[Curing cancer and protecting the heart : Challenges in cardio-oncology in the era of modern tumor treatment]. / Krebserkrankungen heilen und das Herz schützen : Herausforderungen der Kardioonkologie im Zeitalter moderner Tumortherapien.

Recent advances in the medical oncological treatment options for cancer have led to a clear improvement in the survival rate worldwide; however, many of the recently developed new drugs are directly or indirectly associated with cardiovascular side effects. Cardiovascular diseases are already the most frequent non-cancerous cause of death in tumor patients. Prevention, early detection of these complications, correct management and timely initiation of specific cardiac medical treatment are the key for an improvement of the cardiovascular prognosis. This article provides an overview and comprehensive summary of the possible cardiotoxic side effects of important oncological therapies and offers possible practical strategies with respect to risk stratification, cardiological follow-up care and management approaches for chemotherapy-induced left ventricular dysfunction.

The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.

BACKGROUND: Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. METHODS: In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis. FINDINGS: We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001. INTERPRETATION: The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts: an allergic comorbidity cluster.

BACKGROUND: Asthma, rhinitis and eczema often co-occur in children, but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis and eczema using unsupervised statistical techniques. METHODS: We included 17 209 children at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age of onset and treatments of asthma, rhinitis and eczema; immunoglobulin E sensitization; weight; and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organizing maps. RESULTS: Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70% and 79% of children, respectively) was characterized by a low prevalence of symptoms and sensitization, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitization. Ninety-nine percentage of children with comorbidities (co-occurrence of asthma, rhinitis and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses. CONCLUSION: At 4 and 8 years, at the population level, asthma, rhinitis and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases.

Providing systematic detailed information on medication upon hospital discharge as an important step towards improved transitional care.

WHAT IS KNOWN AND OBJECTIVE: Good communication between hospital and primary care physicians (PCPs) is important for the continuity of patient care in the transition phase following hospital treatment. Drug-related problems and medication errors may occur at that interface. Discharge letters often lack a structured medication report at the end and therefore may not provide the reasons for medication changes, resulting in low adherence rates. The objectives were to develop a structured medication report as part of the discharge letter, to evaluate the impact of the medication report in ischaemic stroke patients and to identify the most important issues in the transitional care process of stroke patients. METHODS: First, a structured medication report was developed. Thereafter, the impact of this new medication report on clinical practice was evaluated with an open, prospective, interventional two-phase study conducted at the Klinikum Fulda gAG (Germany), which included patients with ischaemic stroke and >2 drugs in the discharge medication. In the control group (CG), the neurologist included the current medication in the discharge letter. In the intervention group (IG), the clinical pharmacist added the detailed information to a medication report. To evaluate adherence to discharge medication, the PCP was interviewed 3 months after hospital discharge about the medication. Adherence was measured with respect to the entire medication regimen, antithrombotic and cholesterol-lowering drugs and discontinued medication. The most important issues in the transitional care for patients with ischaemic stroke were identified on the basis of the secondary stroke prevention and cardiovascular risk factors. RESULTS AND DISCUSSION: Overall, 312 patients were enrolled in the study with 156 patients in each group. By providing detailed information in the newly developed discharge letter, adherence increased significantly from 83·3% (CG) to 90·9% (IG; P = 0·01). Significant differences between the CG and IG were found with regard to adherence to both antithrombotic drugs [83·8% CG vs. 91·9% IG (P = 0·033)] and statin therapy [69·8% CG vs. 87·7% IG (P < 0·001)]. WHAT IS NEW AND CONCLUSION: The use of a structured medication report as part of the discharge letter leads to improved adherence to hospital discharge medication.

Exploring the potential impact of hospital ward-based pharmacy interns on drug safety.

