Vessel Wall MRI for Targeting Biopsies of Intracranial Vasculitis.

Central nervous system vasculitides are elusive diseases that are challenging to diagnose because brain biopsies have high false-negative rates. We sought to test the ability of contrast-enhanced, high-resolution 3D vessel wall MR imaging to identify vascular inflammation and direct open biopsies of intracranial target vessels and adjacent brain parenchyma. Eight of 9 specimens revealed vascular inflammation. We conclude that vessel wall MR imaging can identify inflamed intracranial vessels, enabling precise localization of biopsy targets.

Neuropilin-2 and its ligand VEGF-C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients.

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder-sparing therapy can be performed by transurethral resection (TURBT) and radio-chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin-2 (NRP2)/VEGF-C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF-C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow-up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 - 7.86; p = 0.004) and was associated with a 3.85-fold increased risk of an early cancer specific death (95% CI: 0.91 - 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF-C expression have a 2.29-fold increased risk of shorter CSS (95% CI: 1.03-5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF-C expression (p = 0.041). Additionally, NRP2 and VEGF-C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57-36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2-T4) confirmed the prognostic role of NRP2 and NRP2/VEGF-C co-expression in patients with T2-T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF-C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.

Carotid plaque neovascularization and hemorrhage detected by MR imaging are associated with recent cerebrovascular ischemic events.

BACKGROUND AND PURPOSE: Pathologic studies suggest that neovascularization and hemorrhage are important features of plaque vulnerability for disruption. Our aim was to determine the associations of these features in carotid plaques with previous cerebrovascular ischemic events by using high-resolution CE-MRI. MATERIALS AND METHODS: Forty-seven patients (36 men; mean age 72.5 ± 10 years) underwent CE-MRI and MRA examinations for carotid plaque at 3T. IPH presence was recorded. Neovascularity was categorized by the degree of adventitial enhancement (0, absent; 1, <50%; 2, ≥50%). Reader variability was assessed by using weighted κ. Associations with events were determined by using multivariable logistic regression. RESULTS: Intra- and inter-reader agreement for grading adventitial enhancement were good to excellent. IPH was present in 49% of patients and was associated with events (P = .03). Patients grouped by categories 0, 1, and 2 adventitial enhancement had increasing frequencies of events (14% category 0, 48% category 1, 65% category 2; P = .02). Events were associated with IPH (OR, 10.18; 95% CI, 1.42-72.21) and adventitial enhancement (compared with category 0: OR, 14.90, 95% CI, 0.98-225.93 for category 1; OR, 51.17, 95% CI, 3.4-469.8 for category 2) after controlling for age, sex, cardiovascular risk factors, wall thickness, and stenosis. Stenosis was not associated with events. CONCLUSIONS: Adventitial enhancement and IPH are independently associated with previous events and may provide important insight into stroke risk not achievable by stenosis.

Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye.

PURPOSE: The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are hypothesized to play an important role in vertebrate eye development because of their patterned expression in the developing and adult neuroretina, their regulated response to retinal and optic nerve injury, and the effects of altered neurotrophin signaling on retinal development. To further characterize the role of these neurotrophins in mammalian eye development and maintenance, the pattern of expression of BDNF and NT-3 was analyzed in the developing and mature mouse eye. METHODS: Using mouse strains in which the reporter gene lacZ, encoding the enzyme beta-galactosidase, was targeted to either the BDNF or NT-3 locus, the expression of BDNF and NT-3 in the eyes of mice heterozygous for these mutations was analyzed by enzyme histochemistry during embryogenesis, postnatal development, and adulthood. RESULTS: BDNF and NT-3 expression were first observed in the inner and outer segments of the developing optic cup at embryonic days 10.5 to 11.5. As the retina matured, BDNF expression was restricted to retinal ganglion cells and a subset of cells in the inner nuclear layer (INL), whereas NT-3 expression was confined to a small subset of cells in the INL and ganglion cell layer. Both neurotrophins were expressed within the developing retinal pigment epithelium. In the anterior segment, BDNF and NT-3 were expressed at high levels in the developing and mature ciliary epithelium. In the lens and cornea, however, these neurotrophins displayed distinct patterns of expression during development and adulthood. BDNF expression was found in the lens epithelium, immature trabecular meshwork, corneal endothelium, and corneal epithelium, whereas NT-3 expression was confined to the corneal epithelium. CONCLUSIONS: BDNF and NT-3 exhibit different, yet overlapping, patterns of expression during the development and differentiation of the mouse eye. In addition to the neuroretina, the spatiotemporal expression of BDNF and NT-3 may play an important role in the development and maintenance of the lens, ciliary body, trabecular meshwork, and cornea.

Oral infections in home-living elderly patients admitted to an acute geriatric ward.

Little is known about the oral health of the frail and home-living elderly. The effects of dentogenic infections on the general condition of the elderly are also unknown. We therefore set out to investigate 191 elderly patients referred to an acute geriatric hospital due to sudden worsening of their general health. The patients' mean age was 81.2 +/- 6.4 years (range, 67 to 96 years), and they had lived at home before hospitalization. The patients were examined and their diagnoses set by a team of physicians. The dentist's examination was also made bedside. Panoramic x-rays were taken for those who were able to stand (n = 148). Particular attention was paid to the occurrence of dental infection foci and systemic infection parameters of blood. Only patients free from other than dental infections were included in the statistical analyses (n = 184). Panoramic x-rays revealed dentogenic infection foci in 71.1% of the dentate patients. Periodontal condition was poor in 96.2% of the patients (CPI score, 2 to 4). All infection parameters were high in patients with high periodontal treatment need, but the differences were not statistically significant. Neither were there statistically significant correlations between the number of dentogenic infection foci recorded from the radiographs and infection parameters of blood. More of the edentulous patients had positive salivary yeast counts than did the dentate patients (84.4% vs. 66.1%; P < 0.05). No correlation was found between the main systemic diagnoses and dental infections. Since the prevalence of dentogenic infection foci in our subjects was high, and they did not cause marked increase in the hematological infection parameters investigated, it seems clear that geriatricians should refer their patients for dental examinations. Although our patients represent the home-living elderly population in a Nordic country with a high standard of living and good medical care, dental care had been neglected regardless of the patients' systemic disease.

Experience with ambulatory preoperative bowel preparation at the Johns Hopkins Hospital.

A transition to ambulatory preoperative antibiotic bowel preparation was carried out. The protocol included a liquid diet for 40 hours preceding surgery and coordination of purging with buffered oral saline laxative, 45 mL containing 8 g sodium phosphate and 22 g sodium biphosphate (Fleet Phospho-Soda, C.B. Fleet Co, Lynchburg, Va) and bisacodyl preparation with an oral erythromycin base-neomycin routine. Enemas were omitted. Personnel in the preoperative evaluation center had the responsibility of instructing patients, distributing directions and drugs, and reviewing for compliance and possible problems during the preoperative period. All patients scheduled for any of a variety of gastrointestinal procedures, as well as some other complex operations, were included in this study. Follow-up data were obtained. Surgeons' comments regarding efficacy were highly favorable. In only five cases was there comment regarding liquid stool, and this was no impediment to surgery. This incidence was comparable with that of the inpatient experience, as was the spectrum of postoperative complications. Transfer of responsibility to the department proceeded with ease. Results were entirely comparable with those of the former inpatient experience.