Intravitreal injection of bevacizumab for choroidal neovascularisation associated with pathological myopia.

AIM: To assess the efficacy and safety of an intravitreal injection of bevacizumab (Avastin(R)) for myopic choroidal neovascularisation (mCNV). METHODS: Intravitreal bevacizumab (1 mg) was injected into eight eyes of eight patients with mCNV in this non-randomised, interventional case series. The best-corrected visual acuity (BCVA) was measured and the optical coherence tomography (OCT) and fluorescein angiography findings were examined before and after treatment. The minimum follow-up time was 3 months. RESULTS: The mean BCVA was 0.26 before treatment and 0.51 at the last visit (p = 0.009). The BCVA improved to two or more lines in six eyes (75%) and remained the same in two eyes (25%). Leakage from the mCNV on fluorescein angiography decreased in seven eyes (87.5%). The choroidal neovascularisation area on fluorescein angiography (p = 0.049) and the foveal thickness on OCT images decreased significantly (p = 0.027) after the treatment. No major complications developed. CONCLUSION: Intravitreal injection of bevacizumab seems to be an effective and safe treatment for mCNV.

Primary pericardial mesothelioma detected by gallium-67 scintigraphy.

We present a case report of a 73-yr-old woman with progressive systemic sclerosis who showed extensive pericardial uptake of 67Ga by scintigraphy. At autopsy, primary pericardial mesothelioma was found.

Attenuation of experimental proliferative vitreoretinopathy by inhibiting the platelet-derived growth factor receptor.

PURPOSE: The work from numerous laboratories has led to the idea that the growth factors such as platelet-derived growth factor (PDGF) contribute to proliferative vitreoretinopathy (PVR) in experimental models of the disease, as well as in humans. In support of this idea, the authors have previously reported that cells unable to respond to PDGF had a greatly reduced PVR potential, compared with PDGF-responsive versions of the same cells. The goal of this study was to test the effect of blocking the output of the PDGF receptor in an experimental model of PVR. METHODS: Polymerase chain reaction-based site-directed mutagenesis was used to generate point mutations in the human PDGF alpha receptor (alphaPDGFR) cDNA, which resulted in single amino acid substitutions. These changes were based on naturally occurring point mutations in the c-kit receptor tyrosine kinase, which suppresses the function of wild-type c-kit. A truncated alphaPDGFR was also made, in which the receptor ended just after the juxtamembrane domain. As with the point mutants, truncated receptors have been shown to block the action of wild-type receptors. All the alphaPDGFR mutants were introduced into cells that naturally express the wild-type receptor, and the PDGF-dependent output of the resultant cell lines was determined. In addition, the PVR potential of cell lines expressing the mutant receptors was tested in a PVR rabbit model. RESULTS: Although the mutants differed in their ability to suppress PDGF-dependent signaling of the wild-type receptor, each mutant effectively blocked cell cycle progression. When expressed in rabbit conjunctival fibroblasts, a cell line that effectively induces PVR, the mutant receptors blocked PVR to various degrees. The most effective receptor was the truncated mutant. CONCLUSIONS: These data suggest that the alphaPDGFR plays an important role in PVR. In addition, these mutant receptors appear to have therapeutic potential for prevention of this blinding disease.

Characterization of new non-T, non-B acute lymphoblastic leukemia cell lines: analysis of surface antigens by quantitative cellular radioimmunoassay and flow cytometry.

Two novel acute lymphoblastic leukemia (ALL) cell lines, HOON and HYON, have been established from patients with non-T, non-B ALL. The cell lines have been characterized and shown to express phenotypic markers on non-T, non-B ALL. By indirect immunofluorescence and flow cytometry they express Ia and common ALL (CALLA) antigens and are reactive with monoclonal antibodies BA-1, BA-2 and OKT-9. However, the cells do not express detectable amounts of B1 antigen or of cytoplasmic mu chain, which are markers of pre-B cells. Quantitation of Ia and CALLA antigens on HOON and HYON cell lines using a cellular radioimmunoassay revealed that both cells bind high levels of anti-Ia antibodies, 110 X 10(4) molecules per cell, and low levels of anti-CALLA antibodies, 7 X 10(4) molecules per cell. Although both HOON and HYON carry equivalent amounts of Ia on their surface, only the former is a good stimulator of the one-way mixed lymphocyte reaction.

