Dissecting aneurysm of the peripheral posterior inferior cerebellar artery.

Dissecting aneurysms of intracranial posterior circulation have recently been shown to be less uncommon than previously thought. However, those involving the posterior inferior cerebellar artery (PICA) and not vertebral artery at all are extremely rare. We report here a case of a patient with a dissecting aneurysm of the lateral medullary segment of PICA which presented as subarachnoid haemorrhage. The aneurysm was treated by trapping surgery and the distant PICA was anastomosed to the occipital artery. The patient showed a slight ataxia immediately after surgery but recovered fully. Recovery from immediately postoperative cerebellar symptoms due to intra-operative ischemia seemed to be due largely to recovery of flow in the region of cortical branches of PICA.

The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma.

OBJECT: Hypothalamic hamartoma is generally diagnosed based on its magnetic resonance (MR) imaging characteristics and the patient's clinical symptoms, but the relationship between the neuroradiological findings and clinical presentation has never been fully investigated. In this retrospective study the authors sought to determine this relationship. METHODS: The authors classified 11 cases of hypothalamic hamartoma into two categories based on the MR findings. Seven cases were the "parahypothalamic type," in which the hamartoma is only attached to the floor of the third ventricle or suspended from the floor by a peduncle. Four cases were the "intrahypothalamic type," in which the hamartoma involved or was enveloped by the hypothalamus and the tumor distorted the third ventricle. Six patients with the parahypothalamic type exhibited precocious puberty, which was controlled by a luteinizing hormone-releasing hormone analog, and one patient was asymptomatic. No seizures or mental retardation were observed in this group. All patients with the intrahypothalamic type had medically intractable seizures, and precocious puberty was seen in one. Severe mental retardation and behavioral disorders including aggressiveness were seen in two patients. The seizures were controlled in only one patient, in whom stereotactically targeted irradiation of the lesion was performed. This topology/symptom relationship was reconfirmed in a review of 61 reported cases of hamartoma, in which the MR findings were clearly described. The parahypothalamic type is generally associated with precocious puberty but is unaccompanied by seizures or developmental delay, whereas the intrahypothalamic type is generally associated with seizures. Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. CONCLUSIONS: Classification of hypothalamic hamartomas into these two categories based on MR findings resulted in a clear correlation between symptoms and the subsequent clinical course.

[Relationship between body type, subjective symptoms and health awareness in junior high school students].

This study investigated the relationship between body type, subjective symptoms and health awareness among junior high school students. The subjects were 410 students (208 males and 202 females) at a junior high school in Okayama City. The survey was conducted in May, 1992. The results obtained were as follows. 1. As to the level of health awareness, those who consider themselves healthy account for 11.7%, generally healthy, 65.1% and little unhealthy, 23.2%. 2. The average Rohrer Index was 125.8 (+/-18.1). Comparison between both sexes revealed that the average was significantly higher for females. 3. In the case of body type classification based on the Rohrer Index, obesity type was 12.4%, standard type was 73.4% and Iptosomic type was 14.2%. 4. The percentage of persons complaining of any of the 30 subjective symptoms was 20.2%, and the average number of symptoms for the individual respondent was 6.1 (+/-5.2). 5. The leptosomic type showed a tendency toward more subjective symptoms than the standard type. 6. Those with more subjective symptoms or obesity and leptosomic type showed a tendency toward a sense of a little unhealthy in level of health awareness.

Simultaneous determination of a new anticancer agent (NB-506) and its active metabolite in human plasma and urine by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic method with ultraviolet detection has been developed to quantify NB-506 and its active metabolite in human plasma and urine. This method is based on solid-phase extraction, thereby allowing the simultaneous measurement of the drug and metabolite with the limit of quantification of 0.01 microgram/ml in plasma and 0.1 microgram/ml in urine. Standard curves for the compounds were linear in the concentration ranges investigated. The range for the drug in plasma was 0.01-2.5 micrograms/ml, and for the metabolite 0.01-1 microgram/ml. In urine, the range for both compounds was 0.1-10 micrograms/ml. The method was validated and applied to the assay of plasma and urinary samples from phase I studies.

Large molecule fraction of plasma separated with polyethylene glycol in treatment of chronic relapsing thrombotic thrombocytopenic purpura.

