The AJO: electronic augmentation on the Internet.
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Internet↗
Biomedical subjects
H Lewis
Publications and source records attributed to H Lewis.
Lipopolysaccharide binding protein in acute pancreatitis.
OBJECTIVE: To assess the expression of plasma lipopolysaccharide binding protein (LBP) concentrations and its relationship to markers of the systemic inflammatory response syndrome during acute pancreatitis. DESIGN: A prospective study. SETTING: General surgical units of university teaching hospitals in the Belfast area. PATIENTS: The study included 18 patients admitted with established diagnosis of acute pancreatitis on the basis of elevated serum amylase or by contrast radiology. Patients were retrospectively stratified using the Modified Glasgow Criteria into severe (n = 7) and mild (n = 11) disease. INTERVENTIONS AND MEASUREMENTS: Blood samples were obtained at admission (day 1) and for a further 3 days for the measurement of LBP, C-reactive protein (CRP), tumor necrosis factor, and interleukin (IL)-6. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated on day 1 and day 2. MAIN RESULTS: LBP and CRP concentrations were significantly increased from healthy control values in acute pancreatitis patients at presentation. In the mild group LBP, CRP and IL-6 concentrations remained relatively constant throughout the study period. By comparison, severe acute pancreatitis was associated with significantly higher LBP concentrations and a marked systemic inflammatory response as evidenced by increased CRP, IL-6, and APACHE II scores. The rise in LBP occurred after the observed increase of these markers. Significant correlations were found among CRP and LBP, IL-6 and LBP, and IL-6 and APACHE II scores. There were no fatalities in the mild group, whereas four of the seven patients with severe disease died. CONCLUSIONS: LBP was significantly raised in patients with severe acute pancreatitis but would seem to be of limited use in predicting disease severity. This acute phase protein may have a role in the progression of systemic complications associated with acute pancreatitis.
APACHE↗
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↗
Management of glaucoma implants occluded by vitreous incarceration.
PURPOSE: To review the authors' experience in the management of aphakic or pseudophakic patients without an intact posterior capsule who had undergone glaucoma implant surgery complicated by vitreous incarceration in the tube, resulting in increased intraocular pressure or combined rhegmatogenous and tractional retinal detachment. METHODS: Retrospective review of the clinical features, treatment, and outcomes of eight patients who had vitreous incarceration in a glaucoma implant drainage tube. In each patient, a model 425 (7 patients) or model 350 (1 patient) Baerveldt glaucoma implant was used. RESULTS: Vitreous incarceration in the tube was first diagnosed 1 day to 49 weeks after surgery (mean, 7.5 weeks; median, 1 week). The interval between glaucoma implant surgery and pars plana vitrectomy ranged from 22 to 365 days (mean, 125 days). Before management with pars plana vitrectomy or neodymium:yttrium-aluminum-garnet laser vitreolysis, intraocular pressure ranged from 25 to 62 mm Hg (mean, 40 mm Hg). Four patients were initially treated with neodymium:yttrium-aluminum-garnet laser vitreolysis, which was successful in only one patient. Six patients were successfully treated with pars plana vitrectomy, and one patient declined surgery. Follow-up after treatment of the incarceration ranged from 5 weeks to 15 months (mean, 8.3 months). After pars plana vitrectomy, intraocular pressure ranged from 9 to 24 mm Hg (average, 14 mm Hg). Postoperative visual acuity remained within one line of the preoperative visual acuity in each of the six patients undergoing pars plana vitrectomy. CONCLUSIONS: Pars plana vitrectomy is effective in managing vitreous incarceration in glaucoma implant tubes. Previous anterior vitrectomy does not prevent incarceration.
Adult↗
Tissue plasminogen activator in the treatment of vitreoretinal diseases.
Tissue plasminogen activator (tPA) is a thrombolytic agent that activates plasminogen into plasmin almost exclusively in the presence of fibrin. Intraocular injection of tPA has been proposed for the treatment of vitreoretinal diseases, such as vitreous hemorrhage, postvitrectomy fibrin formation, submacular hemorrhage, retinal vascular occlusive disorders, suprachoroidal hemorrhage and endophthalmitis. Currently, intraocular tPA is only used in the treatment of postvitrectomy fibrin formation and submacular hemorrhage. For other indications, tPA has not been shown to be safe or effective. This article reviews the use of tPA in the treatment of vitreoretinal disorders.
