miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas.

In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma.

Epidemiology of pediatric brain tumors in Greece (1991-2008). Experience from the Agia Sofia Children's Hospital.

BACKGROUND: We set out to determine the epidemiology of pediatric brain tumors in a single Greek institute. METHODS: We reviewed all cases of brain tumors in children, under the age of 15 years, that were treated surgically in the Neurosurgical Department of Children's Hospital "Agia Sofia", between January 1991 and December 2008. RESULTS: From January 1991 through December 2008, we encountered 335 cases of pediatric brain tumors. The mean age was 7.2 years and there was a slight male predominance. Astrocytomas made up the largest component, with pilocytic astrocytomas accounting for 25.6% of all tumors. The second most common entity was medulloblastoma, accounting for 18% of all tumors, whereas ependymomas were the third most frequent tumor. There was an increase in the total number of brain tumors during the last decade. Furthermore, examining low-grade astrocytoma, medulloblastoma and ependymoma trends over the last 2 decades, we found a trend for a decrease of low-grade astrocytomas and an increase of the more aggressive medulloblastomas and ependymomas. CONCLUSION: This study presents the first epidemiological data of pediatric brain tumors in Greece. Astrocytomas were the most common tumor followed by medulloblastomas and ependymomas. Furthermore, a trend for an increase of malignant tumors over the last decade has been observed.

Malignant progression of a pleomorphic xanthoastrocytoma in a child.

Pleomorphic xanthoastrocytoma (PXA) is a recently recognized rare cerebral neoplasm that predominantly affects young patients. We report on the case of a 3-year-old boy who presented with a 2-week history of headaches and seizures. Radiological investigation revealed a lesion in the right parietal-occipital lobe. The lesion was excised and histology disclosed the presence of a PXA with anaplastic features. 1 year later follow-up magnetic resonance imaging (MRI) revealed tumor relapse. An MRI of the spine was also performed and demonstrated leptomeningeal dissemination. The patient underwent a second operation. Histology revealed that the presence of a malignant PXA with anaplastic features. The patient received radiotherapy and 9 months later on follow-up MRI a new tumor recurrence was noted. A third craniotomy was performed and the tumor removed. Histological examination revealed dedifferentiation to glioblastoma multiforme. The patient was referred to the oncology department and received chemotherapy with temozolamide. 8 months later the patient was stable without tumor recurrence. PXAs require close follow-up because of their unpredictable biological behaviour.

Tratamiento quirúrgico de mal formaciones arteriovenosas grado V en una niña / Surgical treatment of grade 5 arteriovenous malformation in a girl

Presentamos el caso de una niña de 12 años que fue tratada en nuestro servicio, quejándose de cefalea prolongada acompañada de vómitos y diplopia durante los últimos 10 días. En examinación neurológica se notó tremor en la extremidad superior derecha y rigidez cervical. Lasometimos a TC craneal e IRM, cuyos resultados indicaron la existencia de una lesión frontotemporal gigante. La lesión era heterogénea con calcificaciones y hemosiderina, rodeada de edema y provocando desplazamiento de la media línea. Tras la administración de gadolinio se aumentó un poco la señal. El último hallazgo nos hizo concluir que había una anormalidad vascular. La paciente se operó mediante craneotomía frontotemporal izquierda. Logramos extirpar la lesión totalmente. La histopatología demostró la presencia de una MAV. En el posoperatorio, la paciente estaba neurológicamente intacta, pero se notó una colección subcutánea de líquido cefalorraquídeo que se trató con drenaje sin ningún problema. Aunque el tratamiento quirúrgico de una MAV gigante y situada profundamente en el hemisferio dominante del habla y de las destrezas motoras puede resultar peligroso provocando daño neurológico, una intervención quirúrgica cuidadosa es muy posible que tenga resultado favorable (AU)

We report on a case of a 12-year-old girl that was admitted under our care complaining of headache for over a month which was accompanied by vomiting and diplopia over the last 10 days. On neurological examination a right upper limb tremor and cervical rigidity were noted. CT and MRI scan was performed and revealed a giant left front temporal lesion. The lesion was heterogenous with calcifications and hemosidirin, surrounded by brain swelling and causing midline shift. There was little enhancement after gadolinium administration. The last finding led us to consider the presence of a vascular abnormality as a possible diagnosis. The patient was operated upon via a left fronto-temporal craniotomy. We managed to excise the lesion totally. Histopathology revealed the presence of an AVM. Postoperatively the patient was neurologically intact but a subcutaneous collection of CSF was noted that was successfully treated by drainage. Although surgical treatment of deeply seated giant AVM’s in the dominant hemisphere of speech and motor-sensory area have a relative high proportion of postoperative neurological deficit, careful surgical intervention can produce excellent outcome (AU)

[Surgical treatment of grade 5 arteriovenous malformation in a girl]. / Tratamiento quirúrgico de malformaciones arteriovenosas grado V en una niña.

