Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Background: and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. Methods: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. Results: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. Conclusions Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

BACKGROUND: Small proportions of all the elderly stroke patients receive recombinant tissue plasminogen activator (r-tPA) therapy, although old age is not a proven contraindication to intravenous thrombolytic therapy for acute ischemic stroke. The purpose of this study was to identify reasons for exclusion from r-tPA therapy and factors associated with the decision of r-tPA use in elderly patients with acute ischemic stroke. METHODS: From the acute stroke registries of 22 domestic university hospitals taking the r-tPA therapy from January 2007 to May 2010, we extracted data of all acute ischemic stroke patients who were aged 80 or over and arrived within onset 3 hours. For all patients, we assessed the eligibility of r-tPA therapy using National Institute of Neurological Disorders and Stroke (NINDS) r-tPA trial criteria. For eligible patients, we compared all clinical variables between patients who were treated with r-tPA and those who were not, and analyzed potential factors related to the decision of r-tPA use. RESULTS: A total of 494 patients were included in this study. 255 patients (51.6%) were excluded by NINDS r-tPA trial criteria and the major reasons for exclusion were minor neurological deficit (53.7%) and clinical improvement (17.3%). Among 239 patients who were eligible for r-tPA, 162 (32.8%) patients received r-tPA and 77 (15.6%) did not. Multivariable analysis showed that younger age, shorter time-delay from onset to admission, non-smoker, no history of prior stroke, good pre-stroke functional status and severe initial neurological deficit were independently associated with the decision of r-tPA use in the elderly stroke patients predictors for r-tPA treatment. CONCLUSION: In very elderly patients, mild neurological deficit on arrival and rapid clinical improvement in neurological symptoms were the main reasons for exclusion from thrombolytic therapy.
Aged ; Hospitals, University ; Humans ; National Institute of Neurological Disorders and Stroke ; Registries ; Stroke ; Thrombolytic Therapy ; Tissue Plasminogen Activator

PURPOSE: The relationship between the biophysical and biochemical processes of gallbladder bile and nitric oxide is still not well known. In this study, the correlation between nitric oxide production and the degree of biliary tract inflammation was investigated and the levels of nitrate/nitrite (NOx) and stable metabolite of nitric oxide in the serum proposed for assessing the severity of biliary tract inflammation. METHODS: Eighty two patients with biliary tract inflammation who underwent operative treatment between March and July 2002 were included in this study. Of the 82 patients, there were 31 and 51 men and women, respectively. The mean age was 53, ranging from 21 to 82 years. The subjects were divided into three groups, GB stone (n=42), and acute cholecystitis (n=27), and cholangitis (n= 13). The severity of biliary tract inflammation was assessed using the WBC count, total bilirubin count, GB wall thickness on pathology, bile duct stone detected on ultrasonography, open conversion of cholecystectomy, pyrexia and tenderness/rebound tenderness on physical examination. The serum NOx concentrations were analyzed according to the groups, clinicopathological, laboratory and radiological findings. The serum NOx levels were measured using the Griess reaction after conversion of all nitrates to nitrites. RESULTS: The nitrate/nitrite levels in the GB, acute cholecystitis and cholangitis groups were 70.0+/-44.6, 126.8+/-54.5 and 142.0+/-44.6mumol/L, respectively, with statistical differences between the three groups (P< 0.05). The NOx level in patients with pyrexia, hyperbilirubinemia, leukocytosis, GB wall thickness on pathology and open conversion were markedly increased compared with the control group (P<0.05). These data demonstrate the relationship between the intensity of nitric oxide and the severity of biliary tract inflammation. CONCLUSION: Measurement of the NOx concentration in patients with biliary tract inflammation provides information about the severity and course of the disease. These results suggest there is a correlation between nitric oxide and the degree of biliary tract inflammation.
Bile ; Bile Ducts ; Biliary Tract* ; Bilirubin ; Biochemical Processes ; Cholangitis ; Cholecystectomy ; Cholecystitis ; Cholecystitis, Acute ; Female ; Fever ; Gallbladder ; Humans ; Hyperbilirubinemia ; Inflammation* ; Leukocytosis ; Male ; Nitrates ; Nitric Oxide ; Nitrites ; Pathology ; Physical Examination ; Ultrasonography

