Purpose: This study was designed to evaluate the effectiveness of postoperative radiotherapy for patients with low-grade astrocytomas and to define an optimal radiotherapeutic regimen and prognostic factors. Materials and Methods: A total of 69 patients with low-grade astrocytomas underwent surgery and postoperative radiotherapy immediately following surgery at our institution between October 1989 and September 2006. The median patient age was 36 years. Forty-one patients were 40 years or younger and 28 patients were 41 years or older. Fourteen patients underwent a biopsy alone and the remaining 55 patients underwent a subtotal resection. Thirty-nine patients had a Karnofsky performance status of less than 80% and 30 patients had a Karnofsky performance status greater than 80%. Two patients were treated with whole brain irradiation followed by a coned down boost field to the localized area. The remaining 67 patients were treated with a localized field with an appropriate margin. Most of the patients received a dose of $50\sim55$ Gy and majority of the patients were treated with a dose of 54 Gy. Results: The overall 5-year and 7-year survival rates for all of the 69 patients were 49% and 44%, respectively. Corresponding disease free survival rates were 45% and 40%, respectively. Patients who underwent a subtotal resection showed better survival than patients who underwent a biopsy alone. The overall 5-year survival rates for patients who underwent a subtotal resection and patients who underwent a biopsy alone were 57% and 38%, respectively (p<0.05). Forty-one patients who were 40 years or younger showed a better overall 5-year survival rate as compared with 28 patients who were 41 years or older (56% versus 40%, p<0.05). The overall 5-year survival rates for 30 patients with a Karnofsky performance status greater than 80% and 39 patients with a Karnofsky performance status less than 80% were 51% and 47%, respectively. This finding was not statistically significant. Although one patient was not able to complete the treatment because of neurological deterioration, there were no significant treatment related toxicities. Conclusion: Postoperative radiotherapy following surgery is a safe and effective treatment for patients with low-grade astrocytomas. The extent of surgery and age were noted as significant prognostic factors in this study. However, further effective treatment might be necessary in the future to improve long-term survival rates.
Go, Jun;Choi, Sun Il;Kim, Ji Eun;Lee, Young Ju;Kwak, Moon Hwa;Koh, Eun Kyoung;Song, Sung Hwa;Sung, Ji Eun;Hwang, Dae Youn
Journal of Life Science
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v.23
no.6
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pp.812-824
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2013
Reserpine, an anti-hypertensive drug, is able to positively modulate several phenotypes associated with $A{\beta}$ toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD). We investigated into the therapeutic effects of reserpine on mammalian neurodegenerative disorders, and found that significant alteration of the key factors influencing AD was detected in Tg2576 mice after reserpine treatment for 30 days. The aggressive behavior of Tg2576 mice was significantly improved upon reserpine treatment, whereas their social contact was consistently maintained. Furthermore, the levels of $A{\beta}$-42 peptide in the hippocampus of the brain and blood serum were lower in the reserpine-treated group than in the vehicle-treated group. Among g-secretase components, the expression levels of PS-2, Pen-2, and APH-1 were slightly lower in reserpine-treated Tg2576 mice, although a significant change in nicastrin (NCT) expression was not detected. Furthermore, the serum level of nerve growth factor (NGF) increased in reserpine-treated Tg2576 mice compared with vehicle-treated mice. Among down-stream effectors of the NGF receptor TrkA signaling pathway, reserpine treatment induced elevation of TrkA phosphorylation and reduction of ERK phosphorylation. In addition, in the NGF receptor $p75^{NTR}$ signaling pathway, the expression levels of $p75^{NTR}$ and Bcl-2 were enhanced in reserpine-treated Tg2576 mice compared with vehicle-treated mice, whereas the expression level of RhoA declined. Overall, these results suggest that reserpine can help relieve AD pathogenesis in Tg2576 mice through downregulation of $A{\beta}$-42 deposition, alteration of ${\gamma}$-secretase components, and regulation of NGF metabolism.
