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Maria A Henriquez,1 Lisett Perez,1 Gustavo Hernandez-Sahagun,1 Rolando P Rojas,1 R Doyle Stulting,2 Luis Izquierdo Jr1,3 1Research Department, Oftalmosalud Institute of Eyes, Lima, Perú; 2Stulting Research Center, Woolfson Eye Institute, Atlanta, GA, USA; 3Ophthalmology Department, Universidad Mayor de San Marcos, Lima, PerúCorrespondence: Maria A Henriquez; Luis Izquierdo Jr, Email mariahenriquez1610@gmail.com; izquierdojrluis@gmail.comPurpose: We evaluate the long-term visual, refractive, and keratometric outcomes after corneal crosslinking (CXL) in patients with progressive keratoconus (KC) and the incidence of an extreme corneal flattening effect.Settings: Oftalmosalud Institute of Eyes, Lima, Perú.Design: Retrospective cohort study.Methods: Forty-five eyes that underwent CXL with epithelial removal between June 2006 and September 2011. Data analysis was performed at preoperative evaluation, 1 year postoperatively, and at least 10 years or more postoperatively. Outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and Scheimpflug (Pentacam) analysis. Progression was defined by an increase in steep keratometry (Ks) of 1.5D or greater between 2 examinations. Extreme flattening effect was defined as a decrease in K values equal to or greater than 5 diopters (D).Results: Mean follow-up time was 11 ± 1.07 years (range 10– 13 years). There was a significant improvement in Ks, UCVA, CDVA, and spherical equivalent at the last visit. The overall rate of progression was 2.22% (1/45). Extreme flattening was observed in 15.5% (7/45) of the eyes, and this was associated with a loss of CDVA in 4.44% (2/45) of the eyes. One eye with corneal flattening of 11.5 D lost 7 lines of CDVA and required corneal transplantation.Conclusion: CXL is a safe and effective procedure to stop the progression of KC with a good overall long-term success rate. Extreme corneal flattening may be more common than commonly recognized, and severe corneal flattening associated with a decrease in CDVA may occur.Keywords: crosslinking, keratometric flattening, keratoconus, CXL

The dynamics of pinned domain walls is described by an equation of motion whose displacement term represents wall bulging. The equation is not capable of describing domain wall displacement in real materials as the bulging and threshold fields are highly complex. The equation of motion for bulging mechanisms is consistent with the method of equivalent circuits.

Purpose: The purpose of this study was to evaluate and compare the 5-year efficacy and safety of accelerated transepithelial (A-epi-on) corneal collagen cross-linking (CXL) with standard CXL (epi-off) in children with progressive keratoconus (KC)., Methods: This prospective cohort study included 78 eyes of patients aged 18 years old or younger with progressive KC who underwent CXL at the Oftalmosalud Institute of Eyes, Lima, Peru. A-epi-on CXL was performed in 32 eyes (30' of impregnation/5' of irradiation at 18 mW/cm2) and epi-off CXL was performed in 46 eyes (30'of impregnation/30' minutes of irradiation at 3 mW/cm2). Visual acuity, refraction, and the Scheimpflug imaging parameters were evaluated preoperatively and postoperatively at 1 and 5 years., Results: The best corrected visual acuity improved to 0.06 logarithm of the minimum angle of resolution (SD: 0.19, P = 0.03) and 0.09 logarithm of the minimum angle of resolution (SD: 0.13, P < 0.001) in the A-epi-on and epi-off groups, respectively. The mean flattening in the mean keratometry was 0.09 diopters (D) (SD: 0.68, P = 0.33) and 3.18 D (SD: 5.17, P < 0.001) in the A-epi-on CXL and Epi-off groups at the 5-year follow-up. Significant differences were found in the change at 1 and 5 years between the groups for cylinder reduction, flat and mean K, and pachymetry (all P < 0.05). The KC progression rate was 9.37% (3/32) in the A-epi-on CXL; no progression was found in the epi-off CXL group at the 5-year follow-up., Conclusions: Both procedures halted the progression of KC at the 5-year follow-up; however, epi-off CXL was safer and more effective when compared with A-epi-on CXL.

Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 μL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

Introduction: Disturbances in spinal subarachnoid space (SSAS) patency after SCI have been reported as an incidental finding, but there is a lack of information on its in vivo extent and time course. For substances and cells carried in the cerebrospinal fluid (CSF) to reach damaged neural tissue and promote reparative processes, CSF must be able to flow freely in SASS., Objective: To characterise the extent and time course of SSAS patency disruption in vivo in a rat model after graded SCI., Materials and Methods: Anaesthetised rats were subjected to mild or severe cord contusion at T9. Estimation of SSAS patency was carried out at 1h and 1, 3, 7, 15, 30 and 90 days postinjury, as well as in naïve rats, by quantifying the passage of superparamagnetic beads injected into the CSF at the cisterna magna and recovered at spinal level L2. CSF volume recovery was measured simultaneously. Data were analysed by the two-way ANOVA test., Results: Estimation of SSAS patency revealed nearly complete blockage early after contusion that was unevenly restored entering the chronic stages. Volume of CSF recovered was also significantly decreased early after injury compared to naïve rats, but was fully restored by 1 month postinjury. Overall, although modestly different from each other, changes in both parameters were more pronounced after severe rather than mild injuries for each time point examined., Conclusions: SCI alters SSAS patency. Its extent is a function primarily of time elapsed after lesion and secondly of injury severity. It is reasonable to expect that disturbances in SASS patency might alter CSF dynamics and impair self-reparative mechanisms and intrathecal therapeutics, making SSAS patency blockage a key target for SCI management., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Spontaneous repair or treatment-induced recovery after spinal cord injury (SCI) is very limited and might be related to extramedullary alterations that have only briefly been documented. Here we report on the morphological changes of the spinal subarachnoid space (SAS) in a clinically relevant model of SCI. Anesthetized rats were subjected either to mild or severe spinal cord contusion at T9. Spine blocks from the site of injury and adjacent segments were harvested at acute (1 h and 1 day [d]), subacute (3 and 7 d), and chronic (1 and 3 months) stages post-injury. Histopathology and morphometry at each decalcified vertebral level were assessed. At acute and subacute stages, reduction of SAS lumen was observed after both mild and severe injuries. Acutely, after severe injuries, SAS occlusion was associated mainly with cord swelling and subarachnoid hematomas; a trend for dural sac constriction was observed for mild injuries. At 7 d, cord swelling diminished in both instances, but dural sac constriction increased for severe injuries. At early stages, in the epicenter and vicinity, histopathology revealed compression of neurovascular elements within the SAS, which was more intense in severe than in mild injuries. In the chronic stage, SAS lumen increased notably, mostly from cord atrophy, despite dural sac constriction. Myelograms complemented observations made on SAS lumen permeability. Post-traumatic arachnoiditis occurred mainly in animals with severe injury. In conclusion, early extramedullary SAS changes described here might be expected to produce alterations in cerebrospinal fluid (CSF) dynamics and cord blood perfusion, thereby contributing to the pathophysiology of SCI and becoming novel targets for treatment.

Objective: The purpose of this study was to evaluate the efficacy of traditional treatment and minimal invasive flexible endoscopy surgery (MIFNES) in the treatment of intraventricular and subarachnoid basal cisterns neurocysticercosis (NCC)., Methods: This was an observational comparative study of two independent series with a total of 140 patients with extremely severe forms of NCC from two different institutions. All 83 patients submitted for traditional treatment series received albendazole, and some of them received additionally praziquantel. Each cycle of both regimens lasted 4 weeks. The majority of these patients had at least one ventriculoperitoneal (VP) shunt. The rest 57 patients were submitted to the MIFNES treatment. The follow-up period was at least 6 months., Results: In all patients of both series cysticercal cysts disappeared, became calcified, or were removed. Symptoms of 136 patients improved. Four patients died. The average in the quality of life measured using the Karnofsky scale improved from a mean of 52.22 and 52.44 at the beginning to 85.48 and 90.37 at 6 months (p < 0.003), in the traditional treatment and MIFNES series, respectively. From traditional treatment, almost all patients remained with at least one VP shunt, and from the MIFNES series only 12 patients., Conclusions: The authors postulate that MIFNES is a good alternative for the management of intraventricular and subarachnoid basal cisterns NCC because it allows removal of most of the parasites, rapid recovery of the patients, and removal and placement of shunt under direct vision when necessary. Traditional treatment is a second option where the MIFNES procedure is not available.

