Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis

Background  

We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.     

Comparative genomic hybridization analysis of astrocytomas: prognostic and diagnostic implications

Astrocytoma is comprised of a group of common intracranial neoplasms that are classified into four grades based on the World Health Organization histological criteria and patient survival. To date, histological grade, patient age, and clinical performance, as reflected in the Karnofsky score, are the most reliable prognostic predictors. Recently, there has been a significant effort to identify additional prognostic markers using objective molecular genetic techniques. We believe that the identification of such markers will characterize new chromosomal loci important in astrocytoma progression and aid clinical diagnosis and prognosis. To this end, our laboratory used comparative genomic hybridization to identify DNA sequence copy number changes in 102 astrocytomas. Novel losses of 19p loci were detected in low-grade pilocytic astrocytomas and losses of loci on 9p, 10, and 22 along with gains on 7, 19, and 20 were detected in a significant proportion of high-grade astrocytomas. The Cox proportional hazards statistical modeling showed that the presence of +7q and -10q comparative genomic hybridization alterations significantly increased a patient's risk of dying, independent of histological grade. This investigation demonstrates the efficacy of comparative genomic hybridization for identifying tumor suppressor and oncogene loci in different astrocytic grades. The cumulative effect of these loci is an important consideration in their diagnostic and prognostic implications.     

Is the long-term survival of patients with intracranial glioblastoma multiforme overstated?

BACKGROUND: The 5-year survival rate for intracranial glioblastoma multiforme (GBM) has remained at 4-5% for the last 30 years, in spite of multiple randomized prospective trials. The authors hypothesized, based on the literature, that even this remarkably poor survival rate is an overstatement. They investigated this hypothesis using the the Duke University Medical Center Tumor Registry. METHODS: The authors reviewed all patients with the diagnosis of intracranial GBM recorded in the Duke University Medical Center Tumor Registry from the registry's inception in 1976 through 1996. This search identified a population of patients with a minimum of 5 years of follow-up. Each of the long-term survivors was assigned a code number for clinical information. The pathology slides were provided to a neuropathologist in a coded fashion so that the patients could not be identified. The neuropathologist reviewed the slides to analyze the presence or absence of nine histologic factors. A match technique was used to identify a control population of patients with GBM who were not 5-year survivors and were all deceased. The control population was compared with the study population to ascertain if there are histologic correlates associated with long-term survivorship. RESULTS: The authors identified 766 patients recorded by the tumor registry as having an intracranial GBM with a minimum of 5 years of follow up. Of the total population, 32 patients initially appeared to be 5-year survivors (4%). Upon review of the medical records for these 32 patients, however, the authors found only 17 patients who were truly 5-year survivors. The most common reason for miscoding was the presence of a low-grade astrocytoma that subsequently dedifferentiated into GBM. The 17 long-term survivors included 11 males and 6 females. Their mean age at diagnosis was 40.2 years. Therapy consisted of a macroscopic total resection in 4 patients (22%), a biopsy in 1 patient (6%), a subtotal resection in 10 patients (56%), and unknown extent of resection in 2 patients (11%). All patients received partial brain irradiation (mean dose, 62.6 Gy) and chemotherapy. Thirteen different single-agent or combination chemotherapy programs were used. Two patients also received I-131 monoclonal antibody therapy. Analysis of the nine histopathologic factors studied showed that intermediate fibrillary elements were more common and small anaplastic elements were less common in the long-term survivors than in the control population. CONCLUSIONS: Survival data on intracranial GBM, based on tumor registry data, should be interpreted cautiously. Reliable conclusions can only be drawn when such data are supplemented with clinical information and the histopathology is reviewed carefully. The group of long-term survivors in the current study were younger than the typical GBM population. Conventionally treated patients with GBM, chosen from an unselected population from a tumor registry, have a smaller chance of long-term survival than is generally believed.     

唐古特大黄提取物不同成分泻下作用的比较研究

目的：研究唐古特大黄提取物不同成分的泻下作用。方法：采用炭末推进方法、酚红排空方法进行肠推进实验,观察大黄提取物各成分(15 g·kg^-1)对小鼠小肠推进和肠水分吸收、大鼠大肠运动的影响。结果：唐古特大黄提取物不同成分与对照组相比,对小鼠小肠推进和肠水分吸收、大肠推进作用均有显著性差异(P<0.01)；与大黄水煎液、醇提液相比,泻下活性存在一些差异。结论：唐古特大黄提取物不同成分均有显著的泻下作用,但与大黄水煎液和醇提液相比有一些差异。     

Topotecan treatment of adults with primary malignant glioma. The Brain Tumor Center at Duke

BACKGROUND: Topotecan activity was evaluated for the treatment of malignant glioma. METHODS: Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan [AU: Please verify all dosages here and throughout text.]at a dose of 2.6 mg/m2 over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3). RESULTS: Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GBM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GBM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression. CONCLUSIONS: These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used.     

Decellularized dermis in combination with cultivated keratinocytes in a short- and long-term animal experimental investigation

Decellularized human dermis as a potentially ideal scaffold for dermal substitution in severe burns was examined in a two‐staged animal experiment. In an initial step, an in vitro generated composite graft consisting of human keratinocytes and decellularized dermis (AlloDerm®) was transplanted onto nude mice in a short‐term trial (n = 20, 14 days). Subsequently, a combined one‐step grafting of full thickness wounds with both decellularized dermis (in part preincubated with fibroblasts) and cultivated autologous keratinocytes as a cell suspension in fibrin glue was done in a long‐term porcine animal model (n = 10, 6 months). In both series, macroscopic wound healing was evaluated by planimetry. Histological investigations included morphological as well as immunohistochemical parameters. The short‐term study showed both successful integration of the composite grafts and reduction of wound contraction compared with the control group (epithelial grafts). The long‐term porcine study displayed reduced myofibroblast formation and contraction in the wounds that had been treated with fibroblast‐preincubated dermis. After 4 weeks, a decline of the structural integrity of the dermal matrix could be noticed. The utility of decellularized dermis as template for both dermal reconstitution and keratinocyte delivery vehicle was shown. The closure of full thickness wounds by a single‐step combination of an autologous keratinocyte fibrin sealant suspension and acellular dermis in a pig animal model could be shown. Incorporation of fibroblasts led to reduced wound contraction but could not prevent the loss of dermal integrity. The engineered ‘skin’ remained viable and stable over a period of 6 months.     

Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction

Twenty-six patients (4 months to 6 years old) with achondroplasia complicated by sleep apnea and/or other neurologic manifestations underwent plain computed tomography (CT) of the craniocervical junction; six also underwent CT myelography. For objectification, multiplanar reconstruction was used to complement axial plane measurements by providing coronal and sagittal measurements; multiplanar reconstruction also improved perception of the longitudinal relationships between the brain stem and subarachnoid space. A narrow subarachnoid space was found in all 26 patients; marked cord compression was present in nine, six of whom underwent CT myelography. These six had marked focal obliteration of the subarachnoid space on both plain CT and CT myelography. Since the subarachnoid space immediately above and below the craniocervical junction is normally capacious, when marked constriction was present, no additional information could have been gained from CT myelography. Thus, plain CT was shown to be sufficient for surgical planning (suboccipital decompression) in nine patients with cord compression due to achondroplasia.