High body mass index and triglyceride levels at health checkups increase the risk of new-onset chronic kidney disease and worsening renal function: the TAMA MED Project-CKD.

BACKGROUND: Health checkups are important in patients with chronic kidney disease (CKD), which is not easily accompanied by subjective symptoms. CKD can be caused or aggravated by factors that have not yet been identified. METHODS: This retrospective cohort study included 7 483 patients who underwent specific annual health checkups at a medical institution in Tama City, did not have CKD in 2012, and continued to undergo checkups (aged 40-74 years). We examined the risk factors for new-onset CKD and 1.5-fold increase in serum creatinine levels among laboratory values from 2012 to 2020. RESULTS: Age, body mass index (BMI), triglyceride levels, atrial fibrillation, and medication for hypertension (HT) and diabetes mellitus were independent risk factors for proteinuria, whereas current smoking, BMI, systolic blood pressure (SBP), and medication for HT were independent risk factors for estimated glomerular filtration rate < 60 mL/min/1.73 m2. SBP, triglyceride levels and medication for HT were risk factors for a 1.5-fold increase in serum creatinine levels during course of the study. The cut-off values of BMI for eGFR < 60 mL/min/1.73 m2 were 22.2 (men 24.7, women 22.1) kg/m2 and fasting triglyceride levels for a 1.5-fold increase in serum creatinine level were 171 (men 247, women 170) mg/dL, respectively. CONCLUSIONS: Health checkups provide information to prevent new-onset CKD and worsening of renal function. It is necessary to increase the rate of health checkups and visits to medical institutions after health checkups as well as to use these results for health guidance.

Impact of COVID-19 pandemic on behavioral changes and glycemic control and a survey of telemedicine in patients with diabetes: A multicenter retrospective observational study.

AIMS/INTRODUCTION: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. MATERIALS AND METHODS: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. RESULTS: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician-patient interaction and the impossibility of consultation and examination were cited as sources of concern. CONCLUSIONS: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.

Factors Influencing Sarcopenic Changes in YUBI-WAKKA Finger-Ring Test Results After One Year: A Retrospective Observational Study.

Background: The YUBI-WAKKA (finger-ring) test was developed and validated as a predictor of sarcopenia, physical disability, and even mortality. We focused on the sarcopenic status and subsequent changes after 1 year using this test and analyzed factors related to these changes. We also examined the robustness of this test by administering it alongside annual checkups held in local clinics. Methods: We conducted the study to investigate the data of the annual checkup of National Health Insurance at primary care clinics in 2017 and 2018 in Tama City. We studied the participants in a retrospective observational way. The participants of the YUBI-WAKKA test were a total of 5,405 and 4,391 residents between the ages of 65 and 74 years. We first compared anthropological biomarkers of two groups, those that had calves larger than their own finger-ring and those that had calves smaller than their own finger-ring. Then, we compared these results to those from the previous year's 1,048 pairs of data. We were particularly interested in changes from larger to smaller, which we defined here as a sarcopenic change, and performed multivariate logistic regression analysis with forced entry methods to determine the related factors. We also calculated the concordant rate of the test results after 1 year. Results: In total, 14% (men) and 16% (women) each year received a positive (sarcopenic) YUBI-WAKKA test result. The factors related to this sarcopenic change in 1 year were low uric acid in men and a low or decreasing body mass index and increased hemoglobin and alanine aminotransferase in women. The concordant rates of the larger, just fit and smaller groups following finger-ring testing were 72.8%, 63.5%, and 52.0%, respectively. Conclusions: We propose that low uric acid and low or reducing body weight were related to low muscle mass and that ALT and Hb may be indirectly related to sarcopenia. These could be predictive factors to determine sarcopenia-prone individuals. The YUBI-WAKKA (finger-ring) test results and their change were considered to be a sustainable and reasonable way to use in the community with small effort to find those who are at high risk for sarcopenia among the elderly population and who may require intervention.

Sarcopenia and coexistent risk factors detected using the 'Yubi-wakka' (finger-ring) test in adults aged over 65 years in the public annual health check-up in Tama City, Tokyo: a cross-sectional study.

