bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports
Authors: Moore R Andrew , Derry Sheena , Makinson Geoffrey T , McQuay Henry J 
Published: March 2005

AbstractThe objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted from company clinical trial reports of randomised trials of celecoxib in osteoarthritis or rheumatoid arthritis lasting 2 weeks or more. Outcomes were discontinuations (all cause, lack of efficacy, adverse event, gastrointestinal adverse event), endoscopically detected ulcers, gastrointestinal or cardio-renal events, and major changes in haematological parameters. The main comparisons were celecoxib (all doses) versus placebo, paracetamol (acetaminophen) 4,000 mg daily, rofecoxib 25 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs) (naproxen, diclofenac, ibuprofen, and loxoprofen). For NSAIDs, celecoxib was compared both at all doses and at licensed doses (200 to 400 mg daily). Thirty-one trials included 39,605 randomised patients. Most patients had osteoarthritis and were women of average age 60 years or above. Most trials lasted 12 weeks or more. Doses of celecoxib were 50 to 800 mg/day. Compared with placebo, celecoxib had fewer discontinuations for any cause or for lack of efficacy, fewer serious adverse events, and less nausea. It had more patients with dyspepsia, diarrhoea, oedema, more adverse events that were gastrointestinal or treatment related, and more patients experiencing an adverse event. There were no differences for hypertension, gastrointestinal tolerability, or discontinuations for adverse events. Compared with paracetamol, celecoxib had fewer discontinuations for any cause, for lack of efficacy, or diarrhoea, but no other differences. Compared with rofecoxib, celecoxib had fewer patients with abdominal pain and oedema, but no other differences. Compared with NSAIDs, celecoxib had fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuations for adverse events or gastrointestinal adverse events. Fewer patients had any, or a gastrointestinal, or a treatment-related adverse event, or vomiting, abdominal pain, dyspepsia, or reduced haemoglobin or haematocrit. Discontinuations for lack of efficacy were higher. No differences were found for all-cause discontinuations, serious adverse events, hypertension, diarrhoea, nausea, oedema, myocardial infarction, cardiac failure, or raised creatinine. Company clinical trial reports present much more information than published papers. Adverse event information is clearly presented in company clinical trial reports, which are an ideal source of information for systematic review and meta-analysis.
Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells
Authors: van Wetering Sandra , Tjabringa G Sandra , Hiemstra Pieter S 
Published: March 2005

AbstractMost antimicrobial peptides have been discovered based on activity-guided purification procedures, which used assays to determine their antimicrobial activity. Nevertheless, recent studies have shown that antimicrobial peptides also exert a range of other functions. Based on these observations, antimicrobial peptides are now not only implicated in host defense against infection but also in other immune reactions, inflammation, and wound-repair processes. The activities of neutrophil defensins and the cathelicidin hCAP-18/LL-37, antimicrobial peptides that are abundantly expressed in the human neutrophil, are the subject of an increasing number of studies. Exposure to neutrophil defensins and hCAP-18/LL-37 results in increases in mediator expression and release, chemotaxis, and proliferation of inflammatory and epithelial cells and fibroblasts, and the mechanisms underlying these effects have been partly elucidated. This review is focused on the effects of neutrophil defensins and hCAP-18/LL-37 on airway epithelial cells.
Estrogen and Estrogen Receptor-β (ERβ)-Selective Ligands Induce Galanin Expression within Gonadotropin Hormone-Releasing Hormone-Immunoreactive Neurons in the Female Rat Brain
Authors: Merchenthaler Istvan , Hoffman Gloria E. , Lane Malcolm V. 
Published: March 2005

