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Biomedical subjects

C Tanner

Publications and source records attributed to C Tanner.

At least 19 recordsLinked to original sources

Anisotropic multi-scale fluid registration: evaluation in magnetic resonance breast imaging.

Registration using models of compressible viscous fluids has not found the general application of some other techniques (e.g., free-form-deformation (FFD)) despite its ability to model large diffeomorphic deformations. We report on a multi-resolution fluid registration algorithm which improves on previous work by (a) directly solving the Navier-Stokes equation at the resolution of the images, (b) accommodating image sampling anisotropy using semi-coarsening and implicit smoothing in a full multi-grid (FMG) solver and (c) exploiting the inherent multi-resolution nature of FMG to implement a multi-scale approach. Evaluation is on five magnetic resonance (MR) breast images subject to six biomechanical deformation fields over 11 multi-resolution schemes. Quantitative assessment is by tissue overlaps and target registration errors and by registering using the known correspondences rather than image features to validate the fluid model. Context is given by comparison with a validated FFD algorithm and by application to images of volunteers subjected to large applied deformation. The results show that fluid registration of 3D breast MR images to sub-voxel accuracy is possible in minutes on a 1.6 GHz Linux-based Athlon processor with coarse solutions obtainable in a few tens of seconds. Accuracy and computation time are comparable to FFD techniques validated for this application.

Algorithms↗

Potential biogas scrubbing using a high rate pond.

The potential to scrub biogas in a high rate pond (HRP) was evaluated using apparatus designed to maximize gas-liquid contact. Experiments compared the removal of carbon dioxide from synthetic biogas by an "in-pond angled gutter" to that by a simulated "counter-current pit." Results showed that the counter current pit has potential for use in biogas scrubbing, with synthetic biogas carbon dioxide composition consistently reduced from 40% to < 5%. The in-pond angled gutter was less effective due to bubble coalescence which reduced the total bubble surface area available for gas transfer. Measurement of oxygen levels in the scrubbed biogas showed that despite supersaturation of oxygen in the HRP water, there was little transfer to the biogas, so that explosive methane/oxygen mixtures would not be formed. Theoretical calculations indicated that the amount of biogas likely to be formed during anaerobic treatment of municipal wastewater could be scrubbed in the HRP of the same advanced pond system with little influence on HRP pH, algal growth and treatment performance. These encouraging results justify further research on this method of biogas purification.

Agriculture↗

Comparison between radiological and artificial neural network diagnosis in clinical screening.

The imaging protocol of the UK multicentre magnetic resonance imaging study for screening in women at genetic risk of breast cancer aims to assist in detecting and diagnosing malignant breast lesions. In this paper, we evaluate a three-layer, feed-forward, backpropagation neural network as an artificial radiological classifier using receiver operating characteristic (ROC) curve analysis and compare the results with those obtained using a proposed radiological scoring system for the study which currently supplements the radiologist's clinical opinion, in comparison with histological diagnosis. Based on the 76 symptomatic cases evaluated, descriptive features scored by radiologists showed considerable overlap between benign and malignant, although some features such as irregular contours and heterogeneous enhancement were more often associated with malignant pathology. In this preliminary evaluation, ROC analysis showed that the proposed scoring scheme did not perform well, indicating further refinement is required. When all 23 features were used in the neural network, its performance was poorer than that of the scoring scheme. When only ten features were used, limited to descriptors of enhancement characteristics, the neural network performed similar to the scoring scheme. This comparison shows that the neural network approach to clinical diagnosis has considerable potential and warrants further development.

Breast Neoplasms↗

Freezing of gait in PD: prospective assessment in the DATATOP cohort.

OBJECTIVE: To study the development of freezing of gait in PD. BACKGROUND: Freezing of gait is a common, disabling, and poorly understood symptom in PD. METHODS: The authors analyzed data from 800 patients with early PD from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) clinical trial who were assigned either placebo, deprenyl, tocopherol, or the combination of deprenyl and tocopherol. The primary outcome measure was the time from randomization until the freezing of gait score on the Unified Parkinson's Disease Rating Scale (UPDRS) became positive. RESULTS: Fifty-seven patients (7.1%) had freezing of gait at study entry and 193 (26%) of the remaining patients experienced the symptom by the end of the follow-up period. Those with freezing of gait at baseline had significantly more advanced disease than those without the symptom, as measured by total UPDRS and Hoehn and Yahr stage. High baseline risk factors for developing freezing of gait during the follow-up period were the onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration. In contrast, tremor was strongly associated with a decreased risk for freezing of gait. At the end of follow-up, the signs most strongly associated with the freezing phenomenon were gait, balance, and speech disorders, not rigidity or bradykinesia. Deprenyl treatment was strongly associated with a decreased risk for developing freezing of gait; tocopherol had no effect. CONCLUSIONS: Freezing of gait is directly related to duration of PD. Risk factors at onset of disease are the absence of tremor and PD beginning as a gait disorder. The development of freezing of gait in the course of the illness is strongly associated with the development of balance and speech problems, less so with the worsening of bradykinesia, and is not associated with the progression of rigidity. These results support the concept that the freezing phenomenon is distinct from bradykinesia. Deprenyl, in the absence of L-dopa, was found to be an effective prophylactic treatment and should be considered for patients with PD who have an onset of gait difficulty.

