Management of acute metabolic decompensation in maple syrup urine disease: a multi-center study.

BACKGROUND: Therapeutic modalities in acute metabolic decompensation in maple syrup urine disease (MSUD) are variable, and outcomes of each therapeutic measure have been known only individually. Factors that affect neurological outcome are not clear. METHODS: A questionnaire was sent throughout Japan to each pediatrician treating any of the 42 MSUD patients. RESULTS: Necessary information was available for 13 patients through the questionnaire, and through a publication for one patient. In nine of the 14 patients episodes of metabolic decompensation developed in the neonatal period. In the other five, the onset of disease was delayed until infancy or later. In the nine patients with neonatal onset, a pretreatment level of plasma leucine greater than 40 mg/100 mL or a duration of altered level of alertness longer than 10 days was associated with a poor neurological outcome. The therapeutic measures employed included intravenous infusion of glucose and electrolyte solution or hypertonic glucose and electrolyte solution, exchange transfusion, peritoneal dialysis, a large dose of thiamine and intravenous hyperalimentation. All patients had survived the episodes and were alive at the time of the survey. Five of the nine patients with neonatal onset have developed neurological sequelae to varying degrees. Episodes of metabolic decompensation in infancy or thereafter did not affect, or only minimally affected, the neurological outcome. CONCLUSION: Therapeutic goals to improve neurological outcome are to shorten the duration of the altered level of consciousness, and to minimize the peak plasma leucine level as much as possible.

Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis.

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.

Serological and clinical characteristics of measles vaccine failure in Japan.

In 1991, in Fukuoka, Japan, a measles outbreak occurred in which we observed 15 cases of measles vaccine failure (MVF). We examined these patients both clinically and serologically. Seven of them, with a response pattern of an early rise in and attainment of a high hemagglutination inhibition (HI) antibody titre, were considered to be secondary vaccine failures (EH group). Eight others showed a normal (relatively late rise and low titre) HI antibody response pattern and were considered to be primary vaccine failures (LL group). In both MVF groups, measles-specific IgM antibody was detected by enzyme immunoassay. The EH group had a milder rash than did the LL group and unvaccinated controls. We believe they had an immunological memory that modified the clinical manifestations of measles. Two cases of encephalitis were observed in the EH group; both patients recovered without sequelae. These data suggest that the mere presence or absence of IgM antibody is not sufficient to differentiate primary from secondary MVFs. A two-dose measles vaccination scheme should be recommended to secure a booster effect, because immunity is waning in the population in which the measles vaccination rate is not high enough and in which natural measles still exists.

Human macrophage colony-stimulating factor levels in cerebrospinal fluid.

Macrophage colony-stimulating factor (M-CSF) levels in the cerebrospinal fluid of 14 patients with meningitis and of 14 patients suffering from a disease other than meningitis were measured using an enzyme-linked immunosorbent assay. All four bacterial meningitis patients had M-CSF levels in the cerebrospinal fluid which exceeded 1540 U/ml, and the mean value was 3333 +/- 1481 U/ml. The mean M-CSF level in the cerebrospinal fluid of the ten aseptic meningitis patients was 393 +/- 175 U/ml, which was higher than that of patients who suffered from a disease other than meningitis (179 +/- 90 U/ml) (P < 0.01). There was no clear correlation between the M-CSF levels and the numbers of white blood cells, granulocytes, or monocytes in the cerebrospinal fluid. These elevated M-CSF levels were thought to be of a local origin, since most patients with high M-CSF levels in the cerebrospinal fluid had relatively low M-CSF levels in the serum.

Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection.

Gamma delta T cell receptor-positive cells (gamma delta T cells) have recently been implicated to play a role in the protection against infectious pathogens. Serial studies on gamma delta T cells in 14 patients with salmonella infection have revealed that the proportions of gamma delta T cells (mean +/- SD: 17.9 +/- 13.2%) in salmonella infection were significantly increased (P less than 0.01) compared with 35 normal controls (5.0 +/- 2.6%) and 13 patients with other bacterial infections (4.0 +/- 1.4%). Expansion of gamma delta T cells was more prominent in the systemic form (28.9 +/- 10.8%) than in the gastroenteritis form (10.5 +/- 7.9%) of salmonella infection (P less than 0.01). Most in vivo-expanded gamma delta T cells expressed V gamma 9 gene product. Increased activated (HLA-DR+) T cells were observed in all the six patients with the systemic form and four of the seven with gastroenteritis form. Especially in the six with systemic form, gamma delta T cell activation was significantly higher than alpha beta T cell activation at the early stage of illness (P less than 0.01). When peripheral blood lymphocytes from normal individuals were cultured with live salmonella, gamma delta T cells were preferentially activated and expanded and most of them expressed V gamma 9. Purified gamma delta T cells also responded to live salmonella in vitro. The present study suggests that human gamma delta T cells play a role in the protection against salmonella infection in vivo.

[Ofloxacin in the treatment of infection caused by Salmonella paratyphi A].

