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Functional analysis of CLIP-115 and its binding to microtubules.

Cytoplasmic linker proteins (CLIPs) bind to microtubules and are proposed to link this cytoskeletal network to other intracellular structures. We are interested in CLIP-115, since this protein is enriched in neuronal dendrites and may operate in the control of brain-specific organelle translocations. Each CLIP monomer is characterized by two microtubule-binding (MTB) motifs, surrounded by basic, serine-rich regions. This head domain is connected to the C-terminal tail through a long coiled-coil structure. The MTB domains are conserved as a single domain in other proteins involved in microtubule based transport and dynamics, such as p150(Glued). Here we provide evidence that efficient binding of CLIP-115 to microtubules is sensitive to phosphorylation and is not mediated by the conserved MTB domains alone, but requires the presence of the basic, serine rich regions in addition to the MTB motifs. In transfected COS-1 cells, CLIP-115 initially accumulates at the distal ends of microtubules and coincides with CLIP-170, indicating that both proteins mark growing microtubule ends. However, when expressed at higher levels, CLIP-115 and -170 affect the microtubule network differently. This might be partly due to the divergent C-termini of the two proteins. We demonstrate that, similar to CLIP-170, CLIP-115 forms homodimers, which, at least in vitro, are linked by disulfide bridges. Cysteine(391) of CLIP-115, however, is specific in that it controls the microtubule bundling capacity of certain mutant CLIP-115 molecules. Therefore, both similar and specific mechanisms appear to regulate the conformation of CLIPs as well as their binding to microtubules.

Amino Acid Sequence↗

Clip-ablation. A model of experimental hypertension in the rat.

A model of experimental hypertension has been developed in which the features of the two kidney-one clip and renal ablation models are combined in a single rat. It has been designated the clip-ablation model. It is produced by the placement of a silver clip with an opening of 0.13 mm on a branch of the left renal artery supplying one-third of that kidney, followed by right nephrectomy. In this way the effects of renin-dependent hypertension may be studied in glomeruli which are undergoing compensatory changes in response to reduction in renal mass. Clip-ablation rats were compared to rats with 1 1/3 reduction of renal mass at various intervals up to 28 days after operation. Systolic blood pressure rose with increasing time after operation in both groups with the increase being greater in the clip-ablation rats (177 +/- 10 mm Hg) as compared to the ablation rats (153 +/- 6 mm Hg) at 28 days. Plasma renin activity was increased slightly at 3 days in the ablation rats but had returned to normal levels by 28 days. By contrast, the plasma renin activity rose throughout the experimental period in the clip-ablation rats and attained a level of 32.3 +/- 8.0 ng/ml/hour by 28 days. Urine protein was significantly higher than normal only in the 28-day clip ablation rats (71.2 +/- 23.9 mg/24 hour). Glomerular damage index (GDI), a measure of glomerular injury, increased with longer intervals from operation in both experimental groups, paralleling the rise in systolic blood pressure. Beginning on day 14 and onward the GDI was always numerically higher in the clip-ablation rats than in the ablation rats. Stepwise multiple regression analysis indicated that the strongest predictor of GDI was the change in blood pressure. Plasma renin activity had an additional independent effect on GDI in the clip-ablation rats. The finding of more glomerular damage in the clip-ablation rats than in those with simple removal of comparable amounts of renal tissue is in contrast to the lesser amount of damage found in the two kidney-one clip model when compared with the model of removal of renal substance. It is likely that the compensatory hemodynamic changes in response to reduction in renal mass in the glomeruli of clip-ablation rats make them more vulnerable to injury when exposed to a renin-angiotensin induced hypertension.

Animals↗

CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms.

