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Biomedical subjects

G Becker

Publications and source records attributed to G Becker.

At least 37 records · Page 2Linked to original sources

[Heidelberg Centenarian Study: theoretical and methodological principles for social science research of the oldest old].

This paper addresses two important issues of oldest old research. First, we try to answer the question whether differences between extremely old persons are based on enduring aging processes of physical, social and psychological functions, or whether they are the result of selective survival weeding out the frail. Both trajectories predict low variability, but on different levels. Second, we investigate to which extent the variability of extremely old persons can be assessed by traditional psychosocial instruments. One hundred and fifty six centenarians were contacted, of whom 91 centenarians and 86 proxies participated in this study. The distribution of the cognitive status reveals a high amount of variability. In contrast, with respect to functional capacity 83% receive support from the German Statutory Insurance System for Long-Term Care. The higher variability in the psychological variable points to adaptive potential. We assume that in extreme old age various resources are used to maintain physical functioning above a critical threshold.

Activities of Daily Living↗

Echogenicity of the substantia nigra in Parkinson's disease and its relation to clinical findings.

Recently an increased echogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD) was demonstrated by transcranial ultrasound (TCS). In this study we set out to compare SN echogenicitiy with disease characteristics (time of onset, duration, toxin exposure) in a large patients sample. Patients' history and exposure to toxins were recorded from 112 PD patients who underwent a thorough neurological examination including assessment of disease stage according to Hoehn and Yahr and CURS (Columbia University Rating Scale). Personality was assessed according to the Freiburg Personality Inventory. In all patients the area of SN echogenicity was encircled and measured by TCS. All except 9 patients had hyperechogenic SN areas exceeding the mean plus standard deviation values of an age matched control group (0.19 cm2). The age of disease onset was lower in patients who displayed an area of SN echogenicity above this value. The area of SN echogenicity was larger contralateral to the side with more severe symptoms. None of the other characteristics correlated with ultrasound findings. We conclude that SN hyperechogenicity is a typical finding in PD. The cause of hyperechogenicity is so far unknown. Investigation of the underlying reason might disclose a pathogenic factor in PD.

Aged↗

Morphine in tardive and idiopathic dystonia (short communication).

Opioids have been shown to improve L-Dopa induced dyskinesias in patients with Parkinson's disease. In this pilot trial of five patients with tardive and four patients with idiopathic dystonia we tested the effect of morphinsulfate in a retarded form with a dosage of 20-60 mg per day. A substantial improvement of dystonic movements could be observed in four patients with tardive and one patient with idiopathic dystonia. The effect was only transient in tardive dystonia while pain relief mediated by morphine overlasted the effect on involuntary movements.

Adult↗

Clinical indications and biological mechanisms of splenic irradiation in chronic leukaemias and myeloproliferative disorders.

Splenic irradiation (SI) was the first efficient treatment for chronic leukaemia, but with the emergence of effective drugs its use has been more and more restricted to advanced cases presenting with splenomegaly. But in selected patients who are not responsive or not suitable to drug treatment, SI may offer still an effective, low toxic and cost-effective palliative modality. Eight studies of SI in chronic lymphatic leukaemia (CLL) including 198 patients, six reports about SI in prolymphocytic leukaemia (PLL), including 18 patients, one study and six case reports about SI in hairy cell leukaemia (HCL) and nine studies about SI in myeloproliferative disorders has been analyzed. In CLL, symptoms of splenomegaly have been improved in 50-87% of all patients with overall doses between 4 and 10 Gy in mostly 1-Gy fractions. PLL seems to be more resistant to SI with a median response rate of 66%. Casuistic reports described also efficacy of SI in HCL patients using similar radiation schedules. Symptomatic relief is also provided by SI in myeloproliferative disorders using lower overall doses between 1 and 9 Gy with small single fractions of 0.25 Gy (median). Acute toxicity was low in lymphoid disorders, but higher in myeloproliferative disorders with severe cytopenia in 10-30% of all cases, indicating the need for a cautious fractionation schedule. Interestingly, even complete systemic remissions after SI in all types of lymphoproliferative disorders have been described. Different mechanisms underlying SI such as direct cell kill, immune modulation via changes in lymphocyte subsets or cytokine induction or "radiotherapeutic" splenectomy with high doses are discussed.