Yun, Kyong-Ah;Lee, Young Ah;Shin, Choong Ho;Yang, Sei Won;Shin, Hee Young;Ahn, Hyo Seop;Kim, Il Han
Clinical and Experimental Pediatrics
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v.50
no.1
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pp.65-73
/
2007
Purpose : Short stature is an important complication that impairs the quality of life in survivors of childhood brain tumors. We studied their final adult height (FAH) to evaluate risk factors for short stature. Methods : We reviewed the medical data of 95 survivors of childhood brain tumors (64 males and 31 females) who had been followed up from 1982 to 2006, reached FAH, and had a more than five year-disease-free survival. Results : Final adult height standard deviation score (FAHTSDS: $mean{\pm}SD$) of the patients was lower than those of general population ($-1.15{\pm}1.72$), HTSDS at diagnosis ($-0.13{\pm}1.57$), and target HTSDS ($-0.49{\pm}0.69$). FAHTSDS of craniopharyngioma patients did not decrease ($0.57{\pm}1.17$), but those of germ cell tumor and medulloblastoma patients were significantly reduced ($-1.20{\pm}1.45$, $-2.70{\pm}1.46$; P<0.05). The patients treated with craniospinal radiation or chemotherapy had lower FAHTSDS ($-1.93{\pm}1.58$, $-2.27{\pm}1.44$; P<0.01). In the spinal irradiation group, the younger the age at diagnosis was, the more the loss of FAH (r=0.442, P<0.01). Growth hormone replacement (GHR) didn't improve FAHTSDS, but starting GHR under 12 years was an independent factor for improving FAH once treatment methods were taken into account (P=0.01). Conclusion : The younger age at diagnosis, spinal radiation and chemotherapy were all important risk factors of height loss, and height gain was expected in patients who received GHR under the age of 12 years. Therefore, regular check-ups of growth and early intervention with growth hormones are needed for high risk groups to improve FAH.
Purpose: Bed, living a long time is required in adult patients with brain lesions such as stroke, traumatic brain injury, and Parkinson's disease, causing pneumonia and respiratory diseases may be due to aspiration of food or saliva. In patients with recurrent pneumonia or pulmonary symptoms, there is a need to determine the possibility of pulmonary aspiration due to aspiration of saliva. Materials and Methods: Saliva due to aspiration pneumonia diagnosis in patients with brain lesions request for inspection to the Department of Nuclear Medicine, 10 patients (male 6, female 4) were included in this study. Patients were fasted before the test, $^{99m}Tc_{O4}$ 185 MBq (5 mCi) of less than 1 mL of solution was administered in the oral cavity. Administration and 20 minutes of dynamic imaging acquisition, and immediately after that the static images were acquired. Delayed scan after 2-4 hours if necessary. Results: Positivity rate of all 10 patients was 60%. In 4 patients showed positive reactions after the administration of oral cavity in a 20-minute dynamic imaging were able to confirm whether the aspiration. In the remaining 2 patients, four hours of additional delay tests were able to confirm whether the aspiration. Conclusion: Does not require changes in patient posture compared to the other checks that can be diagnosed with aspiration pneumonia. A simple test and takes less time. Therefore be useful in providing information for the diagnosis and treatment modality.
Purpose : Menkes disease is an X-linked recessively inherited disorder caused by the mutation of the ATP7A gene encoding copper-transporting P-type AT Pase. The phenotypic features are progressive neurological degeneration, mental retardation, loose skin, and vascular complications. Early diagnosis and treatment are very important for the prognosis of Menkes disease. Here, we describe nov el mutations of the ATP7A gene and prenatal diagnosis by mutation analysis. Methods : Five unrelated Korean Menkes patients were included in this study. They presented with depigmented wool-like hair, progressive neurologic deterioration, and hypotonia in infancy. Serum copper and ceruloplasmin levels w ere decreased. Brain magnetic resonance imaging revealed tortuous intracranial vessels. Mutation analysis has been carried out using cDNA from cultured skin fibroblasts or genomic DNA from peripheral leukocytes. Prenatal diagnosis was performed in two cases using chorionic villi samples or amniocytes. Results : Four novel mutations have been identified from four different families; c.3511+1G>A (p.E1099_N1171delinsMfsX 18), c.4005+5 G>A (p.V1268_R1335del), c.1870_2172del (p.S624_Q724del), and c.3352 G>A (p.G1118S). T he remaining one was previously reported (c.1933 C>T (p.V 1268_R1335del)). On prenatal DNA analysis, one w as diagnosed as normal, while the other turned out to be a female heterozygote with p.S624_Q724del mutation of the ATP7A gene. Conclusion : We identified 4 novel mutations of the ATP7A gene. Prenatal diagnosis in families at risk is critical in order to choose preventiv e options including an early treatment with copper-histidine therapy or therapeutic termination. Most mutations of the ATP7A gene were frame-shift mutations and prenatal diagnosis has been successfully carried out.
