Trace Element Homeostasis During Continuous Sedation With Propofol Containing EDTA Versus Other Sedatives in Critically Ill Patients

Objective: To evaluate changes in serum and urinary zinc, cobalt, copper, iron, and calcium concentrations in critically ill patients receiving propofol containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA]) versus sedative agents without EDTA. Design: This was a randomised, open-label, parallel-group study with randomisation stratified by baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Setting: Intensive care units (ICU) in 23 medical centres. Patients: Medical, surgical, or trauma ICU patients 17 years of age or older who required mechanical ventilator support and sedation. Interventions: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace metal excretion. Twenty-four–hour urine samples were collected on days 2, 3, and 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The first 143 patients were assessed for serum concentration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collection. Measurements and Results: For the assessment of trace metals, patients receiving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sedatives demonstrated increased urinary excretion of zinc and copper above normal reference values. Compared with the non-EDTA sedative group, the propofol EDTA group demonstrated increased urinary excretion of zinc and iron. Mean serum concentrations of zinc and total calcium were decreased in both patient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal function, measured by blood urea nitrogen, serum creatinine, and creatinine clearance, did not deteriorate during ICU sedation with either regimen. Conclusion: This study showed that critical illness is associated with increased urinary losses of zinc, copper, and iron. Propofol EDTA– treated patients had greater urinary losses of zinc and iron and lower serum zinc concentrations compared with the non-EDTA sedative group. No adverse events indicative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.     

Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental ceils show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PRA) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B.     

Estrogen receptor-mediated down-regulation of corticotropin-releasing hormone gene expression is dependent on a cyclic adenosine 3＇ ,5＇-monophosphate regulatory element in human placental syncytiotrophoblast cells

Placental CRH plays a major role in the mechanisms controlling human pregnancy and parturition. Understanding how placental CRH production is regulated is therefore of importance. Previously we have shown that placental expression of CRH peptide and mRNA are inhibited by estrogens, in contrast to the stimulatory effects of estrogen on hypothalamic CRH production. Our current study found that in placental cells cotransfected with a CRH promoter construct and an estrogen receptor-alpha expression vector results in a differential regulation whereby 17beta estradiol (E2) decreased and the putative pure estrogen antagonist, ICI 182780,     

Steroids for intubated croup masking airway haemangioma

Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion.     

Population genetics of phenylketonuria

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a large number of mutations at the phenylalanine hydroxylase (PAH) locus, most of which are strongly associated with specific RFLP or VNTR haplotypes. One of the major questions remaining in PKU research is why this apparently maladaptive disorder has been maintained at a frequency of approximately 1 in 10000 among Caucasians. A growing number of studies have provided evidence that both the relatively high frequency of PKU and the strong mutation/haplotype associations might reflect the existence of multiple founding populations for PKU. Examples of putative founding populations for PKU in both Europe and Asia will be presented. Some PAH mutations are associated with multiple haplotypes, suggesting recurrence. Evidence for and against recurrence as the mechanism responsible for the association of the R408W mutation with RFLP haplotypes 1 and 2 will be discussed.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

Prevalence of behaviour disorders in low birthweight infants

OBJECTIVE--To determine the prevalence of behaviour disorders in low birthweight infants. DESIGN--Children of birth weight < or = 2000 g born to mothers resident in Merseyside in 1980-1 assessed using the Rutter parent and teacher behaviour questionnaires and the Conner modification of the Rutter teacher questionnaire. Children attending normal schools were assessed with controls matched for age, sex, and class in school. Children attending special schools were assessed unmatched. SUBJECTS--233 matched case-control pairs attending normal primary schools and 46 unmatched children attending special schools. SETTING--Primary and special schools. MAIN OUTCOME MEASURES--Emotional, conduct, and undifferentiated behaviour disorders and hyperactivity. RESULTS--On the parental questionnaire screen, 36% of the cases and 22% of the controls had a behaviour disorder and on the teacher questionnaire the proportions were 27% and 12% respectively. Hyperactivity was significantly more common among male cases than their controls (21% v 5.0%) but differed little among female cases and controls (9% v 7%). CONCLUSIONS--Improving neonatal survival of low birthweight infants is accompanied by a higher prevalence of behaviour disorders. The long term implications for psychiatric morbidity and other adult disease must be monitored.     

Rotator cuff tear: clinical experience with sonographic detection

Between June 1986 and April 1988, 86 sonographic examinations of the shoulder were performed on patients suspected of having rotator cuff tears. Major sonographic diagnostic criteria included (a) a well-defined discontinuity usually visible as a hypoechoic focus within the cuff, (b) nonvisualization of the cuff and (c) an echogenic focus within the cuff. Seventy-five patients underwent both sonography and arthrography. Compared with arthrography alone, ultrasound examinations enabled detection of 92% of rotator cuff tears (24 of 26 tears), with a specificity of 84% and a negative predictive value of 95%. Correlation was obtained in 30 of these patients who underwent surgery for rotator cuff tear or other soft-tissue abnormality. In this group, the sensitivity of sonography for detection of a tear was 93%, with a specificity of 73%, while for arthrography sensitivity was 87% and specificity was 100%. These data indicate that sonography is a useful, noninvasive screening procedure for patients suspected of having rotator cuff injury.     

Quality assessment and assurance in diagnostic imaging. Theoretical and practical considerations and a quality audit of the excretory urogram

Concepts necessary to an understanding of the basics of quality assurance audits are presented. Included are specific examples that bridged theory and practice by applying the protocol to a real-life diagnostic imaging situation. This method meets the present requirements of the Joint Commission of the Accrediation of Hospitals.