Natan Noviski

Exercise but not methacholine differentiates asthma from chronic lung disease in children.

Bronchial provocation challenges with exercise and methacholine were performed on the same day or within a short interval in 52 children with asthma, 22 with other types of chronic lung disease (including cystic fibrosis), and 19 control subjects with no evidence of chronic lung disease. There were no significant differences in the baseline lung function before the two types of challenge in the individual groups and differences between the patients with asthma and with chronic lung disease were minor. When the mean -2 SD of the methacholine response of the control group was taken as the lower limit of normal, 49/52 (94%) patients with asthma and 18/22 (82%) with chronic lung disease responded abnormally. In contrast, with the mean +2 SD of the exercise response of the control group as the upper limit of normal, 41/52 (79%) asthmatic patients responded but none of those with chronic lung disease. Thus the response to the two types of challenge helps to distinguish asthma from other types of chronic lung disease in children.

Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension.

The steroid sparing effect of nebulised budesonide suspension was assessed in a double blind placebo controlled parallel group study of 36 preschool children with severe asthma who were dependent on treatment with oral steroids. Nebulised budesonide suspension significantly reduced the requirement for treatment with oral steroids, and produced a marked improvement in overall health as scored on a visual analogue scale during the clinic visits. This study shows a significant step forward in the prophylactic treatment of asthma in children under the age of 3 years, in whom the efficacy of many other nebulised treatments has been questioned.

Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients

The kidneys are thought to be a major site of net de novo arginine synthesis, but the quantitative status of arginine metabolism and its substrate precursor relationship to nitric oxide (NO) synthesis in end stage renal disease (ESRD) patients have not been characterized. We have investigated kinetic aspects of whole body arginine metabolism in six patients with ESRD. They received two pre- and two post-hemodialysis intravenous tracer infusion studies with L-[guanidino-(15)N(2)]arginine and L-[(13)C]leucine during the first study, and L-[5-(13)C]arginine and L-[5-(13)C-ureido,5,5, (2)H(2)]citrulline during the second study. Arginine homeostasis in ESRD patients was found to be associated with a lower rate of arginine oxidation, and despite the decrease in renal function, the rate of de novo arginine synthesis appeared to be preserved. Plasma citrulline concentrations and flux were also elevated in these subjects compared with healthy adults. The rate of whole body NO synthesis was increased in the ESRD patients, but apparently not different pre- and post-hemodialysis therapy. The anatomic site(s) responsible for the maintenance of net de novo arginine synthesis and for the elevated NO synthesis and its pathophysiological importance in ESRD remain to be established.

Arginine and nitric oxide metabolism in critically ill septic pediatric patients.

ObjectiveTo investigate whole body, in vivo arginine metabolism and nitric oxide synthesis rates in septic, critically ill pediatric patients. DesignProspective study. SettingPediatric intensive care unit at a general hospital. PatientsTen consecutive septic patients age 6–16 yrs. InterventionsSeptic patients received an 8-hr primed, constant intravenous tracer infusion of l-[guanidino-15N2]arginine, l-[1-13C]leucine, and [13C]urea. A 24-hr urine collection was obtained for determination of [15N]nitrate enrichment (15NO3−) and urinary nitrogen. The next day they received an infusion of l-[5-13C]arginine and l-[5-13C-ureido, 5,5,2H2]citrulline. Blood samples were obtained for determination of plasma isotopic enrichment of the tracers given and of derived [15N]citrulline (nitric oxide synthesis), l-[13C-guanidino 5,5, 2H2]arginine (M+3 arg) (arginine synthesis), and [15N2]urea (urea formation). Data are compared with historic controls from studies in healthy young adults. Measurements and Main ResultsPlasma arginine fluxes were 67 ± 21 and 72 ± 17 &mgr;mol·kg−1·hr−1, respectively, for the [15N2 guanidino] and the [13C] arginine labels, which were not different from reported adult values. The rates of arginine oxidation were 22.9 ± 10.8 &mgr;mol·kg−1·hr−1 and were higher than de novo arginine synthesis rates of 9.6 ± 4.2 &mgr;mol·kg−1·hr−1 (p < .01); therefore, these patients were in a negative arginine balance. The rates of nitric oxide synthesis as estimated by the [15N]citrulline method were 1.58 ± 0.69 &mgr;mol·kg−1·hr−1 for septic patients and higher (p < .05) than values of 0.96 ± 0.1 &mgr;mol·kg−1·hr−1 in healthy adults. Septic patients were in a negative protein (leucine) balance of about −1.00 ± 0.40 g·kg−1·day−1. ConclusionsHomeostasis of plasma arginine in septic patients was impaired compared with reported adult values. The rates of arginine oxidation were increased whereas de novo net arginine synthesis was unchanged, leading to a negative arginine balance. The rates of nitric oxide synthesis and the fraction of plasma arginine used for nitric oxide and urea formation were increased. These findings suggest that under condition of sepsis, arginine becomes essential in critically ill children.

Bronchial provocation determined by breath sounds compared with lung function.

Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each others results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children.

