Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment.

BACKGROUND: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: To assess the inflammation in the skin of patients with EBS-gen sev. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. CONCLUSIONS: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.

Right subclavian artery aneurysm in an adolescent with a bicuspid aortic valve.

Bicuspic aortic valve is the most common congenital cardiac anomaly (Fedak et al. 106:900-904, 2002), and it is associated with other structural anomalies of the aorta, such as coarctation, suggesting a common embryologic developmental mechanism (Mergan et al. 104:118-119, 2004). In more than a half of patients, it is associated with progressive dilation and aneurysm formation of the aorta (Warnes 89:965-966, 2003) despite normally functioning bicuspid aortic valves. In this context, aneurysms of the right subclavian artery are extremely rare, and even more so when associated with a right-sided aortic arch that has a left aberrant subclavian artery with a Kommerell diverticulum, as found in the reported case. These aneurysms represent a significant risk for thromboembolism and rupture, and elective surgical management should be advised, even for asymptomatic cases.

Assessment of essential and nonessential metals and different metal exposure biomarkers in the human placenta in a population from the south of Portugal.

The general population is exposed to metals as trace amounts of metallic compounds are present in air, water, and food. Information on background exposures and biomarker concentrations of environmental chemicals in the general Portuguese population is limited. Therefore, the purpose of this study was to determine the levels of important nonessential metals with recognized toxicity cadmium (Cd) and lead (Pb) and essential metals copper (Cu), nickel (Ni), chromium (Cr), and zinc (Zn) in placentas of mothers living in south Portugal (Algarve). Due to the difficulty in establishing the effects of chemicals in a complex and variable environment, this study also aimed to examine the response of biomarkers, such as biochemical changes that occurs at subcellular levels in the presence of contaminants. The investigated biomarkers in placentas indicative of metal exposure or damage included the metallothioneins (MT), delta-aminolevulinic acid dehydratase (ALAD) (specific for Pb), and lipid peroxidation (LPO) as an index of oxidative stress damage. Moreover, HJ-BIPLOT was applied in order to identify and categorize mothers vulnerable to environmental contamination in this region. Metal concentrations in the placenta were not excessive but within the range found in most European studies. In general, the biomarkers MT and LPO were positively correlated with metal levels, while with ALAD the opposite occurred, indicating the selected battery of biomarkers were suitable to study the effects of metals on human placenta. Further, the application of multivariate analysis with HJ-BIPLOT showed that most significant factors contributing to maternal and fetal exposures via placenta were dietary and smoking habits.

Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists.

BACKGROUND: Although topical treatments and phototherapy are available for more than 40 years, there is a paucity of evidence-based recommendations regarding their use. OBJECTIVES: The aim of this work was to develop evidence-based recommendations on topical treatments and phototherapy in psoriasis for daily clinical use. METHODS: A scientific committee selected clinically relevant questions on efficacy and safety of topical agents and phototherapy in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2011, including 42 dermatologists. Recommendations for use of topical treatments and phototherapy were made during interactive workshops where the evidence was presented and discussed. Agreement among participants was assessed on a 10-point scale. The participants systematically assessed the impact of the recommendations on clinical practice. RESULTS: A total of 3555 references were identified, among which 312 articles were included in the systematic reviews. Three recommendations were issued on phototherapy including both PUVA and narrow-band UVB. The recommendations related to administration schedule, clearance rate and risk of side-effects. The mean agreement between participants was good varying from 8.5 to 9.5. Six recommendations were issued on topical treatments focusing on administration schedule, clearance rate, risk of side-effects, cost-effectiveness and measures to improve treatment adherence. The mean agreement between participants varied from 7.3 to 9.9. CONCLUSIONS: These recommendations for the use of topical agents and phototherapy in psoriasis are evidence-based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the opinion of physicians who were not involved in generating the recommendations.

Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and Narrowband UV-B (NB-UVB or UVB TL-01) are well established treatments for chronic plaque psoriasis but there is limited evidence regarding their respective efficacy. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of oral 8-methoxypsoralen-UV-A and Narrowband UV-B in psoriasis, a systematic review to assess respective response rates, remission duration and predictive factors of efficacy was performed. METHODS: A systematic search was carried out in PubMed, Cochrane and Embase databases, using the key words 'Psoriasis', 'UVB therapy', 'UVA therapy' for the period from 1980 to December 2010. RESULTS: The initial literature search identified 773 articles. The final selection included 29 randomized controlled trials: 18 were about the efficacy of PUVA, eight about the efficacy of NB-UVB and three directly compared PUVA vs. NB-UVB. The response rate defined by 75% or more improvement in PASI was 80% with PUVA vs. 70% with NB-UVB. The meta-analysis of the three comparative studies found a higher probability of remission at 6 months with PUVA than with NB-UVB [OR = 2.73 (95% CI 1.19-6.27), P = 0.02]. The choice of initial dose, according to skin type, the minimal erythemal dose or minimal phototoxic dose, incremental regimen and periodicity of the sessions did not appear to be predictive factors of efficacy for PUVA or NB-UVB. Despite methodological limitations in trials, the number of sessions needed for psoriasis clearance appeared to be lower with PUVA than with NB-UVB (approx. 17 vs. 25, respectively). CONCLUSION: PUVA and NB-UVB are both effective therapies in treatment of psoriasis. Our results suggest that compared with NB-UVB, PUVA tends to clear psoriasis more reliably, with fewer sessions, and provides with longer lasting clearance. However, the long-term safety of PUVA, especially its cutaneous carcinogenic risk, and the easier administration procedure often lead dermatologists to prefer NB-UVB as first line phototherapy treatment in plaque type psoriasis.

Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and narrowband UV-B (NB-UVB or UVB TL-01) are effective and widely used treatments for chronic plaque psoriasis. Although the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated, there is still controversy regarding the risk of skin cancer with NB-UVB. Furthermore, there is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime. OBJECTIVES: To assess the respective cutaneous carcinogenic risks of PUVA or NB-UVB in psoriasis; to estimate the respective dose-relationship between skin cancers and PUVA or NB-UVB; to estimate a maximum number of sessions for PUVA or NB-UVB not to be exceeded in a lifetime. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from1980 to December 2010 in English and French, with the keywords 'Psoriasis' AND 'UVB therapy' AND 'UVA therapy' AND 'cancer' AND 'skin' OR 'neoplasm' OR 'cutaneous carcinoma' OR 'melanoma'. RESULTS: Of 243 identified references, 49 published studies were included. Most of them (45/49) concerned PUVA therapy, with 41 assessing the risk of non-melanoma skin cancers (NMSC) following PUVA. All publications referring to the US prospective PUVA follow-up study revealed an increased risk of NMSC with the following characteristics: risk most pronounced for squamous cell carcinomas developing even with low exposures and increasing linearly with the number of sessions, tumors occurring also on non-exposed skin including invasive penile tumors, risk persisting after cessation of treatment. An increased risk of basal cell carcinomas was observed in patients receiving more than hundred PUVA sessions. The four prospective European studies selected in our review and most of the pre-1990 European and US retrospective studies failed to find a link between exposure to PUVA and skin cancer. Only the most recent cohorts, including three large long-term retrospective European studies comparing records with their respective national cancer registries reported on an independent increased risk of NMSC with PUVA, The risk was lower as compared to the US prospective PUVA follow-up study. Six studies assessed the risk of melanoma following PUVA therapy: two of the three US publications coming from the same PUVA prospective follow-up study revealed an increased risk with more than doubled incidence of both invasive and in situ melanoma among patients exposed to at least 200 PUVA treatments compared with patients exposed to lower doses, whereas the three retrospectives European studies, comparing the incidence of melanoma in PUVA users with national cancer registers, did not find any increased risk of melanoma. No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB. CONCLUSION: There is an increased risk of skin cancer following PUVA, shown by both US and European studies. The greater risk measured by the US studies may be at least partly explained by high UVA dose exposure and the lighter phototypes of the treated patients. The lack of prospective studies in psoriasis patients treated with NB-UVB constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy technique.

