Spinal Cord Sarcoidosis Occurring at Sites of Spondylotic Stenosis, Mimicking Spondylotic Myelopathy: A Case Series and Review of the Literature.

Sarcoidosis is a multisystem granulomatous disease, with intramedullary spinal cord involvement seen in <1% of cases. This case series illustrates the clinical presentations and imaging findings of 5 patients with intramedullary spinal neurosarcoidosis occurring at sites of spondylotic spinal canal stenosis, which can be indistinguishable from spondylotic myelopathy with cord enhancement. Both entities are most common in middle-aged men and present with weeks to months of motor and sensory symptoms. On imaging, both can have focal spinal cord enhancement and longitudinally extensive signal abnormality centered at or just below the level of spinal canal stenosis. On the basis of our experience, we suggest that in patients with cord enhancement centered at or just below a site of spinal canal stenosis, consideration should be given to chest imaging and lymph node biopsy when applicable, to assess for the possibility of underlying sarcoidosis before surgical decompression.

The Updated Neuroradiology Milestones: Synapsing from 1.0 to 2.0.

The Accreditation Council for Graduate Medical Education is currently in the process of specialty-by-specialty revision of the Milestones. As a result, the Neuroradiology Milestones 2.0 Workgroup was created to refine a system of competency-based assessments for fellow educational growth and development. Strengths of the new Milestones include decreased complexity and uniformity within a subcompetency as it relates to a specific educational development trajectory. The Supplemental Guide serves to decrease clutter in the Milestones 2.0 document and provides a more practical resource for guidance. This article serves to review the history of the Neuroradiology Milestones, followed by a summary of the timeline of events and discussions of the workgroup for development of Neuroradiology Milestones 2.0 and a synopsis of major changes. The plan is for the updated Neuroradiology Milestones to take effect in 2021 or 2022 based on public commentary.

Biomechanical model of corneal transplantation.

PURPOSE: Refractive consequences of corneal transplants are analyzed using corneal biomechanical models assuming homogeneous and inhomogeneous stiffness distributions across the cornea. Additionally, refractive effects of grafts combined with volume removal procedures are also evaluated to develop methods to reduce postoperative refractive management of patients. METHODS: Refinements of a two-dimensional finite element model are applied to simulate the biomechanical and refractive effects of different corneal transplant procedures: anterior lamellar keratoplasty, posterior lamellar keratoplasty, and penetrating keratoplasty. The models are based on a nonlinearly elastic, isotropic formulation. Predictions are compared with published clinical data. RESULTS: The model simulating the penetrating keratoplasty procedure predicts more change in the postoperative corneal curvature than models simulating anterior lamellar keratoplasty or posterior lamellar keratoplasty procedures. When a lenticle-shaped tissue with a central thickness of 50 microns and a diameter of 4 mm is removed from the anterior corneal surface along with the anterior lamellar keratoplasty or posterior lamellar keratoplasty, the models predict a refractive correction of -8.6 and -8.9 diopters, respectively. CONCLUSIONS: Simulations indicate that a posterior lamellar keratoplasty procedure is preferable for obtaining a better corneal curvature profile, eliminating the need for specific secondary treatments.

A finite element model for ultrafast laser-lamellar keratoplasty.

A biomechanical model of the human cornea is employed in a finite element formulation for simulating the effects of Ultrafast Laser-Lamellar Keratoplasty. Several computer simulations were conducted to study curvature changes of the central corneal zone under various physiological and surgical factors. These factors included the combined effect of corneal flap and residual stromal bed thickness on corneal curvature; the effect of the shape of the lenticle on the surgical procedure outcomes and the effect of flap thickness on stress distribution in the cornea. The results were validated by comparing computed refractive power changes with clinical results. The effect of flap thickness on the amount of central flattening indicates that for flap thickness values 28% over the corneal thickness, central corneal flattening decreases. Moreover, the change in corneal curvature induced by subtraction of a plano-convex lenticle under a uniform flap, naturally imply a smaller change in the structure of the anterior layers of the cornea, but a bigger deformation in the structure of the posterior layers that are left behind the resection of the lenticle. In addition, the model also verified that the corneal curvature increased peripherally with simultaneous thinning centrally after subtraction of corneal tissue. This result shows that not only the treated zone is affected by the surgery, indicating the important role of the biomechanical response of the corneal tissue to refractive surgery, which is unaccounted for in current ablation algorithms. The results illustrate the potentialities of finite element modeling as an aid to the surgeon in evaluating variables.

