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// Otto Hemminki 1 , Suvi Parviainen 1 , Juuso Juhila 1 , Riku Turkki 2 , Nina Linder 2 , Johan Lundin 2, 3 , Matti Kankainen 4 , Ari Ristimaki 5 , Anniina Koski 1 , Ilkka Liikanen 1 , Minna Oksanen 1 , Dirk M. Nettelbeck 6 , Kalevi Kairemo 7 , Kaarina Partanen 7 , Timo Joensuu 7 , Anna Kanerva 1, 8 , Akseli Hemminki 1, 7, 9 1 Cancer Gene Therapy Group, Transplantation Laboratory & Haartman Institute, University of Helsinki, Helsinki, Finland 2 Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland 3 Division of Global Health/IHCAR, Karolinska Institutet, Stockholm, Sweden 4 CSC - IT Center for Science Ltd, Helsinki, Finland 5 Department of Pathology, HUSLAB and Haartman Institute, Helsinki, University Central Hospital and Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland 6 German Cancer Research Center (DKFZ), Heidelberg, Germany 7 Docrates Cancer Center, Helsinki, Finland 8 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland 9 TILT Biotherapeutics Ltd, Helsinki, Finland Correspondence to: Akseli Hemminki, e-mail: akseli.hemminki@helsinki.fi Keywords: Oncolytic, immunotherapy, cancer, ATAP Received: September 17, 2014 Accepted: December 14, 2014 Published: February 24, 2015 ABSTRACT Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site (“Δ24”). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor- and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication.

Magnetic resonance imaging (MRI) has been suggested as a useful tool in early diagnosis of Alzheimer's disease (AD). Based on MRI-derived volumes, we studied the hippocampus and entorhinal cortex (ERC) in 59 controls, 65 individuals with mild cognitive impairment (MCI) and 48 patients with AD. The controls and individuals with MCI were derived from population-based cohorts. Volumes of the hippocampus and ERC were significantly reduced in the following order: control > MCI > AD. Stepwise discriminant function analysis showed that the most efficient overall classification between controls and individuals with MCI subjects was achieved with ERC measurements (65.9%). However, the best overall classification between controls and AD patients (90.7%), and between individuals with MCI and AD patients (82.3%) was achieved with hippocampal volumes. Our results suggest that the ERC atrophy precedes hippocampal atrophy in AD. The ERC volume loss is dominant over the hippocampal volume loss in MCI, whereas more pronounced hippocampal volume loss appears in mild AD.

To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up.Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy.46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (por = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome.Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

Purpose: We evaluated the reproducibility of three visual scoring methods of emphysema and compared these methods with pulmonary function tests (VC, DLCO, FEV1 and FEV%) among farmer's lung patients and farmers. Material and Methods: Three radiologists examined high-resolution CT images of farmer's lung patients and their matched controls (n=70) for chronic interstitial lung diseases. Intraobserver reproducibility and interobserver variability were assessed for three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as spirometry and diffusing capacity were measured. Results: Intraobserver κ-values for all three methods were good (0.51-0.74). Interobserver κ varied from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with pulmonary function tests, especially DLCO and FEV1. Conclusion: The Sanders' method proved to be reliable in evaluating emphysema, in terms of good consistency of interpretation and good correlation with pulmonary function tests.

Background. Prostate cancer (PCa) patients with metastatic disease often suffer from skeletal pain and urinary retention impairing their quality of life. Prophylactic radiotherapy to bone metastases planned concomitantly with primary PCa radiotherapy could enable more precise control of combined dose in healthy tissues when compared to sequential palliative treatment.Materials and methods. Volumetric modulated arc therapy (VMAT) was planned for 14 PCa patients with primary bone metastases. The bone planning target volume (PTVbone) was contoured together with the PTVs of prostate (pr), pelvic lymph nodes (ln) and seminal vesicles (sv). Another virtual plan was calculated excluding PTVbone for dose volume histogram (DVH) comparison. DVHs were additionally compared to a set of actual VMAT treatment plans of a control cohort of 13 high risk PCa patients treated with PTVpr, PTVsv and PTVln. The prescribed doses varied between 42 and 76 Gy for PTVbone.Results. Recommended healthy tissue tolerances (Quantec) were not exceeded except for one patient's rectum V50Gy value. Rectum doses did not increase significantly due to the inclusion of PTVbone. For bladder, there was a slight increase for V65Gy and V50Gy (2.7% and 7.4%). The DVHs of metastatic and non-metastatic patients were comparable. There were no differences in the PTVpr DVH parameters, while mean PTVln dose increased by 3.7 Gy–4.4 Gy due to the increased treatment volume related to PTVbone. All side effects were < grade 3 during the mean follow-up duration of 25 months.Conclusions. VMAT offers a good optimization tool for adding extra PTVs to the radiotherapy plan. Radiotherapy of bone metastases concomitantly with irradiation of the primary prostate tumor is a safe and well-tolerated approach and deserves to be studied in a randomized setting.

Molecular imaging is the only way of defining biological target volume (BTV) for externalbeam radiation therapy (EBRT) and may be used for advanced targeting in dose planning and dose painting. There are, however, no reports about the EBRT response when dose planning is based on BTV target definition in advanced prostate cancer. Clinical and biochemical results of two clinically equal group of patients with advanced prostate cancer patients were compared. Both groups were treated with volumetric modulated arc therapy (VMAT) based on target definition by PET/CT (1(st) group) or conventional imaging (2(nd) group). Biochemical relapse occurred in 16.6% (in 1 out of 6) of the patients in the first group and 50% (3 out of 6) patients in the second group during the follow up period. Clinical manifestation of disease occurred in 33% (2 out of 6) patients of the first group and in 5 out of 6 (83,3%) patients in the second one. 4 patients in the first group had no biochemical relapse and no clinical manifestation during the follow up period. The difference in the duration of progression free period was statistically significant between the groups (p

Background.In this retrospective analysis we assessed the role of [18F]-FACBC-PET/CT in the prostatic cancer staging.Procedure.30 first [18F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging.Results.On 16 [18F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [18F]-FACBC findings was 9.5 ± 16.9 μg/L (0.54–69 μg/L) and in patients with negative [18F]-FACBC findings was 1.96 ± 1.87 μg/L (0.11–5.9 μg/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3–6 months) versus 31.2 ± 22.02 months (8–84 months),P<0.0001. There was a strong positive correlation between PSA value and number of metabolically active lesions (R=0.74) and a negative correlation between PDT and number of metabolically active lesions (R=-0.56). There was a weak negative correlation between PDT andSUVmax⁡(R=-0.30).Conclusion.According to our preliminary clinical experience, [18F]-FACBC-PET may play a role inin vivorestaging of an active prostate cancer, especially in patients with a short S-PSA doubling time.