OBJECTIVES: To examine the positive rate of sarcopenia using the 'Yubi-wakka' (finger-ring) test and associated risk factors among adults aged 65 years and older. DESIGN: Cross-sectional study. SETTING: We used the Yubi-wakka test, which has been developed and validated as a predictor of sarcopenia, frailty, disability and mortality. A positive test result is indicated by a smaller calf circumference than the finger-ring. The test was administered during annual health check-ups among residents of Tama City, Japan. PARTICIPANTS: During the 2019 fiscal year, 12 894 individuals aged 65 years and older underwent the Yubi-wakka test at primary care clinics. INTERVENTIONS: Examinees conducted the test themselves in a seated position. They formed a ring around their calf using both thumbs and index fingers and judged whether their calf was larger, the same or smaller than their finger-ring. PRIMARY AND SECONDARY OUTCOME MEASURES: We compared anthropometric and serological data between the positive (smaller calf) and negative (larger calf) test result groups. RESULTS: The positive rate was 15.4% among men and 18.5% among women. The prevalence of a positive result was higher in those aged ≥80 years than in younger age groups in both sexes (men: 22.8%; women: 28.8%). Multivariate logistic regression analysis showed that a diagnosis of metabolic syndrome was a risk factor for detecting a positive test result in women aged 65-74 years (OR 3.445; 95% CI 1.44 to 8.29) and ≥75 years (OR 3.37; 95% CI 1.97 to 5.78). CONCLUSIONS: Because the Japanese population is healthy and lives long, interventions against sarcopenia are important, especially for older adults aged >75 years. The presence of metabolic syndrome may be a risk factor for sarcopenia (as detected by the Yubi-wakka test) and future frailty, and requires closer attention, especially among women.

Anemia and atrial fibrillation as independent risk factors for new-onset chronic kidney disease: the TAMA-MED Project-CKD and AF.

BACKGROUND: Various risk factors have been identified for the new onset or rapid deterioration of chronic kidney disease (CKD). However, it is thought that many risk factors that have not yet been clarified remain. METHODS: Based on the results of specific annual health checkups at Tama City (n = 18 383) in 2017 and 2018, we analyzed the factors that cause new-onset CKD and the risk factors that rapidly worsen renal function. For new-onset CKD, proteinuria and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were examined separately. Rapid deterioration of renal function was defined as an eGFR ≥25% less than the previous year. RESULTS: Multivariate analysis showed that in addition to age and impaired glucose tolerance, anemia and atrial fibrillation (AF) were risk factors for the new appearance of proteinuria. Risk factors for a decrease in eGFR to <60 mL/min/1.73 m2 were age and hyperuricemia. Age, systolic hypertension, urinary protein and urinary occult blood, high triglycerides and anemia were significant risk factors for the rapid deterioration of renal function in patients with CKD Stage ≥3. CONCLUSIONS: From the results of specific annual health checkups at Tama City, AF, anemia and hyperuricemia were identified as risk factors for new-onset CKD over a short period of 1 year. Anemia was also a factor for the rapid deterioration of kidney function in subjects with renal dysfunction.

Nondestructive Analysis of Mummification Balms in Ancient Egypt Based on EPR of Vanadyl and Organic Radical Markers of Bitumen.

The black matter employed in the funeral context by ancient Egyptians is a complex mixture of plant-based compounds with variable amounts of bitumen. Asphaltene, the most resistant component of bitumen, contains vanadyl porphyrins and carbonaceous radicals, which can be used as paramagnetic probes to investigate embalming materials without sample preparation. Electron paramagnetic resonance (EPR) at the X-band, combining in-phase and out-of-phase detection schemes, provides new information in a nondestructive way about the presence, the origin, and the evolution of bitumen in these complex materials. It is found that the relative EPR intensity of radicals and vanadyl porphyrins is sensitive to the origin of the bitumen. The presence of nonporphyrinic vanadyl complexes in historical samples is likely due to the complexation of VO2+ ions by carboxylic functions at the interface between bitumen and other biological components of the embalming matter. The absence of such oxygenated vanadyl complex in natural bitumen and in one case of historical human mummy acquired by a museum in the 19th century reveals a possible, nondocumented, ancient restoration of this mummy by pure bitumen. The linear correlation between in-phase and out-of-phase EPR intensities of radicals and vanadyl porphyrins in balms and in natural bitumen reveals a nanostructuration of radicals and vanadyl porphyrin complexes, which was not affected by the preparation of the balm. This points to the remarkable chemical stability of paramagnetic probes in historical bitumen in ancient Egypt.

