OBJECTIVES: To investigate the role of ATP-sensitive potassium channel (KATP) during sustained ventricular fibrillation (VF), the effects of gliburide, a specific blocker of KATP channel and PCO400, an KATP opener, were studied in isolated and perfused swine right ventricular free walls (n=). METHODS: Recording of single cell transmembrane potentials was performed and constructed action potential duration restitution (APDR) curve by plotting APD 90%(APD90) versus preceding diastolic interval (DI). RESULTS: All isolated tissues fibrillated spontaneously. In this preparation, stable VF could persist over a 4-hour period if it was allowed to continue undisturbed (n=). Gliburide (1-5 uM) increased DI without significant changes in APD90 during VF, resulting in more regularization of VF. Higher concentration (10-20 uM) increased both APD90 and DI, and converted to monomorphic ventricular tachycardia (MVT) through the transitional period characterized by APD alternans. PCO400 (1-2.5 uM) caused a significant shortening of APD during MVT and a period of APD alternans became more evident before conversion from MVT to VF. Gliburide eliminated profibrillatory effect of PCO400. This antifibrillatory action of gliburide was accompanied by gradual decrease in the maximum slope of APDR curve during VF. CONCLUSION: KATP channel blockade causes a transition from VF to MVT via lengthening of DI and APD alternans, concomitantly with a reduction of the slope of APD restitution curve.
Action Potentials ; Membrane Potentials ; Potassium Channels ; Swine ; Tachycardia, Ventricular ; Ventricular Fibrillation*

PURPOSE: To evaluate the effects of the different regimens of immobilization after surgery in a rabbit model. MATERIALS AND METHODS: The study was performed on the right Achilles tendon of 30 rabbits. Modified Kessler method was used to suture the transected tendon. Rabbits were divided into three groups, Group I (n=10) underwent long leg cast with equinus position for 6 weeks, Group II (n=10) underwent weekly cast correction to full dorsiflexion from 1 week after surgery, and Group III (n=10) underwent daily correction of equinous position with external fixator from 1 week after surgery. The contralateral Achilles tendon served as an unoperated control. And three groups were compared at 6 weeks after surgery. RESULTS: The maximal load at rupture (N) was 55.50, 97.46, 140.27, 180.98 for group I, II, III and control respectively. The strain was 0.44, 0.49, 0.74, 0.67. The stiffness (N/mm) was 9.63, 17.87, 19.01, 23.33. The absorbed energy to rupture (J) was 12.23, 23.98, 51.20, 60.78. Values among groups were significantly different considering the maximal load, strain, stiffness, and absorbed energy to rupture (p<0.05). Histological finding was revealed more mature restoration and more parallel arrangement of fiber bundles in the group II, and especially group III. Achilles tendon rupture, Maximal load, Strain, Stiffness, Tensile loading. CONCLUSION: Tensile loading of the healing tendon by postoperative continuous correction leads to changes in more similar to the normal Achilles tendon, biomechanically and historically.
Achilles Tendon* ; External Fixators ; Immobilization ; Leg ; Rabbits ; Rupture ; Sutures ; Tendons

BACKGROUND: Ductal adenocarcinoma (DAC) of the prostate is an uncommon histologic subtype whose prognostic factors and immunoprofile have not been fully defined. METHODS: To define its prognostic factors and immunoprofile, the clinicopathological features, including biochemical recurrence (BCR), of 61 cases of DAC were analyzed. Immunohistochemistry was performed on tissue microarray constructs to assess the expression of prostate cancer-related and mammalian target of rapamycin (mTOR) signaling-related proteins. RESULTS: During the median follow-up period of 19.3 months, BCR occurred in 26 cases (42.6%). DAC demonstrated a wide expression range of prostate cancer-related proteins, including nine cases (14.8%) that were totally negative for pan-cytokeratin (PanCK) immunostaining. The mTOR signaling-related proteins also showed diverse expression. On univariate analysis, BCR was associated with high preoperative serum levels of prostate-specific antigen (PSA), large tumor volume, predominant ductal component, high Gleason score (GS), comedo-necrosis, high tumor stage (pT), lymphovascular invasion, and positive surgical margin. High expressions of phospho-mTOR (p-mTOR) as well as low expressions of PSA, phospho-S6 ribosomal protein (pS6) and PanCK were associated with BCR. On multivariable analysis, GS, pT, and immunohistochemical expressions of PanCK and p-mTOR remained independent prognostic factors for BCR. CONCLUSIONS: These results suggest GS, pT, and immunohistochemical expressions of PanCK and p-mTOR as independent prognostic factors for BCR in DAC. Since DAC showed diverse expression of prostate cancer–related proteins, this should be recognized in interpreting the immunoprofile of DAC. The diverse expression of mTOR-related proteins implicates their potential utility as predictive markers for mTOR targeted therapy.
Adenocarcinoma* ; Carcinoma, Ductal ; Follow-Up Studies ; Immunohistochemistry ; Neoplasm Grading ; Prognosis ; Prostate* ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Recurrence ; Ribosomal Proteins ; Sirolimus ; Tumor Burden

