Biomedical subjects

W Block

Publications and source records attributed to W Block.

At least 19 recordsLinked to original sources

PubMed2002

Perfusion and molecular diffusion-weighted MR imaging of the brain: in vivo assessment of tissue alteration in cerebral ischemia.

The combined use of perfusion imaging (PI) and diffusion-weighted imaging (DWI) is opening a new window into the processes that occur during the first hours of ischemia. DWI detects changes in molecular diffusion associated with cytotoxic edema. PI characterizes the degree of regional hypoperfusion. Regions showing mismatches between DWI and PI, i.e. hypoperfused areas with normal diffusion behavior are considered potentially salvageable. We present results of 11 patients with an occlusion of the middle cerebral artery stem and spontaneous stroke evolution. Whereas the infarct was clearly visible on initial DWI and PI, surrounding tissue at risk of infarction was marked in all patients by an increased blood volume and transit time, but only in a subgroup (n = 3) where alteration were more pronounced this tissue at risk was progressively infarcted. These human DWI and PI data show alterations in the area of tissue at risk which correlates with infarct progression.

Adolescent↗

PubMed2002

In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration.

Proton magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive method to investigate changes in brain metabolite composition in different cerebral diseases. We performed proton spectroscopy in patients with dementia of the Alzheimer's type (AD) and in patients with motor neuron disease (MND) with the aim to detect the specific metabolic pattern for these neurodegenerative disorders. In the MND group we found a significant reduction of NAA/tCr metabolite ratios in the motor cortex, which correlates with the disease severity and the clinical lateralization of neurological symptoms and further decreases in the time course of the disease. In AD patients a reduction of NAA/tCr was observed in the medial temporal lobe. Since NAA is exclusively expressed in neurons as shown by immunohistochemical studies, reduced NAA levels suggest neuronal loss or dysfunction in the observed regions. The observed regional metabolic alterations reflect the neuronal basis of the characteristic neurological symptoms in AD (dementia) and MND (muscular palsy) and mirrors the disease progress over time.

Aged↗

PubMed2002

[1H-MR Spectroscopy of brain tumors in the course of radiation therapy: Use of fast spectroscopic imaging and single-voxel spectroscopy for diagnosing recurrence].

PURPOSE: To improve differential diagnosis of residual or recurrent tumor vs. tissue necrosis in the course of radiation therapy of neurosurgically-treated brain tumors by application of fast (1)H-MR spectroscopic imaging in combination with single-voxel spectroscopy (SVS). METHODS: 54 patients after with malignant brain tumor (44 cases of glioblastoma, 10 other high-grade gliomas) were examined post-surgically in a total of 140 proton MRS examinations in the course of radiotherapy and in follow-up controls. Fast SI acquisition was performed as single-slice or double-slice TSI sequence with 32 x 32 phase encodings within 11 or 15 minutes, respectively. SVS with TR/TE 2000/272 ms yielded relative metabolite ratios, and in 15 patients the time courses of the absolute concentrations of brain metabolites were also determined. RESULTS: In the group of 44 patients that could be tracked by MRS until therapy completion, TSI localized in 23 patients a persistent or newly arisen distinct choline accumulation indicating residual or recurrent tumor after radiation therapy. In all these cases MRS diagnosis was confirmed histologically or by short-term follow-up. However, in 6 of 15 patients showing a normal choline pattern in the TSI acquisition, tumor recurrence appeared within three months. SVS provided early recognition of recurrent tumor when detecting characteristic alterations of metabolite concentrations oin therapy follow-up. CONCLUSION: TSI and SVS represent complementary MRS techniques and are able to diagnose tumor recurrence early and unambiguously in cases where focal choline accumulation is detected.

Adult↗

PubMed2001

Proton magnetic resonance spectroscopy and transcranial magnetic stimulation for the detection of upper motor neuron degeneration in ALS patients.

