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Biomedical subjects

Peter Wolf

Publications and source records attributed to Peter Wolf.

At least 19 recordsLinked to original sources

Basic principles of the ILAE syndrome classification.

The basic principles of the ILAE syndrome classification can be summarised as: clear definitions; reference to the seizure classification; expert consensus based on literature research; providing a taxonomy rather than a diagnostic manual; use of the dichotomies generalised versus localisation-related and idiopathic versus symptomatic; openness for the incorporation of new findings; and promotion of nosological thought. In fact, the publication of the classification stimulated research, especially in the fields of genetics, reflex epileptic mechanisms and advanced imaging, which will probably lead to a major revision of the nosology of epilepsies. Both localisation-related and "generalised" idiopathic epilepsies are about to be understood as related variants of system disorders of the brain, with an ictogenesis making pathological use of existing functional anatomic networks.

Epilepsy↗

Cold atom clock test of Lorentz invariance in the matter sector.

We report on a new experiment that tests for a violation of Lorentz invariance (LI), by searching for a dependence of atomic transition frequencies on the orientation of the spin of the involved states (Hughes-Drever type experiment). The atomic frequencies are measured using a laser cooled 133Cs atomic fountain clock, operating on a particular combination of Zeeman substates. We analyze the results within the framework of the Lorentz violating standard model extension (SME), where our experiment is sensitive to a largely unexplored region of the SME parameter space, corresponding to first measurements of four proton parameters and improvements by 11 and 13 orders of magnitude on the determination of four others. In spite of the attained uncertainties, and of having extended the search into a new region of the SME, we still find no indication of LI violation.

Journal Article↗

Decline in seizure propensity in seizure-free patients as reflected in the evolution of the therapeutic antiepileptic drug threshold.

To better understand mechanisms of remission, the decline in seizure propensity in seizure-free patients was investigated. Plasma antiepileptic drug levels were measured in 199 adults seizure-free for 2 or more years, who consented to reduction and eventual discontinuation of therapy. Among 117 patients on monotherapy, drug dosage was reduced in 82 and therapy was terminated in 35. The initial therapeutic threshold was known in 51 cases, and the new threshold was determined in all cases of relapse. Four types of evolution were observed: no decline in seizure propensity; restricted decline and relapse; greater decline but relapse; and decline below the intrinsic seizure threshold (no relapse). Patients with seizure control immediately after onset of treatment were more likely to obtain remission. Our findings indicate that in seizure-free patients, seizure propensity only rarely remains unchanged, remission is attained by both qualitative and quantitative mechanisms, and there may be different mechanisms underlying quantitative declines in seizure propensity.

Adult↗

Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.

OBJECTIVE: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ. DESIGN: Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment. SETTING: Forty outpatient dermatology centers in 11 European countries. PATIENTS: Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression. INTERVENTIONS: Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated. MAIN OUTCOME MEASURES: Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale). RESULTS: At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months. CONCLUSION: Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis.

Administration, Cutaneous↗

Long-term operation and performance of cryogenic sapphire oscillators.

Cryogenic sapphire oscillators (CSO) developed at the University of Western Australia (UWA) have now been in operation around the world continuously for many years. Such oscillators, due to their excellent spectral purity are essential for interrogating atomic frequency standards at the limit of quantum projection noise; otherwise aliasing effects will dominate the frequency stability due to the periodic sampling between successive interrogations of the atomic transition. Other applications, which have attracted attention in recent years, include tests on fundamental principles of physics, such as tests of Lorentz invariance. This paper reports on the long-term operation and performance of such oscillators. We compare the long-term drift of some different CSOs. The drift rates turn out to be linear over many years and in the same direction. However, the magnitude seems to vary by more than one order of magnitude between the oscillators, ranging from 10(14) per day to a few parts in 10(13) per day.

Aluminum Oxide↗

Successful thalidomide therapy for actinic prurigo in a European woman.

Actinic prurigo is a rare, often difficult-to-treat, idiopathic photodermatosis. Actinic prurigo is divided into a hereditary form appearing in the Native American population and a sporadic form occurring in non-Native Americans. We present a 28-year-old Caucasian woman who developed typical clinical signs and symptoms of actinic prurigo, just as had her mother and grandmother. The patient and her mother were HLA-A24 and HLA-DR 4 with the subtype HLA-DRB1*0408. Based on clinical symptoms and the HLA pattern, the diagnosis of actinic prurigo was made. Treatment with thalidomide led to resolution of the disease. This case report of a Caucasian woman suffering from a hereditary form of actinic prurigo questions the established classification of actinic prurigo into a hereditary Native American form and a sporadic form occurring in the non-Native American population.

