Lymphoproliferative disorders of the ocular adnexa

Immunodysregulation appears to play a prominent role in the evolution of some lymphomas, as evidenced by the strong associations between congenital and acquired immunodeficiencies and lymphoid neoplasia, and abnormal ratios of helper T cells in lymphoid proliferations. Lympho-proliferative diseases of the ocular adnexa encompass a spectrum of lesions that may present with similar clinical and radiological features. Most primary lymphoid proliferations of the ocular adnexa consist of small lymphocytes of B-cell origin. Employing morphological, immunohistochemical, and molecular genetic criteria, proliferations may be separated into polyclonal and monoclonal categories. Increased insight into the biology and behavior of these tumors tells us that seemingly benign, as well as frankly malignant proliferations, might disseminate to nodal or extranodal sites. The diagnosis of lymphoproliferative disease of any type necessitates a complete workup for systemic lymphoma. Major prognostic criteria for lymphomas are anatomical site, stage, and histological features. Radiotherapy is employed for localized lymphoid proliferations, with chemotherapy recommended for disseminated disease. Long-term follow-up with semiannual examination is recommended. A significant percentage of primary ocular adnexal lymphoid lesions are MALT-type lymphomas, extranodal low-grade B-cell lymphomas usually associated with mucosal tissues or glandular epithelia. The pathogenesis of this lymphoma in orbital soft tissue, which normally is devoid of lymphoid tissue, lymphatic vessels, and epithelium, is unclear. MALT-type lymphomas of the ocular adnexa follow an indolent course, with long periods between relapses, and are responsive to therapy. Dissemination, when it occurs, preferentially affects other extranodal sites.     

Late effects of radiation on the eye and ocular adnexa

The N-methyl-D-aspartate receptor/nitric oxide synthase (NOS)/guanylate cyclase pathway, which plays a crucial role in synaptic plasticity in the brain, is modulated by ethanol. We studied the effect of ethanol in vitro on NOS in rat cerebellum and showed that ethanol (25-200 mM) inactivated NOS in a dose-dependent manner. This inactivation was prevented by the biopterin cofactor tetrahydrobiopterin (BH4) as well as by L-arginine, a NOS substrate, but not by NADPH. These results suggest that ethanol reduces NOS activity by modulating the conformation of the enzyme and thereby its stability, probably by interacting with the binding sites of BH4 and/or of L-arginine. Our data also suggest that inactivation of NOS may contribute to the decrease in the cGMP level, and thus may play a role in the pharmacological actions of ethanol in vivo.     

Incidence and characteristics of fall-related emergency department visits

BACKGROUND: Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies. METHODS AND RESULTS: In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004). CONCLUSIONS: Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.     

Kaposi's sarcoma of the ocular adnexa

During the last 15 years, KS has been elevated from a position of only limited academic interest to the distinction of being the most common malignancy seen in HIV-infected patients. Ophthalmologists need to become versed in the proper diagnosis and management of this condition, as ocular involvement may be seen in up to 1 in 5 patients with KS. The possibility of occult HIV disease should be entertained in a young person with an atypical hordeolum or subconjunctival hemorrhage, as KS sometimes mimics these common lesions and represents the initial presenting sign of AIDS. The patient with ocular lesions must also be evaluated appropriately for life-threatening visceral disease. Current concepts regarding the pathogenesis of KS center on a model in which an initial event, possibly infection by human herpesvirus 8, transforms normal mesenchymal cells such that they become abnormally sensitive to the high levels of cytokines present during HIV infection. Subsequent proliferation and additional mutational events result in clinically apparent disease. Present treatments include systemic chemotherapy for widespread disease and local methods such as excision, cryotherapy, radiotherapy, and intralesional injection. However, the majority of ocular lesions may be followed up with observation only. The appropriate strategy to pursue depends on the overall clinical scenario, including the patient's general health, the extent of disease, the degree of morbidity secondary to local ocular tumors, and the size of the lesions to be treated. Future therapeutic options will be aimed at modulating specific pathogenetic factors responsible for tumor development, including host cytokines, viral replication factors, and angiogenic mediators.     

