A mild case of nesidioblastosis with diagnostic and therapeutic difficulty

A female infant with nesidioblastosis who showed mild clinical symptoms is reported. In this patient, insulin levels and insulin to glucose ratios (IRI/G) were often normal. Regular milk feedings supplemented with continuous glucose infusion (0.7-2 mg/kg per min) or oral glucose feedings (4.5 mg/kg per min) prevented hypoglycemia. As leucine-sensitivity was diagnosed at 2 months of age, she was started on diazoxide. This was, however, ineffective, and adverse effects appeared. Subtotal pancreatectomy (95%) was therefore attempted at 5 months of age, and persistent normoglycemia as well as normal growth and development followed up to 3 years after the operation. The pancreas showed characteristic signs of nesidioblastosis. The above clinical observation suggests that a patient with nesidioblastosis whose blood glucose level is easily controllable may develop an unexpected episode of hypoglycemia in the presence of a leucine sensitivity. In such a patient, diazoxide or, when it is of no avail, surgical intervention should promptly be instituted to prevent possible neurologic sequelae induced by hypoglycemia.     

Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1

A new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM). established from the pleural of fusion and bone marrow, respectively, of the same patient. Since I2BM expresses CD20, CD38, and PCA-I antigens, while 12PE has lost CD20. 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE than to 12BM. Thus, a clone, D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myeloma cell line, U266, was negative for D2 antigen. Staining various cell lines by D2 and other antiplasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases except one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-I expression was related to extramedullary invasion. The morphology of the myeloma cells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expression should provide more information about the heterogeneity of myeloma cells.     

Detection of Monocyte Chemotactic and Activating Factor (MCAF) and Interleukin (IL)-6 in Human Seminal Plasma and Effect of Leukospermia on These Cytokine Levels

PROBLEM : To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia. METHODS : Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated. RESULTS : Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 ± 2.75 μg/1) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 ± 0.53 μg/1) and the fertile men (2.78 ± 0.35 μg/1) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 ± 4.49 ng/1) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 ± 1.92 ng/1) and the fertile men (6.94 ± 1.27 ng/1) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma. CONCLUSIONS : These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.     

The novel histamine H2 receptor antagonist FRG-8813 prevents delay of wound repair induced by hydrogen peroxide in a rabbit gastric epithelial cell system

Abstract The effects of a novel histamine H₂ receptor antagonist (FRG-8813) on the restoration process of gastric epithelial wounds were assessed using an in vitro wound healing model. FRG-8813 (1, 10 mol/L) was added to a complete confluent monolayer cell sheet after artificial wounding. The restoration process was analysed by a time-lapse video system and cell migration, proliferation and apoptosis were assessed. Hydrogen peroxide (1, 3 mmol/L) inhibited restoration after wounding by suppressing cell migration and proliferation and induced epithelial cell apoptosis around the wound. The addition of FRG-8813 abolished the hydrogen peroxide-induced retardation and prevented apoptosis, although FRG-8813 itself did not enhance wound healing. FRG-8813 may act as a radical scavenger as well as having an anti-secretory action and may have favourable effects on peptic ulcer healing.     

Natural Killer Activity and Antibody-Dependent Cell-Mediated Cytotoxicity in Multiple Myeloma

Natural killer (NK) activity and antibody-dependent cell-mediatedcytotoxicity (ADCC) were studied by routine methods in 11 patientswith untreated malignant monoclonal gammopathy. NK and/or ADCCactivity was clearly reduced in three patients with advanceddisease. Moreover, sera from some myeloma patients impairedthe ADCC and NK activity. A large quantity of purified monoclonalIgG from one patient appeared to inhibit NK and ADCC activityas did high concentrations of pooled polyclonal immunoglobulinfrom healthy persons. In two of these 11 patients, other malignancieswere diagnosed prior to chemotherapy. One of these patients,who had nonsecretory myeloma, had marked impairment of NK andADCC activity; the other, with IgG myeloma, had normal NK andADCC activity.     

Anthracycline-induced cardiotoxicity in children with malignancies

The anthracyclines (ATC) have been used in the treatment of many pediatric patients with malignancies. Their use, however, has been limited by a serious and potentially irreversible cardiotoxicity. The medical records of pediatric patients with malignancies who received ATC at the Department of Pediatrics, Kyushu University, from January 1985 to December 1994 were reviewed. Among the 120 children with malignancies who received ATC, six patients (5%) developed congestive heart failure, 33 (28%) had subclinical cardiac dysfunction, whereas 81 (66%) showed no evidence of cardiac dysfunction. The incidence of ATC cardiotoxicity increased at higher cumulative doses. The earliest cardiotoxicity, however, was observed in a patient who received 180 mg/m² unassociated with other risk factors, showing the marked individual variations in its development. Children younger than 4 years had a higher incidence of cardiotoxicity compared with those older than 4 years (P < 0.01) and are therefore more vulnerable to ATC cardiotoxicity. Because serial myocardial biopsies and stress testing are not practical in younger children, and radionuclide angiogram is rather costly and not appropriate for frequent evaluation, non-invasive tests such as echocardiography and electrocardiography (ECG) still play the main role for serial cardiac monitoring in these age groups. Radionuclide angiogram should be added as the confirmatory test modality.     

Effective treatment of the anaemia associated with multiple myeloma by recombinant human erythropoietin

We administered recombinant human erythropoietin to an anaemic patient with multiple myeloma (IgD, λ type) who had been dependent on blood transfusions. The recombinant human erythropoietin (60 units/kg) was given intravenously three times weekly and transfusion requirements, haemoglobin level, and reticulocyte responses were monitored. The patient had an increase in haemoglobin level and reticulocyte counts within 14 days, and no longer needed transfusions. No organ dysfunction or other toxic effects were observed. We consider that recombinant human erythropoietin may be a new method to treat anaemia associated with multiple myeloma.