Differential Response to Mechanical Cues in Uterine Fibroid Versus Paired Myometrial Cells.

Uterine leiomyomas, or fibroids, are common, benign tumors for which hysterectomy is the only definitive treatment. The extracellular matrix of fibroids is disorganized and stiffer than the surrounding myometrial tissue. To understand how stiffness affects fibroid cells, patient-matched fibroid and myometrial cells were cultured on substrates with stiffnesses varying from 0.2 to 150 kPa. Fibroid cells grew more slowly than myometrial cells overall, and only the myometrial cells altered their growth rate in response to stiffness. In both cell types, cell proliferation decreased with inhibition of PI3K and increased with inhibition of IGF-1. The cellular area was greater for the fibroid cells. The only significant effect of stiffness on the cell area was between the 0.2 and 64 kPa substrates, and this was true for both cell types. To investigate intracellular stiffness, intracellular particle tracking microrheology was used. Fibroid cells exhibited a more than 100-fold increase in elastic modulus at a frequency of 1 Hz in response to the addition of external stress, while myometrial cells showed little change in elastic modulus. Overall, the responses of both cells followed similar trends in response to stiffness and inhibitors, although the response was attenuated in the fibroid cells. The changes that were demonstrated by the change in intracellular stiffness with response to compression suggest that other mechanical forces may provide insight into differences in the two cell types.

Social implications of blepharoptosis and dermatochalasis.

PURPOSE: To investigate the social implications of blepharoptosis and dermatochalasis. METHODS: Two hundred ten individuals rated whole-face photographs of a series of patients based on 11 different personal characteristics: intelligence, threat, friendliness, health, trustworthiness, hard work, mental illness, financial success, attractiveness, alcoholism, and happiness. Preoperative and postoperative photographs of both male and female patients with bilateral blepharoptosis and/or dematochalasis were used. The paired t test was used to compare preoperative versus postoperative ratings on the 11 characteristics. RESULTS: The preoperative photographs were rated more negatively than were the postoperative photographs (p < 0.01) on all 11 characteristics for both male and female patients by the 210 study subjects. CONCLUSIONS: Members of our society view individuals with blepharoptosis and dermatochalasis negatively. These social attitudes may lead to unjust bias toward affected patients, and surgical correction probably provides benefits beyond improved visual function.

Psychosocial implications of blepharoptosis and dermatochalasis.

PURPOSE: To investigate, for the first time, the psychosocial implications of blepharoptosis and dermatochalasis. METHODS: Two hundred ten individuals rated whole-face photographs of a series of patients on the basis of 11 different personal characteristics: intelligence, throat, friendliness, health, trustworthiness, hard work, mental illness, financial success, attractiveness, alcoholism, and happiness. Preoperative and postoperative photographs of both male and female patients with bilateral blepharoptosis and/or dermatochalasis were used. The paired t test was used to compare preoperative and postoperative ratings on the 11 characteristics. RESULTS: The preoperative photographs were rated more negatively than the postoperative photographs (P < .01-P < .001) on all 11 characteristics for both male and female patients by the 210 study subjects. CONCLUSIONS: Members of society seem to view individuals with blepharoptosis and dermatochalasis negatively. These psychosocial attitudes may lead to unjust bias toward affected patients, and surgical correction likely provides benefits beyond improved visual function.

Mechanisms of orbital floor fractures: a clinical, experimental, and theoretical study.

PURPOSE: The purpose of this study was to investigate the two accepted mechanisms of the orbital blowout fracture (the hydraulic and the buckling theories) from a clinical, experimental, and theoretical standpoint. METHODS: Clinical cases in which blowout fractures resulted from both a pure hydraulic mechanism and a pure buckling mechanism are presented. Twenty-one intact orbital floors were obtained from human cadavers. A metal rod was dropped, experimentally, onto each specimen until a fracture was produced, and the energy required in each instance was calculated. A biomathematical model of the human bony orbit, depicted as a thin-walled truncated conical shell, was devised. Two previously published (by the National Aeronautics and Space Administration) theoretical structural engineering formulas for the fracture of thin-walled truncated conical shells were used to predict the energy required to fracture the bone of the orbital floor via the hydraulic and buckling mechanisms. RESULTS: Experimentally, the mean energy required to fracture the bone of the human cadaver orbital floor directly was 78 millijoules (mJ) (range, 29-127 mJ). Using the engineering formula for the hydraulic theory, the predicted theoretical energy is 71 mJ (range, 38-120 mJ); for the buckling theory, the predicted theoretical energy is 68 mJ (range, 40-106 mJ). CONCLUSION: Through this study, we have experimentally determined the amount of energy required to fracture the bone of the human orbital floor directly and have provided support for each mechanism of the orbital blowout fracture from a clinical and theoretical basis.

