Endoleaks after endovascular graft treatment of aortic aneurysms: classification, risk factors, and outcome

PURPOSE: Incomplete endovascular graft exclusion of an abdominal aortic aneurysm results in an endoleak. To better understand the pathogenesis, significance, and fate of endoleaks, we analyzed our experience with endovascular aneurysm repair. METHODS: Between November 1992 and May 1997, 47 aneurysms were treated. In a phase I study, patients received either an endovascular aortoaortic graft (11) or an aortoiliac, femorofemoral graft (8). In phase II, procedures and grafts were modified to include aortofemoral, femorofemoral grafts (28) that were inserted with juxtarenal proximal stents, sutured endovascular distal anastomoses within the femoral artery, and hypogastric artery coil embolization. Endoleaks were detected by arteriogram, computed tomographic scan, or duplex ultrasound. Classification systems to describe anatomic, chronologic, and physiologic endoleak features were developed, and aortic characteristics were correlated with endoleak incidence. RESULTS: Endoleaks were discovered in 11 phase I patients (58%) and only six phase II patients (21%; p < 0.05). Aneurysm neck lengths 2 cm or less increased the incidence of endoleaks (p < 0.05). Although not significant, aneurysms with patent side branches or severe neck calcification had a higher rate of endoleaks than those without these features (47% vs 29% and 57% vs 33%, respectively), and patients with iliac artery occlusive disease had a lower rate of endoleaks than those without occlusive disease (18% vs 42%). Endoleak classifications revealed that most endoleaks were immediate, without outflow, and persistent (71% each), proximal (59%), and had aortic inflow (88%). One patient with a persistent endoleak had aneurysm rupture and died. CONCLUSIONS: Endoleaks complicate a significant number of endovascular abdominal aortic aneurysm repairs and may permit aneurysm growth and rupture. The type of graft used, the technique of graft insertion, and aortic anatomic features all affect the rate of endoleaks. Anatomic, chronologic, and physiologic classifications can facilitate endoleak reporting and improve understanding of their pathogenesis, significance, and fate.     

Locoregional response and increased natural killer activity after intratumoral injection of HLA-B7/beta2-microglobulin gene in patients with cancer

The purpose of this study was to assess the therapeutic potential of injecting the gene for HLA-B7/beta2-microglobulin into the subcutaneous metastatic nodules of patients who are refractory to conventional treatments. The nine patients evaluated were divided into three groups and given escalating doses of DNA (20, 40, and 100 microg of the HLA-B7 plasmid DNA/lipid complex for each group) every 2 weeks. Biopsy specimens from the treated tumor nodules of all nine patients were positive for the presence of DNA and for HLA-B7 mRNA expression. Moreover, in six of the nine patients, immunohistology of tumor biopsy samples revealed the expression of recombinant HLA-B7 protein. Also, all nine patients showed an increase in NK activity in their circulating peripheral blood lymphocytes. In two lung cancer patients, one partial and one mixed response was observed after gene transfer. These responses were confined to the treated nodules and the untreated locoregional lymph nodes; the lung masses showed no regression. Remission durations were 14 and 6 weeks, respectively, and in a total of 35 cycles no significant toxicities were observed. Immunohistologic analysis revealed an increased infiltration of CD4+ T cells, macrophages, and NK cells after therapy. In two responding cases, direct intratumoral injection of an allogeneic class I gene could elicit an antitumor response in locoregional areas, possibly through the activation of NK cells.     

Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays

Mutational analysis of large genes with complex genomic structures plays an important role in medical genetics. Technical limitations associated with current mutation screening protocols have placed increased emphasis on the development of new technologies to simplify these procedures. High-density arrays of >90,000-oligonucleotide probes, 25 nucleotides in length, were designed to screen for all possible heterozygous germ-line mutations in the 9.17-kb coding region of the ATM gene. A strategy for rapidly developing multiexon PCR amplification protocols in DNA chip-based hybridization analysis was devised and implemented in preparing target for the 62 ATM coding exons. Improved algorithms for interpreting data from two-color experiments, where reference and test samples are cohybridized to the arrays, were developed. In a blinded study, 17 of 18 distinct heterozygous and 8 of 8 distinct homozygous sequence variants in the assayed region were detected accurately along with five false-positive calls while scanning >200 kb in 22 genomic DNA samples. Of eight heterozygous sequence changes found in more than one sample, six were detected in all cases. Five previously unreported sequence changes, not found by other mutational scanning methodologies on these same samples, were detected that led to either amino acid changes or premature truncation of the ATM protein. DNA chip-based assays should play a valuable role in high throughput sequence analysis of complex genes.     