Finite element analysis applied to cornea reshaping.

A 2-D finite element model of the cornea is developed to simulate corneal reshaping and the resulting deformation induced by refractive surgery. In the numerical simulations, linear and nonlinear elastic models are applied when stiffness inhomogeneities varying with depth are considered. Multiple simulations are created that employ different geometric configurations for the removal of the corneal tissue. Side-by-side comparisons of the different constitutive laws are also performed. To facilitate the comparison, the material property constants are identified from the same experimental data, which are obtained from mechanical tests on corneal strips and membrane inflation experiments. We then validate the resulting models by comparing computed refractive power changes with clinical results. Tissue deformations created by simulated corneal tissue removal using finite elements are consistent with clinically observed postsurgical results. The model developed provides a much more predictable refractive outcome when the stiffness inhomogeneities of the cornea and nonlinearities of the deformations are included in the simulations. Finite element analysis is a useful tool for modeling surgical effects on the cornea and developing a better understanding of the biomechanics of the cornea. The creation of patient-specific simulations would allow surgical outcomes to be predicted based on individualized finite element models.

Body attitude, gender, and self-concept: a 30-year perspective.

Two comparable samples of college men and women from 1966 and 1996 were compared using the Kurtz Body Attitude Scale (BAS; R. M. Kurtz, 1966). As predicted, women in 1996 reported a significantly more negative body attitude than women in 1966 did. No significant differences in the 2 samples of men were found. With the 1996 sample, the relationship between body attitude and self-esteem was also examined using Marsh's Self-Description Questionnaire-III (SDQ-III; H. W. Marsh & R. O'Neill, 1984). There was a significant relationship between body attitude and general self-esteem, and there were also complex gender differences in the relationships of various SDQ-III facets to body attitudes.

An analytically solvable model for biomechanical response of the cornea to refractive surgery.

An analttically solvable model that considers the elasticity of the cornea is developed for use in the current and novel corneal refractive surgery procedures. The model assumes that the cornea is a thin spheroid shell with an elastic response to intraocular pressure. The value of the Young's modulus of the post-operative cornea and its dependence on the geometric parameters of the ablation zone are estimated employing "best-fit" approach to nomograms currently used in corneal refractive surgery. These elasticity parameters are applied for quantitative modeling of different types of refractive surgery for myopia.

Efficacy of induction and difficulty level in durability of post-hypnotic suggestions.

We examined whether participants instructed to reenter a hypnotic state as part of the post-hypnotic suggestion (PHS) show less decay in responding over an 8-week period than participants who do not receive such instructions. We also attempted to replicate Trussell, Kurtz, and Strube's (1996) finding on impact of difficulty level of suggestion on response curve. Fifty-nine highly susceptible participants were selected by the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) and were assigned to one of four groups (two levels of Difficulty [easy-hard] x two levels of Condition [hypnotic PHS, non-hypnotic PHS]). Participants were tested for PHS at 1, 3, 6, and 8 weeks. A 2 x 2 x 4 (Difficulty x Condition x Time) factorial ANOVA was conducted, with Time as a repeated-measure. The outcome variable at each time was either pass or fail for relevant suggestion. None of the effects containing Condition as a term were significant indicating there is no advantage to using Berrigan, Kurtz, Stabile, and Strube's (1991) atypical induction technique to influence the durability of PHS. We found a significant Time effect but failed to replicate Trussell et al.'s findings for Difficulty level. The differing results found in these three recent studies (Berrigan et al., Trussell et al., and the current study) suggest the effects for durability of PHS may be quite fragile in spite of rigorous experimental controls used in all three studies.

Filled versus empty intervals in prospective hypnotic time estimation with a real-simulator design.

