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Biomedical subjects

Wen-Ming Hsu

Publications and source records attributed to Wen-Ming Hsu.

90 records · Page 5Linked to original sources

Retinoblastoma in Taiwan: survival rate and prognostic factors.

PURPOSE: The mortality rate of patients with retinoblastoma still varies in developing countries, and data for Asia and Taiwan are relatively scarce. In this retrospective study, we aimed to describe the survival characteristics and prognostic factors of 54 retinoblastoma cases diagnosed at the Taipei Veterans General Hospital between 1982 and 2004. METHODS: From medical records, we retrospectively analyzed the data of 54 consecutive children diagnosed in our hospital between 1982 and 2004 as having retinoblastoma. Data on sex, laterality, age at diagnosis, presenting signs, family history, duration of symptoms, lag time for treatment, spread of tumor, treatment mode, and survival time were collected. RESULTS: Seventy-five percent of the cases were unilateral and 25% of the cases were bilateral. The mean patient age at the time of diagnosis was 26.3 months. The mean duration of symptoms was 2.96 months. After diagnosis, the mean lag time before treatment was 2.59 months. The most common presenting signs were leukocoria (71.4%), red, painful, or tearing eye (18.4%), strabismus (14.3%), and blurred vision (14.3%). Only 3 of 52 cases (5.8%) were familial. The most common sites of extraocular invasion included the central nervous system (seven cases) and the orbit (seven cases). In 13.7% of the cases, parents had refused the treatment suggested by the doctors. None of the patients developed a secondary neoplasm. The 5-year overall survival rate was 80.9% (unilateral, 88.1%; bilateral, 64.3%). The survival rate of patients with an interval between onset and treatment of <5 months was 90.9%, and that for an interval of >5 months was 60.9%. The survival rate of those with a lag time of <2.5 months was 90.0%, and that of those with one of >2.5 months was 31.3%. The survival rate of patients with intraocular and extraocular disease was 96.9% and 39.2%, respectively. Extraocular disease was an independent factor indicating a poor prognosis, determined by multivariate analysis. CONCLUSIONS: The mortality rate of patients with retinoblastoma is higher in Taiwan than in developed countries. The proportion of patients' parents refusing or delaying treatment in Taiwan is high. The factors for a poor prognosis were an interval between onset and treatment of >5 months, a lag time before treatment of >2.5 months, and extraocular disease. The duration of symptoms was not a prognostic factor. The only independent factor indicating a poor prognosis was extraocular disease.

Age Distribution↗

Leber's hereditary optic neuropathy--the spectrum of mitochondrial DNA mutations in Chinese patients.

PURPOSE: To investigate the spectrum of mitochondrial DNA (mtDNA) mutations in Chinese patients with Leber's hereditary optic neuropathy (LHON), optic atrophy of unknown etiology, and optic neuropathy of known etiology. METHODS: Twenty-seven patients from 25 LHON pedigrees, 22 patients with bilateral optic atrophy of unknown etiology, 21 patients with optic neuropathy of known etiology, and 25 normal healthy controls were included in this study. Twelve pairs of primers that covered the 21 reported mtDNA mutations were utilized. Single-strand conformation polymorphism analysis and DNA sequencing were used to detect base substitutions in mtDNA. RESULTS: Twenty-three LHON pedigrees (92%) had the 11778 mtDNA primary mutation. Two pedigrees (8%) had the 14484 mutation. No 3460 mutations were detected in this group. Thirteen other sequence changes were found in these patients, but only the 4216 mutation had been reported previously. Thirteen pedigrees had multi-mutation patterns consisting of one primary mutation together with other sequence changes. No primary mutations were found in patients with optic atrophy of unknown etiology or in patients with optic neuropathy of known etiology. CONCLUSIONS: High frequency of 11778 mtDNA mutation was found in Chinese patients with LHON. No specific multi-mutation pattern such as the European mtDNA haplogroup J was found.