Transcranial magnetic stimulation (TMS) was compared to proton magnetic resonance spectroscopy (1H-MRS) for the detection of upper motor neuron loss or dysfunction in 49 ALS patients classified according to the El Escorial criteria. Abnormal NAA/Cho ratios were detected in 53% of ALS patients. Abnormal TMS results (i.e. cortical inexcitability or prolonged CMCT's) were obtained in 63% of ALS patients. If one or both methods were considered for diagnosis of upper motor neuron degeneration/dysfunction, the percentage of abnormal findings was 77%, whilst in 39% of all patients both methods produced abnormal results. Compared to TMS, 1H-MRS detected more patients with upper motor neuron involvement in the suspected El Escorial subgroup (42% versus 25%), whereas TMS detected more patients with upper motor neuron involvement in the possible (81% versus 50%), probable (71% versus 57%) and definite El Escorial subgroup (71% versus 64%). We conclude that the combined use of 1H-MRS and TMS increases diagnostic accuracy for the detection of upper motor neuron involvement in ALS patients.

Adult↗

PubMed2001

Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients.

In this (1)H-MRS follow-up study of the medial temporal lobe (MTL) in patients with AD, the authors report a correlation of N-acetylaspartate (NAA)/creatine (Cr) with cognitive decline. Severely progressed patients showed a reduction, whereas stable or mildly progressed subjects showed a slight increase of NAA/Cr. The reduction of NAA/Cr in the MTL represents a correlate of cognitive deterioration in AD, whereas it is of limited use to detect subtle changes over time in clinically stable patients.

Aged↗

PubMed2001

Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate proton magnetic resonance spectroscopy for detection and monitoring of upper motoneuron degeneration in patients with amyotrophic lateral sclerosis. METHODS: Seventy patients with amyotrophic lateral sclerosis according to the El Escorial criteria were compared with 48 healthy control subjects. Single-volume proton magnetic resonance spectroscopy (echo time, 272 milliseconds; repetition time, 2000 milliseconds) was performed in both motor cortices for detection of N-acetylaspartate (NAA), phosphocreatine + creatine ([P]Cr), and choline-containing compounds (Cho) to calculate the metabolite ratios NAA/Cho, NAA/(P)Cr, and Cho/(P)Cr. In addition, absolute metabolite concentrations of NAA, (P)Cr, and Cho were obtained in 30 patients and 15 controls with the unsuppressed water signal used as an internal reference. RESULTS: Absolute concentrations of NAA (P<.001) and (P)Cr (P<.05) were reduced in motor cortices of patients, whereas Cho concentrations remained unchanged. The NAA/Cho and NAA/(P)Cr ratios were reduced in all El Escorial subgroups (P<.001). The Cho/(P)Cr ratio was elevated in patients with definite amyotrophic lateral sclerosis (P<.05). Metabolite ratio changes corresponded to the lateralization of clinical symptoms and were weakly correlated with disease duration and disease severity. In follow-up observations of 16 patients during a mean (+/-SD) of 12.1 +/- 8.7 months, NAA/Cho dropped by 9.1% (P<.01), and Cho/(P)Cr increased by 7.0% (P<.01). Changes of metabolite ratios were significantly correlated with progression of disease severity. CONCLUSIONS: Measurement of NAA concentrations and NAA/Cho ratios appear to be most suitable for detection of motor cortex degeneration by single-volume proton magnetic resonance spectroscopy. Reduced NAA/Cho ratios correspond to aspects of the clinical presentation and reflect disease progression in follow-up measurements.

Adult↗

PubMed2001

Experimental studies of ice nucleation in an Antarctic springtail (Collembola, Isotomidae).

