bluuebunny/crossref_metadata_2025_split huggingface dataset:
Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease
Authors: Maeda Yoshinobu , Levy Robert B. , Reddy Pavan , Liu Chen , Clouthier Shawn G. , Teshima Takanori , Ferrara James L. M. 
Published: October 2004

AbstractFas ligand (FasL) and perforin pathways not only are the major mechanisms of T cell–mediated cytotoxicity but also are involved in homeostatic regulation of these T cells. In the present study, we tested whether CD8+ donor T cells that are deficient in both perforin and FasL (cytotoxic double deficient [cdd]) could induce graft-versus-host disease (GVHD) in a major histocompatibility complex class I–mismatched lethally irradiated murine model. Interestingly, recipients of cdd CD8+ T cells demonstrated significantly greater serum levels of interferon gamma and tumor necrosis factor alpha and histopathologic damage from GVHD than wild-type (wt) T cells on day 30 after allogeneic bone marrow transplantation (P &lt; .05). Wt and either perforin-deficient or FasL-deficient CD8+ T cells expanded early after transplantation followed by a contraction phase in which the majority of expanded CD8+ T cells were eliminated. In contrast, cdd CD8+ T cells exhibited prolonged expansion and reduced apoptosis to alloantigen stimulation in vivo and in vitro. Together these results suggest that donor cdd CD8+ T cells expand continuously and cause lethal GVHD, and that both perforin and FasL are required for the contraction of allo-reactive CD8+ T cells.
Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis
Authors: Lisman Ton , de Groot Philip G. , Meijers Joost C.M. , Rosendaal Frits R. 
Published: October 2004

AbstractThe role of the fibrinolytic system in the development of deep vein thrombosis (DVT) is unclear. We determined the plasma fibrinolytic potential of patients enrolled in the Leiden Thrombophilia Study (LETS), a population-based case-control study on risk factors for DVT. Plasma fibrinolytic potential was determined in 421 patients and 469 control subjects by means of a tissue factor–induced and tissue-type plasminogen activator (tPA)–induced clot lysis assay. Using clot lysis times above the 70th, 80th, 90th, 95th, and 99th percentiles of the values found in control subjects as cut-off levels, we found a dose-dependent increase in risk for DVT in patients with hypofibrinolysis (odds ratios of 1.4, 1.6, 1.9, 2.1, and 2.2, respectively). This indicates a 2-fold increased risk of DVT in subjects with clot lysis times above the 90th percentile. The risk increase was not affected by age or sex (adjusted odds ratio for 90th percentile, 2.0), and after correction for all possible confounders (age, sex, and levels of procoagulant proteins shown to associate with clot lysis times in the control population), the risk estimate was marginally reduced (odds ratio, 1.6 for 90th percentile). Taken together, these results indicate that plasma hypofibrinolysis constitutes a risk factor for venous thrombosis, with a doubling of the risk at clot lysis times that are present in 10% of the population.
HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia
Authors: Nückel Holger , Rebmann Vera , Dürig Jan , Dührsen Ulrich , Grosse-Wilde Hans 
Published: October 2004

AbstractThe human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution and exerts multiple immunoregulatory functions. Recent studies indicate an ectopic up-regulation in tumor cells that may favor their escape from antitumor immune responses. The role of HLA-G in B-cell chronic lymphocytic leukemia (B-CLL) has not been defined. HLA-G expression was studied retrospectively in circulating B-CLL cells from 47 patients by flow cytometry using the anti-HLA-E specific monoclonal antibody MEM/G9. The proportion of leukemic cells expressing HLA-G varied from 1% to 54%. Patients with 23% or fewer HLA-G-positive cells (according to receiver operating characteristics [ROC] analysis; designated as HLA-G-negative group) had a significantly longer progression-free survival (PFS) time than patients with more than 23% positive cells (median PFS: 120 versus 23 months; P = .0001). In multivariate analysis, HLA-G expression (hazard ratio: 4.8; P = .002) was an even better independent prognostic factor than the zeta-associated protein 70 (ZAP-70) or CD38 status. Humoral and cellular immunosuppression were significantly more prominent in the HLA-G-positive compared with the HLA-G-negative patient group. In B-CLL, the level of HLA-G expression is correlated with the degree of immunosuppression and prognosis. HLA-G may contribute to the impairment of immune responses against tumor cells and infections. Thus, these findings need to be confirmed in a prospective study. (Blood. 2005;105:1694-1698)
Polyadenylation of ribosomal RNA by Candida albicans also involves the small subunit
Authors: Fleischmann Jacob , Liu Hong , Wu Chieh-Pin 
Published: October 2004

