• Title/Summary/Keyword: Nervous System

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Experimental Studies on Lead Toxicity in Domestic II. Histopathology (고양이의 납중독에 관한 실험적 연구 2. 조직병리학적 소견)

  • Hong Soon-Ho;Han Hong Ryul
    • Journal of Veterinary Clinics
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    • v.11 no.1
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    • pp.485-505
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    • 1994
  • Lead toxicity was evaluated in forty-five cats on a balanced diet, treated with 0(control), 10, 100(low), 1, 000, 2, 000 and 4, 000(high)ppm of lead acetate orally on a body weight basis. The objectives were to describe the gross and histopathologic changes and to demonstrate what tissue lead concentrations correlate with the known dosages of lead. In subclinical lead toxicity, greater than 80% of the absorbed lead was deposited in the bone, whereas in more acute lead toxicity, 42% of absorbed lead was deposited in the bone and 36% and 20% of absorbed lead was deposited in the kidneys and in the liver, respectively. No gross lesions were found in the nervous system. Yellow-brown colored livers appear to be associated with lead toxicity. Neuronal necrosis in the cerebrum was the most predominant histopathologic finding. Astrocytic proliferation in the cerebral gray matter was observed in 1 high dose cat. Gliosis was noted in the cerebral cortex of 6 high dose cats. Two high dose cats had demyelination in the deepest layer of the cortical gray matter of the cerebrum. Extravasation of red cells and cavitation around the vessels were found in the cerebrum of 1 high dose cat. Six high dose cats had degeneration of Purkinje cells in the cerebellum. The microscopic findings in the peripheral nerves were ambiguous. In more acute toxicity, the cats had lead inclusions in the epithelial cells of proximal tubules of the kidneys of 7 cats and hepatocytes of the liver of S cats. These inclusions could be seen wlth H&E, but were more prominent with orcein staining. Two high dose cats had granulomas and connective tissue hyperplasia between tubules of the kidneys. Periportal hepatocyte vacuolization was observed in the liver of 22 cats. Vacuolization of seminiferous tubules and a reduced number of spermatogonia(indicative of reduced spermatogenesis) were found in the testis of 5 treated cats. Cystic ovaries were observed in 3 high dose cats and poor development of oogonia was found in 2 cats. The diagnosis of lead toxicity in cats can be suspected on the basis of the histopathologic lesions described, and can be of value in contributing to a diagnosis. A reliable diagnosis of lead poisoning can be helped utilizing tissue lead analysis(post molten)

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The Preventive Measures On Terrorism Against Overseas Korean Businessmen(A view of recent ethnic minority separation movement) (해외근무(海外覲務) 기업체(企業體)에 대(對)한 테러 방지책(防止策) - 최근(最近) 소수민족분리주의운동지역(小數民族分離主義運動地域)을 중심(中心)으로 -)

