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Effects of chronic treatment with angiotensin converting enzyme inhibitor or an angiotensin receptor antagonist in two-kidney, one-clip hypertensive rats.

The effects of chronic angiotensin II (Ang II) receptor blockade (losartan) or converting enzyme inhibition (enalapril) on blood pressure (BP), urinary albumin excretion (Ualb V), renal histology and the hemodynamic and excretory function of the clipped and nonclipped kidneys were studied in two-kidney, one-clip (2-K 1-C) rats. One day after clipping the right renal artery, male Wistar rats were divided into three groups receiving: (1) losartan, 20 mg/kg/day (N = 7), (2) enalapril, 20 mg/kg/day (N = 8), or (3) no treatment (controls, N = 9) for three weeks. Both losartan and enalapril treatments maintained conscious BP at comparably lowered levels compared to control animals (116 +/- 6 mm Hg and 113 +/- 2 mm Hg vs. 188 +/- 11 mm Hg, respectively, P < 0.01). Treatment also prevented the increase in Ualb V, observed for the untreated group, three weeks after clipping (1.7 +/- 0.5 and 0.7 +/- 0.1 mg/24 hr vs. 17.8 +/- 7 mg/24 hr, respectively, P < 0.01). After three weeks of treatment, acute study of renal function during pentobarbital anesthesia revealed higher values of GFR and RPF and lowered vascular resistance for nonclipped kidneys from the losartan and enalapril groups compared to the corresponding kidneys from control animals. Despite the lower BP of both treated groups, clipped kidney GFR and RPF were unchanged compared to the control group. Ualb V for nonclipped kidneys from untreated rats was approximately 5- to 10-fold higher than in the nonclipped kidneys from the treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

The relation between the excretion of sodium and water and the perfusion pressure in the isolated, blood-perfused, rabbit kidney, with special reference to changes occurring in clip-hypertension.

1. The sodium and water excretion rates of rabbit kidneys were studied when isolated and perfused at known pressure with blood from another normal anaesthetized rabbit. Studies at several different perfusion pressures confirmed that a small rise in perfusion pressure caused a large rise in sodium excretion and that the potential sodium-excreting ability of the isolated kidney was high. The curve obtained could be closely fitted by a quadratic equation which allowed an estimate to be made of the blood pressure below which no urine is formed, i.e. the 'theoretical perfusion pressure threshold'. For normal kidneys this was 55-4 mmHg. 2. A group of rabbits had a silver clip applied to the left renal artery and, 3-6 weeks later, the eight most hypertensive animals were selected to provide their kidneys for perfusion. Both kidneys were perfused simultaneously. The clip on the left renal artery was removed immediately before perfusion and the cannula placed distal to the stenosis in the post-stenotic dilatation. The function curves of these kidneys were compared with the curves obtained from normal kidneys. 3. The untouched kidney contralateral to the clip was found to require a significantly higher perfusion pressure (71-7 mmHg) for it to achieve a given sodium excretion rate and, surprisingly, the clipped kidney showed a similar functional change (76-4 mmHg). In other words the positions of both function curves were shifted though their slopes were not much changed. 4. Both kidneys in single-clip-hypertension appear to adapt or reset their sodium excretory behaviour. The resetting in the untouched kidney allows hypertension to be sustained without undue sodium loss. Aldosterone probably contributes little to the resetting. We infer, indirectly, that the normal kidney may, to a significant extent, restrain sodium excretion by virtue of its sympathetic innervation. We also opine that the kidney cannot be assigned fixed intrinsic functional properties on which a renal sodium-handling theory of long-term blood pressure regulation can be firmly based.

Animals↗

Pre-oxygenation using face mask or mouthpiece with and without nose clip: patient preferences and efficacy.

We assessed the effectiveness of mouthpieces for oxygenation before induction of anaesthesia. In part 1 of the study we asked 52 day case patients whether they would prefer mask, mouthpiece, or mouthpiece with nose clip, and which they would be willing to use. In part 2 we pre-oxygenated 18 volunteers using each of the three methods in a crossover study. We measured time to 90% end tidal oxygen concentration (FE'O2), or maximum FE'O2 after 3 min if less than 90%. Of the patients surveyed, 20 (39%) preferred mask, 23 (44%) mouthpiece, one mouthpiece with nose clip and nine (17%) expressed no preference. Only 88% would be willing to use the face mask, but all would accept either the face mask or the mouthpiece with nose clip. In part 2 of the study, the mouthpiece alone proved significantly worse than the mask or mouthpiece with nose clip. The latter two did not differ significantly. Offering the alternative of mouthpiece with nose clip would increase patient acceptance of effective pre-oxygenation.