Bilateral basal ganglial necrosis after allogeneic bone marrow transplantation in a child with Kostmann syndrome.

A 6-year-old girl underwent allogeneic BMT from a matched sibling donor for the treatment of Kostmann syndrome. She suddenly became drowsy on day 30 after BMT, and lost consciousness 2 days later. Cranial CT scan showed symmetrical lesions suggesting bilateral necrosis in the basal ganglia. Clinical and laboratory investigations failed to reveal any evidence of neurometabolic disease.

Donor leukocyte infusion after allogeneic bone marrow transplantation was not effective for relapsed rhabdomyosarcoma.

A 10-year-old boy with metastatic rhabdomyosarcoma had an HLA-identical sibling and received an allogeneic BMT. Recurrence was detected in the BM as the only site of treatment failure 12 months after BMT. Donor leukocyte infusion (DLI) was chosen as salvage therapy. Although sufficient cells (a total of 29.7 x 10(7)/kg) were infused, no signs of acute GVHD nor BM aplasia occurred and the patient died of disease progression 9 months after DLI.

Adsorption and pharmacokinetics of cyclosporin A in relation to mode of infusion in bone marrow transplant patients.

Two main factors that affect the pharmacokinetics of cyclosporin A (CsA) during 24-h durable intravenous (DIV) administration have been reported, namely physiological changes after bone marrow transplantation, and blood sampling through indwelling lines. In addition, it has been found that infusion sets made of polyvinyl chloride (PVC) markedly adsorb CsA. We conducted in vitro adsorption studies of CsA on infusion sets, and the administration routes that are used in the treatment of patients with bone marrow transplantation. We also examined the effects of administration route on CsA pharmacokinetics in clinical practice. The in vitro adsorption study using 30-mm segments of lumen from commercially available infusion sets showed that the degree of CsA adsorption per area of lumen made of PVC was significantly higher than that in those made of polyethylene (PE) or polybutadiene (PB), which showed no adsorption of CsA. Due to its adsorption, use of infusion sets made of PVC resulted in about a 40-50% loss of CsA dose, which affected the pharmacokinetic parameters during 24-h DIV, while those made of PE and PB did not. The use of non-PVC infusion sets should allow for accurate monitoring of CsA results, and provide cost benefit in the treatment of bone marrow transplantation.

Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children.

Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m2), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m2). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n = 1), interstitial pneumonitis (n = 1) and veno-occlusive disease of the liver (n = 1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69 +/- 15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well.

Clinical and prognostic implications of bone lesions in childhood leukemia at diagnosis.

We studied 168 children with acute lymphoblastic leukemia (ALL) and 57 with acute nonlymphoblastic leukemia (ANLL) by retrospectively analyzing clinical symptoms, bone or joint involvement, and hematological findings to verify the clinical features and prognosis of children with acute leukemia who showed radiographic bone changes at the time of diagnosis. Of these, 36 with ALL (21.4%) and 6 with ANLL (10.5%) had symptoms referable to the bones or joints. Thirteen patients (7.7%) with ALL showed bone lesions radiographically. Phenotypically, 12 of the 13 had common ALL, 8 were incorrectly diagnosed and had received treatment for osteomyelitis or juvenile rheumatoid arthritis for 1 to 7 months prior to diagnosis of ALL. Leukocyte count was nearly normal with few or no blasts, and anemia and thrombocytopenia were mild or absent in all patients. Twelve of them remained in a complete remission for 26 to 148 months. Our data suggest that children with bone lesions related to acute leukemia exhibit clinical features that mimic infectious or collagen disease at diagnosis, and may belong to a subgroup of ALL with a better prognosis.

Complete epiretinal membrane separation in highly myopic eyes with retinal detachment resulting from a macular hole.

