Mindfulness vs psychoeducation in adult ADHD: a randomized controlled trial.

BACKGROUND: Mindfulness training is a promising treatment approach in adult ADHD. However, there has not yet been a randomized controlled trial comparing mindfulness to an active control condition. In this study, we assessed the efficacy of a mindfulness training program (MAP) compared to structured psychoeducation (PE). METHODS: After randomization 81 medication-free adult ADHD patients participated either in an 8-week MAP or PE group program. At baseline (T1), after 8 weeks (T2) and after 8 months (T3), severity of ADHD and associated symptoms (depression, general psychopathology, quality of life) were measured with the Conner's ADHD Rating Scales (CAARS), the Beck Depression Inventory (BDI), the Brief Symptom Inventory (BSI) and the SF-36 by self and blind observer ratings. RESULTS: Both groups showed significant pre-post improvements in observer-rated Inattention scale (p < .001, partial η2 = 0.18) and in associated symptomatology, which persisted through 6 months of follow-up. There were no significant differences regarding symptom reduction between the treatment groups. Women benefited more compared to men irrespective of treatment group. Men showed the most pronounced changes under MAP. CONCLUSIONS: In the current study, MAP was not superior to PE regarding symptom reduction in adult ADHD. Both interventions, mindfulness meditation and PE, were efficacious in reducing symptom load in adult ADHD. Furthermore in exploratory post hoc tests the study provides evidence for a potential gender-specific treatment response in adult ADHD.

Childhood craniopharyngioma - changes of treatment strategies in the trials KRANIOPHARYNGEOM 2000/2007.

BACKGROUND: Prognosis in childhood cranio-pharyngioma, is frequently impaired due to sequelae. Radical surgery was the treatment of choice for decades. Even at experienced facilities radical surgery can result in hypothalamic disorders such as severe obesity. OBJECTIVE: We analyzed, whether treatment strategies for childhood craniopharyngioma patients recruited in GPOH studies have changed during the last 12 years. MATERIALS AND METHODS: We compared the grade of pre-surgical hypothalamic involvement, treatment, degree of resection and grade of surgical hypothalamic lesions between patients recruited in KRANIOPHARYNGEOM 2000 (n=120; 2001-2007) and KRANIOPHARYNGEOM 2007 (n=106; 2007-2012). RESULTS: The grade of initial hypothalamic involvement was similar in patients treated 2001-2007 and 2007-2012. The realized treatment was more radical (p=0.01) in patients recruited 2001-2007 (38%) when compared with patients treated 2007-2012 (18%). In patients with pre-surgical involvement of anterior/posterior hypothalamic areas, the rate of hypothalamus-sparing operations resulting in no (further) hypothalamic lesions was higher (p=0.005) in patients treated 2007-2012 (35%) in comparison with the 2001-2007 cohort (13%). Event-free-survival rates were similar in both cohorts. CONCLUSIONS: A trend towards less radical surgical approaches is observed, which was accompanied by a reduced rate of severe hypothalamic lesions. Radical surgery is not an appropriate treatment strategy in patients with hypothalamic involvement. Despite previous recommendations to centralize treatment at specialized centers, a trend towards further decentralization was seen.

Systemic Chemotherapy using FLOT - Regimen Combined with Cytoreductive Surgery plus HIPEC for Treatment of Peritoneal Metastasized Gastric Cancer. .

BACKGROUND/AIMS: The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer. METHODOLOGY: Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2. RESULTS: All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival. CONCLUSION: Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

[Regional coordination of paediatric oncological care in northwestern Lower Saxony, Germany--network funded by health insurance companies]. / Verbund PädOnko Weser-Ems--Regionale ambulante Versorgung pädiatrisch-onkologischer Patienten aus der Weser-Ems-Region im Rahmen einer Integrierten Versorgung.

