Management of pain in children with burns.

Burn injuries are common in children under 10 years of age. Thermal injury is the most common mechanism of injury and scalds account for >60% of such injuries. All children with burns will experience pain, regardless of the cause, size, or burn depth. Undertreated pain can result in noncompliance with treatment and, consequently, prolonged healing. It is acknowledged that the monitoring and reporting of pain in children with burns has generally been poor. Due to the adverse physiological and emotional effects secondary to pain, adequate pain control is an integral and requisite component in the management of children with burns. A multidisciplinary approach is frequently necessary to achieve a robust pain relief. Key to successful treatment is the continuous and accurate assessment of pain and the response to therapy. This clinical review article discusses the essential aspects of the pathophysiology of burns in children provides an overview of pain assessment, the salient principles in managing pain, and the essential pharmacodynamics of commonly used drugs in children with burn injuries. Both pharmacological and nonpharmacological treatment options are discussed, although a detailed review of the latter is beyond the scope and remit of this article.

Klippel-Trenaunay syndrome and spinal arteriovenous malformations: an erroneous association.

BACKGROUND AND PURPOSE: KTS is a rare limb overgrowth disorder with slow-flow vascular anomalies. This study examines the presumed association between KTS and spinal AVMs. MATERIALS AND METHODS: We performed a MEDLINE search of articles and reviewed textbooks of spinal diseases to study the association between KTS and spinal AVM. Our goal was to ascertain the basis on which the diagnosis of KTS was established and to evaluate the evidence of its association with spinal AVMs. In addition, the data base of the Vascular Anomalies Center at Children's Hospital Boston was queried for patients with KTS, and the association with spinal AVM was investigated. RESULTS: Twenty-four published reports on spinal AVMs in 31 patients with KTS were reviewed. None of these references provided solid evidence of the diagnosis of KTS in any patient. Clinical data were either incompatible with the diagnosis of KTS or were inadequate to establish the diagnosis. Alternative possible diagnoses (CLOVES syndrome and CM-AVM) were suggested by the first author for 9 of the patients reported in these articles. The medical records of 208 patients with the diagnosis of KTS were analyzed; not a single patient had clinical or radiologic evidence of a spinal AVM. CONCLUSIONS: An association between KTS and spinal AVM, as posited in numerous references, is most likely erroneous. The association has neither been reliably proved in the limited published literature nor encountered in a large cohort.

Advancing newborn health: The Saving Newborn Lives initiative.

Until recently, newborn health was virtually absent from the global health agenda. Now, assistance agencies, national governments and non-governmental organisations are increasingly addressing this previously neglected issue of close to four million newborns dying every year. The experience of the Saving Newborn Lives initiative documents some of the progress that has been made and the challenges and opportunities that lie ahead. Since the start of the initiative in 2000, targeted research, focused on overcoming the key barriers to improved newborn survival, has demonstrated low-cost, community-based interventions and strategies that can significantly reduce newborn mortality. Building on what has been learned from this and other efforts to date, the challenge now is to reach the millions of newborns still at risk.

Comparison of capillary pressure relationships of organic liquid-water systems containing an organic acid or base.

The presence of surface-active solutes such as organic acids and bases may have a profound influence on the transport of organic liquid contaminants through their impact on the constitutive relationship of capillary pressure vs. saturation. This relationship is a function of the interfacial tension and wettability of the system, which, in turn, depend on the pH and the concentration of organic acids and bases that are present. This study examines the impact of pH and the concentration on the interfacial tension, contact angle, and capillary pressure of systems consisting of tetrachloroethylene, water, and quartz containing either octanoic acid or dodecylamine. In general, the ionic form of the solute tended to remain in the aqueous phase and reduced the capillary pressure through its impact on the interfacial tension and contact angle; on the other hand, the neutral form of the solute partitioned into the organic liquid phase and had a lesser impact on the capillary pressure for the same total mass of solute. A comparison of these data with data generated in previous research in similar systems where o-xylene was the organic liquid showed that the trends are analogous. Thus, the behavior of these two solvent systems seems to be driven primarily by the aqueous phase speciation of the solute, and the differences between the capillary pressure relationships for the two systems could be attributed to the pure system interfacial tension.

Crash and injury reduction following installation of roundabouts in the United States.

