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Biomedical subjects

J Brandt

Publications and source records attributed to J Brandt.

At least 19 recordsLinked to original sources

Examining Ambrosia pollen episodes at Poznań (Poland) using back-trajectory analysis.

The pollen grains of Ambrosia spp. are considered to be important aeroallergens in parts of southern and central Europe. Back-trajectories have been analysed with the aim of finding the likely sources of Ambrosia pollen grains that arrived at Poznań (Poland). Temporal variations in Ambrosia pollen at Poznań from 1995-2005 were examined in order to identify Ambrosia pollen episodes suitable for further investigation using back-trajectory analysis. The trajectories were calculated using the transport model within the Lagrangian air pollution model, ACDEP (Atmospheric Chemistry and Deposition). Analysis identified two separate populations in Ambrosia pollen episodes, those that peaked in the early morning between 4 a.m. and 8 a.m., and those that peaked in the afternoon between 2 p.m. and 6 p.m.. Six Ambrosia pollen episodes between 2001 and 2005 were examined using back-trajectory analysis. The results showed that Ambrosia pollen episodes that peaked in the early morning usually arrived at Poznań from a southerly direction after passing over southern Poland, the Czech Republic, Slovakia and Hungary, whereas air masses that brought Ambrosia pollen to Poznań during the afternoon arrived from a more easterly direction and predominantly stayed within the borders of Poland. Back-trajectory analysis has shown that there is a possibility that long-range transport brings Ambrosia pollen to Poznań from southern Poland, the Czech Republic, Slovakia and Hungary. There is also a likelihood that Ambrosia is present in Poland, as shown by the arrival of pollen during the afternoon that originated primarily from within the country.

Air↗

An outbreak of East Coast Fever on the Comoros: a consequence of the import of immunised cattle from Tanzania?

In 2003 and 2004, a severe epidemic decimated the cattle population on Grand Comore, the largest island of the Union of Comoros. Fatalities started soon after the import of cattle from Tanzania. Theileria parva and its vector, Rhipicephalus appendiculatus, could be identified as the main culprits of the epidemic. Characterisation by multilocus genotyping revealed that the T. parva parasites isolated on the Comoros were identical to the components of the Muguga cocktail vaccine used in Tanzania to immunise cattle. Therefore, it is believed that East Coast Fever reached the Comoros while some of the imported livestock got infected in Tanzania by ticks of which the immature stadia fed on Muguga cocktail vaccinated animals. Since the Comorian government neither has the financial means nor the competent staff to pursue an adequate epidemiosurveillance, the danger exists that without external assistance and in a context of continuing globalisation more transboundary diseases will affect the Comorian livestock sector in the future.

Animals↗

Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease.

OBJECTIVES: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease (AD) and examine the effects of patients' characteristics on cost longitudinally. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status (measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements. RESULTS: Total direct cost increased from approximately 9,239 dollars per patient per year at baseline, when all patients were at the early stages of the disease, to 19,925 dollars by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting. CONCLUSIONS: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time.

Aged↗

Clinical features associated with costs in early AD: baseline data from the Predictors Study.

BACKGROUND: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics. OBJECTIVE: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs. METHODS: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness. RESULTS: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a $2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed. CONCLUSIONS: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living.

Aged↗

The association of CAG repeat length with clinical progression in Huntington disease.

OBJECTIVE: To determine whether the rate of clinical progression in Huntington disease (HD) is influenced by the size of the CAG expansion. METHODS: The dataset consisted of 3,402 examinations of 512 subjects seen through the Baltimore Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with mean follow-up of 6.74 years. Subjects were administered the Quantified Neurological Examination, with its subsets the Motor Impairment and Chorea Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living (ADL) Scale. RESULTS: In an analysis based on the Random Effects Model, CAG length was significantly associated with the rate of progression of all measures except chorea and ADL. There was a significant interaction term between CAG length and disease duration for all measures except chorea. Further graphical exploration of the data supported these linear models and suggested that subjects at the low end of the expanded CAG repeat range may experience a more benign late course. CONCLUSIONS: CAG repeat length has a small effect on rate of progression that may be clinically important over time. Individuals with the shortest expansions appear to have the best prognosis. These effects of the CAG length may be relevant in the analysis of clinical trials.