CLIP-170 is a "cytoplasmic linker protein" implicated in endosome-microtubule interactions and in control of microtubule dynamics. CLIP-170 localizes dynamically to growing microtubule plus ends, colocalizing with the dynein activator dynactin and the APC-binding protein EB1. This shared "plus-end tracking" behavior suggests that CLIP-170 might interact with dynactin and/or EB1. We have used site-specific mutagenesis of CLIP-170 and a transfection/colocalization assay to address this question in mammalian tissue culture cells. Our results indicate that CLIP-170 interacts, directly or indirectly, with both dynactin and EB1. We find that the CLIP-170/dynactin interaction is mediated by the second metal binding motif of the CLIP-170 tail. In contrast, the CLIP-170/EB1 interaction requires neither metal binding motif. In addition, our experiments suggest that the CLIP-170/dynactin interaction occurs via the shoulder/sidearm subcomplex of dynactin and can occur in the cytosol (i.e., it does not require microtubule binding). These results have implications for the targeting of both dynactin and EB1 to microtubule plus ends. Our data suggest that the CLIP-170/dynactin interaction can target dynactin complex to microtubule plus ends, although dynactin likely also targets MT plus ends directly via the microtubule binding motif of the p150(Glued) subunit. We find that CLIP-170 mutants alter p150(Glued) localization without affecting EB1, indicating that EB1 can target microtubule plus ends independently of dynactin.

Amino Acid Motifs↗

Experimental animal studies of clip-induced microvascular trauma.

This study was designed to evaluate microvascular clip potential for causing changes in vessel-wall tissue and the extent to which this potential is influenced by features of the clip. Light and scanning electron microscopy were used to examine vessel-wall changes after temporary clip occlusion. Vessel patency is shown to be influenced by anastomosis and clip site, changes in occlusion force due to material fatigue are described, and novel clip features to reduce vessel trauma are proposed. Evaluation of mechanical clip properties showed that material fatigue does not lead to relevant loss of precision in alpha-type clips. While the modified clip designed to reduce trauma cannot abolish trauma altogether, it significantly reduces the associated changes and hence the risk of thrombosis. Arteries were more sensitive than veins to clip-induced trauma, with increased occlusion force producing more severe damage than increased clipping time. Maximal changes were seen in the tunica media. These results indicate the paramount importance of applying modest clip pressure commensurate with the requirements of microvascular Surgery.

Anastomosis, Surgical↗

Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score).

A clinical staging system for cancer patients provides guidance for patient assessment and making therapeutic decisions. It is useful in deciding whether to treat a patient aggressively, and in avoiding the overtreatment of patients who would not tolerate the treatment or patients whose life expectancy rules out any chance of treatment. Clinical staging is also an essential tool for comparison between groups in therapeutic trials and for comparison between different studies. The current classifications most commonly used for hepatocellular carcinoma (HCC) are the Okuda stages, the Child-Pugh staging system, tumor node metastasis (TNM) staging, and the Cancer of the Liver Italian Program (CLIP) score. Among these, the CLIP score is currently the most commonly used integrated staging score, including both tumor stage and liver disease stage. Although the CLIP score has been well validated by many authors in terms of its prognostic value in HCC patients, this score has some problems and limitations when applied to currently diagnosed HCC patients, who are diagnosed in the early stage of disease. First, the CLIP score can discriminate score 0- to 3-patient populations, but it is not able to discriminate score 4- to 6-patient groups. Second, the definition of tumor morphology in the best prognostic group is too advanced, i.e., uninodular and a tumor extent of less than 50% of the liver. As a result, the prognosis of the CLIP system best prognostic group is not so good. In other words, this system cannot identify the best prognostic group who would benefit from curative and aggressive treatment. Third, nearly 80% of the patient population is classified as having a CLIP score of 0-2, as confirmed by many studies, which shows poor stratification ability. In contrast, a new staging system based on the Liver Cancer Study Group of Japan (LCSGJ), the Japan Integrated Staging (JIS) score is currently proposed in Japan. This staging system combines Child-Pugh grade (grade A, score 0; grade B, score 1; grade C, score 2) and TNM staging by the LCSGJ criteria (stage I, score 0; stage II, score 1; stage III, score 2; stage IV, score 3). The stratification ability of the JIS scoring system is much better than that of the CLIP scoring system. The JIS scoring system also performed better than the CLIP scoring system in selecting the best prognostic patient group. The cumulative 10-year survival rates of the best prognostic groups in the CLIP staging system (CLIP score 0) and JIS staging system (JIS score 0) were 23% and 65%, respectively (P < 0.01). All scoring systems arise as a compromise between simplicity and discriminatory ability. We confirmed that the JIS score increases predictive efficacy, while remaining simple compared with the CLIP score. Because the JIS score is quite easily obtained and is objective, we strongly propose it for widespread use as a prognostic staging system for HCC in clinical practice.

