Anchoring device to prevent membrane detachment and preterm premature rupture of membranes after fetal intervention.

OBJECTIVE: Anchoring the fetal membrane to the uterine wall via a novel suture delivery system could reduce the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery. This study assesses the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. METHODS: We tested the suturing device both ex vivo and in vivo. In the ex vivo studies, 12-French trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For in vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at ~79-90 days gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane anchoring integrity when the defect was created and at delivery. RESULTS: Fetal membranes were successfully anchored to the uterine myometrium using this device in all five trials performed ex vivo. The in vivo trials also revealed successful membrane anchoring compared with controls both at the time of device deployment and five-to-eight weeks after the procedure. CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium via suturing device both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human subjects. This article is protected by copyright. All rights reserved.

Angioplasty of communicating veins to the brachial vein in haemodialysis patients with obliterated superficial veins of the upper arm.

AIM: To evaluate the outcomes of angioplasty of the communicating veins when superficial veins of the upper arm were almost totally obliterated in haemodialysis patients. MATERIALS AND METHODS: Twenty-one angioplasties of the communicating veins that were performed for failing haemodialysis fistulas in patients with almost totally obliterated superficial veins of the upper arm from December 2006 to March 2011 were retrospectively reviewed. Fistulas were of the following types: native radiocephalic fistulas (n = 20) and radio-antecubital fistulas (n = 1). All angioplasties were performed using 5-8 mm conventional balloons. Cutting balloon angioplasty was additionally performed in five patients. The primary, secondary, and target lesion patency rate was calculated using Kaplan-Meier analysis. RESULTS: The communicating vein was located in the antecubital fossa. Technical and clinical success rates were 100% and 95.2%, respectively. Follow-up duration was 1-52 months (mean 20 months). The primary patency rates were 76%, 43%, and 29% at 3, 6, and 12 months, respectively, and target lesion patency rates were 81%, 62%, and 43% at 3, 6, and 12 months, respectively. The secondary patency rates were 81%, 76%, and 57% at 3, 6, and 12 months, respectively. There were no major or minor complications. CONCLUSION: Angioplasty of the communicating vein is effective in restoring function in failing haemodialysis fistula in patients with obliterated superficial veins of the upper arm.

Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.

BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.

Endovascular treatment for immature autogenous arteriovenous fistula.

AIM: To evaluate the anatomical causes of maturation failure and to assess clinical outcomes after the causative lesions of immature arteriovenous fistula (AVF) have been corrected by endovascular treatment. MATERIALS AND METHODS: The medical records and radiological data from 141 patients who underwent endovascular treatment for immature AVF were retrospectively reviewed. Clinical outcomes, such as the success rates and the patency rates following the procedure, were included. The variables, including patients' age, gender, co-morbidities, fistula age, fistula type, numbers of lesions, degree of stenosis, presence of accessory veins, were analysed as the potential predictors of primary and secondary patency. RESULTS: Technical and clinical success rates were 95.7% (135 of 141 AVFs) and 86.5% (122 of 141 AVFs), respectively. The primary and secondary patency rates were 71.9% and 82.8% at 1 year, 60.1% and 82.0% at 2 years, and 54.5% and 82.0% at 3 years, respectively. By multivariate analysis using Cox proportional hazards model, stenosis of >90% was the only independent predictor for both the primary and secondary patency rates [hazard ratio (HR) 5.026, 95% confidence interval (CI) 2.47-10.24, p < 0.0001 for primary patency and HR 11.076, CI 1.49-82.58, p = 0.019 for secondary patency, respectively]. CONCLUSION: All immature AVFs had significant anatomical causes of failure to mature, which could be safely and effectively salvaged with endovascular treatment. A degree of stenosis >90% was an independent predictor for both the primary and secondary patency after the treatment.

Clinical significance of upper-arm cephalic vein patency in autogenous radial-cephalic wrist fistulas for hemodialysis.