The cure rates in pediatric oncology have been substantially improved due to standardized treatment strategies and centralization of therapy. Close clinical and hematological monitoring is mandatory for patients between periods of chemotherapy for early detection and treatment of therapy-related complications such as infections. This results in frequent and time-consuming outpatient examinations for the patient and family at the oncological center in order to evaluate clinical condition and hematological findings. In widespread regions such as the Weser-Ems area in northwest Lower Saxony, Germany, the long distances between patients' home and the oncological center lead to higher risks and impairment of quality of life (QoL) for the patients and their families. Accordingly, in 2001 pediatric hospitals and practices, patient care services and patients' support groups in Weser-Ems founded a network (Verbund PädOnko Weser-Ems). The "Verbund PädOnko" aims at coordinated, high-quality regional outpatient patient treatment in order to reduce risks of long-distance transports to reach the oncological center. Since 2005 a newly established mobile care team realized 1 443 home visits covering a total of 150 300 km. Since 2007 the network has been funded by health insurance organisations. Internal and external benchmarking was performed showing that the rate of short term inpatient treatments were reduced. Treatment quality was assured and the QoL of the patients and their families was improved through the work of the network. The "Verbund PädOnko Weser-Ems" network represents a promising prototype model for the regional coordination of outpatient treatment and care of patients with rare diseases in wide spread areas.

Vitamin D3 deficiency enhances contact hypersensitivity in male but not in female mice.

To ascertain the influence of vitamin D3 and its metabolites on the function of the skin immune system and the induction of the contact hypersensitivity (CHS) response, a population of vitamin D3-deficient BALB/c mice was established, through dietary vitamin D3 restriction and limitation of exposure to UVB irradiation. Vitamin D3 normal female mice had higher CHS responses than their male counterparts, and dietary vitamin D3 deficiency significantly increased the CHS responses in male, but not in female, mice. This change in the vitamin D3-deficient male mice was not due to an alteration in skin dendritic cell function including antigen carriage, migration or costimulatory molecule expression. In addition, 18 h after sensitisation, the lymph node populations in the vitamin D3-deficient and normal male mice showed similar proliferation and IFN-gamma production. However, during the sensitisation phase of CHS, there was lower lymphocyte recruitment to the skin draining lymph nodes of the vitamin D3-deficient and normal male mice compared with their female counterparts which could account for the difference between the sexes in the extent of the CHS response. These results indicate the vitamin D system can influence cutaneous immune responses in male mice, but this did not occur through the modulation of the dendritic cell functions analysed.

Effect of UV radiation on the neonatal skin immune system- implications for melanoma.

The neonatal immune environment and the events that occur during this time have profound effects for the adult period. While protective immune responses can develop, the neonatal immune system, particularly the skin immune system (SIS), tends to promote tolerance. With this information we undertook a number of studies to identify unique aspects of skin during the neonatal period. Proteomics revealed proteins uniquely expressed in neonatal, but not adult, skin (e.g. Stefin A, peroxiredoxins) and these may have implications in the development of SIS. Vitamin D was found to have a modulating role on SIS and this was apparent from the early neonatal period. Exposure of the neonatal skin to UV radiation altered the microenvironment resulting in the generation of regulatory T cells, which persisted in adult life. As the development of UV radiation-induced melanoma can occur following a single high dose (equivalent to burning in adults) to transgenic mice (hepatocyte growth factor/scatter factor or TPras) during the neonatal period, the early modulating events which lead to suppression may be relevant for the development of UV radiation-induced human melanoma. Any attempt to produce effective melanoma immunotherapy has to accommodate and overcome these barriers. Margaret Kripke's pioneering work on UV-induced immunosuppression still remains central to the understanding of the development of melanoma and how it frequently escapes the immune system.

[Improvement in stroke care in a non-urban community hospital--quality of procedures before and after participating in a telemedical stroke network]. / Verbesserung der Schlaganfall-Behandlung in einem regionalen Versorgungskrankenhaus--Prozessqualität vor und nach Einbindung in ein telemedizinisch unterstütztes Schlaganfall-Netzwerk.

