Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma.

Brain metastasis is a frequent complication of the progression of malignant melanoma. In a previous study aquaporin 1 (AQP1) protein expression was found to be associated with increased mortality and decreased progression free survival in cutaneous melanoma. To explore further the potential of this marker we studied the AQP1 protein expression in 67 metastatic melanoma patients using immunohistochemistry. Primary tumor samples were acquired from patients with brain (BR) (n = 44) and extra-cranial (EC) (n = 23) metastases, while brain metastatic samples were collected during neurosurgical resection (n = 5). Patients with brain metastases had shorter overall survival (p = 0.02) and significantly higher AQP1 expression in the primary tumors (median H-score = 250 vs. 140, p = 0.044) as compared to patients of the EC metastasis group. AQP1 expression was found to be significantly lower in the brain metastases compared to the corresponding primary tumors (median H-score = 35 vs. 300 p = 0.01). However, in brain metastases AQP1 expression was heterogenous, AQP1 protein was more abundant in the melanoma cells far away from the capillaries as compared to tumor cells adjacent to vessels indicating a hypoxia-driven expression of AQP1. We suggest that AQP1 expression could well be a prognostic marker of brain metastatic potential of human cutaneous melanoma.

Early experiences with image-guided transoral surgery for the pathologies of the upper cervical spine.

STUDY DESIGN: Technical note. OBJECTIVES: Three years of convincing experience with cranial neuronavigation suggested the application of the cranial software and registration method for the transoral access to the C1-C2 vertebrae. BACKGROUND DATA: The C1-C2 vertebrae are located in close vicinity to the cranial base. If the intersegmental movements of the C0-C1/C1-C2 segments are prevented with HALO fixation, the upper cervical spine can be considered as a caudal part of the skull base and included in the extended navigation space of the skull. METHODS: Three patients were selected for navigation-assisted transoral odontoidectomy. Before surgery the patients were fixed and scanned in a HALO device. The fiducials were attached supraorbitally and to both mastoids, determining a wide registration area and allowing the caudal extension of the navigation space. The BrainLAB VectorVision navigation system was used in cranial mode during the operations. RESULTS: Neuronavigation and fluoroscopy-controlled transoral surgery were performed with success in all three cases. The registration accuracy was 1.5, 2.7, and 3.1 mm. CONCLUSION: Image guidance during transoral exposure of the upper cervical spine offered excellent three-dimensional guidance on the ventral surface of the craniocervical junction, allowing a safer, more controlled surgery. As the targets of the transoral spinal surgery are fixed bony and ligamentous structures, no shifting occurs and continuous high navigation accuracy can be achieved. The use of the navigation can reduce the significance of the intraoperative fluoroscopy, diminishing the radiograph load of the patient and the operating room team.

[The role and importance of CT-guided stereotaxic brain biopsy in neurosurgery. Experiences with 523 cases]. / CT vezérelt stereotaxiás agyi biopszia jelentösége és szerepe az idegsebészetben. Tapasztalataink 523 eset kapcsán.

Between 1989 and 1996, 523 stereotactic biopsies of different intracranial lesions were performed at our institution. In 96.3% of the cases accurate histological diagnosis was made. In 59 cases the drainage of the abscess or cyst was carried out. In 48 cases the lesion was axial, in 27 parasellar, 7 pineal and 37 infratentorial. In the rest of the cases the lesion was in the supratentorial hemispheres. Transient neurological deficits were observed in 3.4% of the cases and craniotomy with haematoma evacuation had to be carried out in one case following the biopsy. There was no mortality associated with the interventions in our material. Our experience supports that CT guided biopsy is a safe and efficient method for obtaining histological diagnosis in different intracranial lesions and showed to be very useful in planning te appropriate treatment for each patient.

Apoptosis and p53 expression in human gliomas.

