2',5'-Oligoadenylate synthetase activity and T cell subset in the cerebrospinal fluid and peripheral blood of aseptic meningitis.

2',5'-oligoadenylate synthetase activity, which is assumed to be induced by interferon, is reported to be one of the useful markers reflecting interferon activity. The enzyme activity of patients with aseptic meningitis and febrile convulsion were compared in order to evaluate interferon activity as one of the local immuno-defense mechanisms of aseptic meningitis. The surface antigen of mononuclear cells in cerebrospinal fluid and peripheral blood of some patients with aseptic meningitis was also measured. The enzyme activity of patients with aseptic meningitis was 191.4 pmol/dL in the cerebrospinal fluid and 395.8 pmol/dL in the serum during the acute phase, while that of patients with febrile convulsion was 45.2 pmol/dL in the cerebrospinal fluid and 326.0 pmol/dL in the serum. The enzyme activity of the former patients significantly decreased during the recovery phase in both the cerebrospinal fluid and serum. CD3 positive cells in the peripheral blood were 56.3% of the total mononuclear cells during the acute phase and 65.2% during the recovery phase, whereas in the cerebrospinal fluid mononuclear cells, they were 87.1 and 85.5%, respectively. During the acute phase, CD4 positive cells were the predominant T lymphocyte subset in the cerebrospinal fluid cells, while CD8 positive cells were predominant during the recovery phase. The relative proportions of CD4 positive and CD8 positive cells during the acute and recovery phase in the cerebrospinal fluid mononuclear cells were quite high compared to the recovery phase, although that ratio of peripheral blood mononuclear cells was not changed throughout the course. It was concluded that T lymphocytes and increased 2',5'-oligoadenylate synthetase activity in the cerebrospinal fluid may be one of the important components in the local inflammatory process independent of the systemic host defense mechanism in aseptic meningitis.

In vitro proliferation and differentiation of erythroid progenitors of cord blood.

Stem cell factor (SCF) is known to synergize with erythropoietin (EPO) for erythropoiesis in vitro. Clonogenic assay and suspension culture were used to assess the effect of EPO alone or its combination with SCF on the proliferation and differentiation of erythroid progenitors of cord blood. Colony formation, increase in cell count, and cell cycling status for the proliferation as well as expression of Glycophorin A (Gly A) and hemoglobinization as the marker of differentiation were determined with each stimulation. The cell cycle status of the cells in suspension cultures was determined using FACScan after labeling of cells with propidium iodide. Expression of Gly A and degree of hemoglobinization were determined by FACScan and spectrophotometer on the cells plucked from colonies in semisolid culture. Larger increases in cell counts in suspension culture were observed with EPO + SCF after 12 days of inoculation than with EPO alone. Mean doubling time was 14.2 h with EPO + SCF and 22.7 h with EPO alone. The proportion of cells in S and G2 + M phase in day 14 suspension culture was 48% with EPO + SCF and 43% with EPO alone (no significant difference). Mean colony counts per 10(5) nonadherent mononuclear cells were 76 +/- 14 with EPO + SCF and 51 +/- 15 with EPO at day 14 (p < 0.05). The number of macroscopic colonies with > 0.5 mm diameter was 10.7 +/- 1.2 with EPO + SCF and 0.3 +/- 0.5 with EPO (p < 0.05). Percent of Gly A+ cells was 75% for both EPO + SCF and EPO colonies at day 14. Hemoglobin concentration/10(5) cells at day 14 was 0.70 +/- 0.17 microgram with EPO + SCF, and 1.16 +/- 0.32 micrograms with EPO alone (p < 0.05). In conclusion, SCF in the combination with EPO showed a synergistic effect for erythroid proliferation in colony number as well as colony size derived from cord blood, while SCF with EPO decreased hemoglobin synthesis but not Gly A expression at day 14.

Successful hematopoietic reconstitution by transplantation of umbilical cord blood cells in a transfusion-dependent child with Diamond-Blackfan anemia.

