A population-based study identifies an association of THBS2 with intervertebral disc degeneration.

OBJECTIVE: To clarify the genetic mechanisms underlying intervertebral disc degeneration (IDD), we examined the associations between single-nucleotide polymorphisms (SNPs) and indicated as coefficient of interaction term (IDD) in a general population in Japan. METHODS: This was a cross-sectional study. In 1,605 participants, C2-3 to L5/S1 in the total spine magnetic resonance imaging (MRI) were evaluated using the Pfirrmann's scoring system. Disc scores of 4 and 5 were defined as IDD. Eight SNPs in eight genes associated with IDD were examined at each disc level, considering the non-genetic risk factors of age, sex, and body mass index (BMI). RESULTS: The highest odds ratio was found for rs9406328 in the THBS2 gene at disc level T12-L1 (OR 1.27, 95%CI 1.05 to 1.53), and this association was strengthened after adjustment for age using logistic regression (OR 1.37, 95%CI 1.12 to 1.67). Among participants aged <50 years and 50-59, the average IDD score in those with 2 risk alleles of rs9406328 was markedly higher than in those with 0 or 1 risk allele, and the difference is much wider than the elderly participants. It indicates the genetic effect of rs9406328 is stronger in the younger age groups. Finally, multiple linear regression analyses of the association between rs9406328 and IDD, adjusted for age, sex, and BMI at each disc level, showed a statistical interaction between age and the number of risk alleles at C7-T1, T3-4 and T4-T5 as well as T12-L1. CONCLUSION: CONCLUSION: The association between rs9406328 in THBS2 and IDD was replicated. The contributions of genetic and environmental factors to IDD differed by disc level.

Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

OBJECTIVE: The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. METHODS: We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. RESULTS: DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). CONCLUSION: This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort.

Prevalence and progression of radiographic ossification of the posterior longitudinal ligament and associated factors in the Japanese population: a 3-year follow-up of the ROAD study.

SUMMARY: The prevalence of radiographic cervical ossification of the posterior longitudinal ligament (OPLL) in 1,562 Japanese from a population-based cohort was 1.9 %. The presence of OPLL showed a significant association with the femoral neck bone mineral density (BMD), presence of diffuse idiopathic skeletal hyperostosis (DISH) and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects. INTRODUCTION: The purpose of this study was to clarify the prevalence and progression of radiographic OPLL and the associated factors, using the population-based cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: In the ROAD study, 1,690 participants underwent X-ray examination of the entire spine and both knees. Radiographic OPLL, lumbar spondylosis, knee osteoarthritis and DISH were diagnosed by a single, well-experienced orthopaedic surgeon. An interviewer-administered questionnaire and tests for anthropometric measurements were administered, and the BMDs of the lumbar spine and proximal femur were determined. A new OPLL case was considered if heterotopic ossification in the posterior longitudinal ligament was absent at baseline but present during follow-up. Progression was defined as an increase in the maximum length or width of the ossification at follow-up over that at baseline. RESULTS: Radiographic OPLL was detected in 30 (17 men, 13 women) of 1,562 individuals who underwent X-ray examination of the cervical spine (prevalence = 1.9 %). Its prevalence was significantly higher in men than in women (p = 0.007), but no association with age was observed. In a logistic regression analysis, OPLL showed a significant association with the femoral neck BMD, presence of DISH and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects. CONCLUSION: This population-based study clarified the prevalence of radiographic OPLL in the Japanese population as well as its progression. OPLL showed significant association with plasma pentosidine levels, BMD and DISH.

Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study.

OBJECTIVES: The purposes of this study were to investigate the prevalence and distribution of intervertebral disc degeneration (DD) over the entire spine using magnetic resonance imaging (MRI), and to examine the factors and symptoms potentially associated with DD. DESIGN: This study included 975 participants (324 men, mean age of 67.2 years; 651 women, mean age of 66.0 years) with an age range of 21-97 years in the Wakayama Spine Study. DD on MRI was classified into Pfirrmann's system (grades 4 and 5 indicating DD). We assessed the prevalence of DD at each level in the cervical, thoracic, and lumbar regions and the entire spine, and examined DD-associated factors and symptoms. RESULTS: The prevalence of DD over the entire spine was 71% in men and 77% in women aged <50 years, and >90% in both men and women aged >50 years. The prevalence of an intervertebral space with DD was highest at C5/6 (men: 51.5%, women: 46%), T6/7 (men: 32.4%, women: 37.7%), and L4/5 (men: 69.1%, women: 75.8%). Age and obesity were associated with the presence of DD in all regions. Low back pain was associated with the presence of DD in the lumbar region. CONCLUSION: The current study established the baseline data of DD over the entire spine in a large population of elderly individuals. These data provide the foundation for elucidating the causes and mechanisms of DD.

