Search PubMed⌕ Search

Biomedical subjects

H Beck

Publications and source records attributed to H Beck.

At least 73 records · Page 4Linked to original sources
PubMed1998

CSF dynamics in a rodent model of closed head injury.

Using ICP measurements and the bolus injection technique dynamic parameters of the cerebrospinal fluid system as there are pressure-volume-index (PVI) and resistance to CSF outflow (Rout) were investigated in a new model of diffuse closed head injury (CHI) in the rat. It was found that in the absence of brain oedema and ICP alterations an increase in PVI and Rout was present in the early (4h) period following head injury. This may be indicative for a reduction in cerebral blood flow and cerebral blood volume, both shown previously to occur after CHI. Furthermore an early impairment of CSF absorption mechanisms is evident. To answer the question, whether bolus injection techniques are advisable for clinical routine and whether results might have a predictive value, further investigations covering longer observation intervals and in the presence of secondary insults to the brain are necessary.

Animals↗
PubMed1998

Sinusoidal intrathecal infusion for assessment of CSF dynamics in kaolin-induced hydrocephalus.

OBJECTIVE: To evaluate whether changes of CSF outflow resistance and compliance in hydrocephalus can be assessed by an intrathecal infusion which is performed at a sinusoidal varying rate. METHODS: Hydrocephalus was produced in 10 Sprague Dawley rats by instillation of 0.0375 g of kaolin in 0.9% saline into the cisterna magna. Measurements were performed 4 weeks later: With each animal both, three successive constant rate infusions (0-0.02 ml/min) and a sinusoidal infusion (0-0.02 ml/min, frequency 0.006 Hz) were performed. 6 normal animals served as control. The pressure recordings of both infusion techniques were used for the assessment of the CSF outflow resistance. The time constant and the pressure volume index were calculated only from the sinusoidal input testing. RESULTS: The sinusoidal test as well as the constant rate infusion both demonstrated a severe impairment of CSF absorption. By the sinusoidal input, a decreased compliance was confirmed additionally. Thus, the sinusoidal infusion test demonstrated a high resistance and low compliance hydrocephalus in the kaolin-treated group. A simple graphical procedure is presented which allows an easy assessment of CSF dynamics by the sinusoidal infusion test.

Animals↗
PubMed1998

Voltage-dependent Ca2+ currents in epilepsy.

Voltage-dependent Ca2+ channels (VCCs) represent one of the main routes of Ca2+ entry into neuronal cells. Changes in intracellular Ca2+ dynamics and homeostasis can cause long-lasting cellular changes via activation of different Ca2+ dependent signalling pathways. We have investigated the properties of VCCs in human hippocampal dentate granule cells (DGCs) using the whole-cell configuration of the patch-clamp method. Classical high-threshold Ca2+ currents were composed mainly of omega-CgTx-sensitive N-type and nifedipine-sensitive L-type currents that were present in similar proportions. In addition, a Ca2+ current component that was sensitive to low concentrations of Ni2+, but not to nifedipine or omega-conotoxin GVIA (omega-CgTx GVIA) was present. This latter component showed a half-maximal inactivation at more hyperpolarized potentials than high-threshold currents and a more rapid time-dependent inactivation. This current was termed T-type Ca2+ current. Current components with similar pharmacological and kinetic characteristics could be elicited in acutely isolated control rat DGCs. The current density of high threshold and T-type Ca2+ components was significantly larger in human DGCs and in the kainate model compared to DGCs isolated from adult control rats. These differences in current density were not accompanied by parallel differences in the voltage-dependence of VCCs. Taken together, these data suggest that an up-regulation of Ca2+ current density may occur in hippocampal epileptogenesis without consistent changes in Ca2+ current properties.

Adult↗
PubMed1998

Neuroticism in relation to recovery and persisting pain after laparoscopic cholecystectomy.

BACKGROUND: Persisting pain is seen in 20%-30% of patients after cholecystectomy for symptomatic gallbladder stones. The only preoperative factor that seems predictive is psychic vulnerability or neuroticism. Findings with regard to the influence of psychologic factors on recovery are contradictory, too. The aim of the present study was to examine a possible relationship between neuroticism and recovery and the outcome of operation. METHODS: Ninety-four patients who had had a laparoscopic cholecystectomy performed were tested psychologically with a Danish psychic vulnerability scale and with the Eysenck Neuroticism Scale before and 1 year after operation. The course of recovery was registered 1 month after operation, and outcome with regard to persisting pain 1 year postoperatively. RESULTS: No correlations were found between neuroticism scores and postoperative hospital stay or time to regain work/normal activities (P > 0.05). Persisting pain was found in 18% of the patients 1 year after operation. Although the patients with persisting pain had higher neuroticism scores preoperatively, the difference from the patients with successful outcome of the operation first became statistically significant 1 year postoperatively (P < 0.01-0.05). CONCLUSIONS: The results do not indicate that neuroticism influences the short recovery process after laparoscopic cholecystectomy. With regard to persisting pain, the higher neuroticism scores in these patients 1 year after the operation could be the consequence of the pain rather than aetiologic factors.

