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BACKGROUND: Twenty percent of children outgrow peanut allergy and 10% outgrow tree nut allergy. Resolution can be confirmed by a food challenge. Little is known about the psychosocial impact of the challenge. We aimed to investigate effects of a food challenge on anxiety, stress and quality of life (QoL) in children and their mothers on the day of a food challenge to peanuts or nuts, and in the months following the challenge. METHODS: One hundred and three families participated. Forty children undergoing food challenges to access resolution of allergy, and their mothers, completed validated questionnaires to measure generic and food specific quality of life, stress and anxiety prior to challenge, on the day of investigation and 3-6 months later. Sixty-three children with no clinical indication to challenge (i.e. in the opinion of the allergist had persistent allergy) acted as comparison group completing questionnaires 3-6 months apart. RESULTS: Mothers reported raised anxiety on the day of challenge (P = 0.007), but children were less anxious. The children (P = 0.01) and mothers (P = 0.01) had improved food-related, but not general, QoL 3-6 months following challenge. Children reported lower anxiety levels following the challenge (P = 0.02), but anxiety remained unchanged in mothers. The improvements in maternal and children's QoL and anxiety levels were irrespective of the challenge outcome and despite co-existing food allergies in 50% of children. CONCLUSIONS: Mothers experienced increased anxiety on the day of food challenge, unlike the children, perhaps reflecting the differences in their perceived risks. Food challenges are associated with improved food-related QoL in the following months even in those with a positive challenge.

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Food allergy affects 6% of children but there is no cure, and strict avoidance of index allergens along with immediate access to rescue medication is the current best management. With specialist care, morbidity from food allergy in children is generally low, and mortality is very rare. However, there is strong evidence that food allergy and food hypersensitivity has an impact on psychological distress and on the quality of life (QoL) of children and adolescents, as well as their families. Until recently, the measurement of QoL in allergic children has proved difficult because of the lack of investigative tools available. New instruments for assessing QoL in food allergic children have recently been developed and validated, which should provide further insights into the problems these children encounter and will enable us to measure the effects of interventions in patients. This review examines the published impact of food allergy on affected children, adolescents and their families. It considers influences such as gender, age, disease severity, co-existing allergies and external influences, and examines how these may impact on allergy-related QoL and psychological distress including anxiety and depression. Implications of the impact are considered alongside avenues for future research.

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BACKGROUND: Medical colleges, which face dwindling financial resources, are often forced to rely on inexpensive means of providing students with relevant learning opportunities. PURPOSES: In this article, we present an evaluation of a novel animal model to be used to teach medical students, resident physicians, and allied health personnel advanced airway management skills, namely, endotracheal intubation. METHODS: Over 3 years of regularly scheduled teaching laboratories, 140 students had exposure to both a traditional teaching manikin and a whitetail deer head on which to learn rescue airway techniques. We measured participants on successfully completing an intubation, and we timed them to determine length of time to complete it. Participants also rated the experience across a variety of dimensions. RESULTS: Students reported being very satisfied with the learning experience and were able to perform the techniques more quickly and accurately using the animal model. CONCLUSIONS: The deer airway model is superior to the manikin airway model in teaching endotracheal intubation to students. It should be considered as a viable alternative in medical education settings.

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Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53-442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 > 8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

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The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.

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BACKGROUND: Airway management skills are a vital part of emergency medicine training. Mastery of these skills requires didactic, model, and real-patient experiences. Practice with the use of relevant models greatly enhances these skills. DESCRIPTION: This study evaluated the effectiveness of deer heads as a novel, low-cost animal model for teaching 7 separate intubation procedures. EVALUATION: One hundred and forty people at various levels of clinical training learned from 1 to 7 intubation techniques and practiced on the animal model. Each procedure was rated using a 5-point scale (excellent-poor) on the quality of instruction associated with teaching the procedure and perceived usefulness of the model when compared with human patients. CONCLUSION: Combined results across all procedures showed that 94.8% believed the deer head models to be excellent, very good, or good models for demonstrating the techniques (range of favorable responses across all techniques was 87.5% to 98.8%). Deer heads serve as good to excellent aids for practicing advanced airway management skills. They are readily available and free of cost. This model should be considered in airway skills training.

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Acute dissection of the aorta can be one of the most dramatic of cardiovascular emergencies. Its symptoms can occur abruptly and progress rapidly. Prompt recognition and appropriate intervention is crucial. However, not all aortic dissections present with classic symptoms of abrupt chest, back, or abdominal pain, and the diagnosis may be missed. A 63-year-old woman presented with transient loss of lower extremity motor and sensory function as the only symptom of an acute thoracoabdominal aortic dissection. Aortic dissection presenting as a transient neurologic syndrome is quite unusual. The sudden onset of weakness and parasthesia can result from the interruption of blood flow to the spinal cord. These symptoms of acute spinal cord ischemia, suggestive of a serious cardiovascular event, must be recognized and thoroughly investigated.

