Weaning of epoprostenol in a small infant receiving concomitant bosentan for severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia

Endothelin receptor antagonism is an important therapeutic tool of pulmonary arterial hypertension (PAH). Bosentan was the first orally active, dual antagonist of endothelin receptors in human adults, and has been recently considered for children as well. However, little is known about bosentan treatment in children weighing less than 10 kg. We describe the use of bosentan concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she presented subsystemic PAH secondary to severe BPD, she was treated with oxygen, digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100% oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old, when HFOV and NO were slowly discontinued due to improved oxygenation index. Regular echocardiographic measurements of systolic right ventricular pressure were recorded by the method of tricuspidal atrio-ventricular gradient. A four-month combined epoprostenol and bosentan treatment decreased systolic right ventricular pressure from 68% to 40% of the systemic level, till its normalization at 11 months old. Later, when bosentan and epoprostenol were discontinued and sildenafil was started, severe PAH was reported again. Our patient died due to septic shock and refractory hypoxia at 14 months old.     

Connective Tissue Disease Presenting With Signs and Symptoms of Pulmonary Hypertension in Children

Our case series describes three children who were initially diagnosed as having severe pulmonary arterial hypertension (PAH) and subsequently found to be positive for specific autoantibodies suggestive of an underlying autoimmune process. The signs and symptoms of PAH are subtle and may be part of the initial presentation of childhood connective tissue disease (CTD). Evaluation for connective tissue disease in the newly diagnosed pulmonary hypertension (PH) patient is important because early diagnosis of PH as well as CTD is crucial in the successful management of these complex patients. Ongoing monitoring for CTD in patients with severe PAH is warranted.     

Incontinentia pigmenti in combination with decreased IgG subclass concentrations in a female newborn

Incontinentia pigmenti (IP) is a rare neurocutaneous disorder caused by mutations in the NEMO (NF-kappaB essential modulator) gene. Skin lesions are typically the first manifestation of IP though they may be accompanied by multiple malformations. This report presents the case of a female newborn with early onset of IP lesions within the 1st day of life. After the age of 1 month she developed frequent episodes of severe gastroenteritis. Examination of the immune system revealed low concentrations of IgG subclasses. This study suggests that, contrary to previous belief, IP is associated with immune deficiency.     

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??Objective To evaluate the effect of plugging tests in the diagnosis and interventional treatment of pediatric patients with patent duct arteriosus complicated with severe pulmonary hypertension ??PAH??. Methods??All the clinical data of 5 patients of PDA with severe PAH were retrospectively reviewed??including the heart catheterization data??the relevant parameters before and after acute pulmonary vasodilator tests and the changes of Pp??Ps??PVRI??and aortic blood oxygen saturation before and after the plugging tests. Results??Only 1 patient was with dynamic PAH according to heart catheterization test??however??for the other 4 patients it was difficult to judge the property of PAH. Acute pulmonary vasodilator tests were performed in 5 patients and 4 were diagnosed with dynamic PAH. Plugging tests were conducted in 5 patients and all of them were diagnosed with dynamic PAH. All the patients underwent interventional therapy well and the follow-up results were good. Conclusion??For PDA patients with severe PAH??plugging test diagnosis can be made on the properties of the PAH and if the determination is dynamic??the intervention treatment can be completed at the same time. This method can effectively avoid the limitations of cardiac catheterization and acute pulmonary vasodilator testing evaluation of PAH properties.     

Siblings with infantile cerebral stroke and delayed multivessel involvement—A new hereditary vasculopathy?

We describe an unusual vasculopathy in two sisters of non-consanguineous parents. The first child developed an acute hemiparesis and focal seizures at the age of 6 months during a febrile illness. Magnetic resonance imaging (MRI) of the brain showed bilateral cortical-subcortical infarction not confined to a vascular territory. Subsequently, the child had a persistent stable neurological deficit. Her younger sister had a similar encephalitis-like episode at the age of 4 months, with left-sided cortical-subcortical ischaemic lesions. Two months later she had left-sided focal seizures. MRI showed a right-sided cortical enhancement, magnetic resonance angiography (MRA) was normal. The neurological deficit was stable and she was seizure free. These episodes were initially interpreted as metabolic strokes, but work-up was normal and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was excluded. In their teens both sisters were diagnosed with pulmonary and systemic hypertension and, due to the arterial hypertension, myocardial hypertrophy. Renal artery stenosis, pathological pulmonary arteries, and stenosis and rarefication of coronary arteries were found; the aorta and retinal vessels were normal. Repeat cranial MRI and MRA showed multiple collaterals, while the carotid and basilar arteries were extremely narrowed (moyamoya appearance). We suggest the diagnosis is a hereditary systemic vasculopathy of unknown origin.     

