Dalit Modan-Moses

Peak bone mass in patients with phenylketonuria

SummaryObjective: Several studies have suggested a compromised bone mass in phenylketonuria patients but most reported on heterogeneous or small patient groups. Our aim was to evaluate peak bone mass in adult PKU patients and to relate BMD to nutritional parameters. Patients and methods: BMD was measured by dual-energy x-ray absorptiometry in 31 adult PKU patients (18 female), mean age 25 ± 5.3 years. Nutritional intake was calculated based on food diaries. Diet adherence was determined based on patients’ report. Results: Mean blood phenylalanine (Phe) concentration was 968 ± 526 μmol/L (16 ± 8.7 mg/dl). Eight patients (32.2%) met the recommended blood Phe concentration of <726 μmol/L (<12 mg/dl), and there was no significant difference in Phe concentrations between diet-adherent and non-adherent patients. Osteopenia was detected in 11 patients (38.7%), while osteoporosis was detected in 2 patients (6.5%). No correlation was found between BMD and age, blood minerals, Phe, vitamin D and alkaline phosphatase levels, calcium and protein intake, body mass index, and body fat percentage. Conclusions: Peak bone mass is decreased in PKU patients. Possible explanations include long-standing dietary deficiency in protein, calcium, vitamin D or trace elements, or a primary defect in bone turnover inherent to the disease itself. Our data do not favour any of these hypotheses. Further studies are needed to elucidate the cause of low bone density in PKU patients.

Long term nutritional rehabilitation by gastrostomy in Israeli patients with cystic fibrosis: clinical outcome in advanced pulmonary disease.

Objectives: Several studies have shown a linear correlation between nutritional status and pulmonary function in patients with cystic fibrosis. Our study aims were: 1) To evaluate the effect of nutritional supplementation via gastrostomy on nutritional, clinical, and pulmonary parameters, and 2) To identify predicting factors for success of long-term nutritional rehabilitation. Methods: Twenty-one Israeli patients, aged 8 months to 20 years, underwent gastrostomy insertion from 1992 to 2001. All patients were pancreatic insufficient, and all carried severe mutations (W1282X in 62% of the patients). Anthropometric and clinical data were obtained for each patient: 0−12 months before and 6−12 months and 18−24 months after gastrostomy placement. Standard deviation scores (SDS) for height, weight, and body mass index as well as percent of height-appropriate body weight were calculated. Results: The mean percent-of-predicted forced expiratory volume in 1 second (FEV1) decreased significantly during the first year of gastrostomy feeding (n = 16), from 44.2% ± 13.9 to 41% ± 13.3 (P = 0.05). However, during the second year of therapy (n = 10), a trend toward improvement was observed (from 39.4 ± 12.1 to 41.4 ± 16.1). Weight, and BMI z-scores as well as weight percent-of ideal body weight increased significantly. Height z-score for age decreased during the first year (from −1.9 ± 1.3 to −2.1 ± 1.4), However, a trend toward improvement was observed during the second year. A significant correlation was found between the change in weight z-score and height z-score during the first (r = 0.488, P = 0.016) and the second (r = 0.825, P < 0.001) years. There was no difference between compliers and noncompliers regarding height, weight, and BMI either before or after gastrostomy placement. A significant correlation between age at insertion of gastrostomy and improvement in height z-score (r = 0.52, P = 0.016) was observed. Cystic fibrosis related diabetes (n = 8) did not affect the response to supplemental feeding. Conclusions: We observed a trend toward improvement of pulmonary disease during the second year, and a significant improvement in weight, height, and BMI z-scores. Compliance, diabetes, and young age prior to tube insertion did not predict success of nutritional rehabilitation.

Endobronchial adrenaline: should it be reconsidered? Dose response and haemodynamic effect in dogs

BACKGROUND Tracheal drug administration is a route for drug delivery during cardiopulmonary resuscitation when intravenous access is not immediately available. However, tracheal adrenaline (epinephrine) injection has been recently shown to be associated with detrimental decrease in blood pressure. This was attributed to exaggerated early beta2 mediated effects unopposed by alpha-adrenergic vasoconstriction. We hypothesized that endobronchial adrenaline administration is associated with better drug absorption, which may abolish the deleterious drop of blood pressure associated with tracheal drug administration. OBJECTIVE To determine haemodynamic variables after endobronchial adrenaline administration in a non-arrest canine model. DESIGN Prospective, randomized, laboratory study. METHODS Adrenaline (0.02, 0.05, 0.1 mg/kg) diluted with normal saline was injected into the bronchial tree of five anaesthetized dogs. Injection of 10-ml saline served as control. Heart rate, blood pressure and arterial blood gases were monitored for 60 min after drug instillation. The protocol was repeated after 1 week. RESULTS Adrenaline at a dose of 0.02 mg/kg produced only a minor initial decrease in diastolic (from 90 +/- 5 to 78 +/- 3 mmHg, P=0.05), and mean blood pressure (from 107 +/- 4 to 100 +/- 3 mmHg, P=0.05), in all dogs. This effect lasted less then 30 s following the drug administration. In contrast, higher adrenaline doses (0.05 and 0.1 mg/kg) produced an immediate increase in diastolic (from 90 +/- 5 to 120 +/- 7 mmHg; and from 90 +/- 5 to 170 +/- 6 mmHg, respectively), and mean blood pressure (from 107 +/- 4 to 155 +/- 10 mmHg; and from 107 +/- 4 to 219 +/- 6 mmHg, respectively). All adrenaline doses resulted in an immediate increase in systolic blood pressure and pulse. Endobronchial administration of saline (control) affected none of the haemodynamic variables. CONCLUSIONS In a non-arrest model, endobronchial adrenaline administration, as opposed to the effect of tracheal adrenaline, produced only a minor decrease in diastolic and mean blood pressure. We suggest that endobronchial adrenaline administration should be investigated further in a CPR low-flow model when maintaining adequate diastolic pressure may be crucial for survival.

Flexible bronchoscopy and bronchoalveolar lavage in pediatric patients with lung disease.

Objective: The use of flexible bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in investigating pediatric patient with airway abnormalities and pulmonary infiltrates are indispensable and are now a routine procedure in many centers. Immunocompromised and cancer patients, especially after bone marrow transplantation, and children who have undergone surgery for congenital heart disease (CHD) are at high risk for pulmonary disease. Our aim was to study the diagnostic rate, safety, and clinical yield of FOB in critically ill pediatric patients. Design: Retrospective chart review. Setting: Pediatric intensive care unit in a tertiary university hospital. Patients: Three hundred nineteen children who underwent 335 FOB procedures. The indications for bronchoscopy included infectious agent identification in immune-competent patients with new pulmonary infiltrates seen on chest radiograph (46%) and in patients with fever and neutropenia with respiratory symptoms (18%), airway anatomy evaluation in patients with upper airway obstruction (16%), CHD (15%), and airway trauma (5%). Data were obtained by reviewing the patients’ charts, bronchoscopy reports, and laboratory results. Measurements and Main Results: The diagnostic rate of FOB procedures was 79%. FOB and BAL resulted in alteration of management (positive clinical yield) in 70 patients (23.9%). A definite infectious organism was identified in 56 patients (17.6%). The clinical yield in patients with cancer or primary immune deficiency (38.7%) was significantly higher compared with patients with CHD (20.4%, p < 0.01) and pneumonia (17%, p < 0.01). Major complications were observed in two procedures (prolonged apnea), and minor complications (transient desaturation, stridor, and minor bleeding) were observed in 45 patients (14%). Conclusions: FOB and BAL have an important role in the evaluation of airway abnormality and pulmonary infiltrate in pediatric patients, in whom rapid and accurate diagnosis is crucial for survival. We suggest that FOB should be considered as an initial diagnostic tool in those critically ill patients.

