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Clinical observations indicate that many non-urological diseases seem to be associated with lower urinary tract symptoms (LUTS). This has also been shown in studies usually concerning single diseases. This study investigated the impact of non-urological diseases on LUTS in the general population.A questionnaire on LUTS and medical history was mailed to all 50-, 60- and 70 year-old men in Tampere and in 11 municipalities in the same county, in total 3143 subjects. Day-time frequency, nocturia, urge, urge incontinence, hesitancy and incomplete emptying were used to form an index for LUTS. The men were asked to report any disease that they had. The number of the following diseases reported by the participants was large enough for statistical analysis: lower back pain, hypertension, arthritis, heart disease, pulmonary disease, diabetes, constipation. stroke, transient ischaemic attack, cancer (other than prostate or bladder), neurological disease, inguinal hernia, rheumatoid arthritis and faecal incontinence. The association between LUTS and non-urological diseases was estimated by logistic regression as a prevalence odds ratio (OR) with 95% confidence intervals (CI).In the multivariate analysis a significant association was found between LUTS and the following diseases: faecal incontinence (OR 4.5, CI 2 .3-9.1), neurological disease (OR 2.4, CI 1.3-4.4), constipation (OR 2.3, CI 1.5-3.3) and arthritis (OR 1.5, CI 1.2-2.0).According to this population-based study LUTS is an important part of the symptomatology of faecal incontinence, neurological disease, constipation and arthritis. Thus, the patients with these diseases and presenting with LUTS require careful investigation, at least in the cases in which the primary therapy of LUTS has failed.

Purpose: Breast cancer brain metastases (BCBM) are detected with increasing incidence. Therefore, identification of genes involved in BCBM formation is of great interest. Eperimental Design: In order to detect potential genes involved in BCBM, we first screened for genes down-regulated by methylation in cell lines with site-specific metastatic ability. The expression of five genes, CADM1, SPARC, RECK, TNFAIP3 and CXCL14, which were also found down-regulated in gene expression profiling analyses of BCBM tissue samples, were verified by qRT-PCR in a larger patient cohort. CADM1 was chosen for further down-stream analyses. Results: A higher incidence of CADM1 methylation, correlating with the expression levels, was found in BCBM as compared to non-matched primary BC. Similarly, loss of CADM1 protein expression was detected more commonly among BCBM samples as well as among primary breast tumors with subsequent brain relapse. The prognostic role of CADM1 expression was finally verified in two publicly available data sets (n=418) and in two large independent primary breast cancer TMA tumor cohorts (n=1718). The immunohistochemical analyses revealed an association between loss of CADM1 protein expression and risk factors such as disease stage, lymph node status, and tumor size in primary BC. Furthermore, all analyses revealed a significant association between CADM1 and shorter survival. In multivariate analyses, survival was significantly longer for patients with CADM1-positive primary tumors for both TMA data sets (p= 0.04 and p=0.01). Conclusions: Loss of CADM1 expression is an independent prognostic factor especially associated with the development of brain metastases in breast cancer patients. Citation Format: Harriet Wikman, Laura Westphal, Felicitas Schmid, Markus Glatzel, Jakob Matschke, Manfred Westphal, Sirkku Pollari, Kristiina Iljin, Luigi Terracciani, Heini Huhtala, Anne Kallioniemi, Guido Sauter, Volkmar Müller, Isabell Witzel, Katrin Lamszus, Dirk Kemming, Klaus Pantel. Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 46. doi:10.1158/1538-7445.AM2014-46

