Rare presentation of tuberculous hypertrophic pachymeningitis diagnosed by a biopsy of abdominal lymphadenopathy.

A 59-year-old man with medical history of diabetes mellitus and hypertension presented with a persistent fever of unknown origin and developed a headache. Laboratory tests, including polymerase chain reaction assays for Mycobacterium tuberculosis, showed no specific abnormal findings in blood or cerebrospinal fluid. Contrast-enhanced computed tomography revealed abdominal paraaortic lymphadenopathy. Abdominal lymph node biopsy showed caseous necrosis and suggested tuberculous lymphadenopathy. Intensive examinations revealed positive T-SPOT.TB test and multiple dural nodular hypertrophic lesions in brain magnetic resonance imaging. After antitubercular treatment, all clinical manifestations and dural nodular lesions improved. Finally, we diagnosed the patient with tuberculous hypertrophic pachymeningitis. To our knowledge, this is the first report of tuberculous hypertrophic pachymeningitis concomitant with abdominal tuberculous lymphadenopathy and no other dissemination. Systematic investigation of tuberculosis is important for pachymeningitis.

Diffuse Large B-Cell Lymphoma of the Trachea in a Child With Symptoms of Bronchial Asthma.

Tracheal tumors are rare in children and manifest symptoms of airway obstruction. A 14-year-old boy with a 5-month history of dyspnea and wheezing was referred to our hospital. Although he had been initially diagnosed with bronchial asthma, computed tomography revealed tracheal tumors. Histologic examination showed only necrotic tissue. Thereafter, the systemic steroid treatment for bronchial asthma was tapered off. A second computed tomography scan revealed new lesions in the pancreas and lung. Biopsy of the pancreatic lesion revealed a diffuse large B-cell lymphoma. The patient was administered standard chemotherapy, following which he went into complete remission.

A successful treatment of tadalafil in incontinentia pigmenti with pulmonary hypertension.

We describe a female infant with incontinentia pigmenti complicated by severe pulmonary arterial hypertension that was markedly improved by tadalafil administration. The infant was referred to our institution because of neonatal seizures and generalized skin rash at the age of 1 day. She was diagnosed with incontinentia pigmenti on skin biopsy findings. In addition to incontinentia pigmenti, she had pulmonary arterial hypertension without structural heart disease. The pulmonary hypertension rapidly worsened at the age of 2 months and was confirmed by cardiac catheterization. The pulmonary artery pressure was equal to systemic pressure but it decreased in response to nitric oxide inhalation. We, therefore, initiated treatment with tadalafil of 1 mg/kg/day. The follow-up cardiac catheterization performed at 9 months revealed dramatic improvement in the pulmonary artery pressure. An IKBKG mutation with deletion of exons 4-10 was detected in the blood of both the patient and her mother. Our experience indicates that tadalafil may be beneficial in treating pulmonary arterial hypertension associated with incontinentia pigmenti.

Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis.

Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease.

Fingolimod suppresses bone resorption in female patients with multiple sclerosis.

Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the inflammatory activity of multiple sclerosis (MS), and has been shown to suppress osteoporosis in mouse models. In this study, levels of bone turnover markers were quantified in serum and urine samples from MS patients treated with fingolimod. Compared with untreated MS patients and healthy controls, fingolimod-treated MS patients had a significantly lower level of the bone resorption marker type I collagen cross-linked N-telopeptide in urine. This finding was prominent in female but was not seen in male subjects. Our results suggest that fingolimod may have a beneficial effect on bone mass loss in female MS patients.

Application of Cone Reconstruction for Neonatal Ebstein Anomaly or Tricuspid Valve Dysplasia.

BACKGROUND: Outcomes of surgical intervention for severe tricuspid regurgitation related to Ebstein anomaly or tricuspid valve dysplasia in the neonatal period, particularly when associated with pulmonary atresia, are extremely poor. However, owing to emerging innovative surgical techniques, such as cone reconstruction, outcomes of tricuspid valve plasty in the neonatal period have gradually improved. METHODS: The study retrospectively reviewed the medical records of 12 neonates who were diagnosed with severe tricuspid regurgitation and pulmonary atresia related to Ebstein anomaly (n = 9) or isolated tricuspid valve dysplasia (n = 3) between 2000 and 2013. RESULTS: The first 6 patients underwent palliative therapy in anticipation of future functional single-ventricle palliation (Starnes operation). Biventricular repair was performed in the 6 patients born after 2012. As tricuspid valve plasty, cone reconstruction has been applied since 2013. Five patients underwent a Starnes operation, and 5 patients underwent biventricular repair, including 4 cone reconstructions. Four of the 5 patients who underwent a Starnes operation died in-hospital; the remaining patient underwent a Fontan operation at age 2 years. Three of the 5 patients who underwent biventricular repair survived. On echocardiogram, the 3 survivors who were treated with biventricular repair had a preoperative tricuspid regurgitation flow velocity greater than 3.0 m/s. CONCLUSIONS: Biventricular repair with cone reconstruction can be applied for severe tricuspid regurgitation due to neonatal Ebstein anomaly or tricuspid valve dysplasia with associated pulmonary atresia. A tricuspid regurgitation flow velocity greater than 3.0 m/s may be an indicator of successful biventricular repair.