Bronchial compression in an infant with isolated secundum atrial septal defect associated with severe pulmonary arterial hypertension

Symptomatic pulmonary arterial hypertension (PAH) in patients with isolated atrial septal defect (ASD) is rare during infancy. We report a case of isolated ASD with severe PAH in an infant who developed airway obstruction as cardiomegaly progressed. The patient presented with recurrent severe respiratory insufficiency and failure to thrive before the repair of the ASD. Echocardiography confirmed volume overload on the right side of heart and severe PAH (tricuspid regurgitation [TR] with a peak pressure gradient of 55 to 60 mmHg). The chest radiographs demonstrated severe collapse of both lung fields, and a computed tomography scan showed narrowing of the main bronchus because of an intrinsic cause, as well as a dilated pulmonary artery compressing the main bronchus on the left and the intermediate bronchus on the right. ASD patch closure was performed when the infant was 8 months old. After the repair of the ASD, echocardiography showed improvement of PAH (TR with a peak pressure gradient of 22 to 26 mmHg), and the patient has not developed recurrent respiratory infections while showing successful catch-up growth. In infants with symptomatic isolated ASD, especially in those with respiratory insufficiency associated with severe PAH, extrinsic airway compression should be considered. Correcting any congenital heart diseases in these patients may improve their symptoms.     

Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case

A 15-month-old girl with severe hemolytic anemia and progressive respiratory failure is presented. She was well until the age of six months when she developed a pulmonary infection. During the next six months, she had frequent respiratory infections and her paleness became evident. At the age of 12 months, she was observed to have easy fatigability and muscle weakness, and she received her first blood transfusion. She was referred to our hospital at the age of 15 months. The physical examination revealed a malnourished girl with hypotonia, nystagmus, generalized muscle weakness and severe breathing difficulty requiring ventilatory support The hemoglobin (Hb) was 9.7 g/dl; hematocrit (Hct) 29%, mean corpuscular volume (MCV) 101 fl and reticulocyte count 15%. Peripheral blood smear revealed macrocytosis and stomatocytosis (30% of the red cells) and polychromasia. Sweat chloride test was 90 and 94 mEq/L on two separate occasions. The serum vitamin E level was 0.26 mg/dl (N: 0.44-0.68). She was found to be heterozygous for factor V Leiden mutation. Although malnutrition, low serum vitamin E and elevated sweat chloride test were suggestive of cystic fibrosis, this diagnosis failed to account for all the findings in the patient. A search for a red cell enzyme deficiency revealed that the red cell triosephosphate isomerase (TPI) activity was low. DNA analysis showed the 315 G-C (105 Glu-Asp) TPI mutation, thus confirming the diagnosis of TPI deficiency.     

Cardiac failure 30 years after treatment containing anthracycline for childhood acute lymphoblastic leukemia

In 1977, a 5-year-old girl diagnosed with acute lymphoblastic leukemia was treated on Dana-Farber Cancer Institute Childhood Acute Lymphoblastic Leukemia Protocol 77-01, receiving a cumulative doxorubicin dose of 465 mg/m(2), cranial radiation, and other drugs. After being in continuous complete remission for 34 months, she developed heart failure and was treated with digoxin and furosemide. At 16 years of age, she was diagnosed and treated for dilated cardiomyopathy. Over the years, she continued to have bouts of heart failure, which became less responsive to treatment. At 36 years of age, she received a heart transplant. Six months later, she stopped taking her medications and suffered a sudden cardiac death.     

Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

We report a 14-year-old girl with juvenile dermatomyositis (JDM) complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day) of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.     

Leigh's disease with clinical manifestations of Cornelia de Lange syndrome.

Leigh's disease was found postmortem in a 5-year-old girl who was diagnosed clinically as Cornelia de Lange syndrome at age 1 year. The child's neurological status began to deteriorate rapidly at age 4.5 years and she died suddenly 6 months later. Postmortem examination of the brain revealed bilateral necrosis of the hypothalamus, subthalamic nuclei, midbrain, pons, and medulla. Previous studies have linked Cornelia de Lange syndrome to hypothalamic lesions. This case demonstrates that Leigh's disease, which also damages the hypothalamus, could present with phenotypic features of Cornelia de Lange syndrome.     