Ice nucleation was studied in field-fresh and acclimated (4 degrees C without food for 11-20 days) samples of the springtail Cryptopygus antarcticus Willem (Collembola, Isotomidae) at Rothera Research Station, Adelaide Island on the Antarctic Peninsula. Ice nucleator activity (INA) was measured by a freezing droplet technique in addition to supercooling point (SCP) profiles and polyol, sugar, and water contents. Field and acclimated samples showed bimodal SCP distributions with a distinct high group (HG; mean SCP -8 to -10 degrees C) and low group (LG: mean SCP -23 to -25 degrees C), which were significantly different. Acclimation at 4 degrees C increased the proportion of individuals in the LG relative to that in the HG without significant effects on the mean SCP of both groups. INA of the HG was significantly greater than that of the LG, and acclimation further reduced the INA of the LG. The number of active ice nucleator agents (INAs) calculated for the HG of field samples increased by 23-100 times over the temperature range -5 to -8 degrees C compared to only 7 times for the LG over the same range. These differences were accentuated in the acclimation experiments. Glucose and galactose were the main carbohydrates in both field and acclimated springtails, with the latter compound occurring in almost twice the concentration in the LG compared with that in the HG. Acclimation reduced the concentration of both compounds (glucose by 77% and galactose by 54%), whereas water content increased significantly. Digestion of food may have continued during acclimation at 4 degrees C, which could reduce the LG INA. Lowering of temperature over time is more likely to elicit a cold hardening response than constant temperature acclimation. INA numbers calculated at the nucleation temperatures for C. antarcticus samples were higher in the LG than in the HG. However, inactivation of INAs may be a key mechanism underlying cold hardening in this species, either by sequestration within the cellular matrix or by being only seasonally active.

Acclimatization↗

PubMed2001

Phenotype assignment in symptomatic female carriers of X-linked adrenoleukodystrophy.

However, only very few studies have systematically investigated the extent and distribution of nervous and endocrine system involvement in female carriers of X-ALD. To define the phenotype in symptomatic female carriers of X-ALD we performed a prospective study including eight symptomatic women who were followed for a mean period of 3.4+/-1.8 years (range 1-6) using standardized clinical examination protocols, magnetic resonance imaging and spectroscopy, evoked potential studies including visual, brainstem auditory, somatosensory and magnetic evoked potentials, neurographic recordings and endocrine studies. Spastic paraparesis and decreased vibration sense in the lower extremities were the most frequent clinical findings. Slightly hyperintense symmetric parieto-occipital white matter lesions on magnetic resonance imaging were detectable in two of seven cases, and the N-acetylaspartate/choline ratios on magnetic resonance spectroscopy were decreased in three of seven patients. P40 latencies were abnormal in all patients, and central motor conduction times to the lower extremities in seven of eight patients. Prolonged latencies of brainstem auditory evoked potential waves III-V or interpeak latencies of waves I-III, I-V and III-V were detectable in all patients. The degree of walking impairment was positively correlated with the duration of clinical disease (r=0.58, P < 0.05) and inversely correlated with the N-acetylaspartate/choline ratios (r=0.85; P < 0.05). Neurographic recordings revealed only subtle abnormalities, suggesting that nervous system involvement in symptomatic female carriers of X-ALD is confined mainly to the central nervous system. No evidence of adrenal insufficiency was detected in any of the patients.

Adrenal Insufficiency↗

PubMed2001

Effects of summer frost exposures on the cold tolerance strategy of a sub-Antarctic beetle.