Impact of Chronic Kidney Disease Classification on New-Onset Atrial Fibrillation in the General Population　- The TAMA MED Project-AF and CKD.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) are known risk factors for each other. In Tama City in Tokyo, 12-lead ECG and serum creatinine concentration have been included as essential examinations in specific health checkups to diagnose AF and CKD. In the present study, we investigated the impact of CKD classification on new-onset AF in the general population.Methods and Results:Among 13,478 subjects aged 40-74 years at entry (age, 65.6±7.8 years; men, 42.0%), renal impairment with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2and proteinuria were found in 15.5% and 4.6%, respectively. CKD severity in individual subjects was classified according to a heatmap of the Japanese Society of Nephrology as 81.3% in the green, 15.1% in the yellow, 2.5% in the orange, and 0.9% in the red. Of those without AF in 2012, it had developed in 115 up to 2017; thus, the new-onset AF incidence rate was 2.6/1,000 person-years. Hazard ratios and 95% confidence intervals for new-onset AF in each CKD classification were 1.50 (0.93-2.41, P=0.097) in the yellow, 2.53 (1.03-6.23, P=0.044) in the orange, and 4.65 (1.47-14.70, P=0.009) in the red compared with the green as a reference. CONCLUSIONS: CKD classification was significantly associated with new-onset AF in the general population. Thus, it would be useful for risk stratification of new-onset AF. Renal function evaluation is recommended in health checkups.

Medical and Dental Visits of Chronic Kidney Disease-Diagnosed Participants Analyzed From the Specific Health Checkups Results in Japan: TAMA MED Project-CKD.

BACKGROUND: Since 2012, Tama City has promoted the early detection of chronic kidney disease (CKD), through an initiative that measures serum creatinine as part of the specific health checkups. We examined preventive measures against CKD deterioration based on the outcomes of this initiative. METHODS: The complications, medication status, body mass index, smoking status and other determining factors were surveyed among CKD-diagnosed participants over 3 years between 2013 and 2015. Moreover, factors aggravating CKD were investigated via a survey of medical and dental visits based on health insurance claim data over the same period. RESULTS: There was an increased rate of comorbid hypertension with each increase in the CKD stage. Comorbidity rates of diabetes mellitus, dyslipidemia, obesity, and smoking increased until CKD stage G4, and then decreased from stage G5. A substantial number of participants with CKD stage G3b and above were not medicated despite comorbidities like hypertension, diabetes mellitus and dyslipidemia. While the rate of regular visits at medical institutions was seen to increase significantly in accordance with the worsening degree of CKD, there were also individuals who, despite having severe CKD, did not visit medical institutions specializing in internal medicine. The rate of dental visits decreased as the CKD stage increased, and further decreased as the diabetic control status worsened. CONCLUSIONS: CKD patients should become aware of the importance of the dental visit because only a limited number of patients with advanced CKD received dental care.

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT-5): 52-week results from a randomized, open-label, phase III clinical trial.

