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Jkns.or.krLetters to the Editor
The authors well present that in vitro cytotoxicity by com- bination of chemotherapeutic agents with anti-malaria drugs against malignant glioma cell lines. The cell viability was found to be markedly decreased when hydroxychloroquine was addedon malignant glioma cell lines. The possible mechanism in their experiments is to bind P-glycoprotein (P-gp) and competiti- To the Editor : We have read the paper by Yong Sook Park, vely interact with chemotherapeutic agents-binding site of P-gp.
and colleagues (Jea Young Choi, Jong Hee Chang, Yong Gou As result, anti-malaria drugs enhance the intracellular conc- Park, Jin Woo Chang : Effects of Hydroxychloroquine Co- entration of cytotoxic drugs. This is a nice experimental pre- administered with Chemotherapeutic Agents on Malignant clinical work. It would be of interest to know this drug com- Glioma Cell Lines : in vitro Study. J Korean Neurosurg Soc bination had similar effects in glioma model (in vivo study).
We’d like to say one more things. The authors are looking atthe interaction of two agents (chemotherapeutic agents and Abstract
anti-malaria drugs) and need to determine if the effects are sy- Objective : Anti-malaria drugs may modulate tumor resistance
nergistic or additive1-3). There are statistical methods for doing to chemotherapeutic agents, but it has not been proven effective this (such as isobologram method). This type of analysis needs in the treatment of malignant gliomas. The aim of this study to be done since the implications of something being syner- was to determine whether adequate pre-clinical data on co- gistic is different from just being additive and it could have administration of chemotherapeutic agents with anti-malaria mech-anistic implications as well. Anyway, thanks again and drugs on malignant cell lines could be obtained that would congratulations for their great experimentation.
warrant its further potential consideration for use in a clinicaltrial for malignant gliomas.
Methods : Two malignant glioma cell lines (U87MG, T98G)
1. Achenbach TV, Muller R, Slater EP : Synergistic antitumor effect of chemotherapy and antisense-mediated ablation of the cell cycle inh- were treated with chemotherapeutic agents alone or with an- ibitor p27KIP-1. Clin Cancer Res 6 : 3006-3014, 2000
timalaria drugs. Cells were incubated with drugs for 4 days.
2. Jain A, Slansky JE, Matey LC, Allen HE, Pardoll DM, Schulick RD : Synergistic effect of a granulocyte-macrophage colony-stimulating Following the 4-day incubation, drug sensitivity assays were factor-transduced tumor vaccine and systemic interleukin-2 in the performed using 3-(4,5-dimethyl-2-thiazol-2-yl) 2,5-diphe- treatment of murine colorectal cancer hepatic metastases. Ann Surg
Oncol 10 : 810-820, 2003
nyltetrazolium bromide (MTT) assay following optimization 3. Kang SG, Kim JS, Park K, Kim JS, Groves MD, Nam DH : Comb- of experimental conditions for each cell lines and cell viability ination celecoxib and temozolomide in C6 rat glioma orthotopic model.
Oncol Rep 15 : in press, 2006
Results : In all of four chemotherapeutic agents(doxorubicin,
vincrisitne, nimustine, and cisplatin), the cell viability was found
The Catholic University of Korea College of Medicine to be markedly decreased when hydroxychloroquine was co- administered on both U87MG and T98G cell lines. The twoway analysis of variance(ANOVA) yielded a statistically sign-ificant two-sided p-value of 0.0033(doxorubicin), 0.0005(vincrisitne), 0.0007(nimustine), and 0.0003(cisplatin) on Preliminary Study on Effectiveness of De- U87MG cell lines and .0006(doxorubicin), .0421(vincrisitne), 0.0317(nimustine), and 0.0001(cisplatin) on T98G cell lines, respectively. However, treatment with chloroquine and prim-aquine did not induce a decrease in cell viability on both U8- 7MG and T98G cell lines.
