SU-E-T-216: TPS QC Supporting Program by a Third-Party Evaluation Agency in Japan.

PURPOSE: To equalize the quality of radiation therapy in Japan by supporting quality control of radiation treatment planning system. METHODS: Center for Cancer Control and Information Service in National Cancer Center supports the QA-QC of the cancer core hospitals in Japan as a third-party evaluation agency. Recently, a program for assessing the quality of treatment planning system (TPS) began as a part of our QA-QC supporting activities. In this program, a questionnaire about TPS was sent to 45 prefectural cancer core hospitals in Japan. The object of this questionnaire is to assess the proper commissioning, implement and applications of TPSs. The contents of the questionnaire are as follows; 1) calculate MUs which deliver 1000 cGy to the point of SSD = 100 cm, 10 cm depth with field sizes ranging from 5×5 to 30 × 30 cm2 , and obtain doses at several depths for the calculated MUs, 2) calculate MUs which deliver 1000 cGy to the point of SSD = 100 cm, 10 cm depth for wedge fields whose angles are from 15 to 60 degrees, and obtain doses at several depths with the MUs, 3) calculate MU which deliver 1000 cGy to the point of STD = 100 cm, 10 cm depth with 10×10 cm2 field size and obtain doses at several depths with the MU. RESULTS: In this program, 179 beam data from 44 facilities were collected. Data were compared in terms of dose per MU, output factor, wedge factor and TMR. It was found that 90% of the data agreed within 2%. CONCLUSIONS: The quality of the treatment planning system was investigated through the questionnaire including the information of essential beam data. We compared 179 beam data in TPSs sent from 44 facilities and 90% of the data showed good agreement.

Clinical study of the effectiveness of a dual amplified immunoassay (IDEIA PCE Chlamydia) for the diagnosis of male urethritis.

A clinical study of patients with male urethritis (n=316) was undertaken to determine the sensitivity potential for a new dual amplified immunoassay (IDEIA PCE Chlamydia). Increased sensitivity (98.8%, 84/85) was obtained for IDEIA PCE Chlamydia compared to a conventional antigen detection test (IDEIA Chlamydia, 81.2%, 69/85) when testing urine samples. In a smaller patient population (n=104) the positivity rate for the first-void urine tested with IDEIA PCE Chlamydia of 30.8% (32/104) was similar to the 27.9% (29/104) obtained from urethral swabs tested with a DNA probe assay (PACE 2). The increased sensitivity of the test was confirmed with a commercial PCR kit (Amplicor) and nested PCR. The IDEIA PCE Chlamydia kit has the sensitivity potential to be a clinically reliable alternative for detecting Chlamydia trachomatis.

Evaluation of the Actillume wrist actigraphy monitor in the detection of sleeping and waking.

This study evaluated the Actillume instrument and the modified Action 3 sleep-wake scoring algorithm, in which the scoring factor (P) was set at 0.10, 0.14, 0.20, 0.30, 0.40 and 0.50. Fifteen subjects, each of whom underwent polysomnography with simultaneous wrist actigraphy four times, yielded a total of 60 sleep studies. The sleep data from each subject were divided into four groups. In the high sleep efficiency index groups of the calibration and validation samples, the accuracy of the algorithm significantly differed within six P-values and was highest at P=0.14. In the low sleep efficiency index groups of both samples, however, there were no significant differences in the accuracy. Thus, these results indicate that P=0.14 should be most appropriate for this actigraph and algorithm.

A case of insufficient sleep syndrome.

All night polysomnographic evaluation (PSG) soon after admission and at the late period of admission revealed an atypically high sleep efficiency and a prolonged total sleep time. Sleep onset latency and distribution of REM and NREM sleep stages were like those of normal sleepers. On REM latency, while it was remarkably reduced (25.0 min) soon after admission and sleep onset REM period (SOREMP) was found, at the late period of admission it was prolonged and SOREMP was not found. Giving multiple sleep latency test with polysomnography, soon after admission subjective excessive daytime sleepiness had already improved and mean sleep latency (13.2 min) was within normal range. However, SOREMP appeared twice in five tests. We considered that the appearance at the early period of admission was the result of REM pressure growing.