High hepatic extraction drugs--such as phenacetin, methylprednisolone, and cyclosporine--exhibit an increased bioavailability after acute spinal cord injury (SCI) due to an impaired clearance. For these drugs, metabolic clearance depends on hepatic blood flow. Thus, it is possible that pharmacokinetic alterations can be reversed by increasing liver perfusion. Therefore, we evaluated the effect of L-arginine, a nitric oxide precursor, on the pharmacokinetics of a prototype drug with high hepatic extraction, and on hepatic microvascular blood flow (MVBF) after acute SCI. Pharmacokinetics of i.v. phenacetin was studied in rats 24 h after a severe T-5 spinal cord contusion; animals being pretreated with L-arginine 100 mg/kg i.v. or vehicle. MVBF was assessed under similar experimental conditions using laser Doppler flowmetry. SCI significantly altered phenacetin pharmacokinetics. Clearance was significantly reduced, resulting in a prolonged half-life and an increase in bioavailability, while volume of distribution was decreased. Pharmacokinetic alterations were reversed when injured rats were pretreated with L -arginine. It was also observed that L-arginine significantly increased hepatic MVBF in injured rats, notwithstanding it exhibited a limited effect on sham-injured animals. Our data hence suggest that L-arginine is able to reverse SCI-induced alterations in phenacetin pharmacokinetics due to an impaired hepatic MVBF, likely by increased nitric oxide synthesis leading to vasodilation. Further studies are warranted to examine the potential usefulness of nitric oxide supplementation in a clinical setting.

Therapeutic approaches that promote both neuroprotection and neuroregeneration would be valuable for spinal cord (SC) injury therapies. Cyclosporin-A (CsA) is an immunosuppressant that, due to its mechanism of action, could both protect and regenerate the neural tissue after injury. Previous studies have already demonstrated that intraperitoneal administration of CsA at a dose of 2.5 mg/kg/12 h during the first 2 days after SC contusion, followed by 5 mg/kg/12 h orally, diminishes tissue damage and improves motor recovery. In order to evaluate the effect of this CsA dosing regimen on axonal growth, we assessed motor recovery, presence of axons establishing functional connections and expression of GAP-43 in rats subjected to a complete SC transection. The Basso-Beattie-Bresnahan rating scale did not show difference in motor recovery of CsA or vehicle-treated rats. Moreover, somato-sensorial evoked potentials demonstrated no functional connections in the SC of these animals. Nevertheless, histological studies showed that: i) a significant number of CsA-treated rats presented growing axons, although they deviated perpendicularly at the edge of the stumps, surrounding them, ii) the expression of GAP-43 in animals treated with CsA was higher than that observed in the control group. Finally, anterograde tracing of the corticospinal tract of rats subjected to an incomplete SC transection showed no axonal fibers reaching the caudal stump. In summary, CsA administered at the dosing-regimen that promotes neuroprotection in SC contused rats induces both GAP-43 expression and axonal growth; however, it failed to generate functional connections in SC transected animals.

To compare the effectiveness of cyclosporin-A (CsA) with methylprednisolone (MP) or a combination of both upon inhibition of lipid peroxidation (LP) after spinal cord (SC) injury, rats were treated with either CsA, MP, CSA+MP or vehicle starting 1 h after SC contusion at T9 level. LP was assessed 24h after injury by the lipid fluorescent product formation method. The survival rate was also evaluated in other series of rats by the Kaplan-Meier curves. Lipid peroxidation was similarly inhibited in rats treated with CsA, MP, or CSA+MP (p>0.05). Animals receiving MP (alone or combined with CsA) showed the poorest surviving rate. LP was inhibited by CsA to the same extent as by MP but without the lethal effect of the latter.

