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Objective:Free oxygen radicals and proinflammatory cytokines are important causes for brain injury in neonates with hypoxic ischemic encephalopathy (HIE). Our objectives were to test the hypothesis that a combination of antioxidants (ascorbic acid) and anti-inflammatory agents (ibuprofen) can ameliorate the brain injury in HIE and improve neurodevelopmental outcomes when given to term infants immediately after birth.Study Design:In a prospective, randomized, double-blinded controlled trial, 60 asphyxiated term infants were assigned to one of two groups, intervention and control. The intervention group (n=30) received intravenous ascorbic acid and oral ibuprofen for 3 days; and the control group (n=30) received similar volumes of a placebo. We measured a panel of cytokines at enrollment and administered the treatment drugs within 2 h after birth. Neurological evaluations and developmental screenings were performed for all survivors at 6 months of age.Result:The Intervention and Control groups did not differ in the severity of HIE at enrollment, the concentrations of IL-1β and IL-6, the incidence of mortality (37 vs 33%), the incidence of neurological abnormalities at hospital discharge (47 vs 55%) and the incidence of developmental delay at 6 months of age (32 vs 40%), respectively. None of the observed complications were related to intervention. Serum interleukin (IL)-1β and IL-6 concentrations correlated positively with the severity of HIE at birth (P<0.01), whereas only serum IL-6 correlated with neurodevelopmental outcome at 6 months (P<0.001).Conclusion:Early administration of ascorbic acid and ibuprofen did not affect outcomes in infants with perinatal asphyxia. This study does not explain whether our intervention was not effective in blocking free radicals and inflammatory cytokines, if the dosing and route of administration were inadequate, or if other mediators existed that could have a more powerful role in brain injury during hypoxia–ischemia.Journal of Perinatology (2009) 29, 438–443; doi:10.1038/jp.2009.1; published online 26 February 2009 [ABSTRACT FROM AUTHOR]

Rationale: Cyamemazine (Tercian) is an anti-psychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT2A receptors, which was fourfold higher than its affinity for dopamine D2 receptors (Hameg et al. 2003). Objectives: The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. Methods: Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D2 and serotonin 5-HT2A receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [11C]raclopride and [11C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. Results: Cyamemazine induced near saturation of 5-HT2A receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D2 receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D2M receptor occupancy was fourfold higher than that for 5-HT2A receptors. Accordingly, individual 5-HT2A/D2 RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. Conclusion: This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT2A receptors compared to dopamine D2 receptors. In the dose range 37.5-300 mg, levels of dopamine D2. [ABSTRACT FROM AUTHOR]

Summary:To decrease red blood cell (RBC) transfusion requirements during high-dose therapy (HDT) for hematological malignancies, we conducted a pilot study to assess the effect of recombinant human erythropoietin (rHuEpo) given during chemotherapy before HDT and autologous peripheral stem-cell transplantation (APSCT). The transfusion histories of 15 HDT and APSCT for hematological disease performed in 11 consecutive patients who received rHuEpo (10?000?U subcutaneously three times/week) were compared to those of 22 HDT and ASCT performed in 17 consecutive historical controls matched for hematological parameters. rHuEpo increased the hemoglobin (Hb) level from 10.3±2.3?g/dl at diagnosis to 12.9±2.2?g/dl at the time of HDT in 11 patients; no major adverse effects occurred. Compared to historical controls (95%, 21/22), RBC transfusion requirements were significantly lower for rHuEpo recipients (26%, 4/15) (P=0.00001) and rHuEpo responders (15%, 2/13) (P=0.000002). After HDT and APSCT, fewer RBC transfusions were needed: 3.3, 1.2 and 0.3 RBC units for controls, rHuEpo recipients and rHuEpo responders, respectively (P=0.006 and 0.00002). Therefore, rHuEpo should be administered before, and not after HDT and APSCT, to lower RBC transfusion requirements after HDT and APSCT.Bone Marrow Transplantation (2005) 35, 903-907. doi:10.1038/sj.bmt.1704899 Published online 14 March 2005 [ABSTRACT FROM AUTHOR]

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCR?gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.Leukemia (2005) 19, 792-798. doi:10.1038/sj.leu.2403722 Published online 17 March 2005 [ABSTRACT FROM AUTHOR]

Background: Increased knowledge on the underlying pathophysiological mechanisms in acute pancreatitis (AP) and abdominal sepsis (AS) is essential, not least for the development of novel ways of treatment. The present study aims at determining dynamic changes in the systemic inflammatory response in AP and AS. Methods: AP was induced by the intraductal injection of sodium taurodeoxycholate in the rat, while AS was induced by caecal ligation and puncture. The animals were killed 1, 3, 6 and 9 h after challenge. Plasma exudation of radiolabelled albumin, myeloperoxidase (MPO), TNF-α, MCP-1, superoxide and hydrogen peroxide was measured. Results: Leakage index of human serum albumin showed a significant increase early (1 h) after induction of AP and later (9 h) in AS compared to controls ( P < 0.05). Hydrogen peroxide generation by circulating monocytes/macrophages was high early (1 h) in AP and after 3 and 6 h in AS. Superoxide generation increased by time after both challenges. MPO activity increased significantly, starting at 3 h in both AP and AS ( P < 0.05). TNF-α increased significantly at 6 and 9 h in both models. Conclusion: Our results indicate differences in the release of systemic inflammatory mediators and cellular response in AP and AS. However, potential similarities in end-effect, such as the development of remote organ injury (lungs), may exist as implied by the MPO results. Further investigations of the mechanisms are crucial. [ABSTRACT FROM AUTHOR]

