Diagnosis and treatment for obstructive sleep apnea: Fundamental and clinical knowledge in obstructive sleep apnea.

PURPOSE: This review article covers the diagnosis and treatment of obstructive sleep apnea (OSA) from a dental perspective. It addresses the issue of when and how to screen for and then, if indicated, refer the patient for a more comprehensive. STUDY SELECTION: Our focus in this article was on identifying current unanswered questions that relevant to OSA problems that dental scientists have to pursue and on providing valuable information on that problems, consequently the previous studies which investigated or reviewed the diagnosis and treatment of OSA were included. In addition, we included studies on jaw movements during sleep and on the use of a lateral cephalometric film related to the diagnosis and treatment of OSA. RESULTS: The role of portable sleep monitoring devices versus full laboratory polysomnography is discussed. This review also describes what is known about the efficacy of mandibular advancement devices and when and how they fit in to a treatment program for a patient with obstructive sleep apnea. Finally some basic research is presented on jaw movements during sleep and how a lateral cephalometric film can be used to assess the changes of the airway with body posture and head posture. CONCLUSION: This article provides the valuable suggestions for the clinical questions in the diagnosis and treatment of OSA.

Age-adjusted level of circulating elastin as a cardiovascular risk factor in medical check-up individuals.

AIMS: The level of circulating soluble elastin (CSE) is reported to increase proportionally with the degree of clinical atherosclerosis; however, its diagnostic use is limited because CSE also increases with age. We aimed to investigate whether alterations in CSE concentrations are implicated in potential cardiovascular dysfunctions (indicated by standard physiological parameters) in medical check-up individuals, taking age into consideration. METHODS: In a total of 531 individuals (age 20-89 years), CSE levels were correlated most significantly with age. The groups of male and female individuals were each further divided into two subgroups: those with higher and those with lower CSE levels than the reference values determined by polynomial regression. RESULTS: Male participants with lower CSE levels (n = 128) than the age-adjusted reference baseline levels showed higher serum glucose (P < 0.008), uric acid (P < 0.008) and triglyceride (P < 0.02) levels than those with higher CSE levels (n = 126). However, most of the parameters tested in female participants with lower CSE levels (n = 140) were statistically comparable to those with higher CSE levels (n = 137). The ratio of CSE level to the age-adjusted reference level was calculated in each of the male participants, and declines in the ratio were significantly correlated with increases of serum glucose, uric acid and triglyceride levels (P < 0.005, P < 0.02 and P < 0.006, respectively). CONCLUSION: The decrease in age-adjusted CSE levels is a potential indicator of eventual cardiovascular dysfunction in medical check-up individuals, as predicted by the risk factors dyslipidemia, hyperuricemia or diabetes.

Effects of implant surgery on blood pressure and heart rate during sedation with propofol and midazolam.

PURPOSE: Intravenous (IV) sedation is commonly used in dentistry. However, no report has yet been published regarding age, hypertension, and antihypertensive drugs during implant surgery and their relationship with changes in blood pressure (BP) and heart rate in implant surgery under IV sedation with propofol and midazolam. MATERIALS AND METHODS: Medical records of 252 patients who underwent implant surgery were retrospectively analyzed. Patients were classified into four groups according to their age (in years) and hypertension status: A=≤64, no hypertension; B=≥65, no hypertension; C=≤64, hypertension; or D=≥65, hypertension. Hypertensive patients were further characterized by their antihypertensive medications: E=calcium channel blockers (CCBs), F=angiotensin II receptor blockers (ARBs), G=CCBs+ARBs, or H=no medication. IV sedation was administered in two stages. After midazolam injection to prevent angialgia, propofol was infused at the rate of 4 mg/kg/h, followed by a dose reduction. Systolic and diastolic BP and heart rate were recorded before, during, and after surgery. RESULTS: Systolic BP increased significantly after patients were draped in groups A, C, and D, with group D showing the most pronounced increase. Sedatives decreased BP in all groups. Diastolic BP in group F decreased significantly compared to group H after induction and before infiltration of local anesthetic. After infiltration, systolic BP decreased more significantly in group G than in group H. Intraoperative hypotension was observed in 25% of patients. The incidence of intraoperative hypertension in group D was markedly higher than in group A (23% vs 4%). CONCLUSION: IV sedation using midazolam and propofol reduces hypertensive risks during implant surgery. Nevertheless, care must be taken, especially in older hypertensive patients and in hypertensive patients on ARBs or ARBs+CCBs.

