INTRODUCTIONThe aim of this study was to determine the effectiveness of intraocular injections of bevacizumab for neovascularisation of the iris and neovascular glaucoma.

CLINICAL PICTUREThree patients with neovascularisation of the iris due to various causes were recruited.

TREATMENTPatients were treated with intraocular bevacizumab.

OUTCOMENeovascularisation of the iris was noted to have completely regressed as early as 3 days after the injection and in all the patients (100%) within 8 days after injection. They were followed up for at least 1 month with no clinical evidence of recurrence. Visual acuity remained stable or improved, and the intraocular pressure was controlled in all the 3 patients' eyes. Vitreous haemorrhage also cleared. No signs of inflammation or complications were observed.

CONCLUSIONIntraocular injection of bevacizumab is effective and safe for patients with neovascularisation of the iris and neovascular glaucoma with or without vitreous haemorrhage.

Adult ; Aged ; Angiogenesis Inhibitors ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Glaucoma, Neovascular ; drug therapy ; Humans ; Iris ; blood supply ; Male

Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-alpha) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF-alpha agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis.
Antibodies, Monoclonal/blood/*therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Clinical Trials as Topic ; Colitis, Ulcerative/*drug therapy ; Drug Administration Schedule ; Humans ; Treatment Outcome ; Tumor Necrosis Factor-alpha/immunology

To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.
Antibodies, Monoclonal ; blood ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Humans ; Infliximab ; blood ; therapeutic use ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood

Due to an extreme shortage of cadaveric kidneys, many centers in Japan successfully performed ABO-incompatible kidney transplantations using plasmapheresis, splenectomy and immunosuppression. Recently, a protocol including anti-CD20 monoclonal antibody (rituximab) and antigen-selective immunoadsorption has been used for ABO-incompatible transplantation in Europe. In Korea, ABO-incompatible kidney transplantation has been rarely performed. We report an experience of successful ABO-incompatible kidney transplantation using plasmapheresis and rituximab. The patient was a 32-yr-old female suffering from chronic renal failure, and her blood type was O, Rh+. The donor was her husband, and his blood type was B, Rh+. A combination therapy including 5 times of plasmapheresis starting from 10 days before transplantation with 2-day interval, intravenous gammaglobulin, rituximab at 2 weeks before transplantation and potent immunosuppression successfully decreased the titers of anti-A and anti-B antibodies to 1:2 and 1:1, respectively. The kidney transplantation was successful without any sign of hyperacute or acute rejection.
*ABO Blood-Group System ; Adult ; Antibodies, Monoclonal/*therapeutic use ; *Blood Group Incompatibility ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; *Kidney Transplantation ; Plasmapheresis ; Transplantation Conditioning

OBJECTIVEThis review aims to summarize the progress of current clinical studies in ocular angiogenesis treated with anti-vascular endothelial growth factor (VEGF) therapy and to discuss the benefits and challenges of the treatment.

DATA SOURCESPubmed, Embase and the Cochrane Library were searched with no limitations of language and year of publication.

STUDY SELECTIONClinical trials and case studies presented at medical conferences and published in peer-reviewed literature in the past decade were reviewed.

RESULTSAnti-VEGF agents have manifested great potential and promising outcomes in treating ocular neovascularization, though some of them are still used as off-label drugs. Intravitreal injection of anti-VEGF agents could be accompanied by devastating ocular or systemic complications, and intimate monitoring in both adult and pediatric population are warranted. Future directions should be focused on carrying out more well-designed large-scale controlled trials, promoting sustained duration of action, developing safer and more efficient generation of anti-VEGF agents.

CONCLUSIONSAnti-VEGF treatment has proved to be beneficial in treating both anterior and posterior neovascular ocular diseases. However, more safer and affordable antiangiogenic agencies and regimens are warranted to be explored.