While ica gene of Staphylococcus epidermidis is known to undergo phase variation by insertion of IS256, the phenomenon in Staphylococcus aureus has not been evaluated. Six biofilm-positive strains were tested for the presence of biofilm-nega-tive phase-variant strains by Congo red agar test. For potential phase-variant strains, pulsed-field gel electrophoresis was done to exclude the possibility of contamination. To investigate the mechanism of the biofilm-negative phase variation, PCR for each ica genes were done. Changes of ica genes detected by PCR were confirmed by southern hybridization, and their nucleotides were analyzed by DNA sequencing. Influence of ica genes and biofilm formation on capacity for adherence to biomedical material was evaluated by comparing the ability of adhering to polyurethane sur-face among a biofilm-negative phase-variant strain and its parent strain. A biofilm-negative phase-variant S. aureus strain was detected from 6 strains tested. icaC gene of the phase-variant strain was found to be inactivated by insertion of additional gene segment, IS256. The biofilm-negative phase-variant strain showed lower adher-ing capacity to polyurethane than its parent strain. This study shows that phase variation of ica gene occurs in S. aureus by insertion of IS256 also, and this biofilm-neg-ative phase variation reduces adhering capacity of the bacteria.
Bacterial Adhesion/*physiology ; Biofilms/*growth & development ; Cell Adhesion Molecules/genetics/*metabolism ; Comparative Study ; Equipment Contamination/prevention & control ; Mutagenesis, Insertional/methods ; Mutagenesis, Site-Directed/genetics ; Phase Transition ; Polysaccharides, Bacterial/genetics/*metabolism ; *Polyurethanes ; Species Specificity ; Staphylococcus aureus/cytology/*physiology ; Structure-Activity Relationship

PURPOSE: Nitric oxide synthesized by neuronal nitric oxide synthase (nNOS) has been described as a mediator of smooth muscle relaxation in the mammalian gastrointestinal tract. Impaired expression of the nNOS gene is suggested in the development of infantile hypertrophic pyloric stenosis (IHPS). We examined the expression of nNOS mRNA in pyloric muscle biopsy specimens obtained from 8 patients with IHPS and attempted to correlate the results with the clinical characteristics. METHODS: The expression of nNOS mRNA in pyloric muscle biopsy specimens for 8 patients with IHPS was examined using a reverse transcription- polymerase chain reaction (RT-PCR) technique. For the control, a smooth muscle layer specimen of a neonate with a normal pylorus was used. RESULTS: In the control specimen, the level of nNOS mRNA expression was 48.4% of beta-actin mRNA. In the two thinnest (each 3 mm) of pyloric muscle thicknesses as determined by ultra-sonography, the expressed nNOS mRNA were 16.7% and 30.3%. The two thickest (each 8.3 mm) expressed as 35.3% and 22.9% nNOS. The two samples from the earliest age of symptomatic onset (1 day, 7 days after birth) expressed as 25.6% and 4.8%. The two from the latest age of onset (each 30 days) expressed as 7.4% and 10.5%. The control specimen revealed a higher level of nNOS mRNA expression than those of the IHPS specimens. There was no significant correlation between the clinical characteristics and the levels of nNOS mRNA in the IHPS specimens. CONCLUSION: Since a low level of nNOS mRNA expression may lead to impaired production of NO, our observations indicate that the hypertrophic pyloric muscle of an IHPS patient may be the result of a reduced expression of the nNOS gene at the mRNA level. In IHPS patients, there was no correlation between the clinical characteristics and the levels of expressed nNOS mRNA.
Actins ; Age of Onset ; Biopsy ; Gastrointestinal Tract ; Humans ; Infant, Newborn ; Muscle, Smooth ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase Type I* ; Polymerase Chain Reaction ; Pyloric Stenosis, Hypertrophic* ; Pylorus ; Relaxation ; RNA, Messenger*

