Double-balloon Catheter Research Articles

Balloon Catheter for Cyst Aspiration in a Thoracoscopic Resection of Mediastinal Cysts

In a thoracoscopic resection of mediastinal cysts, aspiration of the cyst contents at the beginning of the procedure is often helpful because it allows the cyst to be more easily grasped and manipulated. Spillage of the cyst contents into the thoracic cavity may, however, occur during aspiration when an ordinary aspiration needle is used. If the cyst contents are infective, then a subsequent contamination of the thoracic cavity may develop. We therefore use a specially designed double-balloon catheter for aspiration to minimize spillage of the cyst contents into the thoracic cavity. We describe herein the usefulness of this aspiration technique.

Sutureless coronary artery bypass with biologic glued anastomoses: Preliminary in vivo and in vitro results

Objective: As heart surgery becomes increasingly focused on minimally invasive techniques, it has become apparent that conventional techniques of anastomosis will need to be severely altered or abandoned. Toward that end, we developed and tested in vitro and in vivo coronary artery bypass graft anastomoses using a biologic glue formulated from bovine albumin and glutaraldehyde. We used a double-balloon catheter as a temporary internal stent to create and seal the anastomosis during gluing. Methods: Initially, anastomoses were made between cryopreserved human saphenous vein segments and coronary arteries in vitro on 12 intact bovine hearts. A total of 42 anastomoses were created with the catheter system introduced into the distal end of the graft, exiting the back wall, and entering the anterior wall of the coronary artery. Two balloons (one in the graft and one in the coronary artery) held the anastomosis stable while the biologic glue was applied externally and allowed to set for 2 minutes. The balloon catheter was then removed from the end of the graft simulating a side-to-side internal thoracic artery anastomosis. After the graft had been flushed to assure distal end patency, the open end of the graft was clipped, turning the anastomosis into an end-to-side graft. A pressure transducer was then attached to the graft and saline solution forcefully infused. Results: All grafts easily held a pressure of 300 mm Hg; 10 grafts were tested up to 560 mm Hg without leaks. Distal and proximal coronary artery patency was checked by examining flow out of the coronary ostia and by cutting arteries distal to the grafts. All anastomoses were patent on being opened and no glue was seen intraluminally. Subsequently, 3 anastomoses of the left internal thoracic artery to the left anterior descending artery have been constructed in goats, with autopsies at 24 hours, 10 months, and 1 year revealing patent anastomoses. Conclusion: A biologic glue and catheter system has been developed that allows a coronary anastomosis with a high bursting strength to be performed. When the system has been further developed and tested, truly minimally invasive heart surgery may be possible. (J Thorac Cardiovasc Surg 2000;120:473-7)

Chimiothérapie par perfusion isolée du foie avec clampage cave endovasculaire : expériences préliminaires chez le porc

Very high concentrations of cytotoxic drug may be obtained with chemotherapy performed with vascular exclusion. Objective : To study the pharmacokinetics and toxicity of melphalan during in situ isolated liver perfusion, and to test an endovascular occlusion catheter. Methods : Isolated liver perfusion with melphalan (15 mg bolus) was performed in 6 pigs (50–60 kg) for 30 min, with non-oxygenated Ringer’s solution. Hepatic outflow, collected by a double balloon catheter inserted into the retrohepatic inferior vena cava, was pumped into the gastro-duodenal artery, while the common hepatic artery and portal vein were clamped. Results : A maximum concentration of 30,000 ng/mL was obtained in the circuit before an exponential decrease, while the concentration in systemic blood was less than 500 ng/mL ( n = 3). Before closing the abdomen, melphalan concentrations were about 2,000 ng/mg in the liver, and undetectable in the muscle. Postoperative course (2 weeks, n = 2) was uneventful with minor alterations in blood tests and hepatic histology. Conclusion : This method of local chemotherapy with melphalan appears to be safe with minor leakage and minimal toxicity.

Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo

OBJECTIVEThe aim of this study was to evaluate the potential of paclitaxel to prevent restenosis in vivo.BACKGROUNDPaclitaxel (Taxol) is a microtubule-stabilizing compound with potent antitumor activity. It influences the cytoskeleton equilibrium by increasing the assembly of altered microtubules, thereby inducing cellular modifications that result in reduced proliferation, migration and signal transduction.METHODSBefore the in vivo study, delivery efficiency was determined with radiolabeled paclitaxel in porcine hearts. After induction of a defined plaque in the right carotid arteries of 76 New Zealand rabbits by electrical stimulation, 27 animals underwent balloon dilation and subsequent local paclitaxel delivery (10 ml, 10 μmol/liter) with a double-balloon catheter. Twenty-nine animals served as control with angioplasty only, 10 animals underwent local delivery of vehicle only (0.9% NaCl solution) and 10 animals were solely electrostimulated. Vessels were excised one, four, and eight weeks after intervention.RESULTSThe extent of stenosis in paclitaxel-treated animals was significantly reduced compared with balloon-dilated control animals (p = 0.0012, one, four and eight weeks after intervention: 14.6%, 24.6% and 20.5%, vs. 24.9%, 33.8% and 43.1%, respectively). Marked vessel enlargement compared with balloon-dilated control animals could be observed (p = 0.0001, total vessel area after one, four and eight weeks: paclitaxel group: 1.983, 1.700 and 1.602 mm2, control: 1.071, 1.338 and 1.206 mm2, respectively). Tubulin staining and electron microscopy revealed changes in microtubule assembly, which were limited to the intimal area. Vasocontractile function after paclitaxel treatment showed major impairment.CONCLUSIONSLocal delivery of paclitaxel resulted in reduced neointimal stenosis and enlargement in vessel size. Both these effects contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton.

Local Adenovirus-Mediated Delivery of Hirudin in a Rabbit Arterial Injury Model

Intravascular delivery of an E1/E3 deleted adenovirus encoding the hirudin protein reduces neointimal formation in the rat arterial injury model. Given the interspecies variability in response to adenoviral vectors, we tested this same construct in the hirudin-sensitive cholesterol-fed rabbit arterial balloon injury model. We hypothesized that local delivery of an E1/E3-deleted adenovirus encoding hirudin (Ad-Hir) in addition to early hirudin infusion would limit neointimal formation compared to early hirudin alone. Methods and Results: Local delivery of Ad-Hir, 2.5 × 10¹⁰ PFU/ml, using a double balloon catheter [n = 6 vessels (v)] produced a 79% reduction in vessel wall thrombin activity at 48 h after balloon angioplasty (BA) compared with vehicle (Veh, n = 6v; p = 0.05). In chronic experiments, hypercholesterolemic rabbits underwent femoral BA, and received either early hirudin alone (n = 9v) or early hirudin plus locally delivered Ad-Hir (early hirudin + Ad-Hir; n = 9v), an E1/E3-deleted adenovirus encoding β-galactosidase (early hirudin + AdGal; n = 7v), or Veh (early hirudin + Veh; n = 10v). Early hirudin + Ad-Hir did not limit the arterial response to injury versus the other groups at 4 weeks after BA. Plaque area, cross-sectional luminal area narrowing by plaque, and T cell infiltration were significantly increased in the adenovirus- versus non-adenovirus-treated arteries. Plaque area correlated with T cell density. Conclusion: Following BA in cholesterol-fed rabbits, local transduction with A-Hir produced a marked reduction in vessel wall-associated thrombin activity. However, this strategy increased rather than decreased the arterial response to BA injury. Our results suggest that the lack of therapeutic effect resulted from adenovirus-stimulated plaque formation, possibly resulting from a T cell-mediated inflammatory response.

OUTCOME OF KIDNEYS FROM OLDER DONORS IN NON-HEART-BEATING CADAVERIC TRANSPLANTATION AND THEIR EFFECTVE USE

158 INTRODUCTION AND OBJECTIVES: To clarify the influence of donor age on transplant outcome and to investigate the effective usage of the older donor kidneys, outcome of 295 cadaveric renal allografts in non-heart-beating cadaveric transplatation was evaluated. METHODS: We examined graft survival of primary cadaveric kidney transplants, who were treated with immunosuppressive therapy in ciclosporine- or FK506-base between December 1982 and March 1997. All kidneys were harvested from non-heart-beating donors. We performed in situ cooling, in which the kidneys were perfused by 1∼2°C, 20∼30 ℓ Lactate Ringer solution througt the double balloon catheter placed in the aorta between cardiac arrest and removal of the kidneys. There were 105 recipients of kidneys from donors aged 55 and older, and 190 recipients of kidneys from donors aged less than 55. RESULTS: There was a significant difference (p<0.001) between the groups of older and younger donors as graft survival was 77 and 87% at 1 year, 56 and 79% at 3 years, and 42 and 70% at 5 years. In the group of older donors, pre-transplant body weight of the recipient was found to be a factor significantly influencing graft survival. There was a significant difference (p<0.05) between recipients who weighed less than and recipients who weighed more than or equal to 56 kg at the time of transplantation as graft survival was 77 and 78% at 1 year, 62 and 46% at 3 years, and 50 and 29% at 5 years. In the group of younger donors, pre-transplant body weight of the recipient was not a significant factor. CONCLUSIONS: Our findings indicate that graft survival is poor in patients receiving primary cadaveric kidneys from non-heart-beating donors aged 55 and older. However, kidney transplants from older donors can be quite effective in lighter recipients, whose body weight were less than 56 kg. Kidneys grafts from the aged 55 and older donors should be transplanted in the lighter patients.

