Janet Stone

Impaired fatty acid oxidation in propofol infusion syndrome

Propofol infusion syndrome is a rare but frequently fatal complication in critically ill children given long-term propofol infusions. We describe a child who developed all the clinical features of propofol infusion syndrome and was treated successfully with haemofiltration. Biochemical analysis before haemofiltration showed a large rise in plasma concentrations of malonylcarnitine (3.3 micromol/L) and C5-acylcarnitine (8.4 micromol/L), which returned to normal after recovery. Abnormalities are consistent with specific disruption of fatty-acid oxidation caused by impaired entry of long-chain acylcarnitine esters into the mitochondria and failure of the mitochondrial respiratory chain at complex 11.

Serum Gentamicin Concentrations in Encephalopathic Infants are Not Affected by Therapeutic Hypothermia

OBJECTIVE. Mild hypothermia for 72 hours is neuroprotective in newborns with moderate or severe hypoxic-ischemic encephalopathy. A core temperature of 33.5°C might reduce drug clearance leading to potential toxicity. Gentamicin is nephrotoxic and ototoxic at high serum concentrations. No study has investigated the influence of 72 hours of hypothermia on serum gentamicin concentrations (SGCs) in children of any age. We aimed to compare the SGCs in encephalopathic infants who underwent intensive care with therapeutic hypothermia or normothermia. METHODS. Data were collected retrospectively from 2 NICUs in Bristol, United Kingdom, that offered cooling therapy within clinical trials since 1998. Eligible infants (n = 55) developed grade 2/3 encephalopathy after birth and fulfilled the entry criteria defined in the CoolCap trial. Encephalopathic infants with similar demographic values were either nursed under normothermia or 72 h-hypothermia. Once-daily gentamicin dosage (4–5 mg/kg) was administered, and trough SGC was recorded with corresponding creatinine concentrations. The time and number of omitted drug doses were noted. RESULTS. Mean trough SGC (pre–second dose) and mean plasma creatinine concentrations for both treatment groups were similar (gentamicin: 2.19 ± 1.7 [hypothermia] and 2.30 ± 2.0 [normothermia] mg/L; creatinine: 115.6 ± 42.8 [hypothermia] and 121.0 ± 45.1 [normothermia] μmol/L). Forty percent of the trough SGCs in both groups were above the recommended trough concentration of 2.0 mg/L. A significant correlation (r2 = 0.36) was found between high SGCs and impaired renal function assessed by raised plasma creatinine levels regardless of treatment options. CONCLUSIONS. Our data confirm that impaired renal function is strongly associated with high SGCs. Reduced body temperatures do not affect the clearance of gentamicin.

Delayed Hypothermia as Selective Head Cooling or Whole Body Cooling Does Not Protect Brain or Body in Newborn Pig Subjected to Hypoxia-Ischemia

The neuroprotective efficacy of hypothermia (HT) after hypoxia-ischemia (HI) falls dramatically the longer the delay in initiating HT. Knowledge is scarce regarding protective or adverse effects of HT in organs beyond the brain. In addition, the relative effectiveness of selective head cooling (SHC) and whole body cooling (WBC) has not been studied. We aimed to examine whether 24 h HT, initiated 3 h after global HI is brain- and/or organ-protective using pathology, neurology, and biochemical markers. Fifty, ≤1-d-old pigs were subjected to global HI causing permanent brain injury. Animals were randomized to normothermia (NT), (Trectal) 39.0°C, SHCTrectal 34.5°C, or WBCTrectal 34.5°C for 24 h, all followed by 48 h NT. There was no difference in injury to the brain or organs between groups. There was no gender difference in brain injury but females had significantly more organs injured [2.3 (± 1.3) [mean ± SD] vs. 1.4 ± (1.0)]. The postinsult decline in lactate was temperature independent. However, HT animals normalized their plasma-calcium, magnesium, and potassium significantly faster than NT. Delayed SHC or WBC, initiated 3 h after HI, does not reduce pathology in the brain nor in organs. Delayed HT improves postinsult recovery of plasma-calcium, magnesium, and potassium. There were no differences in adverse effects across groups.

An ultrastructural and systemic analysis of glycosaminoglycans in thyroid-associated ophthalmopathy

Purpose To determine the ultrastructural localisation of glycosaminoglycans (GAGs) in the extraocular muscles (EOMs) of patients with thyroid-associated ophthalmopathy (TAO) and to see whether the quantity and type of GAGs present in blood and urine are markers of the disease.Methods Biopsies of affected EOMs were taken and studied by transmission electron microscopy (TEM). These were either fixed conventionally for TEM, or in 0.5% tannic acid and others for immunogold staining. Serum hyaluronan (HA) was measured using a radioimmunoassay in patients with TAO as well as control subjects, and urinary GAG levels assessed by photometric quantitation of hexuronic acid after reaction with carbazole. The excretion pattern of the urinary GAGs was determined by discontinuous electrophoresis.Results TEM showed that there is a marked ficpansion of the endomysial space in TAO EOM biopsies as compared with non-TAO strabismus specimens. This is caused by an increased number of collagen fibres. interspersed with a granular amorphous material surrounding striated collagen fibres shown to be hyaluronan by immunogold ftaining. In contrast, serum hyaluronan concentrations were similar in TAO and control patients, although there was a statistically significant difference in the ttrinary GAG excretion between the two groups of patients examined. By discontinuous electrophoresis, chondroitin ivlphate and heparan sulphate were present in both patients and controls.Conclusion GAGs and in particularly HA are present at the EOM level in patients with jecently inactive TAO. However, serum levels of HA and urinary GAGs are not sensitive indicators for their presence within the EOMs.

