Depressed levels of interferon-gamma and HLA-DR+CD3+ T cells in infants with transient hyperferritinemia.

Familial hemophagocytic lymphohistiocytosis (FHL), which typically has its onset during infancy, is uniformly fatal if not treated. It therefore requires prompt therapeutic intervention. Although hyperferritinemia has been emphasized as a useful marker for FHL, some nonfatal cases in infants with spontaneous remission also manifest with hyperferritinemia. However, distinguishing them is difficult because initial clinical features of these infants are similar. The authors encountered 14 infants with hyperferritinemia (serum ferritin >674 ng/mL), which normalized within 3 weeks following a benign clinical course. The authors compared the levels of HLA-DR+CD3+ T-cell subsets and interferon-gamma (IFN-γ) in the peripheral blood between these infants and FHL cases: one of the authors' own patients and others from the literature. Serum IFN-γ was not detected in infants with hyperferritinemia. Moreover, levels of HLA-DR+CD3+ T cells were extremely depressed. In contrast, serum IFN-γ was elevated and HLA-DR+CD3+ T cells were not depressed in FHL. Measurement of activated T cells and serum IFN-γ might help differentiate FHL in febrile infants with transient hyperferritinemia.

Hereditary spherocytosis in 3 children coexisting with UDP-glucuronyl transferase 1A1 deficiency.

Simultaneous presence of hemolytic anemia and bilirubin UDP-glucuronosyltransferase deficiency is a possible cause of misdiagnosis. Seven-year-old and 17-year-old brothers and a 15-year-old sister consecutively suffered from aplastic crises. Although few spherocytes were present, the siblings and their mother had diagnoses of hereditary spherocytosis with flow cytometric analysis of eosin-5'-maleimide-labeled red blood cells in addition to osmotic fragility test. However, inappropriately high values of bilirubin compared with mild hemolysis persisted. Further analysis of UDP-glucuronyltransferase 1A1 revealed all 3 siblings were heterozygous for A(TA)7TAA-P229Q. We report here the importance of careful evaluation of mild hereditary spherocytosis masking UDP-glucuronyltransferase 1A1 deficiency.

Split notochord syndrome with congenital unilateral Horner's sign.

A 2-year-old boy exhibited congenital right Horner's sign and right finger, wrist, and elbow flexion arthrogryposis. He had dyspnea and feeding difficulty 12 hours after birth. Radiologic examination revealed a thoracoabdominal intestinal tube and mediastinal cystic lesion at the right side, with vertebral anomaly at the cervical level. Histopathologically, the intestinal tube was diagnosed as bowel duplication. Because the mediastinal lesion could not be resected surgically, no histopathological diagnosis was made. Embryologically, the combination of transdiaphragmatic duplication, mediastinal cystic lesion, anterior spina bifida, and hemivertebra suggested notochord malformation. The diagnosis was split notochord syndrome, an extremely rare embryological malformation syndrome. Congenital unilateral Horner syndrome often has unknown etiology. In this case, cervical vertebral anomalies and mediastinal cystic lesion implied a compressed nerve root, resulting in Horner syndrome and right finger, wrist, and elbow flexion joint contracture. Split notochord syndrome should be included in differential diagnosis of congenital unilateral Horner syndrome.

Usefulness of plasma brain natriuretic peptide levels in predicting dobutamine-induced myocardial ischemia.