BACKGROUND: Since the bioavailability of itraconazole capsule is influenced by patients gastric acidity, it results in treatment failure due to its low dissolution and subsequent low absorption when administered in fasting. Itraconazole Melt-Extrusion tablet has been lately developed in order to improve its dissolution profile. It is the first clinical study to evaluate the efficacy and safety of itraconazole Melt-Extrusion tablet in Korea. OBJECTIVE: This study was conducted to evaluate the efficacy and safety of itraconazole melt-extrusion tablet 400mg daily for 1 week(pulse therapy) for hyperkeratotic type of tinea pedis and manus. METHODS: A clinical and mycological investigation was made of 812 outpatients with hyperkeratotic type of tinea pedis and/or tinea manus who had visited at 52 general hospitals under the lead of the Korean Dermatological Association from June to December, 1998. Patients confirmed by clinically and microscopically as hyperkeratotic type of tinea pedis and/or tinea manus were administered 2 tablets twice a day for one week and followed up for 8 weeks from the start of the medication. RESULTS: The results were summarized as follows; 1. Clinical symptoms of hyperkeratotic type of tinea pedis and/or tinea mauns were significantly improved at the end of study, week 8(p<0.001). 2. Clinical response rate, defined as more than 50% decrease of the sum of the clinical symptom scores, was 79.3%(512/646). 3. Mycological cure rate, dafined as both culture and KOH negative at week 8, was 78.2%(244 /312). 4. 40(5.5%) patients, of the 727 patients evaluable for drug safety evaluation, were reported to have adverse event. CONCLUSION: Itraconazole Melt-Extrusion tablet 400mg/day for 1 week (pulse therapy) is effective and safe in the treatment of hyperkeratotic type of tinea pedis and/or tinea manus.
Absorption ; Biological Availability ; Fasting ; Gastric Acid ; Hospitals, General ; Humans ; Itraconazole* ; Korea ; Outpatients ; Tablets ; Tinea Pedis* ; Tinea* ; Treatment Failure

Previous studies implied association of osteoporosis with estrogen deficiency, immobilization and low calcium absorption only through epidemiological studies. There have been only a few experimental studies verifying the etiologic factors of osteoporosis in vivo condition. Authors conducted an experimental study using white rats(Sprague Dawley) in order to find out what the endocrinological and biochemical changes of experimentally induced osteoporosis are and how they behave with or against each other. White rats, eighty five in number of 3 to 6 months females and weighing 220±12.7gm were divided into four groups. They consisted of Group I(n=10) for control, Group II(n=25) for bilateral oophorectomy, Group III(n=25) for bilateral division of sciatic nerve and hip spica cast immobilization, and Group IV(n=25) for bilateral oophorectomy and bilateral division of sciatic nerve plus hip spica cast immobilization. Blood samples were taken preoperatively and postoperatively at six weeks to check Estradiol and Osteocalcin levels there of. And then, rats were sacrified immediately after the second sampling to retrieve femora for bone mineral density measurement and torsional stress test. Estradiol levels before operation were 21.4±13.3pg/ml for Group I, 31.6±3.1pg/ml for Group II, 25.6±4.5pg/ml for Group III and 33.7±4.5pg/ml for Group IV, respectively. There were no significant differences observable among the groups. Estradiol levels at six weeks postoperatively were 42.3±18.8pg/ml for Group I, 5.4±2.7pg/ml for Group II, 40.8±5pg/ml for Group III and 6.2±2.3 pg/ml for Group IV, respectively. Apparent reductions in group II and IV were proved of statistical significance. Osteocalcin levels preoperatively were 1.2±0.6ng/ml for Group I, 1.7±0.4ng/ml for Group II, 1.5±0.1lng/ml for Group III and 1.5±0.1.lng/ml for Group IV, respectively. At six weeks postoperatively they were 1.6±0.1lng/ml for Group I, 1.7±0.3ng/ml for Group II, 1.8±0.3ng/ml for Group III and 1.2±0.1lng/ml for Group IV, respectively. The differences and changes among the groups and measurements were not of statistical significance. Bone mineral contents at six weeks postoperatively were 0.248±0.03g for Group I, 0.177±0.03g for Group II, 0.226±0.04g for Group III and 0.092±0.01g in Group IV, respectively. Low values of Group II and IV compared to those of Group I and III were of statistical significance.(P=0.0001) Torsional strength of bones at six weeks postoperatively were 4.0±0.2N/m for Group I, 1.5±0.1N/m for Group II, 1.5±0.1N/m for Group III and 1.4±0.1N/m for Group IV, respectively. Decreases of experimental groups(II, III, IV) compared to that of control group(I) were of statistical significance, but differences among the experimental groups were not of significance(p>0.05). For above observations, it was possible to conclude that osteoporosis measurable by bone mineral content and torsional stress test was caused by oophorectomy and immobilization in vivo, the former of which was more rapid and profound than the latter during early phase. When both factors, i.e., oophorectomy and immobilization are exerated simultaneously. the resultant osteoporosis was found in higher degree than either factor only, but not at incremental degree as one may expect.
Absorption ; Animals ; Bone Density ; Calcium ; Epidemiologic Studies ; Estradiol ; Estrogens ; Exercise Test ; Female ; Hip ; Humans ; Immobilization ; Osteocalcin ; Osteoporosis ; Ovariectomy ; Rats ; Sciatic Nerve