Adolescent↗

The cytoplasmic linker protein CLIP-170 is a human autoantigen.

The purpose of this study was to identify autoantigens that are recognized by human sera and are associated with a speckled cytoplasmic fluorescent staining pattern on tissue culture cells, and to determine clinical features associated with specific autoantibodies. A serum from a patient with systemic lupus erythematosus was used to identify a 3.7-kb cDNA insert from a HeLa cell expression library. The purified cDNA (VLK2.1) encoded a peptide of 1051 amino acids that shared 98.4% similarity with the carboxyl terminal portion of a previously reported 170 kD protein named cytoplasmic linker protein-170 (CLIP-170). Antibodies affinity purified with the recombinant CLIP-170 protein, the prototype human serum and a monoclonal antibody raised against CLIP-170 exhibited identical speckled staining of the cytoplasm in HEp-2 cells. The human autoantibodies reacted with the purified recombinant protein in a Western immunoblot and immunoprecipitated the in vitro translated recombinant protein. Three additional human sera also immunoprecipitated the recombinant CLIP-170 protein. The clinical diagnoses in these patients were limited scleroderma, glioblastoma and idiopathic pleural effusion. This is the first report that identifies CLIP-170 as a human autoantigen.

Autoantigens↗

Hemodynamic efficacy of the new resolution clip device in comparison with high-volume injection therapy in spurting bleeding: a prospective experimental trial using the compactEASIE simulator.

BACKGROUND AND STUDY AIMS: Peptic ulcers are the most frequent cause of gastrointestinal bleeding. The use of hemoclips has become established as an effective form of treatment in addition to injection therapy. However, hemoclips have not previously been compared with injection therapy in an experimental setting using objective parameters. MATERIALS AND METHODS: In a prospective, randomized, and controlled trial, the disposable Resolution hemoclip device (Boston Scientific, n = 40) was compared with conventional injection therapy (n = 40) in an experimental setting, using the compactEASIE simulator equipped with an upper gastrointestinal organ package to simulate bleeding. Four investigators with different levels of endoscopic experience participated in the study. On a randomized basis, each investigator treated 20 bleeding sites either by applying one clip (n = 10) or by carrying out high-volume four-quadrant injection (4 x 10 ml saline) of a spurting vessel. The efficacy of the hemostasis was assessed by continuous measurement of pressure within the afferent vessel before and after clip application or injection therapy and calculating the relative reduction in the vessel's diameter with each treatment method. The system pressure was recorded 1 min before and 1 min after treatment. The ease of application of each method was rated by the endoscopist and by the assisting nurse using a visual analogue scale (0 - 100, with 100 being best). RESULTS: All of the 40 hemoclipping and injection treatments were carried out successfully. Both methods led to a significant increase in peak pressure (Resolution clip 71.8 +/- 66.8 mm Hg, P < 0.001; injection 71.9 +/- 53.8 mm Hg, P < 0.001), representing a significant relative reduction in the vessel diameter. There were no significant differences in peak pressure between the two treatments ( P = 0.995). The mean increase in pressure during the first minute after the intervention (clip 49.3 +/- 67.0 mm Hg vs. injection 19.9 +/- 41.6 mm Hg) was significantly greater with the hemoclipping procedure ( P = 0.021). More experienced investigators achieved a greater increase in system pressure, but the difference was not significant. The assessments of the ease of application by the assistants (84 +/- 13) and endoscopists (86 +/- 16) did not show any significant differences ( P = 0.402) for the clipping device. CONCLUSIONS: No significant differences between the two treatment methods were detected with regard to the immediate efficacy of hemostasis. However, long-term hemostasis was better with hemoclipping. The endoscopist's level of experience also appears to play a role, particularly when hemoclips are used.

Animals↗

Endoscopic clipping of anastomotic leakages in esophagogastric surgery.

