Suitability of abdominal aortic aneurysms for endovascular repair: it's not the size....
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Biomedical subjects
Publications and source records attributed to R C Allen.
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The present study addresses the question of a possible linkage between the cystic fibrosis (CF) genetic autosomal recessive disorder and disturbance in neutrophil function. Neutrophil-dominated chronic airway inflammation is present at an early age in children with CF, even in the absence of detectable infection. As evidenced by extracellular superoxide anion release (measured by lucigenin luminescence) or intracellular hydrogen peroxide production (measured by 2',7'-dichlorofluorescein (DCF) fluorescence), no significant difference in the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity of isolated neutrophils was observed in noninfected CF children (homozygotes), their mothers or fathers (CF heterozygotes), and controls. In contrast, both myeloperoxidase (MPO)-dependent oxygenation activity (measured by luminol luminescence) and chloramine release were increased significantly in both CF homozygotes and heterozygotes as compared with controls. In the presence of either amiloride (a sodium channel inhibitor and sodium/proton antiport blocker) or EIPA (5-ethyl-N-isopropyl-amiloride, a specific inhibitor of the antiport), or choline buffer, intracellular MPO activity was decreased significantly in controls and in the CF homozygotes and heterozygotes, thus bringing intracellular MPO-dependent activity in CF subjects back to the level of controls. Extracellular release of MPO, measured by an ELISA to provide an activity-independent assessment of the enzyme, was increased only in CF homozygotes, and was decreased by amiloride and choline buffer, but not by EIPA. We conclude that a modification of intracellular pH and/or ionic concentrations may be related to the altered MPO enzymatic activity observed in CF neutrophils.
Hepatic artery aneurysms (HAAs) are being encountered with increasing frequency. A retrospective study of the management of HAAs at a single institution over an 18-year period is presented. The medical records of all patients diagnosed with HAA were reviewed. There were 22 patients who collectively had 23 HAAs. They were of equal gender distribution with a mean age of 53 +/- 16 years. Sixteen patients were symptomatic. Angiography was definitive in all cases and was necessary for determining therapy. There were 16 true aneurysms and 7 pseudoaneurysms. The method of treatment depended on the anatomic location of the aneurysm and the status of the patient. Treatment was by surgery (n = 10 patients), embolization (n = 8 patients), or by observation (n = 3 patients). There were two acute deaths; one patient died on admission without therapy, and one patient died following surgery. Two patients had surgical complications. Three of seven patients required repeat embolization, and one had open surgery after failed embolization. Three patients died of unrelated causes. The follow-up period was 2 months to 8 years. Thus, early HAA mortality and morbidity rates were 9.1 and 22.7%, respectively. Unless precluded by significant comorbidities, active treatment is advocated in the management of patients with HAAs. Surgery is the preferred treatment for extrahepatic lesions, while embolization is appropriate for intrahepatic aneurysms, the majority of which are pseudoaneurysms. Increased clinical awareness and aggressive, definitive management are necessary in obtaining optimal outcomes.
Hydroxylamine and hydroxamic acid derivatives of a known nonsteroidal antiinflammatory dibenzoxepine series display both cyclooxygenase (CO) and 5-lipoxygenase (5-LO) inhibitory properties. Many of these new dual CO/5-LO inhibitors also exhibit potent topical antiinflammatory activity in the arachidonic acid-induced murine ear edema model. On the basis of their promising profile of in vitro and in vivo activities, hydroxamic acids 24h, 3-(6,11-dihydro-11-oxodibenz[b,e]oxepin-2-yl)-N-hydroxy-N-++ +methylpropanamide (HP 977), and 25, 3-(6,11-dihydrodibenz[b,e]oxepin-2-yl)-N-hydroxy-N- methylpropanamide (P10294), were selected as developmental candidates for the topical treatment of inflammatory skin disorders.