BACKGROUND: Although treatment in a stroke unit has been proven to be effective, most stroke patients in rural areas have no access to it. The community hospital of Ebersberg (Bavaria/Germany) joined the Telemedic Project for Integrative Stroke Care (TEMPiS) in order to optimize the quality of stroke care. This analysis focuses on changes in stroke management using generally accepted indicators for quality of acute stroke treatment. METHODS: The core elements consisted of the setting up of a stroke ward in the community hospital, continual stroke education and a 24-hour telemedical consultation service offered by stroke centers. Treatment of stroke patients was documented during two 12-months periods before the project was started start (i.e. retrospectively) and during the course of the project (prospectively). In addition, data on fatal outcome and institutionalization of patients who had lived at home before the qualifying event were collected 12 months after stroke onset. RESULTS: There were 299 admissions for stroke or transient ischemic attacks between 1 Nov 2001 and 31 Oct 2002, and 305 between 7 July 2003 and 6 June 2004. Length of in-hospital stay decreased from 12.1 to 9.2 days. More patients (10.3 vs. 1.3%) were transferred to other acute hospitals during the later period. Indicators for stroke care quality improved: numbers of cerebral imaging rose from 56.5% to 96.4%, of duplex sonography of cervical arteries from 43.5 to 72.8 %, of speech therapy from 0% to 50.8% and of occupational therapy from 0 to 33.4%. One year after admission, 18.9% and 17.2%, respectively, of the patients had died, while 10.2% and 6.1% were living in institutions. CONCLUSION: Participation in the TEMPiS network substantially improved stroke care quality according to national and international guidelines. These improvements may lead to a better prognosis after a stroke.

[Are there predictors for proliferative retinopathy of prematurity and is supplemental oxygen a useful conservative treatment option?]. / Gibt es Prädiktoren für proliferierende Stadien der Retinopathia praematurorum und ist eine Sauerstoffsupplementation als konservative Therapiemöglichkeit sinnvoll? Eine Analyse anhand des eigenen Patientenguts.

BACKGROUND: Especially very immature preterm babies develop retinopathy of prematurity (ROP). This study aims at analysing risk factors for proliferative ROP and realizing the efficiency of supplemental oxygen therapy. PATIENTS: 180 preterm babies with birth weight < or = 1 500 grams were included retrospectively. METHODS: To determine potential predictors all preterm babies with ROP grade > or = 3 were matched to pairs with similar immature babies with ROP 1 or 2. Additionally we examined the influence of supplemental oxygen therapy on the coagulation rate of high grade retinopathy. RESULTS: 44 % of the preterm babies showed ROP. A longer duration of ventilation (21 vs. 33 days), a longer duration of oxygen supplementation (59 vs. 78 days), relapsing sepsis (10 vs. 19 babies with sepsis > 2 times), a large total volume of transfusions (median: 150 mL vs. 105 mL), chronic lung disease (CLD) (6 vs. 15 babies with oxygen requirements at 36 weeks post-menstrual age), a duration of intubation for more than 28 days (13 vs. 6 babies) and the lack of phototherapy (21 vs. 9 babies) were risk factors associated with ROP > or = 3 using univariate analysis [p < 0.05]. Only the both last criteria correlated with high grade ROP after logistic regression. The supplemental oxygen therapy showed no influence on the coagulation rate of high grade ROP. Possibly this therapy influences the frequency of surgical treatment of amotio- and of putting on a cerclage, but this remains still speculative because of the low case number. We saw no negative effect on the frequency of CLD and on the survival of the babies. CONCLUSIONS: Especially measures against long duration of intubation could help to prevent high grade ROP. The supplemental oxygen therapy may have a positive effect on course.

Differential diagnosis of suprasellar tumors in children.

In contrary to the adult age the most common suprasellar tumors in children are with decreasing frequency craniopharyngiomas, chiasmatic/hypothalamic low-grade gliomas, germinomas and lesions attributable to a Langerhans cell histiocytosis. For differential diagnostic purposes also the rare hypothalamic hamartoma and meningeal metastases in the infundibular recess of the third ventricle are included. The typical aspects of the various tumors on computed tomography (CT) and magnetic resonance imaging (MRI) together with important clinical differences are illustrated. On the basis of imaging results and clinical symptoms differential diagnosis between the various tumor entities should be feasible in many cases. Of course, only in strictly defined cases like typical chiasmatic/hypothalamic and optic pathway gliomas or bilocular germ cell tumors a histological confirmation is dispensable.

Prognosis and sequela in patients with childhood craniopharyngioma -- results of HIT-ENDO and update on KRANIOPHARYNGEOM 2000.