The elevation and fusion of palatine are essential processes in the completion of the palatal development. It is believed that the mesenchyme plays a major role in the ascent of the palatal process, and that the palatal epithelium is involved in its fusion. The mechanism of fusion requires several different morphologic and molecular changes prior to the completion of the mesenchymal continuity between different palatine processes. The mechanism of removing the epithelial cells from the fusion zone could include either programmed cell death, epithelial-mesenchymal transformation or migration to adjacent epithelia. Retinoic acid has been known to induce cleft palate by disturbing mesenchymal growth and/or epithelial fusion. The effect of retinoic acid on the epithelium of the palatine process was studied in the fetus of the Sprague- Dawley rat with feeding 100 mg/kg of retinoic acid mixed in olive oil on the 10th day of fetal age and controlled with feeding pure olive oil. The epithelium of the palatine process was examined by PAS reaction and electron- microscopy on the 14th, 15th, 16th and 18th day of fetal age. The obtained results were as follows: 1. In the control group, glycogen was plentiful at the entire epithelium of the palatine process during the pre-fusion period(14th and 15th day), but it diminished in contact epithelium at the fusion stage(16th day). On the contrary, in the experimental group treated with retinoic acid, glycogen was plentiful and did not change from the 14th to 18th day of gestation. 2. In the control group at fusion stage(16th and 18th day), PAS-positive cells increased in the nasal and oral epithelium adjacent to the fusion site, and in the mesenchyme around the fusion site. 3. As a result of electronmicroscopic findings, the epithelium in the experimental group with retinoic acid seemed to be injured by retinoic acid; RER was composed of flattened cisternas and ribosomes were detached, mitochondrial crista and membrane were destructed and sacculated, and Golgi complex was extremely atrophied. According to the results, it seems that apoptosis as well as cell migration and transformation happen in the mechanism of cleaning the epithelium at the contact site, and that retinoic acid injures directly intracytoplasmic organelles and disturbs apoptosis, a sort of normal developmental process. More studies should be done to verify relations between apoptosis and large-sized glycogen granule in superficial epithelium.
Animals ; Apoptosis ; Cell Death ; Cell Movement ; Cleft Palate ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Epithelium* ; Fetus* ; Gestational Age ; Glycogen ; Golgi Apparatus ; Membranes ; Mesoderm ; Microscopy ; Olea ; Organelles ; Periodic Acid-Schiff Reaction ; Pregnancy ; Rats* ; Ribosomes ; Tretinoin* ; Olive Oil

PURPOSE: Diabetic foot wound (DFW) is known as a major contributor of nontraumatic lower extremity amputation. We aimed to evaluate overall amputation rates and risk factors for amputation in patients with DFW. MATERIALS AND METHODS: From January 2014 to December 2017, 141 patients with DFW were enrolled. We determined rates and risk factors of major amputation in DFW and in DFW with peripheral arterial occlusive disease (PAOD). In addition, we investigated rates and predictors for amputation in diabetic foot ulcer (DFU). RESULTS: The overall rate of major amputation was 26.2% in patients with DFW. Among 141 DFWs, 76 patients (53.9%) had PAOD and 29 patients (38.2%) of 76 DFWs with PAOD underwent major amputation. Wound state according to Wagner classification, congestive heart failure, leukocytosis, dementia, and PAOD were the significant risk factors for major amputation. In DFW with PAOD, Wagner classification grades and leukocytosis were the predictors for major amputation. In addition, amputation was performed for 28 patients (38.4%) while major amputation was performed for 5 patients (6.8%) of 73 DFUs. Only the presence of osteomyelitis (OM) showed significant difference for amputation in DFU. CONCLUSION: This study represented that approximately a quarter of DFWs underwent major amputation. Moreover, over half of DFW patients had PAOD and about 38.2% of them underwent major amputation. Wound state and PAOD was major predictors for major amputation in DFW. Systemic factors, such as CHF, leukocytosis, and dementia were identified as risk factors for major amputation. In terms of DFU, 38.4% underwent amputation and the presence of OM was a determinant for amputation.
Amputation ; Arterial Occlusive Diseases ; Classification ; Dementia ; Diabetic Foot ; Heart Failure ; Humans ; Leukocytosis ; Lower Extremity ; Osteomyelitis ; Risk Factors ; Ulcer ; Wounds and Injuries

