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Biomedical subjects

R Hopf

Publications and source records attributed to R Hopf.

At least 19 recordsLinked to original sources

NON-activated protein C as post-treatment after spinal cord compression injury in rats.

BACKGROUND: Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI. METHODS: Twelve rats were subjected to 40 g compression of the spinal cord at TH11 for 20 minutes and randomly allocated to either the NON activated PC (25 IU/kg) or the Placebo group (saline).Results. 25 IU treatment yielded improved recovery from SCI compared to placebo and the triple fold dose of PC (75 IU/kg) was subsequently tested to detect treatment associated complications (TAC). Treatment was administered as a single shot via the right vena jugularis forty minutes after onset of compression. The observation period was 5 weeks in 25 IU treated and 1 week in the 75 IU treated rats. Improvement of motor function recovery was measured with behaviour tests and electrophysiology. FINDINGS: Single shot treatment with 25 IU/kg of NON activated PC led to improved recovery in terms of behaviour and electrophysiology. TACs neither occurred in the 25 IU nor in the 75 IU group within one week. CONCLUSION: NON activated PC is a potent and safe drug in experimental SCI and should be considered for treatment in neurotrauma.

Animals↗

The effect of ketamine/xylazine anesthesia on sensory and motor evoked potentials in the rat.

STUDY DESIGN: Experimental laboratory investigation of the effect of anesthesia on evoked potentials in rats. OBJECTIVES: To define the optimal ketamine/xylazine anesthesia levels for the recording of different evoked potentials. SETTING: BioSurgery Preclinical Department, Baxter BioScience, Vienna, Austria. METHODS: Rats were implanted with cranial screws that allow stimulation and recording of evoked potentials. Somatosensory evoked potentials (SEPs), brainstem-derived motor evoked potentials (BMEPs) and corticomotor evoked potential (CMEPs) were recorded under different levels of anesthesia. The recorded signals were evaluated by measuring their latencies and amplitudes. The level of anesthesia was assessed by scoring the hind limb withdrawal reflex. RESULTS: All three signals showed a strong dependency on the level of anesthesia. The observed effects, however, differed between the three signals. SEP amplitudes and latencies declined as animals slowly transgressed from deep to light anesthesia. In contrast, BMEP amplitudes were larger and latencies shorter in light anesthesia than in deep anesthesia. CMEPs finally were hard to record under deep anesthesia, but were easily recorded in light anesthesia. BMEPs that were recorded during light anesthesia also showed a significant change in configuration that was coupled with a notable increase in the variability of its amplitudes. CONCLUSIONS: The level of ketamine/xylazine anesthesia affects evoked potentials and thus should be controlled during electrophysiological recording. Our results suggest that SEPs should be best recorded during deep anesthesia, while BMEPs and CMEPs are best recorded during intermediate and light anesthesia.

Adrenergic alpha-Agonists↗

Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.

BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.

Animals↗

Serial recording of sensory, corticomotor, and brainstem-derived motor evoked potentials in the rat.

A method is presented for serial recording of corticomotor evoked potentials (CMEPs), brainstem-derived motor evoked potentials (BMEPs), and somatosensory evoked potentials (SEPs) via permanently implanted cranial screws. One screw was positioned posterior to lambda (posterior screw), and two screws were positioned over the cortical hind limb areas (cortical screws). SEPs were elicited by stimulation of the hind paw and recorded from the contralateral cortex. BMEPs were stimulated via the posterior screw and recorded from both hind limbs, whereas CMEPs were elicited by repeated bipolar stimulation of the cortex and recorded from the contralateral hind limb. BMEPs and CMEPs differed in several points and can be considered as completely separate motor evoked potentials. While BMEPs consisted of a prominent negative peak with short latency (5-7.5 ms), CMEPs were represented by polyphasic signals with long latencies (17-22 ms). The cortical origin of the CMEPs was confirmed by transecting the corticospinal tracts, which abolished the CMEPs but spared the BMEPs. SEPs consisted of three consecutive peaks with mean latencies of the initial peak ranging between 15 and 17 ms. Dorsal column transection also abolished SEPs. In healthy rats, all three signals were recorded for six consecutive weeks. Signal parameters did not change significantly within this observation period. Rats tolerated the screws and the repeated measurements very well and no negative affect on animal behavior was noted. Thus, this method allows serial recording of SEPs, CMEPs, and BMEPs in chronic rat models.

