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1.
Kyobu Geka ; 77(8): 574-578, 2024 Aug.
Article in Japanese | MEDLINE | ID: mdl-39205409

ABSTRACT

We encountered a rare case of infective endocarditis caused by a common Gram-positive anaerobic coccus Parvimonas micra, originating from colorectal cancer. The patient was a 78-year-old female, presented with fever, speech disorder, and right hemiplegia resulting from stroke. Transthoracic echocardiography revealed mitral regurgitation and a mobile vegetation on the mitral valve. Computed tomography( CT) of the abdomen revealed a mass lesion or abscess in the abdomen that was highly suggestive of relevance with infective endocarditis. An urgent surgery was initially performed to prevent further cerebral infarction, with abdominal surgery planned as the second stage. During the cardiac surgery, we observed a large defect following the partial resection of an infected posterior leaflet, and the adjacent calcified annulus was repaired using autologous pericardium. This effectively controlled mitral regurgitation. Both blood cultures yielded Parvimonas micra, which has recently become known as a biomarker for colorectal cancer. Subsequently, the patient's colorectal cancer was excised. Following the surgery, the patient was free from infection and underwent a rehabilitation program.


Subject(s)
Mitral Valve , Humans , Aged , Female , Mitral Valve/surgery , Gram-Positive Bacterial Infections/complications , Firmicutes , Endocarditis, Bacterial/surgery , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/microbiology , Tomography, X-Ray Computed , Endocarditis/surgery , Endocarditis/complications , Endocarditis/microbiology , Colorectal Neoplasms/surgery
2.
Mol Biol Rep ; 49(3): 2015-2024, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34845648

ABSTRACT

BACKGROUND: GABAergic system dysfunction has been implicated in the etiology of schizophrenia and of cognitive impairments in particular. Patients with treatment-resistant schizophrenia (TRS) generally suffer from profound cognitive impairments in addition to severe positive symptoms, suggesting that GABA system dysfunction could be involved more closely in patients with TRS. METHODS AND RESULTS: In the present study, exome sequencing was conducted on fourteen TRS patients, whereby four SNPs were identified on GAD1, GABBR1 and GABBR2 genes. An association study for five SNPs including these 4 SNPs and rs3749034 on GAD1 as then performed among 357 patients with TRS, 682 non-TRS patients and 508 healthy controls (HC). The results revealed no significant differences in allelic and/or genetic distributions for any of the five SNPs. However, several subanalyses in comparisons between schizophrenia and HC groups, as well as between the three groups, showed nominal-level significance for rs3749034 on GAD1 and rs10985765/rs3750344 on GABBR2. In particular, in comparisons of female subjects, rigorous analysis for rs3749034 showed a statistical difference between the schizophrenia and HC groups and between the TRS and HC groups. CONCLUSIONS: Several positive results in subanalyses suggested that genetic vulnerability in the GABA system to schizophrenia or TRS could be affected by sex or sampling area, and overall, that rs3749034 on GAD1 and rs10985765 on GABBR2 could be related to TRS. In the present study, only a few SNPs were examined; it is possible that other important genetic variants in other regions of GABA-related genes were not captured in this preliminary study.


Subject(s)
Schizophrenia , Female , Genetic Association Studies , Glutamate Decarboxylase/genetics , Humans , Receptors, GABA-B/genetics , Schizophrenia/genetics , Schizophrenia, Treatment-Resistant
3.
Ann Vasc Surg ; 81: 121-128, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34780952

