Extraluminal Space Research Articles

Anti-reflux devices for preventing intraluminal reflux through double-J stents using elastomer casting process

This study develops check valve-shaped flexible devices for perfect prevention of intraluminal reflux in patients with indwelling double-J (DJ) stent, with side hole effects ignored. These can be assembled with the penta-shaped extraluminal anti-reflux device, developed in our previous work to determine anti-reflux efficiency via in vitro study. The intraluminal anti-reflux devices (IADs) were fabricated by casting process with various elastomers, with a three-dimensional printer. Based on the elastomers, four types of IADs were manufactured, and intraluminal anti-reflux performances were demonstrated with respect to the elastomers. Consequently, the Ecoflex 00–50 based IAD demonstrated the best anti-reflux performance that perfectly prevented reflux in our J-shaped experimental setup and ensured the highest broken load between a valve and body of the IAD. Moreover, the IAD provided smooth urine drainage and was durable under 4500 open and close cycles without significant change in anti-reflux performance. In experimental results, the IAD with the DJ stent prevented the intraluminal reflux perfectly when both the side holes were closed, and extraluminal space was blocked. To mitigate vesicoureteral reflux symptoms, the IAD is expected to be used in case of side holes-free DJ stent located in the bladder and blocked extraluminal space.

S2167 Chronic, Massive Pneumoperitoneum in a Patient Without Signs of Peritonitis: A Case Report

Introduction: Pneumoperitoneum is the presence of free air in the abdominal cavity. This alarming symptom can be due to a wide variety of etiologies, including infection, trauma, perforation, and others. However, pneumatosis intestinalis, which is the presence of free air in the extraluminal space, can be due to other pathology unrelated to the GI tract. It can be seen in pulmonary disease, such as COPD and asthma, autoimmune conditions, and drug-induced causes as well. It can present with more benign symptoms. We present a case of chronic pneumatosis intestinalis that was present in the patient for over 2 years and presented with relatively minor, nonspecific symptoms. Case Description/Methods: This patient was a 62-year-old male who presented with concerns of bloating and cramping, ongoing for 2 years. Previous work-ups had not revealed a clear cause for his ongoing symptoms. He had undergone CT of the abdomen, which was significant for massive pneumoperitoneum, as well as fluid-filled prominent loops of small bowel concerning for ileus or obstruction. There was no site of bowel perforation that could be visualized. Upper endoscopy and colonoscopy had been performed, which showed normal mucosa and colonic diverticulosis. After further workup at an additional institution, diagnostic laparotomy was recommended to further evaluate his small bowel. At the lower anterior diaphragm, the peritoneal surface had subperitoneal emphysema, suggesting a potential thoracic source for the pneumoperitoneum. Thoracic surgery were consulted for exploratory right-sided thoracoscopy since he was noted to have peritoneal blebs along the diaphragm most notably, with one also being identified on the liver. It was concluded that the etiology was most likely due to an alveolar-peritoneal fistula through the right hemidiaphragm (Figure). Discussion: Pneumatosis Intestinalis can be a benign presenting symptom. Pneumoperitoneum can be due to primary (idiopathic) or secondary causes. Secondary causes are numerous, and these can be seen in the setting of COPD, immunodeficiency, or acute GI pathology. Increased pressure in the abdomen or the mediastinum can result in gas diffusing across tissues and into the bowel wall. Treatment and management varies depending on the patient's presentation. More serious abdominal pathology requires surgical management, while benign causes in the setting of chronic lung pathology can be asymptomatic, or present with mild symptoms that require only conservative medical management.Figure 1.: Pneumatosis Intestinalis on CT Scan.

Axilary Block Ultrasound Guiding in Patient with Pseudoaneurysm Regio Brachii Sinistra pro Repair Pseudoaneurysm

