BACKGROUND: Immune tolerance is regarded as the goal of the organ transplantation (TPLx), but the mechanism of tolerance induction remains to be established. Microchimerism (MC) development in long-surviving recipients after solid organ TPLx might be linked to tolerance. OBJECTIVE: We investigated the development and clinical relevance of donor specific MC in living related renal transplants with good graft function more than 3 years after TPLx. The relationship between MC and mixed lymphocyte reaction (MLR) hyporeactivity was also evaluated. MATERIALS AND METHODS: Eighteen recipients were included in this study among recipients whose renal function were stable for more than 3 years and have at least one mismatch of HLA DR loci. Donor-specific MC was examined with nested PCR method using HLA DRB1 gene probe in DNA extracted from peripheral blood and forearm skin tissue samples. Mean age at TPLx was 28.9 yrs (range: 13~42 yrs) and mean follow-up period was 67.4 months (range: 36~173 mos). Male to female ratio was 11:7. Acute rejection occurred in 4 and were reversed with steroid pulse therapy. All donors were alive (parent:8, sibling:9, offspring:1). Immunosuppression regimens were CSA(+)PDS in 11, AZA PDS in 1, AZA CSA(+)PDS in 5, and CSA monotherapy in 1. Mean serum BUN/Cr at the point of this study were 22.2+/-6.7 / 1.54+/-0.81 (mg/dL). The sensitivity of nested PCR using HLA DRB1 probe was 1/105~1/106. RESULTS: Donor-specific MC was detected in 6 (33.3%) (5 in blood, 5 in skin tissue). Nested PCR method was more sensitive than single round SSP-PCR method which showed only 2 positive recipients (11.1%). Two of four acute rejection experienced recipients were MC positive. Recipients were divided into two groups according to the follow-up period of 5 years. Two groups showed equal number of MC positivity. MLR was decreased in a group of more than 5 yrs follow-up. However, there was no difference in the decrement of MLR between MC positive and negative groups. CONCLUSION: MC was detected in 33.3% patients with nested PCR method. Since the MC positivity and MLR hyporesponsiveness shows no relationship, the significance of MC relevant to tolerance is to be determined through further study.
Chimerism* ; DNA ; Female ; Follow-Up Studies ; Forearm ; HLA-DRB1 Chains ; Humans ; Immune Tolerance ; Immunosuppression ; Kidney Transplantation ; Lymphocyte Culture Test, Mixed ; Male ; Organ Transplantation ; Polymerase Chain Reaction ; Skin ; Tissue Donors ; Transplants

BACKGROUND: Immune tolerance is regarded as the goal of the organ transplantation (TPLx), but the mechanism of tolerance induction remains to be established. Microchimerism (MC) development in long-surviving recipients after solid organ TPLx might be linked to tolerance. OBJECTIVE: We investigated the development and clinical relevance of donor specific MC in living related renal transplants with good graft function more than 3 years after TPLx. The relationship between MC and mixed lymphocyte reaction (MLR) hyporeactivity was also evaluated. MATERIALS AND METHODS: Eighteen recipients were included in this study among recipients whose renal function were stable for more than 3 years and have at least one mismatch of HLA DR loci. Donor-specific MC was examined with nested PCR method using HLA DRB1 gene probe in DNA extracted from peripheral blood and forearm skin tissue samples. Mean age at TPLx was 28.9 yrs (range: 13~42 yrs) and mean follow-up period was 67.4 months (range: 36~173 mos). Male to female ratio was 11:7. Acute rejection occurred in 4 and were reversed with steroid pulse therapy. All donors were alive (parent:8, sibling:9, offspring:1). Immunosuppression regimens were CSA(+)PDS in 11, AZA PDS in 1, AZA CSA(+)PDS in 5, and CSA monotherapy in 1. Mean serum BUN/Cr at the point of this study were 22.2+/-6.7 / 1.54+/-0.81 (mg/dL). The sensitivity of nested PCR using HLA DRB1 probe was 1/105~1/106. RESULTS: Donor-specific MC was detected in 6 (33.3%) (5 in blood, 5 in skin tissue). Nested PCR method was more sensitive than single round SSP-PCR method which showed only 2 positive recipients (11.1%). Two of four acute rejection experienced recipients were MC positive. Recipients were divided into two groups according to the follow-up period of 5 years. Two groups showed equal number of MC positivity. MLR was decreased in a group of more than 5 yrs follow-up. However, there was no difference in the decrement of MLR between MC positive and negative groups. CONCLUSION: MC was detected in 33.3% patients with nested PCR method. Since the MC positivity and MLR hyporesponsiveness shows no relationship, the significance of MC relevant to tolerance is to be determined through further study.
Chimerism* ; DNA ; Female ; Follow-Up Studies ; Forearm ; HLA-DRB1 Chains ; Humans ; Immune Tolerance ; Immunosuppression ; Kidney Transplantation ; Lymphocyte Culture Test, Mixed ; Male ; Organ Transplantation ; Polymerase Chain Reaction ; Skin ; Tissue Donors ; Transplants

