Beta-cell secretory defect caused by mutations in glucokinase gene.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
R Turner
Publications and source records attributed to R Turner.
Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.
Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P less than 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (M1) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology.
Animals↗
A quantitative model for the mechanism of action of the cytochrome c peroxidase of Pseudomonas aeruginosa.
Each of the elementary reaction steps in both the activation process and catalytic cycle of the cytochrome c peroxidase of Pseudomonas aeruginosa was characterized using stopped-flow methods. A synthesis of these data led to the establishment of a quantitative model for the action of this enzyme. Comparisons were made between experimental data and calculations over a wide range of enzyme, reductant and H2O2 concentrations. Close agreement was found between empirical and simulated reaction time courses from millisecond to tens of seconds time ranges, giving us confidence in the validity of the quantitative model of this enzyme's actions.
Azurin↗
Diazoxide no longer marketed.
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Diazoxide↗
The capillary network: a link between IVIM and classical perfusion.
MR measurements based on motion encoding gradients, such as intravoxel incoherent motion imaging, could provide, in principle, information on flowing blood volume and blood velocity. This note shows that, in addition, the knowledge of the capillary network organization may provide a link between these measurements and those obtained by conventional and MR perfusion techniques based on tracer uptake by tissues.
Capillaries↗
Multilocus markers for mouse genome analysis: PCR amplification based on single primers of arbitrary nucleotide sequence.
Polymerase chain reaction (PCR) based on single primers of arbitrary nucleotide sequence provides a powerful marker system for genome analysis because each primer amplifies multiple products, and cloning, sequencing, and hybridization are not required. We have evaluated this typing system for the mouse by identifying optimal PCR conditions; characterizing effects of GC content, primer length, and multiplexed primers; demonstrating considerable variation among a panel of inbred strains; and establishing linkage for several products. Mg2+, primer, template, and annealing conditions were identified that optimized the number and resolution of amplified products. Primers with 40% GC content failed to amplify products readily, primers with 50% GC content resulted in reasonable amplification, and primers with 60% GC content gave the largest number of well-resolved products. Longer primers did not necessarily amplify more products than shorter primers of the same proportional GC content. Multiplexed primers yielded more products than either primer alone and usually revealed novel variants. A strain survey showed that most strains could be readily distinguished with a modest number of primers. Finally, linkage for seven products was established on five chromosomes. These characteristics establish single primer PCR as a powerful method for mouse genome analysis.
Animals↗
Reliability and validity of a health-related quality of life battery for evaluating outpatient antidepressant treatment.
This study was designed to evaluate the reproducibility, validity and responsiveness of a health-related quality of life (HRQOL) battery that was assembled for the evaluation of antidepressant therapy. The Montgomery-Asberg Depression Rating Scale was used to measure severity of depression. The HRQOL battery contained measures of energy and fatigue, social behaviour, cognitive function, home and work role function, and general well-being (i.e., health perceptions, life satisfaction) selected from previously developed and validated instruments. The clinical investigators and research nurses reported on difficulty in using the HRQOL battery. Most patients were able to complete the questionnaire without problems within 10 min. Reproducibility was very good with intraclass correlation coefficients ranging from 0.74 to 0.97. The HRQOL scales showed evidence of good concurrent validity. The scales were moderately correlated with MADRS scores (r = 0.30-0.62). The magnitude of these correlations indicate that HRQOL scales are related to depression measures, but they are not alternative measures of depression. Changes in MADRS scores were associated with changes in all scales, except for work behaviour, indicating that improvements in depression ratings also resulted in improvements in health status and well-being. The HRQOL scales included in this study were found to be reliable, reproducible, and valid and no appreciable burden was placed on patients or investigators participating in the study. With the exception of the Work Behaviour scale, the HRQOL scales were very responsive to changes in depression severity. This brief HRQOL instrument can provide a comprehensive assessment of the outcomes of antidepressant treatment.
