Discomfort and Bleeding in Relation to Bedrest Time after Bone Marrow Examination among Hemato-oncology Patients / 임상간호연구

PURPOSE: The purpose of this study was to investigate hemato-oncology patients' discomfort and bleeding in relation to the bedrest time after bone marrow examination. METHODS: A descriptive correlational study was conducted. The data were collected using self-report questionnaire from total of 131 patients who underwent bone marrow examination from January 2017 to September 2017. Data were analyzed with descriptive statistics, Wilcoxon Signed-rank test, McNemar's test and logistic regression. RESULTS: The level of discomfort after 4 hours of bedrest was significantly higher when compared to 2 hours of bedrest(p<.001). The occurrence of bleeding after 2 hours of bedrest was significantly higher than 4 hours of bedrest(p<.001), however the degree of bleeding was slight. No bleeding occurred in 84% of the patients after 2 hours of bedrest. CONCLUSION: The results of this study demonstrated that shortening the bed rest time after bone marrow examination was helpful in improving the patient's well-being. Bedrest time could be shortened according to the site of bone marrow examination and patient's condition.

Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

Ischemic preconditioning (IP) is one of the most important endogenous mechanisms that protect the cells against ischemia-reperfusion (I/R) injury. However, the exact molecular mechanisms remain unclear. In this study, we showed that changes in the level of agmatine were correlated with ischemic tolerance. Changes in brain edema, infarct volume, level of agmatine, and expression of arginine decarboxylase (ADC) and nitric oxide synthases (NOS; inducible NOS [iNOS] and neural NOS [nNOS]) were analyzed during I/R injury with or without IP in the rat brain. After cerebral ischemia, brain edema and infarct volume were significantly reduced in the IP group. The level of agmatine was increased before and during ischemic injury and remained elevated in the early reperfusion phase in the IP group compared to the experimental control (EC) group. During IP, the level of plasma agmatine was increased in the early phase of IP, but that of liver agmatine was abruptly decreased. However, the level of agmatine was definitely increased in the ipsilateral and contralateral hemisphere of brain during the IP. IP also increased the expression of ADC—the enzyme responsible for the synthesis of endogenous agmatine—before, during, and after ischemic injury. In addition, ischemic injury increased endogenous ADC expression in the EC group. The expression of nNOS was reduced in the I/R injured brain in the IP group. These results suggest that endogenous increased agmatine may be a component of the ischemic tolerance response that is induced by IP. Agmatine may have a pivotal role in endogenous ischemic tolerance.

Pipeline Embolization Device for Large/Giant or Fusiform Aneurysms: An Initial Multi-Center Experience in Korea / 신경중재치료의학

PURPOSE: The purpose of this study was to assess the safety and early outcomes of the Pipeline device for large/giant or fusiform aneurysms. MATERIALS AND METHODS: The Pipeline was implanted in a total of 45 patients (mean age, 58 years; M:F=10:35) with 47 large/giant or fusiform aneurysms. We retrospectively evaluated the characteristics of the treated aneurysms, the periprocedural events, morbidity and mortality, and the early outcomes after Pipeline implantation. RESULTS: The aneurysms were located in the internal carotid artery (ICA) cavernous segment (n=25), ICA intradural segment (n=11), vertebrobasilar trunk (n=8), and middle cerebral artery (n=3). Procedure-related events occurred in 18 cases, consisting of incomplete expansion (n=8), shortening-migration (n=5), transient occlusion of a jailed branch (n=3), and in-stent thrombosis (n=2). Treatment-related morbidity occurred in two patients, but without mortality. Both patients had modified Rankin scale (mRS) scores of 2, but had an improved mRS score of 0 at 1-month follow-up. Of the 19 patients presenting with mass effect, 16 improved but three showed no changes in their presenting symptoms. All patients had excellent outcomes (mRS, 0 or 1) during the follow-up period (median, 6 months; range, 2-30 months). Vascular imaging follow-up (n=31, 65.9%; median, 3 months, range, 1-25 months) showed complete or near occlusion of the aneurysm in 24 patients (77.4%) and decreased sac size in seven patients (22.6%). CONCLUSION: In this initial multicenter study in Korea, the Pipeline seemed to be safe and effective for large/giant or fusiform aneurysms. However, a learning period may be required to alleviate device-related events.