Adolescent↗
PubMed1998

Altered patterns of Ca2+/calmodulin-dependent protein kinase II and calcineurin immunoreactivity in the hippocampus of patients with temporal lobe epilepsy.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin represent neuronal Ca2+-dependent enzymes which dynamically modify several common substrates in the mammalian brain via phosphorylation/dephosphorylation cycles. Studies in animal models indicate that altered expression and activity of these enzymes may be involved in epilepsy. We have analyzed their immunohistochemical distribution in hippocampi of 28 temporal lobe epilepsy (TLE) patients and 13 controls. TLE specimens were classified as Ammon's horn sclerosis (AHS) or focal lesions without alteration of hippocampal cytoarchitecture. Compared to control and lesion-associated TLE specimens, striking changes in the distribution pattern of both enzymes were found in the dentate gyrus (DG) of AHS specimens: Whereas CaMKII labeling was significantly increased in the granule cell somata and their proximal dendrites, calcineurin immunoreactivity was significantly reduced in the granule cell somata. Furthermore, calcineurin staining in controls showed high levels in the inner molecular layer with a sharp demarcation towards the outer molecular layer. In AHS, calcineurin staining was reduced in the inner molecular layer, with partial loss of this demarcation. These findings raise the possibility, that an up-regulation of CaMKII with a concomitant down-regulation of calcineurin in the DG of AHS specimens may cause a pathogenetically relevant imbalance of neuronal Ca2+/calmodulin-dependent phosphorylation/dephosphorylation systems.

Adult↗
PubMed1998

Effects of phenytoin, carbamazepine, and gabapentin on calcium channels in hippocampal granule cells from patients with temporal lobe epilepsy.

PURPOSE: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current modulation has been proposed to contribute to the antiepileptic activity of these drugs. The purpose of this study was to determine the effects of these anticonvulsants on voltage-dependent calcium channels in pathologically altered neurons from patients with chronic temporal lobe epilepsy. METHODS: Acutely isolated human hippocampal granule cells were examined by using the whole-cell configuration of the patch-clamp technique. RESULTS: PHT and CBZ produced a reversible, concentration-dependent inhibition of high-voltage-activated (HVA) Ca2+ currents without affecting voltage-dependent activation. The concentration-response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%, respectively, with half-maximal inhibition being obtained at 89 and 244 microM, respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ showed a reduction of HVA currents of 16% at a therapeutic whole-brain concentration of 80 microM. In contrast to CBZ, PHT produced a small hyperpolarizing shift in the voltage dependence of steady-state inactivation. PHT, 80 microM, shifted the potential of half-maximal inactivation by -3.1 +/- 0.5 mV (p < 0.05). GBP, which was recently found to bind to the alpha2delta subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances. CONCLUSIONS: These results suggest that, in contrast to GBP and CBZ, modulation of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT in human hippocampal granule cells.

Acetates↗
PubMed1998

Surgical correction of trigonocephaly: theoretical basis and operative procedures.

Trigonocephaly involves premature fusion of both the metopic suture and the sutures in the skull base. Surgical treatment by opening of the prematurely fused metopic suture and expansion of the anterior cranial base by creating "neosutures" was used to treat three children with trigonocephaly. The combination of lateral canthal advancement and radical forehead remodeling achieved excellent results. These procedures can also prevent the development of midface hypoplasia such as hypotelorism. The two younger patients, aged 0 and 6 months, achieved rapid bone growth in the defects and normalization of intercanthal and interpupillary distances. The older patient, aged 8 years, retained some skull defects at follow-up. The optimal age for surgery is 3-6 months, which allows good cosmetic results and minimizes visual repercussions with relatively low perioperative risks.

Cephalometry↗
PubMed1998

Acute traumatic subdural hematoma originating from a convexity meningioma--case report.

A 68-year-old male presented with a traumatic subdural hematoma originating from a convexity meningioma the day after a motorcycle accident. Computed tomography disclosed a right temporal subdural and/or epidural mass. Emergent craniotomy revealed a convexity meningioma with thin subdural hematoma. The underlying brain was apparently healthy. The histological diagnosis was angiomatous meningioma with hemorrhagic foci. The operative and histological findings indicated that the tumoral tissue was the source of the subdural hematoma.

Accidents, Traffic↗
PubMed1997

Metabotropic glutamate receptors modulate synaptic transmission in the perforant path: pharmacology and localization of two distinct receptors.

