Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease and Diabetes.

There is a scarcity of data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and diabetes. The Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention study multivessel cohort was a prospective, multicenter, single-arm trial enrolling 1,021 patients who underwent multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared the clinical outcomes between those patients with and without diabetes. The primary end point was a composite of death, myocardial infarction, stroke, or any coronary revascularization. There were 560 patients (54.8%) with diabetes and 461 patients (45.2%) without diabetes. The mean age was not different between the 2 groups (70.9 ± 9.7 vs 71.7 ± 10.4 years, p = 0.17). Patients with diabetes more often had chronic kidney disease and complex coronary artery disease, as indicated by the greater total number of stents and longer total stent length. The rate of meeting the OPTIVUS criteria was not different between the 2 groups (61.2% vs 60.7%, p = 0.83). The cumulative 1-year incidence of the primary end point was not different between the 2 groups (10.8% vs 9.8%, log-rank p = 0.65). After adjusting for confounders, the risk of diabetes relative to nondiabetes remained insignificant for the primary end point (hazard ratio 0.97, 95% confidence interval 0.65 to 1.44, p = 0.88). In conclusion, in patients who underwent multivessel IVUS-guided PCI and were managed with contemporary clinical practice, patients with diabetes had similar 1-year outcomes to patients without diabetes.

Cryoglobulinemic Vasculitis Associated with Monoclonal Gammopathy of Undetermined Significance Developed after Sustained Virologic Response of Hepatitis C.

A 72-year-old woman had a history of chronic hepatitis C virus (HCV) infection previously treated with interferon to achieve a sustained virologic response. Thereafter, she developed polyarthritis and purpura of the lower extremities as well as progressive renal dysfunction with hypertension and proteinuria that had occurred in the last three months. Laboratory investigations revealed seropositivity for cryoglobulin but negative findings for HCV RNA. She was ultimately diagnosed with cryoglobulinemic glomerulonephritis complicated by monoclonal gammopathy of undetermined significance (MGUS) based on the pathological findings of the kidney and bone marrow, indicating that MGUS-induced cryoglobulinemic vasculitis may occur even after HCV elimination.

Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial.

PURPOSE: We aimed to assess onabotulinumtoxinA treatment outcomes by sex in patients with overactive bladder (OAB) and then explore the impact of serum prostate-specific antigen (PSA) levels in men. METHODS: Patients inadequately managed with OAB medications were randomized to receive single-dose onabotulinumtoxinA (100 U) or placebo intravesical injection in a phase III trial in Japan. We performed subgroup analyses by sex and post-hoc subgroup analyses using male PSA categories. RESULTS: In women (n = 186), onabotulinumtoxinA demonstrated statistically significant and clinically relevant improvements in all urinary symptoms at Week 12. In men with lower PSA (< 1.5 ng/mL, n = 40), onabotulinumtoxinA also showed numerically greater reductions in urinary symptom frequency than placebo; the between-group differences (onabotulinumtoxinA minus placebo) in change from baseline in the average daily number at Week 12 for urinary incontinence (UI), urgency UI, micturition, urgency, and nocturia were - 1.43, - 1.79, - 2.81, - 2.45, and - 0.32 episodes, respectively. In men with higher PSA (≥ 1.5 ng/mL, n = 22), onabotulinumtoxinA did not reduce urinary symptom frequency. Some patients treated with onabotulinumtoxinA showed elevated post-void residual urine volume at Week 2 (≥ 200 mL): 4 of 91 women, none of the men with lower PSA and 3 of 11 men with higher PSA. CONCLUSIONS: OnabotulinumtoxinA was efficacious and well tolerated in women and in men with lower PSA levels. Given our post-hoc subgroup analyses which suggested that onabotulinumtoxinA treatment is a good treatment option for OAB males with lower PSA levels, future studies having prostate volume data with larger sample size are warranted to verify our findings. CLINICALTRIALS. GOV IDENTIFIER: NCT02820844 (first posted July 1, 2016). https://clinicaltrials.gov/ct2/show/NCT02820844 .

Inspiratory/expiratory xenon-enhanced area-detector CT: Capability for quantitative assessment of lung ventilation changes in surgically treated non-small cell lung cancer patients.