Twenty-five human gliomas of different histological grade and type were studied for p53 expression by immunohistochemistry and for apoptosis using ApopTag method. p53 expression (percentage of positive cells) was highest in anaplastic astrocytomas, followed by low grade astrocytomas and surprisingly in glioblastomas. Granular cytoplasmic p53 positivity appeared in 4/5 low grade oligodendroglioma and in 2/5 low grade mixed oligoastrocytomas. The means of apoptosis index in the different tumor types ranged between 0.8 and 11.5 with the highest values in anaplastic astrocytoma and glioblastomas. Although the number of cases per group were relatively low and the individual vales showed differences it seems that p53 expression is related to the biological aggressiveness of gliomas. It is also suggested that high level of apoptosis in malignant glioma could represent a p53 independent pathway.

Treatment of cystic craniopharyngiomas with yttrium-90 colloid solution.

The authors analyzed long-term follow-up data to assess the value of intracavitary irradiation with stereotactically implanted beta-emitting radioisotope (90)Y-silicate colloid for the treatment of craniopharyngiomas. Fifty-seven craniopharyngiomas in 42 patients were selected for retrospective analysis. The yttrium-90 was implanted intracavitally, using computerized tomography-guided and three-dimensional stereotactic treatment planning. The cumulative dose aimed at the inner surface of the cyst wall was 300 Gy. An average of 75% shrinkage of the initial cyst volume was observed. In 18 cases the reduction was more than 91%, and the cyst disappeared totally in 11 cases. A 50% decrease in cyst volume was usually apparent between the 2nd and 4th months. A 70% decrease in cyst volume was seen by the 5th and 6th months and an 80% reduction by the 7th and 8th months. Cysts that were unchanged remained so throughout the observation period. The time course of volume reduction could be expressed mathematically by the formula of 0.73 X e(-0.62 X T) + 0.27, where "e" is the basic number of natural logarithm and "T" is the time expressed in months. Mean survival duration after intracavitary irradiation was 9.4 years. The shrinkage of the cyst was a consequence of fibrosis of the wall, as seen on histopathological examination. The neuroophthalmological prognosis was favorable only when the optic disc was normal or nearly normal at the time of the treatment. In the presence of preexisting optic atrophy, visual deterioration proved to be irreversible. The long-term results support the view that intracavitary (90)Y-irradiation is a noninvasive and very effective method of treatment for craniopharyngioma cysts. Because of the 1.1 mm half-life decay of beta irradiation, it cannot influence the solid part of the tumor; therefore, the best result can be expected in solitary cysts.

[Clinical outcome of stereotaxic radiosurgery of the brain]. / Az agyi stereotaxiás sugársebészet eredményei.

Authors render an account of their four years clinical experiences with linac-based stereotaxic radiosurgery. The first Hungarian stereotaxic radiosurgery team have treated 166 patients between 01. 07. 1991 and 01. 11. 1995: 86 suffered from brain metastases, 13 of them had primary brain tumors 35, benign brain lesions and 32 arteriovenous malformations. The local control rate was found similar to presented in the literature (83, 77, 57 and 82%). During 9 months of median follow up 44% of brain metastatic cases are alive and only 12% died because of cerebral propagation. The primary brain tumors were mostly recurrences (77%) after surgery and/or conventional radiotherapy, 31% died in 11 months of median follow up. Treating benignomas and arteriovenous malformations there was no need for craniotomy at 68 patients. No fatal complications were observed, the rare side-effects seemed to be manageable. The method is an effective possibility for the non-invasive treatment of the above mentioned brain lesions.

Slit-ventricle syndrome in shunt operated children.

Chronic intracranial hypotension is considered as a frequent complication in shunted hydrocephalus, besides obstruction and shunt-infections. In the last twenty years 32 cases of slit-ventricle were diagnosed among the more than one thousand operations on hydrocephalic children at the Paediatric Department of the National Institute of Neurosurgery, Budapest, Hungary. Most of them have been operated on in infancy. Time from the first operation to the development of slit-ventricle ranged from one to twelve years, the mean was 6.5 years. Seven patients were symptomless (22%), while 25 patients (78%) had more or less severe slit-ventricle syndrome with headache (25 cases), nausea/vomiting (23 cases), altered consciousness (21 cases), brainstem signs (12 cases), and epileptic fits (2 cases). Ten patients with moderate clinical signs improved under conservative treatment. In 15 cases an anti-siphon device (ASD) was implanted. In five of them the clinical result was good, but in the remaining 10 cases typical hypertensive signs were seen. In these cases low flow rate valves were implanted instead of the middle flow rate valve and ASD. In one case the intracranial hypertension persisted, so a middle flow rate shunt system was "reimplanted" and finally the patient improved. In this study the experiences with these 32 cases will be analysed and discussed. The authors stress the primary use of combined valves to avoid the slit-ventricle syndrome.

