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Biomedical subjects

J Dichgans

Publications and source records attributed to J Dichgans.

377 records · Page 21Linked to original sources

Cryptococcal meningitis with severe visual and hearing loss and radiculopathy in a patient without immunodeficiency.

Cryptococcosis is an important cause of lymphocytic meningitis, especially but not necessarily in immunocompromised patients. We present the case of a 23-year-old man with a severe and rapid course of a cryptococcal meningoencephalitis, which led to visual and hearing loss, psychotic illness and radiculopathy. There was no evidence of immunodeficiency. Treatment with amphotericin B and flucytosine led to improvement of the symptoms but did not eradicate the micro-organisms from the cerebrospinal fluid (CSF). Maintenance therapy with fluconazole was necessary and led to improvement of the CSF pathology.

Adult↗

Computer analysis of optokinetic nystagmus in patients with spontaneous nystagmus of peripheral vestibular origin.

The bias of slow phase velocity (SPV) of optokinetic nystagmus (OKN) caused by an acute labyrinthine lesion was examined in 8 patients using differnet optokinetic stimulus velocities. In all patients a directional preponderance of OKN-SPV was found corresponding to spontaneous nystagmus. This was due to enhancement of nystagmus SPV to the side of the lesion and depression of SPV in the opposite horizontal direction. The preponderance of OKN on the average increased with the intensity of spontaneous nystagmus and decreased along with recovery. These vestibularly induced differences in OKN-SPV range up to 70%. A differentiation is discussed between OKN preponderances caused by labyrinthine lesions and brain stem lesions.

Acute Disease↗

The effect of lateral head tilt on horizontal postrotatory nystagmus I and II and the Purkinje effect.

The influence of an active lateral head tilt on postrotatory nystagmus I and II (PI, PII) was explored in normal humans. During postrotatory nystagmus the head was tilted laterally either towards the direction of the previous rotation (ipsilateral tilt) or towards the opposite direction (contralateral tilt) or the head was kept erect. Both ipsi- and contralateral head tilts led to a substantially weaker and shorter PI and PII as compared with the trial without head tilt. The time constants of the decline of PI were shortened to the ones observed in the peripheral nerve of animals. The reduction of PI and PII suggests a position-dependent tonic inhibition of the vestibular storage mechanism in the vestibular nuclei probably by the otoliths. The stronger reduction of time constant and cumulative amplitude of PI after contralateral as compared with ipsilateral head tilt may be explained by different combinations of asymmetric responses in canal and otolith afferents.

Adult↗

Direction and angle of active head tilts influencing the Purkinje effect and the inhibition of postrotatory nystagmus I and II.

Postrotatory nystagmus I and II (P I, P II) were evoked in four normal humans by velocity steps (prior velocity of rotating chair 90 degrees/s). 4 s after the stop the head was actively tilted by the subject 90 degrees forwards, backwards, to the shoulder of the previous direction of rotation -'ipsilaterally', or to the other shoulder-'contralaterally'. In control trials, the head was kept in the previous erect position. Compared with the control experiments, P I was significantly reduced by all head tilts. Inhibition of P I was strongest with forward and weakest with backward tilts. This difference is explained by the inclination of the utricular base by 30 degrees backward with respect to the horizontal of the skull and by the elastic properties of the sensory matrix. A smaller amplitude (45 degrees) of head tilt about the roll axis leads to a weaker inhibition (28.5%) than a 90 degree tilt, which corresponds to the difference of the sine of the tilt angle and thereby reflects the mechanical force acting on the receptor layer.

Adult↗

Fixation suppression of the vestibulo-ocular reflex (VOR) during sinusoidal stimulation in humans as related to the performance of the pursuit system.

Fixation suppression (FS) of the vestibulo-ocular reflex (VOR) was tested during passive sinusoidal body rotation with a frequency of 0.1 to 1.0 Hz and stimulus amplitudes ranging from 10 degrees to 240 degrees. To test whether FS can be explained by an internal pursuit signal opposite to the VOR, pursuit and the VOR under different instructional sets were studied. Both pursuit and FS decrease with increasing frequency and stimulus amplitude and seem to be limited by stimulus acceleration. Gains in FS calculated on the basis of the VOR during mental arithmetic correspond closely to the frequency and amplitude dependent pursuit gain, suggesting that an internal pursuit signal plays a major role in VOR suppression.

Adult↗

Pursuit opposite to the vestibulo-ocular reflex (VOR) during sinusoidal stimulation in humans.

