Correlation between structural changes and acute thrombogenicity in transcatheter pericardium valves after crimping and balloon deployment.

INTRODUCTION: Transcathether heart valve replacement has gained considerable acceptance during the last decades. It is now part of the armamentarium for aortic valve replacement. The procedure proved to be highly efficient. However the issues of the blood compatibility and tissue durability were not raised and the adverse events were probably under-reported, according to observations of thrombosis after deployment. MATERIAL AND METHOD: Bovine pericardium leaflets were sewn inside a 26mm diameter stainless steel stent to manufacture these valves (one control and two experimental). The correlation between the trauma and the acute thombogenicity of bovine pericardium leaflets, after crimping and ballooning, was investigated via an in vitro blood flow with labeled platelets. These leaflets were processed for histology: scanning electron microscopy, light microscopy, and transmission electron microscopy. RESULTS: The control specimens showed a regular pericardium structure with some blood cells deposited on the collagen fibrous surface (inflow) and scarce blood cells deposited on the serous surface (outflow). After crimping and ballooning, the structure of the pericardium was severely injured, eventually with delaminations and ruptures. The blood cell uptake was considerably increased compared to the control. CONCLUSION: It would therefore be appropriate to pay more attention to the design of the valves. Specifically, the incorporation of a buffer tissue or fabric between the pericardium and the metallic stent is suggested. The issue of ballooning deserves detailed and in depth investigation regarding the lifetime of the device.

Pharmacokinetics and safety of an 8 week continuous treatment with once-daily versus twice-daily inhalation of tobramycin in cystic fibrosis patients.

OBJECTIVES: We evaluated the pharmacokinetics, safety and tolerability of two different continuous treatment regimens of tobramycin inhalation solution (TIS) in 29 cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. PATIENTS AND METHODS: In this randomized, multicentre, open-label, two-period crossover study, TIS (300 mg/5 mL) was administered via PARI eFlow(®) rapid once daily and twice daily each for 8 weeks. Serum pharmacokinetics of these two regimens was analysed. Tobramycin levels were determined before the morning dose and at 30, 60 and 90 min after the end of nebulization in the middle and at the end of each 8 week cycle. At these timepoints, trough and peak serum tobramycin concentrations (Cmax, mg/L) as well as the area under the curve for 0-90 min of tobramycin (AUC0-90min) were assessed in order to evaluate the risk of systemic toxicity. Safety parameters and forced expiratory volume in 1 s (FEV1) were assessed. RESULTS: For once-daily treatment, tobramycin levels were 10% higher after 8 weeks compared with 4 weeks (AUC0-90min ratio = 1.096, 90% CI = 0.860-1.396, P = 0.5237). For twice-daily treatment, tobramycin levels after 8 weeks showed a 40% decrease compared with 4 weeks (AUC0-90min ratio = 0.608, 90% CI = 0.461-0.802, P = 0.0055). The AUC0-90min ratio at 8 weeks (once daily versus twice daily) did not differ significantly (AUC0-90min ratio = 0.749, 90% CI = 0.514-1.092, P = 0.2009). The mean FEV1 did not differ markedly compared between treatment periods or with baseline. No audiological or nephrotoxic side effects were noted. CONCLUSIONS: Continuous treatment with TIS (once daily or twice daily) over 8 weeks appears to be safe and tolerable.

[Function of oesophagus and gastro-oesophageal reflux in patients with cystic fibrosis]. / Funktion der Speiseröhre und gastroösophagealer Reflux bei Patienten mit zystischer Fibrose.

Gastro-oesophageal reflux (GER) has a special meaning for patients with cystic fibrosis (CF). Twelve voluntary patients with CF up to the age of 25 underwent an oesophageal manometry and a 24-hour impedance-pH monitoring. These patients were without symptoms of GER. The examination proved an acid GER in 42 %. In the total population the frequency is ≤ 10 %. In 11 of 12 patients a pathologically low pressure of the lower oesophageal sphincter (LES) was found. No significant correlations between the DeMeester score and the pressure of the LES, the reflux and respiratory symptomatology, the lung function as well as the quality of life could be proven. However, there was a significant correlation between the DeMeester score and the acid clearance time. 37 % of the registered cough pushes were related to a GER, of which 78 % were associated with an acid GER. Therefore, coughing in patients with CF must not necessarily be caused by the underlying disease. The timely detection of a pathological GER in patients with CF, but without symptoms of GER, and its prompt therapy could protect the lung function.

