Spatial S-R compatibility with centrally presented stimuli. An event-related asymmetry study on dimensional overlap

Lateral presentation of relevant information facilitates manual responses if the side of relevant information corresponds to the side of the response. Recently, temporally overlapping EEG asymmetries over the central motor cortex and posterior sites were reported as a possible correlate of the sensory-motor integration of spatial information. The present study investigated whether sensory-motor integration of spatial information can occur with symbolic spatial information the same way as with laterally presented stimuli. The task required participants to respond to arrows (target stimuli), which were "flanked" (from above and below) by neutral stimuli or by other arrows (compatible or not). In Experiment 1, this task was compared to the same task with letters as stimuli and to an incompatible task where participants had to respond "against" the arrow direction. The effect of the flankers on response times was largest if subjects had to respond to the arrows in the common way. This was also the only task of Experiment 1 for which marked EEG asymmetries related to the direction of the flankers were observed. In Experiment 2, the onsets of target stimulus and flankers differed in time. Event-related lateralizations of the EEG over sensory and primary motor areas--as a lateralized readiness potential--were always, apparently automatically, evoked by flanking arrows, indicating automatic response activation evoked by symbolic spatial information. In accordance to recent theories of temporally decaying response activation, manual responses were affected only if the target was either shortly preceded by or appeared simultaneously with the flankers. The temporal overlap of EEG asymmetries related to direction encoding, automatic response activation, and to response preparation indicated that a widespread cortical network is activated by a salient directional information that enables subjects to respond quickly if the directional code of the stimulus overlaps with the directional code of the response.     

Penetrating keratoplasty in patients with atopic dermatitis with and without systemic cyclosporin A

PURPOSE: Clinical experience suggests that atopic dermatitis is a considerable risk factor in penetrating keratoplasty. The scientific evidence, however, has been equivocal. Systemic cyclosporin A reduces the threat of immune reactions and simultaneously improves atopic dermatitis. The purpose of this study was to evaluate to what extent and for how long systemic cyclosporin A improves graft prognosis in patients with atopic dermatitis. PATIENTS AND METHODS: Between November 1986 and July 1994, 173 penetrating keratoplasties were performed on keratoconus patients without skin disease (I). Fifteen penetrating keratoplasties were performed on patients with keratoconus associated with slight atopic dermatitis (II), 24 on patients with keratoconus associated with severe atopic dermatitis (III), and 13 on patients with keratitis in atopic dermatitis but without keratoconus (IV). Systemic cyclosporin A was administered for at least 6 months in groups III and IV. Clear graft survival was estimated according to Kaplan and Meier, and statistical significance was evaluated via log-rank test. RESULTS: Six months/6 years postoperatively 99.5 and 96.5% (I), 80 and 80% (II), 96 and 83.2% (III), and 100 and 65.8% (IV) of the grafts were clear. Only the differences between the survival curve of group I and the curves of each of groups II-IV were statistically significant (p < 0.001). CONCLUSIONS: To our knowledge, this is the first study proving that atopic dermatitis with and without keratoconus deteriorates graft prognosis statistically significantly. The application of systemic cyclosporin A improves graft prognosis in atopic dermatitis as long as the drug is applied, and this effect slowly fades thereafter.     

Surgical correction of astigmatism after perforating keratoplasty]

Microsurgical control of astigmatism after perforating keratoplasty has widely remained an unsolved problem in spite of many sophisticated suggestions and inventions. The frequent irregularity in the recipient cornea and poor predictability with respect to wound healing are the major obstacles. If spectacles or contact lenses cannot provide useful vision, postoperative surgical correction is needed. Ablative or thermal laser techniques have not been sufficiently tried for such cases to be justified, and one may hesitate anyway to apply destructive methods in transplants. We therefore still use T-incisions and wedge resections, which are said to be rather imprecise. Only 3 out of more than 700 keratoplasties performed in our clinic from 1987 through July 1991 required such procedures. Two more cases were referred by surgeons outside the hospital. All five surgical corrections resulted in a good longterm effect with considerable improvement of vision. Thus, as long as alternative methods for surgical correction of postkeratoplasty astigmatism have not proved to be superior, we should continue to practice these "old" methods, which, indeed, are not bad if properly applied.     

Production of Forskolin by Axenic Coleus forskohlii Roots Cultivated in Shake Flasks and 20-l Glass Jar Bioreactors*

Root cultures of COLEUS FORSKOHLII Briq. were initiated from primary callus or IBA-treated suspension cultures and maintained on Gamborg's B5 medium containing 1 mg/l IBA. Transformed root cultures were established by infecting surface-sterilized leaves with AGROBACTERIUM RHIZOGENES strain 15834. Transformation was confirmed by mannopine detection. These cultures displayed the typical characteristics of hairy root cultures, with the sole exceptions of slow growth in hormone-free medium and accelerated growth on medium containing phytohormones. All root cultures examined formed forskolin and its derivatives in amounts ranging from 500 to 1300 mg/kg dry weight, corresponding to about 4 to 5 mg/l. During cultivation roots could be cut into small pieces without affecting growth and forskolin production. Scale-ups of the cultivation procedure were performed in 20-l glass jars with a working volume of 10 to 13l. Forskolin production in bioreactors was better than in shake flasks. Levels of almost 14 mg/l could be reached after 21 d of cultivation. As in the shake flask experiments cutting the roots did not affect growth or productivity in a negative way.     

Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter

Summary The aim of the present study was to answer the question whether amines other than 5-hydroxytryptamine (5-HT) and tryptamine act as substrates of the platelet 5-HT transporter. To this end, a large number of tryptamines, 5-HT receptor agonists and phenethylamines (which had IC₅₀ values for ³H-5-HT uptake inhibition of 145–24500 nmol l^–1) was examined in rabbit platelets in order to determine their ability to induce an outward transport of ³H-5-HT Platelets (the MAO of which was blocked) from reserpine-pretreated animals were loaded with ³H-5-HT and then exposed for 5 min to various concentrations (ranging from 0.25 to 40 times the IC₅₀) of each compound. The concentration-effect curves for the drug-induced increase in ³H-5-HT efflux served to determine values of E_max (maximum increase in efflux expressed in % of the ³H-5-HT content of cells) and EC₅₀ (drug concentration producing E_max/2).For the 24 compounds studied here (which included the 5-HT uptake inhibitors imipramine, citalopram, fluoxetine and cocaine) a linear correlation between EC₅₀ and IC₅₀ (r = 0.975) and a mean ratio of EC₅₀/IC₅₀ of 2.4 was found. Most of the compounds [e.g., (±)8-hy-ydroxy-2-(N,N-dipropylamino)tetralin, S(+)-methyl-5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine] gave rise to E_max values (15.8–32.5%) that exceeded that brought about by imipramine (6.6%), indicating that they act as substrates of the 5-HT transporter; the ³H-5-HT outward transport observed in response to these substances was abolished in the presence of imipramine. Others (e.g., 2-methyl-5-HT and 5-methylurapidil) produced Emax values (3.4–14.3%) not significantly different from that of imipramine and, therefore, can be classified either as poor substrates or as inhibitors of the 5-HT transporter.Hence, many tryptamines and 5-HT receptor agonists are substrates of the platelet 5-HT transporter. The property of being substrates gives them the latent capacity to bring about release of endogenous 5-HT and, as a result, to cause indirect 5-HT receptor-mediated effects.Abbreviations MAO monoamine oxidase - 5-HT 5-hydroxytryptamine - 2-M-5-HT 2-methyl-5-HT - N-M-5-HT N-methyl-5-HT - N,N-DM-5-HT N,N-dimethyl-5-HT - S(+)-M-5-HT S(+)-methyl-5-HT - 5-CT 5-carboxamidotryptamine - 5-M-tryptamine 5-methyltryptamine - 5-MO-tryptamine 5-methoxytryptamine - 7-M-tryptamine 7-methyltryptamine - N-M-tryptamine N-methyltryptamine - N,N-DM-tryptamine N,N-dimethyltryptamine - N,N-DM-5-MO-tryptamine N,N-dimethyl-5-methoxytryptamine - (±)8-OH-DPAT (±)8-hydroxy-2-2-(N,N-dipropylamino)tetralin - 5-M-urapidil 5-methyl-urapidil Send offprint requests to R. Wölfel at the above address     

The release profiles of intact and enzymatically digested hyaluronic acid from semisolid formulations using multi-layer membrane system.

A multi-layer membrane system was used to measure in vitro release of hydrophilic macromolecules such as hyaluronic acid (HA) from semisolid formulations. One enzymatically digested HA-derivative with molecular mass of 22 kDa (HA-D) and 1200 kDa intact HA (HA) were incorporated into three semisolid formulations: water-containing hydrophilic ointment (WHO), amphiphilic cream (AC) and water-containing wool wax alcohol ointment (WWO). Because of the high hydrophilic properties of HA-D and HA, the artificial model membranes consisted of collodion as the matrix and glycerol as the hydrophilic acceptor phase. The area under the concentration-time curve and the mean dissolution time were used as a quantitative parameter to characterise the rate and extent of release in vitro. This study showed that the HA-D and HA release as hydrophilic substances from WHO was higher than both from AC and WWO. It was observed that 83% of HA-D1 was released from WHO after 2 h; in contrast, only 10% was released from 2% HA from the same vehicle during the same time. In conclusion, the in vitro availability of enzymatically digested HA-D was higher for WHO than for the other formulations, AC and WWO. Similarly, the availability of HA-D was higher than that of HA from the same formulations.     

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer.

PURPOSE: To evaluate treatment outcome of 3D conformal high dose rate (HDR) brachytherapy and external beam irradiation (EBRT) combined with temporary androgen deprivation for patients with localized prostate cancer. PATIENTS AND METHODS: Between January 1997 and September 1999 we treated 102 patients with stage T1-3 N0 M0 prostate cancer. Stage T1-2 was found in 71, T3 in 31 patients. Median pretreatment PSA level was 15.3 ng/ml. After ultrasound-guided transrectal implantation of four afterloading needles, CT based 3D brachytherapy planning was performed. All patients received four HDR implants using a reference dose per implant of 5 or 7Gy. Time between each implant was 14 days. After brachytherapy EBRT followed up to 39.6 or 45.0 Gy. All patients received temporary androgen deprivation, starting 2-19 months before brachytherapy, ending 3 months after EBRT. RESULTS: Median follow-up was 2.6 years (range 2.0-4.1 years). Actuarial biochemical control rate was 87% at 2 years and 82% at 3 years. In 14 patients we noted biochemical failure, in five patients clinical failure. Overall survival was 90%, disease specific survival 98.0% at 3 years. Acute grade 3 toxicity occurred in 4%, late grade 3 toxicity in 5%. One patient developed a prostatourethral-rectal fistula as late grade 4 toxicity. The conformal quality of 300 HDR implants was analyzed using dose volume histograms. CONCLUSIONS: 3D conformal HDR brachytherapy and EBRT combined with temporary androgen deprivation is an effective treatment modality for prostate cancer with minimal associated toxicity and encouraging biochemical control rates after a median follow-up of 2.6 years.     

Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.