Biomedical subjects

H C Hansen

Publications and source records attributed to H C Hansen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Treatment of chronic pain with antiepileptic drugs: a new era.

BACKGROUND: Shortcomings of traditional pain relief agents have led physicians to investigate other alternatives, such as antiepileptic drugs. Safe, effective, nonhabituating agents are currently available to enhance pain treatment strategies. METHODS: In this article, various pharmacologic options and their mechanisms of action are reviewed briefly, with a focus on treatment of chronic pain with antiepileptic drugs (AEDs). RESULTS: Antiepileptic drugs have been widely studied and prescribed for the relief of acute and chronic pain. Similarities in the neurophysiology of pain and epilepsy suggest that AEDs may be a suitable adjunct in the management of chronic pain. Of the newer AEDs, gabapentin shows the greatest potential and appears to be well tolerated by patients. CONCLUSIONS: Treatment of chronic pain remains a challenge for physicians and patients. Further research is required to identify the role of various agents and their effect on patient return to function and quality of life.

Acetates↗

PubMed1999

Outcome after endovascular treatment of Hunt and Hess grade IV or V aneurysms: comparison of anterior versus posterior circulation.

BACKGROUND AND PURPOSE: The most common cause of poor treatment outcome in patients suffering aneurysmal subarachnoid hemorrhage is cerebral vasospasm, especially in cases of poor Hunt and Hess grades (IV and V). A further prognostic factor in surgically treated patients is aneurysm localization. The aim of the present retrospective study is to compare the endovascular treatment outcome in such poor-grade patients according to aneurysm localization in either the anterior (AC) or posterior (PC) circulation. METHODS: Forty poor-grade patients admitted between 1993 and July 1998 were treated by endovascular approach within 23 days after aneurysm rupture. Eighteen had aneurysms in the AC, 22 in the PC. Mean treatment delay was 4 days after rupture and median, 2 days. One patient showed multiple aneurysms. In 36 cases, aneurysms were occluded by Guglielmi detachable coils; in 4 cases, by parent vessel balloon occlusion. RESULTS: The incidence of delayed ischemic neurological dysfunction or cerebral infarct due to vasospasm did not differ significantly between the AC and PC groups. Two procedure-related complications with clinical effect were observed in each group. At 6 months' follow-up, the result was good in 5 patients and poor in 13 in the AC group and good in 11 patients and poor in 11 in the PC group. CONCLUSION: Given comparable incidence of vasospasm in poor-grade patients, a tendency toward better treatment outcome was found in patients with aneurysms in the posterior circulation (chi(2)=2.04; P=0.15) than in the anterior circulation. Endovascular therapy for poor-grade patients is recommended, as are further studies to determine treatment differences.

Adolescent↗

PubMed1999

The burst-suppression electroencephalogram.

The burst-suppression (BS) pattern of the EEG occurs in a rather limited number of conditions. It has been observed in deep stages of general anesthesia and in conjunction with sedative overdoses. It is also known to occur in the wake of cardiorespiratory arrest. Undercutting of the cortex has been found to result in BS activity. Rare neonatal epileptic encephalopathies also give rise to BS. Our personal interest was prompted by the consistent finding of BS activity in rats following cerebral anoxia (nitrogen inhalation, airway obstruction): after periods of EEG flatness, BS activity developed, followed by periodic bursts and diffuse slowing. On the other hand, earlier literature (before 1960) showed virtually no observation of BS, neither in anoxic patients, nor in animal experiments. It is likely that the introduction of modern intensive care treatment has engineered episodes of BS activity, probably due to modifications of the anoxic cerebral pathology.

Anesthetics↗

PubMed1999

The impact of raised intracranial pressure on cerebral venous hemodynamics: a prospective venous transcranial Doppler ultrasonography study.

OBJECT: The effect of increased intracranial pressure (ICP) on cerebral venous blood flow has been the subject of very few clinical and experimental studies. The authors assessed the usefulness of venous transcranial Doppler (TCD) ultrasonography as a noninvasive monitoring tool for predicting raised ICP. METHODS: Serial venous TCD studies of the basal vein of Rosenthal and the straight sinus (SS) were prospectively performed in 30 control volunteers and 25 patients with raised ICP. Correlations with ICP data were calculated using a multivariate regression model. Venous blood flow velocities (BFVs) in the basal vein of Rosenthal showed, within a certain range, a linear relationship between mean ICP and maximal venous BFV (r = 0.645; p<0.002). Moreover, a linear relationship was found for maximal venous BFVs in the SS and mean ICP (r = 0.928; p<0.0003). CONCLUSIONS: Venous TCD studies may provide an additional noninvasive monitoring tool for raised ICP and give further insights into the cerebral venous hemodynamics present during raised ICP.

