Fluorescence lifetime imaging of the skin PO2 supply. Instrumentation and results.
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Biomedical subjects
Publications and source records attributed to W Ziegler.
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This study reports on a woman who suffered left anterior cerebral artery hemorrhage with a focal lesion undercutting the left supplementary motor area. After almost complete recovery of language the patient was left with dysfluent, halting speech. In a series of four experiments we examined the major factors influencing the patient's articulation. There was a significant effect of lexicality and syllabic length on repetition and articulatory learning (Experiments 1 and 2). The number of syllables was also found to influence, in a simple reaction task, onset latencies, but not inter-response times (Experiment 3). On the contrary, articulatory intricacy had no particular effect on either repetition or vocal reaction (Experiments 1 and 3). While repetition of real words was preserved, single word production in word generation tasks was impaired. Rhyme generation and alliteration, both of which rely on phonological processing, were particularly involved, whereas semantic word generation tasks like verb generation and generation of category members were relatively spared (Experiment 4). Control tasks revealed that the observed phonological processing deficit was confined to the condition of generating spoken language output. These experimental findings suggest that the patient's dysfluent speech could neither be attributed to a deficit of linguistic processing proper, nor to one of motor execution. Her speech disorder rather resulted from an impairment of initiating sequential articulations, particularly in association with the process of downloading temporarily stored multisyllabic strings from an articulatory buffer. This deficit could obviously be overcome in real word repetition through the use of a semantic lexical route.
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Protein kinase C (PKC) is a family of serine/threonine protein kinase isoforms that is important to intracellular enzymes for both tyrosine kinase receptors and G protein coupled receptors. However, which isoforms are linked to which class of receptors in endothelial cell signaling is not known. Moreover, the PKC isoforms in endothelial cells have not been thoroughly characterized. We tested the hypothesis that specific PKC isoforms are involved in different signaling pathways. PKC isoform expression was assessed by using reverse transcription polymerase chain reaction and Western blotting. The spatial distribution of PKC after stimulation of the cells with basic fibroblast growth factor (bFGF) and thrombin was examined by using confocal microscopy. Expression of PKC alpha, delta, epsilon, theta, and zeta was detectable on both the mRNA and protein levels. In resting cells, PKC alpha and epsilon were mostly distributed in the cytosol, while PKC alpha and epsilon were also present in the nucleus. Nuclear immunoreactivity of PKC alpha and epsilon increased significantly between passages 1 and 3. The phorbol ester TPA induced a rearrangement of PKC delta and a translocation of PKC alpha and epsilon to the nucleus. Treatment of endothelial cells with TPA for 24 hours caused PKC alpha, delta, and epsilon to disappear, while PKC zeta was not influenced by TPA. bFGF induced a rapid assembly of PKC alpha along cytosolic structures, followed by a translocation of the isoform toward the perinuclear region and into the nucleus. bFGF had a smaller effect on PKC epsilon. In contrast, thrombin had a similar effect on nuclear translocation of PKC alpha, did not influence PKC epsilon, and induced a rapid nuclear translocation of PKC zeta. Thus, tyrosine kinase receptor activation via bFGF induced a rapid association of PKC alpha and epsilon with nuclear structures, while activation of the G protein-coupled thrombin receptor increased mostly nuclear PKC zeta. The translocation of PKC isoforms into the nucleus by growth-promoting factors may be important for the induction of endothelial cell growth.
We studied syllabic timing in patients with ataxia (10 with cerebellar atrophy, 6 with Friedreich's ataxia) under two conditions: in a "natural" sentence production context and in the context of a rapid syllable repetition task. The two tasks included comparable articulatory maneuvers. We measured syllable durations from the speech signal and analyzed variables describing average syllabic rate and within-trial variation of syllable durations. Among the observed measures, slowed syllable repetition was a particularly powerful predictor of the severity of dysarthric impairment. In sentence production, patients often performed at normal syllabic rates. Irregular pacing of syllable repetitions was frequent. Different patterns of between-articulator variation emerged in the two tasks. All patients except one were slower in rapid repetitive articulation than in sentence production. These data suggest that sentence production and rapid repetitive articulation are governed by basically different motor processes. The disproportionate slowing of ataxic patients in the repetitive task can be ascribed to adaptation to novel motor tasks being impaired in cerebellar disease.