We report on a case of a 12-year-old girl that was admitted under our care complaining of headache for over a month which was accompanied by vomiting and diplopia over the last 10 days. On neurological examination a right upper limb tremor and cervical rigidity were noted. CT and MRI scan was performed and revealed a giant left frontotemporal lesion. The lesion was heterogenous with calcifications and hemosidirin, surrounded by brain swelling and causing midline shift. There was little enhancement after gadolinium administration. The last finding led us to consider the presence of a vascular abnormality as a possible diagnosis. The patient was operated upon via a left fronto-temporal craniotomy. We managed to excise the lesion totally. Histopathology revealed the presence of an AVM. Postoperatively the patient was neurologically intact but a subcutaneous collection of CSF was noted that was successfully treated by drainage. Although surgical treatment of deeply seated giant AVM's in the dominant hemisphere of speech and motor-sensory area have a relative high proportion of postoperative neurological deficit, careful surgical intervention can produce excellent outcome.

Successful embolization of a giant perimedullary arteriovenous fistula of the cervical spine in a 6-year-old child.

CASE: We report a case of a 6-year-old boy with a giant perimedullary arteriovenous fistula of the cervical spine who presented with progressive tetraparesis. METHOD: Transarterial glue embolization was performed and complete occlusion of the fistula was achieved. RESULT: The patient's symptoms resolved completely during the next year.

Outcomes of gynecologic oncology patients admitted to the intensive care unit following surgery: A university teaching hospital experience.

The objective of this study was to determine the outcomes of gynecological oncology patients requiring intensive care unit (ICU) admission following surgery. A computerized database identified postsurgical ICU admissions from January 1, 1999 to December 31, 2004 at a university hospital. Abstracted data included: demographics, preoperative diagnosis, reason(s) for ICU admission, consultations, interventions, length of stay (LOS), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and 30-day mortality. Statistical analysis was performed with the Student's t-test. A total of 185 surgical gynecological oncology ICU patients was identified. Median age was 60 years (range, 21-92 years), and 63% of patients were white. Only 72% of patients had ovarian, endometrial, or cervical cancer. The most common indications for ICU admission were volume resuscitation (108 patients) and respiratory insufficiency (80 patients). Median ICU LOS was 1 day (range, 1-55 days). Patients surviving their hospital admission had a mean APACHE II score of 11.5 (range, 2-37) compared to a mean of 21.2 (range, 13-44) for patients who died prior to hospital discharge (P < 0.001). The overall mortality rate was 12%. A substantial number of gynecological oncology patients will be admitted to the ICU following surgery. Patient outcomes are favorable if APACHE II scores are low and ICU LOS is short.

Safety and pharmacokinetics of once-daily regimens of soft-gel capsule saquinavir plus minidose ritonavir in human immunodeficiency virus-negative adults.

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors have dramatically improved treatment options for HIV infection, but frequent dosing may impact adherence to highly active antiretroviral treatment regimens (HAART). Previous studies demonstrated that combined therapy with ritonavir and saquinavir allows a decrease in frequency of saquinavir dosing to twice daily. In this study, we evaluated the safety and pharmacokinetics of combining once-daily doses of the soft-gel capsule (SGC) formulation of saquinavir (saquinavir-SGC) and minidose ritonavir. Forty-four healthy HIV-negative volunteers were randomized into groups receiving once-daily doses of saquinavir-SGC (1,200 to 1,800 mg) plus ritonavir (100 to 200 mg) or a control group receiving only saquinavir-SGC (1,200 mg) three times daily. Saquinavir-SGC alone and saquinavir-SGC-ritonavir combinations were generally well tolerated, and there were no safety concerns. Addition of ritonavir (100 mg) to saquinavir-SGC (1,200 to 1,800 mg/day) increased the area under the concentration-time curve (AUC) for saquinavir severalfold, and the intersubject peak concentration in plasma and AUC variability were reduced compared to those achieved with saquinavir-SGC alone (3,600 mg/day), while trough saquinavir levels (24 h post-dose) were substantially higher than the 90% inhibitory concentration calculated from HIV-1 clinical isolates. Neither increasing the saquinavir-SGC dose to higher than 1,600 mg nor increasing ritonavir from 100 to 200 mg appeared to further enhance the AUC. These results suggest that an all once-daily HAART regimen, utilizing saquinavir-SGC plus a more tolerable low dose of ritonavir, may be feasible. Studies of once-daily saquinavir-SGC (1,600 mg) in combination with ritonavir (100 mg) in HIV-infected patients are underway.

Stability in the HIV vDNA pool in peripheral CD4+ T cells of untreated patients by single tube quantitative PCR.

