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Biomedical subjects

Robert J Young

Publications and source records attributed to Robert J Young.

At least 19 recordsLinked to original sources
PubMed2006

Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.

Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

Alanine↗
PubMed2006

Design and synthesis of orally active pyrrolidin-2-one-based factor Xa inhibitors.

A series of novel, non-basic 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group, was designed and synthesised. Within this series, the N-2-(morpholin-4-yl)-2-oxoethyl derivative 24 was shown to be a potent, selective fXa inhibitor with good anticoagulant activity. Moreover, 24 possessed highly encouraging rat and dog pharmacokinetic profiles with excellent oral bioavailabilities in both species.

Administration, Oral↗
PubMed2006

Brain MRI: tumor evaluation.

The designation "brain tumors" is commonly applied to a wide variety of intracranial mass lesions that are distinct in their location, biology, treatment, and prognosis. Since many of these lesions do not arise from brain parenchyma, the more appropriate term would be "intracranial tumors." The term "tumor" is used to include both neoplastic and non-neoplastic mass lesions, and should be considered in its broadest sense to simply indicate a space-occupying mass. This review describes an imaging-based approach for evaluating intracranial tumors. Conventional MRI is discussed in the setting of a regional classification system. This system provides a framework for analysis, and imaging clues can then be applied to narrow the differential possibilities. Emphasis is placed on advanced MRI techniques and their utility for deciphering common diagnostic problems.

Brain Neoplasms↗
PubMed2006

Molecular orientation distributions in a biaxially oriented poly(L-lactic acid) film determined by polarized Raman spectroscopy.

Molecular orientation distributions in the crystalline and amorphous regions of a biaxially oriented poly(L-lactic acid) film were analyzed fully by polarized Raman spectroscopy. Raman bands at 926 and 875 cm(-1) were chosen for the determination of the most probable molecular orientation distribution functions for the crystalline and amorphous regions in the film. It was revealed that the PLLA molecules were oriented biaxially in both the crystalline and amorphous regions. The orientation distribution normal to the film surface was found to be broader in the amorphous regions than in the crystalline regions. Furthermore, a predominant unidirectional molecular orientation was observed in the crystalline regions, whereas the molecular orientation distribution in the amorphous regions was isotropic in the plane parallel to the film surface. The different behavior of the crystalline and amorphous regions suggests that each region underwent different deformation mechanisms during the film formation.

Biocompatible Materials↗
PubMed2005

Synthesis and evaluation of mimetics of UDP and UDP-alpha-D-galactose, dTDP and dTDP-alpha-D-glucose with monosaccharides replacing the key pyrophosphate unit.

A series of 5'-O-glycosyl-uridine and thymidine derivatives have been prepared as potential mimics of sugar nucleotides and nucleotide-diphosphates. These compounds proved not to be inhibitors of bovine beta-1,4-galactosyltransferase although some showed moderate inhibition of Salmonella dTDP-alpha-D-glucose 4,6-dehydratase (RmlB).

Animals↗
PubMed2005

Neuroimaging of metastatic brain disease.

This review discusses imaging techniques for the diagnosis, treatment, and monitoring of brain metastases. It assesses the various modalities on the basis of their respective advantages and limitations. Recent advances in imaging technologies provide evaluation that is more accurate for tumor localization, morphology, physiology, and biology. When used in combination, these technologies provide clinicians with a powerful diagnostic and prognostic tool for managing metastatic brain disease.

Brain Neoplasms↗
PubMed2005

Pro-active call center treatment support (PACCTS) to improve glucose control in type 2 diabetes: a randomized controlled trial.

