Determination of the median effective dose of propofol in combination with different doses of ketamine during gastro-duodenoscopy in children: a randomised controlled trial.

BACKGROUND: Propofol is used to induce deep sedation or general anaesthesia for procedures in children. Adjuvants, such as ketamine, are routinely added to reduce the dose of propofol required and propofol-related adverse events. We conducted a randomised controlled trial to determine the effective bolus dose of propofol in combination with ketamine that induces adequate depth of anaesthesia in 50% of children (ED50) undergoing gastro-duodenoscopy. METHODS: Children were randomised to one of four doses of ketamine: 0 (control), 0.25, 0.5, and 1 mg kg-1, followed by a dose of propofol according to Dixon's up-and-down methodology. Excessive movement, coughing, gagging, or airway obstruction that prevented endoscope insertion was considered a failure. RESULTS: The ED50 of propofol (median, 95% CI) was greater in the ketamine 0, 0.25, and 0.5 mg kg-1 groups compared with the ketamine 1 mg kg-1 group (6.1, 4.1-8.1; 4.5, 2.9-6; 4.7, 3.1-6.2 mg kg-1vs 1.1, 0.5-1.8 mg kg-1, respectively, P<0.008). Total dose of propofol administered during the procedure was reduced with ketamine 1 mg kg-1. The mean arterial pressure was lower in the ketamine 0 mg kg-1 group compared with the 1 mg kg-1 group during and immediately after the procedure. The ketamine 1 mg kg-1 group experienced a higher incidence of nausea and visual disturbances. CONCLUSIONS: Ketamine at 0.5-1 mg kg-1 reduces the dose of propofol required to provide general anaesthesia for gastro-duodenoscopy in children and may reduce the incidence of propofol-related changes in haemodynamics. CLINICAL TRIAL REGISTRATION: NCT 02295553.

Quantum behavior of water nano-confined in beryl.

The proton mean kinetic energy, Ke(H), of water confined in nanocavities of beryl (Be3Al2Si6O18) at 5 K was obtained by simulating the partial vibrational density of states from density functional theory based first-principles calculations. The result, Ke(H) = 104.4 meV, is in remarkable agreement with the 5 K deep inelastic neutron scattering (DINS) measured value of 105 meV. This is in fact the first successful calculation that reproduces an anomalous DINS value regarding Ke(H) in nano-confined water. The calculation indicates that the vibrational states of the proton of the nano-confined water molecule distribute much differently than in ordinary H2O phases, most probably due to coupling with lattice modes of the hosting beryl nano-cage. These findings may be viewed as a promising step towards the resolution of the DINS controversial measurements on other H2O nano-confining systems, e.g., H2O confined in single and double walled carbon nanotubes.

On the mean kinetic energy of the proton in strong hydrogen bonded systems.

The mean atomic kinetic energies of the proton, Ke(H), and of the deuteron, Ke(D), were calculated in moderate and strongly hydrogen bonded (HB) systems, such as the ferro-electric crystals of the KDP type (XH2PO4, X = K, Cs, Rb, Tl), the DKDP (XD2PO4, X = K, Cs, Rb) type, and the X3H(SO4)2 superprotonic conductors (X = K, Rb). All calculations utilized the simulated partial phonon density of states, deduced from density functional theory based first-principle calculations and from empirical lattice dynamics simulations in which the Coulomb, short range, covalent, and van der Waals interactions were accounted for. The presently calculated Ke(H) values for the two systems were found to be in excellent agreement with published values obtained by deep inelastic neutron scattering measurements carried out using the VESUVIO instrument of the Rutherford Laboratory, UK. The Ke(H) values of the M3H(SO4)2 compounds, in which the hydrogen bonds are centro-symmetric, are much lower than those of the KDP type crystals, in direct consistency with the oxygen-oxygen distance ROO, being a measure of the HB strength.

Determining the band gap and mean kinetic energy of atoms from reflection electron energy loss spectra.