Apolipoprotein E polymorphism and susceptibility to early- and late-onset sporadic Alzheimer's disease in Hokkaido, the northern part of Japan.

Apolipoprotein E (ApoE) phenotypes and corresponding allele frequencies were examined in 72 patients (50-90 years of age) with sporadic Alzheimer's disease (AD) and 83 elderly controls (61-96 years of age) in Hokkaido, the northern part of Japan. The frequency of the ApoE-epsilon 4 allele was significantly higher in the patients with either early-onset (age < 65 years) AD (0.40) or late-onset AD (0.26) than in controls (0.07), while the patients developing AD before 50 years of age had no epsilon 4 allele. The mean age at onset of AD was significantly lower in the ApoE-epsilon 4 homozygotes compared to that in the patients with either one or no epsilon 4 allele (60.2, 71.3 and 70.3 years, respectively). Our results indicate that the ApoE-epsilon 4 allele is associated with susceptibility to Japanese sporadic AD developing after 50 years of age and homozygosity for the epsilon 4 allele shifts the onset to earlier age.

A case with fear of emitting body odour resulted in successful treatment with clomipramine.

A patient with fear of emitting body odour of about 20 years' duration is reported. The patient was improved with clomipramine, a tricyclic antidepressant. Generally in Japan, he would be classified as having anthropophobia. However, according to the criteria advocated by Munro and Chmara (1982), he could be classified as having monosymptomatic hypochondriasis (MH). There are some reports that antidepressants have been effective in patients with either anthropophobia or MH. Therefore, a subgroup of patients which respond to antidepressants may exist in these disorders.

Distinct sites of dopaminergic and glutamatergic regulation of haloperidol-induced catalepsy within the rat caudate-putamen.

Previous studies have indicated that corticostriatal glutamatergic pathways are implicated in the regulation of neuroleptic catalepsy. To obtain a better understanding of the way in which dopamine (DA) and glutamate interact within the caudate-putamen (CP) in the development of catalepsy, we investigated the regional distribution within the rat CP of the cataleptogenic effect of haloperidol and its antagonism by D(-)-2-amino-5-phosphonopentanoic acid (D(-)AP5), a selective antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. Bilateral injections of haloperidol (3 micrograms/side) into the rostral ventromedial (VM) CP induced potent catalepsy with a short latency after the injection. In contrast, only a weak cataleptic response, of slower onset, was observed after haloperidol injections into the rostral ventrolateral (VL), rostral dorsomedial (DM), or rostral dorsolateral (DL) CP, or into the nucleus accumbens. D(-)AP5 (5 micrograms/side) injected bilaterally into the dorsorostral CP (DM and DL) strongly inhibited the catalepsy induced by systemic haloperidol (1 mg/kg, i.p.), and this effect lasted longer when the drug was injected into the DM than when it was injected into the DL. D(-)AP5 did not affect haloperidol-induced catalepsy when injected into the ventrorostral (VM and VL) or intermediate dorsal CP. D(-)AP5 injected into the DM, the region most sensitive to the anticataleptic effect of the drug, had no effect on basal levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, or on the modification of these levels by haloperidol in either the DM or VM. These findings suggest that, while the catalepsy resulting from DA receptor blockade by haloperidol originates mainly from the VM, the expression of this phenomenon depends on an intact glutamatergic transmission within the dorsorostral CP. In the development of neuroleptic catalepsy, the mesencephalostriatal DAergic and corticostriatal glutamatergic pathways seem to be functionally linked through an indirect, rather than a direct, interaction.

[Spinocerebellar ataxia 1--clinical study of 17 patients in a large pedigree].

