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Biomedical subjects

G Hagberg

Publications and source records attributed to G Hagberg.

At least 19 recordsLinked to original sources

In vivo multiple spin echoes imaging of trabecular bone on a clinical 1.5 T MR scanner.

In vivo multiple spin echoes (MSE) images of bone marrow in trabecular bone were obtained for the first time on a clinical 1.5 T scanner. Despite of a reduced sensitivity of the MSE trabecular bone images with respect to the cerebral matter ones, it is possible to observe some features in the MSE trabecular bone images that may be useful in the diagnosis of osteopenic states. Two different CRAZED-type MSE imaging sequences based on spin-echo and EPI imaging modalities were applied in phantom and in vivo. Preliminary experimental results indicate that EPI imaging readout seems to conceal the MSE contrast correlated with pore dimension in porous media. However it is still possible to detect anisotropy effects related to the bone structure in MSE-EPI images. Some strategies are suggested to optimize the quality of MSE trabecular bone images.

Adult↗

Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors.

UNLABELLED: Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants. The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32-36 wk), born in 1983-90, were included and matched with a control group (n = 296). In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk. Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups. Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group. CONCLUSION: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.

Apgar Score↗

Head growth in Rett syndrome.

The longitudinal development of head growth was investigated in girls with Rett syndrome (RS). Growth retardation was expressed in standard deviation (SD) scores. In classic types, the mean head circumference fell successively to 2 SD scores below the norm at the age of 4 years. After the age of 8 it stabilized close to -3 SD scores. In forme fruste variants, the mean head circumference was within normal limits; however, it was significantly below the norm, -0.8 SD scores. In girls with classic RS, head growth had decelerated by less than 1 SD score in 20% of the girls at the age of 6 years and in 10% at the age of 12 years. In forme fruste variants only a small decline in head growth occurred. Head growth decline may thus be very small in classic RS and is usually not present at all in forme fruste variants. In the future, it should, therefore, neither be regarded as a necessary diagnostic criterion for classic RS, nor as a valid one for forme fruste variants.

Aging↗

PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy.

OBJECTIVES: This study compares positron emission tomography (PET) using 11C-deuterium-deprenyl (DED) with PET using 18F-fluorodeoxyglucose(18F-FDG) for examining epileptogenic regions in patients with focal epilepsy. MATERIAL AND METHODS: Twenty-three patients undergoing evaluation for epilepsy surgery were subjected to PET with DED. Fourteen patients had mesial temporal lobe epilepsy (TLE) and 9 patients had seizures of neocortical origin. In addition, 6 healthy control subjects were examined. Pixel-by-pixel analysis was used to generate graphical images of tracer distribution volume (intercept) and the accumulation rate (slope). Asymmetries with respect to relative intercept and slope were compared in patients with temporal lobe epilepsy (TLE), in patients with extra-temporal lobe epilepsy (exTLE), and in the control subjects. The results were compared with 18F-FDG-PET. RESULTS: Among the patients with TLE, significant differences between the epileptogenic and the contralateral lobe were found with DED intercept and FDG-uptake. No significant differences were found with DED slope. The exTLE and the control groups showed no significant differences between sides or lobes. CONCLUSIONS: This study indicates that PET with 11C-deuterium-deprenyl is a useful method for identifying TLE and is equivalent to PET with 18F-FDG in this sense. The method has little localizing value in seizures originating from neocortical structures.

Adolescent↗

Epilepsy in a representative series of Rett syndrome.

UNLABELLED: In a representative series of 53 females with Rett syndrome (RS), aged 5-55 y, a history of epilepsy was present in 50 (94%), 45 of whom had 5-y active epilepsy. Compared with severe mental retardation in general, the median age of seizure onset was significantly later (4 vs 0.8 y) and partial complex seizures were more frequent (54% vs 23%). Neonatal seizures had occurred in only one and infantile spasms in none compared with 26% and 12%. After teenage, the severity of epilepsy tended to decrease, i.e. lower seizure frequency and relatively more partial seizures. The rate of being seizure-free for 1 y was 8% after 10 y and 40% after 27 y of epilepsy duration. Frequent seizures were associated with smaller head circumference. CONCLUSION: This epilepsy profile could fit in with present-day knowledge of RS as a form of dendrito-synaptogenic developmental failure with mainly late postnatal consequences, as well as being a relatively stationary condition in adulthood.