Objective: The aim of this study was to assess patient tolerance of unsedated routine upper endoscopy using a 6-mm ultrathin (UT) video endoscope (Olympus XGIF-N200H) and to compare its optical quality to a standard endoscope (Olympus GIF100)., Methods: A total of 62 outpatients were recruited for unsedated UT endoscopy using topical spray followed by sedated endoscopy using a standard endoscope. After unsedated endoscopy, patients were asked to complete a questionnaire assessing tolerance. When both endoscopies were completed, the endoscopist recorded findings and optical quality of the UT., Results: Of 62 patients, 19 refused unsedated endoscopy because of anxiety (12), fear of gagging (3), and unwillingness to be study patients (4)., Tolerance: Of 43 patients, 37 (86%) had a complete, unsedated UT exam (five patients did not have a GIF100 exam). During insertion, 60% of the patients reported none/mild discomfort, whereas, during the remainder of the examination, 73% had none/mild discomfort. Of 37 patients, 30 (81%) were willing to undergo future unsedated endoscopy with the UT and they tolerated UT endoscopy better than the patients who were unwilling (none/mild discomfort: 83% vs 29%). Of 43 patients, six (14%) failed UT endoscopy because of severe gagging (all were male, mean age 44 yr). OPTICS: Optical quality was rated as good 84%, 65%, and 78% of the time in the esophagus, stomach, and duodenum, respectively. Optical quality was diminished by excessive fluid and tenacious secretions. The UT missed five of 59 lesions: three hiatal hernias and two gastric erosions., Conclusion: A total of 69% of outpatients agreed to undergo peroral unsedated endoscopy with a UT endoscope. A total of 86% of patients tolerated a complete unsedated examination, and 81% of these were willing to undergo future unsedated examinations. Diagnostic accuracy of this ultrathin video endoscope was good, with 92% of lesions discovered when compared with a standard instrument.

Objective: Our aim was to evaluate the gastrointestinal tract in patients with serum ferritin values < or = 50 ng/ml for the presence of serious gastrointestinal pathology, including neoplasia and acid peptic disease., Methods: In this prospective observational study, patients with serum ferritin values < or = 50 ng/ml who did not have an obvious cause of iron deficiency underwent colonoscopy and/or esophagogastroduodenoscopy., Results: Between October 1, 1994, and February 29, 1996, 725 of 3015 patients who had serum ferritin determinations were found to have values < or = 50 ng/ml. To date, 143 patients have been fully evaluated and 77 were found to have serious gastrointestinal pathology including acid peptic disease (N = 46), cancer (N = 15), and large adenomas (N = 6). Colon cancer was discovered in five asymptomatic patients. The prevalences of serious gastrointestinal pathology did not differ between patients with serum ferritin values < or = 20 ng/ml and those with values between 21-50 ng/ml (63% vs 48%, p = 0.07). However, multivariate analysis showed that the presence of upper or lower gastrointestinal symptoms and serum ferritin value < or = 20 ng/ml is predictive of finding serious pathology (p = 0.0002 for the whole model), with odds ratios of 3.8 (95% confidence interval of 1.84-7.70) for presence of gastrointestinal symptoms and 2.2 (95% confidence interval of 1.09-4.57) for serum ferritin value < or = 20 ng/ml., Conclusions: Endoscopic examination is warranted in patients with serum ferritin values < or = 50 ng/ml to detect serious gastrointestinal pathology, present in 54% of such patients.

Objectives: One hundred consecutive patients with recurrent or refractory acute variceal hemorrhage treated with a transjugular intrahepatic portosystemic shunt (TIPS) from June 1990 to June 1993 at Oregon Health Sciences University or the Portland Veterans Affairs Medical Center were evaluated to assess shunt patency and clinical outcome, including complications of TIPS, rebleeding, and survival., Methods: Success of shunt placement, reduction in portal pressure, complications, survival, recurrent hemorrhage, severity of ascites, hepatic encephalopathy before and after TIPS, and shunt patency were assessed in each patient., Results: The mean follow-up period was 17.7 months (range, 0.1-56.7 months). TIPS was successfully completed in all patients, with a mean reduction in portosystemic gradient from 24 to 11 mm Hg. Major complications occurred in 11 patients, including one death. Survival after TIPS was 85% at 30 days, 71% at 1 yr, and 56% at 2 yr. Variceal bleeding stopped within 24 hours after TIPS in all eight patients with active hemorrhage. Recurrent variceal hemorrhage occurred in 18 patients at a mean of 4.3 months (range, 1-713 days) after TIPS. The cumulative rate of recurrent variceal bleeding was 20% at 1 yr and 25% at 2 yr after TIPS. Recurrent variceal bleeding was associated with shunt stenosis or occlusion in all patients with endoscopically documented variceal hemorrhage, which was successfully managed by reopening obstructed shunts and performing variceal embolization. The prevalence of ascites was significantly reduced among surviving patients evaluated 3 months after TIPS (67 vs 25%, p < 0.005). Three months after TIPS, the incidence of new or worsening hepatic encephalopathy was 20%, but encephalopathy improved in an equal proportion of patients. Seventy-three of 77 (95%) shunts examined for patency were open at the last follow-up examination. However, most shunts required intervention to maintain patency, and only 48% (37 of 77) were primarily patent at a mean of 168 days (range, 2-538 days) of follow-up. Shunt stenosis or occlusion, as determined by venography, became increasingly frequent with longer follow-up (52% at 3-9 months and 70% at 9-15 months)., Conclusions: TIPS is effective in lowering elevated portal pressures in patients with refractory variceal hemorrhage, has acceptable postprocedure complication and mortality rates, ameliorates ascites, and in, a minority of patients, worsens encephalopathy. Shunt stenosis occurs in the majority of patients but can be effectively treated by interventional techniques to maintain patency. The incidence of recurrent variceal hemorrhage is low and is associated with shunt stenosis or occlusion.

