[Whole-body-CT in Severely Injured Children. Results of Retrospective, Multicenter Study with Patients from the TraumaRegsiter DGU®]. / Ganzkörper-CT bei schwerverletzten Kindern. Ergebnisse einer retrospektiven Multizenterstudie anhand des TraumaRegister DGU®.

BACKGROUND: A fast and comprehensive diagnostic by means of whole-body CT has been shown to reduce mortality in the adult trauma population. Therefore whole-body CT seems to be the standard in adult trauma-patients. Due to the higher radiation exposure of whole-body CT the use of this diagnostic toll in pediatric trauma patients is still under debate. It is not yet clear if whole-body CT in children can increase the probability of survival. METHOD: In a retrospective, multicenter study, we used the data recorded in the TraumaRegister DGU(®) to calculate the probability of survival according to the revised injury severity classification (RISC) and standardized mortality ratio (SMR). The SMR reflects the ratio of recorded to expected mortality. Included in the study were all children (1-15 years) and adults (16-50 years) with an Injury Severity Score (ISS)>9, who were directly admitted to the hospital from the scene of accident. We compared the groups of patients given whole-body CT or non-whole-body CT. Subgroup analysis was performed for children 1-9 years, children 10-15 years and adults. RESULTS: A total of 1,456 pediatric trauma patients (mean age 9.9 years) and 20,796 adults (mean age 32.7 years) were included in the study. In contrast to adult trauma patients, were the SMR in the whole-body CT group was significant lower; we observed no advantage for the whole-body CT in pediatric trauma patients. CONCLUSION: Due to the missing advantage of whole-body CT in the pediatric trauma population and the higher radiation exposure of whole-body CT a non-whole-body CT approach seems equivalent with a lower radiation exposure.

Failure to phytosanitize ash firewood infested with emerald ash borer in a small dry kiln using ISPM-15 standards.

Although current USDA-APHIS standards suggest that a core temperature of 71.1 degrees C (160 degrees F) for 75 min is needed to adequately sanitize emerald ash borer, Agrilus planipennis Fairmaire-infested firewood, it is unclear whether more moderate (and economical) treatment regimes will adequately eradicate emerald ash borer larvae and prepupae from ash firewood. We constructed a small dry kiln in an effort to emulate the type of technology a small- to medium-sized firewood producer might use to examine whether treatments with lower temperature and time regimes successfully eliminate emerald ash borer from both spilt and roundwood firewood. Using white ash (Fraxinus americana L.) firewood collected from a stand with a heavy infestation of emerald ash borer in Delaware, OH, we treated the firewood using the following temperature and time regime: 46 degrees C (114.8 degrees F) for 30 min, 46 degrees C (114.8 degrees F) for 60 min, 56 degrees C (132.8 degrees F) for 30 min, and 56 degrees C (132.8 degrees F) for 60 min. Temperatures were recorded for the outer 2.54-cm (1-in.) of firewood. After treatment, all firewood was placed under mesh netting and emerald ash borer were allowed to develop and emerge under natural conditions. No treatments seemed to be successful at eliminating emerald ash borer larvae and perpupae as all treatments (including two nontreated controls) experienced some emerald ash borer emergence. However, the 56 degrees C (132.8 degrees F) treatments did result in considerably less emerald ash borer emergence than the 46 degrees C (114.8 degrees F) treatments. Further investigation is needed to determine whether longer exposure to the higher temperature (56 degrees C) will successfully sanitize emerald ash borer-infested firewood.

Prediagnostic human T lymphotropic virus type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia.

In a recent clinical analysis of 308 Jamaican children, human T lymphotropic virus type I (HTLV-I) infection was found to be associated with significantly higher incidence rates of seborrheic dermatitis, eczema, and persistent hyperreflexia of the lower limbs and with nonsignificantly increased rates of severe anemia and abnormal lymphocytes. Results of examination of HTLV-I viral markers in the 28 HTLV-I-infected children provided virologic support for the epidemiologic associations of HTLV-I with seborrheic dermatitis and severe anemia in childhood.

Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells.

Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VkappaI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vkappa locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the D(H), Vkappa, and Vlambda loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.

