Comparison of speed versus complexity effects on the hemodynamic response of the trail making test in block designs.

The use of functional near-infrared spectroscopy (fNIRS) in block designs provides measures of cortical activity in ecologically valid environments. However, in some cases, the use of block designs may be problematic when data are not corrected for performance in a time-restricted block. We sought to investigate the effects of task complexity and processing speed on hemodynamic responses in an fNIRS block design. To differentiate the effects of task complexity and processing speed, 20 subjects completed the trail making test (TMT) in two versions (TMT-A versus TMT-B) and three different speed levels (slow versus moderate versus fast). During TMT-A, subjects are asked to connect encircled numbers in numerically ascending order (1-2-3…). In the more complex TMT-B, subjects are instructed to connect encircled numbers and letters in alternating ascending order (1-A-2-B…). To illustrate the obscuring effects of processing speed on task complexity, we perform two different analyses. First, we analyze the classical measures of oxygenated blood, and second, we analyze the measures corrected for the number of processed items. Our results show large effects for processing speed within the bilateral inferior frontal gyrus, left dorsolateral prefrontal cortex, and superior parietal lobule (SPL). The TMT contrast did not show significant effects with classical measures, although trends are observed for higher activation during TMT-B. When corrected for processed items, higher activity for TMT-B in comparison to TMT-A is found within the SPL. The results are discussed in light of recent research designs, and simple to use correction methods are suggested.

Farnesyltransferase inhibitor FTI-277 prevents autocrine growth stimulation of neuroblastoma by BDNF.

PURPOSE: Autocrine growth stimulation by IGF-II and BDNF is frequently observed in neuroblastoma. The signals of the receptors of these growth factors are transduced to the nucleus via the Ras-MAP-kinase pathway where they induce proliferation. Inactivation of Ras-proteins by farnesyltransferase inhibitors such as FTI-277 disrupts growth stimulation of ras-transformed cells. We investigated whether FTI-277 is also active against tumor cells with constitutively activated growth factor receptors but lacking ras-mutations. METHOD: We analyzed eight different neuroblastoma cell lines for the expression of BDNF and its receptor trkB. Two of these cell lines with a complete autocrine BDNF loop were treated with FTI-277, and the effects of Ras-inactivation on the signal transduction of BDNF were analyzed. RESULTS: Treatment of neuroblastoma cells with 10 microM FTI-277 for 4 days reduced the amount of membrane-bound Ras-protein to almost 50%. Activation of MAP-kinase, induction of N-myc expression, and proliferation were clearly reduced in the treated cells. In addition, we observed some cytotoxic effects of FTI-277 accompanied by morphological changes of the neuroblastoma cells and a delayed induction of apoptosis. CONCLUSION: Farnesyltransferase inhibitors are active against neuroblastoma cells but the mechanism of action is not limited to inactivation of Ras. Further investigations on the targets of FTI-277 are recommended.

Induction of N-myc in neuroblastoma by autocrine IGF-II depends on farnesylated Ras. Application of farnesyltransferase inhibitors.

Genetic aberrations are the primary events leading to carcinogenesis in various tissues and are characteristic for certain tumor types. Amplification of N-myc and deletion of 1p significantly correlate with poor prognosis of neuroblastoma patients. Very little informations is available on the regulation of N-myc expression by external factors. Insulin-like growth factor-II (IGF-II) has been identified as an autocrine growth factor in neuroblastoma. Four neuroblastoma cell lines were examined for their expression of IGF-II and IGF-receptor. Stimulation of neuroblastoma cells with IGF-II leads to an increased activity of the MAP-kinase Erk1, an induction of N-myc expression and an enhanced proliferation rate. In order to disrupt the signal transduction of the IGF-receptor, we inactivated the Ras-proteins in neuroblastoma cells by inhibition of the farnesyl-protein transferase by FTI-277. This inactivation prevented activation of MAP-kinase Erk1 and induction of N-myc expression by IGF-II. Inactivation of Ras by farnesyltransferase inhibitors might become a promising new approach in future treatments of neuroblastoma tumors.

