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The Determination of Blood-Brain Barrier Permeability and Pharmacokinetics of a Rat Transferrin Receptor Monoclonal Antibody by Brain Perfusion Method and Intravenous Injection Technique in Mice (마우스에서 뇌관류법과 정맥투여법에 의하여 흰쥐 트란스페린 단일항체의 체내동태 및 혈액-뇌 관문 투과성의 검토)

  • 강영숙
    • Biomolecules & Therapeutics
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    • v.10 no.1
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    • pp.37-42
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    • 2002
  • Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [$^{}125}I$] 8D3 in Balb/c mice. Brain uptake of [$^{}125}I$] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [$^{}125}I$] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [$^{}125}I$] 8D3 was $0.50{\pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [$^{}125}I$] 8D3 in brain was $22.3 {\mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice.

A Case of Successful Endoscopic and Conservative Treatment for Intentional Ingestion of Sharp Foreign Bodies in the Alimentary Tract (고의로 섭취한 커터칼날의 내시경 및 보존적 치료 증례 보고)

  • Park, Jong-Min;Kim, Seong Yup;Chung, Il Yong;Kim, Woo-Shik;Shin, Yong-Chul;Kim, Yeong Cheol;Park, Sei Hyeog
    • Journal of Trauma and Injury
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    • v.26 no.4
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    • pp.304-307
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    • 2013
  • Food bolus impaction is the most common cause of esophageal foreign body obstruction in adults. Other causes include intentional ingestion in psychiatric patients or prison inmates. We experienced successful treatment of a patient with intentional ingestion of multiple sharp foreign bodies(25 cutter and razor fragments). A 47-year-old male patient who was suffering from chronic alcoholism was admitted, via the emergency room, with dysphagia and neck pain. He was suffering from alcoholic liver cirrhosis and psychiatric problems, such as chronic alcoholism, anxiety disorder and insomnia. The patient had intended to leave the hospital after having swallowed the sharp objects. Plain radiographs and computed tomography (CT) scan showed multiple, scattered metal fragments in the esophagus, stomach, and small bowel. We performed emergent endoscopy and successfully removed one impacted blade in the upper esophagus using by a snare with an overtube. The rest of the fragments had already passed through the pylorus, so we could not find them with endoscopy. We checked the patient with simple abdominal radiographs and careful physical examinations every day. All remaining fragments were uneventfully excreted through stool during the patient's 6 day hospital stay. Finally, we were able to confirm the presence of the objects in the stool, and radiographs were negative. The patient was discharged without complications after 14 days hospital stay and then was followed by the Department of Psychiatry.

The Effect of Ipidural Pain Block After Thoracotomy (개흉술후 지속적 경막외마취가 통증감소에 미치는 영향)

  • 최덕영;원경준
    • Journal of Chest Surgery
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    • v.30 no.8
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    • pp.809-814
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    • 1997
  • Continuous epidural pain block with a local anesthetic agents is a commonly employed technique for pain relief after thoracotomy. In this study, we evaluated the effectiveness of the continuous epidural pain block in 19 patients undergoing elective lateral or posterolatrral thoracotomy with control group(n=19) from November 1994 to July 1995, Epidural lidocaine and morphine mixtures were injected via an epidural catheter as a bolus after operation, and then bupivacaine and morphine mixtures were injected continuously following 5 or 6 days. The pain score, upper arm elevation(ROM score), and respiratory rate were significantly changed(P<0.05) from 30min after injection. The CO2 tension of arterial blood was decreased significantly(P<0.05) from 2hr after injection. The postoperative hospital days were decreased significantly(P<0.05). Side effects of the epidural pain block were urinary retention(n= 10), urticaria(n=2) and a case of headache. There was no postoperative lung atelectasis. We conclude that the continuous epidural pain block is good for prevention of the postoperative lung complication and early recovery after thoracotomy.

