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Biomedical subjects

H Urbach

Publications and source records attributed to H Urbach.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Detectability of new medial infarcts by CT: appearance of ischemic signs].

PURPOSE: To evaluate the detectability of acute middle cerebral artery (MCA) infarctions by CT with regard to the time interval after symptom onset and to the infarction size. Analysis of the chronological appearance of signs of ischaemia. MATERIAL AND METHODS: Two examiners retrospectively and independently evaluated CT scans from 171 patients with acute MCA infarctions performed within 24 hours after onset of symptoms. RESULTS: 92, respectively 87% of the Infarctions were correctly diagnosed. The detection rate did not increase after the first hour after onset of symptoms. All MCA infarctions involving the lentiform nucleus, but only 83% of the infarctions covering < 33% of the MCA area, were recognised. The hyperdense middle cerebral artery sign (HMCA5) was present in 75% of the infarctions in the first 90 minutes and in 15% from hour 12 to 24. Hypodensity of the lentiform nucleus appeared within 150 minutes, hypodensity of the convexity cortex at the earliest 60 minutes after onset of symptoms. CONCLUSIONS: The detection rate of acute MCA infarctions corresponds with the infarction size, but does not significantly change after the first hour after symptom onset.

Adult↗
PubMed1997

Preoperative risk assessment for carotid occlusion by transcranial Doppler ultrasound.

OBJECTIVES: An endovascular carotid balloon occlusion test with continuous intracranial monitoring by transcranial Doppler sonography was performed in 55 patients for prediction of tolerance of a required permanent occlusion of the carotid artery. METHODS: Blood flow velocities of the ipsilateral middle cerebral artery during occlusion were recorded and compared with clinical tolerance during an occlusion test as well as with postoperative outcome after an eventual permanent occlusion. To stress the capacity of the cerebral circulation to tolerate the occlusion acetazolamide was injected before occlusion in all patients. RESULTS: The onset of neurological symptoms during temporary occlusion was dependent on the percentage fall of mean blood flow velocity relative to baseline rather than on absolute flow velocities during the time of occlusion. Patients with a fall of mean flow velocity of less than 30% tolerated temporary and permanent occlusion, with the exception of two patients who developed an infarction due to thromboembolism after iatrogenic sacrifice of the carotid artery. Patients with a major decrease developed neurological symptoms during occlusion in 55% and, in cases of carotid ligation, a haemodynamic infarction occurred. CONCLUSION: The results show that transcranial Doppler monitoring as a part of an endovascular balloon occlusion test may be a reliable technique for preoperative risk assessment for permanent occlusion of the carotid artery.

Adult↗
PubMed1996

Herniation of the spinal cord 38 years after childhood trauma.

We report an unusual post-traumatic spinal cord herniation, which became symptomatic 38 years after the trauma. A 44-year-old man presented with a 2-year history of increasing impotence, neuropathic bladder dysfunction and dissociated sensory loss below the level of T6. At the age of 6 years he had a severe blunt spinal injury with transient paraparesis. MRI revealed right lateral and ventral displacement of the spinal cord at the T5/6 level. The spinal cord was surgically exposed and found to herniate through a ventral defect of the arachnoid membrane and the dura mater. As there were no other events that could have precipitated spinal cord herniation the reported blunt trauma in childhood is the most likely cause for the spinal cord herniation in this patient.

Adult↗
PubMed1996

[Endovascular balloon occlusion test of the internal carotid artery with increased hemodynamic monitoring for determination of circulatory reserve before planned carotid occlusion].

PURPOSE: To evaluate stroke risk assessment of balloon test occlusion of the internal carotid artery (ICA) with enlarged haemodynamic monitoring prior to permanent ICA occlusion. MATERIAL AND METHODS: 24 patients with cervical metastasis (n = 18), cavernous meningiomas (n = 3) or inoperable cavernous aneurysms (n = 3) were examined. The test occlusion was monitored by EEG, neurological examinations and transcranial Doppler sonography of the ipsilateral middle cerebral artery with evaluation of the cerebrovascular reserve capacity. Additionally 99mTc-HMPAO-SPECT imaging was added showing the perfusion during test occlusion. RESULTS: In one (4%) patient the test occlusion had to be interrupted previously due to an acute neurological deficit. This patient and two (8%) patients with highly pathological test results in SPECT and TCD were excluded from permanent carotid occlusion. In 6 (25%) patients quantitative TCD monitoring could improve the stroke risk assessment by differentiating the patients in a low and high risk group. 6 (25%) patients were definitely occluded without haemodynamic complications, but two patients suffered from embolic infarctions which cannot be predicted by this procedure. CONCLUSIONS: The multimodal balloon test occlusion with enlarged haemodynamic monitoring allows haemodynamic stroke risk assessment prior to permanent occlusion of the ICA.

