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Biomedical subjects

G S Park

Publications and source records attributed to G S Park.

17 recordsLinked to original sources

Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study.

OBJECTIVE: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). PARTICIPANTS AND METHODS: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. RESULTS: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40-0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15-0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9-14.2 (0.86-1.77 effect size) on the mRSS and 0.21-0.55 (0.32-0.83 effect size) on the HAQ-DI score. CONCLUSION: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.

Adult↗

The role of nitric oxide in ocular surface diseases.

For the first time, the current series of studies provide a possible pathophysiologic mechanism of NO-induced ocular surface disease. NO is present in tear and aqueous humor and is suspected of having an important physiological role in maintaining normal homeostasis of the ocular surface. NO concentrations are higher in aqueous humor compared to tears, though some variability exists between different species. When inflammation was induced by PTK wounding or LPS, three forms of NOS expression were seen in corneal cells. Each isoform of NOS was expressed uniquely according to the specific location of inflammation. When concentrations of NO peaked, the levels of iNOS were markedly increased in fibroblasts and inflammatory cells. The correlation between NO and inflammation was confirmed by treatment with NOS inhibitor, which abrogated the amount of both NO and inflammation. The tissue damage by NO was measured by nitrotyrosine formation. Damage was detected mainly in inflammatory cells, especially those localized in and around the limbal vessel. It is likely that expression of iNOS in limbal fibroblasts has other roles related to survival of limbal stem cells and fibroblasts as well. Because the main source of NO are fibroblasts, we were able to determine the effect of various concentrations of NO on cell viability using a fibroblast culture system. Cell viability increased in dose dependent manner from 10 microM to 500 microM of the NO generator SNAP, but decreased at concentrations above 1000 microM, suggesting that the in vivo mechanism of cell death was indirect, through specific biologic pathways. Therefore, the pathophysiological mechanism of NO action is bimodal with a toxicological component in ocular surface diseases. Furthermore, its concentration and interaction with other oxygen mediators appear to vary depending on the degree of inflammation.

Animals↗

Efficacy of heparin-coated stent in early setting of acute myocardial infarction.

Primary stenting has been reported to be superior to balloon percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) for recurrent ischemia, target lesion revascularization, and restenosis. However, concerns about early reocclusion or thrombosis after stenting in the very thrombotic environment of acute myocardial infarction still remain. Therefore, postprocedural short-term heparin or GpII(b)/III(a) receptor blockades has been used. The aim of our study was to evaluate the safety, feasibility, and long-term efficacy of heparin-coated stent in the early setting of AMI without postprocedural heparin or GpII(b)/III(a) receptor blockade infusion. We studied 102 consecutive patients presenting to cardiac catheterization laboratory < or = 6 hr from the onset of chest pain. No patients who were implanted with heparin-coated stents received heparin or GpII(b)/III(a) receptor blockade infusion after the procedures, not even patients who showed an angiographically large thrombus burden before stenting. Patients were evaluated for clinical endpoints at 30 days and 6 months. Coronary angiography was required for all patients at 2 weeks and 6 months after the procedure. Angiographic and procedural successes were 100% and 98%, respectively. Two patients (2%) died of heart failure without evidence of reocclusion of stented vessel during the hospitalization and 4 (4%) additional patients died of refractory heart failure within the first 6 months. Major bleeding complication occurred in one patient (1%). Recurrent myocardial infarction developed in one patient at 4 months. Early angiographic follow up at 2 weeks was performed in 88% of all patients, none of whom showed thrombotic stent occlusion. Six-month angiographic follow-up was completed in 71%(64/91) of eligible patients and binary restenosis was present in 17.2% of stented vessels. Eight(8%) patients underwent repeat PTCA. Cardiac event-free survival rate at 6 months was 86.3%. This study demonstrates that heparin-coated stents are safe in the early setting of acute myocardial infarction and no additional heparin infusion after stenting is necessary, which may reduce bleeding complications. Angiographic restenosis rate compares favorably to the binary restenosis rate from other studies with uncoated stents.

Adult↗

Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet.