PURPOSE: Epiretinal membranes (ERMs) in highly myopic eyes may result in macular holes and subsequent retinal detachment. However, removing friable, thin ERMs from detached retinas is often difficult. We report the efficacy of a diamond-dusted silicone cannula in the removal of ERMs from detached retinas. METHODS: Seventeen consecutive highly myopic eyes (16 patients) with retinal detachment underwent pars plana vitrectomy with gas tamponade. Peeling of the ERM adjacent to the macular hole was performed using either conventional tools (n = 11) or a diamond-dusted silicone cannula (n = 6). The rate of complete membrane peeling and the effect of membrane removal on the anatomic success rate were compared between groups. RESULTS: Retinal reattachment occurred in 13 (92.9%) of the 14 eyes in which the ERM was removed completely; redetachment occurred in the other three eyes, with further surgical interventions in two eyes. The reattachment rate was significantly higher (P = .005) when ERM removal was complete than when there was residual ERM. In the initial surgery, the ERM was successfully removed in all 6 eyes (100%) in the diamond-dusted silicone cannula group and in 5 of 11 eyes (45.5%) in the conventional group (P = .041); the reattachment rate was 100% in the diamond-dusted silicone cannula group and 45.5% in the conventional group (P = .005). When a second surgery was performed, the use of the diamond-dusted silicone cannula was also better than conventional tools for removing the residual ERMs, resulting in retinal reattachment. CONCLUSION: In highly myopic eyes with a macular hole and subsequent retinal detachment, complete ERM removal is closely related to successful retinal reattachment. The diamond-dusted silicone cannula appears to be more effective than conventional tools for removing ERM and may increase the anatomic success rate. Because of the limitations of a small series, a prospective, randomized trial is required to confirm the current beneficial results of using a diamond-dusted silicone cannula.

Surgical removal of submacular hemorrhage using tissue plasminogen activator and perfluorocarbon liquid.

PURPOSE: To assess the result of surgical removal of submacular hemorrhage by using tissue plasminogen activator and perfluorocarbon liquid. METHODS: In 22 consecutive patients (22 eyes), subretinal hemorrhage associated with age-related macular degeneration, which involved the fovea and completely obscured the choroidal vascular pattern, was treated by pars plana vitrectomy. The hemorrhages were liquefied with tissue plasminogen activator, squeezed into the vitreous cavity with perfluorocarbon liquid, and then evacuated. RESULTS: Efficacy of the procedure was judged by the best postoperative corrected visual acuity, which was 20/100 or better in 16 eyes (73%). Submacular hemorrhage recurred in four (18%) eyes, epiretinal membrane formed in three (14%) eyes, and retinal detachment occurred in three (14%) eyes. Best-corrected final visual acuity was improved postoperatively in 18 (82%) of the 22 eyes, unchanged in three (14%) eyes, and decreased in one (5%) eye, final visual acuity was 20/200 or better in 15 eyes (68%) and limited in other eyes by subretinal hemorrhage of greater than 30 days' duration or subfoveal neovascularizations. CONCLUSIONS: Use of tissue plasminogen activator and perfluorocarbon liquid in surgical removal of submacular hemorrhage may improve the outcome of surgery by reducing surgically induced retinal damage.

Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration.

PURPOSE: To report the results of three methods of foveal translocation in the presence of subfoveal choroidal neovascular membrane resulting from age-related macular degeneration. METHODS: We treated 51 eyes of 51 consecutive patients with subfoveal choroidal neovascular membranes resulting from age-related macular degeneration with one of three techniques of foveal translocation surgery: foveal translocation with partial retinotomy (n = 6), limited translocation (n = 9), and translocation with 360-degree retinotomy (n = 36). All patients were followed for at least 6 months postoperatively. The size of the choroidal neovascular membrane and the amount of foveal displacement, the best-corrected visual acuity, and complications were recorded preoperatively and postoperatively. RESULTS: The mean distance of the foveal translocation was greater in the 360-degree retinotomy group (3340 microm) than in the partial retinotomy (1060 microm, P <.001) and the limited translocation groups (1120 microm, P <.001). A final visual acuity of 20/200 or better was achieved in two eyes (33%) in the partial retinotomy group, seven eyes (78%) in the limited translocation group, and 23 eyes (64%) in the 360-degree retinotomy group. The final visual acuity improved by 0.2 logarithm of minimal angle of resolution (logMAR) unit or more in one eye (17%), one eye (11%), and seven eyes (19%), respectively. The final visual acuity was maintained within 1 line in zero eyes, five eyes (56%), and 19 eyes (53%), respectively. A retinal detachment developed postoperatively in five eyes (83%), zero eyes (0%), and 15 eyes (42%), respectively. CONCLUSIONS: A significant number of patients improved or maintained best-corrected visual acuity after translocation with 360-degree retinotomy, and limited translocation, whereas translocation with 360-degree retinotomy is suitable for larger choroidal neovascular membranes because it resulted in the greatest foveal displacement among the three translocation procedures.

