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PubMed2001

QT dispersion within the first 6 months after an acute myocardial infarction: relationship with systolic function, left ventricular volumes, infarct related artery status and clinical outcome.

INTRODUCTION: We analysed QT dispersion within the first 6 months postinfarction, its relationship with the main established risk stratifiers and its clinical value. METHODS AND RESULTS: In 55 patients with a first Q-wave myocardial infarction the 12-lead electrocardiogram was scanned and digitised for analysis of QT dispersion (QT maximum-QT minimum) at first day (72 [61-96] ms), first week (69 [47-90] ms), first month (67 [46-88] ms) and sixth month (47 [40-74] ms; P<0.0001 vs. first day). Cardiac catheterization was performed at first week and at sixth month; QT dispersion was not related to ejection fraction, left ventricular volumes, infarct related artery status or contractile reserve (improvement of the infarcted area with low-dose dobutamine); no relation was found between QT dispersion decrease from first week to sixth month with regional systolic function improvement. Finally, during a mean follow-up period of 35+/-22 months QT dispersion was not independently related to clinical events. CONCLUSION: QT dispersion decreases progressively during the first months after myocardial infarction. These changes should be taken into account to define cut-off values of clinical interest in this phase. This variable does not seem related to the classic prognosis predictors. In a nonselected postinfarction population it has a low clinical value.

Coronary Vessels↗

PubMedDate not supplied

The growth and metastasis of four commonly used tumour lines implanted into eight different sites: evidence for site and tumour effects.

The growth and metastasis of four commonly used experimental tumour lines have been compared after the implantation of cells into a lobe of the liver, the spleen, the left kidney, the peritoneal cavity, the thorax, the right thigh muscle, subcutaneously into the dorsolumbar region and intravenously into the tail vein or the right femoral vein. This was done to assess the importance of site in affecting metastatic distribution, and to determine whether any general conclusions could be drawn as to the role of this factor. Tumours grew at variable rates in different sites, but this did not affect the extent or distribution of metastasis. Each line gave a characteristic pattern that could be considerably modified by site. For example, in the spleen, metastasis was always extensively to the liver; in the kidney, and to some extent in the muscle, metastasis was similar to that obtained for intravenously injected cells; in the peritoneal cavity or thorax, metastasis was usually lower than from other sites; and in the liver, the metastasis to other lobes of the liver and to the lungs was modified. Many of these findings could be explained by both specific and non-specific factors operating at each site. It is suggested that interactions at the primary site of tumour growth may be very important in affecting metastasis, and that in the future more attention should be given to this factor in order to make progress in understanding tumour spread.

Animals↗

PubMed2002

Anatomically standardised 99mTc-ECD brain perfusion SPET allows accurate differentiation between healthy volunteers, multiple system atrophy and idiopathic Parkinson's disease.

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion single-photon emission tomography (SPET) with anatomical standardisation and automated analysis in the differentiation of IPD and MSA. This was achieved by discriminant analysis in comparison with a large set of age- and gender-matched healthy volunteers. Technetium-99m ethyl cysteinate dimer SPET was performed on 140 subjects: 81 IPD patients (age 62.6+/-10.2 years; disease duration 11.0+/-6.4 years; 50 males/31 females), 15 MSA patients (61.5+/-9.2 years; disease duration 3.0+/-2.2 years; 9 males/6 females) and 44 age- and gender-matched healthy volunteers (age 59.2+/-11.9 years; 27 males/17 females). Patients were matched for severity (Hoehn and Yahr stage). Automated predefined volume of interest (VOI) analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Between MSA and IPD, the only regions with highly significant differences in uptake after Bonferroni correction were the putamen VOIs. Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3%, a specificity of 84% and an accuracy of 83.6%. Additional input from the right caudate head and the left prefrontal and left mesial temporal cortex allowed 100% discrimination even after cross-validation. Discrimination between the IPD group alone and healthy volunteers was accurate in 94% of the cases after cross-validation, with a sensitivity of 91.4% and a specificity of 100%. The three-group classification (MSA, IPD and healthy volunteers) resulted in an overall accuracy of 86% post hoc, with 98% of normals, 78% of IPD and 93% of MSA correctly classified. These values were slightly lower after cross-validation: 96% for healthy volunteers, 77% for IPD and 67% for MSA. In conclusion, using age- and gender-matched healthy volunteer data and anatomical standardisation, it is possible to differentiate between IPD and MSA with high discriminating power in clinically relevant circumstances.