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Hepatoscintiangiography of Normal Liver and Its Alteration in Hepatomas and Liver Abscess (간혈관신티그램의 정상성과 간암 및 간농양에서의 변화)

  • Bahk, Yong-Whee;Chung, Soo-Kyo
    • The Korean Journal of Nuclear Medicine
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    • v.20 no.1
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    • pp.25-31
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    • 1986
  • This study was performed to establish normal hepatoscintiangiographic(HSA) pattern of hepatic blood flow and to investigate dynamic differential HSA findings of primary and metastatic carcinomas and abscess of the liver. HSA was carried out after intravenous bolus injection of 10 mCi of Tc-99m-phytate by obtaining sequential anterior images of 1-second exposure for 16 seconds. Observations included (1) baseline study of normal hepatic blood flow pattern by correlating with contrast angiogram, (2) time sequence phasing of normal HSA, and (3) analysis of altered patterns in primary and metastatic carcinomas and abscesses of the liver. Materials consisted of 20 normal subjects, 28 primary hepatocellular carcinomas, 16 metastatic carcinomas and 7 liver abscesses. Results were: (1) Normal HSA demonstrated 3 distinct phases of arterialization(AP), of arterial hepatogram(AHP), and of portal venous hepatogram(PVHP). The means of each phase were 5.3, 6.3 and 8.3 seconds, respectively. Portal vein could be seen in all but one of 20 normal subjects. (2) Pattern changes in diseases groups were early start of AP in carcinomas and very early start of AP in abscesses. AP became prolonged in all disease group. (3) Distinction between AHP was sharp in metastasis and abscesses but un sharp in primary hepatoma. Cold area or areas became vascularized in primary hepatoma but not in abscess. Cold areas of metastasis were inhomogeneously vascularized in late AP and throughout AHP and became relatively vascular as PVHP began. The cold area of abscess showed rim enhancement during AH and APH. These differences in HSA pattern were very useful in differential diagnosis of the diseases studied.

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The Effect of Continuous Infusion of Ketorolac on Morphine IV PCA (Ketorolac의 지속적 정주가 Morphine정맥 PCA에 미치는 효과)

  • Choi, Duck-Hwan;Chung, Ik-Soo;Kim, Seung-Oh
    • The Korean Journal of Pain
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    • v.10 no.2
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    • pp.179-184
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    • 1997
  • Background: Ketorolac($Tarasyn^{(R)}$) is a non-steroidal anti-inflammatory drug(NSAID) which has shown to be an effective postoperative analgesic available parenterally, and when combined with morphine can reduce its requirement. The analgesic efficacy and adverse effects of continuous infusion of ketorolac added to morphine IV PCA was evaluated in 60 women after abdominal hysterectomy. Methods: Patients were assigned to receive either morphine intravenous(IV) bolus followed by morphine IV patient controlled analgesia(PCA), or ketorolac 30mg IV and continuous IV infusion at 4.0mg/hr in combination with the above regimen. The authors evaluated PCA morphine used, pain assessment(verbal pain intensity score and visual analogue scale) and side effects at 2, 4, 6 and 24hrs during pain control. Results: Continuous infusion of ketorolac decreased the PCA morphine usage significantly(30.4 ---> 19.6 mg : p=0.007) at 24hrs postoperatively. Significant differences were seen favoring ketorolac infusion in pain intensity and visual analogue scale both at rest and during movement. There were no differences in incidences of deep sedation, nausea & vomiting. But the ketorolac group they complained of dizziness more than morphine only group. Little pruritus was recorded in either groups. Conclusions: The authors conclude continuous IV infusion of ketorolac in conjunction with morphine PCA provide effective analgesia after low abdominal surgery.

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Effects of Morphine and Morphine-Ketorolac Tromethamine Intravenous Infusion for Postoperative Pain (Morphine과 Morphine-Ketorolac Tromethamine의 지속적 정주에 의한 술후 통증치료 효과 비교)

