When a trauma becomes a key to identity: Enhanced integration of trauma memories predicts posttraumatic stress disorder symptoms

The Centrality of Event Scale (CES) measures the extent to which a traumatic memory forms a central component of personnal identity, a turning point in the life story and a reference point for everyday inferences. In two studies, we show that the CES is positively correlated with severity of PTSD symptoms, even when controlling for measures of anxiety, depression, dissociation and self-consciousness. The findings contradict the widespread view that poor integration of the traumatic memory into one's life story is a main cause of PTSD symptoms. Instead, enhanced integration appears to be a key issue. Copyright © 2006 John Wiley & Sons, Ltd.

Nurse-led behavioral management of diabetes and hypertension in community practices: a randomized trial.

BACKGROUND: Several trials have demonstrated the efficacy of nurse telephone case management for diabetes (DM) and hypertension (HTN) in academic or vertically integrated systems. Little is known about the real-world potency of these interventions. OBJECTIVE: To assess the effectiveness of nurse behavioral management of DM and HTN in community practices among patients with both diseases. DESIGN: The study was designed as a patient-level randomized controlled trial. PARTICIPANTS: Participants included adult patients with both type 2 DM and HTN who were receiving care at one of nine community fee-for-service practices. Subjects were required to have inadequately controlled DM (hemoglobin A1c [A1c] ≥ 7.5%) but could have well-controlled HTN. INTERVENTIONS: All patients received a call from a nurse experienced in DM and HTN management once every two months over a period of two years, for a total of 12 calls. Intervention patients received tailored DM- and HTN- focused behavioral content; control patients received non-tailored, non-interactive information regarding health issues unrelated to DM and HTN (e.g., skin cancer prevention). MAIN OUTCOMES AND MEASURES: Systolic blood pressure (SBP) and A1c were co-primary outcomes, measured at 6, 12, and 24 months; 24 months was the primary time point. RESULTS: Three hundred seventy-seven subjects were enrolled; 193 were randomized to intervention, 184 to control. Subjects were 55% female and 50% white; the mean baseline A1c was 9.1% (SD = 1%) and mean SBP was 142 mmHg (SD = 20). Eighty-two percent of scheduled interviews were conducted; 69% of intervention patients and 70% of control patients reached the 24-month time point. Expressing model estimated differences as (intervention--control), at 24 months, intervention patients had similar A1c [diff = 0.1 %, 95 % CI (-0.3, 0.5), p = 0.51] and SBP [diff = -0.9 mmHg, 95% CI (-5.4, 3.5), p = 0.68] values compared to control patients. Likewise, DBP (diff = 0.4 mmHg, p = 0.76), weight (diff = 0.3 kg, p = 0.80), and physical activity levels (diff = 153 MET-min/week, p = 0.41) were similar between control and intervention patients. Results were also similar at the 6- and 12-month time points. CONCLUSIONS: In nine community fee-for-service practices, telephonic nurse case management did not lead to improvement in A1c or SBP. Gains seen in telephonic behavioral self-management interventions in optimal settings may not translate to the wider range of primary care settings.

Two Cases of Late Shone Syndrome With Pulmonary Hypertension: Heart-Lung Transplant or Valve Surgery?

Two cases of Shone syndrome with severe mitral and aortic valve problems and pulmonary hypertension were referred for heart-lung transplantation. Severely elevated pulmonary vascular resistance (PVR) was confirmed as was severe periprosthetic mitral and aortic regurgitation. Based on the severity of the valve lesions in both patients, surgery was decided upon and undertaken. Both experienced early pulmonary hypertensive crises, one more than the other, that gradually subsided, followed by excellent recovery and reversal of pulmonary hypertension and PVR. These cases illustrate Braunwald's concept that pulmonary hypertension secondary to left-sided valve disease is reversible.

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI.

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

Association of fever and severe clinical course in bronchiolitis

Little attention has been given to the relation between fever and the severity of bronchiolitis. Therefore, the relation between fever and the clinical course of 90 infants (59 boys, 31 girls) hospitalised during one season with bronchiolitis was studied prospectively. Fever (defined as a single recording > 38.0°C or two successive recording > 37.8°C) was present in 28 infants. These infants were older (mean age, 5.3 v 4.0 months), had a longer mean hospital stay (4.2 v2.7 days), and a more severe clinical course (71.0%v 29.0%) than those infants without fever. Radiological abnormalities (collapse/consolidation) were found in 60.7% of the febrile group compared with 14.8% of the afebrile infants. These results suggest that monitoring of body temperature is important in bronchiolitis and that fever is likely to be associated with a more severe clinical course and radiological abnormalities.

Application of regularization methods to damage detection in large scale plane frame structures using incomplete noisy modal data

This paper presents an approach for detecting local damage in large scale frame structures by utilizing regularization methods for ill-posed problems. A direct relationship between the change in stiffness caused by local damage and the measured modal data for the damaged structure is developed, based on the perturbation method for structural dynamic systems. Thus, the measured incomplete modal data can be directly adopted in damage identification without requiring model reduction techniques, and common regularization methods could be effectively employed to solve the developed equations. Damage indicators are appropriately chosen to reflect both the location and severity of local damage in individual components of frame structures such as in brace members and at beam-column joints. The Truncated Singular Value Decomposition solution incorporating the Generalized Cross Validation method is introduced to evaluate the damage indicators for the cases when realistic errors exist in modal data measurements. Results for a 16-story building model structure show that structural damage can be correctly identified at detailed level using only limited information on the measured noisy modal data for the damaged structure.