Brain↗

PubMed2002

Apolipoproteins E and C1 and brain morphology in memory impaired elders.

Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

Aged↗

PubMed1987

Examination of cardiac alpha-adrenoceptors from pharmacological responses and radioligand binding. Comparison of rat and guinea pig tissues.

The object of this study was to determine suitable experimental conditions for the pharmacological evaluation of cardiac alpha-adrenoceptors. Atrial and ventricular preparations of the guinea pig and rat were employed, and the alpha-adrenoceptor responsiveness was compared with the binding of the alpha-adrenoceptor radioligand [3H]prazosin in membranes prepared from these cardiac regions. The experimental variables examined were the pacing frequency, bath temperature, choice of agonist, and cardiac region. In guinea pig atria the optimum alpha-adrenoceptor-mediated positive inotropic response to phenylephrine was at 32 degrees C and a pacing frequency of 1 Hz. A comparison of phenylephrine with methoxamine showed that the former yielded biphasic concentration-response curves in guinea pig left atria; the lower portion was alpha-adrenoceptor mediated and the upper, more substantial portion, was beta mediated. Methoxamine produced monophasic curves due entirely to alpha-adrenoceptor stimulation and was therefore used for comparisons between rat and guinea pig tissues. Of the guinea pig tissues, only the left atrium produced positive inotropic responses. Negative chronotropy was obtained with right atria and negative inotropy with ventricular strips and papillary muscles. The rat tissues all responded with positive responses, the largest maximum being in the left atrium. Binding data showed a larger number of alpha-adrenoceptors in the rat tissues, of which the ventricles had the greatest number. The lack of response of guinea pig ventricular tissues was therefore reflected in the low binding. From this study, the most appropriate model for characterizing cardiac alpha-adrenoceptors is therefore the rat left atria at 32 degrees C and paced at 1 Hz with methoxamine as the agonist.

Animals↗

PubMed2006

Time-resolved fMRI of mental rotation revisited--dissociating visual perception from mental rotation in female subjects.

Functional neuroimaging studies have demonstrated that mental rotation paradigms activate a network of spatially distributed cortical areas rather than a discrete brain region. Although the neuro-anatomical nodes of the rotation network are well established, their specific functional role is less well identified. It was the aim of the present study to dissociate network components involved in the visual perception of 3D cubic objects from regions involved in their mental spatial transformation. This was achieved by desynchronizing the time course of the perceptional process (i.e., stimulus duration) from the duration of the cognitive process (i.e., reaction times) and by comparing these with the temporal characteristics of the hemodynamic response functions (HRFs) in regions of interest. To minimize intersubject variability, an all-female subject group was chosen for this investigation. Time-resolved fMRI analysis revealed a significant increase in the full width at half maximum (FWHM) of the HRF with reaction times in the supplementary motor area (pre-SMA), in the bilateral premotor cortex (PMd-proper), and in the left parietal lobe (PP). The FWHM in visual system components such as the bilateral lateral occipital complex (LOC) and dorsal extrastriate visual areas (DE) was constant across trials and roughly equal to the stimulus duration. These findings suggest that visual system activation during mental rotation reflects visual perception and can be dissociated from other network components whose response characteristics indicates an involvement in the mental spatial transformation itself.

Adult↗

PubMed2003

Cognitive reserve modulates functional brain responses during memory tasks: a PET study in healthy young and elderly subjects.