Chronic Disease↗

Basal limbic system alteration in major depression: a hypothesis supported by transcranial sonography and MRI findings.

The pathogenesis of major depression (MD) remains unclear despite intensive research in the last decades which brought up a multitude of findings illustrating the complexity of this disorder. In this paper we will summarize the evidence pointing towards a structural alteration of the basal limbic system in MD and depression in Parkinson's disease (PD). Transcranial ultrasound and MRI studies in both depressive syndromes revealed altered signal intensity of the brainstem midline comprising fibre tracts of the basal limbic system. The hypothesis of a structural disruption of the basal limbic system is supported by biochemical and histopathological findings. The similarity of findings in MD and depression in PD might reflect a relationship between MD and neurodegenerative disorders.

Brain Stem↗

Role of activator site position and a distal UP-element half-site for sigma factor selectivity at a CRP/H-NS-activated sigma(s)-dependent promoter in Escherichia coli.

Transcription initiation by the stress-associated sigma(S)-containing RNA polymerase holoenzyme (E sigma(S)) in Escherichia coli is often subject to complex regulation that involves multiple additional regulators and histone-like proteins. csiD is a stationary phase-inducible sigma(S)-dependent gene in E. coli that requires activation by cAMP-CRP (bound to a site centred at -68.5 nucleotides upstream of the transcriptional start site) and is positively modulated by the abundant nucleoid-associated proteins H-NS and Lrp. By shifting the CRP box to positions between -80.5 and -60.5, we could demonstrate that: (i) activation is equally helix phase dependent as at classic class I promoters; (ii) E sigma(S) prefers a CRP box location at -68.5/-70.5, whereas E sigma(70) is nearly inactive with such an arrangement; and (iii) with the CRP site moved to -60.5, transcription can be initiated efficiently by both holoenzymes. The csiD promoter region also contains a distal UP-element half-site located downstream of the CRP box, as demonstrated by mutational studies, in which this element was either eliminated or completed to a full UP-element. The UP-element half-site favours E sigma(S)-mediated expression, whereas with the full UP-element, nearly wild-type levels of csiD transcription were observed in the absence of sigma(S). Finally, we show that the two histone-like proteins, H-NS and Lrp, both act by influencing activation by cAMP-CRP, but do so by different mechanisms. In particular, H-NS directly or indirectly increases positional stringency for the CRP binding site. The implications of these findings with respect to sigma factor selectivity, activation mechanisms used by the two holoenzymes and the architecture of sigma(S)-dependent promoters are discussed.

Bacterial Proteins↗

Brain iron pathways and their relevance to Parkinson's disease.

A central role of iron in the pathogenesis of Parkinson's disease (PD), due to its increase in substantia nigra pars compacta dopaminergic neurons and reactive microglia and its capacity to enhance production of toxic reactive oxygen radicals, has been discussed for many years. Recent transcranial ultrasound findings and the observation of the ability of iron to induce aggregation and toxicity of alpha-synuclein have reinforced the critical role of iron in the pathogenesis of nigrostriatal injury. Presently the mechanisms involved in the disturbances of iron metabolism in PD remain obscure. In this review we summarize evidence from recent studies suggesting disturbances of iron metabolism in PD at possibly different levels including iron uptake, storage, intracellular metabolism, release and post-transcriptional control. Moreover we outline that the interaction of iron with other molecules, especially alpha-synuclein, may contribute to the process of neurodegeneration. Because many neurodegenerative diseases show increased accumulation of iron at the site of neurodegeneration, it is believed that maintenance of cellular iron homeostasis is crucial for the viability of neurons.

Animals↗

Influence of an infectious disease consulting service on quality and costs of antibiotic prescriptions in a university hospital.

