Failure of normal glycaemic regulation in a patient with severe hypothermia

This report describes the case of an 88-year-old non-diabetic female who presented to the emergency department following a presumed hypoijtycaemic collapse due to self-neglect. Subsequent rewarming and resuscitation demonstrated a number of the significant consequences of severe hypothermia, including apparent secondary impairment of glycaemic autoregulation. The phenomenon of reversible inhibition of insulin secretion due to severe hypothermia has been documented previously in the field of cardiac surgery. The hyperglycaemia was not treated with any antihyperglycaernic agent, and her recovery was uneventful. Subsequent blood sugar level monitoring was normal. If insulin is administered to the hypothermic patient, intensive monitoring of blood glucose is essential due to the increase in endogenous insulin secretion on rewarming. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Effect of cooling and re-warming on cerebral and whole body electrical impedance

Cerebral electrical impedance is useful for the detection of cerebral edema following hypoxia in newborn infants. Thus it may be useful for determining neurological outcome or monitoring treatment. Hypothermia is a promising new therapy currently undergoing trials, but will alter impedance measurements. This study aimed to define the relationship between temperature and both cerebral and whole body electrical impedance, and to derive correction factors for adjustment of impedance measurements during hypothermia. In eight anaesthetized 1-2 day old piglets rectal, tympanic and scalp temperatures were monitored continuously. Following baseline readings at a rectal temperature of 39degreesC, piglets were cooled to 32degreesC. Four piglets were re-warmed. Cerebral and whole body impedance were measured at each 0.5degreesC as rectal temperature decreased. There was a strong linear relationship between both cerebral and whole body impedance and each of the temperatures measured. There was no difference in the relationship between impedance and rectal, tympanic or scalp temperatures. The relationship for impedance and rectal temperature was the same during cooling and re-warming. Using the correction factors derived it will be possible to accurately monitor cerebral and whole body fluid distribution during hypothermic treatment.

Thermal injuries in three children caused by an electrical warming mattress

Peroperative hypothermia is recognized to increase mortality and morbidity, and the paediatric anaesthetist faces specific challenges resulting from the increased body surface to volume ratio, particularly in smaller children. We describe three children who were consecutive patients on one operating list and sustained severe thermal injuries. These were due to a malfunctioning electrical heating mat, despite appropriate use and monitoring by the attending anaesthetist. It is rare for thermal warming devices to cause injury. We review the use of heating mats, and suggest modifications in their manufacture which may minimize the risks associated with heating devices.

Will the new CB1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?

Obesity and alcoholism are two common modern-day diseases. The cannabinoid CB, receptor antagonist rimonabant is in Phase III clinical trial for the treatment of obesity with preliminary results showing that it decreases appetite and body weight. Animal studies have shown that rimonabant is effective in the treatment of alcoholism. SR-147778 is a new potent and selective CB1 receptor antagonist. In animals, SR-147778 has been shown to inhibit CB1 receptor-mediated hypothermia, analgesia and slowing of gastrointestinal transit. In rats trained to drink sucrose, the oral administration of SR-147778 3 mg/kg, before the presentation of sucrose, decreased the consumption of sucrose. SR-147778 3 mg/kg also reduced spontaneous feeding in rats deprived of food and also in non-deprived rats. In Sardinian alcohol-preferring (sP) rats, in the alcohol-naive state, SR-147778 slowed the development of a preference for alcohol. in alcohol-experienced sP rats SR-147778 (2.5, 5 and 10 mg/kg p.o.) reduced the alcohol intake. When alcohol-experienced sP rats are deprived of alcohol for 15 days, there is a large intake of alcohol on reintroduction of alcohol, and this response was almost abolished by treatment with SR-147778. From the preclinical studies published to date, there is no obvious major point of difference between rimonabant and SR-147778, and both are promising agents for the treatment of obesity and alcoholism.

Control of culture environment for improved polyethylenimine-mediated transient production of recombinant monoclonal antibodies by CHO cells

In this study we describe optimization of polyethylenimine (PEI)-mediated transient production of recombinant protein by CHO cells by facile manipulation of a chemically defined culture environment to limit accumulation of nonproductive cell biomass, increase the duration of recombinant protein production from transfected plasmid DNA, and increase cell-specific production. The optimal conditions for transient transfection of suspension-adapted CHO cells using branched, 25 kDa PEI as a gene delivery vehicle were experimentally determined by production of secreted alkaline phosphatase reporter in static cultures and recombinant IgG(4) monoclonal antibody (Mab) production in agitated shake flask cultures to be a DNA concentration of 1.25 mu g 10(6) cells(-1) mL(-1) at a PEI nitrogen: DNA phosphate ratio of 20:1. These conditions represented the optimal compromise between PEI cytotoxicity and product yield with most efficient recombinant DNA utilization. Separately, both addition of recombinant insulin-like growth factor (LR3-IGF) and a reduction in culture temperature to 32 degrees C were found to increase product titer 2- and 3-fold, respectively. However, mild hypothermia and LR3-IGF acted synergistically to increase product titer 11-fold. Although increased product titer in the presence of LR3-IGF alone was solely a consequence of increased culture duration, a reduction in culture temperature post-transfection increased both the integral of viable cell concentration (IVC) and cell-specific Mab production rate. For cultures maintained at 32 degrees C in the presence of LR3-IGF, IVC and qMab were increased 4- and 2.5-fold, respectively. To further increase product yield from transfected DNA, the duration of transgene expression in cell populations maintained at 32 C in the presence of LR3-IGF was doubled by periodic resuspension of transfected cells in fresh media, leading to a 3-fold increase in accumulated Mab titer from similar to 13 to similar to 39 mg L-1. Under these conditions, Mab glycosylation at Asn297 remained essentially constant and similar to that of the same Mab produced by stably transfected GS-CHO cells. From these data we suggest that the efficiency of transient production processes (protein output per rDNA input) can be significantly improved using a combination of mild hypothermia and growth factor(s) to yield an extended activated hypothermic synthesis.