Mutations in the gene for CD40 ligand are responsible for the X-linked form of hyper IgM syndrome. However, no clinical or laboratory findings that reliably distinguish X-linked disease from other forms of hyper IgM syndrome have been reported, nor are there tests available that can be used to confidently provide carrier detection. To identify efficiently mutations in the gene for CD40 ligand, eight pairs of PCR primers that could be used to screen genomic DNA by single strand conformation polymorphism (SSCP) were designed. 11 different mutations were found in DNA from all 13 patients whose activated T cells failed to bind a recombinant CD40 construct. The exact nature of four of these mutations, a deletion and three splice defects, could not be determined by cDNA sequencing. In addition, SSCP analysis permitted rapid carrier detection in two families in whom the source of the mutation was most likely a male with gonadal chimerism who passed the disorder on to some but not all of his daughters. These studies document the utility of SSCP analysis for both mutation detection and carrier detection in X-linked hyper IgM syndrome.
PURPOSE: This study was undertaken to determine the safety and efficacy of percutaneous transluminal angioplasty (PTA) in the treatment of chronic mesenteric ischemia (CMI) in very high-risk surgical patients. METHODS: Twenty-four focal mesenteric stenoses treated from 1984 to 1994 by PTA in 19 patients with CMI were reviewed. All 19 patients were considered poor surgical candidates. Seventeen patients had classic symptoms of CMI, and two patients had atypical abdominal complaints. Vessels dilated included the superior mesenteric artery (18), celiac artery (3), inferior mesenteric artery (1), aorta-superior mesenteric artery vein graft (1), and aorta-splenic artery vein graft (1). Complete follow-up was possible in all patients, with the exception of one patient who had no symptoms when last seen 17 months after the procedure. RESULTS: PTA was technically successful in 18 of 19 patients (95%) and 23 of 24 stenoses (96%). The lone technical failure resulted in superior mesenteric artery dissection with thrombosis and bowel infarction; the patient died despite emergent laparotomy and revascularization (mortality rate, 5%). Complete symptomatic relief was attained in 15 patients (79%), with follow-up showing continued relief of symptoms for a mean of 39 months (range, 4 to 101 months). Partial symptomatic relief was attained in three patients. Recurrent symptoms developed in three patients (20%) at a mean interval of 28 months (range, 9 to 43 months). Repeat PTA performed in two patients provided good technical results and relief from clinical symptoms. One patient had a symptomatic axillary sheath hematoma that required surgical decompression. CONCLUSIONS: Mesenteric PTA is a valuable treatment option in patients who have CMI and are considered very high operative risks. The initial technical success rate is excellent, with the majority of patients having complete symptomatic improvement and continued relief of symptoms at short-term follow-up.
The redox metabolism of myeloperoxidase-deficient rooster (chicken) polymorphonuclear leukocytes (PMNL) was analyzed by differential chemiluminigenic probes. Chicken complement-opsonified zymosan, a phagocytosable particulate stimulus, and phorbol myristate acetate, a chemical stimulus, were used to activate the PMNL respiratory burst. The two probes used were luminol (5-amino-2,3-dihydro-1,4-phthalazinedione), a general probe of oxidase-peroxidase activities, and lucigenin (dimethylbiacridinium binitrate), a selective probe of oxidase activity. Rooster PMNLs yielded dimethylbiacridinum binitrate-dependent chemiluminescence (CL) comparable to those of myeloperoxidase-containing human PMNLs after stimulation with opsonified zymosan and to a lesser extent with phorbol myristate acetate. However, the luminol-dependent CL of opsonified zymosan or phorbol myristate acetate-stimulated rooster PMNLs were approximately two orders of magnitude lower than responses observed with human PMNLs. At physiologic pH, luminol is a highly sensitive, but not specific, probe of myeloperoxidase activity. Rooster erythrocytes yielded no CL with any of the probe-stimulus combinations described. Rooster PMNL viability and oxygen were required for CL. No strong correlation could be drawn between CL responses and eosinophil leukocyte concentration. The major conclusion is that rooster PMNLs, which do not have myeloperoxidase, present a significant and reproducible oxidative burst to chemical and particulate stimuli. Although lacking in peroxidase, rooster PMNLs can still present small luminol-dependent responses.