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OBJECTIVE: To determine whether treatment with the levorotatory form of hydroxytryptophan (L-5-hydroxytryptophan), a controversial experimental drug, can improve the conditions of patients with ataxia. DESIGN: A double-blind crossover study with the levorotatory form of hydroxytryptophan was performed in 39 patients with degenerative cerebellar diseases. SETTING: Patients were selected from an ongoing prospective follow-up study at two university hospitals. PATIENTS: We studied 19 patients with Friedreich's ataxia, 13 with cerebellar atrophy, and seven with olivoponto-cerebellar atrophy. INTERVENTION: The levorotatory form of hydroxytryptophan was given orally in a dose of 1000 mg/d. Each treatment phase, with the levorotatory form of hydroxytryptophan or the placebo, lasted 10 months, after which the treatment of patients was crossed over to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified by using a clinical score, posturography, and measurement of grip force and the rapid-syllable repetition rate. RESULT: The levorotatory form of hydroxytryptophan had no significant effect on cerebellar symptoms. CONCLUSION: Long-term treatment with a high dose of the levorotatory form of hydroxytryptophan does not improve the conditions of patients with ataxia.
Cairns and coworkers (1941) introduced the term "akinetic mutism" to denote a syndrome characterised by lack of responsiveness in the presence of apparently preserved vigilance. The present paper reviews clinical data as well as results of animal experimentation to outline the functional-neuroanatomic basis of this constellation. The clinical literature following the original publication of Cairns et al. (1941) reported syndromes of "akinetic mutism" in bilateral mesodiencephalic or frontal lesions of various aetiology. At least two pathomechanisms of akinetic mutism can be differentiated: (a) reduced "arousal" of cortical functions due to lesions at or rostral to the mesodiencephalic junction; (b) impaired activation of the motor system following bilateral damage to the frontal lobes. Since perceptual and cognitive functions are disturbed as well in mesodiencephalic akinetic mutism, the latter notion does not seem to be adequate. The terms "apallic syndrome" or "vegetative state" are rather more appropriate in these instances. The label "akinetic mutism" can then be restricted to a pathophysiologically distinct syndrome, i.e. reduced motor activation following bilateral frontal damage.
We tested the hypothesis that low-density lipoprotein (LDL) and its acetylated form influence surface expression of vascular adhesion molecules on human endothelial cells. Vascular adhesion molecule surface expression was assessed with flow cytometry on cultured endothelial cells with a modified enzyme-linked immunosorbent assay. LDL acetylation was determined by chromatography. Monocyte adhesion to endothelial cells was assessed with U937 cells by direct counting. Tumor necrosis factor-alpha (10 ng/mL), a positive control, induced a time-dependent expression of vascular adhesion molecules (P < .05), which peaked at 5 hours. Incubation of endothelial cells with LDL (1.3 to 26.0 mmol/L) led to an increase in expression at 2 and 5 hours (P < .05). Prolonged (24-hour) exposure to LDL resulted in a second peak. The effect of acetylated LDL on expression was not different from that of native LDL. Incubation with the protein kinase C inhibitor staurosporine (5 x 10(-8) mol/L) blocked the effects of both native and acetylated LDL completely (P < .05). The calcium channel blocker nitrendipine (10(-7) mol/L) did not influence the expression of vascular adhesion molecule at 2 and 5 hours but did reduce the effect of LDL on expression at 24 hours. LDL (2.6 mmol/L) also induced a significant increase in the surface expression of intercellular adhesion molecule-1 but did not affect the expression of endothelial adhesion molecules. LDL (2.6 mmol/L) induced a significant increase in monocyte binding. We conclude that LDL can induce the expression of vascular adhesion molecules on endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Dilation and evacuation is the most common and safest means of pregnancy termination during the first and early second trimesters. The major complication is uterine perforation. This can lead to significant sequela including hemorrhage, infection, and embolism. This case illustrates how these complications present and how they can be effectively controlled with aggressive medical and surgical management. As long as the procedure is done in a setting where these problems can be addressed, dilation and evacuation remain the method of choice for first and early second trimester terminations.