Hepatic drug metabolizing enzyme activity and tumorigenesis in mice following perinatal exposure to benzo(a)pyrene

It is known that in utero exposure to polycyclic aromatic hydrocarbon carcinogens (PAH) results in a high incidence of pulmonary and other tumors in the offspring, usually after a long latency period. The present study tested the hypothesis that perinatal exposure to benzo(a)pyrene (BP) produces alterations in microsomal mixed-function oxidase (MFO) activity that modify the response to postnatal challenge with a PAH in such a way as to render the offspring to be more susceptible to tumorigenesis, and to determine whether the gestational age at which BP exposure occurred was a determinant of the proposed alterations. Swiss mice were treated with BP on day 3, 8, 10, 12, 14, or 18 of gestation. Subgroups from each gestational-age treatment group and appropriate controls were studied for enzyme activity or were challenged with 3-methylcholanthrene (3-MC) when three months old. Female offspring of BP-treated mice had significantly elevated hepatic microsomal aminopyrine demethylase activity; cytochrome P-450 concentrations were significantly lower in male offspring. The most striking finding was the increased susceptibility to tumorigenesis of female offspring. Latency for local tumors was decreased by two weeks; tumors were more frequent and grew more rapidly. Significantly more female offspring had both local and pulmonary lesions, and the total number of pulmonary adenomas was also significantly higher. Further studies are required to determine if the developmental alterations in hepatic (MFO) activity resulting from perinatal exposure to PAH relate in a causative way to the enhanced susceptibility of female offspring to tumorigenesis.     

儿童先天性心脏病血清Apelin水平与肺动脉压关系的初步探讨

目的 初步探讨先天性心脏病患儿血清Apelin 水平与肺动脉压的关系.方法 手术治疗的先心病患儿126 例,检测患儿术前及术后第7 天的血清Apelin 水平.建立体外循环前检测并计算肺动脉收缩压/体循环收缩压(Pp/Ps)的比值,依据Pp/Ps 分组:无肺动脉高组压(PAH)组、轻度PAH 组、中度PAH 组和重度PAH 组;术后第7 天超声心动图估测肺动脉平均压(PAMP).结果 无PAH,以及轻、中、重度PAH 各组术前及术后的血清Apelin 水平依次降低,差异有统计学意义(PPr=-0.51,-0.54,P结论 先心病患儿并发肺动脉高压及其发展与血清Apelin 水平降低有关系,血清Apelin 对诊断先心病患儿是否并发肺动脉高压及其程度的意义值得深入研究.     

Mid-Term Outcome After Partial Left Ventriculectomy in Pediatric Patients

From May 1998 to April 2000, we performed partial left ventriculectomy (PLV) in 3 pediatric patients with dilated cardiomyopathy (DCM). At the time of the surgery, their age ranged from eight months to three years. The first patient eventually had to receive a heart transplant, but all patients treated with PLV are alive to this day. Patient #1 was diagnosed with DCM at the age of five months, PLV was done on a semi-urgent basis at the age of eight months, when medium dose IV catecholamine therapy and mechanical ventilation were required. Fraction shortening (FS) as shown by echocardiography increased postoperatively from 8% to 15% along with marked clinical improvement. Her heart failure deteriorated three months after the surgery, and received a heart transplant in the United States when she was one year and two months old. Patient #2 developed severe heart failure two months after correction of a ventricular septal defect. Aggressive medical therapy failed to improve his condition, therefore PLV was done on an elective basis at the age of three years and five months. [The patient was initially hospitalized and underwent low dose catecholamine.] Postoperative course was well. The ventriculography one year after surgery showed an improvement of the left ventricular FS from 12% to 27% after PLV. He was still doing well at his most recent check up. Patient #3 was diagnosed with DCM as a neonate. PLV was done on an elective basis at the age of two years and five months. Her postoperative course was generally well. FS on echocardiography increased postoperatively from 10% to 25% along with marked clinical improvement. The timing of performing PLV is the most essential factor for postoperative course in our experiences. We consider that the best timing is when aggressive catecholamine infusion or mechanical ventilation is required. The mid-term outcome of PLV of pediatric patients is considered to be acceptable. We believe that PLV should be considered as a viable option for severe DCM patients.     

Neuroblastoma in a patient with dihydropteridine reductase deficiency

Tetrahydrobiopterin (BH₄) deficiency is a rare cause of hyperphenylalaninaemia (HPA) and usually leads to progressive neurological deterioration despite early dietary control of plasma phenylalanine concentrations. Dihydropteridine reductase (DHPR) deficiency is the most severe cause with respect to a fatal outcome. We report a 7-year-old girl with HPA diagnosed on neonatal Guthrie screening who at the age of 6 months had cytotoxic therapy for an adrenal neuroblastoma which secreted catecholamines. When 4 years old she was found to have DHPR deficiency. Although developmentally retarded and microcephalic she has failed to develop the florid neurological features often associated with the condition.     