Baltimore↗

Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial.

OBJECTIVES: To assess the effect of sulfasalazine (SSZ) on inflammatory back pain (IBP) due to active undifferentiated spondyloarthritis (uSpA) or ankylosing spondylitis in patients with symptom duration <5 years. METHODS: Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >3 from 12 centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or placebo. The primary outcome variable was the change in BASDAI over 6 months. Secondary outcomes included measures of spinal pain, physical function and inflammation. RESULTS: 230 patients (50% men, age range 18-64 years, 67% human leucocyte antigen B27 positive) were treated with either SSZ 2x1 g/day or placebo for 6 months. Enthesitis was found in 50%, and peripheral arthritis in 47% of the patients. The mean (SD) BASDAI dropped markedly in both groups: by 3.7 (2.7) and 3.8 (2.4), respectively, as did most secondary outcome measures. No noticeable difference in treatment was observed between groups. Patients with IBP and no peripheral arthritis had significantly (p = 0.03) more benefit with SSZ (BASDAI 5.1 (1.3) to 2.8 (2.3)) than with placebo (5.2 (1.6) to 3.8 (2.4)). Spinal pain (p = 0.03) and morning stiffness (p = 0.05) improved with SSZ in these patients, but other secondary outcomes were not markedly different. CONCLUSION: SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA; however, SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis.

Adolescent↗

[A 46-year-old-patient with granulomatous prostatitis, arthralgia and haemorrhagic rhinitis].

HISTORY AND ADMISSION FINDINGS: A 46-year-old, having developed developed gross haematuria and pain in the genital region, was referred to a urological unit. Because palpation of his prostatic gland was abnormal, a transurethral prostatic resection was performed. The histology showed a necrotizing and granulomatous inflammation of the prostate with small-vessel vasculitis and eosinophilic infiltrates. As the patient had also developed arthralgia and symptoms in the upper respiratory tract, he was admitted to our hospital. The test for c-ANCA with specifity for proteinase 3 was positive. There was no history or symptoms of asthma. DIAGNOSIS: Wegener's granulomatosis. TREATMENT AND COURSE: To achieve remission bolus therapy with cyclophosphamide and prednisolone was initiated and planned to be the first of three pulses But when the patient developed epididymitis and a neuropathy associated with Wegener"s granulomatosis, the dose was increased and cyclophosphamide was given for a longer period. CONCLUSION: The early manifestation of Wegener"s granulomatosis at the prostatic gland is rare in this disease. This case presented with an impressive variation of symptoms, which may occur especially in the early course of vasculitis. The findings of c-ANCA with specifity for proteinase 3 is important for the diagnosis of this disease.

Anti-Inflammatory Agents↗

[Effectiveness and safety of radium chloride in the treatment of ankylosing spondylitis. Results of an observational study].

After radium chloride was approved for the therapy of ankylosing spondylitis (AS) in Germany on October 23, 2000, an open, non-comparative prospective observational study was planed. The assessment involved 308 patients with the diagnosis of AS and radiological evidence of spinal involvement who were treated with at least one injection of radium chloride. 278 of these patients received the full cycle of 10 injections (a total of 10 MBq radium-224) one injection one per week for a period of 10 successive weeks. Validated outcomes were measured before therapy and six months after therapy according to the recommendations of the "assessment in ankylosing spondylitis working group"(ASAS). The primary endpoint was disease activity assessed using the BASDAI ("Bath Ankylosing Spondylitis Disease Activity Index"). Secondary endpoints included the BASFI ("Bath Ankylosing Spondylitis Functional Index"), as well as self-reported pain and global patient ratings. Patients showed significant improvement in all of the parameters assessed (BASDAI, BASFI, pain, global patient rating) at 6-months post-treatment. At this time, the mean BASDAI and BASFI scores improved from 5.5 to 3.5 and from 5.6 to 3.7, respectively. Pain decreased from a mean of 7.3 to 4.1, and disease activity (as rated by patients) also decreased from 7.2 to 4.1 (p < 0.001 for all of them). Drug tolerance was good. Six adverse events were documented, none of which was serious and none led to discontinuation of treatment. According to the data provided here medical treatment with radium chloride seems to be effective and safe during an observation period of 6 months. Nevertheless, a randomized placebo-controlled study should be performed in the near future in order to safeguard the level of evidence.

