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Biomedical subjects

D P Han

Publications and source records attributed to D P Han.

At least 19 recordsLinked to original sources

Development of a safe and rapid neutralization assay using murine leukemia virus pseudotyped with HIV type 1 envelope glycoprotein lacking the cytoplasmic domain.

Neutralizing antibody (NAb) is a critical component of an immune system that can potentially provide sterilizing protection against human immunodeficiency virus type 1 (HIV-1). Therefore, an in vitro assay that can rapidly, safely, and accurately evaluate the NAb response vaccine candidates elicit, especially against a large number of HIV-1 variants, would be highly valuable. It has been demonstrated that HIV-1 envelope glycoprotein lacking the cytoplasmic domain can pseudotype murine leukemia virus encoding the beta-galactosidase gene and that this pseudovirus can specifically infect CD4(+) cells (Schnierle BS, Stitz J, Bosch V, et al.: Proc Natl Acad Sci USA 1997;94:8640-8645). Because the pseudovirus is not biohazardous and because the infection can be quantitatively determined within 2 days, we examined the feasibility of using the pseudovirus for high-throughput neutralization assays for HIV-1. We have generated viruses pseudotyped with gp140 of six different HIV-1 isolates (LAI, RF, Bal, AD8, 89.6, and DH12). All six pseudoviruses were infectious and exhibited expected coreceptor usage phenotype in HOS-CD4 cells expressing either CCR5 or CXCR4. More importantly, the neutralization sensitivity profile of these pseudoviruses was virtually identical to that observed from more conventional neutralization assays using either HIV-1 or SHIV. All pseudoviruses could be neutralized by broadly reactive human monoclonal antibody IgG1 b12. Our results indicate that the pseudoviruses are ideal for high-throughput evaluation of immune sera for their capacity to broadly neutralize a large number of HIV-1 isolates.

Base Sequence↗

Vitrectomy for large vitreous opacity in retinitis pigmentosa.

PURPOSE: To describe a patient with bilateral retinitis pigmentosa and visually disabling vitreous opacities, who benefited from vitrectomy in both eyes. METHODS: A 37-year-old man with retinitis pigmentosa and severely constricted visual fields developed a large, dense, vitreous floater and visual obscuration in the right eye. Subsequently, diffuse vitreous opacification and visual obscuration developed in the left eye. RESULTS: Bilateral pars plana vitrectomy relieved the patient's visual obscurations. Electron micrographs of the excised vitreous opacity from the left eye showed collagen fibrils and cellular debris. CONCLUSION: Visually significant vitreous opacities may develop as a complication of retinitis pigmentosa. The visual impact of such opacities may be magnified by its superimposition on limited visual fields. Vitrectomy may be of benefit in such cases.

Adult↗

The new genotypic human calicivirus isolated in Seoul.

A new type of human calicivirus (HuCV) showing the classic cup-shaped surface morphology was identified in the stool sample from a child with symptoms of acute gastroenteritis in Seoul, Korea (SK virus). Genomic RNA was extracted directly from the stool sample, and the nucleotide sequence of 3.2 kb of the 3' end of SK virus was determined from cDNA. This region spanned sequences from the RNA-dependent RNA polymerase (RDRP) region in the open reading frame 1 (ORF1) to the 3' poly A tail. The non-structural and capsid protein coding sequences were fused in a single ORF as observed in Manchester type (Genogroup III). However, ORF2 of Manchester virus was missing in SK virus. In RDRP region, SK virus showed amino acid and nucleotide identities of 74-75% and 68-69% respectively, with those of Manchester virus, while showed 34-46% and 55-60% identities respectively with those of other human caliciviruses. However, capsid protein of SK virus showed a partial (29-46%) amino acid identity with those of other caliciviruses including Manchester type. The closest resemblance in amino acid (97-99%) and nucleotide sequence (85-86%) identities were found in RDRP region with Vanderbijlpark and Pretoria isolates recently found in South Africa. These results suggest that SK virus together with Vanderbijlpark and Pretoria isolates belong to a new type different from Manchester virus.