Pursuit opposite to a simultaneously activated vestibulo-ocular reflex (VOR) was tested during passive sinusoidal body oscillations (0.1-1.0 Hz, amplitudes 10-80 degrees) about the vertical axis in 4 healthy humans, while subjects were asked to pursue a small target moving in phase with the rotating chair with about half its amplitude relative to the head and 1.5 times its amplitude with respect to space. The decrease in gain of the pursuit opposite to the VOR occurred at lower stimulus frequency, stimulus velocity and stimulus acceleration than pure visual pursuit when gain was calculated in relation to target motion in head coordinates. It resembles that of pure pursuit when calculated in relation to target motion in space (earth coordinates, sum of the displacements of the mirror image and of the chair) thus taking the oppositely directed VOR into account. The data fit the assumption of a linear interaction of the VOR (in counterphase) and pursuit.

Eye Movements↗

The contribution of vestibulo-spinal mechanisms to the maintenance of human upright posture.

The maintenance of upright stance in humans requires the integrative evaluation of vestibular, visual, and proprioceptive information. Recent experiments prove the existence of fast vestibulo-spinal reactions in humans. Their physiological significance for the compensation of sudden external displacements of the body is minor. For low frequency stabilization of the body, however, vestibulo-spinal afferents as well as vision and proprioception are important. Unilateral loss of vestibular function initially causes a tendency to fall to the ipsilateral side as well as nystagmus and vertigo. After the first days of compensation, the remaining functional disturbance can only be detected by exposing the patient to conflicting sensory reafferents or by reducing proprioceptive and visual inputs simultaneously. The loss of vestibular function not only alters low frequency stabilization and to some extent also reflex-like fast motor patterns, but also interferes with the selection of preprogrammed motor synergies.

Afferent Pathways↗

The clinical significance of head-shaking nystagmus in the dizzy patient.

The clinical significance of horizontal head-shaking nystagmus (HSN) was evaluated in 85 patients who complained of dizziness and vertigo. This was done by comparison of the horizontal head-shaking test with routine rotatory and caloric vestibular testing. We found that HSN evoked by horizontal head-shaking is a highly sensitive way to detect unilateral vestibular hypofunction. Except in patients with additional central vestibular imbalance or in patients with Meniere's disease, the direction of horizontal HSN is highly significant in indicating the side of the lesion, with the fast phase beating toward the intact side. However, horizontal HSN is not specific in distinguishing peripheral hypofunction from more central vestibular imbalances. Peripheral vestibular hypofunction as well as a central asymmetry of the vestibular velocity storage mechanism can each separately or in combination produce horizontal HSN. Thus, while the head-shaking manoeuvre is an excellent bedside-test to detect unilateral vestibular hypofunction, further rotatory and caloric testing is still necessary to clarify the patient's condition.

Adult↗

Head-shaking nystagmus during vestibular compensation in humans and rhesus monkeys.

Nystagmus evoked after rapid horizontal head-shaking is believed to be a sensitive indication of the existence and location of a unilateral vestibular lesion. Its origin is the directional asymmetry in vestibular responses of the healthy labyrinth (Ewald's second law). For nystagmus to appear after the head has stopped moving, however, the directionally asymmetric responses must have been stored during the head-shaking to be discharged afterwards. Our results confirm the notion that head-shaking nystagmus is most likely generated by a directional preponderance in vestibular responses but only in combination with a functioning central velocity-storage mechanism. If velocity-storage is lost completely, as may occur during the acute phase of a unilateral peripheral vestibular lesion, even a large vestibular preponderance does not lead to head-shaking nystagmus. Thus, to interpret the results of the head-shaking test the condition of the velocity-storage mechanism must be taken into account.

Adolescent↗

Irradiation induced clonogenic cell death of human malignant glioma cells does not require CD95/CD95L interactions.

