Lifelong cardiovascular care in Turner syndrome: two cases with review of literature.

Cardiovascular disease is one of the most important complications in girls and women with Turner syndrome (TS). Although the latest international guideline provides useful suggestions for the management of cardiovascular diseases in TS, some unknown cardiac conditions warrant physicians' attention and awareness. Here, we have reported two adult cases wherein significant cardiovascular diseases were detected during the transition period. The first case patient was diagnosed with aortic crank deformity and left subclavian artery aneurysm at 14 years based on the report of cardiac catheterization, computed tomography angiography, and cardiac magnetic resonance imaging, which had remained undetected by annual evaluations using transthoracic echocardiography (TTE). This case emphasizes the importance of cardiac reevaluation during the transition period. The second case patient was diagnosed with moderate mitral valve regurgitation (MR) due to mitral valve prolapse at 18 years through TTE, although the first evaluation at 7 years by TTE detected slight MR without any clinical concerns. The condition however progressed to severe MR at 28 years, requiring mitral valvuloplasty. MR is the most common valve disease worldwide, which makes it challenging to comprehend whether the condition is a complication. However, the condition requiring surgery at this age is extremely rare, which implies the possibility of early progression. Because almost all literature on cardiovascular complications in TS is cross-sectional, further information about longitudinal cardiovascular conditions is vital for optimal care for girls and women with TS. The two cases reported in this article provide significant information for improving lifelong cardiovascular health issues in TS.

Modulation of 11ß-hydroxysteroid dehydrogenase 1 by ß2-adrenoceptor in the ischaemia-reperfused rat kidney.

BACKGROUND: 11ß-Hydroxysteroid dehydrogenase Type 1 (11ßHSD-1) amplifies intracellular levels of active glucocorticoids which possess protective effects against organ ischaemia and reperfusion (I/R). However, the mechanisms by which 11ßHSD-1 is modified after a renal I/R challenge remain unclear. This study investigated the effect of ß(2)-adrenoceptor (ß(2)-AR) activation and the subsequent signalling pathways on renal 11ßHSD-1 gene expression following renal I/R. METHODS: Renal I/R was induced using 25 min of bilateral renal artery occlusion in 4-week-old Wistar rats followed by an intraperitoneal injection of various doses of adeno-ß(2)-AR gene. Following renal I/R, kidneys, plasma and urine were collected to assay 11ßHSD messenger RNA (mRNA) levels, ß(2)-AR signalling cascades and renal function. RESULTS: On the second day after the renal I/R challenge, there was a reduction in renal 11ßHSD-1 mRNA levels associated with a decrease in stimulatory G protein α (Gsα) and adenylate cyclase-1 (ACY-1) in the kidney. The addition of the adeno-ß(2)-AR gene resulted in greater increases in 11ßHSD-1 mRNA and ß(2)-AR-Gsα-ACY-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) activity in the kidney but had no effect on 11ßHSD-2 mRNA or protein kinase C levels in the kidney. CONCLUSIONS: Over-expression of ß(2)-AR resulting from the gene delivery improved renal function and 11ßHSD-1 production following renal I/R, which were actions exerted through the cAMP-PKA pathway. The stimulatory effect of functional ß(2)-AR activation on renal 11ßHSD-1 expression may offer a means of protection from renal I/R injury.

Regional cerebral blood flow abnormalities in patients with kawasaki disease.