Headaches in overweight children and adolescents referred to a tertiary-care center in Israel.

Objective: To assess the association between obesity and primary headaches in children and adolescents.

Should vasopressin replace adrenaline for endotracheal drug administration

ObjectiveArginine vasopressin was established recently as a drug of choice in the treatment of cardiac arrest and in retractable ventricular fibrillation; however, the hemodynamic effect of vasopressin following endotracheal drug administration has not been fully elucidated. We compared the effects of endotracheally administered vasopressin vs. adrenaline on hemodynamic variables in a canine model, and we investigated whether vasopressin produces the same deleterious immediate blood pressure decrease as did endotracheal adrenaline in the canine model. DesignProspective controlled study. SettingAnimal laboratory in Tel-Aviv University, Israel. SubjectsFive adult mongrel dogs weighing 6.5–20 kg. InterventionsDogs were anesthetized; each dog was intubated orally, and both femoral arteries were cannulated for the measurement of arterial pressure and for sampling blood gases. Each dog was studied four times, 1 wk apart, by using the same protocol for injection and anesthesia: endotracheal placebo (10 mL NaCl 0.9%,), endotracheal vasopressin (1 units/kg), endobronchial adrenaline (0.1 mg/kg), and endotracheal adrenaline (0.1 mg/kg). Following placebo, vasopressin, and adrenaline instillation, five forced manual ventilations were delivered with an Ambu bag. Each dog was its own control. Measurements and Main ResultsFollowing placebo or drug administration, heart electrocardiography and arterial pressures were continuously monitored with a polygraph recorder for 1 hr. Endotracheal vasopressin produced an immediate increase of diastolic blood pressure (from 83 ± 10 mm Hg [baseline] to 110 ± 5 mm Hg at 1 min postinjection). This response lasted >1 hr. In contrast, both endotracheal and endobronchial administration of adrenaline produced an early and significant (p < .05) decrease in diastolic and mean blood pressures. The diastolic blood pressure increase from 85 ± 10 mm Hg to 110 ± 10 mm Hg took an ill-afforded 55 secs following endotracheal adrenaline. Diastolic blood pressure was significantly (p < .05) higher following vasopressin compared with adrenaline administration in both routes. ConclusionsVasopressin accomplishes its hemodynamic effect, particularly on diastolic blood pressure, more rapidly, vigorously, and protractedly and to a significant degree compared with both endotracheal and endobronchial adrenaline. Evaluation of the effects of endotracheal vasopressin in a closed chest cardiopulmonary resuscitation model is recommended.

Treatment of Congenital Hyperinsulinism with Lanreotide Acetate (Somatuline Autogel)

CONTEXT Congenital hyperinsulinism (CH) may be treated conservatively in many children with octreotide given by multiple sc injections or via an insulin pump. OBJECTIVE We describe two children treated with a once-monthly injection of a long-acting somatostatin analog. PATIENTS AND METHODS Both patients presented with hypoglycemia 30 min after birth and were subsequently diagnosed with CH. Patients were initially treated with diazoxide, hydrochlorothiazide, frequent feedings, and octreotide via an insulin pump. With this therapy, they were normoglycemic with a good growth rate, normal weight gain, and excellent neurodevelopment. Treatment with the long-acting somatostatin analog lanreotide acetate (Somatuline Autogel), administered by deep sc injection of 30 mg once a month, was started at the ages of 4½ and 4 yr, respectively. Octreotide infusion was gradually weaned over 1 month. Continuous glucose monitoring after discontinuation of pump therapy showed normoglycemia. The first patient has now been treated with the lanreotide acetate for over 5 yr, and the second for 3 yr. Treatment is well-tolerated, and both the patients and their parents are satisfied with the transition from pump therapy to once-a-month injection and prefer it to pump therapy. CONCLUSION Lanreotide acetate may be a safe and effective alternative to octreotide pump therapy in patients with CH, offering an improved quality of life. Longer follow-up of a larger patient group is needed.

Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism

BACKGROUND Congenital hyperinsulinism (CH) is treated surgically in many centers (near-total and partial pancreatectomy for diffuse and focal disease respectively). Most patients treated with near-total pancreatectomy developed diabetes during childhood/puberty. CH patients are at increased risk of neurodevelopmental disorders, some being severe, which are reported to occur in 14-44% of patients from highly heterogenous cohorts. Over the last few decades, we have treated children with CH conservatively without surgery. The aim of this study was to assess the neurodevelopmental outcome of these patients. DESIGN AND METHODS The study included 21 Ashkenazi CH medically treated patients: 11 homozygotes (diffuse disease) and 9 heterozygotes with mutations on the paternal allele (presumed focal disease). The mean age was 13.7 years (range 8-23). Neurodevelopmental outcomes were assessed by telephone interviews of parents, using a standard questionnaire. Closest age siblings of CH patients served as controls. RESULTS Ten CH patients had perinatal seizures of short duration. Four had post-neonatal seizures, which remitted entirely. During early childhood, four patients (19%) had hypotonia, eight (38%) had fine motor problems, seven (33%) had gross motor problems (clumsiness), and one had mild cerebral palsy. Three patients (14%) had speech problems. Eight patients required developmental therapy, compared to one in the control group. Most of these problems were resolved by age 4-5 years. At school age, all were enrolled in regular education, some excelled in their studies, 6 out of 21 patients (29%) had learning problems (2 out of 21 controls). None had overt diabetes. CONCLUSIONS Good neurodevelopmental outcome was observed in our conservatively treated CH patients, with no diabetes as reported in patients undergoing pancreatectomy.

Fiberoptic bronchoscopy and bronchoalveolar lavage for the evaluation of pulmonary disease in children with primary immunodeficiency and cancer.

Patients with childhood cancer or primary immunodeficiencies (PID) are at high risk for developing pulmonary infections and non‐infectious complications. The broad differential diagnoses and the critical condition of these patients often drive physicians to start broad‐spectrum antibiotic therapy before a definite diagnostic procedure is performed. A definite diagnosis may be achieved in these situations by fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL).

Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery.

Objective Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters. Design Investigative study. Setting University-affiliated tertiary care hospital. Participants and Interventions Twenty-nine consecutive patients, aged 6 days to 15 yrs, operated upon for the correction of congenital heart defects were studied. Surgery in 20 patients (group 1) involved conventional CPB techniques, and 9 (group 2) underwent closed-heart surgery. The time courses of leptin, cortisol, and IL-8 levels were determined. Serial blood samples were collected preoperatively, on termination of CPB, and at six time points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at −70°C until use. Measurements and Main Results The leptin levels in group 1 decreased during CPB to 51% of baseline (p < .001), then gradually increased, reaching 120% of baseline levels at 12–18 hrs postoperatively (p < .001), returning to baseline levels at 24 hrs (p < .01). In patients undergoing closed-heart surgery (group 2), leptin levels displayed a pattern resembling the first group: they decreased during surgery to 71% of baseline levels (p = .002) and showed a tendency to return to baseline thereafter. All group 1 patients’ cortisol levels increased significantly during the first hour of surgery, then decreased, returning to baseline levels at 18–24 hrs postoperatively. There was a significant negative correlation between leptin and cortisol levels (r = −2.8, p < .01). In group 2, cortisol levels increased during and after surgery, peaking 4 hrs postoperatively and decreasing thereafter. IL-8 levels determined in 15 group 1 patients increased significantly during CPB, peaked at the end of surgery, and then decreased but remained slightly elevated even at 48 hrs postoperatively. There was a significant correlation between cortisol and IL-8 levels (r = 2.55, p < .05). Children with leukocytosis, tachycardia, and hypotension had lower leptin levels and less variation over time as opposed to those with an uncomplicated course. Conclusions CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol. Further studies of the prognostic and therapeutic roles of leptin after CPB should be investigated.