ABSTRACT

BACKGROUND: This study investigated the impact of aortic diameter on late aortic dilation of the residual dissected aorta after tear-oriented aortic replacement for acute DeBakey type I aortic dissection. METHODS: Of 133 patients who underwent aortic replacement for acute DeBakey type I/II aortic dissection between 2008 and 2019, 45 patients with a residual dissected aorta after surgery for acute DeBakey type I aortic dissection and who underwent computed tomography at predischarge and after 1 year were retrospectively assessed. The aortic diameter and false lumen area were measured at 3 levels: the maximal aortic site, seventh thoracic vertebra, and celiac axis. Multivariable Cox regression analysis was employed to identify the predictors of late aortic dilation, defined as an aortic growth rate of ≥5 mm/year or a maximal aortic diameter of ≥55 mm. RESULTS: During a median follow-up of 75 [range: 13-152] months, 6 patients (5 men; mean age: 57 ± 14 years) experienced aortic dilation. All 6 patients had the maximal aortic diameter between the distal aortic arch and seventh thoracic vertebra level at the last computed tomography. Multivariable Cox regression analysis showed that the predischarge maximal aortic diameter was an independent determinant of late aortic dilation (hazard ratio: 2.28/mm, 95% confidence interval: 1.10-5.86). CONCLUSIONS: Predischarge maximal aortic diameter is a significant predictor of late aortic dilation in patients with a residual dissected aorta after tear-oriented surgical repair of acute DeBakey type I aortic dissection.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Adult , Aged , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Aorta/diagnostic imaging , Aorta/surgery , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Dilatation , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
4.
Kyobu Geka ; 75(13): 1094-1097, 2022 Dec.
Article in Japanese | MEDLINE | ID: mdl-36539225

ABSTRACT

A 57-year-old man was transferred with sudden onset chest pain and evolving paralysis and numbness in the left leg. Contrast computed tomography (CT) revealed Stanford type A acute aortic dissection from the ascending aorta to bilateral internal and external iliac arteries with blood flow obstruction to the left kidney and left lower limb. Surgery was initiated 10 hours after onset of ischemic symptoms in the leg. Femoro-femoral bypass was carried out first, and we ensured sufficient phlebotomy from the ischemic limb during reperfusion and continuous hemodiafiltration to prevent myonephropathic metabolic syndrome. Total aortic arch replacement was then performed. Our treatment strategy was effective in this case of Stanford type A aortic dissection with prolonged lower limb ischemia. Although left hip disarticulation was subsequently required due to intractable infection, the patient became able to walk with an artificial limb after post-rehabilitation.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Male , Humans , Middle Aged , Aortic Dissection/complications , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Ischemia/surgery , Aorta, Abdominal , Kidney , Vascular Surgical Procedures/methods , Syndrome , Aortic Aneurysm, Thoracic/complications , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery
5.
Int J Clin Oncol ; 22(6): 1034-1041, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28623448

ABSTRACT

BACKGROUD: Laryngeal preservation is an important consideration when treating cervical esophageal cancers (CECs) such as laryngeal cancer. The standard treatment for CEC allowing laryngeal preservation is chemoradiotherapy. However, in cases of laryngeal cancer, chemoselection has also been applied as a treatment strategy that promotes larynx preservation. This strategy involves assigning the appropriate radical treatment according to the primary tumor's response to induction chemotherapy. Since there have been no studies of the application of chemoselection in CEC cases, the present study compared the results, including laryngeal preservation rates, obtained upon applying chemoselection and chemoradiotherapy to CEC. STUDY DESIGN: This was a retrospective cohort study of cervical esophageal squamous cell carcinoma patients treated using chemoselection or chemoradiotherapy at Aichi Cancer Center Hospital between January 2000 and March 2013. A total of 42 patients were enrolled. RESULTS: The 2-year overall survival and laryngeal preservation rates for the chemoselection group versus the primary radiotherapy group were 65.1 and 57.3 versus 40 and 83.3%, respectively (P = 0.017 and P = 0.122, respectively). The 2-year locoregional control rates for the chemoselection and primary radiotherapy groups were 68 and 25%, respectively (P = 0.045). CONCLUSION: The chemoselection group achieved favorable results. Therefore, chemoselection can be applied as a treatment strategy for CEC.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Induction Chemotherapy/methods , Organ Sparing Treatments/methods , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Chemoradiotherapy , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma , Female , Humans , Laryngectomy/methods , Larynx/surgery , Male , Middle Aged , Neoplasm Recurrence, Local , Pharyngectomy/methods , Retrospective Studies , Survival Rate
6.
J Chest Surg ; 57(5): 496-499, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38835208

