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Biomedical subjects

A Barnett

Publications and source records attributed to A Barnett.

At least 19 recordsLinked to original sources

DPP-4 inhibitors and their potential role in the management of type 2 diabetes.

The dipeptidyl peptidase 4 (DPP-4) inhibitors enhance the body's own ability to control blood glucose by increasing the active levels of incretin hormones in the body. Their mechanism of action is distinct from any existing class of oral glucose-lowering agents. They control elevated blood glucose by triggering pancreatic insulin secretion, suppressing pancreatic glucagon secretion, and signalling the liver to reduce glucose production. The leading DPP-4 inhibitors have shown clinically significant HbA1c reductions up to 1 year of treatment and offer many potential advantages over existing diabetes therapies including a low risk of hypoglycaemia, no effect on body weight, and the potential, based on animal and in vitro studies, for the regeneration and differentiation of pancreatic beta-cells. They are efficacious as monotherapy and also in combination with commonly prescribed antidiabetic agents and are suitable for once-daily oral dosing. Consequently, many DPP-4 inhibitors such as vildagliptin (Galvus; LAF-237), sitagliptin (Januvia; MK-0431), and saxagliptin (BMS-477118) have advanced into late-stage human clinical trials. Search strategy and selection criteria This review was built on a systematic MEDLINE search for publications on the subject with the key words: DPP-4 inhibitor; vildagliptin (LAF-237); sitagliptin (MK-0431); saxagliptin (BMS-477118); and type 2 diabetes; up to August 2006. Meeting abstracts were also searched, as much of the data currently only exists in abstract form. Take home message for clinician The DPP-4 inhibitors appear to have great potential for the treatment of type 2 diabetes, but time will tell if this will be realized. While they do not lower glucose to a greater extent than existing therapies, they offer many potential advantages, including the ability to achieve sustainable reductions in HbA1c with a well-tolerated agent that has a low risk of hypoglycaemia and no weight gain, and which can be administered as a once-daily oral dose.

Adamantane↗

Open splenectomy in Jamaican children with sickle cell disease.

A total of 110 patients with sickle cell disease who had open splenectomy at the University Hospital of the West Indies over a 10-year period are reviewed Patients with homozygous sickle cell disease numbered 94, S beta0 and S beta+ thalassaemias (11 and 4 respectively) and one patient with SC disease. Postoperative acute chest syndrome was the most common complication (9 of 110). There were no life threatening emergencies and no mortalities. Eleven patients received preoperative blood transfusion and operative times were short averaging 60 minutes among the 110 patients. Open splenectomy remains the gold standard for patients with sickle cell disease requiring splenectomy.

Anemia, Sickle Cell↗

Caregiver burden, time spent caring and health status in the first 12 months following stroke.

OBJECTIVE: To quantify time caring, burden and health status in carers of stroke patients after discharge from rehabilitation; to identify the potentially modifiable sociodemographic and clinical characteristics associated with these outcomes. METHODS: Patients and carers prospectively interviewed 6 (n=71) and 12 (n=57) months after discharge. Relationships of carer and patient variables with burden, health status and time analysed by Gaussian and Poisson regression. RESULTS: Carers showed considerable burden at 6 and 12 months. Carers spent 4.6 and 3.6 hours per day assisting patients with daily activities at 6 and 12 months, respectively. Improved patient motor and cognitive function were associated with reductions of up to 20 minutes per day in time spent in daily activities. Better patient mental health and cognitive function were associated with better carer mental health. CONCLUSIONS: Potentially modifiable factors such as these may be able to be targeted by caregiver training, support and education programmes and outpatient therapy for patients.

Activities of Daily Living↗

Association of simple anthropometric measures of obesity with visceral fat and the metabolic syndrome in male Caucasian and Indo-Asian subjects.