Mutism can be defined as "a condition in which there is no, or very little, oral-verbal expression, whereas comprehension of speech ... is normal or at least at a considerably higher level" (Lebrun, 1990). Benson (1979) enumerates five neuroanatomical correlates of mutism: (a) damage to the Broca region, (b) lesion of the supplementary motor area of the dominant hemisphere, (c) dysfunction of the mesencephalic reticular system, (d) thalamotomy, and (e) bilateral pathology of cortical and subcortical motor structures. The last item refers to syndromes of mutism resulting from central motor disorders. Depending on location and size of the lesion this pathophysiological interpretation should hold true for the fourth point as well. In mutism due to central motor disturbances lacking verbal expression represents the most severe degree of dysarthria, i.e. anarthria. The present review provides a detailed description of mutism following corticobulbar, striatal, and cerebellar dysfunctions.
Mutism in the sense of a complete inability to produce oral language is a rare symptom in aphasic disorders and most often occurs as a transient initial sign. Among the pathomechanisms causing muteness in aphasia, disturbances of speech initiation and of limbic aspects of speech production on the one hand and speech motor programming impairments on the other are considered. This article reviews clinical reports of extremely reduced speech or complete muteness in the context of aphasia, discussing the observed symptom patterns as well as their neuroanatomic correlates and aspects of their recovery.
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Acoustic analysis of vocal instability during the production of isolated vowels, including computation of mean fundamental frequency (F0), period-to-period variability (jitter), pitch fluctuations, and between-trial variation of F0, was performed in 20 patients with cerebellar cortical dysfunction. Eleven subjects suffered from purely cerebellar atrophy (CA). In the remaining 9 patients olivopontocerebellar atrophy (OPCA) had been diagnosed. A subgroup of both the CA and OPCA subjects presented with enlarged pitch fluctuations and/or increased jitter values. It is conceivable that asymmetrically distributed motor deficits at the laryngeal level and altered gain settings of laryngeal and/or respiratory reflexes account for the observed phonatory instability. Moreover, 5 of the 20 cerebellar patients had a pitch level exceeding the upper limit of the normal range. Presumably, this deviation reflects increased vocal effort.
A patient suffering from bilateral thalamic infarction in the region supplied by the paramedian arteries sparing the internal capsules underwent acoustic analysis of sentence utterances. The results were compared with the findings obtained in parkinsonian subjects, in patients with upper motor neuron lesions, and in normal subjects. Acoustic measurements revealed increased pitch, monotonous speech, rough voice quality, and normal speech tempo concomitant with articulatory impreciseness in terms of incomplete closure productions. This constellation resembled parkinsonian dysarthria. Damage to the thalamic projection area of the pallidal efferents, therefore, seems to be the most probable cause of the patient's speech disorders. In parkinsonian subjects stereotactical lesions of this structure ameliorate rigor, but not akinesia. Thus, our patient's speech deficits, and by analogy the corresponding parkinsonian dysarthric disturbances, may be considered akinetic signs.
We describe a new multipurpose method for corneal refractive surgery by using a focused excimer laser beam, which allows the application of a small, compact low-energy excimer laser. It is possible to ablate any area desired in the cornea without masking by scanning the focused beam. The ablation depths in freshly enucleated swine eyes were measured in relation to the number of laser pulses (at fixed fluence) and the pulse fluence at wavelengths lambda = 248 nm and lambda = 193 nm. The irradiation conditions were investigated to obtain smooth ablation of the corneal material over an area of about 1 cm2. The experiments show that smooth ablation is obtained when the ratio of the excimer laser beam spot diameter on the corneal surface and the displacement for one scanning step is given by a whole number. A simple model based on rectangular beam profiles is presented to exemplify this.