Biomedical subjects
Publications and source records attributed to K Otani.
There has been few reports on the effective treatment for SOD, which is phenomenologically similar to TD. A 66-year-old female with SOD was successfully treated by CNZ 2 mg/day. Even after one year of continuous treatment, tolerance, which is the major problem in the CNZ treatment for TD, did not develop. This report suggests that CNZ is effective at least for some patients with SOD.
1. A 52-year-old female with refractory depression had not responded to various treatments including electroconvulsive therapy and augmentation therapy with lithium or triiodothyronine. 2. Addition of bromocriptine 2.5-5 mg/day to imipramine improved her depressive symptoms. However, when the dose was increased to 15 mg/day to treat residual depressive symptoms, her clinical status deteriorated and returned to the original level. The dose reduction to 5mg/day again improved her depressive symptoms. 3. This report confirms the augmentation effect of bromocriptine for refractory depression. It also suggests that there is dose-dependency in this effect.
The effects of a genetic polymorphism of inducibility of cytochrome P450 (CYP) 1A2 on the steady-state plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine, were studied in order to clarify if these steady-state plasma concentrations are dependent on the CYP1A2 polymorphism. Fifty-eight Japanese depressed patients received trazodone 150 mg/day at bedtime. The steady-state plasma concentrations of trazodone and m-chlorophenylpiperazine were measured in duplicate using high performance liquid chromatographic method, and were corrected to the mean body weight for analyses. A point mutation from guanine (wild type) to adenine (mutated type) at position -2964 in the 5'-flanking region of CYP1A2 gene was identified by polymerase chain reaction fragment length polymorphism method. The mean steady-state plasma concentration of trazodone, but not m-chlorophenylpiperazine was significantly (P<0.05) lower in smokers than in non-smokers. Twenty-two smokers had 16 homozygotes of the wild type allele, 5 heterozygotes of the wild type and mutated alleles, and one homozygote of the mutated allele. There was no significant difference in the mean steady-state plasma concentration of trazodone or m-chlorophenylpiperazine between smokers with no mutation and those with mutation, although one homozygote of the mutated allele had the highest steady-state plasma concentration of trazodone in smokers. The present study thus suggests that CYP1A2 polymorphism does not necessarily have predictive value of the steady-state plasma concentration of trazodone or m-chlorophenylpiperazine in most of the smokers treated with trazodone.
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Pantoprazole, a proton pump inhibitor, is administered as a racemic mixture. To determine the role of cytochrome P450 (CYP) 2C19 in the stereoselective metabolism of pantoprazole, we investigated the pharmacokinetic disposition of (+)- and (-)-pantoprazole in 7 extensive metabolizers and 7 poor metabolizers of S-mephenytoin. All of the subjects received an oral 40-mg dose of racemic pantoprazole as the enteric-coated formulation. In the extensive metabolizers, the mean clearance of (-)-pantoprazole was only slightly lower than that of (+)-pantoprazole and no significant differences in the other pharmacokinetic parameters between (+)- and (-)-pantoprazole were observed. The mean (+)/(-) ratios for maximum concentration, area under the plasma concentration-time curve from 0 to infinity, and elimination half-life were 0.94, 0.82, and 0.90, respectively. In contrast, in the poor metabolizers, the clearance values of both enantiomers were significantly lower than those in the extensive metabolizers, and a significant difference in pharmacokinetics between (+)- and (-)-pantoprazole was observed. The mean elimination half-life for (+)-pantoprazole was 3.55-fold longer than that of (-)-pantoprazole, and the mean maximum concentration and area under the plasma concentration-time curve from 0 to infinity for (+)-pantoprazole were 1.31- and 3.59-fold greater, respectively, than those for (-)-pantoprazole. These results indicate that the stereoselective metabolism of pantoprazole depends on S-mephenytoin 4'-hydroxylase (CYP2C19). The metabolism of (+)-pantoprazole was impaired to a greater extent than (-)-pantoprazole in the poor metabolizers.
