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Biomedical subjects

B Bauer

Publications and source records attributed to B Bauer.

At least 91 records · Page 5Linked to original sources

11C-methionine and 18F-2-fluorodeoxyglucose positron emission tomography: a tool for diagnosis of cerebral glioma and monitoring after brachytherapy with 125I seeds.

Forty-six patients with suspected brain tumors were investigated by positron emission tomography (PET). Using 11C-methionine PET, the spatial extent of increased uptake in gliomas was larger than that of contrast enhancement on CT/MR images in 67% or the same in 33%. Ten of 46 patients treated with brachytherapy for low-grade gliomas were also investigated with 18F-2-fluorodeoxyglucose (FDG)-PET. One year after seed implantation, the glucose metabolism had not changed, but the decline of methionine uptake was significant. In conclusion, 11C-methionine PET may improve tumor delineation and, following brachytherapy, provides more information on the therapeutic effects than FDG.

Adult↗

Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats.

BACKGROUND AND PURPOSE: Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [11C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia. METHODS: In 11 cats, cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, and FMZ binding were studied repeatedly by positron emission tomography before, during, and up to 12 hours after transient middle cerebral artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120 minutes in 2 cats, respectively). Development of the defects in energy metabolism were compared with the defects in FMZ binding (2 to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed glucose metabolism (determined 12 hours after MCAO), and with the size of the infarcts (determined approximately 15 hours after MCAO). RESULTS: Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images. CONCLUSIONS: The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.

Animals↗

Cognitive processing in primary headache: a study on event-related potentials.

BACKGROUND: There is experimental evidence for loss of cognitive habituation in migraine but not in other types of headache and not by visual event-related potentials (ERP). OBJECTIVE: Determining the latencies (msec) and amplitudes (microV) of ERP components and the differences of these values in a two-trial analysis representing the amount of cognitive habituation. PARTICIPANTS: Two hundred thirty-three patients with a headache diagnosis according to the criteria of the International Headache Society: migraine without aura (N = 77); migraine with aura (N = 31); cluster headache during period (N = 26); cluster headache during interval (N = 11); chronic paroxysmal hemicrania (N = 8); episodic tension-type headache (N = 33); ergotamine-induced headache (N = 47). Thirty age-matched healthy subjects served as a control group. METHODS: ERPs were evoked by a visual oddball paradigm consisting of 2 x 200 flashes of light (85% white light; 15% red light). Evaluation of ERP components was done separately for the first 200 and the second 200 stimuli as well as for the entire series of stimuli. RESULTS: We found an acceleration of the P3 latency during the second trial in migraine with and without aura, but not in the other headache types, and not in healthy controls. Ergotamine and sumatriptan abolished this loss of habituation in migraine patients. Increased ERP latencies as compared with healthy controls were present in patients with cluster headache, tension-type headache, ergotamine-induced headache, and migraine with aura, but not in migraine without aura. CONCLUSION: There is a loss of cognitive habituation in migraine, which may serve as a specific but not sensitive diagnostic tool. The pathophysiologies of migraine and cluster headache have a specific modifying property on cognitive processing reflected by a loss of cognitive habituation or an increased cognitive processing time. These effects can, in part, be counterbalanced by antimigraine medication.

Adolescent↗

Symptomatic hemangiomas and venous malformations in infants, children, and young adults: treatment with percutaneous injection of sodium tetradecyl sulfate.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of percutaneous sclerosis therapy using sodium tetradecyl sulfate for treatment of symptomatic hemangiomas and venous malformations in infants, children, and young adults. MATERIALS AND METHODS: Fifty-two sclerosis procedures were performed in 21 patients who were 13 months to 24 years old. Six of these patients had hemangiomas, and the remaining 15 patients had venous malformations. Sodium tetradecyl sulfate was injected solely percutaneously in 49 procedures, by both percutaneous and arterial routes in two procedures, and intraarterially only in one procedure. Thirteen patients had sclerosis therapy alone, and eight patients had sclerosis therapy followed by surgery within 48 hr. RESULTS: Sclerosis therapy alone or sclerosis therapy followed by surgery was judged beneficial in 18 (86%) of 21 patients, including five of the six patients who had hemangiomas and 13 of the 15 patients who had venous malformations. Two patients had an equivocal response to the therapy, and one patient had no apparent benefit. Three of the 21 patients had minor complications (skin ulcers) but no long-term sequelae. CONCLUSION: Percutaneous injection of sodium tetradecyl sulfate, either alone or before surgery, is a safe and effective method of managing symptomatic hemangiomas and venous malformations.

Adolescent↗

Chemopreventive effect of difluoromethylornithine (DFMO) on mouse skin squamous cell carcinomas induced by benzo(a)pyrene.