Background: An aneurysm may be a true aneurysm or a pseudoaneurysm. Pseudoaneurysm is defined as a defect in the arterial wall, making a connection between the lumen and the extraluminal space. The main etiology of brachial artery pseudoaneurysm is incidental arterial puncture during venous cannulation for hemodialysis. Case:: Anesthetic management was performed on a female patient 56 years old, body weight 45 kg, height 150 cm. The patient had other comorbidities such as hypertension, diabetes mellitus, chronic renal kidney with a diagnosis of left brachial pseudoanuerysm. Pro Pseudoanurysm repair surgery. The anesthetic technique uses axillary peripheral nerve block with ultrasound guiding. The duration of surgery is ± 120 minutes. After the operation, the patient was treated in the hospital ward. Conclusion: Choosing the most appropriate anesthetic technique for patients with renal impairment is necessary to maintain normovolemia and normotension in order to avoid unexpected complications. Using regional anesthetic technique for sympathetic nerve block may be favorable in these patients. With ultrasound guiding, the incidence of failure is lower, the time required is shorter, the latency is shorter, the blockade is longer, and the risk of accidental vascular puncture is lower so that vascular lesions are less likely.

Pseudoaneurysm of the popliteal artery. Complication of knee arthroscopic procedures. Case raport

A pseudoaneurysm refers to a defect in an arterial wall, which allows the communication of arterial blood with the ad­ja­cent extraluminal space. Blood extravasates out of the ar­te­ry, but is contained by surrounding soft tissue which forms a cavity or sac. Pseudoaneurysms are typically the result of traumatic arterial injury. With the increasing uti­li­sa­tion of percutaneous arterial interventions worldwide, iatrogenic arterial injury has become the predominant cause of pseudoaneurysm formation. The highest inci­dence of iatrogenic pseudoaneurysm formation is observed in the common femoral artery as a result of inadequate hae­mo­sta­sis of the arterial puncture site following catheterisation pro­cedures, followed by the popliteal artery. Patients with popliteal pseudoaneurysms typically present with pain and swelling of the affected area (calf), along with a palpable mass which may be pulsatile with a thrill or bruit. Small pseu­do­­aneurysms can resolve spontaneously without in­ter­ven­tion. Persistent pseudoaneurysms may increase and lead to complications related to compression of the vein, nerve and overlying tissues. This can lead to swelling of the legs, deep vein thrombosis, compressive neuropathy and skin necrosis. Although rare, pseudoaneurysms can spread and eventually rupture. Imaging is a mandatory part of the di­ag­nostic protocol for popliteal artery pseudoaneurysms. Dop­pler ultrasound, CT or MRI examinations performed with contrast and angiography are useful in determining pseudoaneurysmal masses. Doppler ultrasound is the most commonly chosen method for diagnosing pseu­do­aneu­rysms, with a sensitivity of 94% and a specificity of 97% in the detection of pseudoaneurysms. On Doppler ul­tra­sound, a pseudoaneurysm appears as a hypoechoic sac adjacent to the affected artery, with the color flux ob­served inside it. Computed tomography angiography is another effective way of diagnosis, especially in centers with­out easy access to vascular ultrasound services. It is also useful in cases where Doppler ultrasound findings are ambiguous or the anatomy is not well defined. Open sur­gi­cal treatment has been considered the gold standard for ia­tro­genic pseu­do­aneu­rysms because the arterial defect is per­ma­nent­ly repaired.

Tu1028 POST-SURGICAL OR SPONTANEOUS RECALCITRANT LEAK MANAGEMANT USING NOVEL APPROACHES: ENDOSCOPIC DUPLICATION OF GUT VIA EXTRALUMINAL STENT (EDGES) & SUTURE OBTRUDED COVERED STENTS (SOCS)

