Lars Kjærsgaard Hansen

Diagnostic value of chest radiography and electrocardiography in the evaluation of asymptomatic children with a cardiac murmur

We investigated the diagnostic value of the chest radiograph and ECG in the evaluation of whether asymptomatic children with a cardiac murmur had a heart disease as defined by echocardiography. One hundred children aged 1 month to 15 years (median 30.1 months) were included. After physical examination, a tentative diagnosis was made: 53 children had no heart disease, 24 had a probable heart disease and 23 children were thought to have heart disease on the basis of clinical assessment alone. After information from chest radiography and electrocardiography was obtained, the diagnoses were re‐evaluated. This resulted in a change of the tentative diagnosis in three children. However, the diagnosis in relation to the definite diagnosis by colour Doppler echocardiography was not changed to the correct diagnosis in any of these cases. In 24 cases, radiography suggested the presence of heart disease; however, only 10 of these had heart abnormalities on the colour Doppler echocardiogram (CDE). Three children had an abnormal ECG; all of these had abnormalities on the CDE, but they were already diagnosed as having heart disease by physical examination. We conclude that chest radiography and electrocardiography is of no help in the discrimination between heart disease and no heart disease in asymptomatic children referred for a cardiac murmur.

Initial evaluation of children with heart murmurs by the non-specialized paediatrician.

To analyse the ability of the non-specialized paediatrician to evaluate children with a heart murmur and the consequences of this evaluation for the need of further investigations, we undertook a prospective and consecutive study of 100 children, referred for initial evaluation of a heart murmur. Except for 1 child with a slight peripheral pulmonary artery stenosis, 53% of the children were correctly diagnosed as having no heart disease. In a project design where 47% of the children were referred for an echocardiographic study, no clinically significant heart disease was missed.ConclusionClinical evaluation without laboratory tests performed by paediatricians without any special training in cardiology could correctly acquit 50% of the children of heart disease, with no need for further investigation.

Does a positive end-expiratory pressure-induced reduction in stroke volume indicate preload responsiveness? An experimental study

Background:  Increases in positive end‐expiratory pressure (PEEP) are often associated with cardiovascular depression, responding to fluid loading. Therefore, we hypothesized that if stroke volume (SV) is reduced by an increase in PEEP this reduction is an indicator of hypovolemia or preload responsiveness, i.e. that SV would increase by fluid administration at zero end‐expiratory pressure (ZEEP). The relationship between the cardiovascular response to different PEEP levels and fluid load as well as the relation between change in SV as a result of change in preload (Frank–Starling relationship) were evaluated in a porcine model. In addition, other measures of fluid status were assessed.

Selective recruitment maneuvers for lobar atelectasis: effects on lung function and central hemodynamics: an experimental study in pigs

We investigated whether selective lung recruitment of a lobar collapse would improve oxygenation and lung volume as well as a general (global) lung recruitment maneuver, with fewer circulatory side effects. In 10 ventilated, anesthetized pigs, a bronchial blocker was inserted in the right lower lobe, which was selectively lavaged to create a dense lobar collapse. The pigs were randomized into two orders of lung recruitment maneuvers (40 cm H2O airway pressure for 30 s): either a selective lung recruitment maneuver (using the inner lumen of the bronchial blocker) followed by a general lung recruitment maneuver, or vice versa. Median end-expiratory lung volume and median Pao2 increased significantly by approximately 100 mL and 16 kPa, respectively, with no significant differences between the two recruitment methods. There were no circulatory changes during the selective lung recruitment maneuver, but during the general lung recruitment maneuver, mean arterial blood pressure decreased significantly by 36 (21, 41) mm Hg (median, 25th and 75th percentiles), cardiac output by 2.1 (1.6, 2.5) L/min and left ventricular end-diastolic area by 4.4 (3.5, 4.5) cm2. In conclusion, a selective recruitment maneuver improved lung function similar to a general lung recruitment maneuver but without any circulatory side effects.

Are Selective Lung Recruitment Maneuvers Hemodynamically Safe in Severe Hypovolemia? An Experimental Study in Hypovolemic Pigs with Lobar Collapse

BACKGROUND:We have previously shown, in normovolemic pigs, that a selective lung recruitment maneuver (S-LRM), i.e., insufflation of air-oxygen via a balloon catheter with its tip located in the bronchus of a collapsed lung lobe, effectively improves oxygenation and lung volume without affecting hemodynamics negatively. In this study, we examined the respiratory and circulatory effects of S-LRM during hypovolemia with compromised circulation. METHODS:In eight ventilated (fraction of inspired oxygen, Fio2 1.0) and anesthetized pigs a balloon catheter was inserted in the bronchus of the right lower lung lobe. The lobe was selectively lavaged to create a dense lobar collapse. The pigs were then subjected to S-LRM (40 cm H2O airway pressure for 30 s) at normovolemia, after venesection of 20% and 40% of the blood volume, respectively. Blood gases, compliance of the respiratory system (Crs), vascular pressures, and cardiac output were registered before, during, and after the S-LRM. RESULTS:Pao2, venous admixture, and Crs improved significantly with S-LRM at all three volume levels. No change in hemodynamics with S-LRM occurred in normovolemia and 20% hypovolemia. For 40% hypovolemia, cardiac output was unchanged by S-LRM, whereas minor decreases in mean arterial blood pressure were seen: 48 (37–52) mm Hg (median, 25th and 75th percentiles) 3 min before S-LRM, 40 (35–44) mm Hg at the end of S-LRM (P = 0.0207), and 47 (39–54) mm Hg 3 min after S-LRM. CONCLUSION:A S-LRM effectively improved oxygenation and Crs and had only minor circulatory side effects, even in severe hypovolemia in this animal model of lobar collapse.