BACKGROUND: This study investigated the protective mechanism of Prostagladin E1 (PGE1) against intimal hyperplasia after vein interposition grafts in rabbits. It has been demonstrated that active oxygen species contribute to vascular smooth muscle cell growth via early cell cycle gene activation. We attempted to study whether PGE1 had an effect on the inhibition of the oxidative stress injury index (8-OHdG, MDA). METHODS: Forty-eight jugular vein grafts were inserted into the carotid arteries of male hyperlipidemic New Zealand white rabbits, which were divided into 2 groups (saline group and PGE1 group). Saline and Prostaglandin E1 (0.1 microgram/kg/min) were administered as a continuous infusion for 2 hours every day from just before graft interposition to harvest. The vein grafts were harvested at 6 hour, 1 day, 1 week, and 2 week after grafting and rapidly stored in liquid nitrogen ( 70oC). 8-OHdG was measured by using high performance liquid chromatography coupled with electrochemical detection (HPLC-EC), and malondialdehyde (MDA) was measured by using thiobarbituric acid (TBA) assay. PC 10 index and intimal thickness of the grafts were measured with a computer digitalized image analyzer. RESULTS: There was no difference in 8-OHdG levels between the saline and the PGE1 groups. PGE1 had more inhibitory effect on the MDA level as an oxidative stress injury index, but its action was restricted to 1 day. A morphometric analysis and an immunohistochemical study showed that the PGE1 group had more suppressive effects both in intimal thickeness and proliferating cell nuclear antigen (PCNA) expression than the saline group (p<0.05). CONCLUSION: These results suggest that PGE1 is effective in preventing intimal hyperplasia after vein interposition grafts in rabbits and may play a role in inhibiting oxidative stress injury.
Alprostadil ; Carotid Arteries* ; Chromatography, Liquid ; Genes, cdc ; Humans ; Hyperplasia ; Jugular Veins ; Male ; Malondialdehyde ; Muscle, Smooth, Vascular ; Nitrogen ; Oxidative Stress* ; Proliferating Cell Nuclear Antigen* ; Rabbits ; Reactive Oxygen Species ; Transplants* ; Veins*

