Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function.

Delivery of neurotrophic factors in acute models of spinal cord injury in adult rats can rescue axotomized neurons, promote axonal growth, and partially restore function. The extent to which repair and recovery of function can be achieved after chronic injury has received less attention. In the companion paper we show that transplanting fibroblasts genetically modified to produce neurotrophic factors into chronic (6-week) hemisection injuries results in sprouting, partial neuroprotection, but only limited regeneration. Here we describe functional consequences of this treatment using a series of behavioral tests. Adult rats received a complete unilateral C3/C4 hemisection and recovery from the injury was assessed over 5 weeks. At 6 weeks postoperative, the experimental group received grafts of a combination of fibroblasts modified to secrete BDNF or NT-3. The operated control groups received grafts of either gelfoam or gelfoam with fibroblasts expressing GFP into the lesion site. Behavioral recovery in the three groups was assessed over the next 10 weeks. Severe deficits with no recovery in any of the groups were observed in several tests (BBB, limb preference, narrow beam, horizontal rope test) that measure primarily motor function. Recovery was observed in the grid test, a measure of sensorimotor function, and the von Frey test, a measure of response to mechanical stimulation, but there were no differences between the operated control or experimental groups. Both groups also showed recovery from heat-induced hyperalgesia, with the experimental group exhibiting greater recovery than the operated control groups. In this test, delivery of neurotrophic factors from transplanted fibroblasts does not worsen responses to nociceptive stimuli and in fact appears to reduce hypersensitivity. Our data also demonstrate that additional damage to the spinal cord upon placement of a graft further compromises behavioral recovery for locomotor and postural function. Additional therapeutic interventions will be necessary to provide greater levels of recovery after chronic injuries.

Day to day variations in ocular surface staining of the bulbar conjunctiva.

PURPOSE: The purpose of this study was to characterize the variability of bulbar conjunctival staining over time in response to a single application of fluorescein. METHODS: Sixteen subjects were stained Monday through Friday for a 2-week period. Appointments were scheduled from 9:00 a.m. to 12:00 p.m. to minimize variance due to diurnal variation. Fluorescein stain was applied by touching a separate Ful-Glo strip wetted with nonpreserved saline to the lower palpebral conjunctiva of each eye, with the right eye being stained first. Immediately after application of the fluorescein, conjunctival staining was graded in a randomized order by two examiners, using cobalt blue illumination and a no. 15 Wratten enhancement filter. Conjunctival staining was assessed based upon a 0 to 4 grading scale with 0.5 grade increments. By evaluating the variability in staining over time for each subject, a representation of overall fluctuation for the group was obtained. RESULTS: The average duration for an episode of staining graded higher than the group median (grade 0.5) was found to be 2.0 +/- 2.4 days. Overall, a mean staining grade of 0.5 for the right eye and 0.6 for the left eye was found. Right and left eyes were found to correlate well (r = 0.67, p < 0.01, Spearman's correlation) and the mean difference was not statistically significant [p = 0.73, multi-way, repeated measures analysis of variance (ANOVA)]. The mean difference in grading between the two examiners was 0.1 grades (p = 0.67, multi-way, repeated measures ANOVA), with a correlation coefficient of r = 0.68 (p < 0.01, Spearman's correlation). CONCLUSIONS: Characterization of conjunctival staining over time may be useful in evaluating clinically suspect staining, and in determining its potential duration. The appearance and variability of the conjunctival staining patterns noted in this study indicate a potential relationship to normal physiological processes, such as desquamation. This study also demonstrated a low amount of variability between right and left eyes, supporting the use of contralateral studies in the assessment of conjunctival staining. It also demonstrated a good consistency between separate examiners despite not being standardized.

Corneal staining patterns in normal non-contact lens wearers.

Corneal fluorescein staining was evaluated in 16 subjects over a 2-week period by 2 practitioners. Using a scale of 0 to 4 with 0.5 grade steps, the average duration for an episode of staining above the group median (grade 0.5) was found to be 1.2 +/- 0.4 days. For both eyes, the most prevalent location of staining was the inferior region (50%), followed by the nasal region (20%). Overall, a mean staining grade of 0.5 for the right eye and 0.6 for the left eye was found. Practitioners also demonstrated a difference in grading of 0.1 in the right and left eyes. These data may be most useful in determining the normality of suspect corneal fluorescein staining and its duration until resolution. This study demonstrated a low amount of variability between right and left eyes, and established a good consistency between separate examiners.

Characteristics of corneal staining in hydrogel contact lens wearers.

Corneal fluorescein staining is widely used in clinical practice and research, but little information exists on the distribution of staining in a large group of asymptomatic contact lens wearers. This cross-sectional study took place at 3 centers, and investigated the pattern of corneal fluorescein staining in both eyes of 98 hydrogel contact lens wearers. We also investigated the strategies used by three experienced clinicians to grade corneal staining. Overall corneal staining was graded using a scale from 0 to 4 in one-half steps, and five corneal zones, superior, inferior, nasal, temporal, and central, were also graded. The average overall staining grade for both eyes of our subjects was 0.50, with an average of 0.57 for the right eye and 0.44 for the left. This difference between the eyes was statistically significant (p = 0.011). In addition, a comparison of the zones within each eye showed a significant difference (p = 0.0001) among the zones. Corneal staining between the two eyes was also positively and significantly correlated (r = 0.58; p = 0.0001). Grading strategies among clinical investigators were significantly different (p = 0.0001), indicating a potential source of bias in multi-centered studies. The difference in corneal staining between the eyes may represent a source of systematic bias, and could be due to grading the right eye before the left. The correlation in corneal staining between the eyes indicates that the two eyes of a subject cannot serve as independent data points. One-third of the subjects who participated in this study had notable corneal staining. This finding underlines the importance of regularly checking corneal staining in clinical practice.

Concurrent dissection and intracaval rupture of an abdominal aortic aneurysm: CT findings.

The CT findings of a concurrent dissection and intracaval fistula of an arteriosclerotic aortic aneurysm are reported. Recognition of the CT features of this severe and unusual complication is important for planning effective surgical treatment.

Obsidian hydration dates glacial loading?

Three different groups of hydration rinds have been measured on thin sections of obsidian from Obsidian Cliff, Yellowstone National Park, Wyoming. The average thickness of the thickest (oldest) group of hydration rinds is 16.3 micrometers and can be related to the original emplacement of the flow 176,000 years ago (potassium-argon age). In addition to these original surfaces, most thin sections show cracks and surfaces which have average hydration rind thicknesses of 14.5 and 7.9 micrometers. These later two hydration rinds compare closely in thickness with those on obsidian pebbles in the Bull Lake and Pinedale terminal moraines in the West Yellowstone Basin, which are 14 to 15 and 7 to 8 micrometers thick, respectively. The later cracks are thought to have been formed by glacial loading during the Bull Lake and Pinedale glaciations, when an estimated 800 meters of ice covered the Obsidian Cliff flow.