Carcinoma, Hepatocellular↗

Clip induced analgesia and immobility in the mouse: activation by different sensory modalities.

In the present study we have attempted to characterize, in mice, a situation which appears to simulate real life predation and elicits simultaneous analgesia and immobility. We utilized pinch produced by clip application to various regions of the body and examined its effect on responsiveness to noxious stimuli and motor behavior. Intense noxious clip was applied to the nape of the neck, back and base of the tail. The area most effective for the elicitation of both clip induced analgesia and immobility was the nape of the neck while tail pinch resulted in analgesia but not immobility. Evidence is provided that different systems are responsible for clip induced immobility and analgesia. Temporal dissociation of clip induced analgesia and immobility could be demonstrated with continuous clip application for 30 min showing a different time course for the analgesic and immobilizing effects. Different stimuli were effective in eliciting clip induced analgesia and immobility with noxious stimuli essential for the induction of clip induced analgesia and innocuous stimuli sufficient for clip induced immobility. Thus, low analgesic doses of local anesthetics injected into the nape of the neck prevented noxious clip from inducing analgesia but immobility was still evident. In contrast, nonnoxious pinch to the nape of the neck elicited immobility but not analgesia and clip induced immobility could still be induced after the administration of high doses of morphine which completely blocked responses to noxious stimuli. These results demonstrate that in a situation resembling natural predation both analgesia and immobility are produced concurrently but that these behavioral phenomena can be elicited differentially and may be mediated by different independent systems.

Afferent Pathways↗

A prospective evaluation of interrupted nitinol surgical clips in arteriovenous fistula for hemodialysis.

BACKGROUND: The use of a self-closing nitinol surgical clip (Coalescent Surgical U-Clip) is a novel technique of creating an interrupted vascular anastomosis, which also eliminates the knot tying associated with a conventional vascular anastomosis. The purpose of this study was to compare the clinical outcome of arteriovenous fistulae (AVF) for hemodialysis as constructed using interrupted U-Clip devices and conventional continuous polypropylene sutures. METHODS: We prospectively studied the clinical course of 132 patients (149 access) undergoing either forearm autologous arteriovenous fistula (FAVF, n = 69) or upper arm autologous arteriovenous fistula (UAVF, n = 80) or creations during a 39-month period. Among the FAVF, U-Clips and polypropylene sutures were used in 37 and 32 anastomoses, respectively. Among the UAVF, U-Clips and polypropylene sutures were used in 41 and 30 anastomoses, respectively. Primary patency, complication, and maturation rates were analyzed. RESULTS: Clipped FAVF had an improved maturation rate at 6 weeks (32 of 37, 86%) when compared with sutured FAVF (22 of 32, 69%, P <0.05). There was no difference in the maturation rate among UAVF constructed with either U-Clips or sutures (88% versus 87%, not significant). The primary patency rates at 12, 24, and 36 months were 91%, 84%, and 75% for the clipped FAVF; and 83%, 74%, and 61% for the sutured FAVF (P <0.05) There was no difference in the patency rate of UAVF constructed with either U-Clips or polypropylene sutures at either 12, 24 or 36 moths (91%, 80%, and 75% versus 83%, 77%, and 69%, respectively). CONCLUSIONS: The U-Clips are a viable alternative to sutures for creating vascular anastomosis. It provides a improved maturation and patency rates when compared with the conventional sutured AVF in the forearm. The clinical benefit of the U-Clips may be due in part to the improved compliance created by the interrupted anastomotic technique.

Adult↗

The validity of surgical clips as a radiographic surrogate for the lumpectomy cavity in image-guided accelerated partial breast irradiation.