Prevalence and predictors of haemostatic complications in 412 Fontan patients: their relation to anticoagulation and haemodynamics.

OBJECTIVES: Our aim in the present study was to determine the prevalence of haemostatic events in our Fontan patients, to identify predictive factors and to determine their association with haemodynamics and anticoagulant therapy. METHODS: We retrospectively evaluated 424 Fontan patients and examined correlations between postoperative haemodynamics and anticoagulant regimens with haemostatic events. RESULTS: After exclusion of 12 patients with a mechanical valve at the time of Fontan operation, our 412 patients were sub-divided into 21 groups based on the therapeutic duration of warfarin and antiplatelet agent therapy. During the early 5- to 10-year postoperative period, patients receiving warfarin showed higher central venous pressure and lower arterial oxygen saturation (Sat) (P < 0.05-0.001). During a mean follow-up of 11.2 years, 29 (7.0%) haemostatic events occurred. With regard to haemorrhagic events, haemoptysis was most common (n = 13, 45%), followed by cerebral bleeds in 3 (10%). Of thrombo-embolic events, thrombosis in the Fontan pathway was the most common (n = 7, 24%), followed by cerebral infarction in 3. Early haemorrhagic events were associated with late Fontan operation and use of preoperative renin-angiotensin system blockers, while late events were related to heterotaxy syndrome, male gender and low Sat (P < 0.05-0.01). A low Sat was the only predictor of early postoperative thrombo-embolic events (P = 0.0192). Among the three subgroup analyses of fixed anticoagulant regimens, the most frequent haemorrhagic events were associated with long-term use of warfarin (P = 0.0033). None of the anticoagulant regimens that included warfarin and/or antiplatelet agents were independently associated with haemostatic events throughout the follow-up. CONCLUSIONS: Anticoagulant regimens in Fontan patients varied widely with a significant trend for warfarin use in patients with impaired haemodynamics. Low arterial oxygenation may predict haemostatic events. The relatively high prevalence of haemorrhagic complications indicates the need for individualized anticoagulant administration throughout the follow-up.

Antenatal glucocorticoid therapy accelerates ATP production with creatine kinase increase in the growth-enhanced fetal rat heart.

BACKGROUND: Previous study has demonstrated the increase of several cardiac function-related proteins, including creatine kinase (CK) as an important enzyme in the process of ATP synthesis in the fetal heart of rats administered glucocorticoid (GC) antenatally. In the present study the effect of antenatal GC administration on the CK expression in fetal and neonatal hearts was demonstrated. METHODS AND RESULTS: Dexamethasone was administered to pregnant rats on days 19 and 20 of gestation. The mRNA levels of the CK isoforms, CK-M and Mi-CK, in 21-day-old fetal and 1-day-old neonatal hearts were significantly increased after antenatal GC administration. CK protein levels were also increased in both cultured cardiomyocytes and the mitochondria of the hearts. Uptake of 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl-benzimidazolocarbocyanine iodide by mitochondria was significantly increased. An increased ATP level accompanied the CK increase in the neonatal hearts. Furthermore, in vitro these effects were mediated though the GC receptor of cardiomyocytes. Peroxisome proliferator-activated receptor gamma as the upstream transcription factor of CK was significantly increased in fetal hearts. CONCLUSIONS: These results suggest that antenatal GC administration accelerates ATP synthesis through increased CK and may contribute to maturation of the premature heart so that it is ready for preterm delivery. (Circ J 2010; 74: 171 - 180).

Antenatal glucocorticoid therapy increase cardiac alpha-enolase levels in fetus and neonate rats.

AIMS: Antenatal glucocorticoid therapy has been shown to prevent acute diseases including infant respiratory distress syndrome and reduce mortality, although little is known about the effects on cardiac function-related proteins in the fetus or neonate. We investigated whether cardiac function-related proteins were altered in cardiac tissues of fetuses and neonates born to pregnant rats treated by glucocorticoid. MAIN METHODS: Dexamethasone (DEX) was administered to pregnant rats for 2 days on day 17 and 18 or day 19 and 20 of gestation to simulate antenatal DEX therapy, and cardiac tissues of 19- and 21-day fetuses and 1-, 3-, and 5-day neonates were analyzed using a proteomic technique with liquid chromatography-mass spectrometry/mass spectrometry. KEY FINDINGS: The identified five proteins; alpha-enolase, creatine kinase-M type, beta-tubulin, troponin T, and ATP synthase beta-chain, were significantly increased in fetal cardiac tissues with DEX administration. We observed that significant increase of alpha-enolase in the 19-day fetuses by DEX using Western blotting and immunohistochemistry. ATP and cAMP levels were also increased in the fetal heart tissue. In addition, pyruvate levels were significantly increased in the fetus groups by DEX. SIGNIFICANCE: These results suggest that increased alpha-enolase may contribute to acceleration of glycolysis in the preterm heart.