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Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 55 records · Page 3Linked to original sources
PubMed2002

Pathobiology of epiretinal and subretinal membranes: possible roles for the matricellular proteins thrombospondin 1 and osteonectin (SPARC).

Epiretinal and subretinal membranes are fibrocellular proliferations which form on the surfaces of the neuroretina as a sequel to a variety of ocular diseases. When these proliferations complicate rhegmatogenous retinal detachment (a condition known as proliferative vitreoretinopathy or PVR), the membranes often contain numerous retinal pigment epithelial (RPE) cells and a variety of extracellular proteins. The extracellular proteins include adhesive proteins like collagen, laminin and fibronectin. In addition, several matricellular proteins with potential counter-adhesive functions are present in the membranes. Two such matricellular proteins, thrombospondin 1 and osteonectin (or SPARC: Secreted Protein Acidic and Rich in Cysteine), tend to be co-distributed with the RPE cells in PVR membranes. By virtue of their counter-adhesive properties, thrombospondin 1 and SPARC may reduce RPE cell-matrix adhesion and so permit key RPE cellular activities (for example, migration or shape change) in periretinal membrane development. Furthermore, within a 'cocktail' containing other proteins such as the metalloproteinases and growth factors like the scatter factor/hepatocyte growth factor family, matricellular proteins may play a role in the RPE cell dissociation from Bruch's membrane, which characterises early PVR.

Epiretinal Membrane↗
PubMed2002

Vitreous penetration of levofloxacin in the uninflamed phakic human eye.

AIMS: To assess the vitreous penetration of oral levofloxacin (a new fluoroquinolone antibiotic with improved Gram positive activity) in uninflamed phakic eyes. METHODS: 15 patients for macula hole surgery were recruited to the study. 10 received a single 500 mg dose of levofloxacin by mouth preoperatively. Five acted as controls. Serum and undiluted vitreous samples were obtained at surgery and analysed by HPLC. RESULTS: Levofloxacin was detectable 2.5 hours after administration in the vitreous. A peak concentration of 1.6 microg/ml (or mg/l) was measured between 2.5 and 4 hours post-dose. CONCLUSION: Oral levofloxacin reaches the vitreous rapidly in the uninflamed phakic eye. Levels did not reach MIC(90) for the commonest infecting organisms. Nevertheless, levofloxacin would be expected to be active against a higher proportion of infecting organisms than either ciprofloxacin or ofloxacin.

Administration, Oral↗
PubMed2002

Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice.

Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ transplantation, is increasingly being used to treat autoimmune diseases including systemic lupus erythematosus (SLE). Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus nephritis. We evaluated the effect of MMF on the severity of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The mice were killed after 12 weeks of treatment. Treatment with MMF significantly decreased the amount of proteinuria, prolonged survival and reduced the histological severity of glomerulonephritis. Urinary nitrite/nitrate excretion in the MMF-treated mice was significantly reduced during the first 8 weeks of treatment. However, by the end of the 12 weeks' treatment period, there was no significant difference between vehicle and MMF-treated mice in terms of urinary nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS protein and induction of iNOS mRNA. We conclude that MMF is effective in attenuating the severity of nephritis in MRL/lpr mice. The beneficial effects of MMF on lupus nephritis during the early phase of the disease might be partly attributed to the inhibition of NO production. The inhibitory effect of MMF on NO production diminishes as the disease progresses. MMF probably has additional, as yet undefined mode of actions to fully account for its beneficial effects on lupus nephritis.

Animals↗
PubMed2001

Five-color-based high-information-content fingerprinting of bacterial artificial chromosome clones using type IIS restriction endonucleases.

We have developed a high-information-content fingerprinting (HICF) system for bacterial artificial chromosome (BAC) clones using a Type IIS restriction endonuclease, HgaI, paired with a Type II restriction endonuclease, RsaI. In the method described, unknown five-base overhangs generated with HgaI are partially or fully sequenced by modified fluorescent dideoxy terminators. Using an in-lane size standard labeled with a fifth dye, fragments are characterized by both the size and the sequence of its terminal one to five bases. The enhanced information content associated with this approach significantly increases the accuracy and efficiency of detecting shared fragments among BAC clones. We have compared data obtained from this method to predicted HICF patterns of 10 fully sequenced BACs. We have further applied HICF to 555 BAC clones to assemble contigs spanning 16p11.2 to 16p13.1 of human chromosome 16.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression.