We reported a case of salmonellosis treated with ofloxacin (OFLX) which showed excellent clinical and bacteriological effect in a 22 year-old Japanese male with Salmonellosis paratyphi A. He had stayed in India from Sept. 6, 1990 to Oct. 13, 1990. On Oct. 25, 1990, he complained of a high fever and headache. On Oct. 29, he was admitted to our hospital and was diagnosed as Salmonellosis paratyphi A by the blood culture. He was treated with 2.0 g/day of chloramphenicol (CP) for 7 days, but the clinical efficacy was not sufficient. Therefore, we added 900 mg/day of OFLX for 10 days. He was treated successfully with them, the temperature became on the 2nd day. No side effect and no changes of laboratory data were observed and no recurrence was observed clinically and bacteriologically for three months after his discharge.

[A case of Plasmodium vivax malaria with findings of DIC].

We reported a rare case of Plasmodium vivax malaria who showed findings of disseminated intravascular coagulation (DIC). A 50-year-old Japanese male was sent to our hospital with the diagnosis of Plasmodium vivax malaria on the 26th of April, 1990. He had stayed in the Solomon Islands from Oct. 1987 to Dec. 1989, and had febrile episodes during his stay in the island. On April 18, 1990, he complained of a high fever with chills, and showed the same episodes on the 20th, 22th and was diagnosed as malaria. He was treated successfully with the sulfadoxine 500 mg and pyrimethamine 25mg (Fansidar), following the normal temperature on the 4th day and disappearance of malarial parasites in the peripheral blood smear on the 6th day. Interestingly, he had thrombocytopenia and a high titer serum level of fibrin degradation product (FDP) supporting the questionable diagnosis of DIC. Even on the 12th day after improved thrombocytopenia by treatment with Gabexate (FOY), the serum level of FDP, D-dimer and thrombin-nati-thrombin (TAT)III complex still remained at high titer levels. One month later he was readmitted for a relapse of Plasmodium vivax malaria, when he showed thrombocytopenia but the serum level of FDP, D-dimer, TAT III complex and PM.alpha 2 PI complex were normal levels. We concluded that the thrombocytopenia and the high titer of FDP at his first admission was a manifestation of DIC.

Detection of granulocyte-macrophage colony-stimulating factor in cerebrospinal fluid of patients with aseptic meningitis.

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cerebrospinal fluid from 14 infants and children with meningitis and 6 patients who suffered other diseases besides meningitis was measured by our sensitive enzyme linked immunosorbent assay for GM-CSF. The minimal detection level of GM-CSF was 40 pg/ml. Six of 9 patients (67%) with aseptic meningitis had detectable GM-CSF in cerebrospinal fluid and the concentrations of GM-CSF ranged from 49 to 114 pg/ml (mean 72 pg/ml), whereas none of 5 patients with bacterial meningitis or 6 patients with other diseases besides meningitis had detectable GM-CSF levels. There was no clear correlation between the GM-CSF levels in cerebrospinal fluid and the leukocyte count in either peripheral blood or cerebrospinal fluid, or the concentration of protein or glucose in cerebrospinal fluid.

Thrombocytopenia: a complication of Kawasaki disease.

Thrombocytopenia was observed in 10 (2.0%) of 486 children with Kawasaki disease. In nine of the ten, the minimal platelet count of 94,000 +/- 38,000 (SD)/mm3 was seen on day 6.8 +/- 2.2 (SD) of illness and the platelet counts were elevated to the normal level in 1-2 weeks. Thrombocytopenia in the nine appeared to be caused via coagulation-mediated platelet consumption, while the remaining child was diagnosed as having idiopathic thrombocytopenic purpura. One of the two who had severe coagulation-mediated thrombocytopenia of less than 50,000/mm3 developed coronary aneurysms persisting over 1 year.

The synergistic contribution of macrophages and antibody to protection against Salmonella typhimurium during the early phase of infection.

The contribution of phagocytes and antibody to protection against Salmonella typhimurium during the early phase of infection in mice was analysed. Following intravenous injection, most of the bacteria were trapped in the liver and spleen within 10 to 60 min and killed within 6 h; surviving organisms began to multiply in these tissues after 24 h and reached a maximum at 5 to 7 d. The transient killing phase was abrogated by treatment with carrageenan, a macrophage blocker, but not by whole-body X-irradiation. These observations suggest that carrageenan-sensitive, but radio-resistant macrophages play an important role in the early phase of the infection. Actively immunized mice showed accelerated trapping and killing; the protection observed at the early stage of infection in immunized mice could be passively transferred to normal mice, whereas carrageenan-treated mice did not kill the bacterial even after receiving immune serum. It seems that the synergistic action of macrophages and antibody provided the main initial primary defence in immune animals.

Enhanced elimination of Listeria monocytogenes at the site of delayed footpad reaction.

The protective activity against a challenge infection with Listeria monocytogenes was investigated at the site of a delayed footpad reaction in mice immunized with viable or killed listeria. Delayed footpad reactivity was induced only in mice immunized with viable bacteria. Rapid and marked elimination of challenge bacteria was observed only at the site of reaction in mice immunized with viable bacteria but not in mice immunized with killed bacteria. Macrophage migration inhibitory activity was observed equally in both groups of mice. These results suggest that the delayed footpad reaction contributes directly to the elimination of bacteria irrespective of macrophage migration inhibitory activity.