Behavior of SD-OCT-detected hyperreflective foci in the retina of anti-VEGF-treated patients with diabetic macular edema.

PURPOSE: Hyperreflective foci (HFs) are observable within the neurosensory retina in diabetic macular edema (DME) using spectral domain optical coherence tomography (SD-OCT). HFs have also been seen in wet age-related macular degeneration (AMD), although the origin is still unknown; however, they reduced significantly during anti-VEGF (vascular endothelial growth factor) therapy, and their baseline amount seemed to correlate with treatment success. In this study the behavior of HFs was evaluated during anti-VEGF therapy for DME. METHODS: Fifty-one patients (mean age: 67 years) underwent SD-OCT before and one month after one anti-VEGF injection (ranibizumab: n = 30; bevacizumab: n = 21). The HFs were semiquantitatively counted, assigned to three groups (group A: HFs n = 1-10; group B: n = 11-20; group C: n > 20), and correlated to the course of visual acuity and foveal thickness (paired t-test). Additionally the baseline HbA1c was categorized and correlated to baseline HFs (Spearman Rho). RESULTS: In all eyes, HFs of various amounts were detected in the foveal and parafoveal area. The mean number of HFs reduced significantly from 16.02 to 14.32 in all patients (P = 0.000), whereas foveal thickness reduced from 445.5 to 373.9 µm (P = 0.000) and visual acuity increased from 62.0 to 66.0 ETDRS letters (P = 0.003). Regarding the three HF groups, a reduction of the level stages was observed in 43.1% (stable: 54.9%; more: 2.0%). This reflects a HF distribution change from 31.4% to 62.7% (group A), from 45.1% to 31.4% (group B), and from 23.5% to 5.9% (group C). The HbA1c correlated significantly to the overall HF amount at baseline (0.880; P = 0.000); however, no distinct overall correlation was found between the HF reduction and the course of visual acuity or retinal thickness. Only in cases of complete edema resolution (25%) did HFs reduce significantly (P = 0.008). CONCLUSIONS: As in wet AMD, HFs are frequently found in DME and behave similarly under anti-VEGF therapy. Thus, a HF reduction was observable mainly in cases of complete edema resolution; however, no distinct correlation with visual acuity was noticed, presumably mainly due to the enhanced inhomogeneity in the disease progress of DME. Interestingly, the baseline HF amount seems to correlate positively with HbA1c values indicating the severity of disease.

Repeated pull-through surgery for complicated Hirschsprung's disease--principles derived from clinical experience.

BACKGROUND: In some patients, an initial pull-through procedure for Hirschsprung's disease fails, and obstructive symptoms persist or recur. Then a repeated pull-through operation may be necessary. METHODS: Seventeen patients with Hirschsprung's disease aged 2 to 9 years (median, 4.6 years) have undergone a repeated pull-through procedure because of unresponsive symptoms after an initial operation. The initial procedure was Soave in 3 patients, Rehbein in 13 patients, and Duhamel in 1 patient. Surgical revision was indicated by incomplete resection of the transition zone in 16 patients, anastomotic strictures in 9 patients, and fistulas in 2 patients. All 17 patients have undergone Redo Duhamel pull-through procedure. Median follow-up after Redo operation was 9 years (range, 1-23 years). RESULTS: In 15 patients, the stooling pattern normalized immediately after Redo procedure. Two, including 1 with Down's syndrome, are prone to constipation with occasional use of laxatives. Soiling is seen in the patient with Down's syndrome, but only with episodes of diarrhea. In spite of large formation of scars surrounding the neoanorectum in most patients, Duhamel pull-through reconstruction was possible in all children of this series. CONCLUSIONS: The predominant cause for persistent or recurrent unresponsive obstructive symptoms after initial pull-through procedure is incomplete resection of the transition zone. Less frequently, anastomotic strictures, rigidity of the anorectal cuff, and fistulas cause obstruction. Preoperative workup must focus on these complications. The courses after initial pull-through procedure show that laxatives, Malone procedure, dilatations of the anorectum, myectomy, V-Y-plasty, and injections of botulinum toxin cannot eliminate the mechanical or functional obstruction. Although a large formation of scars in the pelvis resulting from the initial operation, myectomies, dilatations, and other surgical modalities render a Redo revision more difficult, Redo Duhamel pull-through procedure is able to provide the definitive solution to the problem.