AIMS: The aims of this study were first, to investigate the relationship between simple anthropometric measures of obesity with visceral fat as assessed by a single slice magnetic resonance imaging (MRI)-scan in patients attending a hospital clinic. Second, to determine which anthropometric measure best relates to the adverse metabolic profile of the metabolic syndrome. METHODS: Forty-one male subjects [body mass index (BMI): 30.2 + 5.8 kg/m(2), age: 50.3 + 13.6 years] were studied by MRI-scan to measure visceral fat at L4/L5 level and to investigate its relationship with simple anthropometric measures. Second, we studied 83 male subjects to determine which anthropometric measure best predicts the metabolic complications (using the ATPIII criteria) of obesity in the setting of a hospital clinic. RESULTS: Waist circumference was the best anthropometric measurement that correlated with MRI-visceral fat mass assessed at L4/L5 in 41 subjects who had an MRI scan (P = 0.0001, r(2) = 0.36, beta = 0.56) amongst variables which also included age, BMI, sagittal diameter, diabetes and ethnicity. Stepwise multiple regression analysis showed sagittal diameter (P = 0.001, r(2) = 0.4, beta = 0.406), age (P = 0.003, beta = 0.271) and waist circumference (P = 0.012, beta = 0.297) were the best predictors of the adverse metabolic profile of the metabolic syndrome in all 83 male subjects amongst BMI, waist-hip ratio (WHR), ethnicity and diabetes-related factors. CONCLUSIONS: Waist circumference is a simple anthropometric parameter that best correlates with single slice MRI-scan, but sagittal diameter (measured using abdominal calipers) better predicts the adverse metabolic profile of the metabolic syndrome. Although there is considerable variation in abdominal fat topography between ethnic groups, and also within populations, sagittal diameter assessment is a technique that is simple and best predicts the metabolic syndrome.

Adult↗

Analysis and generalized correction of the effect of spatial gradient field distortions in diffusion-weighted imaging.

Nonuniformities of magnetic field gradients can cause serious artifacts in diffusion imaging. While it is well known that nonlinearities of the imaging gradients lead to image warping, those imperfections can also cause spatially dependent errors in the direction and magnitude of the diffusion encoding. This study shows that the potential errors in diffusion imaging are considerable. Further, we show that retrospective corrections can be applied to reduce these errors. A general mathematical framework was formulated to characterize the contribution of gradient nonuniformities to diffusion experiments. The gradient field was approximated using spherical harmonic expansion, and this approximation was employed (after geometric distortions were eliminated) to predict and correct the errors in diffusion encoding. Before the corrections were made, the experiments clearly revealed marked deviations of the calculated diffusivity for fields of view (FOVs) generally used in diffusion experiments. These deviations were most significant farther away from the magnet's isocenter. For an FOV of 25 cm, the resultant errors in absolute diffusivity ranged from approximately -10% to +20%. Within the same FOV, the diffusion-encoding direction and the orientation of the calculated eigenvectors can be significantly altered if the perturbations by the gradient nonuniformities are not considered. With the proposed correction scheme, most of the errors introduced by gradient nonuniformities can be removed.

Anisotropy↗

Generalized reconstruction of phase contrast MRI: analysis and correction of the effect of gradient field distortions.

To characterize gradient field nonuniformity and its effect on velocity encoding in phase contrast (PC) MRI, a generalized model that describes this phenomenon and enables the accurate reconstruction of velocities is presented. In addition to considerable geometric distortions, inhomogeneous gradient fields can introduce deviations from the nominal gradient strength and orientation, and therefore spatially-dependent first gradient moments. Resulting errors in the measured phase shifts used for velocity encoding can therefore cause significant deviations in velocity quantification. The true magnitude and direction of the underlying velocities can be recovered from the phase difference images by a generalized PC velocity reconstruction, which requires the acquisition of full three-directional velocity information. The generalized reconstruction of velocities is applied using a matrix formalism that includes relative gradient field deviations derived from a theoretical model of local gradient field nonuniformity. In addition, an approximate solution for the correction of one-directional velocity encoding is given. Depending on the spatial location of the velocity measurements, errors in velocity magnitude can be as high as 60%, while errors in the velocity encoding direction can be up to 45 degrees. Results of phantom measurements demonstrate that effects of gradient field nonuniformity on PC-MRI can be corrected with the proposed method.

Blood Flow Velocity↗

Neonatal cerebral infarction and visual function at school age.

OBJECTIVE: To assess various aspects of visual function at school age in children with neonatal cerebral infarction. PATIENTS AND METHODS: Sixteen children born at term, who had cerebral infarction of perinatal onset on neonatal magnetic resonance imaging (MRI) were assessed using a battery of visual tests. This included measures of crowding acuity (Cambridge Crowding Cards), stereopsis (TNO test), and visual fields. The results of the visual assessment were compared with the type and the extent of the lesion observed on neonatal MRI. RESULTS: Only six of the 16 children (28%) had some abnormalities of visual function on these tests. Visual abnormalities were more common in children with more extensive lesions involving the main branch of the middle cerebral artery and were less often associated with lesions in the territory of one of the cortical branches of the middle cerebral artery. The presence of visual abnormalities was not always associated with the involvement of optic radiations or occipital primary visual cortex. Abnormal visual fields were only found in children who also developed hemiplegia. CONCLUSIONS: Abnormality of visual function is not common in children who had neonatal infarction and, when present, tends to be associated with hemiplegia and more extensive lesions.

