Targeting danger-associated molecular patterns after myocardial infarction

Introduction: Myocardial infarction (MI) provokes an intense inflammatory response that can lead to left ventricular adverse remodeling and heart failure (HF). The prognosis of HF patients is poor and related to a decreased quality of life and considerable health care costs. Hence, targeting the early inflammatory response after MI provides an interesting target to attenuate left ventricular remodeling and prevent HF.

Areas covered: In the current review, we discuss the theory that our immune system does not distinguish between self and non-self, but rather senses danger. So-called danger-associated molecular patterns (DAMPs) serve as ligands for pattern recognition receptors (PRRs), which act as signal transduction molecules to induce a pro-inflammatory state. Many different DAMPs and PRRs have been identified recently. Here, we provide a concise overview of their interactions as well as their role in the inflammatory response after MI.

Expert opinion: Interference with Toll-like receptor (TLR) 2, TLR4 and NLRP3-inflammasome signaling has consistently shown to reduce infarct size and preserve cardiac function post-MI in experimental animal models. Since clinically applicable inhibitors have been developed for these pathways, the path has been cleared to assess whether these promising results can be translated into the human situation.     

Axillary lymph node clearance in patients with positive sentinel lymph node biopsy

Introduction

The use of adjuvant radiotherapy is standard practice following breast conserving surgery and mastectomy in selected patients. Prospective clinical trials are currently being designed to assess the effect of omitting axillary lymph node clearance (ALNC) in selected patients. The aim of this study was to identify the percentage of patients understaged and not considered for postmastectomy radiotherapy (PMRT) and/or supraclavicular fossa radiotherapy (SCFRT) with positive sentinel lymph node (SLN) macrometastasis if the proposed prospective trial inclusion/exclusion protocols are followed.

Methods

A total of 38 women who were found negative for axillary metastases preoperatively but positive at SLN biopsy and who had ALNC were analysed. PMRT or SCFRT was offered to patients if ≥4 positive lymph nodes (including sentinel nodes) were positive for macrometastasis and/or a tumour size of ≥5cm was detected. Fisher’s exact test was used to determine the statistical significance of omitting ALNC.

Results

The mean age of the 38 patients was 55 years. A fifth (21.1%) of patients had T1, 76.3% had T2 and 2.6% had T3 disease. The percentage of positive SLNs was 52.6% (1 node), 34.2% (2 nodes) and 13.1% (3 nodes). The number of positive nodes at clearance was 0–3. If the inclusion criteria for trials that consider omitting ALNC are followed (eg POSNOC trial), 23.7% of patients (p=0.0001) with ≥4 positive nodes (including SLNs) would not be offered SCFRT and PMRT. Similarly, if multicentric disease were to be excluded from the trial criteria, the proportion of undertreated patients would reduce by 15.7%.

Conclusions

Our study has shown a significant risk of missing patients for PMRT or SCFRT if no ALNC is offered in the presence of SLN macrometastasis. Tumour multicentricity is an important factor in predicting high axillary nodal involvement. Consequently, exclusion of T2 tumours with multicentric involvement in trials considering omitting ALNC may be more appropriate.     

The effect of exclusion of cases with unrecorded best estimate of gestational age on the estimates of preterm birth rate

Objectives  To investigate the effect of excluding cases with unrecorded best estimate of gestational age at birth on pregnancy outcome reporting and to determine the reasons for unrecorded gestational age data.
Design  Prospective study.
Setting  Fifteen maternity units in North West London.
Population  497 105 women who booked for antenatal care from 1988 to 1998.
Method  Multiple logistic regression analysis.
Main outcome measures  Preterm birth rate of, and the factors associated with, cases with unrecorded best estimate of gestational age at birth.
Results  Of the 53 981 cases with an unrecorded best estimate of gestational age at birth, by using additional data, it was possible to compute a new best estimate of gestational age in 80%. In this latter group, the preterm birth rate was 42% (95% CI 41.5–42.6). The corrected, overall preterm birth rate in North West London (9.8%, 9.7–9.9) was higher than the original estimate (7.6%, 7.5–7.7), which included only cases with recorded data on gestational age at birth. The most significant factors associated with an unrecorded gestational age were no ultrasound scan (OR 49, P  <   0.001), and preterm birth <31 weeks (OR 30, P  <   0.001).
Conclusions  The incidence of preterm birth are likely to be under-reported in studies where only cases with readily available gestational age data are included. In routinely collected maternity data, human omission is an important contributing factor for an unrecorded best estimate of gestational age at birth. This is associated with the urgent transfer of babies to the neonatal intensive care unit.     

MR evaluation of developmental venous anomalies: medullary venous anatomy of venous angiomas.