We report a new variant type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, gastroesophageal reflux, and fibrous thickening of splenic and hepatic capsules. This patient had 1 D409H allele. He differed from other reported cases with a 1342G to C (D409H) homozygous mutation (onset at 4 months, no cardiac involvement until the age of 12 years, and massive hepatosplenomegaly with fibrous thickening of spleen and liver capsules). Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement.
STATEMENT OF PROBLEM: A durable repairing system for denture base fracture is desired to avoid recurrent fracture. Purpose. This study evaluated the strength and modulus of elasticity of repaired acrylic specimens reinforced with various processes. MATERIAL AND METHODS: Transverse strength and modulus of elasticity of repaired acrylic denture base specimens were evaluated with a 3-point bending test and compared with a heat-polymerized control. Autopolymerizing acrylic resin was used with woven metal fiber and glass fiber with and without methylene chloride surface treatment (n = 6 per group). The specimens were cut in half and fixed in a metal mold to obtain a space for placing the repairing resin. A cavity was prepared when metal or glass fiber was used. All specimens were stored in 37 degrees C distilled water for 48 hours before the test. All data were statistically analyzed with 1-way ANOVA, and differences among groups were analyzed with Fisher test (P< or =.05). RESULTS: The mean value of the transverse strength for the control was 87.2 MPa. The specimens repaired by glass fiber with methylene chloride surface treatment exhibited the highest transverse strength (96.8 MPa), which was significantly higher than that of the control (P< or =.05). The elastic modulus of the specimens repaired by glass fiber with methylene chloride surface treatment (4189.3 MPa) was significantly greater than that of the control (2683.7 MPa) at a 95% level of confidence. The values of transverse strength and elastic modulus were highest when the surface treatment was combined with a reinforcing glass fiber. CONCLUSION: Reinforcement with glass fiber and methylene chloride pretreatment produced transverse strength and a modulus of elasticity higher than the control.
The complete lip alveolus and cleft palate is the most difficult of all bilateral clefts to treat because of the deformity of and tissue insufficiency in the prolabium. A bilateral concomitant procedure is impractical for treatment of this condition because of the problems that have to be resolved postoperatively, including a short columella, a lack of philtrum, labial horizontal and vertical insufficiency, and vermilion and alveolar vestibulum insufficiency. A two-stage procedure called the transformation method has been developed to circumvent these problems, and the authors present it here. With this method one side is closed completely using the maximum amount of tissue available. Concomitantly, incomplete closure is performed on the other side. The result at the end of the first stage of the procedure is a condition approximating unilateral incomplete closure. The results were obtained from 6 patients who underwent complete bilateral closure and were followed for at least 2 years with satisfactory results.
Changes in blood flow after chronic compression were observed in 19 dogs after 10 mmHg compression for 1 week before and 1 hour after the intravenous administration of one of three doses of beraprost sodium (BPS; 30 ng x kg(-1) x min(-1), n = 7; 100 ng x kg(-1) x min(-1), n = 7; and 300 ng x kg(-1) x min(-1), n = 5). The speed of blood flow was calculated using a specially designed microscope equipped with a video camera. Dogs treated with BPS had lesser degrees of reduction in their nerve conduction velocity compared with controls. A vascular mechanism of injury likely explains why BPS-treated dogs had a lesser degree of reduction in their nerve conduction velocities compared with the control population.
The purpose of this study was to present a simple method of measurement of blood flow in the nerve root, assess the reliability of this method, and examine the changes of blood flow in chronic cauda equina compression in an experimental setting. A total of 15 dogs were used to determine the blood flow of cauda equina in normal (n = 5), sham (n = 5), and 10 mm Hg compressed cauda equina for 1 week (n = 5). The speed of blood flow was calculated using a specially designed microscope supplied with a video camera. Blood flow in chronic 10 mm Hg compression decreased compared with the sham and normal groups. The kappa value was between 0.75 and 0.96. We conclude that this method might be useful for measurement of blood flow in the nerve root and for confirming the reduction in blood flow of compressed cauda equina.
