Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment / 한국유방암학회지

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

The Therapeutic Effect of Sauchinone on Inflammatory Arthritis in Mice

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease, mainly involving joints and bones. Sauchinone is an anti-inflammatory agent isolated from Saururus chinensis, which was used in oriental medicine. The aim of this study was to evaluate the therapeutic effect of sauchinone on inflammatory arthritis and underlying mechanism of anti-arthritic effect. METHODS: Mice with collagen induced arthritis (CIA) was intraperitoneally injected with sauchinone (20 mg/kg) or vehicle. The clinical and histological evaluations were performed with arthritis scoring and hematoxylin-eosin staining, respectively. CD4+ interleukin (IL) 17+ T cells were determined under Th17 skewing condition treated with sauchinone. To evaluate the effect of sauchinone on osteoclastogenesis, mice bone marrow macrophages (BMMs) and human peripheral blood mononuclear cells (PBMCs) were cultured with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand in the absence or presence of sauchinone. RESULTS: Sauchinone significantly attenuated the inflammatory arthritis in CIA mice both clinically and histologically. The proportion of Th17 cells were decreased with treatment with sauchinone in vivo and in vitro. The expressions of Th17 cell markers (IL-17 and retinoic acid receptor-related orphan receptor gamma t) and B cell markers (activation-induced cytidine deaminase) were downregulated in the presence of sauchinone. Sauchinone also suppressed the formation of tartrate-resistant acid phosphatase positive cells from mice BMMs and human PBMCs, and the expression of osteoclastogenic markers. CONCLUSION: Sauchinone alleviates inflammatory arthritis in mice through inhibition of Th17 differentiation and osteoclastogenesis. Sauchinone, one of traditional herbal medicine, could be a therapeutic candidate for the treatment of RA.

Eupatilin Ameliorates Collagen Induced Arthritis

Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-alpha and then treated with eupatilin, and the levels of IL-6 and IL-1beta mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-alpha treatment of synoviocytes increased the expression of IL-6 and IL-1beta mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.

In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis

Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4+CD25+Foxp3+ Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4+ T cells, and the effect was associated with retinoic acid-related orphan receptor gammaT and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4+ (cytotoxic T-lymphocyte antigen 4), PD-1+ (programmed cell death protein 1) and GITR+ (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4+ cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.

Staphylococcus aureus Pericardial Abscess Presenting as Severe Sepsis and Septic Shock After Acupuncture Therapy

Pericardial abscess is an extremely rare complication of Staphylococcus aureus bacteremia. We report a case of a 72-year-old woman with multiple acupuncture scars on both knees who presented with shortness of breath and general weakness. Transthoracic echocardiography and pericardiocentesis confirmed the presence of pericardial fluid collection. Staphylococcus aureus grew in both pericardial fluid and blood. Although an aggressive medical treatment including intravenous antibiotics and percutaneous drainage, the patient died 2 days after admission.

Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis

Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P < 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1beta and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.

Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis

Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P < 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1beta and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to components of the cell nucleus with diverse clinical manifestations, predominantly in women during reproductive years. SLE is caused by interaction between susceptibility genes and environmental factors, which result in abnormal immune response. SLE is caused by failure in regulating the production of pathogenic autoantibodies and the formation of immune complex. Abnormalities in the immune responses regulation display a decreased ability to clear immune complexes and apoptotic cells. Genetic predisposition to SLE involves multiple genes. Genetic variants predisposing to SLE may influence clearance of immune complexes or apoptotic bodies, activation of B cells or T cells, and inflammation related to dendritic cell activation. Environmental factors that predispose to or activate SLE include ultraviolet B light, infection with Epstein-Barr virus, female gender, and exposure to estrogencontaining medications. The diagnosis of SLE is based on characteristic clinical features and autoantibodies. The diagnostic criteria of the American College of Rheumatology (ACR) reflect the major clinical features of the disease (mucocutaneous, articular, serosal, renal, neurologic) and incorporate the associated laboratory findings (hematologic and immunologic). Four or more criteria are required for diagnosis. There is no effective cure for SLE, and complete sustained remissions are rare. The treatment should be tailored based on the clinical manifestations in an individual patient. Conservative therapies for management of non-life-threatening manifestations of SLE comprise NSAIDs, corticosteroids and antimalarials. Treatment of severe organ damage requires immunosuppressive agents. Targeted biologic therapies are under development and appear to be promising.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to components of the cell nucleus with diverse clinical manifestations, predominantly in women during reproductive years. SLE is caused by interaction between susceptibility genes and environmental factors, which result in abnormal immune response. SLE is caused by failure in regulating the production of pathogenic autoantibodies and the formation of immune complex. Abnormalities in the immune responses regulation display a decreased ability to clear immune complexes and apoptotic cells. Genetic predisposition to SLE involves multiple genes. Genetic variants predisposing to SLE may influence clearance of immune complexes or apoptotic bodies, activation of B cells or T cells, and inflammation related to dendritic cell activation. Environmental factors that predispose to or activate SLE include ultraviolet B light, infection with Epstein-Barr virus, female gender, and exposure to estrogencontaining medications. The diagnosis of SLE is based on characteristic clinical features and autoantibodies. The diagnostic criteria of the American College of Rheumatology (ACR) reflect the major clinical features of the disease (mucocutaneous, articular, serosal, renal, neurologic) and incorporate the associated laboratory findings (hematologic and immunologic). Four or more criteria are required for diagnosis. There is no effective cure for SLE, and complete sustained remissions are rare. The treatment should be tailored based on the clinical manifestations in an individual patient. Conservative therapies for management of non-life-threatening manifestations of SLE comprise NSAIDs, corticosteroids and antimalarials. Treatment of severe organ damage requires immunosuppressive agents. Targeted biologic therapies are under development and appear to be promising.

