Proteasome.

Mol Plant Microbe Interact. 2012 Sep;25(9):1198-208

Authors: Ramel C, Baechler N, Hildbrand M, Meyer M, Sch�deli D, Dudler R

Abstract
Many strains of the phytopathogenic bacterium Pseudomonas syringae pv. syringae synthesize the virulence factor syringolin A, which irreversibly inactivates the eukaryotic proteasome. Syringolin A, a peptide derivative, is synthesized by a mixed nonribosomal peptide/polyketide synthetase encoded by five clustered genes, sylA to sylE. Biosynthesis of syringolin A, previously shown to be dependent on the GacS/GacA two-component system, occurs in planta and in vitro but only under still culture conditions in a defined medium. Here, we show that the sylC, sylD, and sylE genes of P. syringae pv. syringae B301D-R form an operon transcribed by promoter sequences located between the sylCDE operon and the sylB gene residing on opposite strands. Assays of overlapping sylB and sylCDE promoter deletions translationally fused to the lacZ gene defined promoter sequences required for gene activity both in vitro and in planta. Activation of both promoters depended on the sylA gene encoding a helix-turn-helix (HTH) LuxR-type transcription factor which was shown to directly bind to the promoters. Activity of the sylA gene, in turn, required a functional salA gene, which also encodes an HTH LuxR-type transcription factor. Furthermore, evidence is presented that acyl-homoserine lactone-mediated quorum-sensing regulation is not involved in syringolin A biosynthesis but that oxygen concentration appears to play a role.

PMID: 22852810 [PubMed - in process]

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The treatment of West syndrome: a Cochrane review of the literature to December 2000.

The treatment of West syndrome: a Cochrane review of the literature to December 2000.

Brain Dev. 2001 Nov;23(7):624-34

Authors: Hancock E, Osborne JP, Milner P

PMID: 11701267 [PubMed - indexed for MEDLINE]

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