Diagnostic performance of quantitative Ga-SPECT/CT for patients with lower-limb osteomyelitis.

BACKGROUND: Patients with lower-limb osteomyelitis (LLOM) may experience major adverse events, such as lower-leg amputations or death; therefore, early diagnosis and risk stratification are essential to improve outcomes. Ga-scintigraphy is commonly used for diagnosing inflammatory diseases. Although the diagnostic performance of planar and SPECT imaging for localized lesions is limited, SPECT/CT, which simultaneously acquires functional and anatomical definition, has resulted in significant improvements to diagnostic confidence. While quantitative Ga-SPECT/CT is an emerging approach to improve diagnoses, its diagnostic performance has not been sufficiently evaluated to date. Therefore, this study aimed to evaluate the diagnostic performance of Ga-SPECT/CT with quantitative analyses for patients with LLOM. METHODS: A total of 103 consecutive patients suspected of LLOM between April 2012 and October 2016 were analyzed. All patients underwent Ga-scintigraphy with SPECT/CT imaging. Findings were assessed visually, with higher than background accumulation considered positive, and quantitatively, using Ga-SPECT/CT images to calculate the lesion-to-background ratio (LBR), the maximum standardized uptake value (SUVmax), and total lesion uptake (TLU). Diagnoses were confirmed using pathological examinations and patient outcomes, and diagnostic performances of planar, SPECT, and SPECT/CT images were compared. To evaluate prognostic performance, all patients were observed for 5 years for occurrences of major adverse events (MAE), defined as recurrence of osteomyelitis, major leg amputation, or fatal event. Multivariate Cox regression was performed to evaluate outcome factors. RESULTS: The overall diagnoses indicated that 54 out of 103 patients had LLOM. LBR, SUVmax, and TLU were significantly higher in patients with LLOM (12.23 vs. 1.00, 4.85 vs. 1.34, and 68.77 vs. 8.63, respectively; p < 0.001). Sensitivity and specificity were 91% and 96% for SPECT/CT with LBR, 89% and 94% for SPECT/CT with SUVmax, and 91% and 92% for SPECT/CT with TLU, respectively. MAE occurred in 23 of 54 LLOM patients (43%). TLU was found to be an independent prognostic factor (p = 0.047). CONCLUSIONS: Ga-SPECT/CT using quantitative parameters, namely LBR and TLU, had better diagnostic and prognostic performances for patients with LLOM compared to conventional imaging. The results suggest that Ga-SPECT/CT is a good alternative for diagnosing LLOM in countries where FDG-PET/CT is not commonly available.

The effect of combination therapy with an L/N-Type Ca(2+) channel blocker, cilnidipine, and an angiotensin II receptor blocker on the blood pressure and heart rate in Japanese hypertensive patients: an observational study conducted in Japan.

Recently, the use of combination therapy with a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) has been rapidly increasing. Although this combination therapy is accepted as a standard treatment hypertension, there have been few large-scale, multicenter studies examining its safety and efficacy. The present study was designed to investigate the safety and efficacy of adding cilnidipine, a dual L/N-type CCB, to the regimen of patients whose blood pressure had been poorly controlled (systolic blood pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] >90 mmHg) by antihypertensive monotherapy with an ARB. The percentage achievement of the blood pressure goals recommended by the JSH 2000 guidelines was also assessed for at least 12 weeks of treatment. A total of 2,920 patients were enrolled in the study at 471 institutions in Japan from February 2003 to July 2004. The incidence of adverse reactions related to cilnidipine was as low as 2.5%. A significant reduction from the baseline was found both in SBP (from 164.1 +/- 15.3 to 139.2 +/- 15.3 mmHg, p<0.0001) and DBP (from 91.7 +/- 11.4 to 79.3 +/- 10.7 mmHg, p<0.0001). A total of 31.5% of the patients achieved the blood pressure goals recommended by the JSH 2000 guidelines. Moreover, the heart rate also significantly decreased in these patients, particularly in those with a higher baseline heart rate. Our results indicate that cilnidipine can be used in combination with an ARB to control blood pressure without any significant adverse effects, and also that cilnidipine successfully reduces elevated heart rate, which is a possible risk factor for cardiovascular events.

Study of nateglinide in Japan: long-term treatment of patients with type 2 diabetes.

Nateglinide is an oral antidiabetic medication that acts through rapid, short-term stimulation of insulin production. This study undertook to identify the nature of any adverse effects of nateglinide and to assess its clinical efficacy in long-term use in clinical practice. Patients (n=1014) were recruited from centers in Japan and were followed over a 15-month treatment period. Pretreatment and posttreatment values were obtained for fasting blood glucose, postprandial blood glucose, hemoglobin A1c (HbA1c), triglycerides, and total cholesterol. All adverse reactions were noted, along with standard laboratory blood variables. The efficacy value was rated as 78.76% by the treating physicians; this was indicated by a postprandial glucose decrease of 53.2 mg/dL (from 223.8+/-61.1 mg/dL to 170.6+/-40.7 mg/dL), a fasting glucose decrease of 9.3 mg/dL (from 155.1+/- 40.0 mg/dL to 145.4+/-35.1 mg/dL), and an HbA1c decrease of 0.68% (from 7.51+/- 1.36% to 6.83+/-1.09%). In patients previously treated with sulfonylurea, a decrease in HbA1c was not observed. Changes in HbA1c had no association with age, body mass index (BMI), duration of diabetes, or concomitant disease. No change in BMI was noted after 15 months of nateglinide treatment. Adverse reactions occurred at an incidence of 10.07% (100/993 cases), with hypoglycemic symptoms being the most prevalent (1.91%). Adverse reactions were sometimes associated with extant renal dysfunction, a condition about which the physician had to be aware. No problems such as increased incidences of adverse reactions or deterioration in severity were detected in this long-term study. This study showed the efficacy and safety of long-term treatment with nateglinide of patients with diabetes from various backgrounds.

