Widespread Hyperalgesia in Adolescents With Symptoms of Irritable Bowel Syndrome: Results From a Large Population-Based Study

Widespread hyperalgesia is well documented among adult patients with irritable bowel syndrome (IBS), but little is known about pain sensitivity among adolescents with IBS. We examined pain sensitivity in 961 adolescents from the general population (mean age 16.1 years), including pain threshold and tolerance measurements of heat (forearm) and pressure pain (fingernail and shoulder) and cold pressor tolerance (hand). Adolescents with IBS symptoms (Rome III criteria) had lower heat pain thresholds compared to controls after adjustments for sex, comorbid pain, and psychological distress (mean difference = –.8°C; 95% confidence interval [CI] = ?1.6 to ?.04). Similar results were found for pressure pain threshold at the shoulder (mean difference = ?46 kPa; 95% CI = ?78 to ?13) and fingernail (mean difference = –62 kPa; 95% CI = ?109 to ?15), and for an aggregate of all 3 threshold measures (z-score difference = ?.4; 95% CI = ?.6 to ?.2), though pressure pain threshold differences were nonsignificant after the final adjustments for psychological distress. No difference of pain tolerance was found between the IBS cases and controls. Our results indicate that adolescents in the general population with IBS symptoms, like adults, have widespread hyperalgesia.PerspectiveThis is the first report of widespread hyperalgesia among adolescents with IBS symptoms in the general population, with lower pain thresholds found to be independent of sex and comorbid pain. Our results suggest that central pain sensitization mechanisms in IBS may contribute to triggering and maintaining chronic pain symptoms.     

Lower airway bacterial colonization in asymptomatic smokers and smokers with chronic bronchitis and recurrent exacerbations

Bacterial colonization of the lower airways in patients with chronic bronchitis (CB) has been described mainly in patients with co-existing chronic obstructive pulmonary disease (COPD). Although smoking has been identified as a risk factor for bacterial colonization it is not known whether asymptomatic smokers (AS) can be colonized. The aim of this study was to study lower airway bacterial colonization in smokers with stable CB and recurrent exacerbations and compare with AS and healthy never-smokers (NS). Thirty-nine smokers with CB and recurrent exacerbations (median FEV1 85% of predicted normal), 10 AS and 10 NS, underwent bronchoscopy and a two-step bronchoalveolar lavage (BAL) procedure where the first portion (20 ml, 'pre-BAL') was recovered separately from the rest (140 ml, 'BAL'). The degree of oropharyngeal contamination of pre-BAL and BAL samples was evaluated by cytology. Semiquantitative bacterial cultures were performed on all samples. Higher bacterial numbers than 10(3) colony-forming units (cfu) x ml(-1) in BAL were found only in the two smoking groups. Using 10(3) cfu x ml(-1) as cut-off, 6/10 (60%) in the AS-, and 7/35 (20%) in the CB-group were colonized in the lower airways. In all, 29% of all smokers had bacterial colonization. Only bacteria belonging to the normal oropharyngeal flora were found. The proportion of samples with oropharyngeal contamination was significantly lower in BAL than in pre-BAL (5% vs. 21%, P=0.039). The proportion of sterile samples was significantly higher in BAL than in pre-BAL (49% vs. 26%, P=0.002). Lower airway bacterial colonization was found both in asymptomatic smokers and in patients with CB. Colonization with potential respiratory pathogens is uncommon in patients with CB and recurrent exacerbations without severe airflow obstruction. The two-step BAL procedure seems to decrease oropharyngeal contamination.     

Prognostic significance of recurrent chromosomal aberrations detected by comparative genomic hybridization in sporadic colorectal cancer

Colorectal carcinomas are characterized by frequent recurrent gains and losses of chromosomal material, especially gains of chromosome arms 20q and 13q, and losses of chromosome arms 18q and 4q. These may be important in the development and progression of colorectal carcinomas. Chromosomal aberrations detected by comparative genomic hybridization in 67 sporadic colorectal carcinomas were examined for their possible associations with patient survival. Dukes' stage, tumor DNA ploidy status, and TP53 genotype/phenotype were also examined for the same. Patients with losses of chromosomal arms 1p, 4q, 8p, 14q, or 18q or gain of chromosomal arm 20q had significantly shorter survival times than those without these aberrations (univariate relative risk 3.45, 2.71, 3.32, 3.26, 3.32, 3.91, respectively), as did patients with more than six chromosomal aberrations per tumor than those with fewer than six aberrations (univariate relative risk 3.26, P = 0.013). DNA aneuploidy and Dukes' stage C + D resulted in poor patient survival (univariate relative risk 3.58, 3.39, respectively). Dukes' stage C + D, 1p loss and 8p loss emerged as the only independent prognostic parameters (relative risk 3.22, 2.53, 2.45, respectively) when entered into multivariate survival analysis together with other significant parameters from univariate survival analysis. Loss of chromosome arm 1p, 4q, 8p, 14q, or 18q or gain of chromosome arm 20q thus results in shortened survival times in colorectal cancer patients. 1p loss and 8p loss were shown to be independent predictors of poor prognosis.     