Plasma exchange and plasma infusion are effective in the treatment of patients with thrombotic thrombocytopenic purpura (TTP). It has been proposed that some component in normal plasma may be deficient in TTP patients. In this experiment normal plasma was fractionated and an effective fraction for the treatment of TTP was sought. Plasma was fractionated with 5% polyethylene glycol and a large molecule fraction was obtained which was composed mainly of proteins and lipoproteins with molecules larger than that of IgG. The fraction was dissolved in physiological saline and infused in two patients with chronic relapsing TTP who had been successfully treated periodically with plasma infusion. Peripheral platelet counts and serum LDH levels were measured, and the efficacy of the treatment was assessed. Infusion of the large molecule fraction elevated platelet counts and lowered the LDH level. However, the efficacy of the large molecule fraction was 25 to 50% that of plasma. Components in the fraction may have been inactivated partially during preparation. We propose that the large molecule fraction contains factors which are effective in some patients with TTP.

Transcranial magnetic coil stimulation of motor cortex in patients with central pain.

We report two patients with deafferentation pain secondary to central nervous system lesions who were evaluated by noninvasive magnetic coil stimulation of the motor cortex followed by electrical motor cortex stimulation with epidural electrode array implantation. Magnetic coil stimulation was very useful to estimate the effect of electrical stimulation. Our first patient was a 52-year-old man who experienced a left putamenal hemorrhage at the age of 48. Two years later, he had paresthesias and intractable pain in the extremities and face on the right side. Pain was resistant to barbiturates but responded to magnetic coil stimulation of the motor cortex. Electrical motor cortex stimulation provided excellent relief from the pain. The second patient was a 43-year-old man who was suffering from congenital cerebral palsy for which left thalamotomy was performed two times, at the ages of 9 and 13. He began to experience intractable pain on the right side 20 years later. Although barbiturate administration was effective for pain relief, neither magnetic coil stimulation nor electrical stimulation of the motor cortex gave relief from pain.

Antitumor effects of human recombinant macrophage colony-stimulating factor against rat brain tumors.

The tumoricidal effects of M-CSF were examined using two subcutaneously-transplanted rat brain tumor cell lines, 9L and T9 gliomas. In rats treated with high-dose M-CSF (16 million U/kg administered for 4 days a week for 3 weeks), 9L glioma growth was inhibited by 81.9% following subcutaneous (s.c.) injection and by 70.5% after intraperitoneal (i.p.) injection and T9 glioma growth was inhibited by 69.2% after i.p. injection. After short-term treatment with high-dose M-CSF (32 million U/kg administered s.c. for 6 consecutive days, 9L glioma growth was inhibited by 82.1%. All these inhibitory effects differed significantly compared with the respective untreated control groups. However, treatment with low-dose M-CSF (1.6 million U/kg administered s.c. for 4 days a week for 3 weeks) showed no significant effects against 9L and T9 glioma growth compared with the untreated controls. No significant effects of M-CSF against cell proliferation, measured as PCNA expression, were observed in any group. Significant hematopoietic effects on the leukocyte counts were observed only in the groups treated with high dose M-CSF. These results suggest that M-CSF at a high dose which produces hematopoietic effects on peripheral leukocytes inhibits the growth of gliomas. This inhibitory effect may have been due to a tumoricidal mechanism of M-CSF that depended on the production or release of some hematopoietic soluble factors, but was independent of PCNA expression by the tumors.

Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line.

The antitumor effects of TNF and G-CSF on a xenograft line of human medulloblastoma were examined. (Method):1) A human medulloblastoma xenograft line was transplanted into nude mice. Tumor bearing nude mice were divided into the following eight groups: untreated controls (C); those receiving a subcutaneous injection of G-CSF for one week (G1); for four weeks (G2); those receiving an intratumoral injection of TNF for four weeks (Tit); an intravenous injection of TNF (Tiv); those receiving a combination of G1 and Tit (G1 + Tit); a combination of G2 and Tit (G2 + Tit); and a combination of G2 and Tiv (T2 + Tiv). The relative tumor weight in each group was calculated and any antitumor effects were examined by calculating a tumor growth inhibition ratio. 2) Tumor bearing nude mice were divided into the following two groups: those receiving a subcutaneous injection of G-CSF and an intravenous injection of TNF (G+T); and only an intravenous injection of TNF (T). We evaluated the pathological findings from the tumors at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the TNF injection. Routine H.E. staining and immunostaining using antigranulocyte and antimacrophage antibodies were performed. (Results): 1) The tumor growth inhibition ratio was 0.112, 0.190, 0.287, 0.451, 0.347, 0.635, and 0.622 at G1, G2, Tit, Tiv, G1 + Tit, G2 + Tit, G2 + Tiv group. A combined antitumor effect was clearly seen in the G2 + Tit and the G2 + Tiv groups. 2) The tumor was fragmented by the infiltration of many inflammatory cells 24 hours after TNF injection. Many more macrophages were observed in the tumors of G+T mice than in the T mice. Granulocytes were observed only in the tumors of the G+T mice.

