Mark P. Hatton

Twenty Year Trends (1975-1995) in the Incidence, In-hospital and Long-Term Death Rates Associated With Heart Failure Complicating Acute Myocardial Infarction A Community-Wide Perspective

OBJECTIVES To describe from a population-based perspective, recent and temporal (1975-1995) trends in the incidence, in-hospital and postdischarge case-fatality rates of heart failure (HF) complicating acute myocardial infarction (AMI). BACKGROUND Extremely limited data are available describing the incidence and case-fatality rates associated with HF complicating AMI from a community-wide perspective. METHODS The medical records of 6,798 residents of the Worcester, Massachusetts metropolitan area with validated MI and without previous HF hospitalized in 10 annual periods between 1975 and 1995 were reviewed. RESULTS The proportion of AMI patients developing HF during hospitalization declined between 1975-1978 (38%) and 1993-1995 (33%) (p < 0.001). After controlling for potentially confounding factors, the risk of developing HF declined progressively, albeit modestly, over time. In-hospital case-fatality rates of patients with AMI complicated by HF declined by approximately 46% between 1975-1978 (33%) and 1993-1995 (18%) (p < 0.001). Improving trends in hospital survival were observed after adjusting for potentially confounding prognostic factors. The one-year post-discharge mortality rate for hospital survivors of HF did not change over the 20-year period under study, even after controlling for additional prognostic characteristics. CONCLUSIONS The results of this community-wide study suggest encouraging declines in the incidence and hospital death rates associated with HF complicating AMI. Continued efforts need to be directed towards the prevention of HF given the magnitude of this clinical syndrome. Efforts of secondary prevention are needed to identify and improve the treatment of patients with symptomatic left ventricular dysfunction following AMI given the lack of improvement in the long-term prognosis of these patients.

IgG4-Related Systemic Disease as a Cause of “Idiopathic” Orbital Inflammation, Including Orbital Myositis, and Trigeminal Nerve Involvement

IgG4-related systemic disease (IgG4-RD) is an inflammatory condition of unknown etiology that has been identified as the cause of tumefactive lesions in a number of tissues and organs. The role of the IgG4 remains to be clarified fully, but the histopathologic diagnosis hinges upon the finding of IgG4-bearing plasma cells in addition to characteristic morphologic features, with or without elevated seum IgG4. We present a 56-year-old man with orbital pseudotumor in whom, after 30 years of intractable disease, biopsy showed IgG4-RD involving the lacrimal gland, extraocular muscles, intraconal fat, and trigeminal nerve. Six months after initiating treatment with rituximab, his disease remained dormant, with improvement in his proptosis and normalization of serum IgG4 levels. We review the differential of idiopathic orbital inflammatory disease, including IgG4-RD, and emphasize the need for biopsy for accurate diagnosis and to guide appropriate treatment.

Periorbital changes associated with topical bimatoprost.

Purpose: To describe periorbital changes induced by chronic topical therapy with daily bimatoprost 0.03% (Lumigan, Allergan Inc., Irvine, CA, U.S.A.). Methods: A clinical investigation of 5 nonconsecutive patients with unilateral glaucoma treated daily with topical bimatoprost 0.03% for up to 4 years prior to presentation. Results: In eyes treated with bimatoprost 0.03% the authors noted periorbital fat atrophy, deepening of the upper eyelid sulcus, relative enophthalmos, loss of the lower eyelid fullness, and involution of dermatochalasis compared with the fellow untreated eye. By inspecting old photographs the authors confirmed that these unilateral changes were not present prior to starting bimatoprost. In addition, these changes were partially reversible after discontinuation of the medication, whenever that was possible. In 2 cases imaging studies confirmed the clinical impression that these findings were not related to primary orbital pathology. Conclusions: Physicians and patients should be aware of the potential of bimatoprost 0.03% to produce periorbital changes.

Surgical treatment of distal radial fractures with a volar locking plate versus conventional percutaneous methods: a randomized controlled trial.