18F-FDG PET in the management of patients with anaplastic thyroid carcinoma

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18F-FDG PET to the clinical management of patients with ATC. METHODS: All patients with ATC studied with 18F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded. RESULTS: Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management. CONCLUSIONS: ATC demonstrates intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.     

Grading of myocardial dysfunction by tissue Doppler echocardiography: a comparison between velocity, displacement, and strain imaging in acute ischemia.

OBJECTIVES: The aim of the study was to compare the ability of the tissue Doppler echocardiographic imaging (TDI) modalities velocity, strain, and displacement to quantify systolic myocardial function. BACKGROUND: Several TDI modalities may be used to quantify regional myocardial function, but it is not clear how the different modalities should be applied. METHODS: In 10 anesthetized dogs we measured left ventricular pressure, longitudinal myocardial velocity, strain, and displacement by TDI at baseline and during left anterior descending coronary artery (LAD) stenosis and occlusion. Reference methods were segmental shortening by sonomicrometry and segmental work. In 10 patients with acute anterior wall infarction (LAD occlusion) and 15 control subjects, velocity, strain, and displacement measurements were performed. RESULTS: In the animal study, systolic strain correlated well with segmental shortening (r = 0.96, p < 0.01) and work (r = 0.90, p < 0.01), and differentiated well between non-ischemic (-13.5 +/- 3.2% [mean +/- SD]), moderately ischemic (-6.5 +/- 2.8%), and severely ischemic myocardium (7.1 +/- 13.2%). The ratio post-systolic strain/total strain also differentiated well between levels of ischemia. Displacement and ejection velocity had weaker correlations with segmental shortening (r = 0.92 and r = 0.74, respectively) and regional work (r = 0.85 and r = 0.69), and there was marked overlap between values at baseline and at different levels of ischemia. In the human study, systolic strain differentiated well between infarcted and normal myocardium (1.0 +/- 5.0% vs. -17.8 +/- 3.8%), whereas systolic displacement (-0.3 +/- 1.3 mm vs. -2.3 +/- 0.6 mm) and ejection velocity (0.9 +/- 0.6 cm/s vs. 2.2 +/- 0.6 cm/s) showed overlap. In the infarction group, strain was reduced in segments with infarcted tissue, while systolic velocity and displacement were reduced in all segments and did not reflect the extension of the infarct. CONCLUSIONS: Strain was superior to velocity and displacement for quantification of regional myocardial function. Provided technical limitations can be solved, strain Doppler is the preferred TDI modality for assessing function in ischemic myocardium.     

Rapid reductions and millennial-scale variability in Nordic Seas sea ice cover during abrupt glacial climate changes

Constraining the past sea ice variability in the Nordic Seas is critical for a comprehensive understanding of the abrupt Dansgaard-Oeschger (D-O) climate changes during the last glacial. Here we present unprecedentedly detailed sea ice proxy evidence from two Norwegian Sea sediment cores and an East Greenland ice core to resolve and constrain sea ice variations during four D-O events between 32 and 41 ka. Our independent sea ice records consistently reveal a millennial-scale variability and threshold response between an extensive seasonal sea ice cover in the Nordic Seas during cold stadials and reduced seasonal sea ice conditions during warmer interstadials. They document substantial and rapid sea ice reductions that may have happened within 250 y or less, concomitant with reinvigoration of deep convection in the Nordic Seas and the abrupt warming transitions in Greenland. Our empirical evidence thus underpins the cardinal role of rapid sea ice decline and related feedbacks to trigger abrupt and large-amplitude climate change of the glacial D-O events.

