Concomitant hypertension, bradycardia, and loss of transcranial electric motor evoked potentials during pedicle hook removal: report of a case.

Neurophysiologic monitors in the form of transcranial electric motor evoked potentials (tceMEPs) and somatosensory evoked potentials (SSEPs) have become widely used modalities to monitor spinal cord function during major orthopedic spine procedures. In combination with invasive and non-invasive clinical monitoring and an anesthesia information management system (AIMS), we promptly recognized an acute change in hemodynamic and neurophysiologic parameters, managed intraoperative spinal cord contusion, and successfully minimized iatrogenic injury to the spinal cord during corrective spine surgery.

Expression of reverse cholesterol transport proteins ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI) in the retina and retinal pigment epithelium.

AIMS: Excessive lipid accumulation in Bruch's membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move lipid into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI). METHODS: ABCA1 expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting of human RPE cell extracts. Lipid transport assays were performed using radiolabelled photoreceptor outer segments (POS). ABCA1 and SR-BI expression was examined in normal mouse eyes by immunofluorescence staining. BrMs of ABCA1 and SR-BI heterozygous mice were examined microscopically. RESULTS: Human RPE cells expressed ABCA1 mRNA and protein. The ABCA1 and SR-BI inhibitor glyburide (also known as glibenclamide) abolished basal transport of POS-derived lipids in RPE cells in the presence of high-density lipoprotein. Mouse retina and RPE expressed ABCA1 and SR-BI. SR-BI was highly expressed in RPE. BrMs were significantly thickened in SR-BI heterozygous mice, but not in ABCA1 heterozygous mice. CONCLUSION: RPE cells express ABCA1 and SR-BI. This implies a significant role for SR-BI and ABCA1 in lipid transport and RCT in the retina and RPE.

High density lipoprotein mediated lipid efflux from retinal pigment epithelial cells in culture.

BACKGROUND/AIM: [corrected] The transport of radiolabelled photoreceptor outer segments (POS) lipids was investigated by cultured retinal pigment epithelial cells (RPE). Phagocytosis of POS by the RPE is essential to maintain the health and function of the photoreceptors in vivo. POS are phagocytised at the apical cell surface of RPE cells. Phagocytised POS lipids may be either recycled to the photoreceptors for reincorporation into new POS or they may be transported to the basolateral surface for efflux into the circulation. RESULTS: The authors have demonstrated that high density lipoprotein (HDL) stimulates efflux of radiolabelled lipids, of POS origin, from the basal surface of RPE cells in culture. Effluxed lipids bind preferentially to HDL species of low and high molecular weight. Effluxed radiolabelled phosphotidyl choline was the major phospholipid bound to HDL, with lesser amounts of phosphatidyl ethanolamine, phosphatidyl inosotol. Effluxed radiolabelled triglycerides, cholesterol, and cholesterol esters also bound to HDL. Lipid free apolipoprotein A-I (apoA-I) and apoA-I containing vesicles also stimulate lipid efflux. CONCLUSION: The findings suggest a role for HDL and apoA-I in regulating lipid and cholesterol transport from RPE cells that may influence the pathological lipid accumulation associated with age related macular degeneration.

Saxitoxin: an anesthetic of the deepithelialized rabbit cornea.

PURPOSE: The aim of the current study was to define the efficacy of saxitoxin as a corneal anesthetic in rabbits after mechanical corneal abrasion and photorefractive keratectomy (PRK). METHODS: Twelve Dutch belted rabbits were given a single 1.2-microg dose of saxitoxin or vehicle after mechanical abrasion of the cornea. Corneal sensation was evaluated hourly for 6 hours. A second group of 12 Dutch belted rabbits was given a 1.2-microg dose of saxitoxin or vehicle every 5 hours for 30 hours after PRK. Corneal sensation was evaluated after 5, 10, 15, 20, 25, and 30 hours. Pachometry was performed before PRK and again after the epithelial defects had healed. The rate of epithelial defect closure was assessed by measuring the epithelial defect size 25, 42, 65, 88, and 113 hours after PRK. RESULTS: A dose of 1.2 microg of saxitoxin given every 5 hours produced continuous corneal anesthesia after PRK. There was no difference in the rate of wound healing between eyes treated with saxitoxin and vehicle. There was no difference in the degree of wound healing, as measured by pachometry, between eyes treated with saxitoxin and vehicle. There were no apparent ocular or systemic toxic effects from saxitoxin administration. CONCLUSION: At a dose of 1.2 microg, saxitoxin is a safe, effective, long-acting corneal anesthetic in rabbits after PRK.