BACKGROUND: Results of clinical trials of statin therapy demonstrate that an improvement in incidence of cardiovascular end points and coronary stenosis can be achieved. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that affect endothelial function, such as inflammatory responses, formation of thrombi, and stabilization of plaque. OBJECTIVE: To investigate levels of serologic markers, which may be useful surrogates for activity of vascular disease after administration of statin. METHODS: We administered 20-40 mg simvastatin daily for 14 weeks to 13 patients established to have coronary artery disease who remained hypercholesterolemic during step-II diet therapy. RESULTS: Administration of simvastatin significantly lowered lipoprotein levels and the low: high-density lipoprotein cholesterol level ratio and apolipoprotein B:A-I level ratio compared with pretreatment values (P < 0.01). Administration of simvastatin significantly lowered plasma levels of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-I [33+/-46 and 13+/-19%, respectively (P = 0.027 and 0.020, respectively)]. Furthermore, administration of simvastatin tended to lower plasma levels of plasminogen activator inhibitor type-1 and tumor necrosis factor-alpha [by 20+/-44 and 13+/-29%, respectively (P= 0.066 and 0.110, respectively)]. There were significant inverse correlations between pretreatment levels of MMP-9 and the degree of change in those levels after administration of simvastatin (r = -0.714, P= 0.005). However, there was no significant correlation between levels of lipoprotein and levels of MMP-9, monocyte chemoattractant protein-I, and plasminogen activator inhibitor type-1 during administration of simvastatin. CONCLUSIONS: Our current data support the hypothesis that nonlipid mechanisms elicited by administration of simvastatin contribute to the decrease in incidence of cardiovascular events and explain the early clinical benefit observed in clinical trials, independent of changes in levels of lipoprotein.

Aged↗

The role of nitric oxide in ocular surface diseases.

The role of nitric oxide (NO) in ocular surface diseases remains unknown. We investigated the conditions leading to increase NO generation in tears and the main sources of ocular surface tissue. We evaluated the possibility of a dual action (cell survival or cell death) depending on the amount of NO. The concentration of nitrite plus nitrate, the stable end-product of NO, was measured in the tears of various ocular surface diseases. We also examined the main source of nitric oxide synthase (NOS) using immunohistochemical staining & Western blot analysis. When cultured human corneal fibroblasts were treated with NO producing donor with or without serum, the viability of cells was studied. We found that sources of NO in ocular surface tissue primarily included corneal epithelium, fibroblasts, endothelium and inflammatory cells. Three forms of NOS (eNOS, bNOS, & iNOS) were expressed in experimentally induced inflammation. Cell death by NO revealed TUNEL positive staining, however in the EM finding, this NO specific cell death was an atypical necrosis showing perinuclear large vacuolization and mitochondrial swelling. In the fibroblasts culture system, the NO donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of corneal fibroblasts caused by serum deprivation in a dose dependent manner up to 500 m SNAP, although a higher dose decreased cell viability. This study suggested that NO might act as a double-edged sword in ocular surface disease depending on the degree of inflammatory condition related with NO concentration.

Animals↗

Binding of equine infectious anemia virus rev to an exon splicing enhancer mediates alternative splicing and nuclear export of viral mRNAs.

In addition to facilitating the nuclear export of incompletely spliced viral mRNAs, equine infectious anemia virus (EIAV) Rev regulates alternative splicing of the third exon of the tat/rev mRNA. In the presence of Rev, this exon of the bicistronic RNA is skipped in a fraction of the spliced mRNAs. In this report, the cis-acting requirements for exon 3 usage were correlated with sequences necessary for Rev binding and transport of incompletely spliced RNA. The presence of a purine-rich exon splicing enhancer (ESE) was required for exon 3 recognition, and the addition of Rev inhibited exon 3 splicing. Glutathione-S-transferase (GST)-Rev bound to probes containing the ESE, and mutation of GAA repeats to GCA within the ESE inhibited both exon 3 recognition in RNA splicing experiments and GST-Rev binding in vitro. These results suggest that Rev regulates alternative splicing by binding at or near the ESE to block SR protein-ESE interactions. A 57-nucleotide sequence containing the ESE was sufficient to mediate Rev-dependent nuclear export of incompletely spliced RNAs. Rev export activity was significantly inhibited by mutation of the ESE or by trans-complementation with SF2/ASF. These results indicate that the ESE functions as a Rev-responsive element and demonstrate that EIAV Rev mediates exon 3 exclusion through protein-RNA interactions required for efficient export of incompletely spliced viral RNAs.

