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Biomedical subjects

P Wolf

Publications and source records attributed to P Wolf.

At least 127 records · Page 7Linked to original sources

Ultraviolet radiation of melanocytic nevi: a dermoscopic study.

BACKGROUND: UV radiation can lead to clinical, histological, and ultrastructural changes in melanocytic nevi. In this study, we investigated whether exposure to 2 minimal erythema doses of UV radiation induces changes in the dermoscopic image of acquired melanocytic nevi. OBSERVATIONS: Fifteen melanocytic nevi were exposed to 2 minimal erythema doses of UV radiation. Differences in dermoscopic parameters (asymmetry, border, erythema, and telangiectasias in the nevus; pigmentation; hypopigmented areas; presence, regularity, and sharpness of pigment network; and brown-black globules) in digital dermoscopic images taken before and 3, 7, 14, and 28 days after UV irradiation were scored. Three days after UV irradiation, the borders of nevi were more faded (P<.02), the nevi were darker brown (P<.02), the hypopigmented areas were smaller (P<.02), and the pigment network structures were more faded (P<.007) and less prominent (P<.02) than before UV irradiation. Seven days after UV irradiation, pigmented globules have also grown (P<.05). After 28 days, all parameters, except hypopigmented areas, were essentially the same as before UV irradiation. CONCLUSION: UV irradiation of melanocytic nevi with 2 minimal erythema doses induces transient changes in their dermoscopic appearance that are sometimes suggestive of malignant melanoma.

Adult↗

[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin].

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being. Isolated changes of standard laboratory liver parameters are not reliable early indicators. Thus, according to the knowledge of today, prophylactic blood screening cannot predict complications. On the contrary, clinical symptoms are the most relevant indicators of impending complications, eventually supported by laboratory findings. An abrupt withdrawal of valproate and administering carnitin in parallel can interrupt the otherwise fatal course of the complication and induce a subsequent recovery. At a Consensus Conference the current knowledge about early detection and therapy of the valproate-induced serious hepatotoxicity was discussed. The results regarding recommended laboratory screening, as well as diagnostic and therapeutic strategies are reported.

Adolescent↗

Spatio-temporal distribution of epileptiform activity in slices from human neocortex: recordings with voltage-sensitive dyes.

The spatio-temporal distribution of epileptiform activity was investigated in slices from human temporal neocortex resected during epilepsy surgery. Activity was recorded by use of a voltage-sensitive dye and an optical recording system. Epileptiform activity was induced with 10 microM bicuculline and electrical stimulation of layer I. In 10 slices from six patients investigated, epileptiform activity spread across most of the slice. Largest amplitudes were located in layer II/III. Epileptiform activity was characterized by long-lasting potentials with slow rising phases and a low velocity of spread in the horizontal direction (0.044 m/s). This spatio-temporal pattern of epileptiform activity in human slices was similar to that found previously in neocortical slices from guinea pigs with bicuculline. In four of nine human slices investigated under control bath conditions (in non-epileptogenic medium), the spatio-temporal activity patterns were similar to those of guinea pigs in non-epileptogenic medium. In the remaining five human slices, however, the spread in the horizontal direction was significantly larger (4188 microm) in non-epileptogenic medium than that found in slices from guinea pigs (2171 microm). Activity in human slices showing such 'wide spread' in control bath conditions occasionally had characteristic features of epileptiform activity. Further work will have to clarify whether these epileptiform features reflect intrinsic epileptiform properties in human tissue slices.

Animals↗

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Animals↗

Reading epilepsy: report of five new cases and further considerations on the pathophysiology.

