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Biomedical subjects

P Berg

Publications and source records attributed to P Berg.

At least 19 recordsLinked to original sources

[Effectiveness of antiviral therapy in patients with chronic hepatitis C treated by private practice gastroenterologists].

The standard treatment for patients with chronic hepatitis C consists of pegylated interferon (PegIFN) alpha in combination with ribavirin. Information on treatment effectiveness outside clinical trials is sparse. To study community-based health care, a regional network supported by the German network of competence for hepatitis (Hep-Net) was created between gastroenterologists in private practice and a tertiary referral centre. A treatment register containing evidence-based guidelines was established and 212 consecutive patients who were treated with either PegIF Nalpha 2a/ribavirin (n = 126) or PegIFNalpha2b/ribavirin (n = 86) for 24 weeks (HCV genotype 2, 3) and 48 weeks (HCV genotype 1, 4, 5), respectively, were included and followed prospectively. Twenty-four weeks after cessation of antiviral treatment a sustained virological response was achieved in 54 % of the patients. By univariate analyses, infection with HCV genotypes 2 or 3 (p < 0.0001), younger age (p < 0.0001), normal gamma-glutamyltransferase levels before initiation of treatment (p = 0.003), and absence of language communication problems (p = 0.023) were associated with a sustained virological response. The presence of liver cirrhosis in patients with HCV genotype 1, 4, 5 infection was associated with lower sustained response rates (p = 0.025). Patients infected with HCV genotype 1 in whom the PegIFNalpha dose was reduced had higher virological relapse rates (p = 0.049). With regard to the treating physician, sustained virological response rates ranged from 26 - 67 % in patients infected with HCV genotype 1. Our study shows that virological response rates similar to those in international randomised clinical trials can be achieved by private practice gastroenterologists. The presented network allows characterization of the treatment outcome in chronic hepatitis C not only with regard to virus- and host-related factors but also on an individual physician basis.

Adult↗

Udder health shows inbreeding depression in Danish Holsteins.

The purpose of this study was to estimate inbreeding depression for udder health using records on mastitis incidence and somatic cell count (SCC). Data were selected based on a pedigree completeness index so that inbreeding coefficients were reliable. Average inbreeding was 3.3%. The presence or absence of mastitis was considered in first (CM1), second (CM2), and third (CM3) lactations, and was recorded as a binary trait. Somatic cell count was also included and analyzed on the log scale. A minimum of 140,000 cows with records were included per trait. Linear sire models were used and (co)variance components were estimated. Linear and curvilinear effects of the coefficient of inbreeding were included. Inbreeding significantly affected all traits investigated. Three traits, CM1, CM3, and SCC, showed a nonlinear relationship between phenotype and inbreeding coefficient. A cow with 5% inbreeding compared with a cow with 2% inbreeding had a higher SCC and a higher incidence of mastitis. The SCC increased by 1,500 cells/mL in first lactation and the incidence of mastitis increased by 1.08, 0.55, and 0.98% in first, second, and third lactation, respectively. The corresponding reduction in net return from these traits over 3 lactations amounted to 11.00 US dollars under Danish production circumstances. These results are a step on the way to estimating the total cost of inbreeding depression to determine an acceptable rate of inbreeding.

Animals↗

Inbreeding in Danish dairy cattle breeds.

The purpose of this study was to monitor current and predict future rates of inbreeding in the Danish dairy breeds. Calves born from 1999 until 2003 and registered as Danish Holstein (1,883,983), Danish Jersey (336,966), or Danish Red (261,047) were reference populations. Average complete generation equivalent was approximately 7. For calves born in 2003, average inbreeding was 3.9, 3.4, and 1.4% for Holstein, Jersey, and Danish Red, respectively. In recent years, effective population sizes were 49, 53, and 47, respectively. Based on coancestry statistics, future effective population sizes will be 43, 42, and 51, respectively. The effective number of founders, effective number of ancestors, and effective number of founder genomes were calculated. These measures of genetic diversity were all low for Holstein and Jersey and somewhat larger for Danish Red. The most important ancestors of Danish Holstein were Elevation (13.8%), Chief (10.9%), and Bell (8.5%). The most important ancestor of Danish Red was Momentum (9.4%), a Red Holstein-Friesian. The most important ancestor for Danish Jersey was FYN Lemvig (12.1%) with a large number of progeny in the reference population. The results of this study indicate the necessity for active management of the rate of inbreeding in the future.