While interest in hypnotic time perception dates back to the 19th century (St. Jean, 1989) only recently have researchers focused on hypnosis and time estimation under more controlled conditions. Following the work of Jasinski (1986) and Mozenter and Kurtz (1992) we predicted a 2-way interaction between Group (high hypnotizable, low hypnotizable, and simulator) and Condition (waking, hypnotized) across 3 time intervals (30, 60, and 120 seconds). It was further hypothesized that "filled" intervals (with white noise) would be perceived as longer than "empty" intervals across all conditions. Sixty-two undergraduates were screened on the Stanford Hypnotic Susceptibility Scale: Form C and verbally estimated time intervals of 30, 60, and 120 seconds, 5 times each, both while in a waking and a hypnotic condition. Support was found for the predicted 2-way interaction for women only. High hypnotizable women showed a significant increase in overestimation from the waking to hypnosis condition, men did not. The predicted difference between "filled" versus "empty" intervals was not found.

An in vivo model of femtosecond laser intrastromal refractive surgery.

BACKGROUND AND OBJECTIVE: To develop an animal model for evaluation of femtosecond laser intrastromal refractive surgery. METHODS: Intrastromal photodisruption was performed in New Zealand Albino rabbits using a femtosecond laser system. This surgical pattern consisted of a 100 microm-tick pyramid of laser pulses starting 180 microm below the corneal surface. Animals underwent serial slit lamp examinations and corneal thickness measurements at 1,3,7,14, and 28 days, then monthly up to 1 year. RESULTS: Approximately 70 microm of central corneal thinning were seen at 1 week, remaining stable up to 7 months. CONCLUSIONS: Intrastromal photodisruption with femtosecond lasers produced consistent changes in corneal thickness without loss of corneal transparency. These changes were more stable than those produced with excimer laser procedures in a similar animal model.

Lamellar refractive surgery with scanned intrastromal picosecond and femtosecond laser pulses in animal eyes.

PURPOSE: To evaluate the use of scanned intrastromal picosecond and femtosecond laser pulses in lamellar refractive surgical procedures. METHODS: Intrastromal corneal photodisruption was performed in fresh porcine and primate cadaver eyes with a solid-state femtosecond laser. Laser pulses were focused 150 to 200 microns below the epithelial surface and scanned in a spiral pattern to create a plane. A flap was made by scanning an arc pattern from the plane of the spiral to the surface of the cornea. Tissue plane separation was graded using a standard scale, while internal surfaces were analyzed by scanning electron microscopy. Comparison was made to a picosecond laser system using the same delivery system device. Creation of a stromal lenticule for in situ keratomileusis was also demonstrated and compared with both laser systems. RESULTS: For femtosecond pulses, tissue separation was achieved best with pulse energies from 4 to 8 microJ and spot separations from 10-15 microns. Picosecond pulses accomplished less complete separations with pulse energies of 25 microJ and spot separations from 10 to 20 microns. Surface quality corresponded to dissection results, with high-grade dissections resulting in a smooth surface appearance, versus a more irregular surface for low-grade dissections. Although high-grade dissections could be created with picosecond pulses (with optimal parameters) in ex vivo porcine eyes, only femtosecond parameters produced similar results in ex vivo primate eyes. CONCLUSION: In contrast to previous attempts using picosecond lasers which require additional mechanical dissection, high precision lamellar refractive surgery may be practical with femtosecond laser pulses.

Hypnotic susceptibility order effects in waking analgesia.

This study reexamined Spanos, Hodgins, Stam, and Gwynn's (1984) contention that susceptibility testing order effects generated a relationship between waking analgesia pain reduction and level of hypnotic responsiveness. Undergraduate volunteers with no previous hypnosis experience were randomly assigned to two groups. Group 1 (n = 69) first received a cold pressor pain protocol, and then was administered the Standford Hypnotic Susceptibility Scale, Form C (SHSS:C). Group 2 (n = 69) was administered the SHSS:C prior to the cold pressor pain protocol. Our findings do not support Spanos, Hodgins et al.'s contention that susceptibility testing order effects generate the often reported relationship between waking analgesia and level of hypnotic responsiveness. We found significant partial correlation coefficients between the SHSS:C and nonhypnotic pain reduction regardless of order of susceptibility testing. Implications regarding the adequacy of design-generated expectancies to explain hypnotic analgesia phenomena were examined.