Adolescent↗

Comparisons of risk factors and visual field changes between juvenile-onset and late-onset primary open-angle glaucoma.

PURPOSE: To identify the differences in risk factors and visual field (VF) changes between juvenile primary open-angle glaucoma (JOAG) and late-onset chronic open-angle glaucoma (COAG). METHODS: The demographic and presenting clinical data of 27 JOAG and 30 COAG patients were retrospectively reviewed. Comparisons between the two groups were performed using Mann-Whitney U test, Wilcoxon signed-rank test, and Fisher's exact test. RESULTS: A family history of glaucoma (37%) and a history of steroid usage (14.8%) were identified in JOAG patients only. The JOAG patients had a longer axial length (p < 0.001) and more often a myopic refractive state (p < 0.001) than the COAG patients. Patients with COAG showed a deeper (p = 0.016) and a more extensive (p = 0.008) defect in the superior than in the inferior hemifield, as well as a deeper (p = 0.016) and a more extensive (p = 0.001) defect in the superior than in the inferior arcuate area, while JOAG patients showed symmetric VF defects between the superior and inferior hemifields. Purely diffuse VF depression is more common in JOAG than in COAG patients (p = 0.03). CONCLUSIONS: JOAG patients demonstrated more axial myopic changes than patients with COAG as well as a pattern of superior-inferior symmetric VF defects. Axial myopia may play a critical role in the pathogenesis of JOAG.

Adult↗

Apoptosis of human retina and retinal pigment cells induced by human cytomegalovirus infection.

Human cytomegalovirus (HCMV) retinitis is the most common ocular opportunistic infection in immunocompromised patients and AIDS. It often leads to blindness if left untreated. The question as to how HCMV infection causes retinal pathogenesis and visual destruction in AIDS patients remains unresolved. To answer the question, by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, we detected the significant signals of apoptotic cells at the same sites in the HCMV-infected retina of AIDS patients as compared to AIDS patients without HCMV retinitis. In vitro study also revealed apoptosis induced by HCMV infection in human retinal pigment epithelium cells, mediated by activation of caspase 3 and poly(ADP-ribose) polymerase pathway. These results strongly suggest the fundamental role of HCMV-induced apoptosis in mediating cell death in infected human retina and retinal pigment epithelium cells to make severe visual impairment.

AIDS-Related Opportunistic Infections↗

Management of retained intravitreal lens fragments after phacoemulsification surgery.

PURPOSE: To evaluate the clinical features of eyes with retained intravitreal lens fragments after phacoemulsification surgery and to assess the guidelines of management and the visual outcome after vitrectomy. METHODS: Twenty-five consecutive patients referred to our institute for retained intravitreal lens fragments after phacoemulsification cataract surgery were evaluated retrospectively over a 7-year period. RESULTS: The clinical features of retained lens fragments included deceased visual acuity of 6/60 or worse (68%), uveitis (60%), glaucoma (48%), corneal edema (44%) and retinal detachment in 2 patients (8%). There were 24 patients who underwent pars plana vitrectomy; 1 patient was managed with medical therapy. After vitrectomy, 17 eyes (71%) showed visual improvement, and final visual acuity was 6/12 or better in 13 eyes (54%). The causes of poor final visual outcome of 6/60 or worse included retinal detachment and cystoid macular edema. The time interval between vitrectomy and phacoemulsification was within 4 weeks in 17 patients (71%), ranging from on the same day to 97 days. There was only a trend of better visual outcome in early vitrectomy patients (within 1 week). There was no statistical difference between the initial intraocular lens status and final visual acuity. CONCLUSION: Vitectomy with removal of retained intravitreal lens fragments is beneficial for patients with persistent uveitis and glaucoma after phacoemulsification. In the majority of patients, visual improvement was achieved after vitrectomy. However, poor visual outcome may occur secondary to retinal detachment and cystoid macular edema.

Aged↗

Significant variation of the elevated nitric oxide levels in aqueous humor from patients with different types of glaucoma.