AbstractAmong the many factors that integrate the activity of the GnRH neuronal system, estrogens play the most important role. In females, estrogen, in addition to the negative feedback, also exhibits a positive feedback influence upon the activity and output of GnRH neurons to generate the preovulatory LH surge and ovulation. Until recently, the belief has been that the GnRH neurons do not contain estrogen receptors (ERs) and that the action of estrogen upon GnRH neurons is indirect involving several, estrogen-sensitive neurotransmitter and neuromodulator systems that trans-synaptically regulate the activity of the GnRH neurons. Based on our recent findings that GnRH neurons of the female rat coexpress galanin, that galanin is a potent GnRH-releasing peptide, and that ERβ is present in GnRH neurons, we have evaluated the effect of 17β-estradiol and two ERβ-selective agonists (WAY-200070, WAY-166818) on the expression of galanin within GnRH neurons. By combining immunocytochemistry for GnRH and in situ hybridization histochemistry for galanin, we demonstrate that 17β-estradiol (20 μg/kg, sc) stimulates galanin expression within GnRH-immunoreactive neurons in a time-dependent manner. A significant increase was observed 2 h after its administration to ovariectomized rats. However, a more robust expression required 3-d treatment regimen. Treatment with the β-selective ligands resulted in similar observations, although no statistical analysis is available for the 2 hr survival. These observations strongly suggest that estrogen and the ERβ-selective ligands stimulate galanin expression within GnRH neurons via ERβ, although an indirect mechanism via interneurons still cannot be ruled out.
Crystal Engineering with [Mo36O112(H2O)16]8− Anion as Nanosized Building Block
Authors: Eda Kazuo , Iriki Yuichi 
Published: March 2005

Abstract
Successfully we prepared crystalline compounds of [Mo36O112(H2O)16]8− ({Mo36}) anion with various α,ω-alkanediamines (Cn-DA, n = 3–11) aiming at crystal engineering with nanosized building blocks. 2-, 1-, and 0-D frameworks of {Mo36} were obtained depending on length of alkane moiety of Cn-DA. These frameworks were linked by Cn-DA molecules (or protonated cations) using hydrogen bonds. In the crystalline compounds with Cn-DA cations of n = 3–5 some fraction of the cations were captured in the hollows of {Mo36}, indicating the ability of {Mo36} as receptor.
Determination of itraconazole in human plasma by high-performance liquid chromatography with solid-phase extraction
Authors: Ohkubo Tadashi , Osanai Takako 
Published: March 2005

Background: A practical, simple, high-performance liquid chromatographic (HPLC) method is needed for the determination of itraconazole in clinical plasma samples. Methods: Itraconazole and bifonazole (internal standard) were extracted from plasma using a C8-bonded solid-phase cartridge, separated by C8 reversed-phase HPLC, and quantified by ultraviolet absorption at 263 nm. Results: This new method enabled the determination of itraconazole in the concentration range of 10.0-500.0 µg/L. The detection limit of itraconazole was 5.0 µg/L. The mean recovery of itraconazole added to plasma was more than 89.1%, with a coefficient of variation of less than 6.9%. We applied this method for the determination of plasma itraconazole in volunteers treated daily with a 200 mg oral capsule of itraconazole for four days. We monitored the plasma level of itraconazole for the following 24 h and obtained the mean area under the plasma concentration-time curve from 0 to 24 h (AUC0-24 ) value of 4358.9 ± 1933.4 µg h/L. Conclusion: Our new method will be clinically useful for accurately monitoring the plasma concentration of itraconazole in patients under treatment.
Correction and reporting of potassium results in haemolysed samples
Authors: Dimeski Goce , Clague Alan E , Hickman Peter E 
Published: March 2005

Background: Potassium is usually the most important analyte affected by in vitro haemolysis and the result obtained may falsely indicate or disguise a life-threatening abnormality and so give rise to inappropriate treatment. The purpose of the study was to provide a solution to the problem of reporting potassium on haemolysed samples, taking into account both clinical needs and analytical concerns (inter-individual and inter-sample variability). Methods: Using a new procedure that mimics the collection process in an actual clinical setting, haemolysed samples were prepared from 41 volunteers with a range of inter-individual factors - haemoglobin 80-173 g/L, red blood cells 2.42-6.77 x 1012/L, leucocytes 3.0-306 x 109 /L and platelets 31-710 x 109/L - in order to develop a more accurate correction equation using a haemolytic index (HI) corresponding to g Hb/L in plasma. Results: The mean (range) potassium increase was 0.0036 mmol/L (0.0029-0.0053 mmol/L) per unit HI. The following equation was developed to estimate potassium increase per HI, in order to compensate approximately for potassium leakage in haemolysed samples: Corrected K+=Measured K+ -(HI x 0.004). Conclusion: The balanced solution is this: instead of reporting the post-haemolysis corrected potassium result a qualitative comment is given, indicating the likely range of the potassium concentration. If the potassium result is in a critically low or high range, it is communicated promptly to the requesting clinician.
Triplate fixation
Authors: Cobb J. P. , Ashwood N. , Robbins G. , Witt J. D. , Unwin P. S. , Blunn G. 
Published: March 2005