A 4-year-old boy with Diamond-Blackfan anemia and a history of multiple transfusions underwent umbilical cord blood transplantation from his HLA-identical female sibling born by vaginal delivery at 38 weeks. The patient was prepared with busulfan, cyclophosphamide and antilymphocyte globulin. Methotrexate and cyclosporin A were given for the prophylaxis of GVHD. Regimen-related toxicity was not observed and successful engraftment occurred, including the erythroid series. No evidence of acute or chronic GVHD has been observed for 14 months after transplantation. This is the first case of successful umbilical cord blood transplantation to a patient with Diamond-Blackfan anemia.

Mean Platelet Volume in Thrombocytopenic, Preterm Infants.

We evaluated the use of mean platelet volume (MPV) as a reliable indicator of bacteremia in neonates. We first established normal MPV values in very low birth weight neonates (< 1 kg and ≥ 1 kg < 1.8 kg, respectively) in the first 47 days of life. We conclude that MPV is not a reliable predictor of sepsis. However, one subset of thrombocytopenic neonates, with birth weights ≥ 1 kg < 1.8 kg was identified with significantly increased MPV (P < 0.05) compared to the age-matched control. In this group, the thrombocytopenia was not associated with sepsis, and the etiology of the decreased platelet count remained to be determined.

Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: a case report and review of the literature.

As patients with glycogen storage disease type I survive longer, cases with hepatic tumor have been increasingly documented. A 16 year old boy with glycogen storage disease type I was evaluated for multiple liver tumors. He was diagnosed on clinical features at 9 months of age and underwent a mesocaval shunt operation at 5 years of age. The biopsy of one of the masses showed focal nodular hyperplasia. This is uncommon in patients with glycogen storage disease type I, compared to those with adenoma or malignant hepatic tumor. The association of a portacaval shunt with focal nodular hyperplasia is significant compared to other tumors. An environment of high estrogen concentration or sex hormone binding globulin accompanied by shunt operation may cause focal nodular hyperplasia to develop in the liver of patients with glycogen storage disease type I.

Fas receptor (CD95)-mediated apoptosis is induced in leukemic cells entering G1B compartment of the cell cycle.

Apoptotic cell death induced by cross-linking Fas receptor (FasR/CD95) has been investigated in human acute myelogenous leukemia (AML) cells. FasR-mediated growth inhibition and DNA fragmentation could be induced in certain cases of AML. Interestingly, when DNA synthesis and G1 -> S transition in the cell cycle were enhanced by interleukin-3 or granulocyte-macrophage colony-stimulating factor, Fas-insensitive blast cells acquired cellular susceptibility toward FasR-mediated growth inhibition. To further evaluate an association between the Fas-R-mediated action and a specific phase of the cell cycle, a FasR+ leukemic cell line, MML-1, was established from a patient with AML. The morphologic feature of dying cells and DNA fragmentation indicated that FasR cross-linking induced apoptotic cell death in MML-1 cells. Cell cycle arrest in G1A phase with the treatment of phorbol 12-myristate 13-acetate or thymidine rendered MML-1 cells resistant to FasR-mediated apoptosis without downregulation of surface FasR expression. However, S-phase arrest with 5-fluorouracil could neither enhance nor inhibit FasR-mediated apoptosis. Simultaneous DNA/RNA quantification analysis revealed the selective loss of cells in G1B compartment, accompanied by the increase of apoptotic nuclei in sub-G1 fraction. These findings suggested that FasR-mediated apoptotic signals could be transduced into cells in G1B compartment and G1A -> G1B transition might augment the induction of FasR-mediated apoptosis.

Pertussis immunization with acellular vaccines in Ghanaian children.

In the present study, the persistence of antibodies to pertussis antigens was assessed in 51 Ghanaian children immunized with one of two acellular vaccines and one whole cell vaccine in early infancy. The effect of a booster dose 1 year after primary immunization was also examined. Antibody titres to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were measured 1 month and 1 year after primary immunization and 1 month after the booster dose. Although geometric titres (GMTs) to FHA were significantly higher in the two types of acellular vaccinees in the whole cell vaccinees 1 month after primary immunization, GMTs to FHA and PT after 1 year were not significantly different in the three groups. Geometric mean titres to PT and FHA following the booster dose were significantly higher in the acellular vaccinees than in the whole cell vaccinees. Seropositivity rates to PT and FHA in the acellular vaccinees, which were more than 93.3% 1 month after primary immunization, ranged from 50.0 to 77.8% after 1 year. In conclusion, the acellular vaccines did not produce higher antibody levels than the whole cell vaccine 1 year after primary immunization. The booster dose was essential to maintaining sufficient seropositivity to pertussis antigens.