Adult↗

Identifying the European fossil fuel plumes in the atmosphere over the Northeast Atlantic Region through isotopic observations and numerical modelling.

As part of the Danish NEAREX project the origin and variability of anthropogenic atmospheric CO(2) over the Northeast Atlantic Region (NEAR) has been studied. The project consisted of a combination of experimental and modelling activities. Local volunteers operated CO(2) sampling stations, built at University of Copenhagen, for (14)C analysis at four locations (East Denmark, Shetland Isles, Faroe Isles and Iceland). The samples were only collected during winter periods of south-easterly winds in an attempt to trace air enriched in fossil-fuel derived CO(2) due to combustion of fossil fuels within European countries. In order to study the transport and concentration fields over the region in detail, a three-dimensional Eulerian hemispheric air pollution model has been extended to include the main anthropogenic sources for atmospheric CO(2). During the project period (1998-2001) only a few episodes of transport from Central Europe towards NEAR arose, which makes the data set for the evaluation of the method sparse. The analysed samples indicate that the signal for fossil CO(2), as expected, is largest (up to 3.7+/-0.4% fossil CO(2)) at the Danish location closest to the European emissions areas and much weaker (up to approximately 1.5+/-0.6% fossil CO(2)) at the most remote location. As the anthropogenic signal is weak in the clean atmosphere over NEAR these numbers will, however, be very sensitive to the assumed background (14)CO(2) activity and the precision of the measurements. The model simulations include the interplay between the driving processes from the emission into the boundary layer and the following horizontal/vertical mixing and atmospheric transport and are used to analyse the meteorological conditions leading to the observed events of high fossil CO(2) over NEAR. This information about the history of the air masses is essential if an observed signal is to be utilised for identifying and quantifying sources for fossil CO(2).

Air Pollutants↗

Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects.

The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ratio of plasma:CSF concentrations of LY450108 and LY451395 after multiple dosing. This study was an open-label, multiple oral dose study evaluating 1 mg and 5 mg LY450108 and 1 mg and 5 mg LY451395 in 12 (3 subjects per dosing group) healthy subjects, aged 18 to 49 years. Twelve healthy male subjects completed the study. LY450108 and LY451395 were quantifiable in CSF after 1-mg and 5-mg multiple-dose administrations with plasma:CSF ratio of 82:1 and 44:1, respectively. LY450108 and LY451395 1 mg and 5 mg were measured in the CSF. Single and multiple oral doses of LY450108 and LY451395 were determined to be safe and well tolerated in healthy subjects.

Adult↗

Taeniasis-cysticercosis in Southern Ecuador: assessment of infection status using multiple laboratory diagnostic tools.

Taenia solium-taeniasis and cysticercosis were studied in the human and porcine populations of a rural community in the Southern Ecuadorian Andes. From the 1059 inhabitants, 800 serum samples and 958 stool samples could be collected. In addition, 646 from the estimated 1148 pigs were tongue inspected. Circulating antigen was detected by enzyme linked immunosorbent assay (Ag-ELISA) in 2.25% of the human population, whereas intestinal taeniasis was detected in 1.46% by the formalin-ether technique. Following treatment and recovery of tapeworm fragments these were all identified as T. solium. Porcine cysticercosis was diagnosed in 3.56% of the pigs by tongue inspection. In addition, enzyme linked immunoelectrotransfer blot (EITB) was performed on a subset group of 100 humans to confirm the results of the Ag-ELISA. One hundred serum samples from pigs were also analysed by EITB. It appeared that 43 and 74% of humans and pigs had antibodies against T. solium cysticerci, respectively. It is concluded that contrary to the high exposure of the human population to T. solium that is suggested by EITB, the number of active cysticercosis cases, diagnosed by Ag-ELISA, was low, which may indicate endemic stability. The further use of complementary diagnostic methods for a better understanding of the epidemiology of T. solium is suggested.

