Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model

Background@#We first determined the efficacy of lesional injection of tonsil-derived MSCs (mesenchymal stem cells) for the treatment of 5-fluorouracil induced oral mucositis. @*Methods@#Oral mucositis was induced in hamsters by administration of 5-fluorouracil (day 0, 2, 4) followed by mechanical trauma (day 1, 2, 4). The experimental groups included MT (mechanical trauma only), 5-FU + MT (mechanical trauma with 5-fluorouracil administration), TMSC (mechanical trauma with 5-fluorouracil administration, tonsil-derived mesenchymal stem cells injection), DEXA (mechanical trauma with 5-fluorouracil administration, dexamethasone injection), and saline (mechanical trauma with 5-fluorouracil administration, saline injection). @*Results@#On day 10, gross and histologic analyses showed that nearly complete healing and epithelialization of the cheek mucosa of the TMSC group, whereas the other groups showed definite ulcerative lesions. Compared with the MT and DEXA groups, CD31 expression was greater in the TMSC group on days 10 and 14. Tendency towards a decrease in MMP2 expression with the time in the TMSC group was observed. In addition, the TMSC group showed higher expression of TGF-β, and NOX4 on day 10 compared with the other groups. Scratch assay demonstrated that the conditioned media harvested from tonsil-derived MSCs significantly increased migratory efficacy of NIH3T3 cells. Transwell assay showed that the preferential migration of tonsil-derived MSCs to the wound area. @*Conclusion@#Intralesional administration of tonsil-derived MSCs may accelerate wound healing of 5-fluorouracil induced oral mucositis by upregulating neovascularization and effective wound contraction. In addition, tonsil-derived MSCs might contribute to oral ulcer regeneration via the stimulation of fibroblast proliferation and migration.

Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model

Background@#We first determined the efficacy of lesional injection of tonsil-derived MSCs (mesenchymal stem cells) for the treatment of 5-fluorouracil induced oral mucositis. @*Methods@#Oral mucositis was induced in hamsters by administration of 5-fluorouracil (day 0, 2, 4) followed by mechanical trauma (day 1, 2, 4). The experimental groups included MT (mechanical trauma only), 5-FU + MT (mechanical trauma with 5-fluorouracil administration), TMSC (mechanical trauma with 5-fluorouracil administration, tonsil-derived mesenchymal stem cells injection), DEXA (mechanical trauma with 5-fluorouracil administration, dexamethasone injection), and saline (mechanical trauma with 5-fluorouracil administration, saline injection). @*Results@#On day 10, gross and histologic analyses showed that nearly complete healing and epithelialization of the cheek mucosa of the TMSC group, whereas the other groups showed definite ulcerative lesions. Compared with the MT and DEXA groups, CD31 expression was greater in the TMSC group on days 10 and 14. Tendency towards a decrease in MMP2 expression with the time in the TMSC group was observed. In addition, the TMSC group showed higher expression of TGF-β, and NOX4 on day 10 compared with the other groups. Scratch assay demonstrated that the conditioned media harvested from tonsil-derived MSCs significantly increased migratory efficacy of NIH3T3 cells. Transwell assay showed that the preferential migration of tonsil-derived MSCs to the wound area. @*Conclusion@#Intralesional administration of tonsil-derived MSCs may accelerate wound healing of 5-fluorouracil induced oral mucositis by upregulating neovascularization and effective wound contraction. In addition, tonsil-derived MSCs might contribute to oral ulcer regeneration via the stimulation of fibroblast proliferation and migration.

A Case of Mucinous Gland Adenomatoid Hamartoma Originated from Submental Space / 대한두경부종양학회지

Hamartomas are non-neoplastic malformations or congenital errors of tissue development. Hamartoma is composed by an excessive growth of mature tissue present in wrong proportions and abnormal arrangements. The lesion usually presents as a submucosal mass with ill-defined margins. Hamartoma occurs in all areas of the body, especially in the liver, spleen, kidney and lung. However, hamartoma is very rare in the head and neck. Presenting symptoms of hamartoma are typically vague and nonspecific. Treatment of hamartomas consists of adequate surgical excision. We present a 59 year-old male patient who presented with submental swelling. Malignancy could not be ruled out with preoperative radiologic examination, so surgical excision was planned. The mass was excised with transcervical approach. Histopathologic examination has confirmed the mass as a mucinous gland adenomatoid hamartoma.

