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Biomedical subjects

J Shiraishi

Publications and source records attributed to J Shiraishi.

At least 37 records · Page 2Linked to original sources

The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function.

This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P < 0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.

Adult↗

Prolonged but not acute fluoxetine administration produces its inhibitory effect on hippocampal seizures in rats.

This study assessed the effects of acute as well as long-term administration of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor with anti-depressant properties, on hippocampal (HIP) seizures elicited by electrical stimulation in rats. The fluoxetine effect on HIP seizures was also assessed following long-term treatment with gepirone, a 5-HT1A receptor agonist. Acute single administration of fluoxetine (1, 10 mg/kg; IP) was found to produce no significant effect on HIP seizure activity. Following daily IP administration of fluoxetine (10 mg/kg per day) or gepirone (10 mg/kg per day) for 21 days, animals were given a 7-day drug-free period and then challenged with an acute dose of 10 mg/kg fluoxetine. These treatment regimens resulted in a significantly increased afterdischarge threshold of HIP seizures in response to acute fluoxetine administration. The inhibitory effect of fluoxetine, however, was not present 4 weeks after long-term treatment with either fluoxetine or gepirone. The present results indicate that long-term treatment with these compounds enhances the antiepileptic effect of subsequent fluoxetine administration on the generation of HIP seizures. This effect is possibly related to the well-demonstrated evidence that fluoxetine and gepirone, on long-term treatment, facilitate net 5-HT neurotransmission through desensitization of presynaptic 5-HT autoreceptors.

Animals↗

Efficient sampling strategies for forecasting pharmacokinetic parameters of irinotecan (CPT-11): implication for area under the concentration-time curve monitoring.

A linear two-compartment Bayesian pharmacokinetic model was developed using a standard two-stage population method for the novel anti-cancer agent CPT-11 from 11 adult patients with refractory cancer. The accuracy and efficiency of this Bayesian model for estimating pharmacokinetic parameters including the area under the concentration-time curve (AUC) was then evaluated using two different sampling strategies in a new study cohort of 13 patients with cancer. Sampling strategies included either one, two, or three nonsteady-state feedback levels determined empirically and from optimal sampling theory (D-optimality). All 24 patients in this study received CPT-11 (60 mg/m2) as a 90-min infusion. Pharmacokinetic parameters derived from the Bayesian model combined with these limited sampling strategies were compared with those parameters obtained from the full sample data sets (n = 10) analyzed by weighted nonlinear least squares regression (reference method). The least-bias and most precise sampling times for estimating AUC were 3.5; 3.5 and 9.5; and 0.5, 3.5, and 9.5 h, respectively. At these times, only marginal improvement in precision of the AUC estimate was observed using two versus three samples. However, the precision of the estimate of clearance was not improved using two versus three samples. The sampling times derived from optimal sampling theory were 0.25, 3.5, 8.5, and 24 h and correlated closely to the actual and best empirical sampling times of 0.5, 3.5, 9.5, and 24 h. These results strongly suggest that Bayesian estimation combined with only two optimally timed samples accurately predicts the AUC of CPT-11 and should be useful for implementing adaptive control dosing for monitoring CPT-11 systemic exposure in patients with cancer.

Adult↗

Correlation of gene-specific damage with cisplatin between human adenocarcinoma cells and peripheral blood mononuclear cells analyzed by polymerase chain reaction-stop assay.

We investigated gene-specific damage in adenocarcinoma cells, obtained from pleural effusions of 9 primary lung cancer patients, induced by incubation with cisplatin for 3 h in vitro. The 2.7 kb fragment of the hypoxanthine phosphoribosyltransferase (HPRT) gene was amplified by the polymerase chain reaction (PCR) to quantify the DNA damage. A 7-fold difference in the extent of gene-specific damage among the patients was observed. Mononuclear cells (MNC) were obtained from freshly isolated blood from the same patients before they received chemotherapy. These cells were also incubated with cisplatin in vitro, and PCR amplification of the HPRT gene was carried out. A 4-fold variation of DNA damage among the patients was observed. Moreover, there was a linear correlation between the extents of the DNA damage in the tumor cells and MNCs (R2 = 0.676, P = 0.0016). These results suggest that the PCR-stop assay could be used to detect interindividual variations in the extent of gene-specific damage in both tumor cells and MNC from the same patients induced by cisplatin treatment. In conclusion, MNC could be used to analyze cisplatin-induced gene-specific damage in cancer patients whose tumor cells are inaccessible.

Adenocarcinoma↗

[An adult case of bacterial meningitis caused by penicillin-resistant Streptococcus pneumoniae].

Recently the incidence of infectious diseases caused by penicillin-resistant Streptococcus pneumoniae (PRSP) is increasing. Patients with meningitis caused by PRSP have been reported with high mortality especially in the field of pediatrics, and it is crucial to treat with accurate and precise choice of antibiotics. We report the first adult case of bacterial meningitis caused by PRSP in Japan. A 32-year-old male without immunological abnormalities developed acute pneumococcal meningitis. Empiric therapy with ampicillin and cefotaxime was not effective and the S. pneumonia from CSF showed resistance to multiple antibiotics such as penicillin and cefotaxime. He was treated successfully with the combination of panipenem/betamipron, vancomycin, and chloramphenicol. We assume that panipenem/betamipron is recommended to be added to empiric therapy of bacterial meningitis, considering an increasing incidence of PRSP infection.