Effect of PEEP and suction via chest drain on functional residual capacity and lung compliance after surgical repair of congenital diaphragmatic hernia: preliminary observations in 5 patients.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia that limits survival. The authors' knowledge on lung mechanics and lung volumes in these patients with hypoplastic lungs is still limited. Therefore, the authors performed measurements of functional residual capacity (FRC), compliance of the respiratory system (CRS), and tidal volume in 5 full-term infants (gestational age, 38 to 40 weeks; birth weight, 2,800 to 3,530 g) before and after surgical repair of neonatal CDH. METHODS: The authors studied the influence of different levels of positive end-expiratory pressure (PEEP) and suction via inserted ipsilateral chest tube connected to a water seal on lung volume and lung mechanics. A computerized tracer gas (SF6) washout method was used for serial measurements of FRC. Compliance of the respiratory system was determined according to insufflatory method. RESULTS: The authors found a preoperative compliance between 1.5 and 3.9 mL/kPa/kg and a preoperative FRC between 9.1 and 12.9 mL/kg indicating severe hypoplasia of the lungs in all patients. Immediately after surgical repair of CDH, compliance decreased to 85% (78% to 91%) of preoperative value, and FRC increased to 132% (110% to 150%) of preoperative value under mechanical ventilation while at 4 cm of water of PEEP and at -10 cm of water of suction via chest drain with the need of high fraction of inspired oxygen. After reduction of PEEP from 4 to 2 or 1 cm of water and lowering suction from -10 cm of water to -2 or 0 cm of water FRC decreased to 103% (80% to 122%) of preoperative value and compliance, and tidal volume improved to 135% (110% to 147%) of preoperative value resulting in increased alveolar ventilation, correction of acidosis and improvement in oxygenation. During the first days after surgery inadequate high PEEP or strong suction via chest tube drainage resulted in increase in FRC paralleled by decrease in compliance indicating overdistension of these hypoplastic lungs. CONCLUSIONS: The data show that overdistension of hypoplastic lungs in infants with CDH can be detected and excluded by repeated measurements of FRC and compliance in these critical ill infants. These data might help setting appropriate ventilator parameters, adequate suction via chest drain, and thereby improve gas exchange and outcome.

Family poisoned by mercury vapor inhalation.

Acute mercury vapor poisoning is an uncommon but potentially fatal toxicologic emergency. A case series is presented of a family who became exposed to mercury vapor as a result of home gold ore processing. The severity of the poisoning necessitated mechanical ventilation in three of the eight patients who were exposed. Despite aggressive management, two patients died, because their clinical course was dominated by irreversible pulmonary toxicity. The remaining survivors developed varying degrees of mercury toxicity. The pathophysiology, clinical presentation and current treatment guidelines for acute mercury vapor poisoning are emphasized.

E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells.

Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during lymphocyte maturation through site-specific V(D)J recombination events. Here we show that E2A proteins act in concert with RAG1 and RAG2 to activate Ig VK1J but not Iglambda VlambdaIII-Jlambda1 rearrangement in an embryonic kidney cell line. In contrast, EBF, but not E2A, promotes VlambdaIII-Jlambda1 recombination. Either E2A or EBF activate IgH DH4J recombination but not V(D)J rearrangement. The Ig coding joints are diverse, contain nucleotide deletions, and lack N nucleotide additions. IgK VJ recombination requires the presence of the E2A transactivation domains. These observations indicate that in nonlymphoid cells a diverse Ig repertoire can be generated by the mere expression of the V(D)J recombinase and a transcriptional regulator.

Identifying human herpesvirus 8 infection: performance characteristics of serologic assays.

Epidemiologic studies of infection with the oncogenic human herpesvirus 8 (HHV-8) depend on serologic methods to diagnose infection. However, optimal strategies for identifying HHV-8 infection remain undefined. We therefore evaluated four enzyme-linked immunoassays (EIAs) and one immunofluorescence assay (IFA) using sera from 87 individuals with the prototype HHV-8 disease, Kaposi's sarcoma (KS), and 210 participants in a hemophilia study (who were presumed not to be infected with HHV-8). Assays performed reasonably well in distinguishing between infected and uninfected persons, with receiver operator curve areas between 0.86 and 0.96. Nonetheless, IFA had only 86% sensitivity and 88% specificity, and no EIA simultaneously had sensitivity and specificity above 90% for any of the optical density (OD) cutpoints used to define seropositivity. Some assays were markedly less sensitive with diluted KS sera, suggesting that they poorly identify low-titer antibodies present in asymptomatic infection. We also developed a classification tree that categorized individuals as seropositive if they had OD > 2.00 on recombinant K8.1 protein EIA or if they had both K8.1 OD between 0.51 and 2.00 and positive IFA results; this strategy had between 80% and 90% sensitivity and 95% and 100% specificity. Overall, assays performed adequately for use in most epidemiologic investigations, but wider applications will require improved tests.