The overall survival rate of patients with craniopharyngioma, an embryogenic malformation, is high (0.92 +/- 0.03). However, there is considerable morbidity and impaired quality of life, even when the tumor can be completely resected. Aim of our study was to analyze risk factors for severe obesity (body mass index [BMI] > or = 7 SD) and the prognosis of severely obese survivors of childhood craniopharyngioma recruited in our cross-sectional study on 183 patients (HIT-ENDO) and in the prospective study KRANIOPHARYNGEOM 2000. Severe obesity (BMI > or = 7 SD) was present in 16 % of patients and associated with higher tumor volume (p < 0.05), more frequent neurosurgical interventions (p < 0.05) and a higher rate of hypothalamic involvement (p < 0.001). Self-assessed functional capacity (FMH) was lower (p < 0.001) in severely obese survivors (FMH: median 33, range: 4-64) when compared with normal weight patients (FMH: 50; 1-95). Overall survival (20 years) was lower (p = 0.034) in patients with severe obesity in comparison to patients with moderate obesity and normal weight. Cardiovascular morbidity and mortality was high in severely obese patients. Between 10/01 and 03/04 fifty-seven patients (27 female/30 male) were recruited in KRANIOPHARYNGEOM 2000 (www.kraniopharyngeom.com). The impact of tumor localization (3.2 % intrasellar, 22.6 % suprasellar, 74.2 % combined intra/suprasellar; 51.6 % hypothalamic involvement) and treatment (26 complete resections, 22 partial resections followed by irradiation in one case; primary irradiation after biopsy in one case) on quality of life, functional capacity and prognosis will be evaluated longitudinally and prospectively.

[Long-term treatment of phantom- and stump pain with Botulinum toxin type A over 12 months. A first clinical observation]. / Langszeitbehandlung von Phantom- und Stumpfschmerzen mit Botulinumtoxin Typ A über 12 Monate. Eine erste klinische Beobachtung.

Recently we were able to describe the successful treatment of phantom pain and stump pain with botulinum toxin A in a first pilot study. This case report over a 1-year period now demonstrates that long-term treatment for this indication is possible. We injected 4 x 25 IU of botulinum toxin A (Botox) into trigger points of the stump muscles of a lower limb amputee who suffered from severe phantom and stump pain. With four injections performed every 3 months, the patient became almost completely pain-free, and his intrathecal morphine therapy could be reduced to 40% of the initial dose. Intrathecal clonidine was eliminated completely, as were the oral analgesics. A surgical treatment suggested for the stump pain was no longer necessary, and we suppose that botulinum toxin can also improve the tolerance of artificial limbs in cases of stump pain.

Cytoreductive surgery plus intraperitoneal hyperthermic perfusion is an effective treatment for metastasized malignant mixed mesodermal tumours (MMMT)--report of six cases.

BACKGROUND: Malignant mixed mesodermal tumours (MMMT) of the female genital tract are rare and heterogeneous malignancies that impart grim prognosis. These tumours are characterized by an admixture of malignant epithelial and stromal elements comprising carcinomatous and sarcomatous neoplastic cells. Thus far, almost 350 cases of MMMT have been recorded in the international medical literature. Due to its rarity, there is no agreement on the best treatment strategy in women with metastasized MMMT. METHODS: Six women (mean age 59 years) with metastasized MMMT defined to the peritoneal cavity have been treated by cytoreductive surgery plus hyperthermic peritoneal perfusion plus postoperative adjuvant chemotherapy. All patients have been pre-treated by surgery for primary tumour and one by systemic chemotherapy. As cytostatics for hyperthermic peritoneal perfusion, we have used Mitomycin in a dosage of 18 mg/m2 plus Melphalan in a dosage of 25 mg/m2. As adjuvant treatment CDDP 40 mg/m2/dl, Mitomycin 7 mg/md2/dl and Ifosfamid 100 mg/kg 24 h/dl was applicated via intraaortic catheter three times with a treatment free interval of 3 weeks. RESULTS: A complete cytoreduction without remnant tumour formations in the peritoneal cavity could be carried out in all six patients. The postoperative course was uneventful in all cases except for one where a spontaneous small bowel perforation and prolonged gall secretion had to be treated by re-operation. One patient died 4 months later by pneumonia without evidence of disease. Four patients are without evidence of disease after 2, 4, 14 and 19 months, whereas one patient developed liver metastases after 9 months still treated by systemic chemotherapy. CONCLUSION: Complete cytoreduction plus hyperthermic peritoneal perfusion plus adjuvant chemotherapy seems to be an effective treatment for recurrent or metastasized MMMT. Further studies have to define the value of this new treatment strategy for this rare tumour entity.