The Venturi Anaesthesia Circuit I An All‐Purpose Breathing System for Anaesthesia

The Venturi is a flow‐accelerating injector, activated by fresh gas inflow from the anaesthetic machine. The Venturi entrains exhaled gas from the patient through a soda‐lime canister, and carries it to the patient together with fresh gas. The Venturi circuit is a Mapleson D system and the fresh gas requirements are roughly 30 ml kg‐1 min‐1 for anaesthetized, relaxed, adult patients under controlled ventilation.

Molybdenum cofactor deficiency in two siblings : diagnostic difficulties

Two siblings with molybdenum cofactor deficiency are presented. They showed clinical, biochemical and neuroradiological features very similar to those of the few previously described cases. Difficulties in diagnosis are emphasised.

Two novel mutations in RNU4ATAC in two siblings with an atypical mild phenotype of microcephalic osteodysplastic primordial dwarfism type 1

Taybi–Linder syndrome or microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) (MIM # 210710) is a rare autosomal recessive developmental disorder, originally described in 1967 (Taybi and Linder, 1967). The patients present with severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphism, sparse thin hair and dry skin (Meinecke and Passarge, 1991). Radiological findings include dysplasia of the skeleton with cleft vertebral arches, horizontal acetabula and short and bowed long bones (Sigaudy et al., 1998). Neurological findings typically include profound developmental delay, blindness, hearing deficits, central nervous system malformations, early-onset epilepsy and neuroendocrine dysfunction (Pierce and Morse, 2012). MOPD1 has been shown to result from biallelic mutations in the RNU4ATAC gene encoding the small nuclear RNA (snRNA) U4atac, which is a component of the minor spliceosome. Although accounting for splicing of only about 800 introns, the minor spliceosome is involved in the correct splicing of many essential gene products. Thus, minor intron splicing has a critical role in human development (He et al., 2011). At present, only around 40 patients with MOPD1 and 10 different RNU4ATAC mutations have been reported according to the Human Gene Mutation Database. The condition is usually severe, and the patients do not generally live beyond the age of 3 years (Meinecke and Passarge, 1991). A few cases with a slightly milder phenotype have been reported (Abdel-Salam et al., 2012; Nagy et al., 2012), but no patients have yet been reported to survive into adulthood. We report on two adult siblings with MOPD1 presenting with an atypical mild phenotypic appearance compared with the previously reported cases.

Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.

Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.

Both Low Blood Glucose and Insufficient Treatment Confer Risk of Neurodevelopmental Impairment in Congenital Hyperinsulinism: A Multinational Cohort Study

Background/aims Congenital hyperinsulinism (CHI) is a heterogeneous disease most frequently caused by KATP-channel (ABCC8 and KCNJ11) mutations, with neonatal or later onset, variable severity, and with focal or diffuse pancreatic involvement as the two major histological types. CHI confers a high risk of neurological impairment; however, sparsely studied in larger patient series. We assessed the neurodevelopmental outcome in children with CHI at follow-up in a mixed international cohort. Methods In two hyperinsulinism expert centers, 75 CHI patients were included (Russian, n = 33, referred non-Scandinavian, treated in Denmark n = 27, Scandinavian, n = 15). Hospital files were reviewed. At follow-up, neurodevelopmental impairment and neurodevelopmental, cognitive and motor function scores were assessed. Results Median (range) age at follow-up was 3.7 years (3.3 months–18.2 years). Neurodevelopmental impairment was seen in 35 (47%). Impairment was associated with abnormal brain magnetic resonance imaging (MRI); odds ratio (OR) (95% CI) 15.0 (3.0–74.3), p = 0.001; lowest recorded blood glucose ≤1 mmol/L; OR 3.8 (1.3–11.3), p = 0.015, being non-Scandinavian patient, OR 3.8 (1.2–11.9), p = 0.023; and treatment delay from first symptom to expert center >5 days; OR 4.0 (1.0–16.6), trend p = 0.05. In multivariate analysis (n = 31) for early predictors with exclusion of brain MRI, treatment delay from first symptom to expert center >5 days conferred a significantly increased risk of neurodevelopment impairment, adjusted OR (aOR) 15.6 (1.6–146.7), p = 0.016, while lowest blood glucose ≤1 mmol/L had a trend toward increased risk, aOR 3.5 (1.1–14.3), p = 0.058. No associations for early vs. late disease onset, KATP-channel mutations, disease severity, focal vs. diffuse disease, or age at follow-up were seen in uni- or multivariate analysis. Conclusion Not only very low blood glucose, but also insufficient treatment as expressed by delay until expert center hospitalization, increased the risk of neurodevelopmental impairment. This novel finding calls for improvements in spread of knowledge about CHI among health-care personnel and rapid contact with an expert CHI center on suspicion of CHI.