Population-based analysis of the impact of trauma on longer-term functional outcomes.

BACKGROUND: Functional outcome measures are important as most patients survive trauma. The aim of this study was to describe the long-term impact of trauma within a healthcare region from a social perspective. METHODS: People active in work or education and admitted to hospitals in Central Norway in the interval 1 June 2007 to 31 May 2010 after sustaining trauma were included in the study. Clinical data were linked to Norwegian national registers of cause of death, sickness and disability benefits, employment and education. Primary outcome measures were receipt of medical benefits and time to return to preinjury work level. Secondary outcome measures were mortality within 30 days or during follow-up. RESULTS: Some 1191 patients were included in the study, of whom 193 (16·2 per cent) were severely injured (Injury Severity Score greater than 15). Five years after injury, the prevalence of medical benefits was 15·6 per cent among workers with minor injuries, 22·3 per cent in those with moderate injuries and 40·5 per cent among workers with severe injuries. The median time after injury until return to work was 1, 4 and 11 months for patients with minor, moderate and severe injuries respectively. Twelve patients died within 30 days and an additional 17 (1·4 per cent) during follow-up. CONCLUSION: Patients experiencing minor or major trauma received high levels of medical benefits; however, most recovered within the first year and resumed preinjury work activity. Patients with severe trauma were more likely to receive medical benefits and have a delayed return to work. Registration number: NCT02602405 (http://www.clinicaltrials.gov).

[New aspects of immunotherapy in multiple sclerosis]. / Neues aus der Immuntherapie bei Multipler Sklerose.

The spectrum of therapeutic options for immunotherapy of multiple sclerosis is continuously broadening. After the approval of cladribine and ocrelizumab in Europe, two new drugs are now available with ocrelizumab being the first approved option for treatment of primary progressive multiple sclerosis; however, the increased use of highly effective therapies is accompanied by a rise in severe side effects. During recent months, special attention was paid to the new progressive multifocal leukoencephalopathy (PML) risk assessment in natalizumab-treated patients, cardiac side effects of fingolimod, cases of idiopathic thrombocytopenic purpura and listeria meningitis associated with alemtuzumab and cases of daclizumab-treated patients with liver failure or encephalitis. These case reports highlight the importance of careful monitoring of all patients treated with immunomodulatory therapies.

Trauma care in a combined rural and urban region: an observational study.

BACKGROUND: The available information on trauma care in mixed rural-urban areas with scattered populations is limited. The aim of this study is to describe epidemiology, resource use, transfers and outcomes for trauma care within such an area, prior to implementation of a formal trauma system. METHODS: A multicentre observational study including potential severely injured patients from June 2007 to May 2010. All patients received by trauma teams at seven acute care hospitals (ACH) and one major trauma centre (MTC) were included. Major trauma was defined as Injury Severity Score (ISS) > 15. RESULTS: A total of 2323 patients were included. ACH received 1330 patients and delivered definite care to 85% of these. Only 329 (14%) patients were major trauma of which 134 (41%) were initially received at an ACH. Nine per cent of patients were transferred between hospitals. After inter-hospital transfers, 79% of all major trauma patients received definite care at the MTC. Helicopter emergency services admitted 52% of major trauma and performed 68% of inter-hospital transfers from ACH to MTC. Forty-eight patients (2%) died within 30 days. CONCLUSION: In a region with a dispersed network of hospitals, geographical challenges, and low rate of major trauma cases, efforts should be made to identify patients with major trauma for treatment at a MTC as early as possible. This can be done by implementing triage and transfer guidelines, maintaining competence at ACHs for initial stabilization, and sustaining an organization for effective inter-facility transfers.

A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism.