HIV infection leads to loss of CD4 T cells and development of AIDS in most individuals without treatment. While disease progression during HIV infection correlates with the plasma viral load, much less is known about the levels of HIV vDNA. This paper describes the development and validation of a sensitive, quantitative PCR assay for the assessment of HIV vDNA. The system uses novel single tube, multiply competitive PCR technology, which allows five-point competitor competition in a single PCR reaction. The reproducibility and performance characteristics of the assay are extensively studied, which indicate that the system performs well in high DNA backgrounds. Using this assay system on a cohort of protease naïve patients, HIV vDNA was assessed from PBMCs over an average follow-up period of 5 years. The data indicate that the HIV vDNA pool does not appreciably accumulate over the follow-up period, with many of the patients followed for up to 8 years. A reliable, quantitative assessment of vDNA pools will allow a better understanding of the dynamics of HIV pathogenesis.

Evaluation of distinct blood lymphocyte populations in human immunodeficiency virus type 1-infected subjects in the absence or presence of effective therapy.

Virus reservoirs can persist in human immunodeficiency virus type 1 (HIV-1)-infected subjects despite effective plasma virus suppression. To compare viral dynamics in the absence and presence of antiretroviral therapy, blood mononuclear cells from 19 subjects with high plasma RNA levels and 18 subjects following prolonged virus suppression were examined, by use of in situ hybridization, to detect virus RNA expression before and after in vitro T cell activation. This approach reveals circulating lymphocytes expressing HIV-1 RNA before activation and an increase in cells with detectable HIV-1 RNA transcription after in vitro activation. The frequencies of these 2 cell populations are strongly correlated with plasma virus load and appear to be stable once a new steady state is established during therapy. The frequency of viral RNA-positive cells is equivalent to the frequency of cells that produce infectious virus. Thus, in HIV-1-infected subjects there are distinct virus reservoirs comprising both latent and replication-active cells.

Correlation between circulating stromal cell-derived factor 1 levels and CD4+ cell count in human immunodeficiency virus type 1-infected individuals.

Stromal cell-derived factor 1 (SDF-1) is the natural ligand that recognizes CXCR4, which also serves as a coreceptor for some strains of HIV-1. In this study, we explored SDF-1 blood levels among HIV-1-infected individuals exhibiting a wide range of CD4+ cell counts. Plasma or serum concentrations of SDF-1 protein were measured by ELISA in samples from 31 HIV-1-seronegative individuals and 79 HIV-1-infected subjects. Although SDF-1 protein levels were stable for months among seronegative individuals (mean intrasubject variation, 17%), the absolute values varied widely (0.28 to 106.5 ng/ml; mean, 25.6 ng/ml). In HIV-1-infected subjects, there was a direct correlation between SDF-1 level and CD4+ cell count. Subjects with fewer than 50 CD4+ cells per cubic microliter of blood had significantly lower mean SDF-1 levels (+/-SD) than did either HIV-1-infected subjects with higher CD4+ cell counts or uninfected controls: CD4+ cell count <50, mean SDF-1 level of 10.7+/-33.7, 50 < CD4+ cell count <200, mean SDF-1 level of 12.9+/-19.0, 200 < CD4+ cell count <500, mean SDF-1 level of 19.3+/-36.8; CD4+ cell count >500, mean SDF-1 level of 18.5+/-25.2; uninfected control mean SDF-1 level, 25.6+/-34.7. No significant change in SDF-1 level was detected after administration of antiretroviral therapy in nine subjects with advanced disease (mean intrasubject variation, 43%). Analysis of SDF-1 mRNA expression in lymph nodes from HIV-1-infected subjects at different disease stages revealed that the medullary cords contained stromal cells that express SDF-1 mRNA. This preliminary analysis suggests a possible link between lower SDF-1 levels and disease progression.

Dihydrofolate reductase activity in primary brain tumors in children.

PURPOSE: Dihydrofolate reductase is an enzyme involved in cell proliferation and differentiation processes. A cytochemical method was used to detect and quantitate this enzyme at the cellular level in brain tumors in children. MATERIAL AND METHODS: Twenty-six children, aged 1-12 years, with primary brain tumors were studied, eight with medulloblastoma, 10 with glioma, and eight with ependymoma or other tumors. The cytochemical technique was applied on touch preparations performed in the operating room form biopsy specimens. RESULTS: Enzyme activity was apparent as cytoplasmic granules sometimes overlying the nucleus of tumor cells. CONCLUSIONS: Activity of dihydrofolate reductase in the children with medulloblastomas and high-grade gliomas was higher than that reported in leukemic blast cells. In the other brain tumors, low grade gliomas, and ependymomas, the enzyme activity was weaker.

Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions.

The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed.

"Benign" acute subdural haematomas. Analysis of 12 cases.

Twelve cases of acute subdural haematomas, who had a benign course, were studied. During the same period of 8 years, 132 patients with acute subdural haematomas were treated in our unit, an incidence of 9%. From our study it becomes evident that the fate of the patients is determined by the type of injury and especially the conscious level of the patients on admission and their evolution. It also becomes evident from the world literature, that the term "acute" was used in an arbitrary way in most papers and more strict criteria should be used for using this term and for evaluating the ultimate course of these patients.