Antibodies, Monoclonal, Humanized ; therapeutic use ; Aptamers, Nucleotide ; therapeutic use ; Bevacizumab ; Eye ; blood supply ; drug effects ; pathology ; Humans ; Neovascularization, Pathologic ; drug therapy ; Ranibizumab ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors

Alzheimer Disease ; immunology ; therapy ; Amyloid beta-Peptides ; antagonists & inhibitors ; immunology ; metabolism ; Animals ; Antibodies, Monoclonal ; therapeutic use ; Blood-Brain Barrier ; Brain ; drug effects ; immunology ; Enzyme Inhibitors ; therapeutic use ; Humans

OBJECTIVETo investigate the inhibitory effects of humanized monoclonal antibody-3 (huTNT-3) mediated truncated tissue factor (tTF) on the H(22) hepatoma-bearing mice, and to explore its mechanisms.

METHODSThe coagulation activity of the huTNT-3/tTF fusion protein was detected by clotting assay and clotting factor X (FX) activation test in vitro. Mouse hepatoma cell line H(22) cells were inoculated subcutaneously into mice to establish the mouse models of hepatoma. The mice were randomly divided into two groups to be injected once with huTNT-3/tTF fusion protein or tTF protein labeled with rhodamine B isothiocyanate (RBITC), respectively. The localization of huTNT-3/tTF fusion protein in the mouse hepatoma tissue was analyzed by confocal laser scanning microscopy 24 hour after the injection. Fifteen mice were randomly divided into three groups to be injected with the huTNT-3/tTF fusion protein, tTF protein or phosphate buffered saline (PBS) once, respectively. The tumor size was measured every two days to calculate the tumor volume. Ten days after the injection the mice were sacrificed. Samples of the tumor, heart, livers, spleen, lung, kidney and brains of the mice were taken for histopathological examination.

RESULTSBoth the huTNT-3/tTF fusion protein and tTF protein effectively promoted blood coagulation. Under the conditions of Ca(2+), the coagulation time in the 1.5, 3, 6 µmol/L huTNT-3/tTF groups was (12.90 ± 0.60) min, (10.39 ± 0.40) min and(8.15 ± 0.24) min, respectively, and the coagulation time of the 1.5, 3, 6 µmol/L tTF groups was (14.23 ± 0.46) min, (12.10 ± 0.49) min and (9.83 ± 0.52) min, respectively, the difference between the two groups was not significant (F = 0.145, P = 0.705). The huTNT-3/tTF fusion protein was similar to the tTF protein in the ability of activating FX (t = 0.101, P > 0.05). The confocal laser scanning microscopic analysis showed that RBITC-fluorescence labeled huTNT-3/tTF fusion protein was enriched in the hepatoma tissue. The tumor volume of the huTNT-3/tTF fusion protein group was significantly lower than that of the tTF and PBS groups (both P < 0.001), however, there was not significant difference between the tTF and PBS groups (t = -0.616, P > 0.05). The survival time of the huTNT-3/tTF group was (25.5 ± 2.5) d, significantly longer than that of the PBS group (17.3 ± 1.9) d and the tTF group (18.6 ± 1.9) d, (both P < 0.05).

CONCLUSIONThe huTNT-3/tTF fusion protein retains the coagulation ability and has the capability of targeting to tumor vasculature, and induces thrombosis in the tumor vessels, thus to suppress the growth of hepatoma in the mice.

Animals ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Blood Coagulation ; Carcinoma, Hepatocellular ; blood ; pathology ; therapy ; Cell Line, Tumor ; Factor X ; metabolism ; Liver Neoplasms ; blood ; pathology ; therapy ; Male ; Mice ; Neoplasm Transplantation ; Random Allocation ; Recombinant Fusion Proteins ; therapeutic use ; Thromboplastin ; therapeutic use ; Tumor Burden

OBJECTIVETo explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) transplantation.

METHODSSeventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg x d(-1)) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg x kg(-1) on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction.

