Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program

We retrospectively analyzed results for 154 patients with acquired severe aplastic anemia who received bone marrow transplants between 1993 and 2000 from unrelated donors identified through the Japan Marrow Donor Program. Patients were aged between 1 and 46 years (median, 17 years). Seventy-nine donor-patient pairs matched at HLA-A, -B, and -DRB1 loci, as shown by DNA typing. Among the 75 mismatched pairs, DNA typing of 63 pairs showed that 51 were mismatched at 1 HLA locus (18 HLA-A, 11 HLA-B, 22 HLA-DRB1) and 12 were mismatched at 2 or more loci. Seventeen patients (11%) experienced either early or late graft rejection. The incidence of grade III/IV acute graft versus host disease and chronic graft versus host disease was 20% (range, 7%-33%) and 30% (range, 12%-48%), respectively. Currently, 99 patients are alive, having survived for 3 to 82 months (median, 29 months) after their transplantations. The probability of overall survival at 5 years was 56% (95% confidence interval, 34%-78%). Multivariate analysis revealed the following unfavorable factors: transplantation more than 3 years after diagnosis (relative risk [RR], 1.86; P =.02), patients older than 20 years (RR, 2.27; P =.03), preconditioning regimen without antithymocyte globulin (RR 2.28; P =.04), and HLA-A or -B locus mismatching as determined by DNA typing. Matching of HLA class I alleles and improvement of preparative regimens should result in improved outcomes in patients with severe aplastic anemia who receive transplants from unrelated donors.     

Novel Parameter to Predict Left Ventricular Filling Pressure: Product of Log B-Type Natriuretic Peptide and Ratio of Mitral Inflow Early and Late Diastolic Filling Velocities

Background

Several echocardiographic parameters are currently used to evaluate left ventricular (LV) filling pressure. However, these parameters are not always consistent in the clinical setting. We aimed to determine a novel parameter by multiplying log B-type natriuretic peptide (lnBNP) and the ratio of mitral inflow early and late diastolic filling velocities (E/A) for the prediction of pulmonary capillary wedge pressure (PCWP).

Early apoptosis and cell death induced by ATX-S10Na ( Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ).METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-XL,were decreased in Bax- and p53-independent manner.CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizingphotosensitizer ATX-S10Na (Ⅱ) are mediated by p53-Bax network and Iow levels of Bcl-2 and Bcl-XL proteins.Our results might help in formulating new therapeutic approaches in photedynamic therapy.     

Comparison of serum IgA and IgG antibodies for detecting Helicobacter pylori infection

OBJECTIVE: Although the diagnostic utility of serum IgG antibodies to Helicobacter pylori (H. pylori) is well established, the usefulness of IgA-based tests is less well documented. The aim of this study was to evaluate two commercially available ELISAs, both for IgG and IgA. PATIENTS AND METHODS: Rapid urease test and histology analysis were performed in 183 patients. A patient was considered to be H. pylori-positive when either biopsy test was positive, and considered to be noninfected when both tests were negative. Intestinal metaplasia was determined by dye endoscopy with methylene blue. ELISA testing was performed using the EPI HM-CAP IgG and PP-CAP IgA assays and EIAgen IgG and IgA assays. RESULTS: Sensitivity was 94.7, 93.9, 94.8, and 97.0% for HM-CAP IgG, PP-CAP IgA, EIAgen IgG, and EIAgen IgA, respectively. Although sensitivity was excellent for both IgG and IgA antibodies, specificity of both IgA EIAs was low (PP-CAP 72.6%, EIAgen H. pylori IgA 59.2%). Three of 101 H. pylori-infected patients were PP-CAP positive and HM-CAP negative and four were EIAgen H. pylori IgA positive and EIAgen IgG negative. Of eight noninfected patients in whom intestinal metaplasia was found, PP-CAP IgA results were positive in three of five patients with a HM-CAP IgG negative result and EIAgen IgA was detected in one of four patients with an EIAgen IgG negative result. CONCLUSIONS: Since some patients have IgA positive but IgG negative results, great care should be taken not to underestimate the prevalence of H. pylori infection from the results of IgG serology.     

A case of cancerous familial adenomatous polyposis in urinary bladder due to migration of colonic mucosa through rectovesical fistula

The patient was a 50-yr-old man who had undergone low anterior resection for rectal cancer at the age of 24 yr in 1966. At that time, gastric and colonic polyposis were indicated. Postoperative anastomotic dehiscence occurred and, by 1985, a rectovesical fistula had formed. In 1986, when the patient was 44 yr old, he was examined at our hospital for constriction of the rectum due to the rectovesical fistula. Abdominoperineal excision of rectum and surgical closure of the fistula were performed, and the patient was kept under observation because of a diagnosis of familial adenomatous polyposis. In 1988, when the patient was 46 yr old, early ascending colon cancer was discovered and total colectomy was performed. Then, in December, 1991, gross hematuria was found. Further examination revealed a tumor on the posterior wall of the urinary bladder lumen, and biopsy showed adenocarcinoma. Pelvic recurrence of the rectal cancer was diagnosed, and total pelvic exenteration was performed. There were no distant metastases; histologically, the tumor of the bladder was thought to be due to colonic mucosa of familial adenomatous polyposis that had migrated to the bladder lumen via the rectovesical fistula and had become cancerous.     

Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program

There is little information available regarding the outcome of unrelated bone marrow transplantation (BMT) for non-Hodgkin lymphoma (NHL). Therefore, we retrospectively analyzed the data of 124 patients who underwent unrelated BMT through the Japan Marrow Donor Program (JMDP) between July 1992 and August 2001. The overall survival (OS), progression-free survival (PFS), cumulative incidences of disease progression, and nonprogression mortality at 3 years after BMT were 49.7%, 42.6%, 24.5%, and 32.9%, respectively, with a median follow-up duration of 565 days among survivors. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was 40.9%. Recipient age, previous history of autologous transplantation, and chemosensitivity at transplantation were independent prognostic factors for OS and PFS. The development of grades II-IV acute GVHD was associated with lower incidence of disease progression after transplantation, which suggested the existence of a graft versus lymphoma effect. Unrelated BMT should be considered as a treatment option for patients with high-risk NHL without an HLA-matched related donor.     

A multicenter comparison of nicorandil and diltiazem on serum lipid,apolipoprotein, and lipoprotein levels in patients with ischemic heart disease

Summary The effects of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in 37 patients with ischemic heart disease were examined in a randomized, multicenter study. Nicorandil (n=20, 10–40 mg/day, b.i.d.) and diltiazem (n=17, 60–240 mg/day, b.i.d.) were administered for 12 weeks. Both nicorandil and diltiazem administration showed an effective antianginal effect. Diltiazem administration showed a significant hypotensive action. There were no significant changes in serum lipids, apolipoproteins, and lipoproteins for both nicorandil and diltiazem. There were no significant changes in body weight, uric acid, and fasting blood sugar levels during the test period for both drugs. These data show that nicorandil, like diltiazem, does not have any adverse effects on lipid metabolism and that it is a favorable drug to use as an agent for treating arteriosclerotic heart disease.This paper was presented, in part, at the 3rd Cardiovascular Pharmacotherapy International Symposium, October 15–19, 1989, Kyoto, Japan.     

Susceptibility Alleles for Aberrant B-1 Cell Proliferation Involved in Spontaneously Occurring B-Cell Chronic Lymphocytic Leukemia in a Model of New Zealand White Mice

B-cell chronic lymphocytic leukemia (B-CLL) and autoimmune diseaseare a related event, and genetic factors are linked to both diseases.As B-CLL is mainly of B-1 cell type that participates in autoantibodyproduction, genetically-determined regulatory abnormalities inproliferation and/or differentiation of B-1 cells may determinetheir fate. We earlier found that, in H-2-congenic (NZB × NZW) F1mice, while H-2^d/z heterozygosity predisposes to autoimmunedisease, H-2^z/z homozygosity predisposes to B-CLL. Studiesalso suggested the involvement of non-H-2-linked NZW allele(s) inleukemogenesis. Using H-2-congenic NZW and B10 mouse strains, their F1and backcross progeny, we have now identified three major NZWsusceptibility loci for abnormal proliferation of B-1 cells, which formthe basis of leukemogenesis; one H-2-linked locus on chromosome 17 andthe other two non-H-2-linked loci, each on chromosome 13 andchromosome 17. Each susceptibility allele functioned independently, inan incomplete dominant fashion, the sum of effects determining the extent of aberrant B-1 cell frequencies. The development of leukemia was associated with age-related increase in B-1 cell frequencies in theblood. Thus, these alleles probably predispose B-1 cells to accumulategenetic alterations, giving rise to B-CLL. Potentially importantcandidate genes and correlation of the findings with autoimmune diseaseare discussed.     

A patient with symptomatic osteomalacia associated with Fanconi syndrome

We report a patient with renal tubulointerstitial fibrosis and symptomatic osteomalacia associated with Fanconi syndrome. A 55-year-old woman was hospitalized because of an inability to walk. Beginning approximately 2 years previously, she had experienced gradually worsening pain in the hips, shoulders, and trunk, culminating in a bedridden state. Serum urea nitrogen was 38 mg/dl; creatinine, 2.6 mg/dl; uric acid. 3.6 mg/dl; phosphate, 2.3 mg/dl; and alkaline phosphatase, 2111 IU/l. Urinary β2 microglobulin was 72 331 µg/day. Aminoaciduria, renal glucosuria, and proximal renal tubular acidosis with a normal anion gap were also noted. The patient was diagnosed with Fanconi syndrome. Radiography demonstrated typical Looser zones in the proximal portion of the left and especially the right femoral shaft, and at several other sites. A renal biopsy specimen disclosed severe tubulointerstitial fibrosis with little cellular infiltration. Glomeruli were largely intact. A bone biopsy specimen indicated osteomalacia; no tetracycline labeling could be seen along most trabecular bone surfaces, and the ratio of total osteoid volume to bone volume was increased (71.8%). Bicarbonate administration (9 g/day) gradually lessened most symptoms, permitting ambulation. Calcitriol administration decreased excessive intact-parathyroid hormone emerging after 2 months of acidosis correction. Thus, severe acidosis associated with Fanconi syndrome can induce osteomalacia showing serious skeletal complications, but also responsiveness to bicarbonate therapy.