The transmissible spongiform encephalopathies (TSEs) disease group are fatal neurodegenerative disorders affecting a wide range of hosts. The group includes kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats and Bovine spongiform encephalopathy (BSE) in cattle. The exact nature of the infectious agent involved in the transmission of these diseases remains controversial. However, a central event in their pathogenesis is the accumulation in infected tissues of an abnormal form of a host-encoded protein, the prion protein (PrP). Whereas the normal cellular protein is fully sensitive to protease ($PrP^{sen}$), the disease-associated prion protein ($PrP^d$) is only partly degraded ($PrP^{res}$), its amino-terminal end being removed. BSE was first reported in the mid-80s in the UK. Ten years later, a new form of human prion disease, variant CJD (vCJD) developed in the wake of the BSE epidemic, and there is now strong scientific evidence that vCJD was initiated by the exposure of humans to BSE-infected tissues, thus indicating a zoonotic disease. However, the ban on the feeding of animal-derived proteins to ruminants, and the apparent lack of vertical transmission of BSE, have led to a decline in the incidence of the disease within cattle herd and therefore, an assumed decreased risk for human contacting vCJD. The origin of the original case(s) of BSE still remains an enigma even though three hypotheses have been raised. Hypotheses are i) sheep- or goat-derived scrapie-infected tissues included in meat and bone meal fed to cattle, ii) a previously undetected sporadic or genetic bovine TSE contaminating cattle feed or iii) originating from a human TSE through animal feed contaminated with human remains. A host cellular membrane protein ($PrP^C$), which is abundant in central nervous system tissue, appear to be conformationally altered in the diseased host into a prion protein ($PrP^{Sc}$). This $PrP^{Sc}$ is detergent insoluble and partially protease-resistant ($PrP^{res}$). The term $PrP^{res}$ is normally used to describe the protein detected after protease treatment, in techniques such as Western immunoblotting, and enzyme-linked immunosorbant assay using fresh/frozen tissue. Immunohistochemistry may performed with formalin-fixed tissues. Also, clinical signs of the BSE are one of the major diagnostic indicators. Recently, atypical forms (known as H- and L-type) of BSE have appeared in several European countries, Japan, Canada and the United States. An unusual case was also reported in a miniature zebu. The atypical BSE fall into two groups based on the relative molecular mass (Mm) of the unglycosylated $PrP^{res}$ band relative to that of classical BSE, one of the higher Mm (H-type) and the other lower (L-type). Both types have been detected worldwide as rare cases in older animals, at a low prevalence consistent with the possibility of sporadic forms of prion diseases in cattle. This raises the unwelcome possibility that vCJD could increase in the human population. Now, active surveillance program against BSE is going on in Korea. In regional veterinary service lab, ELISA is applied to screen the BSE in slaughter and confirmatory tests by Western immunoblotting and immunohistochemisty are carried out if there are positive or suspect in the screening test. Also, the ruminant feed ban is rigorously enforced. Removal of specified risk materials such as brain and spinal cord from cattle is mandatory process at slaughter to prevent the infected material from entering the human food chain.
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.
Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.
