A prospective study of body size in different periods of life and risk of premenopausal breast cancer.

The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer.     

Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling

Amorphous silica nanoparticles (SiNPs) have previously been shown to induce marked cytokine (interleukin-6; IL-6 and interleukin-8; CXCL8/IL-8) responses independently of particle uptake in human bronchial epithelial BEAS-2B cells. In this study the involvement of the mitogen-activated protein kinases (MAP-kinases), nuclear factor-kappa Β (NF-κΒ) and in particular tumour necrosis factor-α converting enzyme (TACE) and—epidermal growth factor receptor (EGFR) signalling pathways were examined in triggering of IL-6 and CXCL8 release after exposure to a 50 nm silica nanoparticle (Si50). Exposure to Si50 increased phosphorylation of NF-κΒ p65 and MAP-kinases p38 and JUN-N-terminal protein kinase pathways (JNK), but not extracellular signal regulated kinases (ERK). Inhibition of NF-κΒ and p38 reduced the cytokine responses to Si50, whereas neither JNK- nor ERK-inhibition exerted any significant effect on the responses to Si50. Increases in membrane-bound transforming growth factor-α (TGF-α) release and EGFR phosphorylation were also observed after Si50 exposure, and pre-treatment with inhibitors of these pathways reduced the release of IL-6 and CXCL8, but did not affect the Si50-induced phosphorylation of p38 and p65. In contrast, p38-inhibition partially reduced Si50-induced TGF-α release, while the p65-inhibition was without effect. Overall, our results indicate that Si50-induced IL-6 and CXCL8 responses in BEAS-2B cells were regulated through combined activation of several pathways, including NF-κΒ and p38/TACE/TGF-α/EGFR signalling. The study identifies critical, initial events in the triggering of pro-inflammatory responses by nanoparticles.     

Perception of longitudinal body axis in microgravity during parabolic flight

It has been proposed that an internal representation of body vertical has a prominent role in spatial orientation. This investigation investigated the ability of human subjects to accurately locate their longitudinal body axis (an imaginary straight body midline running from head to toes) while free-floating in microgravity. Subjects were tested in-flight, as well as on ground in normal gravity in both the upright and supine orientations to provide baseline measurements. The subjects wore a goggle device and were in total darkness. They used knobs to rotate two luminous lines until they were parallel to the subjective direction of their longitudinal body axis, in the roll (right/left) and the pitch (forward/backward) planes. Results showed that the error between the perceived and the objective direction of the longitudinal body axis was significantly larger in microgravity than in normal gravity. This error in this egocentric frame of reference is presumably due to the absence of somatosensory cues when free-floating. Mechanical pressure on the chest using an airbag reduced the error in perception of the longitudinal body axis in microgravity, thus improving spatial orientation.     

Intramuscular ketorolac versus oral ibuprofen for pain relief in first-trimester surgical abortion: a randomized clinical trial

Objective

Oral nonsteroidal antiinflammatory medications (NSAIDs) have been shown to reduce pain with first-trimester surgical abortion compared to placebo, but it is unclear if one NSAID is better than another. Some providers administer intramuscular ketorolac, though data regarding its efficacy in abortion are limited. This study was designed to compare oral ibuprofen to intramuscular ketorolac for pain management during first-trimester surgical abortion.

Study Design

This was a randomized, double-blind, controlled trial. Women undergoing first-trimester surgical abortion with local anesthesia were randomized to preprocedural oral ibuprofen, 800 mg given 60–90 min preprocedure, or intramuscular ketorolac, 60 mg given 30–60 min preprocedure. The primary outcome was pain with uterine aspiration on a 21-point, 0–100, numerical rating scale. Secondary outcomes included pain with cervical dilation, postoperative pain and patient satisfaction.

Results

Ninety-four women were enrolled; 47 were randomized to ibuprofen and 47 to ketorolac. The groups did not differ with regards to demographics, reproductive history or Depression Anxiety Stress Scale scores. Mean pain scores for suction curettage did not differ between groups (52.3 vs. 56.2, p=.53). There was also no difference in pain with cervical dilation (41.6 vs. 45.4, p=0.48) or postoperative pain (22.3 vs. 15.0 p=.076), though patients in the ketorolac group experienced significantly greater arm pain than those who received a placebo injection (30.4 vs. 15.6, p<.001). Satisfaction with pain control did not differ significantly by group.

Conclusions

Intramuscular ketorolac does not offer superior pain control compared to oral ibuprofen for first-trimester surgical abortion.

Implications

Intramuscular ketorolac does not offer superior pain control over oral ibuprofen during first-trimester surgical abortion, is more expensive and causes patients significant arm discomfort. Its use should therefore be reserved for patients who cannot tolerate oral NSAIDs.     

Pain tolerance after stroke: The Tromsø study

Background

Stroke lesions might alter pain processing and modulation by affecting the widely distributed network of brain regions involved. We aimed to compare pain tolerance in stroke survivors and stroke-free persons in the general population, with and without chronic pain.

Methods

We included all participants of the sixth and seventh wave of the population-based Tromsø Study who had been tested with the cold pressor test (hand in cold water bath, 3°C, maximum time 106 s in the sixth wave and 120 s in the seventh) and who had information on previous stroke status and covariates. Data on stroke status were obtained from the Tromsø Study Cardiovascular Disease Register and the Norwegian Stroke Register. Cox regression models were fitted using stroke prior to study attendance as the independent variable, cold pressor endurance time as time variable and hand withdrawal from cold water as event. Statistical adjustments were made for age, sex, diabetes, hypertension, hyperlipidaemia, body mass index and smoking.