Clinical pharmacists play an important role in improving drug safety on hospital wards. However, little is known about the impact of pharmacy interns. The objective of our study was, therefore, to investigate the impact of hospital ward-based pharmacy interns on drug safety. This study was conducted as part of the project "P-STAT 2: Pharmacy interns on the ward" on 14 surgical wards in seven hospitals in Germany and a total of 27 pharmacy interns participated. All patients admitted to the participating wards from 1st June 2008 until 31st October 2008 and from 1st December 2008 till 30th April 2009 were included. The pharmacy interns were involved in medication reconciliation, and identifying, resolving, and preventing drug-related problems (DRPs) using the classification system APS-Doc. A total of 6,551 patients were included. Patients received on average (+/- SD) 4.4 +/- 3.9 drugs. The pharmacy interns detected a total of 4,085 DRPs and on average 0.6 +/- 1.2 DRPs per patient. Most frequently detected DRPs were potential drug-drug interactions (n = 591, 14%), missing drug strength, when different strengths were available (n = 373, 9%), and incomplete medication record (n = 296, 7%). The pharmacy interns conducted an intervention for 98% (n = 4,011) of all DRPs. According to their documentation, 74% of the DRPs (n = 3,038) were solved. Drugs which were most often related with DRPs were simvastatin, diclofenac, and ibuprofen. This is the very first study exploring the potential impact of pharmacy interns on drug safety on surgical wards in Europe. Pharmacy interns can play an important role to improve drug safety on hospital wards.

Educational level of childhood brain tumor survivors: results from a German survey.

BACKGROUND: Among adult survivors of childhood brain tumors in Germany, we assessed their educational level and examined potentially influencing factors. PATIENTS AND METHODS: A questionnaire was sent to 505 childhood brain tumor survivors listed in the German Childhood Cancer Registry. 203/505 (40.2%) patients with treatment and educational data were included in the analysis.Of the included brain tumor survivors 54.7% (111/203) were male, the median age was 11.0 (1-15) years at diagnosis and 22.0 (19-37) years at the time of the survey. 34.8% (95%-CI 25.1-44.5) of female and 34.9% (26.0-43.8) of male survivors achieved a high school diploma. Survivors who had received irradiation had less likely obtained a high school diploma compared to those without irradiation. However, this association was statistically not significant: for either craniospinal or tumor irradiation adjusted odds ratio was 0.54 (0.08-3.76); for those with a combination of craniospinal and tumor irradiation 0.51 (0.07-3.59). Participants aged 6-10 years at diagnosis achieved a higher educational level 2.24 (0.45-11.25) compared to younger patients. CONCLUSION: A third of the childhood brain tumor survivors who participated in our survey obtained the highest school leaving certificate. This may be biased by an overrepresentation of well-educated survivors without major cancer-related late effects. The influence of the patients' strong motivation following a severe illness combined with the intensive psychosocial and/or pedagogical support on education needs to be examined in future studies.

Impact of cranial irradiation and brain tumor location on fertility: a survey.

As survival rates of patients with childhood brain tumors have increased to 75%, treatment related side effects are of particular importance. The present study evaluated questionnaire-based fertility characteristics in cancer survivors treated with irradiation to the hypo-thalamic-pituitary-axis.A nationwide survey was conducted in collaboration with the German Childhood Cancer Registry. Questionnaire and treatment data could be retrieved for 1110 former childhood cancer patients with cranial irradiation and/or chemotherapy.Survivors receiving ≥30 gray vs. 18-29 gray and 0-17 gray to the pituitary gland reported less pregnancies or less with their partners (7.4% vs. 32.8% vs. 12.4%; p<0.001), were more often infertile (40% vs. 9.4% vs. 12.5%; p<0.001) and the female participants, had a higher frequency of permanent amenorrhea (16.7% vs. 1.7% vs. 0%; p<0.001).Irradiation of the pituitary gland ≥ 30 gray seemed to be associated with less pregnancies and increased permanent amenorrhea in women. Future studies need to be conducted to confirm these results. Increased knowledge of treatment related side effects might help brain tumor patients to improve their family planning if necessary by gonadotropine replacement.

Are implants more reliable than severely compromised endodontically treated teeth as abutments for zirconia-based FPDs? : In vitro results of long-term preclinical load simulation.