Massive endoprostheses using a cemented intramedullary stem are widely used to allow early resumption of activity after surgery for tumours. The survival of the prosthesis varies with the anatomical site, the type of prosthesis and the mode of fixation. Revision surgery is required in many cases because of aseptic loosening. Insertion of a second cemented endoprosthesis may be difficult because of the poor quality of the remaining bone, and loosening recurs quickly. We describe a series of 14 patients with triplate fixation in difficult revision or joint-sparing tumour surgery with a minimum follow-up of four years. The triplate design incorporated well within a remodelled cortex to achieve osseomechanical integration with all patients regaining their original level of function within five months. Our preliminary results suggest that this technique may provide an easy, biomechanically friendly alternative to insertion of a further device with an intramedullary stem, which has a shorter lifespan in revision or joint-sparing tumour surgery. A short segment of bone remaining after resection of a tumour will not accept an intramedullary stem, but may be soundly fixed using this method.
Ulnar focal cortical indentation
Authors: Kazuki K. , Hiroshima K. , Kawahara K. 
Published: March 2005

Deformity of the forearm due to growth disturbance of the ulna occurs in a number of conditions such as ulnar deficiency, multiple exostoses, and neurofibromatosis. We report a previously unrecognised form, caused by focal cortical indentation. We have treated five children with this condition, three girls and two boys; the mean age at presentation was 5 years (2 to 8). The deformity was first recognised about the age of two years, and progressed gradually. The radiological findings were the same in all cases. The focal cortical indentation was seen at the distal end of the ulna with anteromedial bowing and dysplasia. The radial head was dislocated posterolaterally. In one patient the histological findings at the site of indentation were of a fold of tissue resembling periosteum, which interfered with enchondral ossification. Treatment by ulnar lengthening using an external fixator and osteotomy which corrected both the ulnar deformity and reduced the dislocated radial head in two cases gave the best results.
Crystal arthropathy of the lumbar spine
Authors: Mahmud T. , Basu D. , Dyson P. H. P. 
Published: March 2005

There have been very few reports in the literature of gout and pseudogout of the spine. We describe six patients who presented with acute sciatica attributable to spinal stenosis with cyst formation in the facet joints. Cytopathological studies confirmed the diagnosis of crystal arthropathy in each case. Specific formation of a synovial cyst was identified pre-operatively by MRI in five patients. In the sixth, the diagnosis was made incidentally during decompressive surgery. Surgical decompression alone was undertaken in four patients. In one with an associated degenerative spondylolisthesis, an additional intertransverse fusion was performed. Another patient had previously undergone a spinal fusion adjacent to the involved spinal segment, and spinal stabilisation was undertaken as well as a decompression. In addition to standard histological examination material was sent for examination under polarised light which revealed deposition of urate or calcium pyrophosphate dihydrate crystals in all cases. It is not possible to diagnose gout and pseudogout of the spine by standard examination of a fixed specimen. However, examining dry specimens under polarised light suggests that crystal arthropathy is a significant aetiological factor in the development of symptomatic spinal stenosis associated with cyst formation in a facet joint.
VEGF-Targeted Therapy in Metastatic Renal Cell Carcinoma
Authors: Rini Brian I. 
Published: March 2005