AIMS: To investigate the safety and tolerability of 5 and 10 mg dapagliflozin added to insulin therapy over 52 weeks in Japanese patients with inadequately controlled type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This randomized, open-label, parallel-group, multicentre phase III clinical trial was conducted from October 26, 2015 to June 15, 2017. The primary endpoint was the occurrence of adverse events such as hypoglycaemia and diabetic ketoacidosis. Secondary endpoints included changes in glycaemic parameters, total daily insulin dosage and body weight over time. The efficacy of dapagliflozin in patients stratified by body mass index (BMI) <25.0 and ≥25.0 kg/m2 was evaluated in a subgroup analysis. RESULTS: In total, 151 patients received 5 mg (n = 76) or 10 mg (n = 75) dapagliflozin once daily for 52 weeks. Adverse events were observed in 88.2% and 73.3% of patients in the 5 and 10 mg dapagliflozin groups, respectively. Severe hypoglycaemia was reported in 2.6% (n = 2) and 6.7% (n = 5) of patients, and diabetic ketoacidosis in 2.6% (n = 2) and 1.3% (n = 1) of patients in the 5 and 10 mg dapagliflozin groups, respectively. The adjusted mean (95% confidence interval) changes in glycated haemoglobin at week 52 were -0.33% (-0.50, -0.15) and -0.36% (-0.53, -0.18) in the 5 and 10 mg dapagliflozin groups, respectively. There were no differences in efficacy parameters when stratified by BMI. CONCLUSIONS: This study demonstrated the long-term safety and tolerability of dapagliflozin added to insulin therapy in Japanese patients with inadequately controlled T1DM.

"Yubi-wakka" (Finger-Ring) Test: A Tool to Detect Prefrailty in Elderly Populations, a Pilot Study.

BACKGROUND: Preventing frailty of elderly is an urgent issue in Japan. The "Yubi-wakka" (finger-ring) test was developed and validated as a predictor of sarcopenia, disability and even mortality. To clarify the prevalence of "frailty" defined by this test and the relationship between other indexes cross-sectionally and prospectively, we conducted this study. METHODS: Five thousand four hundred and five subjects who were 65 to 74 years old participated in this study. In a sitting position, the subjects surrounded their calf using their own finger-ring, and whether the calf was larger, just fit, or smaller than the finger-ring was determined. We analyzed these "Yubi-wakka" (finger-ring) test results and other clinical indexes. We used Student's t-tests and the Chi-squared tests to compare the data between the groups, and logistic regression tests to adjust for multiple variables. RESULTS: In total, 38.8% of the subjects' calves were judged as being "larger", 45.6% as "just fit" and 15.6% as "smaller", which was the positive test result. The positive rate differed among medical facilities without any known different characteristics. The comparison between the "larger" and "smaller" groups revealed that body weight, red blood cell count, serum lipids, uric acid and liver enzymes were significantly different between the groups. Metabolic syndrome was more common in the "larger" group. In multiple analysis, low body mass index was an independent risk factor in both sexes. Positive urinary glucose, higher aspartate aminotransferase, systolic blood pressure and low alanine transaminase were risk factors for positive test results for males. Smoking, high hemoglobin and old age were risk factors for positive test results in females. CONCLUSIONS: The test was simple and feasible enough for the primary care setting, without the requirement of any devices. However, the positive rate varied among the clinics. The subjects' age was limited to under 75 years, and the test possibly detected individuals without metabolic syndrome and fatty liver. We are also planning to increase the subjects' age range and collect data prospectively.

Clinical features and new diagnostic criteria for the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

AIM: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a common inflammatory disease that presents with periodic fever. We aimed to establish more specific diagnostic criteria for PFAPA based on the clinical characteristics of PFAPA patients in our directory. METHOD: The clinical, laboratory, genetic, and family history details of 257 Japanese PFAPA patients treated at our and other affiliated hospitals between April 2000 and April 2018 were analyzed along with quantitative measurements of the number of CD64 molecules on neutrophils, and the levels of serum inflammatory cytokines. The sensitivity and specificity of the criteria were calculated for several diseases. RESULTS: Because recurrent fevers were crucial findings, they were defined as the required criterion. Tonsillitis/pharyngitis with white moss were important accompanying signs. Other symptoms associated with febrile episodes were cervical lymphadenitis with tenderness, aphthous stomatitis, sore throat, vomiting, and headache but not cough. A total of 159 (62%) patients had a family history of recurrent fevers, indicating autosomal dominant inheritance. C-reactive protein levels were extremely elevated during febrile attacks but normal in attack-free periods. Serum immunoglobulin D levels were high in 72 of the 199 tested patients. Oral glucocorticoid and cimetidine were extremely effective in all and 51.6% of the patients, respectively. We defined the above as supportive criteria. These criteria were sensitive and specific enough to distinguish PFAPA from other recurrent fever diseases. Raised serum interferon-γ levels and remarkable CD64 expression on neutrophils during flare-ups were recognized, indicating they contributed to diagnosis. CONCLUSION: Our new criteria are useful for diagnosing PFAPA.