Though several studies have shown that the biochemical function of nitric oxide (NO) in the eye might play an important role in the regulation of intraocular pressure (IOP), local control of ocular blood flow and loss of retinal ganglion cells by apoptosis, it is unclear whether the role of NO is similar in the pathogenesis of different kinds of glaucoma: primary open-angle glaucoma (POAG), chronic closed-angle glaucoma (CCAG) and neovascular glaucoma (NVG). To further explore this issue, we measured the concentrations of NO in aqueous humor and plasma samples from patients with POAG (n = 31), CCAG (n = 76), NVG (n = 8) and cataract (n = 30). All of the NVG patients suffered from severe proliferative diabetic retinopathy, while other patients were free of any other systemic disease. The NO levels in both aqueous humor and plasma samples were assessed by chemiluminescence assay. We found that the NO levels in aqueous humor samples were greatly varied in patients with POAG (36.2 +/- 3.3 microM), CCAG (47.7 +/- 3.4 microM) and NVG (65.8 +/- 5.4 microM), and all of them were significantly higher than in cataract patients (27.0 +/- 2.9 microM p < 0.05). Except NVG patients whose NO levels in plasma samples were highest (24.1 +/- 3.5 microM) among all groups, the plasma NO levels were not significantly different between the other glaucoma patients and the cataract patients. We therefore concluded that significant variation of the elevated NO levels in aqueous humor samples from the patients with different types of glaucoma may reflect their differences in the pathogenesis.

Aged↗

A feasible tool to detect mRNA expression of matrix metalloproteinases and their tissue inhibitors in human Tenon's capsule.

PURPOSE: To determine the mRNA expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human specimens of Tenon's capsule. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) with specific primers for MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 was performed on tissue specimens obtained from patients with cataract, rhegmatogenous retinal detachment, glaucoma, or diabetes mellitus. RESULTS: Glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA transcripts were detected in 26 (76.5%) of 34 specimens, with almost the same amount of expression in each of these samples. Messenger RNA expression of one or more of the MMPs/TIMPs could also be detected in all of these 26 samples, but not in any sample without GAPDH expression. MMP-2, TIMP-1 and TIMP-2 were detected in 25 (96.2%) of the 26 samples with GAPDH expression, while MMP-1 and MMP-9 were detected with a lower percentage (34.6 and 19.2%, respectively). CONCLUSION: The feasibility of RT- PCR with GAPDH as an internal standard to determine mRNA transcripts of the MMPs and TIMPs in the subconjunctival Tenon's capsule was demonstrated.

Conjunctiva↗

Elevated nitric oxide level in aqueous humor of AIDS patients with cytomegalovirus retinitis.

Human cytomegalovirus (HCMV) retinitis is the most common ocular opportunistic infection in AIDS. It often leads to blindness if left untreated. The questions as to how HCMV infection causes retinal immunopathogenesis and visual destruction in AIDS patients have not been completely established. Here we reported that the nitric oxide (NO) levels in aqueous humor samples in 10 AIDS patients with CMV retinitis (104.3 +/- 27.1 microM) were higher than the levels in 7 AIDS patients without CMV retinitis (36.1 +/- 10.4 micro M; p < 0.001). After ganciclovir treatment, the NO level in the vitreous body of 5 patients declined dramatically (53.4 +/- 11.8 micro M). By using immunohistochemistry assay, we found that the aggregates of macrophages infiltrated in the CMV-infected retina of 4 AIDS patients. Moreover, the expression of inducible-form NO synthase was detected in the infected retina of these patients. These results suggest that NO production in the eye may play a fundamental role in the immunopathogenesis of AIDS patients with CMV retinitis.

Acquired Immunodeficiency Syndrome↗

Possible involvement of nitric oxide in the progression of diabetic retinopathy.

Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of diabetes mellitus. The aim of our study was to elucidate the relationship between the stages of diabetic retinopathy (DR) and the NO levels in aqueous humor and plasma. Using the chemiluminescence assay, we measured the concentrations of NO in aqueous humor and plasma samples obtained during intraocular surgery from 45 diabetic patients and 19 nondiabetic cataract patients. The patients with diabetes were classified into 4 groups: proliferative DR (PDR) with active neovascularization (active PDR; 9 cases), PDR with quiescent neovascularization (regressed PDR; 6 cases), background DR (BDR; 16 cases) and no DR (14 cases). We found that the aqueous NO levels (mean +/- SE) of the active PDR group (83.2 +/- 13.9 microM) were significantly higher than those of the BDR group (45.8 +/- 6.0 microM, p = 0.049) and the diabetics without DR (33.3 +/- 5.2 microM, p = 0.011), and, although not statistically significantly, they were also higher than those of the regressed PDR group (52.1 +/- 10.3 microM, p = 0.224). However, no significant differences were observed between any of the diabetic subgroups in the plasma NO levels (p = 0.345). We therefore concluded that NO present in the ocular tissues may play important roles in the progression of DR.

Aged↗

Transplantation of the autologous submandibular gland to the lacrimal basin in rats.

PURPOSE: In this study, we designed an animal experiment in which we transferred a part of the autologous submandibular gland without performing a microvascular anastomosis. We studied histological changes and functional effects in the transfer glands. METHOD: Thirty male adult Sprague-Dawley rats were divided into three groups. In each animal of the three groups, the right eye was the control eye and the left eye the experimental eye. Surgical removal of the extraorbital lacrimal gland from the control eyes was performed to create a condition simulating keratoconjunctivitis sicca. In the experimental eyes of group 1, in addition to the removal of the extraorbital lacrimal gland, a part of the autologous submandibular gland was transferred to the orbit and fixed to the intraorbital lacrimal gland. In the experimental eyes of group 2, in addition to the removal of the extraorbital lacrimal gland, an aseptic silicon rubber was transferred to the orbit and fixed to the intraorbital lacrimal gland. In the experimental eyes of group 3, there was no removal of the extraorbital lacrimal gland but instead a sham operation was performed. The histological changes and innervation pattern in the transferred submandibular gland of group 1 were observed. Tear secretion of each group was measured to study the functional effect. RESULTS: Three months after the transplantation, the transferred submandibular glands were similar to the unoperated submandibular glands both in histology and innervation pattern. In group 1, the tear secretion in the experimental eyes was significantly greater than that of the control eyes at 2 and 3 months following transfer. In group 2, no significant difference was noted between the experimental eyes and control eyes. In group 3, the difference in tear secretion between the experimental eyes and control eyes was significant. CONCLUSION: The result of this study revealed that although the procedure did not involve vascular anastomosis, the transfer gland showed a normal histological appearance and good reinnervation, even 3 months after the transfer. These transferred submandibular glands continued to secrete tears. This secretion continued to increase up until the end of the experimental period.

Anastomosis, Surgical↗

The HIV RNA Levels of Plasma and Ocular Fluids in AIDS Patients with Ophthalmic Infections.

The aim of the present study was to evaluate the impact of highly active antiretroviral therapy (HAART) on HIV viral load of plasma and intraocular fluids in AIDS patients with ophthalmic opportunistic infections. We further compared the treatment effect of HAART on these patients. From June 1997 to July 2003, we examined and followed up the ophthalmic conditions of 49 patients receiving HAART with ophthalmic diseases during this period. The method of reverse-transcriptase polymerase chain reaction was used to detect and monitor HIV load in plasma and/or aqueous humor of AIDS patients. Before HAART, the HIV levels in the plasma and aqueous humor in 8 AIDS patients with ophthalmic opportunistic infections were significantly higher than those in 6 patients with HIV-related retinopathy (p < 0.05). Compared to the eye findings and clinical improvement, HIV loads of aqueous humor in 10 of 14 AIDS patients (6 with HIV-related retinopathy, 5 with cytomegalovirus retinitis, 2 with toxoplasmic retinitis and 1 with cryptococcal chorioretinitis) declined to undetectable levels (< 400 copies/ml) after 4-8 months of HAART. HIV virus levels in the plasma of AIDS patients were significantly decreased, and the CD4 counts of these patients were significantly increased (Wilcoxon test) after initiation of HAART.