Animals↗
Magnesium ions enhance the transfer of human papillomavirus E2 protein from non-specific to specific binding sites.
The human papillomavirus 16 E2 protein binds to four specific DNA sequences present within the HPV 16 genome and regulates viral gene expression and DNA replication. However, the E2 protein can also bind tightly to non-specific DNA sequences. Here, we show that in binding reactions which contain an excess of non-specific DNA, magnesium ions enhance the binding of E2 to its specific sites. In contrast, in the absence of non-specific DNA, magnesium ions have no effect on the binding of E2 to specific sites. Although these data suggest that magnesium ions decrease the binding of E2 to non-specific DNA, gel retardation assays show that these ions have no effect on the binding of E2 to short non-specific DNA fragments and have only a minor effect on the binding of E2 to long non-specific DNA fragments. We also show that the binding of E2 to long fragments of non-specific DNA is highly cooperative. The E2-non-specific DNA complexes formed in the absence of magnesium ions are highly stable. However, the addition of specific DNA to E2-non-specific DNA complexes formed in the presence of magnesium ions rapidly results in the formation of E2-specific DNA complexes. Our data suggest that magnesium ions facilitate the transfer of E2 from non-specific binding sites to specific binding sites, and help to explain how E2 is able to direct human papillomavirus transcription and DNA replication in intact cells.
Base Sequence↗
PCG boards. Social climbers.
A national survey of PCG chief executives and social services representatives on PCG boards showed that most consider the social services role 'very useful'. Most social services representatives spent two to four days a month on PCG business. Two-thirds felt they needed more time. Almost half felt they had little or no support. Better feedback mechanisms are needed for social services representatives.
Data Collection↗
Fragile X syndrome and selective mutism.
This is the first report that details an association between fragile X syndrome (FXS) and selective mutism (SM). This 12-year-old girl with heterozygous full mutation at FMR1 has a long history of social anxiety and shyness in addition to SM. Her sister also has the full mutation and a history of SM that resolved in adolescence. A beneficial response to fluoxetine and psychotherapy is described. The FMR1 mutation appears to be the first gene mutation associated with SM and further studies are recommended to assess what percentage of patients with SM have the FMR1 mutation.
Child↗
Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study.
PURPOSE: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold. RESULTS: All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye. CONCLUSIONS: Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.
Aged↗
A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits.
PURPOSE: Intravitreal injections of tissue plasminogen activator have been used to lyse fibrin from blood in the subretinal space, despite the lack of proof that tissue plasminogen activator can diffuse across the retina. We tested whether tissue plasminogen activator injected into the vitreous could penetrate the neural retina and enter the subretinal space. METHODS: We injected a mixture of 50 microg of tissue plasminogen activator (70 kD) labeled with fluorescein isothiocyanate and rhodamine B isothiocyanate-labeled dextran, which has a lower molecular weight (20 kD), into the midvitreous cavity of one eye in each of 18 rabbits. The eyes were enucleated after 3, 6, and 24 hours, and cryosections were examined with epifluorescent microscopy to determine the distribution of the labeled molecules. We also evaluated tissue plasminogen activator pharmacokinetics in one eye each of 18 rabbits in which a subretinal clot was induced by injecting autologous blood (50 microL) into the subretinal space through the sclera. Fluorescein isothiocyanate-labeled tissue plasminogen activator was injected into the vitreous 2 days after induction of the subretinal clot. RESULTS: Fluorescein isothiocyanate-labeled tissue plasminogen activator was present at the vitreal surface of the retina in a linear array in all 36 eyes studied, whereas the rhodamine B isothiocyanate-labeled dextran had diffused throughout the neural retina in the same sections. No fluorescein isothiocyanate signal was observed in the neural retina or in the subretinal clot. Vitreous hemorrhage caused by retinal perforation was observed in all eyes with intraretinal hemorrhage in which fluorescein isothiocyanate fluorescence was seen in the neural retina and inside the clot. CONCLUSION: Intravitreal tissue plasminogen activator did not diffuse through the intact neural retina to reach a subretinal clot. This study demonstrates no scientific rationale for the intravitreal tissue plasminogen activator treatment of submacular hemorrhage without vitreous hemorrhage presumably caused by an overlying retinal break.
