Citations

Abstract Background. Small bowel adenocarcinoma is a rare gastrointestinal malignancy that is treated primarily with surgery. Even with optimal resection, however, survival is poor and recurrences are common. Response rates to palliative combination chemotherapy are low, and the median duration of survival for metastatic disease is less than 1 year. This study aimed to document the response rate and survival time for patients with advanced small bowel adenocarcinoma who were not surgically curable and were treated with a regimen of 5-fluorouracil (5-FU), mitomycin C (Mutamycin®; Bristol-Myers Squibb; Princeton, NJ), and doxorubicin (Adriamycin®; Bedford Laboratories; Bedford, OH), the FAM regimen. Methods. This multi-institutional study was performed by the Eastern Cooperative Oncology Group (ECOG). Between November, 1983 and December, 1985, 39 patients with advanced or recurrent disease were enrolled. Chemotherapy was given as follows: 5-FU, 600 mg/m2 on days 1, 8, 29 and 36; mitomycin C, 10 mg/m2 on day 1; and doxorubicin, 30 mg/m2 on days 1 and 29. Eligibility criteria included an ECOG performance status score of 0–2, measurable disease, and adequate baseline organ function. Prior chemotherapy was allowed. Response was measured by examination and imaging techniques. Survival time and time to progression were evaluated by the method of Kaplan and Meier, and these outcomes were stratified by clinical and laboratory covariates. Results. Of the 39 evaluated patients, 38 were eligible and 36 were evaluable for response. Grade 3–5 toxicities were experienced by a total of 26 patients (20 grade 3, 5 grade 4, 1 grade 5). The most common adverse events were neutropenia and vomiting. Responses were seen in a total of seven patients (2 complete responses, 5 partial responses), for a response rate of 18.4% (95% confidence interval of 7.8%–34.4%). The median survival time was 8 months. Conclusions. The FAM regimen was active and tolerable for patients with advanced small bowel adenocarcinoma; however, the results were no better than those seen with other chemotherapy combinations.

ABSTRACTTheiler's murine encephalomyelitis virus (TMEV) infection of the brain induces a virus-specific CD8+T-cell response in genetically resistant mice. The peak of the immune response to the virus occurs 7 days after infection, with an immunodominant CD8+T-cell response against a VP2-derived capsid peptide in the context of the Dbmolecule. The process of activation of antigen-specific T cells that migrate to the brain in the TMEV model has not been defined. The site of antigenic challenge in the TMEV model is directly into the brain parenchyma, a site that is considered immune privileged. We investigated the hypothesis that antiviral CD8+T-cell responses are initiated in situ upon intracranial inoculation with TMEV. To determine whether a brain parenchymal antigen-presenting cell is responsible for the activation of virus-specific CD8+T cells, we evaluated the CD8+T-cell response to the VP2 peptide in bone marrow chimeras and mutant mice lacking peripheral lymphoid organs. The generation of the anti-TMEV CD8+T-cell response in the brain requires priming by a bone marrow-derived antigen-presenting cell and the presence of peripheral lymphoid organs. Although our results show that activation of TMEV-specific CD8+T cells occurs in the peripheral lymphoid compartment, they do not exclude the possibility that the immune response to TMEV is initiated by a brain-resident, bone marrow-derived, antigen-presenting cell.

ABSTRACT Purpose. The Minnesota Low‐Vision Reading Test (MNREAD) has been developed to measure reading speed. An abbreviated version of the MNREAD test was developed that presented only three large paragraphs and would be easier for children to complete. Methods. Fifty children ages 8 to 18 years, with normal eye examinations or refractive error alone, underwent testing of reading speed using the MNREAD test. All the children read the standard MNREAD paragraphs starting at the 1.0 logarithm of the minimum angle of resolution (logMAR) level until they could no longer read the subsequent paragraph. Each eye was tested separately, using the second MNREAD card for the left eye. The standard MNREAD reading speed was calculated by plotting the speed for each paragraph, determining the critical print size, then taking the median value of all the paragraphs above the cutoff paragraph. The proposed abbreviated test reading speed was calculated from the median of three large paragraphs (logMAR, 1.0, 0.9, and 0.8). At a second site, 25 children with a variety of ocular conditions were similarly tested using an alternative abbreviated test (logMAR, 1.3, 1.2, and 1.1). The standard and abbreviated reading speeds were then compared between tests and between eyes using generalized estimating equation and intraclass correlation coefficients. Results. The mean reading method speeds with the standard and abbreviated tests were almost identical [177 words per minute (wpm) ± 46 wpm vs. 178 ± 46 wpm, p = 0.43 for normal children and 140 ± 29 wpm vs. 141 ± 33 wpm, p = 0.35 in children with a variety of ocular conditions]. Conclusion. The new abbreviated version of the MNREAD reading speed test yields similar results to the standard MNREAD test in children. The new abbreviated MNREAD test is faster to administer and appears to be particularly useful for children.