Cell adhesion molecules are cell surface glycoproteins that may act as mediators in the metastatic process. Soluble interleukin-2 receptor (sIL-2R) is an immunological marker that may also serve as an indicator of tumour progression. Normal and neoplastic cells are capable of releasing these molecules into circulation. We evaluated the association between pretreatment serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sIL-2R and metastases and survival in 50 patients with advanced melanoma. The patients with liver and/or bone metastases had significantly higher sICAM-1 levels than those with soft tissue and/or lung involvement ( P =0.002). In addition, there was a trend towards higher sIL-2R levels in patients with more metastatic sites ( P =0.07). In univariate analysis, the number of metastatic sites ( P =0.0001, odds ratio (OR) 3.0, 95% confidence interval (CI): 1.7–5.3), the metastatic site ( P =0.01, OR 2.3, 95% CI: 1.2–4.4) and the levels of sICAM-1 ( P =0.011, OR 2.5, 95% CI: 1.2–5.0), sVCAM-1 ( P =0.036, OR 2.1, 95% CI: 1.0–4.3) and sIL-2R ( P =0.0016, OR 3.0, 95% CI: 1.5–6.0) were found to be statistically significant prognostic factors for survival. In multivariate analysis, the number of metastatic sites was the dominant prognostic indicator. After it was excluded from the analysis, the sIL-2R level and the metastatic site were found to be significant. It can be concluded, that high sICAM-1 levels suggest liver metastases and sIL-2R seems to serve as a marker of tumour load in metastatic melanoma. Furthermore, the sIL-2R level appears to add to clinical data predicting the patient's outcome.

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement.

Introduction Falling asleep is associated with decreasing chemosensitivity and increasing transcutaneous carbon dioxide (tcCO2). We hypothesize that the ventilatory gain for respiratory stimuli can be estimated by measuring the level of tcCO2. Therefore, the level of tcCO2 measured during repetitive episodes of various respiratory events should follow the order of decreasing ventilatory gain (central apnea, mixed apnea, obstructive apnea, hypopnea and flow limitation). To test our hypothesis, we analyzed the tcCO2 levels during wakefulness, steady breathing during sleep and during the above-mentioned respiratory abnormalities. Materials and methods A total of 174 consecutive cardio-respiratory sleep recordings were retrospectively analyzed. Recordings were included if three of the following episodes and corresponding tcCO2 levels could be determined: (1) wakefulness, (2) highest steady level of tcCO2 during steady breathing (to exclude REM), and (3) repetitive respiratory event (central, mixed, obstructive apnea or hypopnea). Inspiratory flow limitation was included when present. Minimum duration of an episode was either five minutes or at least ten similar respiratory events. TcCO2 during the respiratory episodes were tested against those measured during wakefulness and steady breathing during sleep (Wilcoxon signed ranks test). Results Thirty-one recordings (29 m/2f) with 69 episodes were included to the study. Mean age was 51 (range 32–71) and mean AHI was 25.8/h (range 8.6–52.9/h). TcCO2 while awake (5.21 kPa) did not differ from that during central (5.12 kPa, p = 0.128, n = 7) or mixed apnea (5.14 kPa, p = 0.068, n = 4), whereas it did differ from obstructive apnea, hypopnea, steady breathing and flow-limitation (p ⩽ 0.002). TcCO2 during steady breathing (5.63 kPa) was higher during episodes of central apnea (5.12 kPa, p = 0.018) and hypopnea (5.59 kPa, p = 0.014, n = 20) but lower during flow limitation (5.64 kPa, p Conclusion As predicted by our hypothesis, tcCO2 levels reflect the ventilatory gain: respiratory events associated with high ventilatory gain are accompanied by tcCO2 levels higher than wakefulness but lower than steady breathing. In contrast, flow limitation with low ventilatory gain appears with high tcCO2. TcCO2 signal during sleep could be used to rank respiratory events according to their ventilatory gain. Acknowledgement The authors would like to thank Aaro Salminen for providing valuable assistance in the preparation of this work.