The adoptive transfer of naive CD4(+) T cell receptor (TCR) transgenic T cells was used to investigate the mechanisms by which the adjuvant lipopolysaccharide (LPS) enhance T cell clonal expansion in vivo. Subcutaneous administration of soluble antigen (Ag) resulted in rapid and transient accumulation of the Ag-specific T cells in the draining lymph nodes (LNs), which was preceded by the production of interleukin (IL)-2. CD28-deficient, Ag-specific T cells produced only small amounts of IL-2 in response to soluble Ag and did not accumulate in the LN to the same extent as wild-type T cells. Injection of Ag and LPS, a natural immunological adjuvant, enhanced IL-2 production and LN accumulation of wild-type, Ag-specific T cells but had no significant effect on CD28-deficient, Ag-specific T cells. Therefore, CD28 is critical for Ag-driven IL-2 production and T cell proliferation in vivo, and is essential for the LPS-mediated enhancement of these events. However, enhancement of IL-2 production could not explain the LPS-dependent increase of T cell accumulation because IL-2-deficient, Ag-specific T cells accumulated to a greater extent in the LN than wild-type T cells in response to Ag plus LPS. These results indicate that adjuvants improve T cell proliferation in vivo via a CD28-dependent signal that can operate in the absence of IL-2.

[Clinical trials in children--between the expectations of scientific requirements, the assurance of proven treatment and ethical demands]. / Klinische Prüfung an Kindern im Spannungsfeld zwischen wissenschaftlichen Anforderungen, der Sicherstellung der korrekten Behandlung und ethischen Aspekten.

Regulation (EC) No. 1901/2006 of the European Parliament and the Council dated 12 December 2008 on medicinal products for paediatric use is the result of a survey by the European Commission, concluding that children in the European Union are inadequately treated with medicinal products. The Regulation is addressed to the pharmaceutical industry with the intention to place medicinal products on the market and to the Member States to register all information on medicinal products for the treatment of children. The pharmaceutical industry will be obliged to conduct clinical trials in children for new medicinal products and medicinal products still under patent. This will be supported by incentives and rewards. As a consequence of the requirement to conduct clinical trials in children the framework and conditions have to be defined and ethical considerations have to be respected.

[Control of aspirin effect in chronic cardiovascular patients using two whole blood platelet function assays. PFA-100 and Multiplate]. / Vollblutaggregometrie zur Kontrolle der Wirksamkeit von Azetylsalizylsäure bei Patienten mit koronarer Herzkrankheit. Vergleich von PFA-100 und Multiplate.

In this study two aspirin sensitive platelet function tests which are based on the analysis of whole blood were evaluated and correlated with each other. In vitro bleeding time was determined using the PFA-100 analyzer (Dade Behring, Marburg, Germany) using the collagen/epinephrine cartridge and citrated blood. Whole blood aggregometry was performed using the Multiplate analyzer (Dynabyte medical, Munich, Germany) using hirudin blood (25 mug/ml). Aggregatin was triggered using arachidonic acid (ASPItest), collagen (COLtest) or TRAP-6 (thrombin receptor activating peptide, TRAPtest). Following informed consent citrated blood and hirudin blood was drawn from 76 cardiovascular patients which were on long-term aspirin therapy (aspirin patients). In addition hirudin blood was drawn from 57 healthy blood donors for assessment of whole blood aggregometry. PFA-100 closure times of the aspirin patients were 273 +/- 49 s. Based on the cut-off of 170 s a non response to the aspirin therapy was detected in 5 of 76 patients. Whole blood aggregation was comparable in the aspirin patients vs the blood donors AUC values in the TRAP test, whereas in COLtest and ASPItest significantly reduced aggregations were detected (p < 0.05). Of the five patients that had a normal PFA-100 closure time only one had normal aggregation in ASPItest, and also only one had a normal aggregation in COLtest. The high rate of response to the aspirin therapy which was found in PFA-100 and ASPItest can be explained by the assumed high level of compliance of the cohort. In the applied tests different patients were stratified as aspirin-non-responders. This highlights the importance of the assay conditions for the diagnosis of an aspirin-non-response.

B-cell-receptor-dependent positive and negative selection in immature B cells.

This review touches on only a small part of the complex biology of B cells, but serves to illustrate the point that the antigen receptor is the most important of many cell-surface receptors affecting cell-fate decisions. Receptor expression is necessary, but not sufficient, for cell survival. It is also essential that a B cell's antigen-receptor specificity be appropriate for its environment. The need to balance reactivity with self tolerance has resulted in an intricate feedback control (affected by both the recombinase and cell survival) that regulates independent selection events at the level of the receptor and the cell.

Developmental apraxia arising from neonatal brachial plexus palsy.

