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Endoscopic variceal ligation using multiband ligator.

Esophageal variceal bleed in children is treated with endoscopic sclerotherapy (EST), which is associated with significant complications. Endoscopic variceal ligation (EVL) was found to be more effective and safe in adults. Use of EVL in children has not been studied much. Thirteen consecutive children (mean age 9.4 years) with variceal bleed were subjected to EVL by multi band ligator. Varices were eradicated in 2.8 sessions (range 2-4) and one patient had bleed during procedure. No other complications were noted. EVL could not be performed in 2 children less than 3 years of age.

Adolescent↗

[Ligation of the common carotid. Studies of the circumstances and follow up of 42 ligations].

The authors report the results of a series, between 1969 and 1978, of 42 patients who had received ligation to the carotid arterial trunk. In 36 patients, the ligation was performed as an emergency measure, often under extemporary circumstances, because of massive hemorrhage in individuals who had received surgery after previous radiotherapy. The complications after applying these ligatures have been catastrophic for many reasons. Fifteen rapid recurrent hemorrhages occurred, leading to the deaths of 13 patients. Twenty-two patients developed major neurological problems and 12 of these subsequently died. The third complication observed was the onset of extensive necrosis. This necrosis was the direct result of applying a ligature, as a last resort, to the carotid trunk supplying a vascular territory already compromised by previous radiotherapy and surgery. The authors propose different techniques for these subsequent ameliorating operations. They insist, particularly, on performing an arterectomy instead of simply applying a ligature to the carotid trunk.

Carotid Arteries↗

[The risk of ligation of the external carotid in the treatment of cervico-facial angiodysplasia. A plea for this technique to be abandoned, and current radiosurgical solutions; based upon 13 cases of ligation amongst 200 angiomas explored (author's transl)].

After describing the different collateral sytems between the various cervicocephalic arteries, the authors indicate the consequences of ligation of the external carotid. This ligation proves to totally ineffective for distal vascular lesions and severely compromises the possibilities of later treatment.

Carotid Arteries↗

Synthesis of the C-terminal region of opioid receptor like 1 in an SDS micelle by the native chemical ligation: effect of thiol additive and SDS concentration on ligation efficiency.

In the process of developing a method for the synthesis of membrane proteins, the conditions for native chemical ligation, namely, detergent concentration and the chemical characteristics of the thiol additive were investigated in detail. The C-terminal region of the opioid receptor like 1, ORL1(288-370), which contains C-terminal intracellular and transmembrane domains, was chosen as a model. The building blocks, ORL1(329-370) and ORL1(288-328)-SR-Gly-Arg(5)-Leu (-SR- : -SCH(2)CH(2)CO-) were most effectively condensed slightly below the critical micelle concentration of SDS and in the presence of mercaptoethanesulfonic acid as a thiol additive. The results showed that the concentration of SDS and the charge on the thiol additive are crucial factors for the effective synthesis of a membrane protein by native chemical ligation.

Amino Acid Sequence↗

Rapid production of functionalized recombinant proteins: marrying ligation independent cloning and in vitro protein ligation.

Functional genomics and proteomics have been very active fields since the sequencing of several genomes was completed. To assign a physiological role to the newly discovered coding genes with unknown function, new generic methods for protein production, purification, and targeted functionalization are needed. This work presents a new vector, pCYSLIC, that allows rapid generation of Escherichia coli expression constructs via ligation-independent cloning (LIC). The vector is designed to facilitate protein purification by either Ni-NTA or GSH affinity chromatography. Subsequent proteolytic removal of affinity tags liberates an N-terminal cysteine residue that is then used for covalent modification of the target protein with different biophysical probes via protein ligation. The described system has been tested on 36 mammalian Rab GTPases, and it was demonstrated that recombinant GTPases produced with pCYSLIC could be efficiently modified with fluorescein or biotin in vitro. Finally, LIC was compared with the recently developed In-Fusion cloning method, and it was demonstrated that In-Fusion provides superior flexibility in choice of expression vector. By the application of In-Fusion cloning Cys-Rab6A GTPase with an N-terminal cysteine residue was generated employing unmodified pET30a vector and TVMV protease.