AIDS-Related Opportunistic Infections↗

Detection of HIV RNA levels in intraocular and cerebrospinal fluids in patients with AIDS-related cryptococcosis.

The objective of the present study was to evaluate human immunodeficiency virus (HIV) levels in the aqueous humor and vitreous fluid in patients with and those without ocular involvement due to AIDS-related cryptococcosis. We also assessed whether cryptococcosis infection in the central nervous system (CNS) was associated with elevated HIV levels in the cerebrospinal fluid (CSF). From 1993 to 2003, we obtained 16 CSF samples from 9 AIDS patients with cryptococcal meningitis and 7 AIDS patients without CNS opportunistic infection. Samples of intraocular fluids were obtained from all 9 patients with cryptococcal meningitis. Five cases presented with ocular involvement in patients with meningitis. By using the method of reverse transcriptase-polymerase chain reaction, we detected higher HIV loads in aqueous humor (27,244+/-4,123 copies/ml) and vitreous fluid (84,930+/-5,071 copies/ml) in patients with concomitant CNS and ocular involvement due to AIDS-related cryptococcosis (p<0.05). HIV levels in the vitreous fluid were correlated with levels in CSF (r=0.77). Mean HIV level in the CSF (209,761+/-18,787 copies/ml) was significantly elevated in AIDS patients with cryptococcoal meningitis (p<0.05). To our knowledge, this is the first report to study the level of HIV loads in the CSF and intraocular fluid simultaneously in AIDS patients with cryptococcosis. Our results revealed the intrathecal and intraocular HIV replication in patients with cryptococcosis.

AIDS-Related Opportunistic Infections↗

Comparison of the proliferation and differentiation ability between adult rat retinal stem cells and cerebral cortex-derived neural stem cells.

Recent studies have demonstrated that retinal stem cells (RSCs) and stem cells of the central nervous system both exhibited the abilities of self-renewal, proliferation and differentiation into multilineage. In the present study, we compared the proliferation and differentiation abilities between RSCs and cerebral corticex-derived neural stem cells (CNSCs) of adult rats. Stem cells isolated from pigmented ciliary margins of eyes and cerebral cortical tissues of adult rats were cultured in 96-well plates that contained serum-free medium with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In contrast to RSCs, which stopped proliferating after the 8th week, the total cell count of neurospheres in CNSCs increased twofold at the 5th week and more than fourfold at the 10th week after in vitro culture. In contrast, RSCs stopped proliferating after 8 weeks of culture. After adding 2% fetal calf serum and withdrawing EGF and bFGF from the culture medium, the percentages of nestin-positive cells(20.6 +/- 2.7%), microtubule-associated-protein-2-positive neurons (33.2 +/- 3.9%) and glial-fibrillary-acidic-protein-positive glial cells(51.3 +/- 6.2%) in the differentiated CNSCs were significantly higher than those in the differentiated RSCs (10.2 +/- 1.9, 22.3 +/- 1.3 and 44.6 +/- 5.1%, respectively; p < 0.05). We also found that the combination of transforming growth factor beta type III with retinoic acid played an important role in the induction of CNSCs to differentiate into opsin-positive cells. Our data demonstrated that CNSCs displayed a higher ability of proliferation and retinal lineage. This report also offers an alternative protocol of cell reproduction for producing retinal cells.

Animals↗

Retinal arterial macroaneurysms: risk factors of poor visual outcome.