The Effect of Imiquimod on Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Malignant Melanoma Cell Invasion

BACKGROUND: A number of reports have been published regarding the use of imiquimod for the treatment of melanoma in situ and metastatic melanoma. Essential steps in the process of melanoma invasion and metastasis include degradation of basement membranes and remodeling of the extracellular matrix by proteolytic enzymes, including matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). OBJECTIVE: To evaluate the antiinvasive effect of imiquimod in human malignant melanoma cell lines, SK-MEL-2 and SK-MEL-24, in vitro, and to investigate imiquimod-induced changes in the expression of MMPs and TIMPs. METHODS: Invasiveness of melanoma cell lines following imiquimod treatment was evaluated by invasion assays. In order to investigate the mechanism of the anti-invasive effect of imiquimod, mRNA and protein levels of MMP-2, -9, membrane type 1 (MT1)-MMP, TIMP-1, and -2 were assessed by real-time reverse transcription-polymerase chain reaction, gelatin zymography, and western blotting. RESULTS: Imiquimod treatment decreased in vitro viability of melanoma cells in a concentration-dependent manner. Imiquimod also elicited a concentration-dependent suppression of invasion in both melanoma cell lines. A concentration-dependent decrease in MMP-2 and MT1-MMP protein levels and a concentration-dependent increase in TIMP-1 and -2 protein levels by imiquimod was observed in both melanoma cell lines. However, expression of MMP-9 protein was increased in SK-MEL-2 but decreased in SK-MEL-24 with increasing imiquimod concentrations. Imiquimod elicited alterations in MMPs and TIMPs mRNA levels that parallel the observed changes in protein levels. CONCLUSION: Imiquimod may elicit an anti-invasive effect on human melanoma cells by regulating MMPs and TIMPs.

Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma

The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal diseases such as tinea pedis (athlete's foot). In this study, we investigated the antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced by a mutation breeding using gamma ray irradiation, and compared the antifungal activity of H. syriacus Ggoma and its parent type. According to the results, the methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal activity than its parent type against Trichophyton mentagrophytes. Following purification through various column chromatographies, the antifungal substance was identified as nonanoic acid on the basis of spectroscopic analysis.

Fomitoside K, a New Lanostane Triterpene Glycoside from the Fruiting Body of Fomitopsis nigra

In an effort to identify the chemical constituents of fruiting bodies of Fomitopsis pinicola, a new lanostane triterpene glycoside, designated as fomitoside K, has been isolated from its methanolic extract. Its chemical structure was assigned on the basis of various spectroscopic studies.

Clinical Outcomes of Endovascular Coil Embolization for Paraclinoid Aneurysms / 대한뇌혈관외과학회지

OBJECTIVE: Direct surgical clipping of paraclinoid aneurysms is challenging due to nearby anatomic structures. However, as endovascular techniques advance, endovascular coil embolizations for paraclinoid aneurysms are more frequently performed. We reviewed our experience with endovascular coil embolization of paraclinoid aneurysms to evaluate its safety and efficacy. METHODS: From 2005 to 2011, 78 patients underwent endovascular procedures with detachable coils for 86 paraclinoid aneurysms at our institute. A retrospective review of the medical records was performed. RESULTS: Seventy-eight patients with 86 paraclinoid aneurysms were evaluated. Thirteen patients (16.7%) were men and 65 (83.3%) were women. Patient age ranged from 23 to 78 years (mean age, 48 years). Five patients (6.4%) presented with subarachnoid hemorrhage (SAH) with decreased consciousness and visual field defects. In the 86 treated aneurysms, the immediate post procedural angiogram demonstrated complete occlusion in 73 aneurysms (84.9%), near-complete occlusion in eight aneurysms (9.3%) and partial occlusion in five aneurysms (5.8%). We obtained angiographic follow-up in 46 cases. Minor recanalization occurred in two cases and major recanalization occurred in one case. One thromboembolic complication and one blurred vision occurred among the 78 patients. CONCLUSION: Despite difficulties with surgical approaches for paraclinoid aneurysms, these lesions can be successfully managed by endovascular treatment. Favorable outcomes with a low morbidity suggest endovascular techniques as alternatives to microsurgical therapy for treating paraclinoid aneurysms.

