Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344232 (blurred vision)
 2,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reported is the case of a 24-year-old Finnish woman who developed malignant hypertension while taking an oral contraceptive (OC) that contained 30 mcg of ethinyl estradiol. She presented with blurred vision, but reported no other remarkable signs or symptoms during the 5 months in which she had been using OCs. Laboratory tests at admission revealed incomplete systemic lupus erythematosus (SLE) with DNA antibodies and high levels of antiphospholipid antibodies. Her blood pressure was 220-140 mmHg. OC use was discontinued and antihypertensive treatment initiated, with good results. 2 years later, however, the patient developed epileptic seizures and an area of local atrophy in the cerebellum was identified through computerized tomography. In the 4-6th years after initial presentation, the patient experienced 3 miscarriages, all at 7-8 weeks of gestation. 1 year after presentation, the patient satisfied 4 of the criteria for SLE (positive DNA and antiphospholipid antibodies, thrombocytopenia, leukopenia, and proteinuria). At present, the patient's symptoms are being controlled with carbamazepine and metroprolol. The patient's older sister, who had never used OCs, had SLE. It appears that high levels of antiphospholipid antibodies are an additional risk factor for the development of vascular complications in OC users but are not induced by OCs. Similarly, while OCs are not believed to cause SLE, they can exacerbate the disease or unmask a lupus diathesis.
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PMID:Malignant hypertension and antiphospholipid antibodies as presenting features of SLE in a young woman using oral contraceptives. 174 6

Crisnatol is a novel lipophilic arylmethylaminopropanediol with significant antineoplastic activity in a variety of murine and human tumor models which functions as a DNA intercalator. In this Phase I trial, a 6-h infusion of the drug was administered i.v. in 700 to 1500 ml of 5% dextrose in water every 28 days. Eighty-five courses at doses of 7.5 to 516 mg/m2 were administered to 43 patients with refractory solid tumors. Reversible neurological toxicity was dose limiting at 516 mg/m2 and was manifested as somnolence, dizziness, blurred vision, unsteady gait, and alpha-slowing on electroencephalogram at the end of infusion. All neurological signs and symptoms were reversible. No hematological toxicity was observed. Other toxicities included phlebitis, mild to moderate nausea and vomiting, reversible sinus node arrest in one patient, and hypertension. Crisnatol plasma concentrations were determined by high-pressure liquid chromatography. After infusion, plasma concentrations declined biexponentially with a terminal t1/2 of 2.9 h. Using a two-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 58.8 liters/m2 and 18.3 liters/h/m2, respectively, indicative of extensive tissue distribution and rapid hepatic clearance. Peak plasma levels occurred at the end of infusion and correlated with the onset of neurological toxicity. The recommended Phase II dose for this schedule is 388 mg/m2.
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PMID:Phase I and clinical pharmacology trial of crisnatol (BWA770U mesylate) using a monthly single-dose schedule. 339 16

A patient with refractory acute myelogenous leukemia was treated with high-dose cytosine arabinoside (3.0 g/m2 every 12 hours). Following ten doses over five days the patient developed excessive tearing, photophobia, burning ocular pain, and blurred vision. Ophthalmologic examination revealed conjunctival injection, central punctate corneal opacities with subepithelial granular deposits, and decreased visual acuity. Symptoms gradually resolved over the following four days; however, impaired visual acuity persisted for two weeks and corneal opacification did not disappear until four weeks following therapy. Prior and subsequent administration of cytosine arabinoside according to the same dose schedule for only four doses over two days and eight doses over four days were well tolerated and did not produce ocular toxicity. It is suggested that ocular toxicity results from inhibition of corneal epithelial DNA synthesis and is related to both drug dosage and duration of drug exposure. Strategies should be explored to eliminate this treatment-limiting adverse effect of potentially effective therapy.
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PMID:Ocular toxicity from high-dose cytosine arabinoside. 657 99

