Gomez-Lopez-Hernandez syndrome (cerebello-trigeminal-dermal dysplasia) is a condition that includes abnormalities of the cerebellum (rhombencephalosynapsis), cranial nerves (trigeminal anesthesia), and scalp (alopecia). Seven patients with this condition have been documented since 1979. We now report a male with Gomez-Lopez-Hernandez syndrome who, at the age of 19 years, is the oldest patient identified to date. He has been followed since birth, allowing us to report on the progression of his physical findings and psychiatric problems including hyperactivity, depression, self-injurious behavior and bipolar disorder. In addition, he has short stature and growth hormone deficiency.
This study identifies calpain as being instrumental for brush border (BB) microvillus assembly during differentiation and effacement during bacterial pathogenesis. Calpain activity is decreased by 25-80% in Caco 2 lines stably overexpressing calpastatin, the physiological inhibitor of calpain, and the effect is proportional to the calpastatin/calpain ratio. These lines exhibit a 2.5-fold reduction in the rate of microvillus extension. Apical microvillus assembly is reduced by up to 50%, as measured by quantitative fluorometric microscopy (QFM) of ezrin, indicating that calpain recruits ezrin to BB microvilli. Calpain inhibitors ZLLYCHN 2 , MDL 28170, and PD 150606 block BB assembly and ezrin recruitment to the BB. The HIV protease inhibitor ritonavir, which inhibits calpain at clinically relevant concentrations, also blocks BB assembly, whereas cathepsin and proteasome inhibitors do not. Microvillus effacement is inhibited after exposure of calpastatin-overexpressing cells to enteropathogenic Escherichia coli. These results suggest that calpain regulates BB assembly as well as pathological effacement, and indicate that it is an important regulator involved in HIV protease inhibitor toxicity and host-microbial pathogen interactions.Although it is accepted that actin-associated cross-linking and membrane linker proteins such as villin and ezrin, found in intestinal microvilli, are Ca 2ϩ -sensitive, the role that Ca 2ϩ plays in the assembly and stability of microvilli is undetermined. Interest in Ca 2ϩ as a regulator of microvillus remodeling has been focused on its role in disrupting villin crosslinks of the microvillus actin filaments (reviewed in Ref. 1) and the activation of the actin filament severing activity of villin. It has been suggested that the Ca 2ϩ -dependent protease, calpain, cleaves the membrane linker protein ezrin, during cell motility-associated remodeling of cortical -actincontaining structures (2-4). Because -actin is the predominant actin isoform of microvilli (5) and because ezrin, which is abundant in microvilli, associates with -actin in an isoform-specific and calpain-sensitive fashion (2), the question has arisen whether calpain regulates -actin-ezrin interactions in microvilli, and microvillus assembly. Additionally, the finding that calpain levels exceed calpastatin levels in intestinal epithelial cells (6) suggests that calpain could play a role in intestinal differentiation.Calpain has been implicated in cytoskeletal remodeling, including disruption of cell-matrix interactions at the rear of the cell during crawling (7) and lamellipodial and protrusion formation during spreading (4). These examples illustrate the role of calpain in remodeling dynamic actin filament structures at the periphery of the cell. Calpain has not been implicated in assembly of filamentous actin structures in the BB apical domain of enteric epithelial cells or membrane recruitment of ezrin, where it may play an important role in assembly of actin filaments (2,8).A recently developed approach to study the r...
Purpose: To evaluate the clinical outcomes of self-retained cryopreserved amniotic membrane (cAM) for the treatment of corneal ulcers. Methods: This was a single-center, retrospective review of consecutive patients with nonhealing corneal ulcers that underwent treatment with self-retained cAM (PROKERA ® Slim). The primary outcome measure was time to complete corneal epithelialization. Ocular discomfort, corneal staining, corneal signs, and visual acuity were assessed at 1 week, 1 month, 3 months, and 6 months. Complications, adverse events, and ulcer recurrence were also recorded. Results: A total of 13 eyes (13 patients) with recalcitrant corneal ulcers were included for analysis, 9 (69%) of which progressed from neurotrophic keratitis (NK). Prior to cAM application, patients used conventional treatments such as artificial tears (n = 11), antibiotics (n = 11), ointment (n = 11), steroids (n = 6), and antivirals (n = 3). Self-retained cAMs (n = 1.5 ± 0.8) were placed for 6.8 ± 3.4 days, during which time antibiotics were continued. Four cases (31%) were subsequently treated with bandage contact lens (n = 3) and tarsorrhaphy (n = 1). All corneal ulcers healed in a median of 14 days (range: 4-43). This was accompanied by a significant improvement in ocular discomfort, corneal staining, and corneal signs at 1 week, 1 month, 3 months, and 6 months (P<.05). Recurrence was noted in one case. No adverse events were observed. Conclusion: Self-retained cAM may be a valuable, in-office treatment option for healing recalcitrant corneal ulcers of various etiologies, especially those with underlying NK. Further prospective, controlled studies are warranted.