Adult↗

PubMed1998

Abeta-fiber mediated activation of cingulate cortex as correlate of central post-stroke pain.

A patient is presented who suffered a lateral brainstem infarction which selectively abolished pain and temperature sensitivity in the lower right limb. One year later central post-stroke pain had developed in the affected limb with touch and cold allodynia. P40m dipoles calculated from magnetoencephalographic fields after electrical stimulation of both tibial nerves were localized in SI as is seen in normal subjects. However, stimulation of the affected side caused deep pain sensations and elicited a large N80m component, best explained by an additionally active dipole in cingulate cortex. This early co-activation in a limbic structure suggests peripheral Abeta-fiber mediation and lemniscal projection. Abnormal link to the pain system may be due to sensitization and reorganization above the level of nociceptive deafferentation.

Brain Stem↗

PubMed1998

[Congestive myelopathy caused by spinal dural arteriovenous fistulas. Anamnesis, clinical aspects, diagnosis, therapy and prognosis].

Congestive myelopathy, formerly referred to as varicosis spinalis or Foix-Alajouanine syndrome, is caused by a spinal dural arteriovenous fistula (SDAVF). So far, the blood supply from the meningeal arteries draining through the fistula into the medullary venous system can only be verified by spinal angiography. Patients predominantly male and over the age of 60 are afflicted. Initially reversible functional disorders caused by the congestion of the spinal cord veins eventually become irreversible, the most common symptom being an increasingly paretic gait disorder, the signs of which generally begin symmetrically and progress from distal to proximal signs. Simultaneously, predominantly transverse sensory dysfunctions develop, as well as bladder and bowel dysfunctions, most often leading to incontinence. MRI typically shows a central medullary signal enhancement with slight swelling of the afflicted region, initially indicative of a reversible congestive edema and later of an irreversible infarction, and extended perimedullar vessels. Thus, if the clinical course and the characteristic MRI findings suggest the possibility of disease related to congestive myelopathy, spinal angiography becomes indispensable. Since ensuing the success of therapy and prognosis depends on rapid determination of the extent of the illness, a speedy diagnostic reaction is mandatory to institute the treatment necessary to prevent paraplegia.

Adult↗

PubMed1998

Synthesis of some amino and carboxy analogs of galabiose; evaluation as inhibitors of the pilus protein PapGJ96 from Escherichia coli.

The 2'-amino-2'-deoxy, 6-amino-6-deoxy, and 6-carboxy analogs of the reference inhibitors 2-(trimethylsilyl)ethyl (alpha-D-galactopyranosyl)-(1-->4)-ss-D-galactopyranoside were synthesized and evaluated as inhibitors of the binding of the Escherichia coli-derived pilus protein PapGj96, using an ELISA assay. The inhibitory efficiencies (Krel; relative to the reference inhibitor) were: 157,13, and < 8, respectively. The results support the previously proposed combining site model, where the protein carries a negatively charged amino acid residue near HO-2' and HO-6 of the galabio-side.

Adhesins, Escherichia coli↗

PubMed1998

Synthesis of some divalent O- and S-glycosides of galabiose and globotriose.

Derivatives of galabiose (alpha-D-Galp-(1-->4)-D-Galp) and globotriose (a-D-Galp-(1-->4)-beta-D-Galp-(1-->4)-D-Glcp) were coupled to various 1,2- and 1,3-dihydroxymethyl- and dimercapto-methylbenzenes to give the corresponding divalent glycosides, potentially useful as inhibitors of bacterial adhesion.

Carbohydrate Sequence↗

PubMed1998

Clinical changes and EEG patterns preceding the onset of periodic sharp wave complexes in Creutzfeldt-Jakob disease.

