Non-Hodgkin's orbital lymphoma.

BACKGROUND: The non-Hodgkin's lymphomas (NHL) are a group of neoplasms characterized by proliferation of malignant lymphocytes. Patients with NHL have a wide variety of presenting signs and symptoms, depending largely on the site of involvement and aggressiveness of the disease. Many organs in the body may be affected, including the eye and orbit. CASE REPORT: A 47-year-old male with a 3-year history of stage IV non-Hodgkin's lymphoma who had undergone recent monoclonal antibody therapy presented with a complaint of blur in the left eye with occasional diplopia. Significant ocular findings of the left eye included ptosis, mild proptosis, increased intraocular pressure, and choroidal folds. Magnetic resonance imaging of the orbit revealed an orbital lymphoma that completely resolved after 2400 rads of external beam irradiation therapy. Eight months later, the patient developed a secondary radiation retinopathy. CONCLUSION: The prevalence of NHL is on the rise, and orbital involvement may occur at any time during the course of the disease. The standard treatment for non-Hodgkin's orbital lymphoma is external beam irradiation therapy, although the optimal dose for obtaining local tumor control without complications remains to be determined. Non-Hodgkin's lymphoma, orbital lymphoma, and various treatment options are discussed.

Amelanotic choroidal nevus and melanoma: cytology, tumor size, and pigmentation as prognostic indicators.

BACKGROUND: Choroidal nevi are fairly common lesions of the posterior pole that can sometimes transform into melanoma, and it is thought that most choroidal melanomas arise from preexisting nevi. Occasionally, these lesions present as nonpigmented or amelanotic variations of their pigmented counterparts. Recent studies suggest a relationship between tumor pigmentation and risk of growth and metastasis, with a better prognosis for lightly pigmented or amelanotic lesions. CASE REPORTS: A case of an amelanotic choroidal nevus and melanoma are presented. In Case 1, a 26-year-old white female was found to have a large amelanotic nevus in the right eye. After 7 years of periodic observation, the lesion has not changed. In Case 2, a 51-year-old white male was diagnosed with a large amelanotic melanoma in the left eye. Due to extensive involvement of the optic nerve, the patient underwent enucleation. Histological evaluation confirmed the lesion as a mixed-cell type malignant amelanotic melanoma. CONCLUSION: Management of choroidal nevi generally consists of periodic observation, and the most widely accepted management of choroidal melanoma is observation, radiotherapy, and transpupillary thermotherapy or enucleation. The therapeutic modality of choice for melanoma will vary depending on the size, growth, and location of the lesion. In addition, recent studies suggest an association between heavy tumor pigmentation, tumor size, cell type, and risk of metastasis. Although many variables will influence the final treatment option, pigmentation of the lesion should also be considered.

Suprasellar squamous papillary craniopharyngioma: a case report.

BACKGROUND: Craniopharyngiomas are benign neoplasms that are usually suprasellar in origin. They are considered a type of pituitary tumor that can cause hyposecretion of anterior pituitary hormones or hypopituitarism. Clinically, they may cause visual and endocrine deficiencies similar to pituitary adenoma. Histopathologically, they are distinct from pituitary adenoma and are generally classified as either adamantinomatous or squamous papillary. Adamantinomatous tumors are more common in children, whereas the squamous papillary type is found almost exclusively in adults. CASE REPORT: A 45-year-old white man came to our clinic with a history of decreased vision in his left eye for the previous five months that fluctuated. Magnetic resonance imaging of the brain revealed a suprasellar multilobular mass, which was distinguishable from the pituitary gland. The patient underwent a right frontotemporal craniotomy for resection of the tumor. Histopathological analysis showed a benign squamous epithelial-lined mass consistent with squamous papillary craniopharyngioma. CONCLUSION: Craniopharyngiomas are generally considered to be adamantinomatous or squamous papillary in origin. Recently, magnetic resonance imaging has been used to distinguish between these two types of tumors, although clinically no significant difference has been found with respect to resectability. Clinical presentation, treatment options, recurrence, and differential diagnosis of craniopharyngiomas are discussed.

Bilateral occipital lobe stroke with inferior altitudinal defects.