[Study on three patients with malignant glioma showing tumor reduction during maintenance therapy with MCNU].

Tumor regression occurred in three of 19 patients (15.8%) with malignant glioma during maintenance therapy using MCNU. In two patients, the tumor reduced 5 and 8 months after the initial treatment, respectively. In the remaining patient, though the maintenance therapy was interrupted for a while and consequently the tumor size increased, readministration of MCNU reduced the tumor size two months later. Therefore, since the antitumor activity of MCNU against malignant glioma seems to require a certain time depending on the case, it is recommended that MCNU be given as maintenance therapy for at least half a year.

Characterization of adenosine deaminase (ADA)-negative B-lymphoblastoid cells cocultured with ADA-positive fibroblasts.

A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 mumol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 x 10(5) and 1 x 10(6) cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA-negative cells proliferated well when the ratio of ADA-positive cells/ADA-negative cells was over 1/10.

A point mutation in the 5' splice region of intron 7 causes a deletion of exon 7 in adenosine deaminase mRNA.

An adenosine deaminase (ADA;EC 3.5.4.4)-deficient B lymphoblastoid cell line BAD05 derived from a Japanese patient with severe combined immunodeficiency was characterized. As previously reported, one allele of BAD05 expresses undetectable ADA mRNA, and the other allele produces an aberrant mRNA without exon 7. Genomic ADA DNA of BAD05 spanning from a portion of exon 6 to a portion of exon 8 was amplified by PCR. The amplified fragments were cloned into a vector, and 8 clones were isolated and sequenced. The analytical result showed a single base change of G to A at the invariant 5' GT of intron 7 of ADA gene in one allele of BAD05, which accounts for the elimination of exon 7 during splicing.

Prenatal diagnosis of open spina bifida by MRI and ultrasonography.

A case that was diagnosed prenatally as having open spina bifida by magnetic resonance imaging (MRI) and ultrasound (US) examination is reported. At the time of the third US examination, the spina bifida cystica was detected, but it could not be determined by US whether it was open or closed spina bifida. A lumbosacral skin defect was detected on MRI, which permitted prenatal diagnosis of open spina bifida. Surgical repair was performed immediately after delivery. Prenatal intrauterine evaluation of the fetal CNS morphology and malformation has advanced with the improvement of diagnostic tools. Each diagnostic tool, however, has its own advantages and disadvantages. In prenatal intrauterine evaluation, it is important that observation be made through the combined use of multiple diagnostic tools.

[Choroid plexus papilloma of the third ventricle in infancy: a case report].

The incidence of choroid plexus papilloma is about 0.5% of all intracranial tumors, but they are only infrequently found in the third ventricle. This is a case report of choroid plexus papilloma of the third ventricle in an infant. A make child in his 7th month of age was admitted because of large head circumference, on the 28th February, 1989. CT scan demonstrated hydrocephalus caused by a tumor in the third ventricle. Total removal of the tumor was performed on the 8th of March. Histologically the tumor was found to be choroid plexus papilloma. The patient suffered from postoperative subdural effusion and convulsions, so we performed ventriculoperitoneal shunt on the 14th April, and convulsions were controlled by zonisamid.

A case of scalp cavernous hemangioma simulating sinus pericranii.

The authors report a case of cavernous hemangioma in the occipital region, which resembled sinus pericranii, protruded in the recumbent posture. A 28-year-old male was admitted with a chief complaint of an occipital fluctuating mass, 5cm in diameter, accompanied by slight pain. The skull X-P was normal. A direct puncture revealed that the lesion was a blood cyst. A cystogram by percutaneous needle puncture revealed paramedian blood pooling with some draining veins but did not show any transcranial communicating vessels. A T2 weighted MR image demonstrated a well demarcated high intensity lesion just beneath the corium. The subtotally removed specimen turned out to be a cavernous hemangioma. We discerned a conceptual confusion of pseudosinus pericranii with scalp cavernous hemangioma, based on the literature review. And we propose that scalp cavernous hemangioma, even if it changes its size according to posture, should not be simply designated as sinus pericranii.