The effect of the chemopreventive agent D,L-alpha-difluoromethylornithine (DFMO) on the incidence of skin squamous cell carcinoma was studied in SENCAR mice treated weekly with topical applications of benzo(a)pyrene (B(a)P) (0.15 mmol, 2 x /week) on the dorsal skin. Animals were randomized to receive either chow or chow supplemented with DFMO (1 g/1 kg) and studied at 10, 15, 20, 25, and 30 weeks of B(a)P treatment. Morphometric analyses at each timepoint evaluated the epidermal thickness (ET) and the number of epidermal nucleated layers (NL). The ET increased from 12-17 microns as early as 10 weeks after B(a)P treatment, reaching 22 microns at 20 weeks, and 27 microns at 25 weeks (130% increase). The NL also increased markedly. A relatively modest increase in ET was observed in animals treated with B(a)P and DFMO (16% at 15 weeks, 53% at 20 weeks, and 85% at 25 weeks) as compared to controls. The relative increase in NL showed a similar pattern. Although extensive epidermal hyperplasia was seen early, clear-cut focal premalignant lesions were not identifiable before week 20 of B(a)P treatment. At 20 weeks, the most frequently noted focal premalignant lesions in carcinogen-treated animals (without DFMO) were moderate dysplasias. At 25 and 30 weeks, a large increase was seen in the incidence of more advanced dysplastic lesions and invasive carcinomas. In the group treated with B(a)P and DFMO, a marked reduction in the number of carcinomas was observed at 25 and 30 weeks. At 25 weeks, DFMO reduced tumor yield from 5.8 to 3.2 carcinomas per mouse. At 30 weeks, the reduction was from 13.1 to 5.7 carcinomas per mouse (57% reduction). Collectively, these data emphasize the strong chemopreventive effect of DFMO against tumors in the mouse skin complete carcinogenesis model, as indicated by the reduction of overall skin tumor incidence and the decreased epidermal hyperplasia in DFMO-treated animals. Morphometrically defined increases in ET and NL can be used as early biomarkers of DFMO chemoprevention in mouse skin tumorigenesis.

Animals↗

RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein.

The small GTPase Rap 1A is a close relative of Ras that, when overexpressed, is able to revert oncogenic transformation induced by active Ras. We screened a mouse embryonic cDNA library using the yeast two-hybrid system and isolated the cDNA of a novel Rap 1A-interacting protein. The open reading frame encodes for an 84 kDa protein with a Cdc25-homology domain which shares approximately 30% identity with Ral guanine nucleotide dissociation stimulator (RalGDS) and RalGDS-like (Rg1). The C-terminal region reveals a striking conservation of sequences with the Ras-binding domain of RalGDS. We designated this protein Rlf, for RalGDS-like factor. In the yeast system, Rlf interacts with Rap 1A, H-Ras and R-Ras, but not with Rac and Rho. In addition, we found that Rlf interacts with Rap 1Aval12 but not with Rap 1AAsn17. In vitro binding studies revealed that a C-terminally located 91 amino acid region of Rlf is sufficient for direct association with the GTP-bound form of Ras and Rap 1A. The observed dissociation constants are 0.6 microM and 0.4 microM, respectively. No significant association with Ras-GDP or Rap 1A-GDP could be detected. These binding characteristics indicate that Rlf is a putative effector for Ras and Rap 1A.

Amino Acid Sequence↗

Cataract patients in a defined Swedish population, 1986 to 1990. V. Postoperative retinal detachments.

OBJECTIVE: To estimate the risk of retinal detachment after cataract surgery. DESIGN: Prospective study from December 17, 1985, through December 31, 1992 of all cataract surgeries performed in a single referral region of the Lund (Sweden) Health Care District from December 17, 1985, through December 31, 1990. SETTING: The University Hospital of Lund. PATIENTS: Data were collected on 5878 consecutive cataract operations. The study population was complete enough to represent all cataract surgery in the referral region during this period. RESULTS: Two years after cataract surgery, the risk of retinal detachment was 0.18%. The follow-up period after cataract surgery in this study was up to 7 years, with a mean of 50.7 months (>4 years), and the total risk of retinal detachment or detachment-related conditions was 0.71%, all cases included. The relative risk of detachment was 4.9 after YAG laser capsulotomy. It changed by a factor of 1.3 with an increase in the axial length of 1 mm and by 0.94 for each added year of patient age. CONCLUSION: A young patient with axial myopia operated on because of cataract and postoperatively treated with YAG laser capsulotomy runs an important increased risk of developing retinal detachment.

Adolescent↗

MRI-guided flumazenil- and FDG-PET in temporal lobe epilepsy.

