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Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long‐term risk factor in a random cohort of middle‐aged participants. The Opera study took place in years 1991–1993, with a 24‐h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end‐points were non‐fatal and fatal CV events, and deaths of all‐causes. Follow‐up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women, p

Background Taxane treatment may be a suitable therapeutic option for patients with castration‐resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR‐Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR‐V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored. Methods Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm3. Two cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole‐genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis. Results Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, both showed upregulation of the ATP‐binding cassette sub‐family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR‐antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1‐CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment. Conclusions Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR‐V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti‐androgens.

Background Previous studies illustrated that chronic rhinosinusitis and allergic rhinitis represent individual and socioeconomic burdens to a patient. However, few studies exist on the health-related quality of life (HRQoL) amongst other rhinologic patients. Our study investigated the generic HRQoL in different rhinologic diseases. Methodology Unselected adult rhinologic patients requiring special care at the Helsinki University Hospital were enrolled in this cross-sectional, questionnaire-based prospective study in February, May, August and November 2014. Patients were mailed a medical history questionnaire and a generic 15-dimension (15D) HRQoL questionnaire. Diagnostic data were collected from electronic patient records following outpatient visits. Patient HRQoL scores were compared to an age- and sex-standardised general population sample obtained from a large national health examination survey. Results This study consisted of 337 rhinologic patients (mean age 50.2 years, 50.4% men). The mean 15D score amongst rhinologic patients (0.865) was both statistically significant and clinically poorer than that amongst the general population (0.929). Rhinologic patients fared poorly on most dimensions of the 15D instrument, particularly on sleep, discomfort and symptoms, breathing and vitality. Patients with obstructive sleep apnoea (OSA) were particularly affected. Yet, comparing the five most common rhinologic diagnostic groups revealed no significant differences in the mean 15D scores. Conclusions Rhinologic diseases, independent of the underlying cause, substantially and negatively affect patients' HRQoL. OSA decreases HRQoL in these patients, although patients without an OSA diagnosis still suffer from a clinically important impairment of HRQoL and poor quality sleep.

Out-migrating steelhead Oncorhynchus mykiss from four Puget Sound rivers and associated marine basins of Puget Sound in Washington State were examined for the parasite, Nanophyetus salmincola in 2014 to determine whether recent trends in reduced marine survival are associated with the presence of this pathogen. A subset of steelhead from three of these river-marine basin combinations was analyzed for the presence of persistent organic pollutants (POPs) to assess whether exposure to these contaminants is a contributing factor to their reduced marine survival. The prevalence and parasite load of N. salmincola were significantly higher in fish from central and southern Puget Sound than in fish from river systems in northern Puget Sound. The proportion of steelhead samples with concentrations of POPs higher than adverse effects thresholds (AETs) or concentrations known to cause adverse effects was also greater in fish from the central and southern regions of Puget Sound than in those from the northern region. Polybrominated diphenyl ether concentrations associated with increased disease susceptibility were observed in 10% and 40% of the steelhead sampled from central and southern Puget Sound regions, respectively, but in none of the fish sampled from the northern region. The AET for polychlorinated biphenyls was exceeded in steelhead collected from marine habitats: 25% of the samples from the marine basins in the central and southern regions of Puget Sound and 17% of samples from northern Puget Sound region. Both N. salmincola and POP levels suggest there are adverse health effects on out-migrating steelhead from one southern and one central Puget Sound river that have lower early marine survival than those from a river system in northern Puget Sound.