Unusual amino acid usage in the variable regions of mercury-binding antibodies.

Monoclonal antibodies (mAb) specific for mercuric ions were isolated from BALB/c mice injected with a mercury-containing, hapten-carrier complex. The antibodies reacted by enzyme-linked immunosorbent assay with bovine serum albumin-glutathione-mercuric chloride (BSA-GSH-HgCl) but not with BSA-GSH without mercury. Nucleotide sequences from polymerase chain reaction products encoding six of the antibody heavy-chain variable regions and seven light-chain variable regions revealed that all the antibodies contained an unpaired cysteine residue in one hypervariable region, which is unusual for murine antibodies. Mutagenesis of the cysteine to either tyrosine or serine in one of the Hg-binding antibodies, mAb 4A10, eliminated mercury binding. However, of two influenza-specific antibodies that contain cysteine residues at the same position as mAb 4A10, one reacted with mercury, although not so strongly as 4A10, whereas the other did not react at all. These results suggested that, in addition to an unpaired cysteine, there are other structural features, not yet identified, that are important for creating an appropriate environment for mercury binding. The antibodies described here could be useful for investigating mechanisms of metal-protein interactions and for characterizing antibody responses to structurally simple haptens.

The impact of cultural and familial context on behavioral and emotional problems of preschool Latino children.

This study examined the impact of financial, cultural, and family variables on the incidence of behavioral and emotional problems in a group of two- and three-year-old Latino children. The vulnerability of these children to mental health problems stems from the many challenges faced by their families, especially those associated with acculturation and poverty. Results indicate that most problems experienced by the children were related to depression and social withdrawal. Children were at greatest risk whose parents had immigrated from Central America, whose families relied more extensively on internal coping strategies such as passive resignation, and whose parents were dissatisfied with their family's interactions.

Clinically relevant cholesterol elevation in anxiety disorders: a comparison with normal controls.

Recently, several studies reported elevated cholesterol levels in panic disorder, agoraphobia, and general anxiety disorder, but the clinical relevance is still unsettled. All studies so far have disregarded the possible influence of dietary and physical exercise factors. In this study, 30 patients with different anxiety disorders and 30 normal controls were compared for total cholesterol, low-density lipoprotein (LDL), and cholesterol high-density lipoprotein (HDL) ratio. Dietary and physical exercise habits were measured by self-rating questionnaires. Patients with anxiety disorders had significantly elevated total cholesterol, LDL, and cholesterol/HDL ratios. Patients showed borderline-high or high cholesterol levels almost 3 times as often as control participants. Anxiety-specific avoidance of physical exercise and special dietary habits of anxiety patients had a significant but minor impact on differences in cholesterol between both groups. Our data support the assumption that serum cholesterol elevations in anxiety disorder patients are within a clinically relevant range.

Neuroticism, other personality variables, and serum lipid levels in patients with anxiety disorders and normal controls.

OBJECTIVE: This study evaluates the association between certain personality variables, especially neuroticism, and serum lipid levels in patients suffering from anxiety disorders as opposed to normal control individuals. It addresses the question whether in anxiety disorder patients neuroticism is associated with elevated serum cholesterol and serum LDL cholesterol levels. METHOD: Thirty (15 male, 15 female) patients with anxiety disorders as defined by DSM-IV and thirty normal matched controls were enrolled in this study. The patients were either admitted for inpatient treatment or referred to the behavioral therapy outpatient clinic at the Department of Psychiatry of the University Hospital Eppendorf (Hamburg/Germany). Control individuals were selected on a voluntary basis and recruited from the authors' colleagues and peers. Matching included Body-Mass-Index, age, and gender. RESULTS: This study showed a significant positive association of neuroticism and serum cholesterol (r = .29) and serum LDL cholesterol (r = .35) within the entire cohort of participants. An even higher significant positive relation (r = .43) could be detected between neuroticism and serum LDL cholesterol within the psychiatric patient group. As far as differences of personality variables between patients and normal controls are concerned, patients seemed to be significantly less satisfied with life, more generally inhibited, more irritable, more stressed, and more emotionally labile than controls. Anxiety disorder patients also tended to complain significantly more often about physical problems. CONCLUSIONS: Our data suggest that high scores of neuroticism in anxiety disorders patients may be involved in elevated serum LDL cholesterol levels and, thereby, may lead to an increased risk of coronary heart disease.