The use and development of discontinuous buffer systems for the separation of proteins and nucleic acids are reviewed, and the advantages over a continuous buffer system are presented. Emphasis is given to the more recent applications in DNA separations where discontinuous systems have aided in the resolution and mobility tailoring of DNA fragments. Various DNA size ranges can be separated in short time periods by simple choice of buffer components rather than gel alterations. Guidelines for choosing appropriate buffer systems are offered as well as the application of borate complexes to modify the mobility of DNA. This article reviews the historical development of discontinuous buffers in the electrophoresis of proteins and nucleic acids with emphasis on the characteristics and applicability to nucleic acid separations.
Several disease loci have been mapped to the Xq21.3-Xq22 region of the human X Chromosome (Chr) including X-linked agammaglobulinemia (XLA), Fabry disease, Alport syndrome, and Pelizaeus Merzbacher disease. Upon cloning of the XLA gene, Bruton's tyrosine kinase (btk), both Fabry disease and XLA were mapped within the same 50- to 70-kb interval. In order to investigate the genomic organization of the region surrounding btk and the Fabry disease gene, alpha-galactosidase A (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3' of btk. Two of these cosmids spanning most of the coding sequence and the upstream region of btk and gla, U237D10 and U230D1, were sequenced by a random shotgun strategy combined with automated sequencing, resulting in 69 kb of contiguous genomic sequence. Sequencing of U237D10 showed btk to be comprised of 19 exons spanning over 35 kb. Sequencing of U230D1 showed that the 3' end of gla is 9 kb from the 5' end of btk and also demonstrated the presence of two additional genes in the region immediately 5' to btk. The surprisingly high gene density is similar to that seen previously only in the human major histocompatibility locus.
The internal mammary artery (IMA) is the conduit of choice for cardiac revascularization. The phenomenon of retrograde flow in this graft secondary to proximal subclavian artery stenosis is an infrequent but increasingly recognized clinical entity and has been termed the "coronary-subclavian steal syndrome." We report on five patients with this syndrome. All were men. The average age was 65 years (range 56 to 68 years). The mean interval from coronary bypass to presentation was 7.8 years (range 1 month to 18 years). Three patients presented with unstable angina and one with congestive heart failure. One patient was asymptomatic from a cardiac standpoint. The mean arm systolic blood pressure differential was 45 mm Hg (range 30 to 60 mm Hg). Each patient underwent cardiac catheterization, and retrograde IMA flow was demonstrated in 100%. Arteriography confirmed the presence of a proximal high-grade (> 75%) subclavian stenosis in all patients. Stress thallium scanning was performed in two patients and demonstrated anterolateral ischemia in both. Operative intervention in four patients consisted of a left carotid-subclavian bypass using an 8 mm synthetic graft. There was no perioperative morbidity or mortality. Postoperative thallium scanning revealed resolution of the ischemic process. The average length of follow-up was 20 months (range 12 to 25 months) with all patients remaining asymptomatic. The one patient who refused surgery died at 12 months. When IMA grafting is contemplated, proximal subclavian stenosis should be suspected if there is > 20 mm Hg systolic pressure differential between the arms.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Deployment of transfemoral, endovascular stent grafts for treatment of abdominal aortic aneurysms is appealing for several reasons: avoidance of abdominal incision, lack of aortic cross-clamping, potential for regional anesthesia, and shortened hospital stay. Concerns remain, however, regarding the ability of these devices to completely exclude the aneurysm and prevent aneurysm rupture and the long-term integrity of the device. The availability of endografts and the likely development of percutaneous devices have also raised the delicate issue of personnel training for patient selection, endograft implantation, and postoperative follow-up. PATIENTS AND METHODS: The cases of 2 patients are reported in which Dacron endovascular grafts, anchored proximally and distally by Palmaz stents, were deployed for treatment of infrarenal abdominal aortic aneurysms. RESULTS: In a patient with and absent distal cuff, choosing this procedure represented a clear error in patient selection. The endograft failed to reach the aortic bifurcation and the aneurysm ruptured, with the death of the patient 4 months postimplantation. In a patient with anatomy suitable for endograft placement, a perigraft leak persisted at the distal anastomosis following device placement. The aneurysm ruptured 14 days postprocedure. Although the patient survived emergent aneurysm repair, he developed acute renal failure. CONCLUSION: Careful preoperative assessment of aortic anatomy is crucial in selection of patients for transfemoral endovascular graft placement. Lack of a distal cuff of at least 1 cm precludes tube graft implantation. Patients with a perigraft leak are not protected by the endograft from aneurysm rupture. Vascular surgeons must be involved in the preoperative evaluation of these patients and are the only specialty group who can provide the prerequisite care in evaluation and management of postoperative complications.