The sub-Antarctic beetle Hydromedion sparsutum (Coleoptera, Perimylopidae) is common locally on the island of South Georgia where sub-zero temperatures can be experienced in any month of the year. Larvae were known to be weakly freeze tolerant in summer with a mean supercooling point (SCP) around -4 degrees C and a lower lethal temperature of -10 degrees C (15min exposure). This study investigated the effects of successive freezing exposures on the SCP and subsequent survival of summer acclimatised larvae. The mean SCP of field fresh larvae was -4.2+/-0.2 degrees C with a range from -1.0 to -6.1 degrees C. When larvae were cooled to -6.5 degrees C on 10 occasions at intervals of 30min and one and four days, survival was 44, 70 and 68%, respectively. The 'end of experiment' SCP of larvae surviving 10 exposures at -6.5 degrees C showed distinct changes and patterns from the original field population depending on the interval between exposure. In the 30min interval group, most larvae froze between -6 and -8 degrees C, a depression of up to 6 degrees C from the original sample; all larvae were dead when cooling was continued below the SCP to -12 degrees C. In the one and four day interval groups, most larvae froze above -6 degrees C, showing no change as a result of the 10 exposures at -6.5 degrees C. As with the 30min interval group, some larvae froze below -6 degrees C, but with a wider range, and again, all were dead when cooled to -12 degrees C. However, in the one and four day interval groups, some larvae remained unfrozen when cooled to -12 degrees C, a depression of their individual SCP of at least 6 degrees C, and were alive 24h after cooling. In a further experiment, larvae were cooled to their individual SCP temperature at daily intervals on 10 occasions to ensure that every larva froze every day. Most larvae which showed a depression of their SCP of 2-4 degrees C from their day one value became moribund or died after six or seven freezing events. Survival was highest in larvae with SCPs of -2 to -3 degrees C on day one and which froze at this level on all 10 occasions. The results indicate that in larvae in which the SCP is lowered following sub-zero exposure, the depression of the SCP is greatest in individuals that do not actually freeze. Further, the data suggest that after successive frost exposures in early winter the larval population may become segregated into two sub-populations with different overwintering strategies. One group consists of larvae that freeze consistently in the temperature range from -1 to -3 degrees C and can survive multiple freeze-thaw cycles. A second group with lower initial SCPs (around -6 degrees C), or which fall to this level or lower (down to -12 degrees C) after freezing on one or more occasions, are less likely to freeze through extended supercooling, but more likely to die if freezing occurs.

Journal Article↗

PubMed2000

Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD.

BACKGROUND: The reduction of N-acetylaspartate (NAA) detected by proton MR spectroscopy (1H-MRS) represents a robust but unspecific marker for neuronal loss or dysfunction. OBJECTIVE: To apply 1H-MRS in two brain regions that reflect the characteristic spatial distribution of neuronal loss in AD. These regions are the medial temporal lobe (MTL), which is affected early in AD, and the primary motor and sensory cortex (central region), which is affected late in the disease and might serve as an intraindividual control region in mild to moderate disease stages. METHODS: Twenty patients and 18 volunteers underwent 1H-MRS in both brain areas. The metabolic ratios of NAA/creatine and choline/creatine were determined. Additionally, the metabolic ratios of the MTL were divided by the ratios of the central region to assess the relative change in the MTL in individual subjects. All ratios were correlated with psychometric test scores. RESULTS: A significant reduction of NAA/creatine and choline/creatine ratios was detected in the MTL of patients with AD. In the central region, no significant difference between the groups was found. NAA/creatine (MTL/central region) was reduced in patients with AD and showed a correlation with the Mini-Mental State Examination and the cognitive part of the Alzheimer Disease Assessment Scale scores. Choline/creatine (MTL/central region) did not show a significant difference between groups. CONCLUSION: Assessing the distribution of NAA/creatine reduction guided by the expected neuropathologic change can improve the role of 1H-MRS in the assessment of AD. The disease severity can be monitored by relative reduction of NAA/creatine in the MTL in comparison with an intraindividual unaffected control region.

Aged↗

PubMed2000

Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study.

Neuropathological and neuroimaging studies suggest neuronal dysfunction in schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol containing compounds and glutamine/glutamate (Glx) were assessed in the left frontal lobe and basal ganglia of subjects with familial schizophrenia, family members with mixed psychiatric diagnoses, unaffected family members, and community controls. Concentrations of metabolites were analyzed and expressed as ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative correlation with age in the frontal lobe. After covarying for age, subjects with schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio compared with unaffected family members (P=0.018) as well as with community non-familial (P=0.037) controls. These MRS observations support the hypothesis of a disease-related neuronal deficit in the frontal lobe of schizophrenic patients, and relatively normal basal ganglia.

Adult↗

PubMed2000

Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase.