Ocular explosions from periocular anesthetic injections: a clinical, histopathologic, experimental, and biophysical study.

OBJECTIVES: An increasing number of cases are being recognized in which a periocular anesthetic for cataract surgery has been inadvertently injected directly into the globe under high pressure until the globe ruptures or "explodes." The objectives of the current study were to (1) analyze this injury clinically and histopathologically through a series of seven case reports; (2) reproduce the injury experimentally in human eyebank eyes, live anesthetized rabbit eyes, and human cadaveric eyes; (3) investigate the biophysical basis of the injury; and (4) outline recommendations to help decrease the risk of ocular rupture with periocular injections. DESIGNS/PARTICIPANTS: Clinical, histopathologic, experimental animal, autopsy eye, and theoretical biophysical study. METHODS: The clinical and histopathologic findings of the patients' eyes were documented. Human eyebank eyes, live anesthetized rabbit eyes, and human cadaveric eyes were exploded via direct intraocular saline injection. The laws of Bernoulli, LaPlace, Friedenwald, and Pascal were used to investigate theoretically the biophysics of the injury. RESULTS: The findings of anterior and posterior scleral rupture, retinal detachment, vitreous hemorrhage, and lens extrusion were observed clinically and experimentally. In some clinical and experimental cases, the anterior segment appeared entirely normal despite a posterior rupture. The surgeon proceeded with and completed the cataract surgery in two of the seven clinical cases without knowledge of the rupture. The pressure required to produce such an injury is in the range of 2800 to 6400 mmHg, and this pressure is more easily attained with a 3-ml syringe than with a 12-ml syringe. CONCLUSIONS: Explosion of an eyeball during the injection of anesthesia for ocular surgery is a devastating injury that may go unrecognized. The probability of an ocular explosion can be minimized by (1) the use of a blunt needle and a 12-ml syringe, (2) aspirating the plunger and wiggling the syringe before injection, (3) discontinuing the injection if corneal edema or resistance to injection is noted, and (4) inspecting the globe for evidence of intraocular injection before ocular massage or placement of a Honan balloon. On recognition of an ocular explosion, immediate referral to and intervention by a vitreoretinal surgeon is optimal.

Gallium scanning in the diagnosis and management of orbital lymphoma: a case report.

PURPOSE: To illustrate the utility of gallium scintigraphy in the diagnosis and management of orbital lymphoma. METHODS: A patient with an orbital lymphoma is reported. The results of the computed tomography scan and gallium scan are reviewed. RESULTS: Although the orbital lymphoma was readily visible on the gallium scan, it was poorly visualized on the computed tomography scan, which was interpreted as normal. CONCLUSION: Gallium scanning is a valuable adjunct in the diagnosis and management of orbital and systemic lymphoma.

Unusual orbital foreign bodies.

PURPOSE: To describe the clinical features of patients with unusual orbital foreign bodies. METHODS: The clinical histories, preoperative photographs, imaging studies, and surgical pathologic findings of five patients with unusual orbital foreign bodies are presented. Additionally, published reports pertaining to similar cases were reviewed. RESULTS: The five patients treated by the authors had good outcomes. CONCLUSIONS: An orbital foreign body may be overlooked because a small penetrating wound may be accompanied by minimal or no signs of inflammation early in the clinical course. A careful history and physical examination, imaging studies, and a strong suspicion are helpful for establishing the diagnosis of an orbital foreign body.

New insights into pathogenesis and potential therapeutic options for Graves orbitopathy.

Graves disease is an autoimmune disorder that affects the seemingly heterogeneous tissues of the thyroid and orbit. Evidence suggests that these tissues share a common antigen: the thyroid-stimulating hormone receptor protein. It is speculated that this antigen (which is present in orbital tissue in both normal patients and patients with Graves disease), together with the humoral factors present in the serum of patients with Graves disease, forms the basis for the immunologic attack seen in Graves ophthalmopathy. Once the immune response has been activated, a series of pro-inflammatory cytokines propagate inflammation, leading to the clinical findings typical of Graves ophthalmopathy. Knowledge of the specific inflammatory mediators involved may someday lead to the development of specific, clinically available immunomodulatory therapies for Graves eye disease.