We estimate the prevalence of erectile dysfunction in Finland and its effect on frequency of sexual intercourse.A population based study of 3,143, 50, 60 and 70-year-old men in Tampere and 11 municipalities in the same county was conducted by mailed questionnaire. The definition of erectile dysfunction was based on difficulties in achieving an erection before sexual intercourse and maintaining it. Erectile dysfunction was classified into 4 groups as none, minimal, moderate and complete. To estimate the effect of erectile dysfunction on the frequency of sexual intercourse the men were divided into those who had intercourse at least an average of once weekly and those who did not.A total of 2,198 questionnaires (70%) were returned and 1, 983 men (63%) were included in the study. Of these men 26% had no, 48% minimal, 14% and 12% complete erectile dysfunction, which increased with age (compared with 50-year-old men, the odds ratios for complete erectile dysfunction were 4.5 (95% confidence interval [CI] 2.6-7.5) for 60 and 21 (95% CI 12.5 to 34.7) to 70-year-old men. The effect of erectile dysfunction on the frequency of sexual intercourse could not be accounted for by age or marital status. The adjusted effect was strong among men with moderate (odds ratio 3.5, 95% CI 2.2-5.1) and complete (173, 68-443) erectile dysfunction but minimal erectile dysfunction had no impact (odds ratio 0.9, 95% CI 0. 6-1.3) on the frequency of intercourse.Erectile difficulties are common and complete erectile dysfunction increases with age. Erectile dysfunction regulates the sex life of men with moderate or complete dysfunction but this association cannot be accounted for by age or marital status. Although mild erectile dysfunction did not completely regulate sex life, its significance is the risk of progression to a more severe sexual life disturbing dysfunction.

The purpose of the study was to establish whether dietary elements are related to lower urinary tract symptoms (LUTS) and thus to diseases causing LUTS.This population-based study was carried out in 1994; a questionnaire was mailed to all men born in 1924, 1934 or 1944 living in Tampere or 11 rural or semi-rural municipalities in the same county, altogether 3143 men. Of this population, 68% were ultimately included in the study. A modified version of the DAN-PSS-1 questionnaire (10 of the questions) was used to assess urinary symptoms and problems arising from them. A symptom index was formed by multiplying the symptom and problem scores for hesitancy, incomplete emptying, urge, urge incontinence, nocturia and daytime frequency, and totalling the products. The men were also asked to report on their medical history, how often they ate vegetables and meat, whether they used butter, margarine or vegetable oil in food, how much alcohol and coffee they consumed, their smoking history and their weight and height. The risk of LUTS was estimated according to the frequency of meat and vegetable intake and the kind of fat used.The confounder-adjusted risk of LUTS was 0.68 (95% CI 0.54-0.86) among men consuming vegetables daily compared with men consuming vegetables less frequently. Compared with men who eat meat less frequently, the confounder-adjusted risk of LUTS was 2.08 (95% CI 1.00-4.10) among men consuming meat weekly, and 2.56 (95% CI 1.30-5.02) among men consuming meat daily. The confounder-adjusted risk of LUTS was 0.73 (95% CI 0.58-0.93) among men who consumed butter compared to those who did not.Dietary elements may also have an important role in the development of diseases causing LUTS. Direct effects of food components may likewise influence the occurrence of LUTS.

Easy accessibility and availability of emergency contraception raises contradictory opinions. Education about emergency contraception is resisted because of a fear that it might lead to irresponsible sexual behaviour and repeated use of emergency contraception instead of regular contraception.1 In Finland, sales of emergency contraception (the Yuzpe method) increased 10-fold from 1987 to the mid-1990s. In 1994 a national survey among 18-44 year old women showed that knowledge and use of the method was concentrated in the youngest respondents.2 Reports from other countries confirm that young women and even teenagers are well aware of the method.3 4 However, only a few reports have been published on use of emergency contraception among adolescents. We studied knowledge of emergency contraception and frequency of use among teenagers. The school health promotion study was introduced to provide data on adolescent health behaviours in Finland. …

