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Biomedical subjects

D A Lee

Publications and source records attributed to D A Lee.

At least 73 records · Page 4Linked to original sources

Prevalences of ocular conditions among Hispanic, white, Asian, and black immigrant students examined by the UCLA Mobile Eye Clinic.

BACKGROUND: First-and second-generation immigrant children are the fastest-growing component of the U.S. population under 15 years of age. Prevalences of ocular conditions in first-generation immigrant children are described, stratified by ethnicity and sex, and compared to previous UCLA Mobile Eye Clinic (MEC) studies and the National Health and Nutrition Examination Surveys. METHODS: Clinical data from 2,229 newly immigrated students, ages 8 to 16 years of age, examined by the UCLA Mobile Eye Clinic from 1990-1996, were analyzed by chi-squares test. RESULTS: Females have significantly higher prevalences of astigmatism (p = 0.003) and myopia (p = 0.001) than males. Asians have significantly higher prevalences of myopia (p < 0.001) and visual acuity worse than 20/40 without correction (p < 0.001) than Hispanics. CONCLUSIONS: Overall ocular health of this sample is very close to that of age-matched U.S. children, but with markedly lower prevalences of extraocular muscle imbalance and color vision deficiencies. Examiners should be aware of the higher rate of astigmatism and myopia in first-generation female immigrants, as well as the higher prevalence of myopia among Asians.

Adolescent↗

Acute acalculous cholecystitis (AAC) resulting in gallbladder perforation in a solid organ transplant recipient: a case report.

Gallbladder perforation is a frequent complication of acute acalculous cholecystitis (AAC), resulting in substantially increased morbidity and mortality. Two groups of patients are at increased risk for perforation: those with systemic diseases (especially peripheral vascular disease, intrinsic heart disease, or diabetes) and those who are chronically immunosuppressed. The current population of solid organ transplant recipients meets both criteria. We describe an unusual case of gallbladder perforation as a complication of AAC in an otherwise healthy kidney transplant recipient. Because transplant recipients are at increased risk for gallbladder perforation, maintaining a high index of suspicion for this complication will help avoid the increased morbidity and mortality associated with this diagnosis.

Acute Disease↗

Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose.

Articular cartilage is subjected to dynamic compressive loading that is known to influence chondrocyte metabolism. While the exact signalling mechanisms are unclear, it has been proposed that cell deformation plays a role and may stimulate a metabolic response through distinctive pathways. In this study, a well characterized model system in which chondrocytes are embedded in agarose was used to study the effect of dynamic cellular strain on three key metabolic processes, namely the synthesis of glycosaminoglycan, of DNA, and of total protein. Using a specially designed apparatus, 15% compressive strain amplitude was applied to agarose-chondrocyte cylinders statically or dynamically over a range of frequencies (0.3-3 Hz). Static and low-frequency strain (0.3 Hz) inhibited the synthesis of glycosaminoglycan, while a frequency of 1 Hz stimulated synthesis. Static strain reduced the level of thymidine uptake, whereas dynamic strain at all frequencies induced an increase in chondrocyte proliferation. Incorporation of tritiated proline was suppressed by all strain regimens tested. The three parameters investigated were each influenced by the dynamic strain regimens in a distinct manner, implying that the signalling mechanisms involved are uncoupled.

Animals↗

In vitro evaluation of antiproliferative potential of calcium channel blockers in human Tenon's fibroblasts.

The calcium cation has been known to play a central and diverse role in the proliferation of numerous types of cells including fibroblasts. Therefore, ib1p4llows that calcium channel blockers (CCBs) may potentially inhibit fibroblast attachment and proliferation. The time and dose-related effects of five commonly used CCBs-verapamil, diltiazem, nicardipine, trifluoperazine, and dantrolene-on human Tenon's fibroblast attachment and proliferation were studied. Fibroblasts were incubated with different concentrations of each drug. To evaluate the effect of each drug on fibroblast attachment, cell density was quantified by Coulter counter and hexosaminidase assays after 24 hours of incubation. To evaluate the effect of each drug on fibroblast proliferation, cell density was quantified by Coulter counter, hexosaminidase, and 3H-thymidine uptake assays on days 1, 3, and 7. Dantrolene had minimal effect, failing to cause even 20% inhibition at 10(-5) M, the highest concentration tested. Verapamil, diltiazem, nicardipine, and trifluoperazine all inhibited fibroblast attachment and proliferation. Trifluoperazine was the most potent inhibitor of attachment and proliferation with ID50S in the 10(-5) M range. Verapamil, diltiazem, and nicardipine had similar potency in inhibiting attachment and proliferation with ID50S in the 10(-4) M range. Because CCBs seem to inhibit fibroblast attachment and proliferation, future clinical studies may show that these agents reduce collagen production, scar formation, and bleb failure following glaucoma filtration surgery.