Intersex in the clam Scrobicularia plana: A sign of endocrine disruption in estuaries?

The phenomenon of endocrine disruption is currently a source of growing concern. Feminisation of male fish in UK rivers has been shown to occur extensively and has been linked with exposure to endocrine-disrupting compounds present in the environment. Much less is known of the extent and scale of endocrine disruption in estuarine and marine ecosystems, particularly in invertebrates. We present evidence that intersex, in the form of ovotestis, is occurring in the common estuarine bivalve Scrobicularia plana, which is considered to be inherently gonochoristic. We report varying degrees in the severity of ovotestis in male S. plana, and have adopted and developed a grading method to assess the extent of this intersex condition. These findings indicate that S. plana offers potential for widespread screening and investigation of endocrine disruption, helping to focus remediatory strategy.

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

Improving the quality of life for patients with angina pectoris: a team approach to disease management.

The evaluation of outcome of management of angina patients is now inextricably linked with an assessment of quality of life. Angina, as a manifestation of coronary heart disease, is a major cause of morbidity and mortality in many countries. Optimal management of patients with angina is of undeniable national and global significance.

This paper attempts to indicate the importance of a team approach and the implications for patients’ quality of life of involving professionals with a variety of different skills. It outlines current guidelines for the management of angina, including aspects of diagnosis, treatment and rehabilitation. Factors of relevance to the management of patients as individuals are discussed. The association of improved quality of life and reduced severity of symptoms with benefit for both the individual and society is considered.

Effects of trauma on bipolar disorder: the mediational role of interpersonal difficulties and alcohol dependence

Objectives: This study examined: (i) the prevalence of trauma in a bipolar disorder (BD) sample, and (ii) how trauma histories mediated by interpersonal difficulties and alcohol dependence impact on the severity of BD. The prevalence of posttraumatic stress disorder (PTSD) and its relationship to outcomes in BD were also examined.

Methods: Sixty participants were recruited from a geographically well-defined mental health service in Northern Ireland. Self-reported trauma histories, PTSD, interpersonal difficulties and alcohol dependence and were examined in relation to illness severity.

Results: A high prevalence of trauma was found. Trauma predicted the frequency of hospital admissions (R-2 = 0.08), quality of life (R-2 = 0.23) and inter-episode depressive symptoms (R-2 = 0.13). Interpersonal difficulties, but not alcohol dependence, appeared to play an important role in mediating these adverse effects. While only 8% of the sample met criteria for active PTSD, this comorbid disorder was associated with BD severity.

Conclusions: This study indicates that awareness of trauma is important in understanding individual differences in bipolar presentations. The theoretical and clinical implications of evidence that trauma is related to more adverse outcomes in BD are discussed. The finding that interpersonal difficulties mediate the relationship between trauma and BD severity is novel. The need for adjunctive evidence-based treatments targeting interpersonal difficulties is considered.

Use of A192621 to provide evidence for involvement of endothelin ET(B)-receptors in endothelin-1-mediated cardiomyocyte hypertrophy.

Increased plasma levels of endothelin-1 correlate with the severity of left ventricular hypertrophy in vivo. The aim of the study was to determine the relative contribution of stimulation of endothelin ETA and endothelin ETB receptors, and the associated activation of protein kinase C, to the hypertrophic response initiated by endothelin-1 in adult rat ventricular cardiomyocytes maintained in culture (24 h). Endothelin-1 (10-7 M) increased the total mass of protein and the incorporation of [14C] phenylalanine into protein to 26% and 25% greater (P

Modulation of contractile function through NPY receptors during development of cardiomyocyte hypertrophy.

Severity of left ventricular hypertrophy (LVH) correlates with elevated plasma levels of neuropeptide Y (NPY) in hypertension. NPY elicits positive and negative contractile effects in cardiomyocytes through Y(1) and Y(2) receptors, respectively. This study tested the hypothesis that NPY receptor-mediated contraction is altered during progression of LVH. Ventricular cardiomyocytes were isolated from spontaneously hypertensive rats (SHRs) pre-LVH (12 weeks), during development (16 weeks), and at established LVH (20 weeks) and age-matched normotensive Wistar Kyoto (WKY) rats. Electrically stimulated (60 V, 0.5 Hz) cell shortening was measured using edge detection and receptor expression determined at mRNA and protein level. The NPY and Y(1) receptor-selective agonist, Leu(31)Pro(34)NPY, stimulated increases in contractile amplitude, which were abolished by the Y(1) receptor-selective antagonist, BIBP3226 [R-N(2)-(diphenyl-acetyl)-N-(4-hydroxyphenyl)methyl-argininamide)], confirming Y(1) receptor involvement. Potencies of both agonists were enhanced in SHR cardiomyocytes at 20 weeks (2300- and 380-fold versus controls). Maximal responses were not attenuated. BIBP3226 unmasked a negative contraction effect of NPY, elicited over the concentration range (10(-12) to 3 x 10(-9) M) in which NPY and PYY(3-36) attenuated the positive contraction effects of isoproterenol, the potencies of which were increased in cardiomyocytes from SHRs at 20 weeks (175- and 145-fold versus controls); maximal responses were not altered. Expression of NPY-Y(1) and NPY-Y(2) receptor mRNAs was decreased (55 and 69%) in left ventricular cardiomyocytes from 20-week-old SHRs versus age-matched WKY rats; parallel decreases (32 and 80%) were observed at protein level. Enhancement of NPY potency, producing (opposing) contractile effects on cardiomyocytes together with unchanged maximal response despite reduced receptor number, enables NPY to contribute to regulating cardiac performance during compensatory LVH.