OBJECTIVES: To investigate the significance of upper-arm cephalic veins (UACVs) in radial-cephalic arteriovenous fistulas (RCAVFs), the medical records of 183 patients who had undergone RCAVF creation were reviewed retrospectively. METHODS: The patients were divided into two groups according to the status of the UACV upon preoperative venography: group A of 153 cases (83.6%) with a patent UACV and group B of 30 cases (16.3%) with a stenosed or occluded UACV. The clinical outcomes were compared. RESULT: RCAVFs in group B had a significantly higher maturation failure rate (26.7% vs. 9.8%, p = 0.009) and lower primary/secondary patency rates (log-rank test, p < 0.0001) than those in the group A. The patients in group B required more frequent endovascular intervention to maintain access function (p = 0.002). The most common stenosis site was a draining vein in group B, in comparison to juxta-anastomosis in group A. In the multivariate analyses, the status of the UACV was an independent predictor of the primary and secondary patency rates of RCAVFs (p < 0.005). CONCLUSION: UACV patency has a significant impact on clinical outcome for RCAVFs. When planning an RCAVF placement, venous status including the UACV should be considered.

Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia.

Hepatocyte growth factor (HGF) has been shown to induce angiogenesis in vivo and has potential as a candidate gene for 'therapeutic angiogenesis'. In vivo, two isoforms of HGF, HGF723 and HGF728, consisting of 723 and 728 amino acids, are generated through alternative splicing between exons 4 and 5, but the biological effects of their coexpression have not yet been elucidated. In this study, we generated a series of genomic-complementary DNA (cDNA) hybrids of the HGF gene by inserting various truncated intron 4 into the junction of exons 4 and 5 of HGF cDNA and analyzed the biological activities of these hybrid constructs. We showed that: (1) the hybrid called HGF-X7, which contained 1502 base pairs of intron 4, could drive a higher level of HGF expression than other hybrid constructs and cDNAs of each isoform alone; (2) the pCK vector was most efficient for the gene expression of HGF-X7; (3) coexpression of both isoforms of HGF could more efficiently induce the migration of human umbilical vein endothelial cell (HUVEC) and of the mouse myoblast cell line C2C12 myoblasts than a single isoform of HGF and human vascular endothelial growth factor (VEGF)165 at a given concentration; (4) intramuscular administration of pCK-HGF-X7 resulted in transient and localized HGF expression in the injected muscle without an increase in the HGF protein levels in other tissues including serum; and (5) intramuscular injection of pCK-HGF-X7 could more efficiently increase the number of angiographically recognizable collateral vessels, as well as improve an intra-arterial Doppler wire-measured blood flow in the rabbit model of hindlimb ischemia when compared with the identical vector encoding VEGF165 gene. These results showed that transfer of the genomic-cDNA hybrid of the HGF gene could be used as a potential therapeutic approach to human vascular diseases.

Endovascular treatment of acute arterial complications after living-donor liver transplantation.

AIM: The aim of this study was to evaluate the efficacy of endovascular treatment for acute arterial complications following living-donor liver transplantation (LDLT). MATERIALS AND METHODS: Of 79 LDLT patients, 17 (mean age 48+/-8 years, range 33-66 years) who had acute arterial complications and underwent endovascular treatment were evaluated. Transcatheter arterial embolization was performed to control peritoneal bleeding. Catheter-directed thrombolysis using urokinase was performed in hepatic artery thromboses. The locations of complications and materials used were evaluated. The technical and clinical success rates were calculated. RESULTS: Twenty-three acute arterial complications, including four hepatic artery thromboses and 19 cases of peritoneal haemorrhages were identified in 22 angiographic sessions in 17 patients. The mean duration between LDLT and first angiography was 3.2+/-3.5 days (range 1-13 days). Hepatic artery recanalization with catheter-directed thrombolysis using urokinase was achieved in two patients. Transcatheter arterial embolization for peritoneal bleeding was successfully performed in 16 cases. The most common bleeding focus was the right inferior phrenic artery. Additional surgical management was needed in five patients to control bleeding or hepatic artery recanalization. Technical and clinical success rates of transcatheter arterial embolization were 84.2 and 63.1%, respectively. Overall technical success was achieved in 18 of 23 arterial complications (78.2%), and clinical success was achieved in 14 of 23 arterial complications (60.8%). CONCLUSION: Endovascular treatment for the acute arterial complications of haemorrhage or thrombosis in LDLT patients is safe and effective. Therefore, it should be considered as the first line of treatment in selective cases.

Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0-10) and donor's intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Intraarterial thrombolytic treatment for hepatic artery thrombosis immediately after living donor liver transplantation.

Hepatic artery thrombosis (HAT) following living donor liver transplantation (LDLT) remains one of the major causes of graft failure and mortality in liver transplant recipients. This complication requires early diagnosis and revascularization to avoid graft loss. We have reported herein two cases of successful urokinase intraarterial thrombolytic treatment for HAT in the immediate postoperative period after LDLT. Significant elevation of liver transaminases was noted 6 and 4 hours after LDLT and HAT confirmed by three-dimensional computed tomogram and angiogram. Both patients were treated successfully with intraarterial thrombolysis using an urokinase infusion (a total dose of 200,000 to 250,000 IU over 20 to 25 minutes) immediately after HAT was confirmed. One patient underwent laparotomy and bleeder ligation owing to hepatic arterial anastomotic site bleeding after thrombolysis. These two patients remain in good condition without any ischemic graft sequelae at 7 and 8 months follow-up. In conclusion, intraarterial thrombolysis using an urokinase infusion could be considered as one of the treatment modalities of acute HAT following LDLT even in the immediate postoperative period.

The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines.

A 2.4-kb truncated L-plastin promoter was inserted either 5' to the LacZ gene (Ad-Lp-LacZ) or 5' to the cytosine deaminase (CD) gene (Ad-Lp-CD) in a replication-incompetent adenoviral vector backbone. Infectivity and cytotoxicity experiments with the LacZ and CD vectors suggested that the L-plastin promoter-driven transcriptional units were expressed at much higher levels in explants of ovarian cancer cells from patients and in established ovarian or bladder cancer cell lines than they were in normal peritoneal mesothelial cells from surgical specimens, in organ cultures of normal ovarian cells, or in the established CCD minimal deviation fibroblast cell line. Control experiments showed that this difference was not attributable to the lack of infectivity of the normal peritoneal cells, the normal ovarian cells, or the minimal deviation CCD fibroblast cell line, because these cells showed expression of the LacZ reporter gene when exposed to the replication-incompetent adenoviral vector carrying the cytomegalovirus (CMV)-driven LacZ gene (Ad-CMV-LacZ). The Ovcar-5 and Skov-3 ovarian cancer cell lines exposed to the Ad-Lp-CD adenoviral vector were much more sensitive to the prodrug 5-fluorocytosine (5FC), which is converted from the 5FC prodrug into the toxic chemical 5-fluorouracil, than was the CCD minimal deviation fibroblast cell line after exposure to the same vector. A mouse xenograft model was used to show that the Ad-Lp-CD vector/5FC system could prevent engraftment of ovarian cancer cells in nude mice. Finally, injection of the Ad-Lp-CD vector into s.c. tumor nodules generated a greater reduction of the size of the tumor nodules than did injection of the Ad-CMV-LacZ vectors into tumor nodules. The Ad-Lp-CD vectors were as suppressive to tumor growth as the Ad-CMV-CD vectors. These results suggest that an adenoviral vector carrying the CD gene controlled by the L-plastin promoter (Ad-Lp-CD) may be of potential value for the i.p. therapy of ovarian cancer.

Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation.