BACKGROUND AND STUDY AIMS: Anastomotic leakage is a severe complication in gastric surgery and it is associated with a high rate of mortality. Conservative treatment sometimes is not sufficient to stem the leakages and, even when it is sufficient, it takes a long time. The present study describes the first experience in the treatment of anastomotic leakages with endoscopic clipping. PATIENTS AND METHODS: From May 1995 to December 1996, seven patients with postoperative anastomotic leakages after gastric surgery were prospectively treated in our Endoscopy Service. Metallic endoclips (MD 850, Olympus Corp., Tokyo, Japan) with prongs 12 mm long and 6 mm wide were applied, controlling the closure of the leakage by endoscopy, using radiographs to confirm the closure 24 hours later. RESULTS: Complete closure of the leakage was obtained in all seven cases. A single session of endoscopic clipping was needed for five patients while two other required, respectively, two and three sessions. The median time of leakage closure after endoscopic clipping was 2.3 days (range 1-5 days). The clips spontaneously dislodged within 1 month in five patients and within the second month in the other two patients. CONCLUSION: Endoscopic treatment of anastomotic leakages by metallic clips represents a safe and easily repeated method and, compared to conservative treatment, it seems to offer several time and cost advantages. Further studies involving a larger number of patients are needed to verify this finding.

Adenocarcinoma↗

Endoscopic variceal ligation using a clipping apparatus in children with portal hypertension.

BACKGROUND AND STUDY AIMS: Endoscopic variceal sclerotherapy (EVS) is a procedure frequently used to control bleeding from esophageal varices in adults. The use of EVS has been restricted in children due to the associated risks. The present paper describes the safety and efficacy of a new apparatus for endoscopic variceal ligation with clipping (EVLC). PATIENTS AND METHODS: Endoscopic variceal ligation using a clipping apparatus (HX-3 L, Olympus, Tokyo, Japan), was carried out in 12 children with portal hypertension (four with extrahepatic portal vein obstruction and eight with congenital biliary atresia; four boys and eight girls, age range 2-14 years). A total of 417 variceal clipping procedures were carried out in 56 separate EVLC sessions; 118 esophageal varices and 65 gastric fundic varices were ligated using 417 clips. Initially, the EVLC sessions were repeated at approximately monthly intervals until the varices were eradicated, but the interval was gradually extended to twice a year or once a year. RESULTS: Varices were successfully ligated at the first attempt in 414 (99.3%) of the 417 clipping procedures. The esophageal varices were initially eradicated in all patients. The follow-up period ranged from nine to 48 months, and complete variceal eradication or reduction of the grade of the varices was obtained in 11 of the 12 patients after initial eradication during this period. CONCLUSIONS: These data indicate that EVLC offers advantages in the treatment of patients with esophageal varices combined with gastric fundic varices.

Adolescent↗

A new disposable microvascular double clip.

A new disposable microvascular double clip made of polycarbonate has been designed. In order to investigate whether or not the clip causes vascular damage, experiments were conducted with scanning electron microscopy and light microscopy, using the common carotid arteries of Fischer rats. The study revealed that the new clip did not produce any damage to the arterial wall. The clip has also been used in 30 clinical cases, with generally good results. The new microvascular clip is economical, atraumatic to the vascular wall, and is always in the best condition, because of its disposability. The device is very useful for both laboratory and clinical microvascular surgery.

Animals↗

Effects of new titanium cerebral aneurysm clips on MRI and CT images.

We studied the effects of newly developed aneurysm clips made of a titanium alloy (manufactured by Aesculap, A.G.) on the quality of MR and CT images. Prior to clinical application in twenty patients, the effects of five types of conventional aneurysmal clips on MR images were examined utilizing a phantom. When compared with conventional aneurysm clips, the new titanium clips produce only limited artifacts and yielded improved images in patients who underwent aneurysm clipping post-operative.

Aged↗

H2-Mbeta 1 and H2-Mbeta 2 heterodimers equally promote clip removal in I-A(q) molecules from autoimmune-prone DBA/1 mice.