Conclusion : Our data support further consideration of the use
To the Editor : I read with interest Shin et al’ study concer- of hydroxychloroquine prior to systemic chemotherapy to max- ning preliminary result on effectiveness of dexamethasone- imize its tumoricidal effect for patients with malignant gliomas.
soaked gelatin sponges for reducing pain after lumbar micr- Letters to the Editor
odiscectomy. (J Korean Neurosurgical Soc 39 : 11-15, 2006).
associated with the use of Gelfoam. Spine 26 : 485-487, 2001
3. Herndon JH, Grillo HC, Riseborough EJ, Rich JC Jr : Compression Their study is very nicely designed and suggests interesting of the brain and spinal cord following use of Gelfoam. Arch Surg
results although based on preliminary result. 104 :107, 1972
Gelfoam absorbs blood and may expand, especially in the partially moistened status2). Because of this property, Gelfoam should be used in small pieces and should not be used within enclosed spaces. Gelfoam within enclosed space could causedisastrous complications in both brain and spine surgeries1-3).
Response : We wish to thank for your kind interest in our According to the pharmaceutical information provided by paper. It is our pleasure to discuss with a scientific physician, Pharmacia & Upjohn, it is recommended that whenever pos- and to get another chance to express our opinions. Pain is sible, it should be removed after use in laminectomy proced- necessary for survival, but chronic pain can result in anxiety, ures and from foramina in bone, once hemostasis is achieved.
depression and a reduction in the quality of life. If we can This is because expanded Gelfoam could produce nerve damage remove this pain from the life of human beings, our lives will by pressure within confined bony spaces. Therefore, I recom- be tremendously comfortable. This is why spinal surgenon mend the authors to stop using dexamethasone-soaked Gel- should exist. However it still remains most difficult in the field foam in lumbar microdiscectomy although luckily they have of medicine to understand pain. Since Mixter and Barr, our not experienced complications related Gelfoam until now. I great ancestors, found that mechanical compression of nerve myself also use thrombin-soaked Gelfoam during microdisc- root could be a major cause of pain in intervertebral disc disase, ectomy to control epidural bleeding. However, I always remove these concept has been a solid base for spinal operations. But, Gelfoam once hemostasis is achieved, because Gelfoam in lateral we are often confused when a patient complains severe radi- recess can cause severe root compression as mentioned before.
cular pain without obvious herniation of his or her interver- To my clinical experience, patients usually do not complain tebral disc or a person do not have any pain in spite of marked leg pain immediately after microdiscectomy when appropriate herniation. Disc herniation and lumbar spinal stenosis is known decompression of root is performed during surgery. Some to present in between 20 and 50% of asymptomatic subjects1,5).
patients complain mild tingling sensation or numbness after Also, Boos et al. reported 76% incidence rate of disc hernia- surgery, which usually improve spontaneously in time. When tions in asymptomatic patients3). These findings suggest that patient complains moderate leg pain after microdiscectomy, the presence of other factors above mechanical compression.