Background and purpose Atrial fibrillation (AF) and significant carotid artery stenosis (CAS) often coexist in patients with acute stroke but whether CAS affects the stroke recurrence rate in anticoagulated AF patients is largely unknown. The effect of concomitant CAS on both short- and long-term prognosis after stroke in patients with AF was evaluated. Methods The multicentre, retrospective FibStroke registry included AF patients with an ischaemic stroke or transient ischaemic attack (TIA) during 2003–2012. In this sub-study, 165 AF patients with ischaemic stroke or TIA with significant (>50%) CAS (CAS group) and 734 AF patients without CAS (non-CAS group) were identified. The median follow-up time after an index event was 3.5 (interquartile range 3.9) years. Long-term stroke recurrence rate, 30-day mortality, CHA2DS2-VASc score, other risk factors and the use and intensity of anticoagulation were assessed. Results The recurrence rate of ischaemic stroke (21.2% vs. 12.7%, P = 0.005, 8.1 vs. 3.6 events per100 follow-up years) was significantly higher in CAS patients compared to the non-CAS group despite similar anticoagulation/antithrombotic therapy. CAS patients had higher mean CHA2DS2-VASc scores than non-CAS patients (4.3 vs. 3.3, P < 0.001). However, in a multivariate analysis CAS was shown to be an independent risk factor for stroke recurrence (hazard ratio 2.02, 95% confidence interval 1.37–3.01, P = 0.001). The 30-day all-cause mortality was significantly higher in CAS patients (7.9% vs. 1.9%, P < 0.001) and CAS was an independent risk factor also for 30-day mortality (odds ratio 3.34, 95% confidence interval 1.51–7.38, P = 0.003). Conclusions In patients with AF, concomitant CAS was an independent risk factor for both long-term stroke recurrence and 30-day mortality.

Objectives We performed a post hoc analysis of outcome in patients with, versus those without, calcified target lesions from the BASE ACS trial. Background The outcome of contemporary stent implantation in patients with calcified lesions presenting with acute coronary syndrome is unknown. Methods The BASE ACS trial randomized 827 patients (1:1) presenting with acute coronary syndrome to receive either titanium-nitride-oxide-coated stents or everolimus-eluting stents. Calcified lesions were defined as moderate or severe calcification in the vessel wall by coronary angiography. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction or ischemia-driven target lesion revascularization. Follow-up was planned at 12 months, and yearly thereafter for up to 7 years. Results Of 827 patients enrolled in the trial, 352 (42.6%) had calcified target lesions. Median follow-up was 5.0 years. The incidence of MACE was higher in patients with, versus those without, calcified target lesions (19.6% vs. 12.2%, respectively, P = 0.004). This was driven by more frequent cardiac death and non-fatal myocardial infarction events (P 0.05). MACE and the other endpoints were comparable between the 2 propensity-score matched subgroups (P > 0.05 for all). Hypertension and smaller vessel size independently predicted MACE in patients treated for calcified lesions. Conclusions Patients presenting with acute coronary syndrome who were treated for calcified lesions had worse long-term clinical outcome, compared with those treated for non-calcified lesions, mainly due to more frequent safety events. In the propensity score-matched analysis, the outcome was comparable.

OBJECTIVE: Informing the child about his/her diagnosis and treatment plan is essential; research has shown that it is related to the patient's quality of life and adherence to medication.METHODS: F ...

Background Patients with atrial fibrillation (AF) frequently undergo invasive procedures. Optimal perioperative use of oral anticoagulation (OAC) and heparin bridging is not well defined. Hypothesis Discontinuation of OAC for minor procedures/operations places AF patients at risk for thromboembolism. Methods In this study, we assessed perioperative antithrombotic treatment in patients with AF who suffered a postoperative stroke or intracranial bleeding. The FibStroke Study includes AF patients with an ischemic stroke or intracranial bleed identified from the discharge registries of 4 Finnish hospitals. In total, 3632 consecutive patients developed 3252 ischemic strokes and 794 intracranial bleeds. All invasive procedures during the 30 days preceding the stroke or intracranial bleed were identified. Results A total of 194/3252 (6.0%) ischemic strokes and 23/794 (2.9%) intracranial bleeds were preceded by a procedure. Altogether, 69% of the patients were on OAC prior to index procedure, OAC was interrupted in 81.2% of the procedures preceding a stroke, and heparin bridging was used in 27.8% of interruptions. Of the procedures leading to stroke, 42.3% were low-bleeding-risk procedures, and OAC was interrupted in 84.7% of these procedures. The median time from procedure to stroke was 4 days. Heparin bridging was used in 54.5% of OAC interruptions preceding intracranial bleeding and combination of anticoagulation with antiplatelet therapy by 43.5% of patients with postoperative intracranial bleeding. Conclusions Perioperative interruption of OAC is common in patients who suffer a postoperative stroke, even in patients with low-bleeding-risk procedures. Postoperative intracranial bleeding is frequently preceded by perioperative heparin bridging.