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune manifestations. Some patients with ALPS have relatives with these same apoptotic defects, however, who are clinically well. This study showed that the circulating levels of interleukin 10 (IL-10) were significantly higher (P <.001) in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 messenger RNA (mRNA; P <.001 and P <.01, respectively). By fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population, expansion of which is virtually pathognomonic for ALPS. Immunohistochemical staining showed intense IL-10 protein signals in lymph node regions known to contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in patients with inherited apoptotic defects is strongly associated with the overt manifestations of ALPS.

Apoptosis↗
PubMed2001

Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma.

PURPOSE: To determine the acute toxicity, outcome, and sphincter preservation rates in patients with clinically resectable uT3 adenocarcinoma of the rectum treated with preoperative combined modality therapy. METHODS AND MATERIALS: A total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus 2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5 followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU and LV. RESULTS: Individual Grade 3+ toxicities during preoperative therapy included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR rate of 22%. Of the 35 patients who were judged clinically by their operating surgeon to require an abdominoperineal resection (APR) and were therefore treated with the goal of sphincter preservation, 89% were able to undergo sphincter-preserving surgery. Of the 21 patients eligible for analysis, 81% had good to excellent sphincter function. The 3-year actuarial patterns of failure were 2% local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%. CONCLUSIONS: Our data confirm our preliminary reports of encouraging rates of acute toxicity, local control, survival, sphincter preservation and function with preoperative combined modality therapy. It is an alternative approach for the treatment of uT3 clinically resectable rectal cancer.

Adenocarcinoma↗
PubMed2001

Temazepam dangers.

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Adjuvants, Anesthesia↗
PubMed2001

Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch.

Adenine-DNA glycosylase MutY of Escherichia coli catalyzes the cleavage of adenine when mismatched with 7,8-dihydro-8-oxoguanine (GO), an oxidatively damaged base. The biological outcome is the prevention of C/G-->A/T transversions. The molecular mechanism of base excision repair (BER) of A/GO in mammals is not well understood. In this study we report stimulation of mammalian adenine-DNA glycosylase activity by apurinic/apyrimidinic (AP) endonuclease using murine homolog of MutY (Myh) and human AP endonuclease (Ape1), which shares 94% amino acid identity with its murine homolog Apex. After removal of adenine by the Myh glycosylase activity, intact AP DNA remains due to lack of an efficient Myh AP lyase activity. The study of wild-type Ape1 and its catalytic mutant H309N demonstrates that Ape1 catalytic activity is required for formation of cleaved AP DNA. It also appears that Ape1 stimulates Myh glycosylase activity by increasing formation of the Myh-DNA complex. This stimulation is independent of the catalytic activity of Ape1. Consequently, Ape1 preserves the Myh preference for A/GO over A/G and improves overall glycosylase efficiency. Our study suggests that protein-protein interactions may occur in vivo to achieve efficient BER of A/GO.

Amino Acid Sequence↗
PubMed2001

Oral temazepam.

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Anti-Anxiety Agents↗
PubMed2001

Functional heterogeneity of inferior frontal gyrus is shaped by linguistic experience.

A crosslinguistic, positron emission tomography (PET) study was conducted to determine the influence of linguistic experience on the perception of segmental (consonants and vowels) and suprasegmental (tones) information. Chinese and English subjects (10 per group) were presented binaurally with lists consisting of five Chinese monosyllabic morphemes (speech) or low-pass-filtered versions of the same stimuli (nonspeech). The first and last items were targeted for comparison; the time interval between target tones was filled with irrelevant distractor tones. A speeded-response, selective attention paradigm required subjects to make discrimination judgments of the target items while ignoring intervening distractor tones. PET scans were acquired for five tasks presented twice: one passive listening to pitch (nonspeech) and four active (speech = consonant, vowel, and tone; nonspeech = pitch). Significant regional changes in blood flow were identified from comparisons of group-averaged images of active tasks relative to passive listening. Chinese subjects show increased activity in left premotor cortex, pars opercularis, and pars triangularis across the four tasks. English subjects, on the other hand, show increased activity in left inferior frontal gyrus regions only in the vowel task and in right inferior frontal gyrus regions in the pitch task. Findings suggest that functional circuits engaged in speech perception depend on linguistic experience. All linguistic information signaled by prosodic cues engages left-hemisphere mechanisms. Storage and executive processes of working memory that are implicated in phonological processing are mediated in discrete regions of the left frontal lobe.

Adult↗
PubMed2001

Pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with silicone oil injection.