Adult↗

Real-time measurement of PMA-induced cellular alterations by microelectrode array-based impedance spectroscopy.

For a feasible and cost-effective impedance measurement of cellular alterations in real-time, we combined commercially available microelectrode arrays (MEAs), consisting of 60 microelectrodes, with a conventional impedance analyzer. For proof of principle, a breast carcinoma cell line (MCF-7) was cultured on MEAs, and cellular alterations were measured by impedance spectroscopy at a frequency ranging from 10 Hz to 1 MHz. Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) at different concentrations to activate protein kinase C (PKC)-mediated extra- and intracellular changes. By addition of 0.03 microM PMA, an increase of the relative impedance (Z(rel)) was observed after 10 min with a maximum at 1 kHz. Moreover a gradual elevation of the impedance was measured 60 min after stimulation with PMA. If 0.3 microM PMA was applied, the maximal amplitude of the relative impedance after 60 min shifted from 1 kHz (0.03 microM PMA) to 150 Hz. Subsequently, the impedance was further increased up to 90 min after PMA application, after which the impedance reduced after 240 min. Since we could use MEAs for at least 10 times without affecting the sensitivity, our study revealed that commercially available MEAs comprising nanocolumnar titanium nitrite electrodes are suitable microstructures for a highly reproducible and cost-effective multisite measurement of intracellular processes by impedance spectroscopy.

Alloys↗

Dose adaptation of antineoplastic drugs in patients with liver disease.

Dose adaptation for liver disease is important in patients treated with antineoplastic drugs because of the high prevalence of impaired liver function in this population and the dose-dependent, frequently serious adverse effects of these drugs. We classified the antineoplastic drugs marketed in Switzerland at the end of 2004 according to their bioavailability and/or hepatic extraction to predict their kinetic behaviour in patients with decreased liver function. This prediction was compared with kinetic studies carried out with these drugs in patients with liver disease. The studies were identified by a structured, computer-based literature search. Of the 69 drugs identified, 52 had a predominant extrarenal (in most cases hepatic) metabolism and/or excretion. For 49 drugs, hepatic extraction could be calculated and/or bioavailability data were available, allowing classification according to hepatic extraction. For 18 drugs, kinetic studies have been reported in patients with impaired liver function, with the findings generally resulting in quantitative recommendations for adaptation of the dosage. In particular, recommendations are precise for 16 drugs excreted by the bile (e.g. doxorubicin and derivatives and vinca alkaloids). Validation studies comparing such recommendations with kinetics and/or dynamics of antineoplastic drugs in patients with decreased liver function have not been published. We conclude that there are currently not enough data for safe use of cyctostatics in patients with liver disease. Pharmaceutical companies should be urged to provide kinetic data (especially hepatic extraction data) for the classification of such drugs and to conduct kinetic studies for drugs with primarily hepatic metabolism in patients with impaired liver function to allow quantitative advice to be given for dose adaptation.

Antineoplastic Agents↗

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.

Animals↗

Reflection: a critical proficiency essential to the effective development of a high competence in communication.

Reflection, or the ability to step back from an experience and consider it critically, in an analytical, non-subjective manner, is an essential aspect of problem solving and decision making, and also of effective communication with clients and colleagues. Reflective practice has been described as the essence of professionalism and is therefore a core professional skill; rarely, however, has it been explicitly taught in veterinary curricula, and it has only a recent history in undergraduate human medical curricula. We describe here two preliminary case studies, one in a veterinary medical education context and the other within a human medical education framework, as examples of approaches to assessing a student's ability for ''reflection.'' The case studies also illustrate some of the key principles. Both of the case studies described had as their end goal the enhancement of communication skills through critical reflection. At Monash University, Australia, the majority of students were assessed as being at a level of ''reflection in development.'' The students in the Ontario Veterinary College case study showed moderately good use of self-awareness and critical reflection as a basis for modifying and integrating communication skills into practice. While both preliminary case studies point to the fact that students recognize the importance of communication and value the opportunity to practice it, few students in either case study identified the importance of reflection for lifelong learning and professional competence. Opportunities to complete critical reflection exercises in other parts of curricula and outside of communication would likely reinforce its importance as a generic skill. Ongoing scholarly approaches to teaching, learning, and evaluating reflection and self-awareness are needed.

Cognition↗

Descriptions of clinical semiology of seizures in literature.