Adenosine deaminase deficiency due to heterozygous abnormality consisting of a deletion of exon 7 and the absence of enzyme mRNA.

An adenosine deaminase (ADA;EC 3.5.4.4)-deficient B lymphoblastoid cell line BADO5 derived from a Japanese patient with severe combined immunodeficiency disease and two B lymphoblastoid cell lines, BAMO5 from his mother and BAFO5 from his father, were characterized. To identify mutations affecting ADA activity, we prepared cDNAs to ADA mRNAs of the BADO5 cell line for nucleotide sequencing. Sequence analysis of one of the BADO5 ADA cDNA clones revealed deletion of exon 7, and one point mutation of base 629 from G to A that did not affect the amino acid sequence. All clones of the BADO5 cell line so far examined showed the absence of exon 7 by Southern blotting analysis. Ribonuclease protection assay with an RNA probe spanning from exon 5 to exon 11 showed that the BADO5 ADA mRNA had a deletion of exon 7, the BAMO5 mRNA had normal length, and the BAFO5 mRNA had two species with a deletion of exon 7 and with normal length. Consequently, the patient's ADA genes resulted from one allele of the BAMO5 ADA gene that did not produce a detectable mRNA, and the other allele of the BAFO5 ADA gene producing an aberrant mRNA without exon 7.

Subdural hematoma due to ruptured intracranial aneurysm.

Subdural hematoma (SDH) was observed in 15 of 484 cases of aneurysmal subarachnoid hemorrhage (SAH). There were four males and 11 females, with ages ranging from 39 to 75 years. The clinical grades (Hunt and Hess) on admission were 11 in three cases, III in two, IV in four, and V in six. The ruptured aneurysms were located in the middle cerebral artery (MCA) in six cases, anterior communicating artery in three, internal carotid artery in two, and distal anterior cerebral artery (ACA) in two, with two cases unconfirmed. A high proportion of aneurysms occurred in the MCA and distal ACA. Aneurysmal neck clipping and removal of SDH were performed in the acute stage of seven cases, without intraoperative rerupture. The outcomes 1 year after SAH of the seven patients undergoing surgery were good recovery in five, but in two, vegetative state due to preoperative rerupture or medical complications. All eight patients without surgical intervention died. A good prognosis for patients with ruptured intracranial aneurysms accompanied by SDH can be expected with direct surgical intervention in the acute stage, even if the clinical grade on admission is poor.

Intracerebral hemorrhage due to venous thrombosis in venous angioma--case report.

A 26-year-old primipara with a cerebral venous angioma suffered an intracerebral hemorrhage just after delivery. Venous thrombosis was considered a possible cause of the intracerebral hemorrhage on the basis of the neuroradiological findings.

Transfer of the adenosine deaminase (ADA) gene of a B-lymphoblastoid cell line (LCL) to an ADA-deficient LCL by a microcell-mediated chromosome transfer technique.

As a model of somatic cell gene therapy, a normal adenosine deaminase (ADA) gene was introduced into a B-lymphoblastoid cell line (LCL) established from a patient with ADA deficiency by microcell-mediated chromosome transfer (MMCT). A LCL derived from his mother was used as a gene donor. Seven fusion experiments were performed and hybrid cells were pipetted into 123 wells. After selection in the presence of deoxyadenosine, cells grew in 12 wells at Week 9 after fusion. Among these wells, ADA activity of hybrids was low in 4 wells, 130-280% of that of the donor LCL in 7 wells and very high in one well. Hybrid cells in 4 wells with ADA-positive cells were investigated for the time-course of expression of ADA activity. In one well, ADA activity was expressed until Week 36, while, in 3 wells, ADA activity decreased or was lost between 21-36 weeks after fusion. These findings indicate the transfer of chromosome 20 containing a normal ADA gene into recipient cells and the deletion of this chromosome from some part of the hybrid cells. Karyotyping at Week 35 or 37 revealed 47 chromosomes in about 30% of the cells in 2 wells, which suggests that these hybrids were relatively stable in culture.