Although the fetus usually is assessed echocardiographically at midtrimester, modem equipment makes it possible to examine the fetal heart much earlier in pregnancy. This cross-sectional study, conducted in 584 unselected fetuses, was planned to determine whether it is feasible to make 2-dimensional echocardiography of the fetal heart a part of routine first-trimester screening and to formulate reference ranges for cardiac structure at 11 weeks to 13 weeks plus 6 days of gestation. All were viable intrauterine pregnancies. Crown-rump length (CRL), which reflects gestational age, ranged from 41 to 78 mm. A single obstetrician performed all echocardiograms, lasting no longer than 20 minutes, using a 5-to 7.5-MHz vaginal transducer to confirm viability, measure CRL and nuchal translucency, and examine the structure of the heart and great vessels. The 4 cardiac chambers and outflow tracts were well visualized in 67% of examinations. Satisfactory views of all structures in the fetal heart, including a longitudinal view of the aortic arch and ductal arch, were obtained in 43%, 56%, and 62% of fetuses, respectively, at 11, 12, and 13 weeks gestation (58% overall). Reference ranges were derived from measurements of the cardiac ventricles, their outflow tracts, and the ratio of cardiac circumference to thoracic circumference in relation to CRL. There were 6 cardiac malformations among the fetuses. An atrioventricular septal defect was identified at 13 weeks and a case of hypoplastic left heart syndrome was identified at 18 weeks during a follow-up examination done because of an unsatisfactory 4-chamber view and enlarged NT. There were also 4 fetuses with ventricular septal defects, but none were identified prenatally. It is feasible to examine the fetal heart echocardiographically, using the transvaginal approach, at 11 weeks to 13 weeks plus 6 days gestation. It is not yet clear, however, that this can be made part of routine first-trimester ultrasound screening.

Arrested labor secondary to dystocia remains a major indication for acute cesarean section (CS) in many parts of the world. Apart from anatomic problems and malpresentation, the major culprit is uterine dysfunction in the form of weak contractions. Although amniotomy and augmentation with oxytocin are frequently used to augment labor, they have not lessened the frequency of CS. The beta-blocker propranolol, given intravenously, reportedly increases uterine activity, and it has safely augmented labor in a small series of primiparous women. The present study evaluated a combination of intravenous propranolol and oxytocin, compared with oxytocin alone, in women arrested in the first stage of labor. The study, a prospective, randomized, double-blind trial undertaken at a large university hospital, enrolled 107 women whose first-stage arrest of labor was ascribed to inadequate uterine contractions. All of them received oxytocin infusion and, in addition, were randomized to received either 2 mg propranolol intravenously or placebo in a 10-minute period. A second dose was given after 60 minutes if the cervix remained unchanged. Specialists lacking knowledge of the assigned treatment monitored the fetus by cardiotocography (CTG). Women given propranolol had no reduction in rates of CS or vacuum extraction. Rates of spontaneous vaginal delivery were 73% and 85%, respectively, in the propranolol and placebo groups, for a relative risk of 0.86 (95% confidence interval, 0.70-1.05). Excluding women having CS, augmented labor constituted 21% of the entire course of labor in the propranolol group and 29% in placebo recipients. The augmented part of labor was 38 minutes shorter in the propranolol group, a difference that was not statistically significant. Before augmentation, the state of the cervix was the same in the 2 groups. Peak oxytocin infusion rates did not differ significantly. Contractions became stronger over time in both groups, but at no time was there a significant group difference. CTG monitoring disclosed 2 cases of transient bradycardia in each group. In addition, 2 infants in the placebo group had decreased variability and 2 others had missing accelerations. There were no significant group differences in heart rate or blood pressure 1 hour after augmentation. Markers of fetal well-being were comparable in the 2 groups. There was no indication of drug accumulation in women given 2 doses of propranolol.

75 patients had closed treatment for a primary unilateral acute patellar dislocation. All patients were studied clinically, radiographically and for isokinetic thigh muscle performance a median of 11 (6-24) years later. During the follow-up, 37 patients had experienced recurrent dislocations. The functional outcomes were similar in patients with or without recurrence. Radiographically unstable patellar morphology, spontaneous reduction of the dislocation and low volume of hemarthrosis predisposed to recurrence.

Objective. To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. Methods. A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. Results. Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (±SD) pANCA log titers (103 ± 5.6 versus 27 ± 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. Conclusion. Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.