OBJECTIVE: To determine whether motor unit activation is impaired in patients with persisting disability arising from neonatal brachial plexus palsy (NBPP). BACKGROUND: In NBPP patients, the authors previously found more extensive muscle reinnervation than might have been anticipated from the clinical examination. METHODS: Motor skills were tested in a group of nine boys and seven girls with prior NBPP, who then underwent physiologic investigation of proximal and distal muscles in their affected and unaffected arms. The latter tests comprised measurements of maximal evoked muscle compound action potential (M-wave) amplitude, maximal voluntary torque, twitch torque, and twitch interpolation. A group of 17 children of similar ages served as control subjects. RESULTS: In the NBPP group, motor skills were diminished and voluntary torque was reduced relative to M-wave amplitude and twitch torque. Moreover, interpolated twitches could be demonstrated in some NBPP patients but not in control subjects. CONCLUSION: Persisting disability in NBPP patients is due, at least in part, to impaired motor unit activation. The authors suggest that the impairment is a form of developmental apraxia caused by defective motor programming in early infancy.

Intravenous paraldehyde for seizure control in newborn infants.

We studied 14 newborn infants with seizures after birth asphyxia or other causes. Paraldehyde was given as a 200 mg/kg IV bolus followed by an infusion of 16 mg/kg/h (10 cases), or as a 400 mg/kg bolus (4 cases). Serum concentrations of paraldehyde were higher in periods of adequate seizure control than in periods of little or no response. Paraldehyde serum concentrations above 10 mg/dl were associated with anticonvulsant effects and were achieved in most neonates with a 2-hour infusion of 200 mg/kg/h. If there is no effect, serum concentrations are probably below 10 mg/dl and an additional 200 mg/kg can be given safely over 1 hour.

Central nervous system patholgoy associated with mask ventilation in the very low birthweight infant: a new etiology for intracerebellar hemorrhages.

Mask-applied ventilatory support was noted to cause severe head molding in infants with birthweights under 1,501 gm. To determine if this molding was detrimental to the infant, the neonatal course and autopsy findings were reviewed for 106 infants. Twenty significant intracerebellar hemorrhages were found. An association between these hemorrhages and mask-applied positive pressure ventilation was demonstrated (P = .05). This relationship was maintained when all cases of generalized bleeding dyscrasia were removed (P = .021). It is proposed that the distortional forces produced by the mask attachment, together with the buffeting effect of intermittent positive-pressure ventilation, are causally related to the production of intracerebellar hemorrhages by direct contusion, by ischemic stasis, or by altered venous drainage. The authors urge strong caution when dealing with the small premature infant in using any attachment device that causes molding of the cranial vault, particularly in the occipital area.

Thrombin-based antithrombin assays show overestimation of antithrombin III activity in patients on heparin therapy due to heparin cofactor II influence.

An extensive comparison has been performed on the clinical chemistry automate Hitachi 717 between thrombin- and Factor Xa-based methods for determination of antithrombin III activity. In 460 patients who did not receive any heparin therapy the agreement between assays was in general close although the thrombin-based methods resulted in slightly higher assignments of 0.3-2.6% antithrombin III activity. The discrepancy was, however, substantial in plasmas from patients receiving heparin of > or = 20000 IU/day, resulting in plasma levels of heparin of 0.8-1.2 IU/ml. Thus, analysis of 102 patients showed that the thrombin-based methods resulted in, on average, 7-16% higher assignment of antithrombin III activity as compared to the Factor Xa-based method used. Addition of antibodies to antithrombin III and heparin cofactor II revealed that the discrepancy was primarily due to contribution of heparin cofactor II activity in the thrombin-based methods. The results thus suggest that the Factor Xa-based antithrombin III activity method provides more valid results in patients on heparin therapy.

Antigen-specific CD4+ T cells that survive after the induction of peripheral tolerance possess an intrinsic lymphokine production defect.

Injection of soluble foreign antigen without an adjuvant induces a state of antigen-specific immunological unresponsiveness. We investigated the cellular mechanisms that underlie this form of peripheral tolerance by physically tracking a small population of ovalbumin (OVA) peptide/I-Ad-specific, CD4+ T cell receptor (TCR) transgenic T cells following adoptive transfer into normal recipients. Injection of OVA peptide in the absence of adjuvant caused the antigen-specific T cells to proliferate for a brief period after which most of the T cells disappeared. The remaining OVA-specific T cells had converted to a memory phenotype but were poorly responsive in vivo as evidenced by a failure to accumulate in the draining lymph nodes following immunization with OVA peptide in adjuvant. These surviving T cells possessed a long-lasting, but reversible, defect in Il-2 and TNF-alpha production and in vivo proliferation, but did not gain capacity to produce Th2-type cytokines or suppress the clonal expansion of T cells specific for another antigen. Therefore, some antigen-specific T cells survive this peripheral tolerance protocol but are functionally unresponsive due to an intrinsic activation defect.