Adolescent↗

Infectivity of Theileria parva sporozoites following cryopreservation in four suspension media and multiple refreezing: evaluation by in vitro titration.

Theileria parva sporozoite stabilates are used for immunizing cattle against East Coast fever and in in vitro sporozoite neutralization assays. In this study, we attempted to identify a cheaper freezing medium and quantified the infectivity loss of sporozoites due to refreezing of stabilates, using an in vitro technique. Pools of stabilates prepared using Minimum Essential Medium (MEM), Roswell Park Memorial Institute (RPMI 1640), foetal calf serum (FCS) and phosphate-buffered saline (PBS) were compared. All were supplemented with bovine serum albumin except the FCS. RPMI 1640 was as effective as MEM in maintaining sporozoite infectivity while the infectivity in PBS and FCS reached only 59% and 67%, respectively. In a second experiment, a stabiiate based on MEM was subjected to several freeze-thaw cycles including various holding times on ice between thawing and refreezing. Refrozen stabilate gave an average sporozoite infectivity loss of 35% per cycle. The results indicate that RPMI can be used as a cheaper freezing medium for T. parva stabilates and that refrozen stabilate doses need to be adjusted for the 35% loss of infectivity.

Animals↗

Outcome of patients with active ankylosing spondylitis after two years of therapy with etanercept: clinical and magnetic resonance imaging data.

OBJECTIVE: To examine the long-term outcome of patients with active ankylosing spondylitis (AS) clinically and by magnetic resonance imaging (MRI) after continuous treatment with the tumor necrosis factor (TNF) receptor fusion protein etanercept over 2 years. METHODS: Overall, 26 patients with active AS were treated with etanercept 25 mg twice daily subcutaneously, twice weekly with no concomitant disease-modifying antirheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. Inflammatory spinal lesions were quantified by the ASspiMRI-a rating gadolinium-enhanced (T1-weighted gadolinium diethylenetriaminepentaacetic acid) and STIR MRI sequences. The primary outcome was a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement > or =50% after 2 years of etanercept therapy compared with the baseline value of the study. RESULTS: Overall, 21 (70%) of 30 patients completed year 2. In the intent-to-treat analysis, 54% of the patients showed a 50% improvement according to the BASDAI and a 40% improvement according to the Assessment in Ankylosing Spondylitis (ASAS) criteria. In the completer analysis, 9 (43%) of 21 patients were in partial remission according to ASAS criteria. Mean +/- SD BASDAI scores, which were elevated at baseline (6.3 +/- 1.6), remained low: 2.7 +/- 2.4 after 2 years compared with 2.6 +/- 2.2 at week 54. In accordance, all other clinical parameters showed sustained improvement during year 2. The majority of patients had no disease activity flares. MRI evaluation showed a 75% improvement of active spinal lesions, but minor spinal inflammation was still present in 64% of the patients after 2 years. There were 2 serious adverse events leading to discontinuation of etanercept. CONCLUSION: The clinical efficacy and safety of etanercept in patients with active AS without simultaneous administration of DMARDs or steroids over 2 years of continuous treatment is confirmed. Spinal inflammation as depicted by MRI decreased significantly, but a few patients still had some spinal inflammation even after long-term anti-TNF therapy.

Adult↗

MEAD: an interdisciplinary study of the marine effects of atmospheric deposition in the Kattegat.

This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions.

Agriculture↗

Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA.

