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A Gerhard

Publications and source records attributed to A Gerhard.

16 recordsLinked to original sources
PubMed2006

Microglial activation correlates with severity in Huntington disease: a clinical and PET study.

BACKGROUND: Huntington disease (HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process. METHODS: To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using [(11)C](R)-PK11195 PET, a marker of microglia activation, and [(11)C]raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function. RESULTS: In HD patients, a significant increase in striatal [(11)C](R)-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [(11)C]raclopride binding, the Unified Huntington's Disease Rating Scale score, and the patients' CAG index. Also detected were significant increases in microglia activation in cortical regions including prefrontal cortex and anterior cingulate. CONCLUSIONS: These [(11)C](R)-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease (HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that [(11)C](R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.

Adult↗
PubMed2005

Mills' and other isolated upper motor neurone syndromes: in vivo study with 11C-(R)-PK11195 PET.

(11)C-(R)-PK11195 positron emission tomography (PET) was used to explore and delineate in vivo the cortical lesion in three clinically isolated upper motor neurone syndromes of similar presentation, with reference to the syndrome of progressive spastic hemiparesis first described by Mills. Three patients with isolated UMN syndromes underwent (11)C-(R)-PK11195 PET of the brain. One patient fulfilled criteria for PLS. Two others had clinical features similar to the cases described by Mills; one of these had a high cervical cord inflammatory lesion previously noted on magnetic resonance imaging. The patient with PLS showed focal increase in the binding of (11)C-(R)-PK11195, indicating microglial activation, in the motor cortex contralateral to the predominantly affected limbs. Of the other two patients, one demonstrated marked increases in binding in the superior frontal region (supplementary motor region) contralateral to the affected limbs. In contrast, no focal areas of increased binding were seen in the cerebral cortex of the third patient, who had a high cervical cord lesion and was presumed to have extra-cerebral inflammatory disease. (11)C-(R)-PK11195 PET demonstrates in vivo that active pathology may be detectable many years after the onset of symptoms, and that it can occur in disparate sites with clinically similar presentations. We conclude that Mills' syndrome is a purely clinical description that should be reserved for patients with a progressive spastic hemiparesis for which no other explanation can be found.

Adult↗
PubMed2003

[11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy.

Microglia, the brain's intrinsic macrophages, bind (R)-PK11195 when activated by neuronal injury. The authors used [11C](R)-PK11195 PET to localize in vivo microglial activation in patients with multiple system atrophy (MSA). Increased [11C](R)-PK11195 binding was primarily found in the dorsolateral prefrontal cortex, putamen, pallidum, pons, and substantia nigra, reflecting the known distribution of neuropathologic changes in MSA. Providing an indicator of disease activity, [11C](R)-PK11195 PET can thus be used to characterize the in vivo neuropathology of MSA.

Aged↗
PubMed2001

Disturbed neural circuits in a subtype of chronic catatonic schizophrenia demonstrated by F-18-FDG-PET and F-18-DOPA-PET.

Permanent verbal, visual scenic and coenaestetic hallucinations are the most prominent psychopathological symptoms aside from psychomotor disorders in speech-sluggish catatonia, a subtype of chronic catatonic schizophrenia according to Karl Leonhard. These continuous hallucinations serve as an excellent paradigm for the investigation of the assumed functional disturbances of cortical circuits in schizophrenia. Data from positron emission tomography (F-18-FDG-PET and F-18-DOPA-PET) from three patients with this rare phenotype were available (two cases of simple speech-sluggish catatonia, one case of a combined speech-prompt/speech-sluggish subtype) and were compared with a control collective. During their permanent hallucinations, all catatonic patients showed a clear bitemporal hypometabolism in the F-18-FDG-PET. Both patients with the simple speech-sluggish catatonia showed an additional bilateral thalamic hypermetabolism and an additional bilateral hypometabolism of the frontal cortex, especially on the left side. In contrast, the patient with the combined speech-prompt/speech-sluggish catatonia showed a bilateral thalamic hypometabolism combined with a bifrontal cortical hypermetabolism. However, the left/right ratio of the frontal cortex also showed a lateralisation effect with a clear relative hypometabolism of the left frontal cortex. The F-18-DOPA-PET of both schizophrenic patients with simple speech-sluggish catatonia showed a normal F-18-DOPA storage in the striatum, whereas in the right putamen of the patient with the combined form a higher right/left ratio in F-DOPA storage was discernible, indicating an additional lateralized influence of the dopaminergic system in this subtype of chronic catatonic schizophrenia. Most likely, the prominent bitemporal F-18-FDG- hypometabolism in these chronic schizophrenic patients with speech-sluggish catatonia suffering from permanent continuous hallucinations, reflects a deficit in sensoric gating following prenatal cortical neurodevelopmental disturbances. However, the functional disturbances underlying hallucinations in "the schizophrenias" seem to be more complex; in different subtypes of the schizophrenic spectrum disorder hallucinations seem to be based on alterations in additional cortical and subcortical brain regions.