Gastrointestinal fistulas, leaks, & perforations are associated with high morbidity and mortality as well as prolonged hospitalization. In 30-40% of patients the current management strategies such as wait & watch, transcutaneous drainage and endoscopic closure fail to resolve the symptoms adequately. We envisioned novel minimally invasive approaches to manage these defects. EDGES: used for recalcitrant fistulas with a para-luminal abscess cavity in the proximity of the GI tract. A pediatric upper endoscope was advanced through the fistula into the extra-luminal space. Under direct endoscopic view an intentional perforation was created to connect the distal most end of the abscess cavity to the gut lumen. A fully covered metal stent (Gore Viabil 10x100mm) was deployed from the gut lumen, through the fistula, across the abscess cavity, and back through the new perforation into the gut lumen. This approach prevented the entry of gut contents into the abscess to eventually allow the healing (Figure 1-4). SOCS: used in patients with recalcitrant fistulas with an abscess cavity that was not in the proximity of the GI tract to accomplish EDGES. A fully covered metal stent (Gore Viabil 10x100mm) was deployed ex-vivo. One of the ends of the stent was obtruded by proline suture & tested for complete sealing. Using a push or pull technique the obtruded end of the stent was passed from the lumen, through the fistula, into the abscess cavity & the open end remained in the gut lumen plugging the fistulous opening (Figure 5). We assessed the outcome of patients who underwent these techniques between April 2018 to Nov. 2019. The underlying cause of the defect and clinical follow-up as well as endoscopic & radiographic data was collected. We defined an endoscopic response as absence of a leak under endoscopic or fluoroscopic assessment of the GI defect. A total of 15 patients (5 female), mean age of 48 years were managed using EDGES in 6 patients & SOCS in 9 patients. Overall success of these novel approaches was 80%. Mean time to response was 89.5 days with an average follow-up of 166.3 days. EDGES was successful in 83% cases and SOCS was successful in 78% cases. 7(47%) patients had IBD, and one had malignancy; 5(33%) defects were gastric, 3(20%) were jejunal, 3(20%) were ileal, and 4(26.7%) were colonic. The average number of procedures prior to EDGES/SOCS was 5.4. Of the 3 patients who did not respond to endoscopic therapy, two patients failed therapy due to stent migration. Our novel, unconventional EDGES and SOCS approaches are promising to manage recalcitrant leaks. A consideration should be given to these approaches to avert high-risk surgery in a subset of patients.

Sa2009 DEVELOPMENT OF A PER ORAL TRANSESOPHAGEAL ENDOSCOPIC CRUROPLASTY (POTEC) IN AN ACUTE PORCINE MODEL

Transluminal and intramural endoscopic procedures continue to increase in type and variety. Notably, POEM and ESD are now performed regularly in many centers. These procedures have led to additional diagnostic and therapeutic procedures in the extraluminal space via submucosal tunneling. Using an acute porcine model, our goal was to develop a procedure to approach the diaphragmatic hiatus and perform a cruroplasty via an esophageal tunnel. The specific aims were to determine the ideal location for access, ease of display of anatomy, feasibility of the cruroplasty, and to define the key steps of the procedure. An acute study with IACUC approval and veterinary staff assistance using 4 Yorkshire pigs was completed by a single endoscopist. Submucosal tunnels were made at different locations (10 and 20 cm above GEJ) in two animals, one prone and the other supine, and suturing of crura attempted. Lessons from these cases informed the latter two procedures. A 5cm submucosal tunnel was created posteriorly. The mediastinum was entered 2cm into the tunnel via myotomy and trans-mural incision sizable enough to accommodate the suturing device. From within the mediastinum, the esophagus was followed to the hiatus requiring dissection of connective tissue to allow for identification of both vagus nerves and crura on either side of the hiatus. One suture was placed after taking two bites from each crura. Immediate euthanasia and necropsy followed. Safe trans-esophageal access, display of anatomy, and cruroplasty was reliably achieved in all animals. Trans-esophageal access was best performed dorsally about 10-12cm above the GEJ, with the animal in the prone position. One animal was attempted in the supine position and had to be repositioned during the procedure as this position altered ability to navigate the hiatus. An anterior approach to mediastinal access was attempted in one animal and also interfered with ease of identification of structures. Tunnels that were made 10cm proximal to the GEJ allowed for easier access and identification of structures than those made 20cm from the GEJ (directly assessed in the first two animals). Myotomy and mediastinal access was done from the end of a 5 cm tunnel. Attempts to stay in the mediastinum caused micropuncture and tension pneumothorax in the first animal, resolved by making a larger access point. Immediate necropsy showed successful cruroplasty without iatrogenic injury. POTEC procedure is feasible. The procedural steps are defined and mediastinal anatomy can be safely identified and avoided during suturing. The cruroplasty was shown to be successfully placed without iatrogenic injury on necropsy. A survival study will confirm the potential for clinical application, particularly in the treatment of GERD.Figure 2Photo of necropsy showing successful endosuturing of the crura from the superior view of the diaphragm.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A bioartificial kidney device with polarized secretion of immune modulators.