OBJECTIVES: The aim was to study the impact of the defect size of endodontically treated incisors compared to dental implants as abutments on the survival of zirconia two-unit anterior cantilever-fixed partial dentures (2U-FPDs) during 10-year simulation. MATERIALS AND METHODS: Human maxillary central incisors were endodontically treated and divided into three groups (n = 24): I, access cavities rebuilt with composite core; II, teeth decoronated and restored with composite; and III as II supported by fiber posts. In group IV, implants with individual zirconia abutments were used. Specimens were restored with zirconia 2U-FPDs and exposed to two sequences of thermal cycling and mechanical loading. STATISTICS: Kaplan-Meier; log-rank tests. RESULTS: During TCML in group I two tooth fractures and two debondings with chipping were found. Solely chippings occurred in groups II (2×), IV (2×), and III (1×). No significant different survival was found for the different abutments (p = 0.085) or FPDs (p = 0.526). Load capability differed significantly between groups I (176 N) and III (670 N), and III and IV (324 N) (p < 0.024). CONCLUSION: Within the limitations of an in vitro study, it can be concluded that zirconia-framework 2U-FPDs on decoronated teeth with/without post showed comparable in vitro reliability as restorations on implants. The results indicated that restorations on teeth with only access cavity perform worse in survival and linear loading. CLINICAL RELEVANCE: Even severe defects do not justify per se a replacement of this particular tooth by a dental implant from load capability point of view.

Adherence to guidelines for antibiotic prophylaxis in surgery patients in German hospitals: a multicentre evaluation involving pharmacy interns.

BACKGROUND AND AIM: Surgical site infections (SSIs) are associated with a high morbidity, mortality and healthcare costs. The prevention of SSIs is based on a combination of preoperative preparation, surgical techniques, perioperative antibiotic prophylaxis (PAP) and postoperative wound care. Despite an abundance of evidence demonstrating the effectiveness of antimicrobials to prevent SSIs, the use of antimicrobial prophylaxis in this clinical setting is associated with inappropriate timing and selection and excessive duration of administration. To date, pharmacy interns (PIs) have not been involved in this process. The aim of this study was to evaluate feasibility of involving PIs in monitoring adherence to the guidelines for antibiotic prophylaxis in surgery patients. METHODS: The study was conducted in seven hospitals in Germany within the framework of the project "Pharmacy interns on the ward" (P-STAT2). Twenty-seven PIs participated, either from either May to October 2008 or from November 2008 to April 2009. Each patient admitted to the participating wards was consecutively monitored. PIs documented the antibiotic prophylaxis and checked the adherence with the hospital ward's PAP guidelines taking both the choice of antibiotic drug and the duration of PAP into account. The costs of antibiotics, personnel and material were calculated in cases of non-adherence with guidelines. RESULTS: This is the first time that PIs were involved in monitoring antibiotic prophylaxis guidelines. A total of 6,167 patients were enrolled (mean age 58.3 ± 19.6 years; 47.1% male); of these, 5,064 patients underwent surgery and were ultimately available for evaluation. Guidelines for antibiotic prophylaxis were followed in 70.7% of the cases. CONCLUSIONS: The study revealed that many patients do not receive the appropriate antibiotic prophylaxis despite the fact that guidelines are in place. Based on these results, we conclude that PIs may play an important role in antibiotic prophylaxis management.

Development of a classification system for drug-related problems in the hospital setting (APS-Doc) and assessment of the inter-rater reliability.

WHAT IS KNOWN AND OBJECTIVE: Identifying, preventing and resolving drug-related problems (DRP) is an important issue in the pharmaceutical care process. Because DRPs have been detected in a more systematic way, the need for a classification system to document, classify and evaluate the collected data has become necessary. The objective was to develop a classification system for DRPs within the hospital setting, to evaluate the practicality and to assess the inter-rater reliability. METHODS: All DRPs defined in PI-Doc and PCNE, which are relevant in the hospital setting, were included. Further relevant DRPs identified in other projects in a hospital setting as well as DRPs from the daily work on the ward were collected, and a short description of each DRP was written. A prospective study was conducted at Klinikum Fulda, Germany, in both a non-surgical and a surgical setting to explore whether the new classification system is suitable to classify DRPs in clinics with different specifications. For assessing the inter-rater reliability, 24 standardized case reports were provided. All participants classified them independently. The inter-rater reliability was analysed using Kappa coefficient. RESULTS AND DISCUSSION: A classification system for DRPs in the hospital setting (APS-Doc) was established with 10 main categories and 48 subcategories. Practicality was assessed in 250 patients in a non-surgical ward as well as in 100 patients in a surgical ward. The inter-rater agreement was 0·68 (95% CI, 0·66-0·69) for main categories, which comprises substantial agreement. Moderate agreement (κ = 0·58; 95% CI, 0·58-0·59) was demonstrated for the subcategories. WHAT IS NEW AND CONCLUSION: A new hierarchical classification system for DRPs in the hospital setting has been developed. APS-Doc seems suitable for various parts of the medication process such as medication reconciliation and drug therapy within both non-surgical and surgical wards. Inter-rater reliability was found to be substantial in the main categories and moderate in the subcategories.