Animals↗

'CO2-ligated' cytochrome c oxidase: characterization and comparison with the Cl- -ligated enzyme.

A form of fully oxidized bovine heart cytochrome c oxidase that is induced by CO2/HCO3- is described. The ligand-binding properties of this form are similar to those of Cl(-)-ligated oxidase [Moody, Cooper and Rich (1991) Biochim. Biophys. Acta 1059, 189-207]. Both bind cyanide at a rate (0.2 M-1.s-1 at pH 6.5) intermediate between the rate of binding to the fast and slow forms of the enzyme, and binding of formate to both is almost undetectable. They are also similar in showing poor reactivity with H2O2, or with CO in the presence of O2, which, with fast oxidase, induce the formation of the 'ferryl' and 'peroxy' states respectively. However, there is a clear difference in the near-u.v./visible absorption spectra of the two forms; that induced by CO2/HCO3- has a Soret maximum at 427 nm whereas Cl(-)-ligated oxidase has a Soret maximum similar to that of fast oxidase at about 424 nm. It appears that both CO2/HCO3- and Cl- are members of a class of ligands that lowers the reactivity of the binuclear centre but does not impede intramolecular electron transfer from haem a to the binuclear centre, unlike the putative endogenous ligand responsible for slow oxidase.

Animals↗

Video assisted thoracoscopic ligation of patent ductus arteriosus. Technique of sliding loop ligation.

Variant video-assisted thoracoscopic surgical technique for closure of patent ductus arteriosus has been introduced. Although the endoscopic clipping device may be a preferred method for interruption of the patent ductus arteriosus, there is always the risk of inadequate clip placement and limitation of application in width of ductus arteriosus. In an effort to overcome this problem we have used a self-made endoscopic loop ligation in 10 patients and herein report the method. Only a small window and one port of access are necessary to dissect the patent ductus arteriosus from the surrounding tissues and to apply the extracorporeally created sliding loop. Successful ligation without shunt is obtained in all cases. The technique is simple and safe even in the presence of a wide ductus.

Child↗

Ligation activity of FLP recombinase. The strand ligation activity of a site-specific recombinase using an activated DNA substrate.

The FLP protein of the 2-microns plasmid of yeast belongs to the integrase family of site-specific recombinases whose members form a covalent bond between a conserved tyrosine of the recombinase and the 3'-phosphoryl group at the site of cleavage. We have made an activated DNA substrate and have shown that FLP can promote efficient strand ligation without forming a covalent intermediate with the DNA substrate. The strand ligation activity of FLP is independent of its ability to cleave DNA. Since site-specific recombinases are members of the larger class of topoisomerases, these findings may be generally applicable to other members of this class of enzymes.

Base Sequence↗

Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial.

beta-Blockers and endoscopic variceal ligation (EVL) have proven to be valuable methods in the prevention of variceal rebleeding. The aim of this study was to compare the efficacy of EVL combined with nadolol versus EVL alone as secondary prophylaxis for variceal bleeding. Patients admitted for acute variceal bleeding were treated during emergency endoscopy with EVL or sclerotherapy and received somatostatin for 5 days. At that point, patients were randomized to receive EVL plus nadolol or EVL alone. EVL sessions were repeated every 10 to 12 days until the varices were eradicated. Eighty patients with cirrhosis (alcoholic origin in 66%) were included (Child-Turcotte-Pugh A, 15%; B, 56%; C, 29%). The median follow-up period was 16 months (range, 1-24 months). The variceal bleeding recurrence rate was 14% in the EVL plus nadolol group and 38% in the EVL group (P = .006). Mortality was similar in both groups: five patients (11.6%) died in the combined therapy group and four patients (10.8%) died in the EVL group. There were no significant differences in the number of EVL sessions to eradicate varices: 3.2 +/- 1.3 in the combined therapy group versus 3.5 +/- 1.3 in the EVL alone group. The actuarial probability of variceal recurrence at 1 year was lower in the EVL plus nadolol group (54%) than in the EVL group (77%; P = .06). Adverse effects resulting from nadolol were observed in 11% of the patients. In conclusion, nadolol plus EVL reduces the incidence of variceal rebleeding compared with EVL alone. A combined treatment could lower the probability of variceal recurrence after eradication.

