A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan.

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

Immunopathophysiological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen.

We recently discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome-like (TSS-like) exanthematous disease (NTED), which is induced by a superantigen, TSS toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). Here, we analyzed the activation and the response of TSST-1-reactive Vss2(+) T cells in NTED patients during the acute and recovery phases and in asymptomatic infants exposed to MRSA. In the acute phase, Vss2(+) T cells were anergic to stimulation with TSST-1 and underwent marked expansion, but by 2 months after disease onset, their numbers had declined to about 10% of the control level. Although the percentage of Vss2(+) T cells in the ten asymptomatic neonatal MRSA carriers was within the control range, these individuals could be divided into two groups on the basis of Vss2(+) T-cell activation. Vss2(+)CD4(+) T cells from three of these infants (Group 1) highly expressed CD45RO and were anergic to TSST-1, whereas in the other seven asymptomatic neonatal MRSA carriers (Group 2), these cells expressed CD45RO at the control level and were highly responsive to stimulation with TSST-1. The serum anti-TSST-1 IgG Ab titer was negligible in the four NTED patients in the acute phase and the three asymptomatic neonatal MRSA carriers in Group 1, but it was high in the seven asymptomatic carriers in Group 2. We suggest that maternally derived anti-TSST-1 IgGs helps to suppress T-cell activation by TSST-1 and protects infants from developing NTED.

[Analysis of air pollution and prevalence rate of allergic diseases among elementary school children in Kawaguchi and Hatogaya city].

Kawaguchi and Hatogaya City are located on the northern edge of Tokyo. We analysed between air pollution and prevalence rate of allergic diseases among elementary school children in this area. A prevalence rate of allergic diseases in 1996 May and June was as follows; bronchial asthma 13.5%, atopic dermatitis 24.5%, allergic rhinitis and/or conjunctivitis 22.8%, urticaria 12.4%, food allergy 7.8% and drug allergy 2.2%, respectively. Air pollution of this area was analysed to check the levels of nitrogen dioxide (NO2), sulfur dioxide (SO2) and suspended particulate matters (SPM). NO2 pollution was relatively high in urban area, and SPM pollution was especially high around the highways. SO2 pollution was lower than the environmental standard. No relationship was found between the prevalence rate of bronchial asthma, atopic dermatitis, allergic rhinitis and/or conjunctivitis and air pollution, but it was found that these diseases are slightly related to population density (p < 0.1, p < 0.01, p < 0.1, respectively).

Sudden death due presumably to internal use of methamphetamine.

A 26-year-old male was found naked and excited in the backyard of his neighbor's house. He was carried to a nearby hospital, and returned home with his family, but took a sudden turn for the worse and died. In a judicial autopsy, the ethanol concentration of blood was found to be 0.58 milligrams, and methamphetamine (MA) was detected in his blood by thin-layer chromatography. The concentration of MA in his blood was 4.38 mumol/dl, higher than the fatal level. The amount of MA in his stomach was 5.8 mg (34.58 mumol/100 g), indicating that he ingested MA by internal use. Among the autopsy cases of acute MA poisoning reported in Japan, hyperesthesia is known to last 1-3 h before death, whether the administration is by intravenous injection or orally. But the present case is quite unusual, as the death followed 6 h or more of hyperesthesia. This was attributed to the patient's combined intake of alcohol with MA, as it is known to decrease the mortality in mice.

Comparative study of intraneuronal polyglucosan bodies in brains from patients with Lafora disease and aged dogs.

We compared intraneuronal polyglucosan body (PGB) in brains from two patients diagnosed as having Lafora disease and from 18 aged dogs (age range: 10 to 22 years, various breeds). PGBs appeared as various-sized spheroids intensely stained with periodic acid-Schiff (PAS) in both humans and aged dogs. Immunohistochemistry with a monoclonal antibody raised against human polyglucosan showed positive staining of the PGBs. Ultrastructurally, PGBs in both humans and aged dogs were composed of fibril-like structures 4 to 20 nm wide. Electron-dense material formed the central cores of the fibrils, but was also scattered in their peripheral areas. The fibril-like structures were intensely stained upon application of the Thiéry procedure. Immunoelectron microscopy showed that the fibril-like structures were specifically labeled with gold particles. The histological, immunohistochemical and ultrastructural features of the PGBs in humans and aged dogs were quite similar.

Foamy cells associated with phagocytosis of glutaraldehyde-treated red blood cells and red cell membranes.

In order to clarify the mechanism for the formation of foamy cells (macrophages with foamy appearance) associated with increased erythrophagocytosis, we tried to reproduce these cells in mice by subcutaneous injection of intact red blood cells (RBCs), OsO4-treated RBCs (Os-RBCs), glutaraldehyde-treated RBCs (G-RBCs), or isolated red cell membranes, and time-course observation was done by light and electron microscopy. Foamy cells were induced by the latter two methods. Within the macrophages, G-RBCs were fragmented into spherules by newly formed small vacuoles, and with time these spherules lost their hemoglobin content transforming into small vacuoles with translucent matrix. In most of these vacuoles, red cell membrane structure was discernible adjacent to the phagocytic vacuole. Such macrophages containing abundant small vacuoles appear foamy in light microscopy. Foamy cells induced by injection of red blood cell membranes were positive for lipid stains and contained abundant laminated membrane structures in electron microscopy. These results suggest that the foamy cells related with increased erythrophagocytosis are heterogeneous with respect to their pathogenesis and cellular inclusions, and proteinaceous constituents resistant to intracellular digestion are also responsible for the occurrence of foamy cells.

Foamy cells in itp spleens and in granulomas induced by murine platelets, commercialized phospholipids, and erythrocyte membrane. Histological and ultrastructural studies.

A large number of foamy cells were noted in the spleens from fourteen ITP patients, and two patients who received a large amount of platelet rich plasma. Using the unlabelled immunoperoxidase method, these foamy cells were shown to contain platelet antigen. Platelets in varying stages of intracellular digestion, from intact-appearing forms to myelin-like materials, were disclosed in foamy cells. Foamy cells were experimentally induced in granulomas by subcutaneous injection of platelets with or without accompanied administration of steroid, the platelets reacted with anti-murine platelet antibody, commercialized phospholipids (PE, PC, SM, PS, and the mixture of them), and the red blood cell membrane. The foamy cells induced by the subcutaneous injection of platelets are similar to those in the spleens of ITP patients. The lipid in foamy cells is chiefly derived from the membrane phospholipid of injected platelets. Concentric myelin-like materials were also noted in the foamy cells after injection of erythrocyte membrane. The myelin-like materials in these foamy cells are similar to those appearing in macrophages following injection of PC and SM. This suggests that these phospholipids derived from cell membrane are more resistant to intracellular digestion by lysosomal enzymes. We conclude that the foamy appearance of the cordal macrophage in ITP spleens results from incomplete intracellular degradation of platelet membrane.