Impact of primary health care on child morbidity and mortality in rural Ghana: the Gomoa experience [corrected].

The impact of a combination of PHC intervention activities on child survival, growth, morbidity and mortality was assessed in three selected rural communities (Gomoa Fetteh, Gomoa Onyadze/Otsew Jukwa and Gomoa Mprumem) in the Central Region of Ghana from 1987 to 1990. EPI, provision of basic essential drugs and supplies for the treatment of common childhood diseases, treatment of the sick child, growth monitoring, health education, provision of antenatal services, family planning, training and supervision of Community Health Workers, disease surveillance and special studies were the major PHC strategies used to improve the health of the child and the pregnant woman in the three communities. These activities in their totality have had significant impact on morbidity and mortality in children under five and on maternal mortality in children under five and on maternal mortality over the study period 1987 to 1990. Although malaria, acute respiratory infections and diarrhoea diseases continue to be major causes of childhood morbidity, deaths due to these diseases have dramatically declined. Measles and other vaccine preventable diseases no longer contribute significantly to childhood morbidity and mortality. Infant and under five mortality have been reduced from 114.6/1000 and 155.6/1000 live births to 40.8/1000 and 61.2/1000 live births respectively. The crude birth rates however, remain almost the same over the five year period (43 to 48/1000 pop.) but crude death rates have declined (11 to 12.4/1000 pop.).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody response to measles immunization in rural Ghanaian infants.

We investigated optimal age of measles immunization in infants aged 3-11 months in rural villages of Ghana, and determined seroconversion rate in the same infant population following further attenuated measles vaccination with Schwarz vaccine. The prevalence of passively acquired antibody was 11 per cent in infants younger than 6 months, 10 per cent in infants 6 months old, and 3 per cent in infants 7 months old or older. Seroconversion rates in each age group were less than 50, 87, and 92 per cent, respectively. We then immunized 47 7-month-old infants. The seroconversion rate was 92 per cent in this group. There were no clinical adverse effects due to the vaccination. We conclude that measles vaccination could be administered effectively at the age of 7 months with an excellent seroconversion rate.

A randomized controlled trial of two acellular pertussis-diphtheria-tetanus vaccines in primary immunization in Ghana: antibody responses and adverse reactions.

Two acellular pertussis vaccines combined with diphtheria and tetanus toxoids (APDT vaccines) were compared with a whole cell PDT (WCPDT) vaccine in primary immunization in Ghana. One is a liquid vaccine which is used for general immunization in Japan and the other is a freeze-dried vaccine newly developed as a heat-stable vaccine. Eighty-nine infants were recruited in the study. Sixty-eight who completed three doses of the immunization were assessed for immunological responses. Twenty-one dropped out because of sickness or moving from the study area. A total of 242 vaccinations in 89 infants were followed up for adverse reactions. Geometric mean titres (GMTs) to filamentous haemagglutinin in the two APDT vaccinees were significantly higher than in the WCPDT recipients. GMTs to pertussis toxin, diphtheria and tetanus toxoids were not significantly different among the three groups. Seropositive rates to pertussis antigens, tetanus and diphtheria toxoids were 94.4 to 100% in the two APDT vaccines. Systemic reactions within 7 days of inoculation were similarly low in the three groups, but significantly fewer infants had local reactions after either of the two APDT vaccines than after the WCPDT vaccine.

Histological, immunohistochemical, and chromosomal studies on non-adrenal neuroblastomas without increased excretion of catecholamines and their metabolites in urine.

We reviewed our records for the last 10 years and found three of the 36 patients with neuroblastoma did not excrete significantly increased quantities of catecholamine metabolites in urine. All of these tumors were histologically characterized by small round cells and possessed a few dense core granules on the electron microscopic examination. All of them were reacted with anti-neuron-specific enolase (NSE) antibodies, OKB2, PI153/3 monoclonal antibodies (MoAbs). The HNK-1, BA-1, and SJ-9A4 MoAbs reacted with two out of three. One of them demonstrated a reciprocal translocation involving the short arm deletion of chromosome 1. This multidisciplinary study has been helpful in making more accurate diagnoses for neuroblastoma without classical clinical characters.