Adrenergic beta-Antagonists↗

After portal branch ligation in rat, nuclear factor kappaB, interleukin-6, signal transducers and activators of transcription 3, c-fos, c-myc, and c-jun are similarly induced in the ligated and nonligated lobes.

Several studies have emphasized the involvement of transcription factors, cytokines, and proto-oncogenes in initiating the regenerative process after partial hepatectomy. To assess whether these events do specifically occur in a cellular system undergoing regeneration, we studied the induction of nuclear factor kappaB (NFkappaB), interleukin-6 (IL-6), signal transducers and activators of transcription 3 (Stat3), c-fos, c-myc, c-jun, after portal branch ligation (PBL), which produces atrophy of the deprived lobes (70% of the liver parenchyma), whereas the perfused lobes undergo compensatory regeneration. Nuclear extracts and total RNA were prepared from control livers as well as from atrophying and regenerating lobes at 0.5, 1, 2, 5, and 8 after PBL. NFkappaB and Stat3 induction were studied by electrophoretic mobility shift assays and Western blotting. IL-6 and proto-oncogenes expressions were assessed by reverse transcription polymerase chain reaction and Northern blotting, respectively. Assays were also performed after a sham operation. NFkappaB and Stat3 protein expression and DNA binding were rapidly and similarly induced in nuclear extracts from the atrophying and regenerating lobes. IL-6 was elevated in both lobes from 1 to 8 hours after PBL as well as c-fos, c-myc, and c-jun during the first 2 hours. IL-6 and Stat3 but not NFkappaB were also elevated after a sham operation. These findings suggest that the cellular and molecular changes occurring early in a regenerating liver are nonspecific, possibly stress-induced, cellular responses. They do not indicate the future evolution towards atrophy or regeneration.

Animals↗

[Intravenously stimulated insulin reserve of the pancreas following experimental pancreatic duct ligation in the swine--studies 2, 4 and about 60 days following ligation].

After pancreatic duct ligation (PDL) intravenous glucose tolerance tests (i.v. GTT) were performed in 12 pigs. The release of insulin and the corresponding blood sugar levels were controlled, the pancreata were examined histologically and immunohistochemically. In spite of a reduced number of beta-cells no reduction of glucose tolerance could be shown 60 days after PDL. Two days after the i.v. GTT showed an increased release of insulin corresponding with lowered blood sugar levels. This phenomenon is explained as a stimulated state of the beta-cell in the phase of interstitial edema.

Animals↗

Ligation plus low-volume sclerotherapy for high-risk esophageal varices: comparisons with ligation therapy or sclerotherapy alone.

Endoscopic variceal ligation therapy (EVL) seems to be a more effective and safer method than endoscopic injection variceal sclerotherapy (EVS) for treating bleeding esophageal varices. However, EVL may entail a higher recurrence rate than EVS. The aim of this study was to examine whether EVL combined with low-dose EVS reduced the recurrence rate compared to treatment with EVL alone and reduced the complication rate compared to treatment with EVS alone. In this prospective study, 59 patients with cirrhosis and high-risk (F2 or F3, red color sign ++ or ) esophageal varices were enrolled. They were randomly assigned to an EVS group (n = 18), an EVL group (n = 20), and a combination EVL plus low-dose EVS group (n = 21). After the eradication of varices, follow-up endoscopic examinations were carried out for 24 months to determine the recurrence of varices. Complications, e.g., severe dysphagia, fever, renal dysfunction and pleuritis were also evaluated. The recurrence-free rate was significantly lower in the EVL group (60% at 24 months) than in either the EVS group (90%, P < 0.05) or the combination group (88%, P < 0.05). However, no significant difference was found between the EVS group and the combination group. The complication rate was significantly higher in the EVS group (50%) than in either the EVL group (5%, P < 0.01) or the combination group (10%, P < 0.01). The combination therapy seems to be useful to improve the benefits achieved with EVL alone and to reduce the harmful effects induced by EVS alone. EVL plus low-volume EVS is advisable in the treatment of high-risk esophageal varices.

