Sequence interpretation. Functional annotation of mouse genome sequences.
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Biomedical subjects
Publications and source records attributed to D Kingsley.
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The aim of this study was to review a Level 1 trauma center's use of early (< 72 hours from injury) limited MRI to "clear" cervical spine extradural soft tissue injuries in ICU patients sustaining blunt trauma. A retrospective review of the records of patients meeting entry criteria during 1997 was performed. Demographic data, cervical spine radiographic and imaging evaluation, results, and follow-up information were gathered. One hundred and fifty patients met criteria. Forty-one patients had initial static radiographs that revealed cervical spine trauma. Twenty-seven of the 108 patients with normal initial static radiographs had evidence of extradural soft tissue injury on MRI indicating potential spinal column instability. Twenty-one of the 108 patients had negative MRI and were liberated from cervical spine precautions at a mean of 2.9 +/- 0.9 days from injury. The remaining patients were cleared of cervical spine precautions by plain radiographs and reliable clinical examinations, or by dynamic radiographs, or they died before complete evaluation. The diagnosis of acute injury to the cervical spine from blunt trauma in ICU patients must include evaluation of the osseous spine and extradural soft tissues. Dynamic studies such as flexion and extension views place the obtunded ICU patient at risk of potential neurologic injury. MRI is a noninvasive imaging technique that allows evaluation of extradural soft tissue injury with potentially less patient risk and with fewer personnel. MRI allows early liberation of cervical spine precautions in those patients with negative studies. Further studies are needed to compare specific ligamentous injury patterns by MRI with dynamic studies of the C-spine to further define MRI injury patterns indicating risk of acute spinal instability.
BACKGROUND: If they are to be replicable, MRI volume measurements require explicit definitions of structures and of criteria for delineating these structures on MRI. Previously published volumes in healthy subjects show considerable differences in measurements across different studies, including a fourfold variation in estimates of hippocampal volume. Previous neuroimaging reports in patients with Korsakoff syndrome have generally found widespread or non-specific change, whereas in patients with herpes encephalitis the extent of pathological involvement reported beyond the temporal lobes has varied. METHOD: In the present study, a clear set of anatomical criteria and detailed MRI segmentation procedures were applied to measure whole brain, frontal and temporal lobe, and anterolateral and medial temporal volumes, as well as thalamic areas in patients with organic amnesia (from Korsakoff's syndrome, herpes encephalitis, and focal frontal lesions) as well as healthy controls. RESULTS: Patients with Korsakoff's syndrome showed decreased thalamic measurements but no significant changes in the medial temporal lobes, whereas patients with herpes encephalitis showed severe medial temporal but not thalamic atrophy. In the patients with known frontal lobe lesions, quantitative analysis on MRI showed reduced frontal lobe volume but no significant temporal lobe or thalamic atrophy. CONCLUSION: Quantified MRI can be a useful technique with which to examine brain-cognitive relations, provided that detailed techniques are explicitly described. In particular, specific patterns of volume change can be found in vivo in patients with Korsakoff's syndrome and those with herpes encephalitis.
BACKGROUND: Cognitive-MRI correlations have often been studied in disorders in which there are multiple cognitive deficits and widespread cortical atrophy, such as Alzheimer's dementia. In such circumstances, the interpretation of any single cognitive-structural correlation is equivocal. Only by measuring differing cognitive functions and a wide range of brain structures in patients with a varying distribution of lesions or atrophy can specific brain-cognitive relations be determined in neurological disorder. METHOD: In the present study, a clear set of anatomical criteria and detailed MRI segmentation procedures were applied to measure whole brain, and left and right frontal, temporal lobe, anterolateral and medial temporal volumes, as well as thalamic cross sectional areas in 40 patients with organic amnesia (from various diseases) and 10 healthy controls. RESULTS: Within the total patient group, anterograde memory measures correlated significantly with medial temporal, hippocampal, and thalamic measurements. A spatial memory measure correlated significantly with hippocampal volume, and temporal context memory with frontal volume. After a factor analysis of the cognitive measures, the association between anterograde memory and hippocampal volume was corroborated. Forgetting rates and subjective memory evaluations did not show any significant MR correlations and, of executive tests employed, only card sorting categories correlated significantly with frontal volume. CONCLUSION: Loss of volume in key brain structures (for example, hippocampus, thalamus) is detectable on quantitative MRI, and this loss of volume correlates significantly with impaired performance on measures of anterograde memory function. Correlations with hippocampal volume did not indicate a specific role in either recall or verbal memory, as opposed to recognition or visual memory.