In temporal lobe epilepsy (TLE) patients without lesions, major hippocampal sclerosis, or atrophy on magnetic resonance imaging (MRI), the localizing power of [11C]flumazenil (FMZ) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was compared using high-resolution positron emission tomography (PET) studies and individually coregistered MRI scans. Following complete clinical, neuropsychological, and electrophysiological evaluation, benzodiazepine receptor density was assessed using the FMZ equilibrium method. Thirty minutes later, interictal FDG-PET was performed under resting conditions. PET images were matched to three-dimensionally coregistered, T1-weighted MRI. Each temporal lobe (TL) was divided into 12 volumes of interest. The regional FMZ data were normalized with respect to average cortical values. For each patient the right-left asymmetries of rCMRGlc and normalized FMZ data were calculated. In 7 to 10 patients, mesial TL structures showed reduced FMZ binding, with a decrease by at least 10% in the affected TL. Reductions of 10% or more of rCMRGlc usually were more widespread than FMZ reductions and often involved lateral temporal cortex. The regions of most pronounced disturbances are not necessarily identical in both methods. Three patients had a complex correspondence of lateralization with PET, neuropsychological, and EEG data. In 4 patients, lateralization was less clear from EEG or neuropsychological results but was still consistent with lateralization by PET. In 3 of 10 patients, however, major discrepancies were found. These data suggest that the combination of neuropsychological testing, EEG, and MRI-guided FMZ- and FDG-PET will help to select patients with clearly defined epileptogenic foci especially in mesial TLE. Even in cases without MRI lesions, TL epileptic foci can be lateralized with consistency across the methods; FMZ-PET shows the pathologic focus more circumscribed than FDG-PET.

Adult↗

Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy.

We investigated whether 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) and carbon-11 methionine are suitable tracers to monitor the effects of therapy for low-grade gliomas. Ten patients with low-grade glioma without previous treatment were studied with FDG positron emission tomography. Additionally, l-[methyl-11C]methionine uptake was measured in five subjects before and 1 year after computerized tomography (CT)-guided stereotactic and computer-assisted implantation of iodine-125 seeds. All scans were 3D-matched to CT, isodose volumes were determined, and changes in glucose metabolism and methionine uptake were evaluated in tumour and brain tissue as a function of radiation dose. After 1 year glucose metabolism was not significantly altered up to a radiation dose of 300 Gy, whereas methionine uptake showed a significant dose-dependent decrease. Higher rates of decline were found in tumours with high basal methionine incorporation activity before therapy. These data suggest that measurement of methionine uptake is more suitable than measurement of FDG uptake for monitoring therapeutic effects in low-grade gliomas.

Adult↗

Visual search for colour targets that are or are not linearly separable from distractors.

D'Zmura [(1991) Vision Research, 31, 951-966] reported qualitative differences in visual search rates for a target colour in a background of differently coloured distractors depending on their colour configuration in CIE(x,y) space. A target colour that was chromatically mid-way between the distractor colours resulted in steep search slopes. A target off the distractor-distractor line, "popped out". We replicated his finding in several loci, investigated several potential confounds, and discovered boundary conditions for the phenomenon: for a given target, the effect of collinearity dissipates with increasing distractor-distractor colour difference. Furthermore, within limits, performance was dependent on the target to distractor-line distance.

Adult↗

Stimulus dimensionality effects in mental rotation.

Do 3-dimensional (3-D) figures require more time to rotate mentally than do 2-dimensional (2-D) figures? This question was examined in 2 experiments incorporating 15 2-D and 15 3-D stimuli. For 3-D stimuli, block figures were used of the type used by R. N. Shepard and J. Metzler in their classic studies. For 2-D stimuli, block figures were also used, but with all cubes in a single plane, resulting in 2-D and 3-D figures matched on surface features. Three-D figures elicited steeper slopes than did 2-D figures, supporting the view that the mental rotation of visual representations is sensitive to stimulus dimensionality. The authors summarize the results of several mental rotation studies that investigated stimulus dimensionality and suggest that the evidence across studies is consistent with the present finding. They discuss 2 plausible loci for the dimensionality effect in S. M. Kosslyn's (1980) theory of mental imagery.

Adolescent↗

Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes.

