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Premedication is often used to reduce the stress associated with anesthesia-related procedures. However, in some cases, patients may not cooperate with medication delivery because of significant fear and anxiety. We report a case of an uncooperative patient with severe intellectual disabilities who was successfully premedicated with the unique technique of sublingual midazolam administration using a suction toothbrush. The 38-year-old male patient was planned to receive dental treatment under deep intravenous sedation (IVS), but he refused both intravenous cannulation and mask induction. Preanesthetic medication delivery using other routes was attempted but not accepted. As the patient tolerated toothbrushing, we used repeated practice with sublingual water administration through the toothbrush's suction hole to gradually desensitize the patient. Using that same method, sublingual midazolam was administered as a successful premedication to allow placement of a face mask for inhalational induction without distress and completion of the dental treatment under IVS. For patients who refuse other premedication routes, sublingual administration during toothbrushing with a suction toothbrush may provide a successful alternative., (© 2023 by the American Dental Society of Anesthesiology.)

The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation.

Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins.

Objective: To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity., Research Design and Methods: Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups., Results: Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09-55.6], P = 0.005; and OR 4.13 [95% CI 1.01-17.0], P = 0.049, respectively)., Conclusions: Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself.

Objective: Clinically, the ankle-brachial blood pressure index (ABI) and skin perfusion pressure (SPP) are used to screen for subclinical peripheral artery disease. However, the association between the SPP and mortality in hemodialysis patients has not been previously reported. We investigated these factors and compared the ABI and SPP in patients receiving hemodialysis., Methods: A total of 102 patients receiving maintenance hemodialysis were enrolled in this study. The ABI was determined using an ABI-form (Colin, Japan). The SPP was measured using a SensiLase(TM) PAD3000 (Kaneka, Osaka, Japan)., Results: The mean follow-up period was 3.2 ± 1.4 years. A multivariate Cox analysis identified a low ABI (p=0.019) and a low SPP (p=0.047) as being independent predictors of mortality. A receiver operating characteristic (ROC) analysis of the ABI revealed a cutoff point of 1.1 and an area under the curve (AUC) of 0.79, with a sensitivity of 90% and a specificity of 62%. A ROC analysis of the SPP revealed a cutoff point of 54.0 mmHg and an AUC of 0.71, with a sensitivity of 55% and a specificity of 84%., Conclusion: Both low ABI and SPP values were found to be independent risk factors for mortality among hemodialysis patients. The cutoff point for ABI as a predictor of mortality was 1.1, while that for SPP was 54.0 mmHg.

A 17-year-old girl with multiple areas of skin hemangiomas that had been present since birth was referred to our institution complaining of sudden onset of dyspnea. Enhanced CT demonstrated a pulmonary thromboembolism and transthoracic echocardiogram showed a thrombus-like echo in the right ventricle. CT further revealed thrombi in the inferior vena cava (IVC) and peripheral vein. The thrombi, especially those in the RV, were highly life-threatening; therefore, immediate thrombectomy was performed and an IVC filter was placed. Because no major complications occurred, the patient was discharged 34 days after admission. In such young women, carefully using anticoagulation therapy and planning pregnancy are recommended.

The heart failure guideline in Japan has stated the necessity of investigating the role of oral inotropic agents in patients with chronic heart failure (CHF), which are clinically available only in Japan. A total of 1,846 consecutive patients with heart failure (mean: 69.5 years old, 1,279 males) treated at our institute from November 2009 to August 2010 were investigated retrospectively. Thirty-one patients (1.84%) who had taken oral inotropic agents (pimobendan 27, docarpamine 6, and denopamine 4) were extracted for this study, and the efficacy and limitations of the treatments were analyzed. Following the oral inotropic treatment, the NYHA functional class (P = 0.017), cardiothoracic ratio (P = 0.002) and B-type natriuretic peptide levels (P = 0.011) were significantly improved, and the number of emergency room (ER) visits (P < 0.001) and hospitalizations (P < 0.001) were significantly reduced. The nonsurviving patients (n = 7/31, 22.6%) were significantly older (P = 0.02) and tended to have a larger cardiothoracic ratio (P = 0.084) compared with the survivors. An absence of concomitant beta-blocker therapy was significantly associated with a worse prognosis (oneyear mortality 2/21 versus 5/10, log rank, P = 0.011). Oral inotropic agents brought about improvements in the clinical parameters of CHF and a reduction in ER visits and hospitalizations. However, concomitant beta-blocker therapy should be considered for patients receiving oral inotropic treatment.