Metabotropic glutamate receptors (mGluRs) have emerged as an interesting family of eight different receptor subtypes that can be divided into three groups according to their pharmacology and sequence similarity. In the present study, the specific mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed field excitatory postsynaptic potentials (fEPSPs) in the rat dentate gyrus evoked by perforant path stimulation in a concentration-dependent, rapid and reversible manner (EC50: L-AP4 5.9 +/- 1.6 microM, (1S,3R)-ACPD 80 +/- 34 microM). In a 'paired-pulse' stimulation protocol, the first fEPSP showed a stronger reduction, resulting in 'paired-pulse' facilitation. The effects of L-AP4 but not of (1S,3R)-ACPD could be antagonized by the group III mGluR antagonists (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4) and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG). Moreover, (1S,3R)-ACPD was still potently depressing fEPSPs after preperfusion of near saturating concentrations of L-AP4. Together, the results suggest that both substances act on different mGluRs. The effects of (1S,3R)-ACPD could not be further differentiated by selective group I or group II mGluR agonists. Although (2S,1'S,2'S)-2-carboxycyclopropylglycine (L-CCG-I) blocked fEPSPs at concentrations >> 1 microM, these effects, as well as L-AP4 effects, were potently antagonized by MAP4. This suggests that mGluR8 might be responsible for the actions of L-AP4 and L-CCG-I. The two different mGluRs showed a distinct distribution when fEPSPs were recorded simultaneously in the outer and middle molecular layer (OML/MML): The L-AP4 sensitive receptor, possibly mGluR8, seems to be located in the OML while (1S,3R)-ACPD showed its main effect in the MML.

Aminobutyrates↗
PubMed1997

Potassium currents in acutely isolated human hippocampal dentate granule cells.

1. Properties of voltage- and Ca(2+)-dependent K+ currents were investigated in thirty-four dentate granule cells acutely isolated from the resected hippocampus of eleven patients with therapy-refractory temporal lobe epilepsy (TLE). 2. When intracellular Ca2+ was strongly buffered with 11.5 mM EGTA-1 mM Ca2+ in the recording pipette, K+ currents (IK) with a slow activation and biexponential time-dependent decay could be elicited, which showed a threshold for activation around -30 mV. 3. A contribution of Ca(2+)-dependent K+ currents became apparent with intracellular solution containing 1 mM BAPTA-0.1 mM Ca2+. Superfusion of low-Ca2+ extracellular solution blocked 43% of outward currents in this recording configuration. Outward current components could also be blocked by substituting 5 mM Ba2+ for extracellular Ca2+ (78%), or by application of 100 microM Cd2+ (25%). 4. The Ca(2+)-dependent K+ currents could be pharmacologically subdivided into two components. One component was sensitive to 500 microM tetraethylammmonium (TEA; 41%) and 10 nM charybdotoxin (CTX; 47.2%). The blocking effects of 10 nM CTX and 500 microM TEA were not additive, suggesting that both agents block the same conductance. A second, smaller outward current component was blocked by 50 nM apamin (13%). 5. A transient A-type K+ current could be observed in six neurones and showed a fast monoexponential time-dependent inactivation with a steady-state voltage dependence that was distinct from that of IK. The A-type current was blocked by 4-aminopyridine (4-AP) but not by TEA or low-Ca2+ solution. 6. We conclude that outward currents in human hippocampal dentate granule cells can be separated into at least four types by their kinetic and pharmacological properties. These include at least one voltage-dependent current similar to those observed in mammalian hippocampal neurones, and two Ca(2+)-dependent K+ currents that most probably correspond to SK- and BK-type currents. A classical A-type current could be detected in some patients with Ammon's horn sclerosis (AHS) but not in patients with lesion-associated TLE.

Epilepsy, Temporal Lobe↗
PubMed1997

T cell response to myelin basic protein in the context of the multiple sclerosis-associated HLA-DR15 haplotype: peptide binding, immunodominance and effector functions of T cells.

In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.

Alleles↗
PubMed1997

Differential changes of laser evoked potentials, late auditory evoked potentials and P300 under morphine in chronic pain patients.

The present study investigates the differential behavior of laser evoked brain potentials (LEPs), late auditory evoked potentials (AEP) and the endogenous P300 in response to morphine treatment, examined in 6 chronic pain patients. The main result was that in parallel with marked clinical pain relief, amplitudes of the long latency LEP positivity (P400) were significantly reduced under morphine. One patient suffering from extremely painful osteoporosis for 20 years exhibited a large middle latency component (N170) which was prominently attenuated by morphine. In contrast to LEP amplitude reductions, auditory N1 and P2 potentials appeared either unchanged or even enlarged during morphine treatment. Also P300 amplitude was slightly increased under morphine. Reaction time and mood scales also failed to indicate any sedation. Obviously, LEPs reflected specifically the analgesic morphine effect in this study, while stability or enhancement of AEPs and P300 during morphine treatment indicated lack of sedation or even improved perception and concentration due to the removal of persistent pain as a disruptive perceptual-cognitive stressor.