Abstract
Background
Candida albicans is a polymorphic fungus causing serious infections in immunocompromised patients. It is capable of shifting from yeast to germinating forms such as hypha and pseudohypha in response to a variety of signals, including mammalian serum. We have previously shown that some of the large 25S components of ribosomal RNA in Candida albicans get polyadenylated, and this process is transiently intensified shortly after serum exposure just prior to the appearance of germination changes.

Results
We now present data that this process also involves the small 18S subunit of ribosomal RNA in this organism. Unlike the large 25S subunit, polyadenylation sites near the 3' end are more variable and no polyadenylation was found at the reported maturation site of 18S. Similar to 25S, one or more polyadenylated mature sized 18S molecules get intensified transiently by serum just prior to the appearance of hypha.

Conclusions
The transient increase in polyadenylation of both the large and the small subunits of ribosomal RNA just prior to the appearance of hypha, raises the possibility of a role in this process.
Participant characteristics associated with withdrawal from a large randomized trial of spermicide effectiveness
Authors: Raymond Elizabeth G , Chen Pai Lien , Pierre-Louis Bosny , Luoto Joanne , Barnhart Kurt T , Bradley Lynn , Creinin Mitchell D , Poindexter Alfred , Wan Livia , Martens Mark , Schenken Robert , Nicholas Cate F , Blackwell Richard 
Published: October 2004

Abstract
Background
In most recent large efficacy trials of barrier contraceptive methods, a high proportion of participants withdrew before the intended end of follow-up. The objective of this analysis was to explore characteristics of participants who failed to complete seven months of planned participation in a trial of spermicide efficacy.

Methods
Trial participants were expected to use the assigned spermicide for contraception for 7 months or until pregnancy occurred. In bivariable and multivariable analyses, we assessed the associations between failure to complete the trial and 17 pre-specified baseline characteristics. In addition, among women who participated for at least 6 weeks, we evaluated the relationships between failure to complete, various features of their first 6 weeks of experience with the spermicide, and characteristics of the study centers and population.

Results
Of the 1514 participants in this analysis, 635 (42%) failed to complete the study for reasons other than pregnancy. Women were significantly less likely to complete if they were younger or unmarried, had intercourse at least 8 times per month, or were enrolled at a university center or at a center that enrolled fewer than 4 participants per month. Noncompliance with study procedures in the first 6 weeks was also associated with subsequent early withdrawal, but dissatisfaction with the spermicide was not. However, many participants without these risk factors withdrew early.

Conclusions
Failure to complete is a major problem in barrier method trials that seriously compromises the interpretation of results. Targeting retention efforts at women at high risk for early withdrawal is not likely to address the problem sufficiently.
Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases – an evidence-based practice guideline
Authors: Wu Jackson Sai-Yiu , Wong Rebecca KS , Lloyd Nancy S , Johnston Mary , Bezjak Andrea , Whelan Timothy ,   the Supportive Care Guidelines Group of Cancer Care Ontario
Published: October 2004

Abstract
Background
This practice guideline was developed to provide recommendations to clinicians in Ontario on the preferred standard radiotherapy fractionation schedule for the treatment of painful bone metastases.

Methods
A systematic review and meta-analysis was performed and published elsewhere. The Supportive Care Guidelines Group, a multidisciplinary guideline development panel, formulated clinical recommendations based on their interpretation of the evidence. In addition to evidence from clinical trials, the panel also considered patient convenience and ease of administration of palliative radiotherapy. External review of the draft report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from the Practice Guidelines Coordinating Committee.

