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Biomedical subjects

C Peterson

Publications and source records attributed to C Peterson.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.

BACKGROUND: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. AIM: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. PATIENTS: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. METHODS: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. RESULTS: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11,450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). CONCLUSIONS: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

Adolescent↗
PubMed2006

No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease.

The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naïve patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3; 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol; 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35).

Alleles↗
PubMed2006

Impaired transport as a mechanism of resistance to thiopurines in human T-lymphoblastic leukemia cells.

In order to better understand the mechanisms of resistance to thiopurines, we studied two sublines of the MOLT4 T-lymphoblastic leukemia cell line, resistant to 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We found that the underlying mechanism of resistance in both resistant cell lines was a markedly reduction in initial transport of 6-MP (3- and 5-fold, respectively, in 6-MP- and 6-TG-resistant cells). No significant alteration of activities of hypoxanthine-guanine phosphoribosyl transferase, thiopurine methyltransferase or inosine monophosphate dehydrogenase, the key enzymes involved in the metabolism of thiopurines was detected. We conclude that defected initial transport of thiopurines by cells may very well explain their resistance to these drugs.

Antimetabolites, Antineoplastic↗
PubMed2006

Phosphorus appetite in sheep: dissociating taste from postingestive effects.

We hypothesized that lambs discriminate the postingestive effects of P and associate those effects with feed flavor to modify feed choices. Three predictions were tested based on this hypothesis: 1) lambs will modify preference for arbitrary flavors eaten during intraruminal infusions of NaH2PO4, 2) changes in preferences are more specific than changes in osmotic load induced by salts of Na; and 3) preference for P is inversely related to the concentration of inorganic P in blood. Thirty lambs were depleted of P by the offer of a P-deficient diet, allocated to 3 groups (10 lambs/group), and conditioned during 3 periods as follows: During conditioning period 1, lambs in each of 3 groups ate a poorly nutritious feed (grape pomace), flavored differently for each group, while water was infused into the rumen. During conditioning periods 2 and 3, lambs again ate grape pomace, with 2 new flavors now paired with infusion of an aqueous solution (126 mmol) of NaCl (conditioning period 2) or NaH2PO4 (conditioning period 3), rather than with water. After conditioning, all lambs were offered a choice of the 3 flavors during preference tests immediately after conditioning (period 1) and every 3 wk thereafter (periods 2, 3, and 4). During period 1, when serum inorganic P levels were greatest, lambs preferred flavors paired with water > NaCl > NaH2PO4 (P < 0.05). During periods 2 and 3, as inorganic P concentrations decreased in serum, lambs preferred flavors paired with NaH2PO4 > NaCl (period 2, P = 0.10; period 3, P = 0.05). Lambs preferred flavors paired with water > NaH2PO4 in period 2 (P < 0.001), but those differences disappeared in periods 3 and 4 (P > 0.05). During period 4, lambs preferred flavors paired with NaCl > NaH2PO4 (P < 0.10). The estimate of the slope for the linear relationship between intake of flavors paired with NaH2PO4 and serum inorganic P was negative (P < 0.0001), whereas estimates of the slopes for the relationships between intake of flavors paired with NaCl or water and serum inorganic P were not different from 0. Thus, preference for P was inversely related to the concentration of serum inorganic P. Our results suggest lambs discriminated among the postingestive effects of NaH2PO4, NaCl, and water and associated those effects with specific flavors. Lambs avoided flavors paired with NaH2PO4 during periods of P replenishment, and they increased preference for those flavors during periods of P need.

Animals↗
PubMed2005

Circadian function in patients with advanced non-small-cell lung cancer.

This study aimed to evaluate whether patients with advanced non-small-cell lung cancer experience disrupted rest-activity daily rhythms, poor sleep quality, weakness, and maintain attributes that are linked to circadian function such as fatigue. This report describes the rest-activity patterns of 33 non-small-cell lung cancer patients who participated in a randomised clinical trial evaluating the benefits of melatonin. Data are reported on circadian function, health-related quality of life (QoL), subjective sleep quality, and anxiety/depression levels prior to randomisation and treatment. Actigraphy data, an objective measure of circadian function, demonstrated that patients' rest-activity circadian function differs significantly from control subjects. Our patients reported poor sleep quality and high levels of fatigue. Ferrans and Powers QoL Index instrument found a high level of dissatisfaction with health-related QoL. Data from the European Organization for Research and Treatment for Cancer reported poor capacity to fulfil the activities of daily living. Patients studied in the hospital during or near chemotherapy had significantly more abnormal circadian function than those studied in the ambulatory setting. Our data indicate that measurement of circadian sleep/activity dynamics should be accomplished in the outpatient/home setting for a minimum of 4-7 circadian cycles to assure that they are most representative of the patients' true condition. We conclude that the daily sleep/activity patterns of patients with advanced lung cancer are disturbed. These are accompanied by marked disruption of QoL and function. These data argue for investigating how much of this poor functioning and QoL are actually caused by this circadian disruption, and, whether behavioural, light-based, and or pharmacologic strategies to correct the circadian/sleep activity patterns can improve function and QoL.

