Showing papers by "University of Bern published in 1999"

The hazards of scoring the quality of clinical trials for meta-analysis.

Abstract: Results Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.241.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P,.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P = .046). Conclusions Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored. JAMA. 1999;282:1054-1060 www.jama.com

Histopathology in fish: proposal for a protocol to assess aquatic pollution

Abstract: Water pollution induces pathological changes in fish. As an indicator of exposure to contaminants, histology represents a useful tool to assess the degree of pollution, particularly for sub-lethal and chronic effects. However, a standardized method for the description and assessment of histological changes, mainly for use in freshwater fish, is still lacking. In this paper, the present authors propose a standardized tool for the assessment of histological findings which can be applied to different organs. The methodology is based on two factors: (1) the extension of a pathological change is rated with a ‘score value’; and (2) the pathological importance of this alteration is defined as an ‘importance factor’. The sum of the multiplied score values and importance factors of all diagnosed changes results in different indices. With these indices, statistical analysis can be carried out. Assessment methods for the gills, liver, kidney and skin are described.

The Influence of Age on Propofol Pharmacodynamics

Abstract: BackgroundThe authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect.MethodsThe authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in person

LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite

Abstract: Structural remodelling of synapses and formation of new synaptic contacts has been postulated as a possible mechanism underlying the late phase of long-term potentiation (LTP), a form of plasticity which is involved in learning and memory Here we use electron microscopy to analyse the morphology of synapses activated by high-frequency stimulation and identified by accumulated calcium in dendritic spines LTP induction resulted in a sequence of morphological changes consisting of a transient remodelling of the postsynaptic membrane followed by a marked increase in the proportion of axon terminals contacting two or more dendritic spines Three-dimensional reconstruction revealed that these spines arose from the same dendrite As pharmacological blockade of LTP prevented these morphological changes, we conclude that LTP is associated with the formation of new, mature and probably functional synapses contacting the same presynaptic terminal and thereby duplicating activated synapses

Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans.

Abstract: Associations between known or putative virulence factors of Shiga toxin-producing Escherichia coli and disease in humans were investigated. Univariate analysis and multivariate logistic regression analysis of a set of 237 isolates from 118 serotypes showed significant associations between the presence of genes for intimin (eae) and Shiga toxin 2 (stx2) and isolates from serotypes reported in humans. Similar associations were found with isolates from serotypes reported in hemorrhagic colitis and hemolytic-uremic syndrome. The enterohemorrhagic E. coli (EHEC) hemolysin gene was significantly associated with isolates from serotypes found in severe diseases in univariate analysis but not in multivariate logistic regression models. A strong association between the intimin and EHEC-hemolysin genes may explain the lack of statistical significance of EHEC hemolysin in these multivariate models, but a true lack of biological significance of the hemolysin in humans or in disease cannot be excluded. This result warrants further investigations of this topic. Multivariate analysis revealed an interaction between the eae and stx2 genes, thus supporting the hypothesis of the synergism between the adhesin intimin and Shiga toxin 2. A strong statistical association was observed between the stx2 gene and severity of disease for a set of 112 human isolates from eight major serotypes. A comparison of 77 isolates of bovine origin and 91 human isolates belonging to six major serotypes showed significant associations of the genes for Shiga toxin 1 and EspP protease with bovine isolates and an increased adherence on HEp-2 cell cultures for human isolates, particularly from diarrheic patients and healthy persons.

Calmodulin supports both inactivation and facilitation of L-type calcium channels

Abstract: L-type Ca2+ channels support Ca2+ entry into cells, which triggers cardiac contraction, controls hormone secretion from endocrine cells and initiates transcriptional events that support learning and memory. These channels are examples of molecular signal-transduction units that regulate themselves through their own activity. Among the many types of voltage-gated Ca2+ channel, L-type Ca2+ channels particularly display inactivation and facilitation, both of which are closely linked to the earlier entry of Ca2+ ions. Both forms of autoregulation have a significant impact on the amount of Ca2+ that enters the cell during repetitive activity, with major consequences downstream. Despite extensive biophysical analysis, the molecular basis of autoregulation remains unclear, although a putative Ca2+-binding EF-hand motif and a nearby consensus calmodulin-binding isoleucine-glutamine ('IQ') motif in the carboxy terminus of the alpha1C channel subunit have been implicated. Here we show that calmodulin is a critical Ca2+ sensor for both inactivation and facilitation, and that the nature of the modulatory effect depends on residues within the IQ motif important for calmodulin binding. Replacement of the native isoleucine by alanine removed Ca2+-dependent inactivation and unmasked a strong facilitation; conversion of the same residue to glutamate eliminated both forms of autoregulation. These results indicate that the same calmodulin molecule may act as a Ca2+ sensor for both positive and negative modulation.