PURPOSE: Kawasaki disease (KD) is an acute febrile disorder of unknown etiology. Brain single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) help in detecting regional cerebral blood flow abnormalities and brain damage. The usefulness of SPECT and MRI in patients with KD was evaluated. MATERIALS AND METHODS: All 22 patients with KD underwent brain SPECT using Tc-99m-hexamethyl propylene amine oxime from 6 days to 3 years after onset, and 8 patients underwent brain MRI. Of the 22 patients, 4 had neurologic symptoms. Case 1 showed prolonged apnea; case 2, prolonged disturbance of consciousness; and cases 3 and 4 generalized tonic-clonic seizures. Initial brain SPECT showed localized hypoperfusion in 4 and 13 patients with and without neurologic symptoms, respectively. RESULTS: All patients with neurologic symptoms underwent follow-up SPECT; localized hypoperfusion was detected between 1- and 6-month follow-up in 3 of these patients. Six patients without neurologic symptoms underwent follow-up SPECT. Localized hypoperfusion was detected at approximately 1- to 11-month follow-up in 4 of these patients. Diffusion-weighted imaging revealed abnormal high-intensity areas in the corpus callosum in case 1. Case 2 showed a bilateral chronic subdural hematoma with decreased size and ischemic changes, and case 3 showed bilateral hippocampal atrophy and left hippocampal sclerosis. CONCLUSIONS: Because the occurrence of localized hypoperfusion is possibly not restricted to only the acute phase in KD, brain SPECT and MRI should also be performed in KD patients with neurologic symptoms.

Factors influencing cardiovascular risk following termination of glucocorticoid therapy for nephrotic syndrome.

BACKGROUND: This study attempted to identify the cardiovascular risk factors associated with retention of excess weight following termination of glucocorticoid therapy in children with nephrotic syndrome. METHODS: We performed a retrospective study of 30 Japanese children (18 males, 12 females, aged 1-14 years) who had been treated with glucocorticoids for steroid-sensitive nephrotic syndrome and 32 control children (17 males, 15 females, aged 1-15 years). The subjects receiving glucocorticoid therapy were divided into a retention group (n = 14) or a reduction group (n = 16) on the basis of the presence or absence of a maintained body mass index (BMI) following glucocorticoid termination. BMI z-scores, age, gender, blood pressure, serum total cholesterol levels (T-cho), and the dose and duration of glucocorticoid exposure were evaluated in each group during the study period. RESULTS: The retention group had a significantly (P < 0.05) increased dose and duration of glucocorticoid exposure, and of T-cho at the time of last visit compared with the control or reduction group. Moreover, logistic regression analysis showed that the adjusted odds ratio for T-cho at the time of last visit in the retention group was significantly higher (P < 0.05) relative to the reduction group. CONCLUSION: Retention of excess weight during the period of remission from nephrotic syndrome following cessation of glucocorticoid therapy was related to the dose and duration of glucocorticoid exposure and was associated with hyperlipidemia, which might enhance cardiovascular risk.

[Actigraphy for the assessment of sleep quality in pediatric atopic dermatitis patients].

BACKGROUND: Good sleep is essential for the growth and the development of children. However, sleep is often impaired in patients with atopic dermatitis (AD). It is important to assess the sleep quality in pediatric AD patients. For that purpose, we utilized actigraphy as an objective method for the assessment of sleep quality. METHODS: Childhood patients with AD (16 cases) and 8 non-allergic volunteers were recruited. Actiwatch (AW-64) was attached to each subject's wrist for 11 days at maximum. Sleep parameters were calculated with Actiware and compared among various patient groups. RESULTS: Results demonstrate that sleep was significantly compromised in patients with AD, according to the severity. Subjective scoring of the sleep quality by parents showed limited correlation with actigraphy. CONCLUSION: Actigraphy is an objective and unobtrusive method to measure the sleep quality in childhood AD patients and can provide useful outcome in clinical trial.

Renal beta2-adrenoceptor blockade worsens the outcome of an induced Escherichia coli renal infection.