T-lymphocyte stimulation requires activation of several protein kinases, including the major phorbol ester receptor protein kinase C (PKC), ultimately leading to induction of lymphokines, such as interleukin-2 (IL-2). The revelant PKC isoforms which are involved in the activation cascades of nuclear transcription factors involved in IL-2 production have not yet been clearly defined. We have examined the potential role of two representative PKC isoforms in the induction of the IL-2 gene, i.e., PKC-alpha and PKC-theta, the latter being expressed predominantly in hematopoietic cell lines, particularly T cells. Similar to that of PKC-alpha, PKC-theta overexpression in murine EL4 thymoma cells caused a significant increase in phorbol 12-myristate 13-acetate (PMA)-induced transcriptional activation of full-length IL-2-chloramphenicol acetyltransferase (CAT) and NF-AT-CAT but not of NF-IL2A-CAT or NF-kappaB promoter-CAT reporter gene constructs. Importantly, the critical AP-1 enhancer element was differentially modulated by these two distinct PKC isoenzymes, since only PKC-theta but not PKC-alpha overexpression resulted in an approximately 2.8-fold increase in AP-1-collagenase promoter CAT expression in comparison with the vector control. Deletion of the AP-1 enhancer site in the collagenase promoter rendered it unresponsive to PKC-theta. Expression of a constitutively active mutant PKC-theta A148E (but not PKC-alpha A25E) was sufficient to induce activation of AP-1 transcription factor complex in the absence of PMA stimulation. Conversely, a catalytically inactive PKC-theta K409R (but not PKC-alpha K368R) mutant abrogated endogenous PMA-mediated activation of AP-1 transcriptional complex. Dominant negative mutant Ha-RasS17N completely inhibited the PKC-O A148E-induced signal, PKC-O. Expression of a constitutively active mutant PKC-O A148E (but not PKC-alpha A25E) was sufficient to induce activation of AP-1 transcription factor complex in the absence of PMA stimulation. Conversely, a catalytically inactive PKC-O K409R (but not PKC-alpha K368R) mutant abrogated endogenous PMA-mediated activation of AP-1 transcriptional complex. Dominant negative mutant Ha-enRasS17N completely inhibited in the PKC-O A148E-induced signal, identifying PKC-theta as a specific constituent upstream of or parallel to Ras in the signaling cascade leading to AP transcriptional activation.

Animals↗

Activated protein C resistance in young adults with central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion is a disease that is most common in old people. While the disease in old people often is associated with atherosclerosis, hypertension, diabetes, or glaucoma, this is much less evident in young people. However, a new defect in the anticoagulant system has recently been discovered, activated protein C resistance. This hereditary defect may well be associated with central retinal vein occlusion, and so this factor was analysed in patients younger than 50 years with a history of central retinal vein occlusion. METHODS: Blood samples were obtained from 31 patients younger than 50 years with a history of central retinal vein occlusion, and analysed for activated protein C resistance with standard clinical laboratory methods. RESULTS: In this material 26% of all the patients and 36% of the patients younger than 45 years were resistant to activated protein C. The normal incidence of activated protein C resistance is 2-7%. CONCLUSION: Activated protein C resistance seems to be the most common known cause of central retinal vein occlusion in young people.

Adult↗

Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy.

A multinational, double-blind, randomised study was conducted to investigate the efficacy and safety of a low-dose combination of the angiotensin converting enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642 patients with mild to moderate hypertension [supine diastolic blood pressure (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were randomly allocated to once-daily felodipine extended release (ER; 2.5 mg), ramipril (2.5 mg) or felodipine ER/ramipril (2.5/2.5 mg) for 12 weeks. In the intention-to-treat analysis, mean DBP decreased significantly (p < 0.0001) after felodipine ER, ramipril and the combination (-9.1, -9.8 and -11.4 mm Hg, respectively). The decrease was significantly greater with the combination than with felodipine ER monotherapy (p = 0.02). The number of responding patients (final DBP < or = 90 mm Hg or a decrease of > or = 10 mm Hg) was also higher with the combination than with felodipine ER or ramipril monotherapy (65.1%, 53.1%, 55.7%, respectively). There were no differences between the three groups with respect to the incidence of adverse events overall or those considered treatment-related. There were fewer cases of peripheral oedema with combination therapy than with felodipine ER monotherapy. Thirty-three patients (5.1%) withdrew from the study because of adverse events, but there was no clear pattern with regard to the specific events leading to withdrawal. There were no clinically relevant changes in laboratory or clinical safety variables. Ramipril/felodipine ER 2.5/2.5 mg is an appropriate starting dosage when initiating combination antihypertensive therapy.

Adult↗

Fixed dose combinations of ACE inhibitors.

First-line antihypertensive monotherapy is effective in reducing blood pressure to within the normal range in approximately 50% of patients. Normalisation in the remaining patients may require a combination of two or more drugs. This review considers the clinical efficacy and tolerability of combinations involving angiotensin-converting enzyme (ACE) inhibitors. The efficacy of combinations with diuretics or calcium antagonists, as initial therapy or in patients with inadequate responses to monotherapy, has been demonstrated in many trials. With combination therapy, normalisation rates approaching 80% can be achieved using submaximal doses of both components. Therapy with both combinations is well tolerated; with ACE inhibitors reducing the diuretic metabolic effects or counteracting some calcium antagonist-associated vasodilatory effects. Data on ACE inhibitors with beta-blockers are limited. When patients respond inadequately to first-line monotherapy, the increasing availability of drug combinations will allow individual selection of the most appropriate combination, taking account of additional risk factors and concomitant disease.

Adrenergic beta-Antagonists↗