A Case of Systemic Lupus Erythematosus Showing Red Lunulae after PUVA Therapy in a Patient with Mycosis Fungoides / 대한피부과학회지

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a complex etiology, which can include genetic factors, immune or endocrine disorders and ultraviolet light. Red lunulae have been observed in association with several systemic and cutaneous disorders, most of which have an autoimmune origin. We experienced an interesting case of a 56 year-old patient with mycosis fungoides who had been treated with systemic PUVA for 3 months and developed SLE with red lunulae on all of the finger nails. Herein, we review the relationship between PUVA and SLE and suggest red lunulae as a clinical sign of SLE development.

A Case of Primary Aldosteronism with Aortic Dissection / 대한내분비학회지

Hypertension and atherosclerosis are the most important factors contributing to the development of aortic dissection. Primary aldosteronism is a rare cause of hypertension. The concurrence of aortic dissection is very rare in primary aldosteronism. However, when aortic dissection is found as a life-threatening complication of primary aldosteronism, then the diagnosis of primary aldosteronism is important because the therapeutic intervention can be curative. Only 3 cases of primary aldosteronism with aortic dissection have been reported in the literature. We report here on a case of primary aldosteronism with aortic dissection, which was treated by laparoscopic adrenalectomy. We lowered the blood pressure with antihypertensive drugs and potassium replacement was done to treat the aortic dissection. After stabilization of aortic dissection, we removed his left adrenal mass by laparoscopic adrenalectomy. Postoperatively, the patient's blood pressure has been within normal limits and the serum potassium increased to a normal level without supplementation. The aortic dissection has remained in a stable state

A Case of Primary Aldosteronism with Aortic Dissection / 대한내분비학회지

Hypertension and atherosclerosis are the most important factors contributing to the development of aortic dissection. Primary aldosteronism is a rare cause of hypertension. The concurrence of aortic dissection is very rare in primary aldosteronism. However, when aortic dissection is found as a life-threatening complication of primary aldosteronism, then the diagnosis of primary aldosteronism is important because the therapeutic intervention can be curative. Only 3 cases of primary aldosteronism with aortic dissection have been reported in the literature. We report here on a case of primary aldosteronism with aortic dissection, which was treated by laparoscopic adrenalectomy. We lowered the blood pressure with antihypertensive drugs and potassium replacement was done to treat the aortic dissection. After stabilization of aortic dissection, we removed his left adrenal mass by laparoscopic adrenalectomy. Postoperatively, the patient's blood pressure has been within normal limits and the serum potassium increased to a normal level without supplementation. The aortic dissection has remained in a stable state

Proton Magnetic Resonance Spectroscopy in Patients with Neuro-Behcet's Disease / 대한류마티스학회지