PURPOSE: We hypothesize that surgical clips placed in the biopsy cavity during lumpectomy can be used as radiographic markers to facilitate image-guided external beam accelerated partial breast irradiation. METHODS AND MATERIALS: We evaluated 28 patients with surgically placed clips in the lumpectomy cavity and two CT scans on different days. To establish whether the clips remain predictive of the lumpectomy cavity throughout therapy, we analyzed the motion of both cavities with repeat volumetric CT scans. The three-dimensional (3D) locations of each lumpectomy cavity and the associated clips were defined as individual regions of interest (ROIs). A single point of interest (POI) was defined for each ROI. The calculated movements of the lumpectomy cavity POIs between different scans were compared to those of the clip POIs. The second CT data set was then moved in accordance to the calculated clip POI's movement. The volume of the (second) lumpectomy cavity associated with the second scan outside of the (first) cavity of the first scan was measured. In addition, the required amount of a radial margin expansion around the first lumpectomy cavity to ensure coverage of the second lumpectomy cavity both before and after moving the second lumpectomy according to the clip POI movement was calculated. RESULTS: The two CT scans were obtained on average 27 days apart, and the mean lumpectomy size decreased from 35 to 16 cc. The clip and lumpectomy cavity POIs moved a mean of 3 mm along the three principal Cartesian axes. In moving the second lumpectomy cavity according to the clip POI displacement from its original position, the volume of the second lumpectomy cavity outside of the volume of the first decreased from 2.6 cc to 1.0 cc after correction, and the required radial margin on the first lumpectomy cavity to include the second lumpectomy cavity decreased from 5.5 mm vs. 3.8 mm. CONCLUSION: The surgically placed clips after lumpectomy are strong radiographic surrogates for the biopsy cavity. If the clips were used to guide accelerated partial breast irradiation, a planning target volume margin of the order of 5 mm could be used, significantly smaller than the 10-mm margin currently employed.

Breast Neoplasms↗

A multicenter study of permanent hemodialysis access patency: beneficial effect of clipped vascular anastomotic technique.

OBJECTIVE: There is an urgent and compelling need to reduce the morbidity and expense of maintaining hemodialysis vascular access patency. This large, long-term, retrospective, multicenter study, which compared access patency of autogenous arteriovenous fistulas (AVF) and synthetic bridge grafts (AVG) created with conventional sutures or nonpenetrating clips, was undertaken to resolve conflicting results from previous smaller studies. DESIGN: Patency data for 1385 vascular access anastomoses (clipped or sutured) was obtained from 17 hospitals and dialysis centers (Appendix). Five hundred eighteen AVF (242 clip, 276 suture) and 827 AVG (440 clip, 384 suture) were analyzed. Statistical comparisons were made with Kaplan-Meier survival analysis, log-rank test, two-sample t test, and X(2) test. The Cox proportional hazards model was used to confirm Kaplan-Meier analysis. RESULTS: Access patency (primary, secondary, overall, and intention to treat) was significantly improved in access anastomoses constructed with clips. In the intention-to-treat group, primary patency at 24 months was 0.54 for clipped AVF and 0.34 for sutured AVF, and was 0.36 for clipped AVG and 0.17 for sutured AVG. At 24 months, primary patency rate for AVF successfully used for dialysis was 0.67 for clips and 0.48 for sutures, and for AVG was 0.39 for clips and 0.19 for sutured constructs. Interventions necessary to maintain patency were significantly fewer in clipped anastomoses. CONCLUSION: Replacing conventional suture with clips significantly reduces morbidity associated with maintaining permanent hemodialysis vascular access. This beneficial effect may be due to the biologic superiority of interrupted, nonpenetrating vascular anastomoses.

Adult↗

Evidence for invariant chain 85-101 (CLIP) binding in the antigen binding site of MHC class II molecules.