OBJECTIVE: To determine whether Pro-Active Call Center Treatment Support (PACCTS), using trained nonmedical telephonists supported by specially designed software and a diabetes nurse, can effectively improve glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized controlled implementation trial of 1-year duration was conducted in Salford, U.K. The trial comprised 591 randomly selected individuals with type 2 diabetes. By random allocation, 197 individuals were assigned to the usual care (control) group and 394 to the PACCTS (intervention) group. Lifestyle advice and drug treatment in both groups followed local guidelines. PACCTS patients were telephoned according to a protocol with the frequency of calls proportional to the last HbA(1c) level. The primary outcome was absolute reduction in HbA(1c), and the secondary outcome was the proportion of patients reducing HbA(1c) by at least 1%. RESULTS: A total of 332 patients (84%) in the PACCTS group and 176 patients (89%) in the control group completed the study. Final HbA(1c) values were available in 374 patients (95%) in the PACCTS group and 180 patients (92%) in the usual care group. Compared with usual care, HbA(1c) improved by 0.31% (95% CI 0.11-0.52, P = 0.003) overall in the PACCTS patients. For patients with baseline HbA(1c) >7%, the improvement increased to 0.49% (0.21-0.77, P < 0.001), whereas in patients with baseline HbA(1c) <7% there was no change. The difference in the proportions of patients achieving a >/=1% reduction in HbA(1c) significantly favored the PACCTS intervention: 10% (4-16, P < 0.001) overall and 15% (7-24, P < 0.001) for patients with baseline HbA(1c) >7%. CONCLUSIONS: In an urban Caucasian trial population with blood glucose HbA(1c) >7%, PACCTS facilitated significant improvement in glycemic control. Further research should extend the validity of findings to rural communities and other ethnic groups, as well as to smoking and lipid and blood pressure control.

Adult↗
PubMed2005

Acceptability and satisfaction with a telecarer approach to the management of type 2 diabetes.

OBJECTIVE: To examine patients' views of the acceptability of and satisfaction with telephone care center support provided to improve blood glucose control in type 2 diabetes. RESEARCH DESIGN AND METHODS: The Pro-Active Call-Center Treatment Support (PACCTS) Trial randomized patients from 47 general practices in a deprived urban area in northwest England to usual care or to proactive call center support in addition to usual care. Satisfaction with care was assessed in all 591 patients at baseline and the end of the study using the Diabetes Satisfaction and Treatment Questionnaire (DTSQ). Acceptability was assessed in 394 intervention patients after at least three proactive calls from the call center and at the end of the trial. A purposive sample of 25 patients took part in in-depth semistructured interviews. RESULTS: The response rates to the questionnaires were 79% (DTSQ) and 65% (acceptability). Persons receiving the intervention continued to report high levels of satisfaction with their treatment (95% CI 32.3-33.2 at 1 year), and >90% strongly agreed or agreed that the telecarer approach was acceptable. Qualitative comments pointed to the importance of a personalized service; increased feelings of well-being, including confidence and self-control; help with problem-solving; and patients developing rapport and a strong bond with the telecarers. CONCLUSIONS: A personalized PACCTS approach is acceptable to patients. A service giving priority to the interpersonal dimension leads to increased commitment from patients to improve long-term glycemic control.

Aged↗
PubMed2005

Lesion size determines accuracy of thallium-201 brain single-photon emission tomography in differentiating between intracranial malignancy and infection in AIDS patients.

BACKGROUND AND PURPOSE: Discrimination between enhancing mass lesions in acquired immunodeficiency syndrome (AIDS) patients with conventional CT and MR imaging remains difficult. We determined the effect of lesion size on thallium-201 brain single-photon emission tomography (SPECT) imaging in differentiating primary brain lymphoma from cerebral toxoplasmosis. METHODS: We retrospectively identified 35 AIDS patients with a total of 48 focal enhancing mass lesions on contrast-enhanced brain CT and/or MR images who subsequently underwent thallium-201 brain SPECT imaging. The thallium index of each lesion was evaluated on the basis of the ratio of mean uptake in the lesion compared with the corresponding contralateral side. Receiver operator curves were drawn to determine the optimal thallium index threshold. The effect of lesion size on scan accuracy was evaluated. RESULTS: Malignant lesions in 20 patients had a mean thallium index of 2.4 (range, 1-11). Infectious lesions in 15 patients had a mean thallium index of 1.6 (range, 1-3.6). Twenty-five lesions were <2 cm (14 malignant, 11 nonmalignant) and 23 lesions were > or =2 cm (14 malignant, 9 nonmalignant). Thallium index was not a significant predictor of malignancy in the lesions <2 cm by using the logistic regression (P = .27). Receiver operator curve analysis by using thallium index of 2 in small lesions yielded 50% sensitivity and 82% specificity. In contrast, thallium index was a significant predictor of malignancy in lesions > or =2 cm (P < .01), yielding 100% sensitivity and 89% specificity. CONCLUSION: Lesion size is a significant determinant of the accuracy of thallium-201 brain SPECT imaging, which should be the initial diagnostic tool for lesions > or =2 cm.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Collapse of single-wall carbon nanotubes is diameter dependent.