Adolescent↗

Changing panorama of cerebral palsy in Sweden. VIII. Prevalence and origin in the birth year period 1991-94.

UNLABELLED: This 8th Swedish population-based cerebral palsy (CP) report comprises 241 children born 1991-94. The live birth prevalence was 2.12 per 1000. Excluding 7 postnatally-derived cases, the gestational age-specific prevalences were 86 for extremely preterm children, 60 for very preterm and 6 for moderately preterm, and 1.3 for term children per 1000. Spastic hemiplegic, diplegic and tetraplegic subtypes accounted for 33%, 44% and 6%, dyskinetic CP for 12% and simple ataxia for 4%. Neuroimaging had been performed in 90%. Probable aetiology was identified in 73% of preterm and 86% of term children. Among preterm children it was considered prenatal in 12%, peri/neonatal in 61% and unclassifiable in 27%, while it was 51%, 36% and 14% among term children. CONCLUSION: The live birth prevalence for CP in the birth year period 1991-94 continued to decrease slightly. Gestational age-specific prevalences increased marginally in extremely and very preterm births, continued to decrease in moderately preterm births and decreased slightly in term births. Probable aetiology and timing of the brain insult could be revealed in 81%, birth asphyxia being the likely cause in 28% of term children.

Cerebral Palsy↗

Correlation between ICIDH handicap code and Gross Motor Function Classification System in children with cerebral palsy.

The aim of this study was to apply the International Classification of Impairments, Disabilities and Handicap (ICIDH; WHO 1980) parallel to the Gross Motor Function Classification System (GMFCS; Palisano et al. 1997) in a population-based series of children with cerebral palsy (CP). Of the 116 children studied, birth characteristics, data on gross motor function, and level of handicap at 5 to 6 years of age, were retrospectively collected from medical records and documentation made by rehabilitation team members. Low handicap scores and mild levels of gross motor disability were present in children with hemiplegic CP, moderate scores in children with diplegic CP, simple ataxia, and athetotic CP, and high scores in children with dystonic CP and tetraplegic CP. A significant correlation was found between high handicap scores as well as high levels on the GMFCS and the presence of learning disability, epilepsy, and obvious aetiology of CP. A strong correlation was found between the handicap code and the GMFCS, the strongest concerning the dimension of mobility (r = 0.95,p<0.0001). A striking similarity in the grading of disability was present between the ICIDH handicap code and the GMFCS. The GMFCS is considerably less time-consuming and can be evaluated retrospectively. The handicap code requires more detailed information and is more useful for a comprehensive profile of the child.

Cerebral Palsy↗

Head growth in Rett syndrome.

The longitudinal development of head growth was investigated in girls with Rett syndrome. Measurements were taken retrospectively from different kinds of records. Growth retardation was expressed in standard deviation (SD) scores. In classic types, the mean head circumference fell successively to 2 SD scores below the norm at the age of 4 y. After the age of 8 y it stabilized close to -3 SD scores. The degree of deceleration correlated strongly to the age at which a deceleration of 1 SD score had occurred. In forme fruste variants, the mean head circumference was within normal limits; however, it was significantly below the norm (-0.8 SD scores). Body height deviated to -2 SD scores at the age of 6 y and was highly correlated to decline in head growth. When head growth was related to the severity of motor disability, there was a continuum from almost normal head growth with well-preserved gross motor function and some preserved fine motor function to a marked deceleration in head growth with maximum gross and fine motor disability.

Age Factors↗

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.

Administration, Intravesical↗

Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques: absolute metabolic values over 2 years during a clinical pharmacological study.

