Persistent primitive hypoglossal artery associated with arteriovenous malformation--case report.

A case of persistent primitive hypoglossal artery (PPHA) associated with arteriovenous malformation (AVM) is reported. A 46-year-old male suddenly developed severe headache followed by transient unconsciousness and was admitted to our hospital 2 hours later. A computed tomographic scan showed subarachnoid hemorrhage. Angiograms revealed an AVM in the left cerebellar hemisphere and an ipsilateral PPHA. The AVM was completely removed and he was discharged 1 month after surgery without neurological deficit. Only three cases of PPHA associated with intracranial AVM have been reported in the literature. One patient died of rebleeding from the AVM before surgery, and another was conservatively treated because the AVM was too large for resection. The remaining one was surgically treated only by ligation of the feeding arteries. Ours is the first case treated by total removal of the AVM. Since these four cases, including ours, account for 3.0% of 134 cases of PPHA reported, PPHA associated with AVM is considered rare.     

Plastic effect of soiled bedding on the structure of synapses in rat accessory olfactory bulb

The effects of exposure to soiled bedding on synaptic morphology in the accessory olfactory bulb (AOB) were examined in adult male rats. Forty-day-old male rats were isolated. One group was exposed to bedding soiled by male and female rats (EC). Another group was exposed only to male-soiled bedding (SC). A third group was exposed to clean bedding (IC). After 2 months, the animals were sacrificed for electron microscopy. The size and the numerical density of synapses were measured in the glomerulus and the granule cell layer. In the glomerulus, the mean size of the synapses was significantly greater in the EC than in the IC group, whereas that in the SC group appeared to be intermediate between those in the EC and the IC groups but was not significantly different from those in the EC and the IC groups. There was no statistically significant difference in the density of synapses among the three groups. Synapses in the granule cell layer are classified into two types: (1) perforated synapses, which are characterized by discontinuities in their postsynaptic thickenings, and (2) nonperforated synapses. The mean size of perforated synapses was significantly greater in the EC than in the IC and SC groups; however, no statistically significant difference was observed in the size of nonperforated synapses among the three groups. Moreover, no statistically significant difference was observed in the numerical densities of either perforated or nonperforated synapses among the three groups. These results suggested that exposure to a more complex soiled bedding environment (i.e., to bedding soiled by both male and female rats) can induce greater structural changes of the synapses in the AoB of male adult rats. © 1995 Wiley-Liss, Inc.     

Changes in blood ketone body ratio with reference to graft viability after liver transplantation in rats

Arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR), which reflects hepatic mitochondrial redox potential, was measured during a 2-week period after orthotopic liver transplantation in three groups of rats: group 1, the isogenic combination of LEW (RT1¹) graft to LEW recipient as control; group 2, the allogenic combination of ACI (RT1^a) graft to LEW recipient without immunosuppressive treatment; and group 3, the allogenic combination of ACI to LEW with immunosuppressive treatment using cyclosporin (CyA). Isogenic recipients survived indefinitely. Allogenic recipients in group 2 had severe rejection with a mean survival of 10.3±0.54 days, while 77.8% of the allogenic recipients in group 3 survived more than 30 days. KBR of rats surviving more than 2 weeks in groups 1 and 3 gradually increased post-transplantation and was maintained at a high level. By contrast, though KBR in group 2 was restored at 3 days, it gradually fell and remained at a significantly low level (P<0.001). It is suggested that KBR provides an accurate indicator for evaluating metabolic viability of the critically deteriorating liver graft accompanied by severe rejection.     

Phase I trials--clinical studies of antineoplastic agents]

The establishment of the starting dose and the dose escalation are the principal issues of the Phase I trials of anticancer agents. We report the procedures and results of the Phase I studies we participated in Japan in the 1980's concerning 17 intravenous anticancer agents. The drugs indicated a correlation between the mouse LD10 and the man MTD (maximum tolerated dose) in mg/m2. Median mouse LD10 (135 mg/m2) approximated to median man MTD (137 mg/m2) in mg/m2. One fifth of the mouse LD10 was lower than the man MTD. Therefore, as recognized at the 23rd Annual Congress, Japan Society for Cancer Therapy, the lower one of either 1/5 the mouse LD10 or 1/3 the dog TDL (toxic dose low) in mg/m2 has to be determined as safe starting dose. The modified Fibonacci search scheme has been generally adopted for the dose escalation. 14 applicable drugs were examined including 7 drugs in the early 1980's and 7 drugs in the late 1980's. The real number of steps that reached the man MTD was compared to the number of the steps taken in the dose escalation by the Fibonacci's method. The real steps were more than the Fibonacci's ones in the late 1980's. It showed the tendency of a more careful and safer dose escalation, however, to put it critically, the dose escalation was not efficient enough. It is expected that the contradictory problem between safety and efficacy in the Phase I studies will be solved by developing methods like pharmacokinetic study in animals and man.     