Cognitive reserve (CR) is the ability of an individual to cope with advancing brain pathology so that he remains free of symptomatology. Epidemiological evidence and in vivo neurometabolic data suggest that CR may be mediated through education or IQ. The goal of this study was to investigate CR-mediated differential brain activation in 17 healthy young adults and 19 healthy elders. Using nonquantitative H(2)(15)O PET scanning, we assessed relative regional cerebral blood flow while subjects performed a serial recognition memory task under two conditions: nonmemory control (NMC), in which one shape was presented in each study trial; and titrated demand (TD), in which study list length was adjusted so that each subject recognized shapes at approximately 75% accuracy. A factor score that summarized years of education and scores on two IQ indices was used as an index of CR. Voxel-wise, multiple regression analyses were performed with TD minus NMC difference PET counts as the dependent variable and the CR variable as the independent variable of interest. We identified brain regions where regression slopes were different from zero in each separate group, and also those where regression slopes differed between the two age groups. The slopes were significantly more positive in the young in the right inferior temporal gyrus, right postcentral gyrus, and cingulate, while the elderly had a significantly more positive slope in left cuneus. Brain regions where systematic relationships between CR and brain activation differ as a function of aging are loci where compensation for aging has occurred. They may mediate differential ability to cope with brain changes in aging.

Adult↗

PubMed2004

Structure and assembly of the pseudopilin PulG.

The pseudopilin PulG is one of several essential components of the type II pullulanase secretion machinery (the Pul secreton) of the Gram-negative bacterium Klebsiella oxytoca. The sequence of the N-terminal 25 amino acids of the PulG precursor is hydrophobic and very similar to the corresponding region of type IV pilins. The structure of a truncated PulG (lacking the homologous region), as determined by X-ray crystallography, was found to include part of the long N-terminal alpha-helix and the four internal anti-parallel beta-strands that characterize type IV pilins, but PulG lacks the highly variable loop region with a disulphide bond that is found in the latter. When overproduced, PulG forms flexible pili whose structural features, as visualized by electron microscopy, are similar to those of bacterial type IV pili. The average helical repeat comprises 17 PulG subunits and four helical turns. Electron microscopy and molecular modelling show that PulG probably assembles into left-handed helical pili with the long N-terminal alpha-helix tightly packed in the centre of the pilus. As in the type IV pilins, the hydrophobic N-terminal part of the PulG alpha-helix is necessary for its assembly. Subtle sequence variations within this highly conserved segment seem to determine whether or not a type IV pilin can be assembled into pili by the Pul secreton.

Bacterial Proteins↗

PubMed2000

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates.

PURPOSE: A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. METHODS: Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. RESULTS: Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. CONCLUSIONS: These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.

Adult↗

PubMed2000

Digital analysis of myocardial contrast echocardiography: a clinical study using an air-filled agent in normal subjects.

The purpose of the present study was to determine whether direct digital image analysis would allow improved detection of myocardial contrast. Eighteen normal subjects were recruited and separated into two groups. In group 1, the time-brightness curves of the left ventricular cavity and three myocardial perfusion beds were formed from digitized video tape, with output power and imaging time as secondary variables. In group 2, curves constructed from direct polar digital data were compared, with fundamental and second harmonic image formation as variables. In group 1 subjects, using fundamental imaging, the area under the curve in the left ventricular cavity increased slightly with intermittent imaging. No consistent myocardial opacification was identified. In group 2 subjects, using intermittent imaging, the area under the myocardial curve and peak intensity increased with high output, second harmonic imaging in the left anterior descending and right coronary artery regions. Intermittent, second harmonic imaging and digital processing can demonstrate myocardial contrast even with an air-filled agent.

Adult↗

PubMed1985

Variations in the functional electrical coupling between the subendocardial Purkinje and ventricular layers of the canine left ventricle.

Action potential propagation from the subendocardial Purkinje network into the ventricular muscle is an essential link in cardiac activation. Studies of papillary muscles have indicated that ventricular muscle activation by the Purkinje network occurs only at discrete, localized regions near the papillary muscle base. Over the rest of the endocardial surface, however, the spatial distribution of these subendocardial Purkinje to ventricular muscle connections has been less well defined. We therefore studied in vitro 12 canine left ventricular preparations (eight from the septum, four from the lateral wall), using a high-density (1-mm spacings), high-resolution extracellular mapping technique to determine the subendocardial Purkinje and ventricular muscle activation sequences. These studies show that the distribution of subendocardial Purkinje to ventricular muscle electrical coupling is spatially inhomogeneous, and that the junctional regions themselves have variable degrees of electrical coupling. We also attempted to determine whether ventricular muscle coupling to the Purkinje network might influence Purkinje network conduction velocity. We found that on the papillary muscle apex, a region without direct Purkinje to ventricular muscle propagation, Purkinje network conduction velocity was slowed, suggesting that the Purkinje network might be electrically loaded by the underlying ventricular muscle. Finally, we performed numerical simulations using a model consisting of two layers of excitable cells to evaluate the effects that different electrical coupling patterns and/or different coupling resistivities between the two layers might have on activation of each layer. These simulation studies suggest that a coupling pattern having discrete junctional sites between the two layers (similar to our findings for subendocardial Purkinje to ventricular muscle coupling) is beneficial, as this arrangement allows more rapid activation of both layers by minimizing electrical loading of the thin Purkinje layer by the thicker ventricular muscle layer.