Invasive keratoacanthoma of the eyelid and ocular adnexa

PURPOSE: To report three patients with superficially invasive crateriform squamous proliferations of periocular tissue. METHODS: The authors identified three patients with superficially invasive periocular tumors that had clinical features of keratoacanthoma. Clinical histories, radiographs, and surgical pathologic specimens were reviewed. RESULTS: All three tumors arose over several weeks, had a crateriform configuration, and exhibited superficial invasion of underlying tissues, including perineural invasion and infiltration into skeletal muscle. All three tumors were classified as invasive keratoacanthoma. One tumor exhibited late perineural extension into the cavernous sinus and convincing histologic features consistent with squamous cell carcinoma. CONCLUSION: The clinical importance of recognizing invasive keratoacanthoma is that although the tumor has the potential for spontaneous involution, locally aggressive behavior with deep perineural invasion is possible. This tumor is considered to represent a variant of squamous cell carcinoma. The authors recommend complete surgical excision of crateriform squamous proliferations with frozen section control of margins of resection.     

Oncocytic lesions of the caruncle and other ocular adnexa

This is a clinicopathologic study of 18 oncocytic lesions involving the ocular adnexa. These lesions most commonly occur in elderly patients (median age 73), and there is a striking predilection for women. The broad spectrum of lesions included oncocytic adenomatous hyperplasia, oncocytomas, and oncocytic carcinoma. Ten lesions, all of which were oncocytomas, involved the caruncle, four the conjunctiva, and one the mucocutaneous junction of the eyelid. Two tumors involved the lacrimal sac and one the lacrimal gland. A review of the literature disclosed only 17 previously reported oncocytic lesions of the ocular adnexa. A small yellowish-tan or reddish caruncular mass, especially in an elderly woman, should alert the ophthalmologist to consider the possibility of oncocytoma in his differential diagnosis.     

Third-level hospital emergency department visits by patients with acute asthma. 1990

BACKGROUND: In the natural history of an asthmatic patient's disease, emergency room visits can be significant, incidental, or accidental occurrences from the therapeutic, preventive, clinical, or epidemiological perspective. METHODS: In order to find out the characteristics of the severely asthmatic patients who visit the third-level emergency room of the hospital asking for medical attention, we studied their visits, as opposed to those of other patients, for a one-year period. RESULTS: We registered 477 emergency care patients for asthma (1.30/day) which implies visits to the hospital watch of 0.71%. It is maintained 24 hours a day, predominantly in the first three days of the week (52.41%), the last ten days of the month (36.68%), the second trimester of the year (34.48%), and the month of May (20%). Compared to the rest of the population who also went for emergency room care, the asthmatic patient had lower average age (44 vs. 50), a majority of women (67.29% vs. 48%) and more frequent visits (36.74% vs. 18.59%). In comparison with studies in other countries, we register a higher number of admission but a lower of relapses (4.06%). CONCLUSIONS: Emergency room visits by severely asthmatic patients is an epidemiological index of the public health significance of the disease as it is a reflection of the degree of control and type of asthma. It is an important factor in determining demand of emergency care given the frequency of visits and the rates of admission and relapse.     

