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Biomedical subjects

K Lyons

Publications and source records attributed to K Lyons.

At least 37 records · Page 2Linked to original sources

Practice parameter: risk of driving and Alzheimer's disease (an evidence-based review) [RETIRED]: report of the quality standards subcommittee of the American Academy of Neurology.

Studies of automobile accident frequency among drivers with AD have yielded conflicting results about the risk of accidents. To develop a practice parameter regarding driving and AD the authors performed a systematic review of the literature. The authors identified well-designed, controlled studies of driving and AD using the National Library of Medicine's MEDLINE database. The authors also compared the relative rates of crashes and other performance measurements of driving ability in the populations studied. Driving was found to be mildly impaired in those drivers with probable AD at a severity of Clinical Dementia Rating (CDR) 0.5. This impairment was no greater than that tolerated in other segments of the driving population (e.g., drivers age 16 to 21 and those driving under the influence of alcohol at a blood alcohol concentration [BAC] < 0.08%). Drivers with AD at a severity of CDR 1 were found to pose a significant traffic safety problem both from crashes and from driving performance measurements.

Academies and Institutes↗

Early detection of probable idiopathic Parkinson's disease: II. A prospective application of a diagnostic test battery.

We developed a battery of tests, incorporating motor function, olfaction, and mood, that distinguishes between early mild, probable idiopathic Parkinson's disease (iPD), and normal control subjects. Here, we determined the PD Battery's ability to prospectively identify which patients with symptoms and signs suggestive of, but not yet diagnostic of, iPD who would subsequently be diagnosed as having iPD. Of 212 enrolled patients, 194 have been followed for at least 1 year. Among these 194, 59 were diagnosed with iPD, 40 as neurologically normal, and the remaining 106 with other neurologic conditions such as essential tremor. The test battery was 92% specific and 68% sensitive for iPD. The area under the Receiver Operating Characteristics curve was 0.88 for predicting which participants would subsequently be diagnosed as having iPD or as being neurologically normal.

Adult↗

Motor initiation and execution in essential tremor and Parkinson's disease.

Clinical differentiation of essential tremor (ET) from idiopathic Parkinson's disease (iPD) is based on the lack of akinesia and bradykinesia. Nevertheless, early tremor-predominant iPD often is difficult to distinguish from ET. Motor initiation and execution in ET, iPD, and normal control (NC) subjects were investigated. Individuals with iPD, ET and NC performed a reaction-time wrist flexion and extension task. Motor performances were similar between ET and iPD and both were different than normal control subjects. Both the patients with iPD and ET had longer reaction times and slower movement velocities than NC subjects. This may help to explain some of the difficulties in distinguishing patients with these two diseases. The similarities of motor performance suggest that while ET and iPD may be separate disease entities, they may share similar pathogenic motor mechanisms from the perspective of an integrated motor system that drives the motor cortex.

Adult↗

Sentence repetition and processing resources in Alzheimer's disease.

Sentence processing in Alzheimer's disease (AD) has been found to be influenced by several grammatical and extragrammatical factors, including phrase structure and verb-argument relations, number of propositions/verbs, and processing resource capacity. This study examines the effects of these variables on sentence production in AD. Normal control and AD subjects were asked to repeat six types of sentences varying along the above dimensions of complexity. Subjects' processing resource capacity was measured using several verbal working memory tests. AD subjects' sentence-repetition performance was impaired compared to the normal control group. Significant effects were observed for branching direction of phrase structure, canonicity of verb-argument relations, and serial position of errors. Sentence-repetition performance significantly correlated with working memory scores. The findings are interpreted within a resource capacity theory of sentence processing.

Aged↗

The use of ultrasound in the diagnosis of invasive lobular carcinoma of the breast less than 10 mm in size.

AIM: To assess the ability of ultrasound to detect small (<10 mm) invasive lobular carcinoma (ILC) of the breast. Previous reporters have suggested very low sensitivity rates for identifying these tumours on ultrasound. We reviewed our own experience to see how our figures compared. MATERIALS AND METHODS: We retrospectively analysed all cases of pure small ILC diagnosed at Breast Test Wales over the first 9-year period of the National Health Breast Screening Programme. All mammograms and ultrasound examinations were reviewed and findings assessed. We also obtained similar information on small invasive ductal carcinoma (IDC) for comparison. RESULTS: Sixteen cases of pure small ILC were diagnosed during the study period. Fourteen of the 15 patients (93%) who underwent an ultrasound examination had abnormal findings. A definitive pre-operative diagnosis using ultrasound guided sampling was obtained in all 14 patients. A larger number of small IDCs (152) were diagnosed during the same study period and the sensitivity of ultrasound in this group was recorded as 80%. CONCLUSION: Our findings suggest a much higher sensitivity for ultrasound in the detection of small ILC than has been previously described. Its use should be encouraged particularly as it facilitates biopsy and pre-operative diagnosis.

