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Biomedical subjects

Christian Schindler

Publications and source records attributed to Christian Schindler.

At least 19 recordsLinked to original sources
PubMed2005

Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study.

BACKGROUND: The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. METHODS: In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18-60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years. RESULTS: In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC<0.70 compared to other women (-39.4 vs -12.2 mL/yr per pack per day, p < 0.002). CONCLUSION: There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

Adolescent↗
PubMed2005

Heat wave 2003 and mortality in Switzerland.

QUESTIONS UNDER STUDY: During June to August 2003, high temperatures were reported across Europe including Switzerland. In many European countries, particularly in France the heat wave was associated with an increase in mortality. This is the first analysis investigating whether the high temperatures during summer 2003 in Switzerland had a measurable impact on mortality. METHODS: Daily data on all-cause mortality for the period January 1990 to December 2003, and meteorological data from 20 different stations for the same period were analysed. Excess mortality for different age groups, gender and geographic regions was calculated. Daily mortality and temperature in 2003 was correlated with lags of temperature up to 7 days. RESULTS: An estimated 7% increase in all cause mortality occurred during June to August 2003. Excess mortality was limited to the region north of the Alps, to inhabitants of cities and suburban areas and was more pronounced among the elderly and the inhabitants of Basel, Geneva and Lausanne. North of the Alps, deviations in daily mortality were significantly correlated with deviations in maximum daily temperatures and night temperatures. The combination of day temperature above 35 degrees C and night temperatures above 20 degrees C predominantly occurred in Basel and Geneva and might in part explain the regional differences in excess mortality. CONCLUSIONS: As the number of elderly people in Switzerland continues to rise and the occurrence of heat waves is predicted to increase as a consequence of global warming, preventive programmes targeting susceptible populations during heat waves are warranted.

Adult↗
PubMed2005

Low-grade inflammation and estimates of insulin resistance during the menstrual cycle in lean and overweight women.

BACKGROUND: Inflammatory markers and insulin resistance are independent cardiovascular risk factors and are thought to be influenced by sex steroids. We investigated changes of inflammatory markers and estimates of insulin resistance during the menstrual cycle, their variances, and their relationship to each other, sex steroids, and regional body fat distribution. METHODS: Eight normal weight (body mass index, 21.6 +/- 1.9 kg/m(2)) and nine overweight (body mass index, 30 +/- 2.4 kg/m(2)) young women with normal ovarian function were assessed 15 times throughout the menstrual cycle. Regional fat distribution was assessed using dual x-ray absorptiometry. RESULTS: Concentrations of highly sensitive C-reactive protein (hs-CRP) changed significantly during the menstrual cycle and were highest in the early follicular phase (P < 0.00001). SHBG concentrations were stable in the follicular phase but increased in the luteal phase (P < 0.00001). During the follicular phase, estimates of insulin resistance had a higher within-subject variance when determined by the homeostasis model assessment index (42%) than when estimated by SHBG concentrations (5%, P < 0.05). During the menstrual cycle, using repeated measurements, hs-CRP correlated inversely to estradiol (beta-coefficient, -0.23, P < 0.0001) and SHBG concentrations (beta-coefficient, -0.83, P = 0.004). Central accumulation of body fat correlated to the mean hs-CRP concentration (r = 0.63, P = 0.007) and the mean homeostasis model assessment index for insulin resistance (r = 0.75, P = 0.001). CONCLUSION: We demonstrate that serum concentrations of hs-CRP and SHBG significantly change during the menstrual cycle. We reveal a close link between sex steroids, subclinical inflammation, insulin resistance, and body fat distribution in regularly menstruating women.

Absorptiometry, Photon↗
PubMed2005

The value of [18F]FDG-PET in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease.