Ocular sequelae of BB injuries to the eye and surrounding adnexa

BACKGROUND: BB injuries continue to be one of the most common causes of severe ocular injury among adolescent males. Extraocular and nonperforating anterior globe injuries most commonly result in favorable visual outcomes. The appropriate medical management of both perforating and nonperforating anterior globe injuries resulting from BB trauma and their potential ocular sequelae are reviewed. CASE REPORTS: Three cases illustrating typical as well as atypical anterior globe injuries caused by BBs are presented. Two cases involve nonperforating anterior globe injuries--one with intracranial and one with intraorbital involvement. The third involves a retained intraocular foreign body. The biomicroscopic and ophthalmoscopic features of these injuries are discussed, as are potential complications and management strategies associated with these types of trauma. CONCLUSIONS: Injuries associated with intraocular BBs often result in enucleation if functional vision is not salvageable. Sequelae to such injuries include endophthalmitis, traumatic hyphema, ocular siderosis, and sympathetic ophthalmia. Plain-film radiography and axial computed tomography are critical first steps in determination of the position of any intracranial or intraorbital metallic foreign body. Routine observation for the development of ocular sequelae resulting from retained intraocular, intracranial, and intraorbital BB injuries is recommended.     

Lymphoproliferative lesions of the ocular adnexa. Analysis of 112 cases

OBJECTIVE: Lymphoproliferative lesions of the ocular adnexa were analyzed to examine (1) the suitability of the Revised European-American Lymphoma (REAL) classification for the subtyping of the lymphomas in these sites; (2) the predictive value of the REAL classification for the evolution of these tumors; and (3) the frequency and prognostic impact of tumor type, location, proliferation rate (Ki-67 index), p53, CD5 positivity and the presence of monoclonality within these tumors. DESIGN: Retrospective review. METHODS: The clinical, histomorphologic, immunohistochemical, and molecular biologic (polymerase chain reaction [PCR]) features of lymphoid proliferations of the ocular adnexa were studied. STUDY MATERIALS: The ocular adnexal lymphoproliferative lesions were located as follows: orbit in 52 patients (46%), conjunctiva in 32 patients (29%), eyelid in 23 patients (21%), and caruncle in 5 patients (4%). RESULTS: Reactive lymphoid hyperplasia was diagnosed in 12 cases and lymphoma in 99 cases; 1 case remained indeterminate. The five main subtypes of lymphoma according to the REAL classification were extranodal marginal-zone B-cell lymphoma (64%), follicle center lymphoma (10%), diffuse large cell B-cell lymphoma (9%), plasmacytoma (6%), and lymphoplasmocytic lymphoma (5%). Age, gender, and anatomic localization of the lymphomas did not have prognostic significance during a follow-up period of 6 months to 16.5 years (mean, 3.3 years). Extent of disease at time of presentation was the most important clinical prognostic factor: advanced disease correlated with increased risk ratios of having persistent disease at the final follow-up and with lymphoma-related death (P < 0.001). Histomorphologic features and immunohistochemical markers positively correlating with disseminated disease at presentation, stage at final follow-up, and occurrence of lymphoma-related death included cytologic atypia (P < 0.001), MIB-1 proliferation rate (P < 0.001), and tumor cell p53 positivity (P < 0.001). The MIB-1 proliferation rates greater than 20% in extranodal marginal-zone B-cell lymphoma corresponded to at least stage II lymphoma (P < 0.05). CONCLUSION: The REAL classification is suitable for the subdivision of the ocular adnexal lymphomas. The MIB-1 proliferation rate and p53 positivity may aid the prediction of disease stage and disease progression, whereas PCR can support the diagnosis and reduce the number of histologically indeterminate lesions.     

Ambulatory visits to hospital emergency departments. Patterns and reasons for use. 24 Hours in the ED Study Group