High dose methotrexate treatment in childhood ALL: pilot study on the impact of the MTHFR 677C>T and 1298A>C polymorphisms on MTX-related toxicity.

Methotrexate (MTX) is commonly administered in high doses for treatment of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to study the influence of 2 common MTHFR polymorphisms (MTHFR 677C>T and 1298 A>C) on MTX toxicity in children with ALL.Retrospective analysis of 129 MTX courses in 34 pediatric patients with ALL.677C>T variants (CT or TT) were found in 19 (14 heterozygous, 5 homozygous) and 1298A>C variants (AC or CC) in 20 (16 heterozygous, 4 homozygous) patients. The MTHFR 677C>T wild type was associated with an increased frequency of grade III and IV leukopenia (60% vs. 31%, p<0.05) compared to the variants. The rate of severe infections (21% vs. 0%, p<0.05) and grade III-IV anemia (26% vs. 5%, p<0.05) was increased in carriers of the MTHFR 677C>T wild type compared to patients with the TT variant. Grade III-IV anemia was more frequent in patients with the MTHFR 1298A>C CC variant compared to the wild type (56% vs. 21%, p<0.05). The differences were not significant in a patient-based analysis.MTX related toxicity might be influenced by the MTHFR 677C>T or the MTHFR 1298A>C polymorphisms. Differences in MTX toxicity are only partially explainable by these 2 polymorphisms.

Management of oncology patients admitted to the paediatric intensive care unit of a general children's hospital - a single center analysis.

BACKGROUND: The improving prognosis of children with cancer has partially been attributed to the increasing importance of pediatric intensive care units (PICU). We analyze whether outcome of these patients on a PICU improved during the last decade and which factors may influence the outcome in our hospital. PATIENTS AND METHODS: The charts of all oncology patients admitted to the PICU between 1998 and 2009 have been reviewed retrospectively. The survival of patients admitted for life threatening complications has been correlated with basic data, organ failure and the PRISM score. The results of 2 consecutive treatment periods (1998-2003 and 2004-2009) were compared. RESULTS: 644 admissions of 226 patients were recorded. 79 admissions were performed because of potentially life threatening complications (Group A), 236 for monitoring (B) and 329 admissions for interventions (C). 62% of Group A patients and all Group B and C patients were discharged alive. Poor outcome was associated with admission >28 days after initial diagnosis, PRISM >10, organ failure >2 organs, sepsis, allogeneic stem cell transplantation, need for mechanical ventilation or for catecholamines. The PICU survival rate of Group A patients admitted between 2004 and 2009 (78%) was higher than in the period between 1998 and 2003 (48%). CONCLUSIONS: PICU provides essential services to support the pediatric oncology ward. Although children with cancer may have had benefit from advances in pediatric intensive care over the past decade, specific scoring systems for early identification of children with cancer needing PICU treatment are required. These systems might further improve PICU outcome in critical ill pediatric cancer patients.

[Neonatal infection with Salmonella apapa after contact with a reptile in the home]. / Neugeborenensepsis durch Salmonella apapa nach Reptilienkontakt im Haushalt.

Salmonella apapa is transmitted by reptiles, e.g., bearded dragons. To date only few cases of S. apapa-related human infections have been reported. Because the bacteria are transmitted through the feces of animals or direct contact with low infection doses, infection in early infancy is possible. We report an 18-day-old newborn with sepsis caused by Salmonella apapa. Salmonella apapa was isolated from the feces of a bearded dragon living along with the family.

[Umbilical venous catheters - analysis of malpositioning over a 10-year period]. / Nabelvenenkatheter - Retrospektive Analyse der Nabelvenenkatheterlagen über einen 10-Jahres-Zeitraum.

