Effects of inotropes on human leucocyte numbers, neutrophil function and lymphocyte subtypes

We have investigated the effects of inotropes with different adrenergic receptor specificity on differential white cell count, lymphocyte subtypes and neutrophil function in healthy volunteers. Six healthy, male volunteers were enrolled into this randomized, placebo-controlled pilot study. Each volunteer was studied on four separate occasions during a 2-h infusion of various agents, and for 2 h after stopping the infusion. The agents investigated were adrenaline 0.1 microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120 and 240 min. Haemodynamic monitoring was continued throughout the study. Full blood count, white cell differential count and enumeration of lymphocyte subtypes were performed. Neutrophil function tests included chemoluminescence, and assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon signed rank test was used to compare differences between placebo and active drugs at each time compared with baseline. There was a significant increase in white cell count, lymphocyte count and neutrophil count with adrenaline, and a small but significant decrease in these variables with dobutamine and dopexamine. These changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts. Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine increased significantly only with adrenaline at 30 min (P = 0.046). There were no other significant changes in tests of neutrophil function. Infusion of inotropes was associated with changes in white cell numbers, lymphocyte subtypes and neutrophil respiratory burst. In healthy volunteers, adrenaline had effects different from those of dobutamine and dopexamine. The clinical relevance of such effects requires further investigation in critically ill patients.      

Strengthened estimates of individual pain trends in children following bone marrow transplantation.

Pre-transplant conditioning regimens for bone marrow transplantation often cause oral mucositis and severe pain. We evaluated the agreement of self- and parent reports of daily oral mucositis pain in children between the ages of 6 and 16 years. Child patients were asked to report their pain on visual analog scales (VAS) daily for 20 days following their transplants. Daily VAS ratings were also obtained from one of the parents. The analysis sample consisted of ten children aged 7-9, nine children aged 10-12, eight children aged 13-16, and their parents. We modeled individual child and parent reports as quadratic functions of the number of days post transplant. Empirical Bayes/restricted maximum-likelihood estimates were obtained of individual coefficients, treated as random effects, and age group coefficients, treated as fixed effects. Parents exhibited higher average pain curves than their children in each of the three age groups. The middle age group reported the highest average pain. Average within-person error variances representing unreliability were 692.2, 461.9, and 303.9 for young, middle, and old children, respectively; for parents, the corresponding error variances were 375.1, 413.3, and 252.4. These results challenge the presumption that children tend to over-report pain but are consistent with the contention that younger children may be less reliable reporters than adolescents and adults.     

Azygoesophageal recess: normal CT appearance in children.

The azygoesophageal recess is the interface of the subcarinal portion of the mediastinum and the right lower lobe. The configuration of the recess on CT can be used as a sensitive indicator of abnormality in the mediastinum. In normal adults the recess is concave. A convex contour is a normal variant, particularly in young adults. The normal appearance of the azygoesophageal recess in children has not been studied. Accordingly, we reviewed chest CT examinations performed in 253 children ranging from 1 month to 20 years old. Forty patients were excluded from further analysis either because the recess could not be evaluated properly or because underlying disease caused the mediastinum to have an abnormal configuration. An age-related spectrum of normal configurations was observed in the remaining 213 patients. A convex or straight contour was found in 96% of children less than 3 years old. Scans of children 3-12 years old revealed a spectrum of configurations. The typical adult concave configuration was seen in 78% of adolescents more than 12 years old. Overall, in only 90 (42%) of 213 children in this study was a concave recess observed on CT. Our experience shows a convex azygoesophageal recess on CT should be considered the normal configuration in infants and young children. Recognition of this age-related variation is useful in the CT evaluation of the mediastinum in children.     

Cardiovascular responses to heat stress and their adverse consequences in healthy and vulnerable human populations.

This paper reviews the basic thermoregulatory physiology of healthy people in relation to hazards from external heat stress and internal heat loads generated by physical exercise or radiofrequency (RF) radiation. In addition, members of the population are identified who may be particularly vulnerable to the effects of heat stress. These data are examined in relation to current international guidance on occupational and public exposure to RF radiation. When body temperature rises, heat balance of the body is normally restored by increased blood flow to the skin and by sweating. These responses increase the work of the heart and cause loss of salt and water from the body. They impair working efficiency and can overload the heart and cause haemoconcentration, which can lead to coronary and cerebral thrombosis, particularly in elderly people with atheromatous arteries. These adverse effects of thermoregulatory adjustments occur with even mild heat loads and account for the great majority of heat-related illness and death. They are, therefore, particularly relevant to determination of safe population exposures to additional sources of heat stress. It is concluded that exposure to RF levels currently recommended as safe for the general population, equivalent to heat loads of about one tenth basal metabolic rate, could continue to be regarded as trivial in this context, but that prolonged exposures of the general population to RF levels higher than that could not be regarded as safe in all circumstances.     

Diagnosis in Prader-Willi syndrome.

Thirty one patients with the putative diagnosis of Prader-Willi syndrome were reassessed clinically and by DNA analysis. Eleven patients were judged not to have Prader-Willi syndrome and 20 to have the condition. This was confirmed by DNA analysis in all but one case. The diagnosis of Prader-Willi syndrome, especially in early infancy, should be made with caution unless confirmed by molecular genetic studies.     

Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase)

Essential fructosuria is one of the oldest known inborn errorsof metabolism. It is a benign condition which is believed toresult from deficiency of hepatic fructokinase (ketohexokinase,KHK, E.C.2.7.1.3). This enzyme catalyses the first step of metabolismof dietary fructose, conversion of fructose to fructose-1-phosphate.Despite the early recognition of this disorder, the primarystructure of human KHK and the molecular basis of essentialfructosuria have not been previously defined. In this report,the isolation and sequencing of full-length cDNA clones encodinghuman ketohexokinase are described. Alternative mRNA speciesand alternative KHK isozymes are produced by alternative polyadenylationand splicing of the KHK gene. The KHK proteins show a high levelof sequence conservation relative to rat KHK. Direct evidencethat mutation of the KHK structural gene is the cause of essentialfructosuria was also obtained. In a well-characterized family,in which three of eight siblings have fructosurla, all affectedindividuals are compound heterozygotes for two mutations Gly40Argand Ala43Thr. Both mutations result from G     

Granulocyte elastase cleaves human high molecular weight kininogen and destroys its clot-promoting activity

Purified human granulocyte elastase cleaved purified human high molecular weight (HMW) kininogen into multiple low molecular weight fragments, and destroyed the clot-promoting activity of the HMW kininogen. Elastase digestion did not release kinin or destroy the bradykinin portion of the HMW kininogen molecule; kallikrein could release kinin from the elastase-induced low molecular weight digestion products of HMW kininogen. Purified alpha 1-antitrypsin prevented the destruction of the clot-promoting activity of HMW kininogen by elastase; it also delayed the clotting of normal plasma. Elastase may play a significant role in altered hemostasis as well as fibrinolysis, in areas of inflammation to which polymorphonuclear leukocytes have been attracted.