The accumulation of protein-bound toxins in dialyzed patients is strongly associated with their high morbidity and mortality. The bioartificial kidney device (BAK), containing proximal tubule epithelial cells (PTECs) seeded on functionalized synthetic hollow fibre membranes, may be a powerful solution for the active removal of those metabolites. In an earlier study, we developed an upscaled BAK containing conditionally immortalized human PTEC with functional organic cationic transporter 2. Here, we first extended this development to a BAK device having cells with the organic anionic transporter 1, capable of removing anionic uraemic wastes. We confirmed the quality of the conditionally immortalized human PTEC monolayer by confocal microscopy and paracellular inulin-fluorescein isothiocyanate leakage, as well as by the active transport of anionic toxin, indoxyl sulphate. Furthermore, we assessed the immune safety of our system by measuring the production of relevant cytokines by the cells after lipopolysaccharide stimulation. Upon lipopolysaccharide treatment, we observed a polarized secretion of proinflammatory cytokines by the cells: 10-fold higher in the extraluminal space, corresponding to the urine compartment, as compared with the intraluminal space, corresponding to the blood compartment. To the best of our knowledge, our work is the first to show this favourable cell polarization in a BAK upscaled device.

The Experimental Animal Research of Peroral Endoscopic Tunnel Technique in Diagnosis and Treatment of the Diseases Around Abdomen Aorta

Introduction: The emergence of endoscopic tunnel technique makes many diseases which used to need surgical or laparoscopic surgical treatments entered into the endoscopic therapy. The tunnel technique could well prevent the communication between the intra-luminal and the extra-luminal space by sealing the entry incision of the tunnel, gas or fluid within the lumen was prevented from entering the extra-luminal space, which could ensure the endoscopic therapy free of perforation. The procedure is endoscope penetrate from body's natural orifices such as esophagus, gastric, rectum, vagina and so on to body cavity for treatment. But there are few bottlenecks in the development of NOTES. First, it is difficult to close the entrance of natural orifices. Second, the infection which is caused by liquid and air of natural orifices enter into body cavity would occur. Third, it would be lost in body cavity. This research use endoscopic tunnel techniques to perform NOTES in experimental pigs, The tunnel will resolve the problem of closing entrance and infection. Methods: Established an esophagus submucosal tunnel about 5cm long to cardia at the back wall in pigs, Full-thickness myotomy performed and endoscope entered into abdominal cavity through the muscle incision. Exhaust air by puncturing into abdominal cavity. Partial hepatectomy and splenectomy, around the celiac artery ganglion neurolysis, partial tissue resection in the aera of posterior peritoneum were performed. Experimental pigs were prohibited water and diet intake and took antibiotics for 5 days. Their survival situations were observed. Three days later, experimental pigs were executed and were opened to observe the structures of abdominal cavity. Results: Experimental pigs were died after operating splenectomy. Experimental pigs were alive after successfully operating other surgeries. Three days later experimental pigs were executed and were found no injuries in other organs, but adhesion to different degrees of tissues in surgery position. Extensive intra-abdominal endoscopic therapy couldn't be carried out with limit of current endoscopic equipment. Conclusion: Partial hepatectomy and splenectomy, around the celiac artery ganglion neurolysis and partial tissue resection in the area of posterior peritoneum were all successfully performed in experimental animals through endoscopic tunnel technique and the complications were under controlled by internal medicine treatments.

A Rare and Fatal Case of Dobhoff Tube Placement-Associated Small Bowel Perforation Presenting With Acute Leukopenia

