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Biomedical subjects

R Kurth

Publications and source records attributed to R Kurth.

At least 19 recordsLinked to original sources

Clinical evaluation of a new intracranial pressure monitoring device.

BACKGROUND: Continuous monitoring of intracranial pressure (ICP) still plays a key role in the management of patients at risk from intracranial hypertension. Numerous ICP-measuring devices are available. The aim of the present study was to investigate the clinical characteristics and the magnetic resonance imaging (MRI) compatibility of the recently developed Neurovent-P(REHAU AG+CO, REHAU, Germany) ICP monitoring device. METHOD: In a prospective two-center study, a total of 98 patients with severe head injury, subarachnoid haemorrhage, intracerebral haemorrhage, and non-traumatic brain edema underwent intraparenchymal monitoring of ICP using the Neurovent-P. A control group comprising 50 patients underwent implantation of the Camino-OLM-110-4B ICP monitor. The zero drift of the probes was determined before and after the ICP recording period. Technical and medical complications were documented. The MRI compatibility of the Neurovent-P ICP probe was investigated by evaluating artifacts caused by the probe, probe function and temperature changes during MRI, and probe movement caused by the magnetic field. FINDINGS: The mean zero drift was 0.2+/-0.41 mmHg (maximum 3 mmHg) for the Neurovent-P ICP probes and 0.4+/-0.57 mmHg (maximum 12 mmHg) for the Camino-OLM-110-4B ICP probes. No significant correlation was identified between the extent of zero drift following the removal of the probes and the length of monitoring. Intraparenchymal haemorrhage spatially related to the probe occurred in 1 out of 50 (2%) patients with a Camino-OLM-110-4B probe and in 1 out of 98 (1%) with a Neurovent-P. Damage of the probe due to kinking or overextension of the cable or glass fiber occurred in 4 of the 50 (8%) Camino-OLM-110-4B ICP probes and in 5 of the 98 (5%) Neurovent-P probes. On T2-weighted MR images, the Neurovent-P ICP probe induced only small artifacts with very good discrimination of the surrounding tissue. On T1-weighted MR images, there was a good imaging quality but artifact-related local disturbances in signal occurred. There was no temperature change in the Neurovent-P probe and in the surrounding brain tissue during MR imaging. INTERPRETATION: The Neurovent-P ICP measuring system is a safe and reliable tool for ICP monitoring. Handling of the Neurovent-P system is safe when performed properly.

Adolescent↗

Virus safety in xenotransplantation: first exploratory in vivo studies in small laboratory animals and non-human primates.

For xenotransplantation, the transplantation of animal cells, tissues and organs into human recipients, to date, pigs are favored as potential donors. Beside ethical, immunological, physiological and technical problems, the microbiological safety of the xenograft has to be guaranteed. It will be possible to eliminate all of the known porcine microorgansims in the nearby future by vaccinating or specified pathogen-free breeding. Thus, the main risk will come from the porcine endogenous retroviruses (PERVs) which are present in the pig genome as proviruses of different subtypes. PERVs will therefore be transmitted, with the xenograft, to the human recipient. PERVs can infect numerous different types of human primary cells and cell lines in vitro and were shown to adapt to these cells by serial passaging on uninfected cells. Furthermore, PERVs have high homology to other retroviruses, such as feline leukemia virus (FeLV) or murine leukemia virus (MuLV), which are known to induce tumors or immunodeficiencies in the infected host. To evaluate the potential risk of a trans-species transmission of PERV in vivo, naive and immunosuppressed rats, guinea pigs and minks were inoculated with PERV and screened over a period of 3 months for an antibody reaction against PERV proteins or for the integration of proviral DNA into the genomic DNA of the host's cells. Furthermore, we inoculated three different species of non-human primates, rhesus monkey (Macaca mulatta), pig-tailed monkey (Macaca nemestrina) and baboon (Papio hamadryas) with high titers of a human-adapted PERV. To simulate a situation in xenotransplantation, the animals received a daily triple immunosuppression using cyclosporine A, methylprednisolone and RAD, a rapamycin derivative, presently under development by Novartis. None of the small laboratory animals or the non-human primates showed production of antibodies against PERV or evidence of integration of proviral DNA in blood cells or cells of several organs, 3 months after virus inoculation, despite the observation that cells of the animals used in the experiment were infectible in vitro. This apparent difference in the outcome of the in vitro and the in vivo data might be explained by an efficient elimination of the virus by the innate or adaptive immunity of the animals.

Animals↗

[Consequences and challenges due to bioterrorist attacks].

Ever since the terrorist attacks of 11 September 2001 and the cases of inhalational anthrax and other types of anthrax caused by attacks with anthrax spores, responsible authorities and experts must reckon with bioterrorist attacks conducted with much greater criminal "drive" and greater financial resources than had been imagined so far. This consideration triggered cautionary measures in Germany and Europe as briefly summarised here. For more detailed information please refer to internet (www.rki.de) and see the references given below.