Amino Acid Sequence↗

A study of surgical approaches to retinal vascular occlusions.

OBJECTIVE: To develop a surgical approach to retinal vascular occlusive diseases. METHODS: Surgical manipulations were performed on the retinal vasculature to explore the feasibility of retinal vascular surgery. In a human cadaver eye model (25 procedures, 21 eyes), we performed (1) cannulations of retinal blood vessels with a flexible stylet and (2) arteriovenous sheathotomies. Histological findings were correlated with surgical outcomes. In an in vivo model (6 eyes, 5 animals), we examined the technical feasibility and anatomical outcome of surgical penetration of retinal blood vessels. RESULTS: Cannulations of branch retinal arterioles were successful in 7 of 9 procedures, cannulations of branch retinal venules were successful in 1 of 3 procedures, cannulations of central retinal arteries were successful in 0 of 2 procedures, and cannulations of central retinal veins were successful in 2 of 4 procedures. Arteriovenous sheathotomies were successful in 4 of 7 procedures. In the in vivo model, surgical penetration of retinal blood vessels was accomplished in 5 of 6 eyes. Immediately postoperatively, thrombus formation with obstruction of the retinal vasculature was observed. At 2 weeks postoperatively, the retinal vasculature was completely patent. CONCLUSIONS: Multiple surgical techniques aimed at assisting recanalization of occluded retinal vasculature have been evaluated. Retinal vascular surgery has become more feasible and deserves further investigation.

Aged↗

The use of topical aqueous suppressants in the prevention of postoperative intraocular pressure elevation after pars plana vitrectomy with long-acting gas tamponade.

OBJECTIVE: To determine whether topical aqueous suppressant therapy applied after pars plana vitrectomy with gas tamponade prevents postoperative intraocular pressure (IOP) elevation. DESIGN: Prospective, nonrandomized comparative study. PARTICIPANTS: Forty-one patients who met inclusion criteria and underwent pars plana vitrectomy with gas tamponade (SF6 18%-20% or C3F8 12%-16%) over a 1-year period. INTERVENTION: Treatment eyes received topical aqueous suppressants at the end of surgery. MAIN OUTCOME MEASURES: Postoperative IOP at 4 to 6 hours, 1 day, and 1 week. RESULTS: Twenty-one control and 20 treatment eyes met the inclusion criteria. The IOP (in mmHg) measured at 4 to 6 hours (23.05 [control, 14.73 [treatment]) and 1 day (23.24 [control], 17.28 [treatment]) postoperatively showed a statistically significant difference between the groups (P = 0.0038) at 4 to 6 hours and a trend toward significance (P = 0.057) at 1 day. Eleven control and three treatment eyes had an IOP spike above 25 mmHg at 4 to 6 hours or 1 day postoperatively (P = 0.02), and six control eyes and one treatment eye had postoperative IOP greater than 30 mmHg. A pressure rise greater than 40 mmHg was seen in two control eyes and no treatment eyes. CONCLUSIONS: Use of topical aqueous suppressants after pars plana vitrectomy with long-acting gas tamponade is effective in preventing significant postoperative IOP elevation in most cases.

Administration, Topical↗

Vitrectomy update for macular traction in ocular toxocariasis.

PURPOSE: To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis. METHODS: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed. RESULTS: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism. CONCLUSION: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

Adolescent↗

Complications of pneumatic retinopexy.

Pneumatic retinopexy is a retinal reattachment procedure involving transconjunctival injection of gas into the vitreous cavity, combined with cryotherapy or laser retinopexy and followed by postoperative positioning. Although generally a safe procedure, it may be associated with certain adverse outcomes. These most commonly include misplaced gas injection, subretinal gas, vitreous hemorrhage, new retinal breaks, failure to reattach the retina, proliferative vitreoretinopathy, and delayed reabsorption of subretinal fluid. Less common problems include endophthalmitis, macular folds, angle-closure glaucoma, and macular hole. In most cases, complications are successfully managed, and a favorable outcome is achieved.

Cryosurgery↗

Ocular findings in aplastic anemia.