OBJECTIVES: To characterize the reasons ambulatory patients use hospital emergency departments (EDs) for outpatient care and to determine the proportion of ED patients who initially are assessed as having nonurgent conditions, but subsequently are hospitalized. DESIGN: Cross-sectional survey during a single 24-hour period of time. SETTING: Fifty-six hospital EDs nationwide. PATIENTS OR OTHER PARTICIPANTS: Consecutive ambulatory patients presenting for care. Patents who arrived by ambulance were excluded. RESULTS: Of 6441 ambulatory patients (79 percent of all ED visits) who were eligible for study, interviews were obtained from 6187 (96 percent). A total of 5323 patients (86 percent) had clinical reasons or preferences for seeking care at an ED, including 2799 (45 percent) who thought they had an emergency or an urgent condition or were too sick to go elsewhere. Nineteen percent (n=1199) reported that they were sent to the ED by a health care professional. Patients with a regular clinician or with insurance cited similar reasons for seeking care at an ED. A total of 3062 patients (50 percent) cited 1 or more nonfinancial barriers to care as an important reason for coming to the ED, and 949 (15 percent) cited financial considerations. A total of 3045 patents (49 percent of ambulatory patients and 37 percent of total ED visits) were assessed at triage as having a nonurgent condition; 166 of them (5.5 percent; 95 percent confidence interval, 4.7 percent-6.3 percent) were admitted to the hospital. CONCLUSIONS: Most ambulatory patients seek care in an ED because of worrisome symptoms or nonfinancial barriers to care. Although many ambulatory patients appear to have nonurgent conditions based on triage classification, a small but disturbing percentage of nonurgent patients are hospitalized.     

Association between ozone and asthma emergency department visits in Saint John, New Brunswick, Canada

This study examines the relationship of asthma emergency department (ED) visits to daily concentrations of ozone and other air pollutants in Saint John, New Brunswick, Canada. Data on ED visits with a presenting complaint of asthma (n = 1987) were abstracted for the period 1984-1992 (May-September). Air pollution variables included ozone, sulfur dioxide, nitrogen dioxide, sulfate, and total suspended particulate (TSP); weather variables included temperature, humidex, dewpoint, and relative humidity. Daily ED visit frequencies were filtered to remove day of the week and long wave trends, and filtered values were regressed on air pollution and weather variables for the same day and the 3 previous days. The mean daily 1-hr maximum ozone concentration during the study period was 41.6 ppb. A positive, statistically significant (p < 0.05) association was observed between ozone and asthma ED visits 2 days later, and the strength of the association was greater in nonlinear models. The frequency of asthma ED visits was 33% higher (95% CI, 10-56%) when the daily 1-hr maximum ozone concentration exceeded 75 ppb (the 95th percentile). The ozone effect was not significantly influenced by the addition of weather or other pollutant variables into the model or by the exclusion of repeat ED visits. However, given the limited number of sampling days for sulfate and TSP, a particulate effect could not be ruled out. We detected a significant association between ozone and asthma ED visits, despite the vast majority of sampling days being below current U.S. and Canadian standards.     

Treatment and prognosis in a series of primary extranodal lymphomas of the ocular adnexa

BACKGROUND: The aim of this study was to assess clinicopathological characteristics and outcome in a series of primary ocular adnexal lymphomas (POALs). PATIENTS AND METHODS: Nineteen patients with localised (stage IE) POAL were followed for a median of 96 months (24-156). The diagnosis was based on surgical biopsies followed by immunohistochemistry in 16 cases or fine-needle aspiration followed by immunocytophenotypic analysis in three cases. Twelve patients were treated with local radiotherapy (RT), five with chemotherapy (CT), and two refused further therapy after apparently radical tumour removal achieved by the diagnostic excisional biopsy. RESULTS: The histological and immunological pattern was consistent with a diagnosis of MALT-type lymphoma (11 cases), follicular center non-Hodgkin's lymphoma (three cases). a large-cell variant of Burkitt's lymphoma (one case), and large-cell transformed MALT lymphoma (one case). Low-grade lymphoma was diagnosed in the three cases which underwent fine-needle aspiration biopsy. All of the patients achieved and maintained complete remission except for those treated with surgical excision alone (two MALT conjunctival lymphoma cases): one of these relapsed locally, the other experienced the systemic spread of a transformed diffuse large-cell lymphoma and died 72 months after diagnosis. The side effects consisted of two cases of RT-related cataract after 52 and 72 months. CONCLUSIONS: Regardless of histology, prognosis was excellent when surgery plus RT was adopted, and CT seems to be a valid alternative to RT. Surgery alone may be sub-optimal.     

