Allergy to oxidized limonene and linalool is frequent in the U.K.

BACKGROUND: The oxidized forms of the fragrance terpenes limonene and linalool are known to cause allergic contact dermatitis. Significant rates of contact allergy to these fragrances have been reported in European studies and in a recent worldwide study. Patch testing to oxidized terpenes is not routinely carried out either in the U.K. or in other centres internationally. OBJECTIVES: To investigate the prevalence of contact allergy to oxidized limonene and linalool in the U.K. METHODS: Between 1 August 2011 and 31 December 2012, 4731 consecutive patients in 13 U.K. dermatology departments were tested for hydroperoxides of limonene 0·3% pet., hydroperoxides of linalool 1·0% pet., stabilized limonene 10·0% pet. and stabilized linalool 10·0% pet. Doubtful (?+) and equivocal (±) reactions were grouped together as irritant reactions. RESULTS: Two hundred and thirty-seven patients (5·0%) had a positive patch test reaction to hydroperoxides of limonene 0·3% pet. and 281 (5·9%) to hydroperoxides of linalool 1·0% pet. Irritant reactions to one or both oxidized terpenes were found in 242 patients (7·3%). Eleven patients (0·2%) had a positive patch test reaction to the stabilized terpenes alone. CONCLUSIONS: This large, multicentre U.K. audit shows a significant rate of allergy to the hydroperoxides of limonene and linalool plus a high rate of irritant reactions. Testing to the oxidized forms alone captures the majority (97·0%; 411 of 422) of positive reactions; testing to nonoxidized terpenes appears to be less useful. We recommend that the hydroperoxides of limonene and linalool be added to an extended baseline patch test series.

A porcine model of sepsis resulting from the combined insults of hemorrhage and peritonitis.

The physiological responses to either hemorrhage or sepsis have been well documented, however, their simultaneous delivery, as often seen in penetrating trauma, has not been extensively studied. A terminally-anesthetized porcine model of fixed-volume hemorrhage combined with intraperitoneal sepsis was developed. Large White pigs (45-60 kg) were bled 40% of blood volume and peritonitis was induced using an E. coil (O18:K1:H7) culture. Three groups of animals were sequentially studied. Group A (n = 8) received 10(8) bacteria, and Groups B (n = 4) and C (n = 5) received 10(10) organisms. All animals were maintained on a 2.5 mL/kg/h infusion of 0.9% saline. Group C was autotransfused at 1 h. Animals were monitored for up to 24 h. Cardiovascular features of hypovolemia were recorded in all animals. Animals in Group A improved clinically with little microbiological evidence of systemic sepsis. Group B showed rapid cardiovascular collapse, early E. coil-positive blood cultures, and an early rise in serum TNF-alpha levels. Autotransfusion of Group C significantly improved cardiopulmonary parameters, acid-base status, and survival. A reproducible model of hemorrhage and peritonitis, appropriate for abdominal trauma, which allows investigation of resuscitative and pharmacological interventions has been characterized.

Spread of infection, in an animal model, after intramedullary nailing of an infected external fixator pin track.

Implant sepsis. due to previous external fixator pin track infection, is the most common complication of secondary intramedullary (IM) nailing of the tibia. We have developed an animal model, which allows different treatment methods to be studied. Using an established ovine model of a pin track infection, Staphylococcus aureus was used to infect the external fixator pins, two weeks prior to reamed IM nailing. In the control group, the animals were killed at a mean of 10.5 days following nailing, when widespread infection was evident, with septic arthritis, abscess formation, and infection of the entire length of the tibia in all six animals. In the treatment group, before IM nailing, the pin sites were debrided, and both local and systemic antibiotics were administered. All surgical wounds healed without evidence of infection, 4 of the 6 animals survived for 28 days, and bacteria were only isolated from 1 of the 6 implants. Treatment was successful at reducing, but not eliminating, infection after secondary nailing.

Pentoxifylline fails to improve organ dysfunction and survival when used in the resuscitation of a porcine model of haemorrhage and abdominal sepsis.