Sea ice is a critical component of the global climate system as it affects Earth’s albedo, phytoplankton productivity, ocean-atmosphere heat and gas exchange, and ocean circulation (1). Rapid sea ice retreat, as observed in the modern Arctic Ocean, exerts important climate feedbacks that may lead to an accelerated climate warming at northern high latitudes (2). While many climate models have difficulties in reproducing the currently observed Arctic sea ice decline (3), the rates of ongoing atmospheric warming in some Arctic regions are already comparable with those of prominent abrupt climate changes that occurred during the last glacial period (4). The latter are referred to as Dansgaard–Oeschger (D-O) climate events and known from Greenland ice core records as abrupt shifts between cold Greenland stadials (GS) and warmer Greenland interstadials (GI) occurring repeatedly ∼10–110 ka (5, 6). The millennial-scale glacial climate variability was a global phenomenon with different characteristics in the northern and southern hemispheres, but the most striking feature of the D-O events is an extremely abrupt climate transition that includes an atmospheric warming of 5–16.5 °C over the Greenland ice sheet happening in just a few decades (7). Analogous to the modern and future sea ice retreat and resulting warming in the Arctic, the abrupt D-O climate transitions are widely believed to have been amplified by rapid sea ice retreat in the Nordic Seas (8–15).Today, the Nordic Seas are largely ice-free, and warm Atlantic surface waters flow into the Norwegian Sea as far north as Svalbard at ∼80°N (Fig. 1), where the Arctic sea ice cover is being eroded, in particular in the Barents Sea. The warm Atlantic surface waters release heat to the atmosphere as it flows northward, which is accompanied by convective intermediate and deep-water formation between Norway and Greenland, feeding the lower limb of the Atlantic Meridional Overturning Circulation (AMOC) (16). A portion of the Atlantic waters continues flowing into the stratified Arctic Ocean as subsurface waters (17). While the pattern of ocean circulation during GI was fairly comparable to that today, proxy data indicate that the glacial Nordic Seas exhibited a stable surface stratification during GS, similar to the modern Arctic Ocean (13, 18). The AMOC and associated northward surface heat transport into the Nordic Seas were weakened during GS, with most extreme weakening related to Heinrich events signified by massive iceberg discharges to the North Atlantic (19, 20). Intermediate and deep waters in the stadial Nordic Seas were 2–4 °C warmer as compared with GI or modern conditions, resulting from a stable halocline and reduced open-ocean convection (21, 22). Contemporaneously, an extended sea ice cover reaching at least as far south as the Greenland–Scotland Ridge at ∼60°N insulated the high-latitude atmosphere from the deep oceanic heat reservoir (23, 24). Model simulations support a subsurface warming scenario under extended sea ice during GS (22, 25, 26) and suggest that a rapid removal of the sea ice cover might have caused the abrupt and high-amplitude D-O climate warming (11, 12, 14, 15).Open in a separate windowFig. 1.Core sites and regional context of the study area. Yellow diamonds mark the core sites investigated in this study. The map shows the core-top P_BIP₂₅ distribution (42, 43, 63), illustrating the great potential of the biomarker approach for sea ice reconstruction. Orange, yellow, and green dots mark core-top sites north, east, and south of Greenland, respectively, data of which are investigated in this study. Small black dots indicate locations of published core-top data. Purple lines mark the modern sea ice extent during September (dashed) and March (solid), averaged between A.D. 1981 and 2010 (https://nsidc.org/; ref. 64). The thin blue line shows the P_BIP₂₅ = 0.2 isoline, representing best the modern winter/spring sea ice extent. Red arrows illustrate the warm and saline North Atlantic Current (NAC). The map was produced with Ocean Data View software (65).Although there is some evidence of millennial-scale sea ice fluctuations during the last glacial, the few available sea ice proxy records (23, 24, 27–31) are mostly restricted to the southern Norwegian Sea and the Arctic Ocean, often have a limited temporal resolution, and partly reflect opposing trends regarding stadial–interstadial sea ice changes depending on the proxies used. Here we present high-resolution sea ice biomarker records from two key sites that form a North–South transect within the Atlantic inflow region in the Norwegian Sea and are thus ideally suited to record spatiotemporal shifts in sea ice cover in both the entrance and the interior of the ocean basin, oceanic fronts, and Atlantic water inflow during the last glacial (Fig. 1). Furthermore, we combine these marine sea ice proxy records with an independent sea ice record based on bromine-enrichment (Br_enr) values from an East Greenland ice core, which significantly enhances the spatial coverage, the robustness of results, and temporal constraint of the sea ice reconstruction. We focus on five representative glacial D-O cycles between 32 and 41 ka, which comprise long- and short-lasting GI as well as several GS, one of which includes Heinrich Event 4. The application of the cryptotephra-based chronological constraints provides a level of robustness as to the timing, duration, and nature of the events unfolding during abrupt climate changes. Our study provides robust empirical evidence that resolves rapid and widespread sea ice retreat in the Nordic Seas and its role in initiating and amplifying the abrupt climate change of the glacial D-O events.     

