Performance of a randomization test for single-subject (15)O-water PET activation studies.

We adapted and implemented a permutation test (Holmes 1994) to single-subject positron emission tomography (PET) activation studies with multiple replications of conditions. That test determines the experimentwise alpha error as well as location and extent of focal activations in each individual. Its performance was assessed in five normal volunteers, using (15)O-H2O-PET data acquired on a high-resolution scanner, with septa retracted (3D mode), during functional activation by repeating words versus resting (four replications each). Calculated alpha errors decreased and the size of activated tissue volumes (voxels with P < or = 0.05) increased with increasing filter kernel size applied to the difference images. At a filter kernel of 12 mm Gaussian full width at half maximum, significant focal activations were seen bilaterally in superior temporal cortex, including Brodmann's areas 41 and 42, in all five subjects. Additional foci were detected in the precentral gyrus, left inferior frontal gyrus, supplementary motor area, and cerebellum of several subjects. The average CBF increase in activated voxels ranged from 17.6% to 28.7%. Activated volumes were smaller than those detected with a standard parametric test procedure. We conclude that the permutation test is a less sensitive procedure, having the advantage of not depending on unproven distributional assumptions, that detects strong activation foci in individual subjects with high reproducibility.

Collateral inhibition of transcallosal activity facilitates functional brain asymmetry.

The corpus callosum is the largest connection between the functionally asymmetric cerebral hemispheres. The objective of this study was to measure functional activity of callosal fiber tracts during speech processing. We analyzed the regional glucose metabolism of the corpus callosum and of speech-relevant cortical areas in 10 normal individuals at rest and during word repetition. We used three-dimensionally registered magnetic resonance imaging to visualize the individual brain morphology and high-resolution positron emission tomography for metabolic measurements. The task-induced metabolic changes of the callosal midbody and isthmus had a significant negative correlation with key regions of language processing in the left inferior frontal cortex (Brodmann's area 44) and in the right superior temporal cortex (Brodmann's area 22) (e.g., correlation of metabolic changes in the surface aspects of the right Brodmann's area 22 and the callosal midbody/isthmus: r = -0.91, P < 0.001). The study indicates that language processing in asymmetrically organized cortical areas inhibits the reciprocal transcallosal information exchange in favor of the lateralized mental operation. Our data agree with anatomic, electrophysiologic, and pharmacologic experiments that point to the important role of collateral inhibition for the transcallosal information exchange.

Bronchoscopic and roentgenographic correlates of a positive transbronchial needle aspiration in the staging of lung cancer.

A study was conducted to determine the bronchoscopic and chest roentgenographic findings associated with a positive TBNA. One hundred fifty-seven of 465 patients who were diagnosed for the first time as having carcinoma of the lung had a positive aspirate. Bronchoscopic findings associated with a positive TBNA of N2 nodes were carinal widening and endobronchial disease, especially of the right upper lobe. Mediastinal adenopathy noted on chest roentgenograms and subcarinal nodes on CAT scans were associated with a positive aspirate as well. In 34 of 465 patients, TBNA was the only means of establishing the diagnosis of pulmonary malignancy. A useful, simple and safe procedure, TBNA can be used to stage the mediastinum in patients with lung cancer and is most likely to be positive with endobronchial and nodal disease. It can also facilitate therapeutic decision-making in patients whose surgical candidacy is marginal.

Chest roentgenographic evaluation of the severity of aortic stenosis.

The chest radiographs of 44 adult patients with proven valvular aortic stenosis (AS) were analyzed for the evaluation of severity of the disease. Five parameters were correlated with the aortic valve area (AVA) as the determinant of AS severity: the area of aortic valve calcification (AVCa), the cardio--thoracic (C--T) ratio, the Hoffman-Rigler (H-R) sign, left atrial enlargement (LAE), and the transverse diameter of the thoracic aorta (TDAo). There was a significant correlation between AVCa and severe AS only in women over 40 years of age. The increased C--T ratio and evidence of LAE was predictive of severe AS in men over 40 years of age. The positive H-R sign and an increased TDAo were not useful in assessing the severity of AS. Accordingly, the radiographic analysis of signs is a simple, useful, and noninvasive technique for diagnosing AS and for assessing its severity in patients over 40 years of age.

Serial evoked potentials and outcome in cerebrovascular critical care patients.

Median-nerve evoked somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs), examined early in the course of patients suffering from cerebrovascular disease, correlate statistically significantly with outcome. Little is known about the changes of evoked potentials in the course of disease and their correlation to outcome. In a series of 215 patients (75 supratentorial infarctions, 36 infratentorial infarctions, 58 supratentorial hemorrhages, 18 infratentorial hemorrhages, and 28 aneurysmatic subarachnoid hemorrhages) requiring neurologic intensive care treatment, we prospectively examined the correlation between the findings of serial SEPs and BAEPs and outcome at 4 weeks. Evoked potentials were examined after admission, after 1 week, and after 2 weeks. The findings were classified in 4 categories (normal, unilateral or bilateral pathologic findings, unilaterally attenuated, and bilaterally attenuated). Clinical outcome was determined by classification according to the Glasgow Outcome Scale (death, persistent vegetative state, severely incapacitated, mildly incapacitated, and recovery). Statistical evaluation was performed using Fisher's exact test for all variables. In all subgroups, SEPs correlated statistically significantly with outcome at all three examinations. No correlation was found for BAEPs at first examination in infratentorial disease, nor at second examination in subarachnoid hemorrhages. In all other cases, SEPs and BAEPs were correlated statistically significantly with outcome at all three examination timepoints.