Patients with drug-refractory temporal lobe epilepsy (TLE) often have hippocampal and amygdaloid damage. The present study investigated the factors associated with the occurrence and severity of damage in patients with partial epilepsy. Magnetic resonance imaging was used to measure the volumes of the hippocampus and the amygdala in 241 patients with different durations of epilepsy. We also investigated the association of damage with the location of seizure focus and clinical factors (age at onset of seizures, lifetime seizure number and medical history of complex febrile convulsions, intracranial infection or status epilepticus) with regression analysis. We found that high lifetime seizure number ( P P P P P

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic-clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.

Objective: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology.Methods: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model.Results: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis.Conclusion: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.

The entorhinal cortex (Brodmann’s area 28) is located at the anterior aspect of the parahippocampal gyrus ventral to the amygdala and the hippocampus. It is reciprocally interconnected with the hippocampus via glutamatergic pathways. We investigated whether the entorhinal cortex is damaged in human temporal lobe epilepsy (TLE). The volume of the entorhinal cortex was measured using magnetic resonance imaging (MRI) in 36 patients with cryptogenic TLE and in 21 controls. The mean volumes of the entorhinal cortex on the focal side did not differ from controls. In 11 of 36 patients, however, the entorhinal cortex volume was reduced by 25%. Entorhinal volume correlated with hippocampal volume in TLE (ipsilaterally, r= 0.454, P< 0.01; contralaterally, r= 0.340, P< 0.05). Further, 64% of patients with 25% entorhinal cortex damage had ipsilateral hippocampal atrophy. On the other hand, right focal TLE patients with hippocampal atrophy had a 19% volume reduction of the ipsilateral entorhinal cortex (P< 0.05). The volume of the entorhinal cortex correlated with the duration of TLE (r= −0.335, P< 0.05). The present study indicates that the entorhinal cortex might be damaged in a subpopulation of patients with cryptogenic TLE. In most cases, volume reduction was associated with hippocampal damage. These data suggest that entorhinal damage contributes to the symptomatology in TLE.

Background: Due to the progressive nature of Alzheimer’s disease (AD), it has been proposed that serial imaging studies tracking the course of progression might improve the diagnostic accuracy of AD. Methods: Longitudinal changes in hippocampal volumes were evaluated using magnetic resonance imaging (MRI) over a period of 3 years in 27 AD patients and 8 control subjects. Results: A statistically nonsignificant trend towards accelerated volume loss in the AD group compared to control subjects was observed. During the study period, the average shrinkage of the hippocampal volume ranged from −2.2% to −5.8% in control subjects, and from −2.3% to −15.6% in AD patients. Conclusions: The observed changes at an individual level were small, and within the accuracy range of the measurements. Therefore, serial MRI of the hippocampus did not offer any advantage over a single MRI to support the diagnosis of AD in this study sample.

Background. To compare antepartum ultrasonography with magnetic resonance imaging for prenatal diagnosis of malformations in the fetal urinary tract in high risk patients during the last trimester. Materials and methods. The study involved 22 women and 24 fetuses with either severe oligohydramnios or ultrasonographically or clinically suspected abnormality of urinary tract. Ultrasound examination was carried out with 5 MHz abdominal convex probe and magnetic resonance imaging with superconductive 1.5 T equipment. Postnatal findings were used as reference. Results. Correct diagnosis of urinary tract anomaly was done in 15 fetuses on ultrasound and in 20 fetuses on magnetic resonance imaging. Both methods enabled correct diagnosis in 12, only ultrasound in three and only magnetic resonance imaging in eight fetuses. Both methods imaged equivocally in one case. The additional information by magnetic resonance imaging was gained from five fetuses out of 12 pregnancies with oligohydramnios and from three fetuse...

To compare antepartum ultrasonography with magnetic resonance imaging for prenatal diagnosis of malformations in the fetal urinary tract in high risk patients during the last trimester.The study involved 22 women and 24 fetuses with either severe oligohydramnios or ultrasonographically or clinically suspected abnormality of urinary tract. Ultrasound examination was carried out with 5 MHz abdominal convex probe and magnetic resonance imaging with superconductive 1.5 T equipment. Postnatal findings were used as reference.Correct diagnosis of urinary tract anomaly was done in 15 fetuses on ultrasound and in 20 fetuses on magnetic resonance imaging. Both methods enabled correct diagnosis in 12, only ultrasound in three and only magnetic resonance imaging in eight fetuses. Both methods imaged equivocally in one case. The additional information by magnetic resonance imaging was gained from five fetuses out of 12 pregnancies with oligohydramnios and from three fetuses out of ten pregnancies with normal amount of amniotic fluid.MRI is a valuable additional method to ultrasonography of fetal urinary tract if resolution of ultrasound is impaired for reason of oligohydramnios or technical deterioration.

Background. Double reading is a widely used criterion standard in breast cancer screening despite a lack of evidence of the cost‐effectiveness of the second reading. This study evaluates the incremental cost‐effectiveness of such a strategy. Design. Cost‐effectiveness analysis: Nationwide population‐based semi‐annual screening program for women aged 50–59 in Finland. Participation rate was 91%. All mammograms (95,423) performed during 1990–1995 in three screening centers of the Finnish Cancer Society were read by two radiologists with gradings recorded. The effectiveness of the double reading was the difference in cancers detected in the double compared to that of the single reading. Incremental costs of the double reading for the health care and non‐health care and the time costs were estimated. The main outcome measure was the incremental cost per additional cancer found as a result of the double‐reading strategy. Results. The total number of cancers detected with the double and single reading were 290 and 261, respectively. A significantly higher ratio of carcinoma in situ was the causative pathology in cancers detected only by the second reader. The cost per cancer detected with a single reading was US$ 18,340. The incremental cost of any additional cancer found was US$ 25,523, that is, a 39% higher cost per additional cancer found by double reading. Conclusions. The additional cost per cancer detected by double reading is not drastically higher than with single reading. However, the additional cost per life year saved may be much higher.