A 4-Axis Technique for Three-Dimensional Printing of an Artificial Trachea

BACKGROUND: Several types of three-dimensional (3D)-printed tracheal scaffolds have been reported. Nonetheless, most of these studies concentrated only on application of the final product to an in vivo animal study and could not show the effects of various 3D printing methods, materials, or parameters for creation of an optimal 3D-printed tracheal scaffold. The purpose of this study was to characterize polycaprolactone (PCL) tracheal scaffolds 3D-printed by the 4-axis fused deposition modeling (FDM) method and determine the differences in the scaffold depending on the additive manufacturing method. METHODS: The standard 3D trachea model for FDM was applied to a 4-axis FDM scaffold and conventional FDM scaffold. The scaffold morphology, mechanical properties, porosity, and cytotoxicity were evaluated. Scaffolds were implanted into a 7 × 10-mm artificial tracheal defect in rabbits. Four and 8 weeks after the operation, the reconstructed sites were evaluated by bronchoscopic, radiological, and histological analyses. RESULTS: The 4-axis FDM provided greater dimensional accuracy and was significantly closer to CAD software-based designs with a predefined pore size and pore interconnectivity as compared to the conventional scaffold. The 4-axis tracheal scaffold showed superior mechanical properties. CONCLUSION: We suggest that the 4-axis FDM process is more suitable for the development of an accurate and mechanically superior trachea scaffold.

Effect of Drug-Induced Sedation Endoscopy on the Decision of Treatment Plan in Patients with Obstructive Sleep Apnea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Drug-induced sedation endoscopy (DISE) has recently gained popularity among otolaryngologists because it can provide direct information of upper airway obstruction in patients with obstructive sleep apnea (OSA). In that regard, we examined how DISE examination affected the decision of clinician's treatment plan and the consequent patient's compliance in OSA patients. SUBJECTS AND METHOD: All enrolled patients were classified into two groups according to the method of upper airway evaluation employed: a physical examination only group and a physical examination combined with DISE group. The clinician's treatment plan was categorized into the following four groups: sleep surgery, positive airway pressure, oral appliance, and sleep surgery combined with oral appliance. The change of patient's compliance was also evaluated. RESULTS: There were several differences in how DISE evaluation affected the decision of clinician's treatment plan and patient's compliance between the two groups. The rate for sleep surgery fell from 69.6% to 15.9%; on the other hand, the rate for positive airway pressure, oral appliance and sleep surgery combined with oral appliance all increased from 13.0% to 36.2%, 14.5% to 26.6%, and 2.9% to 21.3%, respectively. The patient's compliance also changed after DISE evaluation: sleep surgery, positive airway pressure, oral appliance and sleep surgery combined with oral appliance all increased from 78.1% to 87.9%, 16.7% to 76.0%, 25.0% to 87.3%, and 50.0% to 91.03%, respectively. CONCLUSION: We found that DISE examination influences the decision of clinician's treatment plan and patient's compliance. We suggest additional cohort studies to confirm these findings.

A Case of Sebaceous Carcinoma of the Submandibular Gland / 대한이비인후과학회지

Sebaceous carcinoma of the salivary gland is an extremely unordinary malignancy occurring mainly in the parotid gland. Sebaceous carcinoma arising in the submandibular gland is exceptional and only three cases have been reported in the literature. We herein present a unique case of sebaceous carcinoma of the submandibular gland, the first to be reported in literature in South Korea. An 85-year-old man visited our hospital complaining of a progressively enlarging submandibular mass with tenderness and ipsilateral facial palsy. We performed a wide excision of the mass with superficial parotidectomy and modified neck dissection. Microscopic and immunohistochemical examinations demonstrated sebaceous carcinoma of low grade differentiation. Further adjuvant radiotherapy was rejected and the patient was followed up for five months. The optimal treatment of sebaceous carcinoma of the salivary gland is still not established due to the rarity of the disease. When more cases are reported, the clinicopathologic characteristics will be better understood.