ABSTRACT

Calcification of the mitral valve annulus is common in patients on dialysis. The growing number of individuals receiving dialysis has been accompanied by an increase in cases necessitating surgical intervention for mitral valve annulus calcification. In this report, we present a severe case characterized by bulky calcification of the mitral annulus, which was managed with mechanical mitral valve replacement. A 61-year-old man on dialysis presented with chest pain upon exertion that had persisted for 3 months. Cardiac echocardiography revealed severe mitral stenosis and regurgitation, accompanied by cardiac dysfunction. During surgery, an ultrasonic aspiration system was employed to remove the calcification of the mitral valve annulus to the necessary extent. Subsequently, a mechanical mitral valve was sutured into the supra-annular position. To address the regurgitation, the area surrounding the valve was sewn to the wall of the left atrium. Postoperative assessments indicated an absence of perivalvular leak and demonstrated improved cardiac function. The patient was discharged on postoperative day 22. We describe a successful mitral mechanical valve replacement in a case of extensive circumferential mitral annular calcification. Even with severe calcification extending into the left ventricular myocardium, we were able to minimize the decalcification process. This approach enabled the performance of mitral mechanical valve replacement in a high-risk patient on dialysis, thus expanding the possibilities for cardiac surgery.

7.
Ann Vasc Dis ; 17(2): 175-178, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38919327

ABSTRACT

Ruptured abdominal aortic aneurysms and common iliac artery aneurysms (CIAAs) are rarely associated with an arteriovenous fistula (AVF). In such cases, surgery is frequently extremely difficult and the prognosis is usually poor. We report a case of a ruptured CIAA with a common iliac AVF in a 58-year-old male patient who presented with symptoms of severe edema in his left lower extremity. We used an aneurysm wall patch to repair the fistula and successfully reconstruct the common iliac vein, and a bifurcated prosthetic graft for abdominal aortic and iliac artery replacement.

8.
Int Clin Psychopharmacol ; 38(2): 102-109, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36719338

ABSTRACT

Both the underutilization of clozapine and treatment resistance of patients to clozapine are serious problems worldwide. Identifying clinical markers predicting response to clozapine would help clinicians more effectively utilize clozapine treatment. The present study retrospectively assessed dopamine supersensitivity psychosis (DSP) in addition to other measures such as age at disease onset and delay of clozapine introduction for a total of 47 treatment-resistant schizophrenia (TRS) patients. The response to clozapine was judged with CGI-C at 1 and 2 years from clozapine introduction. Results revealed that the DSP group tended to have a longer delay between designation of TRS and introduction of clozapine and continued to have slightly more severe psychopathology after treatment with clozapine, showing only slight improvement. The logistic regression analysis showed that the age at disease onset was the only significant indicator, predicting responsiveness to clozapine: patients with an onset age <20 years had a significantly better response to clozapine than patients with an onset age ≥20 years. The present study suggests that DSP might be related to a longer delay in clozapine introduction and the persistence of refractory symptoms despite clozapine treatment, whereas early age of disease onset might be related to a better response to clozapine.


Subject(s)
Antipsychotic Agents , Clozapine , Psychotic Disorders , Schizophrenia , Humans , Young Adult , Adult , Clozapine/adverse effects , Schizophrenia/drug therapy , Schizophrenia/diagnosis , Dopamine , Antipsychotic Agents/adverse effects , Schizophrenia, Treatment-Resistant , Retrospective Studies , Psychotic Disorders/drug therapy
9.
J Psychopharmacol ; 37(10): 992-1002, 2023 10.
Article in English | MEDLINE | ID: mdl-37395368