PURPOSE: To evaluate the capability of inspiratory/expiratory Xe-enhanced ADCT for assessment of changes in pulmonary function and regional ventilation of surgically treated NSCLC patients. METHOD AND MATERIALS: Forty consecutive surgically treated NSCLC patients underwent pre- and postoperative inspiratory/expiratory Xe-enhanced ADCT and pulmonary function tests. For each patient, pre- and post-operative data were analyzed and pre- and post-operative wash-in (WI) and wash-out (WO) indexes and ventilation ratio (VR=[WI-WO]/WI) maps generated by means of pixel-by-pixel analyses. Differences between pre- and postoperative WI (ΔWI), WO (ΔWO) and VR (ΔVR) were also determined. To determine the relationship between all ventilation index changes and pulmonary functional loss, Pearson's correlation was used to correlate each ventilation index change with the corresponding pulmonary functional parameter change. In addition, stepwise regression analysis was performed for all ventilation index changes and each corresponding pulmonary functional parameter change. RESULTS: FEV1/FVC% change showed fair or good and significant correlations with ΔWI (r = 0.39, p = 0.01) and ΔVR (r = 0.68, p = 0.001), %FEV1 change good or moderate and significant correlations with ΔWI (r = 0.56, p = 0.0001) and ΔVR (r = 0.76, p < 0.0001), and %VC change moderate yet significant correlation with ΔWI (r = 0.65, p < 0.0001) and ΔVR (r = 0.67, p < 0.0001). Stepwise regression analysis demonstrated that FEV1/FVC% change (r2 = 0.56, p < 0.0001) significantly affected two factors, ΔVR (p < 0.0001) and ΔWI (p = 0.006), as did %FEV1 change (r2 = 0.68, p < 0.0001) [ΔVR (p < 0.0001) and ΔWI (p = 0.0001)], and %VC change (r2 = 0.63, p < 0.0001) [ΔVR (p < 0.0001) and ΔWI (p = 0.0001)]. CONCLUSION: Inspiratory/expiratory Xe-enhanced ADCT has the potential to demonstrate that pre- and postoperative ventilation status of surgically treated NSCLC patients correlates with pulmonary function.

Adult-onset Still's disease complicated by autoimmune hepatitis: successful treatment with infliximab.

A 17-year-old woman was previously diagnosed with autoimmune hepatitis (AIH) by liver biopsy. Adult-onset Still's disease (AOSD) was subsequently diagnosed on the basis of high fever, arthralgia, erythema, leukocytosis (>80% granulocytes), cervical lymph node swelling, splenomegaly, and hyperferritinemia. Her symptoms and liver dysfunction improved with prednisolone of 60 mg daily and subsequently methotrexate was added. However her symptoms and liver dysfunction relapsed when prednisolone was tapered to 20 mg/day. Therefore infliximab was introduced additionally and her symptoms and liver dysfunction subsided. To our knowledge, this is the first reported case of AOSD with AIH diagnosed by liver biopsy.

A concomitant case of giant cell arteritis and microscopic polyangiitis with hemoperitoneum by rupture of the gastroepiploic artery.

Giant cell arteritis (GCA) mainly involves large-sized arteries, while microscopic polyangiitis (mPA), characterized by pauci-immune necrotizing vasculitis, mainly affects small-sized vessels. We report a very rare concomitant case of GCA diagnosed by temporal artery biopsy and mPA with a high titer of myeloperoxidase antineutrophil cytoplasmic antibody, exacerbation of interstitial pneumonia, and suspected rapidly progressive glomerulonephritis. The patient died by sudden rupture of the gastroepiploic artery (medium-sized vessel), which may have been triggered by GCA and/or mPA.

Churg-Strauss syndrome complicated by chronic periaortitis: a case report and review of the literature.

We present a case of Churg-Strauss syndrome complicated by chronic periaortitis. A 68-year-old man presented with wheezing, dyspnea, purpurae, and numbness of the extremities. Antineutrophil cytoplasmic antibodies were absent; however, eosinophilia, a pulmonary infiltrative shadow on chest X-ray, eosinophilic vasculitis on histologic examination of skin and kidney, and mononeuritis multiplex were detected. Churg-Strauss syndrome was diagnosed. Contrast-enhanced abdominal computed tomography revealed a periaortic soft tissue mass extending from the subphrenic abdominal aorta to the proximal area of the bilateral iliac arteries. This indicated chronic periaortitis, probably caused by vasculitic activities. Both disorders improved with steroid therapy.