BACKGROUND The aim of this study was to compare the outcomes of displaced distal radial fractures treated with a volar locking plate with the results of such fractures treated with a conventional method of closed reduction and percutaneous wire fixation with supplemental bridging external fixation when required. Our aim was to ascertain whether the use of a volar locking plate improves functional outcomes. METHODS A single-center, pragmatic, randomized controlled trial was conducted in a tertiary care institution. One hundred and thirty patients (eighteen to seventy-three years of age) who had a displaced distal radial fracture were randomized to treatment with either a volar locking plate (n = 66) or a conventional percutaneous fixation method (n = 64). Outcome assessments were conducted at six weeks, twelve weeks, and one year. Outcomes were measured on the basis of scores on the Patient Evaluation Measure (PEM) and QuickDASH questionnaire (a shortened version of the Disabilities of the Arm, Shoulder and Hand, or DASH, Outcome Measure), EuroQol-5D (EQ-5D) scores, wrist range of motion, grip strength, and radiographic parameters. RESULTS The rate of follow-up at one year was 95%. Patients in the volar locking-plate group had significantly better PEM and QuickDASH scores and range of motion at six weeks compared with patients in the conventional-treatment group, but there were no significant differences between the two groups at twelve weeks or one year. Grip strength was better in the plate group at all time points. The volar locking plate was better at restoring palmar tilt and radial height. Significantly more patients in the plate group were driving at the end of six weeks, but this did not translate to a significant difference between groups in terms of those returning to work by that time. CONCLUSIONS Use of a volar locking plate resulted in a faster early recovery of function compared with use of conventional methods. However, no functional advantage was demonstrated at or beyond twelve weeks. Use of the volar locking plate resulted in better anatomical reduction and grip strength, but there was no significant difference in function between the groups at twelve weeks or one year. The earlier recovery of function may be of advantage to some patients. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Orbital fractures in children.

Purpose To describe the demographics, etiologic factors, clinical presentations, and outcomes of orbital fractures in children. Methods This was a retrospective case series of 96 consecutive patients under 18 years of age with orbital fractures presenting to the Massachusetts Eye and Ear Infirmary, including both hospitalized and nonhospitalized patients. Results Orbital fractures in children were most frequently the result of sports, assault, or motor vehicle accident. The majority of patients did not require hospitalization and were treated as outpatients. The medial wall and floor of the orbit were the most frequent locations of fracture. Approximately half of the patients in this series required surgery, most often for entrapment. There were no cases of persistent diplopia in patients in whom surgery was performed or was not indicated. Associated ocular injuries were observed in half of the patients. Conclusions In this series of hospitalized and nonhospitalized patients, orbital fractures in children had a location pattern similar to that most frequently observed in adult patients (floor and medial wall). Orbital fractures in children frequently require surgery. The high prevalence of ocular injury in children with orbital fractures emphasizes the need for a comprehensive ophthalmic evaluation.

Culture, immortalization, and characterization of human meibomian gland epithelial cells.

PURPOSE Meibomian gland epithelial cells are essential in maintaining the health and integrity of the ocular surface. However, very little is known about their physiological regulation. In this study, the cellular control mechanisms were explored, first to establish a defined culture system for the maintenance of primary epithelial cells from human meibomian glands and, second, to immortalize these cells, thereby developing a preclinical model that could be used to identify factors that regulate cell activity. METHODS Human meibomian glands were removed from lid segments after surgery, enzymatically digested, and dissociated. Isolated epithelial cells were cultured in media with or without serum and/or 3T3 feeder layers. To attempt immortalization, the cells were exposed to retroviral human telomerase reverse transcriptase (hTERT) and/or SV40 large T antigen cDNA vectors, and antibiotic-resistant cells were selected, expanded, and subcultured. Analyses for possible biomarkers, cell proliferation and differentiation, lipid-related enzyme gene expression, and the cellular response to androgen were performed with biochemical, histologic, and molecular biological techniques. RESULTS It was possible to isolate viable human meibomian gland epithelial cells and to culture them in serum-free medium. These cells proliferated, survived through at least the fifth passage, and contained neutral lipids. Infection with hTERT immortalized these cells, which accumulated neutral lipids during differentiation, expressed multiple genes for lipogenic enzymes, responded to androgen, and continued to proliferate. CONCLUSIONS The results show that human meibomian gland epithelial cells may be isolated, cultured, and immortalized.

Gender differences in etiology and outcome of open globe injuries

PURPOSE Patterns of injury and outcomes after multi-system trauma differ between men and women. Few data exist regarding the epidemiology of gender differences in severe eye trauma. We hypothesized that the incidence and patterns of open globe injuries might differ between men and women. METHODS Charts of 220 patients with open globe injuries presenting to the Massachusetts Eye and Ear Infirmary during a three-year period were retrospectively reviewed. The data were analyzed with respect to gender, type of open globe injury (penetrating, perforating, or rupture), and mechanism of globe injury (projectile, non-projectile, assault, fall, sports, motor vehicle crash). RESULTS The majority (78.6%) of patients were men. Women with open globe injuries were older (median age 73 years) than men (median age 36 years). Men were more likely to suffer from penetrating injuries (69.9%) while women were more likely to experience blunt globe rupture (68.1%). Projectile objects accounted for the majority of open globe injuries in men (54.9%) and were an infrequent cause in women (4.3%). Nearly one-third (31.8%) of the projectile injuries in men were work-related, and 19.7% occurred during home improvement projects. Compared with men, falls were more frequently responsible for globe injuries in women (55.3% versus 8.1%). Injuries limited to the cornea were more common in men than women (46.2% versus 23.4%), while more posterior globe injuries were more common among women (46.8% versus 28.3% men). Women were more likely than men to have poor visual acuity at 3 months after injury. CONCLUSIONS The causes and patterns of open globe injuries differ between men and women. In this series, the majority of injuries to men were caused by projectile objects related to work or home improvement projects. Open globe injuries in women were most often resulted from fall, and were more likely to cause rupture posterior to the limbus.