BACKGROUND: Radiotherapy is the single most effective therapy for malignant gliomas. Targeting the CD95 apoptotic pathway is a promising experimental approach to these neoplasms. Here, we asked whether irradiation modulates CD95-mediated apoptosis of human malignant glioma cells in vitro. MATERIALS AND METHODS: LN-18, LN-229 and T98G human malignant glioma cell lines were irradiated with dosages from 0-8 Gy and treated with CD95L (CD95 ligand). CD95 expression was assessed by flow cytometry. Caspase activity was determined by DEVD cleavage. Cytotoxic effects were assessed by crystal violet staining of cells in a 96-well plate assay. Clonogenic cell death was determined by a standard colony forming assay. RESULTS: We find that (i) CD95L-induced apoptosis, but not irradiation-induced clonogenic cell death, involves caspase 3 activation and is blocked by the viral caspase inhibitor, crm-A. (ii) Irradiation does not modulate CD95 expression either in p53 wild-type or in p53 mutant glioma cell lines, and does not enhance CD95L-evoked caspase 3 activity or CD95L-induced clonogenic cell death. CONCLUSIONS: We conclude that endogenous CD95/CD95L interactions are not involved in radiation-induced clonogenic cell death and that the killing cascades of CD95L and irradiation are independent in human malignant glioma cells.

Apoptosis↗

Heat shock protein expression in human gliomas.

BACKGROUND: Heat shock proteins (HSP) are cytoprotective, antiapoptotic proteins which may predict clinical prognosis in various types of cancer. Here, we asked whether the differential response to radiochemotherapy and different overall prognosis for astrocytic and oligodendroglial tumours can be accounted for by differences in HSP expression. MATERIAL AND METHODS: We examined aB-crystallin, HSP27, HSP70, HSC70 (HSP73) and HSP90 expression in 44 human gliomas (5 anaplastic and 5 low-grade astrocytomas, 5 anaplastic and 5 low-grade oligodendrogliomas and 24 glioblastomas) by immunohistochemistry. RESULTS: HSP were expressed in the tumour parenchyma of all high-grade and most low-grade gliomas, including oligodendrogliomas. Endothelial cells were more often positive for HSC70 and HSP90, but more often negative for HSP27, in glioblastomas than in the other tumours. HSP were also observed in macrophages/microglial cells, but not in a tumour-specific pattern. CONCLUSION: Different patterns of HSP expression seem not to account for the differential response of these tumours to adjuvant cytotoxic therapy.

Astrocytoma↗

Adaptive mechanisms of VOR compensation after unilateral peripheral vestibular lesions in humans.

To further elucidate possible central plastic adaptive processes during the recovery from a unilateral peripheral vestibular lesion, we investigated vestibular functions in humans over a period of 2 months after an acute unilateral labyrinthine lesion. A unilateral peripheral vestibular lesion creates both a tonic imbalance that causes spontaneous nystagmus and a decrease and directional asymmetry of dynamic vestibular responses. We establish that the tonic imbalance expressed by the spontaneous nystagmus rapidly decreased (similar to other species), whether the lesion remained complete or not. This rebalancing, in the case of complete lesions, is at least partly due to restoration of central vestibular tone on the lesioned side. This restoration of tone also explains, in the case of a complete lesion, the recovery of dynamic vestibular responses for high-velocity inhibitory stimulation of the remaining labyrinth. A clear recovery of the dynamic response for excitatory stimulation of the remaining labyrinth cannot be proven, as has been shown in monkeys during the first 4 days after a unilateral vestibular lesion. This is probably due to the fact that in our patients the first recording could not be performed before day 3 after the onset of symptoms. Therefore, any fast dynamic recovery may have been missed.

Adaptation, Physiological↗

Recovery of postural control after an acute unilateral vestibular lesion in humans.

Postural control during stance was investigated using the EQUITEST system in 10 patients during recovery after an acute unilateral vestibular lesion and was compared to the time course of recovery of the static and dynamic vestibulo-ocular imbalance. During the acute phase the patients showed a characteristic pattern with normal upright stance as long as at least one accurate sensory input (visual or somatosensory) was provided and severe postural disturbances when they had to rely primarily on vestibular afferences. Both static vestibulo-ocular and vestibulo-spinal balance recovered very fast, showing basically normal results on postural testing within about 2 weeks after the lesion. Thereafter, no pathological pattern was detectable during postural testing even in patients with persistent complete unilateral vestibular lesions. Reflexive postural responses to unexpected rapid displacements of the support surface seemed not to be influenced by vestibular imbalance even in the acute phase of the lesion.

Acute Disease↗

Systemic Candida albicans infection with cerebral abscess and granulomas.

This study reports the case of a 19-year-old Turkish woman who was suffering from a cerebral abscess and granuloma formation caused by Candida albicans. The diagnosis of her illness was established by cytologic analysis of the cerebrospinal fluid. Combined application of amphotericin B and 5-fluorocytosine cured the patient's disorder. Its remission was documented over a period of 2 years by the use of computed tomography.

Adult↗