Enteral feeding with Dobhoff tubes is a common mode of nutrition in acute or chronically ill patients. Common adverse events associated with Dobhoff placement include epistaxis and sore throat. More serious complications such as esophageal perforation and pneumothorax have been reported. We report a case of small bowel perforation after Dobhoff placement with acute leukopenia as an initial laboratory manifestation. A 75-year-old female presented to the hospital with a 3-year history of worsening hoarseness and shortness of breath. Bedside laryngoscopy demonstrated a large laryngeal mass. Biopsy results were positive for squamous cell carcinoma. Bronchoscopy and esophagoscopy (to pre-pyloric region) were unremarkable. Due to severe protein malnutrition, a Dobhoff was placed for pre-operative optimization for laryngectomy. Post-placement KUB showed tube overlying the body of stomach. 12 hours post Dobhoff insertion, vital signs were notable for hypotension to 72/48 mmHg. Physical exam was notable for diminished bowel sounds. Laboratory results showed an acute leukopenia of 1100 mcL, and lactate of 3.6 mmol/L. KUB showed advancement of the Dobhoff tube, with visualization of bowel wall lumen suggesting pneumoperitoneum. The patient remained hypotensive despite fluid resuscitation and was transferred to the ICU for pressor support. A CT scan of the abdomen revealed intraperitoneal and retroperitoneal air, with the enteric tube noted to be extraluminal with suspected perforation of the second part of the duodenum. Surgery was consulted, however due to the patient progressing to multi-system organ failure, and high surgical mortality risk, the patient was made DNR/Comfort Care and expired 6 hours later. Dobhoff placement is a common procedure performed across the country. Although a relatively safe procedure, it can have complications such as bowel perforation. One of the initial presenting clues may be acute leukopenia. Acute leukopenia has also been reported in laparoscopic bowel perforations during urological surgery. The mechanism of acute leukopenia in bowel perforation could be due to peritonitis leading to sepsis. Sepsis has been shown to cause acute bone marrow suppression leading to leukopenia. Another explanation is the marginalization of leukocytes in conditions of decreased blood flow such as hypotension. Leukocytes are shifted outward by RBCs in laminar flow, and in slow flow the leukocytes will adhere to the endothelial surface in larger number.Figure: Enteric tip overlying the gastric pylorus. Arrow showing “Rigler's Sign”, suggesting air on both sides of bowel concerning for extraluminal air.Figure: Large arrow showing intraperitoneal air in the anterior extraluminal space. Small arrow shows enteric tube possibly in extraluminal space.

Life-threatening Rupture of a Femoral Pseudoaneurysm after Cardiac Catheterization.

A pseudoaneurysm refers to a defect in the arterial wall, allowing communication of arterial blood with the adjacent extra-luminal space. Pseudoaneurysms result from traumatic arterial injury. With the increasing utilization of percutaneous arterial interventions, iatrogenic arterial injury has become the predominant cause of pseudoaneurysm formation. Rupture of the pseudoaneurysm comprises a vascular emergency. Clinical suspicion and imaging techniques are the cornerstones of timely diagnosis and appropriate management of the condition. Herein, we report the case of a 69 year-old woman who suffered a life-threatening profunda femoral artery pseudoaneurysm rupture after a routine cardiac catheterization, that was treated surgically.

Fish bone migration to the urinary bladder after rectosigmoid colon perforation

Fish bones are the most common foreign objects leading to bowel perforation. Most cases are confined to the extraluminal space without penetration of an adjacent organ. However, abscess formation due to the perforation of the rectosigmoid colon by a fish bone can lead to the penetration of the urinary bladder and may subsequently cause the fish bone to migrate into the urinary bladder. In the presented case, a 42-year-old female was admitted for lower abdominal pain. The computed tomography (CT) demonstrated a 5 cm pelvic abscess containing a thin and curvilinear foreign body. After conservative management, the patient was discharged. After 1 mo, the subject developed a mechanical ileus. Surgery had to be delayed due to her hyperthyroidism. Migration of the foreign body to the urinary bladder was shown on additional CT. A Yellowish fish bone 3.5 cm in size was removed through intra-operative cystoscopy. The patient was discharged 8 d after the operation without any unexpected event.

Rationale and Feasibility Study of a Mechanical Model for the Testing of Material Fatigue in Metal Ureteral Stents

Stents are used abundantly to maintain ureteral patency. The majority are plastic tubes that adjust easily to upper urinary-tract motion. Recently, a coiled-wire lumenless stent was introduced (ZebraStent, Neo Medical, Munich, Germany) to facilitate expulsion of stone fragments after lithotripsy. Its metal core is composed of Nitinol, with the soft J ends being of titanium. The thin shape considerably increases the extraluminal space. The ZebraStent stretches the ureter and also provides a surface for the fragments to glide along. In our 18-month experience with the ZebraStent, two of them fractured along the shaft. We sought to learn whether this complication resulted from a defect in stent design or from material fatigue secondary to constant movement. Our model is powered by an electric motor that produces a constant displacement similar to stent movements in vivo. The whole ZebraStent is embedded in a 37 degrees C waterbath to simulate physiological conditions within the ureter. We used an average displacement of 16 mm. The average frequency of ventilatory-cycle simulation was 20 times that in vivo, allowing us to collect data in a shorter time. All 10 stents broke within the proximal Nitinol shaft at the equivalent of 4 to 6 months (125-179 days). Our preliminary results show that all stents break after the equivalent of 4 or more months. The fact that this occurs in the homogenous proximal Nitinol shaft rather than at the welding point between the shaft and the titanium curl implies that breakage is secondary to material fatigue and not design error. Extensive testing is under way to confirm material fatigue as the cause of breakage. We hope to determine a safe dwelling time for these stents, which at the moment should not exceed 3 months.