Alternative Splicing↗

Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer.

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling. The key role of the Fas system in negative growth regulation has been studied mostly within the immune system, and somatic mutations of Fas gene in cancer patients have been described solely in lymphoid-lineage malignancies. However, many non-lymphoid tumor cells have been found to be resistant to Fas-mediated apoptosis, which suggests that Fas mutations, one of the possible mechanisms for Fas-resistance, may be involved in the pathogenesis of non-lymphoid malignancies as well. In this study, we have analysed the entire coding region and all splice sites of the Fas gene for the detection of the gene mutations in 65 human non-small cell lung cancers by polymerase chain reaction, single strand conformation polymorphism and DNA sequencing. Overall, five tumors (7.7%) were found to have the Fas mutations, which were all missense mutations. Four of the five mutations identified were located in the cytoplasmic region (death domain) known to be involved in the transduction of an apoptotic signal and one mutation was located in the transmembrane domain. This is the first report on the Fas gene mutations in non-lymphoid malignancies, and the data presented here suggests that alterations of the Fas gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human lung cancers.

Adenocarcinoma↗

Practical synthesis of Taxol side chain.

Practical large scale synthesis of N-benzoyl-(2R,3S)-phenylisoserine methyl ester of the Taxol side chain has been attained from the coupling of chiral imine of N-[(S)-methylbenzyl]benzaldimine with (Z)-alpha-methoxy trimethylsilyl ketene acetal followed by the sequential reactions of lactamization, demethylation, methanolysis and N-benzoylation.

Antineoplastic Agents, Phytogenic↗

Comparison of clinical and laboratory findings between patients with diffuse three-vessel coronary artery spasm and other types of coronary artery spasm.

Our purpose was to compare patients with diffuse three-vessel coronary artery spasm and other types of coronary artery spasm without significant organic stenosis, and to elucidate clinical characteristics and risk factors. Patients were divided into two groups: group I consisted of 26 patients showing other types of coronary artery spasm; group II consisted of 5 patients with diffuse three-vessel coronary artery spasm. The mean age of patients in groups I and II was 52 and 50 years, respectively. The incidence of variant angina was higher in men than in women. The incidence of smoking was high in each group, but not significantly different. Exercise tests showed no significant differences between groups. All mean values of laboratory data, including lipoprotein (a) and low-density lipoprotein cholesterol in the two groups, were within normal ranges. There was no significant difference between groups. The incidence of spontaneous spam was much higher in patients with diffuse three-vessel coronary artery spasm (P < 0.01). Electrocardiographic (ECG) findings before the spasm were almost normal. All 5 patients with diffuse three-vessel coronary artery spasm demonstrated no important ST segment changes with episodes of angina during a coronary angiography on 12-lead ECG, compared to patients with other types of coronary artery spasm (P < 0.01). First, we conclude, diffuse three-vessel coronary artery spasm mostly occurs spontaneously. Second, we emphasize that diffuse three-vessel coronary artery spasm must be considered when 12-lead ECG shows no important ST segment changes with episodes of angina. Third, it is not easy to distinguish diffuse three-vessel coronary artery spasm from other types of coronary artery spasm on the basis of history, laboratory data, or electrocardiographic findings, including exercise tests.

Angina Pectoris, Variant↗

Hematosalpinx with pelvic pain after endometrial ablation confirms the postablation-tubal sterilization syndrome.

Complications after endometrial ablation are uncommon, and published series show that the majority of women who are treated by this technique remain symptom free in the postoperative period. A 39-year-old woman with previous tubal ligation underwent laparoscopic-assisted vaginal hysterectomy for debilitating pelvic pain 1 year after endometrial ablation. Pathologic assessment of the surgical specimen showed bilateral hematosalpinges from continued cyclic occult bleeding. The symptoms and findings in this case confirm the postablation-tubal sterilization syndrome.