The amygdala complex is one component of the temporal lobe that may be damaged unilaterally or bilaterally in children and adults with temporal lobe epilepsy (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging studies of epileptic patients have shown that volume reduction of the amygdala ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been reported in the lateral and basal nuclei. Studies in rats have more specifically identified the amygdaloid regions that are sensitive to status epilepticus-induced neuronal damage. These areas include the medial division of the lateral nucleus, the parvicellular division of the basal nucleus, the accessory basal nucleus, the posterior cortical nucleus, and portions of the anterior cortical and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular and intermediate divisions of the basal nucleus and the central nucleus, remain relatively well preserved. Amygdala kindling studies in rats have shown that the density of a subpopulation of GABAergic inhibitory neurons that also contain somatostatin may be reduced even after a low number of generalized seizures. While analyses of histological sections and MR images indicate that in approximately 10% of TLE patients, seizure-induced damage is isolated to the amygdala, more often amygdala damage is combined with damage to the hippocampus and/or other brain areas. Moreover, recent data from rodents and nonhuman primates suggest that structural and functional alterations caused by seizure activity originating in the amygdala are not limited to the amygdala itself, but may also affect other temporal lobe structures. The information gathered so far on damage to the amygdala in epilepsy or after status epilepticus suggests that local alterations in inhibitory circuitries may contribute to a lowered seizure threshold and greater excitability within the amygdala. Furthermore, damage to select nuclei in the amygdala may predict impairment of performance in behavioral tasks that depend on the integrity of the amygdaloid circuits.

We evaluated the long-term outcome of farmer's lung (FL) patients and matched control farmers using high-resolution computed tomography (HRCT). The study population consisted of 88 FL patients and 83 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yr. The great majority, 82%, of the studied subjects were nonsmokers. Clinical studies included HRCT, spirometry, and pulmonary diffusing capacity. Emphysema was found significantly more often (23%) in FL patients than in control farmers (7%) (p = 0.006). The presence of emphysema was 18% in nonsmoking and 44% in smoking FL patients, the respective values being 4% and 20% in control farmers. Patients with recurrent attacks of FL tended to have emphysema more often (p = 0. 08) than patients who had experienced only a single attack. Fibrosis was observed in 17% of the FL patients and in 10% of the control farmers (p = 0.2). Miliary changes were found in 12% of the FL patients compared with 4% of the control farmers (p = 0.07). Both emphysematous and fibrotic but not miliary changes correlated significantly with impaired pulmonary function. In conclusion, farmer's lung disease seems to be associated with an increased risk of developing emphysema.

To investigate whether recurrent seizures cause hippocampal damage in temporal lobe epilepsy (TLE).Eighteen patients with newly diagnosed cryptogenic TLE, 14 patients with chronic well-controlled cryptogenic TLE, 32 patients with chronic drug-resistant cryptogenic TLE, and 25 healthy subjects were studied.Hippocampal MRI volumetry and T2 relaxometry were used.Chronic drug-resistant patients with seizure focus in the left temporal lobe had an 18% smaller left hippocampus and chronic drug-resistant patients with seizure focus in the right temporal lobe had a 14% smaller right hippocampus than did the control group (p0.05). Chronic drug-resistant patients with seizure focus on the left side had longer T2 relaxation times in the body of the left hippocampus than did the control group (p0.001) and chronic drug-resistant patients with seizure focus on the right side had longer T2 relaxation times in the body of the right hippocampus than did the control subjects (p0.01). In all patients with a left seizure focus, the left hippocampal volume correlated inversely with the estimated total number of partial (r = -0.391, p0.01) or generalized (r = -0.312, p0.05) seizures the patient had experienced. The prolongation of the left T2 relaxation time in the body of the hippocampus correlated with the total number of both partial (r = 0.670, p0.001) and generalized (r = 0.481, p0.001) seizures and with the duration of TLE symptoms (r = 0.580, p0.001).In patients with cryptogenic epilepsy, recurrent seizures may cause damage to the hippocampus throughout the lifetime of the patient.

Antepartum diagnosis of placenta accreta on the scarred myometrium of the isthmus uteri after previous cesarean section was made in 2 pregnancies. Antepartum sonographic examination revealed abnormal bulging of placental tissue toward the bladder cavity and arcuate arteries within the bladder wall. Magnetic resonance imaging revealed the depth and extent of placental invasion into the myometrium of the isthmus and the bladder muscular layer. Low-resistance pulsatile intervillous flow was recorded within the placenta in 1 case. Both magnetic resonance imaging and contrast-enhanced color Doppler sonography were informative in the other of these cases, in which the patient was conservatively managed during pregnancy and after delivery. © 1998 John Wiley & Sons, Inc. J Clin Ultrasound26: 90–94, 1998.

We measured the volumes of the entorhinal, perirhinal, and temporopolar cortices on magnetic resonance images by using a recently designed histology-based protocol in 30 patients with early Alzheimer's disease (AD) and 32 healthy control subjects. Compared to the controls, all of these cortical regions were significantly atrophied in AD patients (p < 0.0001). However, the entorhinal cortex was the most severely involved brain region studied, with 40% volume loss, and this region provided the highest discriminative accuracy (92%) in separating patients with AD from healthy control subjects. Importantly, the entorhinal volume loss was evident already in mild AD. In addition, the volume of the entorhinal cortex was not dependent on age, but it did correlate significantly with the severity of the disease. Because it assesses the major site of initial neuropathological changes in AD, magnetic resonance imaging volumetric measurement of the entorhinal cortex can offer a tool for distinguishing AD patients even in the very early stages of the disease from healthy aged subjects.