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Ureterocystoplasty is a novel procedure well suited for treating children with megaureters and small or noncompliant bladders. It combines the benefits of enterocystoplasty without many of its drawbacks. We performed nephrectomy through a posterior approach with extraperitoneal ureteral augmentation in 6 patients with bladder neck obstruction and reflux into a nonfunctioning kidney (the vesicoureteral reflux dysplasia/vesicoureteral reflux nonfunctioning kidney syndrome). In all patients capacity increased significantly. Bladder pressure at capacity decreased in patients who were evaluated by urodynamics postoperatively, and continence was achieved or preserved. There were no complications and hospital stay was short. Nephrectomy via a posterior approach with extraperitoneal ureteral augmentation is an appropriate procedure for children with the vesicoureteral reflux dysplasia syndrome. It should be considered for all such patients before nephroureterectomy is done and irreversible loss of valuable compliant native urothelium occurs.
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Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80 years) volunteers to evaluate the effects of age on the neutrophil (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day. Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak ANC were similar in both age groups at both doses. The peak ANC was increased 5-fold at 30 micrograms and 15-fold at 300 micrograms in both the young and elderly. Daily tests of PMN function, as measured by an automated chemiluminescence system, showed nearly identical responses to several agonists for both age groups. Marrow proliferative activity as reflected by the percentage of cells in the marrow neutrophil mitotic pool also increased similarly for both age groups at both doses. In contrast, there was an age-related change in blood colony formation as measured by the blood CFU-GM assay. Compared with controls at the 30 micrograms dose, mean colony formation was increased 2-fold in the young versus no change in the elderly and at the 300 micrograms dose 24-fold in the young versus 12-fold in the elderly. These studies indicate that neutrophil responses to rhG-CSF are equivalent in healthy young and elderly volunteers but the mobilization of progenitor cells, as measured by the CFU-GM assay appears to differ substantially.
Patients with end-stage renal disease are being maintained for longer periods with dialysis or renal transplantation. Although renal failure itself is associated with occlusive peripheral vascular disease, such patients often have additional comorbid risk factors. In this series, 88% of patients were diabetic, 93% were hypertensive, and 44% were smokers, all factors that exacerbate the severity of their vasculopathy. As a consequence, the vascular surgeon is increasingly being confronted with limb-threatening peripheral vascular disease in this population. We performed 34 infrainguinal bypasses in 27 patients during a 8-year period from 1986 to 1993. Fifty percent of these were bypasses to the infrapopliteal level. The 12- and 48-month graft patency was 64% and 38%, respectively, by life-table analysis. The limb salvage rate was 65% and 58% at 12 and 48 months. The perioperative mortality rate was 5.9% and the morbidity rate was 37%. Most of the limb loss (66%) occurred during the first 3 months after surgery as a result of acute graft occlusion or nonhealing of an ulcer or minor amputation site. We believe that this reflects an increasingly aggressive approach to limb salvage in patients with end-stage renal disease. Four limbs were lost despite a patent graft. Infrainguinal bypass is a viable management option for limb salvage in patients with end-stage renal disease. These procedures can be undertaken with acceptable perioperative mortality and with a 12-month limb salvage rate of 65%.