The conversion of EEG findings and the evolution of clinical signs was investigated in 7 CJD patients who underwent serial EEG recordings along the course. At the onset of PSWC (mean 8.7 weeks), 5 patients had already progressed to akinetic mutism (characterized by loss of verbal contact and directed responses); and a CJD-typical-movement disorder (myoclonia, exaggerated startle reaction or focal dyskinesia) had started in 5 patients. When akinetic mutism commenced (on average at 7.5 weeks), runs of frontal intermittent non-peaked rhythmical delta activity (FIRDA) were found in all cases. These were later replaced by PSWC in 6 patients (interval 1 to 3 weeks). Occurrence of PSWC was often negatively related to external stimuli (2 of 6 cases), and sedative medication (all patients tested). We conclude that the selection of EEG recording dates to detect PSWC in CJD-candidates should be guided by detailed information about movement disorders and conscious level. Regarding the short survival time after their onset (average 8 weeks), PSWC usually mark the terminal stage of CJD. To detect PSWC, especially, EEG registrations in advanced stages are often necessary. In earlier disease stages, FIRDA-like EEG activities should be regarded as compatible with this diagnosis, and encourage further EEG studies for the demonstration of PSWC in a more advanced stage of CJD.

Aged↗

PubMed1997

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography.

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.

Animals↗

PubMed1997

Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests.

Raised intracranial pressure leads to increased pressure around the optic nerve (ON), which underlies the formation of papilledema and the enlargement of the dural optic nerve sheath (ONS). In clinical practice, the presence of widened ONSs is demonstrable on neuroimaging, but their relationship to cerebrospinal fluid (CSF) pressure remains unknown. The authors investigated the ONS response to pressure during CSF absorption studies in 12 patients undergoing neurological testing. The ONS diameter was evaluated by serial B-mode ultrasound scans of the anterior ON near its entry into the globe. All patients tested showed ONS diameter changes that exhibited covariance with the alteration of lumbar CSF pressure and were completely reversible during the infusion tests. The maximum difference in ONS diameter between baseline and peak pressure conditions was 1.8 mm on average (range 0.7-3.1 mm), corresponding to an average ONS diameter variation of 45% (range 15-89%). Regression analysis yielded a linear covariance between ONS diameter and CSF pressure with different slopes across subjects (0.019-0.071 mm/mm Hg, mean r = 0.78). However, this linear relationship was only present within a CSF pressure interval. This interval differed between patients: ONS dilation commenced at pressure thresholds between 15 mm Hg and 30 mm Hg and in some patients saturation of the response (constant ONS diameter) occurred between 30 mm Hg and 40 mm Hg. With a single exception, definitely enlarged ONS diameters (> 5 mm) were present when CSF pressure exceeded levels of 30 mm Hg. Retrospectively, discrimination between normal and elevated outflow resistance was possible on the basis of the ONS response to intrathecal infusion alone. It is concluded that the human ONS has sufficient elasticity to allow a detectable dilation in response to intracranial hypertension. Because of a variable pressure-diameter relationship, the subarachnoid pressure cannot be predicted exactly by single scans. Therefore, the clinical relevance of this method relies on the demonstration of pathologically enlarged sheaths or ongoing enlargement on serial ultrasonography studies.

Adult↗

PubMed1997

Comparison of psychomotor performance after intravenous and rectal diazepam.

Twenty-four healthy subjects participated in a triple crossover study in which some of the widely used psychomotor tests were applied as indicators of psychomotor ability. Diazepam was administered in doses of 10 mg intravenously, 10 mg rectally, and 35 mg rectally. Plasma levels of diazepam and performance decrement in the Trieger dot test (DOT), the perceptual speed test (PST), the digit symbol substitution test (DSST), and continuous reaction time were measured up to 12 hr after administration. The psychomotor effects were quite similar after administration of 10 mg diazepam intravenously and rectally. When the 35-mg rectal administration was compared to the 10-mg administrations, performance was still affected at 12 hr.

Administration, Rectal↗

PubMed1996

Anticonvulsant profile of the imidazoquinazolines NNC 14-0185 and NNC 14-0189 in rats and mice.