Cerebral Infarction↗

Potential role for advanced trauma life support programme in improving trauma care in Jamaica.

Data from the Road Safety Unit in the Ministry of Transport and Works, Jamaica, show an increase in road traffic accidents from 7861 in 1991 to 11,010 in 1999. The average number of deaths annually was 380 +/- 48 (SD) while injuries averaged 3320 +/- 262 per year. This represents an injury to death ratio of 8.7 compared with 24.9 for Trinidad and Tobago and 40 for Canada. During the period 1991 to 2000, an average of 796 +/- 159 (SD) murders were committed annually. The number of murders increased by over 280 per cent between the decade of the seventies and the nineties. Data from the trauma registry of the University Hospital of the West Indies showed that 29.6 per cent of all admissions to the surgical ward between January 1998 and December 31, 2000, were due to injuries. There were 97 deaths (3%) during this period and 33 occurred in the Accident and Emergency Department with 70 per cent occurring within 120 minutes of their arrival. The Advanced Trauma Life Support (ATLS) Programme emphasizes the resuscitation and stabilization of injured patients in the first few hours after injury. Most Emergency Departments in Jamaica are staffed by relatively junior medical officers and the low injury to death ratio among victims of motor vehicle accidents may be due to suboptimal care. Introduction of an ATLS programme in Jamaica may reduce the number of preventable deaths and also stimulate interest in trauma care thus increasing preventative measures to decrease the high incidence of trauma in Jamaica.

Accidents, Traffic↗

MRI lesions and infants with neonatal encephalopathy. Is the Apgar score predictive?

OBJECTIVE: The aim of this study was to establish whether, in full-term infants presenting with neonatal encephalopathy, the 1 minute Apgar score gives an indication of the presence, site or type of lesions observed on brain MRI in the neonatal period. PARTICIPANTS AND METHODS: The study cohort included 157 full-term infants who had neurological abnormalities during the first 48 hours after delivery. Infants with developmental, genetic, infective or metabolic diagnoses were excluded from the study. The infants were subdivided according to their 1 minute Apgar score into three groups as follows: Apgar score 0 - 3 (n = 108/157, 69 %), 4 - 7 (n = 29, 19 %), 8 - 10 (n = 21, 12 %). Results. Severe and moderate basal ganglia and thalamic (BGT) lesions, with one exception, were only observed in the group with an Apgar score of 3 or below. Minimal BGT lesions were, with one exception, associated with scores below 7 and mainly below 3. However, not all the infants with low Apgar scores had BGT lesions and 28 % of the patients with Apgar scores below 3 had normal scans or only minimal white matter changes. White matter lesions without BGT involvement were equally distributed in the cohort, irrespective of the Apgar scores. Cerebral infarction and scattered white matter haemorrhages were the most common findings in infants with Apgar scores of 4 and above. The Apgar scores were not always predictive of motor outcome at 2 years but the presence and severity of the sequelae mainly reflected the site and severity of MRI findings. CONCLUSIONS: These findings stress the importance of subdividing neonatal encephalopathy into diagnostic categories according to brain lesions if one wishes to study either causative factors or outcome.

Apgar Score↗

Neurological and perceptual-motor outcome at 5 - 6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI.