The region of invariant chain encompassing residues 81-104 is critical for association with MHC class II molecules. This segment of invariant chain, termed CLIP for Class II-associated invariant chain Peptides, has been shown to inhibit antigenic peptide binding and T cell stimulation. Polymorphism affects the ability of CLIP to inhibit antigenic peptide binding, suggesting that CLIP may occupy the MHC II antigen binding site directly. However, CLIP may also mediate inhibition by binding to an alternate site causing an allosteric change to prevent antigenic peptide binding. The relationship between the apparent dissociation constant in the presence of a competitor (Kapp) and the competitor concentration can be examined to determine the nature of competition between two ligands. In competitive binding experiments between CLIP and antigenic peptide we find a linear dependence of Kapp on competitor concentration. These data are consistent with CLIP and antigenic peptide competing for the same site on the MHC class II molecule, thus arguing against an allosteric mechanism of CLIP inhibition. Mildly acidic conditions are thought to promote peptide loading in the endosome compartment by facilitating CLIP dissociation and enhancing antigenic peptide association. We have compared the effect of acidic pH on the equilibrium binding of murine CLIP and antigenic peptide to MHC class II molecules. Like antigenic peptide, CLIP binding can be greatly enhanced at mildly acidic pH, suggesting that a passive competitive mechanism for CLIP removal may not be sufficient to achieve loading of antigenic peptide in the endosome.

Allosteric Regulation↗

Arterial pressure and renal function in two-kidney, one clip Goldblatt hypertensive rats maintained on a high-salt intake.

Arterial blood pressure and renal function of both clipped and non-clipped kidneys of benign two-kidney, one clip (2K1C) Goldblatt hypertension were evaluated in order to determine whether high-salt intake alters the course of the development and magnitude of hypertension or influences renal function. The administration of 0.9% sodium chloride as a drinking solution for 3 weeks suppressed plasma renin activity (PRA) and kidney renin content of the clipped kidney to normal values. Despite suppression of PRA and kidney renin content, the saline-drinking clipped rats still developed hypertension of the same magnitude as the water-drinking clipped rats. However, the onset of hypertension was delayed by 4 days. Urine flow, glomerular filtration rate (GFR) and sodium excretion rate from the clipped kidneys of the saline-drinking clipped rats were higher than the corresponding values in the water-drinking rats, and approached those observed in control animals. Thus, the high-salt intake which was associated with suppression of the activity of the renin-angiotensin system delayed the onset of, but not the final magnitude of, the hypertension. In addition, kidney function in the clipped kidneys of saline-drinking clipped rats was enhanced compared with that observed in the water-drinking clipped rats.

Animals↗

Clip placement after stereotactic vacuum-assisted breast biopsy.

PURPOSE: To assess accuracy and usefulness of placement of a localizing clip after stereotactic, vacuum-assisted breast biopsy. MATERIALS AND METHODS: Retrospective review was performed of 57 lesions that underwent placement of a localizing clip after stereotactic vacuum-assisted biopsy with an 11-gauge (n = 42) or 14-gauge (n = 15) probe. The clip was placed when images obtained after stereotactic biopsy suggested that the lesion seen at mammography was removed. Coordinates of the clip on stereotactic images obtained after placement were compared with lesion coordinates determined before biopsy. Surgery was performed in 25 cases. Mammographic and histopathologic findings were reviewed. RESULTS: The distance from clip to lesion site was less than 1 cm in 40 (95%) of 42 lesions that underwent clip placement with the 11-gauge probe versus 11 (73%) of 15 lesions that underwent clip placement after 14-gauge biopsy (P < .04). The biopsy site was identified in the surgical specimen in 19 (100%) lesions with clips after 11-gauge biopsy and five (83%) of six lesions with clips after 14-gauge biopsy. No complications occurred. CONCLUSION: A localizing clip can be placed in proximity to the stereotactic biopsy site through an 11-gauge probe. Clip placement can enable accurate localization for surgical excision.

Adult↗

Mechanism of enhanced blood pressure rise after reclipping following removal of a renal artery clip in rats.