  • Choi, Yoon-Soo
    • Korean Security Journal
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    • no.1
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    • pp.351-370
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    • 1997
  • This study concerns possible measures to prevent separatists' terrorist acts against overseas Korean businessmen. Of late, many Korean enterprises are helping a number of foreign countries develop their economy, by building factories and manning regional offices in those countries. But recent development of terrorism especially against Korean businessmen is alarming. This report discusses the need for Korean enterprises heading overseas to prepare themselves with awareness of terrorism and possible protective measures against it, besides their routine pursuance of profits; and for the government and prospective enterprises to refrain from investing in those countries having active separatist movements. If an investment has become inevitable, a careful survey of the region in conflict should be conducted and self-protective measures should be put in place through security information exchange, emergency coordination and training of personnel, etc. This study will first review the past terrorist incidents involving employees of overseas Korean enterprises, and then will focuss on seeking effective measures on the basis of the reported incidents. In carrying out the study, related literature from both home and abroad have been used along with the preliminary materials reported and known on the Internet from recent incidents. 1. The separatist movements of minority groups Lately, minority separatist groups are increasingly resorting to terrorism to draw international attention with the political aim of gaining extended self rule or independence. 2. The state of terrorism against overseas Korean enterprises and Koreans Korean enterprises are now operating businesses, and having their own personnel stationed, in 85 countries including those in South East Asia and Middle East regions. In Sri Lanka, where a Korean enterprise recently became a target of terrorist bombing, there are 75 business firms from Korea and some 700 Korean employees are stationed as of August 1996. A total of 19 different terrorist incidents have taken place against Koreans abroad since 1990. 3. Terrorism preventive measures Terrorism preventive measures are discussed in two ways: measures by the government and by the enterprises. ${\blacktriangleleft}$ Measures by the government - Possible measures at governmental level can include collection and dissemination of terrorist activity information. Emphasis should be given to the information on North Korean activities in particular. ${\blacktriangleleft}$ Measures by individual enterprises - Organizational security plan must be established by individual enterprises and there should also be an increase of security budget. A reason for reluctant effort toward positive security plan is the perception that the security budget is not immediately linked to an increment of profit gain. Ensuring safety for overseas personnel is a fundamental obligation of an enterprise. Consultation and information exchange on security plan, and an emergency support system at a threat to security must be sought after and implemented. 4. Conclusion Today's terrorism varies widely depending on reasons and causes, and its means has become increasingly informationalized and scientific as well while its method is becoming more clandestine and violent. Terrorist organizations are increasingly aiming at enterprises for acquisition of budgets needed for their activities. Korean enterprises have extended their business realm to foreign countries since 1970, exposing themselves to terrorism. Enterprises and their employees, therefore, should establish their own security measures on the one hand while the government must provide general measures, on the other, for the protection of the life and property of Korean residents abroad from terrorist attacks. In this regard, set-up of a counter terrorist organization that coordinates the efforts of government authorities in various levels in planning and executing counter terrorist measures is desired. Since 1965, when the hostile North Korea began to step up its terrorist activities against South Koreans, there have been 7 different occasions of assassination attempt on South Korean presidents and some 500 cases of various kidnappings and attempted kidnappings. North Korea, nervous over the continued economic growth and social stabilization of South Korea, is now concentrating its efforts in the destruction and deterioration of the national power of South Korea for its earlier realization of reunification by force. The possibility of North Korean terrorism can be divided into external terrorist acts and internal terrorist acts depending on the nationality of the terrorists it uses. The external terrorist acts include those committed directly by North Korean agents in South Korea and abroad and those committed by dissident Koreans, hired Korean residents, or international professionals or independent international terrorists bought or instigated by North Korea. To protect the life and property of Korean enterprises and their employees abroad from the threat of terrorism, the government's administrative support and the organizational efforts of enterprises should necessarily be directed toward the planning of proper security measures and training of employees. Also, proper actions should be taken against possible terrorist acts toward Korean business employees abroad as long as there are ongoing hostilities from minority groups against their governments.

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Parasympathetic Modulation Plays a Key Role in Initiation of Paroxysmal Atrial Fibrillation