Aged↗

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor.

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.

Aged↗

Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia.

BACKGROUND: The small-conductance calcium-activated potassium channel gene (hSKCa3) contains 2 CAG repeats, 1 of which is highly polymorphic. Although this repeat is not pathologically expanded in patients with schizophrenia, some studies have suggested an allelic association with schizophrenia. CAG expansions in other genes such as the alpha1 subunit of a brain-specific P/Q-type calcium channel gene cause spinocerebellar ataxia type 6, whereas the length of the CAG repeat in the RAI1 gene modifies the age of onset of spinocerebellar ataxia type 2. OBJECTIVES: To evaluate expansions in the hSKCa3 polyglutamine domain as causative for ataxia, and to study the association between the length of the polyglutamine repeat and the presence of ataxia. METHODS: We analyzed this repeat in 122 patients with autosomal dominant cerebellar ataxia, or sporadic ataxia, and compared allele distribution with 750 alleles seen in 2 healthy control groups and 172 alleles in patients with Parkinson disease. RESULTS: The distribution of alleles in ataxia patients and controls was significantly different by Wilcoxon rank test (P <.001). Twenty-two or more polyglutamine tracts were more common in ataxia patients compared with controls by chi2 analysis (P<.001). CONCLUSION: Longer stretches of polyglutamines in a human potassium channel are not causative for ataxia, but they are associated with the presence of ataxia. There is no association with the presence of Parkinson disease.

Age of Onset↗

Lewy bodies and parkinsonism in families with parkin mutations.

Previous work has established that compound mutations and homozygous loss of function of the parkin gene cause early-onset, autosomal recessive parkinsonism. Classically, this disease has been associated with loss of dopaminergic neurons in the substantia nigra pars compacta and locus ceruleus, without Lewy body pathology. We have sequenced the parkin gene of 38 patients with early-onset Parkinson's disease (<41 years). Two probands with mutations were followed up. Clinical evaluation of their families was performed, blinded to both genetic and pathological findings. Chromosome 6q25.2-27 haplotype analysis was carried out independently of the trait; parkin gene expression was examined at both the RNA and protein levels. Haplotype analysis of these families revealed a common chromosome 6, with a novel 40 bp exon 3 deletion that cosegregated with disease. In the proband of the smaller kindred, an exon 7 R275W substitution was identified in addition to the exon 3 deletion; RNA analysis demonstrated that the mutations were on alternate transcripts. However, Lewy body pathology typical of idiopathic Parkinson's disease was found at autopsy in the proband from the smaller kindred. These data suggest that compound heterozygous parkin mutations and loss of parkin protein may lead to early-onset parkinsonism with Lewy body pathology, while a hemizygous mutation may confer increased susceptibility to typical Parkinson's disease.

Adult↗

Pre-processed image reconstruction applied to breast and brain MR imaging.

Magnetic resonance imaging (MRI) has emerged as a powerful tool in medical diagnosis and research. Although high spatial resolution images are essential in medical diagnosis and image analysis, high temporal resolution is equally important in applications of dynamic contrast-enhanced MRI or functional brain MRI. In particular, in breast MRI the ability to differentiate between benign and malignant lesions depends, in part, on the temporal resolution of the dynamic image acquisition. New applications of MRI such as multi-feature analysis of image time series data and full 3D functional MRI or event-related functional MRI require high spatial and high temporal resolution for accurate image analysis on a voxel-by-voxel basis. Currently available partial Fourier reconstruction techniques. which effectively improve the time resolution, suffer from a reduced signal to noise ratio in the reconstructed image, a decrease in spatial resolution or reconstruction artefacts, making numerical image analysis difficult. In this work we present an image reconstruction algorithm based on image recovery theory which effectively doubles the temporal resolution and results in an image quality sufficient for further numerical analysis. The developed algorithm requires a full Fourier space acquisition of a pre-contrast or baseline image prior to the reconstruction procedure of the time series partial Fourier data.

Algorithms↗

Intramolecular electron transfer in the dipeptide, histidyltyrosine: a pulse radiolysis study.

