Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteins

X-Linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by reduced peroxisomal very long chain fatty acid (VLCFA) beta-oxidation. The X - ALD gene product (ALDP) is a peroxisomal transmembrane protein with an ATP binding cassette (ABC). ALDP and three other ABC proteins (PMP70, ALDR, P70R) localize to the peroxisomal membrane. The function of this family of peroxisomal membrane proteins is unknown. We used complementation studies to begin analysis of their role in VLCFA beta-oxidation and on the peroxisomal membrane. Expression of either ALDP or PMP70 restores VLCFA beta- oxidation in X-ALD fibroblasts, indicating overlapping functions. Their expression also restores peroxisome biogenesis in cells that are deficient in the peroxisomal membrane protein Pex2p. Thus it is likely that complex protein interactions are involved in the function and biogenesis of peroxisomal membranes that may contribute to disease heterogeneity.      

Methylprednisolone exacerbates axonal loss following optic nerve trauma in rats

The excitability of human axons can be studied reliably using the technique of threshold tracking, which allows the strength of a test stimulus to be adjusted by computer to activate a defined fraction of the maximal nerve or muscle action potential. The stimulus current that just evokes the target response is considered the 'threshold' for that response. More useful than the resting threshold are other indices of axonal excitability derived from pairs of threshold measurements, such as refractoriness, supernormality, strength-duration time constant and 'threshold electrotonus' (i.e. the changes in threshold produced by long-lasting depolarizing or hyperpolarizing current pulses). Each of these measurements depends on membrane potential and on other biophysical properties of the axons. Together they can provide new information about the pathophysiology underlying abnormalities in excitability in neuropathy.     

Utility of Percutaneous Intervention in the Management of Tunneled Hemodialysis Catheters

A variety of interventional techniques have been developed to restore function to dysfunctional tunneled hemodialysis catheters (THC). The relative efficacies of these techniques were evaluated retrospectively to determine which therapy might be most beneficial. The records of malfunctioning THCs referred to interventional radiology between November 1995 and December 1999 were retrospectively reviewed. Dysfunctional THCs were studied using DSA images obtained while injecting contrast through the lumens of the THCs. The interventions performed were categorized into 1 of 5 groups: no treatment or conservative measures such as vigorous flushing; advancing a guidewire through the THC to reposition the catheter tip or to dislodge a small thrombus; catheter exchange over a guidewire; fibrin stripping of the THC using a loop snare; or prolonged (4 or more hr) direct thrombolytic infusion. A Cox Proportional Hazards model was developed to compare the rate of failure among the procedures. There were 340 THC studies. The catheters were managed as follows: 93 patients received conservative management only, 15 had a guidewire advanced through the catheter, 147 underwent catheter exchange, 62 were treated with a fibrin stripping procedure, and 23 received a thrombolytic infusion. Estimated 30-day patency rates for THCs were 38.2% for conservative management, 30.9% for guidewire manipulation of catheter tip, 53.6% for catheter exchange, 76.1% for fibrin stripping, and 69.8% for thrombolytic infusion. Differences among the treatments were observed (p < 0.01) and pairwise comparisons were made among the treatment groups. Failure rates were significantly higher in the catheter exchange (p <0.01) and guidewire manipulation at catheter tip (p <0.01) groups when compared with the fibrin stripping group. The catheter exchange and guidewire manipulation groups also experienced higher rates of failure when compared with the thrombolytic infusion group, although the differences were not statistically significant (p = 0.08, p = 0.17, respectively). Four procedure-related complications requiring hospitalization or other intervention occurred. Three of these were in the catheter exchange group with one incidence of sepsis, one drug reaction, and one hematoma. Fibrin stripping and thrombolytic infusion provided the greatest efficacy in the treatment of poorly functioning THCs, but all therapies demonstrated wide-ranging results. Central line exchanges did not provide a superior secondary patency and experienced more complications.     

Percutaneous angioplasty and stenting of left subclavian artery stenosis in patients with left internal mammary-coronary bypass grafts: clinical experience and long-term follow-up