In most cases, patients with Bowen disease lesions can be easily treated by surgical excision and direct closure; however, the ultrasonic surgical aspirator, an instrument in common use in many fields, offers a good treatment alternative with few drawbacks for patients with lesions that are large and/or located in joint areas, areas that are hard to heal, or areas that are surgically problematic such as the ears, nose, eyelids, and mucous membranes. The clinical application of the ultrasonic surgical aspirator in the treatment of Bowen disease promises considerable benefit in terms of patient comfort because removal of the lesion is easy, is noninvasive, and does not require hospitalization or result in restricted mobility. All of these factors, although benefiting patients, particularly the elderly, can also substantially lower the cost of treatment.
Previous studies have demonstrated a lower density of dopamine D2 receptor (DRD2) in subjects without Del alleles of the -141C Ins/Del polymorphism in DRD2 gene promoter region than in those with one or two Del alleles. The present study aimed to examine whether the -141C Ins/Del DRD2 promoter polymorphism is related to therapeutic response to selective DRD2 antagonists in the treatment of schizophrenia. Subjects consisted of 49 acutely exacerbated schizophrenic inpatients treated with bromperidol (30 cases, mean dose +/- SD: 11.4 +/- 4.8 mg/day) or nemonapride (19 cases, 18 mg/day). Clinical symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The -141C Ins/Del DRD2 genotypes, the Ins and Del alleles, were determined by a polymerase chain reaction method. Thirty-five patients were homozygous for the Ins allele and 14 were heterozygous for the Del and Ins alleles. The patients without Del allele showed a higher percentage of improvement in anxiety-depression symptoms than those with Del allele (58.5 +/- 44.5% versus 24.1 +/- 48.2%) after 3 weeks of treatment while percentage improvement in total BPRS or other subgrouped symptoms (positive, negative, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that the -141C Ins/Del DRD2 polymorphism is associated with anxiolytic and antidepressive effects of neuroleptic treatment in schizophrenic patients.
OBJECTIVES: Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder epithelium. DESIGN: Eleven noncancerous gallbladders from patients with pancreaticobiliary maljunction, 12 gallbladder carcinomas from patients without pancreaticobiliary maljunction and 14 noncancerous gallbladders from patients without pancreaticobiliary maljunction (control) were studied. METHODS: Immunohistochemistry was performed for 4-hydroxy-2-nonenal-modified protein (as a marker for lipid peroxidation), 8-hydroxy-2'-deoxyguanosine and p53 gene product. RESULTS: Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Densitometric quantitation revealed significantly higher expression of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelial cells from patients with pancreaticobiliary maljunction (index 27.3 +/- 3.1) than in cells from patients with gallbladder carcinoma (11.4 +/- 1.5; P < 0.05) or from control subjects with normal gallbladder (6.4 +/- 1.0; P < 0.05). Positivity of p53 was 27% in gallbladder epithelium associated with pancreaticobiliary maljunction, 75% in gallbladder carcinoma epithelium and 0% in control epithelium. CONCLUSIONS: These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobiliary maljunction and that oxidative DNA injury is related to carcinogenesis in these patients.
OBJECTIVE: The pathophysiology of neuroleptic malignant syndrome is mainly explained by a central hypodopaminergic state. The familial occurrence of neuroleptic malignant syndrome suggests the involvement of a genetic mechanism in the predisposition to the syndrome. Therefore, the authors examined the association between the TaqI A polymorphism of the dopamine D(2) receptor gene (DRD(2)), which alters DRD(2) density and function, and the development of neuroleptic malignant syndrome. METHOD: The subjects were 15 psychiatric patients who had developed neuroleptic malignant syndrome (12 patients with schizophrenia and three with major depression) and 138 patients with schizophrenia who had never developed neuroleptic malignant syndrome. The TaqI A genotypes, A1 and A2 alleles, were determined by the polymerase chain reaction method. RESULTS: The frequency of the A1 allele was significantly higher in the patients who had developed neuroleptic malignant syndrome (56.8%) than in the patients who had not (35.1%). The proportion of the A1 carrier was significantly higher in the patients with neuroleptic malignant syndrome (14 [93.3%] of 15 patients) than in those without the syndrome (79 [57.2%] of 138 patients). CONCLUSIONS: These findings suggest that the TaqI A DRD(2) polymorphism is associated with the predisposition to neuroleptic malignant syndrome.
