José Ramet

Acrodermatitis enteropathica-like cutaneous lesions in organic aciduria

Cutaneous lesions resembling acrodermatitis enteropathica were present in two infants with methylmalonic acidemia and in one infant with propionic acidemia. All three infants were being fed a low-protein diet limited in branched-chain amino acids when the skin lesions developed. A deficiency in plasma levels of essential amino acids, particularly isoleucine, was confirmed. Supplementation of the diet with isoleucine in one of the patients led to a prompt improvement of the skin lesions. We conclude that dietary deficiencies associated with the treatment of organic aciduria should be added to the causes of acrodermatitis enteropathica-like cutaneous lesions.

Female hydrocele of the canal of Nuck: a case report

The processus vaginalis is an evagination of parietal peritoneum which accompanies the round ligament through the inguinal ring into the inguinal canal. The portion of processus vaginalis within the inguinal canal in women is called ‘the canal of Nuck’. When the processus vaginalis fails to close, it can result in a hernia or hydrocele, both in women and men. Female hydrocele of the canal of Nuck is uncommon. A literature search revealed that little has been published on this condition. We present a case of a hydrocele of the canal of Nuck in a 5-month-old female infant.

Treatment of Epidermolysis bullosa with Human Cultured Epidermal Allografts

Junctional epidermolysis bullosa letalis type Herlitz Pearson is a genetically determined, life-threatening disease. Effective therapy has been lacking to date. Therefore any therapy that improves wound healing would be beneficial for these patients. Cultured epidermal grafts are known to enhance wound epithelialization and have been used with success in some epidermolysis bullosa disorders. Encouraged by these reports, we grafted cultured allogeneic keratinocytes to an infant with a junctional epidermolysis bullosa letalis type.

Consultation of parents in actual end-of-life decision-making in neonates and infants

The objective of this study was to assess how frequently end-of-life decisions (ELDs) with a possible or certain life-shortening effect in neonates and infants were discussed with parents, and to determine if consultation of parents was associated with the type of ELD, (clinical) characteristics of the patient, and socio-demographic characteristics of the physician. A retrospective study of all deaths of live born infants under the age of one year was conducted in Flanders, Belgium. For 292 of all 298 deaths in a 1-year period (between 1 August 1999 and 31 July 2000) the attending physician could be identified and was sent an anonymous questionnaire. All cases with an ELD and containing information regarding the consultation of parents were included. The response rate was 87% (253/292). In 136 out of 143 cases, an ELD was made and information on the consultation of parents was obtained. According to the physician, the ELD was discussed with parents in 84% (114/136) of cases. The smaller the gestational age of the infant, the more the parental request for an ELD was explicit (p=0.025). When parents were not consulted, the ELD was based more frequently on the fact that the infant had no chance to survive and less on quality-of-life considerations (p=0.001); the estimated shortening of life due to the ELD was small in all cases, but significantly smaller (p<0.001) if parents were not consulted. It is concluded that the majority of parents of children dying under the age of one year are consulted in ELD-making, especially for decisions based on quality-of-life considerations (95.1%). Parents of infants with a small gestational age more often explicitly requested an ELD.

Two unusual pediatric cases of dilutional hyponatremia.

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na+] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

What the paediatricians need—the launch of paediatric research in Europe

Most parents and many paediatricians are not aware that medicines for children are often not tested, labelled, or approved for their prescribed use. In 1997, the Food and Drug Administration developed incentives for pharmaceutical companies to perform paediatric research in medications. The European Commission brought out its proposal for paediatric incentives after in-depth internal reflection. Now it should be adapted quickly to boost pharmaceutical paediatric research in the EU as soon as possible. Conclusion:The proposal must be balanced and aware that both incentives and requirements are mandatory in order to maintain and stimulate paediatric research on medicines in Europe.

Orphenadrine poisoning in a child: clinical and analytical data

Abstract Orphenadrine is an anticholinergic drug used mainly in the treatment of Parkinsons disease. It has a peripheral and central effect and a known cardiotoxic effect when taken in large doses. We report the successful outcome of the treatment of a 2 1/2-year-old girl who accidentally ingested 400 mg of orphenadrine hydrochloride (Disipal). One hour after ingestion she presented neurological symptoms: confusion, ataxic walking, and periods of severe agitation. Generalized tonic-clonic seizures appeared resistant to the administration of multiple antiepileptics. They ceased after a supplementary dose of intravenous diazepam, endotracheal intubation, and mechanical ventilation. An episode of ventricular tachycardia responded well to i. v. lidocaine. Physostigmine was administered in three successive doses. The initial orphenadrine plasma level (3,55 μg/ml) was in the toxic range, associated with high mortality. The calculated elimination half-life was 10.2 h and the molecule and/or its metabolites were found up to 90 h after ingestion.