Pentoxifylline is a phosphodiesterase inhibitor, known to suppress tumour necrosis factor-alpha production and improve cardiopulmonary parameters and survival in animal models of sepsis. Using a porcine model of abdominal trauma resulting from the combined insults of haemorrhage and infection, a randomised placebo-controlled trial was conducted of pentoxifylline (20 mg/kg bolus followed by 20 mg/kg infusion over 1 h) administered in addition to a colloid resuscitation regimen. Female Large White pigs (45-60 kg) were bled 40% of their blood volume and peritonitis was induced using E. coli (O18: K1: H7) in an autoclaved faecal suspension. Animals were resuscitated with either colloid alone (n=5) or colloid plus pentoxifylline (n=5). Pentoxifylline attenuated increases in mean arterial and pulmonary artery pressures and reduced both systemic and pulmonary vascular resistance. It worsened the lactic acidosis associated with 'septic shock' and failed to reduce serum TNF-alpha levels. Pentoxifylline, in the high doses used in this study, does not have a role as an adjunct to resuscitation in this clinically relevant model of trauma.

Plasma alkaline ribonuclease (EC 3.1.4.22) and nitrogen retention in low-birth-weight infants.

1. Nitrogen retention was determined by classical N balance techniques in fourteen rapidly growing low-birth-weight infants receiving 3 g protein/kg body-weight and during their 3rd week of life. This was compared with plasma free alkaline ribonuclease (EC 3.I.4.22; RNase) activity and other biochemical measurements of protein nutrition. 2. Plasma RNase showed a significant positive correlation with N retention and a corresponding negative correlation with urine urea-N. These results were unexpected and suggest a different relationship between RNase and N retention in infants compared with that found by other workers in children and adults. 3. The most likely explanation of this apparent anomaly is that in all instances high activities of plasma RNase are associated with a need to conserve N. In the infants studied this may indicate some measure of 'protein economy' and they could therefore benefit from a higher protein intake.

Milk pH, acid base status, and growth in babies.

Metabolic acidosis is common in babies fed cows' milk-based formulae. Therefore the effects of adding alkaline salts (sodium and potassium citrate) to a demineralised whey formula were studied in vitro and in 26 low birthweight babies fed on the formula or formula plus citrate. The alkali altered the pH and titratable acidity to a value nearer human milk but it increased the buffering capacity to a value further away. This may effect the bacterial flora of the intestine. The babies fed on formula plus citrate did not make greater gains in weight, length, head circumference, skinfold thickness, or midarm muscle circumference, although they had a greater blood base excess. Some of these babies developed a mild metabolic alkalosis and 3 had hyponatraemia despite their increased sodium intakes. These babies also had lower levels of plasma transferrin but showed no differences in urea, albumin, cholesterol, and calcium levels. No baby fed on the demineralised whey formula without added citrate had a base deficit exceeding 5 mmol/l; late metabolic acidosis is less common in babies fed on this formula and the routine addition of alkali can have untoward metabolic effects.

Curd and whey proteins in the nutrition of low birthweight babies.

Some animals thrive more satisfactorily on a milk that contains whey and curd protein. For this reason human milk protein (which contains about 40% whey) may have some advantages over cows' milk protein (which contains about 15% whey) and so infants feeding formulae based on demineralised whey in which the protein has been modified to achieve a curd:whey ratio similar to that in human milk may also thrive more satisfactorily. As the exact situation in the human newborn is unclear, the effects of feeding a formula containing unmodified cows' milk protein (mainly curd) and one containing the same amount of modified cows' milk protein (curd and whey) were studied in 57 low birthweight babies during the first 3 months of life. During the early weeks of life the curd and whey group grew bigger, absorbed more nitrogen, and excreted proportionately less urea. These results suggest that a curd and whey formula has advantages in the protein nutrition of low birthweight babies, especially the preterm ones. We feel it would be unwise to reduce the protein content of a formula based on cows' milk below 15 g/1 unless it was modified to achieve a larger proportion of whey protein and hence, among other qualities, more cysteine. Although some of the qualities of human milk protein can be mimicked by the use of demineralised whey formulae, others cannot.

Effect of gestational age and intrauterine nutrition on plasma transferrin and iron in the newborn.

Plasma concentrations of transferrin and iron were measured in the cord blood of babies of varying gestational age and birthweight. Tranferrin and iron concentrations rose with gestational age; values in light-for-dates babies did not differ from those in babies of appropriate weight. In the last trimester of pregnancy plasma transferrin and iron concentrations in the fetus are affected by the maturity of the pregnancy but are independent of the nutritional status of the fetus. The low transferrin levels, particularly in preterm babies, may caution the use of iron especially by the parenteral route in the neonatal period, but we are wary of abandoning on this evidence alone the well tried clinical custom of giving oral iron to preterm babies who are not breast fed.