Metal binding properties of a monoclonal antibody directed toward metal-chelate complexes.

A monoclonal antibody that recognizes cadmium-EDTA complexes has been produced by the injection of BALB/c mice with a metal-chelate complex covalently coupled to a carrier protein. The ability of purified antibody to recognize 16 different metal-EDTA complexes was assessed by measuring equilibrium binding constants using a KinExATM immunoassay instrument. The antibody bound to cadmium- and mercury-EDTA complexes with equilibrium dissociation constants of 21 and 26 nM, respectively. All other metal-EDTA complexes tested, including those of Mn(II), In(III), Ni(II), Zn(II), Co(II), Cu(II), Ag(I), Fe(III), Pb(II), Au(III), Tb(III), Ga(III), Mg(II), and Al(III) bound with affinities from 20- to 40,000-fold less than that determined for the cadmium-EDTA complex. With the exception of mercury and magnesium, the binding of divalent metal-chelate complexes was well-correlated with the size of the metal ion. The amino acid sequences of the heavy and light chain variable regions were deduced from polymerase chain reaction-amplified regions of the corresponding genes and subsequently used to construct molecular models of the antigen binding region. The key residue for cadmium binding in the model for 2A81G5 appeared to be histidine 96 in the heavy chain.

Clinical correlates of an elevated diffusing capacity for carbon monoxide corrected for alveolar volume.

The diffusing capacity for carbon monoxide is partially dependent on lung volume at which it is measured. As a consequence, the diffusing capacity for carbon monoxide is often indexed to the simultaneously measured lung volume (VA), giving rise to the term DL/VA. This reflects the diffusing capacity of carbon monoxide per unit area of lung parenchyma. The authors investigated the pulmonary function of 18 patients who had an elevated DL/VA in order to identify factors that could account for this abnormality. Sixteen of the 18 had a reduction in vital capacity. The vital capacity was reduced because of obesity, pleural disease, and diaphragmatic dysfunction. Eight of nine patients with a body mass index > 30 kg/m2 had a reduction in vital capacity. On the basis of these findings, we believe that an elevated DL/VA should alert the physician to the possibility of 1) an increase in pulmonary capillary blood volume (Vc) (obesity, polycythemia, negative pleural pressure), and 2) reduced VA that does not directly affect the pulmonary capillary bed (pleural disease, neuromuscular disease).

Increased norepinephrine variability in patients with sleep apnea syndrome.

OBJECTIVE: To assess the plasma arterial catecholamine response to nocturnal desaturation in a group of patients with a history suggestive of sleep apnea. PATIENTS AND METHODS: At a Veterans Affairs hospital, 10 patients who had a history consistent with sleep apnea syndrome were involved in the study. Arterial plasma catecholamines were measured at varying intervals during a 5 1/2-hour sleep study. Eighteen samples per patient were analyzed. RESULTS: As the hemoglobin saturation decreased, the variability in plasma norepinephrine increased significantly (r = -.78, P = 0.004). As the hemoglobin saturation fell, there was a trend towards higher concentrations of plasma norepinephrine (r = -.53, P = 0.06). As the hemoglobin saturation decreased, the variability in plasma epinephrine concentration was not significant (r = .42). CONCLUSION: The association between the degree of desaturation and the variability in norepinephrine suggests that norepinephrine is released in response to nocturnal desaturation.

Db-binding peptides from influenza virus: effect of non-anchor residues on stability and immunodominance.

Relative affinities were determined for the interaction of H-2Db with all the peptides from the A/PR/8/34 strain of influenza virus that contained the Db-binding motif. The results indicated that, even though 23 peptides with the appropriate motif were identified and analysed, binding of only five of them could be detected at peptide concentrations lower than 10(-7) M. Of these five, only one, TGICNQNII, bound with better affinity than the nucleoprotein-derived natural epitope, ASNENMETM. The origin of the higher binding peptide was the influenza neuraminidase, a protein for which little cytosolic processing would be expected since it is a surface glycoprotein. To establish why many of the influenza-derived peptides did not bind, the role of non-anchor residues on Db-peptide interactions was analysed, using a scheme where QDIENEEKI, a non-binding peptide from the influenza virus polymerase 1, was sequentially converted to ASNENMETI, which binds to Db with an affinity similar to that of ASNENMETM. Although all positions examined influenced peptide binding, peptide residue no. 2 (P2) was of particular importance. Therefore, each of the 20 naturally occurring amino acids were inserted at this position to investigate their effects on peptide-MHC interaction. The results indicated that amino acids having side chains with charged or ring structures were deleterious, while non-polar and polar residues were either neutral or facilitated binding to different degrees. Our data also indicated that every residue of the peptide contributes to the stability of the MHC-peptide complex, and the final affinity is dependent on the nature of the amino acids at each position, not just on those at a small number of anchor positions. The results also suggested that increased stability, as indicated by the half-life of the peptide-MHC class I complex, might play an important role in selecting the immunodominant epitope.