Antigen-presenting cells degrade endocytosed antigens, e.g. collagen type II, into peptides that are bound and presented to arthritogenic CD4(+) helper T cells by major histocompatibility complex (MHC) class II molecules. Efficient loading of many MHC class II alleles with peptides requires the assistance of H2-M (HLA-DM in humans), a heterodimeric MHC class II-like molecule that facilitates CLIP removal from MHC class II molecules and aids to shape the peptide repertoire presented by MHC class II to CD4(+) T cells. In contrast to the HLA-DM region in humans, the beta-chain locus is duplicated in mice, with the H2-Mb1 beta-chain distal to H2-Mb2 and the H2-Ma alpha-chain gene. H2-M alleles appear to be associated with the development of autoimmune diseases. Recent data showed that Mbeta1 and Mbeta2 isoforms are differentially expressed in isolated macrophages and B cells, respectively. The tissue expression and functional role of these heterodimers in promoting CLIP removal and peptide selection have not been addressed. We utilized the human T2 cell line, which lacks part of chromosome 6 encompassing the MHC class II and DM genes, to construct transgenic cell lines expressing the MHC class II heterodimer I-A(q) alone or in the presence of H2-Malphabeta1 or H2-Malphabeta2 heterodimers. Both H2-M isoforms facilitate the exchange of CLIP for cognate peptides on I-A(q) molecules from arthritis-susceptible DBA/1 mice and induce a conformational change in I-A(q) molecules. Moreover, I-A(q) cell-surface expression is not absolutely dependent on H2-M molecules. These data suggest that I-A(q) exhibits a high affinity for CLIP since virtually all I-A(q) molecules on T2 cells were found to be associated with CLIP in the absence of both H2-M isoforms.

Animals↗

The roles of two clip domain serine proteases in innate immune responses of the malaria vector Anopheles gambiae.

The malaria vector Anopheles gambiae is capable of multiple immune responses against Plasmodium ookinetes. Accumulating evidence in several insect species suggests the involvement of serine protease cascades in the initiation and coordination of immune responses. We report molecular and reverse genetic characterization of two mosquito clip domain serine proteases, CLIPB14 and CLIPB15, which share structural similarity to proteases involved in prophenoloxidase activation in other insects. Both CLIPs are expressed in mosquito hemocytes and are transcriptionally induced by bacterial and Plasmodium challenges. Functional studies applying RNA interference revealed that both CLIPs are involved in the killing of Plasmodium ookinetes in Anopheles. Studies on parasite melanization demonstrated an additional role for CLIPB14 in the prophenoloxidase cascade. We further report that both CLIPs participate in defense toward Gram-negative bacteria. Our findings strongly suggest that clip domain serine proteases serve multiple functions and play distinctive roles in several immune pathways of A. gambiae.

Amino Acid Sequence↗

CG-clip expansive open-door laminoplasty: a technical note.

The CG clip is a device designed for use in expansive open-door laminoplasty with both a spacer and means of attachment in a single unit. It provides an effective technique for open-door laminoplasty, which obviates the need for bone grafting or complex internal fixation by providing dynamic stabilization of the open laminae. A number of techniques for expansive open-door laminoplasty have been devised for the decompression of the spinal cord and nerve roots in cervical spondylotic myeloradiculopathy. Each of these techniques requires some degree of internal fixation and/or bone grafting. The CG clip is a single device which is composed of both a spacer and a spring clip for attachment. The spacer ensures a 4-5-mm sagittal expansion of the cervical spinal canal. The spacer is held in place along the lateral cut margin of the laminae by a spring-wound titanium clip, which folds over the central spinous process of the unilaterally elevated laminar block. In all respects except for grafting and internal fixation, the surgery is performed as for a standard expansive open-door laminoplasty. Sixteen of the first 24 patients to undergo this procedure improved at least one point on the Neurosurgical Cervical Spine Scale. Of the remaining eight patients, four remained the same and four deteriorated. The authors have found the CG-clip laminoplasty technique quick and easy to perform, with early results in the treatment of cervical spondylotic myeloradiculopathy consistent with those of other decompressive procedures.

Equipment Design↗

Evidence that binding site occupancy is necessary and sufficient for effective major histocompatibility complex (MHC) class II transport through the secretory pathway redefines the primary function of class II-associated invariant chain peptides (CLIP).

