Weight-based N-acetylcysteine dosing chart to minimise the risk of calculation errors in prescribing and preparing N-acetylcysteine infusions for adults presenting with paracetamol overdose in the emergency department.

Management of paracetamol overdose (POD) is common in the emergency department (ED) and forms part of the clinical effectiveness audit programme of the British Association for Emergency Medicine. N-acetylcysteine (NAC) infusion regimens for the treatment of POD are complicated and prescribing and administration errors have been well documented. This study assessed the ability of doctors and nurses to calculate correct doses using manual calculation skills and a weight-based NAC dosing chart when prescribing and preparing NAC infusions. With manual calculations, errors were made by doctors and nurses in 26% of cases collectively. No errors were made using the dosing chart. The dosing chart ensured 100% accuracy in dose calculations, which may translate into improved patient safety.

Exercise-associated hyponatraemia after a marathon: case series.

OBJECTIVES: To review the presentation, treatment and response of those runners from the London Marathon who presented to St Thomas' Hospital with exercise induced hyponatraemia. DESIGN: Observational case series. SETTING: St Thomas' Hospital, a tertiary hospital situated near the finish line of the 2003 London Marathon. PARTICIPANTS: All runners who presented to St Thomas' Hospital on the day of the 2003 London Marathon with altered mental state whose serum sodium concentration was less than 135 mmol/L. MAIN OUTCOME MEASURES: Presenting symptoms, volume and type of fluids administered and response to treatment (biochemical and clinical). RESULTS: Fourteen patients were diagnosed with exercise associated hyponatraemia with serum sodium concentrations ranging from 116 to 133 mmol/L. Eleven presented with confusion. There were long delays between the finish time and presentation time for some runners. Anecdotal descriptions suggested some runners finished the race with normal mental state then became confused. There was no correlation between running time and serum sodium level. All patients received 0.9% saline and six received 1.8% saline. Despite this, some patients demonstrated falls in serum sodium concentrations. Thirteen to fourteen patients were symptomatically well the following morning, with the remaining patient significantly improved. CONCLUSION: Presentation of exercise associated hyponatraemia may be delayed. Optimal treatment is controversial, but the use of isotonic saline may not result in rises of serum sodium and we would suggest the early use of hypertonic fluids in symptomatic patients.

Cardiac luxation: an unusual complication of a log roll.

Cardiac luxation is a rare but potentially fatal consequence of blunt thoracic trauma. We present a case of a pericardial tear with cardiac luxation following blunt chest trauma. It is hypothesised that the cardiac luxation occurred while log rolling the patient during the initial assessment. This report stresses the need to be aware of the potential for such a complication.

Prehospital activated charcoal: the way forward.

OBJECTIVES: Single dose activated charcoal (SDAC) may be an effective method of gastric decontamination when administered to patients within an hour of drug overdose. However, few patients who may benefit from this treatment attend an emergency department within this timeframe. The authors sought to determine the current attitudes of ambulance NHS trusts to recent recommendations that the administration of SDAC should be considered as a prehospital therapy. METHODS: A postal questionnaire was used to determine the current level of use of prehospital activated charcoal by ambulance NHS trusts, the incidence of associated complications, and barriers preventing the routine use of prehospital SDAC. RESULTS: A completed questionnaire was returned by 36 of the 39 ambulance NHS trusts in the UK (response rate 92%). Currently none of the trusts that responded to the questionnaire provides prehospital SDAC as an intervention. The most common barriers to the provision of prehospital SDAC are the current lack of evidence in the medical literature proving it is effective in improving patient outcome and the lack of a recognised protocol for its administration. Other issues included concerns regarding potential complications, ambulance turnaround times, lack of availability of SDAC, and lack of funding. CONCLUSIONS: A lack of published evidence proving efficacy remains the most important factor in preventing the routine administration of SDAC to appropriate patients in the prehospital environment. Further research in this setting is required to determine the usefulness of this therapy.

Emergency contraception. Has over the counter availability reduced attendances at emergency departments?

