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Biomedical subjects

G Sabatino

Publications and source records attributed to G Sabatino.

At least 19 recordsLinked to original sources

Glioblastoma multiforme in the elderly: a therapeutic challenge.

INTRODUCTION: Elderly patients with glioblastoma multiforme (GBM) are frequently excluded from cancer therapy trials, treated suboptimally or not treated at all. The average survival in elderly patients is 4-8 months. The goal of the present study was to evaluate the efficacy of different treatment options in terms of survival in an elderly population affected with GBM. MATERIALS AND METHODS: About 34 Patients with primary supratentorial GBM aged 65 or higher were included in this study. All patients underwent craniotomy and tumor mass resection. After surgery they received radiation therapy, chemotherapy and radioimmunotherapy in different combinations. RESULTS: Overall median survival was 10.5 months with one patient still alive at 35 months. Survival was longer for patients who underwent total resection instead of partial (13 months vs 4 months, P=0.006). If total en-bloc resection was used a further survival advantage was obtained (16 months for en-bloc resection, 9 months for inside-out resection, P=0.008). Where a second surgical intervention was performed median survival was 21 months (P=0.05). Survival according to adjuvant therapy has been 21 months (radiotherapy, chemotherapy, radioimmunotheraphy), 18 months (radiotherapy, chemotherapy) and 7 months (radiotherapy) (P=0.0001). CONCLUSIONS: We think that single prognostic factor such as age should be not a reason for undertreatment.

Aged↗

Spontaneous haematoma of ligamentum flavum. Case report and literature review.

Spontaneous infarction of the ligamentum flavum is a very rare cause of mielo-radicular compression. In the literature only four cases are reported, all characterized by a clinical history of slowly progressive mielo-radiculopathy and good outcome after surgical treatment. A 70 year-old female patient presented with a four months clinical history of spontaneous, sub-continuous, progressive lumbar pain with bilateral irradiation to the L4-L5 dermatomers, right leg monoparesis and hypoaesthesia affecting tactile, thermal and pain sensivity, urinary incontinence and constipation. CT scan and MRI evidenced an extradural ovalar lesion in correspondence of the L1-L2 levels, that exerted compression over the dural sac, dislocating it anteriorly. The patient underwent a L1-L2 laminectomy and the lesion was totally resected. Rapid improvement of the patient's symptomatology has been noticed in the postoperative period, with complete recovery during the following month. Histologic examinations demonstrated that the mass was a haematoma of the ligamentum flavum. It's our opinion, that a picture of ligamentum flavum haematoma should be taken into account in differential diagnosis of posterior mielo-radicular compression. The progressive growth of the haematoma may explain the long clinical history of these patients and surgical treatment, even if delayed, permits an excel-lent clinical outcome.

Aged↗

Extensive modulation of a set of microRNAs in primary glioblastoma.

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles in animals and plants by repressing translation or cleaving RNA transcripts. The specific modulation of several microRNAs has been recently associated to some forms of human cancer, suggesting that these short molecules may represent a new class of genes involved in oncogenesis. In our study, we examined by microarray the global expression levels of 245 microRNAs in glioblastoma multiforme, the most frequent and malignant of primary brain tumors. The analysis of both glioblastoma tissues and glioblastoma cell lines allowed us to identify a group of microRNAs whose expression is significantly altered in this tumor. The most interesting results came from miR-221, strongly up-regulated in glioblastoma and from a set of brain-enriched miRNAs, miR-128, miR-181a, miR-181b, and miR-181c, which are down-regulated in glioblastoma.

Brain↗

Rosette-forming glioneuronal tumour of the fourth ventricle: report of a case with clinical and surgical implications.

A 32-year-old woman presented with a 2-month history of episodic headache, cervical pain and neck rigidity. Neurological examination showed a moderate dysmetria. Magnetic resonance imaging (MRI) revealed a mass occupying the fourth ventricle. The patient underwent median sub-occipital craniotomy with total excision of the lesion well demarcated except for a portion infiltrating the right side of the IV ventricle wall. In the post-operative course the patient developed VI and VII right cranial nerves palsy and worsening of dysmetria. MRI confirmed the complete removal of the tumour without signs of recurrence. The pathological diagnosis was rosette forming glio-neuronal tumour (RGNT). At present this is the 13th RGNT reported in literature. These lesions are considered low-grade tumours (WHO I). Nevertheless, the case here reported, like in 6 of the 12 cases in literature, developed disabling post-operative deficits. To establish the therapeutic choice long-term follow-up studies are needed.