Plasma brain natriuretic peptide (BNP) levels have been associated with left ventricular dysfunction and acute myocardial infarction. Although natriuretic peptide responses have been linked to exercise-induced myocardial ischemia, it is not known whether BNP levels predict dobutamine-induced myocardial ischemia. The aim of this study was to determine whether elevations in BNP levels immediately before or after dobutamine-induced stress are associated with echocardiographic myocardial ischemia. Plasma BNP was measured before and after stress during dobutamine-stress echocardiography in 317 patients (aged 68 +/- 11 years; 46% women) who had creatinine <1.5 mg/dl and did not have valvular disease. Ischemia, as assessed by blinded echocardiographic interpretation, was noted in 31 patients (10%). In univariable analyses, prestress BNP was predictive of echocardiographic ischemia (rates of ischemia according to tertiles of BNP 4%, 9%, and 16%, chi-square for trend = 8, p = 0.0059). The change in BNP levels with dobutamine stress was not associated with ischemia. In multivariable analyses, after adjusting for age, gender, and left ventricular ejection fraction, BNP before and after stress remained predictive of ischemia (1 SD increase in the log of resting BNP adjusted odds ratio 2.0, 95% confidence interval 1.3 to 3.0, p = 0.002). In this pilot study, resting BNP was predictive of dobutamine-induced ischemia. Future work is needed to confirm these findings.

[Appropriate use of rapid diagnostic testing for influenza].

To determine a more timely acquisition of accurate results for influenza patients, a rapid diagnostic testing for influenza were studied on 877 pediatric patients performed during the 2002-2003 flu season in our hospital. Of these, 337 patients were finally diagnosed as influenza based on the test results and treated with antiviral agents, amantadine or oseltamivir. Ten (29%) of the 34 patients whose tests were negative within 12 hours after onset became positive over 12 hours after onset. On the other hand, diagnoses based on antigen tests over 12 hours after onset were reliable because all 13 patients first confirmed negative were unchanged when tested afterward. These 10 patients missed the opportunity to take antivirals early, which possibly caused them to have significantly longer (p = 0.0003) febrile duration and higher frequency of admission (p < 0.0001) than the 106 patients first confirmed positive within 12 hours after onset. Days from onset until starting antivirals (mean 1.4 days), the febrile duration (mean 2.7 days) and frequency of hospitalization (20.5%) of the 219 patients who tested positive over 12 hours after onset were significantly worse (p < 0.0001, p < 0.0001 and p = 0.0406, respectively) than those of patients testing positive within 12 hours after onset (mean 0.2 days, mean 1.7 days and 11.3%, respectively). The febrile duration (mean 2.3 days) of the patients confirmed positive even over 12 hours, but within 48 hours, of onset was tolerable but significantly longer (p < 0.0001) than that of patients confirmed positive within 12 hours after onset. The frequency (19.6%) of hospitalization of the patients confirmed positive even over 12 hours, but within 48 hours, of onset was not significantly different from that of patients confirmed positive within 12 hours after onset. These results suggested that over 12 hours but within 48 hours after onset of illness is the best period for the rapid diagnosis to correctly determine whether a patient should be treated with antiviral agents based on the result.

Diffusion-weighted imaging in preclinical Leigh syndrome.

We report on a preterm Japanese male baby with Leigh syndrome, i.e., intrauterine growth restriction, central apnea, and feeding difficulty. These signs improved at 41 weeks of corrected age. At that time, brain magnetic resonance imaging revealed increased signal in diffusion-weighted imaging in the parietal white matter, bilaterally and symmetrically not respecting vascular territory or boundaries. However, clinical improvement deterred us from further investigation. About 3 months later, he manifested frequent ictal apnea with myoclonic seizures and deterioration of consciousness to semicoma. Subsequent diffusion-weighted imaging revealed increased signal in the bilateral symmetric thalamus, internal segments of the globus pallidus, substantia nigra, and pontine tegmentum. Laboratory investigation indicated remarkable elevation of lactate levels in cerebrospinal fluid. The diagnosis was of Leigh syndrome. We think this is the first reported case of Leigh encephalopathy with transient abnormality of diffusion-weighted imaging of the white matter before apparent clinical onset. Leigh syndrome should be included in the differential diagnosis of abnormality of diffusion-weighted imaging in white matter without apparent clinical signs.

Quantitative analysis of left atrial function during left ventricular ischemia with and without left atrial ischemia: a real-time 3-dimensional echocardiographic study.

