Oxygenation and lung morphology in a rabbit pediatric ARDS- model under high peak pressure ventilation plus nitric oxide and surfactant compared with veno-venous ECMO

The aim of the study is to investigate which of two treatment options of saline lavage induced ARDS in rabbits is better in terms of oxygenation and prevention of barotrauma: combined high peak pressure ventilation with surfactant administration and inhaled nitric oxide or veno-venous ECMO combined with low peak inspiratory pressure ventilation. MATERIALS AND METHODS: After saline lavage (10 cc/kg repeated as long as foamy retrieval was observed) two combined therapeutic strategies were examined: ventilation with high inspiratory pressures (35 cm H2O) with additional exogenous surfactant administration (100 mg/kg) and inhaled nitric oxide (10 PPM) (n=5, group 1) and low inspiratory pressure (20 cm H2O) ventilation under veno-venous ECMO support (n=5, group 2). The FiO2 was maintained at 1.0 in both groups. The paO2/FiO2 ratio was calculated in 30 minute intervals for 4 hours. After that the animals were sacrificed and the lungs examined macro- and microscopically. Aeration was described in a semiquantitative method using the alveolar expansion index. Oxygenation in group 1 was significantly better than in group 2, it increased significantly after surfactant but not after additional nitric oxide administration. However, the lungs in group 1 showed severe signs of baro/ergotrauma (Hyaline membranes, air leaks, infiltration of polymorphonuclear (PMN) granulocytes and macrophages, break down of alveolar capillary membranes) after 4 hrs of combined therapy, whereas the lungs in group 2 appeared normal. Adding surfactant and NO to a high tidal volume ventilation improved oxygenation, but did not prevent baro/ergotrauma. Ventilation with low inspiratory pressures combined with ECMO caused little baro/ergotrauma but adequate oxygenation could not be achieved, probably due to anatomical features of the rabbit which do not allow appropriate blood flow within the ECMO-circuit.     

Gene × Environment Interactions in the Development of Preschool Effortful Control,and Its Implications for Childhood Externalizing Behavior

This study examined the role of gene × environment interaction (G × E) in the development of effortful control (EC) and externalizing symptoms (EXT). Participants included 361 adopted children, and their Adoptive Parents (APs) and Birth Mothers (BMs), drawn from the Early Growth and Development Study. The primary adoptive caregivers’ (AP1) laxness and overreactivity were assessed when children were 27-months-old, and used as indices of environmental influences on EC. Heritable influences on child EC were assessed by the BMs’ personality characteristics (emotion dysregulation, agreeableness). Secondary adoptive caregivers (AP2) reported on children’s EC at 54 months, and EXT at 7 years. Interactions between BM characteristics and AP1 laxness were related to EC and indirectly predicted EXT via EC. Parental laxness and EC were positively associated if children had high heritable risk for poor EC (BM high emotion dysregulation or low agreeableness), but negatively associated if children had low heritable risk for poor EC (BM low emotion dysregulation or high agreeableness). BM agreeableness also moderated associations between AP1 overreactivity and effortful control, and yielded a similar pattern of results. Our findings suggest that G × E is an important first step in the development of EXT via its effect on EC. Consistent with “goodness of fit” models, heritable tendencies can affect which parenting practices best support EC development.

     

Use of a repetitive DNA probe to type clinical and environmental isolates of Aspergillus flavus from a cluster of cutaneous infections in a neonatal intensive care unit

Aspergillus flavus is second to A. fumigatus as a cause of invasive aspergillosis, but no standard method exists for molecular typing of strains from human sources. A repetitive DNA sequence cloned from A. flavus and subcloned into a pUC19 vector, pAF28, was used to type 18 isolates from diverse clinical, environmental, and geographic sources. The restriction fragment length polymorphisms generated with EcoRI- or PstI-digested genomic DNA and probed with digoxigenin-labeled pAF28 revealed complete concordance between patterns. Eighteen distinct fingerprints were observed. The probe was used to investigate two cases of cutaneous A. flavus infection in low-birth-weight infants in a neonatal intensive care unit (NICU). Both infants were transported by the same ambulance and crew to the NICU on the same day. A. flavus strains of the same genotype were isolated from both infants, from a roll of tape used to fasten their umbilical catheters, from a canvas bag used to store the tape in the ambulance, and from the tape tray in the ambulance isolette. These cases highlight the need to consider exposures in critically ill neonates that might occur during their transport to the NICU and for stringent infection control practices. The hybridization profiles of strains from a second cluster of invasive A. flavus infections in two pediatric hematology-oncology patients revealed a genotype common to strains from a definite case patient and a health care worker. A probable case patient was infected with a strain with a genotype different from that of the strain from the definite case patient but highly related to that of an environmental isolate. The high degree of discrimination and reproducibility obtained with the pAF28 probe underscores its utility for typing clinical and environmental isolates of A. flavus.     