BACKGROUND: An incorrect position of umbilical venous catheters (UVC) is common and associated with a higher complication rate. PATIENTS AND METHODS: From 2 545 neonates admitted between 1/1999 and 6/2008, 142 with UVC were extracted. The following factors that may influence the frequency of correct placement, bacterial growth on the catheter tip and infection were analysed: gestational age (GA), birth weight (BW), indication, sex, insertion site, insertion period (1999 to 2003 vs. 2004 to 2008) and indwelling time. RESULTS: A central position was reached in 73,2%. The first insertion attempt was successful in 48,6%. The rate of successful insertion was higher in our own department compared to catheter insertions performed elsewhere. 4 life-threatening complications were observed (pericardial and pleural effusion, rupture of the catheter into the liver parenchyma, rupture of the catheter into the abdominal cavity). The risk of bacterial colonisation was associated with lower GA and BW. DISCUSSION AND CONCLUSIONS: The rate of central positioning with UVC is about 75%. Positioning was not influenced by GA, BW, indication, sex or insertion period. Severe complications can occur also in catheters with previous correct position. Because of the higher risk of colonisation and infection with longer indwelling times, the UVC should be removed as soon as possible.

[Immune tolerance induction with high-dose FVIII and pulsed intravenous immunoglobulin]. / Immuntoleranzinduktion mit hoch dosiertem FVIII und intravenösen Immunglobulin-Pulsen. Ein Patient mit Hemmkörper-Hämophilie A.

UNLABELLED: The development of neutralizing allo-antibodies against factor VIII (FVIII) or FVIII inhibitors is a severe complication in the treatment of haemophilia A. About 25% of the children with severe haemophilia A develop FVIII inhibitors. Here we report on a boy with severe haemophilia A and intron 22 inversion of the FVIII gene who was diagnosed at ten months of age. After 16 exposure days to FVIII (81 days after initial exposure) he developed a FVIII inhibitor (maximum: 9.76 BU/ml). THERAPY: We started immune tolerance induction (ITI) according to the Bonn protocol with high dose plasma derived FVIII concentrate (100 IU per kg body weight) twice daily. For additional inhibitor elimination treatment the patient received intravenous immunoglobulin (ivIg) at a dose of 1-2 g/kg body weight every 4 to 6 weeks. After start of treatment a rapid decline of the inhibitor level was observed, nevertheless low FVIII inhibitor levels persisted (<5 BU/ml). Furthermore, the FVIII half-life was still accelerated. However, after every course of ivIg the inhibitor level declined and FVIII half-life was prolonged. Currently, the FVIII half-life is approaching normal values after more than seven months of ITI duration. CONCLUSION: Additional application of immunoglobulin is beneficial for immune tolerance induction.

Leukapheresis and exchange transfusion in children with acute leukemia and hyperleukocytosis. A single center experience.

BACKGROUND: The risk of severe complications or death during the initial period of acute leukemia was markedly decreased due to the progress in pediatric oncology and use of simple measures like hyperhydration, forced diuresis, treatment of hyperuricemia, correction of electrolyte and coagulation disturbances and the careful use of antileukemic drugs. The incidence of leukostasis and tumor lysis syndrome depends on absolute initial white blood cell counts and the underlying type of leukemia. Leukapheresis or exchange transfusion may improve the prognosis of high risk patients. METHODS: Records of all pediatric patients who were newly diagnosed with acute leukemia between 1 / 1998 und 12 / 2008 were retrospectively reviewed for presence of hyperleukocytosis(white blood cell count > 100 GPT / l) at diagnosis and subsequent leukapheresis or exchange transfusion in regards to the clinical outcome. RESULTS: At diagnosis 11 (14 % ) of 77 children with acute leukemia (7 acute lymphoblastic leukemia / ALL; 4 acute myeloblastic leukemia /AML) had hyperleukocytosis. 4 patients (2 ALL, 2 AML) received exchange transfusion and 2 others (1 ALL, 1 AML) underwent leukapheresis. Marked cytoreduction was achieved in all patients within 24 h after therapy initiation. There were no procedure-related adverse events. Symptoms due to hyperleukocytosis markedly improved after cytoreduction. CONCLUSION: Leukapheresis or exchange transfusion together with conservative management and specific oncological therapy may contribute to rapid leukocyte reduction with acceptable risk. The exact impact of leukapheresis or exchange transfusion on short and long term outcome in pediatric patients with acute leukemia and initial hyperleukocytosis has to be evaluated in future multicentre studies or by the formation of clinical registries.

[Gentamicin intoxication in a preterm infant]. / Gentamicin Intoxikation bei einem Frühgeborenen.