  • Lee, Kwang-Su;Lee, Kang-Chang;Song, Yoon-Kang;Kim, Tai-Yo;Yun, Jae-Seung
    • The Korean Journal of Pain
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    • v.8 no.1
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    • pp.37-42
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    • 1995
  • The intermittent injection of analgesics is a inadquate method for postoperative pain control. Recently a non-electroic, disposable and portable infusor (Boxter Two Day $Infusor^R$) has been developed which can deliver analgesics with 2 ml/h speed continuousely. The present study examined the effects of three methods of pain management on recovery in 306 patients undergoing elective surgery in Wonkwang University Hospital. Group 1 (n=106) received i.m. $Valentac^R$ on a PRN basis. Group 2 (n=100), initial 2 mg of bolus morphine was followed by 48 mg of continuous infusion. Group 3 (n=100), initial 2 mg of morphine followed by morphine 18 mg-ketorolac 120 mg. We evaluated an analgesic efficacy with NRS (numerical rating scale) at 12, 24, 36, 48, 60 and 72 hours after the operation. The side effects (nausea, vomiting, pruritus, sedation and respiratory depression) were evaluated. In group 1, we asked major concern before operation and efficacy of pain control with pain severity (no pain, mild pain, moderate pain, sever pain). The results were as follows: 1) Major concern before operation is pain (40%). 2) 53% of patients suffered pain in group 1. 3) Morphine and morphine-ketorolac infusion groups were superior to the i. m. ($Valentac^R$) group with respect to postoperative analgesia. 4) In group 3 (morphine-ketorolac), there was no pruritus and mild nausea and vomiting.

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Terminal Cancer Pain Management by Tunnelled Epidural Catheter (경막외 도관 피하매몰법에 의한 말기암환자의 통증조절)

  • Ryu, Sie-Jeong;Han, Sang-Mi;Kim, Doo-Sik;Park, Se-Hoon;Kim, Kyung-Han;Jang, Tae-Ho;Kim, Se-Hwan;Park, Jung-Kie
    • The Korean Journal of Pain
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    • v.12 no.1
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    • pp.95-100
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    • 1999
  • Background: About 75% of terminal cancer patients have severe pain. For the treatment of these patients, physicians usually use potent opioid analgesics. But many of the cancer patients were not controlled by IV or IM injection of opioids. In spite of the untreatable nature of the patient's illness, they should be hospitalized only for pain control. In that case, epidural opioid injection is one of the most effective methods in pain management. Methods: We retrospectively analyzed 126 terminal cancer patients who were treated with epidural morphine for pain management from 1993-97. In the routine procedure, an epidural catheter was inserted into the epidural space and tunnelled subcutaneously, exiting out from the anterior chest or abdomen. Morphine was used as the main analgesic and Multiday Infusor$^{(R)}$ (Baxter, 0.5 ml/h) as a continuous infusion system. Results: 1. Mean treatment time was 55 days (range; 3~373). 2. Mean daily epidural start mg dose of morphine was 8 mg (range; 2~20). 3. Mean daily dose at termination was 19 mg (range; 4~60) 4. 94 patients were controlled with continuous infusion but 32 patients needed additional bolus doses of morphine. 5. heter-associated subcutaneous infection occurred in 2 patients (1.6%). Conclusion: Terminal cancer pain management administered by a tunnelled epidural catheter is a simple, inexpensive method with a very small rate of infection.

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Effects of Preoperative Epidural Block with Low Dose Bupivacaine and Morphine on Postoperative Pain, Plasma Cortisol and Serum Glucose in Total Abdominal Hysterectomy (복식전자궁적출술에서 술전 저용량 국소마취제와 Morphine을 이용한 경막외차단이 술후통증, 혈장 Cortisol, 혈당에 미치는 영향)

  • Park, Han-Suk;Lee, Sung-Chul;Cha, Moon-Seok
    • The Korean Journal of Pain
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    • v.12 no.1
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    • pp.21-26
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    • 1999
  • Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of central nervous system (CNS) and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative low dose epidural bupivacaine and morphine could affect postoperative pain, changes plasma cortisol, and serum glucose. Methods: Thirty patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. General anesthesia was induced in all patients and after that, epidural blocks were done except the control group (n=10) patients. Preoperative block group (n=10) received 0.5% bupivacaine 50 mg and morphine 2 mg epidurally as a bolus before operation and followed by 0.1% bupivacaine $5\;mghr^{-1}$ and morphine $0.2\;mghr^{-1}$ for 10 hours. Postoperative block group (n=10) received the same doses of bupivacaine and morphine under the same method postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative pain by visual analogue scores (VAS), analgesic requirement (first requirement time, total amounts used), side effects, plasma cortisol level and serum glucose level were compared. Results: Until postoperative 6 hrs, VAS of control group was higher than those of the epidural groups. No difference was observed in VAS between the two epidural groups. First analgesics requirement time and total amounts of used analgesics were not different between the two epidural groups, but first analgesic requirement time of preoperative block group was significantly prolonged compared with control group. Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Low dose preoperative epidural bupivacaine and morphine could not reduce postoperative pain, plasma cortisol level and serum glucose level compared with postoperative block group.