BACKGROUND: Cerebrovascular disease is the most common cause of neurological disability in Western countries. Patients who survive cerebrovascular accidents exclusive to the occipital lobe often have no significant neurological deficits other than visual-field loss. Visual-field defects from occipital lobe stroke typically include congruous homonymous hemianopsias or quadranopsias, with or without macular sparing. CASE REPORT: A 61-year-old white man came to us with symptoms of sudden loss of vision and difficulty reading. Visual-field testing revealed a bilateral inferior altitudinal defect with normal optic nerve and fundus appearance in both eyes. On radiological examination, he was found to have had a bioccipital lobe cerebrovascular accident secondary to complete occlusion of the left vertebral artery. An embolic event causing the artery occlusion, in combination with bilaterally compromised cerebellar and posterior cerebral arteries, presumably caused the bilateral stroke. After appropriate medical and neurological consultation, optometric management consisted of maximizing the patient's remaining vision with a prismatic spectacle correction. DISCUSSION/CONCLUSION: Patients with infarction exclusive to the occipital lobe typically have no other neurological deficits except visual-field loss and are often easier to manage than patients with infarctions to other areas of the cerebral cortex or multiple infarctions. Visual-field loss from occipital lobe damage can be successfully managed with optical systems and/or visual rehabilitation. Factors related to management include location and extent of visual-field damage, functional visual needs, and both personal and health concerns of the patient. A discussion is presented on cerebrovascular disease, occipital lobe infarction, imaging techniques, and visual rehabilitation.

Case presentations of retinal artery occlusions.

BACKGROUND: Retinal artery occlusions typically result in sudden, unilateral painless loss of vision and may have varying presentations. They are associated with systemic diseases such as atherosclerosis, hypertension, and valvular heart disease. Additional risk factors include diabetes mellitus, cigarette smoking, giant-cell arteritis, and hyperlipidemia. They most often occur in persons 60 to 80 years of age. METHODS: Four patients have come to our clinics with varying degrees of visual loss as a result of retinal artery occlusions. The types of arteriolar occlusions presented include: precapillary arteriole occlusion, cilioretinal artery occlusion, branch retinal artery occlusion, and central retinal artery occlusion. RESULTS: Patients were followed for their ocular involvement, but also included was medical management of the underlying systemic disease condition. Workup of retinal artery occlusion included laboratory testing, carotid duplex scans, and echocardiograms to uncover the possible systemic etiologies of the artery occlusion. CONCLUSION: Optometrists should recognize the signs and symptoms of the various arterial obstructions and refer patients for systemic treatment as indicated. Patients who manifest retinal or pre-retinal artery occlusions should undergo thorough systemic evaluations for vascular disease, including: atherosclerotic disease, hypertension, and valvular heart disease.

Relapsing polychondritis.

BACKGROUND: Relapsing polychondritis (RPC) is a rare, chronic, and potentially fatal multisystemic inflammatory disorder targeting cartilaginous structures. This disorder is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and/or hematologic disorders. RPC afflicts patients with recurrent and often progressive episodes of inflammation with the potential for destruction of the affected structures. Tissues involved include the ears, joints, nose, larynx, trachea, eyes, heart valves, kidneys,and skin. Ocular manifestations commonly include episcleritis, scleritis, conjunctivitis, iridocyclitis, chorioretinitis, and proptosis. Lid edema, orbital inflammation, muscle palsies, and corneal melting may also occur. CASE REPORT: An 83-year-old man previously diagnosed with RPC presented to our clinic with acute unilateral chemosis, conjunctivitis, lid edema, proptosis, and extraocular muscle restriction. After orbital cellulitis was ruled out, further evaluation revealed posterior scleritis with choroidal detachment OS. A course of oral indomethacin and topical antibiotic-steroid combination drops was implemented in the treatment of the ocular manifestations. The quick positive response to the anti-inflammatory agents confirmed the diagnosis of ocular complications secondary to RPC. DISCUSSION: The presenting ocular signs and symptoms of RPC often resemble other commonly encountered ocular conditions. It is important for the eye care practitioner to be familiar with the ocular manifestations of RPC because the eyes are sometimes the initial site of involvement and may be a marker of severity. Early diagnosis and intervention may significantly improve the patient's outcome. This case report with literature review will hopefully bring to light features of this disease which will help the eye care practitioner in the diagnosis and management of this condition.

The normal optic nerve head.

