Olfactory dysfunction is often observed after severe traumatic brain injury (sTBI). Its diagnosis is difficult because patients with sTBI have a communication disability following impaired ...consciousness and communication disorder. The intravenous thiamine injection (IT) test is one of the representative diagnostic examinations to identify dysfunction, and it is often used in medical certification for liability insurance of automobiles in Japan because it could be judged by a simple reaction. However, the extent of usefulness of the IT test in the diagnosis of olfactory dysfunction in patients with sTBI is unknown. In this study, we validated the usability of the IT test and compared the results with those of the odor stick identification test for the Japanese (OSIT-J) to evaluate the sensitivity of the IT test in patients with sTBI.
The study enrolled 205 subjects, including 10 healthy volunteers and 195 patients with sTBI. First, we examined olfactory dysfunction in sTBI patients using OSIT-J. Subsequently, we performed the IT test among patients with olfactory dysfunction.
In the first part, 41 subjects, including 10 healthy volunteers, were examined by using the OSIT-J test. As a result, 28 patients were diagnosed with olfactory dysfunction (90.3%, p<0.0001), including anosmia and parosmia, compared with healthy volunteers. Among the 12 odors, garlic odor was easily recognized for patients with olfactory dysfunction. As a consequence of the IT test for 11 patients with olfactory dysfunction, four patients recognized thiamine odor, and seven patients did not. All four patients could recognize the garlic odor of OSIT-J, but 2 of the seven patients could recognize the garlic odor of OSIT-J, suggesting that the thiamine odor is linked to garlic odor (p=0.046), but not always. The detection rate of olfactory dysfunction through the IT test was 36.4%.
Our data showed that garlic odor, which is similar to thiamine odor, was easily recognizable for patients with sTBI. However, the IT test might overlook the diagnosis of olfactory dysfunction because it only identifies one odor. In addition, thiamine frequently induces angialgia. We should pay attention to the overconfidence of the IT test for patients with sTBI.
Background:Little is known about the pattern of isotope accumulation in the heart on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography in patients with cardiac sarcoidosis (CS) ...complicated by ventricular aneurysm (VA).Methods and Results:We prospectively enrolled 82 consecutive patients with CS; 54 patients with active CS (presence of abnormal 18F-FDG accumulation in the heart) were subdivided into VA (n=17) and non-VA groups (n=37). Strong 18F-FDG accumulation surrounding the VA and its disappearance in the VA center was observed in all patients with VA, probably because of scar formation at the VA. Peak standardized uptake value was higher around the VA than in the VA center (5.1±2.1 vs. 2.2±0.6, P=0.0003) and the VA center had no 18F-FDG accumulation (VA center: 2.2±0.6 vs. control area: 2.1±0.6, P=0.37). On the other hand, in non-VA patients with LV wall thinning (n=28), 18F-FDG accumulation was significantly high, even in the area of LV wall thinning (LV wall thinning area: 3.1±0.8 vs. control area: 2.0±0.6, P=0.00002).Conclusions:A pattern of strong 18F-FDG accumulation surrounding the VA and its disappearance in the VA center might be characteristic in patients with CS complicated by VA. Careful attention to FDG uptake would further elucidate CS pathophysiology and aid in the early treatment of VA.
RATIONALE:Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in a well-defined region of the cardiac type 2 ryanodine receptor (RyR)2. However, the ...underlying mechanism by which a single mutation in such a large molecule produces drastic effects on channel function remains unresolved.
OBJECTIVE:Using a knock-in (KI) mouse model with a human CPVT-associated RyR2 mutation (R2474S), we investigated the molecular mechanism by which CPVT is induced by a single point mutation within the RyR2.
METHODS AND RESULTS:The R2474S/+ KI mice showed no apparent structural or histological abnormalities in the heart, but they showed clear indications of other abnormalities. Bidirectional or polymorphic ventricular tachycardia was induced after exercise on a treadmill. The interaction between the N-terminal (amino acids 1 to 600) and central (amino acids 2000 to 2500) domains of the RyR2 (an intrinsic mechanism to close Ca channels) was weakened (domain unzipping). On protein kinase A–mediated phosphorylation of the RyR2, this domain unzipping further increased, resulting in a significant increase in the frequency of spontaneous Ca transients. cAMP-induced aberrant Ca release events (Ca sparks/waves) occurred at much lower sarcoplasmic reticulum Ca content as compared to the wild type. Addition of a domain-unzipping peptide, DPc10 (amino acids 2460 to 2495), to the wild type reproduced the aforementioned abnormalities that are characteristic of the R2474S/+ KI mice. Addition of DPc10 to the (cAMP-treated) KI cardiomyocytes produced no further effect.