Hereditary hemorrhagic telangiectasia with growing pulmonary arteriovenous fistulas followed for 24 years.

A 47-year-old man was admitted for follow-up of an abnormal chest x-ray. He had a history of epistaxis and a brain abscess and a family history of pulmonary arteriovenous fistulas. Physical examination showed clubbed fingers and telangiectasia of the tongue. Laboratory data revealed evidence of polycythemia and hypoxia. Contrast echocardiography and pulmonary perfusion scintigraphy were suggestive of a right-to-left shunt. From the oxygen tension and content of blood taken at cardiac catheterization, the shunt ratio was calculated to be 57.8%. Multiple bilateral pulmonary arteriovenous fistulas were confirmed by angiography, and the patient was diagnosed as having hereditary hemorrhagic telangiectasia. A review of x-ray films taken over a 24-year period demonstrated that the fistulas in both lungs had been increasing gradually in size at different rates. A right lower lobectomy relieved the hypoxia, but the patient died unexpectedly on the twelfth postoperative day. There was no evidence of fistula rupture on chest film, but no autopsy was performed.

Comparative biochemical studies of carotenoids in catfishes.

The carotenoids of 12 species of Siluriformes fishes (eight families) were investigated from a comparative biochemical point of view. The patterns of carotenoids in catfishes belonging to the family Siluridae were quite different from those of the other seven families of catfishes (Bagridae, Amblycipitidae, Clariidae, Plotosidae, Ictaluridae, Callichthyidae and Malapteruridae). 7, 8-Dihydro-beta-carotene; 7, 8, 7', 8'- and 7, 8, 9, 10-tetrahydro-beta-carotene; (3R)-7', 8'-dihydro-beta-cryptoxanthin; 7, 8-dihydrolutein A; 7, 8-dihydrolutein B; parasiloxanthin; 7', 8'-dihydroparasiloxanthin; and 4 or 4'-hydroxyparasiloxanthin were characteristic carotenoids found in only one family, Siluridae, and these carotenoids accounted for 24-60% of total carotenoids. In catfishes belonging to the other seven families except Siluridae, the carotenoid patterns were very similar and the most predominant carotenoid was zeaxanthins (23-56%).

Pearls in the management of submacular hematoma.

Subretinal hemorrhage (SRH), complicated by choroidal neovascularization such as age-related macular degeneration, often reduces central vision in middle-aged patients. Although the visual results of SRH removal by surgery seem to have improved recently, the efficacy has not yet been confirmed in a prospective, controlled fashion. Therefore, it cannot be stated with certainty that surgery for SRH is more beneficial than the natural course of the disease. However, we believe surgery is beneficial in selected patients. Herein, we describe our technique for the surgical removal of SRH. The development of safer, more effective techniques should further improve patient outcomes.

[Serum prostate specific antigen for the early detection of prostate cancer in outpatients of internal medicine].

Screening was performed on 102 patients aged 60 years or older who visited the Outpatient Department of Internal Medicine in Tane General Hospital between June 1994 and May 1995. Of those screened, 36 patients (35.3%) had elevated prostate specific antigen (PSA) values, and 20 of them visited the Urological Department, and underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for further screening. Of the 16 patients who underwent ultrasound guided biopsies of the prostate, 7 patients were found to have prostate cancer. Therefore, the cancer detection rate was 6.9%, which was about 4 times higher than that of mass-screening examinations previously reported in the Japanese literature. These findings suggested that the screening using PSA in outpatients of Internal Medicine may be useful for the early detection of prostate cancer.

[Treatment results of bone marrow transplantation in Kyushu Cancer Center. Bone Marrow Transplantation Team].