An infectious disease consulting service was set up at a large tertiary university hospital in 1996 to evaluate and to improve antibiotic prescription patterns. Treatment guidelines for the most common bacterial infections were implemented. On daily ward rounds antibiotic therapies without evidence of an infectious disease were stopped and inappropriate regimens were changed by an infectious disease specialist. During a 6-month prospective intervention period, 3,528 patients were studied on 13 wards of the department of internal medicine; 513 of these patients (14.5%) received antibiotic therapy. These treatment courses were evaluated as adequate in 394 cases (76.8%) and incorrect in 119 cases (23.2%). Inadequate antibiotic substances were chosen in 72 out of 119 cases (60.5%) and there was no indication for treatment in 38 out of 119 cases (32%). Pathogen-specific therapies were inadequate significantly more often than empirical antimicrobial therapies (p < 0.001). In addition, the duration of the perioperative prophylaxis could be limited to 1 d. Comparing the intervention period with a 3-month control interval without an infectious disease consulting service, a total of 31,510 Euro (including the costs for the infectious disease specialist) could be saved. No increase in infection-related mortality or length of stay was observed. These data show that an infectious disease consulting service optimizes antibiotic usage, and is cost-effective as a result of a significant cost reduction in hospitals, while not interfering with the quality of medical care.

Anti-Bacterial Agents↗

What makes an Escherichia coli promoter sigma(S) dependent? Role of the -13/-14 nucleotide promoter positions and region 2.5 of sigma(S).

The sigmaS and sigma70 subunits of Escherichia coli RNA polymerase recognize very similar promoter sequences. Therefore, many promoters can be activated by both holoenzymes in vitro. The same promoters, however, often exhibit distinct sigma factor selectivity in vivo. It has been shown that high salt conditions, reduced negative supercoiling and the formation of complex nucleoprotein structures in a promoter region can contribute to or even generate sigmaS selectivity. Here, we characterize the first positively acting sigmaS-selective feature in the promoter sequence itself. Using the sigmaS-dependent csiD promoter as a model system, we demonstrate that C and T at the -13 and -14 positions, respectively, result in strongest expression. We provide allele-specific suppression data indicating that these nucleotides are contacted by K173 in region 2.5 of sigmaS. In contrast, sigma70, which features a glutamate at the corresponding position (E458), as well as the sigmaS(K173E) variant, exhibit a preference for a G(-13). C(-13) is highly conserved in sigmaS-dependent promoters, and additional data with the osmY promoter demonstrate that the K173/C(-13) interaction is of general importance. In conclusion, our data demonstrate an important role for region 2.5 in sigmaS in transcription initiation. Moreover, we propose a consensus sequence for a sigmaS-selective promoter and discuss its emergence and functional properties from an evolutionary point of view.

Amino Acid Sequence↗

Effects of being uninsured on ethnic minorities' management of chronic illness.

OBJECTIVE: To compare the effectiveness with which insured and uninsured persons with chronic illnesses managed their health care. DESIGN: Recruited volunteers diagnosed with a variety of chronic illnesses who underwent 3 semistructured interviews in a 1-year period. SETTING: Volunteers were recruited through referrals, flyers, and face-to-face contacts from community health clinics, senior centers, acute care hospitals, and home care services in 2 urban counties in California between December 1997 and December 2000. PARTICIPANTS: A total of 297 persons between the ages of 23 and 97 years (35% African American, 33% Latino, and 32% Filipino American), of whom 42 (14%) had no health insurance. MAIN OUTCOME MEASURES: Qualitative analysis of interview data compared insured and uninsured respondents on a series of components of chronic illness management, including control over illness, frequency of health crises, procuring medication, use of medication, understanding of the illness, knowledge of self-care measures, and awareness of risk factors. Whether respondents were under the care of a regular physician was also assessed. RESULTS: Compared with insured respondents, uninsured respondents were much less effective at managing their illnesses. The uninsured had poorly controlled illnesses, frequent health crises, difficulty procuring medication, used medication incorrectly, demonstrated poor understanding of their illness, and displayed little knowledge of self-care measures or risk awareness. They rarely had a regular physician or attended a specific health clinic. CONCLUSIONS: The findings suggest that not only did uninsured persons with chronic health conditions lack adequate health care, their illnesses were also poorly controlled. Inadequately educated about their health, uninsured persons lacked the information, insight, and tools that would have allowed them to manage their illnesses more effectively.

