Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).
Prospective, randomized, ...sham injection-controlled, double-masked, multicenter clinical trial.
We included 392 patients with macular edema after CRVO.
Eligible patients were randomized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. After 6 months, all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab.
Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 12, additional parameters of visual function, central foveal thickness (CFT), and other anatomic changes were assessed.
Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 13.9 (11.2-16.5) and 13.9 (11.5-16.4) in the 0.3 mg and 0.5 mg groups, respectively, and 7.3 (4.5-10.0) in the sham/0.5 mg group (P<0.001 for each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups, respectively, and 33.1% in the sham/0.5 mg group. On average, there was a marked reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group to the level of the ranibizumab groups, which was sustained through month 12. No new ocular or nonocular safety events were identified.
On average, treatment with ranibizumab as needed during months 6 through 11 maintained the visual and anatomic benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after CRVO, with low rates of ocular and nonocular safety events. After sham injections for 6 months, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab treatment groups and an improvement in BCVA, but not to the same level as that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after CRVO.
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The secondary organic aerosol (SOA) yield of β-caryophyllene photooxidation is enhanced by aerosol acidity. In the present study, the influence of aerosol acidity on the chemical composition of ...β-caryophyllene SOA is investigated using ultra performance liquid chromatography/electrospray ionization-time-of-flight mass spectrometry (UPLC/ESI-TOFMS). A number of first-, second- and higher-generation gas-phase products having carbonyl and carboxylic acid functional groups are detected in the particle phase. Particle-phase reaction products formed via hydration and organosulfate formation processes are also detected. Increased acidity leads to different effects on the abundance of individual products; significantly, abundances of organosulfates are correlated with aerosol acidity. To our knowledge, this is the first detection of organosulfates and nitrated organosulfates derived from a sesquiterpene. The increase of certain particle-phase reaction products with increased acidity provides chemical evidence to support the acid-enhanced SOA yields. Based on the agreement between the chromatographic retention times and accurate mass measurements of chamber and field samples, three β-caryophyllene products (i.e., β-nocaryophyllon aldehyde, β-hydroxynocaryophyllon aldehyde, and β-dihydroxynocaryophyllon aldehyde) are suggested as chemical tracers for β-caryophyllene SOA. These compounds are detected in both day and night ambient samples collected in downtown Atlanta, GA and rural Yorkville, GA during the 2008 August Mini-Intensive Gas and Aerosol Study (AMIGAS).
(
E)-5-(2-Iodovinyl)-2′-deoxyuridine (IVDU) and (
E)-5-(2-iodovinyl)-2′-fluoro-2′-deoxyuridine (IVFRU) are potential substrates of Herpes Simplex Virus type 1thymidine kinase (HSV-TK). In the present ...study, cellular uptake of radioiodinated substrates was found to be low in wild type MCA cells, but high in HSV-TK gene expressing cells. The carrier-free substrates, in particular, showed higher cellular uptake than carrier-added compounds. Biodistribution showed that the %ID/g of the MCA-TK/MCA tumor ratio of IVDU injected at 1, 4, and 24
h were 1.1, 0.9 and 1.3, and those of IVFRU were 1.7, 1.7 and 1.8 respectively. Therefore, both IVDU and IVFRU could possibly be used as radiopharmaceuticals to evaluate reporter gene expression. However, IVFRU was more specific and stable than IVDU for selective non-invasive imaging of HSV-TK expression.
We report the identification and characterization of a bacteriophage λ-encoded protein, NinH. Sequence homology suggests similarity between NinH and Fis, a bacterial nucleoid-associated protein (NAP) ...involved in numerous DNA topology manipulations, including chromosome condensation, transcriptional regulation and phage site-specific recombination. We find that NinH functions as a homodimer and is able to bind and bend double-stranded DNA in vitro. Furthermore, NinH shows a preference for a 15 bp signature sequence related to the degenerate consensus favored by Fis. Structural studies reinforced the proposed similarity to Fis and supported the identification of residues involved in DNA binding which were demonstrated experimentally. Overexpression of NinH proved toxic and this correlated with its capacity to associate with DNA. NinH is the first example of a phage-encoded Fis-like NAP that likely influences phage excision-integration reactions or bacterial gene expression.
Immunoscintigraphy with radiolabelled monoclonal antibodies has been widely used to detect solid tumours. The purpose of this study was to investigate its potential for the specific localization of ...syphilitic lesions. F(ab')2 fragments were prepared from murine monoclonal antibodies against Treponema pallidum produced in our laboratory and labelled with 131I. Bilateral testicular infections were created in rabbits by inoculation with T. pallidum or Staphylococcus aureus. Seven to 10 days after inoculation, radiolabelled antibodies were injected intravenously. Serial gamma images were then taken 2 h after the injection and at 24 h intervals thereafter. Beginning as early as 2 h post-injection, the testicles could be visualized with either specific or non-specific antibodies. Gamma images in the monoclonal antibody-treated, T. pallidum-infected group persisted up to 48 h post-injection. Lesions were not discernible from background in the S. aureus-infected group injected with the monoclonal antibody and the S. aureus-infected and T. pallidum-infected groups injected with the polyclonal antibody at 24 h post-injection or later. Therefore, due to its ability to differentiate between specific and non-specific antibody-generated images from 24 h post-injection, immunoscintigraphy using monoclonal antibodies specific for T. pallidum may be employed as one of the methods to diagnose difficult cases of syphilitic internal organ involvement as well as syphilis infection in seronegative HIV-infected patients.