PURPOSE: This study was performed to investigate the value of( 18)F-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease. METHODS: Twenty-six consecutive patients (21 females, 5 males; median age - years, range 17-86 years) with giant cell arteritis or Takayasu's arteritis were examined with [(18)F]FDG-PET. Follow-up scans were performed in four patients. Twenty-six age- and gender-matched controls (21 females, 5 males; median age 71 years, range 17-86 years) were included. The severity of large-vessel [(18)F]FDG uptake was visually graded using a four-point scale. C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured and correlated with [(18)F]FDG-PET results by logistic regression. RESULTS: [(18)F]FDG-PET revealed pathological findings in 18 of 26 patients. Three scans were categorised as grade I, 12 as grade II and 3 as grade III arteritis. Visual grade was significantly correlated with both CRP and ESR levels (p=0.002 and 0.007 respectively; grade I: CRP 4.0 mg/l, ESR 6 mm/h; grade II: CRP 37 mg/l, ESR 46 mm/h; grade III: CRP 172 mg/l, ESR 90 mm/h). Overall sensitivity was 60% (95% CI 40.6-77.3%), specificity 99.8% (95% CI 89.1-100%), positive predictive value 99.7% (95% CI 77-100%), negative predictive value 67.9% (95% CI 49.8-80.9%) and accuracy 78.6% (95% CI 65.6-88.4%). In patients presenting with a CRP <12 mg/l or an ESR <12 mm/h, logistic regression revealed a sensitivity of less than 50%. In patients with high CRP/ESR levels, sensitivity was 95.5%/80.7%. CONCLUSION: [(18)F]FDG-PET is highly effective in assessing the activity and the extent of large-vessel vasculitis. Visual grading was validated as representing the severity of inflammation. Its use is simple and provides high specificity, while high sensitivity is achieved by scanning in the state of active inflammation.

Adolescent↗
PubMed2005

Short-term effects of air pollution on total and cardiovascular mortality: the confounding effect of influenza epidemics.

BACKGROUND: Air pollution is associated with total mortality. This association may be confounded by uncontrolled time-varying risk factors such as influenza epidemics. METHODS: We analyzed independent data on influenza epidemics from 7 European cities that also had data on mortality associated with particulates (PM10). We used 10 methods to control for epidemics (5 derived from influenza data and 5 from respiratory mortality series) and compared those results with analyses that did not control for these epidemics. RESULTS: Adjustment for influenza epidemics increased the PM10 effect estimate in most cases (% change in the pooled regression coefficient: -1.9 to 38.9 for total mortality and 1.3 to 25.5 for cardiovascular mortality). A 10-microg/m increase in PM10 concentrations (lag 0-1) was associated with a 0.48% (95% confidence interval=0.27-0.70%) increase in daily mortality unadjusted for influenza epidemics, whereas under the various methods to control for epidemics the increase ranged from 0.45% (0.26-0.69%) to 0.67% (0.46-0.89%). The corresponding figures for cardiovascular mortality were 0.85% (0.53-1.18%) with no adjustment and from 0.86% (0.53-1.19%) to 1.06% (0.74-1.39%) with the methods of control. CONCLUSIONS: The association between air pollution and mortality is not weakened by control for influenza epidemic irrespective of the method used. To adjust for influenza epidemics, one can use methods based on respiratory mortality counts instead of counts of influenza cases if the latter are not available. However, adjustment for influenza by any method tested did not markedly alter the air pollution effect estimate.

Air Pollution↗
PubMed2005

Stat1 and Stat2 but not Stat3 arbitrate contradictory growth signals elicited by alpha/beta interferon in T lymphocytes.

Alpha/beta interferon (IFN-alpha/beta) triggers antiviral and antiproliferative responses in target cells through modulation of gene expression. The JAK-STAT pathway is the major mediator of these biological effects through the activation of the transcription factors STAT1 and STAT2, and gene ablation studies have demonstrated that both STAT1 and STAT2 are required for most antiviral responses induced by IFN-alpha/beta. However, additional signaling pathways are also activated by IFN. Here, we show that these additional pathways provoke a proliferative response in activated T lymphocytes. While activation of IFN-stimulated gene factor 3 produces a dominant inhibitory signal capable of overriding the mitogenic response, absence of either STAT1 or STAT2 leads to a proliferative response to IFN. Growth stimulation by IFN-alpha/beta is independent of other STAT proteins, particularly of STAT3, since T lymphocytes from STAT1-STAT3 double-knockout mice are growth stimulated by IFN-alpha/beta treatment. IFN-alpha/beta can cooperate with numerous T-cell mitogens, including interleukin-2 (IL-2), IL-4, IL-7, and IL-12, and can contribute to the rapid restoration of the thymus following glucocorticoid-mediated ablation. These results underscore the complexity of the cellular response to IFN and suggest that the ultimate outcome of IFN action results from a balance between growth-inhibitory and -stimulatory effects.