The aim of this study was to evaluate the potential of tumor-necrosis-factor-related apoptosis-inducing ligand TRAIL to eradicate leukemia cell lines, while sparing normal hematopoietic stem cells. Human Jurkat and Molt-4 cell lines were used to optimize the purging process in umbilical cord blood (UCB) mononuclear cells. The Jurkat cell line was TRAIL sensitive and TRAIL-resistant Molt-4 cell line became sensitive after being treated with TRAIL and a low dose of doxorubicin (0.1 micro M), but UCB mononuclear cells remained resistant. DR4 expression was increased when Jurkat cells were treated with TRAIL, and DR5 expression increased after exposing Molt-4 cells to TRAIL plus a low dose of doxorubicin for 24 h. The expression of DR4 and DR5 in UCB mononuclear cells was unchanged after treatment with TRAIL, a low-dose doxorubicin, or TRAIL plus a low dose of doxorubicin. In TRAIL-sensitive Jurkat cells, caspases 8, 9, 3, and 7 were activated by TRAIL treatment and activation of caspases was augmented by TRAIL plus a low dose of doxorubicin than TRAIL or a low dose of doxorubicin alone in Molt-4 cells. Experiments involving mixture of UCB mononuclear cells and Jurkat or Molt-4 cells showed a marked eradication of leukemia cells and the limiting dilution assay demonstrated an eradication rate of more than 4 logs after 24 h incubation with 100 ng/ml of TRAIL in Jurkat cells. In the case of Molt-4 cells, the eradication rate was about 3 logs when TRAIL was used in combination with a low dose of doxorubicin. No significant decrease in the number of granulocyte-macrophage colony-forming unit) (CFU-GM) colonies was detected when UCB mononuclear cells were treated with TRAIL in combination with a low dose of doxorubicin. These results suggest that TRAIL offers the possibility of being used as an ex vivo purging agent for autologous transplantation in hematologic malignancies.

Increased contralateral cerebellar uptake of technetium-99m-HMPAO on ictal brain SPECT.

UNLABELLED: Crossed cerebellar diaschisis (CCD) is a well-known brain SPECT finding in stroke patients. Two reports, however, have described supratentorial and contralateral cerebellar hyperperfusion (crossed cerebellar hyperperfusion) on ictal brain SPECT in epileptic patients. The purpose of this study was to assess the usefulness of crossed cerebellar hyperperfusion (CCH) for the detection of epileptic foci on ictal scan. METHODS: Twelve patients with complex partial seizures having characteristic clinical, electroencephalographic (EEG) and brain SPECT findings were included. Fifteen to 20 mCi 99mTc-HMPAO were injected intravenously during the seizure period or the aura for the ictal SPECT study. The SPECT findings were visually assessed to determine whether the finding of CCH was valuable in the localization of ictal foci. RESULTS: Epileptic foci were found in the right temporal (n = 6), left temporal (n = 4), right occipital (n = 1) and left frontal (n = 1) areas. CCH was observed in 8 (75%) of the 12 patients. In two patients, contralateral cerebellar uptake was more obvious than that in the epileptic foci. In the interictal scans, cerebellar activity, which was increased in ictal period, was equalized in seven of eight patients, while perfusion was diminished in the remaining patient. CONCLUSION: CCH is a frequent finding of ictal brain SPECT and may aid in the lateralization of epileptic foci.

Methods for Chemoprotection and Chemosensitization : MDR-1 For Chemoprotection Using Retroviruses to Modify Hematopoietic Cells and Cytosine Deaminase for Chemosensitization Using Adenoviral Vectors to Modify Epithelian Neoplastic Cells.

Surgery, radiation therapy, and chemotherapy have been applied to the curative therapy of 50% of cancer patients in the United States during the past 100 years. It is clear that the chemotherapeutic agents used to develop curative therapy for leukemias, lymphomas, gestational malignancy, and testicular cancer are not as active in the more numerous epithelial neoplasms, perhaps because of the complexity of genetic change in these latter neoplasms.

Immunohistochemical studies from vitiligo--comparison between active and inactive lesions.

Vitiligo is an acquired, progressive depigmenting disorder of unknown etiology. In this study, to clarify pathogenesis of vitiligo, the marginal skin of actively spreading and stable vitiligo was examined using ICAM-1, HLA-DR, CD4 and CD8 monoclonal antibodies. In immunohistochemical study, ICAM-1 was expressed in four of five epidermis in active lesions, but not in stable lesion. Dermal ICAM-1 was also expressed in all active and stable lesions. HLA-DR was also expressed in all active epidermis in active lesions, but two of five epidermis in stable lesion. Dermal HLA-DR was also expressed in all active and stable lesion. CD4 lymphocytes were expressed more strongly in active lesion, but CD8 lymphocytes were not different in both lesions. There was no significant difference of degree of positivity with CD4 and CD8 in normal control specimens. In conclusion, we think that ICAM-1 and HLA-DR expression, cytokines released from keratinocytes, melanocytes or lymphocytes and infiltration of activated T-lymphocytes play an important role in disease activity.

