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Biomedical subjects

W Beck

Publications and source records attributed to W Beck.

At least 19 recordsLinked to original sources

Qualitative and quantitative observations on the flea population dynamics of dogs and cats in several areas of Germany.

From an ongoing country-wide study on the spectrum, the epidemiology and the population dynamics of flea infestations in dogs and cats, important preliminary results from the three areas of Karlsruhe, Nuernberg and Leipzig are presented. A total of 1922 dogs and 1838 cats from 12 different veterinary practices or clinics in three areas of Germany were systematically examined between July 2003 and June 2004. All dogs and cats appearing for a clinical veterinary consultation on one regular working day per month, per practice, were clinically examined. Dogs and cats were examined irrespective of any kind of prior therapeutic or prophylactic insecticidal treatment. The results show that a total of 99 dogs (5.13%) and 263 cats (14.33%) were infested. Cats were more often flea-infested than dogs (p < 0.05). The highest infestation rates for dogs (x = 7.87%) were detected between July and October, and for cats (x = 21.14%) between July and September, the lowest infestation rates for dogs (x = 2.88%) were observed between November and May, and for cats (x = 12.16%) between November and April (p < 0.05). Although the prevalences were generally higher during the summer months, no statistical differences were detectable when looking at the pattern between the four seasons, neither for dogs, nor for cats. Interestingly, the highest prevalences in dogs (9.9%) were detected in June 2004 and comparatively, in cats (23.86%) in August. The lowest detection rates in dogs were seen (1.28%) in April and in cats (7.26%) in January. The preliminary results did not indicate any tendency for a relationship between climatic conditions and flea infestation rates. Similarly, no differences of the infestations rates were detectable between urban and rural areas, 56% (dogs) and 46% (cats) of the infested pets originated from urban habitats. The flea species collected include Ctenocephalides felis, Ctenocephalides canis, Archaeopsylla erinacei, Pulex irritans, Ceratophyllus gallinae, etc. The overall frequencies reveal that C. felis was the most prominent species (81.5%), followed by C. canis (12.5%), A. erinacei (2.7%) and P. irritans (1.7%).

Animals↗

Occupational risk factors for symptomatic lumbar disc herniation; a case-control study.

BACKGROUND: Previous studies mostly did not separate between symptomatic disc herniation combined with osteochondrosis/spondylosis of the lumbar spine and symptomatic disc herniation in radiographically normal intervertebral spaces. This may at least in part explain the differences in the observed risk patterns. AIMS: To investigate the possible aetiological relevance of physical and psychosocial workload to lumbar disc herniation with and without concomitant osteochondrosis/spondylosis. METHODS: A total of 267 cases with acute lumbar disc herniation (in two practices and four clinics) and 197 control subjects were studied. Data were gathered in a structured personal interview and analysed using logistic regression to control for age, region, nationality, and diseases affecting the lumbar spine. Cases without knowledge about osteochondrosis/spondylosis (n=42) were excluded from analysis. Risk factors were examined separately for those cases with (n=131) and without (n=94) radiographically diagnosed concomitant osteochondrosis or spondylosis. RESULTS: There was a statistically significant positive association between extreme forward bending and lumbar disc herniation with, as well as without concomitant osteochondrosis/spondylosis. There was a statistically significant relation between cumulative exposure to weight lifting or carrying and lumbar disc herniation with, but not without, concomitant osteochondrosis/spondylosis. Cases with disc herniation reported time pressure at work as well as psychic strain through contact with clients more frequently than control subjects. CONCLUSIONS: Further larger studies are needed to verify the concept of distinct aetiologies of lumbar disc herniation in relatively younger persons with otherwise normal discs and of disc herniation in relatively older persons with structurally damaged discs.

Adult↗

Increased reduction of dimethylarginines and lowered interdialytic blood pressure by the use of biocompatible membranes.