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Clinical Experience on Intravenous Patient Controlled Analgesia after Total Abdominal Hysterectomy (전자궁적출술후 시행한 정맥내 통증자가조절법의 임상 경험)

  • Kim, Yun-Hee;Choe, Huhn
    • The Korean Journal of Pain
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    • v.12 no.1
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    • pp.54-58
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    • 1999
  • Background: We studied 150 patients who received intravenous patient controlled analgesia (PCA) after total abdominal hysterectomy to evaluate pain relief, analgesic consumption, patient's satisfaction and side effects. Methods: We made total 40 ml of analgesic mixture with morphine 40 mg, ketorolac 120 mg, droperidol 3 mg and normal saline. Loading/bolus/basal infusion dose and lockout interval was 2 ml, 1.5 ml, 0.5 ml/hr and 10 min, respectively. Numerical rating scale (NRS) pain score, cumulative analgesic consumption, degree of satisfaction, and incidence of side effects were evaluated. Also, correlation of age and edu ion with analgesic consumption were evaluated. Results: The average pain scores using NRS were $3.1{\pm}1.7$ (6 h), $2.1{\pm}1.5$ (24 h), $1.7{\pm}1.5$ (48 h). The average cumulative analgesic consumption were $11.7{\pm}5.0$ ml (6 h), $23.0{\pm}6.7$ ml (24 h), $32.1{\pm}3.7$ ml (48 h). The degree of satisfaction in postoperative pain control was good in 94% of patients. There was no correlation between degree of satisfaction and analgesic consumption. Also age and level of edu ion did not correlated with analgesic consumption. Conclusions: Intravenous PCA with morphine, ketorolac, and droperidol is an effective method of postoperative pain control because it provides adequate pain relief and a few side effects with high patient's satisfaction. However, age and level of education did not correlated with analgesic consumption.

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Kinetic Analysis of the Hepatic Uptake and Biliary Excretion of 1-Anilino-8-Naphthalene Sulfonate (ANS) in Vivo (In Vivo 레벨에서 1-아닐리노-8-나프탈렌 설포네이트(ANS)의 간내 이행 및 담즙배설 과정의 속도론적 해석)

  • Bae, Woong-Tak;Chung, Youn-Bok;Han, Kun
    • Journal of Pharmaceutical Investigation
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    • v.31 no.4
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    • pp.209-216
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    • 2001
  • The purpose of the present study was to investigate the hepatic uptake and biliary excretion of l-anilino-8-naphthalene sulfonate (ANS) in vivo. The plasma concentration and liver concentration of ANS were determined after its i.v. bolus administration at a dose of $30\;{\mu}mol/kg$ in rats. The hepatic uptake clearance $(CL_{uptake})$ of ANS was 0.1 ml/min/g liver. On the basis of the unbound concentration of ANS, the permeability-surface area product $(PS_{influx})$ was calculated to be l0.4 ml/min/g liver, being comparable of in vitro data. On the other hand, we determined the plasma concentration, liver concentration and biliary excretion rate of ANS at steady-state after its i. v. infusion $(0.2-1.6\;{\mu}mol/min/kg)$ in rats. The excretion clearance $(CL_{excretion})$ of ANS showed Michaelis-Menten kinetics with increasing the infusion rate. The permeability-surface area product $(PS_{excretion})$ based on the unbound concentration in the liver was calculated to be 0.0165 ml/min/g liver, which is negligible compared with the intrinsic clearance $(CL_{int}=3.3\;ml/min/g\;liver)$ by rat liver microsomes. The sequestration process of ANS, therefore, was considered to be mainly due to the metabolic process in the liver $(PS_{seq}{\risingdotseq}CL_{int})$. Furthermore, $PS_{efflux}$ value calculated from $PS_{influx}$ and $PS_{seq}$ was 4.4 ml/min/g liver, which was comparable of in vitro data. In conclusion, in vivo parameters such as $PS_{influx}$, $PS_{efflux}$ and $PS_{seq}$ in the present study showed good in vivo-in vitro relationship. Thus, the kinetic analysis method proposed in the present study would be useful to analyze the hepatic transport of drugs in vivo.

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