Post implantation adjustable intraocular lenses.

To eliminate persistent refractive errors after cataract and phakic IOL surgery, photosensitive silicone IOLs have been developed. These IOL formulations enable precise laser adjustment of IOL power to correct spherical and toric errors post-operatively, after wound and IOL stabilization. Initial experience with these laser adjustable IOLs indicate excellent biocompatability and adjustability of more than five diopters.

An economic analysis of interventions for diabetes.

The objective of this article is to stratify interventions for diabetes according to their economic impact. We conducted a review of the literature to select articles that performed a cost-benefit analysis for 17 widely practiced interventions for diabetes. A scale for categorizing interventions according to their economic impact was defined. The 17 interventions were classified as follows: 1) clearly cost-saving, 2) clearly cost-effective, 3) possibly cost-effective, 4) non-cost-effective, or 5) unclear. Clearly cost-saving interventions included eye care and pre-conception care. Clearly cost-effective interventions included nephropathy prevention in type 1 diabetes and improved glycemic control. Possibly cost-effective interventions included nephropathy prevention in type 2 diabetes and self-management training. Non-cost-effective interventions were not identified. Interventions with unclear economic impact included case management, medical nutrition therapy, self-monitoring of blood glucose, foot care, blood pressure control, blood lipid control, smoking cessation, exercise, weight loss, HbA1c measurement, influenza vaccination, and pneumococcus vaccination. Widely practiced interventions for patients with diabetes can be clearly cost-saving and clearly cost-effective. These practices are attractive from both a medical and an economic perspective.

Prevention of positional brachial plexopathy during surgical correction of scoliosis.

Continuous intraoperative monitoring of spinal cord function using somatosensory evoked potentials (SSEP) has gained nearly universal acceptance as a reliable and sensitive method for detecting and possibly preventing neurologic injury during surgical correction of spinal deformities. In several reports, spinal cord injury was identified successfully based on changes in SSEP response characteristics, specifically amplitude and latency. Less well documented and used, however, is monitoring of peripheral nerve function with SSEPs to identify and prevent the neurologic sequelae of prolonged prone positioning on a spinal frame. The authors describe a patient who underwent surgical removal of spinal instrumentation but was not monitored. A brachial plexopathy developed in this patient from pressure on the axilla exerted by a Relton-Hall positioning frame during spinal surgery. In addition, data are presented from 15 of 500 consecutive pediatric patients who underwent surgical correction of scoliosis between 1993 and 1997 with whom intermittent monitoring of ulnar nerve SSEPs was used successfully to identify impending brachial plexopathy, a complication of prone positioning. A statistically significant reduction in ulnar nerve SSEP amplitude was observed in 18 limbs of the 500 patients (3.6%) reviewed. Repositioning the arm(s) or shoulders resulted in nearly immediate improvement of SSEP amplitude, and all awoke without signs of brachial plexopathy. This complication can be avoided by monitoring SSEPs to ulnar nerve stimulation for patients placed in the prone position during spinal surgery.

The environment and violent conflict: a response to Gleditsch's critique and some suggestions for future research.

PIP: This paper provides a summary of the article, "The Environment and Violent Conflict: A Response to Gleditsch's Critique and Some Suggestions for Future Research". Written by Thomas Homer-Dixon and his colleagues at the University of Toronto, the paper serves as a response to Nils Petter Gleditsch's critique of environment, population, and conflict literature in his seminal 1998 article, "Armed Conflict and the Environment: A Critique of the Literature". The paper addresses some of the conceptual and theoretical problems identified by Gleditsch and discusses his selective critique of the literature on the relationship between environmental scarcity and conflict. Also, the article examines underlying methodological issues and addresses Gleditsch's concerns arising from his methodological perspective. The final section of the article looks forward and suggests avenues for future research on the environment-conflict nexus.^ieng

The human fetal retinal pigment epithelium: A target tissue for thyroid hormones.