A 1000-year high precision record of δ 13 C in atmospheric CO 2

Abstract: We present measurements of the stable carbon isotope ratio in air extracted from Antarctic ice core and firn samples. The same samples were previously used by Etheridge and co-workers to construct a high precision 1000-year record of atmospheric CO 2 concentration, featuring a close link between the ice and modern records and high-time resolution. Here, we start by confirming the trend in the Cape Grim in situ δ 13 C record from 1982 to 1996, and extend it back to 1978 using the Cape Grim Air Archive. The firn air δ 13 C agrees with the Cape Grim record, but only after correction for gravitational separation at depth, for diffusion effects associated with disequilibrium between the atmosphere and firm, and allowance for a latidudinal gradient in δ 13 C between Cape Grim and the Antarctic coast. Complex calibration strategies are required to cope with several additional systematic influences on the ice core δ 13 C record. Errors are assigned to each ice core value to reflect statistical and systematic biases (between ± 0.025‰ and ± 0.07‰); uncertainties (of up to ± 0.05‰) between core-versus-core, ice-versus-firn and firn-versus-troposphere are described separately. An almost continuous atmospheric history of δ 13 C over 1000 years results, exhibiting significant decadal-to-century scale variability unlike that from earlier proxy records. The decrease in δ 13 C from 1860 to 1960 involves a series of steps confirming enhanced sensitivity of δ 13 C to decadal timescale-forcing, compared to the CO 2 record. Synchronous with a ‘‘Little Ice Age’′ CO 2 decrease, an enhancement of δ 13 C implies a terrestrial response to cooler temperatures. Between 1200 AD and 1600 AD, the atmospheric δ 13 C appear stable. DOI: 10.1034/j.1600-0889.1999.t01-1-00005.x

Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution

Abstract: Introduction Lower prevalence rates of allergic diseases in rural as compared with urban populations have been interpreted as indicating an effect of air pollution. However, little is known about other factors of the rural environment which may determine the development of atopic sensitization and related diseases. Objective The authors tested the hypothesis that children growing up on a farm were less likely to be sensitized to common aerollergens and to suffer from allergic diseases than children living in the same villages but in nonfarming families. Materials and methods Three age groups of schoolchildren (6–7 years, 9–11 years, 13–15 years) living in three rural communities were included in the analyses. An exhaustive questionnaire was filled in by 1620 (86.0%) parents. A blood sample was provided by 404 (69.3%) of the 13–15 year olds to determine specific IgE antibodies against six common aeroallergens. Results Farming as parental occupation was reported for 307 children (19.0%). After adjustment for potential covariates such as family history of asthma and allergies, parental education, number of siblings, maternal smoking, pet ownership, indoor humidity and heating fuels, farming as parental occupation was significantly associated with lower rates of sneezing attacks during pollen season (adjusted OR 0.34, 95% CI 0.12–0.89) and atopic sensitization (adjusted OR 0.31, 95% CI 0.13–0.73) whereas the association with wheeze (adjusted OR 0.77 95% CI 0.38–1.58) and itchy skin rash (adjusted OR 0.86, 95% CI 0.49–1.50) was not statistically significant. The risk of atopic sensitization was lower in children from full-time farmers (adjusted OR 0.24, 95% CI 0.09–0.66) than from part-time farmers (adjusted OR 0.54, 95% CI 0.15–1.96). Conclusion Factors directly or indirectly related to farming as parental occupation decrease the risk of children becoming atopic and developing symptoms of allergic rhintis.