Fifteen years ago, a role for excitotoxic damage in the pathology of amyotrophic lateral sclerosis (ALS) was postulated. This stimulated the development of riluzole, the only available treatment for the disease. Since then, the identification of abnormal forms of superoxide dismutase as the genetic basis of certain familial forms of ALS has provided a huge impetus to the search for new effective treatments for this devastating disease. Transgenic mouse models have been developed expressing these aberrant mutants that develop a form of motor neurone disease the progress of which can be slowed by riluzole. Studies in these mice have provided evidence for a role for excitotoxic, apoptotic and oxidative processes in the development of pathology. The mice can be used for testing molecules targeting these processes as potential therapies, to allow the most promising to be evaluated in humans. Several such agents are currently in clinical trials. Many previous clinical trials in ALS were insufficiently powered to demonstrate any relevant effect on disease progression. This situation has been to some extent remedied in the more recent trials, which have recruited many hundreds of patients. However, with the exception of studies with riluzole, the results of these have been disappointing. In particular, a number of large trials with neurotrophic agents have revealed no evidence for efficacy. Nonetheless, the need for large multinational trials of long duration limits the number that can be carried out and makes important demands on investment. For this reason, surrogate markers that can be used for rapid screening in patients of potential treatments identified in the transgenic mice are urgently needed. [ABSTRACT FROM AUTHOR]

The low incidence of extrapyramidal effects with atypical neuroleptics has been ascribed to their 5-HT2A- and 5-HT2C-serotonin receptor antagonistic properties. On the other hand, the acute increase in striatal dopamine release by submaximal dopamine D2 autoreceptor blockade can be respectively reduced and increased by 5-HT2A- and 5-HT2C-antagonists. Cyamemazine is a neuroleptic D2- and 5-HT2A-receptor antagonist, with small antagonistic activity at 5-HT2C receptors and low incidence of extrapyramidal side effects. Therefore, submaximal cyamemazine was tested in rats for its acute action on the extracellular concentrations of dopamine and dopamine metabolites (DOPAC: 3,4,dihydroxyphenylacetic acid and HVA: 4-hydroxy-3-methoxy-phenyl-acetic acid) in the corpus striatum. The serotonin metabolite 5-HIAA (5-hydroxy-indole-acetic acid) was measured in parallel. Rats prepared for microdialysis (striatum) were intraperitoneally given cyamemazine 1 mg/kg, 5 mg/kg or vehicle (n=4 in each group). Dopamine, DOPAC, HVA and 5-HIAA concentrations in perfusates under basal conditions and after stimulation by high K+ were measured by HPLC coupled to electrochemical detection. Cyamemazine 1 mg/kg significantly reduced extracellular concentrations of basal dopamine (-77%), DOPAC (-54%), HVA (-54%) and 5-HIAA (-65%). No such effects were seen with the dose of cyamemazine 5 mg/kg or for K+-evoked dopamine release. In conclusion, submaximal cyamemazine can acutely reduce basal dopamine release and metabolism in the rat striatum. Such unusual action can be explained by the original pharmacological profile of cyamemazine (potent D2- and 5-HT2A-antagonist, with small antagonistic activity at 5-HT2C receptors). Further experiments are required to explain the low incidence of extrapyramidal side actions with cyamemazine. [ABSTRACT FROM AUTHOR]

Background: Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP). Methods: AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured. Results: The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0·05), decreased the release of histamine at 1 h (P < 0·05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0·05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation. Conclusion: Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction. [ABSTRACT FROM AUTHOR]

Ilio-psoas abscess is rare in neonates and is usually treated by surgical drainage. We report two cases of ilio-psoas abscess in 15- and 21-day-old infants successfully treated by US-guided percutaneous drainage as a supplement to antibiotic therapy. Clinical improvement was observed within 24–48 h of drainage and subsequent imaging demonstrated resolution of the abscess cavity. The analysis of these cases and of those previously reported indicates that imaging is essential for diagnosis. In neonates, US-guided percutaneous drainage may represent the first-choice treatment of this disease in association with antibiotic therapy. [ABSTRACT FROM AUTHOR]

Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome. Simultaneous use of these monitoring modalities may improve our ability to provide meaningful prognostic information regarding ongoing treatments. Evidence will be summarized in this review for each of these modalities, by describing (1) the methods, (2) the clinical evidence in context of NE both before and with hypothermia, and (3) the research and future directions. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the impact of oil and hydrocarbons on algae Selenastrum (S.) capricornutum. Researchers considered the chlorophyll content, growth rate, effective concentration, carbohydrate and protein contents were chosen as toxicity end points. It has been revealed that water with chlorophyll content decreases as the fuel oil concentration in algal cultures increased. Exposure of S. capricornutum to fuel oil extracts significantly decreased the carbohydrate and protein content of algal cells compared to control cultures. In addition, the cell carbohydrate and protein contents has the ability to retain 14-C labeled photosynthates of S. capricornutum.

