Estrogen receptors in skeletal metabolism: lessons from genetically modified models of receptor function

Estrogens have long been known to be important for skeletal homeostasis, but their precise mechanisms of action in bone are still unclear. Mice with targeted deletions of the estrogen receptors alpha (ERalpha) and beta (ERbeta) have been generated by two research groups and several studies performed characterizing the phenotype of ERalpha knockout (ERKOalpha), ERbeta knockout (ERKObeta), or double deletion of ERalpha and ERbeta (DERKO) mice. Initial studies reported a reduction in bone mineral density in male ERKOalpha mice. More extensive analyses have been puzzling, likely because of compensatory mechanisms in ERKO mice. Furthermore, the existence of a third ER continues to be a potential explanation for some actions of estrogen in bone. Other rodent models, including the testicular feminized mouse and rat, the aromatase knockout mouse, and a rat with a dominant negative ER mutation, have added information regarding estrogen's actions in bone. This review summarizes many reports characterizing available rodent models with genetic alterations relevant to estrogen action. The sum of these reports suggests that the ERbeta is not highly protective in bone because loss of its function results in minimal alterations in the skeleton. Furthermore, loss of both the ERalpha and the ERbeta does not account for loss of estrogen action in bone, because the impact of DERKO is seemingly not as great as the impact of gonadectomy on the skeleton. Finally, through studies of ERKO mice and other rodent models of altered sex steroid action, it appears that estrogen may be more protective in the skeleton than androgens.     

A New Approach to Tertiary Hyperparathyroidism: Percutaneous Embolization: Two Case Reports

Secondary hyperparathyroidism is one of the most common complications of chronic kidney failure. If prolonged, parathyroid hormone release gains autonomy and tertiary hyperparathyroidism with parathyroid adenoma or hyperplasia can be develop. Tertiary hyperparathyroidism is associated with increased risk of mortality and morbidity; thus, treatment is recommended. Medical treatment includes phosphate binders, vitamin D analogues, and calcimimetic agents. Most cases of tertiary hyperparathyroidism can be controlled with medical treatment. When medical treatment options prove insufficient, parathyroidectomy is recommended. However, recurrence after parathyroidectomy is possible, which requires an alternative treatment. We present our percutaneous embolization experience, which has not been tried in the treatment of tertiary hyperparathyroidism in renal transplantation patients diagnosed with tertiary hyperparathyroidism.     

Atopic keratoconjunctivitis

Atopic keratoconjunctivitis (AKC) is a potentially blinding disease characterized by a bilateral chronic keratoconjunctivitis associated with atopic dermatitis. The disease usually manifests as severe itching and burning, excessive tearing, foreign body sensation, and mucoid discharge. The clinical characteristics of AKC show a broad spectrum including lid dermatitis, chronic blepharitis, cicatrizing conjunctivitis with fornix foreshortening and symblepharon formation, punctate epithelial keratitis, persistent epithelial defects, corneal scarring and neovascularization, lipid keratopathy, conjunctivalization of peripheral cornea, and peripheral ulcerative keratitis. The underlying pathophysiologic mechanism in AKC involves a combination of type-I IgE-mediated, and type-IV delayed hypersensitivity reactions. The immunoregulatory defect responsible for the overproduction of allergen-specific IgE antibody, the key component responsible for antigen binding, and subsequent mast cell degranulation, is probably multifactorial. The histopathologic characteristics of the conjunctiva in AKC include a mast cell and eosinophil invasion of the epithelium, epithelial pseudotubule formation, and prominent mast cell and mononuclear cell infiltration of the substantia propria. A number of ocular conditions have been reported to be associated with AKC, including keratoconus, herpes simplex keratitis, and cataracts. Successful long-term control of this potentially blinding disease requires a multidisciplinary approach involving systemic and environmental aspects. Scrupulous long-term environmental control of allergens is the single most important aspect in the management of patients with AKC. Systemic anti-histamine therapy, and long-term topical mast cell stabilizing therapy are also mandatory. Topical steroids should be reserved for exacerbations of the disease.     