Animals↗

[Disturbed sleep caused by sleep apnea. To the sleep laboratory for diagnosis?].

Since it was shown that numerous neurological, psychiatric and internal illnesses have characteristics manifested during, or influenced by sleep, somnology has been playing a clinically more and more important role. Among the 88 diagnoses listed by ICD, not only insomnia, but also sleep-related respiratory disorders, in particular the obstructive sleep apnea syndrome, are of special importance. Sleep apnea is associated with coronary heart disease, myocardial insufficiency and other pathological conditions. Already in the doctor's office, a carefully taken history (nocturnal apnea alternating with irregular snoring, and diurnal sleepiness) can arouse an appropriate suspicion. This can be confirmed by an ambulatory polygraphic exploration. The definitive diagnosis is then established with the aid of polysomnography in the sleep lab where specific treatment is also initiated.

Diagnosis, Differential↗

The long-term effects of pre-treatment with activated protein C in a rat model of compression-induced spinal cord injury.

OBJECTIVES: Recently, we demonstrated that activated protein C (APC) can lessen the severity of spinal cord injury (SCI) in rats during the acute and subacute phases. The purpose of the present study is to determine the long-term effects of pre-treatment with APC following SCI in rats. METHODS: The motor function of rats was assessed using the inclined-plane test during 8 weeks after SCI, and the grid runway test 7 weeks after the trauma. Somatosensory evoked potentials (SEPs), brainstem-derived motor evoked potentials (B-MEPs) and corticomotor evoked potentials (CMEPs) were used to quantify axonal function 8 weeks after SCI. Morphometric analysis of the spinal cord lesion was carried out to determine lesion size. Twelve male Sprague-Dawley rats were randomly allocated to either APC (25 IU/kg) or saline group and then subjected to 20 g compression injury of the spinal cord for 20 min at T12. The sham group (n=6) received laminectomy alone. RESULTS: APC significantly reduced the motor disturbances and electrophysiological impairments induced by SCI. APC-treated animals also showed a trend towards a reduction in lesion size. However, this change, was not significant. CONCLUSION: Pre-treatment with APC attenuates the harmful effects of SCI not only during the acute and subacute phases but also in the chronic stage.

Animals↗

Brainstem-evoked muscle potentials: their prognostic value in experimental spinal cord injury in the rat.

Recording myoelectric motor-evoked potentials is frequently used as an in vivo evaluation technique in experimental studies of spinal cord injury (SCI). The aim of the present study was to determine whether specific neuronal pathways conduct these potentials. Stainless steel screws were permanently implanted into the cranium of 18 rats for stimulation of brainstem-evoked muscle potentials (B-MPs). Twelve rats were subjected to spinal cord lesions that restricted the continuity of the spinal cord to different discrete sections of the lateral and/or ventral white matter (WM) of the left hemicord. Sham rats (n = 6) were subjected to laminectomy only. Left hind limb B-MPs and motor function (open field walking test) were recorded before surgery and weekly thereafter for six consecutive weeks. Motor function was severely affected by SCI in all rats but recovered significantly during the first 14 postoperative days. The degree of functional recovery depended not only on the amount of spared WM but also on the particular section of WM that had been spared. In contrast, B-MP amplitudes also were severely reduced by SCI, but did not recover during the survival period. Moreover, B-MP amplitudes correlated only weakly with the amount of sparedWM and were not influenced by which section ofWM had been spared. While functional recovery correlated significantly with the amount of spared WM, no correlation was found between B-MP amplitudes and functional recovery. B-MP conduction velocities were not affected by SCI. It is therefore believed that B-MPs have little prognostic value for experimental studies of SCI in the rat.

Analysis of Variance↗

Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model.