Adult↗
Toward a more culturally sensitive DSM-IV. Psychoreligious and psychospiritual problems.
In theory, research, and practice, mental health professionals have tended to ignore or pathologize the religious and spiritual dimensions of life. This represents a type of cultural insensitivity toward individuals who have religious and spiritual experiences in both Western and non-Western cultures. After documenting the "religiosity gap" between clinicians and patients, the authors review the role of theory, inadequate training, and biological primacy in fostering psychiatry's insensitivity. A new Z Code (formerly V Code) diagnostic category is proposed for DSM-IV: psychoreligious or psychospiritual problem. Examples of psychoreligious problems include loss or questioning of a firmly held faith, and conversion to a new faith. Examples of psychospiritual problems include near-death experiences and mystical experiences. Both types of problems are defined, and differential diagnostic issues are discussed. This new diagnostic category would: a) improve diagnostic assessments when religious and spiritual issues are involved; b) reduce iatrogenic harm from misdiagnosis of psychoreligious and psychospiritual problems; c) improve treatment of such problems by stimulating clinical research; and d) encourage clinical training centers to address the religious and spiritual dimensions of human existence.
Culture↗
The Worcester Development Project.
"The philosophy of Community Care has resulted in the closure of several mental hospitals in this country. The ethos of the Worcester Development Project saw the closure of St Wulstan's and Powick Hospitals, and their replacement by a community-based service. This paper briefly describes the outcome of a three-year retrospective study completed in 1988 following the closure of both hospitals. The findings provide a comparison of the two hospitals, including details of the destination of all the patients. It is suggested that the term 'hospital replacement' might be preferable to 'hospital closure'." "The Worcester Development Project began in 1968 when the Department of Health and Social Security brought together the Worcester and Kidderminster Hospital Management Committee and the County Council in a co-ordinated joint planning venture. Powick Hospital was chosen as the location for testing the hypothesis that closing a mental hospital and replacing it with general hospital psychiatric units, supported by a variety of community facilities, would provide a more economical and better service. This paper describes the outcome of this unique opportunity to study the problems involved in closing a mental hospital and its replacement with other facilities."
Activities of Daily Living↗
Diffusion MR imaging: clinical applications.
Water self-diffusion, a recently discovered source of contrast on MR images, has already shown promise for some clinical applications. Most studies have been of the brain, essentially for technical reasons. Diffusion is useful in distinguishing the different components of brain tumors (cystic regions, edema, necrosis) from the tumor core itself. Recent studies have shown that diffusion is anisotropic in brain white matter (i.e., dependent on the fiber tract's orientation in space), offering new insights into myelin disorders. Diffusion is also dramatically altered in the minutes following ischemic injury in the cat brain, which may have tremendous impact for the diagnosis and management of hyperacute stroke. With ultrafast acquisition schemes, diffusion imaging has also been used outside the CNS, for instance, in the eye and kidney. Future applications include diffusion-localized spectroscopy and temperature imaging. This article reviews recent progress in this field and suggests potential applications.
Body Water↗
Type II diabetes: search for primary defects.
Type 2 diabetes is a familial disease, but recent analysis of nuclear families indicates it is unlikely to be due to a single dominant gene with high penetrance and that it could be polygenic. Insulin resistance is a major feature, with obesity being a major determinant. Beta cell deficiency is a sine qua non of Type 2 diabetes. It is possible that obesity, insulin resistance independent from obesity and impaired beta cell function are independently inherited factors. None of these can be said to be 'primary' as diabetes usually results from the interaction of several geometric and environmental factors. This makes linkage analysis of Type 2 diabetes of uncertain benefit, since heterogeneity can occur within a pedigree. The only mutation so far discovered is of glucokinase producing maturity-onset diabetes of the young, that has a clearly defined and unusual phenotype. Identification of genes that cause classical Type 2 diabetes is likely to come from population association studies, molecular scanning techniques and direct sequencing of candidate genes rather than linkage analysis.