Analysis of Long-Term Complication on Patients with Obstructive Sleep Apnea Who Treated Mandibular Advancement Device / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Recently, mandibular advancement device (MAD) has been used widely used for the treatment of obstructive sleep apnea (OSA) because it can effectively reduce the collapsibility of upper airway during sleep. Although MAD is widely prescribed by otorhinolaryngologists, several studies described its complications arising from the anterior placement of the mandible with long-term use. However, there is still a lack of studies on long-term complications in Korean patients. SUBJECTS AND METHOD: Retrospectively, we included a total of 57 OSA patients in the study. In this study, all enrolled OSA patients had used MAD over two years with more than 4 hours/day. Dental consulting and cephalometric analysis were conducted to identify the change of dental and skeletal findings at two different times (baseline and after 2 year). RESULTS: The dental findings showed that the overbite and overjet were significantly decreased. Additionally, the proclination of the lower incisors were increased significantly, whereas there was no significant change on the retroclination of the upper incisors. Three patients showed a change of malocclusion type. On the analysis of skeletal findings, we found a significant increase in the sella turcica central point-nasion-supramental point angle and a decrease in the subspinal point-nasion-supramental point angle. Moreover, the anterior lower facial height and anterior facial height were significant increased. CONCLUSION: Consistent with Western studies, our findings suggest that the long-term use of MAD could induce changes in dental and skeletal morphologies in Korean OSA patients. Therefore, clinicians should thoroughly evaluate potential changes in dental and skeletal morphologies when they prescribe MAD to patients with OSA.

Application of a Collagen Patch Derived from Duck Feet in Acute Tympanic Membrane Perforation

We investigated the utility of the duck-feet collagen extraction patching procedure in the traumatic tympanic membrane (TM) perforation via a comparison with spontaneous healing or paper patch. Fifty-six ears of adult male Sprague-Dawley rats, each weighing in the range of 250 to 300 g, were used for the animal studies. Sixteen rats had one-side ear in the control group and the opposite-side ear in the treated groups. The remaining twelve rats had a one-side ear with the duck-feet collagen patch and the opposite-side ear with a paper patch. The proliferating cell nuclear antigen (PCNA) expression cells were calculated among the 200 basal cells, and the expression percentage was identified as the labeling index. The healing of the perforation in the duck-feet collagen patch group was confirmed to be more rapid compared to the healing of the other groups. PCNA staining was observed in the migrating portion of PCNA enhanced cell to collagen scaffold in Post operative day (POD) 7 of collagen patch group. Thus, the adhesive effect of the duck-feet collagen patch to perforated margin was better than that of the paper patch. After completing the healing process, the collagen patch shrank and detached from the tympanic membrane (POD 14). In this study, we confirmed that the use of a duck-feet collagen patch had the advantage of early healing, inducing natural TM contour, and disappearing ability after the patch effect is complete.

Fabrication and Characterization of Hydrocolloid Dressing with Silk Fibroin Nanoparticles for Wound Healing

Hydrocolloid dressings have been developed for many types of wound healing. In particular, dressing is a critical component in the successful recover of burn injuries, which causes a great number of people to not only suffer from physical but also psychological and economic anguish each year. Additionally, silk fibroin is the safest material for tissue engineering due to biocompatibility. In this study, we fabricated hydrocolloid dressings incorporating silk fibroin nanoparticles to enhance the efficacy of hydrocolloid dressing and then use this silk fibroin nanoparticle hydrocolloid dressing (SFNHD) in animal models to treat burn wounds. The structures and properties of SFNHD were characterized using tensile strength and Cell Counting Kit-8 assay. The results indicated the structural stability and the cellular biocompatibility of the hydrocolloid dressing suggesting that SFNHD can be applied to the treatment of wounds. To demonstrate the capacity of a silk fibroin hydrocolloid dressing to treat burn wounds, we compared SFNHD to gauze and Neoderm®, a commercially available dressing. This study clearly demonstrated accelerated wound healing with greater wound structural integrity and minimal wound size after treatment with SFNHD. These observations indicate that SFNHD may be an improvement upon current standard dressings such as Gauze and Neoderm® for burn wounds.