PURPOSE: To describe pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with silicone oil injection. DESIGN: Interventional case series. METHODS: Cases were collected from January 1997 to July 2000 from three tertiary referral centers. RESULTS: Seven phakic patients (seven eyes) and one pseudophakic patient (one eye) presented 1 to 90 days after vitrectomy and silicone oil injection with intraocular pressures of 36 to 70 mm Hg. Five patients had an observed or potential weakness of the iris-lens diaphragm. Treatment with Nd:YAG-laser peripheral iridotomy or inferior iridectomy provided a temporary reduction in intraocular pressure for some patients, but all eventually required removal of silicone oil. CONCLUSION: Pupil block glaucoma after silicone oil injection is well recognized in aphakic patients, but ophthalmologists should be aware that it can occur in phakic and pseudophakic patients, particularly in complicated cases and patients with a weakness of the iris-lens diaphragm.

Adult↗
PubMed2001

Induction of megakaryocytic differentiation in primary human erythroblasts: a physiological basis for leukemic lineage plasticity.

In myelodysplasias and acute myeloid leukemias, abnormalities in erythroid development often parallel abnormalities in megakaryocytic development. Erythroleukemic cells in particular have been shown to possess the potential to undergo megakaryocytic differentiation in response to a variety of stimuli. Whether or not such lineage plasticity occurs as a consequence of the leukemic phenotype has not previously been addressed. In this study, highly purified primary human erythroid progenitors were subjected to stimuli known to induce megakaryocytic differentiation in erythroleukemic cells. Remarkably, the primary erythroid progenitors rapidly responded with morphological and immunophenotypic evidence of megakaryocytic differentiation, equivalent to that seen in erythroleukemic cells. Even erythroblasts expressing high levels of hemoglobin manifested partial megakaryocytic differentiation. These results indicate that the lineage plasticity observed in erythroleukemic cells reflects an intrinsic property of cells in the erythroid lineage rather than an epiphenomenon of leukemic transformation.

Cell Differentiation↗
PubMed2001

Acute respiratory distress syndrome in pregnancy and the puerperium: causes, courses, and outcomes.

OBJECTIVE: To describe causes, courses, complications, and outcomes of patients with pregnancy-associated acute respiratory distress syndrome (RDS). METHODS: Twenty-eight women with ARDS during pregnancy or within a week postpartum formed the study population. Eight cases had been reported previously. Charts were abstracted for maternal demographics, etiology, and treatment of acute RDS, and maternal outcomes. For antepartum acute RDS, newborn charts were also reviewed. RESULTS: The incidence of acute RDS, excluding maternal transports, was one per 6277 deliveries or 0.016% (95% confidence interval [CI] 0, 0.027%). Leading causes were infection (12 cases), preeclampsia or eclampsia (seven cases), and aspiration (three cases). Eleven mothers died, a maternal mortality rate of 39.3% (CI 21.5%, 59.4%). Six of eight women who were ventilated for over 14 days survived. Nine of the acute RDS cases might have been preventable. Ten mothers with living fetuses were ventilated during the third trimester; nine delivered within 4 days. Among six infants delivered because of fetal heart rate abnormalities, one died and at least three had evidence of asphyxia. CONCLUSIONS: Acute RDS occurs more frequently in pregnancy than the 1.5 cases per 100,000 per year reported for the general population. Prolonged ventilator support is warranted. The high rate of perinatal asphyxia in infants who have fetal heart rate abnormalities supports a strategy of expeditious delivery during the third trimester.

Adolescent↗
PubMed2001

New surgical approach in the management of pseudophakic malignant glaucoma.

PURPOSE: To describe a new surgical approach in the management of pseudophakic malignant glaucoma. DESIGN: Noncomparative case series. PARTICIPANTS: Five consecutive patients with pseudophakic malignant glaucoma. METHODS: All patients underwent zonulo-hyaloido-vitrectomy. The procedure involves the performance of zonulectomy, hyaloidectomy, and anterior vitrectomy (zonulo-hyaloido-vitrectomy) through a peripheral iridectomy or iridotomy via the anterior chamber. MAIN OUTCOME MEASURES: Medications, visual acuity, intraocular pressure, and anterior and posterior segment findings were recorded before and after surgery. RESULTS: Resolution of the malignant glaucoma was achieved in all cases. No recurrences were observed after a median follow-up of 5.5 months (range, 1-9 months). In one patient with extensive anterior synechiae, bleb failure occurred after the resolution of the malignant glaucoma. This patient was treated successfully with a guarded filtration procedure supplemented with 5-fluorouracil. No other complications were observed. CONCLUSIONS: Zonulo-hyaloido-vitrectomy via the anterior segment appears to be an alternative option in the treatment of patients with pseudophakic malignant glaucoma.