Thyroid hormone (T(3)) has previously been shown to regulate visual function in experimental animals and humans. To determine if T(3) exerts direct effects on retinal function, cultured human fetal retinal pigment epithelial (RPE) cells were tested for the presence of thyroid hormone receptors (TRs) and T(3) responses. Using TR-isoform-specific reverse-transcriptase polymerase chain reaction techniques, mRNA was detected for alpha1, alpha2 and beta1 TR isoforms. Immunohistochemistry using a polyclonal antibody that simultaneously recognizes alpha1, alpha2 and beta1 TRs showed nuclear staining of the fetal RPE. Specific binding of (125)I-T(3) to RPE cell nuclear extracts was detected, and Scatchard analysis revealed a K(d) of 110 pM. To determine if RPE cells can respond to T(3), hyaluronic acid (HA) levels in cell culture media were measured after 2, 4 or 6 days of growth in medium containing 10(-7) M T(3). T(3) inhibited accumulation of HA in the cell culture medium of RPE cells. This effect was not evident at 2 days, but at 4 days there was 42.8% less HA in cell culture medium of RPE cells grown in 10(-7) M T(3) (p < 0.01, t test). The effect persisted through 6 days, when there was 46.3% less HA in cell culture medium of RPE cells grown in 10(-7) M T(3) (p < 0.001, t test). The data indicate that human fetal RPE cells are a direct target for thyroid hormones.

Evaluation of compensation filters in pedal radiographs.

Compensation filters allow increased visibility of detail in chest, shoulder, spine, hip, knee, and foot radiographs. This study examines use of an anatomic compensation filter to improve imaging in pedal radiographs. Anteroposterior radiographs were obtained of 25 cadaveric feet at two settings with and without the compensation filter. Densitometer readings were taken at ten forefoot anatomic sites. The compensation filter produced statistically significant reductions in densitometer readings at all anatomic sites and at both radiographic settings. Filtration improved imagery of bony structures, provided excellent soft-tissue visualization, and lowered patient exposure.

Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis.

PURPOSE: To determine anatomic and visual acuity outcomes of posterior segment complications after ganciclovir implant surgery. METHODS: We reviewed the medical records of 63 patients with acquired immunodeficiency syndrome who had active cytomegalovirus retinitis in 82 eyes and who underwent 110 consecutive ganciclovir implant procedures. Preoperative and postoperative visual acuity, type of postoperative complication, treatment, and lines of visual acuity change were determined. RESULTS: Thirty-eight eyes of 19 patients had bilateral ganciclovir implant procedures, and 25 eyes of 19 patients underwent two or more ganciclovir implant procedures. Thirteen (12%) of 110 ganciclovir implant procedures developed posterior segment complications: rhegmatogenous retinal detachment in six, vitreous hemorrhage in four, endophthalmitis in two, and cystoid macular edema with epiretinal membrane in one. Treatment included pars plana vitrectomy with silicone oil in two cases and without silicone oil in three cases, scleral buckling in one, intravitreal antibiotic injection in two, and laser photocoagulation in two. Overall, median visual acuity was 20/25 preoperatively. Median follow-up was 6 months for all eyes and 7 months for eyes with complications. Postoperative median visual acuity was 20/25 for eyes without complications vs 20/40 at 1 month, 20/60 at 3 and 6 months, and 20/100 at 12 months in eyes with complications (P < .001). More eyes with than without complications lost 2 or more lines of visual acuity (P < .001). CONCLUSION: Postoperative complications occurred in 12% of the ganciclovir implant procedures and were associated with decreased visual acuity despite treatment.

Human trabecular meshwork cells as a thyroid hormone target tissue: presence of functional thyroid hormone receptors.