Gentamicin is an aminoglycoside that is widely used in neonatology in spite of its known nephrotoxicity and ototoxicity. Because there are only few cases reported in the literature experience with gentamicin overdosage is limited. We report the case of a preterm (gestational age 32+2 weeks) infant with an accidental administration of a ten-fold dose of gentamicin. The baby was treated with a slight increase of fluid intake and monitoring of renal function and gentamicin levels, respectively. A rapid decrease of the gentamicin level (peak level 44.5 mg/L, extrapolated peak level 65 mg/L) was observed. Nephrotoxicity or ototoxicity did not occur. Because of the small number of described cases, a general recommendation for the management of gentamicin intoxication is not possible. The intensity of treatment depends on renal function and gentamicin level. Only isolated patients will need dialysis or exchange transfusion. The case also demonstrates the need for the continuous discussion about hospital-associated damage and error management systems.

Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients.

Pseudomonas aeruginosa and Staphylococcus aureus are thought to cause the majority of lung infections in patients with cystic fibrosis (CF). However, other bacterial pathogens may contribute to the pathophysiology of lung disease. Here, obligate anaerobes were identified in a cross-sectional study, and cell numbers and antibiotic susceptibilities of facultative and obligate anaerobes from 114 sputum samples from nine children and 36 adults with CF were determined. Furthermore, in 12 CF patients, we investigated whether conventional intravenous antibiotic therapy, administered during acute exacerbations, would affect the numbers of obligate anaerobes. Fifteen genera of obligate anaerobes were identified in 91% of the CF patients. Cell numbers (mean: 2.2 x 10(7) +/- standard deviation 6.9 x 10(7) CFU/mL of sputum sample) were comparable to those of P. aeruginosa and S. aureus. Staphylococcus saccharolyticus and Peptostreptococcus prevotii were most prevalent. Infection with P. aeruginosa did not increase the likelihood that obligate anaerobes are present in sputum specimens. Single obligate anaerobic species persisted for up to 11 months in sputum plugs in vivo. Patients with and without obligate anaerobes in sputum specimens did not differ in lung function. Intravenous therapy directed against P. aeruginosa during acute exacerbations increased lung function, but did not reduce the numbers of obligate anaerobes. Obligate anaerobic species differed widely in their patterns of resistance against meropenem, piperacillin-tazobactam, clindamycin, metronidazole and ceftazidime. In 58% of patients with acute exacerbations, obligate anaerobes were detected that were resistant to the antibiotics used for treatment. Antibiotic therapy, optimized to target anaerobes in addition to P. aeruginosa, may improve the management of CF lung disease.

[Liver rupture in preterm infants with a gestational age < 28 weeks]. / Leberrupturen bei Frühgeborenen < 28 Schwangerschaftswochen.

BACKGROUND: Liver rupture is a rare complication in preterm infants and may be associated with birth trauma, cardiopulmonary resuscitation, laparotomy or coagulopathies. Only few patients are reported who have survived neonatal liver rupture. The aim of our study was to identify extremely preterm infants with liver rupture during a 6-year period. PATIENTS AND METHODS: All preterm infants < 28 weeks gestational age admitted to the neonatal intensive care unit between 2001 and 2006 were studied retrospectively by chart review and screening of electronic files. RESULTS: All 113 infants admitted to the neonatal intensive care unit during the study period were included. 4 infants with liver rupture were identified. In 3 cases the liver rupture was associated with cardiopulmonary resuscitation. Bleeding control was achieved only in 1 patient. All patients died, 3 because of haemorrhagic shock and 1 because of pneumopericardium. CONCLUSIONS: Liver rupture should considered in neonates with otherwise unexplained hypovolaemia or anaemia. Neonates with a history of cardiopulmonary resuscitation should be evaluated carefully for possible liver injuries.

Determination of terephthalic acid isopropylamide in urine with a liquid chromatography/mass spectrometry (LC/MS) method.

A sensitive and simple liquid chromatography/mass spectrometry (LC/MS) method was developed for the determination of terephthalic acid isopropylamide, the final metabolite of procarbazine in human urine. A solid-phase extraction with C(18) cartridges was used followed by LC/MS with a single mass spectrometer (SSQ 7000 from Finnigan). Terephthalic acid isobutylamide was the internal standard. The quantification limit was 30 ng/mL in urine (6 x noise). This assay was applied for drug monitoring of terephthalic acid isopropylamide in urine after oral administration of procarbazine in children and adolescents with Hodgkin lymphomas.