Background Assessment of the gluten-induced small-intestinal mucosal injury remains the cornerstone of celiac disease diagnosis. Usually the injury is evaluated using grouped classifications (e.g. Marsh groups), but this is often too imprecise and ignores minor but significant changes in the mucosa. Consequently, there is a need for validated continuous variables in everyday practice and in academic and pharmacological research. Methods We studied the performance of our standard operating procedure (SOP) on 93 selected biopsy specimens from adult celiac disease patients and non-celiac disease controls. The specimens, which comprised different grades of gluten-induced mucosal injury, were evaluated by morphometric measurements. Specimens with tangential cutting resulting from poorly oriented biopsies were included. Two accredited evaluators performed the measurements in blinded fashion. The intraobserver and interobserver variations for villus height and crypt depth ratio (VH:CrD) and densities of intraepithelial lymphocytes (IELs) were analyzed by the Bland-Altman method and intraclass correlation. Results Unevaluable biopsies according to our SOP were correctly identified. The intraobserver analysis of VH:CrD showed a mean difference of 0.087 with limits of agreement from −0.398 to 0.224; the standard deviation (SD) was 0.159. The mean difference in interobserver analysis was 0.070, limits of agreement −0.516 to 0.375, and SD 0.227. The intraclass correlation coefficient in intraobserver variation was 0.983 and that in interobserver variation 0.978. CD3+ IEL density countings in the paraffin-embedded and frozen biopsies showed SDs of 17.1% and 16.5%; the intraclass correlation coefficients were 0.961 and 0.956, respectively. Conclusions Using our SOP, quantitative, reliable and reproducible morphometric results can be obtained on duodenal biopsy specimens with different grades of gluten-induced injury. Clinically significant changes were defined according to the error margins (2SD) of the analyses in VH:CrD as 0.4 and in CD3+-stained IELs as 30%. Public Library of Science open access

Background Evidence suggests that many coeliac disease patients suffer from persistent clinical symptoms and reduced health-related quality of life despite a strict gluten-free diet. We aimed to find predictors for these continuous health concerns in long-term treated adult coeliac patients. Methods In a nationwide study, 596 patients filled validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires and were interviewed regarding demographic data, clinical presentation and treatment of coeliac disease, time and place of diagnosis and presence of coeliac disease-associated or other co-morbidities. Dietary adherence was assessed by a combination of self-reported adherence and serological tests. Odds ratios and 95% confidence intervals were calculated by binary logistic regression. Results Diagnosis at working age, long duration and severity of symptoms before diagnosis and presence of thyroidal disease, non-coeliac food intolerance or gastrointestinal co-morbidity increased the risk of persistent symptoms. Patients with extraintestinal presentation at diagnosis had fewer current symptoms than subjects with gastrointestinal manifestations. Impaired quality of life was seen in patients with long duration of symptoms before diagnosis and in those with psychiatric, neurologic or gastrointestinal co-morbidities. Patients with persistent symptoms were more likely to have reduced quality of life. Conclusions There were a variety of factors predisposing to increased symptoms and impaired quality of life in coeliac disease. Based on our results, early diagnosis of the condition and consideration of co-morbidities may help in resolving long-lasting health problems in coeliac disease.

Background & Aims In patients with celiac disease, gluten-induced lesions of the small-bowel mucosa develop gradually. However, it is not clear whether clinical presentation correlates with the degree of mucosal damage based on histology analysis. We investigated whether the degree of mucosal damage to the small bowel correlates with clinical presentation and serum markers of celiac disease. Methods We collected results from serology tests and mucosal biopsy samples from 638 consecutive patients with celiac disease and compared them with reported gastrointestinal symptoms, health-related quality-of-life scores, results from laboratory tests, and bone mineral densities of patients. We assessed mucosal injury based on the ratio of villous height to crypt depth, numbers of intraepithelial CD3 + cells, and semiquantitative Marsh classification criteria. Correlations were established based on the Pearson or Spearman coefficients. Results The ratio of the villous height to crypt depth correlated with the severity of gastrointestinal symptoms, quality-of-life scores, laboratory test results, numbers of intraepithelial CD3 + cells, and serum levels of antibodies associated with celiac disease. There was no correlation between the ratio of villous height to crypt depth and bone mineral density. The number of intraepithelial CD3 + cells was not associated with symptoms, whereas the Marsh classification and serum levels of antibodies associated with celiac disease correlated with gastrointestinal symptoms, laboratory test results, and numbers of intraepithelial CD3 + cells. Conclusions The ratio of small-bowel villous height to crypt depth and results from serology tests correlate with reported symptoms and quality of life of patients with celiac disease. Patient-reported outcomes are therefore of value, in addition to histology findings, in assessing patients with celiac disease.