CONCLUSIONS:A single point mutation within the RyR2 sensitizes the channel to agonists and reduces the threshold of luminal Ca for activation, primarily mediated by defective interdomain interaction within the RyR2.
Cabozantinib is a multikinase inhibitor that exerts anticancer activity against malignancies such as renal tumors and leukemia. Although other agents that belong to the same category can cause ...cardiotoxicity, there is a paucity of information on the safety profile of cabozantinib. Herein, we present the case of a 62-year-old woman who developed acute heart failure (HF) following the initiation of cabozantinib for a metastatic renal tumor. She had no history of cardiovascular disease. Echocardiography prior to chemotherapy revealed normal cardiac function. However, she developed sudden onset of dyspnea 23 days following cabozantinib initiation. The chest X-ray showed newly developed congestion and cardiomegaly, and echocardiography revealed severe impairment of systolic and diastolic function. She was referred to the intensive care unit for non-invasive positive pressure ventilation and infusion of inotropes. The cardiac function fairly recovered on day 46; thereafter, supportive therapy, followed by guideline-directed medical therapy for HF with reduced ejection fraction was provided. We describe the first case of severe acute HF following cabozantinib initiation without underlying heart disease. Clinicians should plan follow-up schedules and be cautious of the development of HF when they initiate the agent, even if patients appear to have a low cardiovascular disease risk.
•We report the first case of acute heart failure following cabozantinib initiation without an underlying heart disease.•Prompt discontinuation of the agent and supportive therapy with guideline-directed medications can allow adequate recovery of cardiac function, even if the severity of heart failure is high.•Careful follow-up following the initiation is warranted when clinicians plan to initiate cabozantinib, even if patients appear to have low risk of cardiovascular disease.
Novel antioxidants have been synthesized and characterized by their chemical properties as antioxidants with high superoxide scavenging activity. (2R,3R)-diphenylethylenediamine is a spacer in ...antioxidants, and we synthesized targets 11a and 11b by conjugation with o-hydroquinone and p-hydroquinone at the two N-termini, respectively. Superoxide scavenging activities of the plant flavonoid-like 11a and 11b were compared with those of known antioxidants, and shown to increase in the following order: curcumin << ascorbic acid < Trolox < (+)-epicatechin < 11a < quercetin ≤ 11b. Compound 11a also formed a solvated 11a-metal complex with metal ions. The 11a-Cu²⁺ complex was shown to have higher superoxide scavenging activity than that of 11a, 11b, Cu²⁺, and the 11a-Al³⁺ and 11a-La³⁺ complexes, whereas the 11a-Al3+ complex increased rather than decreased superoxide levels. The 11a-Al³⁺ complex did not abstract one electron from the SOMO of O₂⁻· since the HOMO and LUMO phases of Al³⁺ do not exist in the center of the 11a-Al³⁺ complex. However, the SOMO of the 11a-Cu²⁺ complex distributed in the center of Cu²⁺ may abstract one electron from the SOMO of O₂⁻·. These results suggest that 11a and 11b are powerful antioxidants.
•A phase i trial in Japan to investigate the safety of transcranial direct current stimulation after severe brain injury in chronic phase was performed.•No obvious adverse events were observed during ...this phase i trial with constant stimulation or variable stimulation.
Despite evidence regarding the benefits of transcranial direct current stimulation (tDCS) in patients with severe traumatic brain injury, few trials have examined the treatment safety. Therefore, we created a phase I trial in Japan to investigate the safety of tDCS after severe brain injury.
We verified the safety of tDCS through constant left frontal anodal stimulation at 2 mA for 20 min for 5 consecutive days. Additionally, we added a variable stimuli period to explore the effects of stimulus intensity, location, and duration. We adapted a traditional 3 + 3 study design. We assessed the rate of adverse effects, including skin burns and clinical seizure. Changes in neurological symptoms were evaluated using the Glasgow Coma Scale, Coma Recovery Scale-Revised, and 4 states of consciousness (coma, unresponsive wakefulness syndrome, minimally conscious state, and severe disability).
Six patients completed the study. No obvious adverse events were observed during the constant stimulation period or the variable stimulation period (right frontal anodal stimulation, stimulation frequency 2–4 mA, 1 or 5 times per week for a period of 4 weeks). Regarding the Coma Recovery Scale-Revised, patients in 4 out of 6 instances (66.7 %) improved by more than 1 point.
Our phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury. The next step is a phase II trial to investigate the preliminary efficacy and safety of tDCS at 2 mA (in comparison with sham stimulation).
Patients with good recovery after aneurysmal subarachnoid hemorrhage (SAH) are commonly discharged about one month after the event. However, these patients often still show cognitive symptoms, such ...as fatigue, difficulty concentrating, and irritability. Understanding the early cognitive outcome of patients with SAH with good recovery is thought to be crucial for neurosurgical nursing staff. We analyzed patient data to clarify whether cognitive outcome depends on the location of the ruptured aneurysm 1 month after SAH.