Improved survival and quality of life in patients undergoing R1 pancreatic resection compared to patients with locally advanced unresectable pancreatic adenocarcinoma

ObjectiveTo prospectively record the clinical consequences of R1 resection of pancreatic adenocarcinoma compared to patients with locally advanced tumours not undergoing surgery.BackgroundSurgery is the only potentially curative treatment of pancreatic cancer, and postoperative safety is increasing. The rate of R1 resections might also increase unintentionally as surgical procedures with curative goal become more comprehensive, and the clinical outcome requires further prospective evaluation.Material and methodsProspective observational cohort study from October 2008 to December 2010. Outcome after R1 resection (group 1, surgery, n = 32) and conservative palliative chemoradiation/endoscopy (group 2, no surgery, n = 56) is compared with survival and longitudinal patient-reported quality of life (QoL) as endpoints. QoL was assessed by the Edmonton Symptom Assessment System (ESAS).ResultsDemographic characteristics and tumour diameters were similar in both groups: 38.0 (31.3, 49.8) mm in group 1 versus 44.0 (39.6, 49.1) mm in group 2 (p = 0.18). Perioperative morbidity was 25% with no mortality. Disease-specific survival was 18.0 (14.5, 23.8) months in group 1 versus 8.1 (4.8, 10.1) months in group 2 (p < 0.0001). Overall survival was 11 (7.8, 14.4) months. Reduction in fatigue was significantly improved in the surgery group 6, 12, and 19 weeks after baseline, whereas reduction in global health was significantly better in group 2.ConclusionRadical removal (R0 resection) is the primary aim of surgery, but also R1 resection seems to improve survival and QoL, compared to outcome in patients with locally advanced tumours not undergoing surgery.     

Photodynamic treatment of oral lesions.

Photodynamic treatment (PDT) was first started in the oral cavity in the mid 1980s. Hematoporphyrins were rapidly replaced by Photofrin and meta-tetrahydroxyphenylchlorin (mTHPC) as photosensitisers of choice, and over the years these two have been approved by several health authorities for PDT. 5-aminolevulinic acid (ALA) and some dyes (e.g., toluidine and methyene blue) have also been tested. Several different nonthermal lasers have been used and lately light-emitting diodes (LEDs) have been tried. Most of the clinical treatments have been carried out on oral squamous cell carcinoma (OSSC), either primary or metastatic lesions, with good results. The treatment leaves little scarring and can be used before, in conjunction with, and adjunctive to other treatment modalities. The greatest disadvantage is that the patients are photosensitive for several weeks following systemic administration of the photosensitiser. PDT is now an accepted palliative treatment. Systemic administration of ALA has been more successful than local application in the treatment of precancerous lesions such as oral leukoplakia. PDT following topical application of photosensitiser (metylene blue and methyl-ALA) has shown improvement in cutaneous diseases of the oral mucous membrane such as oral lichen planus. The bactericidal effect of PDT has also been tested on oral plaque, but little clinical work has been performed so far. Instead of mechanical cleaning or antibiotic therapy, PDT may also play a role in dental diseases.     

Multiple sclerosis and chronic inflammatory diseases A case-control study

Introduction – Disease associations may provide useful etiological leads in relation to diseases of unknown cause. Material and methods – We conducted a hospital-based case-control study of 155 MS patients and 200 controls in Hordaland County, Norway to investigate the possible association between MS and autoimmune diseases. Results – The MS patients had a statistically significant more frequent coexistence of rheumatoid arthritis, psoriasis, and goitre when compared to the controls (OR = 2.96; 95% CI 1.23–7.66). This difference persisted when analysing the definite MS cases separately (OR = 2.90; 95% CI 1.10–7.96). The familial occurrence of chronic inflammatory diseases was not significantly different in cases and controls. A significant increased risk to develop MS occurred in first degree relatives of MS patients (OR = 12.58; 95% CI 1.73–552). Conclusion – Acknowledging the low figures, the uncertain estimates with large confidence intervals, and thus the obvious role of chance in this study, the results might indicate that a generalized, genetically controlled problem of the immune system could result in aggregates of the reported diseases, all of which are partly characterized by abberrations of the immune system.