The development and clinical application of novel connectors for oral appliance.

PURPOSE: Currently, over 40 different types of oral appliances (OA) are available to dentists to treat sleep disordered breathing. OA can be classified by mode of action or design. One of the major categories is tongue retaining device; the other is a mandibular advancement device (MAD). Each device, however, has its own particular drawbacks, the most common revolving around cost or inherent difficulties in the production process.In this present report, we will introduce a "movable" OA which does not disturb the physiologic function. This approach utilizes novel connectors that are both low in cost and involve a straightforward production procedure. METHODS: Our device is categorized as a MAD. The design of the appliance followed that of the cap clasp, and the undercut was set at 0.25 mm. The polyester sheet was pressed to casts via a pressure molding machine, and cut along the design line mentioned above. In our device, we converted a Co-Cr wire as a connector for the OA. From this we developed and applied 2 new connectors for the clinical setting that were low in cost and allowed for mandible movement. These are lingual-side and labial-side types. In this present study the rate of success was 75.5%; with a good response classified as an AHI with less than 5 events/h, or a 50% decrease in their pre-treatment AHI. The efficacy of our OA was equal to previous studies. CONCLUSION: In this present report, we could propose inexpensive novel connectors which do not disturb the physiologic function.

Acute effects of intravenous nicorandil on hemodynamics in patients hospitalized with acute decompensated heart failure.

BACKGROUND: Nicorandil injection, a potent vasodilator with K(ATP) channel opening action and nitrate-like action, has been used for treatment of unstable angina. In the present investigation, we examined the effect of intravenous nicorandil on hemodynamics in patients with acute decompensated heart failure (ADHF). METHODS: ADHF patients admitted to hospital with pulmonary artery wedge pressure (PAWP)≥18 mm Hg were enrolled. Patients received nicorandil by an intravenous bolus injection of 0.2mg/kg/5 min followed by continuous infusion at a rate of 0.05, 0.10, or 0.20mg/kg/h for 6h. RESULTS: Nicorandil administration caused a significant decrease in PAWP and increase in the cardiac index (CI) that began immediately after the injection and were maintained during the continuous infusion. After 6h, nicorandil administration at 0.2mg/kg/5 min followed by 0.20mg/kg/h resulted in a decrease in PAWP (26.5%, p<0.01), an increase in CI (15.8%, p<0.05), and a decrease in total peripheral resistance (13.8%, p<0.01) in a dose-dependent manner. Nicorandil decreased blood pressure significantly, without an excessive decrease or negative impact even in patients with lower systolic blood pressure. CONCLUSION: Intravenous administration of nicorandil, by bolus injection followed by continuous infusion, improves PAWP and CI in ADHF patients immediately and continuously as a potent vasodilator with combined preload and afterload reduction. These results demonstrate that nicorandil is a safe and effective new medication for the treatment of ADHF.

Acute decompensated heart failure syndromes (ATTEND) registry. A prospective observational multicenter cohort study: rationale, design, and preliminary data.

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

Investigation of trends and characteristics in patients with obstructive sleep apnea.