A language independent approach for detecting duplicated code

Abstract: Code duplication is one of the factors that severely complicates the maintenance and evolution of large software systems. Techniques for detecting duplicated code exist but rely mostly on parsers, technology that has proven to be brittle in the face of different languages and dialects. In this paper we show that is possible to circumvent this hindrance by applying a language independent and visual approach, i.e. a tool that requires no parsing, yet is able to detect a significant amount of code duplication. We validate our approach on a number of case studies, involving four different implementation languages and ranging from 256 K up to 13 Mb of source code size.

Holocene carbon-cycle dynamics based on CO2 trapped in ice at Taylor Dome, Antarctica

Abstract: A high-resolution ice-core record of atmospheric CO2 concentration over the Holocene epoch shows that the global carbon cycle has not been in steady state during the past 11,000 years. Analysis of the CO2 concentration and carbon stable-isotope records, using a one-dimensional carbon-cycle model,uggests that changes in terrestrial biomass and sea surface temperature were largely responsible for the observed millennial-scale changes of atmospheric CO2 concentrations.

Perlecan Maintains the Integrity of Cartilage and Some Basement Membranes

Abstract: Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a null mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

Gastrin-releasing Peptide Receptors in the Human Prostate: Relation to Neoplastic Transformation

Abstract: Bombesin-like peptides such as gastrin-releasing peptide (GRP) have been shown to play a role in cancer as autocrine growth factors that stimulate tumor growth through specific receptors. To search for potential clinical indications for GRP analogues, it is important to identify human tumor types expressing sufficient amounts of the respective receptors. In the present study, we have evaluated the expression of GRP receptors in human nonneoplastic and neoplastic prostate tissues using in vitro receptor autoradiography on tissue sections with 125I-Tyr4-bombesin as radio-ligand. GRP receptors were detected, often in high density, in 30 of 30 invasive prostatic carcinomas and also in 26 of 26 cases of prostatic intraepithelial proliferative lesions, corresponding mostly to prostatic intraepithelial neoplasias. Well-differentiated carcinomas had a higher receptor density than poorly differentiated ones. Bone metastases of androgen-independent prostate cancers were GRP receptor-positive in 4 of 7 cases. Conversely, GRP receptors were identified in only a few hyperplastic prostates and were localized in very low density in glandular tissue and, focally, in some stromal tissue. In all of the cases, the receptors corresponded to the GRP receptor subtype of bombesin receptors, having high affinity for GRP and bombesin and lower affinity for neuromedin B. These data demonstrate a massive GRP receptor overexpression in prostate tissues that are neoplastically transformed or, like prostatic intraepithelial neoplasias, are in the process of malignant transformation. GRP receptors may be markers for early molecular events in prostate carcinogenesis and useful in differentiating prostate hyperplasia from prostate neoplasia Such data may not only be of biological significance but may also provide a molecular basis for potential clinical applications such as GRP-receptor scintigraphy for early tumor diagnosis, radiotherapy with radiolabeled bombesin-like peptide analogues, and chemotherapy with cytotoxic bombesin analogues.

Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2.

Abstract: Glucagon-like peptide-1-(7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis. Recent experimental evidence in animals and healthy subjects suggests that GLP-1 has a role in controlling appetite and energy intake in humans. We have therefore examined in a double-blind, placebo-controlled, crossover study in 12 patients with diabetes type 2 the effect of intravenously infused GLP-1 on appetite sensations and energy intake. On 2 days, either saline or GLP-1 (1.5 pmol. kg-1. min-1) was given throughout the experiment. Visual analog scales were used to assess appetite sensations; furthermore, food and fluid intake of a test meal were recorded, and blood was sampled for analysis of plasma glucose and hormone levels. GLP-1 infusion enhanced satiety and fullness compared with placebo (P = 0.028 for fullness and P = 0.026 for hunger feelings). Energy intake was reduced by 27% by GLP-1 (P = 0.034) compared with saline. The results demonstrate a marked effect of GLP-1 on appetite by showing enhanced satiety and reduced energy intake in patients with diabetes type 2.

Interface shear strength of titanium implants with a sandblasted and acid-etched surface: a biomechanical study in the maxilla of miniature pigs.