Five new cases of reading epilepsy (RE) are reported. This is an epilepsy syndrome belonging to the group of idiopathic localization-related epilepsies. They all have some interesting features which contribute to the understanding of the pathomechanism and nosology of this specific type of reflex epilepsy. In our first patient the precipitating effect of texts in unknown languages depended upon phonematic intricacy. With our second case, changes of script within the text (Latin to Greek) increased the precipitating effect. The visual aura experiences reported in vague terms by some patients with RE may represent ictal dyslexia. For case three RE had been misdiagnosed as phobic neurosis. Even if a patient has a history of development dyslexia, and ictal dyslexia is a feature of the seizures, the onset of RE is not during primary school age but at puberty. Our fourth patient's manifestation factor of (late-onset) RE was a change of scriptural environment (Kyrillic to Latin) . Unilateral myocloni were observed with bilateral spike wave discharge in RE, and carbamazepine possibly increased the epileptic response in RE. With the co-occurrence of RE and juvenile myoclonic epilepsy in case five, the clinical features of both syndromes remained separate. All five patients responded well to treatment with valproic acid, and all confirmed that the syndrome has no tendency to deteriorate in long-term follow-up.

Adolescent↗

Treatment of epilepsy following rejection of epilepsy surgery.

Important progress has been made with the development of both surgical and medicinal treatment of epilepsy but these two developments are rarely seen in a common perspective. Today epilepsy surgery should be discussed with the patient when a reasonable degree of pharmacoresistance has been established, and the chances of an operation clearly outweigh its risks. At that time, there will still be a number of pharmacological options. A study of 15 patients who were evaluated for at least four years after surgery had been considered but rejected after intensive monitoring, pharmacological pursuit was successful in eight, and failed in seven. The successfully treated patients comprise three who became seizure free, and one with isolated auras as the only persisting seizure type. The successful regimens were highly individual, stretching from monotherapies to one four-drug combination. The idea of presenting this small series is not to promote or establish any therapeutic strategies and guidelines but, rather, to draw attention to a neglected interface between surgical and medicinal procedures, and to increase awareness that epilepsy therapy will still be most successful when it is seen as a whole, and must not be split up into competing ideologies. Concerns are not well founded that epilepsy surgery may be seen as the last hope for pharmacoresistant patients, and that, if surgery is declined, a loss of this hope may be intolerable to the patient.

Adolescent↗

Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in vitro model of epilepsy.

1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a change in GABA-metabolism have been suggested as mechanisms of action of gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA-transaminase but it also interferes with GABA-release and GABA-uptake. On the basis of these mechanisms of action, a pharmacodynamic interaction of the two antiepileptic drugs could be supposed which might be of relevance in the sense of a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments were carried out on hippocampal slices (n=107) of guinea-pigs (n=70). Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from the bath solution and recorded in the stratum pyramidale of the CA3 region. Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM, 6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100 microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations up to 600 microM, failed to decrease the repetition rate or duration of e.f.p. (n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h (n=11). With simultaneous administration of vigabatrin (100 microM) and gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased down to 8+/-3%, which is significantly different from the values obtained after administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic effect of vigabatrin alone and the enhancement by gabapentin were blocked by the GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results demonstrate that gabapentin is able to augment the antiepileptic effects of vigabatrin significantly. It is possible that a change in the GABA-release machinery is induced by vigabatrin which then can be augmented by gabapentin.

4-Aminobutyrate Transaminase↗

Comparison of phototherapy with near vs. far erythemogenic doses of narrow-band ultraviolet B in patients with psoriasis.

The therapeutic effectiveness of radiation from a 311 nm ultraviolet B (UVB) lamp (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated in 13 patients with widespread, symmetrically distributed psoriasis. The patients received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED) on one randomly chosen half of the body and 35% of the 311 nm MED on the other half. Therapy was given three to five times a week, and the UVB dose in both regimens was increased simultaneously in the same relation. For the 11 patients completing the study, the mean psoriasis area and severity index (PASI) score for the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 (P = 0.003), 8.2 vs. 12.0 at week 2 (P = 0.004), and 6.6 vs. 15.6 at week 3 (P = 0.005). After 3 weeks, a satisfactory response (i.e. improvement of the initial PASI score by more than 75%) was observed in six of 11 patients on the near erythemogenic treatment side vs. three of 11 patients on the far erythemogenic side. However, the definitive median total number of treatments needed to achieve a satisfactory therapy response on the near vs. far erythemogenic sides was 12 vs. 16 (P = 0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm2 (P = 0.088), respectively. These results suggest that near erythemogenic 311 nm UVB therapy may clear psoriasis faster than far erythemogenic therapy but that the latter regimen may be equally effective as it requires slightly more treatment sessions at a lower (and possibly less carcinogenic) cumulative UV dose.

