Investigation of enteric adenovirus and poliovirus removal by coagulation processes and suitability of bacteriophages MS2 and φX174 as surrogates for those viruses.

We evaluated the removal of enteric adenovirus (AdV) type 40 and poliovirus (PV) type 1 by coagulation, using water samples from 13 water sources for drinking water treatment plants in Japan. The behaviors of two widely accepted enteric virus surrogates, bacteriophages MS2 and φX174, were compared with the behaviors of AdV and PV. Coagulation with polyaluminum chloride (PACl, basicity 1.5) removed AdV and PV from virus-spiked source waters: the infectious AdV and PV removal ratios evaluated by means of a plaque-forming-unit method were 0.1-1.4-log10 and 0.5-2.4-log10, respectively. A nonsulfated high-basicity PACl (basicity 2.1) removed infectious AdV and PV more efficiently than did other commercially available PACls (basicity 1.5-2.1), alum, and ferric chloride. The MS2 removal ratios tended to be larger than those of AdV and PV, partly because of differences in the hydrophobicities of the virus particles and the sensitivity of the virus to the virucidal activity of PACl; the differences in removal ratios were not due to differences in the surface charges of the virus particles. MS2, which was more hydrophobic than the other viruses, was inactivated during coagulation with PACl. Therefore, MS2 does not appear to be an appropriate surrogate for AdV and PV during coagulation. In contrast, because φX174, like AdV and PV, was not inactivated during coagulation, and because the hydrophobicity of φX174 was similar to or somewhat lower than the hydrophobicities of AdV and PV, the φX174 removal ratios tended to be similar to or somewhat smaller than those of the enteric viruses. Therefore, φX174 is a potential conservative surrogate for AdV and PV during coagulation. In summary, the surface hydrophobicity of virus particles and the sensitivity of the virus to the virucidal activity of the coagulant are probably important determinants of the efficiency of virus removal during coagulation.

A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin. Theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery.

A pharmacokinetic two-compartment model for the treatment of brain tumors in man was simulated with the aid of a computer. The parameters necessary for the simulations such as inactivation rate constant, elimination rate constant, distribution volume, blood volume, cerebral blood flow, and cytotoxic drug concentration were either determined in this study or obtained from the literature. A proteinaceous antitumor antibiotic, neocarzinostatin (NCS), was utilized as a prototype drug because it has features making it advantageous in the treatment of brain tumor. In particular, NCS has an extremely short half-life in serum (t 1/2 less than or equal to 3 s), while it is relatively stable in the cerebrospinal fluid (CSF) (t 1/2 approximately 50 s). Therefore, the drug level in the cerebral compartment can be made adequately high with an appropriate infusion velocity into the cerebral compartment; however, it was possible to keep the plasma level of the drug much lower than the toxic level. Thus, few side-effects should result. In an in vitro study, NCS was found to exhibit its cytotoxicity to glioblastoma cells at a concentration as low as 0.005 microgram/ml. In contrast, the cytotoxicity was not apparent for the normal glia cells at 0.1 microgram/ml. The model being considered in this investigation is a two-compartment model, which consists of the cerebral compartment and the rest of the circulatory system of the body. In this case the drug is infused via an internal carotid artery. The results of pharmacokinetic simulation and dose regimens for NCs are presented, based on the effective concentration of the drug to glioblastoma cells in culture and the available pharmacological parameters.

Treatment of intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein.

We treated 10 patients with intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein between 1969 and 1992. Two patients were treated with radiotherapy (RT) only (RT group), and three were treated with RT and cisplatin plus vinblastine plus bleomycin therapy with or without surgery (cisplatin plus vinblastine plus bleomycin group). The most recently treated five patients received cisplatin plus etoposide (PE) therapy with or without RT and/or surgery (PE group). The level of alpha-fetoprotein in serum was elevated in all 10 patients. In the PE group, PE therapy consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given two or three times at 4-week intervals and then once every 4 months; the patients received three to six courses (mean, 4.2 courses). In the RT group (n = 2), one patient died 3 months after diagnosis and the other died at 12 months. In the cisplatin plus vinblastine plus bleomycin group (n = 3), complete remission was obtained in one patient, but the other two patients died 12 and 24 months after diagnosis. In contrast, in the PE group (n = 5), complete remission was obtained in all patients who are all currently alive without recurrence, at 35 to 71 months (average, 53.6 mo) after diagnosis. The results indicate that multidisciplinary treatment including combination chemotherapy with cisplatin and etoposide with or without surgery and/or RT is highly effective in the treatment of patients with alpha-fetoprotein-producing intracranial nongerminomatous malignant germ cell tumor.