OBJECTIVES: Tranexamic acid (t-AMCA) has been shown to cause severe convulsions in humans and cats when applied topically to the central nervous system. We wanted to determine whether pure t-AMCA or fibrin sealant (FS) containing t-AMCA would induce similar effects when applied to the spinal cord in a rat model. METHODS: Following low-thoracic laminectomy, the dura was incised to expose the dorsal surface of the lumbar enlargement. Rats were allocated to one of the following treatments: 1) t-AMCA (10 mg/ml), 2) vehicle (phosphate buffered saline), 3) FS containing t-AMCA, 4) FS containing aprotinin. The response of the rats was evaluated based on neurological and behavioral observations. Additionally, motor function was scored in the rats that had received FS. RESULTS: Application of either 10 mg/ml t-AMCA or FS containing t-AMCA caused severe hind limb spasms that developed into spontaneous generalized convulsions. Two of the three rats that had received FS containing t-AMCA died of respiratory failure. In contrast, application of vehicle or FS containing aprotinin did not cause any abnormal conditions of the animals. CONCLUSION: Tranexamic acid may cause severe complications when used in the central nervous system. Thus, fibrin sealants containing t-AMCA should not be used in neurosurgery.

Animals↗

Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation.

The antihypertensive efficacy of a new controlled-release preparation of nifedipine developed for once daily administration was investigated in comparison with a standard therapy with sustained-release nifedipine given twice daily in a randomised, open crossover trial. Twenty-two patients with mild to moderate essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM) was performed after a wash-out period and after a 3 weeks treatment with 40 mg controlled-release nifedipine once daily and 20 mg sustained-release nifedipine twice daily, respectively. ABPM data were evaluated by conventional linear analysis and by rhythm analysis. Both once daily and twice daily administration of nifedipine significantly reduced systolic blood pressure during the daytime and during the night when compared with baseline. The 24-h diastolic blood pressure was significantly decreased by both treatments, but only the once daily regimen significantly lowered both diastolic daytime and night-time means. Comparing systolic and diastolic blood pressures after both treatments, however, no significant differences were obtained. Both nifedipine treatments did neither greatly modify the circadian blood pressure pattern nor reflexly increase heart rate. In conclusion, once daily application of the controlled-release formulation of nifedipine resulted in a consistent and significant blood pressure reduction. Once daily and twice daily medications of nifedipine were about equally effective in lowering the elevated blood pressures.

Adult↗

In vivo femoral intramedullary pressure during uncemented hip arthroplasty.

There is evidence in several animal and human studies that high intramedullary pressure in the femur is of causal significance for bone marrow release into the circulation, causing pulmonary fatty marrow embolization. A previous clinical study provided evidence that in uncemented hip arthroplasty, high intramedullary pressure and subsequent fat embolism with cardiorespiratory deterioration can occur. In this prospective clinical trial, the effect of five surgical techniques on the femoral intramedullary pressure was recorded intraoperatively in 36 patients during uncemented press fit hip arthroplasty. In Group A, the conventional surgical technique (slide hammer and femoral rasps) showed intramedullary hypertension during opening of the femoral canal, femur preparation, and prosthesis insertion. In Group B, a mechanical high frequency vibration rasp was used, instead of the slide hammer, and provided reduction of the intramedullary pressure peaks during opening of the femoral canal but could not prevent intramedullary hypertension during rasping and prosthesis insertion. In Group C, a modified surgical technique to prevent high intramedullary pressure reduced pressure peaks during opening of the femoral canal and resulted in a significant reduction of intramedullary pressure during femur preparation and prosthesis insertion compared with the conventional surgical technique used with Group A. In Group D the results of the modified surgical technique could be improved additionally by using the high frequency vibration rasp, instead of the slide hammer. In Group E conventional surgical technique in combination with a distal venting hole has not proven to be efficient in uncemented hip arthroplasty. Based on the results of this in vivo study, the proposed modified surgical technique in cementless hip arthroplasty can be recommended to avoid high intramedullary pressure peaks, which should minimize the risk of significant bone marrow release into the circulation and the risk for cardiorespiratory deterioration caused by fat embolism.

Aged↗

[Purulent pericardial effusion with tamponade: a rare initial manifestation of o pneumococcal infection].