Adult↗
PubMed2000

In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke.

Neuroprotective strategies are currently being developed for stroke patients. Although the focus is on the development of early treatment the importance of late pathogenetic events is increasingly recognized. To investigate the microglial reaction in stroke we used a marker for activated microglia, [11C]PK11195, and PET in five patients with ischemic stroke 5-53 days after infarction. In one patient serial measurements were made. We demonstrated in each individual and at each point in time that a microglial reaction takes place in the area where T1 weighted MRI (magnetic resonance imaging) shows intensity changes. We consider this PET method as a promising tool to study the late pathogenetic consequences of cerebral infarction and to evaluate neuroprotective strategies with respect to the consequences of the microglial activation.

Adult↗
PubMed2000

Phosphorescence of pi-conjugated oligomers and polymers.

We observed phosphorescence from a ladder-type poly-(para-phenylene) and an analogous oligomer containing five phenylene rings. The spectra are similar to the intrinsic fluorescence spectra and bear out a singlet-triplet splitting of 5000 cm(-1) (polymer) and 6800 cm(-1) (oligomer). Phosphorescence decay of the polymer occurs on a 10-100-micros scale obeying a power law and suggestive of nonradiative quenching, while that of the oligomer is asymptotically exponential with an intrinsic decay time of approximately 250 ms. The polymer also exhibits delayed fluorescence. It originates from delayed recombination of geminate electron-hole pairs rather than from triplet-triplet annihilation.

Journal Article↗
PubMed1997

No evidence for specific opioid effects on batrachotoxin-modified sodium channels from human brain synaptosomes.

Human central nervous system (CNS) sodium channels modified by batrachotoxin and incorporated inter voltage-clamped lipid bilayers, were exposed to various concentrations of the opioid alfentanil (0.2-8.0 mM). Alfentanil caused a concentration-dependent and membrane potential independent reduction of the single channel amplitude and the fractional channel open-time. The weighted computer fit of the dose-response curve yielded a maximal conductance block of 50% with an EC50 of 1.3 mM. These effects occurred at levels beyond clinically relevant human serum/brain levels (0.003 mM) but within the predicted concentration range using the Meyer-Overton (lipid solubility/anaesthetic potency) correlation. Thus, human CNS sodium channels are probably not a main target site for the clinical effects of alfentanil but they provide a model system to estimate the proportion of the lipophilic interactions contributing to its overall effect.

Alfentanil↗
PubMed1995

Some ethical principles for adult critical care.

State of the art in approaching several of the most disturbing problems involving end-of-life decision-making in an intensive care setting is applicable to other contexts as well. Developed as part of the curriculum at the John A. Burns School of Medicine at the University of Hawaii, the material is intended as a reflection of current work in health care ethics, strongly supported by literature, and generally consistent with current legal trends. But it also has developed into something of a consensus document, having been widely circulated in various versions, repeatedly presented to professional audiences dozens of times in Hawaii, and improved by countless comments and suggestions. The focus here is on the standards for withholding and withdrawing treatment. It should be noted that some important types of ethical problems are not covered: In particular, scarce resource problems (including some related questions involving medical futility), maternal-fetal and pediatric issues, and questions involving the notification of potentially affected third parties.

Adult↗
PubMed1991

Postoperative patient-controlled analgesia with sufentanil: analgesic efficacy and minimum effective concentrations.