Invariant chain (Ii) associates with newly synthesized class II molecules in the endoplasmic reticulum (ER), an interaction that has been shown to interfere with peptide binding to class II molecules. The class II-associated invariant chain peptide (CLIP) region (residues 81-104) of Ii is believed to mediate this inhibition by engaging the binding domain of class II like an antigenic peptide. Together, these findings have given rise to a model in which CLIP association with the class II groove acts to prevent inappropriate presentation of peptides imported into the ER for association with major histocompatibility complex class I molecules. However, the properties of class II molecules synthesized by cells lacking coexpressed Ii are at least superficially inconsistent with this paradigm in that they do not show clear evidence of peptide acquisition. At the same time, we have previously shown the shortest form of Ii still containing CLIP to play an essential role in regulation of early class II molecule assembly and transport in the secretory pathway. Using covalent peptide technology, we now show that occupancy of the class II binding site in the ER regulates class II trafficking to the Golgi complex, an event that is the locus of the major defect in cells of Ii-deficient mice. These data argue that CLIP occupies the class II binding site, not to prevent interaction with short peptides meant for class I, but rather to maintain the structural integrity of class II molecules that are labile without engaged binding regions, and that would also associate with intact proteins in the ER if left unoccupied. By these means, CLIP occupancy of the class II binding site promotes effective export of useful class II molecules for endocytic peptide acquisition.

Amino Acid Sequence↗

Video-assisted thoracoscopic T2 sympathetic block by clipping for palmar hyperhidrosis: analysis of 52 cases.

BACKGROUND: Endoscopic thoracic sympathectomy or sympathicotomy is a standard method in treating palmar hyperhidrosis, but postoperative compensatory sweating may be troublesome in some patients. Therefore, we designed a new technique for only T2 sympathetic blocking by clipping instead of interruption of the sympathetic trunk. PATIENTS AND METHODS: Between September 2000 and July 2001, we saw a total of 100 patients with palmar hyperhidrosis who underwent video-assisted thoracoscopic sympathetic blocking of the T2 ganglion. All patients were placed in a semisitting position under single-lumen intubated anesthesia. We performed sympathetic blocking by clipping of the T2 ganglion at the level of the second and third rib beds using an 8-mm, 0 degree thoracoscope (Storz). RESULTS: We supposed that the postoperative improvement in palmar hyperhidrosis would be perfect. The operation could be accomplished within 30 minutes. All patients were discharged within 4 hours after the operation. Surgical complications were minimal, without surgical mortality. A few patients were willing to receive the reverse operation and should get improvement of compensatory sweating after removal of the endo clips. CONCLUSION: We believe that video-assisted thoracoscopic T2 sympathetic block by clipping will be a safe and effective method of treating patients with palmar hyperhidrosis. Compensatory sweating may be improved by the reverse operation: removal of the endo clip.

Adolescent↗

Laparoscopic ureterocalicostomy: development of a technique simplified by application of Nitinol clips and a wet monopolar electrosurgery device.

PURPOSE: We developed a technique for laparoscopic ureterocalicostomy with the use of intracorporeal suturing and subsequently simplified the technique by application of experimental Nitinol clips. MATERIALS AND METHODS: We performed laparoscopic ureterocalicostomy on 16 domestic swine divided into four groups of four animals each. The kidney was exposed laparoscopically, and the renal artery was atraumatically clamped. The lower pole of the kidney was amputated to expose a lower-pole calix, and hemostasis of the cut renal surface was obtained with a wet monopolar electrosurgical device (Floating Ball device [FB]; TissueLink, Dover, NH). Anastomosis of the ureter to the lower-pole calix was performed over a guidewire using 3-0 Vicryl suture in group 1 and Nitinol clips in group 3. A double-J ureteral stent was then deployed retrograde under fluoroscopic guidance. In addition, we evaluated the use of fibrin glue as a sealant over the sutured or clipped anastomotic site (groups 2 and 4, respectively). Ureteral stents were removed after 3 weeks, and the animals were evaluated and sacrificed after an additional 3 weeks. RESULTS: Laparoscopic ureterocalicostomy was completed in all 16 animals. In each case, excellent renal parenchymal hemostasis was obtained with the FB device, with a mean hemostasis time of 4.1 minutes. The mean anastomotic time with standard suture reconstruction was 37.1 +/- 5.4 minutes, while the anastomotic time with the Nitinol clips was 29.0 +/- 8.0 minutes (P = 0.0339). Retrograde pyelograms in groups 1 and 3 (no fibrin glue) showed a patent anastomosis with no hydronephrosis in three of the four animals in each group. One animal in group 1 and one animal in group 3 developed large urinomas secondary to anastomotic failure. The animals that received fibrin glue over the anastomotic site (groups 2 and 4) all showed narrowed anastomoses with severe hydronephrosis. CONCLUSIONS: With available instrumentation, laparoscopic ureterocalicostomy is technically feasible. Nitinol clip technology significantly reduces collecting-system reconstruction time. Application of fibrin glue as a urinary tract sealant resulted in an unexpected adverse outcome.