A Case of Mammary Analogue Secretory Carcinoma Arising from Parotid Gland / 대한이비인후과학회지

Mammary analogue secretory carcinoma is a recently described salivary gland tumor. Histopathologically, mammary analogue secretory carcinoma resembles both acinic cell carcinoma and secretory breast carcinoma but also exhibit some differences. We present a case of mammary analogue secretory carcinoma of the parotid gland to help further characterize this rare tumor.

Salivary Duct Carcinoma with Unusual Clinical Course of Sialolithiasis / 대한이비인후과학회지

Salivary duct carcinoma is a high-grade malignant tumor that is histologically similar to ductal carcinoma of the breast. It accounts for less than 1-3% of salivary gland tumors and 63-100% of cases arise in the parotid gland. Swelling, pain, facial palsy and mass in the salivary gland are clinical features suggestive of salivary duct carcinoma. CT and MR imaging findings are nonspecific. However, a few reports suggest that ill-defined heterogenous mass containing calcification observed on CT scans may be useful for diagnosis. Although salivary duct carcinoma can show calcifications on CT images (33-50%), it can be confused with sialolithiasis. The authors report two cases of salivary duct carcinoma, which was complicated with sialolithiasis in the submandibular gland (in a 25-year-old man with recurrent distal submandibular duct stone, and a 50-year-old man with intraglandular stone). It is suggested that unusual cases of sialolithiasis should be carefully examined to exclude the suspicion of malignancy before surgery.

Review of Injection Laryngoplasty as Treatment of Voice Disorders / 이화의대지

In the past decade, vocal fold injection (VFI) has re-emerged as a valuable treatment modality for a variety of laryngeal disorders. It offers many advantages for the treatment of glottal insufficiency. It can avoid surgical scar and is easily performed with local anesthesia. In this article, we describe the indication of injection laryngoplasty, variable injection materials and discuss about vocal fold injection approaches.

A Case of Septal Perforation Reconstructed with Alloderm Interposition Graft Resulted from Magnetic Nasal Foreign Bodies / 대한이비인후과학회지

Nasal cavity foreign bodies are common accidents in children, especially between the newly born and four years of age, and sometimes lead to complications such as epistaxis, vestibulitis, sinusitis bronchoaspiration and nasal septal damage etc. Diagnosis is often made with anterior rhinoscopy, but sometimes nasal fibroendoscopy and imaging may be useful. If the diagnosis is confirmed, prompt foreign body removal should be done to avoid complications. We have recently experienced a case of nasal septal perforation secondary to magnetic nasal foreign bodies attracting each other across the nasal septum. After the removal of foreign bodies, the nasal septal perforation was repaired with acellular human dermal allograft.

Steatocystoma Simplex of the Anterior Neck / 대한이비인후과학회지

As a benign adnexal tumor, steatocystoma usually occurs as an autosomal dominant condition known as steatocystoma multiplex. Steatocystoma simplex, the noninherited solitary counterpart of steatocystoma multiplex,was first described by Brownstein in 1982, and is exceedingly rare. We report a case of steatocystoma simplex in a 27-years-old female, who presented with an asymptomatic soft, oval shaped mass on the lower anterior neck. The lesion was completely excised and confirmed as steatocystoma simplex on histopathological examination.

Hemodynamic Effect of Deformation of the Descending Thoracic Aorta by Precordial Chest Compression during Standard Cardiopulmonary Resuscitation in Humans

PURPOSE: There have been no reports concerning the role of the aorta in explaining why blood flow is low below the diaphragm and a pressure gradient is present between central and peripheral arteries during standard cardiopulmonary resuscitation (CPR). The aim of this study was to assess the morphologic changes of the descending thoracic aorta and its effect on aortic pressure during precordial chest compression in cardiac arrest victims. METHODS: Twelve patients with non-traumatic cardiac arrest (8 males, mean age: 58 years) were enrolled. Transesophageal echocardiography was performed to verify the morphologic changes of the descending thoracic aorta during standard manual CPR. The pressure gradient across the maximally compressed site of the aorta was measured by pullback tracing using a pigtail catheter. RESULTS: Focal compression and deformation of the descending thoracic aorta was uniformly observed in all patients during compression systole. The mean systolic blood pressure of the descending thoracic aorta proximal and distal to the maximally compressed site was 135+/-3 6 mmHg and 115+/-21 mmHg, respectively. The mean systolic pressure gradient across the maximally compressed site was 20.5+/-17.7 mmHg. During compression systole, the pressure gradient between the right atrium and the descending thoracic aorta proximal to the maximally compressed site during compression systole was 49 +/-1 2 mmHg while pressure gradient between the right atrium and the descending thoracic aorta distal to the maximally compressed site was 29+/-8 mmHg. CONCLUSION: We found that the descending thoracic aorta was focally compressed and that a pressure gradient developed across the maximally compressed site during compression systole. This may contribute to limiting blood flow to the subdiaphragmatic region during standard manual CPR in humans.