BACKGROUND AND PURPOSE: The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2 years, we compared the absolute concentrations of these metabolites between patients treated with a placebo or 15 +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or secondary-progressive MS. METHODS: Sixteen patients, recruited from a pharmacological study of DSG, and 11 healthy control subjects were investigated by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected volume initially contained a contrast-enhancing plaque, which was followed up for a period of 2 years. RESULTS: In contrast-enhancing plaques, Cho was significantly elevated and showed a significant reduction after both 3 and 12 months. The initially normal Cr significantly increased between 3 and 12 months, and was negatively correlated with plaque volume on T1-weighted MR images. NAA initially showed normal values, a significant decrease at 1 month, and a slow recovery over 2 years. Myo-inositol did not show a clear tendency. The placebo group did not differ from the treated group, nor did the relapsing-remitting group differ from the secondary-progressive group. CONCLUSION: The contradictory time courses of Cr and NAA show that an absolute quantification in proton MR spectroscopy in MS is necessary to avoid a false interpretation of reduced NAA/Cr ratios. The increase in Cr is probably due to remyelination. The initial dip and later recovery of NAA seem to be related to diminishing edema and remyelination.

Adult↗

Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(beta-11C) DOPA and PET.

BACKGROUND: The aim of the present study was to investigate dopamine synthesis in the brain of drug-free schizophrenic patients, not only in the striatum but also in extrastriatal areas like the prefrontal cortex, brain areas that for a long time has been in focus of interest in the pathophysiology of schizophrenia. METHODS: PET was performed in 12 drug-free (10 drug-naive) psychotic schizophrenic patients and 10 healthy volunteers matched for age and gender using 11C-labelled L-DOPA as the tracer. The time-radioactivity curve from occipital cortex (located within Brodman area 17 and 18) was used as input function to calculate L-DOPA influx rate, Ki images, that were matched to a common brain atlas. A significant overall increase of the Ki values was found in the schizophrenic group as compared with healthy controls. RESULTS: In particular, significantly higher Ki were found in the schizophrenic patients compared to the controls in the caudate nucleus, putamen and in parts of medial prefrontal cortex (Brod 24). The Ki value reflect an increased utilization of L-DOPA, presumably due to increased activity of the amino acid decarboxylate enzyme. CONCLUSIONS: The results indicate that the synthesis of dopamine is elevated within the striatum and parts of medial prefrontal cortex in schizophrenia.

Adult↗

Synthesis and characterization of binding of 5-[76Br]bromo-3-[[2(S)-azetidinyl]methoxy]pyridine, a novel nicotinic acetylcholine receptor ligand, in rat brain.

5-[76Br]Bromo-3-[[2(S)-azetidinyl]methoxy]pyridine ([76Br]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [76Br]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/micromol. The binding properties of [76Br]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [76Br]BAP binding was obtained after 60 min. The dissociation half-life of [76Br]BAP was 51 +/- 6 min in cortical membranes and 56 +/- 3 min in thalamic membranes. Saturation experiments with [76Br]BAP revealed one population of binding sites with dissociation constant (K(D)) values of 36 +/- 9 and 30 +/- 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (Bmax) values were 90 +/- 17 and 207 +/- 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were <1, suggesting the presence of a lower-affinity binding site. In vitro autoradiography studies showed that binding of [76Br]BAP was high in the thalamus and presubiculum, moderate in the cortex and striatum, and low in the cerebellum and hippocampus. A similar pattern of [76Br]BAP accumulation was observed by ex vivo autoradiography. In vivo, binding of [76Br]BAP in whole rat brain was blocked by preinjection of (S)(-)-nicotine (0.3 mg/kg) by 27, 52, 68, and 91% at survival times of 10, 25, 40, 120, and 300 min, respectively. In a preliminary PET study in rhesus monkeys, the highest [76Br]BAP uptake was found in the thalamus, and radioactivity was displaceable by approximately 60% with cytisine and by 50% with (S)(-)-nicotine. The data of this study indicate that [76Br]BAP is a promising radioligand for the characterization of nicotinic acetylcholine receptors in vivo.

Alkaloids↗

Regulation of dopaminergic activity in early Parkinson's disease.