Adult↗
PubMed1996

[Radiologic diagnosis of hypophyseal adenomas].

During the last few years the radiological approach to the diagnosis of pituitary adenomas has changed. In the present article we review the current status of techniques and indications for imaging of pituitary adenomas. First the clinical presentation and pertinent biochemical tests for the various types of adenomas are discussed. Then the important questions to be answered by the radiologists are formulated. With the advent of Magnetic Resonance Imaging (MRI) we have a very powerful tool to image the pituitary gland; however, conventional radiographs, computed tomography and angiography continue to play a role in the evaluation of pituitary adenomas under certain circumstances.

Adenoma↗
PubMed1995

Posterior inferior cerebellar artery aneurysm in the fourth ventricle.

We report a patient with a ruptured aneurysm of the choroidal branch of the right posterior inferior cerebellar artery (PICA), lying in and causing an isolated haemorrhage in the fourth ventricle. MRI on the first day after bleeding revealed an abnormal vessel in the fourth ventricle, which was surrounded by a mass of intermediate signal on T1- and T2-weighted images. The aneurysm was clipped via partial splitting of the lower vermis and opening the inferior medullary velum. A postoperative angiogram confirmed complete obliteration of the aneurysm. With PICA aneurysms the rate of intraventricular haemorrhage is high and in most cases due to reflux of blood. If there is an isolated intraventricular haemorrhage, a peripheral PICA aneurysm, lying in or near the fourth ventricle, may be suspected.

Cerebellum↗
PubMed1994

Cauda equina syndrome with multiple lumbar diverticula complicating long-standing ankylosing spondylitis.

A patient with cauda equina syndrome complicating long-standing inactive ankylosing spondylitis is described. The first neurological symptoms started 15 years after the onset of ankylosing spondylitis. Over a follow-up period of 12 years the cauda equina syndrome showed a slowly progressive but disabling course leading to sensory disturbances in the lumbar and sacral dermatomes, weakness and wasting of the muscles innervated by these nerve roots, sphincter disturbances, and impotence. Magnetic resonance imaging, computed tomography, and lumbar myelography showed enlargement of the dural sac with multiple lubar diverticula eroding the lumbosacral vertebrae. The pathophysiology of the cauda equina syndrome in ankylosing spondylitis is unclear. Surgical treatment seems justified only in patients with a short history of neurological symptoms.

Cauda Equina↗
PubMed1994

Effects of the renin inhibitor N-[N-(3-(4-amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histid inyl] -(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2-amide acetate in anesthetized rhesus monkeys.

The renin inhibitory effect of the non-peptide renin inhibitor S 2864 (N-[N-(3-(4-Amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histidinyl]-(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2- amide acetate, CAS 135683-92-0) was characterized in vitro and in vivo in primates. In vitro, S 2864 inhibited the activity of purified human plasma renin with an IC50 of 3.8 x 10(-10) mol/l and did not affect related human aspartyl proteases like human cathepsin E, cathepsin D or pepsin. In vivo, in anesthetized sodium depleted rhesus monkeys S 2864 decreased mean arterial blood pressure after intraduodenal (i.d.) administration of 2 mg/kg significantly by 27% from 94 +/- 8 to 62 +/- 6 mmHg for 90 min. Heart rate was not changed. Cumulative intravenous (i.v.) administration of S 2864 or remikiren in doses of 1, 10 and 30 micrograms/kg significantly decreased systemic blood pressure, dP/dtmax and cardiac output while heart rate was not changed. Plasma angiotensin II (ANG II) levels as well as renin activity were dose dependently reduced after 10, 30 and 60 min. It is concluded that S 2864 is an effective specific inhibitor of human renin eliciting marked blood pressure lowering activities in primates.

Anesthesia↗
PubMed1993

Renin inhibitors containing a pyridyl amino diol derived C-terminus.

Based on the concept of transition-state analogs, a series of nonpeptide renin inhibitors with the new (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-(2-pyridyl)hexane moiety at the C-terminal functionality were synthesized and evaluated for inhibition of renin both in vitro and in vivo. All compounds exhibited potencies in the nanomolar or even subnanomolar range when tested versus human renin in vitro. Selected inhibitors were evaluated in anesthetized, sodium-depleted rhesus monkeys and produced a marked reduction in mean arterial blood pressure (MAP) upon intraduodenal administration of a dose of 2 mg/kg. Compound 38 (S 2864) containing an amino piperidyl succinic acid derived N-terminal is the most promising member in this series. 38 inhibited human renin with an IC50 of 0.38 nM, did not affect other human aspartic proteinases, and decreased mean arterial blood pressure significantly by 27% with a duration of action of 90 min after administration of 2 mg/kg id in anesthetized, sodium-depleted rhesus monkeys.

Amino Acids↗
PubMed1992

Renin inhibitory pentols showing improved enteral bioavailability.