Adult↗

[A case of lobar atrophy with stereotypic unusual laughing].

We report a case of a Pick's disease (frontal predominant type) with unusual laughing. The patient was a 54-year-old, right handed, female. The patient began to show low activity and inappropriate laughing at about 51 years. She did not speak at all and showed weird laughing with a voice "hi hi hi hi hi hi" frequently at first presentation. When asked some questions, she sometimes answered with a nod. Almost all of her laughing did not match with the situation and seemed to lack a relationship between affective change and observed expressions. The laughing could be elicited by non specific and varied stimuli. She often interrupt laughing voluntarily unlike pathological laughing. Neurological examination revealed visual rooting reflex and forced grasping reflex but there was no signs of pseudobulbar palsy often observed in patients with pathological laughing. Her electromyogram of facial expression during the laughing showed that electric discharge of M. corrugator supercilii was over 4 times as much as that in normal laughing. And it showed also that the duration of her laughing was several seconds as normal laughing. CT and MRI scans demonstrated atrophy in the fronto-temporo-parietal lobe bilaterally (L > R), most prominent in the frontal lobe. SPECT scan showed a significant diminution of blood flow in the atrophic region. An EEG was normal. We consider that the laughing of the present case is not due to an emotional disturbance but rather a disorder of affective expression as pathological laughing.

Dementia↗

[Two cases of primary progressive non-fluent aphasia].

Two patients were described with a five to seven-year history of primary progressive non-fluent aphasia. One patient developed atypical trascortical motor aphasia with marked anarthria, which has led to mutism. Magnetic resonance (MR) imaging showed lobar atrophy of the frontal lobe accentuated in the bilateral superior frontal gyri, the left middle frontal gyrus, the left anterior cingulate gyrus and the left operculum with some extension into the left temporal lobe. Single photon emission computed tomography (SPECT) scans demonstrated a decrease of regional cerebral blood flow (rCBF) in the atrophic site. The patient was clinically and neuroradiologically diagnosed as having Pick's disease. Another patient presented with atypical Broca's aphasia, which has worsened with slowly progressive right hemiparesis. Mitigated, sometimes complete, echolalia was also observed. MR imaging and SPECT scans showed mild atrophy and a decrease of rCBF in the left perisylvian region involving the frontal operculum, while a positron emission tomographic study disclosed diffuse hypometabolism in the left hemisphere. We pointed out that the features of primary progressive aphasia were frequently atypical in the light of classical classification of aphasia and that non-fluent aphasia might be observed even in the early stage of cortical degenerative processes.

Aphasia, Broca↗

[Neuropsychological findings of functional cortical mapping in patients with brain tumors].

In 3 patients with brain tumors involving language areas, we investigated functional cortical regions and epileptogenic foci using subdural electrode stimulation before operation. These stimulation studies were useful in preserving postoperatively their language function. The following neuropsychological findings were obtained; (1) Stimulation of Broca area (Brodmann 44 and 45) did not produce anarthria (phonetic disintegration), but semantic and phonemic parahasias and word finding difficulties. (2) Stimulation of lower motor cortex elicited anarthria. (3) Buccofacial apraxia was not produced only by stimulation of frontal operculum. (4) When anarthria was elicited by stimulation, difficulty in retrieving both Kana and Kanji letter-forms and paragraphia in Kana letters were sometimes observed. (5) Stimulation at Exner's writing centre did not produce writing deficits, but elicited word finding difficulties and paraphasias.

Adult↗

Measurement of CT section thickness by using the partial volume effect.

A method to calculate section thickness from mean computed tomographic (CT) numbers of two materials in a section (and by varying the ratio of their volume) was developed. A cylindrical water phantom with an acrylic rod at the center was used, and section thickness was measured with two CT scanners. At actual section thicknesses of more than 4 mm, results with this method differed from results of the aluminum ramp method by only about 10%. At section thicknesses of 1-2 mm, however, the difference was about 30%-50%. Measurement with this method was not influenced by filter function and therefore was more accurate than with the aluminum ramp method.

Algorithms↗

Somatosensory evoked potentials to median nerve stimulation after partial section of the corpus callosum.

Cortical somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve were studied in four patients with intractable epilepsy who had undergone callosotomy and in a patient with infarction in the corpus callosum in order to determine whether the corpus callosum was involved in the generation of ipsilateral frontal components. Both pre- and postoperative SEPs were recorded in three of four epileptic patients. There were no significant differences in the latencies and amplitudes of the bilateral frontal components (P20, N26) between pre- and postoperative recordings. Furthermore, irrespective of the extent of the section or lesion in the corpus callosum, the nature of the impairment and the existence of the disconnection syndrome, the SEP findings showed no significant differences compared with those of normal subjects. It thus appears unlikely that the ipsilateral SEP responses are transmitted from the contralateral hemisphere through at least the anterior portion of the corpus callosum.