Intracranial extracerebral brain heterotopia. Case report.

The authors describe a case of intracranial heterotopic brain located on the medial one-third of the left sphenoid ridge, and enveloped in a huge cystic cavity. The heterotopic brain was resected successfully with satisfactory clinical results. The resected brain was 8 X 4 X 3 cm in diameter, of 7 or 8 months gestational age, and consisted of cerebrum, brain stem, and cerebellum. Anatomical and cytoarchitectural findings of the heterotopic brain are presented.

Rhabdomyosarcoma of the brain.

The authors report a case of rhabdomyosarcoma originating in the fourth ventricle and review the eight comparable previous reports on true rhabdomyosarcoma, composed solely of mesenchymal elements. Tumors in most adults arose in the cerebral hemisphere, while those in children arose exclusively in the midline structures of the posterior fossa. The tumor in the author's case was initially benign and well circumscribed, but within 2 years had changed into a malignant rhabdomyosarcoma. The histological documentation during the interval is presented and discussed.

Preliminary observations for a new treatment in children with primary intracranial yolk sac tumor or embryonal carcinoma. Report of five cases.

The authors evaluated the effect of adjuvant therapy (preoperative chemotherapy combined with radiotherapy) followed by radical tumor removal in the treatment of children with primary intracranial yolk sac tumor, embryonal carcinoma, or mixed germ cell tumors containing yolk sac tumor components. Between 1988 and 1995, five consecutive patients were treated with adjuvant therapy followed by total tumor removal. The diagnosis was based on markedly elevated concentrations of serum alpha-fetoprotein (AFP) and/or beta-human chorionic gonadotropin (beta-HCG) in four children and the results of biopsy sampling in one child. The chemotherapy regimen consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given three times at 4-weeks intervals. Radiotherapy consisted of 30 to 40 Gy to the whole brain or an area including all ventricles and a 15- to 20-Gy boost to the tumor site. Spinal radiation of 25 Gy was added in one patient. In all patients the serum level of AFP and beta-HCG gradually decreased during the adjuvant therapy and disappeared completely on its completion. In two of the five patients the tumor disappeared as well. In the other three patients the tumor size was moderately or markedly reduced and the remaining tumor was totally removed; there were no neurological deficits. Chemotherapy was maintained after the initial treatment and was repeated every 2 to 4 months for less than 2 years. All children are alive and well without recurrence at 33 to 118 months (average 88 months) after the start of adjuvant therapy. Our preliminary results indicate that adjuvant therapy consisting of combination chemotherapy with cisplatin and etoposide and concomitant radiotherapy, followed by removal of the tumor, is highly effective in the treatment of pediatric patients with primary intracranial yolk sac tumor, embryonal carcinoma, or mixed germ cell tumors containing yolk sac tumor components.

Basal encephaloceles with morning glory syndrome, and progressive hormonal and visual disturbances: case report and review of the literature.

We report an 11-year-old girl with progressive hypopituitarism and visual loss of the right eye caused by trans-sphenoidal and sphenoethmoidal encephaloceles associated with morning glory syndrome. She was first seen at the age of 8 years, because of polydipsia and polyuria, and examination at that time revealed pituitary dwarfism and morning glory syndrome with visual disturbance of the right eye. Hormonal examinations revealed deficiency of growth hormone (GH) and anti-diuretic hormone (ADH). MR image showed trans-sphenoidal and sphenoethmoidal encephaloceles. At the age of 9 years, she was found at another institution to be blind in the right eye. Our examination of the patient at the age of 11 years revealed no change of the findings for the encephaloceles or optic system. Hormonal examination disclosed deficiencies of all hormones except for thyrotropin (TSH). This patient showed progressive hormonal and optic disturbances during the follow-up period. The natural course is still unclear, but our review of reported cases of trans-sphenoidal encephalocele with hormonal disturbance revealed that the most frequent findings were GH and ADH disturbance (over 60%), most patients (77.8%) showed progression of hormonal disturbance, and 40% of those with optic dysfunction showed progression. A patient with basal encephalocele with hormonal and / or optic disturbances requires careful long-term follow up.