[Pasteurella multocida as a rare cause of neonatal meningitis]. / Pasteurella multocida als seltener Erreger der neonatalen Meningitis.

Pasteurella multocida (P. multocida), a Gram-negative bacillus is a typical commensal in the oropharynx of animals such as dogs and cats. Human diseases caused by P. multocida are rare and include respiratory infections, sepsis and meningitis. P. multocida infections are described predominantly in patients with underlying chronic disorders, in elderly patients or in infants < or = 1 year. We describe the case of a 3-week-old boy with meningitis due to Pasteurella multocida. P. multocida was also identified in oral swab and stool cultures of the pet cat. A direct contact between baby and cat was negated by the parents. The patient recovered without any neurological sequelae.

[Thrombosis of the iliac artery in a premature neonate: thrombolytic therapy using rt-PA]. / Arteria iliaca-Thrombose bei einem Frühgeborenen: Lysetherapie mit rt-PA.

Thromboembolic events in neonates are very rare. They are often associated with severe disease affecting the newborn or are secondary to central venous lines or arterial catheters. Most of the described cases of thromboses of the iliac or femoral arteries are associated with cardiac catheterisation or femoral invasive blood pressure monitoring. The relationship between single umbilical arteries and an increased incidence of structural and chromosomal anomalies is well known, but a higher rate of thromboembolic disease in infants with single umbilical arteries has not been described. Rt-PA (recombinant tissue plasminogen activator) has been successfully used in small studies and numerous case reports. To date controlled clinical trials giving guidelines for antithrombotic therapy using rt-PA are still lacking. We report the clinical course of a 700 g premature male, who was born by Caesarean section at 29 + 6 gestational weeks. On the fifth day the baby suffered from arterial thrombosis of the right pelvis axis. Antenatally a single umbilical artery was identified. Iliac arteries on the involved site appeared hypoplastic. Additionally, the prothrombin G20210A mutation was found. The patient was treated successfully using recombinant tissue plasminogen activator. In the case of a high risk of limb or organ loss due to arterial thrombosis, thrombolysis using rt-PA is justified. Appropriate rt-PA treatment has been studied for the adult but not the paediatric population. Hence, well-designed clinical trials are necessary to determine the pharmacokinetics and dynamics of thrombolytic agents in children.

Functional properties of cultured endothelial cells derived from large microvessels of human brain.

This report describes the fractional separation of microvessels from human brain for establishment of segmentally derived endothelial cell (EC) cultures. The investigation comprised evaluation of media constituents and purity of the cell culture and focused on functional biochemical characterization of endothelium derived from large microvessels (EC) Cells contained endothelial marker factor VIII (von Willebrand antigen), secreted endothelin-1 (ET-1) and prostaglandins, and took up 86Rb+ as a measure of K+. Exogenous ET-1 stimulated phosphatidylinositol hydrolysis and K+ uptake; BQ-123 (selective ETA receptor antagonist) but not IRL-1038 or BQ-788 (selective ETB receptor antagonists) inhibited both. Ouabain (inhibitor of Na(+)-K(+)-ATPase) and bumetanide (inhibitor of Na(+)-K(+)-Cl- cotransport) reduced (74-80 and 20-40%, respectively) the ET-1-stimulated K+ uptake. Staurosporine [protein kinase C (PKC) inhibitor] selectively reduced Na(+)-K(+)-Cl- cotransport, whereas verapamil but not nifedipine (L-type voltage-dependent Ca2+ channel blockers) decreased Na(+)-K(+)-ATPase activity induced by ET-1. Phorbol 12-myristate 13-acetate (PMA; activator of PKC) stimulated K+ uptake, which was only decreased with bumetanide. N-ethylisopropylamiloride (inhibitor of Na+/H+ exchange) reduced the ET-1-stimulated but not the PMA-induced K+ uptake. Results indicate that phosphatidylinositol hydrolysis and ion transport systems in large microvascular EC are stimulated by ET-1 through activation of ETA receptors. The findings also suggest that the ET-1-stimulated Na(+)-K(+)-ATPase activity, in contrast to Na(+)-K(+)-Cl- cotransport, is not mediated by PKC. In addition, the data suggest a linkage between Na(+)-K(+)-ATPase activity and Na+/H+ exchange.

Interaction between histamine and adenosine in human cerebromicrovascular endothelial cells: modulation of second messengers.

This study demonstrates the presence of histamine H1 and H2 receptors and purinoreceptors A1 and A2 on endothelial cells derived from human brain microvessels (HBEC). Histamine induced formation of both inositol triphosphate (IP3) (EC50 = 10.2 +/- 0.9 microM) and cyclic adenosine monophosphate (cAMP) (EC50 = 5.2 +/- 0.9 microM) in HBEC in a concentration-dependent fashion. IP3 formation was inhibited by H1 receptor antagonists mepyramine maleate and chlorphenyramine, but not by H2 receptor antagonist cimetidine. Production of cAMP was efficiently inhibited by cimetidine. Selective A1 receptor agonists decreased, whereas A2 receptor agonists increased cAMP production in HBEC. When added together with histamine to HBEC cultures, both A1 and A2 receptor agonists diminished histamine-induced IP3 stimulation. This effect was reversed in the presence of specific A1 and A2 receptor antagonists, respectively. Marked augmentation of histamine-induced cAMP production by HBEC was observed in the presence of A2 agonist. This response was dependent on H1 receptors, since it was reduced in the presence of H1-receptor antagonist. It is suggested that interaction between histamine and adenosine modulating induction of second messengers in HBEC may influence endothelium-dependent responses of brain microvascular compartments.

The role of arachidonic acid and oxygen radicals on cerebromicrovascular endothelial permeability.

Arachidonic acid release from tissue membranes and/or formation of free radical species have been considered to affect blood-brain barrier permeability and formation of brain oedema. To determine whether exogenous arachidonic acid or H2O2 may alter blood-brain barrier permeability, we examined their effect on cultured endothelium derived from cerebral microvessels of human and animals. Release of 51Cr from labeled endothelium exposed to these substance was used as a main marker for the assessment of endothelial injury. The results of these studies indicate that endothelial cells (EC) are susceptible to exogenous arachidonic acid or H2O2 insult irrespective of their origin. However human endothelial cells are less affected than animal EC by H2O2-generated systems. The findings suggest that a disturbance of the existing balance between the endogenous antioxidant properties of EC and exogenous oxidant leads to EC injury.

Effect of vasoactive peptides on prostacyclin formation in cerebromicrovascular cellular elements and glia: a comparative study.

The aim of the present study was to determine basal and stimulated release of prostacyclin from the separately cultured endothelial and smooth muscle cells derived from rat brain microvessels and from glial cells. The basal release of PGI(2) (measured as a 6-keto-PGF(1?) formation by radioimmunoassay method) was significantly greater in cultured endothelial cells than in cultured smooth muscle or glial cells (254 +/- 32, 140.7 +/- 17 and 76.8 +/- 5.8 pg/mg protein, respectively). Prostacyclin formation stimulated by angiotensin I, angiotensin II and bradykinin was significantly increased in the smooth muscle cells. A significant enhancement of PGI(2) formation was also observed in the glial cells exposed to angiotensin II or bradykinin. Vasoactive peptides did not affect prostacyclin production in the endothelial cells. Presented results indicate that the smooth muscle cells represent the most sensitive site of prostacyclinpeptide interaction. These data also suggest that the endothelial and the glial cells may protect the cerebromicrovascular smooth muscle by inactivating vasoactive peptides derived from either the blood or the brain.

Cerebromicrovascular endothelial permeability. In-vitro studies.

Permeability of cerebromicrovascular endothelium has been investigated in a new model of cultured cells. The endothelial cells are grown on dextran microcarriers and constitute a barrier for trypan blue (TB) binding to the dextran beads. Changes in the permeability of microcarrier-cultured endothelium have been investigated during the exposure of cells to arachidonic acid or substances involved either in arachidonate metabolism or stimulation of cAMP. The results demonstrate enhanced TB passage through the endothelial barrier during exposure to high concentrations of arachidonic acid and indomethacin, but not to ibuprofen. The effect of indomethacin could be prevented by pretreatment with dexamethasone. Dexamethasone alone did not influence the barrier. Forskolin, a drug which stimulates the catalytic unit of adenylate cyclase, did not affect the endothelial permeability to TB. These findings support the contention that substances derived from a disturbed cellular membrane contribute to the altered blood-brain barrier function found under pathological conditions.