Platelet function analysis with PFA-100 in patients medicated with acetylsalicylic acid strongly depends on concentration of sodium citrate used for anticoagulation of blood sample.

Our data from 214 patients after cessation of long-term therapy with 100 mg/d ASA demonstrate that the determination of platelet-related primary hemostasis in citrated whole blood with PFA-100 is a reliable and sensitive method for the detection of ASA-induced platelet dysfunction. However, the sensitivity of the method is strongly dependent on concentration of sodium citrate used as anticoagulant. The results of PFA-100 testing show a clearly enhanced sensitivity for ASA when blood samples were collected with 0.129 M rather than 0.106 M sodium citrate. According to sample stability, PFA-100 results can only be confirmed up to 1 hour postcollection when blood was anticoagulated with 0.129 M but not with 0.106 M sodium citrate. Therefore, we recommend that testing with PFA-100 in patients with suspected ASA-induced platelet dysfunction should be performed exclusively in blood collected in buffered 0.129 M sodium citrate.

Effects of interferon-beta on Daudi cells and on small cell lung carcinoma cells which over-express the c-myc oncogene.

The effects of human interferon-beta (IFN-beta) on four lung cancer cell lines, two of which over-express the c-myc oncogene, were compared to Daudi cells which also over-express c-myc. The anti-proliferative effect of IFN-beta on Daudi cells was correlated with a decrease in steady state levels of c-myc mRNA. IFN-beta treatment of a classic small cell lung carcinoma cell line and a non-small cell lung carcinoma cell line which express normal levels of c-myc did not decrease the rate of cell proliferation. IFN-beta, however, was found to have dramatic anti-proliferative effects on the two lung cancer cell lines with c-myc over-expression. The growth inhibitory effects of IFN-beta on the two lung cancer cell lines could not, however, be correlated with decreased amounts of c-myc mRNA. Furthermore, Western blot analysis showed that interferon treatment did not detectably affect the c-myc protein levels in these cells. Therefore, the mechanism by which IFN-beta slowed the growth rates of the two lung cancer cell lines did not appear to directly involve down-regulation of the c-myc oncogene, expressed in amplified amounts, in these cells.

An integrated model for haemorrhagic and ischaemic lesions in the newborn brain.

The vascular anatomy of the developing brain changes from a predominantly basal ganglia orientated pattern at 24 wk to a cortically orientated pattern by 34 wk. This information, combined with other known data on cerebral vascular anatomy and physiology, allows us to develop a model for haemorrhagic and ischaemic lesions in the newborn brain based on two main series of reactions. One series involves the effects of hypoxia and hypercapnia in leading to breakdown of the blood--brain barrier with resultant oedema or haemorrhage. The other links a fall in perfusion pressure and factors causing vasoconstriction with the development of ischaemic lesions. Application of the model involves additional consideration of the state of development of the cerebral vessels at the gestational age concerned. The model helps to explain the observed findings in germinal layer haemorrhage/intraventricular haemorrhage, periventricular leukomalacia and venous infarction, in the preterm brain. Its use also suggests that there are three patterns of vulnerability in the term infant brain. The model carries several implications for the neonatal management of preterm infants. Routine continuous monitoring of blood pressure is of critical importance as cerebral blood flow may vary with blood pressure in the ill newborn. It is important to avoid head compression which may lead to impaired cerebral perfusion. Finally, control of the acid--base status is essential for maintenance of the blood--brain barrier. Correction of abnormal values must be carried out without provoking rapid swings in either the serum osmolarity or the blood pressure.

Negative and positive dimensions of schizotypal personality disorder.