To evaluate the neuroprotective effect of transplants placed in the lesion zone after a complete spinal cord (SC) laceration, two independent series of experiments were carried out. In the first, allogeneic or xenogeneic fetal SC was transplanted into the gaps of the damaged lower thoracic SC of adult rats. In the transplanted rats the incidence of life-threatening complications was reduced, and the survival rate was increased compared with the control group (lesion, without implant). Histological examination showed less damage to the neighboring SC parenchyma in the transplanted rats. The measurement of this neuroprotective effect was made in a second series of experiments. Using the same model of SC injury, allogeneic fetal SC, autologous peripheral nerve and/or adipose tissue were implanted. Rats with implants of Gelfoam and damaged rats without implants were the controls. The implanted rats of all groups, including the Gelfoam group, showed a better survival rate than the nonimplanted rats. Significantly less damage to the neighboring SC parenchyma was measured in implanted rats with any of the live tissues tested compared with non-implanted rats, although no significant differences were observed between the Gelfoam group and the nonimplanted rats. Histological evidence of tissue implant survival was observed in all corresponding groups. It is concluded that the transplanted tissues tested here have a neuroprotective effect, possibly by acting as a buffer to neurotoxic substance(s) released by the stumps, and/or by exerting trophic effect(s) on the host.

Fetal brain grafting has been used successfully in the restoration of striatal function in rat and non human primate models of Huntington's disease (HD). This is a report of the first clinical trial of this procedure applied to a 37 year old Mexican female with moderate to severe HD of 9 years evolution. The two striata from a 13 week-old human fetus were homotopically transplanted to 4 cavities in the ventricular wall of the right caudate nucleus. The months after surgery, her neurologic and neuropsychologic evaluations revealed the stabilization of many of her signs and most neuropsychologic parameters, a moderate improvement of her choreic movements, predominantly in the face, of her ability to define and express ideas in oral and written form, and of her articulatory agility, as well as of some activities of her daily life and social behavior. There was a slight deterioration of her gait and posture. Her saccadic system and optokinetic nystagmus, and her visuospatial and visuoperceptual functions were deteriorated.

This article reviews nonmedical factors contributing to maternal mortality in Indonesia, the Philippines, and Thailand. In general, countries or regions should define their own priorities for intervention strategies designed to diminish the influence of such factors.

Griffonia simplicifolia agglutinin (GSA) is a valuable histochemical tool in the identification of endothelium. In this study GSA labeled with fluorescein isothiocyanate (GSA-FITC) was used to purify cultures of murine cerebral microvascular endothelium. Cultures were stained with GSA-FITC, then sorted using a fluorescence-activated cell sorter (FACS). GSA-positive endothelial cells were collected, re-cultured, and subsequently re-analyzed by FACS using GSA-FITC. Cultures that initially contained 80 +/- 3 to 89 +/- 3% (X +/- SE) GSA-positive cells were purified to 98 +/- 1% positivity. Immunohistochemistry with an anti-muscle-action antibody confirmed that FACS sorting of GSA-FITC-stained cells effectively removed contaminating smooth muscle cells from endothelial cell cultures. Viability, proliferation, and prostaglandin production of the cells was unaltered by lectin staining and FACS sorting. Thus, GSA-FITC can be used in conjunction with flow cytometry to enhance the purity of murine endothelial cell cultures without adversely affecting cell viability, growth, or metabolism.