Action Potentials↗

PubMedDate not supplied

Primary malignant rhabdoid tumor of the central nervous system.

Since the initial description of malignant rhabdoid tumor (MRT) of the kidney by Beckwith in 1978, MRTs have been established as a distinct clinicopathologic entity lacking nephrogenic and myogenic differentiation. MRTs are highly aggressive neoplasms with characteristic histopathologic, immunocytochemical, and ultrastructural features. Many reports have appeared documenting primary extrarenal rhabdoid tumors (ERRTs) occurring at diverse sites, including infratentorial and supratentorial compartments of the central nervous system (CNS). The authors report 2 cases of primary CNS-MRT in young male children (6.5 and 7 years of age) and review the literature on CNS-MRTs. Neuroimaging studies showed an inhomogeneous parasagittal mass in the left anterior parietal region involving the motor strip and attached to the lateral aspect of the superior sagittal sinus in one case, and a right parietal parasagittal tumor with a cystic component in the other case. Metastatic workup, including abdominal CT, was negative in both cases. Histologic examination of the resected tumors showed irregular clusters and nests of cells with variable desmoplasia in both cases. Large areas of tumor necrosis and apoptotic tumor cells were present. Prominent eosinophilic cytoplasmic inclusions and eccentric, indented nuclei with conspicuous nucleoli characterized many of the tumor cells. Diffuse strong vimentin reactivity and focal strong reaction for epithelial membrane antigen (EMA) were demonstrated. Cytogenetic analyses reported a normal male karyotype in one case and an abnormal male karyotype with loss of both normal copies of chromosome 22 and gain of one structurally rearranged chromosome 22 in the other case. Ultrastructural examination displayed tumor cells with avoid to indented nuclei, marginated chromatin, and prominent nucleoli. Intercellular junctions were not found. Masses of cytoplasmic intermediate filaments in a characteristic whorled configuration were present. CNS-MRTs are consistently vimentin positive (100%) and usually EMA positive (90%). Glial fibrillary acidic protein, neuron-specific enolase, and S-100 protein are variably expressed. Markers for myogenous differentiation are invariably absent. Ultrastructural characteristics include aggregates of intermediate filaments. Monosomy 22 occurs in some CNS rhabdoid tumors, while most renal rhabdoid tumors are cytogenetically normal with only isolated cases having del(13q), del(11p), del(22)(q11), and unbalanced reciprocal translocation involving chromosomes 8 and 22. The prognosis for CNS rhabdoid tumors is dismal and almost two-thirds of patients are dead of disease shortly after diagnosis; one-third have been reported to be alive with disease, but have been followed for only short periods; and a single patient is reported to be free of disease at 5 years.

Brain Neoplasms↗

PubMedDate not supplied

Effect of a leukocyte-platelet removal filter on ischemia induced reperfusion injury.