Calcium Channel Blockers↗

Corneal endothelial toxicity of topical anesthesia.

PURPOSE: To determine the relative corneal endothelial toxicities of the following topical anesthetic agents: bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, proparacaine HCl 0.5%, and tetracaine HCl 0.5%. METHODS: The experiment was conducted using pigmented rabbits. Approximately nine animals each were randomly assigned to eight groups. Right eyes received injections of 0.2 ml of one of the four anesthetic agents at one of two concentrations and left eyes received injections of 0.2 ml of balanced salt solution. Corneal thickness and clarity were measured before surgery and on postoperative days 1, 3, and 7. RESULTS: A statistically significant increase (P < 0.05) in corneal thickness and opacification over preoperative measurements was noted with injections of bupivacaine, lidocaine, and proparacaine, controlling for changes occurring in control eyes from surgery alone. Proparacaine was statistically more toxic than were the others. The toxicity of tetracaine was statistically indistinguishable from balanced salt solution, although mild toxicity was evident clinically. Injection of 1:10 dilutions of the same anesthetic agents failed to produce a statistically significant increase in corneal thickness or opacification on any postoperative examination. CONCLUSIONS: Anterior chamber injection of bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, and proparacaine HCl 0.5% produces corneal thickening and opacification that is clinically and statistically significant. Tetracaine HCl 0.5% injection produces corneal thickening and opacification that is clinically apparent in some eyes but statistically insignificant. Ophthalmic surgeons should be aware of the potential for endothelial cell injury if anesthetic agents enter or are injected into the eye during cataract surgery in the concentrations supplied commercially.

Administration, Topical↗

Gonioscopic laser sclerostomy versus filtration surgery in a rabbit model.

In a prospective and randomised study, we compared the course of pulsed dye laser ab interno sclerostomy with the course of posterior lip sclerectomy in 25 rabbits. One eye of each rabbit was randomly selected to be treated with laser; the fellow eye underwent posterior lip sclerectomy. Intraocular pressure (IOP) determinations and slit lamp examinations were recorded pre-operatively, then every other day for 3 weeks on 21 of the rabbits. Histological examination was performed on the eyes of 3 randomly selected rabbits that were killed 72 hours post-operatively. Laser sclerostomy resulted in an average maximal drop in IOP of 9.5 mmHg on post-operative day 1, and posterior lip sclerectomy resulted in a similar drop of 10.5 mmHg (p = 0.43, t-test). By life-table analysis, 88% of eyes returned to within 2 mmHg of pre-operative IOP values within 7 days following either laser internal sclerostomy or posterior lip sclerectomy. There was no significant difference between laser internal sclerostomy and posterior lip sclerectomy eyes with respect to the number of days needed to return to within 2 mmHg of preoperative IOP values (p = 0.26, sign test of the life-table analysis). Pulsed dye laser internal sclerostomy appears to be as effective as posterior lip sclerectomy in lowering IOP in the rabbit model.

Animals↗

Determination of ocular toxicity in multiple applications of foscarnet iontophoresis.

This is the first study of multiple applications of drug iontophoresis in the eye. We repeated ocular foscarnet iontophoresis in 10 eyes of 10 rabbits every third day at the same paralimbal site for a total of seven applications over a period of 21 days to determine the efficacy and toxicity of multiple applications of ocular foscarnet iontophoresis. Mean vitreous human foscarnet concentration of 189 +/- 50.6 microM (SD) was achieved four hours after the seventh consecutive iontophoretic application over a period of twenty-one days. These levels were within the therapeutic range (25-800 microM) for the treatment of CMV retinitis and comparable to the intravitreal foscarnet concentrations achieved in eyes treated with a only a single application of ocular iontophoresis. Electroretinography (ERG) and Slit-lamp biomicroscopy responses revealed no evidence of ocular toxicity. Indirect ophthalmoscopy of the retinas and gross examinations of the calottes revealed a single, small burn in the retina and choroid corresponding to the application site of the iontophoresis probe similar to the lesion resulting from a single application of iontophoresis. Light and electron microscopy revealed local tissue injury and fibrosis at the iontophoresis site, but adjacent areas were unaffected.

Animals↗

Initial human experience with ganaxolone, a neuroactive steroid with antiepileptic activity.