Central precocious puberty in multisystem Langerhans cell histiocytosis: a case report

The authors describe a girl with multisystem Langerhans cell histiocytosis (LCH) who developed central precocious puberty (CPP). At the age of 19 months she presented with otorrhea and polypoid formations in the ear canal; polyps were removed and LCH suspected. She subsequently developed diabetes insipidus with a documented lesion of the pituitary stalk; she received chemotherapy and began therapy with 1-desamino-8-D-argininevasopressin. Growth hormone deficiency was diagnosed at the age of 4.4 years and GH replacement therapy started. The patient has been off therapy for LCH since the age of 6. Signs of pubertal development appeared at 7.5 years (bone age 8 years) and gonadotropin-releasing hormone analog (GnRHa) treatment was started. During the observation period she developed central hypothyroidism. Development of CPP during LCH is extremely rare; to the authors' knowledge, no patient has been described so far. The authors believe that CPP was secondary to LCH and did not represent a casual finding, even in the absence of hypothalamic-pituitary axis involvement. The presence of preceding lesions producing excessive cytokine levels, with damage on the neurosecretory apparatus that inhibits the GnRH pulse generator, represents the most intriguing hypothesis. The possibility of CPP development should be considered during the follow-up of these patients.     

Choroid plexus carcinoma: Report of one case with favourable response to treatment

Choroid plexus carcinoma (CPC) is a rare tumor with usually severe prognosis, whose optimal treatment has not yet been established. The exact role of complete surgical resection, chemotherapy, and radiotherapy has been debated but not clarified. We report one girl with CPC diagnosed at age 3 months and apparently cured with minimal surgical resection, chemotherapy, and delayed irradiation. At the age of 8 years, she is well, with minor psychomotor retardation and growth hormone deficiency as the only sequelae. © 1994 Wiley-Liss, Inc.     

Pertussis with severe pulmonary hypertension and leukocytosis treated with extracorporeal membrane oxygenation

Pertussis, or “whooping cough,” is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.     

川崎病合并多发体循环动脉病变1例报告并文献复习

目的报告1例川崎病(Kawasaki disease,KD)合并多发体循环动脉病变并复习文献,以提高对该病的认识和临床诊疗水平。方法根据患儿的症状、体征、心脏超声及体动脉B超等检查结果进行诊断,并结合文献资料进行分析。结果女孩,5个月,诊断川崎病合并双侧冠状动脉瘤,符合静脉注射丙种球蛋白(intra-venous immunoglobulin,IVIG)无反应性川崎病诊断标准,体循环动脉B超提示存在多发体动脉病变。结论川崎病合并多发体循环动脉病变较罕见,应提高认识,及时诊断并长期随诊监测病情变化。     

Identification of a novel mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome presenting with neonatal diabetes mellitus and galactosaemia

We describe a patient with Fanconi-Bickel syndrome diagnosed by clinical manifestations and the identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed with neonatal diabetes mellitus due to hyperglycaemia and glycosuria at 3 days of life. In addition, newborn screening for galactosaemia revealed hypergalactosaemia. Thereafter, she was managed with lactose-free milk and insulin therapy. However, she failed to grow and her liver became progressively enlarged. Her liver function deteriorated with increased prothrombin time. A liver biopsy done at age 9 months showed micronodular cirrhosis with marked fatty changes and she succumbed to hepatic failure with pneumonia at 10 months of age. DNA sequencing analysis of the GLUT 2 gene using her genomic DNA revealed a novel mutation in codon 5, lysine5 stop(K5X).     

Regression of Pulmonary Vascular Disease After Therapy of Abernethy Malformation in Visceral Heterotaxy

A 1-year-old boy who had left isomerism and corrected transposition of the great arteries (c-TGA) with moderate-sized ventricular septal defect, severe pulmonary artery hypertension (PAH), and pulmonary vascular disease with significant right-to-left shunting received a diagnosis of type 2 Abernethy malformation, which was partly responsible for disproportionate PAH in the child. The malformation was treated by plugging of the portosystemic shunt. Follow-up cardiac catheterization on sildenafil demonstrated significant left-to-right shunting (2.16:1) and a fall in pulmonary vascular resistance, making surgical correction possible. This case highlights the importance of searching for additional rare causes of PAH in patients with congenital heart diseases when the degree of pulmonary hypertension is disproportional to the defect size.