HISTORY AND FINDINGS: A 70-year-old man, admitted for a haemorrhoid operation, suddenly went into circulatory shock (heart rate 150/min, blood pressure 100/70 mm Hg), necessitating transfer to an intensive care unit. His neck veins were prominent and he had a paradoxical pulse. Heart sounds were distant and there was an arrhythmia (atrial fibrillation in the ECG). No murmurs were heard. Breath sounds were decreased, especially in the lung bases. INVESTIGATIONS: Differential blood count showed 30% stab cells with 12,200 white cells per microliter. Erythrocyte sedimentation rate was 118 mm in the first hour, C-reactive protein was raised to 11.8 mg/dl. There was a partially compensated respiratory acidosis (pH 7.12; pO 93.4 mm Hg; pCO 16.3 mm Hg; base deficit -22.6 mmol/l). In the chest radiogram the cardiac silhouette was greatly enlarged bilaterally. The echocardiogram demonstrated a large pericardial perfusion with a "swinging heart". TREATMENT AND COURSE: At pericardial needle puncture 700 ml of amber-coloured fluid, containing pneumococci, were aspirated with immediate circulatory improvement. Penicillin, 10 mill.U twice daily for 13 days, was administered intravenously, followed by amoxycillin, 1 g three times daily by mouth, for a further 15 days. In addition he was given anti-inflammatory treatment with diclofenac and methylprednisolone. Despite this pericardial effusion recurred after 14 days and 600 ml of sterile fluid were removed. Subsequently the inflammatory signs disappeared. Three months later no effusion was present and there were no signs of constrictive pericarditis.

Administration, Oral↗

Persisting effect of Ca(2+)-channel blockers on left ventricular function in hypertrophic cardiomyopathy after 14 years' treatment.

Ca(2+)-channel blockers of the verapamil type have been reported to exert a beneficial effect on clinical symptoms and survival rates in hypertrophic cardiomyopathy. The effects of verapamil have been attributed predominantly to an improved diastolic filling. It is unknown whether an effect on diastolic filling persists in these patients after long-term treatment. Fourteen patients (12 men, 2 women, median age fifty-one [thirty-two to fifty-five] years) with hypertrophic cardiomyopathy were included in the study. Patients had been treated with verapamil 240-480 mg/d or gallopamil 150-200 mg/d for fourteen (seven to seventeen) years. The effect of a withdrawal of Ca(2+)-channel blockers on parameters of left ventricular diastolic function was evaluated at rest and during exercise in patients with hypertrophic cardiomyopathy after long-term therapy. Investigations were performed at rest and during supine ergometric exercise during ongoing Ca(2+)-channel blocking therapy and after five (four to nine) days' withdrawal (control). Pulsed Doppler echocardiography was used to record diastolic mitral flow profiles from an apical four-chamber view. Withdrawal of Ca(2+)-channel blockers of the phenylalkylamine type after long-term treatment of hypertrophic cardiomyopathy resulted in a significant reduction of early diastolic inflow velocity at rest and during exercise. In conclusion, these results indicate a persistent improvement of early diastolic filling by Ca(2+)-channel blockers even after long-term treatment.

Adult↗

[Monitoring of bone marrow spilling and cardiopulmonary changes in fat embolism syndrome].

After long bone fractures, as well as hip or knee total arthroplasty, the increase in intramedullary pressure induces bone marrow release into the circulation in more than 90% of patients. Three to four percent of the patients reveal fat embolism syndrome with pulmonary and cerebral involvement and a petechial rash. In about 20% of these patients a fulminant and fatal course is possible. Although fat embolism syndrome was described more than a century ago, there is still no sufficient therapeutic strategy. Because of these facts we try to prevent fat embolism syndrome and monitor patients at risk perioperatively. We have evaluated different diagnostic methods and monitoring facilities and recommend pulse oximetry, capnography, ECG, blood pressure controls and, if indicated, blood gas analyses for perioperative monitoring. Patients at risk and patients who are suffering from fat embolism syndrome require more intensive monitoring, such as transesophageal echocardiography and a pulmonary artery catheter to obtain more detailed information about the hemodynamic and oximetric variables. Furthermore, these patients must be admitted to an intensive care unit.