Mechanisms of orbital floor fractures: a clinical, experimental, and theoretical study.

PURPOSE: The purpose of this study was to investigate the two accepted mechanisms of the orbital blow-out fracture (the hydraulic and the buckling theories) from a clinical, experimental, and theoretical standpoint. METHODS: Clinical cases in which blow-out fractures resulted from both a pure hydraulic mechanism and a pure buckling mechanism are presented. Twenty-one intact orbital floors were obtained from human cadavers. A metal rod was dropped, experimentally, onto each specimen until a fracture was produced, and the energy required in each instance was calculated. A biomathematical model of the human bony orbit, depicted as a thin-walled truncated conical shell, was devised. Two previously published (by the National Aeronautics Space Administration) theoretical structural engineering formulas for the fracture of thin-walled truncated conical shells were used to predict the energy required to fracture the bone of the orbital floor via the hydraulic and buckling mechanisms. RESULTS: Experimentally, the mean energy required to fracture the bone of the human cadaver orbital floor directly was 78 millijoules (mj) (range, 29-127 mj). Using the engineering formula for the hydraulic theory, the predicted theoretical energy is 71 mj (range, 38-120 mj); for the buckling theory, the predicted theoretical energy is 68 mj (range, 40-106 mj). CONCLUSION: Through this study, we have experimentally determined the amount of energy required to fracture the bone of the human orbital floor directly and have provided support for each mechanism of the orbital blow-out fracture from a clinical and theoretical basis.

Coexistence of 3 tumors of neural crest origin: neurofibroma, meningioma, and uveal malignant melanoma.

OBJECTIVE: To describe the clinical findings in a patient who developed a neurofibroma, meningioma, and choroidal melanoma. METHODS: Clinical and histopathological findings of the case are reviewed and presented. RESULTS: The patient had a right superolateral periorbital neurofibroma, a right sphenoid wing meningioma, and a left choroidal juxtapapillary malignant melanoma. All 3 tumors are derived from neural crest cells. CONCLUSIONS: To our knowledge, this is the first report of a patient with this combination of 3 neural crest-derived tumors. This case is most appropriately classified as a complex neurocristopathy, a disorder involving the aberrant and pathological proliferation of multiple tissues derived from neural crest cells.

Anterior uveitis associated with latanoprost.

PURPOSE: To report the association of anterior uveitis with the use of latanoprost. METHODS: We studied four patients with complicated open-angle glaucoma who had anterior uveitis associated with the use of latanoprost. The uveitis was unilateral and occurred only in the eye receiving latanoprost in three patients. In one patient, latanoprost was used in both eyes, and the uveitis was bilateral. Four of five eyes had a history of prior inflammation and/or prior incisional surgery. All patients were rechallenged with the drug. RESULTS: The uveitis improved after cessation of latanoprost with or without topical corticosteroids. It recurred after rechallenging with latanoprost in all eyes. CONCLUSION: There is a possible association between latanoprost and anterior uveitis. Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery. This association may also be possible in eyes that have not had previous uveitis or incisional surgery.

Endogenous endophthalmitis due to Serratia marcescens.

Endogenous or metastatic bacterial endophthalmitis is a severe, sight-threatening infection of the vitreous humor that is only rarely due to Serratia marcescens. We report the case of a hemodialysis-dependent diabetic patient who had endogenous endophthalmitis of the right eye due to S marcescens, presumably from an infected dialysis catheter. The patient had total visual loss in the affected eye, which required enucleation.

Cystoid macular edema and anterior uveitis associated with latanoprost use. Experience and incidence in a retrospective review of 94 patients.