Analysis of development of lesions in mice with serine palmitoyltransferase (SPT) deficiency -Sptlc2 conditional knockout mice-.

Serine palmitoyltransferase (SPT) is the enzyme which catalyzes the first step of the biosynthesis of sphingolipids. However, the precise roles of SPT in vivo are not well understood, since complete knockout (KO) of genes which compose SPT results in a fetal lethal phenotype. A conditional KO (cKO) mouse of SPT long chain base 2 (Sptlc2) was therefore developed, and the effects of Sptlc2 deficiency were examined. Single cell necrosis in the epithelia of the crypts of the small and large intestines was observed as early as 24 h after induction of knockout. At 48 h after induction, decreases in spleen and thymus weights and decreases in numbers of reticulocytes and lymphocytes were observed in cKO mice, and single cell necrosis in the intestine became prominent. At 72 h after induction, decreases in body weight, spleen and thymus weights, and numbers of reticulocytes and lymphocytes became obvious in cKO mice. Histologically, atrophy of gastrointestinal mucosa and lymphoid necrosis as well as depletion of lymphoid and hematopoietic tissues were observed. These findings suggest that SPT plays important roles in the maintenance of the gastrointestinal mucosa, especially in the proliferation of the mucosal epithelial cells, and that deficiency of Sptlc2 induces necrotic lesions in gastrointestinal cells followed by atrophic change of the tissue in short term.

Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion.

Triglyceride ingestion releases gut peptides from enteroendocrine cells located in the intestinal epithelia and provides feedback regulations of gastrointestinal function. The precise mechanisms sensing lipids in the intestinal wall, however, are not well characterized. In the current study, we investigated the release of gut peptides following oral triglyceride loading in mice deficient for monoacylglycerol acyltransferase 2 (MGAT2KO) and diacylglycerol acyltransferase 1 (DGAT1KO), enzymes that sequentially re-synthesize triglyceride to secrete as chylomicron at the small intestine. In wild-type (Wt) mice, oral triglyceride loading resulted in hypertriglycemia. In addition, plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were significantly increased 30 min after triglyceride loading, before decaying in 2h. In MGAT2KO and DGAT1KO mice, oral triglyceride loading did not result in hypertriglycemia and the increase in GIP was significantly suppressed in both KO mouse strains. In contrast, the increases in plasma GLP-1 and PYY in both KO mouse strains were comparable to Wt mice 30 min after triglyceride loading, however, they remained elevated in DGAT1KO mice even 2h after triglyceride loading. In parallel to the changes in GLP-1 and PYY, gastric emptying was delayed after oral triglyceride loading in MGAT2KO mice comparably to Wt type mice and was further delayed in DGAT1KO mice. STC-1 and GLUTag, GLP-1-producing intestinal endocrine L-cell lines, displayed a significant level of DGAT1 activity but not MGAT activity. These findings suggest that synthesis and/or secretion of triglyceride-rich lipoproteins play an important role in the release of GIP. Moreover, DGAT1 may directly regulate the release of GLP-1 and PYY in L-cells.

[Elderly-onset rheumatoid arthritis distinguished from polymyalgia rheumatica with malignancy].

The differential diagnosis between polymyalgia rheumatica and elderly-onset rheumatoid arthritis is difficult because these diseases share similar clinical findings, especially at onset. We report a case of elderly-onset rheumatoid arthritis that was distinguished from polymyalgia rheumatica with malignancy. A 77-year-old woman was admitted to our hospital because of pain and bilateral stiffness in her shoulders and her hips. Tests for rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Bone erosions and joint space narrowing were not detected radiographically, and polymyalgia rheumatica was suspected. Her arthralgia disappeared with a few days after treatment with prednisolone (10 mg per day) was started, and ESR and CRP were normalized. Computed tomographic scanning of the chest showed a nodular lesion in the right lower lobe, and biopsy revealed lung cancer. Positron-emission tomography with 18F-fluorodeoxyglucose (FDG) performed before lung surgery showed increased uptake of FDG in the bilateral shoulder joints and wrist joints. Enhanced MRI showed synovitis and bone erosions in the right acromioclavicular joint and bilateral carpal bones and also radiographically bone erosions were seen in the carpometacarpal joint of the right thumb. Therefore, a diagnosis of elderly-onset rheumatoid arthritis was made. In patients with polymyalgia rheumatica, the detection of rheumatoid synovitis should be routinely evaluated.