OBJECTIVE: To analyze the ocular findings in aplastic anemia. DESIGN: Eighteen patients with aplastic anemia were examined. RESULTS: Ocular findings included cotton wool spots (38%), nerve fiber layer or preretinal hemorrhages (67%), vitreous hemorrhages (13%), a picture resembling central retinal vein occlusion (13%) and optic disk edema (6%). Preretinal hemorrhages were the presenting sign of aplastic anemia in 2 patients (13%). CONCLUSIONS: A blood profile is needed in patients with unexplained retinal hemorrhages. Patients with aplastic anemia need to avoid ocular massage and Valsalva maneuvers to decrease ocular morbidity.

Adolescent↗

Relentless placoid chorioretinitis: A new entity or an unusual variant of serpiginous chorioretinitis?

OBJECTIVE: To characterize an unusual clinical entity resembling acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis but with an atypical clinical course. PATIENTS: We describe 6 patients, aged 17 through 51 years, exhibiting this unusual entity who were seen at 6 different centers from 1984 to 1997. RESULTS: The acute retinal lesions in this series were similar to those of APMPPE or serpiginous choroiditis, both clinically and on fluorescein and indocyanine green angiography. However, the clinical course, number of lesions, and location of these lesions were atypical. These patients had evidence of numerous posterior and peripheral retinal lesions predating or occurring simultaneously with macular involvement. Older, healing pigmented lesions were often accompanied by the appearance of new active white placoid lesions. Additionally, these cases all demonstrated prolonged periods of activity resulting in the appearance of more than 50 and sometimes hundreds of lesions scattered throughout the fundus. Growth of subacute lesions and the appearance of new lesions continued for 5 to 24 months after initial examination, and relapses were common. CONCLUSIONS: This entity has clinical features similar to APMPPE and serpiginous choroiditis but has a prolonged progressive clinical course and widespread distribution of lesions. It may represent a variant of serpiginous choroiditis or may be a new entity. We call it relentless placoid chorioretinitis. Arch Ophthalmol. 2000;118:931-938

Acute Disease↗

11-cis retinol dehydrogenase mutations as a major cause of the congenital night-blindness disorder known as fundus albipunctatus.

PURPOSE: Patients with fundus albipunctatus uniformly experience difficulty with vision at night. Their retinas are spotted with characteristic light yellow flecks of unknown composition that typically spare the macula. A defect in the transport or utilization of visual cycle retinoids is thought to underlie this recessive disorder with variable clinical expression. To elucidate the molecular defect we considered the genes for interphotoreceptor retinoid-binding protein (RBP3) and 11-cis retinol dehydrogenase (RDH5) as candidates for this disease. METHODS: We examined two unrelated families with fundus albipunctatus. The diagnosis was determined clinically and RBP3 and RDH5 were analyzed by molecular screening methods and direct genomic sequencing. RESULTS: Each family had two affected members with typical fundus albipunctatus. The affected members were siblings born to unaffected parents who were seventh cousins in the first family and unrelated in the second family. The probands from both families were clinically similar except for the fundus dots that were more extensive in the second family to the point of involving the parafoveal region. In the initial phase of genetic screening RBP3 defects were ruled-out as the cause of the disease in both families. In contrast, RDH5 mutations were found in the affected siblings in both families. The proband in one had a homozygotic Gly238Trp missense mutation (GGG -> TGG) involving exon 4 and in the other carried compound heterozygotic changes Arg280His (CGC -> CAC) and Ala294Pro (GCC -> CCC) in exon 5. The disease phenotype was only manifested in family members with two abnormal RDH5 alleles consistent with autosomal recessive inheritance in both pedigrees. CONCLUSIONS: These findings strongly implicate defects of RDH5 as the cause of fundus albipunctatus and point to a heterogeneity of RDH5 mutations in this form of congenital stationary night blindness with variable expressivity.

Adult↗

Endophthalmitis from Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for bladder carcinoma.