Repetitive chemoembolization with melphalan plus intra-arterial immuno-chemotherapy within 5-fluorouracil and granulocyte-macrophage colony-stimulating factor (GM-CSF) as effective first- and second-line treatment of disseminated colorectal liver metastases.

BACKGROUND/AIMS: In order to improve local and systemic efficacy of chemotherapeutic interventions we have used a combination of high concentrated plus low continuous regional chemotherapy modulated by GM-CSF cytokine in the treatment of inoperable colorectal liver metastases. METHODOLOGY: Sixty-six patients with disseminated inoperable colorectal liver metastases received continuous intra-arterial chemotherapy with 5-FU plus GM-CSF short time application plus chemoembolization Melphalan via an angiographically positioned hepatic artery catheter. The regimen consisted of the following steps: On day 1 + 2 1400 mg/m2 5-FU administered intra-arterially in a continuous circadian mode, 60 mg/m2 Rescuvolin given i.v. as a 2-hour infusion, 80 micrograms/m2 GM-CSF given i.a. as a 1-hour infusion, day 3 chemoembolization with 25 mg/m2 Melphalan plus Lipiodol and Gelfoam. RESULTS: 66 patients (38 male/28 female) with a median age of 60.4 years and a median Karnofsky index of 87.3 were treated with 299 cycles of immunochemoembolization. Fifty-four percent of these patients had received prior systemic chemotherapy. Side effects were manifested in all patients, mainly upper abdominal pain lasting one to four days and grade 1 or 2 vomiting. Systemic side effects were mild and transient with a very low rate of leukopenia. Using World Health Organization response criteria, the following responses could be demonstrated CR 1.0%, PR 42.4%, MR 24.2%, SD 18.2%, NR 12.1%. Time to progression was 8 months. Median survival has not been reached after an observation time of 28 months. Two-year survival was 66%. There was no statistically significant difference between chemonaive patients and patients pretreated by any kind of systemic therapy. CONCLUSIONS: Repetitive high concentrated regional chemotherapy by use of chemoembolization combined with continuous administered 5-FU and supplemented with GM-CSF is an effective tool in the therapy of disseminated colorectal liver metastases as front line as well as a second-line treatment.

Functional capacity, obesity and hypothalamic involvement: cross-sectional study on 212 patients with childhood craniopharyngioma.

The aim of this study was to analyze the impact of hypothalamic involvement of craniopharyngioma on functional capacity (FC) and obesity in 212 patients with childhood craniopharyngioma. FC could be evaluated using an ability scale (Fertigkeitenskala Münster-Heidelberg [FMH]) in 174 patients with childhood craniopharyngioma. Obesity was quantified in 212 patients at the time of diagnosis and at the time of latest evaluation by body mass index SDS [BMI]. The influence of hypothalamic tumor involvement on FC and BMI was analyzed. Patients with hypothalamic involvement (n = 125) presented with higher BMI SDS at the time of diagnosis (p = 0.001) and at latest follow-up evaluation (p < 0.001). FC as measured by FMH percentiles was lower (p < 0.001) in patients with hypothalamic involvement when compared with patients without hypothalamic involvement. FC negatively correlated (p < 0.001) with BMI SDS (Spearman's Rho = -0.40) only in patients with hypothalamic involvement whereas no correlation between FC and BMI SDS was found in patients without hypothalamic involvement. We conclude that hypothalamic involvement of childhood craniopharyngioma had major impact on FC in survivors. Obesity resulted in impaired FC of patients with hypothalamic involvement. BMI at diagnosis was a sensitive parameter to identify patients at risk of severe obesity. Further analysis on this issue is performed in the prospective, multicenter surveillance study on children and adolescents with craniopharyngioma (KRANIOPHARYNGEOM 2000).

Serum cholesterol predictive equations in product development.