Aged↗

Comparison of characteristics of recurrent esophageal varices after endoscopic ligation versus endoscopic ligation plus sclerotherapy.

BACKGROUND/AIMS: The characteristics of recurrent esophageal varices after endoscopic variceal ligation (EVL) plus endoscopic injection sclerotherapy (EIS) versus EVL alone, including the number of additional treatments and patterns of recurrence have been compared. METHODOLOGY: Thirty-four patients with cirrhosis and esophageal varices were treated by EVL alone (EVL group), and 46 patients were treated by EVL followed by extravariceal injection sclerotherapy (EVL+extraEIS group). RESULTS: Fewer treatment sessions were needed (p<0.005), and more O-rings were required (p<0.0001) in the EVL group than in the EVL+extraEIS group. The 1- and 3-year cumulative recurrence rates were higher in the EVL group (81.3% and 93.8%) than in the EVL+extraEIS group (62.8% and 91.5%) (p<0.05). Endoscopic examination at first recurrence showed varices of a more severe form (p<0.001), but less frequently having the red color sign (p<0.0001), and intramucosal venous dilatation (p<0.0001) in the EVL group than in the EVL+extraEIS group. The number of rehospitalizations for additional treatment was lower (p<0.0001) and more patients could be managed with only endoscopic treatment for recurrent varices in the EVL group than in the EVL+extraEIS group (p<0.05). CONCLUSIONS: Even if the overall rate of variceal recurrence was higher, fewer treatment sessions were needed, and the number of rehospitalizations for these additional treatments was lower in the EVL group than in the EVL+extraEIS group. Multiple sessions of EVL are an effective strategy for the treatment of esophageal varices.

Aged↗

Endoscopic variceal ligation versus endoscopic variceal ligation and endoscopic sclerotherapy: a prospective randomized study.

OBJECTIVE: To compare endoscopic variceal ligation (EVL) with a combination of EVL and endoscopic scelerotherapy (EST) in the secondary prophylaxis of esophageal variceal bleeding. METHODS: Fifty patients with esophageal varices due to cirrhosis of the liver (38), noncirrhotic portal fibrosis (7), or extrahepatic portal venous obstruction (5) were included in the study. These 50 patients were randomized to receive either EVL alone or a combination of EVL and EST for variceal eradication. Twenty-one patients received EVL alone (group A), and 23 patients received EVL and EST (group B). In group B, EVLs were performed until the varices were reduced to grade II size, and, subsequently, these patients underwent low-dose sclerotherapy with 1% polidocanol until variceal eradication was achieved. RESULTS: Combined EVL and EST treatment eradicated the varices in a significantly greater number of patients then EVL alone (87% vs. 24%; p < 0.05). However, significantly more endoscopic sessions were required with combined treatment than with EVL alone (5.87 +/- 2.32 vs. 4.28 +/- 1.82; p < 0.05). Rebleeding episodes before variceal eradication were similar in the two groups (19% vs. 22%). The complications were similar in both the EVL and the EVL-plus-EST group, ie., deep ulcers (16% vs. 20%), transient dysphagia (20% vs. 32%), and stricture (4% vs. 8%). CONCLUSION: Thus, combined EVL and EST treatment eradicates varices in a significantly larger number of patients than EVL alone, with no extra complications.