Characterization of cellular uptake and distribution of coenzyme Q10 and vitamin E in PC12 cells.

Coenzyme Q (CoQ) is a well-known electron transporter in the mitochondrial respiratory chain. Furthermore, ubiquinol (UQH(2))--a reduced form of ubiquinone (UQ)--has been shown to act as a radical-scavenging antioxidant. Some studies have reported the beneficial effect of CoQ addition to cultured cells; however, the cellular uptake and distribution of CoQ have not been elucidated. In the present study, we used rat pheochromocytoma PC12 cells to investigate and compare the cellular uptake and distribution of CoQ(10) and alpha-tocopherol (alphaT). UQ(10) or UQ(10)H(2) treatment resulted in an increase in the cellular content of both CoQ(10) in a time- and concentration-dependent manner. A subcellular fractionation study revealed that the added UQ(10) as well as UQ(10)H(2) mainly localized in the mitochondrial fraction, which is similar to the localization of endogenous CoQ but different from that of alphaT. The cellular distribution of alphaT directly corresponded to the lipid distribution, while the CoQ distribution did not show any relationship with the lipid distribution, particularly in the mitochondrial and microsomal fractions. These results indicate that the cellular distribution of CoQ is completely different from that of alphaT; moreover, a certain system which accumulates CoQ preferentially in mitochondria may be suggested.

[Development of automatic window level and width-setting system for abdominal CT scanning].

Window setting is a very important technique in CT examinations. However, most beginner technologists have difficulty in setting the optimal window. Now, thanks to technical progress, it is easy to obtain a great many CT images. On the other hand, it is impossible to provide the optimal window setting for all images. Therefore, our purpose is to offer optimal CT images for every patient by using the automatic window-level and width-setting system. As a result of this experiment, there was a considerable difference in window setting by an expert technologist and that by a beginner technologist. With our system, we were able always to obtain an optimal window setting, such as that set by an expert technologist, regardless of the CT experience of the radiological technologist. We think that this system will be effective in observing animated examinations even if film is no longer used in the future.

Influences of dosage regimen and co-administration of low-molecular weight proteins and basic peptides on renal accumulation of arbekacin in mice.

OBJECTIVES: The objectives of this study were to characterize renal accumulation of arbekacin, an aminoglycoside antibiotic for treatment of infections with methicillin-resistant Staphylococcus aureus, and to modulate renal uptake of arbekacin, leading to prevention of arbekacin-induced nephrotoxicity. METHODS: In vivo renal uptake studies were performed using mice. Renal concentrations of arbekacin after a bolus intravenous administration at various doses were analysed by HPLC. In addition, renal concentrations were investigated 24 h after an injection of arbekacin alone or in combination with low-molecular weight proteins and basic peptides. RESULTS: When administered by bolus injection at various doses, renal accumulation of arbekacin showed saturation kinetics with increasing dose. Renal concentration of arbekacin after a bolus administration remained constant from 4 to 24 h and subsequently decreased by a first-order process with a half-life of 42.7 h. The influences of three dosage regimens (a single injection of 4 mg/kg, two injections of 2 mg/kg and three injections of 1.33 mg/kg) were investigated. A single injection resulted in lower renal level of arbekacin than the multiple administrations. Co-administration of cytochrome c, lysozyme and N-WASP181-200 decreased renal accumulation of arbekacin in a dose-dependent manner. N-W(N1n), N-W(N1n,I2i,S3s) and N-W(N1n,K20k), in which the N- and/or C-terminal regions of N-WASP181-200 were substituted by one to three D-isomers, more potently decreased renal arbekacin accumulation than N-WASP181-200. CONCLUSIONS: These data may be useful for prevention of arbekacin-induced nephrotoxicity owing to reduction of renal accumulation of the aminoglycoside.

Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice.