Adult↗

Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study.

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

Acute Kidney Injury↗

Craniopagus: the Thessaloniki-Rome experience.

OBJECT: A case of two female Greek twins conjoined at the left frontal and orbital regions is described. These conjoined twins were transferred to the Pediatric Neurosurgical Unit of the Gemelli Hospital, Catholic University Medical School, at the age of 4 months for possible surgical division. METHOD: Multiple diagnostic investigations, which included in particular advanced imaging techniques, demonstrated an independent cerebral vascularization of the two babies and excluded significant intracranial malformations. Such an accurate evaluation of the anatomy of the craniopagus at the level of the cranial junction allowed the feasibility of the surgical correction to be established. CONCLUSIONS: The operation was carried out by a multidisciplinary team in a single stage. The operating team included two distinct teams of neurosurgeons and anesthesiologists as well as a plastic surgeons' team. Both babies survived the operation. The postoperative course was uneventful. Both twins were discharged in good clinical and neurological condition after a 3-week period of hospitalization.

Brain↗

Muenke syndrome.

BACKGROUND: Muenke syndrome is a genetically determined craniosynostosis that involves one or both coronal sutures. In some patients it is associated with skeletal abnormalities such as thimble-like middle phalanges, coned epiphysis, and/or neurological impairment, namely sensorineural hearing loss or mental retardation. In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. Because of the incomplete penetrance of this anomaly, the suspicion of Muenke syndrome must be raised in any child with uni- or bilateral coronal craniosynostosis, and the genetic analysis propounded even in the absence of extracranial features. ILLUSTRATIVE CASES: We report the cases of two sisters who presented with Muenke syndrome and whose affected mother did not have any form of craniosynostosis.

Arginine↗

Neurocutaneous melanosis.

BACKGROUND: Neurocutaneous melanosis (NCM) is a rare phakomatosis characterized by a focal or diffuse proliferation of melanin-producing cells in both the skin and the leptomeninges. This syndrome is believed to result from an error in the morphogenesis of embryonal neuroectoderm. FEATURES: Two-thirds of patients with NCM have giant congenital melanocytic nevi, and the remaining third have numerous lesions but no giant lesions. Most patients present neurological manifestations early in life, which can be secondary to intracranial hemorrhages, to impairment of cerebrospinal fluid circulation, and to malignant transformation of the melanocytes. PROGNOSIS: The prognosis of patients with symptomatic neurocutaneous melanosis is extremely poor, even in the absence of malignancy. Chemotherapy has been ineffective in the few patients in whom it has been tried.

Case-Control Studies↗

Factors influencing hospital infection control policies in Italian hospitals.

A study was undertaken to determine the resources available in Italian hospitals for the control of nosocomial infections and the factors favouring a successful approach. During January-May 2000 a questionnaire about infection control was sent to the hospital health director of all Italian National Health System hospitals treating acute patients and with more than 3500 admissions in 1999. An active programme was defined as a hospital infection control committee (HICC) meeting at least four times in 1999, the presence of a doctor with infection control responsibilities, a nurse employed in infection control and at least one surveillance activity and one infection control guideline issued or updated in the past two years. There was a response rate of 87.5% (463/529). Almost fifteen percent (69/463) of hospitals had an active programme for Infection Control and 76.2% (353/463) had a HICC. Seventy-one percent (330/463) of the hospitals had a hospital infection control physician and 53% (250/463) had infection control nurses. Fifty-two percent (242/463) reported at least one surveillance activity and 70.8% (328/463) had issued or updated at least one guidance document in the last two years. The presence of regional policies [odds ratio (OR) 8.7], operative groups (OR 4.2), at least one full-time nurse (OR 4.6) and a hospital annual plan which specified infection control (OR 2.1) were statistically associated with an active programme in the multivariate analysis.