ABSTRACT

BACKGROUND: Several studies have reported that a switch to the dopamine partial agonist (DPA) aripiprazole (ARP), especially when the switch is abrupt, is likely to fail and sometimes worsen psychosis in schizophrenia patients already under high-dose antipsychotic treatment. Such a switching failure is speculated to be related to be the dopamine supersensitivity state. The risks of switching to the DPA brexpiprazole (BREX) have not been reported. AIMS AND METHODS: We retrospectively analyzed the cases of 106 patients with schizophrenia to identify any factors related to the success or failure of switching to BREX. RESULTS: The comparison between the patients with dopamine supersensitivity psychosis (n = 44) and those without (n = 62) revealed no significant difference in the switching failure judged at the sixth week. A comparison of the patients with successful switching (n = 80) and those who failed (n = 26) revealed that patients with treatment-resistant schizophrenia (TRS) were significantly more likely to fail. A logistic regression analysis also revealed that patients with past failure of switching to ARP are likely to succeed in switching to BREX. The 2-year follow-up of the patients with successful switching to BREX suggested that the patients who were treated with BREX, even temporarily, experienced some improvement in their Global Assessment of Functioning and Clinical Global Impression-Severity scores. CONCLUSIONS: Overall, the results indicate that patients with schizophrenia can be switched more safely to BREX compared to ARP. However, the failure of switching to BREX could be higher in patients with TRS, and thus, starting BREX treatment in refractory patients warrants careful monitoring.


Subject(s)
Antipsychotic Agents , Psychotic Disorders , Schizophrenia , Humans , Schizophrenia/drug therapy , Schizophrenia/chemically induced , Dopamine/therapeutic use , Retrospective Studies , Psychotic Disorders/drug therapy , Antipsychotic Agents/adverse effects , Aripiprazole/adverse effects , Dopamine Agonists/adverse effects
10.
Sci Rep ; 13(1): 6188, 2023 04 15.
Article in English | MEDLINE | ID: mdl-37061623

ABSTRACT

This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Neoplasm Micrometastasis/pathology , Retrospective Studies , Neoplasm Staging , Sentinel Lymph Node Biopsy , Head and Neck Neoplasms/pathology , Lymph Node Excision , Lymph Nodes/pathology
11.
Front Psychiatry ; 14: 1334335, 2023.
Article in English | MEDLINE | ID: mdl-38476817

ABSTRACT

Background: Most genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who respond well to antipsychotic medication have a higher dopamine (DA) state in brain synaptic clefts whereas patients with TRS do not show enhanced DA synthesis/release pathways. Patients and methods: To examine the contribution (if any) of genetics to TRS, we conducted a genetic association analysis of DA-related genes in schizophrenia patients (TRS, n = 435; non-TRS, n = 539) and healthy controls (HC: n = 489). Results: The distributions of the genotypes of rs3756450 and the 40-bp variable number tandem repeat on SLC6A3 differed between the TRS and non-TRS groups. Regarding rs3756450, the TRS group showed a significantly higher ratio of the A allele, whereas the non-TRS group predominantly had the G allele. The analysis of the combination of COMT and SLC6A3 yielded a significantly higher ratio of the putative low-DA type (i.e., high COMT activity + high SLC6A3 activity) in the TRS group compared to the two other groups. Patients with the low-DA type accounted for the minority of the non-TRS group and exhibited milder psychopathology. Conclusion: The overall results suggest that (i) SLC6A3 could be involved in responsiveness to antipsychotic medication and (ii) genetic variants modulating brain DA levels may be related to the classification of TRS and non-TRS.

