The Heart in Systemic Autoimmune Disorders

Egypt J Pediatr Allergy Immunol 2005; 3(2): 44-5

Patent arterial duct

Patent arterial duct (PAD) is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area) is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of pulmonary overcirculation secondary to a left-to-right shunt must be excluded. Coronary, systemic and pulmonary arteriovenous fistula, peripheral pulmonary stenosis and ventricular septal defect with aortic regurgitation and collateral vessels must be differentiated from PAD on echocardiogram. In preterm infants with symptomatic heart failure secondary to PAD, treatment may be achieved by surgical ligation or with medical therapy blocking prostaglandin synthesis (indomethacin or ibuprofen). Transcatheter closure of the duct is usually indicated in older children. PAD in preterm and low birth weight infants is associated with significant co-morbidity and mortality due to haemodynamic instability. Asymptomatic patients with a small duct have a normal vital prognosis but have a lifetime risk of endocarditis. Patients with moderate-to-large ducts with significant haemodynamic alterations may develop irreversible changes to pulmonary vascularity and pulmonary hypertension

Assessment of left ventricular diastolic function in bronchial asthma: can we rely on transmitral inflow velocity patterns?

Background: Left ventricular (LV) diastolic dysfunction has been reported in bronchial asthma (BA), based on the finding of abnormal transmitral inflow velocities on Doppler echocardiography, and attributed to the use of long-term β2-adrenoceptor agonists. However, these indices of LV filling may be affected by other factors. Objectives: We aimed to assess the effect of acute severe asthma in children on Doppler-derived transmitral inflow velocities and determine the factors influencing them. Methods: 23 asthmatic children [14 males, 9 females; age 8.4±4.2 years] and 15 age- and sex-matched, healthy children [10 males, 5 females; age 9.8±4.3 years] were studied clinically, by spirometry and by echocardiography both during and after resolution of acute severe asthma. Pulsed Doppler-derived right ventricular (RV) systolic time intervals [RV pre-ejection period corrected for heart rate (RVEPc), RV ejection time corrected for heart rate (RVETc), acceleration time (AT)], transmitral inflow velocities [peak E velocity, peak A velocity, E/A ratio], and isvolumic relaxation time (IVRT) were measured. Results: During acute exacerbations of BA, patients had significantly shorter RVETc (p < 0.05) and AT (p < 0.05), significantly higher peak A velocity (p < 0.01), significantly lower E/A ratio (p < 0.01), and significantly higher IVRT (<0.05). A highly significant inverse correlation existed between AT and peak A velocity [r= -0.634 (p < 0.01)] during acute asthma exacerbation but disappeared after its resolution. Conclusion: Transmitral inflow velocity patterns during acute severe asthma in children are suggestive of altered LV preload due to an acute transient elevation in pulmonary artery pressure secondary to the altered lung mechanics, and are not reflective of intrinsic LV diastolic dysfunction. Keywords: Bronchial asthma, right ventricular systolic time intervals, left ventricular diastolic function, transmitral inflow velocity; echocardiography, childrenEgypt J Pediatr Allergy Immunol 2006; 4(2): 61-6

Immunomodulatory effects of food

There is a strong consensus that nutrition plays a role in modulating immune function and that the immune system needs adequate supply of nutrients to function properly. The complexity of the immune system supports this idea because its optimal functioning involves a variety of biological activities including cell division and proliferation, energy metabolism, and production of proteins. The micronutrients most often cited as being important to immune function include vitamins A, C, E, and B6, folate, iron, zinc, and selenium. Other nutrients mentioned as playing a role in immune function include beta-carotene (a precursor to vitamin A), vitamin B12, and vitamin D. On the other hand, over-activation of the immune system can lead to detrimental effects such as chronic inflammation or autoimmune diseases. In persons with allergies, a normally harmless material can be mistaken as an antigen. Some individuals develop an exaggerated immune response to food through developing food allergy which may be IgE mediated, non-IgE mediated, or mixed. This review will highlight the interaction between the immune system and some foods and food components in terms of modulation of immune functions by a variety of mechanisms.Egypt J Pediatr Allergy Immunol 2011;9(1):3-1

Pulmonary arterial hypertension in children after neonatal arterial switch operation

OBJECTIVES: Paediatric pulmonary arterial hypertension (PAH) after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA) is a clinically recognised entity with an estimated incidence of 0.6%-1.0%. Nevertheless, a clinical characterisation is lacking. We present an international cohort of children with PAH after neonatal ASO for TGA and describe epidemiology and clinical course. METHODS: Data were collected of children with PAH after neonatal ASO (≤6 weeks after birth) for simple TGA without residual shunt defects, identified in four national paediatric PAH networks in Europe and one US referral centre. RESULTS: Twenty-five children were identified between 1989 and 2014. In 17 children (68%), PAH was detected <1 year after ASO. In the remaining children, PAH was detected after median 64 months (IQR 19.5, 94.5). Nineteen children (96%) received PAH-targeted therapies. During follow-up after ASO (median 5.2 years), eight children died, four underwent lung transplantation and two received a Potts shunt. 1-year and 5-year Potts shunt- and transplantation-free survival after ASO was 100% and 73%. From first PAH detection, this was 100% and 58%, respectively, which did not differ between children with early (<1 year after ASO) or late PAH detection. CONCLUSIONS: The occurrence of PAH after ASO for TGA represents a specific association. PAH onset may be early or late after ASO, with similar fatal course from first PAH detection. Mechanisms leading to PAH in this association are unknown, but may include abnormal prenatal pulmonary haemodynamics and/or genetic susceptibility. Routine, lifelong follow-up for children who undergo ASO for TGA should include screening for PAH

Human vitreous in proliferative diabetic retinopathy: Characterization and translational implications

Diabetic retinopathy (DR) is one of the leading causes of visual impairment in the working-age population. DR is a progressive eye disease caused by long-term accumulation of hyperglycaemia-mediated pathological alterations in the retina of diabetic patients. DR begins with asymptomatic retinal abnormalities and may progress to advanced-stage proliferative diabetic retinopathy (PDR), characterized by neovascularization or preretinal/vitreous haemorrhages. The vitreous, a transparent gel that fills the posterior cavity of the eye, plays a vital role in maintaining ocular function. Structural and molecular alterations of the vitreous, observed during DR progression, are consequences of metabolic and functional modifications of the retinal tissue. Thus, vitreal alterations reflect the pathological events occurring at the vitreoretinal interface. These events are caused by hypoxic, oxidative, inflammatory, neurodegenerative, and leukostatic conditions that occur during diabetes. Conversely, PDR vitreous can exert pathological effects on the diabetic retina, resulting in activation of a vicious cycle that contributes to disease progression. In this review, we recapitulate the major pathological features of DR/PDR, and focus on the structural and molecular changes that characterize the vitreal structure and composition during DR and progression to PDR. In PDR, vitreous represents a reservoir of pathological signalling molecules. Therefore, in this review we discuss how studying the biological activity of the vitreous in different in-vitro, ex-vivo, and in-vivo experimental models can provide insights into the pathogenesis of PDR. In addition, the vitreous from PDR patients can represent a novel tool to obtain preclinical experimental evidences for the development and characterization of new therapeutic drug candidates for PDR therapy

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially