Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study.

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients' disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity.

Significant correlations between the flow volume of patent ductus venosus and early neonatal liver function: possible involvement of patent ductus venosus in postnatal liver function.

BACKGROUND: The biochemical features of portosystemic venous shunt with high flow volume are hypergalactosaemia, hyperammonaemia, prolonged blood coagulation time, and raised serum bile acid concentration. The ductus venosus remains open with shunt flow in most neonates for a certain period after birth. However, the effects of blood flow through the ductus venosus on neonatal liver function remain unclear. OBJECTIVE: To elucidate the effect of patency of the ductus venosus on liver function in early neonates. METHODS: Subjects were divided into three groups by gestational age (group I, 29-32 weeks; group II, 33-36 weeks; group III, 37-41 weeks). The shunt flow volume through the ductus venosus was examined serially using ultrasonography, and correlations between flow volume and liver function in the respective groups were calculated during the first week after birth. RESULTS: Group I had a higher flow volume and later functional closure than the other two groups. Plasma ammonia and serum total bile acid concentrations correlated with flow volume in groups I and II, and blood galactose and galactose 1-phosphate concentrations correlated significantly with flow volume in group III. Percentage hepaplastin also correlated significantly with flow volume in all groups, but plasma vitamin K concentration did not in any group. CONCLUSIONS: Patent ductus venosus has a considerable effect on crucial liver functions such as ammonia detoxification, blood coagulation, and regulation of serum total bile acid concentration in early neonates.

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights.

UNLABELLED: Fifteen appropriate-for-date premature low-birthweight infants with cystic periventricular leukomalacia (PVL) were studied. The infants were stratified into three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500 g, and 1500 g or greater. Reported and new risk factors for PVL were compared with control patients for all patients and each birthweight group. Hypocarbia was significantly related to cystic PVL, especially in infants with birthweight 1000 g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants with birthweight less than 1000 g due to therapy or prematurity. In the group with birthweight less than 1000 g, the proportion of cystic PVL infants on continuous intra-arterial blood-pressure monitoring tended to be lower than the controls, with an almost significant difference (p = 0.05). The duration of tocolysis was significantly longer in the cystic PVL infants than in the controls when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a significant difference or a tendency of difference was demonstrated only after stratifying the birthweight. For others, the difference became insignificant after stratification. Assessing risk factors after stratifying by birthweight or degree of prematurity is therefore useful. CONCLUSION: The results suggest that hypocarbia should be avoided to prevent cystic PVL, especially in infants with birthweight of 1000 g or greater, continuous intra-arterial blood-pressure monitoring may be important in infants with birthweight less than 1000 g, and fetal status should be monitored carefully when the duration of tocolysis is prolonged, especially in infants with birthweight of 1500 g or more.

Changes of neurotransmitters in the brainstem of patients with respiratory-pattern disorders during childhood.

We examined neuropathologically and immunohistochemically the respiratory centers in the brainstem of two patients with Joubert syndrome (JS), three patients with congenital central hypoventilation syndrome (CCHS) and a patient with apneustic breathing (prolonged inspiratory pause) due to unknown etiology. Immunoreactivity (IR) of tryptophan hydroxylase (TPH) was decreased in the dorsal raphe nuclei of two patients with JS compared with age-matched controls, as well as in two patients with Dandy-Walker malformation. The two JS patients showed vermian defect and elongated cerebellar peduncles, and peculiar vascularities in the midline of the whole brainstem were also noted in one of these patients. These findings, as a whole, confirm that the midline structures of brainstem are disordered both structurally and functionally in JS, conceivably resulting in respiratory patterns and psychomotor deficits. IR of serotonin 1A receptor showed no significant changes in the medulla oblongata of these patients, however. In the parabrachial complex, IR of substance P was increased in two patients with CCHS, and one with apneustic breathing. IR of tyrosine hydroxylase was also increased in the latter. The brainstem of these patients showed reactive astrogliosis. These findings suggest preceding hypoxic episodes as well as an increased activity in the parabrachial complex which plays an important role in conducting the driving force to the medullary respiratory neurons from ascending sensory pathways.

Changes in urinary 6beta-hydroxycortisol/cortisol ratio after birth in human neonates.

OBJECTIVE: Urinary 6beta-hydroxycortisol/cortisol (6beta-OHF/C) ratio was measured in human neonates to assess the CYP3A enzyme activity. METHODS: Urinary 6beta-OHF/C ratio was determined on the day of birth in 94 neonates including those born prematurely. In addition, changes in the ratios after birth were also determined in 81 neonates. RESULTS: On the day of birth, a significant positive correlation was found between urinary 6beta-OHF/C ratios and gestational age (r = 0.476) and birth weight (r = 0.283). There was no gender difference in the urinary 6beta-OHF/C ratios in human neonates. Furthermore, delivery modes such as cesarean section and vaginal delivery did not appear to affect the urinary 6beta-OHF/C ratio. The mean ratio of urinary 6beta-OHF/C observed in 39 mature neonates (more than 37 weeks of gestational age) was higher than that observed in adults (16.5 vs 9.9). Within 5 days after birth, the ratio rapidly decreased to less than that in adults. In contrast, the mean ratio of urinary 6beta-OHF/C observed in 42 premature neonates (under 37 weeks of gestational age) was significantly lower than that observed in mature neonates (5.3 vs 16.5) and was virtually unchanged during the 14-days after birth. Therefore, no significant difference was observed in the mean ratio of urinary 6beta-OHF/C between mature and premature neonates at 5 days after birth. CONCLUSION: From these results, it was concluded that on the day of birth, mature neonates might possess a higher activity of CYP3A enzyme compared with premature neonates, and that the CYP3A enzyme activity in mature neonates might be promptly changed at an early stage after birth.

Spinal arachnoid cyst in a newborn infant.

A male infant was born with asphyxia following a prolonged breech delivery at 39 weeks of gestation. He had a chylohemothorax from birth. Soon after birth he exhibited flaccid paraplegia with an absence of deep tendon reflexes in the lower extremities. At 17 days of age, magnetic resonance imaging (MRI) disclosed a hypodense area in the thoracic cord between C7 and Th4 in T1-weighted images, and spinal sonography revealed an echo-free space compressing the spinal cord in the same region observed with MRI. A spinal cyst was removed surgically at 24 days of age. The cyst was confirmed by pathology to be a true arachnoid cyst between C7 and Th4. The cause of this cyst may have been a spinal cord injury during the perinatal period.