Hypertension contributes to cardiac and cerebrovascular complications in HD patients. Endogenous inhibitors of nitric oxide synthase accumulate in renal failure and may interfere with the regulation of vascular tone. We investigated the elimination of asymmetric dimethylarginine (ADMA) by using biocompatible Polyamide Strade mark membranes in low-flux (Polyflux 6L) or high-flux (Polyflux 14S) hemodialysis or hemodiafiltration (HDF) compared with hemodialysis with cellulosic membranes. Removal rates for ADMA, symmetric dimethylarginine (SDMA), and beta2-microglobulin significantly increased in HDF. The plasma total amino acid concentration and the arginine/ADMA ratio increased, and the mean 24-hour blood pressure decreased during the study. In a second study, we investigated whether plasma amino acids and interdialytic blood pressure are influenced by the use of a biocompatible membrane and HDF. Seventeen end-stage renal disease patients were treated for six weeks with hemodialysis using cellulosic membranes, six weeks with low-flux hemodialysis using Polyflux 6L, and six weeks with HDF using Polyflux 14S. Only in the diabetic patients were the hemoglobin concentration (from 10.6 +/- 1.5 to 11.9 +/- 0.6 mg/dL) and hematocrit (from 33.6 +/- 1.9 to 36.2 +/- 1.5%) increased significantly, whereas the mean 24-hour systolic blood pressure decreased (from 154 +/- 22 to 129 +/- 18 mm Hg). No significant changes were observed in nondiabetic patients. We conclude that primarily diabetic patients seem to benefit from the use of biocompatible membranes--most in HDF--after a period of six weeks. The regulation of nitric oxide pathways by ADMA removal and changed ADMA/arginine ratio might be contributing factors. Further prospective studies are required to show whether the long-term application of HDF or other changes of dialysis treatment modalities may help to improve well-being, morbidity, and mortality in hemodialysis patients.

Adult↗

Complement components as uremic toxins and their potential role as mediators of microinflammation.

Cardiovascular disease is the major cause of death in end-stage renal disease (ESRD) patients. There is growing evidence that atherogenesis is an inflammatory rather than a purely degenerative process leading to a state of microinflammation. This raises the issue of whether treatment modalities of ESRD contribute to the microinflammatory state. One potential candidate in this context is the complement system. Here we consider three potential pathways linking complement activation to progression of atherosclerosis: (1) complement activation on artificial surfaces depends on their physicochemical characteristics, the effect of which is amplified because of the accumulation of complement factor D; (2) the exposure of ESRD patients to endotoxin creates a microinflammatory state, and this may amplify complement-induced damage; exposure to endotoxin may result from frequent infections because of the impairment of host-defense mechanisms or from transfer of bacterial contaminants across dialysis membranes into the blood stream; and (3) direct transduction of proinflammatory signals from blood-material interactions to the vascular system. We conclude that the complement system is an important candidate system in the genesis of microinflammation and accelerated atherogenesis in ESRD. We advance the hypothesis that the generation of proinflammatory signals, in which the complement system appears to be involved--both through systemic and local activation--plays a role in the development of late complications of uremia, including coronary heart disease. This hypothesis provides a rationale to maximize the biocompatibility of the dialysis procedure, that is, selection of nonactivating materials, use of ultrapure dialysis fluid, and--still theoretical--high-flux dialysis to remove factor D.

Acute-Phase Reaction↗

Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis.