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We determined whether supplementation with coenzyme Q10 (CoQ10) could decelerate aging in SAMP1 mice and its potential role in aging. Plasma concentrations of CoQ10 and CoQ9 decreased with age in SAMP1 but not in SAMR1 mice. Supplementation with reduced CoQ10 (CoQH2, 250 mg/kg/day) for one week increased plasma CoQ10 concentrations, with an accompanying decrease in plasma CoQ9 concentrations. In two series of experiments, lifelong supplementation with CoQH2 decreased the senescence grading scores from 10 to 14 months, 7 to 15 months, and at 17 months of age. The body weight of female mice increased from 2 to 10 months of age versus controls in the second series of experiments. Lifelong CoQH2 supplementation did not prolong or shorten the lifespan, nor did it alter the murine senile amyloid (AApoAII) deposition rate or cancer incidence. In the second series of experiments, urinary levels of 8-hydroxydeoxyguanosine did not change with age or long-term supplementation with CoQH2. Urinary levels of acrolein (ACR)-lysine adduct increased significantly with age in SAMP1 mice; however, CoQH2 had no effect. Thus, lifelong dietary supplementation with CoQH2 decreased the degree of senescence in middle-aged SAMP1 mice.

A case of cutaneous polyarteritis nodosa manifested by spiking high fever, arthralgia and macular eruption like adult-onset Still's disease.

A 24-year-old Japanese woman was admitted for investigation of recurrent spiking high fever associated with a macular eruption of the upper extremities associated with fever and polyarthralgia. These symptoms were self-limiting but recurrent and seemed to be consistent with a diagnosis of adult-onset Still's disease (AOSD). However, livedo reticularis was detected on the lower extremities, suggesting the presence of vasculitic disease rather than AOSD. Investigation did not reveal any evidence of visceral involvement. Skin biopsy of the affected lower extremity demonstrated a necrotizing vasculitis of small muscular artery and confirmed a diagnosis of cutaneous polyarteritis nodosa (PAN) rather than AOSD. Treatment with 30 mg of prednisolone daily improved the skin lesions and the recurrent spiking high fever and the arthralgia were resolved. PAN and AOSD are clinically similar, and discrimination may be sometimes difficult. The presence of livedo reticularis and the finding of a characteristic skin biopsy appearance may be diagnostically useful to distinguish PAN from AOSD. Indeed, the clinical features of cutaneous PAN may be more similar to AOSD than systemic PAN, and a skin biopsy may be necessary to distinguish cutaneous PAN from AOSD in some cases.

Intracellular signal-responsive artificial gene regulation for novel gene delivery.

We describe two types of artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) or caspase-3. These molecular systems use newly synthesized cationic polymers, PAK and PAC. The PAK polymer includes substrate oligopeptide for PKA, ARRASLG, as receptor of PKA signal, while the PAC polymer possesses oligopeptide that is comprised of a substrate sequence of caspase-3, DEVD, and a cationic oligolysine, KKKKKK. These polymers formed stable complexes with DNA to totally suppress the gene expression. However, PKA or caspase-3 signal disintegrates the PAK-DNA or the PAC-DNA complex, respectively. This liberates the DNA and activated the gene expression. These systems are the first concept of an intracellular signal-responsive gene-regulation system using artificial polymer. We expect that these systems can be applied to the novel highly cell specific gene delivery strategy that is involved in our previously proposed new drug delivery concept, the drug delivery system based on responses to cellular signals.

[A case of pulmonary infiltration with eosinophilia (PIE) syndrome induced by bucillamine treatment of rheumatoid arthritis].

Bucillamine is used mainly in treating rheumatoid arthritis (RA). We report a case of bucillamine-induced pulmonary infiltration with eosinophilia (PIE) syndrome in a 51-year-old woman. When RA was diagnosed, she was treated with bucillamine from December 2000. In April 2001, she was admitted to our hospital because of fever and skin eruptions. Chest radiography and CT revealed both diffuse ground-glass opacity and fine nodular shadows. Laboratory data showed a normal white cell count with eosinophilia. Bronchoalveolar lavage (BAL) studies showed that total cell counts and the proportion of eosinophils were increased, and that the CD4/CD8 ratio of the T-cell subsets was decreased to 0.93. The patch test to bucillamine was positive. After bucillamine was withdrawn, the fever and the abnormal chest shadows improved. We concluded from the patient's clinical course, laboratory data and BAL findings that this was a case of bucillamine-induced PIE syndrome. Since most cases of bucillamine-induced interstitial pneumonitis are lymphocytic alveolitis, we consider that PIE syndrome in such a case is a very rare condition. We concluded that bucillamine should be added to the list of drugs capable of producing PIE syndrome.