Animals↗
Surgical management of subfoveal neovascularization in children.
OBJECTIVE: To report the authors' clinical experience with submacular surgery for subfoveal membranes in children and to evaluate the histopathologic findings of membranes in children with various etiologies of choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 12 consecutive children with subfoveal choroidal neovascularization treated by vitrectomy and excision of the choroidal neovascular complex. INTERVENTION: Vitrectomy, excision of the choroidal neovascular complex, and air-fluid exchange. MAIN OUTCOME MEASURES: Visual acuity and recurrence of choroidal neovascular membrane. RESULTS: Preoperative visual acuities ranged from 20/60 to 20/800 (median, 20/300). Postoperative visual acuities ranged from 20/25 to 20/400 (median, 20/80) after an average follow-up of 20 months (range, 7-62 months). Ten of 12 eyes improved from immediate preoperative visual acuity, and four eyes developed recurrence of neovascular membranes over a mean follow-up of 18 months. Histopathologic examination of six excised membranes showed that the most common components of the membranes were retinal pigment epithelium, fibrocytes, vascular endothelium, and collagen. CONCLUSION: Selected eyes of children with subfoveal neovascular membranes and no evidence of membrane regression may benefit from submacular surgery. The histopathologic findings were similar to adult choroidal neovascularization not associated with age-related macular degeneration.
Adolescent↗
Kupffer cell blockade, tumour necrosis factor secretion and survival following endotoxin challenge in experimental biliary obstruction.
BACKGROUND: Gram-negative sepsis and its sequelae frequently complicate invasive procedures in patients with obstructive jaundice. In response to endotoxin, Kupffer cells secrete tumour necrosis factor (TNF), a pivotal early mediator of sepsis. An investigation was carried out into the specific role of Kupffer cell TNF secretion following endotoxin challenge in obstructive jaundice. METHODS: Survival following intraperitoneal administration of endotoxin (2.0, 0.02 and 0.0002 mg per 100 g) was determined in rats following bile duct ligation (BDL) or sham operation. Plasma TNF concentration was quantified following endotoxin administration (0.0002 mg per 100 g) at 1, 2 and 6 h. Subsequently, the effect of Kupffer cell blockade by gadolinium chloride on survival and plasma TNF concentration was assessed. RESULTS: Jaundiced animals showed a significantly increased mortality rate following intraperitoneal injection of endotoxin 2.0 mg per 100 g (BDL 100 per cent versus sham 0 per cent) and 0.02 mg per 100 g (BDL 70 per cent versus sham 0 per cent; P = 0. 002, Fisher's exact test). Median plasma TNF concentration was significantly greater in jaundiced animals 1 h after endotoxin administration (BDL 943 (interquartile range (i.q.r.) 211-3900) pg/ml versus sham 64 (i.q.r. 47-127) pg/ml; P = 0.002, Mann-Whitney U test). Kupffer cell blockade with gadolinium chloride increased the survival rate following endotoxin administration in BDL animals (BDL-GdCl3 100 per cent versus BDL-saline 40 per cent; P = 0.0003, Fisher's exact test) and decreased median plasma levels of TNF (BDL-GdCl3 88 (i.q.r. 0-1065) pg/ml versus BDL-saline 16 550 (1255-29 360) pg/ml; P = 0.002, Mann-Whitney U test). CONCLUSION: Kupffer cell blockade improved survival and suppressed systemic TNF activity after endotoxin challenge. In obstructive jaundice, hypersecretion of TNF by Kupffer cells may supplement systemic cytokine production and be responsible for significant complications.
Animals↗
Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool.
Studies have shown that ovarian failure is a common side-effect of chemotherapy treatment; however, continuation of regular menses post-treatment does not necessarily imply that the ovaries have escaped damage. This animal study measures directly the primordial follicle (PMF) loss following exposure to chemotherapy and evaluates reproductive outcome following significant destruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were administered different doses of an alkylating agent, cyclophosphamide, and the total number of PMF remaining in both ovaries was counted. Results show that cyclophosphamide causes PMF destruction in proportion to increasing dose (P = 0.0001). Reproductive performance was assessed after exposure to 75 mg/kg cyclophosphamide, a dose which destroys approximately 50% of PMF reserve, by evaluation of ovulation, mating and pregnancy rates. Reproductive potential of treated mice was not affected compared with controls despite the significant loss of PMF. Our results indicate that reproductive performance is not an accurate parameter for assessing ovarian injury. Rather, histological counting of PMF number more directly reflects the damage caused by chemotherapy to the ovary. This method can be used as a sensitive, inexpensive tool to gauge the damage to fertility caused by new chemotherapy agents or protocols.