In this study, magnetic resonance imaging (MRI) of the hippocampus for the diagnosis of early Alzheimer's disease (AD) is evaluated. We measured hippocampal volumes and the area of the medial hippocampus with a 1.5 T MR imager in 160 subjects: 55 patients with probable AD according to the NINCDS-ADRDA criteria, 43 subjects fulfilling the NIMH criteria of age-associated memory impairment (AAMI), 42 cognitively normal elderly controls, and 20 controls younger than 50 years. Three methods for normalization were compared. The hippocampi were atrophied in the AD patients, but not in the AAMI subjects or the elderly controls. There was no significant correlation between hippocampal volumes and age in the nondemented subjects. The discrimination based on volumetry resulted in an overall correct classification of 92% of AD patients vs. nondemented elderly subjects, whereas discrimination based on hippocampal area was less accurate, producing a correct classification in 80% of the subjects. We conclude that the hippocampus as assessed by MRI volumetry is atrophied early in AD, and spared by aging or AAMI. A brief critical review of previous studies is in concordance with the presented data: all the previous studies that have used volumetry, have similarly ended up with a good classification, whereas simpler or subjective measurements, subject to various sources of bias, have produced most variable results.

Little is known about the appearance and severity of amygdaloid damage in temporal lobe epilepsy, particularly in its early stages. In the present magnetic resonance imaging study, we measured amygdaloid volumes and T2 relaxation times in 29 patients with newly diagnosed and in 54 patients with chronic temporal lobe epilepsy. The control population included 25 normal subjects. In the newly diagnosed patients, the mean amygdaloid volume did not differ from that in controls. Also, in the chronic patients the mean amygdaloid volume did not differ from that in controls or in newly diagnosed patients. However, in 19% of the chronic patients the amygdaloid volume was reduced by at least 20%. Moreover, in all of the epilepsy patients, both chronic and newly diagnosed, we found an inverse correlation between the number of epileptic seizures the patient had experienced and the amygdaloid volume on the focal side (focus on the left, r = -0.371, P0.01; focus on the right, r = -0.348, P0.05). The mean T2 relaxation time in newly diagnosed or chronic patients did not differ from each other or from control values. However, the T2 relaxation time of the left amygdala wasor = 111 msec (i.e.,or = 2 S.D. over the mean T2 time of the left amygdala in control subjects) in seven (10%) patients, one of which was newly diagnosed and six were chronic. The T2 time of the right amygdala was prolonged in eight (12%) patients, three of which were newly diagnosed and five were chronic. We did not find any clear asymmetries in amygdaloid volumes or T2 relaxation times between the ipsilateral and contralateral sides relative to seizure focus. According to the present findings, signs of amygdaloid damage were observed in approximately 20% of patients with temporal lobe epilepsy, most of which had chronic epilepsy.

Background and material. In order to evaluate cerebral blood flow changes associated with fetal intracranial hemorrhages, ultrasound and MRI examinations were carried out in four pregnancies with this complication. Results. Increased resistance indices of the blood flow profile of the middle cerebral artery were detected in three of the fetuses, two of them presenting retrograde diastolic flow. Flow became normalized in one case within four weeks, changing on the contralateral side to an increased diastolic flow pattern. Conclusion. Increased intracranial pressure can cause these flow changes, but cerebral blood flow autoregulation need not be completely ruined in this complication.

To determine the long-term outcome of 12 youthful patients with lumbar disc herniation, who, at the time of surgery, were 15 years old or younger (mean age at operation 14.3 years), we assessed their current clinical condition (mean follow-up time 6 years) with a questionnaire inquiring about symptoms and disability, and radiologically with an MRI of the lumbar spine. Clinically, only five patients (40%) were totally asymptomatic and seven patients (60%) had recurring symptoms, both pain and disability. On MRI, seven patients (60%) had persistent stenosing changes at the operated disc levels and eight patients (65%) also had disc degeneration at other lumbar levels. Despite the symptoms and quite severe radiological findings, the long-term outcome was assessed as good or moderate in eleven patients (90%). As far as comparisons are reasonable, our results appear somewhat less favourable than those in two previous paediatric series, but they agree with those in two recent large series of adults.

Objectives:To examine the interobserver variability in measuring the abdominal aorta by ultrasound (US) and computed tomography (CT).Design:A prospective clinical study in a university hospital.Materials:Thirty-three patients whose abdominal aortas were scanned both with CT and US as a part of aneurysm investigation or for a variety of other reasons.Methods:Three radiologists measured abdominal aortic diameters by US and CT. The interobserver differences (IOD) in US and CT and intraobserver differences for CT-US-pairs were analysed by various statistical methods. A new concept of “clinically acceptable difference” (CAD) was adopted denoting differences of less than 5mm.Results:The IOD in US was 2mm or less in 65% of the anteroposterior and 61% of the transverse measurements and 5mm or more in 11% of the anteroposterior and 14% in the transverse measurements in 102 observer pairs for all aortas. The IODs were significantly larger in measuring the aneurysmal aortas compared with normal aortas (p < 0.001). The CAD-value for the aneurysmal aortas was 84% in the anteroposterior and 82% in the transverse directions. In CT the IODs were 2mm or less in 62% of the anteroposterior and 66% of the transverse measurements and 5mm or more in 12% of both anteroposterior and transverse measurements in 94 observer pairs for all aortas. The CAD-value in the aneurysmal aortas was 91% in the anteroposterior and 85% in the transverse directions. There was no significant difference between the US and CT CAD-levels. The absolute CT-US difference of an individual observer was 2mm or less in 54%, 5mm or more in 17% and 10mm or more in 2% of the anteroposterior measurements in the 95 CT-US pairs. In the transverse direction the corresponding figures were: 2mm or less in 63%, 5mm or more 13% and 10mm or more in 2% of the pairs. The diameters obtained by US were smaller in 84% of the cases compared with those of CT in measuring the maximum aortic diameter in anteroposterior direction, whereas the same figure for the transverse measurements was 59%.Conclusions:Both US and CT measurements are subject to significant interobserver variability that must be taken into account in the clinical follow-up of small abdominal aortic aneurysms and in screening studies. Neither of these methods can be considered as a ‘gold standard’.