Animals↗
PubMed2005

A call for reporting the relevant exposure term in air pollution case-crossover studies.

The exposure term in the case-crossover design consists in the difference between the ambient concentration on the event day and the concentration(s) on some control day(s). So far, all air pollution case-crossover studies presented the distribution of the daily ambient pollutant concentrations but do not publish the distributional properties of the relevant exposure term--that is, the concentration difference. This article shows that this difference can be very small for a large fraction of event days, therefore, seriously limiting the statistical power to refute the null hypothesis. Publishing the distribution of the relevant differences will improve the interpretation and discussion of findings from case-crossover studies, particularly in cases with statistically non-significant associations.

Air Pollutants↗
PubMed2005

Effect of self-hypnosis on hay fever symptoms - a randomised controlled intervention study.

BACKGROUND: Many people suffer from hay fever symptoms. Hypnosis has proved to be a useful adjunct in the treatment of conditions where allergic phenomena have an important role. METHODS: Randomised parallel group study over an observation period of two consecutive pollen seasons. Outcome data include nasal flow under hypnosis, pollinosis symptoms from diaries and retrospective assessments, restrictions in well-being and use of anti-allergic medication. We investigated 79 patients with a mean age of 34 years (range 19-54 years; 41 males), with moderate to severe allergic rhinitis to grass or birch pollen of at least 2 years duration and mild allergic asthma. The intervention consisted of teaching self-hypnosis during a mean of 2.4 sessions (SD 1.7; range 2-5 sessions) and continuation of standard anti-allergic pharmacological treatment. RESULTS: Of 79 randomised patients, 66 completed one, and 52 completed two seasons. Retrospective VAS scores yielded significant improvements in year 1 in patients who had learned self-hypnosis: pollinosis symptoms -29.2 (VAS score, range 0-100; SD 25.4; p < 0.001), restriction of well-being -26.2 (VAS score, range 0-100; SD 28.7; p < 0.001. In year 2, the control group improved significantly having learned self-hypnosis as well: pollinosis symptoms -24.8 (SD 29.1; p < 0.001), restriction of well-being -23.7 (SD 30.0; p < 0.001). Daily self-reports of subjects who learnt self-hypnosis do not show a significant improvement. The hazard ratio of reaching a critical flow of 70% in nasal provocation tests was 0.333 (95% CI 0.157-0.741) after having learnt and applied self-hypnosis.

Adolescent↗
PubMed2005

Estimating the exposure-response relationships between particulate matter and mortality within the APHEA multicity project.

Several studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of theses studies linear nonthreshold relations were assumed. We investigated the exposure-response association between ambient particles and mortality in the 22 European cities participating in the APHEA (Air Pollution and Health--A European Approach) project, which is the largest available European database. We estimated the exposure-response curves using regression spline models with two knots and then combined the individual city estimates of the spline to get an overall exposure-response relationship. To further explore the heterogeneity in the observed city-specific exposure-response associations, we investigated several city descriptive variables as potential effect modifiers that could alter the shape of the curve. We conclude that the association between ambient particles and mortality in the cities included in the present analysis, and in the range of the pollutant common in all analyzed cities, could be adequately estimated using the linear model. Our results confirm those previously reported in Europe and the United States. The heterogeneity found in the different city-specific relations reflects real effect modification, which can be explained partly by factors characterizing the air pollution mix, climate, and the health of the population.

Air Pollutants↗
PubMed2004

Use of B-type natriuretic peptide for the management of women with dyspnea.