Ruptures of arteriovenous malformations in children associated with trivial head trauma.

Three cases of ruptured arteriovenous malformations (AVMs) in childhood associated with trivial head trauma are reported. These patients represented 12.5% of 25 consecutive patients with cerebral AVMs. The patients' ages ranged from 5 to 9 years; the patients were younger than their nontraumatic counterparts. The force of the trauma was presumably received in an anteroposterior or posteroanterior direction in all cases. Hematomas accompanying the AVMs were located in the subcortical area of the parietal or temporal lobe and angiographically their feeding arteries were all from the anterior cerebral artery or middle cerebral artery. The possible mechanisms for the rupture of AVMs after trivial head trauma are discussed.

Management outcome for ruptured anterior circulation aneurysms with a Hunt and Hess clinical grade of III in patients in the 9th decade of life.

BACKGROUND: This study was conducted to define general guidelines for rational clinical decision-making with respect to patients older than 80 years who present with ruptured anterior circulation aneurysms and a Hunt and Hess clinical grade of III. METHODS: The 29 consecutive patients enrolled in this study were treated at 4 participating centers between 1995 and 1998. All were 80 years or older on admission and met 7 eligibility criteria. The decision to treat surgically or non-surgically was made individually at each center. The outcome at discharge was assessed using the Glasgow Outcome Scale (GOS); the Barthel Score (BS) was used to determine the patients' quality of life after discharge. RESULTS: Of 15 surgically treated patients, 4 died before discharge and 8 were discharged in poor condition. Of these, 7 died of unrelated causes within 2 years of the SAH and one is living in a nursing home. Three patients with middle cerebral artery (MCA) aneurysms made a good recovery; they are currently living at home. Of the 14 conservatively treated patients, 10 died during their hospital stay mainly because of rebleeding that occurred within 3 weeks of the subarachnoid hemorrhage (SAH). Three others who were discharged in poor condition died of systemic illness within 2 years. The remaining patient is living in a nursing home with a BS value of 0. CONCLUSIONS: The outcomes for patients treated conservatively were catastrophic. Even in surgically treated patients, favorable outcomes were rare; the best results were achieved in surgically treated patients with MCA aneurysms.

Wrapping of intracranial aneurysms with gauze sponge.

A gauze sponge wrapping method to prevent recurrent subarachnoid hemorrhage (SAH) after incomplete obliteration of intracranial aneurysm or a residual neck after clipping was developed and tested. The authors performed the gauze wrapping for aneurysms with incomplete obliteration by clipping alone, abnormal changes of the parent artery wall which had the possibility of regrowth or rerupture, and surgical difficulties. The residual neck of the aneurysm or the abnormal arterial wall was tightly and completely wrapped, including the parent artery, and cemented with plastic adhesive. Seventy-eight (22.3%) of 349 surgically treated aneurysms were treated by gauze wrapping (26 wrapping only, 52 clipping and wrapping). The incidence of complications such as infection, angiospasm, and normal pressure hydrocephalus, and the clinical outcome were not significantly different for the wrapping and non-wrapping groups. No recurrent SAH was observed in the wrapping group during 3 months to 8.5 years follow-up. These results suggest that wrapping with gauze sponge is useful in the treatment for ruptured aneurysms which cannot be totally obliterated.

Cerebellar mutism after posterior fossa surgery--two case reports.

Two adults (aged 71 and 74 years) developed cerebellar mutism after posterior fossa surgery for a mass lesion in the superior cerebellar hemisphere or upper vermis. Histological examination showed one was a hemangioblastoma, the other a metastatic brain tumor. The tumors were totally removed via the occipital transtentorial approach. Both patients developed mutism on the 2nd postoperative day, which persisted for 3-4 weeks and was followed within 2-4 months by cerebellar dysarthria. Thereafter, their condition improved. Transient cerebellar mutism usually occurs in pediatric patients after the removal of a mass lesion in the upper vermis. Cerebellar mutism in adults is rare. The predominance of cerebellar mutism in children may be attributable to the predilection for vermian tumor and their tendency to experience personality and behavioral changes after posterior fossa surgery.