Melanoma inhibitory activity (MIA), also referred to as cartilage-derived retinoic acid-sensitive protein (CD-RAP), an 11-kDa secreted protein, is mainly expressed in cartilaginous tissue during embryogenesis and adulthood. Currently, the function of MIA in cartilage tissue is not understood. Here, we describe that MIA acts as a chemotactic factor on the mesenchymal stem cell line C3H10T1/2, stimulating cell migration significantly at concentrations from 0.24 to 240 ng/ml, while inhibiting cell migration at higher doses of 2.4 microg/ml. When analyzing the role of MIA during differentiation processes, we show that MIA by itself is not capable to induce the differentiation of murine or human mesenchymal stem cells. However, MIA influences the action of bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta 3 during mesenchymal stem cell differentiation, supporting the chondrogenic phenotype while inhibiting osteogenic differentiation. Quantitative RT-PCR analysis revealed the up-regulation of the cartilage markers MIA, collagen type II and aggrecan in human mesenchymal stem cell (HMSC) cultures differentiated in the presence of MIA and TGF-beta 3 or BMP-2 when compared to HMSC cultures differentiated in the presence of TGF-beta 3 or BMP-2 alone. Further, MIA down-regulates gene expression of osteopontin and osteocalcin in BMP-2 treated HMSC cultures inhibiting the osteogenic potential of BMP-2. In the case of human primary chondrocytes MIA stimulates extracellular matrix deposition, increasing the glycosaminoglycan content. Therefore, we postulate that MIA is an important regulator during chondrogenic differentiation and maintenance of cartilage.

Adult↗

Survey on porcine trichinellosis in Ecuador.

A survey on porcine trichinellosis was organised in Ecuador between 2000 and 2003. Blood samples were taken in slaughterhouses (study 1, n=2000; study 2, n=331) and in a remote village where pigs are free roaming (study 3, n=646) and examined by ELISA using excretory/secretory (E/S) antigens. Seven samples (0.35%) in study 1 and none of the samples of study 2 were serologically positive. Thirty-seven (5.72%) village pigs tested positive by E/S ELISA in study 3. Sero-positive results by the E/S ELISA in study 1 were confirmed by ELISA using beta-tyvelose antigen, and by immunoblot. Muscle samples taken from pigs slaughtered in the abattoir (study 2) and from animals that showed a positive serology in study 3 were examined by trichinoscopy and artificial digestion. These techniques failed to demonstrate the presence of muscle larvae. The results of this survey need confirmation, but suggest that Trichinella is present in Ecuador; however, prevalence and parasite burdens are likely to be very low. The likelihood of detecting trichinellosis are higher in traditional settings than in pigs raised on improved farms.

Animals↗

Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent infliximab.

OBJECTIVES: Patients with ankylosing spondylitis (AS) benefit from anti-TNF therapy both on a clinical basis and as depicted by magnetic resonance imaging (MRI). It is not known whether spinal inflammation remains suppressed over time. Our objective was to assess spinal inflammation by MRI in AS patients after 2 yr of continuous infliximab treatment. METHODS: Twenty patients with active AS were examined by MRI at baseline, after 3 months (end of placebo-controlled-phase) and after 2 yr of continuous infliximab therapy (5 mg/kg/6 weeks). T1 pre- and post-gadolinium (T1/gadolinium-diethylenetriamine-pentaacetic acid) and short tau inversion recovery (STIR) MRI sequences were performed and read by one blinded reader using the ASspiMRI score. RESULTS: Spinal inflammation, detected by MRI in all patients at baseline, decreased after 3 months only in the infliximab group in both MRI sequences. Persistent improvement of spinal inflammation was seen after 2 yr by scoring STIR sequences, with a mean score of 4.6 +/- 5.9 vs 15.2 +/- 13.2 at baseline (P = 0.01). On an individual level, inflammatory spinal lesions decreased from 6.7 +/- 5.0 per patient at baseline to 2.2 +/- 1.8 after 2 yr (P = 0.003). Improvement in spinal inflammation was found in all patients by both MRI sequences. Only a minor degree but some spinal inflammation was still present after 2 yrs. CONCLUSION: Spinal inflammation in MRI was persistently reduced in all patients constantly treated with infliximab, but it was not completely eradicated. Disease activity parameters did not directly correlate with MRI, but both pointed in the same direction. Both types of information may be useful for the definition of response to anti-TNF therapy.

Adult↗