BACKGROUND: Renal infections elevate the risk of sepsis and are important causes of septic shock and multiple organ failure. The objective of the present study was to test the hypothesis that renal beta(2)-adrenoceptor (beta(2)-AR) blockade impairs the organ response to renal infection induced by Escherichia coli (E. coli) administration. METHODS: A rat model of renal infection was induced using an intraparenchymal injection of E. coli into the right kidney, either alone or in rats pre-treated with the beta(2)-AR antagonist, ICI 118,551 (3.14 microg/kg). RESULTS: The rat renal infection model significantly raised growth-related oncogene/keratinocyte-derived cytokine, granulocyte-macrophage colony-stimulating factor and cAMP levels in the right kidney and caused an elevation in serum cytokines and nitric oxide (NO), whereas creatinine clearance rate (Ccr) was maintained over the course of the infection. Conversely, treatment of the rat model with the beta(2)-AR antagonist resulted in a decrease of Ccr and serum NO, greater increases in serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6, associated with an elevation of the right renal TNF-alpha and cannabinoid-1 receptor, and a reduction of the right renal Gsalpha and cAMP levels. Moreover, the inhibition of beta(2)-AR activation impaired the clearance of endotoxins from the kidney and was associated with a raised mortality rate. CONCLUSIONS: The blockade of a renal beta(2)-AR signaling cascade aggravates inflammatory responses in the infected kidney, changes serum levels of cytokines, NO, and noradrenaline, and leads to renal dysfunction and a higher rate of mortality.

[Assessment of joint attention skill in at-risk infants during follow-up outpatient examination].

We assessed the joint attention skill of infants by a novel method. One hundred eighty infants who were discharged from the NICU of Teikyo University Hospital and subsequently brought to the outpatient clinic for follow-up examinations between 6 and 12 months of corrected age (297 examinations in total) were entered into the study. Infant were sitting on the mother's knees facing the examiner. After confirming the infant's visual axis to the examiner's eyes, the examiner looked at blocks held in the infant's visual field. When the infant looked at the blocks by perceiving the examiner's gaze, the infant was judged to have joint attention skill. Then, when the infant looked at the examiner again, the attitude was estimated as an action for reconfirmation. Sixty percent of the infants at 6 months of age showed joint attention skill, and more than 90 % of infants showed this skill at 9 months of age. At 6 months of age, boys showed that skill significantly more frequently than girls. This new method is very easy to perform, uses only small blocks and can be completed within a few minutes. Therefore, we considered this new method useful for the assessment of joint attention skill in infants during periodic outpatient health clinic examination.

Protection from sepsis-induced acute renal failure by adenoviral-mediated gene transfer of beta2-adrenoceptor.

BACKGROUND: Sepsis is a common cause of acute renal failure (ARF) and results in a high mortality rate. The objective of the present study was to evaluate adenoviral transgenes containing the human beta(2)-adrenoceptor (adeno-beta(2)-AR) as a possible therapy for subjects at high risk for developing sepsis-induced ARF. METHODS: An endotoxaemic rat model of ARF was induced by renal artery occlusion plus subcutaneous injections of Escherichia coli in 4-week-old Wistar rats. A subset of rats was given intraperitoneal injection of the adeno-beta(2)-AR gene. RESULTS: Sepsis produced a depression in glomerular filtration rate and in the renal beta(2)-AR signalling system, which were both reversed by delivery of the beta(2)-AR gene. While delivery of the adeno-beta(2)-AR gene had no effect on recovery of cytokines and C-reactive protein in the systemic circulation, it did significantly depress (P < 0.01) the expression of the renal cannabinoid-1 (CB-1) receptor, CD14, toll-like receptor 4 (TLR4) and tumour necrosis factor (TNF)-alpha protein. Gene delivery also increased nitric oxide (NO) and decreased angiotensin II (Ang II). Finally, transfer of the beta(2)-AR gene also improved the survival of the rats exposed to sepsis-induced ARF. CONCLUSIONS: A renal-specific over-expression of beta(2)-AR, resulting from gene delivery, appeared to modulate renal dysfunction and inflammation following sepsis by altering cAMP-PKA, CB-1 and CD14-TLR4-TNF-alpha pathways. In addition, gene delivery and activation of beta(2)-AR produced modulation of systemic NO and Ang II, which further protected against renal dysfunction. Administration of the Adeno-beta(2)-AR gene has potential as a therapeutic agent against ARF following the onset of sepsis.

Effective prophylactic therapy for cyclic vomiting syndrome in children using valproate.