OBJECTIVE: A double-blind, placebo-controlled dose-finding study was performed in 237 patients with predominantly unilateral knee osteoarthritis (OA) evaluating efficacy and safety of a new topical NSAID. DESIGN: The patients applied 3 g tid eltenac gel 0.1%, 0.3%, 1% or placebo gel over a period of 4 weeks. The patients were supplied with paracetamol tablets as an escape analgesic. Primary efficacy end-point was mean global pain in the week preceding the examinatio ns, evaluated on a visual analog scale (VAS). Secondary criteria were Lequesne's score ISK, Jezek score, muscle strength and dolorimeter measurements, walking time, clinical examination results of the knee joint and patient's and investigator's overall efficacy estimates. RESULTS: The graphical depiction of VAS and ISK suggested a dose-related efficacy, but the pre-planned statistical analysis did not show significant differences between treatments. In the patient subgroup with a higher degree of baseline severity of knee OA the ISK showed significant and relevant advantages of eltenac gel 1% to placebo at different examination times. Two patients each of the eltenac gel 1% group and the placebo group showed local intolerance reactions which subsided spontaneously. CONCLUSION: This study did not provide confirmatory proof of an efficacy of topical eltenac in patients with knee OA. Methodological pitfalls and possible responder subgroups are described. Despite the difficulties, dose-finding studies seem to be feasible even with topical NSAIDs.

Administration, Topical↗

The role of cumulative physical work load in lumbar spine disease: risk factors for lumbar osteochondrosis and spondylosis associated with chronic complaints.

OBJECTIVES: To investigate the relation with a case-control study between symptomatic osteochondrosis or spondylosis of the lumbar spine and cumulative occupational exposure to lifting or carrying and to working postures with extreme forward bending. METHODS: From two practices and four clinics were recruited 229 male patients with radiographically confirmed osteochondrosis or spondylosis of the lumbar spine associated with chronic complaints. Of these 135 had additionally had acute lumbar disc herniation. A total of 197 control subjects was recruited: 107 subjects with anamnestic exclusion of lumbar spine disease were drawn as a random population control group and 90 patients admitted to hospital for urolithiasis who had no osteochondrosis or spondylosis of the lumbar spine radiographically were recruited as a hospital based control group. Data were gathered in a structured personal interview and analysed using logistic regression to control for age, region, nationality, and other diseases affecting the lumbar spine. To calculate cumulative forces to the lumbar spine over the entire working life, the Mainz-Dortmund dose model (MDD), which is based on an overproportional weighting of the lumbar disc compression force relative to the respective duration of the lifting process was applied with modifications: any objects weighing >or=5 kg were included in the calculation and no minimum daily exposure limits were established. Calculation of forces to the lumbar spine was based on self reported estimates of occupational lifting, trunk flexion, and duration. RESULTS: For a lumbar spine dose >9 x 10(6) Nh (Newton x hours), the risk of having radiographically confirmed osteochondrosis or spondylosis of the lumbar spine as measured by the odds ratio (OR) was 8.5 (95% confidence interval (95% CI) 4.1 to 17.5) compared with subjects with a load of 0 Nh. To avoid differential bias, forces to the lumbar spine were also calculated on the basis of an internal job exposure matrix based on the control subjects' exposure assessments for their respective job groups. Although ORs were lower with this approach, they remained significant. CONCLUSIONS: The calculation of the sum of forces to the lumbar spine is a useful tool for risk assessment for symptomatic osteochondrosis or spondylosis of the lumbar spine. The results suggest that cumulative occupational exposure to lifting or carrying and extreme forward bending increases the risk for developing symptomatic osteochondrosis or spondylosis of the lumbar spine.

Adult↗

p-ethynylphenylalanine: a potent inhibitor of tryptophan hydroxylase.

Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in serotonin biosynthesis. The enzyme activity is dependent on molecular oxygen, a tetrahydropterin cosubstrate, and ferrous iron. The present study demonstrates that TPH is inhibited by a novel compound, p-ethynylphenylalanine (pEPA), produced by the Heck reaction of trimethylsilylacetylene with N-tertbutyloxycarbonyl-4-iodo-L-phenylalanine methyl ester. pEPA is a more potent and specific inhibitor of TPH than p-chlorophenylalanine (pCPA). In the present study, pEPA was demonstrated to inhibit competitively and reversibly TPH in vitro (Ki = 32.6 +/- 6.2 microM vs. tryptophan). pEPA displayed little inhibitory activity toward tyrosine hydroxylase (EC 1.14.16.2), the initial and rate-limiting enzyme for catecholamine biosynthesis, and no inhibition of phenylalanine hydroxylase or tyrosinase. In addition, pEPA was a poor ligand for the serotonin transporter and several serotonin receptors. Administration of pEPA (30 mg/kg) to rats produced a 95 +/- 5% decrease in TPH activity in brain homogenates and a concomitant decrease in serotonin and 5-hydroxyindole-3-acetic acid levels (85%) at 24 h after injection. In contrast, pCPA produced a similar effect (87 +/- 5% decrease in TPH activity) only at 10 times the concentration (300 mg/kg). These results suggest that pEPA is a selective, reversible, and potent inhibitor of TPH both in vitro and in vivo. The potential for pEPA to inhibit selectively and reversibly the biosynthesis of serotonin may contribute to the characterization of the role of serotonin in behavioral and physiological activities.

Alanine↗

Synthesis of 1-(2-aminophenyl)isoquinolines and the biological activity of their cis-dichloro platinum(II) complexes.

The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compounds constitute a new class of ligands for the synthesis of oligocyclic platinum(II) complexes. In vitro cytotoxicity tests indicate that the most basic amine ligands afford the most effective complexes. Two of the new complexes were more potent against L1210 murine leukemia cells than the well-established antitumor compound cisplatinum.

Animals↗

Bis[platinum(II)] and bis[platinum(IV)] complexes with optically active bis(vicinal-1,2-diamines) and their interaction with DNA.

Bis[platinum(II)] [Cl2Pt(LL)PtCl2] complexes 2,5 and 8 with chiral non-racemic ligands: 1a-c (LL = (R,R), (S,S) and (R,S) N,N'-bis(3,4-diaminobutyl)hexanediamide); 4a,b (LL = (R,R) and (S,S) N,N'-bis[3,4-bis(diaminobutyl)] urea); 7a-d (LL' = (R,R), (S,S), (R,S) and (S,R) 4,5-diamino-N-(3,4-diaminobutyl) pentanamide) and bis[platinum(IV)] complex 10-13 with ligands 1a,b and 4a,b have been prepared and characterized by IR, 1H, 13C and 195Pt NMR spectra. The interactions of 2a-c, 5a, 5b, 8a-d and 10a with dsDNA were investigated with the goal of examining whether the chirality, the nature of the spacer and the oxidation state have an influence on platinum-DNA binding properties. All the bis[platinum(II)] complexes form with dsDNA intra- and interstrand crosslinks and crosslinks over sticky ends, whereas the bis[platinum(IV)] complex 10a only forms intra- and interstrand crosslinks. The platinum-DNA coordination sites were determined by the T4 DNA polymerase footprinting method. The results show that all investigated bis(platinum) complexes have high preference towards distinct purines. All isomeric bis(amide) 2a-c and mono(amide) 8a-d complexes exhibit nearly the same binding pattern, whereas the ureide complexes 5a and 5b have other coordination sites with higher sequence preference. Interestingly, the ureides 5a and 5b differ in their coordination sites not only in comparison to the bis(amides) 2a-c and mono(amides) 8a-d, but also between each other. The bis[platinum(IV)] complex 10a also differs in coordination sites in comparison to all the bis[platinum(II)] compounds.

Animals↗

[Farm animals as disease vectors of parasitic epizoonoses and zoophilic dermatophytes and their importance in dermatology].

Different pest arthropods and dermatophytes occurring primarily in farm animals may be transmissible to man and produce human dermatoses. The movement and cutaneous penetration habits of external parasites often cause crusted papules, severe itching and dermatitis or may damage their hosts by blood-sucking or by sensitizing them to their saliva. Furthermore different dermatophytes should be considered a possible cause of human skin lesions. Farm animals (cattle, pig, poultry, and rabbit) can transmit external parasites (ticks: Ixodes ricinus, Argas reflexus; fleas: Ceratophyllus gallinae, Spilopsyllus cuniculi, and mites: Sarcoptes scabiei var. bovis, Sarcoptes scabiei var. suis, Dermanyssus gallinae, Cheyletiella parasitovorax), and dermatophytes (Trichophyton sp., and Microsporum sp.). People who have close contact to infested farm animals are more often exposed to epizoonotic infections. Certain professions, such as farmers, and veterinarians, are especially vulnerable.