The positive (perceptual-cognitive) and negative (social-interpersonal) dimensions of schizotypal personality traits were examined in biological relatives of individuals with Axis I disorder. The subjects were young adult offspring from three contrasting parental groups, including schizophrenic disorder, affective disorder, and normal controls. Cognitive correlates, including digit span (presumed to assess working memory) and P3 amplitudes, were also examined. Preliminary results showed that positive and negative dimensions were distinguished by different prevalence patterns in the offspring subjects, and by a different pattern of correlations with cognitive measures. Negative dimensions were more frequent in offspring from the schizophrenic parental group than in the offspring from affective disorder and normal control parental groups. Digits forward and backward, and P3 amplitude decrements, characterized a subset of offspring with negative features from the schizophrenic parental group. Positive dimensions did not differ between the psychiatric parental groups, and did not covary with digit span or P3 amplitude assessments. These results support the view that positive and negative dimensions may reflect separable pathophysiologic processes.

Continence following electrical stimulation and EMG biofeedback in a teenager with imperforate anus.

A teenage boy with repaired high imperforate anus relied on daily enemas for social continence. After treatment with low intensity transcutaneous electrical stimulation and electromyographic biofeedback home programs, he achieved improved fecal continence requiring only one enema per month.

Necrotizing enterocolitis and volvulus in the premature neonate.

Premature infants presenting to the neonatal intensive care unit at the Hospital for Sick Children with a surgical abdomen over a 5-year period were studied retrospectively to determine the factors leading to the diagnosis of malrotation with volvulus and necrotizing enterocolitis (NEC). Fifteen preterm infants (less than 37 weeks) were diagnosed as having volvulus, and 54 had surgically treated NEC. Those with NEC were more likely to be systematically ill with grossly bloody stools, abdominal tenderness, and thrombocytopenia (P less than .005). Bilious vomiting and bilious gastric residuals were the only hallmarks of volvulus (P less than .005). Although the radiographic findings of thickened bowel walls and intramural air were significantly related to NEC, the accuracy and interobserver reliability in diagnosing these features was variable as was the ability to distinguish NEC from volvulus or normal on plain abdominal radiographs. Volvulus is an important cause of surgical abdomen in the preterm infant and can be misdiagnosed as NEC. An unusual course or the presence of bilious vomiting in any patient thought to have NEC should alert the clinician to the possibility of this diagnosis.

Control, coping, and victimization in dating relationships.

This study examined the role of perceived control and coping in mediating the relationship between violent and nonviolent negative relationship events and women's experience of distress. Results based on the responses of 48 victims of dating relationship violence and 74 nonvictims indicated that perceived control was negatively related to distress for victims but not nonvictims. While both victims and nonvictims engaged in both problem- and emotion-focused coping, and different patterns of coping emerged for the two groups, appraisals of control were not related to choice of coping strategies for violent or nonviolent negative relationship events. Psychological distress was not significantly predicted by coping strategies or the interaction of control and coping for either type of event of for either group. These results suggest that control appraisals may be particularly important in reducing distress for victims. However, appraisals of perceived control may place them at increased risk for abuse in the long run, as victims are unlikely to be able to control the violence as it escalates in both severity and frequency over time.

Psychological abuse: implications for adjustment and commitment to leave violent partners.

The contribution of psychological abuse, beyond that of physical abuse, to battered women's psychological adjustment and their intentions to terminate their abusive relationships was examined. Sixty-eight battered women residing in shelters for battered women provided information on their: (1) physical and psychological abuse; (2) psychological symptomatology; (3) strategies for coping with and perceptions of control over partner violence; and (4) intentions to return to their abusive partners. Multiple regression analyses indicated that frequency and severity of physical abuse was not a significant predictor of posttraumatic stress disorder (PTSD) symptomatology nor of women's intentions to terminate their abusive relationships. However, psychological abuse was a significant predictor of both PTSD symptomatology and intentions to permanently leave abusive partners even after controlling for the effects of physical abuse. PTSD symptomatology moderated the relationship between psychological abuse and intentions to terminate the abusive relationships: resolve to leave the abusive partner as a function of level of psychological abuse was significant only among women characterized by low levels of PTSD symptomatology. Greater use of emotion-focused coping strategies, absolutely and relative to problem-focused coping, had direct effects on PTSD symptomatology. However, neither coping nor perceptions of control moderated the effects of psychological abuse on psychological adjustment. The results of the investigation suggested that psychological abuse and ensuing PTSD symptomatology are important variables to assess among physically battered women.