BACKGROUND: Oral appliance (OA) therapy for obstructive sleep apnea (OSA) has only been part of Japan's National Health care coverage plan since 2004. Subsequently, not enough time has passed to establish the medical trends and characteristics of OSA patients in Japanese Dental Hospitals. AIM: The aim of this study was to investigate the medical trends and the characteristics in patients with OSA who visited our clinic, and to compare our findings with previous studies. SETTING AND DESIGN: Epidemiological survey (retrospective study). MATERIALS AND METHODS: Two hundred and one patients were recruited at the Internal Medicine Division in the Tsurumi University Dental Hospital from February 2006 to December 2008, consecutively. Patients received a medical interview, and a detailed sleep analysis that included a polysomnography (PSG) to verify the exact nature of their condition. The efficacy of OA was assessed in 49 patients who wore an OA and underwent PSG. RESULTS: Of all subjects, 141 patients visited the Prosthodontic Division to receive OA therapy, 38 patients were treated or received a follow up examination in the Internal Medicine Division. The dropout rate was 10.4% in the all subjects, 17.0% in patients who visited the Prosthodontic Division. The male-to-female ratio was 3.3:1, 3.0:1 in patients who visited the Prosthodontic Division. In addition, females had a lower rate of OAS severity than males. In our patients, the major complication was hypertension and cardiac disease. The success rate of OA was 75.5%. CONCLUSION: This approach allowed us to reveal some of the trends and characteristics in our patients.

Effects of carperitide on the long-term prognosis of patients with acute decompensated chronic heart failure: the PROTECT multicenter randomized controlled study.

BACKGROUND: Carperitide is used to treat acute decompensated heart failure (ADHF), but its effects on long-term prognosis have not been studied. METHODS AND RESULTS: A multicenter randomized controlled study of 49 patients with ADHF was performed to clarify the drug's effects on long-term prognosis. Low-dose carperitide (0.01-0.05 microg x kg(-1 ) x min(-1)) was infused for 72 h as the initial treatment (n=26), whereas in the control group (n=23), standard medical treatment other than carperitide was given without limitation. Anti-aldosterone drugs were prohibited in both groups. During carperitide infusion, significant increases of the atrial natriuretic peptide and cyclic GMP levels and a significant decrease in the heart-type fatty acid-binding protein/serum creatinine ratio were observed, suggesting inhibition of myocyte cell membrane damage. On the other hand, no significant differences in the plasma brain natriuretic peptide, troponin T, and creatinine levels were noted in either group. During 18-month follow-up, significant reductions of death and rehospitalization occurred in the carperitide vs control group (11.5% vs 34.8%; p=0.0359). Cox regression analysis revealed that randomization to carperitide (p=0.020), pretreatment systolic blood pressure >or=140 mmHg (p=0.043), and beta-blocker therapy (p=0.016) were independent predictors for freedom from cardiac events. CONCLUSIONS: Acute-phase low-dose carperitide infusion improved the long-term prognosis of patients with ADHF.

Dynamics and source of endothelin-1 and interleukin-6 following coronary reperfusion in patients with acute myocardial infarction.

OBJECTIVES: The goals of this study were to determine the source of circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) in acute myocardial infarction (MI) and to study the effects of coronary reperfusion (CR) on plasma levels of ET-1 and IL-6. METHODS: We serially measured plasma concentrations of ET-1 and IL-6 at different sampling sites before and after CR in patients with acute MI. A femoral vein (FV) catheter, a Swan-Ganz catheter, and a femoral artery (FA) catheter were placed in 25 patients with acute MI who were admitted within 12 hours after onset. For the measurement of ET-1 and IL-6 concentrations, blood samples from the FV, right atrium (RA), pulmonary artery (PA), and FA were collected before and 1 hour, 8 hours, and 24 hours after CR therapy. In 5 of the 25 patients, blood samples were collected through a coronary sinus (CS) catheter. We also assessed the gradient across 3 vascular beds (systemic, pulmonary, and coronary) as indices of the net release of ET-1 and IL-6 from those vascular beds. The maximal serum creatine kinase (CK) levels were assessed as an index of myocardial necrosis. RESULTS: ET-1 levels were higher in the FV than in the RA, PA, or FA. On CR, ET-1 levels peaked after 1 hour and returned to baseline by 24 hours. Calculated net release of ET-1 from the systemic vascular bed (ET-1 at FV-ET-1 at FA) was the highest among the 3 vascular beds. Plasma ET-1 levels correlated with hemodynamic parameters. Plasma IL-6 levels were similar among different sampling sites, whereas calculated net release of IL-6 from the coronary vascular bed was the highest among the 3 vascular beds. IL-6 levels increased throughout 24 hours after coronary reperfusion and closely correlated with maximal CK levels. CONCLUSIONS: The present study suggests that, in acute MI, the major source of ET-1 maintaining baseline plasma levels is the systemic vascular bed and that the ET-1 levels presumably reflect the congestion. ET-1 levels peaked 1 hour after CR. IL-6 increased for 24 hours after CR. The major source of IL-6 is the coronary vascular bed. Only a slight correlation was observed between plasma ET-1 and IL-6 levels.