BACKGROUND: Each year, three to five children per million develop chronic renal failure. Of these, 70% will require dialysis for short periods, and 23% will require prolonged hemodialysis support. It is in the latter group that difficulty is encountered in establishing dialysis access. METHODS: From 1985 to 1992, we provided hemodialysis access for a group of 24 children. There were 16 boys and 8 girls, with a mean age of 11.1 +/- 4 years (range 3 to 17). All children were significantly below the 50th percentile weight for their age and sex. Seven children entered hemodialysis following failed peritoneal dialysis after an average of 21 +/- 10.5 months. Seventeen patients received a renal transplant. Seven of these children have resumed hemodialysis. RESULTS: The technique for establishing hemodialysis was varied: 15 arteriovenous fistulae, 37 expanded polytetrafluoroethylene (ePTFE) bridge grafts, 9 bovine arteriovenous bridge grafts, and 29 chronic central venous catheters. The overall mean functional patency of the fistulae was 6.2 +/- 10.2 months. One third of these fistulae failed to mature sufficiently to permit their use for dialysis purposes. Twenty-one upper extremity ePTFE grafts were implanted, with a mean functional patency of 11 +/- 11.1 months. Sixteen groin loop grafts were utilized, with a primary patency of only 4.1 +/- 5 months. Thrombectomy was performed in 25 cases (patch or interposition in 8 cases), with a secondary patency in these grafts of 10.5 +/- 17 months. An inability to achieve access in 2 children resulted in the creation of unusual types of access: an aorto-caval fistula and an axillo-femoral fistula and a combination of single-needle puncture of an immature fistula with one lumen of a PermCath. There were eight ePTFE graft infections, with graft loss occurring in seven cases. Superior vena caval occlusion occurred in two patients, inferior vena caval thrombosis in one patient, and axillo-subclavian venous occlusion in two patients. Development of central venous occlusions significantly increased the difficulty in establishing dialysis access. The total dialysis period provided by the 90 primary procedures performed in this study was 658 months. Each procedure, therefore, provided access for a mean duration of only 7.3 months. CONCLUSION: Providing dialysis access in the pediatric population is a time-consuming and frustrating challenge. We believe that all patients with renal dysfunction should have their conditions managed as potential long-term dialysis candidates. Therefore, our philosophy is to achieve maximal use from each access site. Although the primary patency of upper-arm ePTFE grafts was greater than that for the forearm fistulae in this study, failure of the upper-arm graft can result in loss of that limb for the purposes of future dialysis access. Consequently, we strongly advocate the "distal before proximal" and "autogenous before prosthetic" dogma in providing pediatric hemodialysis access.
PURPOSE: The durability of renal preservation after surgical intervention has not been well defined, particularly in patients with associated aortic disease. A review of all patients at the Emory University Hospital with renal insufficiency (creatinine level > or = 1.8) and concomitant atherosclerotic aortic and renovascular disease was undertaken. METHODS: Fifty patients underwent both renal revascularization (71 kidneys) and the repair of aneurysmal or symptomatic aortic occlusive disease between 1982 and 1992. Hypertension was present in 96% of patients and diabetes was present in 10%. The preoperative estimated glomerular filtration rate (EGFR) was 25.18 +/- 8.29 ml/min (creatinine level 3.1 +/- 1.5 mg/dl). Operative management included bilateral renal artery repair (n = 21), unilateral repair alone (n = 17), and unilateral repair with contralateral nephrectomy (n = 12). The relative percent change in the postoperative EGFR (> or = 7 days after operation) increased by at least 20% in 42% of the patients, had decreased by 20% or more in only 4%, and was otherwise categorized as unchanged in the remaining 54% of the study group. RESULTS: The 30-day operative mortality rate was 2.0% (1 of 50). Forty-five of the surviving 49 patients (91.8%) were available for follow-up (median 49 months). During this period nine patients (18.4%) eventually required dialysis, four within 6 months of operation, and 19 patients died. Neither subgroup experienced a retrieval of renal function after operation. Five-year survival rate was 61%, and a trend was noted between the risk of death and the relative change in EGFR after operation (p = 0.13). The likelihood of eventually requiring long-term dialysis was highest among those patients with low preoperative functional renal reserve as measured by preoperative creatinine level of 3 mg/dl or greater (p < 0.0001), or preoperative EGFR less than 20 ml/min (p = 0.0001). Blood pressure was cured or improved in 50% at late follow-up. CONCLUSIONS: Early improvement of renal function may be observed in nearly one half of patients subjected to combined aortic and renal revascularization. Nonetheless, renal preservation may not be sustainable in patients with compromised preoperative function. Intervention before marked functional decline remains the best option for minimizing the risk of eventual dialysis.