Topical corticosteroids in plaque psoriasis: a systematic review of efficacy and treatment modalities.

INTRODUCTION: Topical steroids are used for more than 50 years to treat mild-to-moderate plaque psoriasis. The purpose of this systematic review was to evaluate the efficacy but also the optimal modalities of administration of topical corticosteroids in psoriasis i.e. influence of steroid potency on clinical response, putative impact of topical formulation, occlusion procedure, rate of application to control the initial response and the potential interest of a maintenance treatment to prolong psoriasis clearance. MATERIAL AND METHODS: A systematic search was performed between 1980 and January 2011 in Medline, Embase and Cochrane databases (English and French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj. To analyse response across studies, three levels of response were categorized depending on the data available in studies: percentage of patients who achieved more than 50%, 75% or 90% improvement of initial psoriasis severity. RESULTS: From an initial selection of 1269 references, 1166 references were excluded on reading the title or the abstract and 32 on reading the article and 71 were finally retained and analysed. Fifty randomized controlled trials (RCT) assessing topical steroids in the initial treatment of mild-to-severe psoriasis body plaque psoriasis were retained: 40 were parallel-group studies and 10 were within-patient studies. Treatment duration was mostly 4 weeks. Sample size varied from 30 to 1 603 patients. Outcome measures to assess efficacy were highly variable. A total of 30-90% patients across parallel group studies experienced more than 50% of initial mild-to-severe psoriasis improvement while from 7% to 85% experienced more than 75% improvement and from 5% to 85% experienced at least 90% of improvement. The success rate in the within-patient studies varied from 10% to 70%. Eighteen RCT were performed in scalp psoriasis: 16 were parallel-group and two were within-patient studies, with a treatment follow-up time from 2 weeks to 6 months, enrolling 42-1417 patients. A total from 40% to 75% patients across studies experienced more than 75% of initial scalp psoriasis improvement and from 43% to 90% experienced more than 90% initial psoriasis improvement. Only three RCT studies evaluated topical steroids as a maintenance treatment for body psoriasis and one for scalp lesions. Despite heterogeneity in treatment schedule, topical steroid intermittent maintenance treatment was shown to prolong remission. The literature analysis did not provide with high evidence-based quality data on the role of formulation, topical steroid potency, number of applications per day to obtain the highest rate of success excepting occlusion dressing which provided with additional benefit. CONCLUSION: The clinical development of topical steroids in psoriasis did not follow state of the art modern methodology. Treatment success appears to be highly variable across studies. Maintenance intermittent treatment appears to be useful to prolong remission. Recommendations concerning topical steroids treatment modalities in plaque psoriasis should be mostly based on expert opinion.

Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.

