Overcoming of radioresistance in human gliomas by p21WAF1/CIP1 antisense oligonucleotide.

Malignant gliomas are highly resistant tumors against gamma-irradiation and contained overexpression of p21WAF1/CIP1 (p21). Overexpression of p21 enhanced clonogenic survival and suppressed apoptosis after gamma-irradiation in human brain tumor cell lines with or without p53 protein deficiency. The effect of antisense oligonucleotide to p21 against the gamma-irradiation-induced apoptosis and cytotoxicity in malignant glioma cell lines was examined. Antennapedia homeodomain internalization peptide was used as an insertion vector. The high transfection efficiency of Antennapedia homeodomain internalization peptide joined with antisense oligonucleotide was observed. The pretreatment with antisense oligonucleotide enhanced the gamma-irradiation-induced apoptosis and cytotoxicity in radioresistant glioma cells. p21 may represent an important new target for radiosensitization protocols, possibly involving antisense oligonucleotide directed against p21.

[A case of metastatic tumor of the pituitary gland presenting as a subarachnoid hemorrhage].

We reported the case of a 55-year-old man with metastatic tumor of the pituitary gland who suffered from symptomatic pituitary apoplexy with subarachnoid hemorrhage. The patient, who had sigmoid colon carcinoma and left parietal metastatic brain tumor, developed severe headache and decrease of right visual acuity. CT showed a pituitary mass with subarachnoid hemorrhage. Transsphenoidal surgery was performed after replacement therapy with corticosteroids. Histological examination revealed metastasis of adenocarcinoma. Pituitary apoplexy is an unusual manifestation of metastatic pituitary tumor. The case of metastatic tumor of the pituitary gland presenting as subarachnoid hemorrhage such as this case is especial rare.

Experimental study of the embryogenesis of open spinal dysraphism.

This article discusses the experimental studies that have been performed to make clear the embryogenesis of myeloschisis or spina bifida. Some of these theories include: Simple nonclosure; overgrowth and nonclosure; so-called reopening; overgrowth and reopening; and primary mesodermal insufficiency. The authors also discuss recent investigations and give a view into the future.

Hydromyelic hydrocephalus. Correlation of hydromyelia with various stages of hydrocephalus in postshunt isolated compartments.

The clinical features and pathophysiology of specific forms of hydromyelia are analyzed in this report together with the chronological changes of associated hydrocephalus. Nine patients were studied; all had hydromyelia with varying degrees of associated hydrocephalus. Clinically applicable classification systems were used to evaluate the progression of hydrocephalus (Stages I to IV) and to define the compartment isolated after shunting in the previously communicating cerebral ventricles (Types I to IV). Four patients had Stage IV disease (holoneural canal dilatation); one had Stage II and four had Stage I disease (both Stages I and II with supratentorial hydrocephalus). All patients were initially treated by ventriculoperitoneal shunting at an average age of 9.9 years. Five patients had progressive spinal symptoms before or after treatment of their hydrocephalus. Two patients had Type III isolation (an isolated rhombencephalic ventricle) with a functioning ventricular shunt; ventriculography confirmed a communication between the fourth ventricle and the hydromyelia, and both patients improved after placement of a shunt in the fourth ventricle. The remaining patients had Type IV isolation (isolated central canal dilatation) with a functioning ventricular shunt. This study indicates that in some cases the pathophysiology of hydromyelia is closely related to associated hydrocephalus. A new concept of the development of an isolated compartment after shunting is proposed to explain the progression of hydromyelia in these cases.

Radical cranio-orbital reconstructive procedures for cloverleaf skull deformity in adult: operative technique for the longest survivor--case report.

Cosmetic cranio-orbital reconstructive surgery was carried out on a 22-year-old male, the longest surviving case of cloverleaf skull syndrome reported. He previously underwent classical linear suturectomy for synostotic sutures and temporal cranioplasty. Fortunately, hydrocephalus became arrested so did not require continuous cerebrospinal fluid drainage through shunt tube. His intelligence quotient was in the 40s. The present problem was mainly of cosmetic cranio-orbital corrections of shallow orbits with resultant exophthalmos, frontal dysgenesis, and marked temporal bossings. Bilateral orbital advance, lateral canthal/pterional reshaping, frontal remodeling, and temporal reduction cranioplasty were performed. The postoperative outcome was satisfactory. The cloverleaf skull deformity is etiologically and pathologically heterogeneous, so radical surgical reconstructive procedures should be planned and designed individually.

Multicentric glioblastoma multiforme occurring in the supra- and the infratentorial regions--case report.

A 74-year-old male was admitted because of severe headache, vertigo, and vomiting. A computed tomographic scan showed heterogeneously enhanced tumors in the supra- and the infratentorial regions, apparently attached to the cerebellar tentorium. He died 2 months after the onset despite external decompression and a ventriculo-peritoneal shunt. The autopsy showed both tumors were intra-axial and not attached to the dura mater including the cerebellar tentorium. The histological diagnosis of either tumor was glioblastoma multiforme. This case could be classified as multicentric gliomas. In the 23 reported cases, including our case, most died soon after the onset of symptoms. Some, however, with low grade tumors had a comparatively long life span after the onset. It is, therefore, important to investigate the histology of these tumors for correct prognosis.

Flunarizine treatment in poor-grade aneurysm patients.

A cerebral Ca2+ overload blocker--flunarizine hydrochloride--was used with excellent results for prophylaxis of delayed ischaemic neurological deficit (DIND) in severe subarachnoid haemorrhage. The drug was administered orally at a dose of 10 mg, four times daily for four days, followed by three times daily for three days and twice daily for 14 more days. Of 72 patients treated with flunarizine, only one developed permanent DIND. 37 consecutive patients who were in Fisher's group III and were treated with flunarizine from immediately after early surgery were compared retrospectively with the 37 consecutive Control Group patients, who also belong to Fisher's group III. Among the Control Group patients, eight died from DIND and ten developed infarction from DIND, while flunarizine strongly prevented (p less than 0.001) DIND. Furthermore, the only one DIND was attributable to failure of administration of flunarizine. There were no side-effects from flunarizine. The association of severe angiographic vasospasm was less frequent in the Flunarizine Group (18% vs 57%, p less than 0.02). From this evidence, it might be concluded that flunarizine significantly inhibits the occurrence of severe neurological deficit due to delayed vasospasm. This highly beneficial effect on severe delayed vasospasm might be attributable to its intense inhibitory action on intracellular Ca2+ overloads especially in severe pathological situations.