Effects of brief stress exposure during early postnatal development in Balb/CByJ mice: II. Altered cortical morphology.

Early life experience can significantly determine later mental health status and cognitive function. Neonatal stress, in particular, has been linked to the etiology of mental health disorders as divergent as mood disorder, schizophrenia, and autism. Our study uses a Balb/CByJ mouse model to test the hypothesis, that neonatal stress will alter development and subsequent environmental modulation of neocortex. Using a split litter design, we generated stressed mice (STR) and within litter controls (LMC) along with age-matched, untreated animals (AMC), to serve as across litter controls. Short, daily exposure to a psychosocial/physical stressor, during the first week of life, resulted by adulthood in significant changes in neocortical thickness and architecture, which were further modulated by exposure to behavioral testing. Surprisingly, cortical size in LMC mice was also affected. These observations were compared to the effects of environmental enrichment in the same mouse strain. Our data indicate that LMC and STR males share with environmentally enriched males, an increase in thickness in infra-granular cortical layers, while STR also display a stress selective decrease in supragranular layers, in response to behavioral training as adults.

Low inhibin B levels alone are not a reliable marker of dysfunctional spermatogenesis in childhood cancer survivors.

Hormone and semen analyses were carried out to examine the diagnostic value of hormones and hormone combinations as markers of spermatogenesis in male patients who had received oncological treatment in childhood. Hormone analyses from 73 participants and spermiograms from 42 participants were evaluated. Spearman's correlation coefficients and measures of diagnostic accuracy were calculated for the hormone and semen analysis values. Inhibin B levels of <80 ml/ml, follicle-stimulating hormone (FSH) levels of >10 IU l(-1) and a combination of the two parameters showed positive predictive values for azoospermia of 0.423, 0.6154 and 0.6667 respectively. While 32% of the 73 participants showed a combination of abnormal inhibin B and FSH values, which strongly indicates impaired spermatogenesis, 31% of the 42 spermiogram results revealed azoospermia. The hormone and semen analyses showed that approximately one-third of the participants had fertility impairment. Inhibin B alone thus does not reflect spermatogenesis as well as inhibin B in combination with FSH in patients who have undergone cancer treatment in childhood. Both parameters should therefore be evaluated in paediatric cancer follow-up programmes to allow better identification of treatment regimens that cause persistent azoospermia in male childhood cancer survivors.

Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative.

BACKGROUND: Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. OBJECTIVE: The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. METHODS: We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. RESULTS: Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0-2 years: adjusted odds ratios (aOR), 1.39 (95% CI, 1.05-1.84)] and with asthma later in childhood in six cohorts [6-8 years: aOR, 1.09 (95% CI, 0.90-1.32) and 3-10 years: aOR, 1.10 (95% CI, 0.90-1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6-8 years: aOR, 1.12 (1.02-1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09-1.28)]. CONCLUSION: These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.

Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence.