Biological Warfare↗

Cold-attenuated live influenza vaccines, a risk-benefit assessment.

The principle of live attenuated influenza vaccines has been known for many decades. However, the pharmaceutical and clinical development according to current regulations, of modern live influenza vaccines based on cold adapted influenza viruses (CAIV) started only recently and these vaccines will most probably become an alternative within the next couple of years to licensed inactivated influenza vaccines that have been used routinely since the early 1940s. In contrast to contemporary trivalent inactivated influenza vaccines, which are administered intramuscularly, trivalent CAIV-based vaccines will be administered intranasally as a spray. Quality, safety and efficacy aspects related to CAIV vaccines as well as possible risks linked to the widespread use of these vaccines will be discussed in the following overview and compared to established influenza vaccines. Moreover, issues of practicality of CAIV vaccines focusing on the necessity of an annual update of influenza vaccines are addressed.

Animals↗

[Worldwide eradication of poliomyelitis].

Poliomyelitis, an infectious disease with acute and persistent flaccid paralysis is caused by poliovirus (types 1, 2 or 3), an enterovirus. The infection is asymptomatic in 95% of infected subjects. Most of the paralytic cases occur in adolescents or adults in the course of polio type 1 infection. In the prevaccination era, in countries with poor hygienic conditions, infection in early childhood was common, mostly asymptomatic, and immunity in the population prevailed. In developed countries polio often struck adolescents and adults taking its toll in paralytic disease. The introduction of vaccination with the Salk vaccine (IPV Inactivated Polio Vaccine) in the USA and in Europe in 1956 and with the Oral Polio Vaccine (OPV) developed by Sabin worldwide in the early sixties made it possible to control the epidemic in large geographic areas, but it could not eliminate the disease worldwide. Poliomyelitis is still endemic in Central Africa and in the Indian sub-continent. Acts of war led to the reduction in the vaccination rate in different geographic areas, and smaller epidemics with wild virus but also with reverted vaccine strains occurred. In some parts of the world the rate of vaccination also declined due to elimination of poliomyelitis, and it came to small epidemics of paralytic polio mainly caused by reverted vaccine strains circulating in the population. Reverted vaccine strains also remain a central problem in the eradication of poliomyelitis projected for 2005 by the World Health Organisation. A high vaccination rate, preferably with 3 doses of OPV in infancy or early childhood, and exact worldwide monitoring of cases is indispensable for the eradication. For the complete eradication of poliovirus the live vaccine OPV would have to be changed to an inactivated vaccine IPV worldwide. However, this is presently unachieveable, because of logistic problems and high costs.

Adolescent↗

High virus loads in naturally and experimentally SIVagm-infected African green monkeys.

A quantitative RT-PCR assay was developed for SIVagm and was used to measure the levels of viral RNA in the plasma of experimentally and naturally infected African green monkeys. The number of productively infected PBMCs and the number of cells carrying integrated provirus were also measured. Plasma virus loads in experimentally infected animals peaked at 2 weeks postinfection, ranging from 2.9 x 10(5) to 4.2 x 10(7) RNA copies/ml plasma. Set points of 2.1 x 10(3) to 2.8 x 10(6) RNA copies/ml plasma were maintained for one year. Similarly, the number of cells carrying integrated SIVagm provirus remained relatively stable in individual animals for one year with set points ranging from 73 to 810 proviral copies per 10(6) PBMC. However, the number of productively infected cells fluctuated considerably during this period. Virus loads in the 26 naturally infected AGMs ranged from 8.3 x 10(3) to 1.1 x 10(7) (mean 1.7 x 10(6)) RNA copies/ml plasma. These levels of viremia are similar to those seen in pathogenic systems (HIV-1, SIVmac), indicating that control of SIVagm replication is not the reason for the natural host's resistance to disease progression.

Animals↗

Representational overlap of adjacent fingers in multiple areas of human primary somatosensory cortex depends on electrical stimulus intensity: an fMRI study.

Functional magnetic resonance imaging (fMRI) was used to examine the influence of non-painful electrical stimulus intensity on the BOLD response in human primary somatosensory cortex (SI). In ten healthy subjects, index and middle finger of the right hand were stimulated separately at two different stimulus intensities. The activated volume of single finger representations as well as the volume of representational overlap of the two activations increased following an increase in stimulus intensity. This effect was seen in two different subdivisions of SI, one in the depth of the central sulcus, presumably corresponding to Brodmann area (BA) 3b, and one on the crown of the postcentral gyrus, presumably corresponding to BA 1/2. Relative overlap (ratio of overlap volume to volume of individual finger representation) was larger in BA 1/2 than in BA 3b. Additionally, in both areas relative overlap increased significantly from low to high stimulus intensity. Relative overlap did not change when different correlation thresholds were employed arguing against an unspecific 'spillover effect'. Analysis of signal intensity time courses indicated that the response difference to high versus low stimulus strength was not present during the initial seconds of stimulation, during which both led to a similar signal intensity increase. Only during the following maintenance level of the response did the response to high stimulus intensity reach a significantly higher plateau level than the one due to low intensity stimulation, an effect which was present in both areas, BA 3b and BA 1/2, respectively.