Incorporation of a C-terminal pentahydroxy functionality led to potent, low molecular weight hydrophilic renin inhibitors lacking the P1' side chain. As these compounds are easy to synthesize and have sufficient water solubility, they were chosen for further study. Compound 33 was transported across rabbit intestinal brush border membrane vesicles and yielded a hypotensive effect in sodium-depleted rhesus monkeys which lasted for 90 min when dosed at 2 mg/kg id.

Amino Sugars↗
PubMed1990

Interaction of renin inhibitors with the intestinal uptake system for oligopeptides and beta-lactam antibiotics.

The interaction of two renin inhibitors, S 86,2033 and S 86,3390, with the uptake system for beta-lactam antibiotics and small peptides in the brush border membrane of enterocytes from rabbit small intestine was investigated using brush border membrane vesicles. Both renin inhibitors inhibited the uptake of the orally active cephalosporin cephalexin into brush border membrane vesicles from rabbit small intestine in a concentration-dependent manner. 1.1 mM of S 86,3390 and 2.5 mM of S 86,2033 led to a half-maximal inhibition of the H(+)-dependent uptake of cephalexin. Both renin inhibitors were stable against peptidases of the brush border membrane. The uptake of cephalexin into brush border membrane vesicles (1 min of incubation) was competitively inhibited by S 86,2033 and S 86,3390 suggesting a direct interaction of these compounds with the intestinal peptide uptake system. The renin inhibitors are transported across the brush border membrane into the intravesicular space as was shown by equilibrium uptake studies dependent upon the medium osmolarity. The uptake of S 86,3390 was stimulated by an inwardly directed H(+)-gradient and occurred with a transient accumulation against a concentration gradient (overshoot phenomenon). The renin inhibitors S 86,2033 and 86,3390 also caused a concentration-dependent inhibition in the extent of photoaffinity labeling of the putative peptide transport protein of apparent Mr 127,000 in the brush border membrane of small intestinal enterocytes. In conclusion, these studies show that renin inhibitors specifically interact with the intestinal uptake system shared by small peptides and beta-lactam antibiotics.

Animals↗
PubMed1989

Effects of the novel compound, Hoe 065, upon impaired learning and memory in rodents.

The effects of Hoe 065 (n-octyl 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo [3.3.0]octane-3-carboxylate maleate salt) were studied on the performance of mice and rats in different learning tasks. Hoe 065 prevented the disruption of memory induced by scopolamine administered before training. The results indicate that Hoe 065 improves cognitive function in different tasks.

Animals↗
PubMed1989

Inhibition of converting enzyme in brain tissue and cerebrospinal fluid of rats following chronic oral treatment with the converting enzyme inhibitors ramipril and Hoe 288.

A direct central nervous system (CNS)-related component of the cardiovascular actions of converting enzyme (CE) inhibitors will be governed by the ability of these drugs to gain access to the brain. We investigated the inhibitory effect of the two CE inhibitors ramipril and Hoe 288 on CE activity in different brain regions and in the cerebrospinal fluid of rats. One-week oral gavage treatment with ramipril (10 mg/kg/day) and Hoe 288 (10 mg/kg/day) resulted in a marked inhibition of CE activity in the brain cortex (90 and 91%, respectively), the hypothalamus (78 and 82%, respectively), and in the brainstem (67 and 66%, respectively). The complete blockade of plasma CE activity was paralleled by a 84% inhibition of CE activity in cerebrospinal fluid. Both CE inhibitors failed significantly to inhibit CE activity in the striatum. Our results demonstrate that the CE inhibitors Hoe 288 and ramipril were able to pass the blood-brain barrier (BBB) to inhibit central CE activity. The penetration of CE inhibitors into the CNS appears to depend on the lipophilicity of the drugs and on the mode of drug application. The possibility that an inhibition of CE activity in circumventricular organs outside the BBB such as the subfornical organ and the organum vasculosum of the lamina terminalis may be sufficient to explain the central effects of orally applied CE inhibitors is discussed.

Administration, Oral↗
PubMed1989

Inhibition of converting enzyme in the cerebrospinal fluid of rats after oral treatment with converting enzyme inhibitors.

