[A case of drug induced hepatitis and interstitial pneumonia caused by a herbal drug, Dai-saiko-to].
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Biomedical subjects
Publications and source records attributed to M Tomiyama.
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Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.
The aim of the present study was to clarify whether cognitive impairments caused by benzodiazepines (BDZs) are a consequence of their specific direct effects on cognitive function or whether they are explained as secondary effects of increased sleepiness. Ten healthy men (mean age, 33.9 years) participated in two experimental sessions in a randomized cross-over, double-blind study: in one session subjects were given a placebo and in the other they were given 0.125 mg triazolam (TRZ). Each experimental session was conducted on 1 day. After a pre-drug EEG recording and an event-related potential (ERP) recording, under an oddball paradigm, subjects took the TRZ or placebo orally at 1000 hours. Thereafter, EEG and ERP recording sessions, following the same procedure as the pre-drug sessions, were conducted at 1, 2, 4, 6 and 8 h after drug administration. The EEG and ERP recordings from Cz and Pz referred to the bilaterally linked ear electrodes were used. We found that P300 latency was significantly prolonged in TRZ condition at 2 h (Pz) and 4 h (Cz and Pz) after TRZ, and that the P300 amplitude was significantly reduced at 2 h (Cz and Pz) and 4 h (Pz) after TRZ, compared to the same times after placebo. The absolute power values for the theta (4-7 Hz), alpha 1 (8-9 Hz), and alpha 2 (10-12 Hz) bands did not differ at any measurement time between the treatments. Only the beta band (13-19 Hz) power value was significantly elevated after the TRZ administration (versus placebo). No significant sedative effects were detected in subjective measurements. These results indicate that a single oral dose of 0.125 mg TRZ caused cortical changes without distinct general sedation or subjective sleepiness.
The electrophysiological characteristics of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors vary with their subunit composition. The establishment of the subunit distribution is an essential step in the understanding of the function of these receptors. In the spinal cord, AMPA receptors are involved in normal and, possibly, pathological processes. Using in situ hybridization histochemistry with radiolabelled oligonucleotides as probes, we have studied the distribution of AMPA receptor subunit messenger RNAs (spliced flip and flop variants of glutamate receptor subunits A-D) in the human post mortem spinal cord. Transcripts for flip variants were preferentially expressed in the superficial dorsal horn, with a dorsoventral decreasing gradient of the signals. Transcripts for flop variants were also abundantly present in all layers of the gray matter, with the highest signal being observed for glutamate receptor subunit Bflop. Accordingly, flop forms were predominant in areas other than the superficial dorsal horn. This differential distribution of transcripts in the dorsal horn suggests that the subunit composition of AMPA receptors varies with the afferent inputs; AMPA receptors on neurons in the superficial dorsal horn, where terminals of thin primary afferents conducting noxious information are located, contain more flip forms, whereas neurons in the deep dorsal horn, where thick primary afferents mediating innocuous stimuli terminate, have AMPA receptors which are mainly composed of flop forms of glutamate receptor subunits A and B. The relatively high abundance of glutamate receptor subunit B transcripts in the superficial laminae of the dorsal horn indicates that AMPA receptors in these laminae have lower Ca2+ permeability. In addition, the relative abundance of glutamate receptor subunits Bflip and Dflop may show that AMPA receptors in the superficial dorsal horn have slow desensitization, while those of motor neurons have rapid desensitization.