Reflection electron energy loss spectra from some insulating materials (CaCO3, Li2CO3, and SiO2) taken at relatively high incoming electron energies (5-40 keV) are analyzed. Here, one is bulk sensitive and a well-defined onset of inelastic excitations is observed from which one can infer the value of the band gap. An estimate of the band gap was obtained by fitting the spectra with a procedure that includes the recoil shift and recoil broadening affecting these measurements. The width of the elastic peak is directly connected to the mean kinetic energy of the atom in the material (Doppler broadening). The experimentally obtained mean kinetic energies of the O, C, Li, Ca, and Si atoms are compared with the calculated ones, and good agreement is found, especially if the effect of multiple scattering is taken into account. It is demonstrated experimentally that the onset of the inelastic excitation is also affected by Doppler broadening. Aided by this understanding, we can obtain a good fit of the elastic peak and the onset of inelastic excitations. For SiO2, good agreement is obtained with the well-established value of the band gap (8.9 eV) only if it is assumed that the intensity near the edge scales as (E - Egap)(1.5). For CaCO3, the band gap obtained here (7 eV) is about 1 eV larger than the previous experimental value, whereas the value for Li2CO3 (7.5 eV) is the first experimental estimate.

An uncommon pattern of polyneuropathy induced by lifetime exposures to drift containing organophosphate pesticides.

The natural history of chronic peripheral polyneuropathy following lifetime low-level organophosphate (OP) exposure was investigated. A pilot study (1984-1987) conducted in rural communities in Israel detected subtle reversible in-season changes in nerve conduction patterns of 17 field workers out of 214 residents exposed to seasonal drift containing OP's. We examined 60 individuals (males: 50/60; 83.3%) from the original cohort still residing (more than 40 years) in the same communities. Exposure assessment was based on reports by Israeli institutions and the Bureau of Statistics. Information on personal status, work experience, exposures and symptoms was collected by questionnaires. The nervous system was systematically studied, evaluating cortical upper motor neurons, corticospinal tracts, lower motor neurons and peripheral nerves. Electrophysiological studies included conduction velocities, amplitudes and distal latencies of sensory and motor median, ulnar, tibial and sural nerves; F-waves for proximal nerve functions; thermal and pain thresholds for small thinly-myelinated and non-myelinated fibers; transcranial magnetic stimulation for large fibers. Clinical and electrophysiological features of Carpal Tunnel Syndrome were found in 18% of the subjects, atypically in males only. Fingertips' tingling correlated with both axonal and myelin-dependent parameters (lower wave amplitudes and prolonged latency periods, respectively) in the sensory median nerves bilaterally. OP exposure significantly correlated to prolonged distal latency in the right median sensory nerve (r=0.29; p=0.052; n=45) and lower wave amplitude in the right sural nerve (p=0.031). These findings attest to subtle, predominantly sensory peripheral polyneuropathy following lifetime low-level exposures to drifts containing OP.

Drug-induced seizures in children and adolescents presenting for emergency care: current and emerging trends.

CONTEXT: Seizures may be the presenting manifestation of acute poisoning in children. Knowledge of the etiologic agent, or likely drug-class exposure, is crucial to minimize morbidity and optimize care. OBJECTIVES: To describe the agents most commonly responsible for pediatric drug-induced seizures, whose evaluation included a medical toxicology consultation in the United States. METHODS: Using the 37 participating sites of the Toxicology Investigators Consortium (ToxIC) Case Registry, a cross-country surveillance tool, we conducted an observational study of a prospectively collected cohort. We identified all pediatric (younger than 18 years) reports originating from an Emergency Department (ED) which included a chemical or drug-induced seizure, and required a medical toxicology consultation between April 1, 2010 and March 31, 2012. Results. We identified 142 pediatric drug-induced seizure cases (56% male), which represent nearly 5% of pediatric cases requiring bedside consultation by medical toxicologists. One-hundred and seven cases (75%) occurred in children aged 13-18 years, and 86 (61%) resulted from intentional ingestions. Antidepressants were the most commonly identified agents ingested (n = 61; 42%), of which bupropion was the leading drug (n = 30; 50% of antidepressants), followed by anticholinergics/antihistamines (n = 31; 22%). All antidepressant-induced seizures in teenagers were intentional and represented self-harm behavior. Sympathomimetic agents, including street drugs, represent the most common agents in children younger than 2 years (n = 4/19). CONCLUSION: Antidepressants, and specifically bupropion, are presently the most common medications responsible for pediatric drug-induced seizures requiring medical toxicology consultation in the United States. In teenagers presenting with new-onset seizures of unknown etiology, the possibility of deliberate self-poisoning should be explored, since most drug-induced seizures in this age group resulted from intentional ingestion.

Proton dynamics in ice VII at high pressures.