PURPOSETo present characteristic MR findings of developmental venous anomalies (DVAs) in terms of location of caput and draining veins, to correlate these findings with normal medullary venous anatomy, and to suggest an approach to the evaluation of DVAs by means of MR imaging.METHODSWe reviewed the contrast-enhanced MR examinations of 61 patients with DVA, which were selected from 4624 consecutive cranial MR examinations. Site of the DVA and size and direction of draining veins were recorded.RESULTSSeventy-two DVAs with 78 draining veins were located: 18 were juxtacortical, 13 were subcortical, and 41 were periventricular or deep. Twenty-six of the DVA caputs were frontal, 16 were parietal, 13 were in the brachium pontis/dentate, seven were in the temporal lobe, three were in the cerebellar hemisphere, three were in the occipital lobe, three were in the basal ganglia, and one was in the pons. The draining veins were superficial in 29 cases and deep in 49. Of the 36 supratentorial deep draining veins, 16 were in the trigone/occipital horn, 11 were in the mid-body of the lateral ventricle, seven were in the frontal horn, and two were in the temporal horn. Among the 14 infratentorial deep draining veins, five were in the lateral recess of the fourth ventricle, four were anterior transpontine veins, three were lateral transpontine veins, and two were precentral cerebellar veins.CONCLUSIONThe DVA caputs and their draining veins occurred in typical locations that could be predicted from the normal medullary venous anatomy, with the frontal, parietal, and brachium pontis/dentate being the most common locations. Drainage can occur in superficial cortical veins or sinuses or in deep ventricular veins or in both, no matter where the caput is located. Whether drainage was superficial or deep could not be predicted on the basis of the site of the DVA caput. Contrast-enhanced T1-weighted MR images showed the DVAs best, but diagnosis could be made from T2-weighted MR images.     

The antidipsogenic action of peripheral prostaglandin E2

Intraperitoneal (IP) injection of 50 μg/kg prostaglandin E₂ (PGE₂) suppresses water intake elicited by cellular dehydration, intracerebroventricular injection of angiotensin II (A II) and, for a shorter duration, water deprivation. At a dose of 100 μg/kg, IP PGE₂ reduces drinking to all of these stimuli as well as to hypovolemia. A 10 μg/kg dose of PGE₂ has not effect on drinking under any of the conditions tested. Intraperitoneal PGE₂, at either 50 or 100 μg/kg, does not support the formation of a conditioned taste aversion suggesting that PGE may act via specific inhibition of drinking rather than by producing a generalized malaise. Although both central and peripheral administration of PGE suppresses water intake, the findings that peripheral PGE₂ reduces drinking to cellular dehydration but has minimal effects on drinking due to hypovolemia are in marked contrast to the actions reported for intracranial PGE. In addition, peripheral PGE₂ reduces body temperature whereas centrally applied PGE induces thermogenesis. These data may indicate differential roles and/or mechanisms by which central and peripheral PGE may control water intake.     

Copulatory behavior and the initiation of pregnancy in California voles (Microtus californicus).

The copulatory behavior of Microtus californicus and its effect on pregnancy initiation were examined in two experiments. In experiment 1 18 males and 18 females which had received exogenous hormones participated in 54 tests of copulatory behavior, each continued to a satiety criterion of 30 min with no copulations. The basic pattern involved no lock, intravaginal thrusting, ejaculation possible on a single insertion and multiple ejaculation. Ejaculation frequency ranged from 1 to 5, with a mean of 2.2. In experiment 2, it was found that all females receiving satiety tests of copulatory behavior while in male-induced estrus ovulated and became pregnant. Whereas all 10 females receiving one ejaculation ovulated, only 60% became pregnant. Thus, it appears that copulation beyond one ejaculation functions in increasing the likelihood of pregnancy. By comparing different species of Microtus it is proposed that copulatory patterns in which males persist for many thrusts and ejaculations may have evolved in conjunction with ornate penile morphology, large litter sizes, and high stimulus requirements for the initiation of ovulation and a funtional luteal phase.     

导数比率法测定维磷补汁中咖啡因的含量

本文应用国产7520紫外分光光度计,用导数比率法,测定维磷补汁中咖啡因的含量。标准曲线的相关系数r=0.9996。平均回收率为100.2%,CV=0.11%。     

The impact of CNS-directed treatment on quality of life in childhood cancer survivors

Purpose

Pediatric cancer survivors may have lower quality of life (QoL), but most research has assessed outcomes either in treatment or long-term survivorship. We focused on early survivorship (i.e., 3 and 5 years post-diagnosis), examining the impact of CNS-directed treatment on child QoL, as well as sex and age at diagnosis as potential moderators.

Methods

Families of children with cancer (ages 5–17) were recruited at diagnosis or relapse (N?=?336). Survivors completed the PedsQL at 3 (n?=?96) and 5 years (n?=?108), along with mothers (101 and 105, respectively) and fathers (45 and 53, respectively). The impact of CNS treatment, sex, and age at diagnosis on child QoL was examined over both time since diagnosis and time since last treatment using mixed model analyses.

Results

Parent-report of the child’s total QoL was in the normative range and stable between 3 and 5 years when examining time since diagnosis, while child reported QoL improved over time (p?=?0.04). In terms of time since last treatment, mother and child both reported the child’s QoL improved over time (p?=?0.0002 and p?=?0.0006, respectively). Based on parent-report, males with CNS-directed treatment had lower total QoL than females and males who did not receive CNS-directed treatment. Age at diagnosis did not moderate the impact of treatment type on total QoL.

Conclusions

Quality of life (QoL) in early survivorship may be low among males who received CNS-directed treatment. However, this was only evident on parent-report. Interventions to improve child QoL should focus on male survivors who received CNS-directed treatment, as well as females regardless of treatment type.