Aged↗

Pallidotomy microelectrode targeting: neurophysiology-based target refinement.

OBJECTIVE: Microelectrode recording can refine targeting for stereotactic radiofrequency lesioning of the globus pallidus to treat Parkinson's disease. Multiple intraoperative microelectrode recording/stimulating tracks are searched and assessed for neuronal activity, presence of tremor cells, visual responses, and responses to kinesthetic input. These physiological data are then correlated with atlas-based anatomic data to approximate electrode location. On the basis of these physiological properties, one or more tracks are selected for lesioning. This study analyzes the track physiological factors that seem most significant in determining the microelectrode recording track(s) that will be chosen for pallidal lesioning. METHODS: Thirty-six patients with Parkinson's disease underwent microelectrode-guided pallidotomy. Between one and five microelectrode recording tracks were made per patient. Usually, one (n = 23) or two (n = 12) of these tracks were lesioned. Electrode positions in the x (mediolateral) and y (anteroposterior) axes were recorded and related to track neurophysiological findings and final lesion location. The stereotactic location and sequence of microelectrode tracks were recorded and plotted to illustrate individual search patterns. These patterns were then compared with those noted in other patients. Neurophysiological data obtained from recording tracks were analyzed. A retrospective analysis of track electrophysiology was performed to determine the track characteristics that seemed most important in the surgeon's choice of the track to lesion. Track physiological properties included general cell spike amplitude, tremor synchronous neuronal firing, kinesthetically responsive neuronal firing, and optic track responses (either phosphenes reported by the patient during track microstimulation or neuronal firing in response to light stimulus into the patient's eyes). Orthogonally corrected postoperative magnetic resonance images were used to confirm the anatomic lesion locations. RESULTS: In patients who had a single mapped track lesioned, specific track electrophysiological characteristics identified the track that would be lesioned most of the time (20 of 24 patients). Tracks that exhibited a combination of tremor synchronous firing, joint kinesthesia, and visual responsivity were lesioned 17 (85%) of 20 times. Analysis of intraoperative electrode movement in the x and y axes indicated a significant subset of moves but did not result in microelectrode positioning closer to the subsequently lesioned track. Accuracy of initial electrode movement in the x and y axes was most highly correlated with a measure of first-track electrophysiological activity. The number of microelectrode recording tracks did not correlate with clinical outcome. Anatomic analysis, using postoperative magnetic resonance imaging, revealed that all lesions were placed in the globus pallidus. Most patients (35 of 36) improved after surgery. CONCLUSION: The level of electrophysiological activity in the first track was the best predictive factor in determining whether the next microelectrode move would be closer to the ultimately lesioned track. The analysis of electrode track location and neurophysiological properties yields useful information regarding the effectiveness of microelectrode searching in the x and y axes. Within an institution, the application of this modeling method may increase the efficiency of the microelectrode refinement process.

Aged↗

Early detection of probable idiopathic Parkinson's disease: I. Development of a diagnostic test battery.

We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87.

Adult↗

Surgical treatment of essential tremor.

Surgical treatment for essential tremor (ET) has been used since the early 1950s. Initially, different areas were targeted for tremor control. However, the optimal target was eventually determined to be the ventralis intermedius (VIM) nucleus of the thalamus. Thalamotomy improves contralateral tremor in more than 90% of patients. Long-term studies of thalamotomy indicate that the benefits continue in most patients. Persistent morbidity associated with thalamotomy, which occurs in less than 10% of patients, includes dysarthria, dysequilibrium, weakness, and cognitive impairment. Bilateral thalamotomy is associated with substantial morbidity and is usually avoided. Studies demonstrate that chronic stimulation of the VIM is safe and effective for tremor. Adverse effects of chronic stimulation include paresthesia, dysarthria, dysequilibrium, and localized pain. In many patients, bilateral thalamic stimulation is performed without a substantial increase in morbidity. ET patients with disabling medication-resistant tremor are reasonable candidates for these stereotactic procedures.