Evaluation of preclinical atherosclerosis by flow-mediated dilatation of the brachial artery and carotid artery analysis in patients with a history of Kawasaki disease.

Cardiac sequelae of Kawasaki disease are an important cause of ischemic heart disease in young adults. The possibility of early progression of atherosclerosis following Kawasaki disease is therefore of great concern. We examined whether preclinical atherosclerotic changes are seen in patients with a history of Kawasaki disease, and whether these changes appear in all or in only a proportion of patients. Sixty-five patients with a history of Kawasaki disease, aged 13.1 +/- 2.1 years, and 20 aged-matched controls participated in the study. All subjects underwent flow-mediated dilatation (FMD) of the brachial artery and analysis of carotid artery size and pulse-wave transmission. Patients were classified into four groups depending on the severity of the maximum coronary artery lesion: group 0 (normal), group 1 (mild), group 2 (moderate), and group 3 (severe). There was no statistical difference in the carotid artery analyses between the four groups. FMD (mean +/- SD) was significantly lower in groups 2 and 3 than in groups 0 and 1 and the control group (group 0, 19.4 +/- 3.9%; group 1, 19.5 +/-4.1%; group 2, 8.9 +/- 2.8%; group 3, 4.2 +/- 1.5%; control group, 18.8 +/- 2.8%; p < 0.0001). There was a significantly negative correlation between the severity of the coronary artery lesion and FMD (p < 0.0001 for both). Endothelial dysfunction was revealed by FMD in patients with persistent coronary artery lesions subsequent to Kawasaki disease. Preclinical atherosclerosis may be present only in patients with coronary aneurysms.

A case of Kawasaki disease associated with syndrome of inappropriate secretion of antidiuretic hormone.

UNLABELLED: Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied clinical manifestations. Although coronary arteritis is common in the course of KD, central nervous system involvement is rare. We report a case of KD in an infant who developed convulsions and apnoea during his illness associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CONCLUSION: The possibility of severe hyponatraemia should be anticipated in children with KD. Infants with KD are at risk of SIADH and should be monitored closely for its development.

Plasma levels of nitrate in congenital heart disease: comparison with healthy children.

Nitric oxide (NO) is an endothelium- derived relaxing factor, and plasma nitrate is the stable end product of NO production. The aim of this study was to investigate the change in levels of plasma nitrate according to age and to elucidate the effect of pulmonary hypertension (PH) associated with congenital heart disease on NO production. We measured plasma levels of nitrate in 48 healthy children aged 5 days to 12 years to establish the normal range. Forty-six preoperative patients aged 4 months to 12 years with congenital heart disease were studied by cardiac catheterization. Plasma nitrate in healthy children decreased with age, from 1 month to 1 year, and then remained almost constant until the age of 12 years. Plasma nitrate was significantly increased in 22 preoperative patients with PH (mean pulmonary arterial pressure >25 mmHg) compared with age-matched normal controls: (mean 56.9 vs 33.5 micromol/L, p<0.05) and was significantly correlated with pulmonary to systemic pressure ratio (r= 0.83, p < 0.0001). There was no significant difference between plasma nitrate levels in 24 preoperative patients without PH and those in the age-matched normal control (mean 25.6 vs 24.9 micromol/L). In 10 patients with preoperative PH who were examined before and after surgery, plasma nitrate levels remained high in the cases with residual PH but decreased to the normal range in the cases without residual PH. Plasma nitrate level is useful for evaluating PH both before and after operation in patients more than 4 months of age, and it is important to note differences in normal plasma nitrate levels according to age.

Mitral valve plasty using artificial chordae in a 1.5-year-old boy with congenital mitral stenosis and absent anterolateral chordae.

A 1.5-year-old boy with refractory heart failure due to congenital mitral stenosis exhibited fusion of the anterolateral leaflets associated with moderate mitral regurgitation due to absent anterolateral chordae. Fused leaflets were incised and the mitral valve opening improved. Mitral regurgitation increased due to the absence of chordae, so 2 pairs of artificial chordae of 5-0 expanded polytetrafluoroethylene suture were anchored to the hypoplastic anterolateral papillary muscle, then attached to the free margin of incised leaflets. Postoperative examination showed improved mitral opening without exacerbated mitral regurgitation.

Plasma nitric oxide products correlate with cardiac index of congenital heart disease.