PURPOSE: To discriminate patients with severe mental disorders from those complaining of menopausal symptoms, psychological tests were performed on patients who visited the menopausal clinic. The effectiveness of hormone replacement therapy (HRT) in patients with slight mental disorders was also evaluated. SUBJECTS AND METHODS: Patients with menopausal symptoms (n = 150, 41-59 yr. old) were interviewed by a psychiatrist (according to DSM-III-R) and classified as the climacteric syndrome group (C) and the mental disorder group (P). The patients were also evaluated by the Menopausal index (MI), Maudsley Personality Inventory (MPI) and Self-rating depression Scale (SDS). The patients with severe mental disorders were eliminated and the remaining patients with menopausal symptoms were treated with conjugated equine estrogen (0.625 mg/day) and medroxyprogesterone acetate (2.5mg/day) for 24 weeks. RESULTS: 1) Thirty six patients were diagnosed as P (24%) and seven of them were diagnosed as having major depression (4.7% of the all patients). 2) MPI-N (neurosis scale) in C was 16.2 +/- 10, and in P was 30.5 +/- 9.0, and SDS in C and P were 39.0 +/- 8.0, and 51.4 +/- 8.9, respectively. In both psychological test, P shows a significantly higher value than C (p < 0.01). 3) Ninety point six % of the patients responded. HRT was not effective in 63.2% of P, but when psychotropic drugs were combined, significant improvement (p < 0.05) was observed. CONCLUSION: One fourth of the patients were suspected of having mental disorders in the menopausal clinic, and 5% of the patients needed the care of the psychiatrist. And the application of MPI and SDS was useful in helping the gynecologist to differentiate and classify the mental disorders to some extent. The applicability and effectiveness of HRT for patients with mild mental disorders were suggested.
Tumor metastasis to the hypophyseal system has rarely been reported with either clinical or radiographic evidence. A 52-year-old woman presented with polydipsia, polyuria, and loss of appetite. She was diagnosed as having diabetes insipidus caused by pituitary micrometatasis of lung adenocarcinoma. After she had been treated with radiation therapy to the pituitary gland, the gland size was reduced as confirmed by magnetic resonance imaging, and her urine volume decreased. However, meningitis carcinomatosa appeared later. This was a rare case of secondary diabetes insipidus due to pituitary metastasis of lung cancer.
Changes in nasopharyngeal flora were investigated in children with acute otitis media and with acute exacerbations of chronic sinusitis in whom antibiotic therapy of relatively long duration was required until substantial improvement in clinical findings was achieved. 1. The antibiotics used were two cephalosporins, i.e., cefaclor (CCL) and cefixime (CFIX), administered to 18 patients each for 1 week and to 26 and 20 patients, respectively, for 2 weeks. Bacteriologic examination of the nasopharyngeal mucosa was performed at the first visit and at 1 week in those who underwent antibiotic therapy for 1 week, and at the first visit and at 1 and 2 weeks in those treated with antibiotics for 2 weeks. 2. The elimination rates for the infecting microorganisms in the patients in the CCL-treated group were 30% for Haemophilus influenzae, 83% for Staphylococcus aureus, 100% for Streptococcus pyogenes and 100% for Streptococcus pneumoniae at 1 week, and 18% for H. influenzae, 100% for S. aureus and 100% for S. pyogenes at 2 weeks of antibiotic therapy. Replacement of S. aureus and S. pyogenes by H. influenzae was observed. 3. The elimination rates for infecting bacteria in the patients in the CFIX-treated groups were 61% for H. influenzae, 50% for S. aureus, 75% for S. pyogenes, 80% for S. pneumoniae and 100% for Moraxella catarrhalis at 1 week, and 72% for H. influenzae, 0% for S. aureus, 100% for S. pyogenes, and 0% for S. pneumoniae at 2 weeks of antibiotic therapy. The elimination rate for H. influenzae at 2 weeks was significantly higher than the corresponding value for the CCL-treated group. Replacement of H. influenzae by S. aureus and S. pneumoniae and of S. pyogenes by S. aureus was detected. 4. There was one patient with acute otitis media in the CFIX-treated group in whom a clinical relapse occurred due to H. influenzae persisters in the nasopharynx. Thus the diagnosis in this patient was so-called "recurrent otitis media". 5. H. influenzae tended to persist after exposure to therapeutically adequate concentrations of CCL, as did S. aureus and S. pneumoniae following treatment with CFIX. Thus, it would seem that ample heed must be given to persistence, particularly of H. influenzae and S. pneumoniae, the most common causative agents of acute otitis media in childhood. 