Aged↗
PubMed2003

Medical students' perceptions of sexual health issues prior to a curriculum enhancement.

The objectives were to compare first, second and third year medical students on self-perceived sexual health knowledge, comfort in addressing sexual health problems, and attitudes towards the importance of addressing sexual health issues with patients as part of a sexual health medical curriculum enhancement project. A paper-and-pencil questionnaire survey was designed and administered to first and second year medical students at the start of the fall semester, resulting in high participation rates for both years (98% and 86%, respectively). Third year students were surveyed through an on-line version of the questionnaire yielding a lower response rate (52%). Multivariate statistical analyses were used to compare knowledge, comfort and attitudes by year in medical school. Results were as follows: As might be expected, sexual health knowledge and comfort in addressing sexual health problems increased linearly from first to third year (P<0.01) for all questions. Unexpectedly, second year students had significantly higher scores on questions assessing attitudes towards the importance of addressing sexual health issues than either first or third year students (P<0.001). Female medical students reported that addressing sexual health issues with patients was significantly more important than did male medical students; however, male students reported higher levels of self-reported knowledge and comforting related to sexual health issues than did female students in a number of areas. In conclusion, knowledge gained from this survey was used to finalize the design of an enhanced, integrated curriculum on sexual health for medical students. Further investigation of gender differences related to training medical students in this area is suggested.

Attitude of Health Personnel↗
PubMed2002

Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis.

BACKGROUND: Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. OBJECTIVE: To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. METHODS: Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. RESULTS: All 10 patients tolerated the highest accumulated dose, 8.124 microg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. CONCLUSION: The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.

Adult↗
PubMed2001

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.

Journal Article↗
PubMed2001

Topological properties of citation and metabolic networks.

Topological properties of "scale-free" networks are investigated by determining their spectral dimensions d(S), which reflect a diffusion process in the corresponding graphs. Data bases for citation networks and metabolic networks together with simulation results from the growing network model [A.-L. Barabasi and R. Albert, Science 286, 509 (1999)] are probed. For completeness and comparisons lattice, random and small-world models are also investigated. We find that d(S) is around 3 for citation and metabolic networks, which is significantly different from the growing network model, for which d(S) is approximately 7.5. This signals a substantial difference in network topology despite the observed similarities in vertex-order distributions. In addition, the diffusion analysis indicates that the citation networks are treelike in structure, whereas the metabolic networks contain many loops.

Animals↗
PubMed2001

Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns.

To investigate the phenotype associated with estrogen receptor alpha (ER) expression in breast carcinoma, gene expression profiles of 58 node-negative breast carcinomas discordant for ER status were determined using DNA microarray technology. Using artificial neural networks as well as standard hierarchical clustering techniques, the tumors could be classified according to ER status, and a list of genes which discriminate tumors according to ER status was generated. The artificial neural networks could accurately predict ER status even when excluding top discriminator genes, including ER itself. By reference to the serial analysis of gene expression database, we found that only a small proportion of the 100 most important ER discriminator genes were also regulated by estradiol in MCF-7 cells. The results provide evidence that ER+ and ER- tumors display remarkably different gene-expression phenotypes not solely explained by differences in estrogen responsiveness.

Breast Neoplasms↗
PubMed2001

Adsorption and desorption of chemotherapeutic drugs from a magnetically targeted carrier (MTC).