Background: The aim of this study is to determine the prevalence of minute myocardial damage (MMD) in already statin-treated dyslipidemic patients with a low high-density lipoprotein-cholesterol (HDL-C) level, and to evaluate whether pitavastatin could affect the lipid profiles and biomarkers reflecting myocardial stress and injury., Methods: Twenty patients (15 men; age 66 ± 8) being treated with any statin but who had HDL-C < 40 mg/dL, were switched to pitavastatin (2 mg/day) treatment. The patient lipid profiles and the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), and high-sensitive C-reactive protein (hs-CRP) were evaluated for six months., Results: At three months after the statin replacement, the HDL-C significantly increased from 37 ± 3 mg/dL to 40 ± 5 mg/dL (P < 0.05), and the low-density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio significantly reduced (100 ± 28 mg/dL to 86 ± 22 mg/dL, P < 0.05; 2.68 ± 0.67 to 2.17 ± 0.64, P < 0.05, respectively), and these changes were sustained for six months. In the whole study population, no significant changes were observed in the NT-proBNP, hsTnT, or hsCRP for six months. However, in 11 cases who showed a positive (> 0.003 ng/mL) hsTnT at baseline, a significant reduction in the hsTnT was observed (0.016 ± 0.020 ng/mL to 0.014 ± 0.020 ng/mL, P < 0.05), and its percent reduction significantly correlated with the percent increase in HDL-C (r = -0.68, P < 0.05)., Conclusions: MMD (positive hsTnT) was observed in more than half of patients with low HDL-C despite the administration of any statin, and the replacement of their previous statin with pitavastatin further improved their lipid profiles and led to better myocardial protection, possibly mediated via the elevation of the HDL-C level.

Background: Sleep disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease, although it is not clear whether SDB has any link to coronary atherosclerotic burden in patients with stable coronary artery disease (CAD). This study sought to analyze the links between SDB, coronary atherosclerotic burden, and cardiac biomarkers in stable CAD patients., Methods and Results: We studied 83 consecutive patients who underwent coronary angiography or scheduled percutaneous coronary intervention. SDB was evaluated by an ambulatory polysomnographic monitoring device. Coronary atherosclerotic burden was evaluated by the Gensini score, and myocardial stress/injury were assessed by measuring plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hs-TnT). Patients with an apnea hypopnea index (AHI)≧15 events/h (n=32) showed significantly higher Gensini score (35.7±38.0 vs 20.1±19.7, p=0.033) than those with AHI<15. The higher AHI group showed significantly higher NT-proBNP (275.8±402.6 pg/ml vs 131.9±146.3 pg/ml, p=0.047) and hs-TnT levels (0.011±0.005 ng/ml vs 0.008±0.003 ng/ml, p=0.015). Furthermore it was revealed that AHI significantly correlated with the Gensini score (r=0.253, p=0.036), NT-proBNP (r=0.266, p=0.027), and hs-TnT (r=0.274, p=0.023), and multiple stepwise linear regression analysis revealed that AHI (β=0.257, p=0.029) and history of smoking (β=0.244, p=0.038) were independently correlated with Gensini score among clinical and SDB-related parameters., Conclusions: Severity of SDB has a significant link to the severity of coronary atherosclerotic burden, which also reflected elevated NT-proBNP and hs-TnT as silent myocardial ischemia and minute myocardial injury even in stable CAD patients., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients., Methods: One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study., Results: Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH ., Conclusion: Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.

Frequently, focal segmental glomerulosclerosis (FSGS) recurs after renal transplantation, resulting in poor graft survival. Pathological mechanisms of the recurrence are still unknown, but both B and T cell disorders are suspected based on much evidence. This supports theoretical benefits using plasma exchange (PE) and lymphocytapheresis (LCAP). A renal transplant was performed for a 35-year-old woman, who suffered steroid-resistant FSGS and developed to chronic kidney disease stage 5D at 31 years old. We treated the patient with recurrent FSGS by LACP and examined whether peripheral neutrophils were dynamically changed after the therapy. Further, we performed flowcytometric analysis to examine lymphocyte fractions before and after LCAP. The decrease of helper (CD4 positive) and memory (CD4 and CD45RO positive) T cells was prominent after LCAP. Although B cells were at the nadir because of rituximab treatment, LCAP also decreased peripheral B cells. These suggest that LCAP has the potential to suppress the activities of recurrent FSGS after renal transplant.