OBJECTIVES: This study estimated potential reductions in motor vehicle crashes and injuries associated with the use of roundabouts as an alternative to signal and stop sign control at intersections in the United States. METHODS: An empiric Bayes procedure was used to estimate changes in motor vehicle crashes following conversion of 24 intersections from stop sign and traffic signal control to modern roundabouts. RESULTS: There were highly significant reductions of 38% for all crash severities combined and of 76% for all injury crashes. Reductions in the numbers of fatal and incapacitating injury crashes were estimated at about 90%. CONCLUSIONS: Results are consistent with numerous international studies and suggest that roundabout installation should be strongly promoted as an effective safety treatment.

Tumour necrosis factor-alpha (TNF-alpha) enhances lymphocyte migration into rheumatoid synovial tissue transplanted into severe combined immunodeficient (SCID) mice.

Adhesion mechanisms play a major role in the recruitment of peripheral blood lymphocytes (PBL) which characteristically infiltrate rheumatoid arthritis (RA) synovium and other chronically inflamed tissues. Through a sequential series of complex integrated adhesion and signalling events, 'multistep model of migration', specific subsets of PBL are recruited into inflamed tissues. In this process both leucocyte receptors and microvascular endothelial (MVE) counter-receptors play a critical role. The MVE in particular, during an inflammatory state, is the target of various inflammatory mediators that cause the up-regulation of several cell adhesion molecules (CAM). One of the most important factors known to be a powerful inducer of MVE CAM is TNF-alpha. Conversely, blocking TNF-alpha causes a down-modulation of CAM expression. To test directly the capacity of TNF-alpha to induce cell migration into RA synovium we adapted a model in which synovial grafts were implanted into SCID mice subcutaneously. Using this model we demonstrate that: (i) transplants remain viable and become vascularized and fed by mouse subdermal vessels; (ii) the mouse vasculature connects to the transplant vasculature which maintains the ability to express human CAM; (iii) intragraft injections of TNF-alpha up-regulate the expression of human CAM, following the down-regulation which occurred 4 weeks post-transplantation; and (iv) the up-regulation of graft CAM is associated with increased human PBL migration into the transplants. This study provides direct evidence in vivo of the capacity of TNF-alpha to induce cell migration. In addition, it provides the experimental background for the optimal use of this model.

Multiple modes of hepatitis A virus transmission among methamphetamine users.

Methamphetamine users are at increased risk of hepatitis A, but modes of transmission are unclear. The authors conducted a case-control study among methamphetamine users during an outbreak in Iowa in 1997. Twenty-eight reported, laboratory-confirmed, hepatitis A cases did not differ from 18 susceptible controls with respect to age, sex, or number of doses used. When compared with controls in multivariate analysis, case-patients were more likely to have injected methamphetamine (odds ratio (OR) = 5.5, 95% confidence interval (CI): 1.1, 27), to have used methamphetamine with another case-patient (OR = 6.2, 95% CI: 0.95, 41), and to have used brown methamphetamine (OR = 5.5, 95% CI: 0.51, 59). Receptive needle sharing was reported by 10 of the 20 case-patients who injected. Methamphetamine use with another case-patient was also associated with hepatitis A in an analysis restricted to noninjectors (OR = 17, 95% CI: 1.0, 630). During this outbreak, hepatitis A may have been transmitted from person to person among methamphetamine users through the fecal-oral and the percutaneous routes. Methamphetamine users should be vaccinated against hepatitis A and should be given immune globulin if they used methamphetamine with a case-patient in the last 2 weeks. Persons who intend to continue using methamphetamine should be advised about safer practices.

Effects of continuous therapeutic ultrasound on growth and metastasis of subcutaneous murine tumors.