Penetrating keratoplasty in patients with corneal scarring due to trachoma

BACKGROUND AND OBJECTIVE: Trachoma remains the leading cause of preventable corneal blindness. The outcome of penetrating keratoplasty (PK) in these patients is usually poor because of the extensive corneal vascularization, adnexal and ocular surface problems. We evaluated the long-term results of PK in patients with corneal scarring due to trachoma. PATIENTS AND METHODS: The fiels of 16 eyes of 13 patients who underwent PK due to late sequel of trachoma were reviewed. RESULTS: Preoperative visual acuity ranged from light perception to finger counting levels. Preoperatively, dry-eyes, meibomian gland dysfunction, trichiasis and cicatricial entropion were treated. Over a mean postoperative follow-up of 26.1 +/- 15.6 months (range of 14-61 months), eyes required redrafting due to graft rejection and failure, and corneal ulceration (12.5%). Fourteen eyes remained clear grafts (87.5%), and 13 eyes (81.3%) achieved 0.1 or better visual acuity. CONCLUSIONS: These results suggest that although patients with corneal scarring due to trachoma are at high risk, PK may be helpful for visual rehabilitation.     

Retinal tears associated with panuveitis and Behçet's disease

To report retinal tears formation in 3 eyes of 2 patients with active panuveitis and Beh?et's disease. We describe 2 patients that were diagnosed and treated for Beh?et's disease with active panuveitis. Retinal tears developed while the inflammation was active. The patients were treated with topical, oral steroids, and cyclosporine therapy for bilateral panuveitis. One patient presented with a retinal tear located at the periphery of the active retinal lesion. The other had multiple tears associated with active retinal lesions in both eyes. Argon laser photocoagulation was performed in both patients as soon as the tears were detected. Ocular inflammation was controlled with this therapy, and only a few mild flare-ups occurred. The patients have been followed up for 8 and 16 months, respectively. During this period no new retinal tears have developed. Although retinal tear formation is rarely associated with Beh?et's panuveitis, the clinician should be aware of this as a possible complication. When structural changes are present in the vitreous, detailed ophthalmoscopy is indicated to assess for retinal tears. If a tear is detected in a patient with panuveitis and Beh?et's disease, laser photocoagulation therapy should be performed immediately to prevent retinal detachment.     

Microbial keratitis following penetrating keratoplasty.

PURPOSE: To investigate the prevalence of microbial keratitis, predisposing risk factors and treatment modalities in patients who developed keratitis following penetrating keratoplasty (PK). PATIENTS AND METHODS: The records of 285 patients who had undergone PK between January 1991 and December 1995 in a tertiary care center were reviewed. Patients who developed postoperative microbial keratitis were evaluated for predisposing risk factors, microbiological etiology, response to broad spectrum antibiotic therapy and subsequent PK. Patients were mainly treated with fortified topical antibiotics with or without repeat PK. RESULTS: Of the 285 patient records reviewed, microbial keratitis developed in 21 eyes of 21 patients (7.4%). Seventy-one percent of infections occurred within 6 months after grafting. Keratitis initially began from the donor-recipient border in 16 cases (76.2%) and were central or paracentral in 5 patients. Predisposing risk factors included loose or exposed suture (9), suture removal (1), persistent epithelial defect (3), graft failure (3), contact lens wear (1), Stevens-Johnson syndrome (1). Fifteen (71.4%) patients were culture-positive consisting of Streptococcus pneumoniae (7), Staphylococcus aureus (5), Pseudomonas aureginosa (2), and Hemophilus influenzae (1). Forty-three percent of patients were successfully treated with medical therapy only. Seven patients underwent second PK for visual rehabilitation and 4 for tectonic purposes. After medical and surgical therapy, graft clarity was achieved in 17 (81%) of patients. CONCLUSIONS: The microbial keratitis following PK is a major postoperative problem affecting the long term prognosis. Careful selection of patients, and preoperative and postoperative control of risk factors, may decrease the frequency of this complication. Several factors, including loose or exposed sutures, epithelial defects, ocular surface disorders, and graft failure, may predispose patients to develop microbial keratitis following PK.