Une cause rare d’abdomen aigu : la diverticulite jéjunale

Jejunal diverticulitis is a rare cause of acute abdomen and is diagnosed preoperatively only infrequently. A 34-year-old man presented with a history of increasing nonradiating epigastric and left upper abdominal pain and with fever, constipation, nausea and vomiting. His white blood cell count was 18,300/mm(3). Liver function tests and pancreatic enzymes were in the normal range. An abdominal CT scan showed jejunal diverticulitis and bubble gases in the extraluminal space. Perineal irritation led to an emergency midline laparotomy, which discovered diverticulitis of the jejunum at 50 cm from the Treitz ligament, resected the jejunum and performed end-to-end anastomosis. The pathology examination confirmed the diagnosis. Because the clinical presentation of complicated jejunal diverticulitis is generally nonspecific, diagnosis is very difficult. CT scan is a reliable diagnostic tool. Surgery, including resection of the diseased bowel portion with direct anastomosis, is the treatment generally reported for small intestinal diverticulitis complicated by hemorrhage, obstruction, or perforation. Some authors report using medical treatment only for diverticulitis.

Morphine Sulfate Attenuates Hemorrhagic Shock- Induced Hyperpermeability

Morphine sulfate is often administered for patients requiring surgical intervention for the control of hemorrhage. Recent data implicate morphine as an immune modulator that affects white blood cells and increases infection rates. In addition, morphine releases histamine, an inflammatory mediator that increases microvascular permeability. Both of these actions of morphine could aggravate the inflammatory progress after hemorrhagic shock. In this study, we evaluated the role of morphine sulfate on microvascular permeability and its effects on leukocyte adherence after hemorrhagic shock. After a control period, blood was withdrawn to reduce the mean arterial blood pressure to 40 mm Hg for 1 h in urethane-anesthetized Sprague-Dawley rats. Mesenteric postcapillary venules in a transilluminated segment of small intestine were examined to quantify changes in permeability and leukocyte adherence. The rats received an IV injection of fluorescein isothiocyanate-bovine albumin during the control period. The fluorescent light intensity emitted from the fluorescein isothiocyanate-bovine albumin was recorded with digital microscopy within the lumen of the microvasculature and compared with the intensity of light in the extraluminal space over time. These images were downloaded to a computerized image analysis program that quantitates changes in light intensity. This change in light intensity represents albumin extravasation. In addition, bright-field images were recorded on compact disk for playback to determine leukocyte adherence. Leukocytes stationary for more than 30 s or longer in a 100-micron segment of venule was considered adherent. Our results demonstrated a marked increase in fluorescein isothiocyanate-bovine albumin leakage into the extravascular space after hemorrhagic shock. Hemorrhagic shock was also associated with an increase in leukocytes adhering to the postcapillary venular endothelium. Morphine sulfate 10 microg/kg given before the shock period, attenuated both the hyperpermeability (P < 0.05) and the increase in leukocyte adherence (P < 0.05) after hemorrhagic shock. These results suggest that instead of aggravating the inflammatory response after hemorrhagic shock, morphine may provide protection to the microvasculature.