Animals↗

Central pain and complex motoric symptoms after gosarelin therapy of prostate cancer.

A 76-year-old man with prostate cancer T3N0M0 and increasing PSA was treated with goserelin three times in a half year. As soon as the first treatment, he described subjective muscle weakness. After the third treatment, he developed complex motoric symptoms and atypical central pain with a likely association to goserelin. His left arm had signs of spastic movement; pain deteriorated after relaxation. The right hand showed muscle cramps under passive movements of the left arm that were not typical for rigor. He felt aching and partial burning pain in his whole body. There were few allodynic areas, mainly in the left arm. Several treatment approaches failed and the patient died some weeks after the first contact with our pain clinic due to pneumonia.

Aged↗

Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia.

BACKGROUND: Spinal cord stimulation (SCS) may have a place in the treatment of patients with inoperable chronic critical leg ischaemia. METHODS: A systematic review and meta-analysis was performed of all controlled studies comparing SCS in addition to any form of conservative treatment for inoperable chronic critical leg ischaemia. Main endpoints were limb salvage, pain relief and clinical situation. Systematic methodological appraisal and data extraction were performed by independent reviewers. RESULTS: Of the 18 reports found, nine trials, comprising 444 patients, matched the selection criteria. After pooling, limb salvage at 12 months appeared significantly greater in the SCS group (risk difference (RD) -0.13 (95 per cent confidence interval (c.i.) -0.04 to -0.22)). Significant pain relief occurred in both treatment groups, but patients who received SCS required significantly less analgesia and reached Fontaine stage 2 more often than those who did not have SCS (RD 0.33 (95 per cent c.i. 0.19 to 0.47)). Complications of SCS were problems of implantation (8.2 per cent), changes in stimulation requiring reintervention (14.8 per cent) and infection (2.9 per cent). CONCLUSION: The addition of SCS to standard conservative treatment improves limb salvage, ischaemic pain and the general clinical situation in patients with inoperable chronic critical leg ischaemia. These benefits should be weighed against the cost and the (minor) complications associated with the technique.

Ankle↗

Magnetoencephalographic spikes not detected by conventional electroencephalography.

OBJECTIVE: To investigate some of the reasons why magnetoencephalographic (MEG) spikes are at times not apparent in conventional electroencephalograms (EEG) when the data are co-registered, and to explore to what extent modern EEG analysis methods can improve the yield. METHODS: Seventy seconds of MEG-EEG co-registration on a 122 channel Neuromag system were studied in a 10-year-old boy with Landau-Kleffner syndrome. Twenty-six EEG channels were originally recorded with a left ear reference. The EEG data were subsequently reformatted (BESA) to a variety of montages for the 10-20 and 10-10 electrode array. A 10 s data epoch was compared in detail for concordance between MEG and EEG spikes. To detect the characteristics of hidden low voltage EEG spikes, MEG spikes were averaged and compared with the concomitant averaged EEG spike. RESULTS: While there was an abundance of EEG as well as MEG spikes on the left; definite right-sided spikes were not visible in the EEG. Right hemispheric MEG spikes were, however, plentiful with an average strength of 757 fT. When the individual MEG spikes from the right hemisphere were compared with the corresponding EEG events their amplitude ranged between 24 and 31 microV and were, therefore, indistinguishable from background activity. The majority of them became visible, however, with further sophisticated data analysis. CONCLUSIONS: When the relative merits of MEG versus EEG recordings for the detection of epileptogenic spike are investigated the 10-20 system of electrode placement and conventional methods of EEG analysis do not provide optimal data assessment. The use of the 10-10 electrode array combined with modern methods of digital data analysis can provide better concordance with MEG data.

Child↗

The Scandinavian Sarcoma Group Skeletal Metastasis Register. Survival after surgery for bone metastases in the pelvis and extremities.