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Describe the biology underlying clear cell RCC, including inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene and the pathway leading to VEGF overexpression.Describe the mechanisms by which agents currently undergoing clinical testing in metastatic RCC inhibit VEGF.Describe the preliminary clinical results seen with VEGF inhibition in metastatic RCC.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.comPurpose. To review the biology of renal cell carcinoma (RCC) and the clinical results of vascular endothelial growth factor (VEGF) blockade in metastatic RCC.Methods. A review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation, and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken.Results. VHL tumor suppressor gene inactivation is observed in the majority of clear cell RCC cases, leading to VEGF overexpression. Therapy with agents directed against the VEGF protein or the VEGF receptor have demonstrated initial clinical activity in metastatic RCC.Conclusions. Therapeutic targeting of VEGF in RCC has strong biologic rationale. Substantial clinical activity has been reported in initial clinical trials with VEGF-targeting agents. Further investigation is needed to optimally use these agents for maximal clinical benefit.
Never Too Old? Age Should Not Be a Barrier to Enrollment in Cancer Clinical Trials
Authors: Aapro Matti S. , Köhne Claus-Henning , Cohen Harvey Jay , Extermann Martine 
Published: March 2005

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the implications of age bias in clinical trials.Describe the effects of applying clinical trial advances to the elderly as predicted by the available information.Explain the need for designing and implementing clinical trials that include the elderly.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Throughout Europe and the U.S., over 60% of the total incidence of cancer occurs in the elderly (≥65 years) population, a patient group that requires particular consideration when making treatment decisions due to a number of factors. Despite this, elderly patients are generally under-represented in clinical trials such that study data should be interpreted with caution because results in younger cancer patients may not always extrapolate to the typical elderly cancer patient.
Reports suggest that elderly cancer patients represent around 22% of patients enrolled in phase II clinical studies. Barriers to the accrual of elderly patients to clinical trials include lack of appropriate trials, high burden of comorbidity, study-imposed restrictions, and attitudes of physicians. There is a belief that elderly patients may be unable to tolerate various cancer therapies, which may result in this patient population being excluded from prospective trials. However, clinical data demonstrate that age alone is not a sufficient reason to withhold treatment.
Lack of clinical trial data and the associated lack of evidence-based guidelines for elderly patients mean physicians have little to guide them, with the result that patients may not receive the optimal therapy. As clinical trials are the primary method of evaluating the efficacy and safety of adjuvant and palliative cancer therapies, trials that specifically target the elderly cancer patient are required to adequately assess the risks and benefits of treatment in this vulnerable population. This review aims to assess the clinical reality and clinical trial age mismatch to evaluate implications for elderly cancer patients and to identify how this situation may be addressed. Possible reasons for the disparity, and the resulting clinical consequences, are also considered.
Pegylated Liposomal Doxorubicin: Optimizing the Dosing Schedule in Ovarian Cancer
Authors: Rose Peter G. 
Published: March 2005

Abstract
The need for effective, well-tolerated, and convenient therapies for patients with advanced ovarian cancer has led researchers to continually refine chemotherapeutic regimens to balance efficacy with safety and tolerability in order to maintain or improve patient quality of life. In this article, we review current strategies for the optimal dosing of pegylated liposomal doxorubicin (DOXIL®; Tibotec Therapeutics, a division of Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.tibotec.com; Caelyx®, Schering-Plough Corporation, Kenilworth, NJ, http://www.sch-plough.com) in relapsed ovarian cancer. Pegylated liposomal doxorubicin has demonstrated efficacy in the treatment of recurrent/resistant ovarian cancer in several clinical trials utilizing a dose of 50 mg/m2 every 4 weeks. The most common adverse events associated with pegylated liposomal doxorubicin treatment in these studies—hand-foot syndrome (HFS, also known as palmar-plantar erythrodysesthesia) and stomatitis—are schedule and dose dependent, respectively, and do not typically lead to discontinuation of therapy. Several phase II and retrospective studies support the use of pegylated liposomal doxorubicin 40 mg/m2 every 4 weeks (dose intensity of 10 mg/m2 weekly) to optimize clinical efficacy and minimize the occurrence of schedule- and dose-related adverse events in patients with recurrent/relapsed ovarian cancer. Further reductions in dose intensity are necessary for use in combined chemotherapy regimens. Antitumor activity was maintained, with reduced incidences of HFS and stomatitis. Given the chronic course of ovarian cancer, the improved tolerability profile of pegylated liposomal doxorubicin 40 mg/m2 combined with a convenient once-monthly dosing schedule may translate into an improved quality of life for patients with ovarian cancer.
Increased Hemoglobin Levels and Improved Quality-of-Life Assessments During Epoetin Alfa Treatment in Anemic Cancer Patients: Results of a Prospective, Multicenter German Trial
Authors: Reinhardt Uwe , Tulusan Augustinos , Angermund Ralf , Lutz Harald 
Published: March 2005