Methods: We retrospectively reviewed 106 patients with steroid-dependent UC for whom azathioprine was started between October 1998 and May 2009. Six-month and 3-year outcomes after azathioprine therapy were evaluated. Results: Of the 106 patients, 73 (68.9%) were continued on azathioprine for more than six months (azathioprine group) and 33 (31.1%) discontinued azathioprine within six months due to intolerance (intolerance group, n = 20), colectomy (n = 6) or follow-up loss (n = 7). The most common reasons for intolerance were nausea and vomiting (n = 5), elevated liver enzymes (n = 5) and hair loss (n = 5). Six-month and 3-year outcomes for all 106 patients were remission in 70 (66%) and 67 (63.2%), corticosteroid dependence in 17 (16%) and 5 (4.7%), infliximab administration in 3 (2.8%) and 6 (5.6%), colectomy in 8 (7.5%) and 15 (14.2%), follow-up loss in 8 (7.5%) and 12 (11.3%), and death in 0 (0%) and 1 (0.9%), respectively. Six-month and 3-year outcomes for azathioprine group were remission in 57 (78%) and 60 (82.2%), corticosteroid dependence in 16 (22%) and 3 (4.1%), infliximab administration in 0 (0%) and 3 (4.1%), colectomy in 0 (0%) and 2 (2.7%), follow-up loss in 0 (0%) and 4 (5.4%), and death in 0 (0%) and 1 (1.3%), respectively. The azathioprine (n = 73) and the intolerance (n = 20) groups showed no significant difference in median age at diagnosis (37 years vs. 45 years, P= 0.17), proportion of male patients (61.6% vs. 40%, P= 0.12), median age at azathioprine therapy (40 years vs. 46 years, P= 0.27), median duration of UC before azathioprine (35.2 months vs. 17.6 months, P= 0.06), and median dose of azathioprine (1.06mg/kg vs. 0.83mg/kg, P= 0.39). The proportion of the patients remaining in remission was higher (88.2% vs. 36.8%, P< 0.001) in the azathioprine group compared with the intolerance group. Conclusions: Azathioprine is an effective treatment for steroiddependent UC. The efficacy of azathioprine is well sustained for 3 years. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120176).

Methods The relationship between sickness absence and job control among industrial food workers of different ages (n = 114) was studied. Results The number of absence spells, particularly short absence spells, was higher among younger workers, as expected. Using multivariate analysis, low job control was associated with an increased number of all absence spells (P < 0.02). Conclusions Job control may be an important factor in determining sickness absence among industrial workers.

IntroductionRecent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis. High plasma cell free DNA (cf-DNA) concentrations have been shown to be associated with sepsis outcome. The origin of cf-DNA is unclear.MethodsTotal plasma cf-DNA was quantified directly in plasma and the amplifiable cf-DNA assessed using quantitative PCR in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococcae or Escherichia coli. The quality of cf-DNA was analyzed with a DNA Chip assay performed on 8 survivors and 8 nonsurvivors. Values were measured on days 1-4 after positive blood culture, on day 5-17 and on recovery.ResultsThe maximum cf-DNA values on days 1-4 (n = 132) were markedly higher in nonsurvivors compared to survivors (2.03 vs 1.26 ug/ml, p1.52 ug/ml) remained an independent risk factor for case fatality in a logistic regression model. Qualitative analysis of cf-DNA showed that cf-DNA displayed a predominating low-molecular-weight cf-DNA band (150-200 bp) in nonsurvivors, corresponding to the size of the apoptotic nucleosomal DNA. cf-DNA concentration showed a significant positive correlation with visually graded apoptotic band intensity (R = 0.822, pConclusionsPlasma cf-DNA concentration proved to be a specific independent prognostic biomarker in bacteremia. cf-DNA displayed a predominating low-molecular-weight cf-DNA band in nonsurvivors corresponding to the size of apoptotic nucleosomal DNA.