Purpose To evaluate the utilization of scleral lenses and prosthetic replacement of the ocular surface ecosystem devices (SL/PDs) in the management of ocular graft-versus-host disease (oGVHD). Patients and Methods A survey of 15 questions was sent via email to 6032 subjects registered with the Blood and Marrow Transplant Information Network. The survey reviewed transplant history, graft-versus-host disease history, as well as oGVHD symptoms and onset. Additional questions surveyed treatments used for oGVHD, as well as the degree of ocular symptom control and experience with SL/PDs. A total of 306 respondents met the eligibility requirements to be part of the analyzed cohort. Results The mean number of symptoms reported from the analyzed cohort was 4.79 ± 2.44, median (IQR) of 5.0 (3.0 to 7.0), with the most common symptom being gritty, dry eyes (87%). The mean number of treatments utilized across the analyzed cohort was 3.21 ± 2.55, median (IQR) of 2.5 (1.0 to 5.0), with the most common treatment being artificial tears (86%). Wearing scleral lenses resulted in a mean of 5.42 ± 1.86, median (IQR) of 6.0 (4.0 to 7.0) symptoms improving, with improved dryness/grittiness of the eyes (94%), improved eye pain (92%) and improved quality of life (89%) being the most commonly improved symptoms. Fifty-six percent of those wearing scleral lenses wished the lenses had been recommended sooner. The most common reason patients cited for not wearing scleral lenses was that they had never heard of them (63%). Conclusion SL/PDs help to control the symptoms of oGVHD. With their use, clinicians are able to improve the quality of life of this patient population. Despite the known benefits, SL/PDs still remain underutilized in oGVHD care. A majority of current SL/PD wearers wish that they had been recommended sooner as a treatment option. SL/PDs should be considered a component of comprehensive oGVHD management.
Purpose: To evaluate the impact of prosthetic replacement of the ocular surface ecosystem (BostonSight PROSE) treatment on symptom outcomes based on the Ocular Surface Disease Index (OSDI). Patients and Methods: This was a single-center, retrospective analysis of consecutive patients who initiated PROSE treatment between September 2017 and December 2019 by the same clinician. The primary outcome measure was to compare OSDI survey scores at baseline prior to PROSE treatment and at follow-up, after PROSE treatment. Indication for treatment, sex, age, device diameter, average wear time, preexisting mental illness, duration of PROSE wear, and status of PROSE wear at follow-up were also studied. Results: A total of 134 patients underwent PROSE treatment and completed a baseline OSDI survey during the study period. Forty-three patients completed a follow-up OSDI survey and were included in the study analysis. The most common treatment indications were keratoconjunctivitis sicca (n=27) and corneal ectasia (n=16). Baseline average OSDI score was 56.9±23.7 for the 43 subjects who completed a subsequent OSDI survey. The last documented average follow-up OSDI for those 43 subjects was 23.8±15.6, median (IQR) of 22.9 (10.4 to 32.3), and a statistically significant 54.7±27.6% average improvement from baseline (p<0.01). All patients, except for two, showed improvement in OSDI score. Statistically significant improvement occurred regardless of underlying diagnosis with no statistically significant difference based on age, sex, mental illness, or device diameter and no statistical correlation with average wear time, or duration of PROSE wear. Conclusion: PROSE treatment improves visual function and symptom relief as demonstrated by the OSDI survey. Sex, age, preexisting mental illness, device diameter, average wear time, and duration of wear had no statistically significant impact on OSDI outcomes.
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