Three patients with leukemia developed corneal toxicity while receiving high doses (3 g/m2) of systemic cytarabine. Symptoms began five to seven days after initiation of treatment with high doses of systemic cytarabine and consisted of ocular pain, tearing, foreign-body sensation, photophobia, and blurred vision. All three patients developed bilateral conjunctival hyperemia and fine corneal epithelial opacities and refractile microcysts that were more numerous in the central than in the peripheral cornea. The symptoms disappeared without treatment in approximately one week. The corneal changes we observed with high doses of systemic cytarabine resembled descriptions of corneal toxicity from topical cytarabine and were probably secondary to inhibition of DNA synthesis in the corneal epithelium.
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PMID:Corneal toxicity with systemic cytarabine. 693 30

A 32-year-old woman was admitted for evaluation of fever, blurred vision in the left eye, nasal and gingival bleeding and arthralgia. There was a macular hemorrhage, a tender mass in the left lower abdomen and edema of both legs. She also had anemia, mild thrombocytopenia, platelet function abnormalities, kidney dysfunction, and albuminuria. Serology was positive for antinuclear antibodies and double-stranded DNA; complement level was low, and circulating anticoagulants were present. Kidney biopsy established the diagnosis of systemic lupus erythematosus (SLE). Abdominal sonography demonstrated perisplenic and pelvic bleeding. A pulse therapy of corticosteroids with low-dose oral cyclophosphamide, along with platelet transfusions and infusions of deamino-d-arginine vasopressin resulted in symptomatic and laboratory improvement. Bleeding stopped, platelet function became normal, kidney function tests returned to normal and she became seronegative. It is emphasized that platelet function abnormalities are rare in SLE. The thrombocytopenia was too mild to cause spontaneous bleeding, and lupus anticoagulant is usually associated with thromboembolic complications and not with spontaneous bleeding. It is therefore conceivable that in this case platelet function abnormalities were responsible for the spontaneous bleeding, the presenting sign which led to establishing the diagnosis.
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PMID:[Bleeding due to platelet dysfunction as a presenting symptom of systemic lupus erythematosus]. 867 11

A 13-year-old boy presented with a 2-month history of blurred vision. Visual acuity was 20/200 in both eyes. Ophthalmoscopic examination revealed normal discs and "beaten bronze atrophy" in the maculae. Subsequently, progressive vision loss with optic atrophy occurred over the next few years. Fluorescein angiographic findings were compatible with Stargardt's maculopathy. Because his cousin developed sequential vision loss diagnosed as Leber's hereditary optic neuropathy, molecular genetic analysis was performed on blood mitochondrial DNA (mtDNA) from our patient, his cousin with vision loss, and another three asymptomatic cousins. The results showed that they all harbored homoplasmic G to A point mutations at nucleotide position 11778 of the ND4 gene in mtDNA.
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PMID:Stargardt's type maculopathy in a patient with 11778 Leber's optic neuropathy. 879 69

Gelatinous drop-like corneal dystrophy (GDLD; OMIM 204870) is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness, with an incidence of 1 in 300,000 in Japan. Our previous genetic linkage study localized the gene responsible to a 2.6-cM interval on chromosome 1p. Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia and foreign-body sensation. By the third decade, raised, yellowish-grey, gelatinous masses severely impair visual acuity, and lamellar keratoplasty is required for most patients. Here we report DNA sequencing, cDNA cloning and mutational analyses of four deleterious mutations (Q118X, 632delA, Q207X and S170X) in M1S1 (formerly TROP2 and GA733-1), encoding a gastrointestinal tumour-associated antigen. The Q118X mutation was the most common alteration in the GDLD patients examined, accounting for 33 of 40 (82.5%) disease alleles in our panel of families. Protein expression analysis revealed aggregation of the mutated, truncated protein in the perinuclear region, whereas the normal protein was distributed diffusely in the cytoplasm with a homogenous or fine granular pattern. Our successful identification of the gene that is defective in GDLD should facilitate genetic diagnosis and potentially treatment of the disease, and enhance general understanding of the mechanisms of amyloidosis.
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PMID:Identification of the gene responsible for gelatinous drop-like corneal dystrophy. 1019 95