The authors report their experience with percutaneous transluminal angioplasty (PTA) and stenting of the left subclavian artery (LSA) in patients with recurrent angina and a left internal mammary (LIMA)-coronary bypass graft or in patients who will be undergoing LIMA-coronary artery bypass grafting. From November 1990 to February 2001, 21 patients (11 men and 10 women) with significant left subclavian artery stenosis were treated; 18 patients had a prior LIMA bypass graft, and 3 patients were treated before coronary artery bypass surgery. Angiographic follow-up was performed in 12 patients and clinical follow-up was obtained in all patients. All lesions were atherosclerotic in etiology and located in the proximal left subclavian artery. The mean stenosis was 81% (range 50-100%). All patients initially underwent PTA. Stents were placed in 7 patients for suboptimal PTA results. Technical success was achieved in all patients. Pressure gradient measurements were available in 6 patients. Mean pretreatment gradient was 29 mm Hg (range, 10-50 mm Hg) and fell to 3 mm Hg (0-8 mm Hg) posttreatment. There were 2 minor and 2 major complications. The 30-day mortality rate was 9.5% (2 patients). The remaining 19 patients had clinical or angiographic follow-up of 4-68 months (mean, 27 months). Three patients were found to have recurrent stenoses by angiography 8-43 months after PTA and 3 more had clinical signs of recurrent stenosis. Therefore, the long-term clinical patency rate of LSA PTA and stent was 15 of 19 (79%). One was managed with bypass surgery, 1 with repeat PTA and stent placement, and 1 was managed conservatively. Therefore, the assisted patency was 15 of 19 (79%). Eleven of 19 (58%) of the patients in long-term follow-up had cardiac symptoms, but repeat angiography excluded recurrent LSA stenosis as the cause of their symptoms in 7 cases. Only 4/19 (21%) had cardiac symptoms potentially attributable to LSA restenosis. Four patients expired during follow-up, but 3 had no evidence of subclavian stenosis. PTA and stenting is an effective treatment of proximal left subclavian artery stenosis in patients who develop angina after a LIMA-coronary artery bypass, or in patients before a LIMA-CABG. Cardiac symptoms after LSA PTA and stent are most often due to progressive coronary artery disease rather than to recurrent LSA stenosis.     

Initial clinical experience with biopolymer-coated detachable coils (HydroCoil) in peripheral embolization procedures

PURPOSE: To evaluate the technical and clinical success of HydroCoils in patients who underwent peripheral embolization procedures. MATERIALS AND METHODS: Between July 2006 and June 2007, 12 peripheral embolization procedures with HydroCoils in 11 patients (six male patients and five female patients; age range, 4-74 years; mean age, 46 y) were available for this retrospective review. The indications for embolization were hemorrhage (n = 4), aneurysm (n = 1), recurrent pulmonary arteriovenous malformation (n = 1), and protection before radioembolization and chemoembolization (n = 5). HydroCoil-10, -14, and -18 systems were used. Procedural and postprocedural follow-up imaging were reviewed by two interventional radiologists. Digital subtraction angiography (DSA) images were used to evaluate embolization success and vessel diameter. DSA and computed tomography (CT) angiography were used for follow-up, which included evaluation for recanalization and migration of coils. Chart review was also performed. RESULTS: All procedures were successful in occluding the target vessels (100%), which ranged from 1.2 mm to 8.2 mm in diameter (median, 2.2 mm). Immediate clinical success was achieved in all procedures (100%). Follow-up imaging was available in seven cases (four CT angiography and three DSA) at 2-108 days (mean, 42 d). No recanalization or migration of coils was found. There were no procedure-related complications, no clinical evidence of nontarget embolization, and no recurrence of presenting symptoms. CONCLUSIONS: The use of HydroCoils in peripheral arterial embolization procedures is effective and safe. They are viable alternatives to standard coils, particularly in tortuous, small target vessels or in cases in which controlled release is desirable.     

Ultrasound-accelerated thrombolysis for the treatment of deep vein thrombosis: initial clinical experience

PURPOSE: To evaluate the success of lysis and clinical outcomes in patients treated with ultrasound (US)-accelerated thrombolysis for deep vein thrombosis (DVT). MATERIALS AND METHODS: Forty-seven patients with 53 cases of DVT were treated with US-accelerated thrombolysis at eight centers in the United States. Sixty percent of the occlusions were in the lower extremity, 36% were in the upper extremity, and 4% were hepatic. The clot was acute (< or =14 days) in 47% of cases, subacute (15-28 d) in 8%, chronic (>28 d) in 17%, acute-on-chronic in 17%, and not specified in 11%. Patients were treated with urokinase (UK), tissue plasminogen activator (tPA), recombinant plasminogen activator (rPA), or tenecteplase. RESULTS: Complete lysis (> or =90%) was seen in 37 of 53 cases (70%) and overall lysis (complete plus partial) was seen in 48 (91%). No lysis occurred in five cases (9%), four of which were chronic. The median thrombolysis infusion time was 22.0 hours. Major complications (hematoma at site of earlier surgery) occurred in only two patients (3.8%), with no incidence of intracranial or retroperitoneal hemorrhage. US-accelerated thrombolysis exhibited comparable or better lysis with a lower average drug dose and shorter median treatment times than reported in the National Venous Registry and a more recently published study of standard catheter-directed thrombolysis. CONCLUSIONS: US-accelerated thrombolysis was shown to be a safe and efficacious treatment for DVT in this multicenter experience. The addition of US reduces total infusion time and provides a greater incidence of complete lysis with a reduction in bleeding rates.