We studied a large pedigree with dominant spinocerebellar ataxia, genetically and clinically. At now, 27 members over 5 generations have been affected. Linkage study for the disease locus to D6S89 in a total of 44 individuals showed maximum lod scores of 3.99 at theta = 0.000. This result indicates that the disease locus of this pedigree locates near D6S89 on chromosome 6p (SCA 1). We studied 17 patients clinically. Mean age at onset was 37.7 +/- 8.6, and mean duration after onset was 11.3 +/- 6.8 years. Their clinical features were characterized by progressive ataxia, pyramidal involvement with hyperreflexia or spasticity, and mild posterior column involvement. Mild gaze nystagmus at early stage became unclear with the progress of illness. The frequent signs in the advanced stage were diffuse amyotropy, twitching of face or tongue, bulbar palsy, slow saccade, external ophthalmoparesis, mydriasis, coarse postural tremor, and dementia with emotional disturbance. There are so much clinical similarities between our pedigree and other SCA 1 pedigrees in the literature. Generally, SCA 1 shows hyperreflexia, spasticity, and terminal slow saccade. On the other hand, non-SCA 1 type OPCA is characterized by progressive hyporeflexia, slow eye movement from early stage, and frequent choreoathetosis. Gaze nystagmus, external ophthalmoparesis, amyotrophy, and spasticity are common in both SCA 1 and Machado-Joseph disease (MJD). However, they are more frequent in MJD than SCA 1. Moreover, extrapyramidal signs, such as dystonia, are rare is SCA 1. Based on these difference, SCA 1 could be clinically differentiated from other similar hereditary ataxias.

Ultrastructural observations on neuronal lipofuscin (age pigment) and dense bodies induced by a proteinase inhibitor, leupeptin, in rat hippocampus.

The ultrastructure of lipofuscin (age pigment) and dense bodies induced by intraventricular administration of leupeptin, a cysteine proteinase inhibitor, were investigated in the neurons of rat hippocampal dentate gyrus. Four-day treatment with leupeptin (0.5 mg/day) rapidly caused a considerable accumulation of intracytoplasmic dense bodies and swelling of neuronal processes. We demonstrated, as inner structures of the pigments, that penta-laminar structure with a thickness of 12-13 nm and finely granular matrix were exactly common to the leupeptin-induced dense bodies and lipofuscin granules. Furthermore, the transitional stages from lysosomes into the dense granules were observed in the neurons of the leupeptin-treated rats. On the other hand, some morphological differences between the leupeptin-induced dense bodies and lipofuscin granules have been shown: (1) distribution in different cell types, (2) intracytoplasmic location, (3) tendencies to associate with vacuoles, and (4) electron density. The present findings suggested that the decline of the lysosomal protein degradation could play a role in lipofuscinogenesis, especially in the genesis of their electron-dense portion, but some other mechanisms might participate in the formation and accumulation of lipofuscin with aging.

[A case of the panencephalopathic type of Creutzfeldt-Jakob disease with retinal involvement].

Neuropathological study of the visual pathway from the retina to the occipital cortex in Creutzfeldt-Jakob disease (CJD) has been scarcely performed. In the present study, pathological involvement of the visual pathway was observed in a 54-year-old man with CJD. The patient had the onset of visual disturbances in December 1985. He subsequently developed progressive dementia, right hemiparesis, ataxia and dysarthria, and rapidly fell into decerebrate posture in February 1986. In March 1986, myoclonus appeared on the whole body and EEG revealed periodic synchronous discharges, while brain CT and CSF findings showed no abnormalities. Myoclonus was observed most frequently from May to October 1986, and then reduced gradually. Brain atrophy on CT started from April 1986, and was progressive till the end stage of the disease. He died in January 1988, and the total clinical course was about 24 months. Neuropathological examination revealed severe degeneration of the cerebral cortex and the white matter. In the cerebral cortex, marked loss of neurons, astrogliosis, and spongiform changes were observed. In the cerebral white matter, the destruction of myelin sheaths and axons were evident. The cerebellum showed prominent loss of granule cells. These findings are consistent with those of the panencephalopathic type of CJD. In the visual pathway, loss of ganglion cells and bipolar cells in the retina, mild demyelination of the optic nerve, neuronal loss in the lateral geniculate body, and severe degeneration in the visual cortex were observed. The present case suggests that the neuropathological investigation in the visual pathway from the retina to the occipital cortex is important for clarifying the pathological processes in the visual system in CJD.