BACKGROUND Physical functioning may be an important pre-clinical marker of chronic disease, used as a tool to identify patients at risk for future cardiometabolic abnormalities. This study evaluated if self-reported physical functioning was associated with the development of cardiometabolic abnormalities or their clustering (metabolic syndrome) over time. METHODS Participants (n = 2,254) from the Study of Women's Health Across the Nation who reported physical functioning on the Short Form health survey and had a metabolic syndrome assessment (elevated fasting glucose, blood pressure, triglycerides and waist circumference; reduced HDL cholesterol) in 2000 were included. Discrete survival analysis was used to assess the 10-year risk of developing metabolic syndrome or a syndrome component through 2010. RESULTS At baseline, the prevalence of metabolic syndrome was 22.0%. Women with substantial limitations (OR = 1.60; 95% CI: 1.12, 2.29) in physical functioning were significantly more likely to develop the metabolic syndrome compared with women reporting no limitations. Self-reported physical functioning was significantly associated with incident hypertension and increased waist circumference. CONCLUSIONS Simple screening tools for cardiometabolic risk in clinical settings are needed. Self-reported physical functioning assessments are simple tools that may allow healthcare providers to more accurately predict the course of chronic conditions.

Background Data on predictors of failure of electrical cardioversion of acute atrial fibrillation are scarce. Methods We explored 6,906 electrical cardioversions of acute (

Chitosan is a deacetylated product of chitin. Microcrystalline form of chitosan has a large adsorption area claimed to decrease gastrointestinal absorption of cholesterol. However, the long-term effect of chitosan on plasma lipids is variable, the averaged influence being negligible or lacking in mildly-to-moderately hypercholesterolaemic (4.8-6.8 mmol/l) subjects. We evaluated whether this variation and inefficacy depend on apolipoprotein E genotype. 130 middle-aged, otherwise healthy men (n=55) and women (n=75) were randomized into two treatment groups for a 7 month trial. During a 1 month run-in period all participants received placebo. Subsequently, one half first took placebo twice daily for 3 months and then 1.2 g chitosan twice daily for 3 months, and the other half vice versa in a cross-over way. Altogether 84 participants completed the study. Plasma lipids and glucose were determined at the end of each phase of the study, and all subjects undergone to the cross-over phases were apolipoprotein E genotyped. Chitosan altered plasma total, low- and high density cholesterol, triglycerides, and blood glucose in neither apolipoprotein E epsilon 4 allele carriers (n=29) nor non-carriers (n=55), compared to placebo. In conclusions, chitosan is ineffective to decrease plasma lipids in apolipoprotein E epsilon 4 carrier and non-carrier phenotypes with mildly-to-moderately increased plasma cholesterol.

SUMMARY This paper presents achievements of an on-going activity where the applicability of MIMO to satellite communications with Digital Video Broadcasting – Satellite services to Handhelds as the key application is studied. The potential satellite and hybrid satellite-terrestrial MIMO scenarios are described, and the applicable MIMO schemes for each scenario are selected. The performance of the MIMO schemes was studied by performing comprehensive computer simulations, and the main results are presented in this paper. Copyright © 2013 John Wiley & Sons, Ltd.

Background Obesity is a risk factor for glucose intolerance, but the independent role of obesity in the development of peripheral neuropathy is unclear. This study assessed the impact of body size trajectories on prevalent nerve dysfunction in community-dwelling women with and without glucose intolerance.

Bisphosphonates inhibit the development of experimental atherosclerosis and decrease the intima-media thickness of human carotid artery. Since arterial macrophages have a key role in atherogenesis, we studied whether clodronate, an antiatherogenic bisphosphonate, will suppress the appearance of macrophages generated by atheromatous process in the rabbit aorta. The atherosclerosis was caused in rabbits by means of a high-cholesterol (1%) diet, and the animals were treated simultaneously with saline (n = 11) or 25 mg/kg of clodronate disodium (n= 12) intravenously twice a week for 6 to 12 weeks. The cholesterol diet for 6 weeks caused no visible atheromatous plaques in the aorta, but feeding for 6 more weeks produced progressively atheromatous lesions. Immunohistochemistry with specific antimacrophage antibody showed an intensive accumulation of macrophages in the subendothelial layer of the aorta in cholesterol-fed rabbits treated with saline or clodronate for 6 weeks. In the aorta of rabbits treated with cholesterol diet + saline for 12 weeks, the area of immunoreactive macrophages extended from the internal elastic lamina up to the luminal surface of the aorta. However, far less immunoreactive macrophages were present in the atheromatous regions of the aorta of rabbits medicated with clodronate for 12 weeks; in the clodronate-treated animals the macrophages were located closer to the luminal surface of the aorta than in controls on saline. No atheromatous lesions and macrophages appeared in the aorta of rabbits on standard diet (n = 7). The results suggest that clodronate suppresses the appearance of cholesterol-phagocyting macrophages in arterial walls during atherogenesis.