Bone healing capacity of titanium plasma-sprayed and hydroxylapatite-coated oral implants

The authors report preliminary results of Brief Supportive Psychotherapy (BSP) in the Beth Israel Brief Psychotherapy Program for a sample with primarily Cluster C Axis II disorders. This study compares 24 patients treated with BSP with 25 patients treated with Short-Term Dynamic Psychotherapy (STDP). STDP was chosen because its confrontational methods contrast dramatically to BSP, which emphasizes building self-esteem, reducing anxiety, and enhancing coping mechanisms. Videotaped therapies were based on manualized 40-session protocols. Similar degrees of improvement were seen in BSP and STDP at termination and at 6-month follow-up. A study of therapeutic alliance in BSP showed stable and high levels of alliance in good-outcome cases and more variability in poor-outcome cases. These preliminary findings are consistent with other studies and suggest supportive psychotherapy may be effective for many patients, leading to significant and lasting change.     

Activators of the nuclear receptor PPARgamma enhance colon polyp formation

A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene expression in response to fatty acids, lipid-derived metabolites and antidiabetic drugs. To explore the role of the PPARs in diet-induced carcinogenesis, we treated mice predisposed to intestinal neoplasia with a synthetic PPARgamma ligand. Reflecting the pattern of expression of PPARgamma in the gastrointestinal tract, treated mice developed a considerably greater number of polyps in the colon but not in the small intestine, indicating that PPARgamma activation may provide a molecular link between a high-fat diet and increased risk of colorectal cancer.     

Effect of polynucleotides on the inhibition of neutrophil elastase by mucus proteinase inhibitor and alpha 1-proteinase inhibitor

DNA released from neutrophils at sites of inflammation may modulate tissue proteolysis. We used tRNA and synthetic polynucleotides as models of DNA to study the influence of polynucleotides on the inhibition of neutrophil elastase by its endogenous inhibitors alpha1-proteinase inhibitor (alpha1-PI) and mucus proteinase inhibitor (MPI). Affinity chromatography showed that polynucleotides form electrostatic complexes with elastase and MPI but not with alpha1-PI, the highest affinity being for MPI. The tight-binding partial inhibition of elastase by polynucleotides was used to calculate the Kd of the elastase-polynucleotide complexes which ranged from 4 microM to 21 nM. One mole of tRNA was able to bind 9 mol of elastase. Polydeoxycytosine and tRNA significantly impaired the reversible inhibition of elastase by MPI: they moderately increased the rate of enzyme-inhibitor association, strongly enhanced the rate of complex dissociation, and lowered the enzyme-inhibitor affinity by factors of 34 and 134, respectively. The two polynucleotides also decreased the rate of the irreversible inhibition of elastase by alpha1-PI by factors of 30 and 3, respectively. Polynucleotides also changed the mechanism of inhibition of elastase by the two inhibitors from a one-step inhibition reaction to a two-step binding mechanism. Our data may help explain why proteolysis may occur at sites of inflammation despite the presence of active proteinase inhibitors.     

Activity of 72-kDa and 92-kDa matrix metalloproteinases in placental tissues of cows with and without retained fetal membranes

We produced hypertrophic and metaplastic changes of goblet cells in rat nasal respiratory epithelium by the intranasal instillation of endotoxin (ETN). In the present study, we examined in vivo effects of indomethacin (IND), dexamethasone (DEX), and erythromycin (EM) on intraepithelial mucus production using this animal model. Intraperitoneal injection of IND (2 to 4 mg/kg body weight x 4 days) or DEX (4 to 8 mg/kg body weight x 4 days) significantly inhibited intraepithelial mucus production induced after 3 days of ETN instillations. Intraperitoneal injection of EM (100 mg/kg body weight x 8 days), aminobenzylpenicillin (ABPC, 200 mg/kg body weight x 8 days), and cephalothin (CET, 200 mg/kg body weight x 8 days) also inhibited intraepithelial mucus production induced after 7 days of ETN instillations. When compared with ABPC and CET, EM had a greater inhibitory effect. These results indicate that ETN-induced intraepithelial mucus production can be inhibited by treatment with the anti-inflammatory drugs IND and DEX. Antibiotics such as EM, ABPC, and CET will also be effective, probably by preventing secondary bacterial infection, and EM has an additional inhibitory effect on intraepithelial mucus production.     

Spontaneous bilateral carotid and vertebral artery dissection presenting as a Collet-Sicard syndrome

Spontaneous dissection of the internal carotid arteries usually presents with unilateral headache, neck pain, focal ipsilateral cerebral ischaemic symptoms and a Horner's syndrome. Lower cranial nerve palsies are only rarely observed. We report a case of carotid and vertebral dissections presenting as a unilateral palsy of the ninth to twelfth cranial nerves (Collet-Sicard syndrome).