Postmarketing surveillance study of nateglinide in Japan.

Nateglinide is an oral antidiabetic medication that acts through rapid, short-term stimulation of insulin production. This study was undertaken to identify the incidence and nature of adverse effects of nateglinide and to assess its efficacy in clinical practice. Patients (n = 3254) were recruited from 606 centers in Japan with a 12-week observation period. Pretreatment and posttreatment values were obtained for fasting blood glucose, postprandial blood glucose, hemoglobin A1c (HbA1c), triglycerides, cholesterol, and body mass index. All adverse events were reported, along with standard laboratory blood variables. The incidence of adverse events was 7.40%; hypoglycemia, including hypoglycemic symptoms, was reported as the most prevalent (1.62%). Adverse events were observed more frequently in patients with hepatic or renal dysfunction; no significant findings were noted in the remaining patient population. The efficacy rating determined by the treating physicians was 76.40%. HbA1c decreased by 0.81% from 7.70+/-1.53% to 6.89+/-1.22%, postprandial glucose decreased by 54.05 mg/dL from 228.91+/-73.69 mg/dL to 174.86+/-62.86 mg/dL, and fasting glucose decreased by 23.73 mg/dL from 164.15+/-51.42 mg/dL to 140.43+/-42.63 mg/dL. These effects were most marked in patients who were previously medication naïve or who had been diagnosed with diabetes for a short period. Mean body mass index decreased, and nateglinide was equally effective in obese patients. Nateglinide showed good therapeutic effect when used as the first choice in patients with a short duration of diabetes, and in those with no history of previous treatment. Moreover, nateglinide seemed to be useful for the treatment of elderly patients and obese patients.

Postmarketing study of nateglinide in Japan: treatment of medication-naïve patients with type 2 diabetes.

Nateglinide is an oral antidiabetic medication (OAD) that acts through rapid, short-term stimulation of insulin production. This study was conducted to identify the nature of any adverse effects associated with nateglinide and to evaluate its clinical efficacy in patients with type 2 diabetes, with particular attention to hypoglycemia. Patients with type 2 diabetes who were OAD naïve (n=547), whose fasting blood glucose levels were 150 mg/dL or lower, and who had start-ed to take nateglinide alone were recruited from 139 centers in Japan with a 12-week observation period. The incidence of adverse reactions was 7.62%. Hypoglycemia accompanied by hypoglycemic symptoms was the most prevalent adverse event (2.10%; 11/525). Nine of 11 episodes required no therapeutic intervention. Severe hypoglycemia was recognized in only 1 case of diabetes complicated by serious renal dysfunction, for which nateglinide has been contraindicated in Japan. No subject experienced symptoms of nocturnal or prolonged hypoglycemia. After 12 weeks of nateglinide treatment, decreases were noted in hemoglobin A1c (0.82%), postprandial glucose (reduced by 59.4 mg/dL to 158.0 mg/dL), and fasting glucose (reduced by 11.7 mg/dL to 122.4 mg/dL). Nateglinide, which demonstrates limited risk of hypoglycemia and effectively controls blood glucose level, is regarded as a useful drug for the treatment of patients with type 2 diabetes.

[Examination of susceptibility artifact in three-dimensional gadolinium-enhanced chest MR angiography].

Signal loss that is sometimes found in the subclavian artery during chest MR angiography is thought to be caused by the susceptibility effect of highly concentrated contrast medium. In our research project, we examined the conditions under which signal loss occurs. We made vessel phantoms (artery phantom, vein phantom) that contained different concentrations of Gd-DTPA water solutions, and placed them in a 0.5 mmol/l Gd-DTPA water solution. We examined signal loss when the vein phantom was parallel to the magnetic field and when it was perpendicular to the magnetic field. We found that there was no signal loss in the artery phantom when the vein phantom was parallel to the magnetic field. In contrast, signal loss occurred in the artery phantom when the vein phantom was perpendicular to the magnetic field. The higher the concentration in the vein phantom, the closer the distance to the vessel phantom, and the longer the echo time (TE), the greater was the signal loss. Thus, the cause of signal loss in the subclavian artery was found to be the perpendicular orientation of the subclavian vein (through which the highly concentrated contrast medium flows) to the magnetic field. With the MRI devices currently in use, perpendicular orientation of the subclavian vein to the magnetic field cannot be avoided. Furthermore, the subclavian vein and subclavian artery are anatomically in close proximity to one another. These factors cause the susceptibility artifact, which is thought to result in signal loss in the subclavian artery.

Chemical ligation of epoxide-containing fusicoccins and peptide fragments guided by 14-3-3 protein.

The template effect of 14-3-3 protein on the chemical ligation of fusicoccin derivatives containing an epoxide group and the pentapeptide QSYDC was investigated. HPLC analysis of the epoxide-opening reaction demonstrated that 14-3-3ζ protein improves the yield of the conjugate product compared to the protein-free control.