Ichthyosis bullosa of Siemens: report of a sporadic case.

We report a sporadic case of ichthyosis bullosa of Siemens occurring in a Korean boy. In this report, the varied findings of the clinical features in one subject over five years are presented along with an investigation of the ultrastructural alteration. The patient had suffered from blistering, superficial peeling, and dark-grey colored lichenified patches on the extremities since infancy. As he grew older, the lesions were more localized to the elbows, knees, buttock and the dorsal aspects of the hands and feet, and were replaced by yellowish, lichenified plaques. Since the original report of Siemens in 1937, nine families including one sporadic case have been reported in the literature. To our knowledge, this is the second report of sporadic case of IBS.

Partial unilateral lentiginosis associated with segmental neurofibromatosis.

Partial unilateral lentiginosis associated with segmental neurofibromatosis is rate. Therefore, we describe here a patient with partial unilateral lentiginosis associated with ipsilateral segmental neurofibromatosis who developed multiple, rice-sized, brown macules on the right side of her face, trunk, and upper arm and several bean-sized, cafe-au-lait spots on the right upper arm and right upper back. To our knowledge, partial unilateral lentiginosis associated with ipsilateral segmental neurofibromatosis has not been reported in the English literature.

Congenital giant pigmented nevus associated with angiolipoma.

We report a 20-year-old-Korean woman with a congenital giant pigmented nevus and angiolipoma. She was admitted our department with a large, dark, pigmented lesion on the right flank and abdomen and a slowly growing mass on the right flank area since birth. On biopsy, the specimen taken from the giant pigmented patch showed typical findings of compound nevus. The right flank mass was surgically removed. The specimen was composed of mature fat cells with an increased vascular component. These findings are compatible with angiolipoma.

'Swiss cheese' lymphangiectasia in a case of solitary morphea profunda.

Reports of lymphangiectases that occur in lesions of morphea are rare. We describe a 24-year-old woman with a solitary morphea profunda associated with lymphangiectasia. Unlike previously reported cases, our case showed lymphatic dilatation resembling Swiss cheese and developed around a milium.

Bone histomorphometric changes due to differences in calcium intake under metabolic acidosis in rats.

Effects of differences in calcium (Ca) intake on bone metabolism under metabolic acidosis were examined by bone histomorphometry in rats. Rats were divided into 5 diets; low Ca (0.02%) diet (LCD), moderate low Ca (0.3%) diet (LmCD), standard Ca (0.62%) diet (SCD), moderate high Ca (1%) diet (HmCD) and high Ca (3%) diet (HCD). Each diet rats were subdivided into the acidotic group given a 1.8% ammonium chloride solution as drinking water and control group given deionized water. Blood and double labeled bone were collected 30 days later. Arterial blood pH was significantly lower, and plasma ionized Ca level and urinary Ca excretion were higher in the acidotic groups than those in the control groups in all diets. Breaking force in femur and bone volume in tibial proximal metaphysis were significantly lower in the acidotic groups than those in the control groups in LCD, LmCD and SCD. In the acidotic groups, osteoid thickness was significantly higher in LCD than that in LmCD, HmCD and HCD. Mineral apposition rate in the acidotic groups was significantly higher in LCD and LmCD than that in HmCD and HCD. These results suggest that bone mineral loss and bone fragility under metabolic acidosis may be accelerated by high turnover of bone metabolism due to insufficient dietary Ca intake, but can be prevented by adequate supplementation of Ca.

Effects of vitamin D3 injection on activity of thyroid parafollicular cells in pregnant rats.

Effects of vitamin D3 (VD3) injection on the activity of thyroid parafollicular cells (C cells) and calcium (Ca) metabolism were examined in rats of non-(NP), middle (MP) and late pregnancy (LP). At 3 days after injection, the average area of a C cell was significantly wider (P<0.01) in the VD3 groups than that in their control groups in NP, MP, and LP. On the otherhand, the plasma ca concentration in the VD3 groups decreased significantly (P<0.05) in comparison with that in their control groups in NP and LP, and tended to decrease in MP. These results suggest that injection of VD3 may accelerate the activity of C cells, which may result in the decrease of plasma Ca concentration in both non-pregnant and pregnant rats.