Dilated cardiomyopathy and thrombo-embolism

 The purpose of this study was to investigate the incidence, outcome and prevention of thrombo-embolism in children with dilated cardiomyopathy. From 130 patients with dilated cardiomyopathy, 17 (14%) showed evidence of thrombo-embolism. Seven had initial cardiac thrombus, 7 exhibited initial embolus and in 3 thrombo-embolism was only diagnosed at autopsy. All 17 patients showed seriously impaired systolic function of the left ventricle with fractional shortening (FS) of 10 ± 3%, range 5%–17%, as compared to those without thrombo-embolism with FS of 17% ± 6%, range 5%–26% (P <; 0.0001). Seven patients were treated with oral anticoagulants once thrombo-embolism had been diagnosed; one of them experienced a further embolic event as opposed to three out of four patients not treated with anticoagulants. Conclusion All children with dilated cardiomyopathy and fractional shortening below 20% should be treated with prophylactic anticoagulative agents Received: 12 May 1996 / Accepted: 29 July 1996     

Nephrotic syndrome and Hodgkin disease in children: a report of five cases

 This report documents the occurrence of a nephrotic syndrome in five children with Hodgkin disease. In two cases the nephrotic syndrome predated the diagnosis of lymphoma by 6 months and 12 months respectively , while in the other three, the two disorders occurred simultaneously. The nephrotic syndrome resolved in four cases during effective treatment for active Hodgkin disease, while proteinuria remained unchanged in the fifth case with partial control of the lymphoma. The occurrence of a nephrotic syndrome as a manifestation of active Hodgkin disease suggests that some immunological abnormalities play a role in the pathogenesis of the association. Conclusion The possibility of glomerular dysfunction although rare must be considered and actively looked for in all cases of Hodgkin disease. Similarly, any unusual sign or symptom noted in patients with nephrotic syndrome, particularly receiving or having received immunosuppressants, requires thorough investigation to determine the presence or absence of lymphoma. Received: 5 December 1995 / Accepted: 4 July 1996     

Paediatric thrombo-embolism: the influence of non-genetic factors and the role of activated protein C resistance and protein C deficiency

 In many children, the pathogenesis of thrombo-embolism remains unexplained. This study examines the role of non-genetic risk factors in 37 children with venous or arterial thrombosis. Included were 17 patients with portal vein thrombosis following umbilical vein catheterisation, 6 with portal vein thrombosis and an uneventful neonatal period, 4 with deep vein␣thrombosis, 4 with renal vein thrombosis after kidney transplantation, 1 haemodialysis patient with thromboses of arteriovenous shunts, and 5 with arterial thromboses at various sites. In 25 of these 37 patients (68%) exogenic risk factors and particularly vascular manipulations (24/37) were related to the thrombotic event. Resistance to activated protein C was identified in 5 patients and protein C deficiency in 2 (7/37; 19%). This prevalence was significantly higher than that of the control group (14/243; 5.8%; χ², P < 0.008). Conclusion Our data show that non-genetic and particular iatrogenic risk factors can often be identified in children with thrombosis, but activated protein C resistance and protein C deficiency are significant genetic risk factors in this age group. Received: 23 April 1996 / Accepted: 1 August 1996     

Progressive left main coronary artery obstruction leading to myocardial infarction in a child with Williams syndrome

We report a 3-year-old child with Williams syndrome in whom the first vascular feature of the syndrome was a myocardial infarction related to the occlusion of the left main coronary artery trunk. This coronary artery occlusion was not associated with supravalvular aortic stenosis. Conclusion This report emphazises that acute vascular events related to systemic artery anomalies may reveal Williams syndrome. Received: 4 February 1997 / Received in revised form and accepted: 6 May 1997     

The Marshall-Smith syndrome: a review of the laryngeal complications

The Marshall-Smith syndrome is characterised by a triad of facial dysmorphism, failure to thrive and accelerated osseous maturation. We report a further case of this rare syndrome with the unusual but previously reported complication of laryngeal hypoplasia and review the associated laryngeal anomalies that have been reported to date. Conclusion Severe airway obstruction due to congenital anomalies must be excluded in any dysmorphic child presenting with respiratory distress at birth. Rapid airway assessment will enable early and appropriate intervention and may be important when deciding on the long-term plan for the infant. Received: 28 March 1996 and in revised form: 13 November 1996 / Accepted: 13 November 1996     

The value of MRI in diagnosing vascular abnormalities causing stridor

In a 2 year period seven patients who presented with stridor, without respiratory compromise, and three patients without obstructive symptoms were prospectively selected, and underwent MRI. In eight patients with a vascular ring and a pulmonary sling, MRI delineated the vascular abnormality and normal great vessels were found in two patients. Conclusion MRI successfully delineates the great vessels and demonstrates the presence of a vascular ring and pulmonary sling. Received: 15 May 1996 / Accepted: 17 January 1997     