12.
J Psychopharmacol ; 36(4): 479-488, 2022 04.
Article in English | MEDLINE | ID: mdl-35475374

ABSTRACT

BACKGROUND: Although numerous studies reported some changes of cortical silent period (CSP), an indicator of gamma-aminobutyric acid (GABA) function in central nervous system, in schizophrenia patients, it has been unknown how the disease stage and antipsychotic medication affect CSP values. METHODS: The present study conducted a systematic review of previous literature comparing CSP between schizophrenia patients and healthy subjects, and then performed meta-analysis on the effects of (1) the disease stage and (2) antipsychotics on CSP. RESULTS: (1) In the comparison of the disease stage comprising a total of 17 reports, there was no significant difference in CSP between patients under drug-naïve first-episode psychoses and healthy controls, or between patients with antipsychotic medication and healthy controls. (2) In the comparison of the antipsychotic class, patients treated with clozapine were longer in CSP compared to healthy controls. Patients treated with olanzapine/quetiapine or with other type of antipsychotics were not different from healthy controls. Regarding other type of antipsychotics, the iteration analysis after leaving out one literature showed that patients were shorter in CSP than healthy controls. CONCLUSION: The results showed that clozapine seems to surely prolong CSP, indicating the enhancement of GABA transmission via GABAB receptors, suggesting the possible relationship between the CSP prolongation by clozapine and its high efficacy in psychopathology. The finding of shorter CSP in patients with other type of antipsychotics was distinct from clozapine/olanzapine/quetiapine, but was difficult to interpret since this group included a variety of transcranial magnetic stimulation (TMS) methodologies and patients' background.


Subject(s)
Antipsychotic Agents , Clozapine , Schizophrenia , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Clozapine/pharmacology , Clozapine/therapeutic use , Humans , Neural Inhibition , Olanzapine/pharmacology , Quetiapine Fumarate/therapeutic use , Receptors, GABA , Schizophrenia/drug therapy , gamma-Aminobutyric Acid/therapeutic use
13.
Psychiatr Genet ; 31(1): 29-31, 2021 02 01.
Article in English | MEDLINE | ID: mdl-32941384

ABSTRACT

Tardive dystonia is one of the most serious types of extrapyramidal symptoms that antipsychotics can cause. There is no established treatment to relieve this symptom, and its etiology is unclear. Recently, we identified very rare single-nucleotide polymorphisms (SNPs) on ZNF806 and SART3 by exome sequencing in three patients with profoundly severe tardive dystonia. Here, we conducted an association study (case, N = 16 vs. control, N = 96) on the rarest SNP selected from each gene. The results showed that rs2287546 on SART3 was not related to tardive dystonia and that rs4953961 on ZNF806 was a heterozygote in all the subjects, implying the absence of a rare SNP in this locus. We found three other genomic regions with high similarity to the relevant region on ZNF806 by BLAT searches. This strongly suggested a misalignment error in this region in our previous exome sequence. In conclusion, ZNF806 and SART3 are unlikely to be related to tardive dystonia.


Subject(s)
Antigens, Neoplasm/genetics , Genetic Association Studies , Polymorphism, Single Nucleotide , RNA-Binding Proteins/genetics , Tardive Dyskinesia/genetics , Adult , Diagnostic Errors , Female , Genetic Predisposition to Disease , Genotype , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Molecular Sequence Annotation , Tardive Dyskinesia/diagnosis , Exome Sequencing
14.
J Mol Neurosci ; 71(12): 2575-2582, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34125398

ABSTRACT

The projection from dopaminergic neurons to gamma-aminobutyric acid (GABA) interneurons in the prefrontal cortex is involved in the etiology of schizophrenia. The impact of interacting effects between dopamine signals and the expression of GABA on the clinical phenotypes of schizophrenia has not been studied. Since these interactions could be closely involved in prefrontal cortex functions, patients with specific alleles of these relevant molecules (which lead to lower or vulnerable genetic functions) may develop treatment-refractory symptoms. We conducted a genetic association study focusing on COMT and GAD1 genes for a treatment-resistant schizophrenia (TRS) group (n=171), a non-TRS group (n=592), and healthy controls (HC: n=447), and we examined allelic combinations specific to TRS. The results revealed that the percentage of subjects with Met allele of rs4680 on the COMT gene and C/C homozygote of rs3470934 on the GAD1 gene was significantly higher in the TRS group than the other two groups. There was no significant difference between the non-TRS group and HC groups. Considering the direction of functions of these single-nucleotide polymorphisms revealed by previous studies, we speculate that subjects with the Met/CC allelic combination could have a higher dopamine level and a lower expression of GABA in the prefrontal cortex. Our results suggest that an interaction between the dopaminergic signal and GABA signal intensities could differ between TRS patients and patients with other types of schizophrenia and healthy subjects.