Public complaints and the emergency department

The effect of various cytokines including rIL-1, rIL-2, rIL-3, rIL-4, rIL-6, and growth factors including rNGF, rILGF and rEPGF on the post transplant immunodeficiency after allogeneic bone marrow transplantation was explored in 8 patients. The results show that neither cytokine alone was able to increase the proliferative capability in post transplant lymphocytes, however, when added in conjunction a significant increase in PHA driven proliferation was noted. Any significant lack of growth factors is probably not the only cause of immunodeficiency post transplant, since addition of any of these compounds did not have any influence on the lymphocyte proliferation, and so the data presented here suggest that therapeutic application of any of the investigated cytokines or growth factors to such patients is unlikely to be successful in overcoming the defects of T cell function post grafting.     

Epidemiological study of benign tumors and inflammatory pseudotumors of the eye and its adnexa

PURPOSE: Benign tumors and the inflammations of the eye and its adnexa are about twice as frequent as malignant tumours. Because of the aesthetic value or functional importance and the diagnostic difficulties that they can induce, we thought it interesting to conduct an epidemiological study including the localization and the different histological forms of benign tumors and inflammations of theeye. MATERIAL AND METHODS: This study was carried out for a period of 70 years between 1925 and 1995, utilizing case histories and results of the histological examinations of the Pathology Department of the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts in Paris. The statistics included the histological diagnostic, the localization and the civil data. RESULTS: Benign tumors and inflammations of the eye and its adnexa corresponded respectively to 25.9% and 7.1% of the histological results accomplished in the laboratory. Papilloma (31.4%) and cysts (28.2%) were the most frequent benign tumors. Chalazions represent the most frequent aetiology of inflammation (49%), followed by granuloma (30%). Our results are compared to those of other laboratories. CONCLUSION: While malignant tumors account for the majority of endo-ocular tumors, benign tumors and inflammatory processes are almost always extra-ocular involving the conjunctiva and the eye lids (in particular the inferior eye lid). Papilloma and cysts together account for about 50% of the benign tumors and inflammations of the eye.     

Tumors of the eye and ocular adnexal tissues

This article reviews options in dealing with tumors of the cornea and conjunctiva, nictitating membrane neoplasms, and eyelid neoplasms. Orbital tumors, optic nerve and other intraocular tumors are also discussed.     

Caring for Cambodian refugees in the emergency department

BACKGROUND: Platelet utilization has steadily increased throughout the past three decades. At the same time, there has been very little study of the current transfusion practices. STUDY DESIGN AND METHODS: A survey was conducted of institutional members of the American Association of Blood Banks (hospitals) that were actively involved in the care of pediatric and/or adult hematology and/or oncology patients. Inquiries were made relating to the extent of prophylactic versus therapeutic use of platelets, criteria used for prophylactic transfusion of platelets and type, and dose of platelets used. Data were analyzed according to patient age and type of hospital. RESULTS: Of 786 responding hospitals, 630 (80.2%) provided sufficient data for analysis; 126 of that 630 provided care for pediatric patients. The majority (60.9%) of responding hospitals had a minimum of four hematologists and/or oncologists. Eighty-four percent of hospitals reported transfusing some apheresis platelets. The dose of platelet concentrates most frequently used for adults ranged from 6 to 10, with pools of 10 more commonly used in community hospitals. More than 70 percent of hospitals reported transfusing platelets primarily for prophylaxis: 60 percent of hospitals set the threshold platelet count for prophylactic platelet transfusion at 20,000 per microL, with approximately 20 percent each transfusing at higher and lower levels. A platelet count of 50,000 per microL was most frequently required for performance of a minor invasive procedure. CONCLUSION: The data from this study show that the majority of institutions use prophylactic platelet transfusion in both pediatric and adult hematology and/or oncology patients. However, there is considerable variation in platelet transfusion practice.