Intracranial Hemorrhage: Mechanisms of Secondary Brain Injury

ICH is a disease with high rates of mortality and morbidity, with a substantial public health impact. Spontaneous ICH (sICH) has been extensively studied, and a large body of data has been accumulated on its pathophysiology. However, the literature on traumatic ICH (tICH) is limited, and further investigations of this important topic are needed. This review will highlight some of the cellular pathways in ICH with an emphasis on the mechanisms of secondary injury due to heme toxicity and to events in the coagulation process that are common to both sICH and tICH.

Role of infection in the middle lobe syndrome in asthma.

Twenty one children with asthma aged 1.0-10.5 years (mean (SD) 3.3 (2.5) years) were admitted to the hospital to evaluate pulmonary right middle lobe or lingular collapse lasting one to 12 months (mean (SD) 4.4 (3.8) months). Seven children had mild asthma and were treated with inhaled beta 2 agonists as needed. Nine had moderate asthma treated with either sodium cromoglycate or slow release theophylline. Five had severe asthma treated with inhaled steroids. Each child underwent fibreoptic bronchoscopy under local anaesthesia and a bronchoalveolar lavage. Differential cell counts of the lavage fluid revealed predominance of neutrophils in 12 patients (57%). In nine of these patients cultures grew pathogenic bacteria, mainly Haemophilus influenzae and Streptococcus pneumoniae. There was no correlation between the severity of asthma and a positive bacterial culture. There was also no correlation between the duration of the right middle lobe collapse and a positive culture. We conclude that longstanding right middle lobe collapse in asthmatic children is often associated with bacterial infection.

Does the size of nasogastric tubes affect gastroesophageal reflux in children

BACKGROUND To evaluate the effects of nasogastric tube insertion and different nasogastric tube sizes on gastroesophageal reflux in children. METHODS During a prospective randomized study, 29 patients aged 1 month to 4 years (median, 9 months) underwent 24 hours of continuous esophageal pH monitoring to rule out gastroesophageal reflux as the cause of severe pulmonary problems. Each patient was monitored without nasogastric tube for 16 hours (baseline), and thereafter the first nasogastric tube, small (8-Fr) or large (10-Fr or 12-Fr), was placed. Four hours later, the original nasogastric tube was replaced by a new one of large (instead of small) size or of small (instead of large) size. We selected the times of wakefulness in these study periods and compared the number of reflux episodes (NREs), the number of reflux episodes that lasted more than 5 minutes (NRE>5), and the percentage of time with esophageal pH less than 4 (PTP<4). RESULTS The 12-Fr group in comparison with the 8-Fr group and baseline showed significant difference (P<0.05) in the NRE>5 and PTP<4 parameters. No significant differences were found when comparing 8-Fr versus 10-Fr groups and baseline. In children with (n = 20) and without (n = 9) gastroesophageal reflux, comparison of the various reflux parameters between baseline and the different sizes of nasogastric tubes showed the same results. CONCLUSIONS Size of the nasogastric tubes is a significant factor in predisposing the child to gastroesophageal reflux. Large nasogastric tubes interfere with the clearance of the refluxed acid from the esophagus.

Sudden cardiac death under anesthesia in pediatric patient with williams syndrome: A case report and review of literature

Williams syndrome is a complex syndrome characterized by developmental abnormalities, craniofacial dysmorphic features, and cardiac anomalies. Sudden death has been described as a very common complication associated with anesthesia, surgery, and procedures in this population. Anatomical abnormalities associated with the heart pre-dispose these individuals to sudden death. In addition to a sudden and rapid downhill course, lack of response to resuscitation is another significant feature seen in these patients. The authors report a five-year-old male with Williams syndrome, hypothyroidism, and attention deficit hyperactivity disorder. He suffered an anaphylactic reaction during CT imaging with contrast. Resuscitation was unsuccessful. Previous reports regarding the anesthetic management of patients with Williams are reviewed and the potential for sudden death or peri-procedure related cardiac arrest discussed in this report. The authors also review reasons for refractoriness to defined resuscitation guidelines in this patient population.

Toxic epidermal necrolysis in children: medical, surgical, and ophthalmologic considerations.

Toxic epidermal necrolysis is a rare acute inflammatory multisystem life-threatening condition characterized by widespread epidermal necrosis and profound toxic systemic reaction. Implicated etiologic agents in children include drugs, infections, and autoimmune diseases. The pathophysiology includes separation of the epidermis at the dermal–epidermal junction of both skin and extracutaneous epithelium and mucous membranes. The general consensus is that expeditious transfer to a burn center, maintenance of fluid and electrolyte balance, temperature maintenance, control of evaporative losses, avoidance of use of complicating drugs as corticosteroids and topical sulfa compounds, aggressive septic surveillance, vigorous nutritional support via nasoenteric tube, early ophthalmologic consultation, and appropriate wound care with a regimen of therapy relying on basic principles of treatment of partial-thickness epidermal wounds predict better outcome in the treatment of this disease process. The course of toxic epidermal necrolysis in children, even though dramatic at onset, leads to low mortality when managed appropriately. The current limited published evidence does not clearly delineate differences in epidemiology, pathogenesis, and prognosis of severe skin reactions in children as compared with adults. In this article, we review the available literature on the pathogenesis, clinical features, pathophysiology, treatment, and complications of this rare disease in children.