Adult↗

Spontaneous sharp waves in human neocortical slices excised from epileptic patients.

Human neocortical temporal lobe tissue resected for treatment of pharmacoresistant epilepsy was investigated. In slices prepared from this tissue, field potentials sometimes superimposed by population spikes were found to appear spontaneously. In individual slices, they were generalized or highly localized to a field of approximately 200 microns in diameter. Synchronous with these potentials, hyperpolarizing and depolarizing postsynaptic potentials were recorded from neurons in the vicinity of the field potential electrode. Hyperpolarizing postsynaptic potentials appeared to be mainly chloride mediated. All potentials, i.e. sharp field potentials as well as postsynaptic potentials, were reversibly suppressed by blockade of the non-NMDA (non-N-methyl-D-aspartate) glutamate-subreceptor and of the GABAA (gamma-aminobutyric acid) receptor, and by application of the organic calcium channel blocker verapamil. By contrast, all potentials remained unaffected by blockade of the NMDA glutamate-subreceptor and the GABAB receptor. The antiepileptic drugs carbamazepine and phenytoin failed to suppress the spontaneous potentials at therapeutic concentrations. Washout of Mg2+ from the superfusate left the spontaneous potentials unchanged or converted them to ictal-type discharges. This epileptiform activity was not suppressed, but augmented by blockade of the GABAA receptor. As a whole, the spontaneously appearing field potentials may be assumed to reflect a state of increased neuronal synchronization.

Action Potentials↗

Phenotypic markers, sunlight-related factors and sunscreen use in patients with cutaneous melanoma: an Austrian case-control study.

Sunscreens have been advocated to prevent burning in the hope that this will decrease the chance of developing melanoma. In a single-centre case-control study in Styria, Austria, we examined the risk of cutaneous malignant melanoma in relation to phenotypic markers, sunlight-related factors and sunscreen use. In total, 193 melanoma patients and 319 control subjects answered a comprehensive questionnaire regarding phenotypic markers, a variety of sunlight-related factors and sunscreen use. Risk factors for melanoma were examined through the use of unconditional logistic regression analysis, controlling for age and sex. Screening for confounding factors was done by forward and backward elimination of non-significant variables (P < 0.05). The resulting set of factors were investigated further for effect modification by introducing interactions into the model. The factor most significantly associated with increased melanoma risk was the use of sunscreens. Subjects who often used sunscreens had an increased odds ratio (OR) of 3.47 (95% confidence interval [CI]1.81-6.64) compared with subjects who never used sunscreens (P = 0.001), after adjustment for sex, age and other significant sunlight-related factors. Skin colour and higher numbers of sunbaths were significant protective factors. Subjects with medium skin colour had an adjusted OR of 0.63 (95% CI 0.41-0.99) compared with subjects with light skin colour (P = 0.0022). Subjects who took more than 30 sunbaths per year and subjects who took 20-30 sunbaths per year had, in the absence of sunburn(s), a decreased OR of 0.09 (95% CI 0.02-0.39) and 0.28 (95% CI 0.13-0.64), respectively, compared with subjects who took less than 20 sunbaths per year (P = 0.0002). However, sunbaths had no protective value when they were associated with sunburns. Although we cannot exclude the presence of an unknown confounding factor, our results suggest that the use of sunscreens does not help prevent melanoma.

Adolescent↗