G207 is a conditionally replicating derivative of herpes simplex virus (HSV) type-1 strain F engineered with deletions of both ␥ 1 34.5 loci and a lacZ insertion disabling the U L 39 gene. We have demonstrated the efficacy of G207 in treating malignant glial tumors in athymic mice, as well as the safety of intracerebral G207 inoculation in mice and in Aotus nancymai. We sought to determine the safety of G207 inoculation into cerebral malignant glial tumors in humans. Criteria for inclusion into this dose-escalation study were the diagnosis of histologically proven malignant glioma, Karnofsky score у70, recurrence despite surgery and radiation therapy, and an enhancing lesion greater than 1 cm in diameter.
Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The eVects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/ day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances. (Arch Dis Child 2001;84:68-71) Keywords: acetazolamide; cerebrospinal fluid; hydrocephalus; ventriculopleural shunts Congenital and acquired obstructive hydrocephalus are common problems in children, with an incidence of 0.4-0.8 per 1000 liveborns and stillbirths. 1 The majority of these patients are managed with ventriculoperitoneal shunts. The ability of the peritoneal membranes to absorb cerebrospinal fluid (CSF) may be decreased after intra-abdominal infections or surgery, such that a ventriculoperitoneal shunt may not provide adequate decompression of the ventricles. In this situation, CSF may need to be drained from the ventricle into other body cavities, such as the pleural space. The success of ventriculopleural shunts may be limited by the rate of absorption of CSF by the pleural membranes. Respiratory insuYciency may develop with the accumulation of large volumes of CSF in the pleural space. Therefore, attempts to limit CSF production may be beneficial in this situation.Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease CSF production in animal models and is used in both adults and children to treat conditions such as pseudotumor cerebri.2 3 There are, however, no studies reporting the change in CSF volume produced by children after extended treatment with ACTZ. We report our use of ACTZ in two children who had experienced multiple ventriculoperitoneal shunt failures and who were temporarily managed with externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. We evaluated the eVect of ACTZ on CSF production and the subsequent tolerance of the ventriculopleural shunt. Case reportsPatient 1 was a 1 year old male born at 24 weeks gestation with multiple medical problems, including bronchopulmonary dysplasia (BPD) and respiratory failure requiring mechanical ventilatory support via a tracheostomy. He also had a right femoral Broviac type indwelling central catheter for parenteral nutrition and medications. He developed hydrocephalus secondary to an intraventric...
Postpump chorea (PPC) is the development of choreoathetoid movements within 2 weeks following cardiopulmonary bypass. Over a 10-year period, 668 children underwent open cardiac surgery, of whom 8 (1.2%) developed PPC. Age at surgery ranged from 8 to 34 months. The onset of chorea was 3 to 12 days following surgery. Computed tomography and magnetic resonance imaging showed atrophy but no focal lesions. Cerebral positron emission tomography using [18F]fluorodeoxyglucose in a patient following 12 months of chorea showed patchy areas of decreased glucose metabolism. None of the patients were developmentally normal 22 to 130 months following surgery. Three patients have had transient and 5 have persistent chorea. Neurological deficits ranged from a mild learning disability to progressive hypotonia and obtundation ending in death. One of 4 patients who received haloperidol had a decrease in the severity of chorea. We compared PPC patients with 39 randomly selected controls. During surgery, affected patients spent significantly more time on pump and at temperatures under 36 degrees C, were cooled to lower temperatures than controls, and were more likely to have had a circulatory arrest. One patient developed chorea without a history of circulatory arrest. We conclude that (1) there is a strong association between PPC, deep hypothermia, and circulatory arrest, (2) absence of characteristic macroscopic changes suggests a biochemical or microembolic etiology in some cases, (3) chorea is frequently associated with developmental delay, and (4) the prognosis for complete resolution of chorea is guarded.
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