PURPOSE: Studies were conducted to establish the safety, tolerability, and pharmacokinetics of the antiepileptic drug (AED) ganaxolone. Ganaxolone belongs to a novel class of neuroactive steroids called epalons, which specifically modulate the gamma-aminobutyric acid type A (GABA[A]) receptor in the central nervous system (CNS). Chemically related to progesterone but devoid of any hormonal activity, the epalons have potent antiepileptic, anxiolytic, sedative, and hypnotic activities in animals. METHODS: Ninety-six healthy male and female volunteers received ganaxolone in a variety of formulations, doses, and dosing regimens. The pharmacokinetics of ganaxolone were systematically characterized, and adverse events associated with drug use were documented. RESULTS: Ganaxolone was well tolerated after single doses (< or =1,500 mg) and after multiple doses (< or =300 mg b.i.d. for 10 days). Steady-state plasma levels (trough) occurred after approximately 7 days of dosing, with mean steady-state plasma concentrations (Cmax) in multiple dose studies of between 32 ng/ml (50-mg doses) and 376 ng/ml (500-mg doses). No serious or life-threatening adverse events attributed to the drug were observed. The majority of adverse events reported were mild (82%) to moderate (14%) and were limited to headache, dizziness, somnolence, gastrointestinal disturbances, and malaise. CONCLUSIONS: Ganaxolone alone or formulated with pharmaceutical-grade excipients is rapidly absorbed from the gastrointestinal tract after oral administration in doses ranging from 50 to 1,500 mg. Pharmacokinetic analysis revealed a linear and proportional increase in the area under the curve (AUC) and Cmax values with increasing dose within the expected therapeutic dose range. Safety and tolerability in the clinical program were unremarkable.

Administration, Oral↗

Retroperitoneal fibrosis: a report of complete colonic obstruction.

Idiopathic retroperitoneal fibrosis (RPF) is a disease entity rarely encountered by the general surgeon. In most cases, ureteral stricture is the underlying problem requiring lysis of fibrotic adhesions. However, infrequently, the gastrointestinal tract may become involved. The following report describes the complications of intestinal obstruction by RPF in one of our patients. The discussion then focuses on the need for early diagnosis and treatment of gastrointestinal invasion by RPF.

Aged↗

Ophthalmic disorders among the homeless and nonhomeless in Los Angeles.

BACKGROUND: Few studies have addressed ocular disorders among the homeless and nonhomeless poor. METHODS: To better understand the health problems of the homeless, ophthalmic disorders were analyzed among 512 homeless and 413 nonhomeless poor individuals receiving vision-screening examinations in Los Angeles. RESULTS: Significantly, more 4- to 17-year-old nonhomeless poor were diagnosed with uncorrected visual acuity worse than or equal to 20/50 without correction (p = 0.001), total refractive errors (p < 0.0005), astigmatism (p = 0.001), and myopia (p < 0.0005) than were a control group of 4- to 17-year-old homeless individuals. More homeless individuals had extraocular muscle imbalance (p < 0.040), but fewer had external eye diseases (p2 = 0.016) than the nonhomeless poor, when age adjusted. In addition, higher rates of glaucoma and cataracts were observed in both homeless and poor nonhomeless populations than in the general population. CONCLUSIONS: Health care professionals should provide vision screenings intended to detect these ocular disorders. Screening and correction of myopia and glaucoma, in particular, can greatly improve the quality of life for those treated.

Adolescent↗

Effect of normal synovial fluid on the metabolism of articular chondrocytes in vitro.

It is thought that articular cartilage gains most of its nutrition in vivo, via diffusion, from synovial fluid. There have been few studies investigating the effect of synovial fluid on chondrocyte metabolism in vitro. In the current study, bovine articular chondrocytes were isolated and cultured in agarose using normal allogenic synovial fluid as culture medium. Dulbecco's minimal essential medium + 20% fetal calf serum and Earle's balanced salt solution were used as control media. Cell viability at the end of the experiment showed that neither synovial fluid nor Earle's balanced salt solution had a significant effect on viability when compared with Dulbecco's minimal essential medium + 20% fetal calf serum during the period assessed. Results indicate that levels of glycosaminoglycan synthesis can be maintained when Dulbecco's minimal essential medium + 20% fetal calf serum is diluted with Earle's balanced salt solution to levels of 80% Earle's balanced salt solution. When Dulbecco's minimal essential medium + 20% fetal calf serum was diluted with synovial fluid, glycosaminoglycan synthesis was stimulated in a dose dependent manner to 80% synovial fluid. Even at 100% synovial fluid, synthesis levels were significantly higher than for Dulbecco's minimal essential medium + 20% fetal calf serum. Tritiated thymidine uptake decreased with increasing concentrations of either Earle's balanced salt solution or synovial fluid. The results suggest that culture in synovial fluid induces a state similar to that seen in vivo, with high levels of glycosaminoglycan synthesis and low levels of cell division.