Use of Endothelial Cells Containing Superparamagnetic Microspheres to Improve Endothelial Cell Delivery to Arterial Surfaces after Angioplasty

The purpose of this study was to determine if the luminal surface of balloon-dilated arteries can be re-endothelialized circumferentially with use of normal endothelial cells (ECs) and superparamagnetic microsphere-containing endothelial cells (MagECs) to cover gravity-dependent and independent arterial surfaces, respectively. MagECs were obtained after phagocytosis of albumin-coated superparamagnetic polystyrene microspheres by rabbit microvascular ECs. The effect of microsphere internalization on cell adhesion was determined in vitro by comparing ECs and MagECs in terms of time courses of adhesion to fibronectin and cell retention after exposure to a shear stress. In vivo re-endothelialization was performed by delivering fluorescently labeled ECs and MagECs to a balloon-dilated artery with a double-balloon catheter, placing a magnet over the artery, and rotating the rabbit axially. Endoluminal coverage of arterial cross-sections was estimated by epifluorescence microscopy. Under the influence of gravity, in vitro cell adhesion to fibronectin after 5, 10, and 15 minutes was similar for the ECs (34%, 74%, and 70%) and MagECs (40%, 56%, and 93%). In vitro cell retention after exposure to a shear stress (25 dynes/cm2) was greater (P < .05) for ECs than for MagECs (82% vs 69%). Use of ECs plus MagECs in vivo resulted in cell delivery that was nearly circumferential. Delivery of a mixture of ECs and MagECs in combination with animal rotation and a magnetic field provide nearly circumferential delivery of ECs to the luminal surface of balloon-dilated arteries. The presence of superparamagnetic microspheres in cells does not impede cell adhesion but does decrease cell retention after exposure to a fluid shear.

Semiclosed iliac recanalisation by an inguinal approach — Modified surgical techniques integrating interventional procedures

Technical success and early outcome of modified surgical techniques integrating interventional procedures for iliac recanalisation performed through an incision in the groin. Sixty-one consecutive iliac arteries in 59 patients with long occlusions in 16, occlusions of the common iliac in 11, occlusions of the external iliac in 24 and multiple stenoses of the iliac in 10 cases underwent semiclosed recanalisation through a groin incision. Passage of the lesion by guidewire permits retrograde ring-stripper endarterectomy over the wire as a guiding splint or thrombectomy with a double lumen balloon catheter. Residual lesions are corrected by balloon or stent angioplasty. Adequate outflow is established by femoral patch plasty. Conversion to a standard operation was required in 10 limbs (failure to recanalise the lesion in nine, rupture after angioplasty in one). Initial technical success was achieved in the remaining 51 limbs (recanalisation by ring stripper endarterectomy in 36, thrombectomy in 14, both in six, additional intraoperative angioplasty in 42). Five postoperative thromboses were successfully treated by a combined surgical and interventional approach accounting for a 1-month 100% secondary patency. Iliac recanalisation through the groin by modified ring stripper endarterectomy or modified thrombectomy in combination with intraoperative angioplasty is a safe and effective procedure. Long-term results are required to evaluate the procedure.

Vascular gene therapy.

Gene therapy is an exciting frontier in medicine today. Radiologists will be involved in tracking the effects of these new therapies through imaging. Vascular and interventional radiology techniques also are ideally suited for minimally invasive, readily monitored gene delivery. Gene therapy is accomplished through gene augmentation or gene blocking. The latter is accomplished through antisense oligonucleotides or transcription factor decoys. Vectors are agents that facilitate gene delivery and expression and can be viral or nonviral. The vascular wall is an ideal target for gene therapy because of its central role in many biologic processes and its ready accessibility. Recombinant genes can be delivered ex vivo and in vivo, with the latter approaches involving open surgical, percutaneous injection, and endovascular catheter-based methods. Perforated, hydrogel-coated, and double balloon catheters have been used with varying success. Optimal catheter systems for gene transfer will enable delivery of the vector to the precise anatomic location with transfection limited to the cells of interest and will minimize shedding of the vector to distal sites, systemic effects of the therapeutic agent, and morbidity from the delivery method. Radiologists must become familiar with the basic rationale, strategies, and mechanisms of gene therapy and involved in its clinical trials to ensure an active role in this field.