Adult↗

On the far reaching effects of using biased estimates of score reliability: an examination of the problem in 20 data analyses.

Violation of either of two basic assumptions in classical test theory may lead to biased estimates of reliability. Violation of the assumption of essential tau-equivalence may produce underestimates, and the presence of correlated errors among measurement units may result in overestimates. The ubiquity of circumstances in which this problem may occur is not fully comprehended by many workers. This article surveys a variety of settings in which biased reliability estimates may be found in an effort to increase awareness of the prevalence of the problem.

Bias↗

Controlling decremental and inflationary effects in reliability estimation resulting from violations of assumptions.

Two assumptions in classical test theory, essential tau-equivalence and independence of measurement errors, when violated may produce attenuated or inflated estimates of reliability, respectively. Inflation stemming from correlated errors can be controlled by a procedure in which systematically created equivalent halves of a given measuring instrument are administered across two occasions. When poor approximations to equivalent halves are constructed for this purpose, however, distortion in the opposite direction may result, being sometimes quite large when measuring instruments are not essentially tau-equivalent (or, at the practical level, unidimensional). The nature of these decrements are discussed and illustrated, and a number of procedures for eliminating them introduced.

Bias↗

Using temporal information to construct, update, and retrieve situation models of narratives.

Four experiments explored how readers use temporal information to construct and update situation models and retrieve them from memory. In Experiment 1, readers spontaneously constructed temporal and spatial situation models of single sentences. In Experiment 2, temporal inconsistencies caused problems in updating situation models similar to those observed previously for other dimensions of situation models. In Experiment 3, merely implied temporal order information was inferred from narratives, affecting comprehension of later sentences like explicitly stated order information. Moreover, inconsistent temporal order information prevented the creation and storage in memory of an integrated situation model. In Experiment 4, a temporal inconsistency increased processing time even if readers were unable to report the inconsistency. These results confirm the significance of the temporal dimension of situation models.

Adult↗

Reduction of Menkes mRNA and copper in leukocytes of patients with primary adult-onset dystonia.

Studies on postmortem tissue of patients with primary adult-onset dystonia revealed a significant increase in copper levels and a reduction of copper transporting Menkes protein of the lentiform nuclei. Here we demonstrate that patients with idiopathic adult-onset cervical dystonia (n = 14) have reduced Menkes mRNA copies and lower copper levels in leukocytes compared to controls (n = 17; U test, p < 0.05). Changes were less distinct in patients with blepharospasm. Therefore, disturbances of copper metabolism in focal dystonia may not be restricted to the basal ganglia.

Adenosine Triphosphatases↗

[Quality evaluation of the orthodontic practice for certification by ISO 9001. A procedure beneficial for medical, medico-dental or hospital service].

The accreditation of the ISO 9001 certification (ISO = International Standard Organization) is an external evaluation procedure carried out by independent experts, whose object is the analysis of the operational methods and practices of a medical care facility (e.g. hospital, private clinic, general practitioner's or dentist's practice) which decided to assume the concept, implementation and control of its own quality policy. The whole accreditation procedure represents the basic structure of a continuous dynamic progressiveness within a cabinet eager to offer outstanding quality. Moreover, it guarantees active and voluntary participation of every single member of the medical administration or technical team involved in the realization of this primary objective. In other words, we are talking about a very strong dynamic innovation leading to a change of views and the improvement of communication means, while simultaneously enhancing the security and quality aspects of medical care. The continuous guarantee of high quality medical care calls for precise planning and systematization of actions. First of all, these actions are defined, analyzed and listed in precise work procedures. As they are defined with the agreement of the whole team, they implicate respect and self control. This requires of course transparency of the treatment methods, whose different steps and procedures are described in detail in a logogramm set up in common.

Accreditation↗

Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients.

Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinson's disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI = 0.36-0.88; p = 0.012, p(c) = 0.047, chi2 = 6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration.

Aged↗