BACKGROUND: Graft-Versus-Host Disease (GVHD) is known to be associated with bone marrow transplantion. It is very rare in solid organ transplantation, especially in renal transplantation. There were only a few reported cases of GVHD in pancreas, liver transplant recipients or transfusion associated GVHD in immunocompromised patients. CASE: A 36 years-old man received renal transplantation from his mother on May 20th, 1996. Cyclosporine A, azathioprine & prednisolone were used as immunosuppressants. There was no episode of acute rejection after transplantation. After transplantation, he suffered from cytomegalovirus (CMV) cystitis, bile duct stones. He had never been transfused blood products since transplantation. Thereafter, his post-transplantation course was quite favorable until December 20th, 2003, when troublesome diarrhea and weight loss developed. At that time, he was taking 1.25 g/day of MMF (25 mg/kg/day). Hospital course: The MMF dose was reduced to 500mg bid (312 mg/m2/dose or 20 mg/kg/day) under the suspicion of CMV colitis. The results of serologic test and culture for CMV were all negative. The colonoscopic biopsy revealed pathologic features such as crypt drop-out, crypt abscess, crypt atrophy, single cell apoptosis and goblet cell depletion just like in GVHD. He had no necrotic skin lesion and his liver function test was in normal range. However, his complete blood count showed pancytopenic features. The MMF was discontinued immediately after the pathologic results were reported. His diarrhea and other clinical sym-ptoms were disappeared, and the pancytopenic features recovered gradually after discontinuation of MMF. He also gained 2.6 kg weight and discharged with good graft function.
Abscess ; Adult ; Apoptosis ; Atrophy ; Azathioprine ; Bile Ducts ; Biopsy ; Blood Cell Count ; Bone Marrow ; Colitis* ; Cyclosporine ; Cystitis ; Cytomegalovirus ; Diarrhea ; Goblet Cells ; Graft vs Host Disease ; Humans ; Immunocompromised Host ; Immunosuppressive Agents ; Kidney Transplantation ; Liver ; Liver Function Tests ; Mothers ; Organ Transplantation ; Pancreas ; Prednisolone ; Reference Values ; Serologic Tests ; Skin ; Transplantation* ; Transplants ; Weight Loss

PURPOSE: Arterial TOS is a rare condition caused by compression of the subclavian artery at the thoracic outlet area, which is composed of the anterior and middle scalene muscles, the first rib and the clavicle. We have experienced four cases of arterial TOS and we reviewed them to determine the appropriate management of arterial TOS. METHOD: We reviewed the medical records of 26 patients who were diagnosed and managed for TOS at Seoul National University Hospital from 1985 to 2004. We reviewed the clinical manifestations, diagnostic tools, mode of management and the outcomes. RESULT: The four patients with arterial TOS, 3 males and 1 female, had an average age of 41.3 years (range: 30~53 years). They complained of a tingling sense, coldness, weakness, and cyanosis of affected limb, and a gangrenous finger. They were diagnosed with CT angiography, conventional angiography and Doppler US. The findings were stenotic artery segments, post- stenotic dilatation and luminal thrombi of the subclavian artery. Two of them showed multiple peripheral arterial embolic obstructions and numerous collateral vessels. Three patients with arterial TOS underwent surgery. The operation consisted of the excision of the bony abnormality and the scalene muscle, segmental resection of subclavian artery including the aneurismal dilatation, interposition of a saphenous vein graft, and thromboembolectomy. Their symptoms improved after restoration of blood circulation, but the gangrenous finger required amputation. CONCLUSION: Arterial TOS has the definite risk of limb loss. If there is a high clinical suspicion of this lesion, early diagnosis and confirmation by angiogram may be critical to prevent limb loss. Surgical revascularization provides satisfactory results for limb salvage with low operative morbidity.
Amputation ; Angiography ; Arteries ; Blood Circulation ; Clavicle ; Cyanosis ; Diagnosis* ; Dilatation ; Early Diagnosis ; Extremities ; Female ; Fingers ; Humans ; Limb Salvage ; Male ; Medical Records ; Muscles ; Phenobarbital ; Ribs ; Saphenous Vein ; Seoul ; Subclavian Artery ; Thoracic Outlet Syndrome* ; Transplants