Abstract: The purpose of the present study was to evaluate the interface shear strength of unloaded titanium implants with a sandblasted and acid-etched (SLA) surface in the maxilla of miniature pigs The two best documented surfaces in implant dentistry, the machined and the titanium plasma-sprayed (TPS) surfaces served as controls After 4, 8, and 12 weeks of healing, removal torque testing was performed to evaluate the interface shear strength of each implant type The results revealed statistically significant differences between the machined and the two rough titanium surfaces (p <00001) The machined surface demonstrated mean removal torque values (RTV) between 013 and 026 Nm, whereas the RTV of the two rough surfaces ranged between 114 and 156 Nm At 4 weeks of healing, the SLA implants yielded a higher mean RTV than the TPS implants (139 vs 1 14 Nm) without reaching statistical significance At 8 and 12 weeks of healing, the two rough surfaces showed similar mean RTVs The implant position also had a significant influence on removal torques for each implant type primarily owing to differences in density in the periimplant bone structure It can be concluded that the interface shear strength of titanium implants is significantly influenced by their surface characteristics, since the machined titanium surface demonstrated significantly lower RTV in the maxilla of miniature pigs compared with the TPS and SLA surfaces

Mercury in a spanish peat bog: archive of climate change and atmospheric metal deposition

Abstract: A peat core from a bog in northwest Spain provides a record of the net accumulation of atmospheric mercury since 4000 radiocarbon years before the present. It was found that cold climates promoted an enhanced accumulation and the preservation of mercury with low thermal stability, and warm climates were characterized by a lower accumulation and the predominance of mercury with moderate to high thermal stability. This record can be separated into natural and anthropogenic components. The substantial anthropogenic mercury component began ∼2500 radiocarbon years before the present, which is near the time of the onset of mercury mining in Spain. Anthropogenic mercury has dominated the deposition record since the Islamic period (8th to 11th centuries A.D.). The results shown here have implications for the global mercury cycle and also imply that the thermal lability of the accumulated mercury can be used not only to quantify the effects of human activity, but also as a new tool for quantitative paleotemperature reconstruction.

Anterior femoroacetabular impingement after periacetabular osteotomy.

Abstract: As experience with the Bernese periacetabular osteotomy has grown, an unexpected observation in a group of patients has alerted the authors to the risk of a secondary impingement syndrome that may occur some time after the periacetabular osteotomy. This possibly may explain residual pain and limited range of motion in a larger group of patients. The impingement is produced by abutment of the femoral head or head to neck junction on the anterior rim of the properly aligned acetabulum. The symptoms are those of restricted flexion, and limited or absent internal rotation in flexion, with variable groin pain. Magnetic resonance imaging studies may reveal acetabular labral disease and adjacent cartilage damage associated with the impingement. Lack of anterior or anterolateral offset between the femoral neck and head results in neck to rim contact when the hip is flexed and/or internally rotated. Before the periacetabular osteotomy this is compensated by the lack of anterior acetabular coverage, but after proper correction the mismatch becomes apparent. The authors recently have devised a routine during the periacetabular osteotomy procedure whereby after the acetabular fragment is corrected into the desired position, the joint is opened, visually inspected, and palpated for impingement with the hip flexed and internally rotated. When necessary, a resection osteoplasty of the femoral neck to head junction is performed to improve the head and neck offset and reduce the anterior contact. This, in the short term, has provided satisfactory prevention of postoperative impingement.

Performance and reproducibility of a laser fluorescence system for detection of occlusal caries in vitro.