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Chest pain is a common emergency department complaint. Many patients presenting with this complaint are discharged with the nonspecific diagnosis of musculoskeletal chest pain. That was the diagnosis given to the patient in this case at the time of her initial presentation to the ED, a diagnosis that was correct but incomplete. This case illustrates the importance of taking a complete history, including a thorough review of systems in every patient, even when the diagnosis seems obvious.

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1. The in vitro metabolism of 7-ethoxycoumarin in the perfused placental lobule has been investigated and compared with that of androstenedione. 2. Perfusion studies showed that the placental lobule was capable of sustaining the metabolism of 7-ethoxycoumarin to 7-hydroxycoumarin for at least one hour but at a considerably lower rate than that for the conversion of androstenedione to oestrone under the same conditions. 3. Following perfusion with androstendione disproportionately large amounts of oestrone were found in the maternal outflow and ostradiol in the foetal outflow. 4. Appreciably more testosterone was formed when the foetal side of the lobule was perfused with androstenedione than when the maternal side was perfused. 5. The data indicate that the human placenta has only a limited capacity for the metabolism of xenobiotics.

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Human placental homogenates from maternal smokers and non-smokers were fractionated using differential centrifugation techniques. Yields of the various subfractions were determined and their homogeneity assessed using electron microscopic procedures. The distribution and response of 7-ethoxycoumarin O-de-ethylase activity towards inhibition by dimethylsulphoxide, alpha-naphthoflavone and 9-hydroxyellipticine inhibitors in the placental subfractions were investigated. The low yield of microsomal protein obtained following differential centrifugation of placental homogenates (2.5 +/- 0.2 mg protein per g placenta) highlights the extremely refractory nature of human placental tissue towards homogenization. Enzymic studies showed that the majority (75 per cent) of the original O-de-ethylase activity in homogenates from smokers and non-smokers was to be found in the crude nuclear fraction. The 7-ethoxycoumarin O-de-ethylase activity present in both homogenate and crude nuclear preparations from a maternal smoker was found to be inhibited by both alpha-naphthoflavone and 9-hydroxyellipticine to a lesser extent than the O-de-ethylase activity which was present in both mitochondrial and microsomal fractions. While this observation suggests the existence of more than one induced O-de-ethylase activity in the human placenta, the possibility that such differences in inhibitory response may be due to other factors (e.g. inhibitor solubility effects) cannot be excluded. Studies using the above inhibitors also confirmed the results of earlier work by demonstrating that the O-de-ethylase activity in placental homogenates and subfractions from non-smokers is qualitatively different from the O-de-ethylase activities induced as a result of maternal smoking.

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The in vitro effects of cimetidine, metyrapone, SKF-525A and alpha-naphthoflavone on the monooxygenase activity in human placental tissue have been determined by indirect fluorimetric assay methods in placental homogenates from five maternal smokers. The inhibitor concentrations producing half-maximum inhibition (I50 values) were calculated for the O-deethylation of 7-ethoxycoumarin and 7-ethoxyphenoxazone, and the hydroxylation of 2,5-diphenyloxazole. The results indicate that cimetidine is a weak inhibitor of the placental monooxygenase system, resembling metyrapone and SKF-525A in its effects rather than alpha-naphthoflavone. Characterization of the behaviour of the three substrates towards placental monooxygenase activity indicates a much greater enzymic affinity for 7-ethoxyphenoxazone than for 7-ethoxycoumarin or 2,5-diphenyloxazole.

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Published results of pharmacokinetic studies (terminal half-life, t 1/2 beta, elimination constant, kappa e1; apparent volume of distribution in beta-phase, Vd beta and plasma clearance, CLp) in pregnant and non-pregnant women have been compiled and compared. Most of the data relate to the results of pharmacokinetic studies with 20 drugs in women at full-term pregnancy, i.e. about 40 weeks gestation. A review of these data failed to reveal any consistent overall trend in any of the pharmacokinetic parameters listed and no generally applicable changes in the disposition of the drugs as a result of pregnancy can be characterised. However, pregnancy associated changes appear to be discernible in the elimination patterns of certain drugs, for example, ampicillin, caffeine, diazepam, phenytoin and thiopentone, but the factors producing these changes can still only be suggested.