In studies with predominately male patients, B-type natriuretic peptide (BNP) levels have been shown to be helpful in the evaluation and management of patients who present with acute dyspnea. The effect of BNP levels on the management of women has not been defined. This study evaluated a predefined subgroup of 190 women included in a prospective randomized controlled study of BNP testing for emergency diagnosis of acute dyspnea. Patients were randomly assigned to a diagnostic strategy with (n = 93, BNP group) or without (n = 97, control group) the use of BNP levels provided by a rapid bedside assay. Women differed significantly from men in baseline characteristics, symptoms, signs, and final discharge diagnoses. The use of BNP levels decreased the need for hospital admission (73% vs 86%, p = 0.034) and intensive care (12% vs 23%, p = 0.048). Median time to discharge was 6 days in the BNP group versus 10 days in the control group (p = 0.023). Total cost of treatment was $4,781 in the BNP group (95% confidence interval 3,854 to 5,708) versus $6,843 in the control group (95% confidence interval 5,611 to 8,074, p = 0.009). In-hospital mortality rates were 4% in the BNP group and 10% in the control group (p = 0.165). Thus, used in conjunction with other clinical information, rapid measurement of BNP decreased time to discharge and total cost of treatment in women who presented with acute dyspnea.

Acute Disease↗
PubMed2004

Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea.

BACKGROUND: B-type natriuretic peptide levels are higher in patients with congestive heart failure than in patients with dyspnea from other causes. METHODS: We conducted a prospective, randomized, controlled study of 452 patients who presented to the emergency department with acute dyspnea: 225 patients were randomly assigned to a diagnostic strategy involving the measurement of B-type natriuretic peptide levels with the use of a rapid bedside assay, and 227 were assessed in a standard manner. The time to discharge and the total cost of treatment were the primary end points. RESULTS: Base-line demographic and clinical characteristics were well matched between the two groups. The use of B-type natriuretic peptide levels reduced the need for hospitalization and intensive care; 75 percent of patients in the B-type natriuretic peptide group were hospitalized, as compared with 85 percent of patients in the control group (P=0.008), and 15 percent of those in the B-type natriuretic peptide group required intensive care, as compared with 24 percent of those in the control group (P=0.01). The median time to discharge was 8.0 days in the B-type natriuretic peptide group and 11.0 days in the control group (P=0.001). The mean total cost of treatment was 5,410 dollars (95 percent confidence interval, 4,516 dollars to 6,304 dollars) in the B-type natriuretic peptide group, as compared with 7,264 dollars (95 percent confidence interval, 6,301 dollars to 8,227 dollars) in the control group (P=0.006). The respective 30-day mortality rates were 10 percent and 12 percent (P=0.45). CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment.

Acute Disease↗
PubMed2004

IL-6 and the acute phase response in murine atherosclerosis.

Numerous studies have implicated C-reactive protein (CRP) and the acute phase response (APR) in the development of atherosclerotic heart disease. Interleukin (IL)-6, which regulates both CRP expression and the APR, has also been identified as a risk factor for heart disease. To more directly evaluate the role of IL-6 in the development of atherosclerosis, IL-6 knockout mice were crossed with atherosclerosis prone LDL receptor (LDL-R) knockout mice. Lesion development was evaluated on Chow, Western type and Paigen diets. As anticipated, the Paigen diet stimulated the expression of APR genes in LDL-R[-/-] mice, but not IL-6[-/-]/LDL-R[-/-] mice. Despite this difference in acute phase response, only modest and statistically not significant differences were noted in the development of atherosclerotic lesions in LDL-R[-/-] and IL-6[-/-]/LDL-R[-/-] mice. These observations suggest that IL-6 and the acute phase response may not play as significant role in atherogenesis as other studies have indicated.

Acute-Phase Reaction↗
PubMed2004

Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina--on-treatment analysis of the TIME trial.

AIM: To assess treatment effects of optimised medical therapy and PCI or CABG surgery on one-year outcome in patients 75 years old with chronic angina. METHODS AND RESULTS: On-treatment analysis of the TIME data: all re-vascularised patients (REVASC n=174: 112 randomised to revascularisation and 62 to drugs with late revascularisation) were compared to all patients on continued drug therapy (MED n=127: 86 randomised to drugs and 41 to revascularisation only). Baseline characteristics of both groups were similar (age 80 +/- 4 years). Risk of death at one year (adjusted hazard ratio (HR)=1.31; 95%-CI: 0.58-2.99; P=0.52) and of death/infarction (adjusted hazard RATIO=1.77; 95%-CI 0.91-3.41; P=0.09) were comparable between REVASC and MED patients. Furthermore, the risk of death within 30 days was even slightly lower among REVASC patients (unadjusted hazard RATIO=0.73; 95%-CI: 0.21-2.53; P=0.98). Overall, REVASC patients had greater improvements in symptoms and well-being than MED patients (P<0.01). Surgical patients had similar mortality rates as angioplasty patients, but they also had greater symptomatic improvements (P<0.01). CONCLUSION: Treated medically, elderly patients with chronic angina have a similarly high 30-day and one-year mortality as patients of the same age being re-vascularised; however, they can expect lower improvements in symptoms and well being.