A prolonged MR T 2 relaxation time was proposed to mark the presence and severity of Alzheimer's disease (AD). We studied the value of T 2 relaxometry in diagnosing early AD. T 2 was measured from 54 patients with AD, 25 subjects with age-associated memory impairment (AAMI), 18 elderly and 16 young controls. The AD patients had longer T 2 in the right hippocampal head (104 ± 11 ms) and tail (98 ± 10 ms) than age-matched controls (95 ± 5 and 92 ± 9 ms, respectively). This prolongation was not related to age. In the AD group, the T 2 of the left hippocampal head also correlated with the clinical severity. The T 2 of the amygdala did not differ across the groups. Increased T 2 in the temporal and parietal white matter and the thalamus related to increasing age rather than to the diagnostic category. The AAMI subjects had T 2 comparable with those of age-matched controls. Despite the prolongation of T 2 in the AD group the possible diagnostic value was compromized by a substantial overlap between the study groups. We, thus, conclude that the T 2 relaxometry is not a reliable method for diagnosing early AD.

We analyzed hippocampal volumes and T sub 2 relaxation times by MRI from 78 control subjects, 24 patients with temporal lobe epilepsy, and 55 patients with Alzheimer's disease (AD).In the epilepsy group, the hippocampal volumes were 27% smaller than in control subjects (p < 0.001). The T2 relaxation times were prolonged (8 to 20 ms compared with control subjects) in the head, body, and tail portions of the hippocampus on the focal side (p < 0.01) and also on the contralateral side (p < 0.05) compared with control subjects. In the epilepsy group, the prolongation of T2 relaxation time correlated inversely with the hippocampal volume (p < 0.05). In the AD group, the hippocampal volumes were 35% smaller than in control subjects (p < 0.01). The T2 relaxation times were slightly prolonged (5 to 6 ms) in the head and tail portions of the right hippocampus (p < 0.01), but the T2 relaxation times did not correlate with the hippocampal volumes. These data show that the degree of prolongation of T2 relaxation time is associated with severity of hippocampal atrophy in temporal lobe epilepsy but not in AD.NEUROLOGY 1996;46: 1724-1730

Hippocampal atrophy detected by volumetric MRI is a sensitive feature of early Alzheimer's disease (AD), but there are no studies evaluating hippocampal atrophy by MR volumetry in other dementing diseases. We therefore compared hippocampal volumes in a total of 113 subjects: 50 patients with mild to moderate AD, 9 patients with vascular dementia (VaD), 12 patients with idiopathic Parkinson's disease (PD) without dementia, 8 patients with PD and dementia (PDD), and 34 elderly control subjects. Thin, coronal, contiguous images were obtained by a 1.5-T MR imager. All patient groups had significantly smaller volumes of the hippocampus compared with the control group. In the PDD group, the absolute volumes were even smaller than in the AD group. In the PD group, the volumes were diminished to a lesser but significant extent. The volumes in the VaD group varied: of nine patients, two had no atrophy, three had unilateral, and four had bilateral atrophy. We postulate that hippocampal atrophy does not seem to be a specific phenomenon of dementia in AD but also occurs in VaD and PDD, and even in PD when no dementia is present. However, coexistence of AD pathology in our PD and VaD patients cannot be ruled out. Further studies with access to neuropathologic data are needed.

An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-beta-protein and tau protein in vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (-54% of control) and the right amygdala (-37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We designed the present study to investigate the hypothesis that progression of hippocampal pathology may decrease the therapeutic effects of anti-cholinesterase drug, tetrahydroaminoacridine, on memory functioning in Alzheimer's disease (AD) patients. Memory, visuoconstructive, executive and vigilance functions were assessed after administration of placebo (p.o.; two placebo sessions) and tetrahydroaminoacridine (one session for 25 and 75 mg, p.o.). Eight patients performed better on list learning test during tetrahydroaminoacridine 75 mg than after placebo or tetrahydroaminoacridine 25 mg. The responders performed during baseline examination better than the non-responders in executive and some declarative memory functions, and had higher MMSE scores than the non-responders. The responders had larger left and right hippocampi than the non-responders. The hippocampal volume correlated with list learning performance. The results suggest that severe hippocampal atrophy may block memory improving effect of an anticholinesterase drug, tetrahydroaminoacridine.

The neuroanatomical networks involved in the initiation of panic attack and the maintenance of panic disorder are poorly understood. This study aimed to elucidate the possible abnormalities in benzodiazepine receptor uptake in the brain of patients with panic disorder. Seventeen unmedicated patients with panic disorder were investigated using 123 I-iomazenil single photon emission tomography (SPET). Seventeen healthy age- and sex-matched volunteers served as controls. The SPET scan was taken 90 min after injection of tracer. Eleven of 17 patients (65%) showed an increased (>2 s.D. higher than the mean of the controls) right-to-left ratio of benzodiazepine receptor uptake in the prefrontal cortex. Also, the mean right-to-left ratio of benzodiazepine receptor uptake in all 17 patients with panic disorder was higher than in the controls (P

Twenty-five patients with chemotherapy refractory cancer were treated with a fully serotype 3-based oncolytic adenovirus Ad3-hTERT-E1A. In mice, Ad3 induced higher amounts of cytokines but less liver damage than Ad5 or Ad5/3. In humans, the only grade 3 adverse reactions were self-limiting cytopenias and generally the safety profile resembled Ad5-based oncolytic viruses. Patients that had been previously treated with Ad5 viruses presented longer lasting lymphocytopenia but no median increase in Ad3-specific T-cells in blood, suggesting immunological activity against antigens other than Ad3 hexon. Frequent alterations in antitumor T-cells in blood were seen regardless of previous virus exposure. Neutralizing antibodies against Ad3 increased in all patients, whereas Ad5 neutralizing antibodies remained stable. Treatment with Ad3-hTERT-E1A resulted in re-emergence of Ad5 viruses from previous treatments into blood and vice versa. Signs of possible efficacy were seen in 11/15 (73%) patients evaluable for tumor markers, four of which were treated only intravenously. Particularly promising results were seen in breast cancer patients and especially those receiving concomitant trastuzumab. Taken together, Ad3-hTERT-E1A seems safe for further clinical testing or development of armed versions. It offers an immunologically attractive alternative, with possible pharmacodynamic differences and a different receptor compared to Ad5.