We wished to determine the relationship between circulating levels of nitric oxide (NO) and cardiac index (CI) in children with congenital heart diseases. We measured the plasma levels of nitrate/nitrite (NO(x)), the stable end products of NO production as well as tumor necrosis factor-alpha (TNF-alpha), atrial natriuretic peptide (ANP), and brain natriuretic peptide in relation to various parameters determined simultaneously. The plasma NO(x) levels correlated negatively with CI (r = -0.541, p < 0.05). No correlation was observed between NO(x) and cardiac output. TNF-alpha correlated with NO(x) levels (r = 0.593, p < 0.005) but not with either CI or cardiac output. Plasma levels of ANP and TNF-alpha were higher in atrial septal defect than those in the control group (p < 0.001 and p < 0.05, respectively). Elevated plasma NO(x) could explain the increased basal release of endothelial NO due to high pulmonary blood flow. Plasma NO(x) correlate negatively with CI in young patients with left-to-right shunt congenital heart diseases.

Relation between plasma nitrate and mean pulmonary arterial pressure in ventricular septal defect.

BACKGROUND: Nitric oxide (NO) is known to modulate myocardial contraction and coronary tone, and its inhalation reduces pulmonary vascular resistance in patients with pulmonary hypertension. OBJECTIVES: To evaluate the pathophysiological role of NO in patients with a ventricular septal defect (VSD). PATIENTS: Twenty-nine children with VSD, nine of whom had undergone VSD closure surgery, and 14 patients with Kawasaki disease. The mean age of the VSD patients was 3.1 years (range, 2 months to 9 years). METHODS: Using high performance liquid chromatography, nitrate (a more stable NO oxidation product) was measured in plasma specimens of the patients undergoing cardiac catheterisation. RESULTS: Nitrate concentrations in the pulmonary artery bore a significant relation to mean pulmonary artery pressure, pulmonary to systemic systolic pressure ratio, and pulmonary to systemic flow ratio. CONCLUSIONS: The concentration of nitrate was in proportion to the increment in intravascular or cardiac pressure, indicating that endogenous NO is upregulated as a compensatory homeostatic attempt to reduce pulmonary pressure and blood flow.

Multiple hepatoblastomas associated with trisomy 18 in a 3-year-old girl.

A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.

Double-outlet right ventricle with intact ventricular septum.

An infant with double-outlet right ventricle (DORV) with intact ventricular septum (VS) is described. Hypoplastic left ventricle and mitral valve atresia were also associated. To the authors' knowledge, this appears to be the first case in which this rare form has been demonstrated with magnetic resonance imaging (MRI). The patient required balloon atrial septostomy (BAS) three times until 4 months of age because of progressive cyanosis. In such a form of DORV, surgical atrial septectomy should be performed instead of repeating BAS because the tendency to functional closure of the restrictive secundum arterial septal defect caused by incompetent foramen ovale seems to be prominent.

Direct transaortic balloon valvuloplasty under cardiopulmonary bypass for neonatal critical aortic stenosis.

A 1-day-old male infant with critical aortic valvular stenosis underwent balloon aortic valvuloplasty (BAV) under echocardiographic guidance during cardiopulmonary bypass. Left ventricular function dramatically improved after BAV. This technique combined with a surgical approach was safe and efficient.

Early changes in plasma brain and atrial natriuretic peptides in premature infants: correlation with pulmonary arterial pressure.

To define the change in plasma natriuretic peptides in newborns, we prospectively studied 10 premature infants. They were followed sequentially during the first week of extrauterine life by two-dimensional and pulsed Doppler echocardiography, and studied for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We estimated mean pulmonary arterial pressure (MPAP) and measured blood pressure on days 1, 2, 3, 5, 7, respectively. Plasma ANP levels were 81.7 +/- 11.4 pg/ml on day 1 and 67.9 +/- 6.0 pg/ml on day 7, respectively. Between day 2 and day 7, there was a fall in MPAP, i.e. from 37 +/- 4 mmHg to 22 +/- 2 mmHg (P < 0.01), which was associated with a significant decrease in plasma BNP (41.8 +/- 10.1 pg/ml on day 2 vs. 10.4 +/- 0.9 pg/ml on day 7, P < 0.01). There was a positive correlation between MPAP and plasma BNP level (r = 0.643, P < 0.0001), but there was no correlation between MPAP and plasma ANP level. These data suggest that the pattern of secretion of BNP is different from that of ANP and that BNP levels reflect the changes of pulmonary arterial pressure in the neonatal period in premature infants.