PURPOSE: To present clinical and histologic findings of intraocular infection with Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for treatment of bladder carcinoma. METHODS: A 77-year-old man was initially seen with visual acuity of 20/200, focal retinitis, vasculitis, and progressive vitreous opacity in the right eye and visual acuity of light perception, intraocular inflammation, and a dense cataract in the left eye 14 months after intravesicular injection of live bacille Calmette-Guérin organisms. RESULTS: Vitreous cultures in the right eye demonstrated growth of bacille Calmette-Guérin organisms. Bilateral loss of light perception occurred despite systemic antimy-cobacterial therapy. Histopathologic examination demonstrated nongranulomatous inflammation and acid-fast bacilli in both eyes. CONCLUSION: Delayed endogenous endophthalmitis may develop after intravesicular bacille Calmette-Guérin injection that may not respond to systemic agents. Intravitreal therapy may be indicated.

Aged↗

Progression of diabetic retinopathy after endophthalmitis.

OBJECTIVE: To determine the effect of endophthalmitis on diabetic retinopathy. DESIGN: Noncomparative case series. METHODS: The records of all consecutive patients with endophthalmitis treated between 1992 and 1997 at the Medical College of Wisconsin were retrospectively reviewed. Those patients with diabetes mellitus were analyzed. PARTICIPANTS: From 77 reviewed records, 11 patients (12 eyes; 14%) were identified as diabetics with endophthalmitis and were studied. MAIN OUTCOME MEASURES: Stage of diabetic retinopathy, time to retinopathy progression, and visual acuity. RESULTS: Mean patient age was 68 years, and mean duration of diabetes was 11.7 years. Mean patient follow-up was 17 months. Of the six cases without evidence of retinopathy before the endophthalmitis, none went on to develop retinopathy. Of six eyes with pre-existing nonproliferative retinopathy, four showed evidence of progression within 6 months of the infection. Three developed severe proliferative disease and macular edema, and one developed severe nonproliferative disease. More patients without pre-existing retinopathy achieved a final visual acuity of 20/40 or greater. CONCLUSIONS: Patients with pre-existing diabetic retinopathy may be at increased risk for rapid retinopathy progression and a poorer visual outcome after endophthalmitis. These results support the concept that inflammation may exacerbate diabetic retinopathy.

Aged↗

Microbiologic yields and complication rates of vitreous needle aspiration versus mechanized vitreous biopsy in the Endophthalmitis Vitrectomy Study.

PURPOSE: To compare the microbiologic yields and complication rates associated with vitreous needle tap and vitreous biopsy in the Endophthalmitis Vitrectomy Study (EVS). METHODS: Of 420 EVS patients with postoperative endophthalmitis, 201 received immediate vitreous tap or biopsy (without pars plana vitrectomy) by random assignment and 193 completed 9-12 months of follow-up. Vitreous specimens were obtained by biopsy with a 20-gauge vitrectomy cutting instrument or by needle tap with a 22-27-gauge needle. If resistance to aspiration by needle tap was noted, a vitreous biopsy was performed. RESULTS: Of 201 patients undergoing tap or biopsy, 70 (35%) had needle tap, 127 (63%) had mechanized biopsy, and 4 (2%) had initial needle tap that was aborted to mechanized biopsy ("abort" eyes). Intraoperative hyphema occurred in 2 tap eyes (3%), 3 biopsy eyes (2%), and 0 (0%) abort eyes. Postoperative retinal detachment developed in 8 (11%) tap eyes, 10 (8%) biopsy eyes, and 0 (0%) abort eyes (not significant). Respective rates of culture and gram stain positivity were 69% and 42% in tap eyes and 66% and 41% in biopsy eyes (not significant). The rate of severe visual loss (final acuity <5/200) was significantly higher in tap eyes (16 eyes, 24%) compared with biopsy eyes (13 eyes, 11%) and abort eyes (0 eyes, 0%; P = 0.043). The difference was largely explained by the greater proportion of virulent organisms in the tap eyes compared with biopsy eyes. When visual acuity outcome was defined by other thresholds (20/40 and 20/100), the difference was not significant. CONCLUSIONS: This study showed no significant differences between mechanized vitreous biopsy and needle tap with respect to microbiologic yield, operative complications, short-term (9-12 months) retinal detachment risk, or visual outcome. Choice of vitreous sampling procedure must depend on the clinical judgment of the surgeon.