Results
Meta-analysis did not detect a significant difference in complete or overall pain relief between single treatment and multifraction palliative radiotherapy for bone metastases. Fifty-nine Ontario practitioners responded to the mailed survey (return rate 62%). Forty-two percent also returned written comments. Eighty-three percent of respondents agreed with the interpretation of the evidence and 75% agreed that the report should be approved as a practice guideline. Minor revisions were made based on feedback from the external reviewers and the Practice Guidelines Coordinating Committee. The Practice Guidelines Coordinating Committee approved the final practice guideline report.

Conclusion
For adult patients with single or multiple radiographically confirmed bone metastases of any histology corresponding to painful areas in previously non-irradiated areas without pathologic fractures or spinal cord/cauda equine compression, we conclude that:
• Where the treatment objective is pain relief, a single 8 Gy treatment, prescribed to the appropriate target volume, is recommended as the standard dose-fractionation schedule for the treatment of symptomatic and uncomplicated bone metastases.
Several factors frequently considered in clinical practice when applying this evidence such as the effect of primary histology, anatomical site of treatment, risk of pathological fracture, soft tissue disease and cord compression, use of antiemetics, and the role of retreatment are discussed as qualifying statements.
Our systematic review and meta-analysis provided high quality evidence for the key recommendation in this clinical practice guideline. Qualifying statements addressing factors that should be considered when applying this recommendation in clinical practice facilitate its clinical application. The rigorous development and approval process result in a final document that is strongly endorsed by practitioners as a practice guideline.
Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: Preliminary indications from a secondary analysis of the COMACS study data
Authors: Sonuga-Barke Edmund JS , Swanson James M , Coghill David , DeCory Heleen H , Hatch Simon J 
Published: October 2004

Abstract
Background
Methylphenidate (MPH) is commonly prescribed in the treatment of Attention-Deficit/Hyperactivity Disorder or ADHD. Concerta and Metadate CD are once-daily formulations of MPH using different delivery mechanisms resulting in different pharmacokinetic profiles. A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides greater control in the early evening (12 hours post-dose). Non-inferential comparison of effects for different dose levels of the two formulations suggested that equivalent levels of morning symptom control could be obtained with lower daily doses of Metadate CD than Concerta; the situation being reversed in the evening. The current paper presents a secondary analysis that provides a statistical test of these observations.

Method
The COMACS study was a multi-center, double-blind crossover study of Metadate CD, Concerta and placebo with each treatment administered for 1 week. Children were assigned on the basis of their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18 mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7 sessions across the day. For the post-hoc comparisons across dose levels presented here, total SKAMP scores with the active treatments (adjusted for placebo response) were analyzed using an analysis of covariance, with a combined measure modeling placebo response across all time period as the covariate.

Results
Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36 and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5 and 12 hours with Metadate CD giving better control from1.5 through 6.0 hours post-dose.

Conclusions
Different delivery profiles of Metadate CD and Concerta can be exploited to limit total daily exposure to MPH while at the same targeting a specific, especially clinically significant, period of the day. These results need to be confirmed in a study in which children are randomly allocated to different dose levels of the two formulations and plasma MPH concentrations are assessed simultaneously.
Taste and Smell Disturbance with the α-Adrenoceptor Agonist Midodrine
Authors: Young Tim M , Mathias Christopher J 
Published: October 2004

OBJECTIVE To report a case of a disturbance of taste and smell associated with the α-adrenoceptor agonist midodrine. CASE SUMMARY A 64-year-old white man with autonomic failure was started on midodrine 5 mg/day as treatment for orthostatic hypotension. After 3 months, the dose was increased to 12.5 mg/day, whereupon he noted a new onset of taste and smell disturbance. These symptoms made eating so unpleasant that the man greatly reduced his food intake, leading to significant weight loss. In addition, he experienced well-recognized adverse effects of midodrine, such as scalp pruritus, after the dose increase. All symptoms resolved with a dose reduction of midodrine (to 5 mg/day), and the patient increased his food intake, resulting in a return to his initial body weight. DISCUSSION Midodrine is commonly associated with dose-dependent adverse effects, such as scalp pruritus and cutis anserina. Disorders of taste and smell have not been previously reported with midodrine, although it has been suggested that other sympathomimetic drugs may have effects on the olfactory threshold. Severe disorders of taste and smell may impact not only on a patient's quality of life, but also on their physical well-being, with significant weight loss being reported in this case. According to the Naranjo probability scale, this patient's taste and smell disturbance was probably associated with midodrine. CONCLUSIONS The use of midodrine may be associated with taste and smell disturbance. This case suggests that such an association is likely to be dose dependent.
Probable Vancomycin-Induced Neutropenia
Authors: Segarra-Newnham Marisel , Tagoff Shari S 
Published: October 2004