Abstract
This prospective, open-label, multicenter study was undertaken to determine the safety and efficacy of epoetin alfa in increasing hemoglobin levels and improving quality of life (QOL), specifically fatigue, in cancer patients receiving chemotherapy with or without radiotherapy (n = 702). Epoetin alfa, 10,000 IU three times a week s.c. for 8–18 weeks, increased the mean hemoglobin level relative to baseline (1.0 ± 1.5 g/dl by week 4 and ≥1.7 g/dl from week 10 through the end of the trial), with 63.4% of patients experiencing ≥2 g/dl increases in hemoglobin above baseline at some time during the study. Fatigue is an important component of QOL. Physicians, nurses, and patients independently assessed patient fatigue level on a linear-analogue scale. Although all three groups reported improvements in patient fatigue over the course of the study (p &lt; .0001), the magnitude of fatigue ratings and their relationship to tumor response and to hemoglobin level varied by group. Overall, epoetin alfa was well tolerated and effective in improving hemoglobin levels and decreasing fatigue in patients undergoing chemotherapy.
A girl with inverted triplication of chromosome 3q25.3 → q29 and multiple congenital anomalies consistent with 3q duplication syndrome
Authors: Õunap Katrin , Ilus Tiiu , Bartsch Oliver 
Published: March 2005

AbstractWe report a newborn girl with intrachromosomal triplication of 3q25.3 → q29 (mosaicism) who died at the age of 3.5 weeks due to her malformations. She demonstrated disproportionate short stature with short limbs, a prominent and hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, and low set malformed and posteriorly rotated ears, short and webbed neck, hydrocephalus, Dandy–Walker malformation, spina bifida, complex heart defect (ventricular and atrial septal defect, malrotation, and interrupted aortic arch), omphalocele, polycystic kidneys, postaxial polydactyly of left hand, and generalized hirsutism; all signs have been associated with the dup(3q) syndrome previously. The facial appearance (hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, low set malformed and posteriorly rotated ears) showed resemblance to the Brachmann–de Lange syndrome (BDLS), but the patient did not fulfill the diagnostic criteria for BDLS. There has been only one report of a direct triplication of chromosome 3 until now, but in our case the triplicated area is larger, located more proximally, and includes the hypothetical BDLS critical gene region‐CDL1. Our findings lend support to distal chromosome 3q, or chromosome 3q26.3, comprises the critical area for the dup(3q) phenotype resembling the BDLS. © 2005 Wiley‐Liss, Inc.
Malpuech syndrome: Three patients and a review
Authors: Kerstjens‐Frederikse W.S. , Brunner H.G. , van Dael C.M.L. , van Essen A.J. 
Published: March 2005

AbstractWe describe three patients with Malpuech syndrome from two families. Previously, 10 patients from 6 families have been reported. Consanguinity in two families suggests autosomal recessive inheritance. Growth retardation, mental retardation, cleft lip, and/or palate, hypertelorism, urogenital abnormalities, and caudal appendage are the key features. Although the spectrum of the features in the reported patients is variable, we do think this syndrome represents a distinct entity. Chromosomal anomalies should be carefully searched for. We discuss differential diagnosis and possible candidate genes and propose diagnostic criteria for Malpuech syndrome. © 2005 Wiley‐Liss, Inc.