Circadian rhythm of cardiac responses to vagal stimulation tests

To evaluate the existence of a circadian rhythm in cardiac responses to vagal stimulation tests, 10 children without neurologic or cardiopulmonary disease, were studied using a standardized procedure. A trigeminal airstream stimulation test (TAS) and an ocular compression test (OCT) were subsequently performed at 4 nonequidistant hours. These 2 vagal stimulation tests were performed according to well-established, previously published techniques. Prolongation of the RR-interval during TAS and OCT was calculated and compared to the mean control RR-interval preceding the stimulation period. Prolongation of the RR-interval during the stimulation period was obtained in all instances during TAS and OCT. Chronobiologic analysis was determined by the cosinor method and bootstrap analysis. A significant circadian rhythm was found in cardiac responses to vagal stimulation for both TAS and OCT. The maximal response hour for TAS was between 9:06 p.m. and 5:18 a.m. and for OCT between 10:18 p.m. and 4:24 a.m. The mean value and 95% intervals for the cardiac responses to both vagal stimulation tests revealed, when using the bootstrap analysis, an important overlap in the hour of appearance of the maximal responses to these procedures; the bootstrap analysis of the peak of the acrophase was at 2:50 a.m. for TAS and 1:15 a.m. for OCT. Our results indicate that there is a circadian rhythm in cardiac responses to vagal stimulation tests and demonstrate a preponderance of these responses during the early morning hours.

Acute Retroperitoneal Hemorrhage and Shock as Presenting Signs of Neuroblastoma in an Infant

Adrenal hemorrhage after the neonatal period is rare. It most often occurs with coagulation disorders or child abuse. Spontaneous bleeding within an adrenal neuroblastoma has been described, but acute massive hemorrhage is exceptional. We describe a case of neuroblastoma of the adrenal gland presenting with acute life-threatening abdominal hemorrhage.

Sudden death of a child with juvenile chronic arthritis, probably due to indomethacin

Sir: A 14.5-year-old boy with juvenile chronic arthritis was initially treated with acetylsalicylic acid, 5 g (75 mg/kg body weight) daily. Despite a progressive increase in the administered dose up to 135mg/kg, the child remained febrile and presented incipient symptoms of salicylate toxicity. After prednisolone monotherapy (60 mg daily) had failed, indomethacin was added, first at a dose of 100mg daily and then increased to 150mg (2.2mg/kg), resulting in a relief of the fever and a dramatic improvement of the general condition. The dose of prednisolone was reduced to 10 mg daily. Under this therapy the child suddenly developed, 4 months later, nausea, vomiting, malaise and epigastric pain. He was admitted to the hospital and the initial physical examination showed a pale, eutrophic adolescent in a good general state. Palpation of the abdomen revealed a tender epigastrium and right hypochondrium. The liver was palpable at the costal margin. Laboratory investigations included a normal haemogram. The sedimentation rate was 5 mm/h. Urinalysis, electrolytes and blood chemistry were normal, except for a marked elevation of liver enzymes: SGOT and SGPT were 1148 IU/1 and 1426 IU/1, respectively. Indomethacin therapy was immediately stopped, and the prednisolone dosage was increased to 15 mg daily. Over the next few days the liver markedly enlarged, while the patient suffered severe abdominal pain. SGOT rose to 3542 units, total bilirubin to 25.7mg/100ml and ammonia to1320mg/100ml. The child became progressively more lethargic; hyperventilation and coma ensued rapidly. He died on the i0th hospitaI day. The results of monospot and heterophile antibody testing were negative as were cultures of the blood and urine. Tests for hepatitis-B surface antigen, antibodies to hepatitis-B surface antigen and antibodies to hepatitis-A virus were negative. Histological sections of liver tissue showed marked hepatocellular necrosis and important lysis of the remaining hepatocytes. Inflammatory changes were minimal. Electron microscopical examination of the liver cells revealed vesiculated transformation of smooth surfaced endoplasmic reticulum and important swelling of the mitochondria with fragmentation of the cristae, suggestive of drug-induced liver injury. Indomethacin appears as the most probable cause of the hepatocellular necrosis. Other possible causes of liver disease, such as aspirin-induced hepatitis, infectious hepatitis or liver involvement as a manifestation of juvenile chronic arthritis were not supported by the clinical, biological and pathological data. Frank hepatitis due to indomethacin has been reported rarely despite widespread use of the drug. We are aware of five cases [14] including four fatalities [1, 3, 4], three ofwhom were adolescents [3, 4]. Although it cannot be proven beyond doubt that the cytotoxic agent responsible for this case of fatal hepatitis was indomethacin, this occurrence is a cause for disquiet and calls for the greatest caution in the prescription of indomethacin, particularly in childhood.