Three-year follow-up after intravascular gamma-radiation for in-stent restenosis in saphenous vein grafts.

The Washington Radiation for In-Stent Restenosis Trial in Saphenous Vein Grafts (SVG WRIST) demonstrated safety and efficacy of intravascular radiation therapy (IRT) for the treatment of in-stent restenosis (ISR) in SVG at 12 months. In this study, we aimed to examine whether the safety and efficacy of IRT is durable up to 36 months. One hundred twenty patients with diffuse ISR in SVG underwent balloon angioplasty, laser or atherectomy ablation, and/or additional stenting. After successful intervention, patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium (Ir)-192 (n = 60) or nonradioactive seeds (n = 60). The prescribed dose at 2 mm from the source was either 14 or 15 Gy in vessels 2.5-4.0 mm or 18 Gy in vessels > 4.0 mm in diameter. At 36 months, target lesion revascularization (TLR; 43% vs. 66%; P = 0.02) and target lesion revascularization-major adverse cardiac event (TLR-MACE; 49% vs. 71%; P = 0.02) rates continued to be lower in the IRT group, but both target vessel revascularization (TVR; 59% vs. 71%; P = 0.17) and TVR-MACE (63% vs. 77%; P = 0.11) rates were not. In SVG WRIST, patients with ISR treated with IRT had a marked reduction in the need for repeat TLR at 36 months, with sustained clinical benefit at 3 years despite late recurrences, which were more pronounced in the radiation group.     

IL-10 Gene Therapy Is Therapeutic for Dextran Sodium Sulfate-Induced Murine Colitis

The transfer of genes encoding immunoregulatory proteins is a promising new strategy in the treatment of intestinal inflammation. Previous work has demonstrated that daily systemic interleukin (IL)-10 therapy is able to prevent disease onset in animal models of colitis but is not sufficient to treat established disease. This study investigates the therapeutic efficacy of an adenovirus encoding IL-10 (AdvmuIL-10) in the treatment of experimental colitis. Colitis was induced in BALB/c mice by the addition of dextran sodium sulfate to the drinking water for 7 days. A single systemic injection of AdvmuIL-10, empty cassette vector (Adv0), or saline vehicle was administered on day 4 after the onset of colitis. The addition of DSS to the drinking water led to an acute, dose-dependent colitis. A single injection of AdvmuIL-10 led to a marked reduction in both stool markers of inflammation (IL-1beta, IL-6, and TNFRII) and serum IL-6. Furthermore, the histological colitis score was significantly reduced in mice receiving AdvmuIL-10 compared to controls (4.9 +/- 1.1 Vs 9.1 +/- 1.2, respectively; P < 0.05). A single systemic injection of AdvmuIL-10 is therapeutic in mice with established DSS colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammation of the colon such as Crohn's disease.     

Actinomyces viscosus endocarditis requiring aortic valve replacement

We report a case of primary Actinomyces viscosus endocarditis, an unusual manifestation of actinomycosis, in a 43-year-old farmer with an indolent febrile illness. As has occurred in previous cases, diagnosis was delayed in part because blood isolates were misidentified. Months later when she required aortic valve and root replacement, histologic exam of the diseased valve revealed branching filamentous organisms and the original blood isolates were retrospectively confirmed to be Actinomyces viscosus.     

Clinical outcomes following stent implantation in internal mammary artery grafts.

We evaluated our experience with percutaneous coronary intervention (PCI) of internal mammary artery (IMA) grafts. From the institution's database we identified 288 patients with 311 IMA lesions. Of these, 82 (26.4%) had stents placed during PCI. Angiographic success was 92%. Mortality at 1 month was 1.7%, myocardial infarction (MI) 15.7%, and target lesion revascularization (TLR) 0.4%. Cumulative 1-year event rates were mortality 6.4%, MI 20.4%, and TLR 8.0%. TLR rates were significantly higher in the stented lesions than lesions treated with angioplasty alone (19.2% vs. 4.9%; P = 0.004). The higher TLR rate in stented lesions was most apparent at the anastomotic site (25.0% vs. 4.2%; P = 0.006). Percutaneous revascularization of IMA grafts can be performed safely with high procedural success and excellent short- and long-term results. Stenting, particularly at the anastomotic site, was associated with significantly greater rates of TLR than angioplasty alone.     