RESULTSNo primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 +/- 11 micromol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g x d(-1)) for 3 days. OKT3 (0.5 mg x d(-1)) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued.

CONCLUSIONRejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

Adult ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Creatinine ; blood ; Diabetes Mellitus, Type 1 ; surgery ; Diabetes Mellitus, Type 2 ; surgery ; Female ; Follow-Up Studies ; Graft Rejection ; drug therapy ; Humans ; Immunoglobulin G ; therapeutic use ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; Male ; Middle Aged ; Muromonab-CD3 ; therapeutic use ; Pancreas Transplantation ; Prednisone ; analogs & derivatives ; therapeutic use ; Retrospective Studies

During the past few years, new immunosuppressants, such as tacrolimus, mycophenolate mofetil (MMF) and basiliximab, have been shown to successfully decrease the incidence of acute rejection, possibly acting as potent substrates for safe steroid withdrawal. Therefore, clinical outcome of 3 months steroid withdrawal, while using the above immunosuppressants, was analyzed. Clinical trial registry No. was NCT 01550445. Thirty de novo renal transplant recipients were enrolled, and prednisolone was slowly withdrawn 3 months post-transplantation by 2.5 mg at every two weeks, until 8 weeks. During steroid withdrawal, 10 patients (30.0%) discontinued the protocol and they were maintained on steroid treatment. Among 20 steroid free patients, 8 patients (40.0%) re-started the steroid within 12 months post-transplantation. By the study endpoint, 12 (40%) recipients did not take steroid and survival of patients and grafts was 100%. In conclusion, in kidney transplant patients, 3 months steroid withdrawal while taking tacrolimus, basiliximab and mycophenolate mofetil was not associated with increased mortality or graft loss. Despite various causes of failure of steroid withdrawal during the follow-up period, it is a strategy well advised for kidney transplant recipients with regard to long-term steroid-related complications.
Adult ; Anti-Inflammatory Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Blood Urea Nitrogen ; Cholesterol/blood ; Creatinine/blood ; Female ; Graft Rejection/mortality/*prevention & control ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Kidney Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/analogs & derivatives/therapeutic use ; Prednisolone/*therapeutic use ; Prospective Studies ; Recombinant Fusion Proteins/therapeutic use ; Tacrolimus/therapeutic use

During the past few years, new immunosuppressants, such as tacrolimus, mycophenolate mofetil (MMF) and basiliximab, have been shown to successfully decrease the incidence of acute rejection, possibly acting as potent substrates for safe steroid withdrawal. Therefore, clinical outcome of 3 months steroid withdrawal, while using the above immunosuppressants, was analyzed. Clinical trial registry No. was NCT 01550445. Thirty de novo renal transplant recipients were enrolled, and prednisolone was slowly withdrawn 3 months post-transplantation by 2.5 mg at every two weeks, until 8 weeks. During steroid withdrawal, 10 patients (30.0%) discontinued the protocol and they were maintained on steroid treatment. Among 20 steroid free patients, 8 patients (40.0%) re-started the steroid within 12 months post-transplantation. By the study endpoint, 12 (40%) recipients did not take steroid and survival of patients and grafts was 100%. In conclusion, in kidney transplant patients, 3 months steroid withdrawal while taking tacrolimus, basiliximab and mycophenolate mofetil was not associated with increased mortality or graft loss. Despite various causes of failure of steroid withdrawal during the follow-up period, it is a strategy well advised for kidney transplant recipients with regard to long-term steroid-related complications.
Adult ; Anti-Inflammatory Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Blood Urea Nitrogen ; Cholesterol/blood ; Creatinine/blood ; Female ; Graft Rejection/mortality/*prevention & control ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Kidney Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/analogs & derivatives/therapeutic use ; Prednisolone/*therapeutic use ; Prospective Studies ; Recombinant Fusion Proteins/therapeutic use ; Tacrolimus/therapeutic use