BACKGROUND AND OBJECTIVES: We assessed the ability of portable echocardiography (with contrasts) to clearly delineate the cardiac structure, and evaluated the impact of its use on the diagnosis and management of critically ill patients in Korea. SUBJECTS AND METHODS: We prospectively enrolled 123 patients (mean age 66+/-16 years), who underwent portable transthoracic echocardiography (with contrast) for image enhancement at 12 medical centers. The quality of the global left ventricular (LV) images, the number of the regional LV segments visualized, the ability to visualize the LV apex and the right ventricle (RV), and any changes in the diagnostic procedure and treatment strategy were compared before and after the contrast. RESULTS: Of the 123 patients, 52 (42%) were using mechanical ventilators. The amount of poor or uninterpretable images decreased from 48% to 5% (p<0.001), after the contrast. Before the contrast, 15.6+/-1.1 of 16 LV segments were seen, which improved to 15.9+/-0.6 segments (p=0.001) after the contrast. The ability to visualize the LV apex increased from 47% to 94% (p<0.001), while the inability to clearly visualize the RV decreased from 46% to 19% (p<0.001). Changes in the diagnostic procedure (for example, not requiring other types of imaging studies) were observed in 18% of the patients, and the treatment plan (medication) was altered in 26% of patients after the contrast echocardiography. CONCLUSION: The use of a contrast agent during the portable echocardiography, in intensive care settings, can improve the image quality and impact the diagnostic procedures and treatment for Korean patients.
Critical Illness ; Diagnosis ; Echocardiography* ; Heart Ventricles ; Humans ; Image Enhancement ; Critical Care* ; Korea ; Prospective Studies ; Ventilators, Mechanical

BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 microg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48 vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 microg/hr vs. 24.8 microg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
Administration, Cutaneous ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid/*administration & dosage/adverse effects ; Female ; Fentanyl/*administration & dosage/adverse effects ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Neoplasms/*complications ; Pain/diagnosis/*drug therapy/etiology ; Pain Measurement ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Tertiary Care Centers ; Time Factors ; Transdermal Patch ; Treatment Outcome

PURPOSE: Colorectal obstruction develops most frequently by carcinoma, and 7%–30% of these colorectal carcinomas are acute cases. The oncologic safety of self-expanding metal stent (SEMS) insertion as a bridge to surgery has not yet been established. Thus, we investigated the oncologic safety of SEMS insertion as a bridge to surgery in patients with obstructive colorectal cancer.METHODS: This retrospective had 56 patients enrolled requiring emergency management for obstructive colorectal cancer at stage II or III, who had undergone curative surgery between July 2008 and June 2011. These subjects were divided into two groups: patients who had undergone emergency surgery without SEMS insertion (non-stent group) and those who had undergone elective surgery after preoperative decompression with SEMS insertion (stent group). The two groups were compared for clinicopathologic characteristics, postoperative complications, and survival rate.RESULTS: Enterostomy was performed in 25 patients (100.0%) in the non-stent group and 1 patient (3.2%) in the stent group; laparoscopic surgery was carried out in 7 patients (28.0%) in the non-stent group and 19 patients (61.29%) in the stent group, each showing statistically significant differences. There was no statistically significant difference in postoperative complications and 5-year disease-free survival rate (72% vs. 74.19%, P=0.87, respectively).CONCLUSION: In treatment of malignant colorectal obstruction, elective operation after stent insertion had similar oncologic outcomes compared with emergency operation. Preoperative stent insertion not only lowers the incidence of enterostomy but also makes laparoscopic surgery possible, thereby enhancing patients' quality of life. Therefore, preoperative stent insertion is a useful method that may replace emergency surgery in treatment of malignant colorectal obstruction.
Colorectal Neoplasms ; Decompression ; Disease-Free Survival ; Emergencies ; Enterostomy ; Humans ; Incidence ; Intestinal Obstruction ; Laparoscopy ; Methods ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Stents ; Survival Rate

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.