Genetic variants of WNK4 in whites and African Americans with hypertension

Human chromosome 17q has been implicated to contain a gene that influences hypertension susceptibility. This region contains the WNK4 gene that causes the mendelian disorder pseudohypoaldosteronism type II, characterized by high potassium levels and hypertension. The goal of this study was to identify genetic variants in all exons of WNK4 in hypertensive individuals and to examine the association of these variants with essential hypertension. Single-nucleotide polymorphims (SNPs) were identified by sequencing the entire coding region in 32 whites and 32 African Americans with hypertension. A single SNP in whites and 8 SNPs in African Americans were genotyped in a larger cohort of whites (165 hypertensives; 91 normotensives) and African Americans (120 hypertensives; 98 normotensives). The frequency of the rare allele differed significantly between hypertensive whites (13.0%) and normotensive whites (7.1%, P=0.040) for the single intronic SNP (bp 1 156 666). This difference remained significant after adjusting for body mass index and sex (P=0.035). Genotypic frequencies differed significantly between hypertensive and normotensive individuals when a dominant model either with (P=0.027) or without (P=0.028) covariate adjustment was assumed. The odds ratio for hypertension was 2.28 for AA or AG individuals vs those with the GG genotype (95% confidence interval, 1.09 to 4.75). No significant differences in allelic or genotypic frequencies were observed in African Americans for any SNPs. The finding in whites is consistent with the hypothesis that polymorphisms in WNK4 influence the risk of hypertension. However, because the associated SNP does not appear to be a functional variant and the limitations of case/control association studies, confirmation of these results in additional cohorts is warranted.     

Heart rate adjustment of ST-segment depression for reduction of false positive electrocardiographic responses to exercise in asymptomatic men screened for coronary artery disease

The ability of heart rate (HR) correction of exercise-induced ST-segment depression (the delta ST/HR index) to reduce the number of false positive exercise electrocardiograms during initial screening for occult coronary artery disease (CAD) was examined in active, asymptomatic men from the Army Reserve. Among 606 consecutive men given treadmill tests, 62 asymptomatic subjects with normal results on resting electrocardiograms but abnormal outcomes on standard exercise electrocardiograms underwent rest and exercise radionuclide cineangiography, and the 10 subjects with abnormal radionuclide findings then underwent coronary angiography. A previously established delta ST/HR index less than 1.6 microV/beat/min correctly identified 34 of 52 subjects (65%) who, despite abnormal standard exercise electrocardiographic findings, had no rest or exercise radionuclide abnormalities. A delta ST/HR index greater than or equal to 1.6 microV/beta/min detected 7 of 7 subjects with abnormal radionuclide cineangiograms who had CAD at cardiac catheterization, but also identified 2 of 3 subjects with an abnormal radionuclide test who had no CAD. In contrast to the 7 of 62 subjects (11%) with abnormal standard exercise test criteria who had radionuclide and angiographic evidence of CAD, a delta ST/HR index partition of 1.6 microV/beat/min separated subjects into subgroups with 0% (0 of 35) vs 26% (7 of 27) prevalences of CAD by serial diagnostic evaluation (p less than 0.01). Thus, among asymptomatic subjects with abnormal electrocardiographic responses to exercise, simple HR correction of the magnitude of ST-segment depression reduced by 56% the number of subjects with standard exercise test criteria leading to referral for additional diagnostic evaluation, without loss of sensitivity for angiographically proven CAD and with accurate negative predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outpatient case presentations in the conference room versus examination room: results from two randomized controlled trials

PURPOSE: Ambulatory case presentations occur typically in conference rooms, and attending physicians often have little contact with patients. The purpose of this study was to examine the effects of two different ambulatory case presentation formats that involve attending physicians more directly. SUBJECTS AND METHODS: We conducted two randomized controlled trials in a community-based ambulatory internal medicine clinic. Participants comprised 393 adult patients, 40 house officers, and 14 attending physicians. In the first trial, patient encounters were assigned randomly to either exclusive house officer-attending physician conference room discussion or to house officer-attending physician conference room discussion plus attending physician-patient interaction. In the second trial, patient encounters were assigned randomly to either exclusive house officer-attending physician conference room discussion or to exclusive house officer-attending physician discussion in the examining room with the patient present. Patient satisfaction; attending physician contributions to teaching, diagnosis, and therapy; and house officer comfort and autonomy were assessed. RESULTS: Patient visit satisfaction and house officer assessment of attending physician teaching, diagnosis, and therapy were similar in the control and intervention groups of both trials. Patients involved in examination room discussions thought they were more comfortable with the discussion (mean +/- SD, 4.3 +/- 0.9 vs. 3.4 +/- 0.9 on a one- to five-point Likert scale, P <0.001) and more often indicated a preference to listen to the discussion in the future than did the control group (86% [71/83] vs. 63% [52/83], P <0.001). Some house officers (11% [9/83]) but no attending physicians (0/83, P <0.001) were made uncomfortable by examination room presentations, and some house officers (11% [9/83]) thought that examination room presentations diminished their autonomy. CONCLUSIONS: Patients perceive that ambulatory examination room presentations are beneficial, whereas some house officers perceive that examination room presentations are associated with discomfort and diminished autonomy.