Among the populations of Pacific salmon and steelhead Oncorhynchus mykiss (anadromous Rainbow Trout) that inhabit the Columbia River basin there are currently 13 Evolutionarily Significant Units listed as threatened or endangered under the U.S. Endangered Species Act. While habitat loss, dams, overharvest, and climate change have been implicated in declining abundance of Chinook Salmon O. tshawytscha in the Columbia River, chemical contaminants represent an additional, yet poorly understood, conservation threat. In this study we measured concentrations of persistent organic pollutants in juvenile Chinook Salmon from various Columbia River stocks and life history types to evaluate the potential for adverse effects in these threatened and endangered fish. Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDTs), recognized contaminants of concern in the Columbia basin, are the primary focus of this paper; other contaminants found in these fish, such as polybrominated diphenyl eth...

Aim: This prospective study investigated the role of viral infections in the pathogenesis of intussusception, including human herpesvirus 6 (HHV-6), a known lymphotropic virus. Methods: Fifty-three children with intussusception treated in hospital were enroled, and children of comparable age and gender served as controls. Blood, stool and throat swab specimens, as well as mesenteric lymph nodes and pieces of intestine from patients requiring surgery were tested for various viruses by PCR methods. Results: Altogether, 85% of intussusception cases showed evidence of a recent or ongoing viral infection. Among the 53 intussusception cases, adenovirus was detected in 25 (47%), HHV-6 in 24 (45%), rhinovirus in 12 (23%), cytomegalovirus in 7 (13%), enterovirus in 4 (8%) and rotavirus in 3 (6%) patients. Of the 50 whole blood samples, 44% were positive for HHV-6 and of the 16 resected mesenteric lymph nodes, 50% were positive for HHV-6. Simultaneous presence of HHV-6 and adenovirus infection correlated significantly with intussusception (OR 12.1, 95% CI 2.2 to 66.5). Conclusions: A statistically significant association was observed between adenovirus and childhood intussusception. HHV-6 was a common finding and occurred concomitantly with other viruses. A simultaneous infection with HHV-6 and adenovirus carried the highest risk for intussusception.

OBJECTIVE: Patient-physician communication and patient satisfaction are important elements of cancer care. Trust is considered to be crucial for the patient-physician relationship, yet little is to ...

Stefanius K, Ylitalo L, Tuomisto A, Kuivila R, Kantola T, Sirnio P, Karttunen T J & Makinen M J (2011) Histopathology58, 679–692 Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma Aims: To define the occurrence of KRAS and BRAF mutations, microsatellite instability (MSI), and MGMT and hMLH1 methylation and expression in colorectal serrated adenocarcinoma. Methods and results: KRAS codon 12/13 and 59/61 and BRAF V600E mutations, MSI, and MGMT and hMLH1 methylation and expression in 42 serrated adenocarcinomas and 17 serrated adenomas were compared with those in 59 non-serrated colorectal carcinomas (CRCs) and nine adenomas. KRAS and BRAF mutations were observed in 45% and 33% of serrated adenocarcinomas and in 27% and 0% of non-serrated CRCs (P