Cross Infection↗

Mechanisms of perinatal brain injury.

Perinatal brain injury is associated with pathological conditions caused by pathogenetic mechanisms that remain unclear. Brain lesions can result not only from brain injury but may also originate during fetal growth. Fetal encephalopathy includes 4 groups of causes: maternal, fetal, placental and idiopathic. Hypoxic-ischemic lesions (periventricular leucomalacia and subcortical leucomalacia) and hemorrhage lesions (germinal hemorrhage) are discussed.

Brain Diseases↗

Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors.

Safe and efficient genetic modification of liver cells could enable new therapies for a variety of hepatic and systemic diseases. Lentiviral vectors are promising tools for in vivo gene delivery. Previous data suggested that recruitment into the cell cycle was required for transduction of hepatocytes in vivo. We developed an improved vector design that enhanced nuclear translocation in target cells and significantly improved gene transfer performance. Using the new vector and a panel of internal promoters, we showed that rat hepatocytes were transduced ex vivo to high frequency without requirement for proliferation. On intravenous administration of vector into adult severe combined immunodeficient (SCID) mice, we found high levels (up to 30%) of transduction of parenchymal and nonparenchymal cells of the liver, integration of the vector genome in liver DNA and stable expression of the marker green fluorescent protein (GFP)-encoding gene without signs of toxicity. Coadministration of vectors and 5'-bromo-2'-deoxyuridine in vivo proved that cell cycling was not required for efficient transduction of hepatocytes. In addition to the liver, the spleen and the bone marrow were transduced effectively by systemic delivery of vector. GFP expression was observed in all these organs when driven by the cytomegalovirus promoter and by the phosphoglycerate kinase gene promoter. Using the promoter of the albumin gene, we could restrict expression to hepatocytes. By a single vector injection into the bloodstream of SCID mice, we achieved therapeutic-range levels of the human clotting factor IX, stable in the plasma for up to 1 year (the longest time tested), indicating the potential efficacy of improved lentiviral vectors for the gene therapy of hemophilias and other diseases.

Animals↗

Involvement of astrocytes in purine-mediated reparative processes in the brain.

Astrocytes are involved in multiple brain functions in physiological conditions, participating in neuronal development, synaptic activity and homeostatic control of the extracellular environment. They also actively participate in the processes triggered by brain injuries, aimed at limiting and repairing brain damages. Purines may play a significant role in the pathophysiology of numerous acute and chronic disorders of the central nervous system (CNS). Astrocytes are the main source of cerebral purines. They release either adenine-based purines, e.g. adenosine and adenosine triphosphate, or guanine-based purines, e.g. guanosine and guanosine triphosphate, in physiological conditions and release even more of these purines in pathological conditions. Astrocytes express several receptor subtypes of P1 and P2 types for adenine-based purines. Receptors for guanine-based purines are being characterised. Specific ecto-enzymes such as nucleotidases, adenosine deaminase and, likely, purine nucleoside phosphorylase, metabolise both adenine- and guanine-based purines after release from astrocytes. This regulates the effects of nucleotides and nucleosides by reducing their interaction with specific membrane binding sites. Adenine-based nucleotides stimulate astrocyte proliferation by a P2-mediated increase in intracellular [Ca2+] and isoprenylated proteins. Adenosine also, via A2 receptors, may stimulate astrocyte proliferation, but mostly, via A1 and/or A3 receptors, inhibits astrocyte proliferation, thus controlling the excessive reactive astrogliosis triggered by P2 receptors. The activation of A1 receptors also stimulates astrocytes to produce trophic factors, such as nerve growth factor, S100beta protein and transforming growth factor beta, which contribute to protect neurons against injuries. Guanosine stimulates the output of adenine-based purines from astrocytes and in addition it directly triggers these cells to proliferate and to produce large amount of neuroprotective factors. These data indicate that adenine- and guanine-based purines released in large amounts from injured or dying cells of CNS may act as signals to initiate brain repair mechanisms widely involving astrocytes.

Adenine↗