Twenty children with various hematological malignancies (nine with acute lymphoblastic leukemia, eight with acute non-lymphoblastic leukemia, two with chronic myelogenous leukemia, one with malignant lymphoma and one with 7-monosomy) and four with severe aplastic anemia were treated with allogeneic or syngeneic bone marrow transplantation (BMT) between September 1977 and September 1988. Eleven patients are surviving currently and ten are disease free 8 to 51 months after BMT. Conditioning regimen consisted of total body irradiation (TBI) and cyclophosphamide in twenty patients. Two patients did not receive TBI. Graft failure was observed in five patients and complete recovery of recipient marrow was seen in two of them. Eleven patients developed acute graft-versus-host disease (GvHD) with grade I-II in eight patients. Three patients suffered from chronic GvHD. Seven patients with acute leukemia relapsed and all but one died of leukemia. Early death occurred in two undergone BMT in poor clinical conditions. Performance status in 100% in surviving patients except one. Efforts to improve these results are that BMT should be considered early in the course of their disease for patients who are at risk for relapse with conventional chemotherapy and improved conditioning regimens to reduce leukemia relapse after BMT for patient with the second or subsequent remission.

[Prognosis of childhood mediastinal lymphoma].

Between 1973 and 1989, 16 children with non-Hodgkins lymphoma (NHL) with a mediastinal mass (MM) were treated at our institution with multi-agent chemotherapy and radiotherapy. They also received central nervous system (CNS) prophylaxis including intrathecal methotrexate administration (14 cases) and cranial irradiation (7 cases). Twelve were boys and 4 girls. Median age was 11 +/- 3. One patient died of air way obstruction one day after admission. Fourteen of 15 patients entered into complete remission (CR) and one patient partial remission. Five remains in CR 7 to 175 months after diagnosis (median 76 months). Nine patients relapsed in the bone marrow (3 cases), CNS (3), testicles (1), neck lymph node (1) and bones plus kidneys (1). Of these, 7 patients died within 13 months after initial relapse. The disease free survival (DFS) and overall survival of all patients were 27% and 33%, respectively. Analysis of the prognostic factors among patients with MM+ -NHL revealed that the serum LDH level below 1,000IU/l was a good prognostic sign. Other factors such as age, stage, initial WBC count, size of MM and response of the MM to the initial treatment did not correlate with DFS. Because of its rarity and the poor treatment result, we need more aggressive treatment program by a multiinstitutional study for MM+ -NHL.

[Treatment results of acute nonlymphocytic leukemia in childhood--Kyushu Yamaguchi Children's Cancer Study Group].

Seventy-three children with acute nonlymphocytic leukemia (ANLL) have been treated with ANLL-85 and ANLL-88 protocol at Kyushu-Yamaguchi Children's Cancer Study Group between June, 1985 and February, 1993. Ten boys and 10 girls (0y4m-16ylm) were treated with the ANLL-85 protocol. The complete remission (CR) rate was 75% and the 5-year event free survival (EFS) was 20 +/- 9%. It was terminated because of frequent early relapse (within 6 months after CR). Thirty-four boys and 19 girls (0y3m-17ylm) were treated with the ANLL-88 protocol. The CR rate was 85% and the 5-year EFS was 32 +/- 7%. Early relapse rate with ANLL-88 was lower than that of ANLL-85, however 9 cases relapsed after terminating therapy. Although bone marrow transplantation (BMT) from related donors during the first CR was effective in ANLL-88, EFS was not improved. Recognition of risk factors and appropriate chemotherapy regimens with or without the support of stem cell transplantation may be necessary to cure children with ANLL.

[Bone marrow transplantation for a patient with ALL from her 75-year-old mother using cryopreserved bone marrow cells].

We report a 42-year-old woman with acute lymphoblastic leukemia who received allogeneic bone marrow transplantation (BMT) in the first remission from her 75-year-old, HLA-identical, MLC-non-reactive mother. Considering the difficulty to obtain a sufficient number of bone marrow cells from such an old donor, we harvested the cells (2.31 x 10(8)/kg) on day -37 and cryopreserved them until use. BMT was performed on June 3rd, 1993 after conditioning regimen with total body irradiation, high-dose AraC and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxisis was attempted by cyclosporin A and short-term methtrexate. Her hematopoietic recovery was favorable with no signs and symptoms of GVHD as far as day 218.