BACKGROUND: The normal optic nerve head varies from one person to another, and there is often intraindividual variation as well. Factors such as race and age play an important role in distinguishing what may be considered normal variations in optic nerve head appearance. METHODS: A literature search and review of the latest studies on the optic nerve head was conducted. RESULTS: Results of recent studies showed that variations in the average cup-to-disc ratio exist for different races, and with age there is a gradual loss of nerve fibers leading to an overall increase in the cup-to-disc ratio. There is also evidence that congenitally larger optic nerves have larger cup-to-disc ratios and more nerve fibers. Smaller optic nerves, in contrast, have smaller cup-to-disc ratios and fewer nerve fibers. These findings are presented along with sample photographs depicting the normal variations in optic nerve head appearance. CONCLUSION: Over the past 30 years, technology has allowed for changing views about what may be considered normal in reference to the optic nerve head. This information is valuable to the eye care practitioner in helping to make appropriate patient care management decisions.

Iodine-125 plaque radiotherapy of choroidal hemangioma.

BACKGROUND: Circumscribed choroidal hemangioma (CCH) is a benign vascular tumor that is not associated with systemic abnormalities and its pathogenesis is unknown. Most choroidal hemangiomas remain stable in size, and treatment is periodic observation unless complicated by an overlying serous retinal detachment. CASE REPORT: A 43-year-old white man came to our clinic reporting decreased vision in the left eye for 1 year. On funduscopic evaluation, a large elevated nonpigmented red-orange lesion, just temporal to the fovea of the left eye, was observed with surrounding areas of subretinal fluid. On the basis of findings obtained through ophthalmoscopy, fluorescein angiography, and ultrasonography, the patient was diagnosed with a circumscribed choroidal hemangioma. Treatment of the CCH was with iodine-125 plaque radiotherapy, which significantly reduced the tumor size and improved vision. CONCLUSION: CCH is a benign vascular tumor that is characteristically nonprogressive, but in cases of vision loss caused by serous detachment of the fovea, argon laser photocoagulation or radiotherapy is the treatment of choice. Recent studies indicate that iodine-125 plaque radiotherapy is indicated for large choroidal hemangiomas involving the macula or with associated retinal detachment. The main goal of treating CCH is to preserve vision and to prevent the progression of vision loss.

Orbital fibrous histiocytoma: case report and literature review.

BACKGROUND: Fibrous histiocytomas are a diverse group of soft tissue tumors classified histiologically as benign, locally aggressive, and malignant. These tumors are found throughout the body, but seem to have an affinity for the periorbital area. They account for one percent of all ocular masses and are the most common primary mesenchymal tumor of the orbit. Associated ocular signs and symptoms include decreased visual acuity, proptosis, diplopia, pain, restricted extraocular muscle movement, swelling of the eyelids, and conjunctiva, as well as disk edema. CASE REPORT: A case of a benign orbital fibrous histiocytoma is presented. The patient reported intermittent pain and occasional diplopia; severe edema of the right upper eyelid; and proptosis and inferior vertical displacement of the right globe were observed. Computed tomography revealed a well-defined mass that was subsequently surgically removed and histopathological results from the Armed-Forces Pathology Institute confirmed the diagnosis. CONCLUSIONS: Orbital fibrous histiocytomas are rare periocular tumors that can manifest multiple ocular signs and symptoms. Careful histologic examination is necessary for diagnosis, since these tumors have a wide range of morphology. Differential diagnoses include orbital masses with similar radiologic or histologic findings.

Mooren's ulcer.