OBJECTIVE To report a case of vancomycin-induced neutropenia and provide a review of the literature. CASE SUMMARY A 64-year-old white man was treated with intravenous vancomycin 1.5 g/day for finger osteomyelitis. He developed neutropenia after 21 days of vancomycin therapy. The absolute neutrophil count reached a nadir of 418 cells/mm3 during vancomycin use and returned to normal 7 days after its discontinuation. The eosinophil count was also elevated during the neutropenic episode and probably related to vancomycin. Based on the Naranjo probability scale, the reaction was probably related to vancomycin use. DISCUSSION Articles describing cases of vancomycin-induced neutropenia were identified. All patients developed neutropenia as a result of vancomycin therapy 12 days. Neutrophil counts generally increased following discontinuation of vancomycin. One article reported successful resolution of neutropenia and infection by switching the patient's therapy to the structurally related antibiotic agent teicoplanin. Other patients were continued on vancomycin therapy, and neutropenia was treated with moderate to good success with filgrastim. Rechallenge was not generally attempted. The mechanism of neutropenia caused by vancomycin is unclear, but appears to be immune-mediated. CONCLUSIONS Vancomycin therapy should not be prolonged unless absolutely necessary, and therapy should be reserved for patients with clear indications for the drug, such as infections due to gram-positive organisms resistant to other therapies. Patients should have periodic assessment of white blood cell and neutrophil counts with consideration to discontinue vancomycin if neutropenia develops.
Probable Codeine Phosphate–Induced Seizures
Authors: Kuo Shih-Chen , Lin Ya-Chu , Kao Shu-Min , Yang Yea-Huei Kao 
Published: October 2004

OBJECTIVE To report a case of seizure activity associated with oral codeine phosphate administered for analgesia in an elderly woman with end-stage renal disease. CASE SUMMARY A 73-year-old Taiwanese woman with end-stage renal disease received oral codeine phosphate 30 mg 4 times daily for her back and rib pain without adjustment of her dosage regimen. Seven days after starting codeine therapy, the woman became stuporous and developed tonic–clonic seizures. After phenytoin initiation, codeine discontinuation, and naloxone administration, the seizures did not recur. DISCUSSION Codeine is a frequently used opioid analgesic, especially when pain control with acetaminophen or nonsteroidal antiinflammatory drugs fails. Although seizures associated with codeine have been reported, pertinent data are very limited and the exact mechanism is unknown. An objective causality assessment indicated the seizure to be a probable drug-related event in this patient. CONCLUSIONS Elderly patients with end-stage renal disease may be predisposed to seizures with higher doses of codeine phosphate. It is imperative to adjust the codeine dosage regimen based on patients’ renal function to avoid the potential toxicity with overdose.
Evaluation of the Iron Status of the Newborn by Soluble Transferrin Receptors in Serum
Authors: Kuiper-Kramer Ellen P. A. , Baerts Wim , Bakker Reinout , van Eyck Jim , van Raan Jan , van Eijk Henk G. 
Published: October 2004