Inhibition of brain converting enzyme (CE) has been implicated in the antihypertensive action of some CE inhibitors. However, it is still a matter of debate whether these drugs gain access to the central nervous system upon systemic administration. In this study in rats we investigated the ability of p.o. applied CE inhibitors to penetrate from blood into cerebrospinal fluid (CSF) by analyzing the inhibition of CE activity in the CSF after acute bolus and after 1 week overnight treatment with enalapril, ramipril and Hoe 288. Penetration into the CSF closely paralleled the lipid solubility of the drugs. The most lipophilic drug, Hoe 288 (10 mg/kg), inhibited CE activity in the CSF after acute (66%) and after chronic (30%) p.o. treatment. Ramipril (10 mg/kg), being less lipophilic than Hoe 288, was only effective after acute bolus administration (59% inhibition), whereas the most hydrophilic drug, enalapril (30 mg/kg), did not reduce CE activity in the CSF after either regimen. The CE inhibition in the CSF after acute p.o. treatment with ramipril and Hoe 288 was dose-dependent with threshold doses of 3 to 10 mg/kg (ramipril) and less than 1 mg/kg (Hoe 288). The presence of ramipril and Hoe 288 in the CSF was also demonstrated by the inhibitory effect of heat-inactivated CSF from CE inhibitor-treated rats on purified CE from rabbit lung. A comparison of the in vitro activities of the three prodrugs and their parent diacids against CE in plasma and in CSF and against purified CE revealed hydrolysis of the prodrugs to their parent diacids in plasma and CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

A novel high affinity class of Ca2+ channel blockers.

Benzolactams (HOE 166 and analogs) form a new class of molecules acting on the 1,4-dihydropyridine-sensitive L-type Ca2+ channels. The main binding properties of HOE 166 and analogs to rabbit skeletal muscle membranes are as follows. (i) The compounds have a specific binding site to which they associate with a high affinity (0.25 nM for HOE 166). (ii) Unlabeled HOE 166 and analogs completely inhibit 1,4-dihydropyridine binding [(+)-[3H]PN 200-110] in a competitive way. (iii) Affinity values measured for HOE 166 inhibition of (+)-[3H]PN 200-110 (K0.5 = 0.25 nM and K1 = 0.55 nM) and of [3H]HOE 166 binding (K0.5 = 0.5 nM) are in good agreement. They also fit with results from direct binding experiments with tritiated HOE 166 (Kd = 0.27 nM) and from kinetic experiments (Kd = 0.39 nM). (iv) HOE 166 completely inhibits the specific binding of other classes of Ca2+ channel antagonists such as phenylalkylamines [(-)[3H] desmethoxyverapamil], benzothiazepines (d-cis-[3H]diltiazem), diphenylbutylpiperidines ([3H]fluspirilene), and [3H]bepridil. In all these cases the binding inhibition is of a noncompetitive nature. (v) The maximum binding capacity for [3H]HOE 166 binding to transverse tubule membranes, 65 pmol/mg of protein, is the same as that found for other classes of Ca2+ channel antagonists. 45Ca2+ uptake experiments performed with the rat aortic cell line A7r5 and the insulin-secreting cell line RINm5F demonstrate that HOE 166 and analogs fully inhibit the 1,4-dihydropyridine-sensitive 45Ca2+ influx elicited by depolarization. There is a good correlation between inhibitory potencies of compounds in the HOE 166 series measured on (+)-[3H]PN 200-110 binding to A7r5 membranes and on the activity of Ca2+ channels followed by 45Ca2+ fluxes with the same cells. Structure-function relationships of HOE 166 and analogs for Ca2+ channel blockade in A7r5 and RINm5F cells were also in good correlation. Finally, voltage-clamp experiments confirmed that voltage-dependent L-type Ca2+ channels are completely blocked by 100 nM HOE 166 even at a membrane potential held at -80 mV.

Animals↗
PubMed1985

A radioimmunoassay for the angiotensin converting enzyme inhibitor ramipril and its active metabolite.

A radioimmunoassay (RIA) has been developed for the measurement of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)- 2-azabicyclo[3.3.0]octane-3-carboxylic acid (ramipril, Hoe 498) and its active metabolite (diacid: hydrolysis product of ramipril) in serum or plasma. Antibodies to the diacid were raised in rabbits against a lysine analogue conjugated to bovine serum albumin. A 125I-ramipril-diacid derivative was used as radioligand. Separation of the antibody-bound and free radiolabeled ligand was achieved by employing a polyethylene glycol solution. The RIA is specific for the active metabolite (diacid). Studies on specificity showed less than 0.6% cross-reactivity with intact ramipril or with dioxopiperazine metabolites. The levels for intact ramipril were obtained by prior enzymatic hydrolysis to the diacid. The sensitivity of the assay was 0.1 and 0.5 ng/ml for diacid and ramipril, respectively. Intra- and inter-assay coefficients of variation ranged from 3 to 14% at 1 to 30 ng diacid per ml. A recovery experiment yielded an average of 103%. The assay has been used to investigate the pharmacokinetic profile of both ramipril and its pharmacologically active metabolite.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Synthesis of a highly active angiotensin converting enzyme inhibitor: 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498).

The convergent, diastereoselective synthesis of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe acid (Hoe 498), a new ACE-inhibitor with improved bioavailability and pharmacokinetics, is described.

Angiotensin-Converting Enzyme Inhibitors↗