Search PubMed⌕ Search

Biomedical subjects

H Beck

Publications and source records attributed to H Beck.

At least 91 records · Page 5Linked to original sources
PubMed1996

Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures.

Using primary rat hepatocyte cultures, the potency of several garlic-derived organosulfur compounds to inhibit cholesterol biosynthesis in toto as well as at early and late steps of this metabolic pathway was compared. Concerning early steps, allicin significantly inhibited incorporation of [14C]acetate into nonsaponifiable neutral lipids already at concentrations as low as 10 microM, while diallyl disulfide and allyl mercaptan were effective above 100 microM only. Likewise, inhibition in response to the two vinyl-dithiins started at 500 microM. If [14C]acetate was replaced by [14C]mevalonate, inhibition due to allicin, diallyl disulfide, and allyl mercaptan disappeared suggesting that HMGCoA-reductase was the target of inhibition. In contrast, for the vinyl-dithiins a stimulation of mevalonate incorporation was found. Concerning the late step, the potency to exert accumulation of lanosterol presumably by inhibiting lanosterol 14 alpha-demethylase decreased in the order allicin > diallyl disulfide > allyl mercaptan = 1,3-vinyl-dithiin >> 1,2-vinyldithiin, the effect of the latter compound being close to zero. With respect to the total inhibition of [14C]acetate labeling of cholesterol, the half-maximal effective concentration-value of allicin was determined to be 17 +/- 2 microM compared to 64 +/- 7 microM for diallyl disulfide and to 450 +/- 20 microM for allyl mercaptan. Cytotoxicity as determined by the lactate dehydrogenase leakage assay was slightly higher for the two vinyl-dithiins than for diallyl disulfide and allyl mercaptan, but was apparent only at concentrations higher than 10 mM and, consequently, was irrelevant for the effects described. These results demonstrate that different garlic-derived organosulfur compounds interfere differently with cholesterol biosynthesis and, thus, may provoke multiple inhibition of this metabolic pathway in response to garlic consumption. The fact that allicin was the most effective inhibitor argues against the possibility that its degradation products, namely diallyl disulfide or allyl mercapatan, might mediate its effects, a possibility that might be true, however, in the case of the vinyl-dithiins.

Allyl Compounds↗
PubMed1996

Altered distribution of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4) and the N-methyl-D-aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy.

In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 and for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon's horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.

Adolescent↗
PubMed1996

[Priority conflict concerning the discovery of lumbar anesthesia between August Bier and August Hildebrandt].

The history of anaesthesiology like that of other medical branches has not been free of quarrels concerning priority. International disputes between the surgeon August Bier from Kiel and his former colleague August Hildebrandt concerning the question of who was the actual inventor of spinal anesthesia have almost fallen into oblivion. While Hildebrandt and numerous other colleagues frequently stated that the New York neurologist James Leonhardt Corning was the inventor of spinal anesthesia, Bier insisted on having described and developed this method first and without any knowledge of Corning's experiments. Corning's use of the term "spinal anesthesia" in his publications probably caused the error that he was the first to describe and apply this new widespread technique. Only recently, American scientists emphasized the fact that this is not true. There will, unfortunately, not be an answer to the Question why Hildebrandt started this quarrel about priority. His reason might have been hurt feelings as he had not been mentioned as co-author in Bier's epoch-making survey.

Anesthesia, Spinal↗
PubMed1996

Preservation of calretinin-immunoreactive neurons in the hippocampus of epilepsy patients with Ammon's horn sclerosis.

Selective neuronal vulnerability and aberrant axonal reorganization in the hippocampus may play an important role for the pathogenesis of pharmaco-resistant temporal lobe epilepsy (TLE). Interneurons containing calcium-binding proteins (CaBPs) are candidates for pathogenetically relevant neurons in the hippocampus of patients with TLE. Here we have examined the cellular localization and distribution of calretinin (CR), a recently discovered CaBP, in the hippocampus of 35 patients with TLE. There was a striking preservation of CR-immunoreactive neurons in TLE patients with Ammon's horn sclerosis (AHS). No significant differences in the distribution of CR-immunoreactive neurons were observed between patients with lesion-associated TLE and control patients without epilepsy. However, a subpopulation of CR-immunoreactive interneurons with morphological features of Cajal-Retzius-like cells, which are only transiently detectable in the normally developing hippocampus, was markedly increased in epilepsy patients with AHS. This increase did not correlate with the duration of the epileptic disorder. Another significant finding was a striking increase and reorganization of CR-immunoreactive neuropil throughout the entire molecular layer of the dentate gyrus (DG-ML) in patients with AHS as compared to patients with focal lesions and control specimens. Ultrastructural analysis identified the CR-immunoreactive axonal profiles as components of an inhibitory, intrinsic neuronal system. The presence of a CR-positive, aberrant cell population, in combination with sprouting of CR-positive axonal processes may significantly alter the gating function of the dentate gyrus and thereby increase hippocampal epileptogenicity in epilepsy patients with AHS.