Background ST-segment elevation in the right-sided chest lead V 4 R in inferior wall myocardial infarction is recognized as a sign of proximal occlusion of the right coronary artery with evolving right ventricular myocardial infarction. Our objective is to study how often lead V 4 R is recorded in clinical practice and how this might be associated with use of reperfusion therapy and outcome of patients. Methods Recording of lead V 4 R in 814 consecutive patients with acute myocardial infarction, administration of therapy, and outcome of the patients during a median follow-up of 285 days (174-313 days) were studied. Results V 4 R was recorded in 52% of patients with inferior ST-elevation myocardial infarction. Patients with V 4 R recorded were more likely to receive fibrinolytic therapy compared with patients without recording (65% vs 51%; P = .035). In multivariate analysis, recording of lead V 4 R (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.2; P = .006), along with age ( P P = .002), and diabetes (OR 3.9, 95% CI 1.1-2.4; P = .03) correlated to the use of reperfusion therapy. Patients with lead V 4 R recorded had less ( P = .055) reinfarction, unstable angina, stroke, and/or death during follow-up. Conclusions Lead V 4 R was recorded in only half of patients with inferior ST-elevation myocardial infarction. Patients with V 4 R recorded were more likely to receive thrombolytic therapy than those without recording of the additional chest lead.

We studied the relationship of serum rheumatoid factor (RF) and certain other variables to lung diffusion capacity for carbon monoxide (DLCO) in patients with rheumatoid arthritis (RA). In non-smoking patients none of the examined variables correlated significantly to DLCO whereas in smokers RF showed a significant (p < 0.01) negative correlation in this respect. These results indicate that smoking in connection with RF may contribute to reduced DLCO in RA patients.

Editor—The increased risk of venous thromboembolism related to the use of third generation oral contraceptives has been widely discussed in the media since October 1995, about two months before the original research reports were published.1 2 A few months after the negative publicity an increase of 10-11% in the number of induced abortions was reported from the United Kingdom.3 4 In Finland the rate of teenage abortions has been successfully reduced over the past 10 years, the abortion rate being 9 per 1000 girls aged 15-19 in 1994.5 To a great extent this can be explained …

Patients treated with deep brain stimulation (DBS) provide an opportunity to study affective processes in humans with “lesion on demand” at key nodes in the limbic circuitries, such as at the anterior thalamic nuclei (ANT). ANT has been suggested to play a role in emotional control with its connection to the orbitofrontal cortex and the anterior cingulate cortex. However, direct evidence for its role in emotional function in human subjects is lacking. Reported side effects of ANT–DBS in the treatment of refractory epilepsy include depression related symptoms. In line with these mood-related clinical side effects, we have previously reported that stimulating the anterior thalamus increased emotional interference in a visual attention task as indicated by prolonged reaction times due to threat-related emotional distractors. We used event-related potentials to investigate potential attentional mechanism behind this behavioural observation. We hypothesized that ANT–DBS leads to greater attention capture by threat-related distractors. We tested this hypothesis using centro-parietal N2–P3 peak-to-peak amplitude as a measure of allocated attentional resources. Six epileptic patients treated with deep brain stimulation at ANT participated in the study. Electroencephalography was recorded while the patients performed a computer based Executive-Reaction Time test with threat-related emotional distractors. During the task, either ANT or a thalamic control location was stimulated, or the stimulation was turned off. Stimulation of ANT was associated with increased centro-parietal N2–P3 amplitude and increased reaction time in the context of threat-related emotional distractors. We conclude that high frequency electric stimulation of ANT leads to greater attentional capture by emotional stimuli. This is the first study to provide direct evidence from human subjects with on-line electric manipulation of ANT for its role in emotion–attention interaction.