Animals↗

Conformational analysis of pentapeptide sequences matching a proposed recognition motif for lysosomal degradation.

A selective pathway for the degradation of specific long-lived cytosolic proteins is activated in response to starvation in vivo or to serum withdrawal from cultured cells. It involves recognition of a targeting motif by a member of the hsp70 family. A 5-residue targeting motif has been proposed on the basis of sequence comparisons. We investigate whether there is any structural basis for this motif being the true recognition signal. We examine the conformations of four motif peptides in proteins that are either known to be serum regulated or are from related vertebrate species, and two equivalent peptides in bacterial proteins that closely resemble other regulated proteins. Our studies show that all the motif sequences are located near the ends of surface helices with one or more of the residues buried in the structure, yet it is known that members of the hsp70 family tend to interact with extended peptide chains. Furthermore, recognition by these proteins generally requires a specific ordering of key residues, yet the motif implies a largely order-independent sequence characterized by residue type only. We conclude that the proposed motif is unlikely to be the true targeting signal for lysosomal degradation unless additional factors apply.

Amino Acid Sequence↗

Ocular iontophoretic supplementation of intravenous foscarnet therapy.

PURPOSE: Reactivation of cytomegalovirus retinopathy during intravenous antiviral therapy is usually treated with higher doses of drug. We sought to determine whether ocular iontophoresis increases the intravitreal foscarnet concentration attained by intravenous injection. METHODS: We injected foscarnet (120 mg/kg or 180 mg/kg) intravenously into 24 rabbits and determined the time of maximal concentrations in serum and vitreous humor. We injected the same doses into 24 additional rabbits and administered ocular foscarnet iontophoresis one hour later. Vitreous humor concentrations were assayed at one, four, eight, 24, 60, and 120 hours after iontophoresis and compared with those from injection alone. RESULTS: Maximum serum and vitreous humor concentrations were achieved one hour after each intravenous dose. Maximum vitreous humor concentrations were achieved four hours after 120 mg/kg intravenous doses plus iontophoresis and eight hours after 180-mg/kg intravenous doses plus iontophoresis. Vitreous humor levels were significantly higher in eyes receiving intravenous foscarnet (120 mg/kg, P < .0001; 180 mg/kg, P < .0001) plus ocular Foscarnet iontophoresis than in those receiving intravenous foscarnet alone. Vitreous humor foscarnet levels in eyes receiving 120 mg/kg intravenously did not differ significantly from those in the group receiving 180 mg/kg intravenously (P < .1). The intravenous dose did not significantly affect vitreous humor levels after iontophoresis (P < .1). Vitreous concentrations fell below therapeutic levels (25 microM) in all eyes 60 hours after intravenous foscarnet and ocular foscarnet iontophoresis. CONCLUSIONS: Ocular iontophoresis significantly increased intravitreous foscarnet concentrations above those attained by intravenous injection alone and may be an effective alternative to increasing the intravenous drug dose in patients with reactivated cytomegalovirus retinopathy.

Animals↗

Demographic factors in a population-based survey of hospitalized, work-related, ocular injury.

PURPOSE: To obtain population-based estimates of the incidence of severe work-related ocular trauma and to identify demographic factors related to increased risk of this type of injury. METHODS: A statewide population-based survey of severe work-related ocular injury was performed using hospital discharge data. These data were derived from all inpatient admissions to nonfederal, acute-care hospital facilities in the state of California during 1988. Worker's compensation was used as the principal payor code to establish the work-relatedness of a given ocular injury. Census data for the state of California were used to obtain population denominators. RESULTS: Two hundred sixty-nine (approximately 14.3%) of all admissions for which ocular trauma was the principal diagnosis (1,876) were work related. Annual incidence for severe work-related ocular injury was 1.76 per 100,000 employed persons when ocular trauma was the principal diagnosis and 2.98 per 100,000 employed persons when ocular trauma was a principal or secondary diagnosis. Projected to the working-age United States population (128 million) these annual rates correspond to an estimated 2,165 acute hospitalizations for work-related ocular trauma as the principal diagnosis, and an estimated 3,745 acute hospitalizations for work-related ocular trauma as a principal or secondary diagnosis. Incidence of severe work-related ocular injury was highest among men, Hispanics, and individuals 20 to 24 years of age (5.02, 3.72, and 4.64 per 100,000 employed per year, respectively). CONCLUSIONS: The workplace accounts for a substantial proportion of severe ocular injury. Demographic groups at highest risk for this type of injury are men, Hispanics, and young adults.

Accidents, Occupational↗