The Study of Characteristics of Cutaneous Manifestations of Kawasaki Disease in Korean Patients (2006-2010) / 대한피부과학회지

BACKGROUND: Kawasaki disease (KD) is an acute inflammation of middle-sized arteries such as the coronary artery. KD is an important disease due to its high mortality rate, which approaches 1-2% without appropriate treatment. Since the various mucocutaneous lesions of KD are related to the dermatologic field, dermatologists should take an interest in this disorder and understand the lesions. OBJECTIVE: To evaluate the characteristics of cutaneous lesions in Korean patients with KD. METHODS: A total of 919 patients with KD were assessed at the department of pediatric cardiology and dermatology, Myongji hospital between January 2006 and December 2010. RESULTS: Of the 919 patients, 566 (61.6%) were diagnosed with typical KD and 353 (38.4%) with atypical KD. KD was most frequent in the 4 year-old group (22.7%), and the ratio of male to female was 1.5:1. Among the mucocutaneous manifestations, erythema of the oropharyngeal mucosa (75.7%) occurred most frequently, followed by polymorphous trunk rash (41.7%), and changes of palms and soles (25.6%). A total of 606 patients (65.9%) with KD had associated diseases as follows: pneumonia (211 patients; 34.8%), pharyngotonsilitis (168 patients; 27.7%), gastroenteritis (132 patients; 21.8%), asthma (15 patients, 2.5%), atopic dermatitis (11 patients, 1.8%). CONCLUSION: Our study shows that change in the lips or oral cavity is the most common mucocutaneous manifestation in both classic and atypical KD. Also, morbiliform rash is the most common pattern of polymorphous rashes. Interestingly, erythema multiforme-like lesions occupied accounted for a considerable portion of KD cases compared to previous studies.

Wells' Syndrome Associated with Churg-Strauss Syndrome

Churg-Strauss syndrome (CSS) is a multisystem granulomatous vasculitis that is characterized by peripheral eosinophilia and the infiltration of eosinophils into systemic organs. The skin lesions of CSS consist mainly of palpable purpura and nodules. Wells' syndrome (WS) is a rare inflammatory dermatosis that is associated with recurrent granulomatous dermatitis and eosinophilia. Since these two diseases are rare, any overlap between them is very unusual. Herein, we report a patient with CSS, who initially presented a skin eruption of erythematous urticarial-plaques, vesicles, and blisters. Upon biopsy, the histology of these plaques indicated eosinophilic infiltration and "flame figures" within the dermis, which was consistent with a diagnosis of WS. Although the association between WS and CSS that was observed in our patient may be purely coincidental, it could also suggest a common pathogenetic background of these two distinct diseases, as both share several many common features.

The Steroid-sparing Effect of an Emollient APDDR-0801 in Patients with Atopic Dermatitis / 대한피부과학회지

BACKGROUND: Defective skin barrier function is a well recognized feature in atopic dermatitis (AD) and causes symptoms such as xerosis, pruritus and erythematous lesions. Since moisturizers can strengthen a defective skin barrier and reduce the usage of corticosteroid cream, the choice of moisturizer is very significant for AD patients. OBJECTIVE: This study was done to compare the steroid-sparing effects of a ceramide-containing moisturizer, APDDR-0801, with a control moisturizer without ceramide, for relieving symptoms associated with AD. METHODS: A randomized, controlled, double-blinded 6-week study was conducted. Patients with mild to moderate AD topically applied APDDR-0801 or the control moisturizer on the whole body for 6 weeks. They also applied corticosteroid cream (Zemaderm(R)) on the lesion twice daily for 6 weeks. The amount of corticosteroid used was measured by weighing the tubes. Disease severity was evaluated by eczema severity, area index (EASI), and investigator global assessment (IGA). Transepidermal water loss (TEWL) and skin capacitance were also measured. RESULTS: Of the 40 patients enrolled, 32 completed the protocol. The mean age was (12.95+/-1.92) and the average baseline EASI score was (10.45+/-1.17). EASI score, IGA, TEWL and skin capacitance improved in both groups at 3 weeks and 6 weeks. Compared to the control group, the amount of steroid cream used at 3 weeks and 6 weeks decreased by 0.14 g (-18.78%) and 0.76 g (-7.46%), respectively, in the test group. The difference was larger in patients with moderate AD. The consumption of steroids was lower in the test group at 3 weeks [2.65 g (-34.64%)] and at 6 weeks [2.60 g (-19.38%)], respectively. CONCLUSION: The moisturizer APDDR-0801 (Atobarrier cream(R)) which contains physiologic lipid granules including ceramide, has superior steroid-sparing effects than moisturizers without ceramide.