OBJECTIVE: This study aimed to investigate the incidence of cystoid macular edema and anterior uveitis associated with the use of latanoprost. DESIGN: A retrospective review of patients treated with latanoprost in the authors' practice between September 1, 1996, and August 1, 1997, was performed. PARTICIPANTS: Ninety-four patients and 163 eyes were studied. INTERVENTION: Patients presenting with signs and symptoms of ocular inflammation while receiving latanoprost were noted, and their response to the discontinuation of the drug was recorded. MAIN OUTCOME MEASURES: The presence and degree of anterior uveitis and cystoid macular edema were measured. RESULTS: Six (6.4%) of 94 patients (8 [4.9%] of 163 eyes) had anterior uveitis develop, and 2 (2.1%) of 94 patients (2 [1.2%] of 163 eyes) had cystoid macular edema develop while being treated with latanoprost. CONCLUSION: Although latanoprost is an effective ocular-hypotensive agent, the authors' experience with the drug has shown a significant incidence of anterior uveitis and cystoid macular edema. To the authors' knowledge, this is the first study to report the incidence of both cystoid macular edema and anterior uveitis associated with latanoprost therapy. Treating physicians should be aware of these potential complicating side effects of latanoprost.

Ocular explosion during cataract surgery: a clinical, histopathological, experimental, and biophysical study.

INTRODUCTION: An increasing number of cases are being recognized in which a peribulbar anesthetic for cataract surgery has been inadvertently injected directly into the globe under high pressure until the globe ruptures or explodes. We reviewed the records of 6 such cases (one of which was reported previously by us), and one additional case has been reported in the literature. Surprisingly, 2 of these 7 cases went unrecognized at the time, and the surgeons proceeded with the cataract operation; all of the patients ultimately developed severe visual loss and/or loss of the eye. OBJECTIVES: To reproduce this eye explosion in a live anesthetized rabbit model and to perform a clinical, histopathological, experimental, biophysical, and mathematical analysis of this injury. METHODS: Eyes of live anesthetized rabbits were ruptured by means of the injection of saline directly into the globe under high pressure. The clinical and pathological findings of the ruptured human and animal eyes were documented photographically and/or histopathologically. An experimental, biophysical, and mathematical analysis of the pressures and forces required to rupture the globe via direct injection using human cadavers, human eye-bank eyes, and classic physics and ophthalmic formulas was performed. The laws of Bernoulli, LaPlace, Friedenwald, and Pascal were applied to the theoretical and experimental models of this phenomenon. RESULTS: The clinical and pathological findings of scleral rupture, retinal detachment, vitreous hemorrhage, and lens extrusion were observed. In the exploded human and rabbit eyes, the scleral ruptures appeared at the equator, the limbal area, or the posterior pole. In 2 of the 7 human eyes, the anterior segments appeared entirely normal despite the rupture, and cataract surgery was completed; surgery was canceled in the other 4 cases. In 4 of the 5 injected and ruptured rabbit eyes, the anterior segments appeared essentially normal. The experiments with human eye-bank eyes and the theoretical analyses of this entity show that the pressure required to produce such an injury is much more easily obtained with a 3- or 5-mL syringe than with a syringe 10 mL or larger. CONCLUSIONS: Explosion of an eyeball during the injection of anesthesia for ocular surgery is a devastating injury that may go unrecognized. The probability of an ocular explosion can be minimized by careful use of a syringe 10 mL or larger with a blunt needle, by discontinuing the injection if resistance is met, and by inspecting the globe prior to ocular massage or placement of a Honan balloon. When ocular explosion occurs, immediate referral to and intervention by a vitreoretinal surgeon is optimal. Practicing ophthalmologists should be aware of this blinding but preventable complication of ocular surgery.

The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression.

The retinal protein Nrl belongs to a distinct subfamily of basic motif-leucine zipper DNA-binding proteins and has been shown to bind extended AP-1-like sequence elements as a homo- or heterodimer. Here, we demonstrate that Nrl can positively regulate the expression of the photoreceptor cell-specific gene rhodopsin. Electrophoretic mobility-shift analysis reveals that a protein(s) in nuclear extracts from bovine retina and the Y79 human retinoblastoma cell line binds to a conserved Nrl response element (NRE) in the upstream promoter region of the rhodopsin gene. Nrl or an antigenically similar protein is shown to be part of the bound protein complex by supershift experiments using Nrl-specific antiserum. Cotransfection studies using an Nrl-expression plasmid and a luciferase reporter gene demonstrate that interaction of the Nrl protein with the -61 to -84 region of the rhodopsin promoter (which includes the NRE) stimulates expression of the reporter gene in CV-1 monkey kidney cells. This Nrl-mediated transactivation is specifically inhibited by coexpression of a naturally occurring truncated form of Nrl (dominant negative effect). Involvement of Nrl in photoreceptor gene regulation and its continued high levels of expression in the adult retina suggest that Nrl plays a significant role in controlling retinal function.