  • Lee, Won-Jae;Shin, Dong-Gu;Hong, Geu-Ru;Park, Jong-Sun;Kim, Young-Jo
    • Journal of Yeungnam Medical Science
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    • v.24 no.2
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    • pp.216-231
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    • 2007
  • Background : An acceleration or deceleration of the heart rate (HR), which reflects autonomic effects, is observed before the onset of paroxysmal atrial fibrillation (PAF). The purpose of this study was to assess the discrepancy in the autonomic interactions before the onset of PAF for different patterns of change in the HR. Materials and Methods : From 105 Holter tapes with the PAF recorded, 55 episodes (42 patients, 34 men, $58{\pm}12$ years) of PAF (>5 min), preceded by a sinus rhythm for more than 1 hour, were selected and submitted to time-domain and frequency-domain HR variability analyses. Fifty-five episodes were divided into 2 groups: group A PAF (n=30) with acceleration of the HR during the last 2 minutes before the PAF and group B (n=25) with deceleration of the HR. Results : A significant linear decrease in the mean R-R interval was observed in group A ($924{\pm}30$ to $835{\pm}28ms$, $P$=0.001) and an increase from $831{\pm}32$ to $866{\pm}31ms$ in group B PAF episodes ($P$=0.046). In the frequency-domain analyses, the LF/HF ratio exhibited a progressive linear increase before the PAF in group A ($P$=0.005). The HF normalized units (HFnu) and natural logarithm-transformed HF ($In$HF) values decreased from $30.8{\pm}4.0$ to $16.1{\pm}1.8$ ($P$=0.003) and $4.49{\pm}0.25$ to $4.07{\pm}0.22$ ($P$=0.001), respectively. Contrary to the results in group A, a significant increase in the HF components (HFnu and $In$HF) (from $22.6{\pm}3.2$ to $30.2{\pm}4.0$, $P$=0.005, and $4.27{\pm}0.27$ to 4.75 0.33, $P$=0.001, respectively) and a resultant decrease in the LF/HF ratio were observed in group B PAF episodes. No significant changes were observed in the LF components in either PAF group. Conclusion : Autonomic stimuli leading to an acceleration or deceleration of the HR before the onset of AF are due to parasympathetic modulation. Parasympathetic modulation plays a key role in the initiation of PAF.

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Multiple Binding Affinities for Muscarinic Acetylcholine Receptors in Rat Brain (흰쥐 뇌내(腦內)의 무수카린성 콜린 수용체의 이질성(異質性))

  • Lee, Jong-Hwa;El-Fakahany, Esam E.
    • The Korean Journal of Pharmacology
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    • v.23 no.2
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    • pp.101-111
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    • 1987
  • We investigated the binding properties of $(^3H)$ QNB and $(^3H)$ NMS to mAchR to elucidate the characterstics of mAchR in rat brain by using two different preparations (homogemates & intact brain cell aggregates). The binding properties of both ligands demonstrated high affinity and saturability in both experiments, however $(^3H)$ QNB showed a significantly higher maximal binding capacity than tha ot $(^3H)$ NMS 1. In rat brain homogenates; Displacement of both lignands with several mAchR antagonists resulted in competition curves in accoradnce with the law of massaction for QNB, atropine & scopolamine in thie preparation, also a similar profile was found for the quaternary ammonium analogs of atropine & scopolamine (methyl atropine & methylscopolamine) when $(^3H)$ NMS was used to label the receptors in rat brain. But when these hydrophillic antagonists were used to displace $(^3H)$ QNB, they showed interaction with high- and low-affinity binding sites in brain homogenates. Pirenzepine, the nonclassical mAchR antagonist, was able to displace both ligands from binding sites in this preparation. 2. In intact rat brain cell aggregates; Intact bain cell aggregates were used to elucidate the binding characteristics of $(^3H)$ NMS to mAchR in rat. The magnitude of binding of this ligand was related linearly to the amount of cell protein in the binding assay with a high ratio of total to nonspecific binding. mAchR antagonists displaced specific $(^3H)$ NMS binding according to the law of mass-action, while it was possible to resolve displacement curves using mAchR agonist into high-& low-affinity component. 3. Our results indicate that more hydrophilic receptor ligand $(^3H)$ QNB, displacement experiments in both tissues demonstrated that the lipid solubility of a particulr mAchR ligand might play an important role in determining its profile of binding to the mAchR, and the concentrations of mAchR in rat brain are both on the cell surface (membrane-bound receptor) and in the intracelluar membrane (intermembrane-bound receptor). 4. The results are discussed in terms of the usefulness of dissociated intact rat brain cells in studying mAchR in central nervous system.