Leigh syndrome is a progressive neurodegenerative disease frequently associated with mitochondrial abnormalities. The mitochondrial DNA T9176C mutation in the adenosine triphosphatase 6 gene has recently been described as a cause of Leigh syndrome. Leukocyte DNA from 59 children with Leigh syndrome was screened for the T9176C mutation by conventional polymerase chain reaction methods. Two unrelated patients were found to be homoplasmic for this mutation in blood. Both patients had similar clinical and biochemical features. They had first presented acutely at 3 and 5 years, respectively, with ataxia and slurred speech. Magnetic resonance imaging changes were consistent with Leigh syndrome, and the cerebrospinal fluid lactate was elevated. They have both had relatively stable disease since the time of diagnosis. The mother of one of the children had presented at age 29 years with sudden onset of ataxia, headache, and blurred vision. She was heteroplasmic for the T9176C mutation. The T1976C is an important cause of Leigh syndrome especially in the subgroup of patients with more stable disease and normal respiratory chain enzyme analysis.
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PMID:Mitochondrial DNA point mutation T9176C in Leigh syndrome. 1119 6

Primary intraocular lymphoma (PIOL) is a variant of primary central nervous system lymphoma in which lymphoma cells are initially present only in the eyes without evidence of disease in the brain or cerebrospinal fluid. Patients with PIOL are typically older adults who present with blurred vision and floaters. The ophthalmic examination characteristically shows a cellular infiltrate in the vitreous with or without the presence of subretinal infiltrates. Diagnostic evaluation for PIOL includes neuroimaging, cytologic examination of the cerebrospinal fluid, and a diagnostic vitrectomy with special handling of the vitreous specimen, if the former is nondiagnostic. Molecular and cytokine analyses are useful adjuncts to cytology for the diagnosis of PIOL. Recent molecular studies demonstrating viral DNA in the ocular lymphoma cells suggest a role for infectious agents in the pathogenesis of PIOL. To date, the best mode for treatment of PIOL or recurrent primary central nervous system lymphoma involving only the eyes remains undefined.
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PMID:Ocular manifestations of central nervous system lymphoma. 1130 54

Normally light transmission through the eye is benign and serves to direct vision and circadian rhythm. However, with very intense light exposure, or with ambient light exposure to the aged eye and/or young or adult eye in the presence of light-activated (photosensitizing) drugs or dietary supplements, cosmetics, or diagnostic dyes, light can be hazardous, leading to blinding disorders. Light damage to the human eye is avoided because the eye is protected by a very efficient antioxidant system and the chromophores present absorb light and dissipate its energy. After middle age, there is a decrease in the production of antioxidants and antioxidant enzymes and an accumulation of endogenous chromophores that are phototoxic. The extent to which a particular exogenous photosensitizing substance is capable of producing phototoxic side effects in the eye depends on several parameters, including (1) the chemical structure; (2) the absorption spectra of the drug; (3) binding of the drug to ocular tissue (lens proteins, melanin, DNA); and (4) the ability to cross blood-ocular barriers (amphiphilic or lipophilic). For instance, compounds that have either a tricyclic, heterocyclic, or porphyrin ring structure and are incorporated into ocular tissues are potentially phototoxic agents in the eye. The extent to which these substances might damage the eye (photoefficiency) can be predicted using in vitro and photophysical techniques. With simple, inexpensive testing, compounds can be screened for their potential ocular phototoxicity at the developmental stage. It may be that a portion of the molecule can be modified to reduce phototoxicity while leaving the primary drug effect intact. Preclinical safety testing may prevent ocular side effects that can range from mild, reversible blurred vision to permanent blindness.
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PMID:Screening for ocular phototoxicity. 1253 45


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