The anticonvulsant effects of NNC 14-0185 (3-(3-cyclopropyl-5-isoxazolyl)-6-fluoro-5-morpholino-imidazo[1,5- a] quinazoline) and NNC 14-0189 (3-(5-cyclopropyl-1,2, 4-oxadiazol-3-yl)-7-fluoro-5-(4-methyl-1-piperazinyl)-imidazo[1,5- a] quinazoline) in mice and rats were evaluated and compared with those of diazepam, clonazepam and the novel beta-carboline, abecarnil. Following i.p. administration, NNC 14-0185 and NNC 14-0189 prevented audiogenic seizures in DBA/2 mice and the clonic convulsions induced in mice by pentylenetetrazole, DMCM (methyl 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate), 3-mercaptopropionic acid and a low dose of bicuculline. NNC 14-0185 and NNC 14-0189 prevented seizures induced by pentylenetetrazole in rats and were also effective anticonvulsants in amygdala-kindled rats. In general, the anticonvulsant potencies of NNC 14-0185 and NNC 14-0189 were comparable to those of the reference benzodiazepines. However, like abecarnil, they were not effective against the seizures induced in mice by maximal electroshock and a high dose of bicuculline. The anticonvulsant effects of NNC 14-0185 and NNC 14-0189 against pentylenetetrazole-induced seizures were apparent within 5 min of i.p. injection and persisted for at least 2 h. These effects appeared to be mediated by benzodiazepine receptors since they were inhibited by concurrent administration of flumazenil. Both NNC 14-0185 and NNC 14-0189 showed greater separation between their anticonvulsant and muscle relaxant effects (measured as impaired rotarod performance) than did diazepam. In this respect, their therapeutic windows were similar (NNC 14-0185) to or better (NNC 14-0189) than that of abecarnil. Tolerance did not develop to the anticonvulsant effects of NNC 14-0185 and NNC 14-0189 over a 4-day test. In comparison, the anticonvulsant effects of diazepam and abecarnil were attenuated by repeated drug administration. Thus, NNC 14-0185 and NNC 14-0189 have a promising anticonvulsant and side-effect profile in comparison with diazepam, clonazepam and abecarnil. The potential use of these compounds in the treatment of epilepsy should be explored further.

Acoustic Stimulation↗

PubMed1996

Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension. I. Experimental study.

The optic nerve, ontogenetically part of the central nervous system, is surrounded by subarachnoidal cerebrospinal fluid (CSF) and dura mater. Because of the connection with the intracranial subarachnoidal space, CSF pressure variations influence the optic nerve sheath (ONS) diameter. Histologic studies revealed a segment of the optic nerve in which maximal diameter fluctuations could be expected, namely the bulging dura mater region approximately 3 mm behind the papilla. Twenty preparations of optic nerves obtained post mortem were examined sonographically before and after dilatation of the ONS, by means of measurement from three different projections. After gelatine-induced widening of the subarachnoidal space, the mean diameter increased by 60% at 3 mm behind the optic nerve head, but only by 35% at 10 mm distance. Independent measurements by two examiners correlated highly, which indicates excellent reproducibility of the sonographic measurements. The optimal experimental scanning position was at a right angle to the optic nerve (longitudinal section). Under clinical conditions, however, only axial sections can be obtained using anterior probe positions with transbulbar sound directions. Using such axial projections the 3 mm position proved reliably reproducible. The reduced resolution of the optic nerve itself, allowing it to be distinguished from its surrounding sheath, proved to be somewhat disadvantageous from this projection angle.

Adult↗

PubMed1996

Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension II. Patient study.

Up to now, the presence of elevated intracranial pressure (ICP) in acute neurological disorders is suspected by clinical and neuroimaging findings, but its verification depends on invasive techniques. Based on our experimental findings of rapid dilatation of human optic nerve sheaths (ONS), we investigated whether this phenomenon not only happens under chronic, but also under acute conditions of intracranial hypertension. Using optic nerve sonography the ONS was measured at 3 mm behind the papilla in axial transbulbar view. Thirty-nine children admitted to the intensive care unit (ICU) were examined. Of these 24 were being treated for elevated ICP (head trauma, metabolic disorder) and were compared to control patients (outpatients). The ONS diameter (ONSD) found in ICU patients with elevated ICP ranged up to 6.8 mm and was significantly enlarged compared with normal data (Wilcoxon's test, P = 0.007). The ONSD of ICU patients without pressure elevation was in the same range as that of control patients (2.7-4.0 mm). Considering the error of measurement (0.35 mm), the ONSD is regarded as definitely enlarged when 5 mm is exceeded in children above age 4. In younger children, smaller ONSD have to be taken into consideration. We conclude that ultrasound studies of the optic nerve may contribute information about the acutely increased ICP in critically ill patients.

Adolescent↗

PubMed1996

The subarachnoid space surrounding the optic nerves. An ultrasound study of the optic nerve sheath.