Essential Tremor↗

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. METHODS: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. CONCLUSIONS: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Aged↗

Abnormal performance on the PD test battery by asymptomatic first-degree relatives.

OBJECTIVE: To determine whether a sensitive and specific battery of tests (PD Battery) could identify a subset of asymptomatic first-degree relatives (FDRs) of PD patients who were significantly more impaired than age-matched normal control (NC) subjects. The PD Battery incorporates tests of motor function, olfaction, and mood. In previous studies, it has shown high specificity and sensitivity in distinguishing mildly affected PD patients from NC subjects. METHODS: The PD Battery and regression analysis-derived scoring equations were applied to asymptomatic FDRs. RESULTS: Eighty FDRs and 100 NC subjects were tested. Of the FDRs, 22.5% scored in the abnormal range, and 9% of NC subjects had abnormal scores. This difference was statistically significant. Further analysis demonstrated that FDRs with abnormal scores on the PD Battery differed on all three components of the test battery from FDRs who had normal scores. Among the sons and daughters whose scores were abnormal, there was a much higher prevalence of the affected parent being the father. CONCLUSIONS: The proportion of FDRs who demonstrated abnormal performance on the PD Battery was greater than that of NC subjects. Thus, the PD Battery may detect the asymptomatic carrier state or risk for PD. Sons and daughters whose scores were in the abnormal range were more likely to have fathers with PD.

Adult↗

Integrating qualitative and quantitative liquid chromatography/tandem mass spectrometric analysis to support drug discovery.

During the early phase of a drug discovery process, in order to facilitate the selection of drug candidates from a discovery research program, a liquid chromatography tandem mass spectrometry (LC/MS/MS) strategy has been developed to assess the preliminary pharmacokinetics and metabolism of new drug entities. For pharmacokinetic studies using multiple reaction monitoring (MRM), the parent drug concentration and its 'suspected' (predictable) metabolites were monitored in the biological samples simultaneously. For metabolic identification, the general methodologies most frequently used to search for metabolites include full scan, precursor-ion scan, product-ion scan and neutral-loss scan. However, when the metabolites do not produce intense signals for tandem mass spectrometry, a more sensitive and selective assay has to be developed, and MRM would be the method of choice. Likewise, an intelligent guess as to which MRM transitions ought to be used for the metabolites will be considered, based on the product ion mass spectrum of the parent drug.

Acetonitriles↗

The National Breast Referral Guidelines have cut down inappropriate referrals in the under 50s.

AIMS: When the National Breast Referral Guidelines were applied to our local GPs letters immediately prior to their release in January 1996, it was shown that on the basis of the GPs own conclusions that 29% of symptomatic women could have been managed initially by their own GP without missing any carcinomas. We conducted this study at the Rapid Access Breast Clinic at the University Hospital of Wales to determine if the breast referral practices of local GPs have altered due to the breast referral guidelines. METHODS: We studied 2332 referrals from the inception of the Rapid Access Clinic in May 1995 to the issue of the guidelines, and 2421 referrals from May 1996 to the end of the year. Random samples of 600 patients were drawn from each year and the referral letters were scored as within or outside the guidelines. Family history patients were excluded. RESULTS: There was an 11% fall in referrals outside the guidelines in the under 50s (chi-squared=<0.001) but the 7% fall in the over 50s was not significant. CONCLUSIONS: The Breast Referral Guidelines seem to have been effective in reducing the higher level of inappropriate referrals in younger patients at less risk of carcinoma.

Age Factors↗

Psychological distress associated with waiting for results of diagnostic investigations for breast disease.

This paper presents the results of a multi-method research project investigating the psychological distress associated with waiting for results of diagnostic investigations in a delayed-results breast clinic. A cohort of 126 women completed standardized psychometric instruments to assess anxiety, mood and coping over 3 days. Semi-structured interviews were conducted with 20 respondents. The findings indicate that waiting sustained but did not exacerbate psychological distress. Peri-diagnostic anxiety, depression, uncertainty and confusion were associated with anxiety levels immediately following triple assessment. Women leaving the clinic with low anxiety retained this composure throughout the peri-diagnostic period. Those in the moderate and high anxiety groups recorded sustained anxiety, depression, uncertainty and confusion, with mean scores comparable to and exceeding those reported by psychiatric out-patients. Coping during the waiting period was typically accomplished by emotion-focused strategies. Qualitative data suggested the delayed-results clinic structure may facilitate psychological preparation for test results.