BACKGROUND AND PURPOSE: The use of therapeutic ultrasound (US) in the presence of malignant neoplasms has been contraindicated in physical therapy practice despite a lack of convincing scientific evidence. Some studies have shown that high levels of US, which increase tissue temperatures greater than 42 degrees C, can kill tumors. We sought to determine whether the application of continuous therapeutic US would alter the growth or metastasis of methylcholanthrene-induced solid tumors in mice. SUBJECTS: Seventy-one female C57BL/6 mice, age 6 to 8 weeks, received subcutaneous injections of 5 x 10(5) tumor cells. METHODS: When tumors grew to 0.5 cm in diameter, the mice were randomly assigned to either a control group (n = 34) or an experimental group (n = 37). The experimental group received 10 treatments over a 2-week period of 3-MHz continuous US at 1.0 W/cm2 for 5 minutes, using a 0.5-cm2 sound head directly over the tumor. The control group received the same handling except for the US treatment. Tumor dimensions were measured on days 1 (baseline), 7 (midtreatment), and 14 (preexcision and postexcision). Tumors were weighed after excision, and the mice were evaluated by necropsy and histopathology of regional lymph nodes. RESULTS: All tumors grew larger over time, but final tumor volume and weight were larger in the experimental group (789 mm3 and 0.932 g) than in the control group (395 mm3 and 0.506 g). No significant difference existed in the number of metastatic lymph nodes between groups. CONCLUSION AND DISCUSSION: Continuous therapeutic US increased the volume and weight of subcutaneous murine tumors in mice. We urge caution in the use of continuous therapeutic US in the areas of tumors or suspected tumors.

Evaluation of iontophoretically applied dexamethasone for painful pathologic temporomandibular joints.

The effects of iontophoretically applied dexamethasone in a lidocaine vehicle were compared with those of saline placebo in 53 patients with one of three diagnoses of painful temporomandibular joint pathologic conditions: disk displacement with reduction, disk displacement without reduction, and osteoarthritis. Both dexamethasone and the saline placebo produced a significant reduction in pain scores from baseline levels after the first two of three treatments. There were no observed differences, however, in pain report or mandibular range of motion between the dexamethasone and placebo groups. A trend for pain relief was noted in the subgroup that received dexamethasone with a diagnosis of osteoarthritis. Results may reflect varying degrees of inflammation or central nervous system hyperexcitability, or both, in this heterogeneous study sample. Potential confounding variables were lack of knowledge of actual drug penetration, the effects of electric current transmitted by the iontophoresor, and pain reduction caused by cyclic fluctuations in symptoms. These data suggest that iontophoretically applied dexamethasone is no more effective than saline placebo in providing pain relief in patients with temporomandibular joint pain.

The role of intracavernosal vasoactive agents to overcome impotence due to spinal cord injury.

Twenty-two spinal cord injured men (mean age 35.2 years) referred because of impotence were treated with intracavernosal vasoactive agents. Papaverine 2-20 mg, papaverine 40 mg plus phentolamine 0.5 mg or prostaglandin E1 (1-20 micrograms) were used. Nineteen responded and were taught to self administer the medication with varying degrees of assistance from their partners. Fourteen men participated in a postal survey; 12 (86%) continued to use the drugs every 1 to 4 weeks and reported satisfaction with the method. Partner responses were positive in half of the group and when not so it influenced the patients to abandon or reduce the frequency of treatment. Counselling was essential to allay anxiety. Clinical management was not compromised and side effects were minimal. Overall we found this treatment effective, safe and worthwhile.

Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus.

Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one-third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops.

A survey of the monosodium glutamate content of foods and an estimation of the dietary intake of monosodium glutamate.

The MSG contents of a wide range of manufactured foods (over 200 samples) were measured using the AOAC Procedure (ion-exchange chromatography followed by formol potentiometric titration). The results obtained were used, in conjunction with published data on UK food consumption, to calculate tentative estimates of the dietary intake of MSG for specific groups of the UK population.

Regulation and expression of type V (tartrate-resistant) acid phosphatase in human mononuclear phagocytes.

Human type V (tartrate-resistant) acid phosphatase belongs to a unique group of iron-binding proteins that includes uteroferrin and other purple phosphatases. The enzyme is normally restricted to osteoclasts and certain phagocytic cells but its rôle is unknown. We show that phosphatase mRNA is abundant in cells of monohistiocytic phenotype and that enzyme expression in cultured human monocyte-derived macrophages is depressed by gamma-interferon and bacterial lipopolysaccharide, agents that promote functional differentiation in these cells. In contrast, phorbol ester, which stimulates intracellular calcium-mediated events, greatly enhances type V phosphatase expression and mRNA abundance. Lymphokine and phorbol ester-modulated expression of type V acid phosphatase expression thus represents a model system for investigating proliferative responses that are specific to cells of the mononuclear macrophage system.

Molecular analysis of the human MHC class I region in hereditary haemochromatosis. A study by pulsed-field gel electrophoresis.