We calculated the proton kinetic energies Ke(H) of ice under high pressures up to 63 GPa by assuming the harmonic approximation. The input measured optical frequencies of vibration, libration, and translation of ice VII versus pressure as well as the H2O geometry and the distances R(OH) necessary for calculating Ke(H) (at 298 K) were taken from the literature. The resulting Ke(H) values were found to decrease gradually with increasing pressure, approaching the region where the H-atom is symmetrically hydrogen bonded between two oxygens in the OH-O system. Interestingly, the Ke(H) results were found to be consistent with those of other materials such as Rb3H(PO4)2 and KH2PO4 having similar R(OH) and R(OO) distances in the OH-O system. Similar calculations were also carried out for D2O.

Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti-factor Xa levels.

BACKGROUND: Unfractionated heparin (UFH) is a widely used anticoagulant. Current American College of Chest Physicians guidelines for infants extrapolated from adults recommend 28 U kg(-1) h(1) of UFH to achieve an anti-factor Xa level of 0.35-0.7 IU mL(-1). OBJECTIVE: To assess the profile of anti-FXa-based UFH dosing guidelines in infants. PATIENTS/METHODS: We included all infants aged < 6 months treated with per-protocol intravenous UFH at the Hospital for Sick Children, Toronto, over a 3.5-year period. RESULTS: Of 100 infants, 11% achieved sustained therapeutic anti-FXa levels with current dose recommendations. Only 15% achieved target anti-FXa levels within 24 h with per-protocol dose escalations. Seventeen per cent of patients never achieved therapeutic anti-FXa levels, despite up to 60 days of therapy and triple the recommended dose. The median dose needed to achieve therapeutic anti-FXa levels in the remaining 83 infants was 33 U kg(-1) h(-1) (interquartile range, 30-36). Two in three infants had decreased thrombus size at completion of therapy and no thrombus progression/recurrence, and 11/100 infants suffered major bleeding. Without exclusion of extracorporeal membrane oxygenation patients, an activated partial thromboplastin time (APTT) of > 180 s was detected as a risk factor for major bleeding. CONCLUSIONS: UFH monitoring is challenging in infants. Despite their delay in reaching therapeutic anti-FXa levels, infants monitored with the adult-based anti-FXa range have a high thrombus resolution rate, no thrombus progression, but a relatively high bleeding rate. Extreme APTT elevation may contribute to this bleeding risk, particularly in critically ill patients. Current UFH guidelines for young infants may still be inadequate, and laboratory methods with age-appropriate ranges may be required to further improve clinical outcomes within this population.

Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD.

Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (≥ 20mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had ≥ grade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.

Extended family studies for the identification of allogeneic stem cell transplant donors in Jewish and Arabic patients in Israel.

HLA-identified donors are the best source of allogeneic hematopoietic stem cell transplants, and are available in approximately 40% of cases. If no HLA-identical core family member is found, an extended family search may be performed. The aim of the study was to summarize the 10-year (1990-1999) experience of our tertiary care center with extended family donor search. During this period, 356 patients and 2659 of their family members were tissue-typed; 239 patients were Jewish (67%) and 117 were Arabic (33%). An HLA-identical core-family donor was identified for 168 patients (47%): 95 Jewish (40%) and 73 Arabic (62%) (p < 0.0001); 49 patients (14%) had more than one potential donor. An extended family search (grandmother/grandfather, aunts, uncles, etc.) was performed in 38 of the remaining families, which were found to be consanguineous: five Jewish and 33 Arabic. One HLA match was found in the Jewish families (20%) and 21 in the Arabic families (64%). The odds ratio for an Arabic patient to find a donor in the extended family search was 8.75, as opposed to a Jewish patient. Overall, HLA-matched donors were found by core and extended family search for 53% of the patients. The rate for Arabic patients was 80% and for Jewish patients, 40% (p < 0.001). This difference may be explained by the greater number of siblings and higher rate of consanguinity in the Arabic population. In conclusion, an extended family search for potential HLA-matched donors is worthwhile, especially in distinct ethnic populations with high consanguinity, such as Israeli Arabs.

The enigma of Lenin's (1870-1924) malady.