Chronic direct stimulation of adenylyl cyclase induces cardiac desensitization to catecholamine and beta-adrenergic receptor downregulation in rabbits.

Chronic stimulation of beta-adrenergic receptors (betaARs) induces betaAR downregulation. However, it is not known whether continuous activation of adenylyl cyclase without direct stimulation of betaARs leads to receptor downregulation. This study investigated the effects of chronic stimulation of adenylyl cyclase with colforsin, on hemodynamic variables, and on myocardial betaAR density. In all, 55 rabbits received intravenous colforsin (1.6 microg/kg/min, n = 20), isoproterenol (ISO; 0.4 microg/kg/min, n = 16), or saline (n = 19) for two weeks. After chronic drug administration, responses of systolic (Delta% peak LV +dP/dt) and diastolic function (Delta% peak LV -dP/dt), and heart rate (Delta% heart rate), to acute administration of ISO (0.05 to 0.2 microg/kg/min) or colforsin (5 to 20 nmol/kg/min) were decreased compared to those before chronic administration. betaAR density in the colforsin group (69.8 +/- 13.8 fmol/ml protein) was less than that in the saline group (79.8 +/- 15.0 fmol/ml protein, P < 0.05), but was greater than that in the ISO group (56.3 +/- 8.4 fmol/ml protein, P < 0.05). Thus, chronic direct stimulation of adenylyl cyclase elicited systolic and diastolic functional desensitization to betaAR stimulation or adenylyl cyclase stimulation, and myocardial betaAR downregulation.

A case of massive left atrial lipoma occupying pericardial space.

We report a rare case of massive left atrial lipoma occupying pericardial space. A 52-year-old male was admitted because of cardiomegaly of unknown etiology. Computed tomography showed a large epicardial mass located along the anterior surface of the heart, from the diaphragm level through the aortic arch level. The mass showed an attenuation value identical with that of subcutaneous adipose tissue and contained some areas with high density. The mass was not enhanced by contrast media. Histologic examination of the specimen obtained by percutaneous biopsy demonstrated mature adipose tissue. An encapsulated adipose mass weighing 620 g, which originated from the left atrium without any invasion to the pericardium, was completely excised. Microscopic examination revealed mature adipose tissue with partial necrosis, confirming the diagnosis of lipoma.

Effects of the patent false lumen on the long-term outcome of type B acute aortic dissection.