The effect of leukocyte and platelet depletion on reperfusion injury using a leukocyte-platelet removal filter (LRF) in intracoronary thrombolysis is reported. To better define the usefulness of LRF in evaluating the effectiveness of intracoronary thrombolysis with this device, several cardiovascular variables were examined in rabbits during ischemia followed by reperfusion. The rabbits underwent cytoapheresis with LRF (n = 5) and were compared with controls without LRF (n = 5). LRF was composed of a nonwoven polyester fabric (1.8 microns, 4.6 gm). Removal of leukocytes and platelets by LRF was 98% for both. A period of 30 min equilibration was allowed before any experimental intervention, at which time the diagonal artery was occluded for 20 min and then reperfused. All arrhythmias were defined and quantified in accordance with the Lambeth Convention. Regional wall thickening was examined by a pulsed Doppler dimension system. No significant differences were observed in hemodynamic variables between the two groups; however, rabbits treated with a LRF demonstrated greater regional wall thickening (LRF group: 17 +/- 0.9%, control group: 11 +/- 0.3%, p less than 0.01), as well as significant improvement in the frequency of ventricular arrhythmias (LRF group: 12.5%, control group: 47.2%, p less than 0.01). The data suggest that LRF may help prevent arrhythmias, and preserve left ventricular contraction, during and after intracoronary thrombolysis.

Animals↗

PubMed2006

Noninvasive analysis of coronary artery disease with combination of MDCT and functional MRI.

RATIONALE AND OBJECTIVES: We evaluated the diagnostic accuracy of an eight-row multidetector computed tomography coronary angiography (MDCT-CA) in detecting high-grade (>50%) stenoses in the three main coronary arteries in patients with coronary artery disease (CAD). Side branches were excluded. We correlated magnetic resonance imaging (MRI) findings of the myocardium with MDCT-CA of the coronary arteries. MATERIALS AND METHODS: Fourteen CAD patients underwent conventional coronary angiography (CCA), MDCT-CA, and MRI. We determined the calcium burden with non-enhanced MDCT scan. Then MDCT-CA was performed after intravenous contrast injection during a single breathhold. The left ventricular (LV) MR cine imaging was assessed at rest and perfusion defects were observed during pharmacologic stress after contrast administration. Delayed contrast-enhanced MRI was performed to picture infarctions. RESULTS: MDCT-CA had sensitivity 82%, specificity 94%, positive predictive value 79%, and negative predictive value 95% of stenoses of more than 50% in the main coronary arteries when compared with CCA. LV wall dysfunction, perfusion defects, and infarctions were detected in 50%-78% of sectors assigned to calcifications or stenoses, but also in sectors supplied by normally perfused coronary arteries. CONCLUSIONS: CCA and MDCT-CA revealed comparable results in evaluating stenotic lesions above 50% in the main subepicardial coronary branches. There were no significant correlations between the degree of stenosis or calcification at MDCT-CA and the MR findings, but the combined information of MDCT-CA and MRI showed the variability of myocardial changes in regions perfused by significantly stenosed, calcified, and normal main coronary arteries.

Adult↗

PubMed1982

Interobserver variability in interpreting contrast left ventriculograms (CASS).

Randomly selected left ventricular cineangiograms performed by 14 medical centers (clinical sites) participating in a large multicenter study of medical and surgical treatment of coronary artery disease (CASS) were systematically recalled and reread by one of four designated quality control centers. The end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) calculated by the quality control center were compared with those calculated by the clinical site, and correlation coefficients of 0.71, 0.84, and 0.79, respectively, were obtained. Regional left ventricular (LV) wall motion abnormalities were assessed by dividing the LV wall as viewed in the right anterior oblique (RAO) and left anterior oblique (LAO) views into five segments each and grading the motion of each segment according to six categories of increasing abnormalities from normal to aneurysm. When discrepancies based on "nearest neighbor" differences in naming adjacent segments were eliminated and only marked differences of more than one degree of severity of wall motion abnormality were considered, interobserver differences were 7% and 10% for RAO and LAO segments, respectively. Agreement was less frequent in designating a segment "aneurysmal." When each LV segment was assigned a numerical score based on increasing severity of wall motion abnormality and a total LV score for each ventriculogram computed, the quality control and clinical site readings were in good agreement with a correlation coefficient of 0.83.

Cardiac Volume↗

PubMed2004

Variability in subcortical aphasia is due to variable sites of cortical hypoperfusion.