This trial sought to evaluate our experience using the antimigraine prophylactic drug, use of valproate for the prophylactic management of cyclic vomiting syndrome (CVS) in children. Thirteen children diagnosed with severe CVS were enrolled. Prophylactic therapy consisted of valproate administered at a dose of 10-40 mg/kg/day. Upon enrollment in the study, all patients underwent diagnostic tests to rule out organic causes of their symptoms. Vomiting was severe enough in all patients to cause dehydration requiring hospitalization for intravenous rehydration. Nine of 13 patients did not respond to numerous previous medical therapies like propranolol, amitriptyline, cyproheptadine, phenobarbital, phenytoin, and carbamazepine. Three of 13 patients required combination therapy with valproate and phenobarbital. Of the 13 patients, two showed complete resolution of their symptoms, nine had marked improvement in their symptoms, as evidenced by infrequent attacks of reduced severity, and two failed to respond to valproate therapy. Four patients experienced relapse with a decreased dosage of valproate. Side effects associated with long-term valproate administration were not observed. Valproate appears to be effective for the prophylactic management of severe CVS, with 85% of all patients achieving at least a reduction in the frequency of attacks.

Renal beta(2)-adrenoceptor modulates the lipopolysaccharide transport system in sepsis-induced acute renal failure.

The aim of this study was to define the contribution of renal beta(2)-adrenoceptor (beta(2)-AR) system to regulation of the lipopolysaccharide (LPS) transport system in the kidney of endotoxin-induced septic rats. Seven-week-old Wistar rats (n = 6/groups) pre-treated with the beta(2)-AR antagonist (ICI118,551: 3.14 microg/kg) or saline were injected with LPS (10 mg/kg i.p.) or saline, and then 24 hours later, renal function, beta(2)-AR signaling proteins, innate immune proteins, and cytokines were assayed. The injection of LPS depressed creatinine clearance rate (Ccr) associated with the reduction of renal Gsalpha and cAMP levels by a single dose of ICI118,551. On the other hand, renal CD14, toll-like receptor 4(TLR4), and tumour necrosis factor (TNF)-alpha protein expressions were significantly increased (P < 0.05) by the combination of LPS and ICI118,551. The reduction of Ccr by LPS plus ICI118,551 suggests a possibility that renal specific up-regulation of the CD14-TLR4-TNF-alpha signaling cascade by beta(2)-AR inhibition might be involved in sepsis-induced ARF.

[The effect of prophylactic therapy with valproate sodium and phenobarbital in two patients with cyclic vomiting syndrome].

Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting, and other symptoms, separated by intervals of comparative wellness. Associated symptoms include nausea, abdominal pain, headache, and motion sickness. Recently, CVS was categorized as a migraine. Case 1 was a girl aged 4 years and 11 months, who had frequent and severe episodes of vomiting since she was 3 years old. The diagnosis of CVS was established on the basis of clinical symptoms and laboratory data. Her electroencephalogram was normal. Prophylactic therapy using a single drug such as amitriptyline, carbamazepine, phenytoin, cyproheptadine, valproate sodium or phenobarbital was not effective. However, her recurring vomiting disappeared with prophylactic therapy using valproate sodium and phenobarbital. Case 2 was a boy aged 10 years and 7 months, who had frequent episodes of vomiting since he was 1 year and 10 months old. He had been receiving intravenous hyperalimentation therapy at home since infancy because of frequent vomiting and failure to thrive. His electroencephalogram showed no abnormality. Prophylactic therapy using a single drug such as diazepam, phenytoin, valproate sodium or phenobarbital was not effective. However, his recurring vomiting disappeared with prophylactic therapy using valproate sodium and phenobarbital. There were no adverse effects in both patients. The combination therapy with valproate sodium (20 - 26 mg/kg/day) and phenobarbital (4 - 5 mg/kg/day) was effective as a prophylactic therapy in these two patients. The combination therapy with valproate sodium and phanobarbital for prophylaxis of vomiting may be helpful in patients with intractable CVS.