The unknown allele that predisposes to the development of haemochromatosis in man has been localized to the HLA class I region on the short arm of chromosome 6. We have utilized pulsed-field gel electrophoresis in conjunction with probes that map within, or in the vicinity of, this region to search for structural lesions that may further define the disease locus. Using the enzyme Mlu I, fragments that associated specifically with the HLA-A23, A31 and B8 alleles were identified. However, in members of three pedigrees affected by haemochromatosis, and in six unrelated patients with the disorder, no disease-specific differences were detected in the DNA fragments with four restriction enzymes and eight probes when compared with healthy individuals. These data suggest that the lesion responsible for hereditary haemochromatosis lies beyond the resolution of this technique and does not involve large structural deletions or extensive re-arrangements in this highly polymorphic region of the genome.

Effects of a sclerosant, ethanolamine, on the venous drainage system of the dog penis.

To explore the possibility of using venous sclerosant therapy to overcome venogenic impotence we studied the effects of ethanolamine on the veins draining the dog penis. Following injection of the sclerosant into the deep dorsal vein radiological and histological evidence of occlusion was obtained but by one month recanalization of thrombi had occurred and collateral venous channels had formed. These findings cast doubt on the effectiveness of this sclerosant as a means of treating impotence.

Effects of acute alcohol on penile tumescence in normal young men and dogs.

To determine the cause of the inhibition of sexual function observed in normal subjects with elevated blood alcohol concentrations (BAC), nocturnal penile tumescence (NPT) was monitored in 11 subjects over three consecutive nights. On the third night alcohol was administered (BAC = 0.154 g/100 mL). We observed no effect of alcohol on the size, duration, or number of erections. These results were confirmed in dogs. The latent period, magnitude, and duration of corpus cavernosal pressure changes produced by pelvic nerve stimulation were not affected by mean blood alcohol levels of 0.327 g/100 mL in three dogs. These results suggest that the inhibition of sexual response caused in conscious subjects by the ingestion of alcohol is not due to a suppression of the underlying spinal reflex but may be the result of its effect on perceptual or cognitive sexual mechanisms.

Type 5 acid phosphatase. Sequence, expression and chromosomal localization of a differentiation-associated protein of the human macrophage.

The purple acid phosphatases and uteroferrin belong to a diverse multifunctional class of binuclear iron-containing proteins that includes haemerythrin and ribonucleotide reductase. In the pig, uteroferrin has been implicated in the delivery of iron to the foetus, but the role of the related human type 5 acid phosphatase that is principally found in resident tissue macrophages is not yet clear. To define further the function of this metalloenzyme, we have isolated and sequenced a cDNA clone for type 5 acid phosphatase and investigated expression of its gene in human tissues. The phosphatase clone contains an open reading frame of 975 bp and encodes a protein of 325 amino acids, including a signal peptide of 19 residues and two potential sites for N-glycosylation. The type 5 acid phosphatase gene mapped to the short arm of human chromosome 19 and was found to have a restriction fragment length polymorphism on digestion with XbaI. Expression of phosphatase mRNA was restricted to mononuclear phagocytes and the enzyme was induced greater than 20-fold on transformation of normal human monocytes to macrophages by culture in serum-supplemented medium. Type 5 acid phosphatase thus represents a tightly regulated system for the study of molecular events in the differentiation programme of the normal macrophage.

The inheritance of MS susceptibility.

The object of this study was to determine, if possible, the mode of inheritance of the susceptibility to multiple sclerosis (MS). It was known that no single-gene model could fit the observations, so oligogenic models (models involving a small number of genes) were sought. Oligogenic hypotheses were tested against the available population data for MS until a reasonable level of agreement was found. The best-fitting simple hypothesis was this: MS occurs only in people who are homozygous for a recessive gene and carry a dominant X gene, and then only with reduced penetrance. The dangerous allele m- at the autosomal locus appears to be fairly uniformly distributed across England, Ireland and Canada, occurring in 10-30% of the gene pool. There are large variations in the frequency of the allele s- at the X-locus, ranging from 10% up to 72% of the gene pool. The penetrance varies significantly with geographical location, but nowhere approaches unity, so that the environmental factors are of great importance. The hypothesis explains the broad features of the population pattern of the occurrence of MS and it gives an outstanding fit to the best available data on MS in relatives. The result may assist attempts to map the genetic data on MS, opens the way for a reassessment of the attempts to identify the environmental factors, and it makes possible the completion of nonempirical risk tables for various countries. Similar techniques may be applied to other disorders with a genetic component in their aetiology.