Pre-treatment with elastase improves the efficiency of percutaneous adenovirus-mediated gene transfer to the arterial media.

The endothelium and internal elastic lamina (IEL) appear to be the main barriers to adenovirus-mediated gene transfer to medial smooth muscle cells (SMC). The present randomized study tested whether controlled incubation with elastase enhanced the efficiency of catheter-based gene transfer to medial SMC by adenoviral vectors. After an initial safety dose ranging study, rabbits underwent balloon abrasion of the iliac endothelium followed by local incubation of either elastase (2 x 10(-7) IU over 5 min) or saline using a double balloon catheter (DBC). Then, adenoviral vectors (5 x 10(9) p.f.u.) carrying Cmv-Luc or RSV-beta gal reporter genes were instilled for 30 min. Three days later, the number of medial SMC expressing lacZ was increased in the elastase-treated arteries compared with saline-treated arteries (7.2 +/- 2.5 versus 2.3 +/- 0.9 cells per section, P = 0.003). Likewise, the amount of luciferase protein product was increased (70 +/- 32 versus 36 +/- 15 pg luciferase/mg tissue, P = 0.03). No vessel enlargement, light or electron microscopic evidence of injury or inflammation was seen in elastase-treated arteries up to 7 weeks. Preincubation with elastase increased transduction efficiency of catheter-based gene delivery of replication-defective adenoviral vectors to rabbit iliac arteries without detectable arterial damage.

Left Ventricular Perforation During Percutaneous Balloon Mitral Valvuloplasty With Emergency Surgery

Two cases of left ventricular (LV) perforation by balloon catheter following successful balloon mitral valvuloplasty are presented. The first patient was dilated first with a single straight‐tip balloon catheter and after with a double balloon catheter. The second patient underwent a valvuloplasty with a double balloon catheter only. The subsequent tamponade was treated by immediate aspiration but without hemodynamic improvement. Both patients required emergency surgery with surgical repair of the LV apex, and both of them could be weaned. Both patients are well 18 months after the procedure. We discuss the mechanism of this serious complication and technical considerations to prevent it.

INHIBITION OF PLATELET DEPOSITION WITH LOCAL DELIVERY OF HEPARIN USING A DOUBLE BALLOON CATHETER

Heparin is an effective agent in the treatment of unstable angina and myocardial infarction. The clinical utility of heparin is limited by bleeding complications. This study was performed to determine whether static delivery of heparin could effectively inhibit further platelet deposition. Thrombogenic graft segments were incorporated into chronic arteriovenous shunts in pigs. Autologous platelets were labeled with 111Indium. Platelet deposition was quantitated with gamma camera imaging. The grafts were exposed to blood flow for 15 min in order to induce platelet deposition on the thrombogenic surface. Heparin was delivered locally either by direct exposure or with a double balloon catheter. After a 15 minute exposure period, the heparin solution was removed and subsequent platelet deposition was monitored for 90 minutes. Heparin, administered with the double balloon catheter in doses as low as 12.5 U, effectively inhibited further platelet deposition. An intravenous injection of 100 U of heparin, the highest dose use for local delivery, did not perturb bleeding time or the activated partial thromboplastin time. In conclusion, platelet deposition can be inhibited with static local delivery of heparin at doses that are not associated with systemic bleeding. © 1997 Elsevier Science Ltd

Liposome mediated gene transfer into the rat oesophagus

Background—Cancer of the oesophagus has so far eluded every attempt at pharmacological treatment. The recent advent of somatic gene therapy offers a new therapeutic approach to malignant tumours.Aim—To investigate whether...