Results

In total 21,837 participants were included, 311 of them with previous stroke. Stroke was associated with decreased cold pain tolerance time, with 28% increased hazard of hand withdrawal (hazard ratio [HR] 1.28, 95% CI 1.10–1.50). The effect was similar in participants with (HR 1.28, 95% CI 0.99–1.66) and without chronic pain (HR 1.29, 95% CI 1.04–1.59).

Conclusions

Stroke survivors, with and without chronic pain, had lower cold pressor pain tolerance, with possible clinical implications for pain in this group.

Significance

We found lower pain tolerance in participants with previous stroke compared to stroke-free participants of a large, population-based study. The association was present both in those with and without chronic pain. The results may warrant increased awareness by health professionals towards pain experienced by stroke patients in response to injuries, diseases and procedures.     

Advanced life support performance with manual and mechanical chest compressions in a randomized,multicentre manikin study

Aim of the studyClinical mechanical chest compression studies report diverging outcomes. Confounding effects of variability in hands-off fraction (HOF) and timing of necessary tasks during advanced life support (ALS) may contribute to this divergence. Study site variability in these factors coupled to randomization of cardiopulmonary resuscitation (CPR) method was studied during simulated cardiac arrest prior to a multicentre clinical trial.MethodAmbulance personnel from four sites were tested in randomized, simulated cardiac arrest scenarios with manual CPR or load-distributing band CPR (LDB-CPR) on manikins. Primary emphasis was on HOF and time spent before necessary predefined ALS task (ALS milestones). Results are presented as mean differences (confidence interval).ResultsAt the site with lowest HOF during manual CPR, HOF deteriorated with LDB-CPR by 0.06 (0.005, 0.118, p = 0.04), while it improved at the two sites with highest HOF during manual CPR by 0.07 (0.019, 0.112, p = 0.007) and 0.08 (0.004, 0.165, p = 0.042). Initial defibrillation was 29 (3, 55, p = 0.032) s delayed for LDB-CPR vs. manual CPR. Other ALS milestones trended toward earlier completion with LDB-CPR; only significant for intravenous access, mean difference 70 (24, 115, p = 0.003) s.ConclusionIn this manikin study, HOF for manual vs. mechanical chest compressions varied between sites. Study protocol implementation should be simulation tested before launching multicentre trials, to optimize performance and improve reliability and scientific interpretation.     

Intestinal injury after thoracic aortic cross-clamping in the pig

BACKGROUND: The mucosal surface epithelium is an essential part of the functional intestinal barrier, but its structural response to ischemia/reperfusion is only partly characterized. The purpose of this study was to provide a detailed morphological evaluation of intestinal surface epithelium after aortic cross-clamping. MATERIAL AND METHODS: Pigs were subjected to thoracic aortic cross-clamping for 60 min and subsequent reperfusion for 120 min. Tissue blood flow and high-energy phosphates were measured with microspheres and HPLC, respectively. Urinary excretion of (14)C polyethylene glycol (MW 4000 Da) (PEG-4000), loaded into an intestinal loop, provided an index of intestinal permeability. RESULTS: Jejunal blood flow was restored at 10 min after aortic declamping. Denudation of the basement membrane of the intestinal villi tips, as a consequence of epithelial shedding, increased markedly during the initial 60 min of reperfusion (P = 0.002). During the following 45 min, the denuded basement membrane was partly covered with low cuboidal and squamous-shaped cells extending lamellipodia over a wavy basement membrane. Restoration of ATP at 60 min after aortic declamping correlated inversely to the extent of denuded basement membrane (r = 0.75, P = 0.032). Permeability of PEG-4000 increased markedly after aortic declamping and was linearly correlated to the area of denuded basement membrane (r = 0.87, P = 0.01). CONCLUSIONS: Reperfusion for 2 h after aortic cross-clamping is associated with initial aggravation of ischemia-induced injury in the porcine jejunum, but thereafter with restitution of the surface epithelium. Restoration of ATP may be important to avoid intestinal injury after ischemia. Increased permeability of a macromolecule in response to reperfusion is closely correlated to injury of the surface epithelium.     

Risk for invasive and borderline epithelial ovarian neoplasias following use of hormonal contraceptives: the Norwegian-Swedish Women's Lifestyle and Health Cohort Study

The risk of ovarian epithelial neoplasia following use of hormonal contraceptives (HC) was examined in data from the Norwegian-Swedish Women's Lifestyle and Health cohort including 103551 women aged 30-49 years in 1991-92. Follow-up through 2000 produced 214 incident cases of histologically confirmed epithelial ovarian neoplasias (135 invasive and 79 borderline cases). Using the Cox proportional hazard models, ever having used HC was associated with a decreased relative risk of epithelial ovarian cancer of 0.6 (95% CI 0.5-0.8). The effect of duration of HC use was convincing (P for trend <0.0001), and more important than age at start of use or time since first or last use. There was no significant difference between the effects of combined oral contraceptives and progestins-only contraceptives on risk (P=0.98). Similarly, there was no significant difference between the effects of ever use of HC on invasive and borderline ovarian neoplasia (P=0.37). In this cohort, use of HC seems to reduce the risk of epithelial ovarian neoplasia markedly and persistently in relation to the duration of use.