Adolescent↗
PubMed1996

Properties of a delayed rectifier potassium current in dentate granule cells isolated from the hippocampus of patients with chronic temporal lobe epilepsy.

PURPOSE: Properties of potassium outward currents were investigated in human hippocampal dentate gyrus granule cells from 11 hippocampal specimens obtained from patients with temporal lobe epilepsy (TLE) during resective surgery. METHODS: Dentate granule cells were isolated enzymatically and outward currents analyzed by using the whole-cell configuration of the patch-clamp method. Hippocampal specimens were classified neuropathologically with respect to severe segmental cell loss, gliosis, and axonal sprouting (Ammon's horn sclerosis, AHS), or the presence of a focal lesion in the adjacent temporal lobe. RESULTS: A delayed rectifier outward current (IK), but not an A-type potassium current (IA) or inwardly rectifying potassium currents, was observed in all cells. The average current density of IK, the time-dependent decay of IK, and the resting membrane characteristics were not significantly different between patients with and without AHS. The voltage of half-maximal activation V1/2(act) was 5.4 +/- 1.8 mV in AHS compared with -2.9 +/- 1.8 mV in lesion-associated epilepsy (NS). In contrast, V1/2(inact) was shifted in a hyperpolarizing direction in AHS (-67.7 +/- 0.6 mV) compared with that in hippocampi not showing AHS (-47.7 +/- 2.6 mV; p = 0.0017). CONCLUSIONS: The altered steady-state voltage-dependence of IK may result in abnormal excitability of dentate granule cells in AHS and exert a marked influence on input-output properties of the dentate gyrus.

Adult↗
PubMed1996

A fixed-dose combination of low molecular weight heparin with dihydroergotamine versus adjusted-dose unfractionated heparin in the prevention of deep-vein thrombosis after total hip replacement.

The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily. In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 +/- 7,150 IU/day (mean +/- SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distalproximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean +/- SD) was 751 +/- 339 mL (LMWH/DHE) and 736 +/- 380 mL (UFH), whereas postoperative drain-loss volume (mean +/- SD) was found to be 523 +/- 333 mL (LMWH/DHE) and 581 +/- 404 mL (UFH). Whole blood transfusion volumes (mean +/- SD) were 570 +/- 202 mL (LMWH/DHE) and 748 +/- 455 mL (UFH). Additionally, red cell replacement volumes (mean +/- SD) were 804 +/- 435 mL (LMWH/DHE) and 720 +/- 328 mL (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant. Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

Aged↗
PubMed1995

Controlled superfusion of the rat spinal cord for studying non-synaptic transmission: an autoradiographic analysis.

Recently, evidence has been raised that long-term changes in the central nervous system are mediated by extrasynaptic spread of neuropeptides ('volume transmission'). To study the effects of volume transmission in the spinal cord we developed the technique of controlled superfusion of the rat cord dorsum. This paper presents quantitative data about the spread, local spinal tissue concentration and redistribution of (2-[125I]iodohistidyl)neurokinin applied for 15, 30 or 60 min to the spinal cord dorsum in concentrations of 0.05 or 50 microM (10 microliters). Analysis of autoradiograms of sagittal and transverse spinal cord sections was done by computer-assisted densitometry. Under all experimental conditions, the spread of radiolabel into the superfused spinal cord segments reached Rexed's laminae V and VI; maximal spread (1.6 +/- 0.3 mm) was measured after superfusion for 30 min. The amount of radiolabel decreased in ventral direction as a function of distance. Highest tissue concentrations of neurokinin A (NKA) were obtained within the superficial spinal cord up to a depth of 0.5 mm and ranged from 700 to 2000 pmol/g following superfusions for 15 or 30 min with 50 microM NKA. Thus, these tissue concentrations were 25-70 times lower than the concentration of NKA in the superfusate. Since pool content was not exchanged, the radioactivity within the spinal cord was lower after superfusion periods of 60 min than after 15 or 30 min. Detection of radiolabel in blood and urine suggests that capillary clearance is relevant and limits the accumulation of the peptide within the spinal cord tissue and the spread into deeper laminae. The controlled superfusion of the rat cord dorsum is a useful method to mimick the spinal release of endogenous neuropeptides such as NKA during intense noxious stimulation, and it can be employed for versatile investigations of the effects of neuroactive molecules on the processing of sensory information in the intact spinal network.

Animals↗
PubMed1995

[Hemiprosthesis in femoral neck fracture].

From 1968 to 1993 835 hemiarthroplasties were performed at the Department of Trauma Surgery of the University of Erlangen. Until 1984 Moore (297) and Thompson (148) prostheses were implanted. After this period 390 patients were treated with a bipolar headneck replacement. Average age of patients at the time of surgery was 80.2 years from 1968 to 1980 and 83.1 from 1981 to 1993. All hemiarthroplasties were performed due to intracapsular fractures of the femoral neck. 5.9% of the Thompson and Moore prostheses were revised to total hip arthroplasty, the rate of revisions of bipolar prostheses was 4.9%. Main causes of revision for Thompson and Moore prostheses were acetabular erosion and protrusion (5.2%). Revision of bipolar prostheses became necessary because of recurrent luxation in 4.1%. The social status of the patients was examined 1 year after the operation. From 1968 to 1980 67% of the patients lived in their own home or with their families, compared to 39% from 1981 to 1993. The percentage of patients in retirement homes tripled from 9% to 29% for the same period.