Accessory middle cerebral artery and duplication of middle cerebral artery--terminology, incidence, vascular etiology, and developmental significance.

A series of 455 bilateral carotid angiographies included 14 accessory middle cerebral arteries (Acc-MCAs) and seven duplication of middle cerebral arteries (Dup-MCAs). The branching patterns of Dup-MCA could be classified as "direct bifurcation" from the internal carotid artery, since most lacked the essential bifurcation or trifurcation at the distal end of the M1 portion. On the other hand, Acc-MCAs are probably residual congenital arteries. These anomalous MCAs were apparently associated with epilepsy. Five Acc-MCAs were associated with anterior communicating artery aneurysm at the origin. In addition, a rare case of Dup-MCA with arteriovenous malformation at its origin was found.

[Studies on cyclic 3', 5'-AMP system in human brain and its clinical application in Neurosurgical practice (author's transl)].

Literatures showed that cyclic AMP of cultured neoplastic cells of any kind was very low in concentration and also the effect of cyclic AMP and its derivatives on the malignant cells, especially on the malignant glioma, was already reported in vivo or in vitro from several neurosurgical units. The intrinsic content of cyclic AMP of the human cerebrum and the human brain tumors was first reported by authors in 1971. In this presentation the authors intended to confirm that the lower concentration of the cyclic AMP the more histologically malignant cerebral neoplasm, as well as in the cerebrospinal fluid, was observed. Concentration of cyclic AMP in the subcortical white matter, glioma, meningioma and medullobalstoma was much lower than in the gray matter tissue, however, it was not clear that the difference of the cyclic AMP concentration be possibly related to the malignancy of the human brain tumor. Furthermore, the cyclic AMP content of the cerebrospinal fluid of the patients with various brain tumor was not clearly different. The activity of adenyl cyclase was reported the highest in the synaptosome-containing fraction of the rat brain homogenate and this fact was significantly consistent with the finding that the highest concentration of the cyclic AMP was found in the human grey matter tissue. With the human brain gray matter authors determined successfully the activity of the human cerebral phosphodiesterase, which was probably localized in the post-synaptic membrane and was 158 nmole/mg protein/min. Its apparent Km was 0.9 x 10(-4) M. The results reported above have suggested the important participation of the cyclic AMP to cerebral synaptic transmission of nerve impulses, which was studied by light and electron-microscopic autoradiography utilizing the pulse labeling method with 3H-adenine. According to our study the majority of the adenyl cyclase of the human cerebrum was located synaptic structure and the finding obtained was quite compatible, as the first morphological study, with previously reported biochemical analyses. It was indicated that the cyclic AMP in the human brain was concerned to the cerebral synaptic transmission of nerve impulses and this should be very interesting and important to the clinical application for recovering cerebral function of neurosurgical patients.

[Actinomycotic brain abscess -case report- (author's transl)].

Actinomycosis of the central nervous system is rare. There has been considerable discussion as to whether it can be primary, but several cases have been reported occasionally. Authors presented a case of cerebral actinomycosis involving primarily the right frontal lobe through an obsolete stick wound. Patient is a 18-year-old man and when he was 8 years of age, he received right frontal penetrating injury due to fall on wire about 3 mm in diameter. Wound had healed sustaining any abnormal effect to note. Eleven years later, he was admitted to our institution because seizure attack characterized by automatism, and plain skull X-ray showed intracranial frontal calcification. EEG, angiography, RI scan and CT scan were performed. At operation, a granuloma was found and total removal was performed. The histological examination showed actinomycotic brain absess. Patient was treated with antibiotics and he returned to the previous occupation. Primary actinomycosis of the central nervous system was discussed with previously reported cases in the literature.

[Traumatic aneurysm of the frontopolar artery developing after evacuation of the subdural effusion in a 6-month-old girl (author's transl)].