Adult↗

[Mite infestation rate of pet dogs with ear dermatoses].

This study aimed to investigate the incidence of the canine ear dermatoses caused by mites and the relativity of the causative mites of canine dermatoses to the pruritic dermatoses of the families possessing the pet dogs. Total 970 samples were collected from the lesional hairs and scales of the ear of pet dogs referred to Chung-Woon animal clinic in Seoul from January, 1990 to December, 1995. The mites were collected from the samples by means of the washing method. Presence of pruritic dermatoses in the families possessing the pet dog was evaluated. Among 2,147 mites collected from 970 samples, 2,117 specimens were Octodectes cynotis and others were Sarcoptes canis (30 mites). O. cynotis were found in 382 samples out of total 970 samples (39.4%) and S. canis were found in 3 samples (0.3%). Although two families out of 382 families that possessed the diseased pet dog by O. cynotis had the family histories of pruritic dermatoses, their pruritic dermatoses were not related to the infestation by O. cynotis. In conclusion, O. cynotis, the most common canine mite producing pruritic ear dermatoses, does not cause pruritic dermatoses in man.

Animals↗

Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in combination with digoxin to control ventricular rate in chronic atrial fibrillation: randomized crossover study.

BACKGROUND: The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period. OBJECTIVES: The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function. METHODS: We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication. RESULTS: (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed. CONCLUSION: Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy.

Adrenergic beta-Antagonists↗

Interaction of intravenous heparin and organic nitrates in acute ischemic syndromes.

We evaluated whether a drug interaction between intravenous nitroglycerin or isosorbide dinitrate and heparin exists. Ninety-six patients with a diagnosis of acute myocardial infarction, unstable angina, or other thromboembolic disorders were divided into 3 groups: group I (control group, n = 35) received intravenous heparin alone; group II (n = 31) received combined intravenous nitroglycerin and heparin; and group III (n = 30) received combined intravenous isosorbide dinitrate and heparin. We determined the mean of 2 separate measurements of heparin dosage requirement, antithrombin III activity, and the dose of intravenous nitroglycerin or isosorbide dinitrate at the time that the ratio of activated partial thromboplastin time (aPTT) to baseline aPTT was 1.5 to 2.0. The mean therapeutic heparin dose standardized to total body weight of each group was 13.8, 15.4, and 15.5 U/kg/hour, respectively. At that time, patients were receiving intravenous nitroglycerin at doses of 58.8 +/- 38.6 micrograms/min or intravenous isosorbide dinitrate at doses of 3.7 +/- 2.0 mg/hour. The mean antithrombin III activity of each group was 22.2, 22.8, and 21.3 mg/dl, respectively. The overall results for groups I, II, and III, and results for the subgroup of patients with acute ischemic syndromes in those groups, did not differ significantly. The heparin dose did not show a significant correlation to the dose of intravenous nitroglycerin (r = -0.26, p > 0.05) nor to that of isosorbide dinitrate (r = 0.30, p > 0.05).

Acute Disease↗

Surgical treatment of stress urinary incontinence: a comparison of the Kelly plication, Marshall-Marchetti-Krantz, and Pereyra procedures.

Six hundred eighty patients surgically treated for stress urinary incontinence were observed annually for up to ten years to compare the efficacy and complications of three types of repair procedures. Although Marshall-Marchetti-Krantz procedures yielded the most effective repair in the immediate postoperative period, Kelly plications were equally corrective more than three years after surgery (69 and 66%, respectively). Both were superior to the original Pereyra urethropexies at all times. Repeat operations were more likely to fail than primary repairs. The efficacy of the Pereyra procedure was increased with the use of permanent suture. Marshall-Marchetti-Krantz procedures were not affected by suture selection. Pereyra procedures had more complications, many related to intravesical suture. Success rates of all procedures declined steadily with lengthening periods of observation. We conclude that Kelly plications and Marshall-Marchetti-Krantz procedures have similar long-term efficacy and complication rates. The use of intra-operative cystoscopy and permanent suture with the Pereyra procedure might make it competitive.

Absorption↗