I consider the possibility of incomplete root compression due Recent studies have identified cells and molecules contribut- to remained disc herniation or postoperative epidural hema- ing to pain4). We often neglect these facts, and sometimes toma. Therefore, in such cases, I usually perform postopera- make a mistake to guide patients to unnecessary surgery. It tive magnetic resonance image or computed tomography scans is known that there are the unmyelinated nerve terminals, as to confirm whether decompression of the root was complete you know, bathed in by the interstitial fluid within the tissues or not. According to the result of Shin et al’s study, the mean in both the interstitial and perivascular receptor systems of the postoperative visual analogue scale score(VAS) of leg pain at spine2). They are exposed to all solutes present within that day 1 in control group was 5.0 (This means moderate leg pain, interstitial fluid. If these solutes are depolarizing agents, and I think). The decrease of VAS score of leg pain was less than if they accumulate in sufficient quantities, then chemical irr- expected (from 8.5 to 5.0). Therefore, I wonder whether the itation of the nociceptors will occur and will give rise to pain authors perform foraminotomy during microdiscectomy. I in the lower back. Some of the known chemical irritants include think it better to perform foraminotomy thoroughly rather prostaglandin E, potassium ion, histamine, substance P, and than to use dexamethasone-soaked Gelfoam during microd- vasoactive-intestinal peptide6,7). The dead space which is formed after decompression can be filled with these chemicals especiallyin immediate postop period. In addition, radicular pain of References
intervertebral disc disease has not only the characteristics of 1. Alander DH, Stauffer ES : Gelfoam-induced acute quadriparesis nociceptive pain, which is activated by a terminal of pain system, after cervical decompression and fusion. Spine 20 : 970-971, 1995
2. Friedman J, Whitecloud TS 3rd : Lumbar cauda equina syndrome but also those of neuropathic pain, which is activated by a tract Letters to the Editor
of pain system (the nerve root is not a terminal, it is a kind of that effective decompression is always able to remove radicular tract), so the pain will not easily surrender to a physician who pain of intervertebral disc disease. We would like to emphasize is armed only with removal of noxious stimulus. We think those that overlooked insights of chemical factors of pain will partly can be a potential source of persistent pain and numbness in alter our approach to spinal pain control and enable the dev- post-laminectomy patients. Our study was performed to de- elopment of new treatments. Thanks again for your comments.
velop a method to efficiently remove chemical factors. As youpointed out, the immediate pain scores of the control group References
was somewhat higher than usual laminectomy series. But it 1. Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW : Abn- ormal magnetic-resonance scans of the lumbar spine in asymptom- was derived from not using patient controlled analgesia(PCA) atic subjects. A prospective investigation. J Bone Joint Surg 72A :
system, and not using strong analgesics including opioids. We 2. Bogduk N, Tynan W, Wilson AS : The nerve supply to the human did not use those for not masking the true effects of our de- lumbar intervertebral discs. J Anat 132 : 39-56, 1981
xamethasone-soaked gelatine sponges. In our investigative stage, 3. Boos N, Rieder R, Schade V, Spratt KF, Semmer N, Aebi M : 1995 Volvo Award in clinical sciences. The diagnostic accuracy of ma- we also found that gelatine sponge can cause serious compl- gnetic resonance imaging, work perception, and psychosocial fact- ications in very rare circumstances. For preventing complic- ors in identifying symptomatic disc herniations. Spine 20 : 2613-
ations, we did not use this in patients with diabetes mellitus, 4. Hunt SP, Mantyh PW : The molecular dynamics of pain control.
old ages, poor general health status, and previous operations Nat Rev Neurosci 2 : 83-91, 2001
5. Kent DL, Haynor DR, Larson EB, Deyo RA : Diagnosis of lumbar in same site, because in these patients serious infection could spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, be happened. Also, we had performed routine foraminotomy, and myelography. AJR Am J Roentgenol 158 : 1135-1144, 1992
6. Saal JS, Franson RC, Dobrow R, Saal JA, White AH, Goldthwaite which you worried about, and applied gelatine sponges after N : High levels of inflammatory phospholipase A2 activity in lumbar full decompression and meticulous hemostasis for not exerting disc herniations. Spine 15 : 674-678, 1990
7. Weinstein J, Claverie W, Gibson S : The pain of discography. Spine
mass effects. Currently we are searching for various methods 13 : 1344-1348, 1988
minimizing inflammatory responses and preventing postop-erative adhesions, for example, tissue-engineered autologous fat tissues which temporarily secrets analgesics or steroid. In conclusion, on the contrary to your experience, we don’t think
e-Circus internal meeting : Monday 8th May 2006 10:30 - 12:30 Present: Sarah, Scott, Steve, Megan, Rafal, Kerstin Purpose of meeting: review progress with: scenarios, refugee workshop plans. Receive report from Steve. Items covered • scenarios (cultural issues; fleshing of scenarios) • refugee workshop • report from Steve • I Power I National Anti-Bullying Conf.