Lactate dehydrogenase in hypothermia-treated newborn infants with hypoxic-ischaemic encephalopathy

Aims:  We investigated whether plasma lactate dehydrogenase (LDH) predicts outcome in hypothermia (HT)‐treated term infants with moderate/severe hypoxic‐ischaemic encephalopathy (HIE) and additionally whether LDH differs between infants with evidence for acute and nonacute perinatal insults and postnatal collapse (PNC).

Effect of cardiac compressions and hypothermia treatment on cardiac troponin I in newborns with perinatal asphyxia

BACKGROUND The American Heart Association, the European Resuscitation and the International Liaison Committee issued new neonatal resuscitation guidelines (2010) where therapeutic hypothermia is introduced after hypoxic-ischaemic encephalopathy (HIE) in term infants to prevent brain injury. Our study aimed to investigate whether hypothermia can reduce the release of a cardiac cellular marker, cardiac troponin I (cTnI), in HIE infants compared to normothermia care, if cTnI can be used as a prognostic marker for long term neuro-developmental outcome and if cardiac compression at birth affects the level of cTnI. METHODS We retrospectively collected resuscitation data at birth and cTnI levels for the first 3 days in HIE infants who fulfilled cooling entry criteria. These infants received either normothermia care or induced hypothermia treatment in the neonatal period and were then followed up and tested by standard cognitive and motor assessments. The outcome is defined as death, disability or good. RESULTS We confirmed an increase in cTnI after cardiac compressions (p=0.003, Mann-Whitney test). We found that hypothermia significantly reduced the release of cTnI (peak level and area under the curve within 24h of age), p=0.002, linear regression. Receiver operating characteristic curves showed a level of cTnI at 24 h of age <0.22 ng/ml for normothermic and <0.15 ng/ml for hypothermic infants predicts a good outcome. CONCLUSIONS Our results suggest that hypothermia is cardio protective after HIE. The level of cTnI at 24h of age is a good prognostic marker for neuro-developmental outcome at 18-22 months in both normothermia and hypothermia infants.

Cost-effective strategy for the serological investigation of coeliac disease

Increased numbers of requests for serological investigation of coeliac disease, and a local trend to request both anti-gliadin antibodies (AGA) and anti-endomysium antibodies (AEA) simultaneously, resulted in cost pressures that prompted a review of our practice. Serology results from all patients (771 children, 511 adults) investigated for coeliac disease over a 3-year period were compared with small intestine histology where available. IgG AGA and IgA AGA were measured by enzyme-linked immunosorbent assay (in-house), IgA AEA by immunofluorescence (send-away contract). Overall diagnostic performance was as follows: AGA sensitivity 84%, specificity 88%, positive predictive value (PPV) 24%, negative predictive value (NPV) 99%; AEA sensitivity 88%, specificity 97%, PPV 65%, NPV 99%. Results showed AGA, with its high NPV, to be a suitable first-line test to exclude coeliac disease. The high specificity of AEA makes it a suitable confirmatory test when AGA is positive. Introduction of this step-wise approach to coeliac disease investigation resulted in cost savings of at least £5000 per year without detriment to the clinical service.

Results of a Quality Assurance Exercise for Urinary Glycosaminoglycan Excretion

Urine samples collected from four patients with a mucopolysaccharide storage disease (MPS) and two non-MPS patients were distributed to up to 33 laboratories as a test of their ability to detect abnormal glycosaminoglycan excretion. Seven national reference laboratories made a correct diagnostic assignment to all samples analysed. Qualitative turbidity and spot tests were shown to be unreliable. Failure to identify the excretion pattern occurred when reliance was placed on one-dimensional electrophoresis or thin layer chromatography as the sole method for glycosaminoglycan identification. Two-dimensional electrophoresis appeared to be the method of choice provided that staff had adequate experience in interpretation. Clinically unacceptable delays in analysis were common, with 80% of laboratories taking longer than 10 days to issue a report.

Contents Vol. 96, 2009

S. Andersson, Helsinki E. Bancalari, Miami, Fla. G. Buonocore, Siena W. Carlo, Birmingham, Ala. V.P. Carnielli, Ancona W.J. Cashore, Providence, R.I. I. Choonara, Derby T. Curstedt, Stockholm O. Dammann, Boston, Mass. C. Dani, Florence B. Darlow, Christchurch P.D. Gluckman, Auckland M. Hallman, Oulu B. Jonsson, Stockholm S.E. Juul, Seattle, Wash. A.J. Llanos, Santiago R.J. Martin, Cleveland, Ohio C.J. Morley, Cambridge J. Neu, Gainesville, Fla. P.C. Ng, Hong Kong M.W. Obladen, Berlin A.G.S. Philip, Sebastopol, Calif. M. Post, Toronto E. Saliba, Tours O.D. Saugstad, Oslo B. Schmidt, Philadelphia, Pa. E.S. Shinwell, Rehovot J. Smith, Tygerberg B. Sun, Shanghai H. Togari, Nagoya F. van Bel, Utrecht N. Vain, Buenos Aires M. Vento Torres, Valencia M. Weindling, Liverpool J.A. Widness, Iowa City, Iowa Fetal and Neonatal Research

Diagnosis of Neonatal Hypoglycemia at the Cotside. A Comparison of Precision Q.I.D., Hemocue and Hexokinase Methods

Diagnosis of Neonatal Hypoglycemia at the Cotside. A Comparison of Precision Q.I.D., Hemocue and Hexokinase Methods