Prevalence and Incidence of Atrial Fibrillation in the General Population Based on National Health Insurance Special Health Checkups　- TAMA MED Project-AF.

BACKGROUND: Although National Health Insurance special health checkups have been useful for the diagnosis of metabolic syndrome, they are insufficient to identify atrial fibrillation (AF). In Tama City in Tokyo, 12-lead electrocardiogram has been included as an essential examination in special health checkups to diagnose AF since 2008. Methods and Results: In subjects aged 40-74 years at entry, prevalence of AF was 0.8% (men, 1.7%; women, 0.2%) in 2008 and 1.4% (men, 2.9%; women, 0.4%) in 2015. Of 10,430 subjects without AF in 2008 (mean age, 64.9±7.1 years; men, 40.4%), AF developed in 133 between 2008 and 2015. The incidence rate of new-onset AF was 2.5/1,000 person-years during an observation period of 52,707 person-years. On multivariate Cox regression analysis in subjects without a history of cardiac disease, hypertension (HR, 1.58; 95% CI: 1.01-2.47, P=0.045) and body mass index (BMI; /1-kg/m2increase; HR, 1.07; 95% CI: 1.00-1.12, P=0.049) were significant risk factors for new-onset AF in addition to age and male sex. CONCLUSIONS: Prevalence of AF increased between 2008 and 2015. Age, male sex, hypertension, and BMI were significant predictors for future incidence of AF in the general population without overt cardiac disease. Controlling hypertension and BMI may prevent new-onset AF in the general population.

Comparison of the analgesic efficacy of ultrasound-guided rectus sheath block and local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children.

BACKGROUND: Ultrasound-guided rectus sheath block and local anesthetic infiltration are the standard options to improve postoperative pain for children undergoing surgery with a midline incision. However, there is no study comparing the effect of ultrasound-guided rectus sheath block with local anesthetic infiltration for children undergoing laparoscopic surgery. AIMS: The aim of this trial was to compare the onset of ultrasound-guided rectus sheath block with that of local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children. METHODS: We performed an observer-blinded, randomized, prospective trial. Enrolled patients were assigned to either an ultrasound-guided rectus sheath block group or a local anesthetic infiltration group. The ultrasound-guided rectus sheath block group (n = 17) received ultrasound-guided rectus sheath block with 0.2 ml·kg-1 of 0.375% ropivacaine per side in the posterior rectus sheath compartment. The local anesthetic infiltration group (n = 17) received local anesthetic infiltration with 0.2 ml·kg-1 of 0.75% ropivacaine. The Face, Legs, Activity, Cry, and Consolability (FLACC) pain scores were recorded at 0, 30, 60 min after arrival at the postanesthesia care unit. RESULTS: Of the 37 patients enrolled in this study, 34 completed the study protocol. A significant difference in the pain scale between the ultrasound-guided rectus sheath block group and local anesthetic infiltration group was found at 0 min (median: 0, interquartile range [IQR]: 0-1.5, vs median: 1, IQR 0-5, confidence interval of median [95% CI]: 0-3, P = 0.048), but no significant difference was found at 30 min (median: 1, IQR: 0-4 vs median: 6, IQR: 0-7, 95% CI: 0-5, P = 0.061), or 60 min (median: 0, IQR: 0-2 vs median: 1, IQR: 0-3, 95% CI: -1 to 1, P = 0.310). No significant difference was found in anesthesia time between the ultrasound-guided rectus sheath block and local anesthetic infiltration groups. No procedure-related complications were observed in either group. CONCLUSION: Ultrasound-guided rectus sheath block is a quicker way to control postoperative pain for pediatric patients undergoing laparoscopic extraperitoneal closure than local anesthetic infiltration, and thus may provide a clinical benefit.

[Pilot Study of "Japanese Model of Asheville Project"～How Did It Work?].