Sufentanil has so far seldom been used for intravenous postoperative patient-controlled analgesia (PCA), and the resulting serum concentrations have not yet been determined. Forty ASA I-III patients recovering from major gynecological operations were investigated to evaluate analgesic efficacy, side effects, patient acceptance and threshold concentrations of sufentanil in serum during the early postoperative period, using the On-Demand Analgesia Computer (ODAC). Following an individualized intravenous loading dose of 19.1 +/- 35.7 micrograms (mean +/- 1 s.d.), sufentanil demand doses were 6 micrograms with a concurrent infusion of 1.15 micrograms/h and a maximum hourly dose of 40 micrograms/h; the lockout time was set to 1 min. The duration of PCA was 17.3 +/- 2.1 h. During this time 16 +/- 11 demands per patient were recorded, resulting in an average sufentanil consumption of 131.1 +/- 69.4 micrograms or 7.5 +/- 3.7 micrograms/h (including loading dose). analgesia was mostly judged good. Side effects were only of minor intensity. Sufentanil proved to be about 2.2 to 3.8 times as potent an analgesic as fentanyl when both analgesic effect and duration were considered. Minimum effective sufentanil serum concentration (MEC) as determined by radioimmunoassay varied greatly and could be best described by a log-normal distribution (range less than 0.01-0.56 ng/ml, median 0.024 ng/ml). Intraindividual MEC variability was slightly lower than intersubject variability (76.0 vs. 84.8%). It is concluded that sufentanil is suitable for postoperative PCA. To get into the therapeutic window for analgesia, a serum sufentanil concentration of more than 0.03 ng/ml seems to be necessary.

Adult↗
PubMed1990

Intraperitoneal application of fibrinogen gluing in the rat for adhesions prophylaxis.

The suitability of fibrinogen gluing for prophylaxis of intraperitoneal adhesions was investigated experimentally. Small bowel slings, traumatized previously, were covered by a layer of fibrinogen 2-3 mm thick to see whether formation of adhesions could be prevented. In the experiments 50 rats of both sexes were observed over 21 days. Following mechanical traumatization of the terminal ileum the visceral peritoneum was coated with fibrinogen, whereas animals of the control group did not receive fibrinogen coating. Macroscopic and microscopic findings after 1, 3, 7, 14 and 21 days yielded the following results: 1. Fibrinogen dissolution and resorption occurred for 3-14 days following operation. 2. On autopsy, all animals of the control group showed massive, extended adhesions; two of the controls died on the 6th postoperative day from peritonitis. 3. None of the treated animals exhibited extended adhesions. 4. Histological examinations revealed regeneration of the injured serosa and healing of the bowel wall below the fibrinogen coating. 5. Fibrinogen applied to intact peritoneal serosa (without injury) is entirely resorbed without formation of adhesions.

Animals↗
PubMed1976

[Metabolic products of microorganisms. 156. Synthesis and biosynthesis of substituted tryptanthrins (author's transl)].

Candida lipolytica synthesizes the antibiotic tryptanthrin from 1 mole tryptophan and 1 mole anthranilic acid. When feeding tryptophan and substituted anthranilic acids, or substituted tryptophans and anthranilic acid, we could isolate and identify the expected derivatives of tryptanthrin. The enzymes of the biosynthesis of tryptanthrin, with the exception of bromotryptophan, had no specifity for these substrates. In addition to these experiments substituted tryptanthrines were chemically synthesized. We checked them for antibiotic action; the halogen compounds turned out to be especially effective.

Anti-Bacterial Agents↗
PubMedDate not supplied

Psychopathology of stable and unstable mixed states: a historical view.

The concept of mixed states was proposed at the end of last century by Kraepelin and Weygandt to confer unity to manic-depressive illness and to better differentiate this disease from dementia praecox. The concept has been further elaborated by the Hamburg and Vienna schools (Mentzos and Berner, respectively), and dichotomized in stable and unstable mixed states. Stable mixed states represent a condition of the synchronic copresence of symptoms of both polarities; unstable mixed states, or "mixed pictures," are characterized by the rapid cycling of these symptoms. The former represent clinical expressions of bipolar disorder, and the latter represent trans-nosological conditions with multiple outcomes. Current North American nosology retains the original Kraepelinian concept of stable mixed states and ignores the concept of unstable mixed states, which is very close to the concept of ultradian cycling proposed by Kramlinger and Post in 1996.

Austria↗