Alloys↗

Reported failures of the polymer self-locking (Hem-o-lok) clip: review of data from the Food and Drug Administration.

BACKGROUND AND PURPOSE: New technology has played an important role in the proliferation of laparoscopy within urology. A central issue remains meticulous hemostasis, particularly for larger vessels (e.g., renal artery and vein). This paper presents available information regarding failure of the widely utilized nonabsorbable polymer Hem-o-lok clip (Weck Closure Systems, Research Triangle Park, NC), introduced in 1999. METHODS: The Food and Drug Administration Center for Devices and Radiological Health maintains a compendium of reports of adverse events involving medical devices (MAUDE). We performed multiple searches of MAUDE using a variety of key words, including Weck, Hem-o-lok, laparoscopy, nephrectomy, and clip. RESULTS: Within the MAUDE database, we identified 27 reports of problems with the Hem-o-lok clip until July 6, 2005. Of these events, only 1 (4%) involved application during open surgery, with the remainder occurring during laparoscopy. Minimal morbidity resulted from applicator difficulty during laparoscopic cholecystectomy (N = 7; 26%), with one case of open conversion. Forty-eight percent (N = 13) of the failures occurred during urologic laparoscopy; of these, bleeding was the primary problem in 77%. Delayed exploration, immediate open conversion, and death resulted in 38% (N = 5), 8% (N = 1), and 15% (N = 2), respectively. No clear etiology for the events could be found, although in all situations, multiple clips had been applied with apparent initial vessel control intraoperatively. CONCLUSIONS: Reported difficulty with the Hem-o-lok clip occurs primarily during laparoscopic surgery. Cases of failure after laparoscopic nephrectomy require urgent exploration, although it is unclear whether device or user error is the underlying cause. Regardless, care must be taken in securing the renal vessels, surgeons must be educated regarding proper use and techniques, and consideration should be given to using transfixing techniques.

Equipment Failure↗

The use of absorbable clips in laparoscopic cholecystectomy.

A prospective randomized controlled study was conducted to evaluate the use of absorbable clips in elective laparoscopic cholecystectomy. Fifty consecutive patients, 36 females and 14 males, were randomized into two groups. Group 1 patients had metal clips, and group 2 patients had absorbable clips applied on the cystic duct and cystic artery. These patients were followed for 3 months postoperatively. There was no difference between the two groups with regard to operative time, hospital stay, and postoperative complications. The absorbable clips were as effective as the metal clips in providing hemostasis and securing on the cystic duct stump.

Adolescent↗

Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170.

The flow of material from peripheral, early endosomes to late endosomes requires microtubules and is thought to be facilitated by the minus end-directed motor cytoplasmic dynein and its activator dynactin. The microtubule-binding protein CLIP-170 may also play a role by providing an early link to endosomes. Here, we show that perturbation of dynactin function in vivo affects endosome dynamics and trafficking. Endosome movement, which is normally bidirectional, is completely inhibited. Receptor-mediated uptake and recycling occur normally, but cells are less susceptible to infection by enveloped viruses that require delivery to late endosomes, and they show reduced accumulation of lysosomally targeted probes. Dynactin colocalizes at microtubule plus ends with CLIP-170 in a way that depends on CLIP-170's putative cargo-binding domain. Overexpression studies using p150(Glued), the microtubule-binding subunit of dynactin, and mutant and wild-type forms of CLIP-170 indicate that CLIP-170 recruits dynactin to microtubule ends. These data suggest a new model for the formation of motile complexes of endosomes and microtubules early in the endocytic pathway.

Animals↗