Antibody response to measles immunization at seven months old in rural Ghanaian infants

A serological study was carried out in three rural communities in Southern Ghana in order to determine the optimal age for measles immunization. The live hyperattenuated measles vaccine (Schwarz strain) was inoculated subcutaneously into infants aged three to eleven months. The maternal measles antibodies in the infants started decreasing after 7 months; while the seroconversion rate after the immunization was increasing after 6 months. Forty seven infants were given the measles vaccines at the age of 7 months. The seroconversion rate was 91.5 per cent. There were no side effects. These results indicate that measles immunization can be administered effectively at the age of 7 months

Development of autologous specific reactivity to human neuroblastoma.

Antigenic analysis of neuroblastoma cells was performed by autologous typing and indirect immunofluorescent test combined with absorption tests. Serum of a patient with neuroblastoma before treatment showed weak reactivity with cultured autologous neuroblastoma cells, while serum obtained from the same patient 3 months after chemotherapy exhibited strong reactivity with the same indicator cells. This reactivity was absorbed with neither cultured autologous fibroblasts nor allogeneic tumor cells from seven neuroblastoma and two melanoma patients. In addition, cultured hematopoietic cells from two subjects, normal fetal and adult tissues also failed to remove the reactivity. This reactivity, however, was completely removed by the absorption with the cultured autologous neuroblastoma cells and the homogenate, suggesting that these neuroblastoma cells may express tumor specific antigen(s), located on neither normal cells in any stage of the development nor other malignant cells, although the cells and tissues we tested may not be adequate to confirm this.

[Studies on adequate intervals of cisplatin administration to ameliorate cisplatin-induced nephrotoxicity].

Experimental studies were designed in order to ameliorate cisplatin-induced nephrotoxicity. Cisplatin was injected intravenously into DS mice at a dose of 5.0 mg/kg. Plasma platinum levels declined in a biphasic fashion and were undetectable after 5 days post-infusion. Renal platinum levels decreased in the same manner as the plasma levels and revealed detectable plateau levels 5 days after single injection. Cisplatin was administer once a week for 3 consecutive weeks; serial plasma and renal platinum levels and BUN were measured 7 days after each injection. The results showed that there was no significant change in the levels of plasma platinum and BUN but that the renal platinum levels increased progressively (1.6 +/- 0.3, 3.1 +/- 0.4, 4.8 +/- 2.7 micrograms/g wet wt.). After another 6 successive weeks of cisplatin administration, 55% of mice died. The renal platinum levels and BUN of the survivors were highly increased. The renal tissue revealed histologically acute renal failure. However the renal concentration of platinum was decreased to a low level of 1.1 +/- 0.4 micrograms/g wet wt. 4 weeks after the third injection. These results suggested that cisplatin-induced nephrotoxicity could be ameliorated by adequate intervals of cisplatin administration.

[Basic and clinical studies of ceftizoxime suppositories in the pediatric field].

Pharmacokinetic and clinical studies of ceftizoxime suppository (CZX-S) were performed in 10 children with the following results. CZX-S attained a peak serum concentration of 6.85 micrograms/ml 30 minutes after dosing with the drug 5.6 mg/kg (one suppository of CZX-S contains 250 mg of CZX in potency). The mean 6-hour urinary excretion rate in 4 children was 18.9%. The subjects consisted of 8 patients comprising 1 with pharyngitis, 3 with tonsillitis, 1 with gingivitis and 3 with urinary tract infection. The overall effect of CZX-S was "excellent" in 5 patients and "good" in 3, with an effectiveness rate of 100%. No side effects ascribable to CZX-S were encountered in any of the patients. A few patients complained of discomfort after the first or second insertion of the drug. However, the discharge of the suppository was as infrequent as 1.5% of the total 133 insertions. CZX-S is therefore well tolerated for clinical use in children. It is concluded that the unique suppository formulation of CZX-S is useful in the treatment of infections in children with heavy psychophysiologic disorders and in children who cannot take oral drugs because of severe vomiting.