Placement of Endothelial Cells on the Luminal Surface of Denuded Arteries In Vitro and In Vivo

Experiments were performed to determine if the percutaneous placement of endothelial cells on denuded arterial surfaces is feasible. For in vitro adhesion assays, rabbit microvascular endothelial cells were stained with a fluorescent marker and placed on the luminal surface of disks of denuded rabbit aorta. At varying times thereafter, the nonadherent cells were removed, and the adherent cells were quantitated with use of fluorescence microscopy. For in vivo studies, angioplasty was performed on external iliac arteries in five rabbits, and a double-balloon catheter, positioned at the dilatation site, was used to deliver fluorescent rabbit microvascular endothelial cells. Ten minutes (n = 2), 1 hour (n = 2), 1 day (n = 1), or 3 days (n = 1) after cell placement, the number of fluorescent cells remaining on each artery was determined. In vitro rabbit microvascular endothelial cell attachment was (a) serum-dependent, peaking with media containing 25% autologous serum; (b) time-dependent, peaking at 30 minutes; and (c) cell density-dependent. In vivo rabbit microvascular endothelial cell attachment was (a) noncircumferential, (b) appeared to be gravity-dependent, and (c) appeared unchanged over 3 days with respect to number of cells per cross-section and length of artery having endothelium. Percutaneous delivery of endothelial cells onto denuded arterial surfaces with use of optimal conditions is feasible and these cells remain adherent for at least 3 days.

Stent-Grafts for Revision of TIPS Stenoses and Occlusions: A Clinical Pilot Study

To assess the clinical and technical results of stent-graft placement for revision of transjugular intrahepatic portosystemic shunt (TIPS) stenoses and occlusions. Six patients who developed recurrent TIPS stenosis or occlusion of the parenchymal tract underwent shunt revision with use of polytetrafluoroethylene (PTFE) stent-grafts anchored at both ends by Z stents and centrally supported by Wallstents. Before graft placement, mean primary patency was 50 days (range, 9-100 days). Patients underwent one to eight revisions with angioplasty or stent placement (mean, 3.2). Three patients had biliary-TIPS fistulas documented with use of a prototype double occlusion balloon catheter. Stent-grafts were successfully placed within the obstructed shunt, creating an excellent lumen in all cases. The portosystemic gradient was decreased from a mean of 24.3 mm Hg (range, 12-35 mm Hg) to a mean of 10.3 mm Hg (range, 7-16 mm Hg). Five of six patients were asymptomatic and no complications occurred (median clinical follow-up, 331 days). One patient died of pre-existing multi-organ system failure. The duration of primary patency after stent-grafting was improved (mean, 229 days; range, 27-324 days) and the difference approached statistical significance despite the small sample size (P = .056, paired t test). Three patients remained primarily patent at a mean venographic follow-up of 315 days. One shunt occluded at 1 month from residual thrombus in the portal vein, and one stenosis occurred that was secondary to misplacement of the original stent-graft. Patency was re-established in each of these patients. PTFE covered stent-grafts are effective for shunt revision in patients with tract stenosis or occlusion and appear to improve TIPS patency.

Broad Neck Basilar Tip Aneurysm Treated by Neck Plastic Intra-Aneurysmal GDC Embolisation with Protective Balloon

A 56-year-old male was found to have a basilar artery aneurysm by magnetic resonance imaging. Angiography demonstrated a broad neck basilar tip aneurysm. He refused surgical clipping but accepted intravascular embolisation. Introducing catheters were inserted into each of the bilateral vertebral arteries. A microcatheter was introduced into the aneurysm through one of the introducing catheters and a double lumen balloon catheter was introduced into the left posterior cerebral artery (PCA) through the other. The balloon was located from the left PCA to the basilar artery across the aneurysmal neck with the aid of a guidewire passed through the inner lumen of the balloon catheter. The balloon was inflated, and a Guglielmi detachable coil (GDC) was inserted until the platinum part was placed inside the aneurysm. The balloon was deflated to confirm the stability of the GDC, and then the GDC was electrically detached. This procedure was repeated until nine GDCs were successfully inserted. The aneurysm was tightly embolised despite its broad neck. Angiography comfirmed complete neck closure and stable preservation of the basilar artery and bilateral PCAs immediately, 1 week, 3 months, 6 months, and 12 months after embolisation without evidence of thrombo-embolic complications. Neck plastic intra-aneurysmal GDC embolisation using a protective balloon can be used to treat broad-neck aneurysms.

Direct gene transfer into the colon using a double-balloon catheter.