Biopsy, Needle↗

Preoperative use of tissue plasminogen activator for large submacular hemorrhage.

BACKGROUND AND OBJECTIVE: Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacular hemorrhage. It is usually used intraoperatively, but may not provide enough time for effective fibrinolysis, especially for a large hemorrhage. The present study was conducted to evaluate the efficiency and safety of preoperative use of TPA for large submacular hemorrhages. METHODS: Five eyes with large submacular hemorrhage secondary to age-related macular degeneration underwent subretinal injection of TPA in the office 24 hours before surgery. All hemorrhages were less than seven days old and at least 3 mm thick. RESULTS: Preoperative visual acuity ranged from counting fingers to hand motion (HM). Patient follow-up ranged from 3 months to 24 months (mean, 11 months). Final visual acuity ranged from 20/30 to HM. Four of the five eyes (80%) showed improved visual acuity after surgery and 3/5 (60%) attained visual acuity of 20/200 or better. CONCLUSION: Preoperative use of TPA for drainage of large submacular hemorrhage appears to be safe and may result in efficient clot removal. The true efficacy of TPA in the treatment of submacular hemorrhage can only be proven by a prospective randomized trial.

Aged↗

Long-term follow-up of iatrogenic phototoxicity.

OBJECTIVE: To evaluate the outcomes of a group of patients who suffered iatrogenic phototoxic injury. METHODS: The medical records of 24 patients (24 eyes) with iatrogenic phototoxicity from 3 medical centers were reviewed. We report the findings from long-term follow-up of these patients with particular attention to visual outcome, type and duration of procedure, and location of the phototoxic lesion. RESULTS: Phototoxic injury occurred after anterior segment surgery in 20 eyes and after vitrectomy in 4 eyes. The mean duration of surgery was 109 minutes; there was no statistically significant difference in duration between the anterior segment procedures and the vitrectomies. Mean final visual acuity was 20/40 for all cases (range, 20/15 to counting fingers) and 20/25 for all anterior segment cases. In vitrectomized eyes, the mean final visual acuity was 20/900. Phototoxic lesions tended to spare the fovea after anterior segment surgery and involve the foveal center after vitrectomy. CONCLUSIONS: In general, patients who suffer phototoxicity do well, and the prognosis is good for extrafoveal lesions. Foveal injury, which often occurs with vitrectomy, usually leads to a worse visual outcome. The development of choroidal neovascularization may have an effect on the ultimate visual outcome as well.

Aged↗

Visual outcomes following lensectomy and vitrectomy for combined anterior and posterior persistent hyperplastic primary vitreous.

OBJECTIVE: To determine the visual outcome after surgery for persistent hyperplastic primary vitreous using modern vitreoretinal techniques. DESIGN: Retrospective medical record review during a 5-year period (June 1992 to June 1997). Information recorded for each patient included age, medical history, sex, results of preoperative ocular examination, age at diagnosis, procedure performed, intraoperative and postoperative complications, location and number of sclerotomy sites, type of aphakic rehabilitation, amblyopic therapy given, final visual acuity, and length of follow-up. RESULTS: Fourteen patients who underwent surgical management of combined anterior and posterior persistent hyperplastic primary vitreous were identified. Eleven patients underwent aphakic rehabilitation and aggressive amblyopic therapy consisting of occlusive therapy for several waking hours each day. One additional older patient received aphakic rehabilitation only. Ten eyes (71%) achieved a visual acuity of 20/300 or better, and 8 (57%) obtained a final visual acuity of 20/100 or better. Average length of follow-up was 22 months (range, 4-57 months). Nine patients were fitted with an aphakic soft contact lens, 2 older patients had a posterior chamber intraocular lens placed at the time of vitrectomy, and 1 patient wore aphakic spectacles. CONCLUSIONS: With modern vitreoretinal techniques, aphakic rehabilitation, and aggressive amblyopic therapy, useful vision can be obtained in the majority of patients with combined anterior and posterior persistent hyperplastic primary vitreous.

Amblyopia↗