Solitary Type of Congenital Self-healing Reticulohistiocytosis

Congenital self-healing reticulohistiocytosis is a rare, congenital, benign, self-healing variant of Langerhans cell histiocytosis. It usually appears as multiple papules or nodules; however, occurrence of the solitary type is very rare. We report on a case of solitary congenital self-healing reticulohistiocytosis in a 29-day-old girl who presented with a papule on her sole. Two months later, the lesion regressed with a slight scar. Based upon clinical and histologic findings, we made a diagnosis of solitary congenital self-healing reticulohistiocytosis. In this report, we summarized reported cases of solitary congenital self-healing retioculohistiocytosis in Korea with a review of the literature.

Benefits of Surgical Treatment for Unruptured Intracranial Aneurysms in Elderly Patients

OBJECTIVE: Due to longer life spans, patients newly diagnosed with unruptured intracranial aneurysms (UIAs) are increasing in number. This study aimed to evaluate how management of UIAs in patients age 65 years and older affects the clinical outcomes and post-procedural morbidity rates in these patients. METHODS: We retrospectively reviewed 109 patients harboring 136 aneurysms across 12 years, between 1997 and 2009, at our institute. We obtained the following data from all patients : age, sex, location and size of the aneurysm(s), presence of symptoms, risk factors for stroke, treatment modality, and postoperative 1-year morbidity and mortality. We classified these patients into three groups : Group A (surgical clipping), Group B (coil embolization), and Group C (observation only). RESULTS: Among the 109 patients, 56 (51.4%) underwent clipping treatment, 25 (23%) patients were treated with coiling, and 28 observation only. The overall morbidity and mortality rates were 2.46% and 0%, respectively. The morbidity rate was 1.78% for clipping and 4% for coiling. Factors such as hypertension, diabetes mellitus, hypercholesterolemia, smoking, and family history of stroke were correlated with unfavorable outcomes. Two in the observation group refused follow-up and died of intracranial ruptured aneurysms. The observation group had a 7% mortality rate. CONCLUSION: Our results show acceptable favorable outcome of treatment-related morbidity comparing with the natural history of unruptured cerebral aneurysm. Surgical clipping did not lead to inferior outcomes in our study, although coil embolization is generally more popular for treating elderly patients. In the treatment of patients more than 65 years old, age is not the limiting factor.

Anti-Platelet Drug Resistance in the Prediction of Thromboembolic Complications after Neurointervention

OBJECTIVE: The aim of this study was to analyze the correlation between thromboembolic complications and antiplatelet drugs before and after neurointervention. METHODS: Blood samples and radiographic data of patients who received a neurointervention (coil embolization, stent placement or both) were collected prospectively. Rapid platelet function assay-aspirin (RPFA-ASA) was used to calculate aspirin resistance in aspirin reaction units (ARU). For clopidogrel resistance, a P2Y12 assay was used to analyze the percentage of platelet inhibition. ARU > 550 and platelet inhibition < 40% were defined as aspirin and clopidogrel resistance, respectively. RESULTS: Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures. The mean resistance values of all patients were 484 ARU and < 39%. Ten (17.0%) of 53 patients showed resistance to aspirin with an average of 597 ARU, and 33 (62.3%) of 53 patients showed resistance to clopidogrel with an average of < 26%. Ten patients demonstrated resistance to both drugs, 5 of which suffered a thromboembolic complication after neurointervention (mean values : 640 ARU and platelet inhibition < 23%). Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU, and mean clopidogrel resistances of < 33.8% and < 40.7%, respectively. CONCLUSION: Identifying individuals with poor platelet inhibition using standard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future. Neurointerventional research should focus on ideal doses, timing, choices, safety, and reliable measurements of antiplatelet drug therapy, as well as confirming the clinical relevance of aggregometry in cerebrovascular patients.