The safety of oncolytic viruses for treatment of cancer has been shown in clinical trials while antitumor efficacy has often remained modest. As expression of the coxsackie-adenovirus receptor may be variable in advanced tumors, we developed Ad5-D24-RGD, a p16/Rb pathway selective oncolytic adenovirus featuring RGD-4C modification of the fiber. This allows viral entry through alpha-v-beta integrins frequently highly expressed in advanced tumors. Advanced tumors are often immunosuppressive which results in lack of tumor eradication despite abnormal epitopes being present. Granulocyte-macrophage colony stimulating factor (GMCSF) is a potent activator of immune system with established antitumor properties. To stimulate antitumor immunity and break tumor associated immunotolerance, we constructed Ad5-RGD-D24-GMCSF, featuring GMCSF controlled by the adenoviral E3 promoter. Preliminary safety of Ad5-D24-RGD and Ad5-RGD-D24-GMCSF for treatment of human cancer was established. Treatments with Ad5-D24-RGD (N = 9) and Ad5-RGD-D24-GMCSF (N = 7) were well tolerated. Typical side effects were grade 1-2 fatigue, fever and injection site pain. 77% (10/13) of evaluable patients showed virus in circulation for at least 2 weeks. In 3 out of 6 evaluable patients, disease previously progressing stabilized after a single treatment with Ad5-RGD-D24-GMCSF. In addition, 2/3 patients had stabilization or reduction in tumor marker levels. All patients treated with Ad5-D24-RGD showed disease progression in radiological analysis, although 3/6 had temporary reduction or stabilization of marker levels. Induction of tumor and adenovirus specific immunity was demonstrated with ELISPOT in Ad5-RGD-D24-GMCSF treated patients. RGD modified oncolytic adenoviruses with or without GMCSF seem safe for further clinical development.

We studied a family with late-onset (fifth or sixth decade) or asymptomatic hereditary myopathy of the anterior tibial muscle. The occurrence of the disease in two successive generations pointed out an autosomal dominant pattern of inheritance. The initial symptom was uni- or bilateral foot drop resembling peroneal paresis. Surprisingly many of the diagnosed patients were asymptomatic and considered themselves healthy whether there was any foot drop or not. The anterior tibial muscles were atrophic in patients with foot drop but the long toe extensors were usually and the short ones were always spared. Apparently the toe extensors could relieve the foot drop symptom. As shown by computed tomography there was often an early uni- or bilateral involvement of the semimembranosus muscle in males. The proband showed also a late involvement of the femoral biceps and the minor gluteal muscles. The muscles of the upper extremity were spared. The anterior tibial muscles had a characteristic myopathic alteration with rimmed vacuoles in histopathological study. This picture was most evident in latent cases without atrophy of the anterior tibial muscle, but with distinctly abnormal EMG of that muscle. Non-affected muscles showed only slight non-specific histopathological changes. We suggest that this disease is a new mild variety of autosomal dominant distal myopathy with rimmed vacuoles.

We used proton magnetic resonance spectroscopy (1H MRS) to determine concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz) and in vitro (400 MHz) in seven patients undergoing surgical treatment of intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1, respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0) mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure focus in patients with temporal lobe epilepsy.

The serum values of tumour-associated trypsin inhibitor (TATI) were measured in a prospective series of 97 patients with jaundice, 36 patients with unjaundiced cholestasis and 21 patients with suspicion of chronic pancreatitis or a pancreatic tumour, to assess its value in diagnosing pancreatic cancer. There were altogether 15 patients with cancer of the pancreas and 2 patients with cancer of the papilla of Vater. The highest serum TATI values were noticed in patients with choledocholithiasis, and raised values were also seen in patients with malignant disease of the liver or bile ducts. In the patients with pancreatic cancer, chronic pancreatitis or benign liver disease, the serum TATI values showed lower levels. The sensitivity of TATI in diagnosing pancreatic cancer was 41.1% with a specificity of 63.5% and an efficiency of 61.0%. In comparison to carcinoembryonic antigen (CEA), carbohydrate antigens CA 50, CA 242, tissue polypeptide antigen and tissue polypeptide-specific antigen, TATI showed a lower diagnostic value. When TATI was analysed in combination with the other markers (two tests positive), the combination of CEA with TATI reached the highest specificity (95.6%), efficiency (89.6%) and positive likelihood ratio (9.3). The results suggest that the diagnostic value of TATI is inferior to that of the established markers, but because of its different nature, it may be of help when used in combination as a complementary serum tumour marker in the diagnosis of pancreatic cancer.

We evaluated the clinical utility of a new tumor marker tissue polypeptide specific antigen (TPS) in the diagnosis of pancreatic carcinoma. Serum concentrations were determined in 113 patients with jaundice, in 18 patients with laboratory values suggesting cholestasis and in 60 patients with suspicion of chronic pancreatitis or pancreatic tumor. Twenty-four of these 191 patients had pancreatic carcinoma and 2 patients had carcinoma of the papilla of Vater. The highest median serum TPS value was detected in patients with malignant liver disease, but high median values were also measured in patients with pancreatic cancer, bile duct cancer or benign liver disease. The sensitivity of TPS was 50.0%, with a specificity of 73% and an efficiency of 70%. In comparison with carcinoembryonic antigen (CEA), CA 50 and CA 242, the TPS test showed lower sensitivity, but the differences in specificity and negative predictive value were considerably smaller. The utility of TPS as a complementary test was also analyzed. When TPS was combined with other marker tests, their specificities clearly improved, being highest in the combination of TPS and CA 242 (92.5%). In this combination, efficiency and positive likelihood ratio were also clearly better (85% and 5.6) than those of the marker tests alone. In conclusion, TPS seems less accurate than CEA, CA 50 or CA 242 in the diagnosis of pancreatic cancer, but because of its different nature it may be considered to be used as a complementary test.