Left atrial (LA) systolic and diastolic function were analyzed in an animal model of acute left ventricular ischemia with LA ischemia by proximal left circumflex coronary artery occlusion or without LA ischemia by midleft anterior descending coronary artery occlusion (7 sheep in each group). LA pressures and LA volumes were simultaneously recorded using a catheter and real-time 3-dimensional echocardiography, respectively. LA stroke volume represented 63% of left ventricular stroke volume during left anterior descending coronary artery occlusion, but only 32% during left circumflex coronary artery occlusion. This animal study with 3-dimensional echocardiographic determination of absolute LA volumes demonstrated dramatic depression of LA function during proximal left circumflex coronary artery occlusion as compared with left anterior descending coronary artery occlusion.

Plant-specific microtubule-associated protein SPIRAL2 is required for anisotropic growth in Arabidopsis.

In diffusely growing plant cells, cortical microtubules play an important role in regulating the direction of cell expansion. Arabidopsis (Arabidopsis thaliana) spiral2 (spr2) mutant is defective in directional cell elongation and exhibits right-handed helical growth in longitudinally expanding organs such as root, hypocotyl, stem, petiole, and petal. The growth of spr2 roots is more sensitive to microtubule-interacting drugs than is wild-type root growth. The SPR2 gene encodes a plant-specific 94-kD protein containing HEAT-repeat motifs that are implicated in protein-protein interaction. When expressed constitutively, SPR2-green fluorescent protein fusion protein complemented the spr2 mutant phenotype and was localized to cortical microtubules as well as other mitotic microtubule arrays in transgenic plants. Recombinant SPR2 protein directly bound to taxol-stabilized microtubules in vitro. Furthermore, SPR2-specific antibody and mass spectrometry identified a tobacco (Nicotiana tabacum) SPR2 homolog in highly purified microtubule-associated protein fractions from tobacco BY-2 cell cultures. These results suggest that SPR2 is a novel microtubule-associated protein and is required for proper microtubule function involved in anisotropic growth.

Determinants of LV diastolic function during atrial fibrillation: beat-to-beat analysis in acute dog experiments.

Left ventricular (LV) diastolic function during atrial fibrillation (AF) remains poorly understood due to the complex interaction of factors and beat-to-beat variability. The purpose of the present study was to elucidate the physiological determinants of beat-to-beat changes in LV diastolic function during AF. The RR intervals preceding a given cardiac beat were measured from the right ventricular electrogram in 12 healthy open-chest mongrel dogs during AF. Doppler echocardiography and LV pressure and volume beat-to-beat analyses were performed. The LV filling time (FT) and early diastolic mitral inflow velocity-time integral (E(vti)) were measured using the pulsed Doppler method. The LV end-diastolic volume (EDV), peak systolic LV pressure (LVP), minimum value of the first derivative of LV pressure curve (dP/dt(min)), and the time constant of LV pressure decay (tau) were evaluated with the use of a conductance catheter for 100 consecutive cardiac cycles. Beat-to-beat analysis revealed a cascade of important causal relations. LV-FT showed a significant positive linear relationship with E(vti) (r = 0.87). Importantly, there was a significant positive linear relationship between the RR interval and LV-EDV in the same cardiac beat (r = 0.53). Consequently, there was a positive linear relationship between LV-EDV and subsequent peak systolic LVP (r = 0.82). Furthermore, there were significant positive linear and negative curvilinear relationships between peak systolic LVP and dP/dt(min) (r = 0.95) and tau (r = -0.85), respectively, in the same cardiac beat. In addition, there was a significant negative curvilinear relationship between dP/dt(min) and tau (r = -0.86). We have concluded that the determinants of LV diastolic function in individual beats during AF depend strongly on the peak systolic LVP. This suggests that the major benefit of slower ventricular rate appears related to lengthening of LV filling interval, promoting subsequent higher peak systolic LVP and greater LV relaxation.

Quantitative estimation of myocardial salvage after primary percutaneous transluminal coronary angioplasty in patients with angiographic no reflow.

Angiographic Thrombolysis in Myocardial Infarction (TIMI) flow grade