Clinical Course of Abnormalities in the Liver Function of Patients Resuscitated after Cardiac Arrest

PURPOSE: Little is known about the clinical courses or outcomes of abnormalities of liver function in patients resuscitated after cardiac arrest. We conducted this study to investigate the clinical features and courses of abnormalities of liver function during the post-resuscitation period. METHODS: Twenty-five patients (18 males, mean age: 43 years), who had survived cardiac arrest, were enrolled in this study. Blood samples for the liver function test were obtained immediately and at 1, 2, 4, 7, 10, and 14 days after return of spontaneous circulation. Clinical characteristics, variables associated with cardiac arrest, data during resuscitation, and clinical course during the post-resuscitation period were obtained from our cardiac arrest database. RESULTS: Seventeen patients (68%) had abnormalities of liver function. Those abnormalities included, in order of frequency, increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), or total bilirubin in blood, and a decrease in serum albumin. The highest values of AST, ALT, gamma-GT, and total bilirubin were observed on the second day of postresuscitation period. The abnormalities were normalized in all patients within two weeks after the cardiac arrest. There was no deaths from hepatic failure. There was no difference in downtime, CPR time, number of defibrillations, dose of administered epinephrine, blood pressure, or heart rate after return of spontaneous circulation between the patients with normal liver function and the patients with abnormal liver function (increase of AST or ALT > 50 U/L). Multiple logistic regression analysis revealed that the duration of cardiac arrest was associated with the elevation of liver enzymes. CONCLUSION: Hepatic dysfunction after cardiac arrest is a transient, benign phenomenon. Development of hepatic dysfunction was associated with the duration of cardiacarrest.

The Cardiopulmonary Resuscitation in the Massive Pulmonary Thromboemolism: The Use of t-PA in 2 Cases

The massive pulmonary thromboembolism is serious illness that can lead to death within an hour after its occurrence. The incidence of cardiac arrest caused by massive pulmonary thromboembolism has been known as about 7%. Invasive therapeutic modalities to treat massive pulmonary thromboembolism during cardiac arrest including thoracotomy or cardiopulmonary bypass have been shown little effect. Administration of a thrombolytic agent is an alternative choice of treating massive pulmonary thromboembolism during cardiac arrest. This report describes our experience of cases with massive pulmonary thromboembolism that were treated with administration of a thrombolytic agent during CPR.

Clinical Significance of Myocardial Injuries in Patients with Nontraumatic Intracraninal Hemorrhage

OBJECTIVE: The aim of this study was to investigate the clinical significance of myocardial injuries in patients with nontraumatic intracranial hemorrhage by identifying the occurrence of myocardial injury and defining its correlation with subsequent cardiovascular events. SUBJECTS AND METHODS: One hundred twenty-four patients with nontraumatic intracraninal hemorrhage presented to the emergency department within six hours from onset of symptoms were enrolled. Brain CT, serial electrocardiography, and echocardiography were done at the emergency center. Blood samples for troponin I and creatine kinase(CK)-MB were drawn immediately and eight hours after admission. Troponin I and CK-MB were measured using a chemiluminescent immunoassay, respectively. RESULTS: Electrocardiographic and echocardiography abnormalities were found in 65 cases(52.4%) and 21 cases(17%), respectively. Serum troponin I and creatine kinase-MB were increased in 35 cases (28.2%) and in 58 cases(46.8%), respectively. Abnormal findings of echocardiography and ECG, as well as elevated levels of serum troponin I and creatine kinase-MB, were associated with an increased risk of cardiovascular event and survival. Logistic regression analysis revealed that an abnormal echcocardiographic finding and elevation of serum troponin I were factors associated with the occurrence an adverse cardiovascular event and that electrocardiographic abnormalities and initial mental status were factors associated with poor prognosis. CONCLUSION: This study reveals that actual myocardial injury develops in a significant proportion of patients with nontraumatic intracranial hemorrhage and that the development of the myocardial injury is associated with an adverse cardiovascular event that occurs during admission.