PURPOSE: To determine whether human trabecular meshwork cells (HTM) are a potential target tissue for thyroid hormone (3,3',5-triiodothyronine, T3). METHODS: Cultured HTM were assayed for the presence of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) by reverse-transcriptase polymerase chain reaction (RT-PCR) to detected TR and RXR mRNA, and by immunohistochemistry to detect nuclear TR and RXR proteins. Functionality of the TR was determined by analysis of 125I-T3 binding affinity and capacity in HTM nuclear extracts. Effects of T3 on modulation of hyaluronic acid (HA) levels in HTM were measured as a function of dose and duration of T3 administration. RESULTS: Analysis of RT-PCR and immunohistochemistry demonstrated that cultured HTM expressed TRalpha1, TRalpha2, and TRbeta1 but not TRbeta2; and RXRalpha but not RXRbeta and RXRgamma isoforms. Saturation binding and analysis of 125I-T3 to HTM nuclear extracts revealed Kd of 57 pM. The number of T3 binding sites extrapolated from a Scatchard plot was 7.3 x 10(10)/microg of HTM nuclear protein extract. T3 supplementation reduced the concentration of HA in the cell medium by 32-43% compared to cells grown in the absence of T3. CONCLUSIONS: Cultured HTM express three TR isoforms and one RXR isoform, bind T3 with an affinity similar to that of TR in responsive cells, and modulate their HA production in response to T3. These findings indicate that the human trabecular meshwork tissue has the capacity to respond to thyroid hormones.

Tetrodotoxin: anesthetic activity in the de-epithelialized cornea.

BACKGROUND: Tetrodotoxin (TTX) binds with high affinity to sodium channels and produces local anesthesia. We investigated whether TTX is an effective, long-acting corneal anesthetic in rabbits. METHODS: After mechanical debridement of the central corneal epithelium, topical TTX (1 mM, 0.1 mM, or 0.01 mM) was applied to one eye each of 18 New Zealand White rabbits. The fellow eye of each rabbit was treated with control vehicle. Blink response to a mechanical stimulus was assessed. Blink response was also assessed every 3 h for 30 h in 6 rabbits treated with 1 mM TTX administered every 6 h. In a separate group of 12 rabbits with central epithelial debridement, the rate of epithelial healing was compared between animals treated with topical 1.0 mM TTX and animals receiving no treatment. RESULTS: After 4 h, eyes treated with 1.0 mM and 0.1 mM TTX were anesthetic. At 6 h, five of six rabbit eyes treated with 1.0 mM TTX were still partially anesthetic. By 8 h, the mean anesthesia score for 1.0 mM TTX was approaching normal. With multiple dosing, all six rabbit eyes remained anesthetic for the duration of the experiment. There was no significant difference in the rate of re-epithelialization between eyes treated with TTX and untreated controls. There was no evidence of systemic or local toxicity from topical TTX. CONCLUSION: In a rabbit model, TTX is a long-acting topical anesthetic that retains its effectiveness when administered repeatedly over 24 h and does not inhibit epithelial healing. It may have application in management of pain after photorefractive keratectomy.

Expression of CD44 isoforms in cultured human trabecular meshwork cells.

PURPOSE: To determine the expression of CD44 isoforms in cultured human trabecular meshwork (HTM) and to discuss their possible relationship with outflow facility. METHODS: CD44 isoform expression in cultured HTM was qualitatively examined using immunohistochemistry and RT-PCR analysis. RESULTS: Immunohistochemistry of cultured HTM showed intense staining with a CD44s antibody, and with antibodies against CD44 exon 7, exon 11-12 and exon 14. By RT-PCR, at least three isoforms of CD44 were expressed in HTM: CD44s, CD44v-III and CD44v-I. CONCLUSIONS: At least three isoforms of CD44 are expressed in the HTM. CD44 may play a role in binding and turnover of hyaluronic acid in the trabecular meshwork, thereby regulating outflow facility.

Experimental study of tetrodotoxin, a long-acting topical anesthetic.