Abstract: The diagnosis of occlusal caries at non-cavitated sites remains problematic, especially since clinical visual detection has limited sensitivity. Electrical methods of detection show considerable promise, but specificity is reduced. The aims of this in vitro study were: (1) to assess the validity of a new laser fluorescence device--the DIAGNOdent--(and compare the values with those of a fixed-frequency electrical device); (2) to determine the optimum cut-off points of the new device for different stages of the caries process, and (3) to assess the reproducibility of the new laser device. For validity and determination of optimum cut-off points, 105 extracted teeth with macroscopically intact occlusal surfaces were measured by a single examiner, using both the laser fluorescence device (on both moist and dried teeth) and an Electronic Caries Monitor. The teeth were subsequently examined histologically to determine the specificity, sensitivity and likelihood ratio at the D2 (caries extending through more than half of the enamel thickness) and D3 (caries involving dentin) levels. The values obtained for the laser device ranged from 0.72 to 0.87 (specificity), 0.76 to 0.87 (sensitivity) and 3.0 to 5.6 (likelihood ratio). Those for the ECM ranged from 0.64 to 0.78 (specificity), 0. 87 to 0.92 (sensitivity) and 2.4 to 4.1 (likelihood ratio). To determine intra- and interexaminer reproducibility of the DIAGNOdent, 11 dentists recorded two different measurements at the same site on a separate set of 83 extracted molar teeth, and these were compared using Cohen's kappa (at D2 and D3 levels) and Spearman's correlation coefficient. The average intra-examiner kappa scores were 0.88 (D2) and 0.90 (D3), with a Spearman correlation of 0.97. For interexaminer reproducibility, the average kappa values were 0.65 (D2) and 0.73 (D3), with a Spearman correlation of 0.84. It is concluded that for occlusal caries (1) the new laser device has a higher diagnostic validity than the ECM, and (2) in vitro, measurements using the device are highly reproducible. Thus, the laser device could be a valuable tool for the longitudinal monitoring of caries and for assessing the outcome of preventive interventions.

Interdependence of peat and vegetation in a tropical peat swamp forest

Abstract: The visual uniformity of tropical peat swamp forest masks the considerable variation in forest structure that has evolved in response to differences and changes in peat characteristics over many millennia. Details are presented of forest structure and tree composition of the principal peat swamp forest types in the upper catchment of Sungai Sebangau, Central Kalimantan, Indonesia, in relation to thickness and hydrology of the peat. Consideration is given to data on peat geochemistry and age of peat that provide evidence of the ombrotrophic nature of this vast peatland and its mode of formation. The future sustainability of this ecosystem is predicted from information available on climate change and human impact in this region.

Baryon chiral perturbation theory in manifestly Lorentz invariant form

Abstract: We show that in the presence of massive particles, such as nucleons, the standard low-energy expansion, in powers of meson momenta and light-quark masses, in general converges in only part of the low-energy region. The expansion of the scalar form factor $\sigma(t)$ , for instance, breaks down in the vicinity of $t=4M_\pi^2$ . In the language of heavy baryon chiral perturbation theory, the proper behaviour in the threshold region results only if the multiple internal-line insertions generated by relativistic kinematics are summed up to all orders. We propose a method that yields a coherent representation throughout the low-energy region, while keeping Lorentz and chiral invariance explicit at all stages. The method is illustrated with a calculation of the nucleon mass and of the scalar form factor to order $p^4$ .

Long-term forest fire ecology and dynamics in southern Switzerland

Abstract: 1 Pollen and charcoal analysis at two lakes in southern Switzerland revealed that fire has had a prominent role in changing the woodland composition of this area for more than 7000 years. 2 The sediment of Lago di Origlio for the period between 5100 and 3100 bc cal. was sampled continuously with a time interval of about 10 years. Peaks of charcoal particles were significantly correlated with repeated declines in pollen of Abies, Hedera, Tilia, Ulmus, Fraxinus excelsior t., Fagus and Vitis and with increases in Alnus glutinosa t., shrubs (e.g. Corylus, Salix and Sambucus nigra t.) and several herbaceous species. The final disappearance of the lowland Abies alba stands at around 3150 bc cal. may be an example of a fire-caused local extinction of a fire-intolerant species. 3 Forest fires tended to diminish pollen diversity. The charcoal peaks were preceded by pollen types indicating human activity. Charcoal minima occurred during periods of cold humid climate, when fire susceptibility would be reduced. 4 An increase of forest fires at about 2100 bc cal. severely reduced the remaining fire-sensitive plants: the mixed-oak forest was replaced by a fire-tolerant alder–oak forest. The very strong increase of charcoal influx, and the marked presence of anthropogenic indicators, point to principally anthropogenic causes. 5 We suggest that without anthropogenic disturbances Abies alba would still form lowland forests together with various deciduous broadleaved tree taxa.

Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle

Abstract: mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1α and HIF-1β in human skeletal muscle was studied ...