Aims: We sought to present the 5-year clinical outcome of the titanium-nitride-oxide-coated bioactive stents (BAS), as compared to paclitaxel-eluting stents (PES), in a real-world patient population. Methods: From May 2003 to November 2004, we enrolled 405 consecutive patients who underwent percutaneous coronary intervention with either BAS or PES implantation. Patients were prospectively followed up for 5 years. The primary end-point was major adverse cardiac events (MACE) at 5-year follow-up including cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization. Results: A total of 201 patients received BAS (218 lesions/221 stents) while 204 patients received PES (244 lesions/247 stents). Clinical follow-up for 5 years was completed in all patients. Cumulative MACE at the end of 5-year follow-up occurred in 34 (16.9%) patients in the BAS group, as compared to 53 (26%) in the PES group (OR 1.7, 95% CI 1.1–2.8, P = 0.03). This difference was mainly driven by a lower incidence of MI in the BAS group as compared with the PES group (9.5% vs. 20.6%, OR 2.5, 95% CI 1.4–4.4, P = 0.002). Stent thrombosis occurred in 16 (7.8%) patients in the PES group, while no one suffered stent thrombosis in the BAS group. Conclusion: BAS implantation in a real-world patient population achieves an excellent clinical outcome over 5-year follow-up, with a significantly lower incidence of MI, MACE, and stent thrombosis as compared to PES. (J Interven Cardiol 2011;24:1–8)

Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.

Previous studies have reported elevated chemical contaminant concentrations in out-migrant juvenile salmon from the lower Columbia River. Hatchery rearing is a potential exposure pathway, as contaminants have been measured in hatchery fish and feed from other regions. In this study, we analyzed for polychlorinated biphenyls (PCBs), organochlorine pesticides including dichloro-diphenyl-trichloroethanes (DDTs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs) in juvenile fall Chinook salmon Oncorhynchus tshawytscha and feed from eight hatcheries (Big Creek Hatchery, Oregon Department of Fish and Wildlife; Elochoman, Cowlitz, Washougal, Klickitat, and Priest Rapids hatcheries, Washington Department of Fish and Wildlife; Little White Salmon National Fish Hatchery; and Spring Creek National Fish Hatchery) that release fish into the lower Columbia River. In feed samples, the mean concentrations of summed PCBs, summed DDTs, and summed PAHs were 14, 27, and 370 ng/g wet...

The distribution into cerebrospinal fluid (CSF) of five 3H- or 14C-labelled beta-adrenoceptor blocking drugs given intravenously was studied in urethane-anaesthetized rats. The doses (mg/kg) were: alprenolol 5, metoprolol 1, oxprenolol 5, pindolol 0.5, propranolol 0.1 and 5. Within 15 min. a marked fraction of the given radioactivity appeared in CSF with all substances. During the follow-up period of 315 min., only propranolol, independently of dose, caused high CSF/plasma ratios (0.54-0.73) of radioactivity. The other four beta-adrenoceptor blocking drugs caused levels of CSF radioactivity which were 0.05-0.28 of that in plasma and 0.05-0.14 of the calculated levels of activity in the whole body. Since propranolol is bound to plasma proteins to a higher degree than the other drugs studied, the penetration of the unbound fraction of propranolol into rat CSF is even more pronounced than what would be expected on the basis of CSF/plasma ratio measured.

Quantitative vibratory perception threshold (VPT) measurements were performed on 102 healthy children and 79 children receiving anti-epileptic medication. Their ages ranged from three to 16. The VPTs correlated significantly with age and height. The rise in VPT with age may be associated with decreased receptor density. The level of mental alertness seemed to have no significant effect on vibratory perception. Only three of the children on anti-epileptics showed elevated VPTs. On the basis of this study, epileptic children seem to be free of the adverse effects of medication which occur later in adulthood. Children as young as three or four are quite capable of co-operating in this examination. The method can be recommended for use in follow-up studies of children and as a diagnostic aid when a disturbance of the sensory tract is suspected.