Journal of Physiology & Pathology in Korean Medicine
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v.24
no.6
/
pp.1034-1041
/
2010
The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction and it is originally from the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to reduce ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. The toxicity of LMK02 was investigated in SD rats by oral repeated adminstration for 4 weeks and we tried to determine test does for 13 weeks repeated study. Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02 was investigated in 6 weeks old specific pathogen free (SPF) Sprageu-Dawley rats by oral administration. Each test group were consist of 5 male and 5 female and they received doses of 500, 1,000 and 2,000 mg/kg/day of test substance for 4 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of control group. Urinalysis : We observed increase of PRO(p<0.01), SG(p<0.01) in female rats of 1,000 mg/kg/day and 2,000 mg/kg/day(p<0.01). Also, we observed increase of pH and KET in female rats of 1,000 mg/kg/day(p<0.05) and of 2,000 mg/kg/day(p<0.01). WBC in female rats in 1,000 mg/kg/day and 2,000 mg/kg/day were on increase. Hematological test : We observed increase of MCV in male rats of 250 mg/kg/day. (p<0.05) Serum biochemistry test : We found increase of CHO in female rats of 2,000 mg/kg/day(p<0.05). During the experimental period, there were no animals dead or moribund. There were no treatment related changes of general symptom, food and water consumption, organ weight and autopsy According to the results of 4-week repeated dose range finding study, the highest dose was established as 1000 mg/kg for 13-week repeated dose toxicity study and we determined to put 2 more groups by common ratio two.
It is generally accepted that the delivery of health care is undergoing many changes specially those related to acute, contagious disease care and to the increase of chronic illnesses which can not be cured but are controlable. The health care practitioner can not be soley responsible for the control of their clients' care. Because the clients will play a vital role in controlling their illnesses, long term participation by both the health care provider and the client is necessary. Since most individuals with hypertension do not experience signs or symptoms, the disease is difficult to detect and even when diagnosed, clients do not comply well with their hypertension regimens. The noncompliant client is at increased risk for compliants involving the heart, brain, kidney and other organs. In an effort to explore methods of increasing patient participation in and adherence to treatment programs for hypertension, the researcher used health contracting to promote self care. The research questions are; 1) Will the health contracting increase compliance in health behavior and reduce the blood pressure\ulcorner 2) If clients comply with their regimens will this reduce their blood pressure\ulcorner The research design utilized in this study was a quasi-experimental design. A purposive sample, was abtained from two churches in the 1. area, consisting of 64 clients with hypertension. The data was collected from the middle of January to the 1st of September 1985. Randomization was only of the two church groups into experimental and control groups. Compliance with health behavior related to the hypertensive regimen, blood pressure and body weight were measured, compared and analyzed. In the experimental group measurements were made 6 times; one month before the education program after education program when health contracting was done and 4 more times once a month for 4 months. In the control group measurements were made 3 times; one month before the education program after the education program, and once 4 months later. There was no health contracting. The data were analyzed by t-test, Pearson correlation and ANOVA according to purpose of the study. The result of this study may be summarized as follows: The result related to the hypothesis on the effect of health contracting are as follows: H$_1$; “The hypothesis that the experimental group, with a health contractual agreement will demonstrate increased compliance levels for health behavior than the control group” was supported(t=-5.29, df=62, p=.000). H$_2$; “The hypothesis that the experimental group, with a health contractual agreement, will demonstrate a greater reduction in blood pressure than the control group” was supported (for systolic blood pressure t=2.72, df=62, p=.009, for diastolic blood pressure t=1.95, df=62, p=.050). H$_3$; The hypothesis that the greater the compliance of the client with health behavior the lower the client's blood pressure will be was partially supported (for systolic pressure r=-.2981, p=.008, for diastolic pressure r=-.1720, p=.087). From the examination of the results of this study it can be concluded that the interaction between the nurse and the client, contracting to define goals and reinforcing compliant behavior, leads to improved compliance with health care behaviors and thus to an increase in the effectiveness of nursing care. Further consideration need to be given to the inclusion of the concept of health contracting in primary nursing and to further research in this area.
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