Aldehydes are an important class of products from atmospheric oxidation of hydrocarbons. Isoprene (2-methyl-1,3-butadiene), the most abundantly emitted atmospheric non-methane hydrocarbon, produces a ...significant amount of secondary organic aerosol (SOA) via methacrolein (a C sub(4)-unsaturated aldehyde) under urban high-NO sub(x) conditions. Previously, we have identified peroxy methacryloyl nitrate (MPAN) as the important intermediate to isoprene and methacrolein SOA in this NO sub(x) regime. Here we show that as a result of this chemistry, NO sub(2) enhances SOA formation from methacrolein and two other a, b-unsaturated aldehydes, specifically acrolein and crotonaldehyde, a NO sub(x) effect on SOA formation previously unrecognized. Oligoesters of dihydroxycarboxylic acids and hydroxynitrooxycarboxylic acids are observed to increase with increasing NO sub(2)/NO ratio, and previous characterizations are confirmed by both online and offline high-resolution mass spectrometry techniques. Molecular structure also determines the amount of SOA formation, as the SOA mass yields are the highest for aldehydes that are a, b-unsaturated and contain an additional methyl group on the a-carbon. Aerosol formation from 2-methyl-3-buten-2-ol (MBO232) is insignificant, even under high-NO sub(2) conditions, as PAN (peroxy acyl nitrate, RC(O)OONO sub(2)) formation is structurally unfavorable. At atmospherically relevant NO sub(2)/NO ratios (3-8), the SOA yields from isoprene high-NO sub(x) photooxidation are 3 times greater than previously measured at lower NO sub(2)/NO ratios. At sufficiently high NO sub(2) concentrations, in systems of a, b-unsaturated aldehydes, SOA formation from subsequent oxidation of products from acyl peroxyl radicals+NO sub(2) can exceed that from RO sub(2)+HO sub(2) reactions under the same inorganic seed conditions, making RO sub(2)+NO sub(2) an important channel for SOA formation.
Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an ...inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.
Acute renal allograft rejection is usually seen within the first 3 months posttransplant, and is characterized by an intense infiltrate of T cells. Some acute rejections, however, contain many plasma ...cells and/or appear late posttransplant.
We have investigated 27 cases of intensely plasma cell-rich acute rejections (PCAR) from 1987 to 1997 and have compared them to 21 control cases (CAR) of typical acute rejection. Each group was divided into early (<6 months) and late (>6 months) subgroups. PCAR and CAR cases were matched for histological features of chronic allograft nephropathy. In all four groups, most cases had Banff '97 type IB and IIA acute rejection.
A significantly greater number of PCAR cases experienced graft failure due to chronic allograft nephropathy or complications of acute rejection (P<0.05). There was no significant difference between PCAR and CAR in HLA matching, occurrence of posttransplant acute tubular necrosis, presence versus absence of previous allografts, number of previous or subsequent acute rejection episodes, Banff '97 sum scores for acute rejection, cyclosporine A or FK506 levels, or percent change from baseline creatinine at time of biopsy. Plasma cells in PCAR cases showed IgG predominance whereas those in CAR had comparable staining for IgG and IgA. Kappa and lambda light chain immunostaining of all PCAR cases revealed polyclonality. Three of 18 PCAR cases studied for the presence of Epstein-Barr virus RNA showed scattered positivity in 2-7% of lymphoid cells, although the remainder was negative. None of the PCAR cases developed post-transpland lymphoproliferative disorder.
We conclude that PCAR can occur from 1 month to many years posttransplant, is associated with poor graft survival, and is not a manifestation of concomitant chronic allograft nephropathy or viral infection, including posttransplant lymphoproliferative disorder.
Radioimmunoassay of Pinellia ternata lectin Kim, J R; Park, K B; Awh, O D
The International journal of applied radiation and isotopes,
12/1985, Letnik:
36, Številka:
12
Journal Article
Radioimmunoassay of Pinellia ternata lectin (PTL) in rabbit serum and in root extract has been tried. The PTL was labelled with 125I using chloramine-T, and the labelled product was purified by gel ...chromatography. Standard suppression lines were obtained and the parallelism in serum or buffer was demonstrated. The assay time was 48 h with an intra- and inter-assay coefficient of variation of less than 12%. The PTL content in dried Pinellia ternata roots was about 28 +/- 3 mg/g. More than 40% of the i.v. injected PTL to rabbits was retained in serum at 1 h post administration.
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