Background: Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings., Methods and Results: Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P<0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0), the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm(2) versus 0.62±0.68 mm(2) and 16.6±5.4° versus 65.1±38.4°; P<0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who had cross sections with ESL., Conclusions: The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

Most published reports indicate that intensified hemodialysis results in better pregnancy outcomes. Here we studied clinical characteristics and the outcomes of 28 pregnant women receiving hemodialysis. We found an association between maternal blood data and birth weight, and gestational age and outcomes. There were 18 surviving infants who were followed up for one year. In the others there were 4 spontaneous abortions, 1 stillbirth, 3 neonatal deaths and 2 deaths after birth. Analysis of blood chemistry for 20 pregnancies from 12 weeks of gestation until delivery showed that the average hemoglobin level was significantly higher in the group that successfully delivered than in the unsuccessful group. There were significant negative relationships between the blood urea nitrogen (BUN) level and the birth weight or gestational age in the latter cohort. A birth weight equal to or greater than 1500 g or a gestational age equal to or exceeding 32 weeks corresponded to BUN levels of 48-49 mg/dl or less. Whether the low BUN is the direct cause of the improved outcome remains to be examined.

Background: Dialysis-related amyloidosis is one of the chronic the complications of haemodialysis. We conducted an investigation of dialysis-associated amyloidosis in extremely long-term survivors., Methods: Twenty-one patients on haemodialysis for more than 30 years ('30+' group) and 13 patients on haemodialysis for 20-30 years ('20-30' group) at Sangenjaya Hospital were enrolled in this study. The frequencies of operations for conditions related to haemodialysis-related amyloidosis were examined., Results: The mean age at the start of haemodialysis was younger in the '30+' group (29.1 +/- 7.3 years) than in the '20-30' group (40.5 +/- 8.2 years, P = 0.0003). Eighteen (85.7%) patients had undergone surgery for CTS, six (28.6%) had undergone surgery for trigger finger and six (28.6%) had undergone surgery for cervical destructive spondyloarthropathy (DSA) at 30 years after the start of haemodialysis therapy. Patients who were over the age of 30 years at the start of dialysis therapy more frequently underwent CTS operations (100%) than those who were under 30 years of age at the start of dialysis (76.9%; P = 0.025) in the '30+' group at 30 years after the start of haemodialysis. The frequencies of operations for CTS did not differ significantly between the '20-30' group and the '30+' group., Conclusions: Haemodialysis-associated amyloidosis was common in extremely long-term survivors. Even though the mean age at the start of haemodialysis was younger in the '30+' group than in the '20-30' group, the frequency of operations for CTS did not differ. This may be attributable to the recent advances in haemodialysis technologies.

Background: Retrospective studies of haemodialysis patients from large dialysis organizations in the United States have indicated that intravenous vitamin D may be associated with a survival benefit. However, patients prescribed vitamin D are generally healthier than those who are not, suggesting that treatment by indication may have biased previous findings. Additionally, no survival benefit associated with vitamin D has been shown in a recent meta-analysis in CKD patients. Because treatment-by-indication bias due to both measured and unmeasured confounders cannot be completely accounted for in standard regression or marginal structural models (MSMs), this study evaluates the association between vitamin D and mortality among participants in the Dialysis Outcomes and Practice Patterns Study (DOPPS) using standard regression and MSMs with an expanded set of covariates, as well as by instrumental variable models to minimize potential bias due to unmeasured confounders., Methods: Data from 38 066 DOPPS participants from 12 countries between 1996 and 2007 were analysed. Mortality risk was assessed using standard baseline and time-varying Cox regression models, adjusted for demographics and detailed comorbidities, and MSMs. In models similar to instrumental variable analysis, the facility percentage of patients prescribed vitamin D, adjusted for the patient case mix, was used to predict patient-level mortality., Results: Vitamin D prescription was significantly higher in the USA compared to other countries. On average, patients prescribed vitamin D had fewer comorbidities compared to those who were not. Vitamin D therapy was associated with lower mortality in adjusted time-varying standard regression models [relative ratio (RR) = 0.92 (95% confidence interval: 0.87-0.96)] and baseline MSMs [RR = 0.84 (0.78-0.98)] and time-varying MSMs [RR = 0.78 (0.73-0.84)]. No significant differences in mortality were observed in adjusted baseline standard regression models for patients with or without vitamin D prescription [RR = 0.98 (0.93-1.02)] or for patients in facility practices where vitamin D prescription was more frequent [RR for facilities in 75th versus 25th percentile of vitamin D prescription = 0.99 (0.94-1.04)]., Conclusions: Vitamin D was associated with a survival benefit in models prone to bias due to unmeasured confounding. In agreement with a meta-analysis of randomized controlled studies, no difference in mortality was observed in instrumental variable models that tend to be more independent of unmeasured confounding. These findings indicate that a randomized controlled trial of vitamin D and clinical outcomes in haemodialysis patients are needed and can be ethically conducted.