ATM is mutated in the human genetic disorder ataxia telangiectasia, which is characterized by ataxia, immune defects, and cancer predisposition. Cells that lack ATM exhibit delayed up-regulation of p53 in response to ionizing radiation. Serine 15 of p53 is phosphorylated in vivo in response to ionizing radiation, and antibodies to ATM immunoprecipitate a protein kinase activity that, in the presence of manganese, phosphorylates p53 at serine 15. Immunoprecipitates of ATM also phosphorylate PHAS-I in a manganese-dependent manner. Here we have purified ATM from human cells using nine chromatographic steps. Highly purified ATM phosphorylated PHAS-I, the 32-kDa subunit of RPA, serine 15 of p53, and Chk2 in vitro. The majority of the ATM phosphorylation sites in Chk2 were located in the amino-terminal 57 amino acids. In each case, phosphorylation was strictly dependent on manganese. ATM protein kinase activity was inhibited by wortmannin with an IC(50) of approximately 100 nM. Phosphorylation of RPA, but not p53, Chk2, or PHAS-I, was stimulated by DNA. The related protein, DNA-dependent protein kinase catalytic subunit, also phosphorylated PHAS-I, RPA, and Chk2 in the presence of manganese, suggesting that the requirement for manganese is a characteristic of this class of enzyme.

Androstadienes↗

PubMed2000

Ultra-fast three-dimensional MR perfusion imaging of the entire brain in acute stroke assessment.

We sought to evaluate a three-dimensional (3D) whole-brain perfusion technique based on echo-shifting (PRESTO) for its performance in evaluation of acute stroke. Twenty-six patients were scanned within 6 hours after onset of hemispheric symptoms, and the results were compared with results of diffusion-weighted imaging (DWI) and digital subtraction angiography (DSA). The signal-to-noise ratio of the images was 61 +/- 3 pre-contrast and 47 +/- 3 at the bolus peak. Brain coverage on perfusion parameter maps was 95% +/- 2% compared with that displayed on T2-weighted images, with only minor artifacts related to susceptibility at the skull base. Measured regional cerebral blood volume (rCBV) reduction closely correlated to lesion size on initial DWI and to final clinical outcome (P = 0.006), consistent with results previously reported for 2D perfusion methods. Mismatches between DWI and perfusion imaging characterized the total extent of tissue at risk, and the contrast timing correlated with the amount of collateral circulation as shown on DSA. In conclusion, 3D imaging using the PRESTO technique permits high-quality perfusion imaging of the entire brain.

Adolescent↗

PubMed2000

Humoral immune responses and safety of experimental formulations of inactivated Neospora vaccines.

Antibody titers to Neospora antigens ranged from 40 to 160 before vaccination, from 80 to 5,120 2 weeks after the first dose of vaccination, and 320 to 40,9602 weeks after the second (booster) vaccination. A peak antibody titer of 40,960 was also detected 28 days after the booster vaccination among animals vaccinated with Neospora vaccine formulated with Bay R1005 adjuvant. In heifers inoculated with experimental formulations of Neospora vaccines, transient development of injection site reactions resulted in 1 out of 15 animals. This injection site reaction was not detectable 14 days after the first observation and measurements were made. We have also demonstrated that vaccines derived from tissue-culture-grown Neospora tachyzoites are safe and would be expected to be efficacious.

Animals↗

PubMed2000

[The diagnostic problems in magnetic resonance tomography of the bone marrow in patients with malignomas under G-CSF therapy].

AIM: To study the effect of G-CSF therapy directly by MRI and 1H MRS in the lumbar and femoral bone marrow and differentiate between malignant bone marrow infiltration (MBMI) and reconversion of red marrow. METHODS: Thirteen patients could be examined twice, before and during G-CSF medication and another six only during treatment. T1 weighted spin-echo and opposed-phase gradient-echo images as well as the spectroscopic data (T2 values, water content) were analysed. RESULTS: After G-CSF a pathologic bone marrow signal intensity was seen in 8/13 (lumbar) and 11/13 (femoral) patients respectively. The majority of the signal alterations were diffuse (6 and 8), the minority focal (2 and 3). If a patient was successfully stimulated, a significant increase in water content occurred (21% lumbar, 34% femoral). T2 values did not change significantly, nor did they correlate with the stimulation success. CONCLUSIONS: MR tomography and -spectroscopy are suitable to detect lumbar and femoral bone marrow stimulation by G-CSF quantitatively and qualitatively. The changes may simulate MBMI. The adequate judgement of G-CSF treated bone marrow without pretherapeutic images is not possible.