We present classical molecular dynamics simulations demonstrating that single-wall carbon nanotube (SWNT) bundles collapse under hydrostatic pressure. The collapse pressures obtained as a function of nanotube diameter are in excellent quantitative agreement with new data presented here for small diameter (d approximately 0.8 nm) SWNTs, and the majority of previously published results, although there remain some unreconciled contradictions in the literature. The collapse pressure is found to be independent of the nanotube chirality, and a lower limit on the largest SWNT that remains inflated at atmospheric pressure is established (d>4.16 nm).

Journal Article↗
PubMed2003

Do domestic pigs in controlled environments contrafreeload?

Many experiments report that animals will work (lever press) for food in the presence of freely available identical food. This phenomenon has attracted the attention of applied ethologists because it seems to prove that animals have a need to express appetitive behavior. If this is the case, then it has implications for the provision of environmental enrichment for animals in captivity. In this experiment, we maintained 6 pigs in closed economy environments for three 120-hr choice periods in which they had continuous free access to operant and identical free food. In the experiment, we tested pigs using 2 different operant schedules, fixed ratio (FR) 5 and variable ratio (VR) 5. We used a VR schedule because many enrichment studies claim that unpredictability is an important characteristic that makes an enrichment device attractive. The results show that pigs exhibited a negligible level of contrafreeloading (M +/- standard error of the mean proportion = 0.05 +/- 0.01). Furthermore, there were no significant differences between FRs and VRs of reinforcement.

Animals↗
PubMed2002

Do domestic dogs show any evidence of being able to count?

Numerical competence has been demonstrated in a wide range of animal species. The level of numerical abilities shown ranges from simple relative numerousness judgements to true counting. In this study we used the preferential looking technique to test whether 11 pet dogs could count. The dogs were presented with three simple calculations: "1+1=2"; "1+1=1"; and "1+1=3". These calculations were performed by presenting the dogs with treats that were placed behind a screen that allowed manipulation of the outcome of the calculation. When the dogs expected the outcome they spent the same amount of time looking at the result of the calculation as they did on the initial presentation. However, when the result was unexpected dogs spent significantly longer looking at the outcome of the calculation. The results suggest that the dogs were anticipating the outcome of the calculations they observed, thus suggesting that dogs may have a rudimentary ability to count.

Animal Feed↗
PubMed2002

The crystal structure of IgE Fc reveals an asymmetrically bent conformation.

The distinguishing structural feature of immunoglobulin E (IgE), the antibody responsible for allergic hypersensitivity, is the C epsilon 2 domain pair that replaces the hinge region of IgG. The crystal structure of the IgE Fc (constant fragment) at a 2.6-A resolution has revealed these domains. They display a distinctive, disulfide-linked Ig domain interface and are folded back asymmetrically onto the C epsilon 3 and C epsilon 4 domains, which causes an acute bend in the IgE molecule. The structure implies that a substantial conformational change involving C epsilon 2 must accompany binding to the mast cell receptor Fc epsilon RI. This may be the basis of the exceptionally slow dissociation rate of the IgE-Fc epsilon RI complex and, thus, of the ability of IgE to cause persistent allergic sensitization of mast cells.

Carbohydrate Conformation↗
PubMed2002

Imaging of traumatic intracranial hemorrhage.

Traumatic intracranial hemorrhage is a leading cause of morbidity and mortality in the United States. CT remains the primary imaging modality for initial evaluation of patients who have sustained head trauma. MR imaging, which has always been important for the evaluation of subacute and chronic head trauma, has been gaining popularity and recognition as an alternative primary imaging modality.

Brain↗