PURPOSE: Venous reflux in primary varicose vein arises from the saphenofemoral junction (SFJ), and the saphenopopliteal junction (SPJ) and it can arise from the non-junctional great saphenous vein (GSV) tributaries and, the non-saphenous veins. Superficial venous surgery (SVS) is associated with a significant improvement in the lower leg venous hemodynamics. We performed a retrospective study to examine the prevalence of the reflux pattern in the primary varicose veins and, to observe any change of non-junctional GSV reflux. METHOD: From May 2004 to July 2005, 481 patients (766 limbs) were diagnosed with venous incompetence by performing a duplex ultrasound examination. A follow-up duplex ultrasound examination was performed for a group of non-junctional GSV reflux patients and for a group of patient having both superficial vein reflux and deep vein reflux. RESULT: The prevalence of SFJ reflux, SPJ reflux, below the knee GSV reflux with competent SFJ and, non saphenous vein reflux was 82%, 13%, 10% and, 4.5% respectively. In the patients with SVS who had deep vein reflux (DVR), DVR was absent in only on two patients (6%). Eight patients (9.1%) of the 88 primary varicose vein patients had asymptomatic left iliac vein obstruction detected by performing an ascending venogram during radiofrequency ablation (RFA). On the duplex findings after SVS, the reflux pattern of left deep venous system was not different from the right deep venous system. CONCLUSION: Varicose veins may occur in any vein, even if junctional reflux is predominant. Careful duplex ultrasound evaluation will delineate the changing pattern of venous reflux with/without SVS. Although superficial venous surgery must fit the patient's map, the results might be variable. Prospective studies are needed to analyze the dynamics of venous reflux after SVS.
Catheter Ablation ; Follow-Up Studies ; Hemodynamics ; Humans ; Iliac Vein ; Knee ; Leg ; Prevalence ; Retrospective Studies ; Saphenous Vein ; Ultrasonography ; Varicose Veins* ; Veins

Splenic artery aneurysms (SAA) are the third most common intra-abdominal aneurysm and most common splanchnic artery aneurysm. They remain the subject of continued interest since the first case reported by Beaussier in 1770. The cause and indications for surgical treatment are controversial. In most cases, SAAs are detected as incidental findings. Their importance lies in their potentially fatal consequence due to rupture. We reviewed clinical features and treatment results of patients with splenic artery aneurysm experienced in Seoul National University Hospital from January, 1987 to June, 1997. Six patients of SAAs were treated during this period. Male to female ratio was 3:3, and median age was 56 years. The mean parity of all women was 3.7 and there were no pregnant women. Common symptoms were abdominal pain, hematemesis, and abdominal mass. Two patients(33.3%) were asymptomatic. The associated diseases that might cause the aneurysms were pancreatitis in 2 patients, portal hypertension in 1, operative trauma in 1, and mycotic aneurysm in 1 patient. Rupture occurred in 2 patients. One patients presented repeated hematemesis due to formation of gastro-aneurysmal fistula. Except one patient diagnosed as SAA incidentally during gastrectomy, all aneurysms were confirmed by angiography. Abdominal sonography was performed in 4 patients, and CT scan in 3. The size of the aneurysms ranged from 1 cm to 8 cm in diameter, with larger than 3 cm in 66%, smaller than 2 cm in 33% of aneurysms. About location, 33% located at proximal vessels, 17% at mid-third and 50% at distal. Five patients underwent surgical treatment. Splenectomy was performed in 3 patients, and exclusion of aneurysm in 2. We could preserve spleen in 1 case of distally located aneurysm by aneurysmal exclusion and end-to-end anastomosis of splenic artery. One patient underwent percutaneous embolization of the lesion and successfully treated. Two postoperative complications developed in ruptured cases and were managed conservatively. There was no postoperative mortality. In conclusion, complication and mortality in elective operation of SAA decreased due to recent improvement of radiologic tools and operative techniques. Considering severe fatality and morbidity of rupture of aneurysm, prompt and aggressive treatment is required in patients with high risk of rupture.
Abdominal Pain ; Aneurysm ; Aneurysm, Infected ; Angiography ; Arteries ; Female ; Fistula ; Gastrectomy ; Hematemesis ; Humans ; Hypertension, Portal ; Incidental Findings ; Male ; Mortality ; Pancreatitis ; Parity ; Postoperative Complications ; Pregnant Women ; Rupture ; Seoul ; Spleen ; Splenectomy ; Splenic Artery ; Tomography, X-Ray Computed

After craniotomy, bone flap fixation can be performed using wires, sutures, microplates, and Craniofix®. Well-margined and fixed bone flaps are important not only for postoperative brain protection but also for esthetics. Herein, we report a case of cranioplasty due to bone flap dislocation by Craniofix® clamp loosening after craniotomy with acute subdural hemorrhage removal. Iatrogenic outward force during epidural drain removal adjacent to Craniofix®, insertion of the clamp around the circumference of the bone flap, increased intracranial pressure due to brain swelling and fluid collection, and external shock during postoperative patient management are thought to be the causes of bone flap dislocation. To our knowledge, this is the second reported case of craniotomy with a Craniofix® clamp release.