BACKGROUND: Topical steroids have been used for more than 50 years in mild-to-moderate plaque psoriasis and carry a theoretical risk of adverse events. OBJECTIVES: The aim of this systematic literature review was to evaluate the risk of hypothalamo-pituitary-adrenal (HPA) axis suppression and the risk of skin atrophy with topical steroids in the treatment of plaque psoriasis. METHODS: A systematic search between 1980 and January 2011 in Medline, Embase and Cochrane databases (English, French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj, RESULTS: Altogether 1269 references were found. Of these 1124 articles were excluded by reading the abstract and 123 by reading the article. A total of 22 randomized trials were selected. Effects on HPA axis: Thirteen studies, with a sample size varying from 7 to 341 patients, were selected. The effect on HPA axis was evaluated by the morning cortisol level (11 studies), the 24 h urine steroid levels (five studies) and/or by the Synacthen test (three studies). Reduction of morning cortisol was observed in 0-25% of patients in 10 short-term studies (two in scalp psoriasis, eight in body psoriasis) and in 48% of patients in the remaining short-term study (body psoriasis). Only four of these studies with three on body psoriasis evaluated the effect of long-term treatment defined as 6-month treatment duration or longer and did not identify HPA axis suppression by cortisol level measurement. The Synacthen test, considered as the gold standard to assess HPA axis, was always normal. There was no evidence of clinically significant HPA axis suppression due to absorption of topical steroids even when treating the scalp or in patients with extensive disease. Risk of skin atrophy: Thirteen studies with topical steroid evaluating treatment durations from 4 weeks to 1 year were analysed. The frequency of skin atrophy assessed clinically, varied from 0% to 5% of patients. CONCLUSIONS: The literature analysis on topical steroids in psoriasis is reassuring although the quality of safety studies is limited with a majority of short-term studies. Although short-term biological effects of topical steroids on the HPA axis were observed in several clinical studies, they were not associated with clinical signs. Adequately designed long-term studies would be necessary to better determine the risk of skin atrophy using modern methods of evaluation such as dermoscopy and echography.

Miocardio ventricular no compactado. Un caso de diagnóstico prenatal / Non-compaction of the ventricular myocardium: A case with prenatal diagnosis

El miocardio ventricular no compactado, anteriormente denominado miocardio esponjoso, es una cardiomiopatía congénita rara. Esta anomalía de la morfogénesis endomiocárdica se caracteriza por la persistencia de numerosas trabeculaciones ventriculares prominentes y espacios intertrabeculares profundos.Esta enfermedad es frecuentemente familiar y fue incluida en el grupo de las cardiomiopatías no clasificadas. La ecocardiografía es el método de elección para el diagnóstico, realizado generalmente en el período posnatal, siendo pocos los casos descritos de detección prenatal.Los autores describen un caso de miocardio no compactado diagnosticado in utero a las 28 semanas de gestación, tras un examen ecográfico de rutina. Por tratarse de una patología con espectro variable se decidió proseguir el embarazo. A las 33 semanas la ecografía reveló hidropesía fetal con derrame pericárdico, procediéndose a realizar una cesárea electiva. El recién nacido presentó una insuficiencia cardíaca con anasarca, quedando internado en cuidados intensivos durante 1 mes.La investigación de este caso reveló que tres miembros de la familia (madre, hermano y abuela materna) tenían miocardiopatía dilatada, sugeriendo un patrón de transmisión autosómico dominante.Actualmente el paciente tiene 5 años, encontrándose en la clase II NYHA, con tratamiento con inibidor de enzima de conversión de la angiotensina, diuréticos y antiagregantes plaquetarios

Isolated non-compaction of the ventricular myocardium, previously known as spongy left ventricular myocardium is a rare cardiomyopathy. This anomaly of endomyocardial morphogenesis is characterised by an excessive number of prominent trabeculations in the ventricular myocardium and by deep intertrabecular recesses.The disease is often familial and has been categorized in the group of unclassified cardiomyopathies. The diagnosis is based on echocardiography findings, often made post natally with a few cases of antenatal diagnosis reported.We describe a case of isolated ventricular non-compaction detected at 28 weeks gestation after a routine fetal scan. Since the disease has un uncertain prognosis it was decided to continue pregnancy. At 33 weeks of gestation, fetal echocardiography verified the presence of fetal hydrops with pericardic effusion, and elective caesarean was made. At birth he presented a heart failure with generalized oedema and was admitted in intensive care unit during 1 month.The family investigation identified dilated cardiomyopathy in three relatives (mother, sister and grandmother), suggesting an autosomal dominant inheritance.He has now 5 years old and is in NYHA class II, treated with angiotensin-converting enzyme (ACE) inhibitors, diuretics and platelet antiaggregant (AU)

[Digoxin. The drug of choice for the in-utero treatment of paroxysmal supraventricular tachycardia]. / Digoxina. A droga de escolha para o tratamento in utero da taquicardia paroxística supraventricular.