Arcuate ligament vascular compression syndrome in infants and children.

BACKGROUND: Arcuate ligament vascular compression syndrome has not been described previously in the pediatric or pediatric surgical literature. However, it is mentioned in the literature of vascular and general surgery and in journals of radiology and orthopedics. In this review, the intraoperative pathological anatomy and the principles of treatment for 8 children will be presented. METHODS: The chart records and the anatomical sketches that were documented by the surgeon immediately after each procedure were analyzed retrospectively. In addition, preoperative courses and long-term follow-up (range, 3-18 years) were evaluated by a defined program. RESULTS: The diagnosis of celiac artery compression by an arcuate ligament was suspected in children presenting with a history of several years of recurrent acute abdominal pain associated with a typical arterial bruit in the midline of the epigastric region. CONCLUSIONS: Other diseases with recurrent abdominal pain and an arterial bruit must be excluded before making the decision for an operative intervention. Duplex ultrasound and angiography are possibly helpful tools to establish the respective diagnosis, but in the patients of the present series, these techniques neither confirmed compression of the celiac axis nor demonstrated decreased perfusion of the superior mesenteric artery. However, as the clinical symptoms clearly announce the disease, these diagnostic measures are not mandatory.

Primary peritonitis in a child caused by Haemophilus parainfluenzae.

A case of primary peritonitis caused by Haemophilus parainfluenzae in a previously healthy child is presented. To our knowledge, this is the first such documented case.

Significance of heparin-binding growth factor expression on cells of solid pediatric tumors.

BACKGROUND: The heparin-binding growth factors pleiotrophin (PTN), midkine (MK), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) stimulate tumor cell proliferation and angiogenesis. In this study the authors wanted to know if these growth factors are expressed by cell lines and tumor tissue of solid pediatric tumors, growth factor expression is influenced by proinflammatory cytokines, and local growth factor concentration has an influence on experimental tumor growth. METHODS: Growth factor mRNA expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and protein secretion by enzyme-linked immunosorbent assay (ELISA). Neuroblastoma cells were suspended in solutions containing different growth factor concentrations before injection into the nude mice, which were given pentosan polysulfate (PPS) for antagonism. RESULTS: The analyzed growth factors were expressed by most cells of solid malignant pediatric tumors. Their expression was not influenced by proinflammatory cytokines. The inhibition of tumor growth by PPS in the nude mouse model was dependent on the local growth factor concentration. High concentration excluded significant tumor suppression. CONCLUSIONS: Because of the redundancy of growth factor expression and the abolishment of PPS efficacy by a high local growth factor concentration, the authors conclude that overall targeting of growth factors is a promising approach to cancer therapy in childhood.

Transjugular intrahepatic portosystemic shunts in children with biliary atresia.

PURPOSE: We retrospectively evaluated the technical and long-term clinical results of transjugular intrahepatic portosystemic shunts (TIPS) in children with portal hypertension and biliary atresia (BA). METHODS: Nine children with BA and recurrent bleeding from esophagogastric and/or intestinal varices were treated by TIPS at the age of 34-156 months and followed-up in two centers. Different types of stents were used. RESULTS: Shunt insertion succeeded in all patients, but in two a second procedure was necessary. Seven procedures lasted more than 3 hr, mainly due to difficult portal vein puncture. Variceal bleeding ceased in all patients; however, 16 reinterventions were performed in eight patients for clinical reasons (n = 11) and sonographically suspected restenosis (n = 5). Four patients underwent successful liver transplantation 4-51 months after TIPS and five are in good clinical conditions 64-75 months after TIPS. CONCLUSION: TIPS in children with BA is technically difficult, mainly due to periportal fibrosis and small portal veins. Frequency of reinterventions seems to be higher compared with adults.