Treatment with the angiotensin-converting enzyme inhibitor, quinapril, has been shown to normalize increased dihydropyridine sensitivity and impaired potassium relaxation, characteristic features of arterial smooth muscle in spontaneously hypertensive rats, and also reduce the concentration of plasma digoxin-like immunoreactivity in these animals. However, whether angiotensin II receptor blocker therapy can beneficially influence these variables is not known. Therefore, we compared the effects of 10-week losartan and enalapril treatments (15 and 4 mg/kg/day, respectively) on functional responses of mesenteric arterial rings in spontaneously hypertensive rats and Wistar-Kyoto rats. Both losartan and enalapril normalized blood pressure, cardiac mass, and media to lumen ratio without significantly changing the media cross-sectional area in the mesenteric artery of spontaneously hypertensive rats (i.e. induced outward remodelling). The inhibitory effect of the calcium entry blocker nifedipine on calcium-evoked contractions was similar and less marked in arterial preparations from Wistar-Kyoto rats and losartan- and enalapril-treated spontaneously hypertensive rats than in those from untreated spontaneously hypertensive rats. Furthermore, the relaxations of arterial rings induced by the return of potassium to the organ bath (upon precontractions elicited by potassium-free solution) were used to evaluate the function of vascular Na + ,K + -ATPase. The rate of potassium relaxation was faster in losartan- and enalapril-treated spontaneously hypertensive rats and all Wistar-Kyoto groups than in untreated spontaneously hypertensive rats, and the response was effectively inhibited by the sodium pump inhibitor ouabain. Both treatments especially augmented the ouabain-sensitive part of the potassium-relaxation in spontaneously hypertensive rats, indicating the involvement of the sodium pump in this response. However, no significant changes in plasma digoxin-like immunoreactivity were observed. In conclusion, the outward remodelling following long-term AT 1 -receptor blockade and angiotensin-converting enzyme inhibition in spontaneously hypertensive rats was associated with normalization of the increased dihydropyridine sensitivity of arteries. Both losartan and enalapril treatments also augmented arterial potassium relaxation in spontaneously hypertensive rats, suggesting enhanced function of Na + ,K + -ATPase, but this effect could not be attributed to changes in circulating sodium pump inhibitor concentration.

Hypothesis: Standard of care in laryngopharyngeal reflux (LPR) is acid suppression therapy. Its treatment efficacy and mechanism of action are not well documented. No objective study investigating the molecular patterns of inflammation in LPR or in response to proton pump inhibitor (PPI) treatment has been accomplished. We hypothesized that gene expression levels of mediators of inflammation—interleukin 6 (IL6), interleukin 8 (IL8), interleukin 1a (IL1a), interleukin 1b (IL1b), transforming growth factor beta 1 (TGFβ1), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and tumor necrosis factor alpha (TNFα)—in posterior larynx tissue would be increased in those with diagnosed LPR and would be then reduced with PPI treatment. Study Design: Prospective uncontrolled trial. Methods: Biopsies from the posterior larynx were taken from 25 participants with LPR before and after a 10-week period with rabeprazole (40 mg). RNA isolation and real-time PCR was used to measure gene expression levels. Results: No significant differences were measured for any of the cytokines, either for the entire participant group (n = 25) or for the subset of participants who did not have a previous history of PPI usage (n = 15). In those participants who had a history of PPI usage (n = 10), a significant increase in gene expression levels post medication was measured for TGFβ1 (P = .0396), VEGF (P = .0216), IL8 (P = .0297), after adjusting for compliance, subjective improvement, and reflux severity. Conclusions: Our findings are provocative and speak to the unresolved understanding of the pathophysiology of LPR, its diagnosis, and its differences from gastroesophageal reflux disease.

Background: Central vein leads are known to predispose to venous obstruction. Although usually asymptomatic, obstruction may render electrode removal difficult. This study aimed at quantifying changes in venous calibers in a prospective fashion by intravenous contrast venography (ICV) before and after pacemaker (PM) or cardioverter-defibrillator implantation. Methods: One hundred and fifty (mean age 67; 61% male) consecutive patients were enrolled, and followed for 6 months. A successful ICV was done at baseline prior to implantation and at 6-month follow-up in 136 (91%) patients. Minimum (Dmin) and maximum (Dmax) vessel diameters were obtained from both ICVs. A new stenosis was defined as a 50% diameter reduction in a venous segment when compared to baseline. We implanted a total of 230 electrodes: 47 (34.6%) single lead, 84 (61.8%) 2-lead, and 5 (3.7%) 3-lead systems. Results: At baseline ICV, 10 patients (7%) were found to have venous anomalies, including 8 patients with obstructive lesions, 1 patient with a persistent left superior vena cava, and 1 patient with double axillary vein. At 6 months, a new obstructive venous lesion had developed in a total of 19 (14%) patients, none of whom exhibited any local symptoms. Of these patients 14 (10%) had a stenosis (mean Dmin 4.6 mm and diameter 38% of baseline), and 5 (3.6%) had a complete venous occlusion. In most cases the new stenosis developed in a location where the vessel was narrowest at baseline. Clinical predictors for the development of stenosis were atrial fibrillation at baseline and biventricular PM implantation. Conclusions: This is the first systematic study to quantify venous changes after PM or ICD implantation. Our study shows that venous anomalies rendering PM implantation difficult are not infrequent. The incidence of new venous obstruction was 14%. Atrial fibrillation and biventricular PM implantation were independent predictors of venous obstruction.