For 186 patients (72 men and 114 women; median age, 57 years; age range, 21–83 years) who had experienced SAH (Hunt & Kosnik grade I to III), we retrospectively analyzed data on the location of the ruptured aneurysm, Fisher grade at admission, treatment modality (coil embolization, clipping, or no surgical treatment), neuropsychological assessments 1 month after SAH, and modified Rankin Scale 6 months after SAH.
Crystallized intelligence (i.e., IQ, assessed using the Mini-Mental State Examination and Kohs Block Design Test) improved to almost normal levels in all patients, irrespective of the location of the ruptured aneurysm. In contrast, fluid intelligence (e.g., executive function and attention, assessed using the Frontal Assessment Battery; Trail Making Test, Part A; and the Japanese Kana-hiroi test) did not improve as much, specifically in patients with a ruptured aneurysm in the basilar artery.
These results may help nursing staff to identify mild- to moderate-grade patients at greater risk of problems and to arrange appropriate support strategies for patients after discharge.
Objectives: Renal scintigraphy is widely used to evaluate residual function of a transplanted kidney from the donor. Dynamic computed tomography (CT) imaging can evaluate both kidney morphology and ...regional renal function. The aim of this study was to develop an imaging protocol and a calculation method using dynamic CT for assessing the effective renal plasma flow (ERPF) by model analysis, and to evaluate the validity of the obtained ERPF values.Methods: Preoperative dynamic CT examination with a low radiation dose exposure system was performed for 25 renal transplant donors, and ERPF was calculated from the obtained images (CT-ERPF). To calculate CT-ERPF, we set the region of interest (ROI) in the renal cortex using automatic ROI-setting software developed in our laboratory. We compared the processing time with automatic and manual ROI settings. To evaluate the validity of CT-ERPF, we examined the correlation of age with CT-ERPF and compared with reported ERPF values. We also compared the uptake rates of technetium-99m-dimercaptosuccinic acid and CT-ERPF in terms of the right-to-left ratio.Results: There was good agreement of CT-ERPF assessed using automatic and manual ROIs. CT-ERPF was negatively correlated with age and showed values below the reference ERPF range in 21 cases. The right-to-left ratio of CT-ERPF showed a significant correlation with that of technetium-99m-dimercaptosuccinic acid.Conclusions: Using our method, CT-ERPF was a useful indicator for preoperative evaluation of donor’s renal function.
Cardiac hypertrophy is a well-known major risk factor for poor prognosis in patients with cardiovascular diseases. Dysregulation of intracellular Ca
is involved in the pathogenesis of cardiac ...hypertrophy. However, the precise mechanism underlying cardiac hypertrophy remains elusive. Here, we investigate whether pressure-overload induced hypertrophy can be induced by destabilization of cardiac ryanodine receptor (RyR2) through calmodulin (CaM) dissociation and subsequent Ca
leakage, and whether it can be genetically rescued by enhancing the binding affinity of CaM to RyR2. In the very initial phase of pressure-overload induced cardiac hypertrophy, when cardiac contractile function is preserved, reactive oxygen species (ROS)-mediated RyR2 destabilization already occurs in association with relaxation dysfunction. Further, stabilizing RyR2 by enhancing the binding affinity of CaM to RyR2 completely inhibits hypertrophic signaling and improves survival. Our study uncovers a critical missing link between RyR2 destabilization and cardiac hypertrophy.
Microscopic polyangiitis (MPA) affects various organs. However, echocardiographic findings of MPA are unclear. We aimed to evaluate the echocardiographic features of acute-phase MPA in Japanese ...patients.
This single-centre retrospective study included 15 patients with MPA who underwent echocardiography within 2 weeks of commencing steroid therapy for induction or reinduction. The echocardiography parameters of thetients were compared with those of 30 age- and sex-matched controls.
No significant differences in left ventricular (LV) diameter, LV ejection fraction, or e' were observed between the two groups. However, the MPA group showed a significantly higher left atrial (LA) diameter and LA volume index, as well as higher early diastolic filling velocity, diastolic pulmonary venous flow velocity, and trans-tricuspid pressure gradient, and a shorter deceleration time (DCT). Serum C-reactive protein levels were positively correlated with E wave, E/A, and DCT. These results may indicate that increased LV stiffness, rather than impairment of LV relaxation, contributed to LV diastolic function, resulting in LA enlargement.
Patients with acute-phase MPA had LA dilatation associated with LV diastolic dysfunction. This finding indicates the importance of cardiac assessment in patients with MPA, especially in patients with a strong inflammatory reaction.
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