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Preliminary Results of Management for Primary CNS Lymphoma (원발성 중추신경계 림프종의 치료에 관한 예비적 결과)

  • Ahn, Seung-Do;Chang, Hye-Sook;Choi, Eun-Kyong
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.79-82
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    • 1993
  • From October 1989 to March 1992, ten patients diagnosed as primary central nervous system (CNS) lymphoma were treated with radiation therapy at Asan Medical Center. To obtain pathologic diagnosis, five patients had stereotactic biopsy and the others underwent craniotomy & tumor removal. According to the classification by International Working Formulation, seven of 10 patients showed diffuse large cell types and the remaining 3 had diffuse mixed cell types. Computed tomographic scans of the brain disclosed solitary (6 cases) or multiple (4 cases) intracranial lesions. All patients received 4000 cGy/20 fx to the whole brain followed by an additional 2000 cGy/10 fx boost to the primary lesion. Six patients with initial cerebrospinal fluid (CSF involvement were treated with whole brain irradiation and intrathecal Methotrexate (IT-MTX) chemotherapy. One of them received an additional spinal irradiation after 3 cycles of IT-MTX chemotherapy because of MTX induced arachnoiditis. One patient received 3 cycles of systemic chemotherapy prior to rodiation therapy and one received 5 cycles of salvage chemotherapy for recurrence. With a median follow up time of 8 months, all patients were followed from 7 to 26 months. Radiologically seven patients showed complete remission and the remaining three showed partial remission at one month after radiotherapy. The 1 and 2 year survival rate was $86{\%}\;and\;69{\%}$ respectively. Until now, two patients expired at 7 and 14 months. These patients developed extensive CSF seeding followed by local failure. Considering initial good response to radiation therapy and low incidence of extraneural dissemination in primary CNS lymphoma, we propose to increase total tumor dose to the primary lesion by hyperfractionated radiotherapy or stereotactic radiosurgery. For the patients with CSF involvement at diagnosis, we propose craniospinal irradiation with IT MTX chemotherapy.

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Expression of Jun and p53 Genes from the Brain of Rats Irradiated with $^{60}Co{\gamma}$-ray (감마선 조사에 의한 뇌조직의 Jun 및 p53유전자 발현)

  • Kim Yong Seok;Woo Chong Kyu;Lee Yong Sung;Koh Jai Kyung;Chun Ha Chung;Lee Myung Za
    • Radiation Oncology Journal
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    • v.14 no.4
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    • pp.265-279
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    • 1996
  • Damage produced by radiation elicits a complex response in mammalian cells, including growth rate changes and the induction of a variety of genes associated with growth control and apoptosis. At doses of 10,000 cGy or greater, the exposed individual was killed in a matter of minutes to a couple of days, with symptoms consistent with pathology of the central nervous system(CNS) including degenerative changes. The nature of the damage in irradiated cells underlies the unique hazards of ionizing radiation. Radiation injury to CNS is a rare event in clinical medicine, but it is catastrophic for the patient in whom it occurs. The incidence of cerebral necrosis has been reported as high as 16% for doses greater than 6,000 cGy. In this study, the effect of radiation on brain tissue was studied in vivo. Jun and p53 genes in the rat brain were induced by whole body irradiation of rat with 600Co in doses between 1 Gy and 100 Gy and analyzed for expression of jun and p53 genes at the postirradiation time up to 6 hours. Northern analyses were done using 1.8 Kb & 0.8 Kb-pGEM-2-JUN/Eco RI/Pst I fragments, 2.0 Kb-php53B/Bam HI fragment and ,1.1 Kb-pBluescript SK--ACTIN/Eco RI fragment as the digoxigenin or [${\alpha}^{32}P$] dCTPlabeled probes for Jun, p53 and ${\beta}$-actin genes, respectively. Jun gene seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 1 hour after irradiation of $^{60}$Co in dose of 30 Gy. Jun was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in doses of 1 Gy and 10 Gy. After irradiation of $^{60}$Co in dose between 20 Gr and 100 Gy, the expression of Jun was however increased to peak in 2 hours and decreased thereafter. p53 gene in this study also seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 6 hours after irradiation of $^{60}$Co in dose of 1 Gy, p53 was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in dose between 1 Gy and 40 Gy. After irradiation of $^{60}$Co in doses of 50 Gy and 100 Gy, the expression of p53 was however increased to peak in 2 hours and decreased thereafter. The expression of Jun and p53 genes was not correlative in the brain tissue from rats. It seemed to be very important for the establishment of the optimum conditions for the animal studies relevant to the responses of genes inducible on DNA damage to ionizing radiation in mammalian cells. But there are many limitations to the animal studies such as the ununiform patterns of gene expression from the tissue because of its complex compositions. It is necessary to overcome the limitations for development of in situ Northern analysis.