Journal Article↗

Adenosine challenge and boost protocols: new tools for myocardial perfusion imaging.

The validity of pharmacologic stress testing and subsequent myocardial perfusion imaging is uncertain in those patients who may have taken caffeine within the 24 hours before testing. For such patients, two new challenge tests have been developed. An intravenous bolus dose of adenosine is given at a dose of 6 mg in a period of 1 or 2 seconds. A physiologic response qualifies the patient to proceed with the scheduled stress test. In the occasional patient who exhibits no pharmacologic symptoms during an infusion test, a similar bolus dose of 6 mg adenosine can validate perfusion tests. These two applications are successful regardless of whether adenosine or dipyridamole infusions are performed. Based on this multicenter experience over 4 years, the authors estimate that 5% to 10% of patients undergoing pharmacologic testing are appropriate candidates for a challenge test.

Adenosine↗

Double-blind controlled trial of gabapentin in essential tremor.

Gabapentin has been reported to be effective for essential tremor (ET) based on open-label trials. We studied gabapentin (1800 mg/day) and placebo in a double-blind crossover design in 20 ET patients. Eighteen patients completed the study and two patients dropped out as a result of adverse effects which resolved when the medication was discontinued. Tremor was assessed at baseline and after 2 weeks of gabapentin and placebo treatment. One patient was mildly improved and another was moderately improved with placebo. Similarly, one patient reported mild improvement and another patient had marked improvement with gabapentin. All the remaining patients either reported no change or were worse with both treatment arms. There was no significant difference for total tremor score, hand tremor score, handwriting scores, or pouring scores. Sickness Impact Profile scores were no different between placebo and gabapentin. Our results suggest that as an adjuvant therapy in ET, gabapentin has limited benefit.

Acetates↗

Magnetic resonance imaging of acute intraosseous disc herniation.

Schmorl's nodes, the result of previous intraosseous disc herniation (IODH), are a common incidental finding on plain radiographs, computed tomography (CT) and magnetic resonance imaging (MRI). Acute IODH can, however, cause severe back pain, and the radiological features may also lead to inappropriate suspicion of malignancy or infection. We present eight cases of acute IODH in order to illustrate how the correct diagnosis can be made by MRI. In six cases isotope bone scintigraphy had been performed, demonstrating focal increased activity at the site of IODH. MRI can reinforce the concern about serious underlying pathology by the demonstration of marrow oedema, which may be localized around the disc herniation or extensive, extending throughout the vertebral body and into the pedicles. The key to the correct diagnosis is the recognition of the endplate defect and disc herniation. In three cases the diagnosis may have been possible from plain radiographs in which disc calcification visible on previous radiographs had migrated into an intraosseous location.

Acute Disease↗

MR imaging of suspected acute spinal instability.

Twenty-two patients with suspected acute vertebral instability were imaged within 48 h of injury using a 0.5 Tesla magnet. In all patients plain radiographs, T1 weighted gradient echo (GE) and STIR sequences were performed. Two radiologists blindly evaluated the magnetic resonance imaging (MRI) scans defining injuries with bony or soft tissue disruption of both columns as unstable. Indirect signs of instability such as soft tissue haemorrhage were recorded and correlated where possible with operative findings. Sixteen patients were radiologically unstable on MRI, five more than on plain films alone. Instability was confirmed operatively in 10 patients. The six other patients with unstable injuries were treated conservatively. Two of these patients had evidence of increased deformity before fracture union. The radiologically stable patients were treated as such and at 6-month review showed no evidence of progressive instability. The presence of soft tissue haemorrhage in the interspinous gap was not associated with ligament rupture unless actual discontinuity was demonstrated at that level. We conclude that using MRI acutely, most unstable spinal injuries can be rapidly and accurately evaluated without the need for further imaging.

Acute Disease↗

Cricothyroid joint injury.

Cricothyroid joint injuries may result in severe voice dysfunction and may be associated with laryngeal pain. Otolaryngologists and radiologists should be familiar with this rarely recognized injury.

Adult↗