A variety of fluent and nonfluent aphasias have been reported after left basal ganglia stroke. It has been speculated that this heterogeneity may reflect variations in cortical hypoperfusion resulting from large vessel stenosis. To test this hypothesis, a consecutive series of 24 patients with left caudate infarct identified with diffusion-weighted imaging underwent language testing and perfusion-weighted imaging < 24h from onset of symptoms. Specific regions in perisylvian cortex were rated for the percentage of the region that was hypoperfused. Aphasia type was determined on the basis of speech fluency, comprehension, and repetition performance on the language tests. Association between aphasia type/language impairment and regions of hypoperfusion were identified with Fisher's exact tests. Results demonstrated that in patients with acute left caudate infarct, the presence and type of aphasia reflected regions of hypoperfusion, and generally followed predictions based on chronic lesion studies, regarding anatomical lesions associated with classic aphasia types.

Adult↗

PubMed2002

Definition of gross tumor volume in lung cancer: inter-observer variability.

BACKGROUND AND PURPOSE: To determine the inter-observer variation in gross tumor volume (GTV) definition in lung cancer, and its clinical relevance. MATERIALS AND METHODS: Five clinicians involved in lung cancer were asked to define GTV on the planning CT scan of eight patients. Resulting GTVs were compared on the base of geometric volume, dimensions and extensions. Judgement of invasion of lymph node (LN) regions was evaluated using the ATS/LCSG classification of LN. Clinical relevance of the variation was studied through 3D-dosimetry of standard conformal plans: volume of critical organs (heart, lungs, esophagus, spinal cord) irradiated at toxic doses, 95% isodose volumes of GTVs, normal tissue complication probabilities (NTCP) and tumor control probabilities (TCP) were compared for evaluation of observer variability. RESULTS: Before evaluation of observer variability, critical review of planning CT scan led to up- (two cases) and downstaging (one case) of patients as compared to the respective diagnostic scans. The defined GTVs showed an inter-observer variation with a ratio up to more than 7 between maximum and minimum geometric content. The dimensions of the primary tumor had inter-observer ranges of 4.2 (transversal), 7.9 (cranio-caudal) and 5.4 (antero-posterior) cm. Extreme extensions of the GTVs (left, right, cranial, caudal, anterior and posterior) varied with ranges of 2.8-7.3 cm due to inter-observer variation. After common review, only 63% of involved lymph node regions were delineated by the clinicians (i.e. 37% are false negative). Twenty-two percent of drawn in lymph node regions were accepted to be false positive after review. In the conformal plans, inter-observer ranges of irradiated normal tissue volume were on average 12%, with a maximum of 66%. The probability (in the population of all conformal plans) of irradiating at least 95% of the GTV with at least 95% of the nominal treatment dose decreased from 96 to 88% when swapping the matched GTV with an unmatched one. The average (over all patients) inter-observer range in NTCP varied from 5% (spinal cord) to 20% (ipsilateral lung), whereas the maximal ranges amounted 16% (spinal cord) to 45% (heart). The average TCP amounted 51% with an average range of 2% (maximally 5%) in case of matched GTVs. These values shifted to 42% (average TCP) with an average range of 14% (maximally 31%) when defining unmatched GTVs. Four groups of causes are suggested for the large inter-observer variation: (1) problems of methodology; (2) impossible differentiation between pathologic structures and tumor; or (3) between normal structures and tumor, and (4); lack of knowledge. Only the minority of these can be resolved objectively. For most of the causal factors agreements have to be made between clinicians, intra- and inter-departmentally. Some of the factors will never be unequivocally solved. CONCLUSIONS: GTV definition in lung cancer is one of the cornerstones in quality assurance of radiotherapy. The large inter-observer variation in GTV definition jeopardizes comparison between clinicians, institutes and treatments.

Carcinoma, Non-Small-Cell Lung↗

PubMed1987

Anomalous dominance in sibling stutterers: evidence from CT scan asymmetries, dichotic listening, neuropsychological testing, and handedness.

Two left-handed siblings with developmental stuttering are comprehensively described. The methods of study included speech and language evaluation, neurological and neuropsychological examinations, dichotic listening, auditory evoked responses, electroencephalogram, and CT scan asymmetry measurements. The data from each sibling showed evidence of anomalous cerebral dominance on many of the variables investigated. The CT scan measurements showed atypical asymmetries, especially in the occipital regions. These findings support the theory that stuttering may be related to anomalous cerebral dominance, both on functional as well as structural bases. Implications of anomalous dominance and the resultant effect of hemispheric rivalry on speech fluency are discussed.

Adolescent↗