Adult↗

Intracranial image-guided neurosurgery: experience with a new electromagnetic navigation system.

BACKGROUND: The aim of image-guided neurosurgery is to accurately project computed tomography (CT) or magnetic resonance imaging (MRI) data into the operative field for defining anatomical landmarks, pathological structures and tumour margins. To achieve this end, different image-guided and computer-assisted, so-called "neuronavigation" systems have been developed in order to offer the neurosurgeon precise spatial information. METHOD: The present study reports on the experience gained with a prototype of the NEN-NeuroGuard neuronavigation system (Nicolet Biomedical, Madison, WI, USA). It utilises a pulsed DC electromagnetic field for determining the location in space of surgical instruments to which miniaturised sensors are attached. The system was evaluated in respect to its usefulness, ease of integration into standard neurosurgical procedures, reliability and accuracy. FINDINGS: The NEN-system was used with success in 24 intracranial procedures for lesions including both gliomas and cerebral metastases. It allowed real-time display of surgical manoeuvres on pre-operative CT or MR images without a stereotactic frame or a robotic arm. The mean registration error associated with MRI was 1.3 mm (RMS error) and 1.5 mm (RMS error) with CT-data. The average intra-operative target-localising error was 3.2 mm (+/- 1.5 mm SD). Thus, the equipment was of great help in planning and performing skin incisions and craniotomies as well as in reaching deep-seated lesions with a minimum of trauma. INTERPRETATION: The NEN-NeuroGuard system is a very user-friendly and reliable tool for image-guided neurosurgery. It does not have the limitations of a conventional stereotactic frame. Due to its electromagnetic technology it avoids the "line-of-sight" problem often met by optical navigation systems since its sensors remain active even when situated deep inside the skull or hidden, for example, by drapes or by the surgical microscope.

Adult↗

Somatotopic organization of human secondary somatosensory cortex.

This fMRI study investigated the human somatosensory system, especially the secondary somatosensory cortex (SII), with respect to its potential somatotopic organization. Eight subjects received electrical stimulation on their right second finger, fifth finger and hallux. Within SII, the typical finding for both fingers was a representation site within the contralateral parietal operculum roughly halfway between the lip of the lateral sulcus and its fundus, whereas the representation site of the hallux was found more medially to this position at the fundus of the lateral sulcus, near the posterior pole of the insula. Somatotopy in SII seems to be less fine-grained than in primary somatosensory cortex (SI), as, in contrast to SI, no separate representations of the two fingers in SII were observed. A similar somatotopic representation pattern between fingers and the hallux was also observed within ipsilateral SII, indicating somatotopy of contra- as well as ipsilateral SII using unilateral stimulation. Further areas exhibiting activation were found in the superior and inferior parietal lobule, in the supplementary and cingulate motor area, and in the insula.

Adult↗

Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury.

BACKGROUND: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. METHODS: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. RESULTS: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution. CONCLUSIONS: The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.

Almitrine↗

A neural substrate for nonpainful phantom limb phenomena.

Activity in the cerebral cortex associated with non-painful phantom limb sensation was studied in 14 upper extremity amputees. In four subjects, repetitive tactile stimulation of the digits or the lower corner of the mouth elicited non-painful phantom sensation in the amputated limb, in the remaining 10 patients no sensation could be evoked. Neuroelectric source imaging revealed significantly elevated activity in SI and posterior parietal cortex, and significantly decreased activity in ipsilateral SII cortex when referred sensations were present. However, nonpainful referred phantom sensations were not associated with a shift of the cortical representation of the mouth into the hand region, as previously suggested. Nonpainful phantom limb experiences seem to have widely distributed neural networks in multiple cortical regions.

Adult↗

fMRI shows multiple somatotopic digit representations in human primary somatosensory cortex.

Using electrical finger nerve stimulation in normal human subjects, fMRI detected separate representations for all 5 fingers in the primary somatosensory cortex. Responses were located in the posterior wall of the deep central sulcus (most likely corresponding to Brodmann Area (BA) 3b), and the anterior (BA 1) or posterior crown of the postcentral gyrus (BA 2) with rare activations in BA 3a and 4. In BA 3b we found a regular somatotopic mediolateral digit arrangement for fingers 5 to 1 with a mean Euclidean distance of 16 mm between fingers 1 and 5. In contrast BA 1/2 showed a greater number of adjacent activation foci with significantly more overlap and partly even reversed ordering of neighbouring fingers.

Adult↗