Adult↗

Memory loss due to transient hypoperfusion in the medial temporal lobes including hippocampus.

A typical case of transient global amnesia (TGA) was investigated with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) with 1.5-tesler scans. During the amnesic episode, a marked decrease of cerebral blood flow was observed in the areas confined to the territory of the bilateral posterior cerebral arteries including the hippocampus. After the episode, cerebral blood flow returned to normal and a circumscribed lesion was detected in the middle portion of CA 1 field of the left hippocampus. The SPECT findings prove direct evidence that the medial temporal structures are involved in the establishment of new memories, as well as in process of recalling only recently acquired memories, but not in retrieval of memories acquired long ago. The MRI findings indicate that a unilateral partial damage to CA 1 sector of the hippocampus does not develop a definite memory impairment and that high-resolution MRI study on the hippocampus is necessary in TGA patients.

Amnesia↗

[Left unilateral apraxia].

A 32-year-old right-handed man suffered a traffic accident with head injury, resulting in loss of spontaneity, right hemiparesis, severe aphasia, and unilateral apraxia, which was noticed on his non-paralyzed left hand. An MRI scan conducted 11 months after onset revealed a large lesion in the left frontal lobe, a small lesion in the right frontal lobe and a striking thinning of the trunk of the corpus callosum with remarkable dilatation of the lateral ventricles. An IMP-SPECT scan, performed 1 year after onset, showed a diffuse hypoperfusion extending to the left temporo-parietal area further than the MRI verified abnormal density areas. The patient's praxic abilities were precisely evaluated 1 year after onset. The performance on the object use task was characterized by content errors. For example, when using a match with his left hand, he always treated with it like a cigarette. The right hand performance of this task was clumsy due to his right hemiparesis but successful. The performance on his left hand did not improved even when the patient was given visual examples. The term "ideational apraxia" proposed by Liepmann, which was characterized by content errors, implies a conceptual deficit. Morlaas defined ideational apraxia as a agnosia of usage. Ideational apraxia has been so far investigated mainly on patients with these difficulties in both hands. On the other hand, left unilateral apraxia has been explained by callosal disconnection. Liepmann and Maas thought that a lesion of the corpus callosum would prevent the space-time engrams in the left hemisphere from reaching the right sensorimotor area necessary to carry out the skilled act with the left hand, thereby inducing apraxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A case of slowly progressive aphasia without generalized dementia in a Japanese patient.

A Japanese patient with a 4-year history of slowly progressive aphasia without generalized dementia is described. From 1985 on, this 61-yr-old right-handed dentist showed insidiously progressive deterioration in his speech and auditory comprehension, but has no memory disturbance, disorientation of space, time or persons, acalculia or other impairments in his behavior. His personality changes are unremarkable. He still treats patients at his clinic. General physical and neurological examinations were normal. CT and MRI (1.5T) scans showed widening of the left sylvian fissure and lateral ventricle without any vascular lesions. A PET scan demonstrated focal hypometabolism restricted to the left temporal lobe. The clinical course and picture of our patient corresponds, well to those of slowly progressive aphasia without generalized dementia, described by Mesulam.

Aphasia↗

Tactile extinction to simple (elementary) and complex stimuli.

Thirty patients with cerebrovascular disease and 85 control subjects were examined using both the classical tactile extinction test and a modified Quality Extinction Test (modified QET) in order to investigate the so-called tactile extinction phenomenon to complex stimuli from the qualitative standpoint. As a result, 1) the patients with tactile extinction to simple (elementary) stimuli also manifested extinction to complex tactile stimuli in the modified QET; 2) there were patients who exhibited extinction only to complex tactile stimuli. Our results provide support for the concept that the so-called tactile extinction phenomenon could result from competition between tactile stimuli presented to both hands at at least 2 different levels of tactile processing, i.e. the process of perception and the process of recognition. When discussing the phenomenon of extinction to complex tactile stimuli, therefore, one should consider these 2 forms of extinction separately.

Adult↗

A case of acquired conduction aphasia in a child.

A 10-year-old right-handed boy showed conduction aphasia with left-ear verbal extinction (paradoxical ipsilateral ear extinction) after removal of a arteriovenous malformation in the left parietal lobe. Buccofacial and ideomotor apraxia were not observed. Recovery from aphasia was dramatic. Postoperative computed tomography (CT) and magnetic resonance imaging scans demonstrated damage confined to the left supramarginal gyrus invading the arcuate fasciculus. Together with recently reported cases of acquired fluent aphasia in children with CT-verified left posterior lesions, this case seems to support the current view that both fluent and nonfluent aphasia that share many similarities with the symptoms and lesion localization associated with adult cases may exist in children.

Aphasia↗

Conduction aphasia and arcuate fasciculus.

Three patients are presented who developed conduction aphasia after a small infarction almost exclusively confined to the arcuate fasciculus. All of them were diagnosed as conduction aphasia within a week after the stroke and showed a rapid amelioration. On the basis of the 3 patients and conduction aphasics in the literature, the relation between conduction aphasia and the arcuate fasciculus is discussed.

Aged↗