Magnetic resonance imaging (MRI)and computed tomography had been used to detect the neurologic lesions of the Behcet's disease.However,there are a number of cases which can not be detected by conventional imaging studies in neuro-Behcet's disease.To overcome this problem,magnetic resonance spectroscopy (MRS)has been introduced in several autoimmune diseases involving central nervous system such as neuropsychiatric lupus,but which was rarely performed in Behcet's disease.In the present study,we report two cases of neuro-Behcet's disease that showed normal MRI but abnormal proton MRS (1HMRS)findings.MRS in two cases revealed a reduction of the N-acetyl aspartate (NAA)/creatine (Cr)ratio in the substantia nigra and thalamus,respectively, which were the areas without abnormality on MRI,suggesting a functional defect of neurons in these areas.In a case with thalamic dysfunction,abnormal NAA/Cr ratio was normalized in parallel with clinical improvement after treatment with high-dose steroids and immuno-suppressive agents.These observa-tions suggest that MRS may be useful to early detect the functional abnormality in neuro-Behcet's disease and to monitor neurologic status after treatment with immuno-suppressive agents.

Clinical Study of Ketamine Anesthesia for Cesarean Section / 대한마취과학회지

The pharmacological actions of ketamine in human volunteers were reported by Domino et al. in 1965, and use in 130 patients by Corssen and Domino (1966). Since then, its use in a wide variety of surgical procedures has been reported throughout the world. Several authors(Galloon, 1971; Gallon and Dick, 1971; Spoerel, 1971)reported that katamine has several advantages over conventional anesthetics. The advantages of using katamine anesthesia are: preservation of pharyngeal reflex and airway maintenance during induction of anesthesia, stimulation of the cardiovascular system, wide safety margin, short duration, fast recovery, little nausea and vomiting after anesthesia, little depression of the fetus and good uterine contraction with minimal bleeding. On the other hand, ketamine has also disadvantages: elevation of arterial pressure and pulse rate temporarily during induction of anesthesia, poor muscle relaxation and post-operative psychotic reactions are not uncommonly found. The authors tried to find out the feasibility of ketamine anesthesia for Cesarean section over the conventional method of thiopental muscle relaxant N2O with IPPV technique. Materials and Methods.52 Korean parturients were selected for Cesarean section including emergency and elective operation for this study. Thiopental Group. 25 cases were induced for anesthesia with 3.5+/-1.64mg/kg of thiopental and intubated with the help of 1 mg/kg of succinylcholine followed by N2O with controlled ventilation. After delivering the baby, anesthesia was maintained with N2O-O2-ether throughout the procedures. Ketamine A Group. 9 cases, just before skin incision, were injected intravenously with katamine 1.67+/-0.03mg/kg slowly for over one minute with or without N2O: O2(2: 1 L/min) through a mask. After delivering the fetus, a supplement of ketamine and diazepam 10mg I.V. was given intermittently. Ketamine B Group. Anesthesia was induced by 1.72+/-0.05mg/kg ketamine and 1mg/kg of succinylcholine with endotracheal intubation. After delivery, N2O with O2 and additional ketamine were given to 9 patients. Ketamine C Group. Anesthesia was performed with 1. 30+/-0.15mg/kg of ketamine, 0.08mg/kg of pancuronium, N2O, with endotracheal intubation for 9 patients, ether supplement was given following delivery .Conclusion .With these mentioned methods of anesthesia, the authors formed several conclusions about ketamine anesthesia in Cesarean section. 1. Ketamine can be used as the main anesthetic or for induction in elective and emergency Cesarean section because of its rapid onset and intense analgesic effect. 2. As in the method of anesthesia, it is useful to combine N2O-O2 mixture and muscle relaxants such as succinylcholine or pancuronium. This technique is more suitable for maintenance of anesthesia because of the poor muscle relaxation of ketamine alone. 3. For induction of anesthesia, under 1.6mg/kg of ketamine is advisable. Exceeding this dose, the infant respiration is more likely to be depressed because of hypertonicity of the skeletal musculature. 4. Ketamine has a maternal cardiovascular stimulation effect particularly diastolic blood pressure and pulse rate in the Ketamine-pancuronium-N2O-intubation group. 5. Less bleeding was found during and after the delivery, possibly due to an increased uterine contraction from ketamine. 6. Disadvantages of ketamine included a prolonged maternal recovery period, and newborn respiratory depression end these seemed to be dose related. Fro the above, ketamine anesthesia appears to be another safe and satisfactory method of anesthesia for Casarean section, provided that toxema of pregnancy patients with hypertension and patients who have had psychotic problems previously are avoided.