Multiple intracranial melanoma metastases treated with surgery and radiosurgery with long term control. A case report.

A case of malignant melanoma with multiplex brain metastases is described, where both surgical and radiosurgical treatment was applied. Due to CNS manifestations the patient was operated on in two sessions. First the symptomatic large tumor was removed, and the other, small lesion which could not be reached from the same approach was operated later. The primary skin lesion was discovered and removed between the two operations. A CT scan three months after the second operation revealed recurrence at the site of the first operation, and the appearance of two new tumors. The intracranial neoplasms were treated in one session by stereotactic radiosurgery using a linear accelerator. Six months after this treatment a new skin lesion was removed and the patient received DTIC therapy. Successive CT scans after the irradiation showed a steady regression of the radiosurgically treated tumors, and more than one year after the irradiation no tumor could be detected on the CT scans.

Abscess formation in Rathke's cleft cyst.

Two patients are discussed who presented at our Institute with endocrine dysfunction and sellar enlargement. CT scans revealed intra and suprasellar expanding lesions with ring enhancement. The postoperative histological examination showed remnants of Rathke's cleft cyst together with signs of inflammation. CT and MRI pictures, and possible mechanisms of abscess formation in this region are discussed.

Peripheral vasodilatation after spinal cord stimulation: animal studies of putative effector mechanisms.

Spinal cord stimulation has been reported to relieve ischemic pain and to enhance peripheral circulation. To elucidate the still unknown mechanisms behind these effects, changes in the peripheral blood flow in the skin of the hind paw after stimulation applied to the dorsal column was studied in the normal rat. A substantial flow increase, monitored by laser Doppler technique, was observed in response to stimulation with an intensity comparable to that used clinically in man, recruiting only low-threshold neuronal elements. The response remained after transection of the dorsal roots, as well as after spinal cord section rostrally to the stimulating electrode. Furthermore, monitoring of antidromic compound action potentials in a peripheral nerve indicated that the stimulus intensity applied to dorsal columns recruited solely low-threshold, large-diameter fibers. Stimulation failed to produce an increase in blood flow in addition to that produced by guanethidine and hexamethonium, but high-intensity dorsal column or dorsal root stimulation still was effective. The results indicate that spinal mechanisms are essential and that antidromic activation of primary afferent fibers is unlikely to account for the peripheral vasodilatation induced by low-intensity spinal cord stimulation. Our observations suggest a transitory inhibition of sympathetic vasoconstriction as the principal underlying mechanism.

Electrophysiological aid in high thoracic sympathectomy for palmar hyperhidrosis.

High upper thoracic sympathectomy using microsurgical techniques aided by electrical stimulation of the sympathetic chain is described. Use of the microscope facilitates identification and dissection of the sympathetic chain and minimizes the risk of pleural damage. Electrical stimulation of the sympathetic chain establishes the correct functional level for surgical excision. At the correct level, the threshold for piloerection, sudomotor response, and decrease in blood flow of the ipsilateral hand to electrical stimulation was minimal, and a six-fold increase in stimulus current causing current spread was required to dilate the ipsilateral pupil. After identification of the proper level, surgical excision can be done without risking postoperative Horner's syndrome. Excision of the appropriate ganglia and intervening sympathetic chain with placement of surgical clips on the proximal and distal nerve stumps provides tissue for histological analysis, decreases the opportunity for regeneration, and facilitates localization on postoperative x-rays.

Is vasodilatation following dorsal column stimulation mediated by antidromic activation of small diameter afferents?