OBJECTIVE: To determine the most effective treatment, we performed a detailed comparative study of the clinical course of patients with type B aortic dissection with a patent or thrombosed false lumen who did not undergo surgery in the acute period. We examined the effect of patency of the false lumen on outcome. METHODS: Computed tomography scans of 138 patients with type B acute aortic dissection were reviewed. Of 138 patients, 110 were medically treated and survived the acute period. We focused on the outcome of these 110 patients, 62 with medically treated thrombosed false lumen (thrombosed group) and 48 with medically treated patent false lumen (patent group). We investigated factors influencing outcome among the 110 patients. The follow-up period was up to 10 years after the onset of aortic dissection. The three study endpoints were death from any cause, dissection-related death (aortic rupture, perioperative death, or death due to organ ischemia), and a dissection-related event (aortic rupture or surgery). In the patent group, we investigated factors influencing long-term outcome. RESULTS: Patency of the false lumen was an independent risk factor for dissection-related death (P = 0.038, hazard ratio=5.6, confidence interval=1.1-28) and for a dissection-related event (P = 0.000, hazard ratio=7.6, confidence interval=2.7-22) but not for death from any cause (P = 0.769, hazard ratio=1.2, confidence interval=0.45-2.91). In the patent group, location of the most dilated aortic segment at the distal arch was an independent risk factor for dissection-related death (P = 0.026, hazard ratio=13.6, confidence interval=1.4-135) and for a dissection-related event (P = 0.048, hazard ratio=2.6, confidence interval=1.0-6.9). CONCLUSIONS: Patency of the false lumen is a strong independent prognostic factor for type B aortic dissection. Location of the most dilated aortic segment at the distal arch is a significant risk factor in the patients with a patent false lumen.

Internal medicine education in dentistry: knowledge required varies according to dental specialty.

BACKGROUND: With recent increases in the number of elderly and medically compromised patients, dentists are required to have a more comprehensive understanding of medical problems. There is, however, little awareness of the importance of internal medicine at dental schools in Japan. OBJECTIVE: The aims of the present study were to examine whether dentists need medical knowledge, to examine how often they experience difficulties regarding internal medicine in dental practice, and to determine whether their specialty or career influences their needs or difficulties. DESIGN: A questionnaire based on the above objectives was designed and was sent to all the faculty members in the department of dentistry at Tsurumi University and all dentists who work at the university hospital. RESULTS: Of 408 surveys, 307 (75%) responded. Ninety-nine per cent of respondents recognized the necessity of internal medicine. The dentists specializing in gerodontology, dental anesthesiology or oral and maxillofacial surgery (group S) felt the need of knowledge of internal medicine more frequently than those of other specialties (group O) (Odds ratio 17.5, 95% CI: 2.4 approximately 129.9; P = 0.000). Seventy-four per cent of the dentists experienced difficulties in day-to-day practice caused by a lack of medical knowledge. Those in group S, experienced difficulties more frequently than those in group O (Odds ratio 5.3, 95% CI: 2.1 approximately 12.9; P = 0.000). While the more experienced dentists in group S encountered difficulties more often, the more experienced dentists in group O encountered difficulties less often. CONCLUSIONS: The need for instruction in internal medicine varies according to dental specialty. Even very experienced dentists might fail to find solutions because of a lack of knowledge of internal medicine.

Limitation of infarct size and ventricular remodeling in patients with completely reperfused anterior acute myocardial infarction--the potential role of ischemia time.

BACKGROUND: Experimental studies suggest that coronary reperfusion does not result in appreciable myocardial salvage beyond 3 to 4 h. HYPOTHESIS: The present study was undertaken to examine the potential role of ischemia time as a determinant of infarct size and cardiac function in humans. METHODS: Ninety patients (69 men, 21 women, aged 61 +/- 1 years) presented within 24 h of onset of a first anterior infarct had ST-segment elevation on electrocardiogram. All patients underwent coronary intervention within 24 h of onset of symptoms and obtained complete reperfusion of the infarct-related artery. RESULTS: Infarct size expressed as a percentage of the area at risk (IS/RA) and left ventricular end-diastolic volume (LVEDV) were significantly (p < 0.017) smaller and left ventricula rejection fraction (LVEF) assessed by left ventriculography (35 +/- 4 days) was significantly higher in patients treated within 4 h after onset (IS/RA:55 +/- 4%, LVEDV: 127 +/- 7 ml, LVEF: 62 +/- 2%) than in those treated 4 to 12 h (97 +/- 2%, 140 +/- 13 ml, 52 +/- 3%) and 12 to 24 h (93 +/- 2%,163 +/- 14 ml, 49 +/- 5%) after symptom onset. Left ventricular end-diastolic volume was significantly smaller in patients treated 4 to 12 h after onset than in those treated 12 to 24 h after onset. CONCLUSIONS: Patients with < 4 h of myocardial ischemia exhibited significant myocardial salvage and better left ventricular function and patients with 4 to 12 h of myocardial ischemia exhibited significantly smaller LVEDV than those with more prolonged ischemia, although there was no difference in final infarct size.