Correlation of glucose consumption and tumor cell density in astrocytomas. A stereotactic PET study.

To determine histological correlates of the variability of glucose consumption in astrocytomas, the authors performed positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and matched the PET scans three-dimensionally with computerized tomography scans obtained in a stereotactic frame before biopsy. Ten patients with astrocytomas of World Health Organization Grade 2 or 3 were studied; patients with glioblastomas, oligodendrogliomas, or oligoastrocytomas were excluded from the study to avoid any confounding effects of different cell types and necroses. In samples of pure tumor, glucose consumption correlated significantly with cell density, but not with nuclear polymorphism. It is concluded that tumor cell density is a major determinant of glucose consumption in astrocytomas. The use of PET with FDG may help to locate the highest cell density and thus improve the diagnostic yield of stereotactic biopsy.

Genetic variations of the SLC7A9 gene: allele distribution of 13 polymorphic sites in German cystinuria patients and controls.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Both gene products form the renal amino acid transporter rBAT/b0,+AT affected in cystinuria. In the present study a total of 59 patients with different ethnic background were screened for sequence variations in SLC7A9, out of these 32 were of German origin. For determination of allele frequencies of detected polymorphisms, 58 healthy German controls were investigated. Molecular-genetic analysis was performed using single-strand conformation polymorphism analysis, restriction assays and sequencing. Allele frequencies were analyzed statistically for the detected polymorphisms. In addition to the 6 already known variants we identified 7 new polymorphisms. Statistical analyses showed a significantly different distribution of alleles between German patients and German controls in case of the polymorphisms c. 147C>T (exon 2), c.386C>T (exon 3), IVS3+22T>G, c.584C>T (exon 4), c.610T>C (exon 4), c.692C>T (exon 5), c.852C>A (exon 6) and c.872C>T (exon 6). In summary, our results show that cystinuria is a complex disease which is not only caused by mutations in SLC7A9 and SLC3A1, but also influenced by other modifying factors such as variants in SLC7A9.

Bell's palsy: electrodiagnostics are not indicative of cerebrospinal fluid abnormalities.

Electrodiagnostic testing (electromyography, electroneuronography, and blink reflex) and cerebrospinal fluid (CSF) examination (cell count, immunoglobulins, and antigen-specific intrathecal immunoglobulin G synthesis against herpes simplex virus, varicella zoster virus, cytomegalovirus, and Borrelia burgdorferi sensu latu) were performed in 56 patients with Bell's palsy. The CSF was normal in 45 patients and abnormal in 11 patients. Acute borreliosis was the most common specific pathological CSF finding (4 of 11). Electromyography revealed abolished volitional activity in 22% of patients with normal CSF and in 36% with pathological CSF. Electroneuronographic tests with an amplitude decrease of more than 90% on the affected side or abolished responses were found in 20% of patients with normal CSF and in 18% with pathological CSF. Abolished orbicularis oculi reflexes were seen in 67% of patients with normal CSF and in 82% with pathological CSF Concerning electrodiagnostic testing, no statistically significant difference between patients with normal and abnormal CSF was found, so we conclude that electrodiagnostic testing has no indicative value for abnormal CSF in Bell's palsy.

[The acute physiology score as a stratification and prognostic criterion in patients in a surgical intensive care ward]. / Der "acute physiology score" als Stratifikations- und Prognosekriterium bei Patienten einer chirurgischen Intensivstation.

In order to compare different groups of intensive-care patients and therapeutic interventions a measuring system is needed reflecting the patient's pathophysiologic status with great accuracy. The APACHE-system designed by Knaus et al. (APS) meets the requirements when comparing groups of patients. This prospective study was undertaken to determine whether APS is useful to forecast survival and death of 764 individual patients of a surgical ICU. The results were compared to daily statements obtained from the head surgeon of the intensive-care department. Both the physician and APS gave true judgements in 95% of the cases. Overestimation of the operative procedures by the physician was revealed to be a major source of error in wrong statements. When a combination of APS and physician's judgement was used the forecasts were found true in 99% of the patients. The authors conclude that APS by itself is not able to give a sufficient prognosis in an individual ICU patient but is an excellent tool to assure or modify the physician's opinion.

Pitfall in the CT diagnosis of abdominal abscess--the full stomach.

A case is presented to illustrate that the CT appearance of the unenhanced full stomach may be misinterpreted as an abdominal abscess in the appropriate clinical setting. The need for administering oral contrast material prior to the study is emphasized.

CT of the esophagus: I. Normal appearance.