6. A significant rise in the MICs of the cephalosporins was observed in 4 of 43 patients in whom the same type of organism was isolated from the nasopharynx at weekly intervals during antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Among cases of infantile acute pharyngolaryngitis with cough as a chief complaint, 21 cases that the involvement of bacterial infections has been demonstrated were given minocycline (MINO) and the effectiveness and safety of MINO were investigated. 1. Regarding the clinical effectiveness, the number of cases assessed as markedly effective was 9 (43%) and that as effective was 8 (38%), so that the effectiveness rate was 81%, and particularly, in the infections caused by Haemophilus influenzae, MINO showed a high effectiveness. 2. Five strains of Streptococcus pneumoniae, 2 strains of Streptococcus pyogenes and 16 strains of H. influenzae, a total of 23 strains of pathogenic bacteria were isolated, and MINO showed high activities against not less than 80% of these strains. 3. The bacteriological effect in terms of the rate of eradication was 71%, and that of H. influenzae was as high as 88%, while S. pneumoniae remained in 3 of 5 cases. 4. Adverse reactions were observed in 2 cases (10%), 1 case each of abdominal pain and stomatitis, and both of them were improved after the treatment termination. 5. Regarding the usefulness, which was comprehensively assessed using clinical effectiveness and safety as criteria, the number of cases evaluated satisfactorily useful was 8 (38%) and that as useful was 8 (38%), so that the overall usefulness rate was 76%. From the above results, it was confirmed that MINO is a drug having high efficacy and safety against infantile acute pharyngolaryngitis with cough as a chief complaint caused by H. influenzae.(ABSTRACT TRUNCATED AT 250 WORDS)
We measured GABAA and GABAB receptor densities in the cerebellar cortex from 3-acetylpyridine-induced ataxic rats using receptor autoradiography. GABAA and GABAB receptor densities were significantly reduced both in the molecular layer and the granule cell layer. Reduction of GABA receptor densities may be induced by loss of GABA receptors on the degenerated climbing fibers or by secondary or compensatory changes of neuronal activities in the cerebellum.
The reduction of glutamate content has been observed in the spinal cord of the wobbler mouse, a purported model of amyotrophic lateral sclerosis (ALS). To elucidate glutamate receptors in the wobbler spinal cord, we measured densities of N-methyl-D-aspartate (NMDA), kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) and metabotropic glutamate (mGlu) binding sites using in vitro autoradiography. In wobbler mice, NMDA, kainate, and AMPA binding sites were increased in the dorsal horn and kainate binding sites were also increased in the intermediate zone. However, mGlu binding was unchanged. These results disagree with those observed in ALS spinal cords, in which NMDA and kinate binding sites are decreased. The wobbler mouse may have the glutamate dysfunction, but in a different way from ALS.
The nucleotide sequence of the S3 genome segment of rice gall dwarf virus, a phytoreovirus, consisted of 3224 bp and sequence analysis showed that the segment potentially encoded a 116K major core capsid protein of the virus. This 116K protein and the 114K major core capsid protein of rice dwarf virus are similar in size and were found to have amino acid sequence homology as high as that between the major outer capsid proteins of the two viruses. Core particles and outer capsids of these viruses were interchangeable, suggesting conformational similarity in the three-dimensional architecture of their core and outer capsid proteins.
Changes in susceptibilities to oral antimicrobials were investigated in 189 children, in whom Haemophilus influenzae was detected by nasopharyngeal culture, among the children who were diagnosed as having acute otitis media or chronic sinusitis with acute exacerbation in the Department of Otolaryngology in 1986, 1988 and 1991. The minimum 50% inhibitory concentration (MIC50) and minimum 90% inhibitory concentration (MIC90) of ampicillin (ABPC), cefaclor (CCL) and erythromycin (EM) in the subjects examined in 1986 were almost the same as the levels in those examined in 1991. The MIC50 level of minocycline (MINO) in the subjects examined in 1991 was lower by 2 test tubes than that determined in 1986, showing improvement in susceptibilities. The prevalence of resistance to antimicrobials was compared between 1986 and 1991. The prevalence to ABPC tended to decrease very slightly, while the prevalence to CCL tended to increase very slightly. The prevalence of EM tended to increase slightly. Many CCL-resistant strains detected in 1991 showed resistance to ABPC and EM, but showed favorable susceptibilities to cefixime and norfloxacin. Future trends of CCL-resistant strains should be carefully observed. There was no marked change in the prevalence of resistance to ABPC or CCL. ABPC and CCL were considered to be the first choice drugs, even at present, for pediatric patients with acute otitis media due to infection with H. influenzae and in those with acute exacerbation of chronic sinusitis due to the infection.