Background: This clinical trial was conducted to determine whether combined use of magnesium sulfate and vitamin C more significantly reduced postoperative fentanyl consumption and pain than magnesium sulfate or vitamin C alone. Methods: The prospective, double-blinded, randomized controlled study enrolled 132 patients scheduled for laparoscopic gynecologic surgery. The patients were randomly allocated to one of the four groups (n = 33 for each group; Group M [magnesium sulfate 40 mg/kg], Group V [vitamin C 50 mg/kg], Group MV [magnesium sulfate 40 mg/kg and vitamin C 50 mg/kg] and Group C [isotonic saline 40 ml]). Cumulative postoperative fentanyl consumption (primary endpoint measure), postoperative pain score by numeric rating scale, and postoperative nausea and vomiting were recorded at 1, 6, 24, and 48 h after discharge from the postanesthesia care unit. Results: Cumulative postoperative fentanyl consumption was significantly less in Groups M, V, and MV than in Group C at all time points. Group MV showed significantly less cumulative postoperative fentanyl consumption than Group M at postoperative 24 h (mean ± standard deviation, 156.6 ± 67.5 vs. 235.6 ± 94.6 μg, P = 0.001), as well as significantly less consumption than Groups M and V at postoperative 48 h (190.8 ± 74.6 vs. 301.0 ± 114.8 or 284.1 ± 128.6 μg, P < 0.001, P = 0.003, respectively). Conclusions Combined use of magnesium sulfate and vitamin C provides an additional benefit in postoperative pain management after laparoscopic gynecologic surgery in comparison to single administration of magnesium sulfate or vitamin C.

BACKGROUND: Liver failure due to ischemia-reperfusion injury is a serious problem in liver transplantation and radical wide resection of the liver. This injury is believed to be closely related to the generation of oxygen free radicals. Gabexate mesilate, a synthetic protease inhibitor, has an effect on the suppression of extracellular release of oxygen free radicals in the microvascular endothelium, as well as on protease inhibition. In order to understand the effects of gabexate mesilate on ischemia-reperfusion injury to the liver, we performed animal experiment with rats. METHODS: We divided the rats into two ischemia-reperfusion groups:the experimental group which received a 30 minutes ischemic injury along with the infusion of gabexate mesilate and a control group which received only the injury. Each group was subdivided into 4 sub-groups:ischemic injury only and ischemic injury plus 60, 120 or 180 minutes reperfusion injury. The test parameters were TNF-a and IL-6 in the serum, and superoxide dismutase(SOD), catalase, and malondialdehyde(MDA) in liver and lung tissues. RESULTS: The group receiving gabexate mesilate had a significantly higher level of liver SOD and liver catalase and a significantly lower level of liver MDA and lung MDA than the control groups. The TNF-a levels in the gabexate mesilate groups were significantly lower in the early phase, and a comparison of the IL-6 levels between two main groups yielded no significant results. The levels of lung catalase and SOD showed no significant difference between the two main groups. CONCLUSIONS: Protease inhibitor has the beneficial effect of liver ischemia-reperfusion injury suppression due to an increase in antioxidants or oxygen-free-radical suppression. The roles of TNF-a and IL-6 in liver reperfusion injury was not clear in our investigation. However, TNF-a might have an effect in the early phase. The mechanism of reperfusion injury to the lung in liver ischemia-reperfusion injury might be different from that to the liver.
Animal Experimentation ; Animals ; Antioxidants ; Catalase ; Endothelium ; Free Radicals ; Gabexate ; Interleukin-6 ; Liver Failure ; Liver Transplantation ; Liver* ; Lung ; Oxygen ; Protease Inhibitors* ; Rats* ; Reperfusion Injury* ; Superoxide Dismutase ; Superoxides