The thoracic esophagus is easily demonstrable throughout its entire length on thoracic computed tomography (CT). The soft tissue planes separating the esophagus from its adjacent mediastinal structures are normally distinct. Blurring or distortion of these tissue interfaces is a reliable indicator of disease. The normal CT anatomy of the esophagus and mediastinal relationships are described. Air in the esophagus is considered a normal finding.

Mycoplasma pneumonia.

M. pneumoniae is a common cause of pneumonia. The diagnosis is suspected when the patient presents with symptoms suggesting primary atypical pneumonia including cough, fever, chills, headache, and malaise in association with a segmental or subsegmental pulmonary infiltrate(s), the white blood cell count is normal or only slightly elevated, and the Gram stain of the sputum (if any can be obtained) reveals polymorphonuclear leukocytes and few bacteria. The diagnosis is more difficult when the patient presents with symptoms not suggestive of pneumonia including lethargy, dyspnea, and a 1- to 4-week history of shortness of breath without cough or fever in association with diffuse reticulonodular or interstitial pulmonary infiltrates. The disease in the previously healthy host is usually benign and self-limiting. However, the course is shortened by the administration of tetracycline derivatives or erythromycin. M. pneumoniae pneumonia can occur in association with other diseases including sickle cell anemia, sarcoidosis, systemic lupus erythematosus, Hodgkin's disease, and various other immunodeficiency states. In these patients mycoplasma pneumonia can be very serious. Although there is no pathognomonic clinical or radiographic presentation, careful consideration of epidemiologic, clinical, laboratory, and radiographic data are usually sufficient to suggest the diagnosis in most patients.

CT of the esophagus. II. Carcinoma.

Thoracoabdominal computed tomography (CT) scanning was performed prior to treatment on 30 patients with proven carcinoma of the esophagus. Operative, bronchoscopic, and/or autopsy data were reviewed and showed that CT correctly identified the extent of medistinal spread in 27 patients and intraabdominal metastases in 22 patients. The ability of CT to reliably predict the extent of disease should help the surgeon and radiation oncologist plan optimal therapy.

Computed tomography in the diagnosis of intra-abdominal abscesses.

The diagnosis of intra-abdominal abscess by radiographic means often relies on combining the results of several different imaging modalities. Computed tomography (CT) has been shown to be a safe, accurate and rapid diagnostic method of diagnosing these abscesses. Five patients with a variety of intra-abdominal abscesses are presented in whom the CT scan alone provided the correct diagnosis. The various imaging modalities available for the radiologic diagnosis of intra-abdominal abscess are described and are compared to CT diagnosis regarding their pitfalls.

Individual functional anatomy of verb generation.

Examination of the individual functional anatomy of language is of particular interest in clinical neurology to explain the variability of aphasic symptoms after focal lesions and to avoid damage of language-related brain areas by surgery. For a silent verb generation task, we examined whether activation PET with 3D data acquisition, multiple replication of conditions, and coregistration with MRI provides results that are consistent and reproducible enough to be useful clinically. Visual analysis was performed on PET-MRI fusion images, including renderings of the brain surface. Quantitative analysis was based on volumes of interest. In seven right-handed normals, activation of the triangular part of the left inferior frontal cortex [Brodman area (BA) 45] was the most significant finding that was present in each subject. Two subjects showed minor anatomical variants of the ascending or horizontal ramus of the sylvian fissure that were associated with the least activation of BA 45. In the left hemisphere the other frontal gyri, the superior temporal and posterior part of the middle temporal gyrus, and the paracingulate gyrus were also significantly activated. There was significant bilateral cerebellar activation, but it was significantly more intense on the right than on the left side. The consistency and high interindividual reproducibility of these findings suggest that this technique may be useful for clinical assessment of language-related areas.

Intraabdominal abscess: current concepts in radiologic evaluation.

Forty patients with suspected abdominal abscess had computed tomography (CT) and plain film examinations; 15 also had ultrasound study. CT was found to be the most consistently accurate examination, both for the detection of abscess and evaluation of its extent. Ultrasound was positive in a high percentage of cases in which it was used. Although plain films correctly suggested the presence of an abscess in over half the proven cases, confirmatory evidence from CT or ultrasound was often required to persuade clinicians of the presence of an abscess and to provide detailed information regarding its extent and configuration.

Impairment of neocortical metabolism predicts progression in Alzheimer's disease.

Progression rates of Alzheimer's disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment. Copyrightz1999S.KargerAG, Basel

Comparison of plain radiography, conventional tomography, and computed tomography in detecting intrathoracic lymph node metastases from lung carcinoma.

Forty-two patients with T2 bronchogenic carcinoma were evaluated with plain radiography, conventional 55 degrees oblique hilar and anteroposterior mediastinal tomography, and computed tomography (CT) to compare their accuracy in assessing mediastinal and hilar nodal metastases. Definitive staging was achieved by thoracotomy and histopathological evaluation of resected specimens. All modalities demonstrated about the same accuracy; however, in the 25 patients with hilar and/or mediastinal lymphadenopathy, CT of the mediastinum was more sensitive but not more specific than the other two and conventional tomography was no more accurate than CT for hilar evaluation. Overall, no technique was accurate enough for routine staging; their value may lie in directing biopsy or in treatment planning in patients with inoperable disease.