OBJECTIVE: The aims of this study were 1) to determine the incidence of minor neurological dysfunction and perceptual-motor difficulties in children aged 5-1/2 -- 6-1/2, who had been born full-term but presented with neonatal encephalopathy (NE) and low Apgar scores and 2) to examine the relationships between the presence/absence of these difficulties with neonatal brain MRI. PARTICIPANTS AND METHODS: Sixty-eight full-term infants with one minute Apgar scores less than or equal to 5 and neurological abnormalities during the first 48 hours after birth were included in the study. All children had a neonatal MRI brain scan. Surviving infants were assessed between the age of 5 and 6 years using the Touwen Examination, the Movement ABC and the WPPSI-R. RESULTS: Fifteen of the 68 infants (22 %) died in the neonatal period. Of the 53 surviving infants, 19 (36 %) had cerebral palsy. The remaining 34 were considered normal at 2 years of age but, when assessed at school age, 8 (15 %) had minor neurological dysfunction and/or perceptual-motor difficulties, 1 (2 %) had only cognitive impairment and 25 (47 %) were normal. The outcome largely reflected the pattern of lesions on brain imaging. While 83 % of those with a normal outcome had normal scans or minimal white matter lesions, 80 % of those with minor neurological dysfunction and/or perceptual-motor difficulties had mild or moderate basal ganglia or more marked white matter lesions. CONCLUSION: Continued surveillance is recommended for children with apparently normal outcome at two years of age after NE, particularly when abnormalities are detected on brain MRI.

Age Factors↗

Parametric evolution for a deformed cavity.

We consider a classically chaotic system that is described by a Hamiltonian H(Q,P;x), where (Q,P) describes a particle moving inside a cavity, and x controls a deformation of the boundary. The quantum eigenstates of the system are /n(x)>. We describe how the parametric kernel P(n/m)=/ /(2), also known as the local density of states, evolves as a function of deltax=x-x(0). We illuminate the nonunitary nature of this parametric evolution, the emergence of nonperturbative features, the final nonuniversal saturation, and the limitations of random-wave considerations. The parametric evolution is demonstrated numerically for two distinct representative deformation processes.

Journal Article↗

Comments on "gradient-induced acoustic and magnetic field fluctuations in a 4T whole-body MR imager".

The results published in the article Gradient-Induced Acoustic and Magnetic Field Fluctuations in a 4T Whole-Body MR Imager by Wu et al. (Magn Reson Med 2000;44:532-536) appear to be consistent with the response of a time-stationary linear system. Since a linear system is more simply described than a nonlinear system, the authors are urged to reanalyze their data to test the linear-system hypothesis.

Acoustics↗

Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture.

This study investigates water diffusion changes in Wallerian degeneration. We measured indices derived from the diffusion tensor (DT) and T2-weighted signal intensities in the descending motor pathways of patients with small chronic lacunar infarcts of the posterior limb of the internal capsule on one side. We compared these measurements in the healthy and lesioned sides at different levels in the brainstem caudal to the primary lesion. We found that secondary white matter degeneration is revealed by a large reduction in diffusion anisotropy only in regions where fibers are arranged in isolated bundles of parallel fibers, such as in the cerebral peduncle. In regions where the degenerated pathway crosses other tracts, such as in the rostral pons, paradoxically there is almost no change in diffusion anisotropy, but a significant change in the measured orientation of fibers. The trace of the diffusion tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary fiber loss where the increase in trace is considerably higher. We show that DT-MRI is more sensitive than T2-weighted MRI in detecting Wallerian degeneration. Significant diffusion abnormalities are observed over the entire trajectory of the affected pathway in each patient. This finding suggests that mapping degenerated pathways noninvasively with DT-MRI is feasible. However, the interpretation of water diffusion data is complex and requires a priori information about anatomy and architecture of the pathway under investigation. In particular, our study shows that in regions where fibers cross, existing DT-MRI-based fiber tractography algorithms may lead to erroneous conclusion about brain connectivity.

Aged↗

Allograft aortic root replacement in 418 patients over a span of 15 years: 1985 to 2000.

Allograft aortic root replacement for primary aortic valve or ascending aortic root pathology is the favored method of technical implantation. Results in 418 patients over 15 years demonstrate exceedingly low early mortality (<1%), complete eradication of preoperative endocarditis but poor long-term durability in the young age group of 20 years or less.

Actuarial Analysis↗

Deformations and dilations of chaotic billiards: dissipation rate, and quasiorthogonality of the boundary wave functions

We consider chaotic billiards in d dimensions, and study the matrix elements M(nm) corresponding to general deformations of the boundary. We analyze the dependence of |M(nm)|(2) on omega = (E(n)-E(m))/Planck's over 2pi using semiclassical considerations. This relates to an estimate of the energy dissipation rate when the deformation is periodic at frequency omega. We show that, for dilations and translations of the boundary, |M(nm)|(2) vanishes like omega(4) as omega-->0, for rotations such as omega(2), whereas for generic deformations it goes to a constant. Such special cases lead to quasiorthogonality of the eigenstates on the boundary.

Journal Article↗

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients.

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.

Adult↗