Trends in the prevalence of cerebral palsy in Northern Ireland, 1981-1997

We describe trends in the prevalence of cerebral palsy (CP) by birth weight group, and in the severity of motor impairments and presence of associated intellectual impairment, in Northern Ireland from 1981 to 1997 (n=909; 510 males, 399 females; total population 415 936 live births) using data from a population-based register of CP. Children with suspected CP or who died before 1 year of age and those with CP of postneonatal origin were excluded. Prevalence of CP was 2.2 per 1000 live births without significant change over time. Among very-low-birthweight (<1500g) live births, prevalence was 44.5 per 1000 (95% confidence interval 32.3–59.8) from 1994 to 1997, with evidence of a statistically significant decline in prevalence since the mid- to late 1980s accompanied by a decrease in the severity of motor impairment and likelihood of intellectual impairment. Among moderately-low-birthweight (1500–2499g) children there was weaker evidence of a peak prevalence in the late 1980s. Prevalence among normal-birthweight infants did not change significantly, but outcome in terms of severity of motor impairment and intellectual impairment improved in the 1990s. Occurrence of bilateral spasticity from 1994 to 1997 was associated with greater severity and likelihood of intellectual impairment for normal-birthweight individuals than for low- or very-low-birth weight individuals.

Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis.

Neutrophil elastase (NE) is thought to be the most important protease which damages the cystic fibrosis (CF) lung. Attempts have been made to suppress this activity using the plasma-derived inhibitor, alpha1-antitrypsin (AAT). In this pilot study, the safety and efficacy of inhaled recombinant human AAT (rAAT) as a treatment for CF were investigated. Thirty-nine patients participated in a prospective, double-blinded, randomized, placebo-controlled phase II trial to examine the effect of rAAT (500, 250, and 125 mg) on sputum NE activity. Sputum myeloperoxidase (MPO), interleukin-8, tumor necrosis factor receptors, sputum and plasma NE/AAT complexes, and safety parameters were also measured. Subjects were randomized to receive nebulized treatment once a day for 4 weeks, followed by 2–4 weeks with no study treatment, and then a 2-week rechallenge phase. Trends toward a reduction in NE activity were observed in patients treated with 500 mg and 250 mg of rAAT compared to placebo. Sputum NE/AAT complex and MPO levels were lower on rAAT compared to placebo. No major adverse events and, in particular, no allergic reactions to rAAT were observed. Although significant differences between rAAT and placebo for sputum NE activity were not observed, some improvements were found for secondary efficacy variables. This study demonstrated that nebulized rAAT is safe and well-tolerated, but has a limited effect on NE activity and other markers of inflammation. Pediatr Pulmonol.

Determinants of Child-Parent Agreement in Quality-of-Life Reports: A European Study of Children With Cerebral Palsy

OBJECTIVES: The differences between child self-reports and parent proxy reports of quality of life in a large population of children with cerebral palsy were studied. We examined whether child characteristics, severity of impairment, socioeconomic factors, and parental stress were associated with parent proxy reports being respectively higher or lower than child self-reports of quality of life. METHODS. This study was conducted in 2004–2005 and assessed child quality of life (using the Kidscreen questionnaire, 10 domains, each scored 0–100) through self-reports and parent proxy reports of 500 children aged 8 to 12 years who had cerebral palsy and were living in 7 countries in Europe. RESULTS: The mean child-reported scores of quality of life were significantly higher than the parent proxy reports in 8 domains, significantly lower for the finances domain, and similar for the emotions domain. The average frequency of disagreement (child-parent difference greater than half an SD of child scores) over all domains was 64%, with parents rating their child’s quality of life lower than the children themselves in 29% to 57% of child-parent pairs. We found that high levels of stress in parenting negatively influenced parents’ perception of their child’s quality of life, whereas the main factor explaining parents’ ratings of children’s quality of life higher than the children themselves is self-reported severe child pain. CONCLUSIONS: This study shows that the factors associated with disagreement are different according to the direction of disagreement. In particular, parental wellbeing and child pain should be taken into account in the interpretation of parent proxy reports, especially when no child self-report of quality of life is available. In the latter cases, it may be advisable to obtain additional proxy reports (from caregivers, teachers, or clinicians) to obtain complementary information on the child’s quality of life.