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The mono-oxygenase activity in vitro towards 7-ethoxyresorufin (ERR) and 2,5-diphenyloxazole (PPO) was studied in 108 human placental homogenates obtained from mothers who were either smokers (61), non-smokers (44), or epileptics (3). With both substrates the average placental AHH level among smokers was 50 to 60 times greater than the average level in nonsmokers. Some association was found between levels of placental AHH activity and the number of cigarettes smoked per day by the woman concerned: PPO, r = 0.42, P less than 0.01; ERR, r = 0.39, P less than 0.01. In smokers, placental PPO hydroxylase and ERR O-deethylase activities were highly significantly correlated (r = 0.96, P less than 0.001). In non-smokers the low average levels of AHH activity obtained using both substrates were found to be significantly non-zero: PPO, P less than 0.01; ERR, P less than 0.001. No correlation was found, in either smokers or non-smokers, between placental AHH activity and parameters such as age, body weight, diet (including consumption of tea, coffee and alcohol), number of previous pregnancies or placental and baby birth weights. Women who continued smoking during pregnancy but at a reduced rate still maintained fairly high levels of AHH activity. Administration of carbamazepine appeared to cause some enhancement of placental AHH activity. Phenytoin administration, however, had no apparent effect on the level of enzyme activity.

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1 Epidural administration of opiates for analgesia has recently generated widespread interest and would theoretically be advantageous as a method for relief of pain in labour. 2 Plasma pethidine concentrations were measured after intravenous, intramuscular and epidural administration of pethidine to women in labour and after epidural administration to non-pregnant female surgical patients. 3 Kinetic parameters were derived from the plasma concentration data in each group of subjects and the relationship between plasma kinetics and analgesia in labour were examined. 4 Absorption of pethidine from the epidural space in pregnant women in rapid and excepting the lower initial values, the average plasma concentration and area under the plasma concentration v time curve did not differ significantly (P less than 0.01) from those obtained with intravenous dosage, but were significantly higher (P less than 0.01) during the first 2 h after dosage than the results after intramuscular administration. The analgesia provided by the epidural route of administration was greater than with intravenous or intramuscular administration. 5 It is postulated that the analgesic efficacy of epidural pethidine in women in labour is due to a combination of systemic and local effects and that the local effect is attributable to the local anaesthetic properties of pethidine rather than a selective anti-nociceptive action on the spinal cord.

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1 An investigation has been made of the excretion of alpha-methyldopa, alpha-methyldopa sulphate, lorazepam and lorazepam glucuronide in the urine of neonates. 2 The rate of elimination of both the drugs in the newborn is slow compared with the adult rate, and apparent half-life being 3 to 4 times longer than the reported adult values. 3 The newborn appear able to readily metabolise alpha-methyldopa to alpha-methyldopa sulphate and to slowly conjugate lorazepam with glucuronic acid. alpha-Methyldopa tends to be conjugated to a greater extent and lorazepam to about the same or slightly lesser extent in the newborn than in adults. 4 It is postulated that elimination in the neonate is mainly controlled by the rate of renal excretion in the case of alpha-methyldopa and by the rate of conjugation in the case of lorazepam.

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Analgesia mediated by a direct spinal action of narcotic drugs administered via the epidural route may have considerable advantages over conventional(conduction block) epidural analgesia in labour. The efficacy, mode of action and placental transfer of epidurally administered narcotics in labour has not yet been established. We have compared the systemic absorption, analgesia and other effects on the mothers and transfer of drug to the fetus in primigravidae who received epidural or intramuscular pethidine 100 mg in labour. The superior analgesia following epidural pethidine did not appear to be attributable to a selective spinal action but rather to higher plasma concentrations of pethidine together with a possible weak regional conduction block due to local anaesthetic action of 1% pethidine solution. Epidural pethidine is not an advantageous method for providing analgesia in labour.

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Fifty-three neonates born to 51 mothers treated with lorazepam were followed up for five days after delivery. Lorazepam had been given by mouth to 35 mothers and intravenously to 16. In general, maternal plasma concentrations of lorazepam were higher than the corresponding cord plasma concentrations. Cord plasma concentrations exceeding 45 micrograms/l were associated with three-quarters of the infants requiring ventilation at birth. Neonates conjugate lorazepam slowly to the pharmacologically inactive glucuronide, which is then excreted in the urine, where it is detectable for over seven days. Though lorazepam was detectable in breast milk, the maximum amounts that an infant could absorb would be pharmacologically insignificant. Full-term neonates whose mothers had received oral lorazepam had no complications apart from slight delay in establishing feeding, which in seven out of 29 cases was associated with relatively large doses of lorazepam. Intravenous lorazepam for severe hypertension was associated with significantly low Apgar scores, need for ventilation, hypothermia, and poor suckling. Preterm babies whose mothers had been given lorazepam by either route had a high incidence of low Apgar scores, need for ventilation, hypothermia, and poor suckling. These babies had lower Apgar scores than those whose mothers had received diazepam, but the diazepam group were heavier and more mature. Lorazepam was an effective sedative and anxiolytic by either route, and there were no eclamptic fits among the lorazepam-treated patients. The effects of lorazepam on neonates indicate that its intravenous use at any stage in pregnancy and oral use before 37 weeks should be restricted to hospitals with facilities for neonatal intensive care.

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