BACKGROUND: Mooren's ulcer is a rapidly progressive, painful, ulcerative keratitis which initially affects the peripheral cornea and may spread circumferentially and then centrally. Mooren's ulcer can only be diagnosed in the absence of an infectious or systemic cause and must be differentiated from other corneal abnormalities, such as Terrien's degeneration. Although the etiology remains unknown, recent research has proposed an underlying immune process and a possible association with the hepatitis C virus. The response to medical and surgical intervention is typically poor, and the visual outcome can be devastating. CASE SERIES: Three patients presented to our clinic with inferior peripheral corneal defects characteristic of Mooren's ulceration. The first patient, a 67-year-old white male, presented with an area of progressive peripheral thinning of the left inferior cornea 1 week after a preoperative skin cleanser was inadvertently splashed in both eyes. This occurred during a surgical procedure to remove a basal cell carcinoma. The second patient, a 56-year-old white male, was treated for a recurrent left inferior corneal ulcer with impending risk of perforation. The third patient was a 68-year-old white male referred for a painful left inferior peripheral ulcer, which rapidly progressed into a bilateral corneal melt disorder. All patients were diagnosed with Mooren's ulcerative keratitis after they underwent extensive medical and laboratory testing to rule out an infectious or systemic cause of their corneal melt. The first patient was treated with oral steroids, as well as doxycycline, to control his acne rosacea. The second patient responded to aggressive treatment with topical steroid therapy. This patient also tested positive for hepatitis C. The third patient rapidly developed a perforated left cornea and was treated with a penetrating keratoplasty after a patch graft had failed. DISCUSSION: Mooren's ulcer is an idiopathic, painful, progressive ulceration of the peripheral cornea. These ulcers usually respond poorly to conventional therapy, as there is limited knowledge of the pathophysiology of the disease. Evidence of an autoimmune component advocates the use of steroids and immunosuppressive agents. With further research and understanding of Mooren's ulcer, better treatment options may be available in the future.

Retinitis pigmentosa inversa.

BACKGROUND: Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases, with a prevalence of about 1 in 3500 to 4500. Retinitis pigmentosa inversa is a rare variant of this disorder characterized by areas of choroidal degeneration with pigment migration and bony spicule formation in the macular area. In contrast to more typical forms of RP, this anomaly destroys central vision, leaving peripheral vision intact. CASE REPORT: A 47-year-old white male was followed for about 7 years with evidence of progressive retinal pigment epithelial atrophy and hyperpigmentation affecting both maculae. Since 1970, he had noted difficulty seeing at night as well as an acquired hearing deficit that appeared to be getting worse, ultimately impairing his ability to safely drive a truck. Medical history was positive for either chloroquine or hydroxychloroquine use for 2 to 3 years as malaria prophylaxis while he served in Vietnam. In addition, his father in Louisiana had visual loss of unknown cause. During the 7-year period, the condition progressed rapidly. The patient became virtually blind secondary to visual acuity loss with dense central and paracentral scotomas. The peripheral visual fields remained intact. After several years of extensive examinations, including laboratory, electroretinography, and genetic testing, a definitive diagnosis of RP inversa was made. DISCUSSION: RP inversa is a rare form of tapetoretinal degeneration that is characterized by decreased central vision with normal peripheral vision. A recessive form of inheritance has been postulated but never substantiated. Although there is currently no treatment, recent studies have indicated that 15,000 IU of vitamin A palmitate daily may slow the progression of retinitis pigmentosa; however, it is unknown whether this treatment would be effective for the inverse form of RP. Differential diagnoses include Leber's congenital amaurosis, central gyrate atrophy, central areolar choroidal sclerosis, progressive cone-rod dystrophy, syphilitic retinopathy, retinal toxicity from phenothiazine use, and chloroquine/hydroxychloroquine retinopathy.

BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A.

The breast cancer specific tumour suppressor protein, BRCA1 (refs 1,2), activates transcription when linked with a DNA-binding domain and is a component of the RNA polymerase II (Pol II) holoenzyme. We show here that RNA helicase A (RHA) protein links BRCA1 to the holoenzyme complex. The region of BRCA1 which interacts with RHA and, thus, the holoenzyme complex, corresponds to subregions of the BRCT domain of BRCA1 (ref. 9). This interaction was shown to occur in yeast nuclei, and expression in human cells of a truncated RHA molecule which retains binding to BRCA1 inhibited transcriptional activation mediated by the BRCA1 carboxy terminus. These data are the first to identify a specific protein interaction with the BRCA1 C-terminal domain and are consistent with the model that BRCA1 functions as a transcriptional coactivator.

Family history of hypertension: a psychophysiological analysis.