PURPOSE: To determine the effectiveness and toxicity of tetrodotoxin for use as a long-acting topical anesthetic. METHODS: Four groups of six rabbits each received a 40-microl aliquot of either tetrodotoxin in one of three concentrations (10 mM, 1 mM, or 0.1 mM) or proparacaine 0.5% into the inferior conjunctival cul-de-sac of one eye, with the fellow eye of each rabbit receiving 40 microl of a 60-mM, pH 4.3 sodium citrate vehicle as a control. Corneal sensation was tested for up to 8 hours after administration of drugs, and response was noted by no blink, partial blink without full eyelid closure, and full blink. Slit-lamp examination at 12 and 24 hours after administration and pachymetry before and 24 hours after administration were performed to detect corneal toxicity. RESULTS: Rabbits receiving all three concentrations of tetrodotoxin did not demonstrate any ocular irritation, corneal thickening, or signs of systemic toxicity. At a dose of 10 mM, tetrodotoxin produced an anesthetic effect lasting up to 8 hours. At 1 mM, tetrodotoxin was an effective but shorter-acting anesthetic. At 0.1 mM, tetrodotoxin had no significant anesthetic effect. Proparacaine-treated rabbits initially were anesthetic, but this effect was largely gone by 1 hour and completely gone by 3 hours. CONCLUSIONS: Tetrodotoxin is a long-acting topical anesthetic in the rabbit cornea. Although additional toxicity studies are required, tetrodotoxin may provide an effective, long-lasting topical anesthetic for use in pain control after corneal procedures such as photorefractive keratectomy.

Experimental use of tetrodotoxin for corneal pain after excimer laser keratectomy.

PURPOSE: To determine the duration of anesthesia, effect on corneal reepithelialization, and systemic toxicity of topical tetrodotoxin (TTX) administered after excimer laser keratectomy. METHODS: Two groups of six rabbits each underwent excimer laser keratectomy in the right eye to create a 5-mm-diameter wound, 75 mm in depth. One group then received a 40-microl aliquot of topical 1 mM TTX into the injured eye, whereas the other group received 40 microl of the sodium citrate vehicle as a control. The rabbits were treated with TTX or vehicle again at 6, 12, 18, and 24 h. Corneal sensation was tested at 3, 6, 9, 12, 15, 18, 21, 24, 30, 32, and 40 h. To determine whether TTX inhibited corneal reepithelialization, compared with vehicle-treated control eyes, the healing rate of the epithelial defect was measured. RESULTS: Administration of TTX every 6 h for 24 h produced nearly complete anesthesia for > or = 30 h. At 32 h, 8 h after the final application of TTX, there was still significant anesthesia of the TTX-treated corneas (p = 0.0325, Wilcoxon test). Normal corneal sensation in all TTX-treated animals returned at 40 h, or 16 h after the final dose. In contrast, vehicle-treated eyes all had normal sensation for nearly the entire duration of the experiment. At 40 h, the TTX-treated eyes had slightly larger defects than vehicle-treated eyes, 7.85+/-1.74 versus 4.54+/-1.31 mm2 (p < 0.025, t test). However, at 49 h and thereafter, both groups were equally healed (p > 0.05, t test). No systemic toxicity was observed in any of the rabbits. CONCLUSION: Topical TTX is a long-acting and nontoxic local anesthetic in a rabbit model of excimer laser keratectomy.

Aqueous hyaluronic acid concentration: comparison in pediatric and adult patients.

PURPOSE: To determine if there is an age-related increase in human aqueous hyaluronic acid (HA) concentration. METHODS: HA concentrations were measured in 102 specimens of human aqueous humour obtained during intraocular surgery. Patient age ranged from one month to 93 years. Measurement of the HA concentration in the specimens was performed by a modified ELISA-like assay using a biotinylated HA-binding peptide. RESULTS: An approximate five-fold increase in the mean aqueous HA concentration was observed between the pediatric (0.33 microgram/ml, n = 5) and the adult patients (1.72 micrograms/ml, n = 97, p < 0.0002). Among the adult patients, however, there was a poor correlation between age and aqueous HA concentration. CONCLUSIONS: Adult aqueous humor has a significantly higher HA concentration than aqueous obtained from pediatric patients. The source of this increase is unclear, but may be from anterior segment production of HA, or alternatively, from anterior diffusion of vitreous HA.