It is well-known that high intensity electrical stimulation of peripheral nerves and dorsal root fibres causes vasodilatation. However, the mechanisms underlying the vasodilatory effect of stimulation applied to the dorsal columns (DCS), with an intensity insufficient to recruit small diameter, high threshold fibres are virtually unknown. The present project was planned to elucidate underlying neural mechanisms. Albino rats, anaesthetized, paralyzed and artificially ventilated were used. Electrical stimulation with different parameters was applied to various sites of the exposed spinal cord, root fibres and peripheral nerves. In some experiments the spinal cord, root fibres or peripheral nerves were transected. Peripheral blood flow was recorded using laser Doppler technique. With stimulation of the lower thoracic region at low intensity substantially increased blood flow in the ipsilateral hind paw. The compound action potentials from the gural nerve displayed only components from low threshold, rapidly conducting fibres without detectable late components. Transection of the spinal cord above the stimulation site did not affect the blood flow changes. Also low intensity stimulation of the proximal part of a sectioned dorsal root resulted in a substantial rise in peripheral blood flow, whereas the same intensity proved ineffective when applied to the distal stump. High intensity stimulation of the distal stump not unexpectedly, caused a major increase in blood flow. The findings in the present study implicate the importance of a central circuit for the effect, whereas antidromic activation of primary afferents seems to be a less likely explanation. Possibly, stimulation induces a transitory inhibition of sympathetic vasoconstrictor tone, though activation of sympathetic vasodilatory efferents cannot be excluded.

Formation of potential antigens from radiographic contrast media.

The use of radiographic contrast media is occasionally accompanied by more or less serious adverse effects, evidently of complex etiology, following intravascular administration. Some of these reactions are suspected of having an allergic basis. The in vitro and in vivo formation of iodinated serum proteins following gamma irradiation in the presence of two commonly used radiographic contrast media is demonstrated. Non-toxic concentrations of ascorbate present during the irradiation is shown to prevent the formation of such iodo-proteins in vitro as well as in vivo. The amounts of potentially antigenic iodoprotein formed during radiographic procedures will certainly be very small, but this quantity may be sufficient to elicit a hypersensitivity reaction in cases when an individual has been previously sensitized to immunologically similar iodo-proteins, a mechanism that could account for certain rare and unpredictable reactions. The radiation induced formation of iodo-proteins may also serve as a model for the formation of iodine containing antigens mediated by a free radical mechanism, i.e. in the metabolism of iodinated compounds like erythrosine, a widely used colouring agent for certain foods.

Urethane and hydroxyurethane induce sister-chromatid exchanges in cultured human lymphocytes.

Both urethane and hydroxyurethane induced sister-chromatid exchanges (SCE) in cultured human lymphocytes. Aroclor-induced rat-liver microsome fraction deactivated rather than activated these two agents in the lymphocyte system.

Role of peroxide in the radioprotective action of thiols in E. coli.

The radioprotective action of cysteamine (MEA) and cysteine in E. coli is due partly to autoxidatively generated hydrogen peroxide (H2O2). This effect, which predominates at low concentrations of the thiols (1-2 mM in neutral solution), is regularly correlated with a metabolic block, measured as inhibition of RNA synthesis. In experiments with E. coli 15 (autotroph) under exponential growth in complete medium, the role of H2O2 was demonstrated by (a) a decreased radioprotective action if catalase was present in the medium; (b) a radioprotective action of H2O2 added to the medium; (c) a decreased protective action in the absence of catalytically active copper; and (d) oxygen being required for the radioprotective action to develop. At higher concentrations of the thiols, their radioprotective action, and the accompanying metabolic block, are less dependent on H2O2 generation and presumably due to a different mechanism. The radioprotective action of H2O2 is possibly related to the radioprotective action in mammals of catalase inhibitors.

Cyclization of uridine monophosphate by diethyl pyrocarbonate.

Reaction between diethyl pyrocarbonate and uridine 2'-phosphate or uridine 3'-phosphate leads to the formation in high yields of uridine 2':3'-cyclic phosphate. This reaction product was identified in experiments involving (a) ultraviolet spectrophotometry, (b) paper chromatography, (c) high voltage paper electrophoresis at both pH 3.5 and 7.4, (d) acid hydrolysis, and (e) digestion with pancreatic ribonuclease.