The technique of pulse radiolysis has been used to investigate the possibility of intramolecular charge transfer in the dipeptide histidyltyrosine, following one-electron oxidation of one of its amino acid residues. The radical anion, Br2.- was found to react with the dipeptide at pH 6.0 with a bimolecular rate constant of 2.3+/-0.2 x 10(7) dm3 mol(-1)s(-1) suggesting that it reacts very selectively with the histidine moiety. Spectral observations at, or close to the end of this reaction show only the presence of a tyrosinyl free radical (TyrO.), however, indicating that fast (>10(6) s(-1) intramolecular charge transfer has taken place between histidine radicals (His+.) and tyrosine (TyrOH). This finding was supported by the direct observation of the rate of formation of TyrO. in experiments with the free amino acids, histidine and tyrosine, under conditions where Br2.- reacted selectively with histidine. The bimolecular rate constant for the reaction between His+. and TyrOH was found to be 2.4+/-0.5 x 10(6) dm3 mol(-1)s(-1). Taken together, the results of the study indicate that His+. is a relatively strong oxidising agent where (E (His+./His) > 770 mV at pH 6.0.

Bromides↗

Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group.

The manufacturer of deprenyl (selegeline; Eldepryl) (Somerset Pharmaceuticals, Tampa, FL) recently advised physicians to avoid prescribing the drug in combination with an antidepressant because of potentially serious CNS toxicity that may represent the serotonin syndrome. Manifestations of the serotonin syndrome vary but may include changes in mental status and motor and autonomic function. To better estimate the frequency of the serotonin syndrome in patients with Parkinson's disease (PD) treated with deprenyl and an antidepressant, we surveyed all investigators in the Parkinson Study Group. Based on estimates provided by the 47 investigators (75%) who responded, 4,568 patients were treated with the combination of deprenyl and an antidepressant medication. Eleven patients (0.24%) were reported to have experienced symptoms possibly consistent with the serotonin syndrome. Only two patients (0.04%) experienced symptoms considered to be serious. No deaths were reported. We also reviewed all published case reports and adverse experiences reported to the U.S. Food and Drug Administration and the manufacturer of Eldepryl. Available information indicates that serious adverse experiences resulting from the combined use of deprenyl and an antidepressant medication in patients with PD are quite rare and that the frequency of the true "serotonin syndrome" is even rarer.

Aged↗

Pharmacological options for the management of dyskinesias.

Dyskinesias are abnormal involuntary movements characterised by an excessive amount of movement. Typically, these movements are choreiform in nature. They may be caused by systemic, metabolic, endocrinologic, structural, vascular, infectious or inherited degenerative conditions, or be toxin- or drug-induced. With many non-drug-induced dyskinesias, treatment of the underlying condition may be sufficient to eliminate the movements, although temporary treatment may be required to control the movements if they are severe. Drug-induced dyskinesias often resolve when the offending drug is discontinued. A notable exception is tardive dyskinesia, which is caused by exposure to dopamine receptor blocking drugs, the majority of which are antipsychotic agents. Tardive dyskinesias will persist, or may even develop after the causative agent has been stopped and may not spontaneously remit. Another commonly encountered form of drug-induced dyskinesia is seen in patients with Parkinson's disease who are receiving levodopa. Medications which deplete dopamine are most successful in treating choreiform dyskinesias, although anticholinergics, GABAergics, serotonergics, and calcium channel blocking agents have been reportedly beneficial in some cases. Treatment of levodopa-induced dyskinesias requires manipulation of the patient's antiparkinsonian drug regimen.

Adrenergic Uptake Inhibitors↗

Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions.

Chronic rats, prepared with unilateral injections of kainic acid in the left basal forebrain, displayed prominent large amplitude slow wave activity in the neocortex ipsilateral to the injection. Oxotremorine and pilocarpine, given systemically following pretreatment with methyl scopolamine to block peripheral muscarinic effects, restored low voltage fast activity (LVFA) in a dose-related manner. Oxotremorine was more potent than pilocarpine. Arecoline was not consistently effective. Tetrahydroaminoacridine abolished abnormal 4-6 Hz rhythmical slow waves in the left neocortex but had little effect on large amplitude irregular slow waves. Direct-acting cholinergic agonists can restore near-normal neocortical activity after extensive cholinergic deafferentation of the neocortex.

Animals↗

From beginner to expert: gaining a differentiated clinical world in critical care nursing.

The purpose of this study was to further explicate the Dreyfus Model of Skill Acquisition in the practice of critical care nursing. For this analysis data were used from a sample of 105 nurses practicing in the adult, pediatric, and newborn intensive care units of eight hospitals in three metropolitan areas. The data were composed of group interviews in which nurses gave narrative accounts of exemplars from their practice and close observations and intensive personal history interviews of a subsample of nurses. Two interrelated aspects were found to distinguish four levels of practice, from advanced beginner through expert. First, practitioners at different levels of skill literally live in different clinical worlds, noticing and responding to different directives for action. Second, a sense of agency is determined by one's clinical world and shows up as an expression of responsibility for what happens with the patient.

Clinical Competence↗