Effective permeability of hydrophilic substances through walls of lymph vessels: roles of endothelial barrier

The wall effective permeability of hydrophilic substances labeled with fluorescent dyes was evaluated in an isolated cannulated rat single lymph vessel through a videomicroscope system. Sodium fluorescein (NaFl; 332 mol wt) and FITC-dextrans (4,400, 12,000, and 71,200 mol wt) were administered into the intraluminal space of the lymph vessels and then excited by a Xenon lamp. Changes in the fluorescence intensity of the dyes were continuously measured by a silicon-intensified target camera through appropriate filters. The net flux of each dye in the wall of the lymph vessels was calculated by the relationship between the fluorescence intensity and the concentration of the dyes. NaFl and FITC-dextran 4,400 in the intraluminal space of isolated rat lymph vessels significantly penetrated the wall of the lymph vessels. FITC-dextran 12,000 in the intraluminal space of isolated rat lymph vessels slightly passed through the lymphatic wall, whereas FITC-dextran 71,200 did not penetrate the wall. Intraluminal pressures ranging from 4 to 8 cm H(2)O did not significantly affect the net flux of dyes used in the present study. After administration of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate into the lymph vessels, the net flux of FITC-dextran 4,400 and 12,000 but not 71,200 was augmented significantly. These results suggest that small molecular hydrophilic substances (< or =4,400) are permeable from the intraluminal to extraluminal space of isolated lymph vessels and that the endothelial cell surface structure may play a barrier role in the effective permeability of large molecular hydrophilic substances (4,400 to 12,000) through the wall of the lymph vessels.

An “Endosteal Electrode” for Cochlear Implantation in Cases with Residual Hearing? Feasibility Study: Preliminary Temporal Bone Experiments

Over the years, an increasing number of patients with some degree of residual hearing have received cochlear implants. In these cases, the marginal benefit provided by hearing aids alone is not sufficient; however, as experience has already shown, when hearing aids are used in combination with a cochlear implant, more benefit may be obtained. As a prerequisite, this requires that residual hair cell function must remain intact postoperatively. One of the European pioneers of cochlear implants, Ernst Lehnhardt, questioned whether residual hearing might better be preserved if the implanted electrode permits the fluid-filled inner ear space to remain intact. Subsequently, he proposed insertion of a very flat electrode array design into the extraluminal space between the spiral ligament and the bony cochlear wall (endosteum). Our study aimed to determine whether it is feasible to insert an endosteal electrode model intracochlearly but extraluminarily, anatomically, and ultimately surgically and to determine the impact on surrounding intracochlear structures. Insertion of two silicon models of an endosteal electrode were carried out in 15 human temporal bones. Histologic examination of the temporal bones after electrode insertion was performed on both fresh and fixed specimens to determine whether the desired anatomic site of insertion was achieved. In combination with light reflected and electron microscopic techniques, the extent to which the surrounding structures were impacted was also examined. Successful insertion of the prototype silicon endosteal electrodes was performed intracochlearly and extraluminarly in 11 of the 15 temporal bone specimens, confirming the anatomic feasibility of insertion into the crevice between the spiral ligament and endosteum. On the basis of the anatomy of the human temporal bone, insertion of an "endosteal electrode" is feasible. Subsequently, in vivo animal studies are needed to determine the physical effects of insertion of an endosteal electrode design prototype upon the functionality of the surrounding intracochlear structures and in particularly the ability to preserve hearing function.

Arterial Perforation (by Balloon) During Subintimal Angioplasty

Perforation complicates 3–4% of angioplasties and can be treated by temporary balloon occlusion, coil embolisation, placement of a covered stent or redissection past the perforation using the subintimal angioplasty technique. Our unit has generally been reluctant to place covered stents in the infra-inguinal region, largely because of concerns about in-stent restenosis. Most perforations occurring during subintimal angioplasty (a modification of the traditional angioplasty technique) follow manipulation of the guide wire in the extra-luminal space. A relative minority occur during balloon inflation. It has previously been our experience that arterial perforation does not worsen outcome following angioplasty and we have, therefore, never recommended post-procedural ultrasound surveillance. We report a case of a successfully treated perforation occurring during subintimal angioplasty. The perforation occurred during balloon insufflation of the subintimal channel and then presented secondarily with a large, symptomatic false aneurysm. Awareness of this case has led to a revision of our post-procedural surveillance strategy.