PURPOSE: To evaluate the long-term natural course and to identify the risk factors of a poor visual outcome in patients with retinal arterial macroaneurysms (MA). METHODS: In this observational case series, we retrospectively evaluated the consecutive patients with MA at our institution over a 17-year period. The visual outcomes of the different types of MA (presented as predominantly hemorrhagic or exudative) were compared. RESULTS: A total of 31 patients with 46 confirmed MA were identified. The ocular manifestations of MA included retinal hemorrhage (96.7%), retinal exudate (61.3%), macular involvement (77.4%) and vitreous hemorrhage (12.9%). Among the 10 cases of hemorrhagic-type MA, visual acuity improved by 2 or more lines in 9 (90%) and decreased in 1 patient (10%). In the 15 cases of exudative-type MA, 4 improved (26.7%), 8 remained stationary (53.3%) and 3 had decreased visual acuity (20.0%). The average vision change in the minimum angle of resolution improved by 0.59 log units in hemorrhagic MA and decreased by 0.07 log units in exudative MA (p < 0.01). With respect to change of vision, the eyes with hemorrhagic-type MA showed greater improvement than those with the exudative type, but the final visual outcome was not different in the 2 groups. Foveal exudate was a statistically significant risk factor for final vision equal to or worse than 6/30 (odds ratio = 6.93, p < 0.05). CONCLUSIONS: Different types of MA may have different clinical presentations. In the majority of MA, there is gradual and spontaneous involution. However, poor visual outcome may occur secondary to foveal exudates and subfoveal hemorrhage.

Adult↗

Refractory severe ocular hypertension after intravitreal triamcinolone acetonide injection.

PURPOSE: To report a serious complication following intravitreal triamcinolone acetonide injection. METHODS: Observational case report. RESULTS: In 2 patients, secondary intractable severe ocular hypertension occurred 2 months after a single 4-mg intravitreal injection of triamcinolone acetonide for macular edema. Both patients required trabeculectomy intervention to control intraocular pressure (IOP). CONCLUSION: We highlight the occurrence of intractable high IOP elevation as a serious complication 2 months after intravitreal triamcinolone acetonide. Cautious monitoring of IOP for several months after this therapy is recommended. The risks of this potentially devastating complication need to be weighed against the benefits of intravitreal triamcinolone in the individual patient.

Antihypertensive Agents↗

Corneal burn: a rare complication of radiofrequency diathermy capsulotomy.

We present 2 patients with accidental corneal burns inflicted during clear cornea cataract surgery using radiofrequency diathermy for anterior capsulotomy. During the capsulotomy procedure, the anterior capsule was not opened and only a small air bubble appeared when the energy was turned on. Meanwhile the area of the corneal tunnel that contacted the shoulder of the diathermy tip became opaque and shrank with a small defect in the anterior corneal lip. Postoperatively, focal corneal shrinkage with iris incarceration into the defect of the corneal tunnel and resultant peaking pupil were noted in the 2 patients. The corneal burns resulted in temporary irregular astigmatism with mild visual acuity impairment. To our knowledge, this is the first report of a corneal burn as a complication of radiofrequency diathermy for anterior capsulotomy in clear cornea cataract surgery.

Aged↗

Ovarian cyst with torsion presenting as a wandering mass in a newborn.

A case of ovarian serous cystadenoma with torsion presenting as a wandering abdominal mass is reported. A full-term baby girl was noted to have a left pelvic cyst by prenatal ultrasound at the 34th gestational week. After delivery, a series of work-ups, including ultrasonography and CT scan, revealed a cyst with fluid-debris level in the right pelvis. An ovarian cyst with torsion was suspected and surgical intervention was done when she was 7 days old. The operative findings confirmed a left ovarian cystic mass with torsion. A left salpingo-oophorectomy was performed smoothly. Pathology revealed the typical microscopic findings of ovarian serous cystadenoma, a benign epithelial tumor of ovary. We suggest that a wandering ovarian cystic mass in female fetus and newborn should be considered an indication for surgical intervention due to its high risk of torsion.

Cystadenoma, Serous↗