BACKGROUND: Since prevalence of and reasons for infertility were unclear in survivors of childhood cancer we conducted a two centre survey in 2006 and nationwide in 2008. In 2008/2009 we undertook a study entitled "Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence". PATIENTS AND METHODS: Letters were sent to 748 former paediatric oncological patients who were at least 18 years of age at the time of the survey. Serum and sperm samples were analysed. RESULTS: We obtained 159 blood samples (86 women, 73 men). 42 men took part in the sperm analyses. The average participants' age at the time of the survey was 25 years. The anti-Mullerian hormone levels (AMH) in 14/86 female participants (16 %) were < 0.1 ng/ml. The follicular reserve of these women seemed manifestly impaired, which is consistent with suspected infertility. The AMH levels in 21/86 women (24 %) were 0.1 - 1.0 ng/ml indicating limited follicular reserve and therefore suspected early ovarian failure. Inhibin B levels of < 80 pg/ml and FSH levels of > 10 IU/L were found in 23/73 male participants (32 %), which may indicate impaired spermiogenesis with increased risk of infertility. 13/42 sperm analyses (31 %) revealed azoospermia. DISCUSSION: Paediatric oncological therapy seems to have led to fertility impairment in about 1/3 of the participants. Considering this serious impairment, patients and their families should be given comprehensive counselling ahead of therapy to enable fertility-preserving measures. For persons who wish to have children after undergoing therapy we recommend a hormone and sperm analysis. An early analysis may enable a more successful family planning.

[Are the initial pH and the lactate values after cardiopulmonary resuscitation always crucial?] / Sind initialer pH- und Laktatwert nach kardiopulmonaler Wiederbelebung immer entscheidend?

A 52-year-old man suffered an out-of-hospital cardiac arrest (OHCA) and bystander reanimation was immediately started. The initial electrocardiogram indicated ventricular fibrillation. After repetitive defibrillations as well as intravenous administration of amiodarone, a temporary return of spontaneous circulation (ROSC) could be established. Due to unstable cardiovascular conditions with recurrence of ventricular fibrillation, mechanical resuscitation with the help of the LUCAS™ device was initiated, and the patient was admitted to our hospital for emergency coronary angiography after a cumulative period of approximately 90 min. The initial blood gas analysis displayed a significant lactate acidosis with a pH value of 6.7. Therefore, in a multidisciplinary team, the decision was made against an extracorporeal membrane oxygenation and for a coronary angiography under continuation of mechanical resuscitation. After multiple stenting of the right coronary artery and left anterior descending coronary artery, permanent ROSC could be established. The patient was admitted to our intensive care unit, where he was further treated according to the S3-guideline for infarct-related cardiogenic shock. In the course of time, the patient was quickly extubated without any neurological deficits.

Interaction between plasminogen activator inhibitor type 1 (PAI-1) bound to fibrin and either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). Binding of t-PA/PAI-1 complexes to fibrin mediated by both the finger and the kringle-2 domain of t-PA.

Plasminogen activation is catalyzed both by tissue-type-(t-PA) and by urokinase-type plasminogen activator (u-PA). This reaction is controlled by plasminogen activator inhibitor type 1 (PAI-1) that is either present in plasma or bound to fibrin, present in a thrombus. We studied the mechanism of in vitro inhibition of both t-PA and u-PA activity by PAI-1 bound to fibrin. It is shown that activation of latent PAI-1 unmasks a specific fibrin-binding site that is distinct from its reactive site. This reactive site of activated PAI-1 bound to fibrin is fully exposed to form complexes with t-PA and u-PA, that are unable to activate plasminogen. Upon complex formation with either one of the plasminogen activators, PAI-1 apparently undergoes a conformational change and loses its affinity for fibrin. Consequently, complexes of u-PA and PAI-1 dissociate from the fibrin matrix and are encountered in the fluid phase. In contrast, t-PA/PAI-1 complexes remain bound to fibrin. By employing recombinant t-PA deletion-mutant proteins, that precisely lack domains involved in fibrin binding, we demonstrate that binding of t-PA/PAI-1 complexes is mediated by both the "finger" (F) and the "kringle-2" (K2) domain of t-PA. A model is proposed that explains inhibition of the fibrinolytic process, at the level of plasminogen activation by t-PA, directed by PAI-1 bound to fibrin. An implication of the proposed model is that t-PA/PAI-1 complexes and free t-PA compete for the same binding sites on fibrin.

Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis.