Mouse Mast Cell Secretory Granules Can Function as Intracellular Ionic Oscillators

Fluorescent Ca 2+ probes and digital photo-sectioning techniques were used to directly study the dynamics of Ca 2+ in isolated mast cell granules of normal (CB/J) and beige (Bg j/Bg j) mice. The resting intraluminal free Ca 2+ concentration ([Ca 2+] L) is 25 ± 4.2 μM (mean ± SD, n = 68). Exposure to 3 μM inositol 1,4,5-trisphosphate (InsP 3) induced periodic oscillations of luminal Ca 2+ ([Ca 2+] L) of ∼10 μM amplitude and a period around 8–10 s. The [Ca 2+] L oscillations were accompanied by a corresponding oscillatory release of [Ca 2+] L to the extraluminal space. Control experiments using ruthenium red (2 μM) and thapsigargin (100 nM) ruled out artifacts derived from the eventual presence of mitochondria or endoplasmic reticulum in the isolated granule preparation. Oscillations of [Ca 2+] L and Ca 2+ release result from a Ca 2+/K + exchange process whereby bound Ca is displaced from the heparin polyanionic matrix by inflow of K + into the granular lumen via an apamin-sensitive Ca 2+-sensitive K + channel (ASK Ca), whereas Ca 2+ release takes place via an InsP 3-receptor-Ca 2+ (InsP 3-R) channel. These results are consistent with previous observations of [Ca 2+] L oscillations and release in/from the endoplasmic reticulum and mucin granules, and suggest that a highly conserved common mechanism might be responsible for [Ca 2+] L oscillations and quantal periodic Ca 2+ release in/from intracellular Ca 2+ storage compartments.

TRANSFER OF PORCINE ENDOGENOUS RETROVIRUS ACROSS HOLLOW FIBER MEMBRANES

A porcine endogenous retrovirus (PERV) capable of infecting human cells has been identified. This study was designed to determine whether hollow fiber membranes, such as those used in a bioartificial liver, block the transfer of PERV. Three hollow fiber cartridges (HFCs) were studied in duplicate: cellulose fibers with 70 kD nominal molecular weight cut-off (MWCO), polysulfone fibers with 400 kD MWCO, and mixed cellulose fibers with 200 nm porosity. PK15 cells (porcine kidney cell line), known to produce PERV, were grown in the intraluminal compartment of HFCs fiber cartridges. Samples of medium were collected from both intraluminal and extraluminal compartments of the HFCs fiber cartridge during 14 days of culture. Samples were screened for PERV using reverse transcription polymerase chain reaction. All positive samples were tested for PERV infectivity in human 293 cells. PERV was detected in all samples from the intraluminal space and all intraluminal samples seemed to infect 293 cells. All extraluminal samples from the fibers of 200 nm porosity tested positive for PERV. Detection of PERV in the extraluminal space was delayed by fibers of 400 kD MWCO and 70 kD MWCO until at least day 3 and day 7, respectively, after inoculation of PK15 cells. Positive extraluminal samples from fibers of 400 kD MWCO and 70 kD MWCO did not infect 293 cells. Pore size, membrane composition, and duration of exposure influenced the transfer of PERV across HFCs. Some HFCs decrease the risk of viral exposure to patients during bioartificial liver therapy.

Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries.

The authors investigated selective intra- and extraluminal effects of endothelin (ET) on perfused basilar and extracranial arteries and also studied the interaction between ET and extraluminal oxyhemoglobin (oxyHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extraluminal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET was administered intra- or extraluminally. After extraluminal pretreatment with 10(-5) mol/L oxyHb, 10(-5) mol/L N(G)-monomethyl-L-arginine (L-NMMA), or 10(-6) mol/L indomethacin, 10(-10) to 10(-8) mol/L of ET was administered intra- or extraluminally. Arterial contraction was evaluated by measuring the increase in the perfusion pressure gradient with a differential pressure gauge. Both intra- and extraluminal ET (10(-9) to 3 x 10(-8) mol/L) showed potent and dose-dependent vasoconstricting effects on basilar arteries (p < 0.01). The effect of ET on the basilar arteries was significantly greater than on the femoral or mesenteric arteries (both p < 0.01). The effect of intraluminal ET was enhanced by extraluminal oxyHb (p < 0.05) and L-NMMA (p < 0.01), but not by extraluminal indomethacin. Extraluminal oxyHb did not potentiate the contraction induced by extraluminal ET. These results indicate that the sensitivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent vasoconstrictor intra- as well as extraluminally under conditions such as subarachnoid hemorrhage in which oxyHb is present in the extraluminal space and endothelium-derived relaxing factors are inhibited.