Parkinson's disease (PD) is characterized by an uneven and progressive loss of nigrostriatal dopaminergic neurons. It is hypothesized that the physiological basis for the therapeutic response in early stages of PD is the ability for the partially and unevenly denervated dopaminergic system to restore and normalize dopaminergic influence in functionally segregated subregions of the basal ganglia. To investigate this hypothesis, patients with early and uncomplicated PD were investigated with positron emission tomography by using a two-tracer protocol yielding a measure of dopamine transporter-corrected dopamine synthesis capacity. Compared with controls, patients with PD exhibited a considerable increase in dopamine transporter-corrected dopamine synthesis capacity. The increase showed an inverse dependence on the structural integrity in as much as the highest rate was measured in the most denervated region, the dorsal part of putamen (198% of control value). A therapeutic challenge with antiparkinsonian medication state-dependently decreased dopaminergic activity. Thus, it is demonstrated that dopaminergic degeneration in PD is accompanied by a conspicuous acceleration of presynaptic dopaminergic activity, which is state-dependently down-regulated by dopaminomimetic treatment. It is suggested that homeostatic mechanisms acting to maintain congruity within the dopaminergic system are functionally intact in early PD.

Analysis of Variance↗

N-[11C]methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic.

The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D2 dopamine receptor was investigated using the PET tracers [11C]raclopride and N-[11C]methylspiperone in a group of five schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51% +/- 10% occupancy at the 750 mg dose) was detected with [11C]raclopride (P < 0.01), no such trend was apparent for N-[11C]methylspiperone (P > 0.09, maximal occupancy values were 2% +/- 3%, measured for the group of three patients on 450 mg). The study suggests that N-[11C]methylspiperone cannot be used for the assessment of D2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants.

Adult↗

Infantile hydrocephalus: declining prevalence in preterm infants.

The prevalence and aetiological panorama of infantile hydrocephalus in western Sweden have been followed since the late 1960s. A significant increase in the live birth prevalence of very preterm infants with infantile hydrocephalus was found, from 6.99 per 1000 in the birth year period 1973-78 to 25.37 in 1983-86, and owing to an increased survival of very preterm infants with a high risk of hydrocephalus, secondary to an intraventricular haemorrhage occurring in the perinatal period. In the present study covering the birth years 1991-94, a declining prevalence to 13.69 per 1000 very preterm infants was found. In moderately preterm and term groups, mostly with prenatal aetiologies, the prevalence was unchanged. Outcome in surviving children with infantile hydrocephalus remained essentially the same as in previous studies, indicating that the underlying aetiology is the most decisive factor with respect to ensuing neuroimpairments.

Gestational Age↗

Intractable epilepsy in a population-based series of mentally retarded children.

PURPOSE: The characteristics of intractable epilepsy were analyzed in a population-based study of active epilepsy in mentally retarded children aged 6-13 years. METHODS: Diagnostic registers, EEG laboratory registers, and registers for the Education of the Subnormal were searched. Medical files were scrutinized. Clinical examinations and interviews with parents and caregivers or both were performed. EEG recordings, computed tomography (CT) and magnetic resonance imaging (MRI) of the CNS were reevaluated. RESULTS: Forty-five percent (44 of 98) of the children with mental retardation (MR) and active epilepsy had intractable seizures, defined as one or more seizures every day or week. The median age at onset was 0.8 years, as compared with 3.0 years for those with controlled epilepsy. Predictive factors for frequent seizures were the number of seizure types, severe MR, status epilepticus (SE) and tonic seizures. Epileptiform EEG activity was present in 91%, and focal activity in 65%. Brain lesions were detected on CT and MRI in 70%, with generalized lesions in 60%. Concurrent focal epileptiform activity and focal brain lesions on CT/MRI were detected in 26%. The percentages and prevalence rates for infantile spasms (IS) and Lennox-Gastaut syndrome (LGS) were 18% (0.25 in 1,000) and 7% (0.06 in 1,000), respectively. One of 8 children with IS had had previous neonatal seizures, 3 had SE and 1 later developed LGS. CONCLUSIONS: Children with MR and intractable epilepsy have a high frequency of severe MR and additional major neuroimpairments. EEG recordings frequently showed focal changes despite generalized lesions in neuroradiology.

Adolescent↗