Legislation introduced in January 2001 has meant that progestogen only contraception is now available without prescription for women aged 16 years and over. Patient records of two emergency departments in the South East Thames region between 2000 and 2001 were reviewed and it was found that there was a 52% reduction in the number of women attending these emergency departments with requests for emergency contraception. These findings suggest that the legislation has meant that more women are getting their emergency contraception without prescription from pharmacies as compared with emergency departments.

Posterior dislocation of the sternoclavicular joint: a case report and review of the clinical anatomy of the region.

Posterior dislocation of the sternoclavicular joint is an uncommon injury. Since 1824, when Sir Astley Cooper described the injury, little more than 100 cases have been described, and the majority of these have been in the last decade, identified by computed tomography. The significant morbidity and mortality associated with this injury is based upon serious damage to important anatomical structures found in the vicinity of the joint. We present a case report, describe the relevant clinical anatomy of this region, and review associated complications.

In vitro and in vivo refractoriness to thyrotropin stimulation of iodine organification and thyroid hormone secretion.

Earlier studies indicated that initial exposure of thyroid slices to thyrotropin diminished responsiveness of the adenylate cyclase-cyclic AMP system, glucose oxidation, and (32)P(i) incorporation into phospholipids upon readdition of the hormone. The present studies demonstrate that slices from dog, beef, and human thyroid glands initially incubated with thyrotropin (TSH) were less responsive to subsequent addition of the hormone when organification of iodide was examined. Increasing the amount of TSH did not overcome the refractoriness induced by the initial exposure to the hormone. Furthermore, the stimulatory effects of dibutyryl cyclic AMP and prostagladin E(1) were abolished in slices previously incubated with TSH. Development of such refractoriness did not depend upon new protein synthesis and was not abolished by 1 mM prophylthiouracil in the first incubation. Addition of 0.1 muM thyroxine or triiodothyronine or 1.5 muM iodide during all three incubations did not modify the response to TSH, added for the first time in the third incubation. However, 1 mM iodide in the buffer during all three incubations inhibited the response to TSH during the third incubation. During the refractory period, effects of TSH on colloid droplet formation were also diminished. The in vivo effect of TSH on serum l- triiodothyronine in rats was significantly reduced when the rats had been injected with TSH 8 h earlier. These studies demonstrate that TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone. The results cannot be adequately explained by unresponsiveness of adenylate cyclase because effects of dibutyryl cyclic AMP and prostagladin E(1) were also inhibited by prior exposure to TSH.

Effects of thyroid-stimulating hormone on human thyroid carcinoma and adjacent normal tissue.

Effects of TSH on the adenylate cyclase-cAMP system and some parameters of intermediary metabolism were investigated in human thyroid carcinoma and adjacent normal thyroid tissue. Basal adenylate cyclase activity and cAMP concentrations were significantly higher in carcinomatous tissue. Basal [1-14C]glucose oxidation, 32Pi incorporation into phospholipids, and organification of iodide were similar in both tissues. Stimulation of cAMP by TSH was significantly greater in normal compared to carcinomatous tissue. In neither tissue was there a good correlation between TSH stimulation of adenylate cyclase activity and cAMP concentrations. The TSH stimulation of 32Pi incorporation into phospholipids by TSH was significantly greater in normal tissue. The mean effect of TSH on iodide organification and glucose oxidation was similar in normal and carcinomatous tissue. Although specific binding of TSH was demonstrated in both normal and carcinomatous tissue, it did not correlate very well with stimulation of adenylate cyclase activity. Hormones other than TSH also augmented adenylate cyclase activity in two of the carcinomas. In individual patients, the relative responsivity of carcinomatous tissue compared to normal was not always consistent when all of the metabolic parameters were considered.

Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone.