INTRODUCTION: The assessment of the prognosis for the individual patient is important for the choice of surgical treatment of skeletal metastases. In 1999 the Scandinavian Sarcoma Group (SSG) initiated the Skeletal Metastasis Register as a multicentric, prospective study to provide a scientific basis for treatment recommendations. To improve prognostication we analyzed the survival of patients with skeletal metastases surgically treated at 9 SSG centres. PATIENTS AND METHODS: 460 patients with an average age of 64 years underwent 501 operations for non-spinal skeletal metastases. 7% were operated for more than one metastasis. Carcinoma of the breast, prostate, kidney and lung were the dominating primary tumors. RESULTS: The survival rate was 0.4 at 1 year, 0.3 at 2 years and 0.2 at 3 years. Univariate analysis showed that survival was related to bone localization, skeletal metastatic load, presence of visceral metastases, Karnofsky performance score, primary tumor type, presence of a complete pathological fracture and preoperative hemoglobin content. Multivariate regression analysis showed that pathological fracture, visceral metastases, haemoglobin content < 7 mmol/L and lung cancer were negative prognostic factors for survival. Myeloma was the sole positive prognostic factor for survival.

Bone Neoplasms↗

Genetic variation and heritability of the antibody response to Mycobacterium avium subspecies paratuberculosis in Danish Holstein cows.

The purpose of this study was to estimate the genetic variation and the heritability of the ability to establish an immune response by producing antibodies to Mycobacterium avium subsp. paratuberculosis. Antibody levels were determined using an ELISA and measuring optical density (OD) values from milk samples of 11,535 cows from 99 herds. The pedigree of the 11,535 cows and information about days in milk, parity, milk yield, and others were obtained from the Danish Cattle database. The statistical analyses were made using a bivariate mixed animal model. The bivariate model with daily milk yield and OD as dependent variables showed a significant heritability of the ability to produce Mycobacterium avium subsp. paratuberculosis antibodies of 0.102 (genetic variance=0.054) and a nonsignificant genetic correlation of -0.037 between daily milk yield and OD. When a sire model was used, the estimated heritability was 0.091. To evaluate whether intrauterine infection could be reflected in the OD, variation among 2715 dam-daughter or maternal sister groups was also estimated. Variation in this data was nonsignificant, possibly because only very few clinical cases or end-stage cows, i.e., heavy bacterial shedders may have been represented among the cows sampled. It does not appear that intrauterine transmission is of major importance in the transmission of paratuberculosis.

Analysis of Variance↗

[Patient education in practice-a workshop in a small group].

The aim of the workshop was to work out concrete plans and steps for implementing patient education courses in an outpatient setting by the collaborative arthritis centers in Germany. Primarily the patient education model of Lower Saxony was illustrated as an example of successful implementation of patient education programs in practice. In this state patient education courses are run in cooperation between the Arthritis Center of Hannover and the League against Rheumatism in Lower Saxony. Both institutions are in discussion with the health insurance companies for paying the costs for the patient education courses. Then the group discussed several important aspects which have to be considered when establishing patient education courses such as recruiting and motivating the trainers, recruiting the participants, choosing adequate rooms, fund raising and responsibilities. The participants considered the patient education model of Lower Saxony as a transferable model for every collaborative arthritis center in Germany and recommended to follow that path.

Ambulatory Care↗

Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS).

OBJECTIVE: To determine the effect of spinal cord stimulation (SCS) on limb survival in patients with non-reconstructable critical leg ischaemia, and the value of patient selection on the basis of transcutaneous oxygen pressure (TcpO2) measurements and trial screening. DESIGN: A prospective, controlled, European multicentre study. METHODS: Non-reconstructable patients with stable critical leg ischaemia were divided into three groups. The SCS-Match group comprised patients with a baseline forefoot TcpO2 of < 30 mmHg and both sufficient pain relief and sufficient paraesthesia coverage (> 75%) after a test stimulation period of at least 72 h. If baseline TcpO2 was < 10 mmHg, the TcpO2 should have exceeded 20 mmHg after test stimulation. The SCS-Match group was compared with patients not meeting these criteria, who were treated either with SCS (SCS-No-Match) or without SCS (No-SCS). RESULTS: At baseline, the mean (+/- SD) supine TcpO2 was 14.9 +/- 8.3 mmHg in the SCS-Match group (n = 41), 11.3 +/- 13.3 mmHg in the SCS-No-Match group (n = 32) and 15.3 +/- 17.1 mmHg in the No-SCS group (n = 39). In the SCS-Match group a significant improvement in pain relief (p < 0.005) and TcpO2 (p < 0.001) was seen. After 12 months, cumulative limb survival of patients treated with SCS was significantly better than that of patients not treated with SCS (p < 0.03), and limb survival in the SCS-Match group was significantly higher (p < 0.03) than that in the SCS-No-Match and No-SCS groups (78, 55 and 45%, respectively). CONCLUSION: SCS treatment of non-reconstructable critical leg ischaemia provides a significantly better limb survival rate compared with conservative treatment. Patient selection based on TcpO2 and the results of trial screening further increase the probability of limb survival after SCS therapy.