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Video Assisted Thoracoscopic Sympathetic Ramus Clipping in Essential Hyperhidrosis -Cadaver Fitting Test and Clinical Application (다한증 환자에서 클립을 이용한 교감신경 교통가지 차단술 -사체 연구 및 임상적용-)

  • Lee, Sung-Ho;Cho, Seong-Joon;Jung, Jae-Seung;Kim, Tae-Sik;Son, Ho-Sung;Sun, Kyung;Kim, Kwang-Taik;Kim, Hyoung-Mook
    • Journal of Chest Surgery
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    • v.36 no.8
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    • pp.595-601
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    • 2003
  • Background: It has been known that the most effective treatment method of hyperhidrosis is video-assisted thoracoscopic sympathetic nerve block. Postoperative compensatory hyperhidrosis and anhidrosis are major factors that decrease the postoperative satisfaction. Although sympathetic rami have been selectively blocked to decrease the complications, technical difficulties and excessive bleeding have prevented the universal application. Material and Method: Three pre-fixative cadavers were dissected before clinical application. Bilateral sympathetic chains were exposed in supine position after the whole anterior chest wall was removed. Second and third sympathetic rami were blocked using clips. After the sympathetic chains including ganglia were removed, we evaluated the extents of rami block. Twenty-five patients were subjected to the clinical application. Surgeries were performed in semi-fowlers position under general anesthesia and bilateral ventilation. 2 mm thoracoscopy and 5 mm trocar were intro-duced through third and fourth intercostal space, respectively. Second and third sympathetic rami were blocked using thoracoscopic clips. The postoperative complications, satisfaction, and compensatory hyperhidrosis rate were evaluated retrospectively. Result: Sympathetic rami were completely blocked in cadaver dissection study Hyper-hidrosis symptom was improved in all patients without operative complication. Operative time was shorter than that of traditional ramicotomy. All patients, except four, were satisfied with postoperative palmar hyperhidrosis. Com-pensatory hyperhidrosis was more severely happened in fifteen patients (60%). The remaining six patients had no complaint. Two patients had a minimal degree of gustatory hyperhidrosis. Conclusion: This operative method had shorter operative time and less complication rate, compared with traditional ramicotomy Operative success rate was similar to the traditional syrnpathicotorny; lower extent and occurrence rate of compensatory hyperhidrosis. The thoracic sympathetic rami clipping was suggested as an alternative method for treatment of palmar hyperhidrosis.

Extracts of Allium fistulosum Attenuates Pro-Inflammatory Action in the Lipopolysaccharide-Stimulated BV2 Microglia Cells (Lipopolysaccharide에 의한 BV2 세포의 염증 반응에 대한 파 추출물의 저해 활성)

  • Park, Shin-Hyoung;Kim, Jung-In;Jeong, Yong-Kee;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.6
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    • pp.796-804
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    • 2011
  • Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

Differential Expression of Chemokine MCP-1, MIP-1α, MIP-2 in Lipopolysaccharide-stimulated Neonatal and Adult Rat Brain (LPS 유도에 의한 신생쥐에서 chemokine의 단계별 발현)