Optimal management strategies for placenta accreta

Objective  To determine which interventions for managing placenta accreta were associated with reduced maternal morbidity.
Design  Retrospective cohort study.
Setting  Two tertiary care teaching hospitals in Utah.
Population  All identified cases of placenta accreta from 1996 to 2008.
Methods  Cases of placenta accreta were identified using standard ICD-9 codes for placenta accreta, placenta praevia, and caesarean hysterectomy. Medical records were then abstracted for maternal medical history, hospital course, and maternal and neonatal outcomes. Maternal and neonatal complications were compared according to antenatal suspicion of accreta, indications for delivery, preoperative preparation, attempts at placental removal before hysterectomy, and hypogastric artery ligation.
Main outcome measures  Early morbidity (prolonged maternal intensive care unit admission, large volume of blood transfusion, coagulopathy, ureteral injury, or early re-operation) and late morbidity (intra-abdominal infection, hospital re-admission, or need for delayed re-operation).
Results  Seventy-six cases of placenta accreta were identified. When accreta was suspected, scheduled caesarean hysterectomy without attempting placental removal was associated with a significantly reduced rate of early morbidity compared with cases in which placental removal was attempted (67 versus 36%, P = 0.038). Women with preoperative bilateral ureteric stents had a lower incidence of early morbidity compared with women without stents (18 versus 55%, P = 0.018). Hypogastric artery ligation did not reduce maternal morbidity.
Conclusions  Scheduled caesarean hysterectomy with preoperative ureteric stent placement and avoiding attempted placental removal are associated with reduced maternal morbidity in women with suspected placenta accreta.     

Medulloblastoma: from molecular pathology to therapy.

Medulloblastoma is the most common malignant tumor of central nervous system in children. Patients affected by medulloblastoma may be categorized as high-risk and standard-risk patients, based on the clinical criteria and histologic features of the disease. Currently, multimodality treatment, including surgery, radiotherapy, and chemotherapy is considered as the most effective strategy against these malignant cerebellar tumors of the childhood. Despite the potential poor outcomes of these lesions, the 5-year survival stands, at present, at 70% to 80% for standard-risk patients, whereas high-risk patients have a 5-year survival of 55% to 76%. Attempts to further reduce the morbidity and mortality associated with medulloblastoma have been restricted by the toxicity of conventional treatments and the infiltrative nature of the disease. Over the past decade, new discoveries in molecular biology have revealed new insights in signaling pathways regulating medulloblastoma tumor formation. Recent advances in the molecular biology of medulloblastoma indicate that the classification of these embryonal tumors, solely based on histology and clinical criteria, may not be adequate enough. Better understanding of the growth control mechanisms involved in the development and progression of medulloblastoma will allow a better classification, leading to the improvement of the existing therapies, as well as to the development of new therapeutic approaches.     

Insulin-like growth factor-I produced by seminal vesicles: relationship to intraepithelial basal cell hyperplasia in the prostate.

PURPOSE: This study examined the seminal vesicle fluid (SVF) as a potential local source of insulin-like growth factor-I (IGF-I) in the peripheral zone of the prostate. EXPERIMENTAL DESIGN: IGF-I levels in seminal fluid were measured. The levels of the IGF-I receptor (IGF-IR) in its active, phosphorylated form as well as direct downstream targets were examined in the peripheral zone of the prostate. RESULTS: In situ, we find that the IGF-IR is activated in the peripheral zone in areas of atrophy, prostatic intraepithelial hyperplasia, and cancer. In addition, immunostaining reveals preferential activation of the IGF-IR in p63-positive cells in areas of intermediate basal cell hyperplasia in the peripheral zone, indicating that prostate progenitor cells are highly sensitive to increases in local IGF-I levels. These areas of basal cell hyperplasia occur at high incidence in the peripheral zone of the prostate. Relatively high levels of IGF-I were identified in SVF. In addition, we find that SVF can stimulate the proliferation of both normal and cancer-derived prostate cells. CONCLUSIONS: These results suggest that SVF is a local source of IGF-I that provides chronic stimulation of prostate cells. This chronic stimulation could contribute to the development of prostate cancer in older men.     

Evaluation of a morpholinothiolporphyrin for use in photodynamic therapy.

The photonecrotic effectiveness of a morpholinothiolporphyrin derived from haematoporphyrin was measured in an animal model of cerebral glioma. The dose administered was 20 mg kg-1 and the laser dose varied from 0 to 200 J cm-2. The tumour necrosis was at least as good as that of HpD, and this therapeutic response may be attributed to the targeting of specific ''photopotent'' subcellular sites.