The presence of enlarged optic nerve sheaths (ONS) suggests that raised intracranial pressure is transmitted to the perineural subarachnoid space (SAS). This phenomenon has gained interest because ultrasound methods are able to quantify the optic nerve sheath diameter (ONSD) in-vivo non-invasively with a resolution below 0.5 mm. In order to study the normal variation and distensibility of the human ONS. Histologic techniques and sonographic measurements were applied to 54 human optic n. specimens before and after exposure to pressure. In untreated postmortem specimens, the largest diameters were found 3 mm behind the globe (baseline range: 2.1 to 4.8 mm). Following volume injection into the orbital perineural SAS, all n. sheaths were enlarged (maximum ONSD 6.5 mm). The sheath expansion affected predominantly its anterior section (mean 1.6 mm, e.g. 50.2%); the posterior regions showed markedly less dilatation (31.6%). No relation was found between the change of ONSD and the baseline diameter. Variance analysis of the sonographic results showed that the observed ONSD change depends on (a) the position of measurement along the nerve, as well as on (b) the origin of the nerve (different/same subject), whereas lateral (left/right) or inter-investigator differences proved negligible. Our results suggest that individual factors determine both baseline sheath diameter and distensibility. The different extent of pressure-induced sheath expansion along the nerve may be partly due to the non-uniform distribution of subarachnoid trabecular fibers between nerve and sheath. In conclusion, measurements of the ONSD for clinical purposes should be targeted to the region immediately behind the globe. Under conditions of raised pressure around the intraorbital optic n., bilateral ONSD measurements should give comparable findings.

Humans↗

PubMed1996

Development of 123I-labelled NNC 13-8241 as a radioligand for SPECT visualization of benzodiazepine receptor binding.

[125I]- and [123I]NNC 13-8241 were prepared from the trimethyltin precursor and radioactive iodide using the chloramine-T method. The total radiochemical yields of [125I]- and [123I]NNC 13-8241 were 60-70% and 40-50% respectively, with radiochemical purity higher than 98%. In binding studies with [125I]NNC 13-8241 in rats in vitro and in vivo a high uptake of radioactivity was demonstrated in brain regions known to have a high density of benzodiazepine (BZ) receptors such as the occipital and frontal cortex. SPECT examination with [123I]NNC 13-8241 in a Cynomolgus monkey demonstrated a high uptake of radioactivity in the occipital and frontal cortex. After displacement with flumazenil radioactivity in these brain regions was reduced to the level of a central region including the pons. Four hours after injection about 80% of the radioactivity in monkey plasma represented unchanged radioligand. This low degree of metabolism indicates that NNC 13-8241 is metabolically more stable than the radioligands hitherto developed for imaging of BZ-receptors in the primate brain.

Animals↗

PubMed1996

Recovery from brain-stem lesions involving the nociceptive pathways: comparison of clinical findings with laser-evoked potentials.

Dissociated sensory impairment in brain-stem disorders suggests a lateral lesion involving the spinothalamic tract. Evoked potential studies of the somatosensory system with standard electrical stimulation (SEP) generally fail to establish objective correlates of such sensory deficits, because electrical stimuli predominantly activate large myelinated fibers that project into the medial lemniscal system. In contrast, laser-evoked potentials (LEPs), in response to brief radiant heat pulses, stimulate nociceptive afferents of the superficial skin and allow evaluation of thin fiber and spinothalamic tract function. We describe the recovery of deficits in pain sensitivity in five patients with isolated lateral brain-stem lesions that could be successfully monitored by LEP recordings in the acute stage and after intervals ranging from 7 months to 4 years. Upon first examination, LEPs were abnormal on the affected body side in all five cases of lateral medullary syndrome, irrespective of whether the etiology was vascular or inflammatory. The degree of recovery of pain sensitivity upon reexamination was reflected by the extent of normalization of the LEP. A control patient with vascular pontine lacunar stroke had normal LEPs on both sides, suggesting preserved spinothalamic conduction. The peak-to-peak amplitude of the main LEP component (N250-P400) correlated significantly with clinical pain sensitivity scored by standardized sensory testing (r = 0.76, p < 0.01). In contrast, early and late SEPs, after standard electrical median or tibial nerve stimulation, were normal in all patients, consistent with their intact mechanosensitivity. In conclusion, LEP studies allow the status of nociceptive function to be objectively and reliably documented on repeated examinations and therefore provide a useful supplement to multimodal sensory assessment in brain-stem disorders.

Adult↗