Human retinal pigment epithelial cell interleukin-8 and monocyte chemotactic protein-1 modulation by T-lymphocyte products.

PURPOSE: The purpose of the study was to examine the effect of T-lymphocyte products on human retinal pigment epithelial (HRPE) cell interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) secretion and gene expression. METHODS: HRPE cells were stimulated for 2, 4, 8, or 24 hours with 20% conditioned media (CM) from T-lymphocytes stimulated with CD3 or CD28 monoclonal antibodies (mAbs) or phorbol myristic acid. In some experiments, CM from CD3 mAb-stimulated T-lymphocytes was preincubated with neutralizing anti-(alpha)-tumor necrosis factor (TNF), alpha-interferon-gamma (IFN-gamma), or alpha-interleukin-1 (IL-1) mAb (control) to determine the contributions of each of these cytokines to HRPE chemokine induction by stimulated T-lymphocyte CM. HRPE cells were stimulated for 8 and 24 hours with IL-1 beta (0.2 to 20.0 ng/ml) (positive control), TNF-alpha (0.2 to 20.0 ng/ml) (positive control), IFN-gamma (1 to 1000 U/ml), IFN-gamma + IL-1 beta, IFN-gamma + TNF-alpha. Interleukin-2 (IL-2; 100 ng/ml) alone or in combination with IL-1 beta, TNF-alpha, or IFN-gamma also was tested. Enzyme-linked immunosorbent assay (ELISA) and Northern blot analyses were performed to determine secreted IL-8 and MCP-1 and their steady state mRNA expression, respectively. RESULTS: ELISA showed significant increases in HRPE IL-8 and MCP-1 secretion by CM from T-lymphocytes stimulated with CD3 or CD3 + CD28 mAb. Smaller, but significant, increases in IL-8 and MCP-1 resulted from CM phorbol myristic acid-stimulated T-lymphocytes. CM preincubated with neutralizing alpha-TNF or alpha-IFN-gamma mAb induced significantly less HRPE IL-8 and MCP-1, whereas preincubation of CM with neutralizing alpha-IL-1 mAb failed to inhibit CM-induced IL-8 or MCP-1. Northern blot analysis showed increased HRPE IL-8 and MCP-1 mRNA expression within 2 hours of stimulation and was maintained up to 24 hours. CM from T-lymphocytes stimulated with CD3 mAb or CD3 + CD28 mAb produced the greatest increases in IL-8 and MCP-1 mRNA. IFN-gamma induced dose-dependent increases in HRPE MCP-1, but not IL-8, IFN-gamma potentiated IL-1 beta and TNF-alpha-induced MCP-1 production, but showed little modulation of IL-1 beta and TNF-alpha-induced IL-8 production. IL-2 did not induce HRPE IL-8 or MCP-1, nor did it modulate the effects of the other cytokines. Northern blot analysis confirmed the ELISA results. CONCLUSIONS: T-lymphocyte secretions induce HRPE IL-8 and MCP-1 gene expression and secretion. TNF and IFN-gamma appear to be necessary components of T-lymphocyte CM for the induction of HRPE IL-8 and MCP-1. IFN-gamma alone induces HRPE MCP-1, albeit to a lesser extent than would IL-1 beta or TNF-alpha, and potentiates IL-1 beta- and TNF-alpha-induced HRPE MCP-1. IL-2 does not appear to modulate cytokine-induced HRPE IL-8 or MCP-1.

Dexamethasone and cyclosporin A modulation of human retinal pigment epithelial cell monocyte chemotactic protein-1 and interleukin-8.