Efficacy of interferons in treating children with chronic hepatitis C

Twenty-two children with chronic hepatitis serologically positive for hepatitis C virus (HCV) were treated with interferon-α (IFN-α). Liver biopsy showed chronic active hepatitis in 13 and chronic persistent hepatitis in 9 patients. A sustained clearance of HCV was observed in 8/22 children 12 months after the administration of IFN-α for 26 weeks, associated with normalization of HCV core antibody. Of these eight patients six had HCV genotype III and two HCV genotype II or IV. Hepatitis relapsed in seven other patients after completion of IFN-α with an increase in HCV core antibody titre, five with HCV genotype II, and two with HCV genotype III or IV. A second course of IFN-α suppressed the reactivation of HCV in all seven patients. Three of seven responders who relapsed after the first course remained negative for HCV RNA 12 months after their second course of IFN-α. However, the remaining four patients with HCV genotype II again relapsed after completing their second course of IFN-α. Seven children with the HCV genotype II resistant to IFN, including 8 weeks of IFN-β administration, and showed no significant reduction in HCV core antibody titre. Conclusion The genotype of HCV (III) and a reduction in the core antibody titre appear to be useful parameters for predicting the response to IFN-α therapy. Received: 12 September 1996 and in revised form: 28 January 1997 / Accepted: 11 February 1997     

Inhibitory effect of prolactin secretion by luteinizing hormone releasing hormone agonist (buserelin)

The LH RH agonist Buserelin was continuously administered through the nose over an extended period to 5 patients with endometriosis at daily doses ranging between 300 micrograms and 1,200 micrograms. The clinical findings and endocrinological dynamics, with emphasis on PRL secretion function, were investigated and the findings below were obtained. The clinical findings showed Buserelin to be effective against endometriosis. The administration of Buserelin markedly inhibited the secretion of LH and FSH under LH-RH loading. The administration of Buserelin markedly inhibited the secretion of PRL and the degree of inhibition appeared to be dependent on the dose and duration of Buserelin administration. No correlation between E2 and PRL was observed during Buserelin administration. The findings suggest that Buserelin inhibits PRL secretion by direct CNS activity, not indirectly through inhibition of E2 production.     

Acanthosis nigricans, hypothyroidism, and insulin resistance

Acanthosis nigricans has been associated with multiple endocrinopathies. The common denominator appears to be insulin resistance. Three patients are described (one woman and two men) who presented with hypothyroidism and acanthosis nigricans. All the patients had elevated insulin levels in the fasting state and in response to an oral glucose load. The mechanism for the resistance to insulin was a post-receptor binding defect or a structural abnormality in circulating insulin, since glucose tolerance and plasma cortisol, somatomedin, growth hormone, and insulin receptor concentrations in peripheral monocytes were all normal. Antibodies to insulin or the insulin receptor were absent. Neither insulin resistance nor acanthosis nigricans diminished following correction of the hypothyroidism. It is concluded that hypothyroidism may be associated with acanthosis nigricans, that hyperinsulinemia is a regular correlate of the skin disorder, and that treatment of the hypothyroidism does not resolve the hyperinsulinemia or the acanthosis nigricans.     

Long-term studies on carcinogenicity and promoting effect of phenylbutazone in DONRYU rats

The carcinogenicity and promoting effect of phenylbutazone were investigated in inbred DONRYU rats. In the carcinogenicity study, both sexes were administered the chemical at dietary levels of 0 (control), 0.125, or 0.25% for 2 years. Toxic lesions were associated with phenylbutazone treatment in the kidney and digestive tract, appearing to have an adverse effect on life expectancy. Various tumors were detected in all groups including the controls. With the exception of pheochromocytoma in the female high-dose group, no statistically significant increase in yield of any tumors, including leukemia, was apparent in the treated groups of either sex when the data were analyzed by Fisher's exact probability and/or chi-square tests. Application of an age-adjusted statistical analysis revealed a slight positive effect regarding the occurrence of pheochromocytomas, neoplastic liver nodules, and leukemias in females. However, these tumors are commonly observed to develop spontaneously in this rat strain, and no such effect was apparent in the male groups. In addition, no differences in incidences of relevant preneoplastic lesions were evident between control and treated groups. Thus phenylbutazone showed no carcinogenic activity in DONRYU rats when given continuously in the diet for 2 years. For the investigation of promoting effect, phenylbutazone was given as a dietary supplement for 2 years subsequent to initiation with N-ethyl-N-nitrosourea or N-propyl-N-nitrosourea. No enhancement of nitrosourea-induced leukemogenesis was apparent, although a slight promoting effect was demonstrated for renal and thyroid tumorigenesis.