Transitional vertebrae (TV) may be one of the risk factors for lumbar disc herniation. It is not clear, however, whether the presence of TV can affect the development of nerve-root symptoms. Our aim was to clarify this relationship. A total of 501 patients with lumbar degenerative disease and nerve-root symptoms was studied in respect of their level and the presence of TV. As a control group, 508 patients without low back pain or nerve-root symptoms were studied to establish the incidence of TV. In patients with disc herniation, the incidence was statistically higher and the mean age lower in patients with TV than in those without. In most patients, the symptomatic disc level was just above the TV. Similarly, in those with stenosis of the spinal canal without spondylolisthesis, the symptomatic disc level was most commonly just above the TV.
Studies of the genetic basis of type 2 diabetes suggest that variation in the calpain-10 gene affects susceptibility to this common disorder, raising the possibility that calpain-sensitive pathways may play a role in regulating insulin secretion and/or action. Calpains are ubiquitously expressed cysteine proteases that are thought to regulate a variety of normal cellular functions. Here, we report that short-term (4-h) exposure to the cell-permeable calpain inhibitors calpain inhibitor II and E-64-d increases the insulin secretory response to glucose in mouse pancreatic islets. This dose-dependent effect is observed at glucose concentrations above 8 mmol/l. This effect was also seen with other calpain inhibitors with different mechanisms of action but not with cathepsin inhibitors or other protease inhibitors. Enhancement of insulin secretion with short-term exposure to calpain inhibitors is not mediated by increased responses in intracellular Ca2+ or increased glucose metabolism in islets but by accelerated exocytosis of insulin granules. In muscle strips and adipocytes, exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose transport. Incorporation of glucose into glycogen in muscle also was reduced. These results are consistent with a role for calpains in the regulation of insulin secretion and insulin action.
In order to see the patients with low back pain and/or sciatica, it is most important to consider the pathophysiology of symptoms. We should know that the image findings such as X-ray and MRI do not always show the cause of symptom. Because degenerative changes in lumbar spine are common findings in asymptomatic group compared to symptomatic patients with low back pain and sciatica. According to pathophysiology (nerve root syndrome, cauda equina syndrome, facet syndrome, discogenic pain syndrome and intermittent claudication for low back pain), the treatment for low back pain and sciatica were described.
The relationship between Taq1 A polymorphism of dopamine D(2) receptor (DRD(2)) gene and extrapyramidal adverse effects of bromperidol and nemonapride, which are both antipsychotic drugs with selective and potent DRD(2) antagonistic property, was investigated in Japanese schizophrenic inpatients. Twenty-seven patients were treated with bromperidol at 6 or 12 or 18 mg/day, while 25 patients were treated with nemonapride at 18 mg/day. The duration of treatment was 3 weeks. The A1 and A2 alleles were determined by PCR. The extrapyramidal adverse effects were assessed by the Udvalg for Kliniske Unders¿ogelser side effects rating scale. Six patients were homozygous for the A1 allele, 27 were heterozygous for the A1 and A2 alleles, and 19 were homozygous for the A2 allele. There were no significant differences in the incidences or severity of extrapyramidal adverse effects between the patients with one or two A1 alleles and those with no A1 allele. The present study suggests that Taq1 A polymorphism is not related to the development of extrapyramidal adverse effects during acute phase of bromperidol and nemonapride treatments.