Fetal tachyarrhythmia may constitute a risk for the fetus, therefore early treatment is indicate for all cases of tachydysrhythmia, with or without hydrops, in order to prevent irreversible hydrops. A case report is described of supraventricular paroxysmal tachycardia with digoxin in utero therapy in which pharmacological intervention was successful. Some comments are regarding the experience of the multidisciplinary team at Bissaya-Barreto Maternity in the treatment and orientation of fetal tachydysrhythmias.

[Free thrombi in the left atrium. Report of a clinical case]. / Trombos livres na aurículo esquerda. A propósito de um caso clínico.

The authors describe a case of a floating thrombus in the left atrium, detected by a 2D echocardiography in a female patient suffering from dilated cardiomyopathy. At the follow-up, it was found that the mass was no longer detected inside the left atrium. This occurrence was not associated to any major embolic phenomena. A transesophageal echocardiographic study revealed the presence of a thrombus in the left atrial appendage.

[Rupture of the interventricular septum and the left ventricular wall caused by non-penetrating thoracic trauma. Report of a case]. / Rotura do septo interventricular e da parede livre do ventrículo esquerdo por traumatismo torácico não penetrante. A propósito de um caso.

Heart contusion is one of the many lesions that can result from closed chest trauma. The fatal case of a seven years old boy is presented. A ventricular septum and left ventricle free wall rupture resulted from a backward kick of a cow. Diagnosis, although too late, was made by echo-Doppler cardiography. This examination should be made whenever there is a closed chest trauma.

Preservation of the pulmonary annulus in total correction of tetralogy of Fallot. Decreasing transannular gradients in the early follow-up period.

The integrity of the pulmonary annulus was preserved in 21 of 22 children consecutively subjected to total correction of tetralogy of Fallot. There was one early death (4.8%). The 20 survivors were studied prospectively and constitute the basis of this report. Mean age was 59.3 +/- 35.3 months (range 6 months-12 years). Eight patients (40%) had previous Blalock-Taussig shunts and 3 (15%) had associated cardiac anomalies. Two-dimensional Doppler echocardiography had demonstrated right ventricle to main pulmonary artery peak systolic gradients of 75.4 +/- 12.7 mmHg (range 50-104 mmHg). Ventricular infundibulectomy was carried out in all patients but one, who had abnormal coronary anatomy. Extensive incision or resection of hypertrophied or abnormal muscle bands was performed. Pulmonary valve commissurotomy was performed in 14 patients (70%), 10 (50%) had autologous pericardium supravalvular enlargement of the pulmonary trunk and one (5%) had an infundibular bovine pericardial patch. Intraoperative, postrepair right/left ventricular pressure ratios were 0.67 +/- 0.18 (range 0.41-1.0). All ratios were accepted, because all patients were haemodynamically well and only two required inotropic (dopamine) support. There was no late mortality. During the early follow-up period (mean 13.0 +/- 5.4 months, range 7-25 months), all patients had two-dimensional Doppler echocardiography measured gradients at discharge (mean 44.2 +/- 22.6 mmHg, range 10-86 mmHg; p less than 0.001 vs. preoperative values), at 3 months (mean 31.1 +/- 14.5 mmHg, range 8-64 mmHg; p less than 0.011 vs. values at discharge) and at 6 months (mean 28.5 +/- 14.3 mmHg, range 12-57 mmHg; p = 0.009 vs. values at discharge). A similar favourable evolution of the diameters of the pulmonary annulus and of the right pulmonary artery was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cor triatriatum. Echo/Doppler diagnosis followed by immediate surgical correction. Report of a clinical case]. / Cor triatriatum. Diagnóstico por Eco/Doppler seguido de correcção cirúrgica imediata. A propósito de um caso clínico.