The aim of this study was to assess by a stepwise multivariate discriminant analysis the value of four current serum tumour markers - carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 and tissue polypeptide antigen (TPA) - and a new serum tumour marker, tissue polypeptide specific antigen (TPS), in the diagnosis of pancreatic cancer. The serum values were measured in a prospective series of patients with jaundice, with unjaundiced cholestasis and with a suspicion of chronic pancreatitis or a pancreatic tumour (n = 193). There were 24 patients with a cancer of the pancreas and two patients with a cancer of the papilla of Vater in this series. Our results showed that CA 50 (P < 0.001) and TPA (P < 0.01) were the best marker tests in predicting pancreatic malignancy. Also, the TPS (P = 0.07) and CA 242 (P = 0.08) tests showed marginally significant independent discriminating power, while the CEA test did not (P = 0.12). In order to sum up the contributions of different markers, a diagnostic score (DSI) was developed. The discrimination function was: DS1 = CA 50 x 1.75 + TPA x 0.62 + TPS x (-0.37) + CA 242 x (-1.21). The sensitivity of DS1 in detecting pancreatic cancer was 36% with a specificity of 90% and an efficiency of 82%. When the combination of CA 50 and TPA was used as a test, the discrimination function (DS2) was: DS2 = CA 50 x 0.69 + TPA x 0.67. The sensitivity of DS2 was 44% with a 88% specificity and an efficiency of 82%. According to this analysis, the further advantage gained by a computer-aided scoring system seems to be limited, since despite the considerably high specificity and efficiency its sensitivity remained low. In the present analysis the best combination in diagnosing pancreatic cancer was the combination of CA 50 and TPA.

(2002). Pagetic Bone Lesions in a Patient with Early Breast Cancer. Acta Oncologica: Vol. 41, No. 6, pp. 566-568.

A prospective study of 187 patients with jaundice and 33 patients with unjaundiced cholestasis was carried out to evaluate the value of serum bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gammaglutamyl transferase (GGT), and leucine aminopeptidase (LAP) in the differential diagnosis between benign and malignant diseases causing jaundice and/or cholestasis. In the patients with malignant disease (n = 60), the mean serum bilirubin and ALP concentrations were significantly higher (p < 0.001) than in the patients with benign disease (n = 160). Serum LAP, ASAT, ALAT, or GGT levels did not show any significant differences. A stepwise discriminant analysis was carried out to evaluate the value of laboratory tests in predicting malignancy. The discrimination function is DF = bilirubin x 0.71 + ALP x 0.58 + ASAT x -0.24 + ALAT x 0.18 + LAP x 0.08 + GGT x -0.22. When the discriminant function was considered as a diagnostic score (DS), the sensitivity of it in detecting malignancy was 58% with a specificity of 89% and an efficiency of 81%. The DS of serum bilirubin and ALP reached the sensitivity of 61% with a 87% specificity and an efficiency of 79%. The post-test probability of malignant disease calculated by in this test combination was 69%. The LR+ was 4.8 and LR- 0.44. In conclusion, serum bilirubin and alkaline phosphatase seem to be the most potential tests of these laboratory tests in distinguishing benign and malignant causes of jaundice and/or cholestasis, high levels being suggestive of malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Oncolytic adenoviruses are an emerging treatment option for advanced and refractory cancer. Such patients are often treated with corticosteroids to ameliorate tumor associated symptoms. Thus, it is important to evaluate whether safety is affected by immunosuppression possibly induced by corticosteroids. Concurrent low-dose cyclophosphamide, appealing for its immunomodulatory effects, could also impact safety. In a retrospective case-control study, we evaluated the effect of systemic corticosteroid use in cancer patients receiving oncolytic virotherapy. Four treatment groups were identified: (1) oncolytic adenovirus with oral glucocorticoids, (2) virus alone, (3) virus with glucocorticoids and cyclophosphamide and (4) virus with cyclophosphamide. Adverse events, neutralizing antibody titers, viral DNA in circulation and tumor responses were evaluated. The most common adverse effects were grade 1-2 fatigue, nausea, fever and abdominal pain. Common asymptomatic findings included self-limiting grade 1-3 hyponatremia and aspartate aminotransferase increase. Safety was good and no significant differences were observed between the groups. All patients had an increase in neutralizing antibody titers post-treatment, and no trends for differences between groups were observed. There were fewer post-treatment virus genomes circulating in patients receiving glucocorticoids when compared to their control groups. Overall, glucocorticoid use in cancer patients receiving oncolytic adenovirus, with or without low-dose cyclophosphamide, seems safe.

The usefulness of digital image processing of chest radiographs was evaluated in a clinical study. In 54 patients, chest radiographs in the posteroanterior projection were obtained by both 14 inch digital image intensifier equipment and the conventional screen-film technique. The digital radiographs (512 x 512 image format) viewed on a 625 line monitor were processed in three different ways: (1) standard display; (2) digital edge enhancement for the standard display; and (3) inverse intensity display. The radiographs were interpreted independently by three radiologists. The diagnoses were confirmed by CT, follow-up radiographs and clinical records. Chest abnormalities of the films analyzed included 21 primary lung tumors, 44 pulmonary nodules, 16 cases with mediastinal disease and 17 cases with pneumonia/atelectasis. Interstitial lung disease, pleural plaques, and pulmonary emphysema were found in 30, 18 and 19 cases, respectively. The sensitivity of conventional radiography when averaged overall findings was better than that of the digital techniques (P less than 0.001). The differences in diagnostic accuracy measured by sensitivity and specificity between the three digital display modes were small. Standard image display showed better sensitivity for pulmonary nodules (0.74 vs 0.66; P less than 0.05) but poorer specificity for pulmonary emphysema (0.85 vs. 0.93; P less than 0.05) compared with inverse intensity display. We conclude that when using 512 x 512 image format, the routine use of digital edge enhancement and tone reversal at digital chest radiographs is not warranted.

A prospective study of jaundiced (n = 187) and nonjaundiced (n = 33) cholestatic patients was carried out to evaluate the sensitivity of ultrasonography (US), CT, and endoscopic retrograde cholangiopancreatography (ERCP) in the detection of choledochal stone disease. Altogether 83 patients had the final diagnosis of choledocholithiasis. In the jaundiced patients, the sensitivity of US, CT, and ERCP was 22.5%, 23.2%, and 80.6%, respectively. In cases of cholestasis without jaundice, the values were 20%, 37.5%, and 66.7%. In patients in whom all 3 imaging studies were done (n = 64), the differences between US and ERCP and between CT and ERCP were statistically significant (p < 0.0001). In most false-negative ERCP studies (10/15), the clinical course of the disease strongly suggested a passed choledochal stone. On the basis of this study, we recommend prompt ERCP to be performed if choledochal stone disease is suspected on clinical grounds.