AbstractThe concentration of soluble transferrin receptors in serum has proven to be a reliable predictor of iron status in adults. Its high sensitivity for iron deficiency combined with a small sample size (10 μl) makes it an interesting parameter for the assessment of iron stores in newborn infants.In the present study we investigated the usefulness of the concentration of soluble transferrin receptors in serum in the assessment of iron metabolism in the newborn. Infants born after an uncomplicated labour were compared to infants in the intensive care unit. The concentration of soluble transferrin receptors in serum was found to be elevated compared to normal adults and independently of iron metabolism. The concentration of soluble transferrin receptors did not correlate with serum iron and ferritin concentrations. In contrast to what was found in other studies, no relationship could be demonstrated between soluble transferrin receptors and birth weight or gestational age. The results of this study have shown that care has to be taken in the interpretation of the concentration of soluble transferrin receptors in serum in newborn infants. It seems to be a parameter which is independent of iron metabolism at least during the first days of life.
Quantitation of IgG and IgM Human Anti-Mouse Antibodies (HAMA) Interference in CA 125 Measurements Using Affinity Chromatography
Authors: Koper Norbert P. , Thomas Chris M. G. , Massuger Leon F. A. G. , Segers Martin F. G. , Olthaar André J. , Verbeek André L. M. 
Published: October 2004

Abstract
Currently no available immunoassay system offers complete protection against spuriously elevated or lowered results due to interference by Human Anti-Mouse Antibodies (HAMA). Although routine use of chromatography procedures is not an acceptable option because of the extra cost and workload involved, such a procedure would be highly desirable to ensure accurate immunoassay results. The present report describes a relatively simple affinity chromatography procedure using a HiTrap Protein G column to isolate immunoglobulin G (IgG) HAMA, followed by a HiTrap N-hydroxy-succinimide(NHS)-activated column coupled to goat-anti human immunoglobulin M (IgM) to bind IgM HAMA. To examine the usefulness of this purification procedure we determined CA 125 in forty serum samples prior to and following chromatography. Pre- and post-injection samples were obtained from 20 patients injected with 1 mg of 111In-Iabelled murine OC 125 F(ab′)2 fragments in an immunoscintigraphy study.
It is shown that this analytical procedure provides a technique to determine the extent and the nature of the existing HAMA interference in samples of patients after in vivo use of monoclonal antibodies for diagnostic or therapeutic purposes. The procedure can also contribute to the clarification of clinically discordant CA 125 results. Finally, the availability of such a procedure in the clinical laboratory provides an opportunity to test the robustness of newly developed immunoassay systems towards HAMA interference.
Objectives, Design and Recruitment of a Familial and Longitudinal Cohort for Studying Gene-Environment Interactions in the Field of Cardiovascular Risk: The Stanislas Cohort
Authors: Siest Gérard , Visvikis Sophie , Herbeth Bernard , Gueguen René , Vincent-Viry Monique , Sass Catherine , Beaud Brigitte , Lecomte Edith , Steinmetz Josiane , Locuty Jean , Chevrier Philippe 
Published: October 2004

Abstract
The main objective of the Stanislas cohort is to study the role and the contribution of genetic and environmental factors to cardiovascular status. We plan:

a)
to describe the degree of association of a large number of cardiovascular risk indicators with cardiovascular endpoints,

b)
to evaluate the contribution of genetic and that of environmental factors to this association,

c)
to follow the evolution of these risk indicators during a period of at least ten years,

d)
to search for the determinants influencing this evolution.

The principal variables studied are:

a)
to describe the degree of association of a large number of cardiovascular risk indicators with cardiovascular endpoints,

b)
to evaluate the contribution of genetic and that of environmental factors to this association,

c)
to follow the evolution of these risk indicators during a period of at least ten years,

d)
to search for the determinants influencing this evolution.

a)
blood pressure, cardiac mass, and wall thickness of carotid and femoral arteries,

b)
obesity and fat mass,

c)
indicators of lipid metabolism,

d)
genetic polymorphisms of several cardiovascular risk candidate genes,

e)
food, tobacco and alcohol consumption,

f)
consumption of drugs and anti-oxidant vitamins.

Between September 1993 and August 1995, 1006 families consisting of the two biological parents with at least two children were recruited totalling 4295 individuals. This cohort will be followed up until 2004. There will be two health examinations five and ten years after the initial examination. A bank of blood samples (serum and plasma) in liquid nitrogen and DNA (−80 °C) has been established.