The article examines the accumulation of malathion by the male Tilapia nilotica which is widely distributed in Nile River. Moreover, the in vivo metabolism of the insecticide in exposed fish, both in the normal fish and those injected by phenolbarbital which leads to mixed function oxidases activation was examined. Some of the possible metabolic pathways of malathion in T. nilotica with special emphasis on the relative distribution of malathion residue and its metabolites in the gills, intestine, muscles and the liver were revealed by the study.

The article presents a study which evaluates the role of natural mixed algal population in the formation of trihalomethanes (THMs) and other non-volatile chlorinated organics (NVCO), as well as assesses the yield of such products that are formed at several growth phases of the green alga Scenedesmus sp. The study used mixed algae isolated from Nile River water samples collected near Cairo, Egypt. Moreover, the study revealed that total THMs increase as the contact time was extended to 3 hours.

The article presents a study on the effect of triazine compounds on freshwater algae from the Nile River. The authors investigated the effect of gardoprim and gesapax triazine herbicides at various dosages on algae samples from the Nile River. Results shows that blue-green algae was decreased due to gardoprim, while gesapax had no harmful effect to water algae.

The article presents a study on the formation of halogenated organics and trihalomethanes (THMs) during water treatment at Al-Giza water treatment plant in Cairo, Egypt. The study used water samples from Al-Giza, gas-liquid chromatography (GLC), and external standards including chloroform (CHCl3), bromoform (CHBr3), and dichlorobromomethane (CHCI2Br). Results showed high concentration levels of THMs in CHCl3.

OBJECTIVE: To describe a case of dissection of the postero-inferior cerebellar artery (PICA) after cervical manipulation. Clinical Features: After cervical manipulation, a 42-year-old woman had a cerebellar syndrome related to an infarct in the area supplied by the PICA, confirmed by computed tomography of the brain. Cerebral angiography showed a normal appearance of the vertebral artery, a cervical extradural origin of PICA, and a dissection of the latter at the C1-C2 level. Intervention and Outcome: Anticoagulant treatment with heparin was implemented. A positive outcome was achieved after 3 weeks. CONCLUSION: Anatomical variations of the vertebral arteries and their branches are not infrequent and may constitute a predisposing factor to complications after neck manipulation. [ABSTRACT FROM AUTHOR]

A letter to the editor on improvement in treatment of patients with multiple myeloma, is presented.

Introduction: Pancreatic cancer (PC) remains one of the most lethal malignancies, despite developments in surgical and non-surgical therapies. Significant improvements in long-term survival have not been achieved. Only radical surgical resection has obtained a moderate extension in survival. We aim to identify factors associated with longer survival in patients with PC treated by pancreatoduodenectomy (PD). Material and Method: We designed a case-control study of patients with PC treated by PD in our center between 2002-2015. We compare patients who survived ≥ 3 years (case) with those not achieving it (control). Bio-demographic, clinical, histopathological, morbidity and mortality data were compared between cases and controls using logistic regression. Results: Seventy patients were analyzed; mean age 62 ± 11 years; 40 (57%) women. Morbidity was found in 26 patients (37.1%); Clavien-Dindo ≥ IIIa in 8 (11.4%). The median (range) of hospitalization days was 12 (7-84). The actuarial 1, 3, and 5 years survival was 77%, 32%, and 22%, respectively, for the entire series. Twenty-one cases (30%), and 49 controls (70%) were identified. In the univariate analysis, R0 resection, negative regional lymph nodes, the absence of perineural infiltration, the earliest stages (IA, IB, and IIA) and the absence of diabetes mellitus (DM) at time of diagnosis were variables associated with survival > 3 years (p < 0.05). Hypoalbuminemia (< 3 mg / dL), CA 19-9 (> 100 U / mL), and neo/adjuvant treatments, did not significantly show differences in survival. In the multivariate analysis, no DM at diagnosis (adjusted OR: 12; 95% CI 1.7 - 84.3), no perineural infiltration (adjusted OR: 7; 95% CI 1.3 - 36.3) and early stages IA, IB, and IIA (adjusted OR: 10.3; 95% CI 2.1 - 49.1) were identified as independent factors associated with survival > 3 years. Conclusion: Nondiabetic patients with early stages PC without perineural infiltration, resected R0 by PD can achieve survival over 3 years. [ABSTRACT FROM AUTHOR]