[Potential role of leptin and insulin resistance assessed by the glucose clamp technique in coronary artery disease].

OBJECTIVES: Leptin may correlate with insulin resistance and be an important factor in patients with coronary artery disease. Therefore, we examined whether plasma leptin levels and insulin resistance are linked with coronary artery disease. METHODS: Plasma leptin levels and insulin resistance, assessed by the hyperinsulinemic euglycemic clamp technique, were measured in control subjects (n = 12, mean age 62 +/- 10 years), and in patients with obstructive coronary artery disease (n = 15, mean age 64 +/- 8 years) or vasospastic angina (n = 12, mean age 62 +/- 12 years). RESULTS: Plasma leptin levels were significantly higher (p < 0.017) in patients with obstructive coronary artery disease (8.4 +/- 2.7 ng/ml) and vasospastic angina (7.9 +/- 2.1 ng/ml) than in patients without obstructive coronary artery disease (4.7 +/- 1.4 ng/ml). Mean glucose infusion rate was significantly (p < 0.017) lower in patients with obstructive coronary artery disease (4.39 +/- 1.78 mg/kg/min) and vasospastic angina (3.57 +/- 1.72 mg/kg/min) than in patients without obstructive coronary artery disease (8.74 +/- 1.05 mg/kg/min). The plasma levels of leptin were negatively correlated with mean glucose infusion rate (r = -0.67, p < 0.01). The other coronary risk factors were similar in these three groups. CONCLUSIONS: Plasma leptin levels are correlated with insulin resistance and may be associated with coronary artery disease.

[Left ventricular peak systolic pressure/end-systolic volume ratio change after dobutamine infusion for predicting left ventricular contractile reserve: comparison with Emax].

OBJECTIVES: Genuine left ventricular contractile function is difficult to assess in the clinical setting. Left ventricular peak systolic pressure/end-systolic volume (Pps/Ves) ratio may be misleading because this index takes no account of the left ventricular end-systolic point and V0 intercept in the pressure-volume relation geographic curve. End-systolic pressure-volume relation and maximum chamber elastance derived from left ventricular pressure-volume loops can provide reliable estimates of contractile function. However, the feasibility of this technique for clinical purposes is limited, because it requires instantaneous measurement of left ventricular pressure and volume. This study assessed the feasibility of using Pps/Ves ratio for predicting the left ventricular contractile reserve by direct comparison with maximum elastance (Emax) derived from left ventricular pressure-volume loops. METHODS: Studies were undertaken in 18 consecutive patients aged 60 +/- 9 years who underwent cardiac catheterization. On-line instantaneous left ventricular volume was derived from the acoustic quantification method by transthoracic echocardiography. Pps was determined by pressure manometer tipped wire and Ves was measured automatically from acoustic quantification software in an ultrasound system. Pps/Ves was compared with Emax derived from each simultaneous pressure-volume loop during inferior vena caval occlusion before and after dobutamine infusion. Emax was determined as the slope of end-systolic points for each loop with the use of an automated iterative linear regression technique. Left ventricular contractile reserve was assessed by evaluating its functional response to 10 micrograms/kg/min of dobutamine infusion. RESULTS: Pps/Ves showed significant correlation with Emax in all patients (r = 0.70, p < 0.0001). However, scattered distribution of V0 value differences were noted. Contractile reserve (Pps/Ves) showed strong correlation with contractile reserve (Emax) despite V0 value differences (r = 0.927, p < 0.0001). CONCLUSIONS: Pps/Ves change after dobutamine infusion may minimize individual V0 distribution. This simple index could be used to evaluate left ventricular systolic performance without requiring the left ventricular pressure-volume relationship and volume unloading maneuver.