Activities of Daily Living↗
PubMed1994

Possible involvement of arachidonic acid and eicosanoids in metamorphic events in Hydractinia echinata (Coelenterata; Hydrozoa).

Upon induction of metamorphosis, larvae of the marine hydroid Hydractinia echinata release [14C]-arachidonic acid from previously labeled endogenous sources. The lipoxygenase inhibitors nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid inhibited metamorphosis induced by Cs+ and 1,2-sn-dioctanoylglycerol, whereas the inhibitors of cyclooxygenase, indomethacin, and acetylsalicylic acid were ineffective, suggesting a role for lipoxygenase metabolites of arachidonic acid in induction of metamorphosis. Lipoxygenase products in Hydractinia echinata were isolated and identified by gas chromatography/mass spectrometry. 8- and 12-HETE were the most abundant metabolites. In cytosolic fractions from larvae activity of an arachidonic acid metabolizing enzyme, presumably a lipoxygenase, was found. The metabolic product was identified by 1H-NMR and chiral phase HPLC as 8(R)-HETE. Its production was strongly inhibited by NDGA, but not by indomethacin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Inhibition of cholesterol biosynthesis by allicin and ajoene in rat hepatocytes and HepG2 cells.

Exposure of primary rat hepatocytes and human HepG2 cells to allicin and ajoene resulted in the concentration-dependent inhibition of cholesterol biosynthesis at different steps of this metabolic pathway. At low concentrations of ajoene sterol biosynthesis from [14C]acetate in rat hepatocytes was decreased by 18% with an IC50-value of 15 microM, while allicin was almost uneffective. In HepG2 cells, both compounds significantly inhibited sterol biosynthesis by 14% and 19% with IC50-values of 7 and 9 microM for allicin and ajoene, respectively. This inhibition was exerted at the level of HMG-CoA-reductase as revealed by the absence of inhibition, if [14C]acetate was replaced by [14C]mevalonate as a precursor, and by direct determination of enzyme activity. At somewhat higher concentrations inhibition of cholesterol biosynthesis by both, allicin and ajoene, was also observed at late steps resulting in the accumulation of the precursor lanosterol. Alliin instead was completely inactive. In the case of allicin, small amounts of dihydrolanosterol and 7-dehydrocholesterol were formed at intermediate concentrations of 5-10 microM. From these results it is concluded that a major point of inhibition at the late steps occurs at the level of lanosterol 14 alpha-demethylase.

Acetates↗
PubMed1994

Inhibition of c-Fos protein expression in rat spinal cord by antisense oligodeoxynucleotide superfusion.

Peripheral noxious stimulation leads to a rapid and transient expression of c-fos, c-jun and other immediate-early genes (IEGs) in the spinal cord. However, the role of IEG encoded transcription factors in plasticity of spinal neurons remains speculative. In the present study we have shown that superfusion of rat spinal cord with antisense oligodeoxynucleotides complementary to c-fos mRNA suppresses heat-induced c-Fos protein expression without affecting other members of the Fos and Jun family, thus providing a technique to determine the function of IEGs in vivo.

Animals↗
PubMed1994

Porphyrin studies in TCDD-exposed workers.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to inhibit uroporphyrinogen decarboxylase activity resulting in chronic hepatic porphyria. From a cross-sectional study of 170 workers in chemical industry 68 showed elevated coproporphyrin levels, interpreted as secondary coproporphyrinuria. Three persons suffered from chronic hepatic porphyria in subclinical stages. None of the workers showed an overt porphyria cutanea tarda. A low-grade zinc protoporphyrinemia was observed in three persons. Forty-three of the 170 workers were evaluable for investigating the effect of TCDD on porphyrin levels. No significant correlation was found between TCDD concentration in adipose tissue and the level of uroporphyrin and coproporphyrin. The influence of a chloracne history is described.

Adipose Tissue↗
PubMed1994

Prevention of urethral stricture recurrence using clean intermittent self-catheterization.

OBJECTIVE: To investigate the effect of clean intermittent catheterization (CIC) on prevention of urethral stricture recurrence after internal urethrotomy. PATIENTS AND METHODS: Of 55 men who were randomly selected, 43 completed the investigation. Of these, 21 patients performed CIC weekly for 1 year following Sachse's operation for urethral stricture and 22 patients formed the control group after the same operation. All had an objective examination for urethral stricture every 2 months after surgery. RESULTS: Significantly fewer (P < 0.01) patients developed recurrence of urethral stricture within the first postoperative year in the CIC group (n = 4) compared with the control group (n = 15). No CIC complications were seen, and patients who completed the CIC programme considered the method fully acceptable. CONCLUSION: Weekly CIC is a simple method of reducing the frequency of urethral stricture recurrence after internal urethrotomy.

Adolescent↗