Aged↗
PubMed2001

How to predict proliferative vitreoretinopathy: a prospective study.

PURPOSE: To determine prospectively the accuracy of a predictive risk formula for the development of postoperative proliferative vitreoretinopathy (PVR) when applied in a clinical setting. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Two hundred nineteen subjects undergoing primary vitrectomy for rhegmatogenous retinal detachment were studied. METHOD: By use of a formula-based discriminant rule, subjects were classified as either high or low risk for the development of PVR. All subjects were followed prospectively. OUTCOME MEASURES: Development of postoperative PVR as defined by the updated the Retina Society Classification. RESULTS: Complete data were available on 212 of 219 subjects. There were 130 subjects identified as low risk and 82 subjects as high risk; 9.2% of the low-risk (12 of 130) compared with 28% (23 of 82) of the high-risk subjects had postoperative PVR develop. This difference was statistically significant (P < 0.001). CONCLUSIONS: Our study has shown that using a clinical model it is possible to identify subjects at greater risk of PVR developing after primary vitrectomy.

Adolescent↗
PubMed2001

Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial.

PURPOSE: To assess the safety and efficacy of adjuvant combination therapy using 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) for prevention of proliferative vitreoretinopathy (PVR) after vitrectomy and retinal reattachment surgery. DESIGN: Prospective randomized, double-masked, placebo controlled trial. PARTICIPANTS: One hundred seventy-four high-risk patients were randomized to receive either 5-FU and LMWH therapy or placebo. Patients were selected from all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment. METHOD: Results of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up. MAIN OUTCOME MEASURES: Development of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity. RESULTS: There were 87 patients in the 5-FU and LMWH therapy group and 87 in the placebo group. The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group. In 26.4% (23/87) of the placebo group and in 12.6% (11/87) of the 5-FU and LMWH group, postoperative PVR developed. In the 5-FU and LMWH group, the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations resulting from PVR was 52.9% (9/17). In the placebo group, the number of patients undergoing more than one operation was 25.3% (22/87) and the number of reoperations resulting from PVR was 72.7% (16/22). The difference in visual acuity was not statistically different in the two treatment groups, although those patients in whom postoperative PVR developed tended to have poorer vision (P < 0.0001). There were no differences in complication rates between the two groups. CONCLUSIONS: There is a significant reduction in the incidence of postoperative PVR in patients receiving the 5-FU and LMWH therapy and in the reoperation rate resulting from PVR. This trial shows that incidence of PVR can be reduced with inexpensive and simple pharmacologic treatment with 5-FU and LMWH and should be used routinely in the treatment of patients at risk of developing PVR.

Adolescent↗
PubMed2001

Determinants of visual outcome after pars plana vitrectomy for posteriorly dislocated lens fragments in phacoemulsification.

PURPOSE: To evaluate the visual outcome of patients with posteriorly dislocated lens fragments after phacoemulsification managed with pars plana vitrectomy (PPV) and identify risk factors for poor visual outcome. SETTING: Vitreo-Retinal Service, St. Paul Eye Unit, Liverpool, United Kingdom. METHODS: The medical records of all patients who had PPV for posteriorly dislocated lens fragments after phacoemulsification between March 1993 and August 1998 were retrospectively reviewed. Demographics, preexisting eye conditions, details of the previous cataract surgery, findings at presentation, details of the vitreoretinal procedure, final visual acuity, and complications observed during the follow-up were evaluated. Univariate and multiple regression analyses were used to determine the significance of these clinical variables as determinants of poor visual outcome (visual acuity 6/12 or worse). RESULTS: Of the 106 patients identified, 89 had a full set of data and were included in the study. In 79 patients (89%), PPV was performed from 1 to 357 days (median 15 days) after cataract extraction. In 10 patients (11%), PPV was done on the same day as the cataract surgery. Sixty-two patients (69%) had a final visual acuity of 6/12 or better. Preexisting eye disease (P <.01), PPV delayed for more than 4 weeks (P <.03), occurrence of retinal detachment after vitrectomy (P <.01), and the use of ultrasound (US) fragmentation (P <.01) were statistically significantly correlated with a poor visual outcome. CONCLUSIONS: Posterior dislocated lens fragments after phacoemulsification were safely retrieved using PPV. It appears that intervening early (within 4 weeks) and avoiding the use of US fragmentation are associated with a better visual outcome and reduced rate of postoperative complications.

Aged↗