To objectively evaluate the clinical efficacy and safety in acute tonsillitis, flomoxef (FMOX) was examined for the distribution of sensitivity of clinical strains to it and for its clinical usefulness. 1. The 80% minimum inhibitory concentration of 11 clinical strains of Gram-positive bacteria, 6 of Gram-negative bacteria and 5 of anaerobic bacteria was 0.39 microgram/ml. FMOX showed the strongest, most comprehensive antibacterial action among the drugs tested. 2. Thirty patients received FMOX. Clinical effectiveness was evaluated in 28 patients, and clinical usefulness and safety in 30. 3. The clinical efficacy rate ('excellent' and 'good') was 75% (21/28). 4. As for bacteriological response, bacterial elimination rates were 67% for Gram-positive bacteria, 100% for Gram-negative bacteria, 100% for anaerobic bacteria and 100% for mixed infections. 5. Side effects occurred in 2 (6%) patients: drug eruption and diarrhea in 1 patient each. These symptoms improved rapidly after discontinuation of the drug. 6. Although abnormal clinical test results were found in 7 (23%) patients, i.e., increases in GOT and GPT in 2, in GPT in 4 and in BUN in 1, they were transient. 7. The usefulness of FMOX was assessed in light of its efficacy and safety. It was highly satisfactory in 14 patients, satisfactory in 11, relatively satisfactory in 1, unsatisfactory in 2 and highly unsatisfactory in 2, and rate of usefulness was 83%. FMOX is considered to be highly useful for the treatment of severe acute tonsillitis.
Nasopharyngeal specimens were taken from 29 children with acute otitis media, 14 children with chronic sinusitis at acute exacerbation and 2 children with streptococcal pharyngitis who had received cefaclor for 14 days. The study was designed to compare the microbiologic flora of the nasopharynx before the treatment of these diseases with that after the treatment. In this report the subjects were limited to the children who had not received antibiotics within 1 month. Pathogens detected on initial examination were 49 strains consisting of 40 strains of H. influenzae, 3 strains of S. aureus, 5 strains of S. pyogenes, and 1 strain of S. pneumoniae. Two strains were detected in 4 patients. Pathogens remained after treatment in 29 patient, with an unchanged number of pathogens in 12 patients, a decreased number in 14, and microbial substitution in 3. All of the remaining pathogens were H. influenzae, and minimum inhibitory concentration (MIC) changed in 5 of the 26 patients in whom H. influenzae was detected before and after treatment. In a patients with increased MIC, the strain changed from a sensitive strain with an MIC of lower than 3.13 micrograms/ml to a highly resistant strain with an MIC of 25.0 micrograms/ml or higher. By contrast, in 2 patients with decreased MIC, the strain changed from a highly resistant strain with an MIC of 12.5 micrograms/ml or higher to a sensitive strain with an MIC of lower than 3.13 micrograms/ml. In the other patient, MIC decreased to 3.13 micrograms/ml after it had increased from 3.13 micrograms/ml to 25.0 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy of a combination of cefaclor and fosfomycin otic solution was investigated in 81 children with acute otitis media, who needed myringotomy for severe erythema and swelling of the tympanic membrane. The patients were followed up for one year to investigate correlations between test findings of early treatment and both clinical course and prognosis. These drugs were used for 10 days, and the effects of combined use were evaluated from findings in the tympanic membrane after the 10-day period. Three stages were assessed; cured, recovered and unchanged. In cured and recovered cases, the administration was evaluated to be effective. Within 2 weeks after the start of treatment, views of the ears, nose and epipharynx were roentgenographically examined for shadows of mastoid pneumatization and the paranasal sinuses, and the presence or absence of adenoid vegetation. After the antibiotic administration, the patients were instructed to visit us at least once every 3 months to rule out recurrence of acute otitis media and otitis media with effusion (possibly occurring one year after treatment). The following results were obtained. 1. The two drug combination was effective in 99% of patients, produced no side effects, and was deemed extremely useful. 