Effects of inhaled nitric oxide on the anesthetized, mechanically ventilated, large white pig.

Inhalation of nitric oxide (NO) results in selective pulmonary vasodilation, which may be beneficial in the treatment of acute lung injury. However, NO has toxic effects, and it is important to monitor the effects and fate of inhaled NO. Under intravenous general anesthesia, large white female pigs were instrumented, ventilated with intermittent positive pressure ventilation (IPPV, FiO(2) 0.3; TV 10 ml kg(-1); RR 20 bpm; PEEP 3 cm H(2)O) and monitored for 24 h. Following a period of stabilization, groups were exposed to air (control), or to 10, 40, or 80 ppm NO, delivered via the endotracheal tube in each inspiratory breath. At regular intervals throughout the 24-h period, physiological measurements and arterial blood, plasma, and urine samples were collected. Inhalation of NO acted specifically on the pulmonary vasculature, as no alterations in systemic blood pressure were observed. Administration of NO at 80 ppm resulted in a decreased mean pulmonary artery pressure, decreased pulmonary wedge pressure, and increased methemoglobin and plasma/urine nitrate levels. At post mortem, congestion of the alveolar capillary network was noted in this group. In addition increases in plasma/urine nitrate levels were also observed in the 40 ppm group. In contrast, no significant alterations were observed in the 10 ppm group, compared to the control group. Therefore, 10 ppm inhaled NO is a dose that induced no pathological changes in normal healthy lungs and may be of use as a therapeutic adjunct in the management of acute lung injury.

Pathophysiological responses following phosgene exposure in the anaesthetized pig.

This study aimed to develop a reproducible model of phosgene-induced lung injury in the pig to facilitate the future development of therapeutic strategies. Ten female young adult large white pigs were used. Following induction of anaesthesia using a halothane/oxygen/nitrous oxide mixture, arterial and venous catheters were inserted together with a pulmonary artery thermodilution catheter, and a suprapubic urinary catheter by laparotomy. Anaesthesia was maintained throughout the experiment by intravenous infusion of ketamine, midazolam and alfentanil. On completion of surgery the animals were allowed to equilibrate for 1 h and then were divided into two groups. Group 1 (n = 5) was exposed to phosgene for 10 min (mean Ct = 2443 +/- 35 mg min m(-3)) while spontaneously breathing, whereas control animals (Group 2 n = 5) were exposed to air. At 30 min post-exposure, anaesthesia was deepened in order to allow the initiation of intermittent positive pressure ventilation and the animals were monitored for up to 24 h. Cardiovascular and respiratory parameters were monitored every 30 min and blood samples were taken for arterial and mixed venous blood gas analysis and clinical chemistry. A detailed post-mortem and histopathology was carried out on all animals following death or euthanasia at the end of the 24-h monitoring period. Control animals (Group 2) all survived until the end of the 24-h monitoring period with normal pathophysiological parameters. Histopathology showed only minimal passive congestion of the lung. Following exposure to phosgene (Group 1) there was one survivor to 24 h, with the remainder dying between 16.5 and 23 h (mean = 20 h). Histopathology from these animals showed areas of widespread pulmonary oedema, petechial haemorrhage and bronchial epithelial necrosis. There was also a significant increase in lung wet weight/body weight ratio (P < 0.001). During and immediately following exposure, a transient decrease in oxygen saturation and stroke volume index was observed. From 6 h there were significant decreases in arterial pH (P < 0.01), P(a)O(2) (P < 0.01) and lung compliance (P < 0.01), whereas oxygen delivery and consumption was reduced from 15 h onwards in phosgene-exposed animals. Mean pulmonary artery pressure of phosgene-exposed animals was increased from 15 h post-exposure, with periods of increased pulmonary vascular resistance index being recorded from 9 h onwards. We have developed a reproducible model of phosgene-induced lung injury in the anaesthetized pig. We have followed changes in cardiovascular and pulmonary dynamics for up to 24 h after exposure in order to demonstrate evidence of primary acute lung injury from 16 h post-exposure. Histopathology showed evidence of widespread damage to the lung and there was also a significant increase in lung wet weight/body weight ratio (P < 0.001).