The health of heads of states is not always handled in the same way as an incapacitating disability in ordinary professionals. Instead of suspension of responsibilities, the health status of political leaders is concealed, especially when the illness is perceived as stigmatizing, such as organic mental impairment or sexual disorder. The objective of the present paper is to analyse the malady of Lenin (1870-1924) in the light of relevant and new medical information. It is hoped that this will accentuate the need for transparency when the health of a statesman is concerned.

Ganciclovir treatment in Ménétrier's disease.

UNLABELLED: A 2-y-old girl with severe edema, oliguria and hypoalbuminemia caused by protein-losing gastritis was diagnosed with cytomegalovirus-associated Ménétrier's disease. After almost two weeks, during which the patient required repeated albumin transfusions, she was treated with intravenous ganciclovir. Within five days her condition had improved, and no additional albumin replacement was needed. Complete recovery was observed after several weeks. CONCLUSION: In patients with severe Ménétrier's disease, a course of ganciclovir treatment may be of benefit and should be considered.

Streptococcus acidominimus infection in a child causing Gradenigo syndrome.

UNLABELLED: Gradenigo syndrome is a rare presentation of acute petrositis. The clinical triad of Gradenigo syndrome consists of acute suppurative otitis media, severe unilateral headache and abducens nerve palsy. We report the first case of Gradenigo syndrome caused by Streptococcus acidominimus, a Gram-positive coccus of the Streptococcus viridans group, which rarely causes deep-seated infection in humans. CONCLUSION: Gradenigo syndrome may complicate acute otitis media and should be suspected in case of unilateral headache and abducens nerve palsy. Conservative medical treatment without surgery may be considered in some patients.

Lactic dehydrogenase isoenzyme in cerebrospinal fluid of children with febrile convulsions.

AIM: To study the lactic dehydrogenase isoenzyme values in children with simple and complex febrile convulsions. METHODS: Cerebrospinal fluid samples were collected from 115 children, 57 with simple febrile convulsions, 27 with complex febrile convulsions and 31 with no neurological or intracranial pathology (controls). Lactic dehydrogenase activity and isoenzyme levels were measured on a Hitachi analyser. RESULTS: Mean total lactic dehydrogenase activity was similar in the three groups. In the control group, lactic dehydrogenase-1 was the main fraction, followed by lactic dehydrogenase-2 and lactic dehydrogenase-3; only small percentages of lactic dehydrogenase-4 and lactic dehydrogenase-5 were detected. In the febrile convulsion group, the lactic dehydrogenase-1 fraction percentage was lower and lactic dehydrogenase-2, lactic dehydrogenase-3 percentages were higher than those in the control group; and the differences were statistically significant between the control and study groups (p < 0.01). Values of lactic dehydrogenase-4 and lactic dehydrogenase-5 were similar in all three groups. CONCLUSION: This is the first report on the lactic dehydrogenase isoenzyme pattern in the cerebrospinal fluid of patients with simple and complex febrile convulsions. The important finding that focal and general febrile convulsions are not associated with cell damage and changes in aerobic and anaerobic metabolism as lactic dehydrogenase remained unchanged. Analysis of cerebrospinal fluid lactic dehydrogenase isoenzyme levels can assist clinicians in differentiating febrile convulsions from clinical situations that might mimic them.

Lactic dehydrogenase isoenzymes in cerebrospinal fluid of children with Guillain-Barré syndrome.

BACKGROUND: Increased levels of lactic dehydrogenase (LDH) in the cerebrospinal fluid (CSF) have been reported in association with several intracranial pathologies. No studies have been performed on patients with Guillain-Barré syndrome (GBS). AIMS: To study LDH isoenzymes in CSF of children with GBS. METHODS: CSF samples collected from nine patients with GBS were analysed for total LDH isoenzymes activity, and compared to samples from 15 patients with normal results. RESULTS: Mean total LDH activity was 33.33 (6.63) U/l. All patients had significantly increased LDH-3 isoenzyme compared to controls. LDH-3 was the predominant fraction, accounting for more than 50% of total LDH activity and present in more than twice the percentage of LDH-1 or LDH-2. By contrast, in the control group, there were high percentages of mainly LDH-1 and LDH-2. CONCLUSIONS: GBS is apparently associated with a distinct LDH isoenzyme pattern in the CSF. More studies are needed to confirm the rise in LDH-3, as serial CSF analyses are unavailable, and to determine the optimum time of analysis when this finding first becomes detectable.

Clinical dysentery in hospitalized children.