Prior exposure of thyroid slices to thyrotropin (TSH) induced refractoriness to subsequent stimulation of the cyclic AMP system by the hormone. Although the inhibition is incomplete, we examined whether the reduction in cyclic AMP was sufficient to alter other metabolic effects of TSH. Bovine or dog thyroid slices were incubated with or without 5-100 mU/ml TSH for 1-2h, washed, and then incubated without hormone for 1-2h. Half of the slices not exposed to TSH initially were then incubated with buffer and half were exposed to 5-100 mU/ml TSH. Slices initially incubated with TSH were also incubated with or without TSH in the third incubation. During the refractory period, TSH activation of protein kinase was inhibited even though the hormone still caused some increase in cyclic AMP concentrations. However, protein kinase activity was fully responsive to dibutyryl cyclic AMP when slices were incubated with it during the third incubation. Stimulation of glucose oxidation by TSH was significantly decreased in thyroid slices previously incubated with the hormone. During refractoriness, stimulation of glucose oxidation caused by prostaglandin E1 and dibutyryl cyclic AMP was also significantly diminished but that due to acetylcholine was not. Thus even though dibutyryl cyclic AMP could fully activate protein kinase activity during refractoriness, its effect on glucose oxidation was still inhibited, suggesting that the metabolic block responsible for this refractoriness was distal to activation of protein kinase. Stimulation of 32Pi incorporation into phospholipid by TSH and acetylcholine was also inhibited during refractoriness. Despite reduction of the stimulatory effect of TSH, binding of 125ITSH was not modified by prior incubation of thyroid slices with TSH. These results indicate that changes in the TSH receptor are not responsible for the development of refractoriness and other metabolic sites besides activation of adenylate cyclase appear to be involved.

Activation of protein kinase in thyroid slices by thyroid-stimulating hormone.

Protein kinase activity in homogenates of control thyroid slices and those incubated with thyroid-stimulating hormone (TSH) and prostaglandin EI was assayed and correlated with changes in cyclic adenosine 3':5'-monophosphate (cAMP) concentrations and binding of [3H]cAMP. Both TSH and prostaglandin E1 (25 mug/ml) increased protein kinase activity and the activity ratio (expressed as activity - cAMP to activity plus cAMP). It is unlikely that such activation reflects effects of the increased cAMP liberated at the time of homogenization. Hormone-induced activation of protein kinase persisted even after the homogenate had been diluted so that its cAMP concentration would be insufficient to achieve maximal activation of the enzyme. In contrast to the previous results of J. D. Corbin, T. R. Soderling, and C. R. Park ((1973 J. Biol. Chem. 248, 1813) using adipose tissue, homogenization of thyroid tissue in 0.5 M NaCl and chromatography using Sephadex G-100 did not seem to stabilize dissociation of protein kinase into its receptor and catalytic subunits. However, increasing amounts of NaCl in the homogenizing buffer were associated with an increase in the cAMP independence of enzyme activity. Dilution of the homogenate did not change the protein kinase activity ratio whether the homogenizing buffer contained NcCl or not. Increasing concentrations of NaF inhibited protein kinase activity. Within 1 to 3 min of incubation of thyroid slices with TSH, protein kinase activity and the activity ratio were increased significantly. This correlated quite well with increased cAMP concentrations in the slices and inhibition of [3H]cAMP binding to the homogenates. Maximal activation of the enzyme was achieved by 10 min which corresponds to the time of maximal effect on cAMP concentrations. Activation of protein kinase was achieved by 0.125 milliunit/ml of TSH and maximal effects with 0.5 to 1.25 milliunits/ml. These amounts agree well with those required for other effects of TSH. Although larger amounts of TSH produced even greater increases in cAMP concentrations this was not always associated with augmented inhibition of [3H]cAMP binding. These results are compatible with the concept that the TSH-mediated increase in cAMP is associated with activation of protein kinase in the intact cell. They also suggest that not all of the intracellular cAMP is available for activation of protein kinase.

Conversion of protein nitrogen into gaseous catabolites by the chick embryo.

Chicken eggs incubated under hatchery conditions for 19 days show significant decreases in the total content of water and organic nitrogen, but not of sodium or potassium. The hypothesis is discussed that the formation of gaseous nitrogen is responsible for the nitrogen loss.