For prevention of the aggravation of diabetic nephropathy, a treatment method that combines self-care with medical guidance is becoming increasingly important, leading to the development of programs for lifestyle modification for the patients. To assess the effectiveness of such programs, we have conducted a feasibility study of a patient self-care support program with medical collaboration by registered pharmacists in community pharmacies involving patients with diabetic nephropathy who are under treatment at medical institutions, including our hospital. This study evaluated the two primary measurements, which are A) the actual execution rate versus planned programs, and B) the patient satisfaction rate. In addition, the achievement rate of behavioral objectives, satisfaction rate of diabetes treatment, degree of concerns (Diabetes Treatment Satisfaction Questionnaire; DTSQ, Problem Areas in Diabetes; PAID) and other physiological indicators have been evaluated. With the approval of the IRB at Kitasato University, sixteen out of 18 patients have continued to participate in the support program, and the study has shown high patient satisfaction with pharmacist coaching support. Patients have gained interest in managing their lifestyles, thereby increasing self-efficacy. Also, information shared between the pharmacists and the physicians has clarified patients' issues and concerns pertaining to their lifestyles, which were effectively utilized in the coaching program. Through meetings with pharmacists, patients have been reassured of the expertise of the pharmacist and thus gained mutual trust, which leads to the patient's behavioral change. We believe that the collaboration of patients, pharmacists and physicians has resulted in effective team-based patient care.

Statistical parametric mapping for effects of verapamil on olfactory connections of rat brain in vivo using manganese-enhanced MR imaging.

PURPOSE: We investigated the effect of verapamil on the transport of manganese in the olfactory connections of rat brains in vivo using statistical parametric mapping and manganese-enhanced magnetic resonance (MR) imaging. METHODS: We divided 12 7-week-old male Sprague-Dawley rats into 2 groups of six and injected 10 µL of saline into the right nasal cavities of the first group and 10 µL of verapamil (2.5 mg/mL) into the other group. Twenty minutes after the initial injection, we injected 10 µL of MnCl(2) (1 mol/L) into the right nasal cavities of both groups. We obtained serial T(1)-weighted MR images before administering the verapamil or saline and at 0.5, one, 24, 48, and 72 hours and 7 days after administering the MnCl(2), spatially normalized the MR images on the rat brain atlas, and analyzed the data using voxel-based statistical comparison. RESULTS: Statistical parametric maps demonstrated the transport of manganese. Manganese ions created significant enhancement (t-score = 36.6) 24 hours after MnCl(2) administration in the group administered saline but not at the same time point in the group receiving verapamil. The extent of significantly enhanced regions peaked at 72 hours in both groups and both sides of the brain. The peak of extent in the right side brain in the group injected with saline was 70.2 mm(3) and in the group with verapamil, 92.4 mm(3). The extents in the left side were 64.0 mm(3) for the group with saline and 53.2 mm(3) for the group with verapamil. CONCLUSION: We applied statistical parametric mapping using manganese-enhanced MR imaging to demonstrate in vivo the transport of manganese in the olfactory connections of rat brains with and without verapamil and found that verapamil did affect this transport.

Inflammatory imaging with ultrasmall superparamagnetic iron oxide.

The purpose of this study was to investigate the usefulness and feasibility of magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) (USPIO-enhanced MRI) for imaging inflammatory tissues. First, we investigated the relationship between the apparent transverse relaxation rate (R2*) and the concentration of USPIO by phantom studies and measured the apparent transverse relaxivity (r2*) of USPIO. Second, we performed animal experiments using a total of 30 mice. The mice were divided into five groups [A (n=6), B (n=6), C (n=6), sham control (n=6), and control (n=6)]. The mice in Groups A, B, C and control were subcutaneously injected with 0.1 ml of turpentine oil on Day 0, while those in the sham control group were subcutaneously injected with 0.1 ml of saline. The mice in Groups A, B, C and sham control were intraperitoneally injected with 200 µmol Fe per kilogram body weight of USPIO (28 nm in diameter) immediately after the first MRI study on Days 3, 5, 7 and 7, respectively, and those in the control group were not injected with USPIO. The second and third MRI studies were performed at 24 and 48 h after USPIO administration, respectively. The maps of R2* were generated from the apparent transverse relaxation time (T2*)-weighted images with six different echo times. The phantom studies showed that there was a linear relationship between R2* and the concentration of USPIO (r=0.99) and the r2* value of USPIO was 105.7 mM(-1) s(-1). There was a significant increase of R2* in inflammatory tissues in Group C at 24 h after USPIO administration compared with the precontrast R2* value. Our results suggest that USPIO-enhanced MRI combined with R2* measurement is useful for detecting inflammatory tissues.