The effect of removing a renal artery clip 14 to 18 days after its application was studied in two-kidney, one clip hypertensive rats. Blood pressure decreased to a normotensive level within 24 hours after the removal of the clip. The cardiovascular effects of reapplication of the clip and infusion of renin, angiotensin II, and norepinephrine were assessed at that time. Reapplication of the clip to the unclipped renal artery was followed in 1 hour by an increase in blood pressure to the level of sham-operated renal hypertensive rats. After reapplication of the clip, plasma renin activity increased to the same level as after the initial application. Application of the clip to the contralateral renal artery did not affect blood pressure and failed to increase plasma renin activity. It appears that renin release is a prerequisite for the rapid rise of blood pressure after reapplication of the clip. The infusion of renin, angiotensin II, and norepinephrine for 90 minutes caused an enhanced blood pressure response similar to that observed following reapplication of the clip. The increase in blood pressure in control rats was associated with bradycardia, which was absent in unclipped rats. The enhanced response of unclipped rats to an infusion of renin was abolished by pithing. It is concluded that removal of a renal artery clip unmasks a hyperreactivity of the cardiovascular system to reapplication of the clip.

Angiotensin II↗

Elevated lymphocyte expression of CLIP is associated with type 1 diabetes and may be a useful marker of autoimmune susceptibility.

Type 1 diabetes (T1D) susceptibility in humans and in the non-obese diabetic mouse is linked to MHC class II molecules characterized by an amino acid substitution at position 57 of the beta-chain (nonAspB57). The mechanism whereby nonAspB57 MHC molecules contribute to diabetes susceptibility is not currently known. As CLIP is displaced from MHC class II molecules upon peptide binding, if nonAspB57 haplotypes are associated with high CLIP expression, this may reflect a defect in peptide loading. Non-obese diabetic mice have higher mononuclear cell CLIP expression than non-diabetes prone strains, raising the question of whether humans with T1D also exhibit increased CLIP levels. We therefore sought to test whether subjects with T1D have higher levels of leukocyte CLIP expression. Cell surface expression of CLIP was measured on lymphocytes and monocytes using a FITC-conjugated antibody against human CLIP (Pharmingen). Leukocyte CLIP expression was significantly higher in the blood of T1D patients compared to non-diabetic controls. Increased CLIP expression was not a secondary effect of hyperglycemia as CLIP expression was not increased in subjects with type 2 diabetes. This confirms that elevated CLIP expression is a feature of T1D and may be a useful marker for T1D susceptibility.

Autoimmunity↗

Do surgical clips interfere with radiofrequency thermal ablation?

OBJECTIVE: This study sought to evaluate whether surgical clips affect tissue conductivity and thereby alter the induction of radiofrequency ablation lesions and to determine whether therapy is safe after previous placement of clips in the liver. MATERIALS AND METHODS: An ex vivo porcine hepatic model was used. Three clips were placed around a radiofrequency electrode at 10, 20, and 30 mm from the point of insertion. Clips were arranged in a plane either perpendicular or parallel to the electrode track. After placement of the liver specimen on a grounding pad, radiofrequency energy was applied in a standardized manner for 5 min. Lesion growth and morphology were documented for each minute. RESULTS: Radiofrequency lesions appeared circular and homogeneous after 5 min. Lesion diameter perpendicular to the radiofrequency electrode averaged 30 mm. However, lesion formation was irregular during the early phase of the radiofrequency ablation. The lesion extended irregularly toward the 1-cm clip after 60 sec of ablation. During the second minute, a distinct lesion was observed around the clip 1 cm from the electrode; the primary lesion had not yet reached the clip. During the final 3 min, the primary lesion reached the 1-cm clip and ultimately incorporated the satellite lesion. No lesions were detected surrounding the more distant clips. CONCLUSION: Our data suggest that with the parameters applied in our study, radiofrequency ablation can be safely performed in patients with implanted clips. No aberrant conduction is observed around surgical clips that are located 20 mm and further from the radiofrequency electrode.

Animals↗

Recurrence of ICA-PCoA aneurysms after neck clipping.