Background: Bone and mineral metabolism is abnormal in most chronic haemodialysis patients and is associated with a high mortality risk. Because of possible pathogenic links between anaemia and intact parathyroid hormone (iPTH), the present study evaluated associations of mineral metabolism indicators with haemoglobin (Hb)., Methods: Data were collected from 317 facilities (12 089 haemodialysis patients) in Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the United Kingdom and the United States by the Dialysis Outcomes and Practice Patterns Study (DOPPS). The major outcome studied was probability of haemodialysis patients having a target Hb, per guidelines, of >/=11 g/dl at baseline. Major predictor variables were patient characteristics and laboratory markers of mineral metabolism: albumin-corrected serum calcium (calcium(Alb)), serum phosphorus (PO(4)) and iPTH. Analyses were adjusted for demographics, 15 comorbidity classes, baseline laboratory values, body mass index, years on dialysis, erythropoietin dose, vitamin D and catheter use, cause of end-stage renal disease and country., Results: The adjusted odds ratio (AOR) of having Hb >/=11 g/dl was significantly higher (P<0.0001) in patients with higher calcium(Alb) (AOR = 1.32 per 1 mg/dl), higher PO(4) (AOR = 1.08 per 1 mg/dl) and lower iPTH (AOR = 0.96 per 100 pg/ml). Furthermore, 4 month intrapatient changes in Hb concentration were significantly (P<0.0001) related to 4 month changes in calcium(Alb) (0.17 g/dl Hb rise per 1 mg/dl higher calcium(Alb)) and PO(4) (0.11 g/dl Hb rise per 1 mg/dl higher PO(4)). Mean weekly recombinant human erythropoietin (rHuEpo) doses were higher for patients with high PO(4) or iPTH levels, but lower for patients with calcium(Alb) >9.5 mg/dl, after patient mix and Hb concentration adjustments., Conclusions: The results of this study indicate that higher serum calcium(Alb) and PO(4) levels are each independently associated with better anaemia control. This relationship is independent of vitamin D use, PTH levels and prescribed rHuEpo dose. Despite this benefit of better anaemia control at higher serum calcium(Alb) and PO(4) concentrations, lower calcium and PO(4) levels, as recommended by the K/DOQI guidelines, should still serve as the long-term goal for HD patients in order to minimize tissue calcification and mortality risk.

Objective: To investigate social images associated with dentistry in comparison with nine other medical disciplines., Design: A questionnaire survey among members of the general public. Subjects were asked to state, in not more than five words, the images which they associated with each of the ten disciplines., Setting: Komaki City, Shikatsu Town and Nagoya City in Japan., Participants: 261 respondents from a convenience sample of 300 residents, not associated with any branch of medicine., Outcome Measures: Frequency distribution of word images used on at least five occasions and a correspondence analysis of the responses for the ten disciplines., Results: Of the 163 coded image items, 60 were related to internal medicine, 56 to dentistry, 55 to dermatology, 51 to orthopaedic surgery, 51 to ophthalmology, 50 to surgery, 47 to obstetrics and gynaecology, 43 to otolaryngology, 40 to paediatrics and 33 to psychiatry. Correspondence analysis applied to the 163 items and 10 medical disciplines indicated that three similar paired image groups were found, namely between dermatology and ophthalmology, surgery and orthopaedic surgery, and between dentistry and internal medicine, which were the more commonly encountered disciplines across all age groups. However, compared with the other specialities, dentistry had a significantly greater association with pain, this response being four times more common than for surgery., Conclusions: This group of members of the public in Japan perceived dentistry-associated images in a similar way to internal medicine, but the negative associations with pain need to be addressed by the dental profession and health educators alike.