PURPOSE: To examine the modulation of interleukin-1 beta (IL-1 beta)- and tumor necrosis factor-alpha (TNF-alpha)-stimulated monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) secretion and transcription in human retinal pigment epithelial (HRPE) cells by dexamethasone (DEX) and cyclosporin A (CSA). METHODS: Cultured HRPE cells were stimulated with IL-1 beta (0.2 to 20 ng/ml) or TNF-alpha (0.2 to 20 ng/ml) for 8 or 24 hours without (control) and with DEX (10(-8) to 10(-6) M) or with CSA (0.3 to 30 ng/ml). Secreted levels of HRPE MCP-1 and IL-8 were measured in the media using enzyme-linked immunosorbent assay (ELISA). Both MCP-1 and IL-8 mRNA were analyzed by Northern blot. RESULTS: Although DEX (10(-8) to 10(-6) M) inhibited IL-1 beta-stimulated MCP-1 and IL-8 production, it did not inhibit TNF-alpha-stimulated chemokine secretion. In contrast, CSA significantly inhibited TNF-alpha-stimulated, but not IL-1 beta-stimulated, HRPE MCP-1 and IL-8 secretion. Both DEX and CSA inhibitions showed dose dependence. Northern blot analysis of HRPE steady state MCP-1 and IL-8 mRNA corroborated the ELISA measurements of secreted MCP-1 and IL-8. CONCLUSIONS: Although DEX and CSA inhibit HRPE MCP-1 and IL-8 secretion, this is dependent on whether the inducing inflammatory mediator is IL-1 beta or TNF-alpha. IL-1 beta-induced chemokine secretion is sensitive to DEX, whereas MCP-1 and IL-8 induced by TNF-alpha are inhibited by CSA. This information may be useful in explaining in vivo observations and in suggesting targeted clinical treatments and combinations of immunosuppressive agents.

Ofloxacin penetration into the eye after intravenous and topical administration.

PURPOSE: To determine the aqueous and vitreous fluid penetration of ofloxacin after a combined topical and single intravenous dose protocol before vitrectomy surgery. MATERIALS AND METHODS: Before undergoing vitrectomy surgery, patients were given two drops of ofloxacin 0.3% topically and a single intravenous dose of ofloxacin 400 mg. Aqueous (mean, 43 minutes) and vitreous (mean, 53 minutes) fluid samples were collected at the start of the surgical procedure. The samples were analyzed for ofloxacin penetration. RESULTS: The mean aqueous fluid concentration was 1.083 micrograms/mL +/- 0.406. The mean +/- SD vitreous fluid concentration in nondiabetic patients with intact vitreous was 0.352 microgram/mL +/- 0.301. Vitreous levels obtained more than 50 minutes after administration (0.414 microgram/mL +/- 0.336) were generally higher than those obtained after less than 50 minutes (P = 0.12). Eyes with prior vitrectomies achieved better ofloxacin penetration (0.984 microgram/mL +/- 0.680) than did nonvitrectomized eyes. CONCLUSION: Ofloxacin achieved measurable aqueous fluid penetration after topical and intravenous administration. Aqueous levels were above the minimum inhibitory concentration for most ocular pathogens. Vitreous levels were adequate in vitrectomized eyes to achieve inhibitory concentrations against many common ocular pathogens. Combined preoperative topical and a single dose of intravenous ofloxacin may provide inhibitory aqueous and vitreous antibiotic levels in vitrectomized eyes in cases where intravitreal antibiotics are not considered and oral administration is not practical.

Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product.

Studies of the effects of glucocorticoid (GC) and oxidative stress stimuli in differentiated cultures of human trabecular meshwork (HTM) cells have provided the rationale for our studies of a major new gene termed TIGR (trabecular meshwork inducible GC response). The TIGR clone was isolated by differential library screening using selection criteria based on the induction pattern of a new protein/glycoprotein found in HTM cultures after prolonged but not brief exposure to GCs. This GC induction pattern matched the time course and dose response required for intraocular pressure elevation in patients receiving corticosteroids. The very large, progressive induction of TIGR combined with specific structural features of its cDNA suggested that TIGR should be considered a candidate gene for outflow obstruction in glaucoma. Among the properties of TIGR cDNA were a signal sequence for secretion, several structural features for interactions with glycosaminoglycans and other glycoproteins and putative sites for cell surface interactions. In addition, the leucine zippers in the structure were related to TIGR-TIGR oligomerization that was shown to occur with native and recombinant TIGR protein. The verification that TIGR was a major stress response protein in HTM cells following hydrogen peroxide (or phorbol esters) exposure provided a potential link between GC and oxidative mechanisms thought to be involved in glaucoma pathogenesis. Pharmacological evaluation showed that basic fibroblast growth factory and transforming growth factor beta decreased the GC induction of TIGR, and certain nonsteroidal anti-inflammatory drugs protected against both GC- and oxidation-induced stress responses in HTM cells. Our recent studies of TIGR's genomic structure have shown motifs in the promoter region that suggest a basis by which multiple hormonal/environmental stimuli can regulate TIGR production and by which putative genetic alterations could lead to an overexpression of the protein. Further application of cell biology/biochemistry, molecular biology, genetic and histological approaches will be helpful in understanding the role of TIGR in different glaucoma syndromes.