Adult↗

Exposure assessment to alpha- and beta-pinene, delta(3)-carene and wood dust in industrial production of wood pellets.

The main aim of the study was to measure the exposure to monoterpenes (alpha- and beta-pinene and Delta(3)-carene) and wood dust during industrial production of wood pellets and briquettes. Additional aims were to compare the results from wood dust sampled on a filter with real time measurements using a direct reading instrument and to identify peak exposures to dust. Twenty-four men working at six companies involved in industrial production of wood pellets and briquettes participated in the study. Monoterpenes were measured by diffusive sampling and wood dust was measured as total dust. A data logger (DataRAM) was used for continuous monitoring of dust concentration for 18 of the participants. The sampling time was approximately 8 h. The personal exposure to monoterpenes ranged from 0.64 to 28 mg/m(3) and a statistically significant (Kruskal-Wallis test, P = 0.0002) difference in levels of monoterpenes for workers at different companies was seen. In the companies the personal exposure to wood dust varied between 0.16 and 19 mg/m(3) and for 10 participants the levels exceeded the present Swedish occupational exposure limit (OEL) of 2 mg/m(3). The levels of wood dust during the morning shift were significantly (Mann-Whitney test, P = 0.04) higher compared with the afternoon shift. Continuous registration of dust concentration showed peak values for several working operations, especially cleaning of truck engines with compressed air. For 24 workers in six companies involved in industrial production of wood pellets the personal exposure to monoterpenes was low and to wood dust high compared with the present Swedish OEL and previous studies in Swedish wood industries. Since the DataRAM can identify critical working tasks with high wood dust exposure a reduction in exposure levels could probably be achieved by changes in working routines and by the use of protective equipment.

Alkyl and Aryl Transferases↗

The best TcpO(2) parameters to predict the efficacy of spinal cord stimulation to improve limb salvage in patients with inoperable critical leg ischemia.

AIM: Spinal cord stimulation (SCS) is available as an alternative therapy for patients suffering from inoperable critical limb ischemia (CLI). Selection of patients is essential to achieve the best treatment effect. For this purpose transcutaneous oxygen (TcpO(2)) measurements have frequently been applied. So far, it is unclear which TcpO(2) parameters serve this purpose best. METHODS: Studies in which inoperable CLI patients were treated with conservative treatment with or without SCS, and in whom various TcpO(2) measurements were performed before and during treatment were pooled to investigate which TcpO(2) parameter(s) were best to detect patients who benefit most from SCS treatment as to limb salvage. RESULTS: TcpO(2) in the supine position increased significantly (p<0.001) in patients after a short period of SCS treatment (from 9 to 22 mmHg), but not in those treated conservatively (from 7 to 7 mmHg). Baseline supine TcpO(2) (using a cut-off value of 10 mmHg), the baseline sitting-supine TcpO(2) difference (cut-off value: 17 mmHg), and the difference in TcpO(2) before and after test stimulation (cut-off value: 4 mmHg) were related to a significantly increased limb salvage. SCS patients with a sitting-supine TcpO(2) difference of >17 mmHg had a 1-year limb salvage of 83% vs 68% in the whole SCS-treated group irrespective of TcpO(2) selection. CONCLUSION: The TcpO(2) parameters mentioned above are capable of detecting the effect of SCS treatment. Selection using (a combination of) TcpO(2) measurements substantially improves limb salvage of patients treated with SCS for inoperable CLI.

Aged↗

Hepatotoxic reactions induced by beta-lactamase inhibitors.