Inter- and intraobserver variation and diagnostic accuracy in estimation of heart size and pulmonary vasculature were evaluated for conventional film-screen technique and image intensifier photofluorography. Interpretation of 218 p.a. and lateral chest films by both imaging techniques was performed independently by 4 readers. Heart size relative to body surface area measured from the plain chest films was used as the reference in cardiac size determination. Overall diagnostic accuracies of conventional radiography and image intensifier photofluorography for cardiomegaly were close to each other, 0.70 vs 0.68, respectively. Specificity of film-screen radiography was better than that of photofluorography (0.92 vs 0.84, p

Ultrasonography (US) and computed tomography (CT) were performed on respectively 67 and 42 (altogether 72) patients, for the assessment of intrahepatic cholestasis. The diagnostic ability to differentiate between malignant (17 patients) and benign (55 patients) liver disease was analyzed. Coarse echogenicity of the liver led to inconclusive results in differentiating between cirrhosis (2 out of 29 patients) and malignant infiltration (4 out of 15 patients) by US. Other benign liver diseases in 23 patients, including acute hepatitis, chronic active hepatitis, fatty liver, and liver congestion, were correctly interpreted as benign. CT correctly disclosed malignant liver disease in all cases. A false positive diagnosis of malignancy was encountered in 4 (out of 17) patients with decompensated hepatic cirrhosis because of non-homogeneous expansive areas on CT in 3 cases. The true cause was in 2 patients non-uniform fatty infiltration, and in one patient with acute hepatitis A, small hypodense lesions. Among cholestatic patients, decompensated cirrhosis and malignant liver infiltration could not always be differentiated on US or CT.

Objectives – To assess the correlation of diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) findings with the severity of acute neurologic deficit and their ability to predict short and long-term clinical outcomes of stroke. The ability of DWI and PWI to predict the outcome was compared with the ability of clinical stroke scales to predict the outcome. Methods – Forty-eight patients with acute stroke underwent diffusion DWI and PWI on the first and eighth day after the ictus. Clinical and functional scales were carried out before each scan and 3 months after the stroke. Results – The volumes of both the DWI and the PWI lesions correlated well with the acute neurologic deficit and the final outcome. The first day PWI (r = 0.64) and the National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.70) correlated well with the final outcome. However, in logistic regression analysis, only the NIHSS score at the acute stage was the only independent predictor of the long-term clinical outcome. Conclusion – While the PWI and DWI lesion volumes correlated well with the outcome of the stroke, the imaging measurements did not improve the prognostic power over plain clinical stroke scale scores.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy. The mechanisms of epileptogenesis and seizure semiology of the mesial and neocortical temporal lobe epilepsy are discussed. The evaluation and selection of patients for TLE surgery requires team work: the different clinical aspects of neuropsychological evaluation, magnetic resonance and functional imaging (positron emission tomography, single photon emission computed tomography and magnetoenephalography) are reviewed. In our programme of epilepsy surgery at Kuopio University Hospital, Finland, we have performed 230 temporal resections from 1988 until 2002. Preoperative diagnostic EEG-videotelemetry often required intracranial monitoring and it has proved to be safe and efficient. The indications and technique for tailored temporal lobe resection with amygdalohippocampectomy used in our institution, as well as the complications, are described. Our analysis of outcome after temporal lobe surgery included 140 consecutive adult patients between 1988 and 1999; one year after the operation in unilateral TLE the Engel I-II outcome was observed in 68% of the patients. Outcome of surgery improved significantly after introduction of the standardised MR imaging protocol from 1993; 74% of patients with unilateral TLE achieved Engel I-II outcome.

The objective of this study was to evaluate verbal memory in newly diagnosed and chronic left temporal lobe epilepsy (LTLE). Verbal memory performance of 39 newly diagnosed, previously untreated adult patients with LTLE and 16 patients with chronic LTLE, as well as 46 healthy controls, was analyzed. The patients with newly diagnosed and chronic LTLE had impaired verbal memory performance compared with normal controls. Memory performance was more affected in chronic LTLE. However, preliminary data from 5-year follow-up of 20 newly diagnosed LTLE patients did not show any deterioration in verbal memory performance. The memory impairment was not associated with the etiology of epilepsy or the hippocampal volumes, but was associated with early onset of epilepsy in LTLE and with secondarily generalized seizure type in newly diagnosed LTLE. The results of this study show that verbal memory is impaired not only in chronic LTLE but also in newly diagnosed, untreated LTLE. This suggests that the memory problems observed in patients with chronic LTLE cannot be attributed solely to medication effects or the chronic effects of recurrent seizures.

Molecular and network changes that are proposed to underlie the development of spontaneous seizures are best understood in subjects with symptomatic aetiology for temporal lobe epilepsy (TLE). Symptomatic TLE typically develops in three phases (Fig. 1): brain damage → latency phase or epileptogenesis → appearance of spontaneous seizures or epilepsy which can be easy to control or turn out to be drug-refractory over the time. According to some authors, the primary epileptogenesis is followed by a secondary epileptogenesis; that is, activity of primary focus leads to the appearance of an independent secondary focus over the time [61]. It is still controversial, however, whether and at which conditions secondary epileptogenesis can occur in the human brain.

Background The relationship between reduced glucose metabolism in positron emission tomography with fludeoxyglucose F 18 ([ 18 F]FDG-PET) and hippocampal damage (HD) in patients with temporal lobe epilepsy is still unclear. Objective To determine whether the presence and severity of HD verified by quantitative magnetic resonance imaging (QMRI) and histopathological analysis affect the degree of hypometabolism. Patients and Methods Sixteen patients with drug-resistant temporal lobe epilepsy underwent [ 18 F]FDG-PET and QMRI (hippocampal volumetry and T2 relaxometry) before surgery. Histopathological analysis of the hippocampus included measurements of neuronal loss, proliferation of glial cells, and mossy fiber sprouting. The asymmetry in glucose metabolism described the degree of hypometabolism. Results Temporal hypometabolism was not related to severity of HD as measured by QMRI or histopathological analysis. The degree of hypometabolism did not differ in patients with mild, moderate, or severe HD. In addition, [ 18 F]FDG-PET revealed significant temporal hypometabolism even though hippocampal QMRI findings were normal or showed only mild HD. Thus, glucose consumption was reduced over and above the histopathological changes. Conclusions [ 18 F]FDG-PET is sensitive for localizing the epileptogenic region in patients with temporal lobe epilepsy. However, it is insensitive to reflect the severity of HD.