Molecular modeling of phytochrome using constitutive C-phycocyanin from Fremyella diplosiphon as a putative structural template.

Phytochrome, the ubiquitous photosensor in green plants, is similar to C-phycocyanin in a number of ways. We have produced a model of the phytochrome chromophore binding pocket based on the X-ray crystal structure of C-phycocyanin from Fremyella diplosiphon [Duerring et al. (1991) J. Mol. Biol. 217, 577-592]. Twenty residues around the chromophore binding site of C-phycocyanin were changed to the corresponding residues of Avena phytochrome A for the modeling. In the minimized model, Arg-318, Ala-319, the methylene of Ser-322, Leu-325, Gln-326, and Tyr-327 (using the numbering of the Avena sequence; Cys-323 is chromophore bound) form a pocket on one side of the chromophore. The other side of the chromophore lacks hydrogen-bond donors and is involved only in van der Waals contact with the chromophore. The overall structure of the model may be described as one peptide segment "anchoring" the chromophore hydrophobically, covalently, and electrostatically from several directions, while the other key peptide segment simply provides a hydrophobic surface for the chromophore to rest against. The red light absorbing (Pr) chromophore of the model is buried more deeply in the binding pocket than the far red light absorbing (Pfr) chromophore. This apparently reflects reduced compatibility of the chromophore with the pocket upon photoisomerization, which requires the insertion of hydrophilic parts of ring D into the hydrophobic core of the protein. This concept is consistent with the experimental evidence that photoisomerization of the Pr chromophore is followed by movement of the chromophore from its binding pocket. In the proposed model, increased exposure of hydrophobic portions of the Pfr chromophore compared to the Pr chromophore is consistent with the red shift observed in the first intermediate of the Pr to Pfr photoconversion. The proposed model may be tested by mutation experiments, thus providing a viable model to foster the current rapid progress of molecular biology in this field.

Survival following mechanical ventilation for acute respiratory failure in adult men.

STUDY DESIGN: Survival following mechanical ventilation for acute respiratory failure has important implications for medical decision-making and allocation of expensive resources for critical care. PROCEDURE: We reviewed a 5-year experience with mechanical ventilation in 383 men with acute respiratory failure and studied the impact of patient age, cause of acute respiratory failure, and duration of mechanical ventilation on survival. Survival rates were 66.6 percent to weaning, 61.1 percent to ICU discharge, 49.6 percent to hospital discharge, and 30.1 percent to 1 year after hospital discharge. When our data were combined with 10 previously reported series, mean survival rates were calculated to be 62 percent to ventilator weaning, 46 percent to ICU discharge, 43 percent to hospital discharge, and 30 percent to 1 year after discharge. Of 255 patients weaned from mechanical ventilation, 44 (17.3 percent) required an additional period of mechanical ventilation during the same hospitalization. RESULTS: Age had a significant influence on survival to hospital discharge and on that to 1 year after hospital discharge, and the cause of acute respiratory failure had a significant influence on survival only to weaning. Survival was best in younger patients and those with COPD or postoperative respiratory failure and worst in patients resuscitated after cardiac or respiratory arrest. Increased duration of mechanical ventilation significantly reduced survival only to hospital discharge. Overall survival was significantly affected by age and cause of acute respiratory failure, but not by duration of mechanical ventilation. CONCLUSION: We conclude that age, cause of acute respiratory failure, and duration of mechanical ventilation have specific influences on the generally poor outcome of mechanical ventilation for acute respiratory failure.

[Creativeness and creative personalities--a study of successful entrepreneurs]. / Kreativität und kreative Persönlichkeiten--eine Untersuchung über erfolgreiche Unternehmensgründer.

The term creativity is defined, and the underlying creative process is described. The creative process is developed with the help of the new metaphors. The two most successful and creative from over 130 entrepreneurs involved in a research project are taken as examples. The essentials of the creative process the inexhaustible process of the phantasy concerning certain ideas and problems is enlarged in connection with the results of the Giessen Test S and the two above-mentioned entrepreneurs.