Background and purpose. Risk of acute ischemic stroke has been associated with carotid artery atherosclerosis as well as with periodontal disease. We studied whether oral pathology or carotid atherosclerosis was associated with the presence and quantity of bacterial DNA in their aspirated thrombi. Methods. Thrombus aspirates and control arterial blood were taken from 71 patients (70.4% male; mean age, 67.4 years) with acute ischemic stroke. Tooth pathology was registered using CT scans. Carotid stenosis was estimated with CTA and ultrasonography. The presence of bacterial DNA from aspirated thrombi was determined using quantitative PCR. We also analyzed the presence of these bacterial DNAs in carotid endarterectomies from patients with peripheral arterial disease. Results. Bacterial DNA was found in 59 (83.1%) of the thrombus aspirates (median, 8.6-fold). Oral streptococcal DNA was found in 56 (78.9%) of the thrombus aspirates (median, 5.1-fold). DNA from A. actinomycetemcomitans and P. gingivalis was not found. Most patients suffered from poor oral health and had in median 19.0 teeth left. Paradoxically, patients with better oral health had more oral streptococcal DNA in their thrombus than the group with the worst pathology ( p = 0.028 ). There was a trend (OR 7.122; p = 0.083 ) in the association of ≥50% carotid artery stenosis with more severe dental pathology. Oral streptococcal DNA was detected in 2/6 of carotid endarterectomies. Conclusions. Stroke patients had poor oral health which tended to associate with their carotid artery stenosis. Although oral streptococcal DNA was found in thrombus aspirates and carotid endarterectomy samples, the amount of oral streptococcal DNA in thrombus aspirates was the lowest among those with the most severe oral pathology. These results suggest that the association between poor oral health and acute ischemic stroke is linked to carotid artery atherosclerosis.

Thirty patients with definite rheumatoid arthritis and hydropsy in a knee joint were followed for 42 months in a prospective study. The knee joints were initially aspirated and 15 synovial fluid variables investigated. The patients were split into two groups, those with and those without progress of radiologically detected destruction in the knee joints during the follow-up. Of the synovial fluid variables at the start synovial fluid proteins (P = 0.002) and acid phosphatase (P = 0.03) differed statistically significantly between the groups, both being higher in patients with worsening of knee joint. The results suggest that high synovial fluid proteins and acid phosphatase are predictors of poor prognosis in a joint affected by rheumatoid arthritis.

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Background Due to the restrictive nature of a gluten-free diet, celiac patients are looking for alternative therapies. While drug-development programs include gluten challenges, knowledge regarding the duration of gluten challenge and gluten dosage is insufficient. We challenged adult celiac patients with gluten with a view to assessing the amount needed to cause some small-bowel mucosal deterioration. Methods Twenty-five celiac disease adults were challenged with low (1-3 g) or moderate (3-5g) doses of gluten daily for 12 weeks. Symptoms, small-bowel morphology, densities of CD3+ intraepithelial lymphocytes (IELs) and celiac serology were determined. Results Both moderate and low amounts of gluten induced small-bowel morphological damage in 67% of celiac patients. Moderate gluten doses also triggered mucosal inflammation and more gastrointestinal symptoms leading to premature withdrawals in seven cases. In 22% of those who developed significant small- intestinal damage, symptoms remained absent. Celiac antibodies seroconverted in 43% of the patients. Conclusions Low amounts of gluten can also cause significant mucosal deterioration in the majority of the patients. As there are always some celiac disease patients who will not respond within these conditions, sample sizes must be sufficiently large to attain to statistical power in analysis.

Background Impaired growth is a well-known complication in celiac disease, but factors associated with it are poorly known. We investigated this issue in a large cohort of children. Methods 530 children with biopsy-proven celiac disease were included. The participants were divided into two groups on the basis of the presence (n = 182) or absence (n = 348) of growth disturbance at diagnosis. Histological, serological and clinical characteristics were compared between children with growth failure and those with normal growth. Further, patients with growth failure as the sole clinical presentation were compared to those with poor growth and concomitant other symptoms. Results Children with growth failure were younger (p