Aged↗
PubMed2004

Cost-effectiveness of invasive versus medical management of elderly patients with chronic symptomatic coronary artery disease. Findings of the randomized trial of invasive versus medical therapy in elderly patients with chronic angina (TIME).

AIM: To compare benefits and costs of invasive versus medical management in elderly patients with chronic angina. METHODS AND RESULTS: In a predefined subgroup of 188 patients of the Trial of Invasive versus Medical therapy in Elderly patients with chronic angina (TIME), one-year benefits were assessed as freedom from major events and improvements in symptoms and quality of live. Costs were determined as one-year costs of resource utilisation. Invasive patients had higher 30-day, but lower months 2-12 hospital and intervention costs than medical patients, resulting in somewhat higher one-year costs for invasive management (p=0.08). However, billing data available for a subgroup of patients showed higher practitioner's charges in the medical patients (adjusted p=0.0015). Incremental costs to prevent one major event by invasive management averaged CHF 10100 (95% CI: -800 to 28300) or 6965, ranging from average CHF 5100 (euro 3515) to CHF 11600 (euro 8000) in a best, compared to a worst, case scenario. CONCLUSIONS: Early increased costs of revascularization in invasive patients were balanced after one year by increased practitioners' charges and symptom-driven late revascularizations in medical patients. Therefore, the invasive strategy with improved clinical effectiveness at only marginally higher costs as medical management was cost-effective. Costs should not be an argument against invasive management of elderly patients with chronic angina.

Aged↗
PubMed2004

Quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy for non-resectable liver metastases of colorectal cancer.

OBJECTIVE: Patients with non-resectable liver metastases of colorectal cancer have poor prognosis and are mainly treated by palliative chemotherapy. Laser interstitial thermo-therapy is an innovative minimal invasive procedure for local tumour destruction within solid organs. The aim of the study was to investigate quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy (US-LITT) in patients with liver metastases of colorectal cancer. METHODS: In this prospective non-randomized study, 45 patients with liver metastases of colorectal cancer were palliatively treated by US-LITT. Patient survival was analysed by the Kaplan-Meier method and the quality of life by questionnaire C30 of the European Organisation for Research and Treatment of Cancer before, and 1 week, 1 month, and 6 months after initiation of US-LITT. RESULTS: Median survival after initiation of US-LITT was 8.5 +/- 0.7 months with a range of 1.5-18 months. Body weight was constant 1 month after US-LITT. In the multivariate analyses, quality-of-life symptoms and functioning scales did not deteriorate in patients alive at 6 months after initiation of US-LITT. Univariate analyses outlined a significant increase of the pain subscale before and at 1 week after US-LITT. CONCLUSIONS: This study first describes the quality of life in patients with liver metastases of colorectal cancer treated by US-LITT. Potential benefits of the minimal invasive procedure could be prolonged survival time by preserved quality of life, but this first impression needs to be verified in a comparative study.

Adult↗
PubMed2003

STATs dimerize in the absence of phosphorylation.

Upon activation by tyrosine kinases, members of the STAT family of transcription factors form stable dimers that are able to rapidly translocate to the nucleus and bind DNA. Although crystal structures of activated, near full-length, Stat1 and Stat3 illustrate how STATs bind to DNA, they provide little insight into the dynamic regulation of STAT activity. To explore the unique structural changes Stat1 and Stat3 undergo when they become activated, full-length inactive recombinant proteins were prepared. To our surprise, even though these proteins are unable to bind DNA, our studies demonstrate that they exist as stable homodimers. Similarly, the Stat1 and Stat3 found in the cytoplasm of unstimulated cells also exhibit a dimeric structure. These observations indicate that Stat1 and Stat3 exist as stable homodimers prior to activation.

3T3 Cells↗