Effects of red cell transfusion on pulmonary blood flow and right ventricular systolic time intervals in neonates

Blood transfusion increases blood volume and blood viscosity of the neonate. Since both volume expansion and increase in blood viscosity may be associated with increased pulmonary artery pressure, we studied effects of transfusion (10 ml of red blood cells per kilogramme of body weight) on right ventricular output and right systolic time intervals by means of pulsed-Doppler echocardiography in 38 preterm infants with a mean (SD) gestational age of 28 (5) weeks (range 25–34), birth weight 1060 (395) g (range 480–1910), actual body weight 1875 (450) g (range 820–2790) and postnatal age of 44 (23) days (range 17–105). After transfusion, packed cell volume and haemoglobin increased significantly from 0.26 (0.044) to 0.38 (0.046), and from 8.2 (1.6) g/l to 12.8 (1.9), respectively. Blood viscosity increased from 1.78 (0.3) mPa to 2.68 (0.4) by 33%. Right ventricular output decreased significantly from 320 (57) ml/kg/min to 290 (70) due to decrease in heart rate by 7%. Blood pressure and right ventricular stroke volume did not change. There was a significant increase in pulmonary red cell transport (right ventricular output times packed cell volume) of 21%. Right ventricular pre-ejection period (RPEP), right time peak velocity (RTPV), right ventricular ejection time (RVET), and ratios of RTPV/RVET_(c), RPEP:RVET did not change after transfusion. Conclusion These results suggest that neither pulmonary artery pressure nor right ventricular function changed as a result of transfusion in spite of rising blood volume and blood viscosity. Received: 19 October 1996 / Accepted: 23 December 1996     

Cerebellar defect associated with Schimke immuno-osseous dysplasia

We report the finding of an absent cerebellar hemisphere and partial absence of the cerebellar vermis in a child with dysmorphic features, spondyloepiphyseal dysplasia, steroid resistant nephrotic syndrome secondary to focal segmental glomerulosclerosis and T-cell lymphopenia (Schimke immuno-osseous dysplasia). These findings have not, to our knowledge, been described before and are likely to represent the consequence of a vascular event either in-utero or in early infancy. Conclusion Cerebral imaging should be performed early in the course of the disease and should be repeated if further neurological events develop. Received: 5 December 2000 / Accepted: 24 January 2001     

Respiratory control in children with Prader-Willi syndrome

  Physiological parameters of infants and children with Prader-Willi syndrome were examined in order to clarify whether there were indicators of disturbed respiratory control mechanisms in the pre-obesity stage of the syndrome. From January 1993 to March 1995 in eight patients with Prader-Willi syndrome (five boys, three girls, aged 6 weeks – 12.5 years),␣polysomnography was performed and compared with 28 children matched for gestational age, sex, birth weight and age at sleep study. The recordings included thoracic and abdominal breathing movements, nasal airflow, tcPO₂, tcPCO₂, oxygen saturation, EEG, EOG and ECG. Respiratory responses to hypercapnia during quiet sleep were obtained from five Prader-Willi patients and ten peers. The Prader-Willi group showed an increased number of apnoeas per hour of sleep, a decreased nadir of oxygen saturation, increased maximum of the instantaneous heart rate and decreased respiratory responses to hypercapnia during quiet sleep. Conclusion These findings indicate a primary dis‐turbance of central respiratory control in patients with Prader-Willi syndrome which may be worsened by the development of obesity. Received: 26 January 1996 / Accepted: 21 July 1996     

Septic arthritis of the hip by Fusobacterium necrophorum after tonsillectomy: a form of Lemierre syndrome?

Lemierre syndrome used to be a complication of severe oropharyngeal infection with regional thrombophlebitis, septicaemia and septic metastatic infections caused by Fusobacterium necrophorum in the pre-antibiotic era. A case of septic arthritis of the hip caused by F. necrophorum as a complication of tonsillectomy is reported in a 9-year-old boy. Conclusion Lemierre syndrome, usually seen after an oropharyngeal infection, can also complicate ton-sillectomy. Received: 24 September 1996 / Accepted: 14 January 1997     

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants

The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. Conclusion This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity. Received: 12 October 1995 and in revised form: 30 August 1996 / Accepted: 10 September 1996     

Malignant fibrous histiocytoma of the lung in a child

We describe a 12-year-old patient with a primary pulmonary mass in the left upper lung. The diagnosis of inflammatory pseudotumour was suspected preoperatively. After pathological examination and complete clinical evaluation, a diagnosis of malignant primary pulmonary fibrous histiocytoma was established. This is a very uncommon primary neoplasm of the lung and to our knoweledge only five paediatric cases have been reported. Because of the rarity of these sarcomas and histological similarities to benign inflammatory pseudotumour, care must be taken to avoid confusion between the two disorders particularly in intra-operative frozen sections. Conclusion Primary malignant fibrous histiocytoma of the lung is an uncommon tumour that should be considered in the differential diagnosis of pulmonary neoplasms of childhood. The histological diagnosis can be difficult due to the similarities with␣inflammatory pseudotumour. Received: 29 May 1996 / Accepted: 21 July 1996     