Photodisruption in the human cornea as a function of laser pulse width.

BACKGROUND: We investigated the role of laser pulse width in determining fluence thresholds and efficiency for corneal photodisruption. METHODS: A laser system that delivers a wide range of pulse energies and pulse widths was used to produce ablations at pulse widths from 100 femtoseconds (fs) to 7 nanoseconds (ns). The laser-induced breakdown fluence threshold at each pulse width was determined by monitoring individual plasma emissions. Using multiple shots, the photodisruption threshold and cutting depth at each pulse width were determined histologically. RESULTS: Corneal breakdown thresholds decreased at a faster rate from 7 ns to approximately 10 picoseconds (ps), compared to further reductions in pulse width below 10 ps, where little variation was seen. Breakdown for pulse widths below 10 ps showed little intershot variability, resulting in highly reproducible fluence thresholds. Corneal tissue examined histologically showed similar fluence dependency. CONCLUSIONS: Corneal tissue photodisruption thresholds demonstrate pulse width dependence. At pulse widths less than 10 ps and with fluences near the breakdown threshold, ablations are maximally precise and efficient. These findings suggest optimal laser parameters for corneal surgery.

Durability of posthypnotic suggestions: type of suggestion and difficulty level.

This study investigated the impact of Difficulty Level and Type of Suggestion upon the durability of posthypnotic suggestion over an 8-week period. Seventy-eight highly susceptible subjects selected by both the Harvard Group Scale of Hypnotic Susceptibility: Form A (HGSHS:A) and Stanford Hypnotic Scale of Susceptibility: Form C (SHSS:C) were assigned to six groups (two levels of Difficulty x three Types of Suggestion). S's were tested for posthypnotic suggestion at 1, 3, 6, and 8 weeks. A 2 x 3 x 4 (Difficulty x Suggestion x Time) factorial ANOVA was conducted, with Time treated as a repeated-measure. The outcome variable at each time was either pass or fail for relevant suggestion. We found a significant Time effect, a significant Difficulty effect, and a significant Time x Difficulty interaction. Fewer subjects passed the difficult suggestions than passed the easy suggestions; fewer passed suggestions at a latter time; and the decay in pass rate was more pronounced for the easy suggestion condition, due largely to the higher initial pass rate. Type of Suggestion was not significant, nor were any of the other interactions. Clinical implications were discussed.

The endogenous eyeblink and hypnotic susceptibility in a real-simulator design.

This study investigated the relationship between hypnotic susceptibility and the endogenous eyeblink with 27 subjects who were assigned to groups of high susceptibles, low susceptibles and simulators on the basis of cutoff scores from the Harvard Group Scales of Hypnotic Susceptibility: Form A and the Stanford Hypnotic Susceptibility Scales: Form C. Using a repeated-measures design, oculomotor data were collected during two separate conditions, waking and hypnotized, while subjects performed a visual task requiring the discrimination of short light flashes (200 ms) from long light flashes (400 ms). Although results partially replicated previous studies, with high susceptibles blinking significantly less than low susceptibles across both conditions, no effect was found for the hypnotic state. Failure of the simulating group to meet assumptions in the waking condition allowed no conclusions regarding impact of task demands on the endogenous eyeblink.