The aim of the study was to incorporate trans fatty acids into predictive equations for serum cholesterol and compare their effects with the effects of the individual saturated fatty acids 12:0, 14:0 and 16:0. We have introduced trans fatty acids from partially hydrogenated soybean oil (TransV) and fish oil (TransF) into previously published equations by constrained regression analysis. Prior knowledge about the signs and ordering of existing regression coefficients were incorporated into the regression modelling by adding lower and upper bounds to the coefficients. Oleic acid (18:1) and polyunsaturated fatty acids (18:2, 18:3) were not sufficiently varied in the studies and the respective regression coefficients therefore set equal to those found by Yu et al. (Am J Clin Nutr 1995;61:1129-39). Stearic acid (18:0) considered to be neutral was not included in the equations. The regression analyses were based on results from four controlled dietary studies with a total of 95 participants and including 10 diets differing in fatty acid composition. The analyses resulted in the following equations where the change in cholesterol is expressed in mmol/L and the change in intake of fatty acids is expressed in E%: Delta Total cholesterol = 0.01 delta(12:0) + 0.12 Delta(14:0) + 0.057 delta(16:0) + 0.039 delta(TransF) + 0.031 delta(TransV)- 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3) and deltaLDL cholesterol = 0.01 delta(12:0) + 0.071 delta(14:0) + 0.047 delta(16:0) + 0.043 delta(TransF) + 0.025 delta(TransV) - 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3). The test set used for validation consisted of 22 data points from seven recently published dietary studies. The equation for total cholesterol showed good prediction ability with a correlation coefficient of 0.981 between observed and predicted values. The equation has been used to reformulate margarines into "trans free" products all with more favourable effects on serum cholesterol than previous products. Also a cholesterol reducing margarine has been produced. When tested against butter in an open clinical trial among subjects with mild hypercholesterolemia the observed cholesterol-lowering effect of this margarine corresponded reasonably well with the predicted (0.77 vs. 0.64 mmol/L). We conclude that the equation has practical applicability and can be used to formulate and nutritionally optimise fat products as well as to evaluate already existing products on the market.

Lake Constance--a model for integrated lake restoration with international cooperation.

Lake Constance is the second largest prealpine European lake. Its international catchment area lies in the territories of the four European countries Austria, Germany, Liechtenstein and Switzerland. Since the fifties, a significant degradation of its state was observed as a result of the pollutants of more than 1.2 million inhabitants in its catchment area. To counteract this negative development, international cooperation was realized in the International Commission for the Protection of Lake Constance (IGKB). Thereby the phosphorus concentration in the lake water, after a maximum value of 87 mg/m3 phosphorus in 1979, was reduced to 13 mg/m3 until 2001. To prevent the negative effects of unfavourable climatic conditions resulting in an incomplete vertical circulation, the concentration of phosphorus must be reduced to 10 mg/m3. Crucial points in future are to sustain the present successes in lake protection, to reduce existing loads as much as possible, to compensate for loads which are not avoidable and to avoid future loads. A sustainable use of the lake is ensured only by an intact lake ecosystem.

Facilitation of learning and modulation of frontal cortex acetylcholine by ventral pallidal injection of heparin glucosaminoglycan.

We examined the effects of heparin on learning and frontal cortex acetylcholine parameters following injection of the glucosaminoglycan into the ventral pallidum. In Experiment 1, possible mnemoactive effects of intrapallidal heparin injection were assessed. Rats with chronically implanted cannulae were administered heparin (0.1, 1.0, 10 ng) or vehicle (0.5 microl) and were tested on a one-trial step-through avoidance task. Two retention tests were carried out in each animal, one at 1.5 h after training to measure short-term memory and another at 24 h to measure long-term memory. Post-trial intrapallidal injection of 1.0 ng heparin improved both short- and long-term retention of the task, whereas the lower and the higher dose of the glucosaminoglycan had no effect. When the effective dose of heparin was injected 5 h, rather than immediately after training, it no longer facilitated long-term retention of the conditioned avoidance response. In Experiment 2, the effects of ventral pallidal heparin injection on frontal cortex acetylcholine and choline concentrations were investigated with in vivo microdialysis in anaesthetized rats. Heparin, administered in the dose of 1.0 ng, which was effective in facilitating avoidance performance, produced a delayed increase in cortical acetylcholine levels ipsi- and contralaterally to the side of intrabasalis injection, resembling the known neurochemical effects obtained for another glycosaminoglycan, chondroitin sulfate, which recently was shown to facilitate inhibitory avoidance learning and to increase frontal cortex acetylcholine. The present findings indicate that heparin, like other extracellular matrix proteoglycans, can exert beneficial effects on memory and strengthen the presumptive relationship between such promnestic effects of proteoglycans and basal forebrain cholinergic mechanisms. The data are discussed with respect to the presumed roles of matrix molecules in extrasynaptic volume transmission and in the 'cross-talk' between synapses.