BACKGROUND: Clinical dysentery is a severe presentation of an enteric infection. The aim of the study was to evaluate the impact of a serious bacterial etiology in clinical dysentery in hospitalized children and determine if children at high risk can be identified on the basis of clinical or laboratory parameters. PATIENTS AND METHODS: A prospective study design was used. The study population included 60 children admitted to our department with clinical dysentery over a 16-month period. Fresh stool specimens were collected on days 1, 2 and 3. The clinical and laboratory data of the children were analyzed. RESULTS: Clinical dysentery accounted for 1.7% of all pediatric hospitalizations during this period. Stool cultures were positive for Shigella spp. in 18 children (30%), and Salmonella spp. in 15 children (25%), Campylobacter jejuni was identified in one patient (2%). There were no significant differences in clinical characteristics or laboratory parameters between children with positive and negative stool cultures. CONCLUSION: 40% of the children hospitalized for clinical dysentery were eligible for antibiotic treatment. Early administration of empiric antibiotic treatment is justified in children hospitalized for clinical dysentery in Israel. Clinical or laboratory parameters were unable to differentiate those with clinical dysentery at risk of serous bacterial pathogens in stool.

Adolescent screening for orthopedic problems in high school.

BACKGROUND: The effectiveness of orthopedic screening programs for school-age children are still controversial. We conducted a prospective study in order to determine the frequency of undiagnosed orthopedic problems in an adolescent population. OBJECTIVE: To determine the frequency of undiagnosed orthopedic problems in an adolescent population discovered through routine physical examinations carried out by a general pediatrician in a school clinic. METHODS: We examined 2380 adolescents attending a public high school over a 5 y period in order to determine the frequency of undiagnosed orthopedic abnormalities in this age group. RESULTS: Previously undiagnosed orthopedic findings, especially spinal deformities were found in 14.8%. Scoliosis was detected in 1.6% of the entire group with a threefold predominance of girls over boys. Few cases were progressive and needed surgery. Extra spinal orthopedic findings were found in 2.9% of the patients. CONCLUSIONS: Screening programs can identify previously undetected orthopedic abnormalities in the school-age population. We conclude that screening programs for school age children coupled with subsequent follow-up procedures are worthwhile.

Lactic dehydrogenase isoenzymes in cerebrospinal fluid associated with hydrocephalus.

UNLABELLED: Various neurological disorders are associated with specific changes in the level of total lactic dehydrogenase and concentrations of its isoenzymes in the cerebrospinal fluid. We describe the lactic dehydrogenase isoenzyme values in children with hydrocephalus. Cerebrospinal fluid samples collected from 10 patients (2 to 16 mo) with hydrocephalus were analysed for total lactic dehydrogenase activity and lactic dehydrogenase isoenzymes. Findings were compared with those in samples from 15 paediatric patients, with normal results. Mean total lactic dehydrogenase activity in the cerebrospinal fluid was significantly higher in the patients with hydrocephalus (101 +/- 23.11 U/L) than in the controls (33.53 +/- 5.75 U/L) (p <0.001). In the control samples, lactic dehydrogenase-1 was the main fraction, followed by lactic dehydrogenase-2 and 3; only small concentrations of lactic dehydrogenase-4 and lactic dehydrogenase-5 were detected. By contrast, patients with hydrocephalus had lower concentrations of the lactic dehydrogenase-1 fraction and higher lactic dehydrogenase-2 and lactic dehydrogenase-3 concentrations, the differences between these results and those in the control group being statistically significant (p < 0.001). The values for lactic dehydrogenase-4 and lactic dehydrogenase-5 were similar in both groups. CONCLUSION: Findings should be considered together with computed tomography/magnetic resonance imaging and ultrasound scans. The cerebrospinal fluid lactic dehydrogenase profile may prove to be an important predictor of cerebral injury, obstructive hydrocephalus and long-term neurodevelopmental problems.

Concomitant aseptic meningitis and bacterial urinary tract infection in young febrile infants.

We evaluated the incidence and implications of coexistent bacterial urinary tract infection and aseptic meningitis in 1629 young febrile infants (age 1 to 60 days) who underwent sepsis work-up. Urinary tract infection was diagnosed in 13.2% and aseptic meningitis in 8.8%. Eleven patients (0.7%) had both infections. In view of possible coinfection initial laboratory results may be insufficient for decision-making regarding treatment in young febrile infants.