  • Lee, Jong-Hwan
    • Journal of Life Science
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    • v.16 no.5
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    • pp.840-849
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    • 2006
  • Severe brain injuries induced by toxin pose one of the most important problems on our health care because of their high morbidity and mortality, are implicated to leucocyte infiltration more premature or immature brain than mature brain. Chemokines are the induction meditators for infiltration of inflammatory cells to the inflammation sites. In order to study the mechanism of leucocyte infiltration, the expression of several chemokines, MCP-1, $MIP-1{\alpha}$ and MIP-2 was studied in lipopolysaccharide(LPS)-stimulated neonatal and adult brain. One week old Sprague-Dawley rats or adult male rats weighing 300-350 g were used for the experiment. After anesthetization, $1\;{\mu}l$ LPS (0.5 mg/ml) subsequently was injected in the right caudate nucleus of the brain with stereotaxic frame. Animals were sacrificed at 6 hours, 24 hours, and 72 hours after injection. The present study was carried out using RT-PCR for the mRNA and immunohistochemistry for the expression of the proteins. In the neonatal rat brain, prominent interstitial edema with significant accumulation of leukocytes was detected at 24 and 72 hours after LPS injection. A semiquantitative analysis of RT-PCR revealed that the MCP-1, $MIP-1{\alpha}$, and MIP-2 mRNA expression peaked at 24 hours in neonatal and adult rat brain. Neonatal rats showed about 2.6, 1.4, and 1.2 times more expression of the MCP-1, $MIP-1{\alpha}$, and MIP-2 than that of the adult rats in the brain tissue. Immunohistochemical analysis also showed that MCP-1 immunoreactivity was paralleled with the RT-PCR results. MCP-1 protein was significantly detected at 24 and 72 hours in the brain parenchyma. $MIP-1{\alpha}$protein was highly expressed at 24 hours. The results of leukocyte infiltration in H&E stain was parallelled with that of the immunohistochemistry. Chemokine proteins were markedly detected at 24 hours after injection of LPS and neutrophil influx into intraparenchymal was prominent at 24 hours. These results suggest that the leukocyte infiltration in the intracranial infection may be controlled by mechanisms influenced by chemokine producing cells in the central nervous system such as microglia, astrocyte and endothelial cell.

End-of-Life Care Practice in Dying Patients with Do-Not-Resuscitate Order: A Single Center Experience (심폐소생술 금지 동의 후 사망한 환자의 현황과 연명의료 실태 조사: 단일 의료기관 경험)

  • Yoon, Sang Eun;Nam, Eun Mi;Lee, Soon Nam
    • Journal of Hospice and Palliative Care
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    • v.21 no.2
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    • pp.51-57
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    • 2018
  • Purpose: End-of-life (EoL) decisions are challenging and multifaceted for patients and physicians. This study was aimed to explore how EoL care is practiced for patients with a do-not-resuscitate (DNR) order. Methods: We retrospectively analyzed medical records of patients who died after agreeing to a DNR order in 2016 at a university hospital. Characteristics including cause of death, intensity of EoL care, and other factors were reviewed and statistically analyzed. Results: Of total 375 patients, 170 patients (45.3%) died with malignancies, and 205 patients (54.6%) with other causes involving the central nervous system (19.2%), pulmonary (14.7%), cardiologic (6.7%) and infectious (6.4%) conditions. Both the cancer and non-cancer patient groups showed a short duration from DNR to death (median 3 days vs 2 days, P=0.629). An intensive care group comprising patients who received one or more intensive treatments such as ventilator (n=205) showed a higher number of non-cancer patients and a shorter duration from DNR to death than a group that withheld treatment before DNR (P<0.05). Conclusion: EoL decisions were made very late by both cancer and non-cancer patients. About half of the patients did not have cancer, and two-thirds of them decided DNR during intensive treatment. To make a good EoL decision, a shared decision making with patients should be done at an earlier stage.