In spite of the many advances that have been made in understanding the molecular basis for diseases, a major obstacle to the treatment of human disorders remains the inability to express genes at specific sites in vivo. Recent progress in gene transfer technology has provided access to a variety of recombinant gene products that can be applied in clinical medicine for therapeutic purposes. In an animal model, we describe here the way in which a marker gene can be introduced into the colon using a double-balloon catheter. Cationic liposomes were used as vehicles to introduce DNA into the living organism. RSV-LacZ plasmid coding for the enzyme beta-galactosidase was used as a marker gene. Cells expressing beta-galactosidase can be stained using the chromogen X-gal. Positive cells show a blue coloration in the cytoplasm. Both absorptive cells and goblet cells were successfully transduced with the marker gene. No evidence of similar staining was observed in control animals receiving a control plasmid or liposomes alone. The method used is a simple, safe, and nontoxic way of delivering genes of interest to specific sites in the colon. Gene transfer may offer fresh potential for endoscopic interventions in colonic disease.

内頸動脈狭窄症に対する double balloon catheter を用いた内頸動脈閉塞試験の有用性

内頸動脈狭窄症43症例に対してdouble bolloon catheterを用いた内頸動脈閉塞試験を施行した.検査による合併症はなかった.15分間の内頸動脈閉塞試験にて脳虚血症状の発生を認めなかった36症例に対しては,内シャントを使用せずに血栓内膜剥離術を施行した.一方,脳虚血症状が発生した7症例では内シャントを使用して手術を施行した.術中頸動脈一時遮断による低血流に起因すると考えられる合併症を認めた症例はなかった.本法は,外頸動脈と総頸動脈を同時に閉塞することにより,内頸動脈の狭窄病変部にカテーテルを挿入することなく安全に施行できる閉塞試験であり,血栓内膜剥離術に際して頸動脈一時遮断が安全に行える症例を選択できる有用な術前検査と思われた.

In vivo measurement of chloride and water secretion in the jejunum of cystic fibrosis patients.

In the present study, we have investigated the possible consequences of the chloride channel defect in the intestine of cystic fibrosis (CF) patients for electrolyte and water transport in the jejunum in vivo, using a multilumen, double occluding balloon catheter, and an Ag/AgCl intraluminal electrode. During a chloride-free perfusion, to optimize the sensitivity of our measurements, the transmural potential difference (PD) (lumen with reference to serosal side) was found to be significantly higher in the jejunum of CF patients (+8.0 +/- 2.1 mV; n = 5) than in healthy control subjects (-2.2 +/- 2.0 mV; n = 9). The chloride concentration measured in chloride-free jejunal perfusates of CF patients was significantly lower than in controls (10.9 +/- 2.3 and 41.4 +/- 8.2 mM, respectively). Possible differences in net chloride and water secretion did not reach statistical significance (chloride secretion controls: -2.1 +/- 0.9 mmol/10 cm/h; CF: -0.8 +/- 0.2 mmol/10 cm/h; water secretion controls: -0.8 +/- 2.5 mL/10 cm/h; CF: -11.7 +/- 8.9 mL/10 cm/h). In control subjects, intraluminally applied theophylline stimulated the secretion of water (delta 23.4 +/- 4.6 mL/10 cm/h) and chloride (delta 4.1 +/- 1.1 mmol/10 cm/h), but not in CF patients (respectively delta 3.6 +/- 3.3 mL/10 cm/h and delta 1.1 +/- 1.1 mmol/10 cm/h). In controls, theophylline caused a significant increase in lumen negativity (PD -10.2 +/- 2.6 mV), but no change could be seen in CF patient transmural PD. These observations provide in vivo evidence for a decreased chloride permeability in the jejunum in CF, resulting in a significant reduction in net electrolyte and water secretion in the presence, but not in the absence, of an intestinal secretagogue.

Adenovirus-mediated gene transfer into injured arteries: quantitative analysis of repeated administration.

We evaluated quantitatively the efficiency and safety of, and influence of either prior arterial injury or immunity against adenovirus on adenovirus-mediated gene transfer into injured arteries of a relatively large animal model, the dog. A replication-defective adenovirus expressing bacterial lacZ was introduced percutaneously into balloon-injured femoral arteries through a double balloon catheter. After a single dose of adenovirus, up to 90% of surface and smooth muscle cells in multiple layers of the media showed transgene expression evaluated by X-Gal histostaining without extralocal expression, as assessed by the polymerase chain reaction. High level expression measured as beta-galactosidase activity peaked at 7 days after transfer and was transient, though retained for a month. Gene transfer performed just after balloon injury induced submaximal gene expression. A second administration of the same adenovirus to the same arterial site enhanced lacZ expression significantly despite the presence of an immune response. Expression of lacZ was also detected in preimmunized dogs, although the expression levels correlated inversely to the titer of neutralizing antibodies in their serum. These data may provide a scientific foundation for the use of adenovirus-mediated arterial gene transfer in future clinical practice.