A comparison of intratracheal and intravenous administration of gentamicin during liquid ventilation

Pulmonary absorption of aminoglycosides is poor with intravenous administration, but may be enhanced by direct intratracheal administration of these drugs using perfluorochemical liquid ventilation (LV). To test this hypothesis, gentamicin sulfate was administered to two groups of newborn lambs during LV. Serum and lung tissue levels of gentamicin were compared after either pulmonary intratracheal (IT) or intravenous (IV) routes of administration. Serial serum levels of gentamicin were obtained every 15 min for the 1st h, every 30 min for the 2nd h, and then hourly until sacrifice (maximum 6 h). At sacrifice, representative samples of each lung lobe were homogenized and analyzed for tissue gentamicin content. At 1 h, serum gentamicin levels were similar in both groups: IT administration levels were 3.7 ± 0.55 SE μg/ml and IV levels were 3.5 ± 0.85 SE μg/ml. The peak serum gentamicin level of 4.8 ± 0.8 SE μg/ml for the pulmonary administration group occurred 1.5 h after administration. Lung tissue levels of gentamicin for IT administration (4.04 ± 0.62 SE μg/g) were significantly greater than for IV administration (1.75 ± 0.33 SE μg/g; P < 0.05). There were no significant differences in interlobar gentamicin distribution for either mode of administration. Conclusion Perfluorochemical can be used as a vehicle for intratracheal delivery of antimicrobials. This route provides equivalent serum levels at 1 h, higher lung tissue levels, and uniform interlobar distribution relative to intravenous administration of gentamicin. We speculate that pulmonary administered gentamicin during LV may provide an effective alternative treatment modality in the management of severe neonatal pneumonia. Received: 12 April 1996 and in revised form: 24 July 1996 / Accepted 28 July 1996     

Arginine506 to glutamin mutation in the factor V gene in infancy and childhood: evidence of fibrinolytic impairment

Resistance to activated protein C (APCR), in the majority of cases due to the arginine⁵⁰⁶ (Arg⁵⁰⁶) to glutamine (Gln) mutation in the factor V gene, has emerged as the most important hereditary cause of venous thrombo-embolism. To determine to what extent this relatively common gene mutation influences the fibrinolytic system we investigated a population of APC resistant children (n = 65) in comparison with a control group␣of sex- and age-matched healthy children (n = 100). Compared to the controls, plasma levels of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor (PAI) 1 antigen, D-Dimer and enhanced thrombin generation were significantly (P < 0.0001) increased in children with the common factor V mutation. No difference was found between symptomatic and non-symptomatic children. Whether high concentrations of t-PA, u-PA and PA1 antigen can predict future vascular occlusion in children with APCR requires a more extensive multicentre study. Conclusion Our data indicate that hypercoagulability in children with the Arg⁵⁰⁶ to Gln mutation in the factor V gene is mainly attributed to the genetic aetiology of the disease. Received: 25 May 1996 / Accepted: 3 September 1996     

Vertical transmission of cytomegalovirus, most probably by breast milk, to an infant with Wiskott-Aldrich syndrome with fatal outcome

A 4-month-old boy with prenatally diagnosed Wiskott-Aldrich syndrome became ill with a severe cytomegalovirus (CMV) infection, the outcome of which was fatal. The parents had isolated the infant from other children and adhered to standards of hygiene in order to avoid CMV infection because their first child had died of Wiskott-Aldrich syndrome and CMV infection. The mother breast-fed her child although she was CMV IgG positive. The source of infection was most probably breast milk, which contained CMV at the time the infant developed the generalized CMV infection. Conclusion In infants with immunodeficiency syn‐dromes, CMV infection may have a fatal outcome. Since the virus can be transmitted by breast milk, the advantages and disadvantages of breast-feeding should, therefore, be weighed in newborn infants with an immunodeficiency syndrome whose mother is a CMV carrier. Received 11 November 1996 / Accepted: 14 April 1997     

Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by α-tocopherol supplementation

Natural Killer (NK) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by ⁵¹Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral α-tocopherol (α-Toc) supplementation (100 mg/day), NK cell activity had normalised. When α-Toc supplementation was interrupted for 16 weeks, NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16⁺ CD 56⁻ fraction, which has the most potent NK cell activity. Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of α-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. Conclusion These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16⁺ CD56⁻ NK cells and that this abnormality is reversible with α-Toc supple‐mentation. Received: 30 January 1996 and in revised form: 19 November 1996 / Accepted: 22 November 1996     

Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. Conclusion A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension. Received: 12 June 1998 and in revised form: 13 October 1998 and 21 December 1998 / Accepted: 10 January 1999     

Serum immunoglobulin G, M and IgG:IgM ratio as predictors for outcome of childhood nephrotic syndrome

Background  Nephrotic syndrome is an immune mediated disorder of the kidney associated with T cell dysfunction and secondary disturbance of B cell with changes in levels of immunoglobulin and IgG:IgM ratio. These changes in immunoglobulin levels can be used as a proxy marker to understand the clinical variety and prognosis of nephrotic syndrome. Methods  We studied 43 children with nephrotic syndrome during January 2003 to January 2005 in the Pediatric Nephrology Unit, Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Blood samples were collected from the 43 patients, and serum levels of IgG, IgM and IgG:IgM were measured by liquid phase immunoprecipitation assay. Another 20 healthy children attending the laboratory for blood grouping and hepatitis B screening test were enrolled as controls. Results  In the 43 children with nephrotic syndrome, 24 had steroid sensitive nephrotic syndrome (SSNS) and 19 steroid resistant nephrotic syndrome (SRNS). Compared with healthy children, the IgG level was low, IgM level was high, and IgG:IgM ratio was low (P<0.05). The serum IgG level and IgG:IgM ratio were significantly lower in children with SRNS and in children with frequent relapse (FRNS) combined with steroid dependent nephrotic syndrome (SDNS) than in those with infrequent relapse nephrotic syndrome (IFRNS) (P<0.05, respectively). Conclusions  Management of different nephrotic syndromes is based on the levels of immunoglobulins along with clinical and biochemical parameters. The decrease of IgG level as a predictive marker for unfavorable prognosis of nephrotic syndrome in children needs further evaluation in larger scale studies.     

Plasma endothelin-1 and nitrate levels in Down’s syndrome with complete atrioventricular septal defect-associated pulmonary hypertension: a comparison with non-Down’s syndrome children

Children with Down’s syndrome (DS)-associated complete atrioventricular septal defect (AVSD) have rapid and aggressive development of pulmonary vascular disease when compared with non-Down’s syndrome (ND) children. We aimed to evaluate the role of plasma endothelin-1 (ET-1) and nitrate levels in DS children with complete AVSD-associated pulmonary hypertension (PH) and compare this to ND patients. The study included 20 patients (11 males, nine females) who had complete AVSD associated with PH. Comparisons were made between DS patients (n = 12) aged 4 to 8 months (median 5 months) and ND patients (n = 8) aged 4 to 12 months (median 7 months). Blood samples were drawn from the inferior vena cava, pulmonary artery, pulmonary vein, and aorta. The plasma ET-1 concentrations of the two groups were compared to the peripheral venous and arterial ET-1 levels, and pulmonary vein nitrate was compared to the peripheral arterial nitrate levels of ten healthy infants. The mean pulmonary artery (PA) pressure and pulmonary vascular resistance (Rp) were significantly higher in the DS group than ND patients, and the pulmonary blood flow (Qp) in ND patients was higher than DS patients. There were no differences between the two study groups in regard to plasma ET-1 and nitrate levels obtained from matched sampling sites. The plasma ET-1 and nitrate levels were significantly higher in both study groups compared to the control subjects. The plasma ET-1 and nitrate levels in DS patients with PH were not different when compared to those of ND patients.     

Steroid-resistant nephrotic syndrome associated with steroid sulfatase deficiency—x-linked recessive ichthyosis: a case report and review of literature

Nephrotic syndrome associated with X-linked recessive ichthyosis due to steroid sulfatase deficiency has rarely been reported in English literature. We describe a 4 and a half-year-old boy presenting with steroid-resistant nephrotic syndrome (SRNS) with an underlying ichthyotic skin present since birth. Renal biopsy revealed minimal change disease. As many of the male members of the family also showed similar skin manifestations, genetic analysis was done on the patient, which revealed deletion of the steroid sulfatase (STS) gene spanning both the 3′ as well as the 5′ends. The patient was thus diagnosed with SRNS associated with X-linked recessive ichthyosis. He was started on cyclosporine regimen, and remission was achieved in 5 weeks. We speculate that the deficiency of STS resulting in increased cholesterol sulfate accumulation interferes with the integrity of adherens junctions present between glomerular epithelial cells of the slit diaphragm, and this results in proteinuria and nephrotic syndrome. The nephrotic syndrome remitted with a calcineurin inhibitor medication. Conclusion: We suggest that the deficiency of STS is another one in an increasing list of genetic causes of podocytopathy and nephrotic syndrome. Remission of proteinuria in such a case may be achieved with immunosuppressive medication.