Magnetically targeted carriers (MTCs) are composite microparticles made from metallic iron and activated carbon. Particles, loaded with doxorubicin in the pharmacy (MTC-DOX), are infused intra-arterially through the artery feeding the tumor. With the aid of an externally positioned permanent dipole magnet, they can be localized and retained within a tumor mass. MTC-DOX is currently in use in a Phase I/II clinical study as a delivery vehicle for doxorubicin in primary hepatocellular carcinoma. The adsorption and desorption of doxorubicin, mitomycin C, camptothecin, methotrexate, verapamil and 9AC onto MTCs have been analyzed. Each of these chemotherapeutic agents has a different mechanism of action, suggesting that some benefit may be derived from combined delivery to a tumor using MTCs and magnetic targeting. Each drug displays different behavior with respect to adsorption and desorption. However, this behavior can be described for each drug with a non-linear thermodynamic model. The thermodynamic model predicts a controlled release rate by adjusting a number of parameters, including initial drug loading concentrations. This is confirmed with in vitro extraction experiments using human plasma as the extraction medium.

Adsorption↗
PubMed2001

Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex regolith.

On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft executed a low-altitude flyover of asteroid 433 Eros, making it possible to image the surface at a resolution of about 1 meter per pixel. The images reveal an evolved surface distinguished by an abundance of ejecta blocks, a dearth of small craters, and smooth material infilling some topographic lows. The subdued appearance of craters of different diameters and the variety of blocks and different degrees of their burial suggest that ejecta from several impact events blanketed the region imaged at closest approach and led to the building up of a substantial and complex regolith consisting of fine materials and abundant meter-sized blocks.

Journal Article↗
PubMed2001

Detecting genotype x age interaction.

This paper explores several extensions to the variance component method, which incorporate genotype x age interaction effects. We evaluate the performance of these methods for detecting genotype x age interaction in quantitative genetic analyses of a quantitative trait (Q4), contrasting this with false positive detection rates obtained from a phenotype influenced by the same genes but without genotype x age interaction effects (Q3). We then assess the impact on linkage power and false positive rate of allowing a QTL-specific genotype x age interaction in linkage analysis of these same traits.

Adult↗
PubMed2001

Composition and mass of the bacteriophage phi29 prohead and virion.

The protein composition of the Bacillus subtilis bacteriophage phi29 prohead and virion was determined by combustion of gel bands of (3)H-labeled proteins. Copy numbers of individual proteins were calculated relative to the 12 copies of the head-tail connector protein. The mean numbers of copies of the major capsid protein in the prohead and virion were 241 and 218, respectively, approaching the 235 copies determined previously by cryoelectron microscopy. The mean numbers of copies of the dimeric head fiber on the prohead and virion were 24 and 31, respectively, demonstrating partial occupancy of the 55 fiber binding sites. Measured copies of neck and tail proteins in the virion included 11 of the lower collar, 58 of the appendage, and 9 of the tail; if the true copies of these proteins are 12, 60, and 9, respectively, the entire neck and tail of phi29 has quasi-sixfold symmetry. The mass of the fiberless prohead with pRNA was about 14.2 MDa, and the mass of the prohead determined by scanning transmission electron microscopy was consistent with the biochemical data. The mass of the fiberless virion containing the 12.8-MDa DNA genome was about 30.4 MDa. A full complement of dimeric fibers on the prohead or virion would increase the mass of the particle by about 3.2 MDa. The data complement studies relating the structure of phi29 components to dynamic functions in morphogenesis and infection.

Bacillus Phages↗
PubMed2001

Child sexual abuse, peer sexual abuse, and sexual assault in adulthood: a multi-risk model of revictimization.

This study explored the predictors and consequences of sexual assault occurring after the age of 16 years in a nonclinical sample of women. Child sexual abuse occurring before the age of 16 years was the only predictor of later sexual assault among comorbid risk factors. Peer sexual abuse, number of perpetrators, age at time of sexual abuse, and severity of sexual abuse did not increase the risk for later sexual assault. Adult sexual assault victims showed lower levels of mental health functioning than did survivors of child or peer sexual abuse. We discuss a specificity model of revictimization and the differential effects of child, peer, and adult sexual trauma on the developmental trajectory of sexual violence and psychosocial functioning.

Adolescent↗
PubMed2001

Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks.

The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification. Expression of several of these genes has been reported in SRBCTs, but most have not been associated with these cancers. To test the ability of the trained ANN models to recognize SRBCTs, we analyzed additional blinded samples that were not previously used for the training procedure, and correctly classified them in all cases. This study demonstrates the potential applications of these methods for tumor diagnosis and the identification of candidate targets for therapy.

Burkitt Lymphoma↗