Adult↗

PubMed2000

Primary central nervous system immunocytoma: MRI and spectroscopy.

We report on a young woman with a primary cerebral immunocytoma. Most primary cerebral nervous system lymphomas (PCNSL) are highly malignant undifferentiated B-cell tumours, there are few data on the clinical course, MRI and spectroscopy findings of this rare PCNSL subtype. MRI revealed a radially enhancing tumour with mild perifocal oedema. MR spectroscopy indicated low cell turnover. Slow clinical progression, no significant changes with treatment, and imaging findings were consistent with a low-grade malignant tumour.

Adult↗

PubMed2000

Middle cerebral artery (MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT.

PURPOSE: To describe the radiologic findings of susceptibility changes in acute middle cerebral artery (MCA) thromboembolism detected with three-dimensional (3D) susceptibility-based perfusion magnetic resonance (MR) imaging and to compare the detectability and clinical value of this sign with those of the hyperdense MCA sign at computed tomography (CT). MATERIALS AND METHODS: Twenty-three patients (mean age, 55 years) underwent CT and MR imaging within the first 6 hours after the onset of acute MCA stroke. The hyperdense MCA sign at CT and the presence of susceptibility changes in acute thromboembolism as depicted on T2*-weighted 3D perfusion MR images were assessed. The presence of each sign was correlated with clinical presentation. RESULTS: The sensitivity of the hyperdense MCA sign at CT was 54% (negative predictive value, 71%) compared with 82% (negative predictive value, 86%) for the susceptibility changes at MR imaging. There were no false-positive CT or MR readings. The presence of the MCA susceptibility sign correlated positively with the initial clinical presentation (chi(2) = 7.987, P =.009, Spearman rho = 0.589). However, neither of the signs was a predictor for clinical outcome in cases of spontaneous MCA stroke. CONCLUSION: In addition to the information traditionally provided with reconstructed perfusion parameter maps, 3D susceptibility-based perfusion MR images allow the identification of acute MCA thromboembolism with a sensitivity higher than that of CT.

Acute Disease↗

PubMed2000

MR imaging and cardiac pacemakers: in-vitro evaluation and in-vivo studies in 51 patients at 0.5 T.

PURPOSE: To evaluate the safety and feasibility of magnetic resonance (MR) imaging at 0.5 T in patients with implanted cardiac pacemakers. MATERIALS AND METHODS: Twenty-one models of pacemakers and 44 pacemaker electrodes were exposed to in vitro MR imaging with continuous registration of pacemaker output and temperature at the lead tip. Prior to MR imaging examination, pacemakers were programmed to an asynchronous mode (A00, V00, or D00). Pacemakers were examined before and after MR imaging. Forty-four patients with implanted pacemakers underwent 51 MR imaging examinations under cardiologic surveillance, continuous electrocardiography, pulse oximetry, and capnographic monitoring. RESULTS: MR imaging was safely performed in all patients. None of the pacemakers displayed a pacing dysfunction at MR imaging. No changes occurred in the programmed parameters in any device tested in vivo or in vitro. Maximum increases in the temperature at the lead tips were 8.90 degrees C at a specific absorption rate (SAR) of 0.6 W/kg and 23.50 degrees C under a worst-case radio-frequency (RF) heating condition with an SAR of 1.3 W/kg. CONCLUSION: MR imaging at 0.5 T can be safely performed in patients with implanted pacemakers in carefully selected clinical circumstances when appropriate strategies (programming to an asynchronous mode, adequate monitoring techniques, limited RF exposure) are used.

Capnography↗