Adult↗

Effects on liver functions of gastric variceal therapy by endoscopic ligation using a detachable snare and sclerotherapy with O-ring ligation.

Although various effects of therapy for gastric varices, a complication of portal hypertension, on portal hemodynamics have been suggested, the effects of the therapy on liver functions have not yet been clarified. The aim of this study was to examine the effects of endoscopic gastric variceal therapy on liver functions in patients with hepatic cirrhosis. The subjects were 18 hepatic cirrhosis patients with the complication of gastric varices, who could be monitored for a long term (at least 1-year after therapy). They consisted of patients receiving prophylactic treatments after being confirmed to have a risk of rupture of gastric varices (16 prophylactic cases) and those with a history of bleeding and receiving palliative treatments to prevent rebleeding (two palliative cases). To evaluate liver functions, blood tests before the therapy, just after the therapy and at 1, 3, 6 and 12 months after the therapy were retrospectively examined and the levels of albumin, total bilirubin (T.Bil), ALT, choline esterase (ChE), platelets and the Child-Pugh classification were assessed. The albumin levels tended to increase after the therapy, and the level at 6 months after the therapy was significantly higher than the pre-treatment value (P=0.0311). At 1 year after the therapy, the level was higher than the pre-treatment value, but there was no significant difference. The ChE level tended to decrease just after the therapy, but it tended to be increased at 3 and 6 months after the therapy. Although significant improvement was not seen in T.Bil, ALT, platelet levels or the Child-Pugh classification after the therapy, none of these worsened. Endoscopic gastric variceal ligation therapy significantly improved liver functions, or at least albumin synthesis.

Journal Article↗

Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.

We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help.

Animals↗

Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding.

BACKGROUND AND AIMS: The role of propranolol in addition to EVL in the prevention of first variceal bleed has not been evaluated. This prospective randomized controlled trial compared endoscopic variceal ligation (EVL) with propranolol and EVL alone in the prevention of first variceal bleed among patients with high-risk varices. PATIENTS AND METHODS: One hundred and forty-four consecutive patients with high-risk varices were randomly allocated to EVL plus propranolol (Gr I, n = 72) or EVL alone (Gr II, n = 72). EVL was done at 2-wk interval till obliteration of varices. In Gr I, incremental dosage of propranolol (sufficient to reduce heart rate to 55 beats/min or 25% reduction from baseline) was administered and continued after obliteration of varices. The endpoints of the study were bleeding and death. RESULTS: The two groups of patients had comparable baseline characteristics; follow-up (Gr I: 13.1 +/- 11.5 months, Gr II: 11.2 +/- 9.9 months), number of cirrhotic and noncirrhotic portal hypertension patients [Gr I 64 (88.6%) and 8 (11.4%), Gr II 63 (87.5%) and 9 (12.5%)], and frequency of Child's A (15 vs 18), B (38 vs 35), and C (19 vs 19). The mean daily propranolol dose achieved in Gr I was 95.6 +/- 38.6 mg. Eleven patients had bleeds, 5 in Gr I and 6 in Gr II. All patients bled before the obliteration of varices, the actuarial probability of first bleed at 20 months was 7% in Gr I and 11% in Gr II (p= 0.72). Six patients died in the combination and 8 in EVL group. All deaths in Gr I were due to nonbleed-related causes, while in Gr II, 2 deaths were bleed related, the actuarial probability of death at 20 months was 8% and 15%, respectively (p= 0.37). The probability of bleed-related death was comparable (p= 0.15). At the end of follow-up, 4 patients in Gr I and 11 in Gr II had recurrence of varices (p= 0.03). Side effects on propranolol were seen in 22% patients, in 8% it had to be stopped. There were no serious complications of EVL. CONCLUSIONS: Both EVL plus propranolol and EVL alone are effective in primary prophylaxis of bleed from high-risk varices. Addition of propranolol does not decrease the probability of first bleed or death in patients on EVL. However, the recurrence of varices is lower if propranolol is added to EVL.

Adrenergic beta-Antagonists↗