[Seizure susceptibility in aged rats--pentylenetetrazol-induced seizures and amygdaloid kindling seizures].

Seizure susceptibility in male aged rats (21-25 mo. age) was investigated by pentylenetetrazol (PTZ)-induced seizures and amygdaloid kindling seizures. Male adult rats (3-4 mo. of age) were used as the control group. During 60 min. after the administration of PTZ (70 mg/kg, s.c.), the aged rats had a higher incidence and a significantly longer duration of generalized convulsion than the control group. On the other hand, the kindling rate of the aged rats was significantly slower than that of the control. The aged rats remained longer at stage 1-2 indicative of partial seizures. However, the aged rats skipped stage 3 on their way to stage 4-5 (generalized seizures), and showed a more violent stage 5 seizure than the control group. They had a longer duration of afterdischarges (AD) through the kindling process with a significantly faster propagation of AD to the contralateral amygdala as compared with the control group. The present study suggests that aged rats are prone to convulsion, while they have a difficulty in acquisition of epileptogenesis.

[Serial brain CT and 123I-IMP SPECT in a case with Creutzfeldt-Jakob disease].

Serial brain CT and 123I-IMP SPECT were examined in a case with Creutzfeldt-Jakob disease (CJD). A 61-year-old woman had the onset of progressive dementia and gait disturbance in December 1988. Then, she developed left hemiparesis and dysarthria, and rapidly fell into akinetic mutism within about 2 months. Brain CT, MRI, and CSF findings showed no definite abnormalities. In February 1989, myoclonic movements appeared in several parts of the body and EEG revealed periodic synchronous discharges. Myoclonus was observed most frequently from March to May 1989, and then reduced gradually. She died in June 1990, and the total clinical course was 19 months. Brain atrophy on CT started from about 4 months after the onset, and progressed subacutely. At the end stage of the disease, diffuse brain atrophy including the cerebellum and the brain stem on CT was observed. SPECT revealed decreased perfusion in the cerebral cortex from 5 months after the onset to the end stage, but; perfusion in the cerebellum and the basal ganglia was relatively kept even at the end stage of the disease. The results suggest that SPECT is a useful examination for presumption of the pathological processes in CJD.

Striatal N-methyl-D-aspartate receptors in haloperidol-induced catalepsy.

Bilateral ablation of the frontal cortex of rats markedly reduced the catalepsy induced by haloperidol (1 mg/kg i.p.). Similarly, the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, D(-)-2-amino-5-phosphonopentanoic acid (10 micrograms/side), injected bilaterally into the rostral part of the caudate-putamen (CP) reduced haloperidol-induced catalepsy whereas its injection into the intermediate part of the CP was ineffective. The quisqualate receptor antagonist, L-glutamic acid diethyl ester (100 micrograms/side), did not affect haloperidol-induced catalepsy when injected into the rostral part of the CP. On the other hand, NMDA (1 micrograms/side) injected bilaterally into the rostral part of the CP was able to restore haloperidol-induced catalepsy in frontally decorticated rats without any notable cataleptic effect of its own. These findings suggest that a certain degree of tonic stimulatory effect of corticostriatal glutamatergic pathways on NMDA receptors within the rostral part of the CP is a prerequisite for the expression of the cataleptogenic action of haloperidol.

[A case of temporal lobe epilepsy with recurrent dysphasic seizures].