BACKGROUND: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specific differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood. METHODS: Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male-female ratios for coexisting allergic rhinitis and asthma in children (0-10 years), adolescents (11-17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000-2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratified by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives. RESULTS: From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male-female ratios (95% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male-female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively. CONCLUSIONS: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only.

Effects of high phenolic olive oil on cardiovascular risk factors: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular diseases are the world's leading cause of death. Prevention by nutrition is an easy and effective approach especially by advising foods with nutraceutic properties like high phenolic olive oil (HPOO). AIM: The aim of this review was to systematically access and meta-analyse the effects of HPOO on risk factors of the cardiovascular system and thusly to evaluate its use as a nutraceutical in prevention. DATA SYNTHESIS: Medline/PubMed, EMBase, the Cochrane Library, CAMbase and CAM-QUEST were searched through July 2013. Randomized controlled trials (RCTs) comparing high vs. low (resp. non) phenolic olive oils in either healthy participants or patients with cardiovascular diseases were included. For study appraisal the Cochrane Collaboration's risk of bias tool was used. Main outcomes were blood pressure, serum lipoproteins and oxidation markers. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated and analysed by the generic inverse variance methods using a random effects model. Eight cross over RCTs comparing ingestion (21-90 d) of high vs. low (resp. non) phenolic olive oils with a total of 355 subjects were included. RESULTS: There were medium effects for lowering systolic blood pressure (n = 69; SMD -0.52; CI -0.77/-0.27; p < 0.01) and small effects for lowering oxLDL (n = 300; SMD -0.25; CI [-0.50/0.00]; p = 0.05). No effects were found for diastolic blood pressure (n = 69; SMD -0.20; CI -1.01/0.62; p = 0.64); malondialdehyde (n = 71; SMD -0.02; CI [-0.20/0.15]; p = 0.79), total cholesterol (n = 400; SMD -0.05; CI [-0.16/0.05]; p = 0.33); HDL (n = 400; SMD -0.03; CI [-0.14/0.08]; p = 0.62); LDL (n = 400; SMD -0.03; CI [-0.15/0.09]; p = 0.61); and triglycerides (n = 360; SMD 0.02; CI [-0.22/0.25]; p = 0.90). LIMITATIONS: The small number of studies/participants limits this review. CONCLUSIONS: HPOO provides small beneficial effects on systolic blood pressure and serum oxidative status (oxLDL). HPOO should be considered as a nutraceutical in cardiovascular prevention.

Lesions of the basal forebrain alter stimulus-evoked metabolic activity in mouse somatosensory cortex.

The role that acetylcholine plays in processing sensory stimuli is beginning to be characterized; however, morphological correlates of cholinergic effects on activity patterns in sensory cortex are not available. To study this problem, unilateral neurotoxic lesions that depleted the necortex of acetylcholine were made in the basal forebrains of mice. The aim of these experiments was to study the effect of cholinergic depletion on stimulus-evoked activity in the barrel field of the mouse somatosensory cortex. One month following the lesion, 2-deoxyglucose (2DG) experiments were conducted on the lesioned and on normal mice while the animal received bilateral stimulation to the C3 whisker. The tissue was processed for acetylcholinesterase and cytochrome oxidase histochemistry and 2DG autoradiography. Evaluation of the column-like 2DG label evoked in the somatosensory cortex revealed that the activity on the lesioned side was significantly reduced in dimension and intensity from that in the normal hemisphere. On the normal side, the activated barrels averaged 641 microns in tangential width, were 76.5% above background in density, and extended from lamina I-V. On the lesioned side, the activated barrels were 485 microns in tangential width, 65.4% above background in density, and extended from lamina II-V. In other cortical regions, outside the stimulus-evoked barrel field, 2DG activity values were similar on the normal and lesioned side. Additionally, both the pattern and intensity of the cytochrome oxidase staining within the barrel field displayed no differences in either hemisphere. These studies suggest that acetylcholine plays a significant role in the processing of somatosensory information. Neurotoxic lesions that diminish cortical cholinergic innervation cause a reduction of stimulus-evoked activity levels, while underlying metabolic activity is either not affected or recovers over time.