Adult↗
PubMed1997

Properties of voltage-activated Ca2+ currents in acutely isolated human hippocampal granule cells.

Properties of Ba2+ currents through voltage-dependent Ca2+ channels (IBa) were investigated in 61 dentate granule cells acutely isolated from the resected hippocampus of nine patients with therapy-refractory temporal lobe epilepsy (TLE). Currents with a high threshold of activation (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation (V1/2inact) of -16.4 mV. Application of saturating doses of omega-conotoxin (omega-CgTx) GVIA or nifedipine distinguished characteristic N-type (38%) and L-type (62% of HVA currents) Ca2+ currents. Combined application of both agents blocked HVA currents by > 95%. In a 10-mo-old child but not in adult patients, an omega-agatoxin IVA (omega-AgaTxIVA)-sensitive but omega-CgTx MVIIC-insensitive, noninactivating component of HVA currents (approximately 24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA components on the basis of its steady-state voltage-dependent inactivation (V1/2inact = -71.0 mV). The T-type Ca2+ current isolated by subtraction peaked at more negative potentials (-10 mV), showed a significantly more rapid time-dependent inactivation, and could be selectively blocked by low concentrations of Ni2+. It was insensitive to nifedipine and omega-CgTx GVIA. We conclude that L-, N-, and T-type currents are present in adult human dentate granule cells and an additional P-type current is present in neurons from a 10-mo-old patient. These data may provide a basis for comparison with animal models of epilepsy and for the elucidation of mechanisms of action of drugs intended for use in human disease.

Adult↗
PubMed1997

Hippocampal loss of tenascin boundaries in Ammon's horn sclerosis.

Ammon's horn sclerosis (AHS) is a common finding in patients with temporal lobe epilepsy (TLE). In addition to selective neuronal cell loss and axonal reorganization, AHS is also characterized by a striking astroglial reaction. However, the functional significance of reactive astrogliosis in the pathogenesis of TLE remains to be determined. Reactive astrocytes produce a variety of cell adhesion molecules and other extracellular matrix (ECM) components with potential effects on axonal growth, axonal branching, and neosynaptogenesis in the central nervous system (CNS). In the present study we describe the distribution of the ECM glycoprotein tenascin/cytotactin (TN-C) in 44 human hippocampal specimens from patients with TLE. The distribution of TN-C immunoreactivity was evaluated with the anti-human TN-C monoclonal antibody K8 by densitometrical analysis, and TN-C protein levels were detected by immunoblotting. In the normal human hippocampus, there were distinctive boundaries between areas of high and low TN-C expression. These border zones demarcated areas with major synaptic input, i.e., the dentate gyrus molecular layer (DG-ML) and the gray matter of the Ammon's horn. TN-C and the neurite growth-associated protein GAP-43 exhibited a complementary pattern of distribution. Densitometric and protein biochemical analysis showed a significant, 4.3-fold increase of TN-C in the hippocampus of TLE patients with AHS compared with normal hippocampus obtained at autopsy. This increase in TN-C immunoreactivity was accompanied by a loss of TN-C boundaries and closely correlated with the extent of reactive gliosis, as indicated by immunoreactivity for glial fibrillary acidic protein. Furthermore, a striking colocalization between TN-C and GAP-43 was observed in the DG-ML of patients with AHS. These observations raise the intriguing possibility of pathogenetically relevant glio-neuronal interactions in human TLE.

Antibody Specificity↗
PubMed1996

Improved high-performance liquid chromatographic determination of amoxicillin in human plasma by means of column switching.

A highly sensitive and selective HPLC method was developed for the determination of amoxicillin in human plasma. After addition of buffer and internal standard, the sample was ultrafiltered and injected on to a precolumn to remove polar plasma interferences. Detection was effected with a UV detector set at 230 nm. The limit of quantification for amoxicillin was 50.1 ng/ml with an imprecision of 4.2% using 0.25 ml of plasma. Linearity was confirmed over the whole calibration range (25.4-0.0501 micrograms/ml) and the inter-day variation ranged from 2.0 to 4.5%. The method was validated according to GLP guidelines and its suitability was demonstrated by the analysis of several hundred samples in a bioequivalence study. The method can be used to determine pharmacokinetic parameters of amoxicillin in humans after a single oral dose of 500 mg.

Amoxicillin↗