Subject(s)
Catechol O-Methyltransferase/genetics , Glutamate Decarboxylase/genetics , Polymorphism, Single Nucleotide , Schizophrenia, Treatment-Resistant/genetics , Adult , Female , Humans , Male , Middle Aged
15.
Gen Thorac Cardiovasc Surg ; 69(1): 107-109, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32535818

ABSTRACT

A 73-year-old woman with a narrow aortic root had undergone aortic valve replacement with a 19-mm Mitroflow valve. Aortic annular enlargement with Manouguian's technique was performed, and the bioprosthesis had been implanted on the tilt in a supra-annular position. Four years after the implantation, echocardiography showed a significant de novo aortic regurgitation, which had not been detected 1 year earlier. In the reoperation, the left coronary leaflet of the bioprosthesis had attached and fused to the wall of the sinus of Valsalva, causing deformation of the valve leaflet and a commissural gap between the left and right coronary leaflets, which appeared to have caused the de novo aortic regurgitation. We assessed the cause of early valve deterioration by focusing on the morphology of the aortic root. Preoperative understanding of the aortic root morphology would help to avoid early valve dysfunction for aortic valve replacement with an externally mounted bioprosthesis.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Female , Heart Valve Prosthesis Implantation/adverse effects , Humans , Prosthesis Design , Prosthesis Failure , Reoperation
16.
Psychopharmacol Bull ; 51(2): 20-30, 2021 03 16.
Article in English | MEDLINE | ID: mdl-34092820

ABSTRACT

Objectives: Although clozapine exhibited high efficacy for treating the symptoms of patients with treatment-resistant schizophrenia (TRS), its precise action mechanisms have not been fully understood. Recently, accumulating evidence has suggested the presence of abnormalities in the gamma-aminobutyric acid (GABA) systems in patients with schizophrenia, and the potential effects of clozapine on GABA receptors have gained a great deal of attention. Experimental Designs: In the present study, the cortical silent period (CSP), an electrophysiological parameter of GABA function via GABAB receptors, was measured using with the transcranial magnetic stimulation in patients with schizophrenia and healthy control subjects. Then the CSP of patients treated with clozapine (N = 12) was compared with that of patients treated with other antipsychotics (N = 25) and with that of healthy controls (N = 27). Principal Observations: The CSP of the patients treated with clozapine was significantly longer compared to those of the other two groups. The CSP of patients treated with other antipsychotics was similar to that of healthy subjects. There was a positive correlation between CSP and global assessment of function (GAF) in patients with TRS. Conclusions: The present study indicated that CSP was prolonged in patients receiving clozapine, and suggested that clozapine enhances the transmission signal via GABAB receptors.


Subject(s)
Antipsychotic Agents , Clozapine , Schizophrenia, Treatment-Resistant/drug therapy , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Humans , Transcranial Magnetic Stimulation
17.
J Psychiatr Res ; 138: 219-227, 2021 06.
Article in English | MEDLINE | ID: mdl-33866050

ABSTRACT

Treatment-resistant schizophrenia (TRS) has a quite complex pathophysiology that includes not only severe positive symptoms but also other symptom domains. Much attention has been devoted to the overlapping psychological and biological profiles of schizophrenia and autistic spectrum disorder (ASD). We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on general cognitive and social cognitive impairment and oxytocin system dysfunction. Our analyses revealed that there was no difference in oxytocin concentration among the three groups. The TRS patients' oxytocin blood concentrations were positively correlated with their processing speed and theory-of-mind scores, whereas the RemSZ and ASD groups had no significant relation with any measures. Rs53576, a single nucleotide polymorphism on the oxytocin receptor gene, affected social cognition abilities in the schizophrenia group. Although the overall findings are preliminary, they indicate that oxytocin system dysfunction could be involved in the serious cognitive deficits in TRS patients. Further, these results suggest that patients with TRS might have early neurodevelopmental abnormalities based on their shared biological features with ASD patients.