Since amoxicillin/clavulanate was first introduced in the UK in 1981, beta-lactamase inhibitors are used increasingly worldwide. Two more drugs of this class are currently available, sulbactam and tazobactam. Meanwhile, adverse drug reactions associated with amoxicillin/clavulanate occurring late after the end of therapy have been repeatedly published. In many cases, a cholestatic hepatitis was diagnosed that was most likely caused by the clavulanic acid component of the combination. Symptoms were mostly mild and reversible, whereas a number of cases showing a protracted, even fatal course of the disease have been documented. This article summarizes and analyzes all relevant studies and case reports dealing with hepatotoxicity caused by beta-lactamase inhibitors. The description of a typical case from our own patient population illustrates the clinical challenge associated with this adverse drug reaction.

Chemical and Drug Induced Liver Injury↗

On-ramp simulations and solitary waves of a car-following model.

An on-ramp simulation of a car-following model reveals qualitatively similar results to previous simulations of continuum models carried out by Helbing et al. [Phys. Rev. Lett. 82, 4360 (1999)] and by Lee, Lee, and Kim[Phys. Rev. E 59, 5101 (1999)]. Here, we discuss the solitary solution type in greater detail. It can be approximated by a Kortweg-de Vries equation derived from the analogous continuum version. Hence, this establishes a further link between these two traffic simulation types and supports the idea that models of either kind lead to similar results when they contain a relaxation term.

Journal Article↗

Differential usage of nuclear export sequences regulates intracellular localization of the dioxin (aryl hydrocarbon) receptor.

The dioxin receptor belongs to the basic helix-loop helix/Per-Arnt-Sim (bHLH)/PAS family of proteins and functions as a ligand-dependent transcription factor to activate target genes. The function of the PAS domain of the dioxin receptor is only partially understood. Whereas the C-terminal half of the PAS domain has been shown to harbor ligand binding activity and to function as an accessory dimerization interface, the precise functional role of the N-terminal half of the PAS domain remains unclear. We have previously shown that this domain confers dimerization specificity to the dioxin receptor. Here we report the identification and characterization of a novel nuclear export sequence (NES) motif, located in the N-terminal portion of the PAS domain, in addition to the previously identified NES in the bHLH domain. By point mutagenesis, we have generated a dominant positive form of the PAS domain NES motif that inhibits accumulation of the dioxin receptor in the nuclear compartment of the cell. This mutant form of the receptor was furthermore unable to sustain reporter gene activation. Importantly, we demonstrate that the ligand-free and ligand-occupied forms of the dioxin receptor differentially employ the two NES motifs. In the absence of ligand, nuclear export is sustained via the PAS domain NES, whereas following ligand-dependent activation nuclear export of the receptor is mediated by the NES in the bHLH domain.

Amino Acid Motifs↗

Traveling waves in an optimal velocity model of freeway traffic.

Car-following models provide both a tool to describe traffic flow and algorithms for autonomous cruise control systems. Recently developed optimal velocity models contain a relaxation term that assigns a desirable speed to each headway and a response time over which drivers adjust to optimal velocity conditions. These models predict traffic breakdown phenomena analogous to real traffic instabilities. In order to deepen our understanding of these models, in this paper, we examine the transition from a linear stable stream of cars of one headway into a linear stable stream of a second headway. Numerical results of the governing equations identify a range of transition phenomena, including monotonic and oscillating travelling waves and a time- dependent dispersive adjustment wave. However, for certain conditions, we find that the adjustment takes the form of a nonlinear traveling wave from the upstream headway to a third, intermediate headway, followed by either another traveling wave or a dispersive wave further downstream matching the downstream headway. This intermediate value of the headway is selected such that the nonlinear traveling wave is the fastest stable traveling wave which is observed to develop in the numerical calculations. The development of these nonlinear waves, connecting linear stable flows of two different headways, is somewhat reminiscent of stop-start waves in congested flow on freeways. The different types of adjustments are classified in a phase diagram depending on the upstream and downstream headway and the response time of the model. The results have profound consequences for autonomous cruise control systems. For an autocade of both identical and different vehicles, the control system itself may trigger formations of nonlinear, steep wave transitions. Further information is available [Y. Sugiyama, Traffic and Granular Flow (World Scientific, Singapore, 1995), p. 137].

Journal Article↗