Between 1975 and 1992, 2211 patients underwent aneurysmal neck clipping at the Nara Medical University clinic and associated hospitals. The aneurysm in 931 of these patients was situated at the junction of the internal carotid artery (ICA) and posterior communicating artery (PCoA). Seven patients were readmitted 4 to 17 years after the first surgery because of regrowth and rupture of an ICA-PCoA aneurysmal sac that had arisen from the residual neck. On angiograms obtained following aneurysmal neck clipping, a large primitive type of PCoA was demonstrated in six patients and a small PCoA in one. A small residual aneurysm was confirmed in only two patients and angiographically complete neck clipping in five. Recurrent ICA-PCoA aneurysms were separated into two types based on the position of the old clip in relation to the new growth. Type 1 aneurysms regrow from the entire neck and balloon eccentrically. In this type, it is possible to apply the clip at the neck as in conventional clipping for a ruptured aneurysm. Type 2 includes aneurysms in which the proximal portion of a previous clip is situated at the corner of the ICA and aneurysmal neck and the distal portion on the enlarged dome of the aneurysm, because the sac is regrowing from a portion of the residual neck. In this type of aneurysm, a Sugita fenestrated clip can occlude the residual neck, overriding the old clip. Classifying these aneurysms into two groups is very useful from a surgical point of view because it is possible to apply a new clip without removing the old clip, which was found to be adherent to surrounding tissue.

Adult↗

Intentional body clipping of wide-necked basilar artery bifurcation aneurysms.

OBJECT: Neck clipping or coil embolization cannot always achieve complete neck obstruction in wide-necked basilar artery (BA) bifurcation aneurysms. Clipping of the aneurysm body, leaving a small aneurysm rest, is one clipping method used for this kind of aneurysm to maintain the patency of the posterior cerebral arteries and perforating vessels. However, the long-term efficacy of intentional body clipping has not been well investigated. The authors reviewed their experience with intentional body clipping of wide-necked BA bifurcation aneurysms to determine suitable clipping techniques and the long-term efficacy of the procedure. METHODS: Complete neck occlusion was abandoned and body clipping intentionally performed in 17 patients with BA bifurcation aneurysms; wrapping of the aneurysm rest was made in seven cases. There were 10 ruptured aneurysms (58.8%), and the size of the aneurysm was larger than 10 mm in 11 patients (64.7%). The width between the clip blades and the base of the aneurysm neck was 1 mm in 11 cases, 2 mm in four, and 3 mm in two. Favorable outcome (Glasgow Outcome Scale [GOS] Score 4 or 5) was obtained in 13 cases (76.5%) and unfavorable outcome (GOS Scores 1-3) in four cases (23.5%). Major causes of unfavorable outcome included injury to perforating arteries and major vessel occlusion following surgical manipulation, in addition to the primary damage caused by subarachnoid hemorrhage. Subarachnoid hemorrhage did not occur during a mean follow-up period of 7.4+/-5.6 years (range 0.7-18.1 years) after treatment. CONCLUSIONS: Intentional body clipping of wide-necked BA aneurysms proved to be effective to prevent subarachnoid hemorrhage, although injury to perforating arteries remains problematic. The choice of complete neck clipping or body clipping should be established early during the microsurgical procedure to reduce the risk of injury to perforating vessels.

Adult↗

How secure are laparoscopically placed clips? An in vitro and in vivo study.

We tested the security of laparoscopic, hemostatic clips in vitro and in vivo. In vitro, the force needed to transversely dislodge clips that were applied to silicone (Silastic) tubing ranged from a mean +/- SEM of 1.81 +/- 0.07 N (Endo Clip) to 2.68 +/- 0.04 N (Ligaclip). The force needed to axially dislodge clips that were applied to silicone tubing ranged from 4.08 +/- 0.20 N (Endo Clip) to 4.78 +/- 0.18 N (Ligaclip). In vivo, on mesenteric vessels in anesthetized pigs, 34 of 100 clips that were applied laparoscopically with the Endo Clip were moved or dislodged compared with 11 of 100 of those applied with the Ligaclip. We conclude that laparoscopically placed vascular clips applied with the Ligaclip are more secure than those applied with the Endo Clip. The laparoscopic surgeon should be aware of the relative ease with which clips may be dislodged.

Animals↗