[Long-term follow up of Kawasaki disease].

For the follow up of the patients with Kawasaki disease, it is important to know the patient's condition in acute stage. For this purpose, there is a card named "Kawasaki disease acute stage card". This card is available at the following site, although it is written in Japanese. http://www.kawasaki-disease.org/tebiki/card.html The cases of no coronary aneurysm and the cases, in whom the coronary aneurysm regressed to normal in 30 days, should be checked at one month, two months, six months, one year and five years after acute stage, using echocardiography and ECG and stress ECG if feasible. For this group, aspirin is not necessary during follow up, and restriction of physical exercise is not required. Regression of aneurysm should be confirmed by coronary angiography, as echocardiography is not sufficient for confirmation. The cases with remaining aneurysm should be assessed for possible stenosis and ischemia, using angiography and/or other imaging methods, including MRI, multi-slice CT, cardiac scintigraphy and other methods. These patients are supposed to be followed by pediatric cardiac specialists.

Renal effects of beta2-adrenoceptor agonist and the clinical analysis in children.

The objectives of the present study were to define the contribution of beta2-adrenoceptors (beta2-ARs) agonists to renal physiology and to investigate whether over-expression of renal beta2-ARs might be implicated in the pathogenesis of renal dysfunction in children as an adverse effect of beta2-AR activation. The renal functional responses to the systemic injection of the beta2-AR agonist terbutaline in Wistar rats over-expressing renal beta2-AR were compared with those of nontreated rats. Furthermore, we evaluated intrarenal beta2-AR expression in 34 children (age 2-15 y) and the changes in serum creatinine levels of 99 children (age 1-15 y) who received beta2-AR agonists. The animal study showed that the suppression of glomerular function by terbutaline was associated with a reduction in systemic blood pressure and over-expression of renal beta2-ARs. Moreover, in rats over-expressing renal beta2-ARs, administration of terbutaline resulted in a high mortality rate after a lipopolysaccharide challenge. The clinical study showed that renal beta2-AR expression gradually increased with age and was up-regulated by steroid therapy. These findings indicate that the renal dysfunction caused by beta2-AR agonists can be explained, at least partly, by enhanced beta2-AR expression in the kidney. This may have important implications for the use of beta2-AR agonists in the treatment of sick children with, for example, steroid therapy or endotoxemia.

Renal hypouricemia in school-aged children: screening of serum uric acid level before physical training.

We present two cases of a 12-year-old Japanese boy and a 14-year-old Japanese girl who had exercise-induced acute renal failure (ARF). They experienced general fatigue, nausea/vomiting, and vague discomfort in the abdomen after physical exercise at school. In case of the boy, abdominal pain subsided, but renal dysfunction lasted 17 days, with peak levels of creatinine 9.4 mg/dl and uric acid 11.3 mg/dl. On the other hand, as the girl had suffered from hypouricemia before, she followed a doctor's guidance on prevention of ARF. Consequently, she was promptly diagnosed as having exercise-induced ARF associated with hypouricemia, and rapidly recovered from ARF within a week. The difference between their clinical courses suggested a possibility that previous laboratory evaluation of serum uric acid assisted in the management of exercise-induced ARF associated with hypouricemia. School-aged children, especially Japanese and Asian, may be advised to have their serum uric acid measured before starting physical training at school.

Etiology and clinical study of community-acquired pneumonia in 157 hospitalized children.

