32P-oligodeoxynucleotide-coated coils to prevent arterial recanalization after embolization

BACKGROUND AND PURPOSE: Endovascular treatment of aneurysms with coils, a less invasive alternative to surgery, is too often associated with recurrences. In a canine model, recanalization after coil embolization can be inhibited by in situ beta radiation. METHODS: Radioactive platinum coils were produced by immersion in a (32)P-oligodeoxynucleotide solution. In vitro and in vivo (32)P-oligodeoxynucleotide elution profiles were assessed after incubation or arterial implantation for 14 days or less. Activities within arteries, thrombi, and coils were measured by scintillation counting. Angiographic and pathologic results no more than 12 weeks after standard platinum and radioactive coil embolization of canine maxillary, cervical, and vertebral arteries were compared among 17 animals. RESULTS: Exposure to (32)P-oligodeoxynucleotide solution at 65 degrees C yielded coils with an average activity of 0.3 microCi/cm. Elution profiles in vitro and in vivo showed that 50% of total activities eluted from coils within 24 hours at first, but coil activities then paralleled the natural decay of (32)P. Radioactivity was present in the thrombi and arterial wall throughout the 14-day observation period. Arteries that were embolized with standard coils recanalized at 2 weeks. Implantation of (32)P-oligodeoxynucleotide-coated coils produced total occlusions in 78.6% of arteries throughout the 12-week observation period. Most arteries that were implanted with radioactive coils were filled with fibrous tissue at 3 months. CONCLUSION: Radioactive coils can be produced by using the binding properties of a (32)P-oligodeoxynucleotide to platinum. Use of these coils in an animal model was effective in preventing recanalization. This method could be performed on site to provide coils tailored to each intervention.     

MRI for preoperative staging of renal cell carcinoma using the 1997 TNM classification: comparison with surgical and pathologic staging

OBJECTIVE: The purpose of our study was to determine the accuracy of MRI for preoperative staging of renal cell carcinoma using the 1997 TNM classification. MATERIALS AND METHODS: We conducted a retrospective review of MRI performed in 40 consecutive patients with 42 renal cell carcinomas before radical (n = 35) or partial (n = 4) nephrectomy or exploratory laparotomy (n = 3). The interval between imaging and surgery ranged from 1 to 59 days (mean, 17.9 days). Imaging was performed with T1- and T2-weighted, dynamic gadolinium-enhanced, and time-of-flight sequences. MRI and surgical-pathologic staging was performed using the 1997 TNM staging system. MRI staging was compared with surgical-pathologic staging as the gold standard. Agreement between the two staging methods was assessed using the kappa statistic. RESULTS: Agreement between MRI and surgical-pathologic staging was good for T staging (kappa = 0.72 and 0.78 for reviewers 1 and 2 respectively), poor for N staging (kappa = 0.13, both reviewers), good for M staging (kappa = 0.66, both reviewers), and excellent for the assessment of venous involvement (kappa = 0.93, both reviewers). MRI overestimated the T stage in five patients and the N stage in five and underestimated the T stage in three, the N stage in four, the M stage in one, and the extent of venous thrombosis in two patients. CONCLUSION: MRI is a reliable method for preoperative staging of renal cell carcinoma using the 1997 TNM classification, in particular for assessing venous involvement.     

Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM

BACKGROUND: Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R. METHODS: IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in murine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2-/- mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT. RESULTS: Muscle injury in Cr2-/- mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and Cr2-/- mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2-/- mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition was found only on injured muscle of WT mice or Cr2-/- mice reconstituted with CM22 or WT serum. CONCLUSION: A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury.     

Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes

The Finland-United States Investigation Of NIDDM Genetics (FUSION) study aims to identify genetic variants that predispose to type 2 diabetes by studying affected sibling pair families from Finland. Chromosome 20 showed our strongest initial evidence for linkage. It currently has a maximum logarithm of odds (LOD) score of 2.48 at 70 cM in a set of 495 families. In this study, we searched for diabetes susceptibility variant(s) at 20q13 by genotyping single nucleotide polymorphism (SNP) markers in case and control DNA pools. Of 291 SNPs successfully typed in a 7.5-Mb interval, the strongest association confirmed by individual genotyping was with SNP rs2144908, located 1.3 kb downstream of the primary beta-cell promoter P2 of hepatocyte nuclear factor-4 alpha (HNF4A). This SNP showed association with diabetes disease status (odds ratio [OR] 1.33, 95% CI 1.06-1.65, P = 0.011) and with several diabetes-related traits. Most of the evidence for linkage at 20q13 could be attributed to the families carrying the risk allele. We subsequently found nine additional associated SNPs spanning a 64-kb region, including the P2 and P1 promoters and exons 1-3. Our results and the independent observation of association of SNPs near the P2 promoter with diabetes in a separate study population of Ashkenazi Jewish origin suggests that variant(s) located near or within HNF4A increases susceptibility to type 2 diabetes.     

Neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy

OBJECTIVES: Activation of the neuroendocrine axis in congestive heart failure is of prognostic significance, and neurohumoral blocking therapy prolongs survival. The hypothesis that surgical reduction of left ventricular size and function decreases neuroendocrine activation is less established. We evaluated the neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy. METHODS: Norepinephrine, plasma renin activity, and angiotensin II were measured in 10 patients before and 12 months after left ventricular reconstruction. In an additional 5 patients, brain natriuretric peptide was measured before and 3 months postoperatively. Three-dimensional cardiovascular imaging was used to assess ejection fraction and left ventricular end-diastolic volume index. RESULTS: Concurrent with improvements of New York Heart Association functional class (2.9 +/- 0.5 preoperatively vs 2.0 +/- 0.4 postoperatively, P <.001), ejection fraction (23.9% +/- 6.6% vs 36.2% +/- 6.2%, P <.01), and left ventricular end-diastolic volume index (140.8 +/- 33.8 mL/m(2) vs 90.6 +/- 18.3 mL/m(2), P <.01), considerable reductions were observed for median plasma profiles of norepinephrine (562.0 pg/mL vs 319.0 pg/mL, P <.05), plasma renin activity (5.75 microg/L/h vs 3.45 microg/L/h, P <.05), angiotensin II (41.0 ng/mL vs 23.0 ng/mL, P =.051), and brain natriuretric peptide (771.0 pg/mL vs 266.0 pg/mL, P <.05). The more plasma renin activity or angiotensin II decreased after left ventricular reconstruction, the higher was the increase in ejection fraction (R = -.745, P <.05 [plasma renin activity]; R = -.808, P <.05 [angiotensin II]). CONCLUSIONS: Surgical improvements of ejection fraction and left ventricular end-diastolic volume index by left ventricular reconstruction were accompanied by improvement of both the neuroendocrine activity and the functional status in patients with congestive heart failure. Whether this favorable neurohormonal response is predictive of an improved survival requires further evaluation.     

Size reduction ascending aortoplasty: is it dead or alive?

OBJECTIVE: Reduction ascending aortoplasty is a controversial procedure. Some believe that it can be appropriately applied when the anatomic features are favorable. Others suggest that it should be restricted to those patients who are at unacceptably high risk for more radical procedures, and there are also those who believe that reduction ascending aortoplasty should not be applied at all. The purpose of the article is to draw conclusions on the applicability of reduction ascending aortoplasty in modern cardiovascular surgery. METHODS: The issue was examined in the mirror of the authors' own experiences, by review and scrutiny of the literature available on the subject, and by conducting an extensive survey of the profession. RESULTS: We found that given proper indications (ie, poststenotic dilatations of <6 cm in diameter, absence of cystic medial necrosis, and a technique that decreases aortic diameter to <3.5 cm), nonreinforced reduction ascending aortoplasty performed concomitantly with aortic valve replacement appears to be a simple and safe procedure, with low morbidity and mortality and rare late complications. External reinforcement might extend the scope of indication for reduction ascending aortoplasty to ascending aortic aneurysms associated with aortic regurgitation and to those with primary structural aortic wall disease with comparable results. Experience also has shown that late complications might be further reduced by means of proper proximal anchoring and extending the wrap past the origin of the innominate artery. CONCLUSIONS: We conclude that reduction ascending aortoplasty is certainly alive. Although it does not appear to be an extremely popular operation, about half of the surgeons who responded believe it to be justified. Regardless of which modality is used, lifetime monitoring of ascending aortic size is essential and so advised. Because of recent sporadic reports of "under-the-wrap" aortic wall atrophy and rupture, the issue of reinforcement of reduction ascending aortoplasty requires continued re-evaluation.     

Association of renal adenocarcinoma and BK virus nephropathy post transplantation

While most BK virus infections are asymptomatic, immunosuppression has been associated with BK virus reactivation and impaired graft function or ureteric ulceration in renal transplant patients and hemorrhagic cystitis in bone marrow transplant patients. Oncogenicity is also postulated and this is the first report of a child with a carcinoma of the donor renal pelvis following BK virus allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of secondary tumors and a return to health.