We reported a 40-year-old right-handed female with temporal lobe epilepsy manifesting recurrent dysphasic seizures. At age 25, the patient developed a complex partial seizure, who subsequently showed frequent auditory seizures that often evolved to complex partial or secondarily generalized seizures at age 25-27, and dysphasic seizures (DSs) at age 27 -40. DSs were characterized by total aphasia without impairment of consciousness, which were often accompanied by functional hallucination. Brain CT, cerebral angiography, and brain MRI demonstrated no abnormal findings. At age 39 (May 20, 1989), recurrent aphasic state was unexpectedly observed during medical examinations. An EEG was performed immediately, and the EEG seizure pattern (duration: ca. 8-17 sec) in which 15 -16 Hz spikes began in the left posterior temporal region and spread rapidly to the left midtemporal, inferior frontal, and central regions was detected 14 times within 30 minutes. During the seizure patterns, the patient was aphasic.

[Subjective sleep disturbances and psychosocial states in long-term abstainers].

To evaluate the relation between subjective sleep disturbances and psychosocial factors in alcoholics, we studied the subjective estimate of sleep, occupation, marital status, and economic status in 210 abstainers, using check lists which were given to each patients (169 answerers, 82. 9% recovery). We also performed psychological tests of Yatabe-Guilford Personality Inventory in 145 subjects, Maudsley Personality Inventory in 115, and Cornell Medical Index in 103. The results were as follows: 1. Sleep disturbances were seen in 100 abstainers (59.2%). 2. The abstainers who had abstained for less than 2 years showed higher incidence of sleep disturbances than those who had abstained for 2 years or more (70.7% and 37.5%, respectively). 3. The abstainers with sleep disturbances were more frequently unemployed, more frequently divorced, and had lower economic status than those without sleep disturbances (69.0% vs. 36.3%, 31.0% vs. 17.4%, and 49.0% vs. 23.2%, respectively). 4. Three psychological tests suggested that abstainers with sleep disturbances had more immature and neurotic personalities. The present study suggests that the occurrence of sleep disturbances in abstainers may be relevant to their psychosocial states.

Rat cortical sigma receptors differentially regulated by pentazocine and haloperidol.

Repeated administrations of 7.5 mg/kg of pentazocine (for 14 days) resulted in a significant decrease in the affinity of 3H-haloperidol binding to rat cortical sigma receptors without any changes in the maximal number of binding sites (Bmax). On the other hand, similar treatment with haloperidol (2 or 4 mg/kg) induced a dose dependent decrease in the Bmax values without affecting the affinity of the 3H-haloperidol binding. These findings indicate that rat cortical sigma receptors are differentially regulated by pentazocine and haloperidol.

[Epidemiological and therapeutic study on urethritis of male and cervicitis from viewpoint of STD--a study using NY-198. Sapporo Clinical Research Group for STD].

Urethritis in males and cervicitis in females, which were sexually transmitted diseases, were treated with NY-198, a new quinolone antibiotic, and its efficacy was studied. Seventeen male patients with gonorrheal urethritis were administered a single 300 mg dose of NY-198. The efficacy rate on the 3rd day after administration was 100%, but it was 85.7% on the 7th day due to recurrence in 1 patient. The results of treatment of non-gonorrheal infections were as follow. In this treatment, NY-198 was administered in a daily dose of 600 mg in 3 divided doses for 14 consecutive days. In the treatment of chlamydial urethritis of males, the efficacy rate in 26 patients was 84.6% on the 7th day and 84.0% on the 14th day in 25 patients. In the treatment of chlamydial cervicitis, the efficacy rate was 100% on both the 7th (3/3) and 14th (6/6) days. In the treatment of non-gonorrheal and non-chlamydial cervicitis, the efficacy rate was 100% on the 7th day (1/1) and 50% (1/2) on 14th day. The efficacy rate in all 40 males with non-gonorrheal urethritis was 85.0% on the 7th day and 88.9% for 36 patients on the 14th day, while that in all 4 females with cervicitis was 100% on the 7th day and 87.5% on the 14th day. No side effects were seen in any of the patients. Overall, NY-198 had an efficacy rate of 80% in the treatment of chlamydial infections. NY-198 was found to be a useful drug which is efficacious in the treatment of all STD-related microbes such as gonococci and chlamydia.