Agricultural Workers' Diseases↗

Advanced glycated end-products (AGE) during haemodialysis treatment: discrepant results with different methodologies reflecting the heterogeneity of AGE compounds.

BACKGROUND: There has been much recent interest in accumulation of advanced glycation end-products (AGE) in uraemic patients. Analysis of AGE has been difficult, because commonly used methodologies, i.e. immunodetection assays or fluorescence measurements, reflect group reactivity and are not specific for chemically defined substances. Some investigators measured individual AGE compounds, e.g. pentosidine, carboxymethyllysine, pyrraline or imidazolone, but a systematic assessment of known compounds using specific HPLC methods in diabetic and non-diabetic end-stage renal disease (ESRD) patients during treatment has not been performed. METHODS: For the present study, the concentrations of early and late products of the Maillard reaction in plasma and ultrafiltrate were monitored during high-flux dialysis sessions in diabetic and non-diabetic patients. AGE were analysed by fluorescence spectroscopy and size exclusion chromatography with fluorescence detection. Specific HPLC methods were used to quantify the Amadori product fructoselysine and the AGE compounds pentosidine and pyrraline in acid or enzymatic hydrolysates. RESULTS: Using size exclusion chromatography, we confirmed a similar fluorescent peak distribution for diabetic and non-diabetic ESRD patients. Main fractions were found at approximately 70, approximately 14 and <2 kDa, confirming results obtained by other authors. In diabetic patients, the fluorescence intensity of the low molecular weight fraction was higher. Uraemic patients differed from controls mainly by the fluorescence of the low molecular weight fraction. The peak spectrum in ultrafiltrates was similar to that in plasma regarding low molecular weight fractions and the 14 kDa peak, but no protein-bound fluorescence was found at 70 kDa. HPLC analysis revealed a significant reduction of plasma pentosidine during high-flux dialysis in non-diabetic (from 9.1+/-5.1 to 8.5+/-4.7 pmol/mg protein; P<0.05) and diabetic patients (from 10.0+/-9.1 to 6.8+/-4.0 pmol/mg protein; P<0.05). In contrast, plasma fructoselysine showed only a non-significant trend to decrease in diabetic (from 3.24+/-0.88 to 3.05+/-0.77 nmol/mg protein) and non-diabetic patients (from 2.69+/-0.52 to 2.56+/-0.50 nmol/mg protein). Pyrraline, a nonfluorescent late AGE product derived from reaction of 3-deoxyglucosone with lysine, could not be detected (detection limit approximately 40 pmol/mg protein). Comparing HPLC and size exclusion analysis, it was found that pentosidine accumulated in the range of low molecular weight substances and was removed by high-flux dialysis. CONCLUSIONS: High-flux dialysis reduces the plasma concentration of fluorescent AGE compounds, i.e. pentosidine, but the Amadori product fructoselysine is not removed, indicating that this compound is protein associated.

Adult↗

New aza-dipeptide analogues as potent and orally absorbed HIV-1 protease inhibitors: candidates for clinical development.

On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,8 aza-dipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) or orthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

Administration, Oral↗

[Zoophilic dermatophytes as epizoonoses pathogens and their significance to dermatology].

Different dermatophytes occurring primarily in animals may be transmissible to man and produce human disease; such zoophilic fungi should be considered a possible cause of skin lesions of unclear origin. Several species including Trichophyton verrucosum, Trichophyton mentagrophytes and Microsporum canis may infect human skin, causing a variety of signs and symptoms. People who have close contact to infested cattle or cats are more often exposed to fungal infections. Certain professions, such as farmers, and children are especially vulnerable. Finally, less common ways of transmission of dermatophytoses from other animal species to man are discussed.