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Patients with focal diencephalic, temporal lobe, or frontal lobe lesions were examined on various measures of remote memory. Korsakoff patients showed a severe impairment with a characteristic 'temporal gradient', whereas two patients with focal diencephalic damage (and anterograde amnesia) were virtually unimpaired on remote memory measures. Patients with frontal lobe pathology were severely impaired in the recall of autobiographical incidents and famous news events. Patients with temporal lobe pathology showed severe impairment but a relatively 'flat' temporal gradient, largely attributable to herpes encephalitis patients. From recognition and cued recall tasks, it is argued that there is an important retrieval component to the remote memory deficit across all the lesion groups. In general, the pattern of performance by the frontal lobe and temporal lobe groups was closely similar, and there was no evidence of any major access/storage difference between them. However, laterality comparisons across these groups indicated that the right temporal and frontal lobe regions may make a greater contribution to the retrieval of past episodic (incident and event) memories, whereas the left temporal region is more closely involved in the lexical-semantic labelling of remote memories.
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BACKGROUND: This study presents intermediate follow-up data on a randomized prospective series of patients undergoing either a modified laparoscopic intraperitoneal onlay mesh herniorrhaphy (IPOM) or conventional anterior inguinal herniorrhaphy (CH). METHODS: All patients from two university affiliated hospitals with primary or recurrent inguinal hernias were recruited for randomization to either the IPOM technique utilizing a meshed expanded polytetrafluorethylene (ePTFE) soft tissue patch or CH. Follow-up data were gathered from postoperative clinic visits and telephone and mail surveys. RESULTS: Previously reported early recurrence and complication rates at a mean follow-up of 8 months were 1 of 30 (3%) and 5 of 30 (17%) for IPOM, and 2 of 28 (7%) and 5 of 28 (18%) for CH. Intermediate follow-up with 50 (23 IPOM and 27 CH) of the original 58 patients (86%) at a mean of 41 months reveals a recurrence rate of 10 of 23 (43%) for the IPOM group and 4 of 27 (15%) for the CH group (P = 0.053). Five delayed complications occurred in 4 IPOM patients (port site hernia 4, painful neuroma 1), while 2 delayed complications (unilateral testicular atrophy 2) occurred in 2 patients in the CH group. One IPOM versus 5 CH patients subsequently developed previously unrecognized contralateral hernias. There was 1 death unrelated to previous herniorrhaphy in each group. CONCLUSIONS: IPOM recurrence rates (43%) at a mean follow-up of 41 months are excessively high when compared with CH (15%) or with preliminary results of IPOM at 8 months of follow-up (3%). Despite reduced perioperative pain and disability and promising preliminary results in the IPOM group, these intermediate follow-up data strongly suggest that the IPOM technique should not be used for repair of inguinal hernias.
OBJECTIVES: To determine the sensitivity, specificity, and positive predictive values of a selection of abnormal findings in the putamen and infratentorial structures on routine magnetic resonance imaging for distinguishing between multiple system atrophy, idiopathic Parkinson's disease, and age matched controls. PATIENTS AND METHODS: Two neuroradiologists blindly and independently rated axial T2 weighted and proton density MRI of 44 patients with multiple system atrophy, 47 patients with idiopathic Parkinson's disease, and 45 controls. High field (1.5 T) scans were available in 16 patients with multiple system atrophy, 15 patients with idiopathic Parkinson's disease, and 16 controls. All other patients had 0.5 T scans. RESULTS: On both 0.5 and 1.5 T scans the following items had high specificity but low sensitivity: putaminal atrophy, a hyperintense putaminal rim, and infratentorial signal change. Finding any infratentorial abnormality gave higher sensitivity but lower specificity. Putaminal isointensity or hypointensity relative to globus pallidus, absolute putaminal hypointensity, and altered size of the olives were not useful discriminators. The overall sensitivity was 73% on 0.5 T and 88% on 1.5 T scans. The specificities of these findings for multiple system atrophy in comparison to idiopathic Parkinson's disease and controls on 0.5 T were 95% and 100% respectively, and on 1.5 T were 93% and 91% respectively. Finding any of the described abnormalities on MRI gave a positive predictive value of 93% on the 0.5 T machine, and 85% on the 1.5 T scanner.
Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.