2. The course of acute otitis media tended to be significantly prolonged in patients with mastoid pneumatization and paranasal sinus shadows as revealed by roentgenography.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical, electrophysiological and histopathological findings in 6 children with steroid-responsive acquired demyelinating neuropathy are presented. The clinical features and nerve conduction findings are basically similar to those of chronic inflammatory demyelinating neuropathy (CIDP) in adults, although early-onset cases had prominent pes cavus deformity and thickened nerves, which are rare findings in acquired neuropathies in adults. The diagnostic criteria of adult CIDP can be adopted for most of the cases, however, repeated electrophysiological tests may be required to identify multifocality of the nerve lesion, especially when conduction block is not apparent before treatment. The biopsied sural nerves showed many thinly-myelinated fibers, subperineurial and endoneurial edema, and cellular infiltrations. Varied fascicular involvements were common. Two cases with almost complete or considerable loss of myelinated fibers in the biopsied sural nerve revealed good clinical response to steroid therapy. The degree of nerve degeneration in the sural nerve thus, may not be helpful to estimate the prognosis and the responsiveness to treatment. Therapeutic trials should be employed when the main conduction findings are those of demyelinating neuropathies, even if genetically-determined neuropathy is suggested from the clinical pictures.
A clinical study with 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA) was performed in 10 patients with hepatobiliary disease. In this study, scintigraphic data and images with 99mTc-GSA were compared with several serological liver function tests, the hepatic blood perfusion index and image quality using 99mTc-DTPA-human serum albumin (99mTc-HSA). Dynamic and serial hepatic images were obtained over a 20 min period after 99mTc-GSA injection, and time activity curves from the heart and liver were generated. The blood clearance index (HH15), and the hepatic uptake index (LHL15) were calculated from each curve of the heart and liver, respectively. In addition, using two compartment fitting, the blood clearance (KH1, KH2) index was calculated, and using exponential fitting, the hepatic uptake index (KL) was calculated. The mean HH15 in LC group and non-LC group was 0.81 +/- 0.05, 0.64 +/- 0.10, respectively. The mean LHL15 in LC group and non-LC group was 0.79 +/- 0.04, 0.91 +/- 0.06, respectively. There were significant differences between non-LC group and LC group in HH15, and LHL15, KH1 and KL. There were also significant correlations of KH1 with HH15, and KL with LHL15. Parameters of 99mTc-GSA showed significant correlations with various liver functions. 99mTc-GSA scintigraphy showed clearer liver images in hepatobiliary diseases than 99mTc-HSA. These results suggest that 99mTc-GSA scintigraphy is useful in estimating preserved liver function and hepatic morphology.
We treated two patients with chronic inflammatory demyelinating polyneuropathy (CIDP) with high-dose intravenous immunoglobulin (HIG). The patients received 400 mg/kg of immunoglobulin a day for five days. One patient, who had failed to respond to prednisolone before, was treated with HIG, 18 months after the onset. His motor symptoms resolved immediately after the commencement of HIG. Electrophysiologically, the compound muscle action potentials increased in amplitude in all nerves examined and F wave reappeared in the left median nerve. The electrophysiological changes were compatible with improvement of conduction blocks. This patient had headache and exanthema during the HIG therapy, but they settled after cessation of the infusion. The other patient was administered HIG as an initial treatment, four months after the onset. HIG was of no effect in this case, but he showed remarkable recovery during the following prednisolone therapy. Although corticosteroid therapy is the first choice for CIDP, there are CIDP patients who do not respond to steroid or can not complete the steroid therapy because of adverse effects. HIG is an expectative and recommendable treatment for the steroid resistant CIDP patients.