Family history of hypertension (positive and negative) and gender groups were compared on cardiovascular responses at rest, during stressors and during recovery. Two tasks were employed, mental arithmetic and an anger recall interview. Both levels and reactivity measures of blood pressure, heart rate, cardiac output and total peripheral resistance were included. In addition, participants filled out several questionnaires measuring state feelings during the task and recovery periods, trait anger/hostility and emotions. Both men and women with a positive family history of hypertension exhibited higher tonic levels of blood pressure and heart rate at rest, recovery and during both tasks. They also exhibited greater heart rate reactivity during the mental arithmetic task and greater blood pressure reactivity to both tasks when post-math recovery, but not initial rest, was used as a covariate. Positive family history individuals reported less trust and gregariousness, more depression and aggression, less awareness of somatic responses to the tasks and less effort to relax during the post-task rest periods. Finally, significant correlations were found between low anger expression how anger experience and high anger control and task SBP levels in positive family history individuals.

Factors associated with the mammalian RNA polymerase II holoenzyme.

The RNA polymerase II (Pol II) holoenzyme in yeast is an essential transcriptional regulatory complex which has been defined by genetic and biochemical approaches. The mammalian counterpart to this complex, however, is less well defined. Experiments herein demonstrate that, along with Pol II and SRB proteins, proteins associated with transcriptional regulation as cofactors are associated with the Pol II holoenzyme. Earlier experiments have demonstrated that the breast cancer-associated tumor suppressor BRCA1 and the CREB binding protein (CBP) were associated with the holoenzyme complex. The protein related to CBP, the E1A-associated p300 protein, is shown in these experiments to be associated with the holoenzyme complex as well as the BRG1 subunit of the chromatin remodeling SWI/SNF complex. Importantly, the Pol II holoenzyme complex does not contain some factors previously reported as stoichiometric components of the holoenzyme complex, most notably the proteins which function in repair of damaged DNA, such as PCNA, RFC and RPA. The presence of the p300 coactivator and the chromatin-modifying BRG1 protein support a role for the Pol II holoenzyme as a key target for regulation by enhancer binding proteins.

Paraocular sinus mucoceles.

BACKGROUND: Patients with paraocular sinus masses may manifest ocular complications, including orbital displacement, proptosis, diplopia, restricted extraocular muscles, decreased vision, chemosis, pain, and optic neuritis. METHODS: Two patients with paraocular sinus masses came to our clinic for examination. One had proptosis and orbital displacement and a chief symptom of increasing diplopia, along with dull brow pain and sudden decreased vision of the left eye. He was diagnosed with polypoid disease and mucoceles of the ethmoidal and frontal sinuses. The second patient experienced pain and swelling under his left eye. He had an upper respiratory tract infection with sinusitis, which in turn increased the size of the sinus cyst. RESULTS: Computed tomography (CT) of the sinuses and orbits was ordered for both patients and confirmed the presence of mucoceles in each case. The first patient's signs and symptoms decreased over 2 weeks, so surgical intervention at that time was not necessary. The second patient was treated with 60-mg pseudoephedrine q.i.d. and 250-mg amoxicillin/potassium clavulanate q.i.d. CONCLUSIONS: Mucoceles are slow-growing polyp-like cysts of the sinuses; these cysts may be sterile in composition or harbor purulent infection (mucopyocele). In either case; they are space-occupying lesions that increase in size as mucus secretions continue, and can be exacerbated by active sinusitis. Differential diagnosis includes thyroid eye disease, orbital pseudotumor, infection, trauma, benign or malignant tumors, encephalocele, or meningiocele.

RNA helicase A mediates association of CBP with RNA polymerase II.

The coactivator CBP has been proposed to stimulate the expression of certain signal-dependent genes via its association with RNA polymerase II complexes. Here we show that complex formation between CBP and RNA polymerase II requires RNA helicase A (RHA), a nuclear DNA/RNA helicase that is related to the Drosophila male dosage compensation factor mle. In transient transfection assays, RHA was found to cooperate with CBP in mediating target gene activation via the CAMP responsive factor CREB. As a mutation in RHA that compromised its helicase activity correspondingly reduced CREB-dependent transcription, we propose that RHA may induce local changes in chromatin structure that promote engagement of the transcriptional apparatus on signal responsive promoters.

BRCA1 is a component of the RNA polymerase II holoenzyme.