Volumetric measurement of the hippocampus is of use in localisation of lesions causing focal epilepsy and in lateralisation of epilepsy due to mesial temporal sclerosis. However, it is time consuming and requires specialised equipment. Hence, we compared volumetric measurement with visual detection of hippocampal asymmetry by five trained observers. MRI studies of 19 neurologically normal subjects and of 34 consecutive patients with epilepsy and hippocampal volume ratios below the lowest normal value were employed. Agreement between visual and quantitative diagnoses was 59% for all subjects (kappa = 0.38) and 65% for those with volumetric hippocampal asymmetry. Disagreements in visual and volumetric lateralisation of hippocampal asymmetry were relatively uncommon. Visual estimates of the extent of hippocampal involvement and the observers' confidence in the diagnosis influenced the accuracy of visual inspection. However, discordance in diagnoses occurred even when confidence in the visual diagnosis was high. Reliable visual detection occurred for hippocampal volume ratios below 0.7, suggesting that visual determination of hippocampal asymmetry is of greatest clinical value in the lateralisation of seizure foci in patients already selected for the presence of intractable temporal lobe epilepsy. Volumetric measurements are particularly important if hippocampal asymmetry is used for seizure localisation in groups of patients with temporal or extratemporal epilepsy.
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Ocular motor apraxia (OMA) is a clinical sign involving the intermittent inability to initiate saccades, and a failure of quick phases during optokinetic nystagmus (OKN) and vestibular nystagmus (VN). Some patients have no other associated abnormalities (idiopathic), whereas others have a variety of neurological conditions. We quantified the severity of the saccade failure and correlated it with neuro-radiological and other oculomotor findings in 62 children (aged 17 days - 14 years). Saccades, smooth pursuit, OKN and VN were recorded using electrooculography and the extent of "locking up" (absent quick phases during OKN and VN) was measured. Saccades were usually hypometric. Pursuit and OKN gains were normal in the majority of the idiopathic cases but were low in those with other neurological conditions. Twenty-four patients had essentially normal scans, whereas 38 had abnormal scans: Delayed myelination, cerebellar abnormalities (particularly involving the vermis), and agenesis of the corpus callosum were the most common findings. A significant positive correlation was present between increasing neuro-radiological deficits and severity of "locking up" during OKN. Principal component analysis showed that brainstem and cerebellar vermis abnormalities were the main factors involved. A pathophysiological basis of OMA is discussed in the light of animal and clinical studies.
Cranial computer tomographic (CT) images of 33 patients with multiple system atrophy (MSA) and of 40 age-matched controls were blindly analyzed by two neuroradiologists. All patients had autonomic dysfunction, all but one had parkinsonism, and 13 had cerebellar signs. The scans were judged entirely normal in 21%. Moderate or severe infratentorial atrophy was found in 42%. Cerebellar atrophy was present in 39%, and pontine atrophy was present in 18%. Of the 13 patients with cerebellar signs, only eight had cerebellar atrophy. Of the 20 patients without cerebellar signs, five had cerebellar atrophy. Supratentorial involvement was much less common and less severe. Thus, CT demonstrated system involvement that was not evident clinically in five of 33 cases (15%). However, in all five the clinical diagnosis was already evident from the presence of both autonomic and pyramidal signs in addition to parkinsonism. We conclude that CT imaging is of limited diagnostic use in individual patients with MSA.
Overexpression of glycoprotein-encoding genes in Escherichia coli sometimes results in toxicity to the host and low protein yields. One possible explanation for this phenomenon is the presence of hydrophobic amino acid (aa) domains approx. 15-20 aa in length in the overproduced protein. As an initial test of this hypothesis, regions of hydrophobicity located within the envelope glycoproteins of HIV-1 and HTLV-1 were identified by computer analysis, and subsequently deleted by site-directed mutagenesis. The parent and modified envelope genes were expressed in bacteria using both lambda pL and T7 inducible expression systems. Removal of the hydrophobic domains reduced the apparent toxicity and significantly increased the accumulation of recombinant protein from undetectable levels to approx. 10-15% of total cellular protein.
The CT and MRI appearances of 5 patients with Cockayne's syndrome, 5 with ataxia telangiectasia and 1 with Fanconi's anaemia are reported. These conditions, together with Bloom's syndrome and xeroderma pigmentosum are regarded as disorders of DNA repair. Characteristic CT and MRI features of Cockayne's syndrome include generalised atrophy, calcification in basal ganglia and dentate nuclei and white matter low density. Neuroradiological findings in the other DNA repair disorders are nonspecific.
In the planning of MRI protocols to monitor disease activity in multiple sclerosis (MS), the clinical subtype needs to be considered. In this serial gadolinium-enhanced MRI study, we demonstrated differences between patients with early relapsing/remitting MS and benign MS in both the production of new lesions and the occurrence of enhancement.