The efficacy of hyperimmune bovine colostrum received from cows immunized with simian rotavirus SA11 in the treatment of rotavirus gastroenteritis was compared in a randomized double-blind trial to colostrum and ordinary milk preparations. One hundred and thirty-five children aged 6-30 months with rotaviral gastroenteritis received either hyperimmune bovine colostrum (n=42), ordinary colostrum (n=42) or milk (n=41) as a 100 ml solution four times/d for 4 d. Even though the differences were in favour of hyperimmune bovine colostrum in all the variables evaluated [greater weight gain (403 vs 343 g), shorter duration of diarrhoea (3.1 vs 3.6 d), fewer stools during 6 d (11.5 vs 13.6) and fewer stools during the first 3 d (9.3 vs 11.3)], all the differences were statistically insignificant. Differences of this size are clinically unimportant in well-nourished immunocompetent children, but we suggest that the hyperimmune bovine colostrum tested in our trial had some effects in the treatment of acute rotaviral gastroenteritis and should be evaluated further.

Young age at first sexual intercourse (AFI) is an important risk factor for cervical cancer, but no simple statistical model of its influence has been established. We investigated the relationship between risk of cervical carcinoma and time since first intercourse using data on monogamous women (5,074 cases and 16,137 controls) from the International Collaboration of Epidemiological Studies of Cervical Cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from pooled data on 20 studies using conditional logistic regression. The OR for invasive cervical carcinoma is approximately proportional to the square of time since first intercourse (exponent 1.95, 95% CI: 1.76-2.15) up to age 45. First cervical infection with human papillomavirus (HPV) often occurs soon after first sexual intercourse, so early AFI is a reasonable proxy for early age at first exposure to HPV. In addition, age-specific incidence rates of cervical cancer in unscreened populations remain fairly constant above age 45. Cervical cancer thus resembles other cancers caused by strong early-stage carcinogens, with incidence rates proportional to a power of time since first exposure and also resembles cancers of the breast and other hormone-dependent epithelia, where a similar flattening of age-specific incidence rates is seen at the time menopausal changes start. Taken together, these observations suggest that HPV vaccination may prevent the majority of cervical cancers by delaying HPV infection without necessarily providing lifetime protection against HPV. Copyright © 2011 UICC.

OBJECTIVES: To compare the prevalence of extraesophageal reflux (EER) in patients with heartburn, posterior laryngitis (PL), and in healthy controls.STUDY DESIGN AND SETTING: A retrospective and prospective study including a total of 101 subjects who underwent 24-hour dual-probe pH monitoring.RESULTS: 52% of the subjects with heartburn had EER. No significant differences were found between the PL and heartburn groups for any pharyngeal reflux parameters. However, supine pharyngeal reflux was significantly more prevalent in heartburn patients with GERD than in PL patients and healthy controls (P < 0.05). Significant positive correlation (P < 0.01) was found between the percentage of time pH

The objective of this study was to evaluate the symptoms and clinical characteristics in patients with autoimmune vocal fold deposits. Fourteen patients underwent videolaryngostroboscopic examination and voice recording. Eleven of the 14 patients underwent rheumatological examination. In all cases, endoscopic examination showed transverse white-yellow band lesions in the middle of the membranous portion of the vocal folds. In most cases, the lesions were bilateral but not exactly opposing each other. The most common voice characteristics were instability and intermittent aphonia. Inflammatory disease was present in 10 patients; five of these had rheumatoid arthritis (RA). No immunological signs common for all patients could be found. The histological examination was consistent with rheumatoid nodules. Vocal fold deposits, occurring most often in patients with RA, is an uncommon cause of hoarseness. Because the patients may have hoarseness as their primary symptom, it is important for otolaryngologists to be familiar with this disorder.