A cross-sectional survey of chronic kidney disease and diabetic kidney disease in Japanese type 2 diabetic patients at four urban diabetes clinics.

OBJECTIVE: Management of chronic kidney disease (CKD) is a critical issue in public health in attempt to prevent kidney failure and dialysis dependency. Since 1998, diabetes mellitus has been the leading cause of dialysis dependency in Japan. Previous reports demonstrated that the prevalence of CKD in diabetic patients was high; however albuminuria was not always present. This cross-sectional survey was performed 1) to indicate the prevalence of CKD and co-morbid illness in diabetic patients seen at diabetic clinics, and 2) to demonstrate the relationship between estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). PATIENTS AND METHODS: A total of 288 consecutive adult type 2 diabetic patients seen at four diabetic clinics in the Tokyo Metropolitan Area were enrolled in November 2007. We excluded patients with kidney failure. Estimated GFR was calculated by the MDRD Study equation with the Japanese coefficient. RESULTS: Patients had a mean age (+/- SD), 61 (+/- 12); male, 58%; mean BMI, 25.2 kg/m(2) (+/- 5.2); and mean HbA(1c), 7.1% (+/- 1.3). The prevalence of CKD stage 3 was 38% (109/288) with 64% (70/109) of them being normoalbuminuric. Co-morbid illnesses, including hypertension (p<0.001) and old stroke (p=0.02), were significantly higher in CKD stage 3 patients. CONCLUSION: Our patients were relatively young and obese, reflecting urban clinical settings. The prevalence of CKD stage 3 patients was high. Clinicians need to check both eGFR and ACR to avoid underdiagnosis of CKD and diabetic kidney disease.

Correlation between salivary alpha-amylase activity and pain scale in patients with chronic pain.

BACKGROUND AND OBJECTIVES: The visual analog scale (VAS) is commonly used to assess pain intensity. However, the VAS is of limited value if patients fail to reliably report. Objective assessments are therefore clearly preferable. Previous reports suggest that elevated salivary alpha-amylase may reflect increased physical stress. There is a close association between salivary alpha-amylase and plasma norepinephrine under stressful physical conditions. In this study, we have determined the usefulness of a portable salivary alpha-amylase analyzer as an objective biomarker of stress. METHODS: Thirty patients (male/female = 15/15, age: 60.5 +/- 15.3 years) with chronic low back or leg pain (pain (+) group) and 20 pain-free control patients undergoing elective surgery under general anesthesia with epidural analgesia (pain (-) group) were recruited. Patients received epidural block with 5 to 10 mL 1% lidocaine. VAS, blood pressure, and heart rates were assessed before and 30 and 45 minutes after the epidural block. Salivary alpha-amylase was simultaneously measured using a portable analyzer. The relationship between the VAS and salivary alpha-amylase in chronic pain patients was assessed. RESULTS: After the epidural block both heart rate and systolic blood pressure decreased by approximately 8%. In the pain (+) group, the epidural block markedly decreased the VAS pain scale and salivary alpha-amylase from 56 +/- 22 to 19 +/- 16 mm (P < .01) and from 82 +/- 48 to 45 +/- 28 U/mL (P < .01), respectively, with a significant correlation between the 2 measures (r = 0.561, P < .01). In contrast, salivary alpha-amylase did not change significantly in the pain (-) group. CONCLUSIONS: Because there was a significant correlation between VAS pain scale and salivary alpha-amylase, we suggest that this biomarker may be a good index for the objective assessment of pain intensity. In addition, a simple to use portable analyzer may be useful for such assessment.