The familial breast-ovarian tumor suppressor gene product BRCA1 was found to be a component of the RNA polymerase II holoenzyme by several criteria. BRCA1 was found to copurify with the holoenzyme over multiple chromatographic steps. Other tested transcription activators that could potentially contact the holoenzyme were not stably associated with the holoenzyme as determined by copurification. Antibody specific for the holoenzyme component hSRB7 specifically purifies BRCA1. Immunopurification of BRCA1 complexes also specifically purifies transcriptionally active RNA polymerase II and transcription factors TFIIF, TFIIE, and TFIIH. Moreover, a BRCA1 domain, which is deleted in about 90% of clinically relevant mutations, participates in binding to the holoenzyme complex in cells. These data are consistent with recent data identifying transcription activation domains in the BRCA1 protein and link the BRCA1 tumor suppressor protein with the transcription process as a holoenzyme-bound protein.

Bilateral disc edema in retinitis pigmentosa.

Retinitis pigmentosa (RP), one of the most common forms of hereditary retinal degeneration, is characterized by night blindness and constricted visual fields. In addition to bone spicule pigmentation, other ocular findings may include posterior subcapsular cataracts, cystoid macular edema, and hyaline bodies or drusen of the optic nerve. Rarely, optic nerve head (ONH) edema has been reported to be associated with RP. A 44-year-old white male with RP and neurosensory hearing loss (Usher's syndrome type II) presented to our clinic for routine examination. A dilated fundus examination revealed bone spicule pigmentation, vessel attenuation, several flame hemorrhages on or adjacent to the nerves, and ONH edema in the right eye. B-scan ultrasonography revealed drusen of the right ONH but not of the left. Late stage fluorescein angiography showed hyperfluorescence and dye leakage from both optic discs which was more pronounced in the right eye than the left. Computed tomography (CT) of the head and orbits and cerebrospinal fluid (CSF) examination by lumbar puncture were normal. The differential diagnosis of bilateral ONH edema in this case included ONH drusen or papilledema secondary to increased intracranial pressure. This patient was found to have RP with asymmetric, bilateral ONH edema of unknown cause. One theory regarding the cause of the ONH edema is disc vessel leakage secondary to an inflammatory reaction caused by rapid photoreceptor and retinal pigment epithelium (RPE) degeneration.

Analysis of a cAMP-responsive activator reveals a two-component mechanism for transcriptional induction via signal-dependent factors.

We have examined the mechanism by which the cAMP-responsive factor CREB stimulates target gene expression following its phosphorylation at Ser-133. Using an in vitro transcription assay, we found that two signals were required for target gene activation: a phospho(Ser-133)-dependent interaction of CREB with RNA polymerase II via the coactivator CBP and a glutamine-rich domain interaction with TFIID via hTAF(II)130. The adenovirus E1A oncoprotein was found to inhibit phospho(Ser-133) CREB activity by binding to CBP and specifically blocking recruitment of RNA Pol II to the promoter. Our results suggest that the recruitment of CBP-RNA Pol II complexes per se is not sufficient for transcriptional activation and that activator-mediated recruitment of TFIID is additionally required for induction of signal-dependent genes.

Choroidal metastases resulting from carcinoma of the lung.

BACKGROUND: Choroidal metastases, the most commonly observed tumors of the choroid, are a frequent sequela of lung cancer. Carcinoma of the lung is the most common cancer. Choroidal metastatic tumors can be observed before or after the definitive diagnosis of a lung carcinoma. METHODS: A 42-year-old man, examined 1 month after reporting an ache and blurry vision in his left eye, was found to have an elevated, irregular-shaped choroidal lesion in the eye. The second patient, a 53-year-old man, was examined 1 week after reporting dim vision in the left eye. Diagnosed with non-small-cell lung carcinoma 5 months earlier, he was found to have bilateral choroidal lesions. RESULTS: The first patient was diagnosed with choroidal metastasis from adenocarcinoma of the lung 8 months after the initial presentation, confirmed after a fine-needle aspiration biopsy. The second patient had bilateral choroidal metastases from disseminated lung carcinoma. CONCLUSIONS: Metastases to the eye or orbit develop in approximately 0.7% to 12% of patients with lung cancer. Treatment regimens depend on the size and extent of the choroidal tumor, number of tumors, laterality, the visual status of the affected or nonaffected eye, the stage of cancer, and the age and general health of the patient. Prognosis is contingent on vital organ involvement and response to therapy. Preserving the patient's visual status may enhance the quality of remaining life.