We measured 366 microsatellite markers genome-wide to search for loci contributing to subcortical white matter ischemic damage (leukoariosis) and brain atrophy in 488 non-Hispanic white subjects (193 men, 295 women; mean age±SD=64.1±7.7 years; 79% hypertensive) from 223 sibships recruited through ≥2 members with essential hypertension diagnosed before age 60. Leukoariosis was quantitated by magnetic resonance imaging (MRI), brain atrophy by the difference between intracranial and brain volumes, and calculated mean arterial pressure and pulse pressure provided measures of steady-state level and pulsatile components of blood pressure. After adjustment for sex and age, variance components models estimated significant heritability of leukoariosis (0.72), brain atrophy (0.52), mean arterial pressure (0.084), and pulse pressure (0.294) ( P <0.0001 for each trait). Univariate maximum logarithm of odds scores (MLS) were observed for leukoariosis on chromosome 5 (MLS=1.91; P =0.00150); for brain atrophy on 1q and 17p (MLS=2.76, P =0.00018); for mean arterial pressure on 11p (MLS=1.57; P =0.00354); and for pulse pressure on 11p (MLS=3.02; P =0.00070). Bivariate linkage analyses provided evidence of loci with pleiotropic effects on brain atrophy and pulse pressure on chromosomes 11p (MLS = 5.07 at 16 cM; P =0.00001) and 16q (MLS of 4.56 at 124 cM; P =0.00003). These results demonstrate usefulness of multivariate linkage analyses to detect loci with pleiotropic effects on genetically correlated traits and suggest overlap between the genes influencing blood pressure and those contributing to brain atrophy.

Background— Although segmental or circumferential ablation is effective in eliminating pulmonary vein (PV)–mediated atrial fibrillation (AF), this procedure may be complicated by the occurrence of PV stenosis. Methods and Results— To establish the clinical presentation, diagnostic manifestations, and interventional management of PV stenosis, 23 patients with stenosis of 34 veins complicating ablation of AF were evaluated. Each patient became symptomatic 103±100 days after undergoing ablation. In 8 veins, the ablation producing the PV stenosis was a repeated procedure for continued AF. Nineteen patients presented with dyspnea on exertion, 7 with dyspnea at rest, 9 with cough, and 6 with chest pain. On multirow spiral computed tomography examination, the narrowest lumen of the affected PVs measured 3±2 mm compared with 13±3 mm at baseline ( P ≤0.001). The relative perfusion of affected lung segments on isotope scans was reduced to 4±3% of total perfusion compared with 22±10% in unaffected segments. At percutaneous intervention, these veins showed 80±13% stenosis, with a mean gradient of 12±5 mm Hg. This was significantly reduced to a residual stenosis of 9±8% ( P ≤0.001) and a residual gradient of 3±4 mm Hg ( P ≤0.001). Twenty veins were treated with balloon dilatation alone, whereas 14 veins were stented with standard 10-mm-diameter bare-metal stents. Although the symptomatic response was nearly immediate and impressive, 14 patients developed in-stent or in-segment restenosis, requiring repeated interventions in 13. Conclusions— Percutaneous intervention produces rapid and dramatic symptom relief in patients with highly symptomatic PV stenosis after radiofrequency ablation for AF. Nevertheless, alternative treatment methods will be required to decrease recurrent in-stent or in-segment restenosis.