Animals↗
Development of a multiple-drug delivery implant for intraocular management of proliferative vitreoretinopathy.
A prototype multiple-drug delivery implant has been developed for the intraocular management of proliferative vitreoretinopathy (PVR). Because of the recurrent nature of the disease, PVR causes blindness in approximately 7% of patients who have undergone retinal re-attachment surgery. The poly(dl-lactide-co-glycolide) 50/50 (PLGA) implant consists of three cylindrical segments, each of which contains one of the following drugs: 5-fluorouridine (5FUrd, an antimetabolite), triamcinolone (Triam, a corticosteroid), and human recombinant tissue plasminogen activator (t-PA, a thrombolytic agent). The device can be inserted through a 20-gauge syringe needle into the vitreous body of the eye. The implant also possesses a PLGA coating over the t-PA-containing terminal segment, which creates a lag-time to deliver t-PA when most needed and to decrease the risk of postoperative bleeding. Two methods of cylinder fabrication were investigated: heat and solvent extrusion. The release behavior of several drugs was examined as a function of the processing variables including: extrusion method, drug loading, polymer molecular weight, and drug particle size. The presence of either the organic solvent (acetone) during processing or a highly water-soluble drug (5FUrd) in the formulation increased the polymer porosity, which in turn, increased the drug release-rate. Drug loading effects were consistent with percolation concepts, and a low-molecular-weight PLGA (e.g., Mw=42000 for inherent viscosity=0.58 dl/g) was desirable to produce controlled release close to one month. Based on pharmacological and pharmacokinetic data of these compounds and our clinical experience with this disease, several design criteria for a combined implant were devised. Optimal cylindrical segments from the formulation studies were selected and combined in series to form a contiguous implant. After successful combination and coating procedures were developed, prototype implants were prepared. From the 3-drug prototype, 5FUrd and Triam were released approximately 1 microgram/day for over 4 weeks and 10-190 microgram/day over 2 weeks, respectively. The solvent-extrusion procedure did not significantly alter the stability of the encapsulated t-PA (>94+/-5% serine protease activity after preparation). After a lag-time of approximately 2 days, t-PA was released active at a rate of approximately 0.2-0.5 microgram/day in approximately 2 weeks. The release characteristics from the combined implant largely met our initial design criteria. Hence, controlled-release implants of this kind may have potential use for intraocular treatment of PVR.
Chromatography, High Pressure Liquid↗
Subfoveal choroidal neovascularization: is there a role for submacular surgery?
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Choroid↗
Management of submacular hemorrhage associated with retinal arterial macroaneurysms.
PURPOSE: Experience is reported with intraoperative pharmacologic lysis of recent submacular hemorrhage with tissue plasminogen activator followed by surgical drainage of the unclotted blood in patients with retinal arterial macroaneurysms. METHODS: Nine eyes (nine patients) with a recent (< or = 7 days old) submacular hemorrhage involving the center of the fovea secondary to retinal arterial macroaneurysm that were managed with recombinant tissue plasminogen activator-assisted subretinal hemorrhage evacuation, including subretinal injection of tissue plasminogen activator and removal of the liquefied blood. Patients were followed for a mean 18 +/- 7 months (range, 7 to 30 months). RESULTS: All nine eyes had improved final corrected visual acuity after surgery, and eight eyes (89%) attained a corrected visual acuity of 20/60 or better (mean, 20/40; range, 20/20 to 20/200). Final corrected visual acuity was limited to 20/200 in one eye. Two eyes developed a cataract that required surgery. CONCLUSIONS: Submacular surgery with tissue plasminogen activator-assisted thrombolysis achieved improved best-corrected visual acuity in eyes with recent submacular hemorrhage involving the center of the fovea associated with retinal arterial macroaneurysm.
Aged↗