A 6-month-old girl developed bilateal subdural effusion after head injury. She gradually improved after the partial stripping of the membrane of the subdural effusion although postoperative tappings of the subdural fluid were necessary. Thirty nine days after the injury, she suddenly suffered from a massive intraventricular hemorrhage. A cerebral angiography showed an aneurysm arising from the proximal part of the right frontopolar artery, which had not been revealed in the previous angiograms. It was obscure whether the congenital anomaly of the arterial wall had been existed or not, but this aneurysm might be mentioned as a traumatic aneurysm and definitely developed after the treatment for the traumatic sequence. The mechanism of this aneurysmal formation was supposed that the arterial wall was initially injured by the abnormal traumatic movement of the brain underneath the falx cerebri, and teared arterial wall was further injured by the fluctuating movements of the brain caused by repeated tappings of the effused fluid. Relation of delayed posttraumatic apoplexy and ruptured posttraumatic aneurysms was also discussed, and analysis of the reported cases of the traumatic aneurysm, as well as aneurysm in the infant, was made.

[A case of familial type IIa hyperlipoproteinemia with intracranial xanthoma].

Familial hyperlipoproteinemia associated with intracranial xanthoma belonged to a very rare entity and the authors were able to collect only one reported case in our domestic literature. A 57-year-old house wife was admitted with a six months' history of progressive hearing impairment on the left and some cerebellar signs characterized by ataxic gait. Physical examination revealed several hard and painful subcutaneous masses around the joints of four extremities, which had enlarged slowly within the last three years. Also, remarkable deformity of Achilles tendon was seen on both sides. Neurological examination showed bilateral papilledema, left hemifacial hyp- and dysesthesia, left hearing difficulty and left cerebellar signs. Laboratory examination reported markedly elevated serum cholesterol level as high as 575 mg/dl, and determination of the serum lipoprotein disclosed the findings compatible with Type II a hyperlipoproteinemia. Plain skull X-rays showed osteolytic defect of the left occipital bone and CT scan demonstrated a large irregular low density mass extending into the left posterior fossa, which showed ring like enhancement and spotty high density of calcification. Angiogram suggested the mass was of less vascular lesion and situated extramedullary. Suboccipital craniectomy was performed and an epidural solid mass was resected, although the mass was markedly growing into the posterior cranial cavity. Microscopic examination showed the findings typical to the xanthoma, which was totally coincided with that of biopsy specimen obtained from the tumor over the ankle. Electron microscopic examination was performed and various kinds of lipid inclusions in the cytoplasma of xanthoma cells, such as dense bodies, volute or onion-like figures and lucent large vacuoles, were observed.

Improved virus removal by high-basicity polyaluminum coagulants compared to commercially available aluminum-based coagulants.

We investigated the effects of basicity, sulfate content, and aluminum hydrolyte species on the ability of polyaluminum chloride (PACl) coagulants to remove F-specific RNA bacteriophages from river water at a pH range of 6-8. An increase in PACl basicity from 1.5 to 2.1 and the absence of sulfate led to a reduction of the amount of monomeric aluminum species (i.e., an increase of the total amount of polymeric aluminum and colloidal aluminum species) in the PACl, to an increase in the colloid charge density of the PACl, or to both and, as a result, to high virus removal efficiency. The efficiency of virus removal at around pH 8 observed with PACl-2.1c, a nonsulfated high-basicity PACl (basicity 2.1-2.2) with a high colloidal aluminum content, was larger than that observed with PACl-2.1b, a nonsulfated high-basicity PACl (basicity 2.1-2.2) with a high polymeric aluminum content. In contrast, although extremely high basicity PACls (e.g., PACl-2.7ns, basicity 2.7) effectively removed turbidity and UV260-absorbing natural organic matter and resulted in a very low residual aluminum concentration, the virus removal ratio with PACl-2.7ns was smaller than the ratio with PACl-2.1c at around pH 8, possibly as a result of a reduction of the colloid charge density of the PACl as the basicity was increased from 2.1 to 2.7. Liquid (27)Al NMR analysis revealed that PACl-2.1c contained Al30 species, which was not the case for PACl-2.1b or PACl-2.7ns. This result suggests that Al30 species probably played a major role in virus removal during the coagulation process. In summary, PACl-2.1c, which has high colloidal aluminum content, contains Al30 species, and has a high colloid charge density, removed viruses more efficiently (>4 log10 for infectious viruses) than the other aluminum-based coagulants-including commercially available PACls (basicity 1.5-1.8), alum, and PACl-2.7ns-over the entire tested pH (6-8) and coagulant dosage (0.54-5.4 mg-Al/L) ranges.