Diabetes Mellitus, Type 2↗
Organizing for quality in a base hospital.
This paper examines the current situation regarding the implementation of quality assurance (QA) programmes in relation to the Tamworth Base Hospital and Health Service. The importance of organizational design and the establishment of a Quality Resource Department are examined as means of achieving effective QA.
Hospital Departments↗
The application of continuous quality improvement tools in reducing the length of stay for hip replacement patients: a base hospital's experience.
The quality assurance (QA) initiative has been slow to show results. Quality assurance tools have been underdeveloped, and quality by inspection unacceptable to clinicians. A base hospital's experience with continuous quality improvement (CQI) as a means to more effective quality assurance is described. Discharge data grouped into diagnosis related groups (DRG) and analysed for inter-hospital comparison provided reliable statistical data with which to monitor the hospital's performance. The CQI tools were used to analyse the nature of the problem, and correct the deficiency. The new methodology would seem to indicate greater promise for successful quality assurance programmes in the future.
Hip Prosthesis↗
Echo-planar imaging: magnetic resonance imaging in a fraction of a second.
Progress has recently been made in implementing magnetic resonance imaging (MRI) techniques that can be used to obtain images in a fraction of a second rather than in minutes. Echo-planar imaging (EPI) uses only one nuclear spin excitation per image and lends itself to a variety of critical medical and scientific applications. Among these are evaluation of cardiac function in real time, mapping of water diffusion and temperature in tissue, mapping of organ blood pool and perfusion, functional imaging of the central nervous system, depiction of blood and cerebrospinal fluid flow dynamics, and movie imaging of the mobile fetus in utero. Through shortened patient examination times, higher patient throughput, and lower cost per MRI examination, EPI may become a powerful tool for early diagnosis of some common and potentially treatable diseases such as ischemic heart disease, stroke, and cancer.
Diffusion↗
Intravoxel incoherent motion imaging using spin echoes.
The purpose of this paper is to review the basic principles of diffusion measurement with spin echoes. These principles can be combined with those of MR imaging to generate maps of diffusion coefficients. Diffusion imaging can be extended to imaging of other intravoxel incoherent motions (IVIM), such as blood microcirculation. Some of the technical problems encountered when implementing IVIM imaging are presented.
Diffusion↗
Echo-planar imaging of diffusion and perfusion.
Use of the Stejskal-Tanner sequence for performing diffusion images in the human brain tends to be complicated by the presence of artifacts caused by voluntary or involuntary, sometimes pulsatile, motion. We describe the implementation of the technique of echo-planar diffusion imaging, which avoids these artifacts and allows reproducible quantitative values of the diffusion coefficient to be measured in vivo. The effects of perfusion are easily visible in a phantom containing a gel. The results for human brain show a significant "perfusion fraction" in grey matter, consistent with an extracellular, possibly microvascular, volume of about 10%.
Brain↗
Noninvasive temperature imaging using diffusion MRI.
Efficacy and safety considerations for cancer therapy with hyperthermia require accurate temperature measurements throughout the heated volume. We report the use of molecular diffusion, whose temperature dependence is well known. A dedicated hyperthermia applicator was built, combining a MRI gradient coil and a rf coil. Diffusion and derived temperature images were obtained with a 1 x 2 mm pixel size on a polyacrylamide gel phantom using a clinical 1.5-T whole body MRI system. Temperatures determined from these images using 1 cm2 regions of interest were found to be within 0.2 degrees C of those recorded from the thermocouples and fiber-optic probes placed inside the gel.
Body Temperature↗
Echo-planar time course MRI of cat brain oxygenation changes.
When deoxygenated, blood behaves as an effective susceptibility contrast agent. Changes in brain oxygenation can be monitored using gradient-echo echo-planar imaging. With this technique, difference images also demonstrate that blood oxygenation is increased during periods of recovery from respiratory challenge.
Animals↗