Literary texts are an important part of the cultural history of many fields of medicine. Accounts of epilepsy are frequent, and descriptions of seizure semiology are often included with varying detail. This review looks at these, and considers the authors' background knowledge of epilepsy. The first group of writers suffered seizures themselves. Some of them provide remarkable and novel insights into the subjective symptoms and experiences in and around seizures.A second group draws from their own observations of seizures in others who may have been close relatives or fortuitous strangers. Here, the outside view prevails, and seizures may be described with clinical objectiveness. Commonly, the reactions of onlookers become part of the narrative beyond the seizure description. The third group writes from second-hand knowledge, which may be other observer reports, interviews with people with epilepsy or with experts, information being available in dictionaries, medical textbooks and the like. The professional standard of most writers means that the resulting descriptions are quite accurate, but there are also examples of poor use of such information. Many authors' sources are not known, but can be assumed to belong to one of the above categories, and we can sometimes guess. It appears that even authors with no first-hand knowledge are often aware of seizure types other than the most widely known, generalised tonic-clonic, and there is a widespread interest in warnings and how the afflicted respond to them. The quality of an author's fictional account of epilepsy should not be judged from a translation, because specific aspects and the language involved in the description may have been misunderstood by the translator.

Epilepsy↗

Photodamage to the cutaneous sensory nerves: role in photoaging and carcinogenesis of the skin?

Chronic exposure to ultraviolet radiation (UVR) plays a significant role in aging and carcinogenesis of the skin. Sensory nerve fibers densely innervate all layers of the skin and get in close anatomical as well as functional contact with cellular components of the epidermis and dermis. In this review, we address the impact of acute and chronic UVR exposure on the cutaneous sensory nervous system and its mediators. We suggest that skin cell-derived nerve growth factor (NGF) and skin nerve-derived neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) may play a central role in intrinsic aging as well as extrinsic (photo-) aging of the skin. In addition, we discuss the possible role of these mediators in photocarcinogenesis.

Humans↗

[Epilepsy as a dynamic condition: facilitation and inhibition, establishment and remission].

Epilepsy should not be seen as a stable chronic illness but as a condition that undergoes changes over time, due to antagonistic factors which facilitate or counteract seizures. Some of these are known, and their action can best be observed at onset, when seizure repetition is established or prevented, and at remission, when the decline of the antiepileptic drug therapeutic threshold reflects a fall in the propensity to seizures. A quantitative model is proposed which can explain much of the observed variability.

Anticonvulsants↗

[Valproate-caused encephalopathy].

Valproate is a widely used antiepileptic drug with rarely occurring serious side effects. We observed two cases of valproate-caused encephalopathy of insidious type. Ten months after initiation of valproate treatment, the two patients showed neurologic deficits such as rapid cognitive decline and extrapyramidal manifestations. However, the patients recovered some weeks after termination of the treatment. This side effect must be considered in patients showing signs of rapidly progressing severe dementia who are being treated with valproate.

Aged↗

Test of Lorentz invariance in electrodynamics using rotating cryogenic sapphire microwave oscillators.

We present the first results from a rotating Michelson-Morley experiment that uses two orthogonally orientated cryogenic sapphire resonator oscillators operating in whispering gallery modes near 10 GHz. The experiment is used to test for violations of Lorentz invariance in the framework of the photon sector of the standard model extension (SME), as well as the isotropy term of the Robertson-Mansouri-Sexl (RMS) framework. In the SME we set a new bound on the previously unmeasured kappa(ZZ)(e-) component of 2.1(5.7) x 10(-14), and set more stringent bounds by up to a factor of 7 on seven other components. In the RMS a more stringent bound of -0.9(2.0) x 10(-10) on the isotropy parameter, P(MM) = delta-beta + 1 / 2 is set, which is more than a factor of 7 improvement.

Journal Article↗

Intrinsic excitability, synaptic potentials, and short-term plasticity in human epileptic neocortex.

Although studies of epileptic human hippocampus suggest changes of synaptic and intrinsic excitability, few changes, save the appearance of spontaneous field/synaptic potentials, are known in epileptic neocortical tissue. However, invasive EEG and histological studies suggest that neocortical tissue, even in mesial temporal lobe epilepsy, can play an important role as an irritative zone or extrahippocampal focus. We hypothesized that intrinsic neuronal and synaptic excitability, as well as short-term plasticity, are altered in neocortical areas, particularly with elevated K+ levels as occur during seizures. We analyzed neuronal firing properties, synaptic responses, and paired-pulse plasticity in human neocortical slices from tissue resected during epilepsy surgery, both under normal and under pathological conditions, i.e., after elevating K+ (4/8 mM), with rat neocortical slices as controls. Neuronal firing properties were not different. We did find, however, alterations of synaptic responsiveness in epileptic tissue, i.e., an elevated network excitability with K+ elevations, and reduction of paired-pulse depression.

Adult↗