Utilisation of water soluble iridium catalysts for signal amplification by reversible exchange.

The catalytic hyperpolarisation of pyridine, 3-hydroxypyridine and oxazole by the Signal Amplification By Reversible Exchange (SABRE) process is achieved by a series of water soluble iridium phosphine and N-heterocyclic carbene dihydride complexes. While the efficiency of the SABRE process in methanol-d4 solution or ethanol-d6 solution is high, with over 400-fold (1)H polarisation of pyridine being produced by [Ir(H)2(NCMe)(py)(IMes)(monosulfonated-triphenylphosphine)]BF4, changing to a D2O or a D2O-ethanol solvent mixture leads to dramatically reduced activity which is rationalised in terms of low H2 solubility.

Quantification and genotyping of lipoprotein lipase in patients with diabetic lipaemia.

AIMS: To determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL. METHODS: We conducted a case-control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations. RESULTS: Only one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs. 484 µg/l, P = 0.04). The mean fasting C-peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs. 50 pmol/l; P = 0.001). CONCLUSIONS: Lipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis-prone Type 2, rather than Type 1, diabetes.

Comparison of a Trigger Tool and voluntary reporting to identify adverse events in a paediatric intensive care unit.

Reduction of adverse events depends on accurate detection. The utility of a Trigger Tool to detect and classify severity of adverse events in an intensive care unit of a paediatric university hospital was compared to voluntary reporting. Sixty patient records were randomly selected from 314 admissions over three months. Events detected by the Trigger Tool were classified by two independent investigators as insignificant, minor, moderate, major or catastrophic. Examination of each record required, on average, 40 minutes. Ninety-eight adverse events (1.66/patient) were detected in 59 available records. Mean admission was 2.77 days. The incidence of adverse events was 59.9 per 100 patient days or 0.60 events per patient per day. The number of events detected by the Trigger Tool was related to duration of admission (r=0.70, P <0.0001) and risk of mortality on admission (r=0.50, P=0.0001) but not to age. The inter-rater agreement on detection of adverse events was good. Investigator One detected 66 adverse events while Investigator Two detected 93 events (kappa 0.63). Of the 61 events detected by both investigators, the agreement of classification of severity was very good (kappa 0.89). Of the 56 events rated similarly by both investigators, 13 (23%) were insignificant, 19 (34%) were minor, 17 (30%) were moderate, 4 (7%) were major and 3 (6%) were catastrophic. Only four adverse events had been reported voluntarily, of which two were detected using the Trigger Tool. Whereas the Trigger Tool is a simple, efficient and robust method, voluntary reporting is inadequate and captures very few adverse events in the intensive care unit environment.

Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations.

Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was approximately 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.

Novel mutations in abetalipoproteinaemia and homozygous familial hypobetalipoproteinaemia.

Abetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)-containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat-soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB-30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in-frame deletion of MTP exon 15 (c.2076-39_2303 + 52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat-soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.

Violent behavior associated with hypocholesterolemia due to a novel APOB gene mutation.

A 26-year-old male, the index patient, presented with persecutory delusions and suicidal behavior. He had 10 paternal male relatives in two prior generations. Five of them died by violent suicide and one, of the five, also committed a double homicide. The index patient was found to be hypocholesterolemic due to being heterozygous for a novel mutation of apolipoprotein B (apoB-29.4). His mother and paternal grandmother were normocholesterolemic, whereas a surviving paternal uncle was hypocholesterolemic and heterozygous for the apoB-29.4 mutation. This indicated that the index patient's father and paternal grandfather, both of which died by violent suicide, were obligate heterozygotes for the apoB-29.4 mutation and that the index patient inherited the mutation from his paternal grandfather. The odds ratio for the association between hypocholesterolemia and violent behavior in this family, where cholesterol status was known, was 16.9 (95% confidence interval 1.1-239.3). Therefore, our results support an inheritable relationship between violent behavior and hypocholesterolemia.

An evaluation of physiological demands and comfort between the use of conventional and lightweight self-contained breathing apparatus.

The additional physiological strain associated with the use of self-contained breathing apparatus (SCBA) is mostly linked to the additional weight. Lightweight and conventional SCBA were assessed in a submaximal step test performed in full firekit (total weights 15 and 27 kg, respectively). Factors assessed were: comparative energy expenditure of the two sets, relationship between comparative energy expenditure and aerobic fitness and subjective discomfort. Measured variables were: oxygen consumption, heart rate, estimated VO2max and subjective discomfort (body part discomfort scale). The lightweight SCBA displayed a significant oxygen consumption benefit, which was independent of dynamic workrate and valued at 0.2561 min(-1). Mean heart rate responses were significantly lower with the light set. No relationship was found between comparative energy expenditure and aerobic fitness. The light set was rated as significantly more comfortable than the heavy. Further research is required to assess the extent of the energy consumption benefit in realistic fire suppression protocols and the contribution of ergonomic factors to the energy and comfort benefits.