Adult↗

[Evaluation of an intracutaneous test using a Sarcoptes mite extract solution (Acari: Sarcoptidae) as a method for detection of Sarcoptes mite-infested dogs].

Sarcoptes infestation in dogs, caused by Sarcoptes canis, is a relatively common disease in small animal practice. The parasites may induce severe allergic skin reactions. By means of clinical symptoms a presumptive diagnosis should be made. For ensurement detection of mites in skin scrapings is necessary, but it is not easy to find the parasites. Serodiagnostic methods are helpful to confirm the diagnosis. They indicate specific antibody (circulating IgE) titer. Intracutaneous test by using allergen extracts as possible third way of diagnostic methods was tested comparatively with the existing causaldiagnostic procedures in 45 dogs with suspected scabies. Preconditions of own examinations was mite antigen preparation. A mite extract solution of Sarcoptes suis was prepared and 0.1 ml were applicated intracutaneously. In 14 dogs (31.11%) allergic skin changes (Immediate reaction type 1) became apparent. The results were opposed to both other detection methods--skin scraping (4 positive findings/8.89%) and serodiagnosis (13 positive findings/30.77%).

Animals↗

Molecular interaction of DNA with bisplatinum(II) complexes having bis(vicinal 1,2-diamines) as ligand.

The interaction of novel, tetrafunctional bisplatinum compounds with DNA was investigated. These compounds have bis(vicinal 1,2-diamines) as ligand. The reactions' efficiency, types of cross-links, alterations of the global DNA structure, and sequence selectivity differ significantly from the corresponding features of cisplatin. In particular, they form multiple complexes with dsDNA, which include intrastrand, interstrand and interhelical cross-links and cross-links over sticky ends. The novel compounds are able to untwist but not shorten dsDNA. The reactivity and adduct-forming efficiency of these compounds is, depending on the spacer length, 100-200-fold higher than that of cisplatin. As a consequence, interstrand cross-links are also formed to a higher extent. The chemical stability of the interstrand cross-links against cyanide ions, however, is weaker than that of interstrand cross-links formed by cisplatin, suggesting that each platinum sphere of a bisplatinum compound forms intrastrand cross-links. With dsDNA, they show a preference toward purines, particularly guanines, but they apparently are also coordinated to other nucleobases. Their sequence selectivity toward dsDNA is higher than that of cisplatin. Thus, the novel compounds extend the spectrum of alternative platinum-based compounds with chemical features different from cisplatin.

Antineoplastic Agents↗

[Occupationally-induced degenerative discopathies in the area of the lumbar spine].

A case-control study comprising 188 male and 160 female cases from an orthopedic's cabin explained occupational risk factors for osteochondrosis, spondylosis, and spondylarthrosis of the lumbar vertebra. The controls (109 men, 130 women) steaming mainly from other physician's offices were free from musculoskeletal symptoms. Age-adjusted odds ratio (OR) were calculated for both sexes. In women elevated ORs were found for working in standing position (OR 2.2 CI 1.31-3.85), for repetitive work (OR 1.9 CI 1.17-3.36), for lifting heavy things up to 20 kg (OR 2.1 CI 1.24-3.67), for working as a secretary (OR 1.8 CI 1.16-3.0) or in a supermarket (OR 2.1 CI 1.05-4.56). Men showed elevated ORs for bending (OR 2.2 CI 1.27-4.08), vibrations of the upper limbs (OR 2.3 CI 1.12-5.02), whole-body-vibrations (OR 2.1 CI 1.14-4.11), working in the metal industry (OR 3.6 CI 1.88-6.89) or as motorists for more than ten years (OR 6.5 CI 1.54-27.99) and working in a humid or cold environment (OR 2.2 CI 1.30-3.72).

Adult↗