Blood Gas Analysis↗

[Modified surgical technique for reduction of bone marrow spilling in cement-free hip endoprosthesis].

Since 1970 the fat embolism syndrome (FES) has been recognised as a severe complication of cemented total hip arthroplasty (THA). Initially and still today the toxicity of bone cement has been though to be responsible for the cardiorespiratory problems. Meanwhile several reports have confirmed the causal relationship between intramedullary pressure (IMP), bone-marrow release into the circulation and subsequent cardiorespiratory deterioration during cemented THA. In recent publications it has been reported that bone-marrow release due to increased IMP also occurs during cementless THA. The clinical implication of these observations is controversial. For this reason in the first part of this paper two autopsy-proven FES deaths and five further clinically manifest FES cases are presented. In the second part of the study, IMP courses during four different surgical techniques (2 conventional, 2 modified) are compared. The aim of the modified surgical technique developed in our department was to minimize IMP peaks and bone-marrow release during cementless THA. Both modified techniques showed significantly lower IMPs during opening of the medullary canal, preparation with rasps, and implantation of the prosthesis than the conventional techniques. The observed FES cases for the first time strongly confirm the clinical relevance of the FES, also during cementless THA. On the basis of the data presented we recommend the modified surgical technique to reduce bone-marrow release during cementless THA.

Aged↗

[Modified surgical technique for the reduction of bone marrow spilling in knee endoprosthesis].

In the literature 20 cases of fat embolism syndrome (FES) after total knee replacement (TKR) are reported; 16 cases had cemented hinged TKR and 4 resurfacing TKR. Initially, it was believed that the bone cement was responsible for the FES. Since then, however, Fahmy et al. have published extraordinary data, demonstrating the causal relationship between increased intramedullary pressure (IMP) during the insertion of the intramedullary rod (IR) and cardiorespiratory deterioration. The industry responded by developing a fluted IR, disregarding the overdrilling in the distal femur required by Fahmy. In the first part of this paper clinically manifest FES cases after resurfacing TKR are reported. In the second part of the study the conventional surgical technique is compared with a modified technique, which focuses on a reduction of bone-marrow release into the circulation. In the conventional and the modified group, IRs with and without flutes were compared. It was shown that only the opening of the intramedullary canal and insertion of the IR generated relevant IMP peaks during implantation of resurfacing TKR. When compared with the conventional surgical technique, the modified technique revealed significantly lower IMPs, and in neither group was a difference demonstrated between the IR with or without flutes. In 4 patients (2 conventional, 2 modified) transesophageal echocardiography (TEE) was performed for detection of bone-marrow release into the circulation. In the two patients operated on conventionally, TEE showed a markedly higher bone-marrow release than in the patients with modified operations. In conclusion, we recommend the presented modified surgical technique in order to reduce bone-marrow release into the circulation.

Aged↗

[Therapeutic approach to the management of fat embolism syndrome].

So far, no clinical or experimental study has demonstrated that any drug has a beneficial effect (heparin, cortisone, dextran, etc.) on the course of fat embolism syndrome (FES). Thus, prevention, early diagnosis, and adequate symptomatic treatment are of paramount importance. Besides surgical measures, such as reduction of intraosseous pressure and bone-marrow release during hip or knee replacement, proper treatment of shock in traumatized patients, recognition of risk factors and maintainance of intraoperative cardiorespiratory stability are cornerstones in the prevention of fat embolism syndrome. It is well documented that bone-marrow release into the circulation and pulmonary embolism occurs during any hip or knee arthroplasty. As a result of improvements in anesthesia management, the clinical appearance of FES has moved into the postoperative period. This calls for mandatory cardiorespiratory monitoring up to 24 h postoperatively. When facing a clinically manifest fat embolism syndrome, monitoring and symptomatic treatment must be adapted to the patient's needs in order to ensure adequate oxygenation and acceptable circulatory conditions to protect organ function.

Catheterization, Swan-Ganz↗