Hemodynamic Effects of Simultaneous Sterno-Thoracic Cardiopulmonary Resuscitation (SST-CPR) in Canine Model of Cardiac Arrest

BACKGROUND AND OBJECTIVES: No existing device for cardiopulmonary resuscitation(CPR)isdesignedto exploit both the "cardiac pump" and the "thoracic pump" simultaneously. This study was designed to assess the hemodynamic effects of simultaneous sterno-thoracic CPR (SST-CPR) vs. standard CPR (S-CPR) using a mechanical resuscitator in a canine model of cardiac arrest. DEVICE DESCRIPTION: We have built a device that depresses the sternum and circumferentially constricts the thorax simultaneously. This device has two components. The first component is a piston, which depresses the sternum. The second is a circumferential strap that constricts the thorax as the piston is pushed down on the sternum. MATERIALS AND METHODS: Twelve domestic dogs were enrolled in this study. After catheterizations to measure pressures from the aorta and the right atrium, ventricular fibrillation was induced by passing AC current to the right ventricle. After 4 minutes of cardiac arrest, S-CPR and SST-CPR were performed alternatively. Aortic pressure, right atrial pressure, cardiac output, and end tidal CO2 were measured while each method of CPR was performing. RESULTS: SST-CPR resulted in significantly higher mean arterial pressure than S-CPR (68.9+/-16.1 vs 30.5+/-10.0 mmHg, p<0.01). SST-CPR could generate higher coronary perfusion pressure than S-CPR (47.0+/-11.4 vs 17.3+/-8.9 mmHg, p<0.01). End tidal CO2 tension was also higher during SST-CPR than S-CPR (11.6+/-6.1 vs 2.17+/-3.3 mmHg, p<0.01). CONCLUSION: Simultaneous sternothoracic cardiopulmonary resuscitation is a new method of cardiopulmonary resuscitation, which can generate better hemodynamic effects than standard cardiopulmonary resuscitation.

Hemodynamic Effects of Simultaneous Sterno-Thoracic Cardiopulmonary Resuscitation (SST-CPR) in Canine Model of Cardiac Arrest

BACKGROUND AND OBJECTIVES: No existing device for cardiopulmonary resuscitation(CPR)isdesignedto exploit both the "cardiac pump" and the "thoracic pump" simultaneously. This study was designed to assess the hemodynamic effects of simultaneous sterno-thoracic CPR (SST-CPR) vs. standard CPR (S-CPR) using a mechanical resuscitator in a canine model of cardiac arrest. DEVICE DESCRIPTION: We have built a device that depresses the sternum and circumferentially constricts the thorax simultaneously. This device has two components. The first component is a piston, which depresses the sternum. The second is a circumferential strap that constricts the thorax as the piston is pushed down on the sternum. MATERIALS AND METHODS: Twelve domestic dogs were enrolled in this study. After catheterizations to measure pressures from the aorta and the right atrium, ventricular fibrillation was induced by passing AC current to the right ventricle. After 4 minutes of cardiac arrest, S-CPR and SST-CPR were performed alternatively. Aortic pressure, right atrial pressure, cardiac output, and end tidal CO2 were measured while each method of CPR was performing. RESULTS: SST-CPR resulted in significantly higher mean arterial pressure than S-CPR (68.9+/-16.1 vs 30.5+/-10.0 mmHg, p<0.01). SST-CPR could generate higher coronary perfusion pressure than S-CPR (47.0+/-11.4 vs 17.3+/-8.9 mmHg, p<0.01). End tidal CO2 tension was also higher during SST-CPR than S-CPR (11.6+/-6.1 vs 2.17+/-3.3 mmHg, p<0.01). CONCLUSION: Simultaneous sternothoracic cardiopulmonary resuscitation is a new method of cardiopulmonary resuscitation, which can generate better hemodynamic effects than standard cardiopulmonary resuscitation.