A Case of Herpes Zoster Duplex Bilateralis, a Diagnostic Clue of Human Immunodeficiency Virus Infection / 대한피부과학회지

The skin lesion of herpes zoster is typically limited to a single dermatome. The clinical appearance of herpes zoster in immunocompromised patients is usually identical to typical zoster, but lesions may be more severe and there can be multidermatomal involvement. The appearance of herpes zoster occurring in two non-contiguous dermatomes has been referred to as zoster duplex unilateralis or bilateralis. Herpes zoster duplex bilateralis is a rare manifestation of herpes zoster and almost all reported cases have in immunocompromised patients with hematologic cancer, patients taking immunosuppressant drugs for chronic illnesses and patients receiving chemotherapy for solid cancers. We report a case of herpes zoster duplex bilateralis, which was a diagnostic clue of human immunodeficiency virus infection.

The Influence of Pregnancy and Menstruation on the Deterioration of Atopic Dermatitis Symptoms

BACKGROUND: Female patients with atopic dermatitis (AD) often experience cutaneous deterioration associated with their pregnancy or menstrual cycle. OBJECTIVE: We wanted to determine the prevalence of symptom aggravation as related to pregnancy and the menstrual cycle in female patients with AD. METHODS: One hundred female patients with AD were included in the study and interviews were performed. The total IgE level and the Eczema Area and Severity Index score of the patients were retrospectively reviewed. RESULTS: Ninety seven patients replied the questionnaire, and among them, 23 patients had completed at least 1 pregnancy. Among the 23 women who experienced pregnancy, 14 (61%) had noticed deterioration of their clinical symptoms during pregnancy. Of the 97 females, 31 (32%) patients had noticed deterioration of their AD as related to their menstrual cycle. For the patients who were sub-grouped as the intrinsic type of AD, the prevalence of symptom aggravation as related to pregnancy was significantly higher as compared to that of the extrinsic type of AD patients (p=0.048). CONCLUSION: Of the 97 patients, 45 (46%) females answered that they have experienced deterioration of AD during pregnancy or in relation to their menstrual cycle, and this suggests the relation of a hormonal influence on the clinical manifestations of AD.

Characteristics and Management of Residual or Slowly Recurred Intracranial Aneurysms

OBJECTIVE: Residual aneurysm from incomplete clipping or slowly recurrent aneurysm is associated with high risk of subarachnoid hemorrhage. We describe complete treatment of the lesions by surgical clipping or endovascular treatment. METHODS: We analyzed 11 patients of residual or recurrent aneurysms who had undergone surgical clipping from 1998 to 2009. Among them, 5 cases were initially clipped at our hospital. The others were referred from other hospitals after clipping. The radiologic and medical records were retrospectively analyzed. RESULTS: All patients presented with subarachnoid hemorrhage at first time, and the most frequent location of the ruptured residual or recurrent aneurysm was in the anterior communicating artery to posterior-superior direction. Distal anterior cerebral artery, posterior communicating artery, and middle cerebral artery was followed. Repositioning of clipping in eleven cases, and one endovascular treatment were performed. No residual aneurysm was found in postoperative angiography, and no complication was noted in related to the operations. CONCLUSION: These results indicate the importance of postoperative or follow up angiography and that reoperation of residual or slowly recurrent aneurysm should be tried if such lesions being found. Precise evaluation and appropriate planning including endovascular treatment should be performed for complete obliteration of the residual or recurrent aneurysm.