Changes in Gene Expression in Human Meibomian Gland Dysfunction

PURPOSE Meibomian gland dysfunction (MGD) may be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease is unclear. This study was conducted to identify meibomian gland genes that may promote the development and/or progression of human MGD. METHODS Lid tissues were obtained from male and female MGD patients and age-matched controls after eyelid surgeries (e.g., to correct entropion or ectropion). Meibomian glands were isolated and processed for RNA extraction and the analysis of gene expression. RESULTS The results show that MGD is associated with significant alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including those encoding various small proline-rich proteins and S100 calcium-binding proteins, are significantly increased, whereas the expression of 194 genes, such as claudin 3 and cell adhesion molecule 1, is significantly decreased. These changes, which cannot be accounted for by sex differences, are accompanied by alterations in many gene ontologies (e.g., keratinization, cell cycle, and DNA repair). The findings also show that the human meibomian gland contains several highly expressed genes that are distinct from those in an adjacent tissue (i.e., conjunctival epithelium). CONCLUSIONS The results demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium-binding proteins, suggest that keratinization plays an important role in the pathogenesis of MGD.

TREATMENT OF RELAPSED CYTOMEGALOVIRUS RETINITIS WITH THE SUSTAINED-RELEASE GANCICLOVIR IMPLANT

Purpose: Sustained-release ganciclovir implants are effective in delaying progression of newly diagnosed cytomegalovirus (CMV) retinitis. An uncontrolled case series was assembled to evaluate the efficacy of the intravitreal ganciclovir implant for patients with sight-threatening CMV retinitis who had previously failed to respond to intravenous ganciclovir and/or foscarnet. Methods: Between August 1993 and March 1995, 72 eyes of 55 patients received intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. Results: A total of 56 eyes (77.8%) were available for evaluation after implant surgery. At the 1-month postoperative visit, 48 eyes (85.7%) of 38 patients had no progression. Implants failed to control progression at the 1-month visit in eight eyes (14.3%) of six patients receiving primary implants. A total of 32 eyes (57.1%) of 29 patients did not experience three-line loss of visual acuity through the follow-up period. The median time to three-line loss was 190 days from implantation. Four eyes (7.1%) developed visual acuity of 20/200 or worse by the 1-month follow up. The median time from implantation to development of visual acuity of 20/200 or less was 224 days. The median survival time was 376 days from study entry. The most common postoperative complication was retinal detachment, which was observed in 12 eyes receiving implants. Additional self-limiting complications included significant vitreous hemorrhage (three eyes) and hypotony maculo-pathy (two eyes). Conclusion: Ganciclovir implants were effective in delaying visual loss in a significant proportion of patients who failed ganciclovir or foscarnet therapy. A number of these patients, however, experienced visual loss. Although the implants can be effective as therapy for relapsed CMV retinitis, the efficacy does not appear to match that noted in initial CMV retinitis therapy.

Effect of Growth Factors on the Proliferation and Gene Expression of Human Meibomian Gland Epithelial Cells

PURPOSE We hypothesize that growth factors, including epidermal growth factor (EGF) and bovine pituitary extract (BPE), induce proliferation, but not differentiation (e.g., lipid accumulation), of human meibomian gland epithelial cells. We also hypothesize that these actions involve a significant upregulation of genes linked to cell cycle processes, and a significant downregulation of genes associated with differentiation. Our objective was to test these hypotheses. METHODS Immortalized human meibomian gland and conjunctival epithelial cells were cultured for varying time periods in the presence or absence of EGF, BPE, EGF + BPE, or serum, followed by cell counting, neutral lipid staining, or RNA isolation for molecular biological procedures. RESULTS Our studies show that growth factors stimulate a significant, time-dependent proliferation of human meibomian gland epithelial cells. These effects are associated with a significant upregulation of genes linked to cell cycle, DNA replication, ribosomes, and translation, and a significant decrease in those related to cell differentiation, tissue development, lipid metabolic processes, and peroxisome proliferator-activated receptor signaling. Serum-induced differentiation, but not growth factor-related proliferation, elicits a pronounced lipid accumulation in human meibomian gland epithelial cells. This lipogenic response is unique, and is not duplicated by human conjunctival epithelial cells. CONCLUSIONS Our results demonstrate that EGF and BPE stimulate human meibomian gland epithelial cells to proliferate. Further, our findings show that action is associated with an upregulation of cell cycle and translation ontologies, and a downregulation of genetic pathways linked to differentiation and lipid biosynthesis.