We tried to verify whether the currently employed diagnosis and treatment of community-acquired pneumonia in children were appropriate. For this purpose, we created tentative criteria for the classification of pediatric community-acquired pneumonia. We classified the community-acquired pneumonia into ten categories: (1) bacterial, (2) concomitant viral-bacterial, (3) viral, (4) mycoplasmal, (5) concomitant mycoplasmal-bacterial, (6) concomitant mycoplasmal-viral, (7) chlamydial, (8) concomitant chlamydial-bacterial, (9) concomitant chlamydial-viral, and (10) unknown. Children aged 1 month to 13 years with radiographic and clinical evidence of pneumonia were enrolled. Between October 2001 and September 2002, we enrolled 165 patients. The etiologic agents were determined in 126 of the 157 (80.3%) patients who were finally diagnosed with pneumonia. Two blood cultures were positive for Haemophilus influenzae type b and Streptococcus pneumoniae. A viral infection alone was found in 28 of the 157 patients (17.8%), a bacterial (without mycoplasmal) alone infection in 42 (26.8%), a concomitant viral-bacterial infection in 28 (17.8%), and a mycoplasmal infection in 27 (17.2%) patients. RS virus was identified in 28 patients (17.8%), influenza A in 12 (7.6%), parainfluenza 3 in 8 (5.1%), adenovirus in 8 (5.1%), and influenza B and measles virus in 1 patient each. Streptococcus pneumoniae was the most common cause of bacterial pneumonia. We chose the initial treatment according to clinical and laboratory findings on admission (i.e., patients' age, clinical course, chest X-ray, and laboratory findings). In 68 of the 71 patients with bacterial (without mycoplasmal) pneumonia, an appropriate antibacterial-agent was prescribed. In 25 of the 27 patients with mycoplasmal pneumonia, clindamycin and minocycline were prescribed.

Adenoviral delivery of the beta2-adrenoceptor gene in sepsis: a subcutaneous approach in rat for kidney protection.

Successful gene therapy requires gene delivery that is efficient, has an optimal route of administration and has biosafety. The aims of the present study were to evaluate the safety and applicability of the subcutaneous delivery route for adenoviral transgenes containing the human beta(2)-adrenoceptor (adeno-beta(2)-AR) and to investigate whether this approach prevented renal dysfunction in a rat model of endotoxaemic shock induced by LPS (lipopolysaccharide). Subcutaneous administration of adeno-beta(2)-AR (a total of 10(10) viral particles) significantly increased beta-AR density in the kidney, lung and liver, but was without effect on physiological and plasma biochemical parameters. Moreover, this dose of virus did not cause any of the potential toxic responses of viral administration, such as inflammation and tissue TNF (tumour necrosis factor)-alpha expression. Although the LPS challenge caused a decrease in glomerular filtration rate, fractional excretion of sodium and renal beta-AR density in all groups, the reduction in renal function was significantly less in the rats given adeno-beta(2)-AR compared with non-treated rats. Thus, although further evaluation will be required, this initial study demonstrated that the subcutaneous injection of adeno-beta(2)-AR was efficient, comparatively non-pathogenic and potentially therapeutic to deal with acute renal failure associated with sepsis.

[Beta 2-adrenoceptor function in the kidney].

The majority of beta(2)-adrenoceptor (beta(2)-AR) agonists is eliminated via the kidneys as an unchanged substance. It is likely that such agents will exert pharmacological effects during their passage through the nephron. However, these pharmacological effects have, to our knowledge, not been taken into consideration when using these compounds in clinical practice because the role of beta(2)-AR in the regulation of renal function remains unclear. Renal beta(2)-ARs are predominantly localized to the proximal tubular epithelia and the membranes of smooth muscle cells from renal arteries. From this morphologic evidence, it is proposed that beta(2)-AR activation may regulate glomerular function and thereby sodium and water balance in the nephron segments. Actually, beta(2)-AR agonists given acutely cause a marked decrease in glomerular filtration rate. On the other hand, beta(2)-AR agonists inhibit the renal production of inflammatory cytokines such as TNF-alpha. Furthermore, the administration of beta(2)-AR agonists is found to attenuate apoptosis associated with shigatoxin in the hemolytic uremic syndrome (HUS). Increased understanding of the pharmacological basis of beta(2)-AR function in the kidney provides important new information relevant to the clinical use of beta(2)-AR agonists in airway diseases and potential applications of these drugs in renal inflammation and injury associated with sepsis or HUS.