Distinction between Intradural and Extradural Aneurysms Involving the Paraclinoid Internal Carotid Artery with T2-Weighted Three-Dimensional Fast Spin-Echo Magnetic Resonance Imaging

OBJECTIVE: The precise intra- vs. extradural localization of aneurysms involving the paraclinoid internal carotid artery is critical for the evaluation of patients being considered for aneurysm surgery. The purpose of this study was to investigate the clinical usefulness of T2-weighted three-dimensional (3-D) fast spin-echo (FSE) magnetic resonance (MR) imaging in the evaluation of unruptured paraclinoid aneurysms. METHODS: Twenty-eight patients with unruptured cerebral aneurysms in their paraclinoid regions were prospectively evaluated using a T2-weighted 3-D FSE MR imaging technique with oblique coronal sections. The MR images were assessed for the location of the cerebral aneurysm in relation to the dural ring and other surrounding anatomic compartments, and were also compared with the surgical or angiographic findings. RESULTS: All 28 aneurysms were identified by T2-weighted 3D FSE MR imaging, which showed the precise anatomic relationships in regards to the subarachnoid space and the surrounding anatomic structures. Consequently, 13 aneurysms were determined to be intradural and the other 15 were deemed extradural as they were confined to the cavernous sinus. Of the 13 aneurysms with intradural locations, three superior hypophyseal artery aneurysms were found to be situated intradurally upon operation. CONCLUSION: High-resolution T2-weighted 3-D FSE MR imaging is capable of confirming whether a cerebral aneurysm at the paraclinoid region is intradural or extradural, because of the MR imaging's high spatial resolution. The images may help in identifying patients with intradural aneurysms who require treatment, and they also can provide valuable information in the treatment plan for paraclinoid aneurysms.

Surgery and Perioperative Intralesional Corticosteroid Injection for Treating Earlobe Keloids: A Korean Experience

BACKGROUND: The aesthetic implications of ear keloids, which affect people of all races, are serious and the treatment of earlobe keloids is known to be difficult. The high rate of recurrence following excision alone has led to investigating various types of adjuvant therapy, including intralesional corticosteroid injection. OBJECTIVE: We evaluated the efficacy of excision combined with perioperative intralesional triamcinolone acetonide injection for treating earlobe keloids of Korean patients. METHODS: From 1997 to 2006, eighteen keloids on the earlobes of fifteen Korean patients were treated. The patient age ranged from 15 to 32 years (mean age: 24 years). All the patients were female and the keloids occurred after ear piercing. Preoperative intralesional triamcinolone acetonide (TA) injection was administered twice at a 1-month interval. Postoperative intralesional TA injections were given every 1 month for several months, depending on the patient's clinical progress. RESULTS: The follow-up period ranged from 4 to 42 months (mean: 18.5 months). After the surgery, TA intralesional injections were given 2 to 13 times (mean: 5.2 times). Of the treated keloids, eleven showed good results (61.1%) and three recurred (16.6%). No complications from the TA intralesional injection were observed. CONCLUSION: Among the various treatments for earlobe keloids, we suggest that excision with corticosteroid intralesional injection can be used as the first line therapy when considering its effect and economic advantage.

A Case of Myxoid Neurothekeoma on the Hand / 대한피부과학회지

Neurothekeoma is a benign dermal soft tissue tumor that is probably of nerve sheath origin. It usually presents as a slow-growing, solitary papule or nodule that is mainly located on the head and neck or upper extremities except for the hand. There are three histologic subtypes - myxoid, mixed and cellular type - depending on the amount of myxoid stroma. Immunohistochemical markers such as S-100, glial fibrillary acidic protein, nerve growth factor receptor, NK1C3 (CD57) and Ki-M1p can be applied to the tumor cells to distinguish among thesethree subtypes of neurothekeoma. Only one case has been previously reported on the hand in Korea. Herein, we report a rare case of myxoid neurothekeoma on the hand with a review of the related literature.

A Case of a Giant Cell Tumor of Tendon Sheath in a Child / 대한피부과학회지

A giant cell tumor of tendon sheath is a slow growing benign soft tissue tumor that is known by a variety of names including fibrous histiocytoma of tendon sheath and fibrous xanthoma of the synovium. Clinically, it presents as a 1~3 cm firm, non-mobile, painless, nontender mass, and mostly occurs at interphalangeal joints of fingers. It shows female predominance and can occur at any age, but it is most common between the third and fifth decades and is rare in children. We now report the case of a 10-year-old girl with a giant cell tumor of tendon sheath on the toe.