Subject(s)
Autism Spectrum Disorder , Schizophrenia , Autism Spectrum Disorder/genetics , Humans , Oxytocin/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Oxytocin/genetics , Schizophrenia/drug therapy , Schizophrenia/genetics
18.
Asian J Psychiatr ; 62: 102745, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34216977

ABSTRACT

OBJECTIVES: Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction. METHODS: We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction. RESULTS: Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction. CONCLUSION: Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia.


Subject(s)
Antipsychotic Agents , Clozapine , Antipsychotic Agents/adverse effects , Case-Control Studies , Clozapine/adverse effects , Humans , Japan , Retrospective Studies , Risk Factors
19.
Psychiatr Genet ; 30(2): 57-59, 2020 04.
Article in English | MEDLINE | ID: mdl-31895084

ABSTRACT

Tardive dystonia is one of the most serious adverse events that can be caused by antipsychotic treatment, but few studies have examined the etiology of tardive dystonia, and no genetic study using a next-generation sequencing technique has been performed to date. We conducted exome sequencing in three subjects with severe tardive dystonia. We analyzed the results focusing on candidate genes of primary dystonia, for example, TOR1A, GCH1, TH, THAP1, and SGCE. There were no single-nucleotide polymorphisms of these dystonia genes that were commonly shared among our subjects. Instead, the results revealed the presence of rare mutations (minor allele frequency <0.01) on the ZNF806 and SART3 genes in all three patients. This is the first study to analyze whole-exonic regions of the genomes of patients with tardive dystonia. These results were only preliminary, but they suggest that subjects presenting with tardive dystonia induced by antipsychotic treatment can have a genetic predisposition to tardive dystonia.


Subject(s)
Antipsychotic Agents/adverse effects , Tardive Dyskinesia/etiology , Tardive Dyskinesia/genetics , Adult , Alleles , Antigens, Neoplasm/drug effects , Antigens, Neoplasm/genetics , DNA-Binding Proteins/drug effects , DNA-Binding Proteins/genetics , Exome/genetics , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Humans , Japan , Male , Middle Aged , Mutation/genetics , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide/genetics , RNA-Binding Proteins/drug effects , RNA-Binding Proteins/genetics , Tardive Dyskinesia/metabolism , Exome Sequencing/methods
20.
J Psychopharmacol ; 34(5): 540-547, 2020 05.
Article in English | MEDLINE | ID: mdl-31961236

ABSTRACT

BACKGROUND: Patients with first-episode psychosis respond well to initial antipsychotic treatment, but among patients experiencing a relapse of psychosis, the response rate falls to approximately 30%. The mechanism of this discrepancy has not been clarified, but the development of dopamine supersensitivity psychosis with the underlying up-regulation of post-synaptic dopamine D2 receptors could be involved in this lesser response. It is uncertain whether elevated dopamine synthesis and release occurs in patients with dopamine supersensitivity psychosis, in contrast to those with first-episode psychosis. PATIENTS AND METHODS: We examined a first-episode psychosis group (n=6) and a chronic schizophrenia group, i.e. patients experiencing relapse (n=23) including those who relapsed due to dopamine supersensitivity psychosis (n=18). Following the initiation of treatment, we measured the patients' blood concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol at two weeks and four weeks after the baseline measurements. RESULTS: The first-episode psychosis group tended to show decreased homovanillic acid, accompanied by an improvement of symptoms. The chronic schizophrenia group showed no alteration of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol over the treatment period. These results were the same in the dopamine supersensitivity psychosis patients alone. CONCLUSIONS: Our findings suggest that unlike first-episode psychosis, the release of dopamine from presynaptic neurons did not increase in relapse episodes in the patients with dopamine supersensitivity psychosis. This indirectly indicates that the development of supersensitivity of post-synapse dopamine D2 receptor is involved in relapse in dopamine supersensitivity psychosis patients.


Subject(s)
Antipsychotic Agents/administration & dosage , Dopamine/metabolism , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adult , Aged , Female , Homovanillic Acid/blood , Humans , Male , Methoxyhydroxyphenylglycol/blood , Middle Aged , Receptors, Dopamine D2/metabolism , Recurrence , Young Adult
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