As Cor Triatriatum is a rare congenital cardiopathy and benign after corrective surgery, decisive means of diagnosis are essential. The AA review some descriptive theoretical concepts and make reference to the difficulties, present at times, in diagnosis by cardiac catheterization. They consider Eco-Doppler to be the means of excellence for its recognition describing all aspects that point to the diagnosis of this pathology. Described is the case of a 12 month old baby, in whom some semiological findings had lead to a wrong diagnosis. In the discussion, additional diagnosis is eliminated due to some anatomic characteristics defined by echocardiography.

[Right coronary fistula to the right atrium. Diagnosis using Doppler echocardiography with color coding]. / Fístula coronária direita para a aurícula direita. Diagnóstico por Eco Doppler com codificação em cor.

A case of right coronary fistula draining to the right atrium which was diagnosed by Echo Doppler and colour flow mapping is presented. A patent ductus arterious was initially diagnosed clinically on this child and he was been waiting for 2D Echo and Doppler registration. The patient is now on waiting list for corrective surgery and a cardiac catheterization confirmed totally our diagnosis obtained by non invasive methods.

[Calculation of the pulmonary to systemic flow ratio using echo-Doppler in septal defects--correlation with oximetry]. / Cálculo da relação dos débitos pelo eco-Doppler nos defeitos septais--correlação com a oximetria.

OBJECTIVE: 1. local validation of a protocol of measurement of pulmonary to systemic flow ratio (QP/QS) by echo-Doppler in children with septal defects; 2. to assess continuous wave Doppler efficacy mainly in those patients where peak pulmonary flow velocity was beyond the Nyquist limit of pulsed Doppler. DESIGN: To correlate QP/QS ratio determined by echo-Doppler with that obtained by cardiac catheterization (oximetric method) performed within 48 hours, in children with isolated septal defects. MATERIAL AND METHODS: The QP/QS ratio was evaluated by pulsed and or continuous wave echo-Doppler in 50 children who were submitted within 48 hours to cardiac catheterization. All children had an intracardiac shunt (12 atrial septal defects--ASD; 26 ventricular septal defects--VSD and 12 atrio ventricular septal defects--AVDS). Identical measurements were performed in a group of 20 children without cardiac malformation--control group. To test inter-observer variability, all the measurement in 31 patients were repeated by a second observer. Pulmonary and aortic flow was calculated as: Q = A x V x ET x CF where, A is the valvular orifice area (cm2), V the mean flow velocity (cm/sec), ET the ejection time (sec) and CF the cardiac frequency (cycles/min). The Doppler beam-flow direction angle in the pulmonary (P) artery and ascending aorta (Ao) was less than 20 degrees. Results were correlated with those obtained by catheterization (oximetric method). RESULTS: We obtained a fairly good correlation with both pulsed wave Doppler (n = 43; r = 0.88; p less than 0.001; y = 0.84x + 0.40) and continuous wave Doppler (n = 50; r = 0.91; p less than 0.001; y = 0.86x + 0.35) or with pulsed wave Doppler in the P artery and continuous wave Doppler in the Ao (n = 43; r = 0.92; p less than 0.001; y = 0.86x + 0.27). In the control group, QP/QS ratio was evaluated by echo-Doppler: pulsed wave Doppler at 1.05 +/- 0.15 (mean +/- DS); continuous wave Doppler at 1.05 +/- 0.12 and, pulsed wave Doppler in the P artery and continuous wave Doppler in the Ao at 1.03 +/- 0.12. There was no significant difference in all three groups to the normal range of 1.00 (p less than 0.01). Inter-observer variability was less than 5.5% (p less than 0.001). CONCLUSION: Pulsed and/or continuous wave echo-Doppler measurements are a reliable noninvasive method in evaluating QP/QS ratio in children with isolated septal defects.